Bio


Dr. Chris Holsinger is Professor of Head and Neck Surgery at Stanford University. His research focuses on surgical innovation, AI, and clinical trials. He serves as surgical principal investigator for RTOG920 and coordinated surgeon-credentialing for ECOG 3311, a prospective clinical trial to study robotic head and neck surgery. In 2019, he published the results of an investigational device exemption clinical study to evaluate the safety and efficacy of a next-generation robotic surgical system for head and neck cancer. He currently serves as Co-Chair of the Surgical TaskForce of the NRG Oncology's Head and Neck Committee.

His interests extend beyond robotics, however, and include new technologies for augmenting the surgical vision and improving intra-operative decision-making. How can surgeons do better by incorporating computer vision and AI into routine surgical practice and endoscopy? This question drives ongoing research and development in providing real-time intelligence during H&N endoscopy and surgery. In 2018, work from a prospective clinical trial demonstrated the feasibility of using multispectral imaging of patients with oropharyngeal cancer, in an effort to better identify tumor margins, as well as to evaluate hyper-spectral imaging to improve surgical vision. Recently, he co-founded Photonic Medical Technologies to translate these innovations into practice for open surgery.

Dr. Holsinger received his medical degree from Vanderbilt School of Medicine, completed his internship and residency at Baylor College of Medicine and his Fellowship in head and neck surgical oncology at The University of Texas M. D. Anderson Cancer Center. In 2003, he was awarded Fulbright Scholarship to study surgery at the University of Paris with Professor Ollivier Laccourreye and with Professor Wolfgang Steiner at the Georg-August University in Göttingen.

From 2003-2013, Dr. Holsinger worked at the Department of Head and Neck Surgery at the University of Texas M.D. Anderson Cancer Center where he founded and led the Program in Minimally Invasive and Endoscopic Head and Neck Surgery and co-directed the program in Minimally Invasive Technology in Oncologic Surgery. In 2013, Dr. Holsinger moved to Stanford University to serve as Chief of Head and Neck Surgery and lead the H&N Multidisciplinary Cancer Care Clinical Program.

Dr. Holsinger’s surgical practice focuses on the surgical management of thyroid as well as head and neck cancer. His areas of research interest include endoscopic head and neck surgery, including transoral robotic surgery and transoral laser microsurgery, as well as time-honoured approaches of conservation laryngeal surgery and supracricoid partial laryngectomy.

Board-certified by the American Board of Otolaryngology, Dr. Holsinger is a member of numerous societies including the American College of Surgeons, American Head and Neck Society, the American Thyroid Association, and the American Society of Clinical Oncology.

Clinical Focus


  • Cancer > Head and Neck Cancer
  • Thyroid Surgery
  • Thyroid Cancer
  • Robotic Surgery, Head & Neck
  • Paraganglioma, Carotid Body
  • Thyroid Neoplasms
  • Parathyroid Surgery
  • Oropharyngeal Cancer
  • Throat
  • Otolaryngology

Academic Appointments


Administrative Appointments


  • Director, Head and Neck Cancer Care Program, Stanford Cancer Center (2013 - 2017)
  • Affiliated Faculty, Center for Artificial Intelligence in Medicine and Imaging (2020 - Present)
  • Member, Stanford Cancer Institute (2013 - Present)

Professional Education


  • Residency: Baylor College of Medicine Otolaryngology Residency (2001) TX
  • Internship: Baylor College of Medicine Surgery Residency (1996) TX
  • Fellowship: MD Anderson Cancer Center (2003) TX
  • Board Certification: American Board of Otolaryngology, Otolaryngology (2002)
  • Medical Education: Vanderbilt University School of Medicine (1995) TN
  • Fulbright Scholarship, Université de Paris V, Rene Descartes Sorbonne Paris Cité, France, Post-doctoral Fellowship in Head and Neck Surgery (2003)
  • Fellowship, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Head and Neck Surgical Oncology (2003)
  • Residency, Bobby R. Alford Department of Otolaryngology--Head and Neck Surgery, Baylor College of Medicine, Otolaryngology--Head and Neck Surgery (2001)
  • Internship, Debakey Department of Surgery Baylor College of Medicine, General Surgery (1997)
  • MD, Vanderbilt University School of Medicine (1995)

Current Research and Scholarly Interests


Dr. Holsinger’s surgical practice focuses on the surgical management of benign and malignant diseases of the thyroid, parathyroid and head and neck.

His areas of clinical interest include endoscopic head and neck surgery, including robotic thyroidectomy, transoral robotic surgery and transoral laser microsurgery, as well as time-honoured approaches of conservation laryngeal surgery, supracricoid partial laryngectomy.

Clinical Trials


  • Multidimensional and Multimodal Profiling of Oropharyngeal Carcinoma Recruiting

    The purpose of this study is to better understand the natural history of oropharyngeal carcinoma (OPC), with or without an association with the human papilloma virus (HPV). For this study, the investigators plan to collect blood from OPC patients prior to treatment and at six subsequent time points.

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  • Post-operative Adjuvant Treatment for HPV-positive Tumours (PATHOS) Recruiting

    The main objectives of the PATHOS study are: To assess whether swallowing function can be improved following transoral resection of HPV-positive OPSCC, by reducing the intensity of adjuvant treatment protocols. The aim is to personalise treatment, based on disease biology (HPV status and pathology findings), to optimise patient outcomes. To demonstrate the non-inferiority of reducing the intensity of adjuvant treatment protocols in terms of overall survival in the reduced intensity treatment arms.

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  • Clinical Validation of ThyroidPrint: A Gene Expression Signature for Diagnosis of Indeterminate Thyroid Nodules Not Recruiting

    A clinical trial is proposed, to clinically validate, in a US population, the diagnostic performance of a new genetic test (ThyroidPrint). It will determine the nature of thyroid nodules that have been informed as indeterminate by cytology through a fine needle aspiration (FNA). The Genetic Classifier for Indeterminate Thyroid Nodules is a test that determines the expression of a panel of 10 biomarkers (CXCR3, CCR3, CXCl10, CK19, TIMP1, CLDN1, CAR, XB130, HO-1 and CCR7). Gene expression data is analyzed through an algorithm that generates a composite score that predicts the risk of malignancy. It´s intended use is for patients with thyroid cytology as indeterminate (Bethesda III and IV, according to The Bethesda System for Reporting Thyroid Cytopathology). This test uses a fine needle aspiration (FNA) sample.

    Stanford is currently not accepting patients for this trial.

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  • Multispectral Imaging to Characterize Patterns of Vascular Supply Within Lymphoepithelial Mucosa in Oropharyngeal Cancer Not Recruiting

    The purpose of this study is to characterize the blood supply at the base of the tongue and within the tonsil region. We hypothesize that high-resolution Narrow Band Imaging (NBI) will improve the diagnosis of oropharyngeal carcinoma (OPC). The goal is to provide the better assessment of tumor and thus providing better preoperative expectations to patients with OPC or tumor extent prior to radiation therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nikta Bedi, 650-723-5957.

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  • Prospective, Multicenter da Vinci® SP™ Surgical System TORS Study Not Recruiting

    A prospective, multicenter investigation of the da Vinci® SP™ Surgical System in Transoral Robotic Surgery (TORS) procedures for malignant oropharyngeal tumors.

    Stanford is currently not accepting patients for this trial.

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  • Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer Not Recruiting

    This randomized phase II trial studies how well transoral surgery followed by low-dose or standard-dose radiation therapy works in treating patients with human papilloma virus (HPV) positive stage III-IVA oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet known how much extra treatment needs to be given after surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ekaterina Dib, 650-723-0503.

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2024-25 Courses


All Publications


  • Comorbid Depression in Patients With Head and Neck Cancer Compared With Other Cancers. JAMA otolaryngology-- head & neck surgery Martinez, M. C., Finegersh, A., Baik, F. M., Holsinger, F. C., Starmer, H. M., Orloff, L. A., Sunwoo, J. B., Sirjani, D., Divi, V., Chen, M. M. 2024

    Abstract

    Depression is more prevalent among individuals with cancer than in the general population and is correlated with increased mortality in patients with head and neck cancer (HNC) in particular.To compare the prevalence of depression between patients with HNC and patients with other cancers.This retrospective cohort study used population-level data on patients aged 18 years or older with cancer who participated in the 2019 National Health Interview Survey and had completed the Personal Health Questionnaire-8 (PHQ-8). The analysis was performed between August 7, 2023, and April 5, 2024.Any cancer diagnosis.The main outcome was prevalence and severity of depression based on the PHQ-8. The magnitude of the difference in baseline characteristics was measured between patients with HNC and those with other cancer types, and 95% CIs were used to measure the precision of these estimates. Multivariable logistic regressions were used to evaluate the association of demographic, socioeconomic, anxiety, and clinical variables with depression.From a weighted cohort of 23 496 725 adult patients with cancer, 377 080 were diagnosed with HNC (87.5% aged 51-84 years; 77.9% male). The prevalence of any depression on the PHQ-8 (mild, moderate, or severe) was 40.1% in patients with HNC vs 22.3% in patients with other cancers. Compared with patients with other cancers, patients with HNC were equally likely to screen positive for anxiety (23.6% vs 16.0%; difference, 7.6%; 95% CI, -5.9% to 21.1%), take medication for depression (10.1% vs 13.9%; difference, -3.8%; 95% CI, -11.9% to 4.4%), and state that they never feel depressed (59.7% vs 53.7%; difference, 6.0%; 95% CI, -9.1% to 21.0%). On multivariable logistic regression analysis, having HNC was associated with an increased likelihood of depression (odds ratio [OR], 2.94; 95% CI, 1.39-6.22). Other factors associated with depression were being unmarried or not living with a partner (OR, 1.94; 95% CI, 1.55-2.43) and having anxiety (OR, 23.14; 95% CI, 17.62-30.37).This cohort study found that patients with HNC were twice as likely to screen positive for depression on a validated survey than those with other cancers, despite having similar rates of self-reported depression and depression medication use. These findings suggest that self-reporting of depression may result in underreporting and undertreatment in this population and, thus, a need for further work in developing interventions to improve identification of and optimize treatment for patients with HNC and comorbid depression.

    View details for DOI 10.1001/jamaoto.2024.3233

    View details for PubMedID 39446380

  • Ten-Year Outcome After Supracricoid Partial Laryngectomy in cT3M0 Laryngeal Squamous Cell Carcinoma-A STROBE Analysis. The Laryngoscope Laccourreye, O., Garcia, D., Holsinger, F. C., Weinstein, G. S. 2024

    Abstract

    The aim of this study was to document 10-year outcomes after supracricoid partial laryngectomy (SCPL) in selected cT3M0 laryngeal squamous cell carcinoma (SCC) patients.This real-life retrospective observational study analyzed an inception cohort of 168 patients with isolated, untreated, selected cT3M0 laryngeal SCC, that were consecutively managed by SCPL during the period 1973-2013, and followed up until death or for a minimum of 10 years in 92% of cases at a single French academic and tertiary referral care center. Prior induction chemotherapy, arytenoid cartilage removal, level II-IV neck dissection, and postoperative radiation therapy were performed on 148, 77, 136, and 27 patients, respectively. The main objective was to determine 10-year actuarial local control and laryngeal preservation estimates. Secondary objectives included 10-year actuarial survival and cause-of-death analysis, and assessment of correlations between endpoints and clinical variables. The significance threshold was set at p < 0.005.Ten-year actuarial local control, laryngeal preservation, and survival estimates were 90%, 85%, and 52%, respectively. Salvage treatment resulted in an overall 99% local control rate. Metachronous second primary cancer, intercurrent disease without evidence of SCC, SCPL-related death, and uncontrolled local recurrence accounted for 31%, 26%, 7%, and 2% of causes of death. On univariate analysis, overall local recurrence and laryngeal preservation rates varied significantly, from 5% to 54% and 90% to 46% when resection margins were R0 and R1, respectively.The present study highlighted successful 10-year outcomes after SCPL, providing further evidence in favor of its integration into the conservative armamentarium for endolaryngeal cT3 SCC.4 Laryngoscope, 2024.

    View details for DOI 10.1002/lary.31568

    View details for PubMedID 39152757

  • Artificial intelligence for automatic detection and segmentation of nasal polyposis: a pilot study. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Rampinelli, V., Paderno, A., Conti, C., Testa, G., Modesti, C. L., Agosti, E., Dohin, I., Saccardo, T., Vinciguerra, A., Ferrari, M., Schreiber, A., Mattavelli, D., Nicolai, P., Holsinger, C., Piazza, C. 2024

    Abstract

    Accurate diagnosis and quantification of polyps and symptoms are pivotal for planning the therapeutic strategy of Chronic rhinosinusitis with nasal polyposis (CRSwNP). This pilot study aimed to develop an artificial intelligence (AI)-based image analysis system capable of segmenting nasal polyps from nasal endoscopy videos.Recorded nasal videoendoscopies from 52 patients diagnosed with CRSwNP between 2019 and 2022 were retrospectively analyzed. Images extracted were manually segmented on the web application Roboflow. A dataset of 342 images was generated and divided into training (80%), validation (10%), and testing (10%) sets. The Ultralytics YOLOv8.0.28 model was employed for automated segmentation.The YOLOv8s-seg model consisted of 195 layers and required 42.4 GFLOPs for operation. When tested against the validation set, the algorithm achieved a precision of 0.91, recall of 0.839, and mean average precision at 50% IoU (mAP50) of 0.949. For the segmentation task, similar metrics were observed, including a mAP ranging from 0.675 to 0.679 for IoUs between 50% and 95%.The study shows that a carefully trained AI algorithm can effectively identify and delineate nasal polyps in patients with CRSwNP. Despite certain limitations like the focus on CRSwNP-specific samples, the algorithm presents a promising complementary tool to existing diagnostic methods.

    View details for DOI 10.1007/s00405-024-08809-4

    View details for PubMedID 39001915

    View details for PubMedCentralID 10329964

  • Computer Vision and Videomics in Otolaryngology-Head and Neck Surgery: Bridging the Gap Between Clinical Needs and the Promise of Artificial Intelligence. Otolaryngologic clinics of North America Paderno, A., Bedi, N., Rau, A., Holsinger, C. F. 2024

    Abstract

    This article discusses the role of computer vision in otolaryngology, particularly through endoscopy and surgery. It covers recent applications of artificial intelligence (AI) in nonradiologic imaging within otolaryngology, noting the benefits and challenges, such as improving diagnostic accuracy and optimizing therapeutic outcomes, while also pointing out the necessity for enhanced data curation and standardized research methodologies to advance clinical applications. Technical aspects are also covered, providing a detailed view of the progression from manual feature extraction to more complex AI models, including convolutional neural networks and vision transformers and their potential application in clinical settings.

    View details for DOI 10.1016/j.otc.2024.05.005

    View details for PubMedID 38981809

  • Ten-Year Efficacy of Transoral Surgery for Squamous Carcinoma of the Lateral Oropharynx. The Laryngoscope Laccourreye, O., Garcia, D., Rahman, A., Holsinger, F. C. 2024

    Abstract

    To document the 10-year results of transoral mandibular preservation surgery for patients with T1-2 squamous cell carcinoma (SCC) arising from the lateral oropharynx.This was a retrospective 30-year review using STROBE guidelines at an academic, tertiary referral center. A total of 294 patients with T1-2 SCC of the lateral oropharynx were reviewed. Only 19% of patients were never-smokers, suggesting a predominantly HPV-negative population. All patients had transoral mandibular preservation surgery. Follow-up therapy included neck dissection (76.5%), induction chemotherapy (57.8%), and postoperative radiation therapy (31.6%) Local control, survival, and functional endpoints, as well as the consequences of local recurrence, were analyzed.The 10-year local disease control was 88.3%. Local recurrence was salvaged in 50% of cases, resulting in an overall 94.5% local control rate. The overall 10-year survival was 50%. Mortality was related to metachronous second primary cancer (MSPC) (29.2%), medical comorbidities (25.7%), uncontrolled local recurrence (10%), and complications following transoral resection (4.2%). In multivariate analysis, the development of an MSPC significantly increased (p < 0.005) the risk of death. Overall, 95.2% of patients achieved mandibular preservation. However, gastrostomy and tracheostomy dependence occurred in 1% and 0.3% of cases, respectively.For a patient population with a significant percentage of tobacco-associated oropharyngeal cancer (OPC), transoral surgery was associated with long-term minimal postoperative complications and a high rate of local control. MSPC was the main cause of death during the first 10 postoperative years. Such long-term figures support transoral surgery as an effective first-line treatment for early-stage predominantly tobacco-related OPC.4 Laryngoscope, 2024.

    View details for DOI 10.1002/lary.31574

    View details for PubMedID 38932658

  • Computer Vision Foundation Models in Endoscopy: Proof of Concept in Oropharyngeal Cancer. The Laryngoscope Paderno, A., Rau, A., Bedi, N., Bossi, P., Mercante, G., Piazza, C., Holsinger, F. C. 2024

    Abstract

    To evaluate the performance of vision transformer-derived image embeddings for distinguishing between normal and neoplastic tissues in the oropharynx and to investigate the potential of computer vision (CV) foundation models in medical imaging.Computational study using endoscopic frames with a focus on the application of a self-supervised vision transformer model (DINOv2) for tissue classification. High-definition endoscopic images were used to extract image patches that were then normalized and processed using the DINOv2 model to obtain embeddings. These embeddings served as input for a standard support vector machine (SVM) to classify the tissues as neoplastic or normal. The model's discriminative performance was validated using an 80-20 train-validation split.From 38 endoscopic NBI videos, 327 image patches were analyzed. The classification results in the validation cohort demonstrated high accuracy (92%) and precision (89%), with a perfect recall (100%) and an F1-score of 94%. The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.96.The use of large vision model-derived embeddings effectively differentiated between neoplastic and normal oropharyngeal tissues. This study supports the feasibility of employing CV foundation models like DINOv2 in the endoscopic evaluation of mucosal lesions, potentially augmenting diagnostic precision in Otorhinolaryngology.4 Laryngoscope, 2024.

    View details for DOI 10.1002/lary.31534

    View details for PubMedID 38850247

  • How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck. Head & neck Miller, A., Wang, V., Jegede, V., Necker, F., Curry, J., Baik, F. M., Verma, A., Holsinger, F. C., Tuluc, M., Rahman, M., Lewis, J. S., Rosenthal, E., Topf, M. C. 2024

    Abstract

    Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy.Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave).A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins.Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

    View details for DOI 10.1002/hed.27793

    View details for PubMedID 38702976

  • Vascular Ensheathment Reflects Characteristic Migratory Behavior of Paragangliomas. JCEM case reports Needleman, L., Holsinger, F. C., Annes, J. P. 2024; 2 (4): luae064

    View details for DOI 10.1210/jcemcr/luae064

    View details for PubMedID 38623531

    View details for PubMedCentralID PMC11017112

  • Comparison of da Vinci Single Port vs Si Systems for Transoral Robotic-Assisted Surgery: A Review With Technical Insights. JAMA otolaryngology-- head & neck surgery Oberhelman, N., Bruening, J., Jackson, R. S., Van Abel, K. M., Sumer, B., Holsinger, F. C., Chan, J. Y., Gross, N. D., Clayburgh, D. R., Andersen, P. E., Li, R. J. 2023

    Abstract

    Transoral robot-assisted surgery (TORS) continues to have a major role in the treatment of oropharyngeal cancer. As new iterations of robotic technology are increasingly utilized, it is important to share learning experiences and clinical outcomes data, to optimize technical efficiency and clinical care.This was a retrospective review of a large academic institution's initial clinical use of the da Vinci Single Port (SP) compared with the da Vinci Si (Si) system. A total of 205 TORS cases were reviewed: 109 in the SP group (November 22, 2018, through September 30, 2020), and 96 in the Si group (January 1, 2016, through November 12, 2018). Both groups had comparable operative times, rates of postoperative pharyngeal hemorrhage, length of hospital stay, and duration of nasogastric feeding tube use. There was no difference in pathological characteristics, rates of positive margins, or indications for or time to initiation of adjuvant therapy between the groups. The collective experience of 6 faculty members-who have trained 139 TORS surgeons for the SP system rollout-was compiled to provide a summary of learning experiences and technical notes on safe and efficient operation of the SP system.This Review found that the functional and oncologic outcomes were comparable between TORS cases performed with the Si and SP systems, and they had similar complication rates. Recognized advantages of the SP over the Si system include the availability of bipolar-energized instruments, a usable third surgical arm, and improved camera image quality.

    View details for DOI 10.1001/jamaoto.2023.3994

    View details for PubMedID 38127360

  • Influence of Otolaryngological Subspecialties on Perception of Transoral Robotic Surgery: An International YO-IFOS Survey. Journal of personalized medicine Maniaci, A., Chiesa Estomba, C., Fakhry, N., Vaira, L. A., Remacle, M., Cammaroto, G., Barillari, M. R., Iannella, G., Mayo-Yanez, M., Saibene, A. M., Baudouin, R., Maza-Solano, J., Mendelsohn, A. H., Holsinger, F. C., Ceccon, F. P., Haddad, L., Hans, S., La Mantia, I., Cocuzza, S., Gulinello, F., Ayad, T., Lechien, J. R. 2023; 13 (12)

    Abstract

    To investigate perception, adoption, and awareness on the part of otolaryngology and head and neck surgeons (OTO-HNS) of transoral robotic surgery (TORS).Several items assessed: awareness/perception; access to TORS; training; indications and advantages/hurdles to TORS practice. A subanalysis was performed to assess differences according to the identified otolaryngological subspecialties.A total of 359 people completed the survey. Among subspecialties, while for otolaryngologists 30/359 (8.4%) and H&N surgeons 100/359 (27.9%) TORS plays an effective role in hospital stay, laryngologists frequently disagreed (54.3%). There was a lower incidence among rhinologists and otologists (1.9%). Pediatric surgeons (0.8%) reported a positive response regarding the adoption of robotic surgery, and head and neck specialists expressed an even greater response (14.2%). Low adherence was related to perceived cost-prohibitive TORS, by 50% of H&N surgeons.Perception, adoption, and knowledge about TORS play a key role in the application of the robotic system, significantly varying across subspecialties.

    View details for DOI 10.3390/jpm13121717

    View details for PubMedID 38138944

    View details for PubMedCentralID PMC10744671

  • Randomized Phase III Trial of Postoperative Radiotherapy with or without Cetuximab for Intermediate-Risk Squamous Cell Carcinoma of the Head and Neck (SCCHN): NRG/RTOG 0920 Machtay, M., Torres-Saavedra, P., Thorstad, W. L., Nguyen-Tan, P. F., Siu, L. L., Holsinger, F. C., El-Naggar, A. K., Chung, C. H., Dorth, J., Lee, N. Y., Chan, J., Dunlap, N., Bar Ad, V., Stokes, W. A., Chakravarti, A., Sher, D., Rao, S. D., Harris, J., Yom, S. S., Le, Q. T. ELSEVIER SCIENCE INC. 2023: E1
  • Circulating Tumor HPV DNA for Surveillance of HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Narrative Review. JAMA oncology Lang Kuhs, K. A., Brenner, J. C., Holsinger, F. C., Rettig, E. M. 2023

    Abstract

    Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection of recurrent disease are imperfect. There is growing interest in improving detection of recurrent disease through the use of plasma-based assays able to detect circulating tumor HPV DNA.Although most circulating tumor HPV DNA assays remain in the research domain, the circulating tumor tissue-modified viral HPV DNA assay became commercially available in the United States in early 2020 and has been increasingly used in the clinical setting. With the rapidly increasing incidence of HPV-positive oropharyngeal squamous cell carcinoma and concomitant expansion of biomarker capabilities for this disease, it is critical to reexamine current posttreatment surveillance practices and to determine whether emerging technologies may be used to improve outcomes for a growing survivor population. However, caution is advised; it is not yet known whether biomarker-based surveillance is truly beneficial, and as is true with any intervention, it has the capacity to cause harm.Using Margaret Pepe's classic 5 phases of biomarker development for early detection of cancer as a framework, this article reviews the current state of knowledge, highlights existing knowledge gaps, and suggests research that should be prioritized to understand the association between biomarker-based surveillance and patient outcomes. Specific attention is paid to the commercially available tumor tissue-modified viral HPV DNA assay, given its increasing clinical use. This review may serve as a road map for future research and a guide for clinicians considering its adoption in practice. Enrollment of patients into clinical trials incorporating biomarker-based surveillance should be prioritized.

    View details for DOI 10.1001/jamaoncol.2023.4042

    View details for PubMedID 37824111

  • Suicide in head and neck oncology. European annals of otorhinolaryngology, head and neck diseases Chakoma, T., Megwalu, U., Holsinger, F. C. 2023

    View details for DOI 10.1016/j.anorl.2023.06.007

    View details for PubMedID 37598064

  • Complications following salvage transoral robotic surgery with and without reconstruction: A systematic review of the literature. Oral oncology Turner, M. T., Chung, J., Noorkbash, S., Topf, M. C., Hardman, J., Holsinger, F. C., Paleri, V. 2023; 145: 106467

    Abstract

    Transoral robotic surgery (TORS) has been used in the salvage setting for head and neck cancers both with and without reconstruction. The complications of salvage TORS and the effect of reconstruction on complications has not been studied.To study the complications of salvage TORS and examine the effect of reconstruction on complication rates.An electronic search of the English- language literature using PubMed, Medline, and the Cochrane database was conducted and a systematic review performed in accordance with PRISMA guidelines (CRD42020181057).A total of 23 studies including 533 patients have been published on salvage TORS.The average patient age was 61.2 years.Prior treatment was described for 420 patients.205 (48.8%) underwent prior definitive radiotherapy (RT).160 (38.1%) underwent definitive chemoradiotherapy (CRT).Only 55 (13.1%) had prior surgery.Overall, there were 158 complications with a pooled rate of 33.6% (95%CI: 25.4-42.3%).77 were major complications requiring surgical intervention with a pooled rate of 18.9% (95% CI: 14.8-23.3%).The number of patients undergoing reconstruction among salvage cases in the literature is 59 (9.19%), with 24 local flaps and 25 microvascular free flaps.Reconstruction was associated with lower overall hemorrhage rates but had no impact on major hemorrhage rates.The pooled incidence rates of major complications, major POH and emergency tracheostomy following salvage TORS are 18.9%, 10.5%, and 4.4%.The rate of death following salvage TORS is 3.6%. Reconstruction was associated with lower overall hemorrhage rate after salvage TORS but had no impact on major postoperative hemorrhage rates.

    View details for DOI 10.1016/j.oraloncology.2023.106467

    View details for PubMedID 37454544

  • Epistemological Challenges of Artificial Intelligence Clinical Decision Support Tools in Otolaryngology: The Black Box Problem. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Babu, C. S., Holsinger, F. C., Zuchowski, L., Ratti, E., Rameau, A. 2023

    View details for DOI 10.1002/ohn.410

    View details for PubMedID 37344955

  • A "royal" total laryngectomy that never was. European annals of otorhinolaryngology, head and neck diseases Laccourreye, O., Holsinger, F. C., Mudry, A. 2023

    Abstract

    With this historical vignette, ending the series dedicated to the pioneers of total laryngectomy, published in the EuropeanAnnals of Otorhinolaryngology Head & Neck Diseases to mark the 150th anniversary of the first description of this surgical procedure in humans, the authors recount what history called "The Crown Prince's illness", and wonder what might have happened if the total laryngectomy proposed for Crown Prince Friedrich had finally been performed.

    View details for DOI 10.1016/j.anorl.2023.03.003

    View details for PubMedID 37003898

  • Treatment of oropharyngeal squamous cell carcinoma: Is swallowing quality better after TORS or RT? Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Campo, F., Iocca, O., De Virgilio, A., Mazzola, F., Mercante, G., Pichi, B., Holsinger, F. C., Di Maio, P., Ramella, S., Pellini, R. 2023; 183: 109547

    Abstract

    BACKGROUND AND PURPOSE: To answer an important question regarding the long-term morbidity of two oncological equivalent treatment for oropharyngeal squamous cell carcinoma (OPSCC), namely a comparison of swallowing function results between patients treated with trans-oral robotic surgery (TORS) versus patients treated with radiotherapy (RT).MATERIALS AND METHODS: Studies included patients with OPSCC treated with TORS or RT. Articles reporting complete data on MD Anderson Dysphagia Inventory (MDADI) and comparing the two treatments (TORS vs RT) were included in the meta-analysis. Swallowing assessed with MDADI was the primary outcome, the evaluation with instrumental methods was the secondary aim.RESULTS: Included studies provided a total of 196 OPSCC primarily treated with TORS vs 283 OPSCC primarily treated with RT. The mean difference in MDADI score at the longest follow-up was not significantly different between TORS and RT group (mean difference [MD] -0.52; 95% CI -4.53-3.48; p=0.80). After treatment, mean composite MDADI scores demonstrated a slight impairment in both groups without reaching a statistical difference compared to the baseline status. DIGEST score and Yale score showed a significantly worse function in both treatment groups at 12-month follow-up compared to baseline status.CONCLUSION: The meta-analysis demonstrates that up-front TORS (+- adjuvant therapy) and up-front RT (+- CT) appear to be equivalent treatments in functional outcomes in T1-T2, N0-2 OPSCC, however, both treatments cause impaired swallowing ability. Clinicians should have a holistic approach and work with patients to develop an individualized nutrition plan and swallowing rehabilitation protocol from diagnosis to post-treatment surveillance.

    View details for DOI 10.1016/j.radonc.2023.109547

    View details for PubMedID 36813176

  • Adoption of otolaryngologist-head neck surgeons toward transoral robotic surgery: An international survey. Laryngoscope investigative otolaryngology Lechien, J. R., Haddad, L., Holsinger, F. C., Mendelsohn, A. H., Hans, S. 2023; 8 (1): 95-102

    Abstract

    To investigate perception, adoption and awareness of otolaryngologist-head neck surgeons (OTO-HNS) toward transoral robotic surgery (TORS).An online survey was sent to 1383 OTO-HNS on the perception, adoption and awareness about TORS to members of many otolaryngological societies. The following aspects were assessed: TORS access; training; awareness/perception; indications and advantages/barriers to TORS practice. The responses were presented for the entire cohort and regarding the TORS experience of OTO-HNS.A total of 359 completed the survey (26%); including 115 TORS surgeons. TORS-surgeons carry out a mean number of 34.4 annual TORS procedures. The primary barriers to TORS were the cost of the robot (74%) and disposable accessories (69%), and the lack of training opportunity (38%). The 3D view of the surgical field (66%), the postoperative quality of life outcomes (63%) and the shorter hospital stay (56%) were the most important benefits of TORS. TORS-surgeons believed more frequently that TORS is indicated for cT1-T2 oropharyngeal and supraglottic cancers than non-TORS surgeons (p < .005). Participants believed that the priorities for the future consisted of the reduction of the robot arm size and the incorporation of flexible instruments (28%); the integration of laser (25%) or GPS tracking based on imaging (18%), all of them to improve accesses to hypopharynx (24%), supraglottic larynx (23%) and vocal folds (22%).The perception, adoption and knowledges toward TORS depend on the access to robot. The findings of this survey may help guide decisions on how improve the dissemination of TORS interest and awareness.

    View details for DOI 10.1002/lio2.1003

    View details for PubMedID 36846408

    View details for PubMedCentralID PMC9948589

  • Adoption of otolaryngologist-head neck surgeons toward transoral robotic surgery: An international survey LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY Lechien, J. R., Haddad, L., Holsinger, F., Mendelsohn, A. H., Hans, S. 2022

    View details for DOI 10.1002/lio2.1003

    View details for Web of Science ID 000903902300001

  • Single-port robotic transcervical long-segment thoracic tracheal reconstruction: Cadaveric proof-of-concept study. JTCVS techniques Lui, N. S., Holsinger, F. C., Ma, M. R., Janus, J. R., Balakrishnan, K. 2022; 16: 231-236

    Abstract

    Slide tracheoplasty is the standard technique to repair congenital long-segment tracheal stenosis. This operation most commonly requires median sternotomy, which has drawbacks in young children. We hypothesized that a transcervical approach without sternotomy would be feasible if done with a single-port robotic system.This proof-of concept study was performed in 2 small adult cadavers using a single-port robotic surgical system via a small neck incision. Relevant information, including operative time and details of operative technique, were recorded.Long-segment slide tracheoplasty was completed successfully in 2 cadavers using a small neck incision and a single-port robotic surgical system. Strengths and pitfalls of the technique were identified, including technical refinements from the first attempt to the second. Operative time for robotic mobilization, incision, and anastomosis of the trachea was comparable to standard open approaches.Small-incision transcervical slide tracheoplasty, assisted by a single-port surgical robotic system, is feasible in a human cadaver. More work is needed to determine safety and applicability in live patients, particularly in children.

    View details for DOI 10.1016/j.xjtc.2022.08.025

    View details for PubMedID 36510525

    View details for PubMedCentralID PMC9735391

  • High prevalence of persistent smell loss and qualitative smell dysfunction during the COVID-19 pandemic in the United States: urgent need for clinical trials. International forum of allergy & rhinology Lechner, M., Liu, J., Counsell, N., Yan, C. H., Paun, S., Eynon-Lewis, N., Sutton, L., Jayaraj, S., Batterham, R. L., Hopkins, C., Philpott, C., Lund, V. J., Hatter, M., Abdelwahab, M., Holsinger, F. C., Capasso, R., Nayak, J. V., Hwang, P. H., Patel, Z. M. 2022

    View details for DOI 10.1002/alr.23100

    View details for PubMedID 36409559

  • Narrow-field supracricoid partial laryngectomy: Procedure development and initial clinical experiences. Auris, nasus, larynx Nakayama, M., Wada, T., Isono, Y., Sano, D., Nishimura, G., Oridate, N., Holsinger, F. C., Orosco, R. 2022

    Abstract

    OBJECTIVES: To evaluate the feasibility of narrow-field supracricoid partial laryngectomy with cricohyoidoepiglottopexy (NF-SCPL-CHEP).METHODS: Between 2019 and 2020, five patients with glottic cancers underwent NF-SCPL-CHEP. The mean durations of surgical drains, tracheostomy canula, and nasogastric tube use were evaluated. Length of stay following NF-SCPL-CHEP was compared with that of our open SCPL historical controls. A case summary is provided for the first patients, with detailed information about postoperative management and function.RESULTS: All five patients achieved uneventful postoperative recoveries without major complications. The average time for surgical drains, tracheostomy canula, and nasogastric tube use were 2, 15, and 46 days, respectively. The mean overall hospitalization period was 36 days for NF-SCPL-CHEP patients. The mean period of hospitalization based on our early experiences between 1997 and 2005 with classical open SCPL was 72 days. All patients were fully functional and local recurrences or distant metastases were not encountered during a mean observation period of 39 months.CONCLUSIONS: NF-SCPL-CHEP with 6 cm cervical access appeared technically feasible and oncologically sound in this initial clinical experience. An extra 2 cm incision, which enabled lateral neck dissection, was not felt to detract from the overall minimally invasive basis of NF-SCPL-CHEP. The clinical results were encouraging with limited complications and predictable postoperative recovery. The length of stay for patients undergoing NF-SCPL was half that of open SCPL historical controls. Less damages to local circulation may associate with the positive influences. Further study with a large patient sample across multiple institutions are needed to carefully evaluate long-term functional and oncological outcomes.

    View details for DOI 10.1016/j.anl.2022.09.011

    View details for PubMedID 36216666

  • Minimally Invasive Surgery in the United States, 2022: Understanding Its Value Using New Datasets. The Journal of surgical research Mattingly, A. S., Chen, M. M., Divi, V., Holsinger, F. C., Saraswathula, A. 2022; 281: 33-36

    Abstract

    INTRODUCTION: While minimally invasive surgery (MIS) has transformed the treatment landscape of surgical care, its utilization is not well understood. The newly released Nationwide Ambulatory Surgery Sample allows for more accurate estimates of MIS volume in the United States-in combination with inpatient datasets.MATERIALS AND METHODS: Multiple nationwide databases from the Healthcare Cost and Utilization Project (HCUP) were used: the Nationwide Ambulatory Surgery Sample and National Inpatient Sample. The volume of MIS and robotic procedures were calculated from 2016 to 2018. An online query system, HCUPNet, was queried for inpatient stays from 1993 to2014.RESULTS: In 2017, 9.8 million inpatient major operating room procedures were analyzed, of which 11.1% were MIS and 2.5% were robotic-assisted, compared with 9.6 million inpatient operating room procedures (11.2% MIS and 2.9% robotic-assisted) in 2018. There were 10.6, 10.6, and 10.7 million ambulatory procedures in 2016, 2017, and 2018, respectively. Ambulatory MIS procedures showed an increasing trend across years, representing 16.9%, 17.4%, and 18%, respectively. HCUPNet data revealed an increase in inpatient MIS cases from 529,811 (8.9%) in 1993 to 1,443,446 (20.7%) in2014.CONCLUSIONS: This study is the first to estimate national MIS volume across specialties in both inpatient and ambulatory hospital settings. We found a trend toward a higher proportion of MIS and robotic cases from 1997 to 2018. These data may help contribute to a more comprehensive understanding of MIS value within surgery and highlight limitations of current databases, especially when categorizing robotic cases on a national scale.

    View details for DOI 10.1016/j.jss.2022.08.006

    View details for PubMedID 36115146

  • Caution Regarding Assessment of Toxic Effects and Survival in Treatment De-escalation With Radiotherapy vs Transoral Surgery for Human Papillomavirus-Associated Oropharyngeal Cancer. JAMA oncology Topf, M. C., Holsinger, F. C., Patel, M. 2022

    View details for DOI 10.1001/jamaoncol.2022.3464

    View details for PubMedID 35980664

  • Head and Neck Virtual Coach: A Randomized Control Trial of Mobile Health as an Adjunct to Swallowing Therapy During Head and Neck Radiation. Dysphagia Starmer, H. M., Klein, D., Montgomery, A., Goldsmith, T., McCarroll, L., Richmon, J., Christopher Holsinger, F., Beadle, B., Jain, P. 2022

    Abstract

    Dysphagia is a common consequence of head and neck radiation and may be mitigated by performance of swallowing exercises during radiation treatment. Given historically poor adherence to such exercise protocols, we created a mobile health application, HNC Virtual Coach as an adjunct to standard clinical care. This randomized control trial investigated the impact of HNC Virtual Coach on adherence as well as swallowing outcomes by comparing those using the mobile app to those receiving only standard clinical care and paper logs. Both treatment groups were provided with the same exercise protocol as well as the same baseline educational information. Outcome measures included adherence rates, physiologic measures obtained during a Modified Barium Swallow Study (PAS, MBS-ImP, DIGEST), patient-reported outcomes (MDADI), diet levels (FOIS, PSS-HN), and quality of information received (INFO-25). Patients using the HNC Virtual Coach tended to have better adherence to treatment recommendations during radiation therapy. Increased adherence was associated with better patient-reported quality of life, but not physiologic function 2-3months following completion of radiation. Results suggest that a mobile health application may provide benefit for some patients undergoing head and neck radiation.

    View details for DOI 10.1007/s00455-022-10506-5

    View details for PubMedID 35960394

  • Transoral Robotic Surgery for Recurrent Tumors of the Upper Aerodigestive Tract (RECUT): An International Cohort Study. Journal of the National Cancer Institute Hardman, J. C., Holsinger, F. C., Brady, G. C., Beharry, A., Bonifer, A. T., D'Andrea, G., Dabas, S. K., de Almeida, J. R., Duvvuri, U., Floros, P., Ghanem, T. A., Gorphe, P., Gross, N. D., Hamilton, D., Kurukulasuriya, C., Larsen, M. H., Lin, D. J., Magnuson, J. S., Meulemans, J., Miles, B. A., Moore, E. J., Pantvaidya, G., Roof, S., Rubek, N., Simon, C., Subash, A., Topf, M. C., Van Abel, K. M., Vander Poorten, V., Walgama, E. S., Greenlay, E., Potts, L., Balaji, A., Starmer, H. M., Stephen, S., Roe, J., Harrington, K., Paleri, V. 2022

    Abstract

    BACKGROUND: Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness.METHODS: A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC.RESULTS: Data for 278 eligible patients were analyzed, with median follow-up of 38.5months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n=22 of 272), and 30-day mortality was 1.8% (n=5 of 272). At 1 year, 10.8% (n=21 of 195) used tracheostomies, 33.8% (n=66 of 195) used gastrostomies, and 66.3% (n=53 of 80) had maintained or improved normalcy of diet scores.CONCLUSIONS: Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting.

    View details for DOI 10.1093/jnci/djac130

    View details for PubMedID 35944904

  • ASO Visual Abstract: Novel Strategies for Managing Retropharyngeal Lymph Node Metastases in Head and Neck and Thyroid Cancer with TransOral Robotic Surgery (TORS). Annals of surgical oncology Garas, G., Roland, N. J., Lancaster, J., Zammit, M., Manon, V. A., Davies, K., Jones, T. M., De, M., Holsinger, F. C., Prestwich, R. J., Fleming, J. C. 2022

    View details for DOI 10.1245/s10434-022-12371-w

    View details for PubMedID 35941346

  • Posttreatment FDG-PET/CT Hopkins criteria predict locoregional recurrence after definitive radiotherapy for oropharyngeal squamous cell carcinoma. Head & neck Miller, J. A., Moradi, F., Sundaram, V., Liang, R., Zhang, C., Nguyen, N. K., Akhtar, F., Liu, Y., Ren, Y., Harandi, N., Weng, Y., Pollom, E. L., Colevas, A. D., Divi, V., Holsinger, F. C., Beadle, B. M., Le, Q., Gensheimer, M. F. 2022

    Abstract

    BACKGROUND: Metabolic response assessment for oropharyngeal squamous cell carcinoma (OPSCC) aids in identifying locoregional persistence/recurrence (LRR). The Hopkins Criteria are a standardized qualitative response assessment system using posttreatment FDG-PET/CT.METHODS: We conducted a retrospective cohort study of patients with node-positive OPSCC treated with definitive (chemo)radiotherapy. We assessed Hopkins Criteria performance for LRR, then developed and validated a competing-risks model.RESULTS: Between 2004 and 2018, 259 patients were included with median follow-up of 43months. The Hopkins Criteria sensitivity, specificity, negative predictive value, and accuracy were 68%, 88%, 95%, and 85%. The 36-month cumulative incidence of LRR was greater with positive scores (45% vs. 5%, HR 12.60, p<0.001). PET/CTs performed ≤10weeks after radiotherapy were associated with a four-fold increase in pathologically negative biopsies/surgeries (36% vs. 9%, p=0.03). The AUC for LRR was 0.89 using a model integrating the Hopkins score.CONCLUSIONS: The Hopkins Criteria predict LRR with high accuracy for OPSCC response assessment.

    View details for DOI 10.1002/hed.27160

    View details for PubMedID 35920790

  • Impact of Histologic Risk Factors on Recurrence Rates for Oral Cavity Squamous Cell Carcinoma. The Annals of otology, rhinology, and laryngology Kligerman, M. P., Moon, P. K., Tusty, M., Cloutier, J. M., Ma, Y., Holsinger, C. F., Divi, V. 2022: 34894221111223

    Abstract

    This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC).Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence.One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence.TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

    View details for DOI 10.1177/00034894221111223

    View details for PubMedID 35899590

  • Novel Strategies for Managing Retropharyngeal Lymph Node Metastases in Head and Neck and Thyroid Cancer with Transoral Robotic Surgery (TORS). Annals of surgical oncology Garas, G., Roland, N. J., Lancaster, J., Zammit, M., Manon, V. A., Davies, K., Jones, T. M., De, M., Holsinger, F. C., Prestwich, R. J., Fleming, J. C. 2022

    Abstract

    Retropharyngeal metastases are encountered in a variety of head and neck malignancies, imposing significant surgical challenges owing to their distinct location and proximity to neurovascular structures. Radiotherapy is the recommended treatment in most cases owing to its oncological efficacy. However, retropharyngeal irradiation affects the superior pharyngeal constrictor muscles and parotid glands, with the potential for long-term dysphagia and xerostomia. A younger oropharyngeal and thyroid cancer patient demographic is trending, fueling interest in treatment de-escalation strategies. Consequently, reducing radiotoxicity and its long-term effects is of special relevance in modern head and neck oncology practice. Through its unique ability to safely extirpate these traditionally difficult-to-access retropharyngeal lymph nodes via a natural orifice, TransOral Robotic Surgery (TORS) can considerably lower the surgical morbidity of retropharyngeal lymph node dissection (RPLND), compared with current existing approaches. This review summarizes the latest developments in the field, exposing current research gaps and discusses specific clinical settings where TORS could enable treatment de-escalation. In early-stage node-negative oropharyngeal cancer, single-modality surgical treatment with TORS RPLND may improve risk stratification of metastasis and recurrence in this region. TORS RPLND is also a potentially viable treatment option in salvage of an isolated retropharyngeal node recurrence or in the primary setting of a thyroid malignancy with a single positive retropharyngeal node. In time, TORS RPLND may provide an alternative de-escalation strategy in these three scenarios. However, with the reported morbidities, further prospective trials with long-term follow-up data are required to prove oncological safety and functional benefits over existing strategies.

    View details for DOI 10.1245/s10434-022-12208-6

    View details for PubMedID 35842533

  • The robotic-assisted extended "Sistrunk" approach for tumors of the upper aerodigestive tract with limited transoral access: First description of oncological and functional outcomes. Head & neck Simon, C., Beharry, A., Paleri, V., Dubi, P., Lambercy, K., Holsinger, F. C., Todic, J. 2022

    Abstract

    We report on the first clinical experience with the robotic-assisted extended "Sistrunk" approach (RESA) for access to constrained spaces of the upper aerodigestive tract. This prospective case cohort study include six patients that underwent RESA if transoral exposure could not be achieved. Three patients received previous radiation. Patients were postoperatively followed until week 16 for perioperative complications, surgical margins, and functional outcomes. In all patients RESA allowed adequate exposure and resection with negative margins. Three patients who underwent salvage surgery experienced a minor or intermediate grade postoperative bleeding. No patient developed a pharyngocutaneous fistula. Three patients recovered their swallowing to their preoperative status and the remaining three experienced an improvement. All patients experienced complete recovery of their voice. RESA has the potential to provide a new organ preservation approach for head and neck cancer (HNC) not amenable to transoral exposure and thus warrants further prospective clinical studies.

    View details for DOI 10.1002/hed.27114

    View details for PubMedID 35656594

  • Long-term results of robotic-assisted nasopharyngectomy for recurrent nasopharyngeal carcinoma. Head & neck Tsang, R. K., Chan, W. C., Holsinger, F. C., Chung, J. C., Chow, V. L., Chan, J. Y., Ho, W., Wei, W. I. 2022

    Abstract

    BACKGROUND: We have previously reported our early experience in robotic-assisted nasopharyngectomy. The current case series is a report of our experience in 33 robotic-assisted nasopharyngectomy.METHODS: Prospective series of patients who underwent robotic-assisted nasopharyngectomy for local recurrent nasopharyngeal carcinoma from January 2010 to March 2019.RESULTS: Thirty-one patients underwent robotic-assisted nasopharyngectomy with two additional second procedure for positive margin. Median age is 55years (29-85). Twenty-five patients had rT1 disease and six patients had tumor invaded sphenoid floor (rT3). Median operative time was 227min and median blood loss was 200ml. The median follow-up period for all patients were 38months. Four patients had local recurrence. Five-year local control rate, overall survival, and disease-free survival are 85.1%, 55.7%, and 69.1%, respectively.CONCLUSION: Robotic-assisted nasopharyngectomy for recurrent nasopharyngectomy was showed to have a high local control rate. The operating time was comparable to open surgery.

    View details for DOI 10.1002/hed.27115

    View details for PubMedID 35642444

  • Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell phenotype. PNAS nexus Viswanathan, V., Cao, H., Saiki, J., Jiang, D., Mattingly, A., Nambiar, D., Bloomstein, J., Li, Y., Jiang, S., Chamoli, M., Sirjani, D., Kaplan, M., Holsinger, F. C., Liang, R., Von Eyben, R., Jiang, H., Guan, L., Lagory, E., Feng, Z., Nolan, G., Ye, J., Denko, N., Knox, S., Rosen, D., Le, Q. 2022; 1 (2): pgac056

    Abstract

    Adult salivary stem/progenitor cells (SSPC) have an intrinsic property to self-renew in order to maintain tissue architecture and homeostasis. Adult salivary glands have been documented to harbor SSPC, which have been shown to play a vital role in the regeneration of the glandular structures postradiation damage. We have previously demonstrated that activation of aldehyde dehydrogenase 3A1 (ALDH3A1) after radiation reduced aldehyde accumulation in SSPC, leading to less apoptosis and improved salivary function. We subsequently found that sustained pharmacological ALDH3A1 activation is critical to enhance regeneration of murine submandibular gland after radiation damage. Further investigation shows that ALDH3A1 function is crucial for SSPC self-renewal and survival even in the absence of radiation stress. Salivary glands from Aldh3a1 -/- mice have fewer acinar structures than wildtype mice. ALDH3A1 deletion or pharmacological inhibition in SSPC leads to a decrease in mitochondrial DNA copy number, lower expression of mitochondrial specific genes and proteins, structural abnormalities, lower membrane potential, and reduced cellular respiration. Loss or inhibition of ALDH3A1 also elevates ROS levels, depletes glutathione pool, and accumulates ALDH3A1 substrate 4-hydroxynonenal (4-HNE, a lipid peroxidation product), leading to decreased survival of murine SSPC that can be rescued by treatment with 4-HNE specific carbonyl scavengers. Our data indicate that ALDH3A1 activity protects mitochondrial function and is important for the regeneration activity of SSPC. This knowledge will help to guide our translational strategy of applying ALDH3A1 activators in the clinic to prevent radiation-related hyposalivation in head and neck cancer patients.

    View details for DOI 10.1093/pnasnexus/pgac056

    View details for PubMedID 35707206

  • Circulating tumor DNA in head and neck cancer: Early successes and future promise. Cancer Soo, J., Jin, M. C., Beadle, B. M., Holsinger, F. C., Finegersh, A. 2022

    Abstract

    LAY SUMMARY: The genetic components (DNA) of human papillomavirus-related throat cancer (in the oropharynx) might be measured after surgery to help to predict whether treatment has been successful.

    View details for DOI 10.1002/cncr.34189

    View details for PubMedID 35298053

  • Open and endoscopic surgery improve survival for squamous and non-squamous cell nasopharyngeal carcinomas: an NCDB cohort study. International forum of allergy & rhinology Finegersh, A., Said, M., Deconde, A., Hwang, P. H., Holsinger, F. C., Orosco, R. K. 2022

    Abstract

    Nasopharyngeal tumors (NPT) are primarily treated with nonsurgical therapy. Recent studies have demonstrated endoscopic salvage surgery for NPT recurrences may improve survival relative to re-irradiation. However, there is very limited data on open compared to endoscopic approaches for NPT. We investigated whether endoscopic and open surgical approaches to the nasopharynx improve overall survival for all histologic subtypes of NPT.A retrospective cohort study using the National Cancer Database (NCDB) was performed. All adult patients with NPT from 2004 - 2016 without distant metastasis who underwent treatment with curative intent were included. We extracted clinical and treatment variables to assess our primary outcome of overall survival.On univariate analysis, patients undergoing endoscopic surgery but not open surgery had significantly improved overall survival relative to those undergoing nonsurgical treatment. Post hoc analysis demonstrated significantly improved overall survival for surgery in patients with minor salivary gland histology but not squamous cell carcinoma (SCC) histology or by T- or N-classification. A Cox proportional hazards model was used for multivariate regression. After adjusting for covariates, both endoscopic and open approaches were associated with improved overall survival relative to nonsurgical treatment for all tumor types. A multivariate regression of SCC found that open but not endoscopic surgery was significantly associated with improved overall survival.Both endoscopic and open surgical approaches are associated with improved overall survival of patients with NPT. These findings offer important oncologic validity as endoscopic and robotic platforms to the nasopharynx become more widely adopted. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/alr.23000

    View details for PubMedID 35313077

  • Post-Treatment FDG-PET/CT Hopkins Criteria Predict Locoregional Recurrence After Definitive Radiotherapy for Oropharyngeal Squamous Cell Carcinoma. International journal of radiation oncology, biology, physics Miller, J. A., Moradi, F., Liang, R., Zhang, C., Nguyen, N., Akhtar, F., Harandi, N. K., Colevas, A. D., Divi, V., Holsinger, F. C., Beadle, B. M., Le, Q. T., Gensheimer, M. F. 2021; 111 (3S): e399

    Abstract

    PURPOSE/OBJECTIVE(S): Surveillance after definitive radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is critical to confirm clinical complete response, as a subset of patients develop locoregional recurrences (LRR). The Hopkins Criteria are a standardized qualitative system for assessing response using post-treatment PET/CT and are validated for overall (OS) and progression-free survival (PFS). We hypothesized that the Hopkins Criteria score is independently prognostic for LRR.MATERIALS/METHODS: We conducted an institutional retrospective study of adult patients with newly-diagnosed node-positive non-metastatic OPSCC treated with definitive (chemo)radiotherapy. Patients were eligible if they completed a pre- and post-radiotherapy PET/CT within 24 weeks after treatment. The primary outcome was the cumulative incidence of locoregional recurrence/persistence. A single board-certified nuclear medicine physician assigned Hopkins scores, which were considered either positive (scores 4-5) or negative (scores 1-3).RESULTS: Between 2004-2018, 259 patients were included in this analysis, while an additional 221 were excluded, most commonly due to lack of post-treatment PET/CT [37%] or N0 disease [22%]. Most patients were men (90%), 47% had never smoked, 86% had p16+/HPV+ tumors, and 39% had T3-4 tumors. Nearly all (98%) received concurrent chemotherapy, while 11% received induction chemotherapy. Median clinical follow-up was 40 months. Following radiotherapy, the first post-treatment PET/CT was positive (score 4-5) at the primary site in 32 patients (12%), cervical lymph nodes in 26 patients (10%), and either the primary site or neck in 50 patients (19%). This PET/CT was performed at a median of 3.3 months [range, 1.6-6.0] after radiotherapy. Thirty-four (13%) LRRs were observed. The sensitivity, specificity, negative predictive value, and overall accuracy of the Hopkins score for LRR were 68%, 88%, 95%, and 85%. The 36-month cumulative incidence of LRR was greater among patients with Hopkins scores 4-5 (45% vs. 5%, multivariable-adjusted HR 14.16, P < 0.001). Positive scores were similarly prognostic for 36-month OS (69% vs. 94%) and PFS (55% vs. 87%). LRR was similar among patients with scores of 3 relative to scores of 1-2. Performance was reduced when PET/CTs were obtained within 2.5 months of radiotherapy (accuracy: ≤2.5 months: 73%; 2.5-3.5 months: 85%; 3.5-6.0 months: 87%). Twenty-two negative biopsies or surgeries were performed among patients without LRR; negative biopsies/surgeries were more common after early PET/CT (≤2.5 months: 36%; 2.5-3.5 months: 9%; 3.5-6.0 months: 9%, P = 0.03).CONCLUSION: There is a lack of consensus reporting standards for response assessment after definitive radiotherapy for OPSCC. The Hopkins Criteria are an easily-implemented standard that appear to offer high accuracy for recurrence and death. These data support an initial PET/CT at least three months after radiotherapy to limit unnecessary diagnostic procedures.

    View details for DOI 10.1016/j.ijrobp.2021.07.1157

    View details for PubMedID 34701362

  • Post-Treatment FDG-PET/CT Hopkins Criteria Predict Locoregional Recurrence After Definitive Radiotherapy for Oropharyngeal Squamous Cell Carcinoma Miller, J. A., Moradi, F., Liang, R., Zhang, C., Nguyen, N., Akhtar, F., Harandi, N. K., Colevas, A. D., Divi, V., Holsinger, F. C., Beadle, B. M., Le, Q. T., Gensheimer, M. F. ELSEVIER SCIENCE INC. 2021: E399
  • Soft robotic manipulator for intraoperative MRI-guided transoral laser microsurgery. Science robotics Fang, G., Chow, M. C., Ho, J. D., He, Z., Wang, K., Ng, T. C., Tsoi, J. K., Chan, P., Chang, H., Chan, D. T., Liu, Y., Holsinger, F. C., Chan, J. Y., Kwok, K. 2021; 6 (57)

    Abstract

    Magnetic resonance (MR) imaging (MRI) provides compelling features for the guidance of interventional procedures, including high-contrast soft tissue imaging, detailed visualization of physiological changes, and thermometry. Laser-based tumor ablation stands to benefit greatly from MRI guidance because 3D resection margins alongside thermal distributions can be evaluated in real time to protect critical structures while ensuring adequate resection margins. However, few studies have investigated the use of projection-based lasers like those for transoral laser microsurgery, potentially because dexterous laser steering is required at the ablation site, raising substantial challenges in the confined MRI bore and its strong magnetic field. Here, we propose an MR-safe soft robotic system for MRI-guided transoral laser microsurgery. Owing to its miniature size (O12 * 100 mm), inherent compliance, and five degrees of freedom, the soft robot ensures zero electromagnetic interference with MRI and enables safe and dexterous operation within the confined oral and pharyngeal cavities. The laser manipulator is rapidly fabricated with hybrid soft and hard structures and is powered by microvolume (<0.004 milliter) fluid flow to enable laser steering with enhanced stiffness and lowered hysteresis. A learning-based controller accommodates the inherent nonlinear robot actuation, which was validated with laser path-following tests. Submillimeter laser steering accuracy was demonstrated with a mean error < 0.20 mm. MRI compatibility testing demonstrated zero observable image artifacts during robot operation. Ex vivo tissue ablation and a cadaveric head-and-neck trial were carried out under MRI, where we employed MR thermometry to monitor the tissue ablation margin and thermal diffusion intraoperatively.

    View details for DOI 10.1126/scirobotics.abg5575

    View details for PubMedID 34408096

  • Soft robotic manipulator for intraoperative MRI-guided transoral laser microsurgery SCIENCE ROBOTICS Fang, G., Chow, M. K., Ho, J. L., He, Z., Wang, K., Ng, T. C., Tsoi, J. H., Chan, P., Chang, H., Chan, D., Liu, Y., Holsinger, C., Chan, J., Kwok, K. 2021; 6 (57)
  • Robotic surgery may improve overall survival for T1 and T2 tumors of the hypopharynx: An NCDB cohort study. Oral oncology Finegersh, A., Voora, R. S., Panuganti, B., Faraji, F., Christopher Holsinger, F., Brumund, K. T., Coffey, C., Califano, J., Orosco, R. K. 2021; 121: 105440

    Abstract

    BACKGROUND: Hypopharyngeal cancer is associated with poor survival. Robotic surgery is emerging as a treatment for hypopharyngeal tumors, but no rigorous data are available to assess its effect on survival.METHODS: The National Cancer Database (NCDB) was used to identify patients with T1 and T2 hypopharyngeal tumors undergoing robotic surgery, laser surgery, and primary radiation with or without chemotherapy from 2010 to 2016. All adult patients with available staging and no distant metastasis were included.RESULTS: We compared 57 patients undergoing robotic surgery, 236 undergoing laser surgery, and 5,742 undergoing primary radiation. Compared to laser surgery, patients undergoing robotic surgery were significantly more likely to have negative margins, neck dissection, lower incomes, and care at an academic center. Rates of robotic surgery also significantly increased from 2010 to 2015. After multivariate regression, robotic surgery was associated with significantly improved overall survival compared to laser surgery and primary radiation.CONCLUSION: Robotic surgery improves overall survival for T1 and T2 hypopharyngeal tumors compared to laser surgery and primary radiation in this NCDB cohort. This effect may be mediated by decreased positive margin rates relative to laser surgery. Rates of hypopharyngeal robotic surgery are expected to increase with wider adoption of robotic platforms and may improve overall survival rates for hypopharyngeal cancer.

    View details for DOI 10.1016/j.oraloncology.2021.105440

    View details for PubMedID 34329867

  • Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment. Proceedings of the National Academy of Sciences of the United States of America Moreno-Nieves, U. Y., Tay, J. K., Saumyaa, S., Horowitz, N. B., Shin, J. H., Mohammad, I. A., Luca, B., Mundy, D. C., Gulati, G. S., Bedi, N., Chang, S., Chen, C., Kaplan, M. J., Rosenthal, E. L., Holsinger, F. C., Divi, V., Baik, F. M., Sirjani, D. B., Gentles, A. J., Newman, A. M., Freud, A. G., Sunwoo, J. B. 2021; 118 (28)

    Abstract

    Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

    View details for DOI 10.1073/pnas.2101169118

    View details for PubMedID 34244432

  • Using deep learning to identify the recurrent laryngeal nerve during thyroidectomy. Scientific reports Gong, J., Holsinger, F. C., Noel, J. E., Mitani, S., Jopling, J., Bedi, N., Koh, Y. W., Orloff, L. A., Cernea, C. R., Yeung, S. 2021; 11 (1): 14306

    Abstract

    Surgeons must visually distinguish soft-tissues, such as nerves, from surrounding anatomy to prevent complications and optimize patient outcomes. An accurate nerve segmentation and analysis tool could provide useful insight for surgical decision-making. Here, we present an end-to-end, automatic deep learning computer vision algorithm to segment and measure nerves. Unlike traditional medical imaging, our unconstrained setup with accessible handheld digital cameras, along with the unstructured open surgery scene, makes this task uniquely challenging. We investigate one common procedure, thyroidectomy, during which surgeons must avoid damaging the recurrent laryngeal nerve (RLN), which is responsible for human speech. We evaluate our segmentation algorithm on a diverse dataset across varied and challenging settings of operating room image capture, and show strong segmentation performance in the optimal image capture condition. This work lays the foundation for future research in real-time tissue discrimination and integration of accessible, intelligent tools into open surgery to provide actionable insights.

    View details for DOI 10.1038/s41598-021-93202-y

    View details for PubMedID 34253767

  • Contralateral transmaxillary approach to the nasopharynx with a flexible robotic system: A cadaveric feasibility study Chan, J., Tsang, R. Y., Holsinger, F., Turner, M. ELSEVIER. 2021
  • Buccal fat pad to improve velum competency after transoral lateral oropharyngectomy. European annals of otorhinolaryngology, head and neck diseases Laccourreye, O., Holsinger, F. C., Weisntein, G. S. 2021

    Abstract

    This technical note documents an easily reproducible technique to improve velar competency after transoral lateral oropharyngectomy extending to the velum.

    View details for DOI 10.1016/j.anorl.2021.06.004

    View details for PubMedID 34176777

  • Preoperative predictors of difficult oropharyngeal exposure for transoral robotic surgery: The Pharyngoscore. Head & neck Gaino, F., Gorphe, P., Vander Poorten, V., Holsinger, F. C., Lira, R. B., Duvvuri, U., Garrel, R., Van Der Vorst, S., Cristalli, G., Ferreli, F., De Virgilio, A., Giannitto, C., Morenghi, E., Colombo, G., Malvezzi, L., Spriano, G., Mercante, G. 2021

    Abstract

    BACKGROUND: Insufficient exposure may require termination of procedure in transoral robotic surgery (TORS). The aim of study was to develop a "Pharyngoscore" to quantify the risk of difficult oropharyngeal exposure (DOE) before TORS.METHODS: Three-hundred six patients undergoing any surgical procedure at one Academic Hospital were prospectively enrolled. Oropharynx was exposed with Feyh-Kastenbauer retractor. Exposure was evaluated by direct and endoscopic visualization of the four oropharyngeal subsites. Preoperative clinical/anthropometric parameters were studied in good oropharyngeal exposure and DOE groups. Logistic regression was performed to explore association between clinical/anthropometric parameters and DOE. Statistically significant parameters at multivariate analysis were incorporated into a nomogram.RESULTS: Sixty-five (21.2%) subjects were characterized by DOE. Variables associated with DOE at univariate analysis were male (p=0.031), modified Mallampati Class (MMC) ≥ III (p<0.001), smaller interincisor gap (p<0.001), and larger neck circumference (p=0.006). MMC, interincisor gap, and neck circumference were significant at multivariate analysis and were presented with a nomogram for creating the Pharyngoscore.CONCLUSIONS: The Pharyngoscore is a promising tool for calculating DOE probability before TORS.

    View details for DOI 10.1002/hed.26792

    View details for PubMedID 34132440

  • Verbalization, Categorization, and Evaluation of Fundamental Surgical Skills: An Expert Consensus in Open Head and Neck Surgery. Annals of surgery open : perspectives of surgical history, education, and clinical approaches Mitani, S., Nishio, N., Kitani, T., Ugumori, T., Wakisaka, H., Tanaka, K., Miao, B., Chan, J. Y., Holsinger, F. C., Hato, N. 2021; 2 (2): e059

    Abstract

    This study aimed to verbalize fundamental surgical skills required for open head and neck surgery (OHNS), to organize them by categorization, and to establish a consensus among surgeons regarding the importance and difficulty of each skill.Improvement of fundamental surgical skills is the core of surgical education; however, surgical skills are not yet organized, and consensus in any surgical field remains uncertain.Fundamental surgical skills during OHNS were collected from surgical textbooks, real surgeries, and expert interviews. The items were analyzed to calculate the frequency of words and were categorized by 2 expert surgeons. After consensus on the importance and difficulty of each item was established by 15 expert surgeons using a Delphi survey, principal component (PC) analysis was performed to integrate importance and difficulty into a single parameter.Sixty skills were verbalized and categorized into 7 categories: "skin flap elevation (n = 6)," "vessel management (n = 9)," "nerve preservation (n = 8)," "instrument handling (n = 11)," "counter traction (n = 7)," "tissue exposure (n = 9)," and "flow and planning (n = 10)." In the Delphi survey, expert consensus was established after 2 voting rounds (Cronbach's α ≥ 0.80). The "counter traction" and "flow and planning" categories had high PC scores, which indicate priority in surgical education.Fundamental OHNS skills were verbalized, categorized, and evaluated via expert consensus. Assessment of surgeons' skills by the structured items hereby developed will help standardize the quality of OHNS and improve patient outcomes.

    View details for DOI 10.1097/AS9.0000000000000059

    View details for PubMedID 37636552

    View details for PubMedCentralID PMC10455147

  • Airway and bleeding complications of transoral robotic supraglottic laryngectomy (TORS-SGL): A systematic review and meta-analysis. Oral oncology Turner, M. T., Stokes, W. A., Stokes, C. M., Hassid, S., Holsinger, F. C., Lawson, G. 2021; 118: 105301

    View details for DOI 10.1016/j.oraloncology.2021.105301

    View details for PubMedID 33940531

  • Precision head and neck surgery: robotics and surgical vision technology. Current opinion in otolaryngology & head and neck surgery Holsinger, F. C., Birkeland, A. C., Topf, M. C. 2021; 29 (2): 161–67

    Abstract

    PURPOSE OF REVIEW: As the molecular basis of head and neck cancer becomes more clearly defined, precision medicine has gradually refined the multidisciplinary treatment paradigm for patients with oropharyngeal cancer. Although precision medicine is often thought to refer to new molecular diagnostics or unique medical therapy, the recent adoption of robotic surgery has ushered in the era of 'precision' head and neck surgery.RECENT FINDINGS: Surgeons now routinely utilize a virtual reality environment to reduce the morbidity of head and neck surgical care and improve oncologic and functional outcomes. The development and subsequent FDA approval of the da Vinci SP system, a single-arm system with a flexible camera, has allowed for improved visualization and access to the deep oropharynx and larynx. Groups investigating anti-EGFR antibodies tagged with fluorescent dye as well as inherent autofluorescence differences between normal and cancerous mucosal tissues show promise for improving positive surgical margin rates.SUMMARY: The evolution of robotics and visualization for oropharyngeal cancer represents a novel and innovative utilization of new technology to improve care. Further advancements in techniques, from refinement of the robotic platform itself, to novel real-time tumour imaging options will be critical to further advance precision care for these patients.

    View details for DOI 10.1097/MOO.0000000000000706

    View details for PubMedID 33664199

  • Robotic transmaxillary approach to the lateral infratemporal fossa: A preclinical cadaveric study using a next-generation single-port robotic system HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Turner, M. T., Topf, M. C., Holsinger, F., Chan, J. 2021

    Abstract

    Robotic transmaxillary skull base surgery has been described using multiport systems. This cadaveric study investigates the feasibility of transmaxillary skull base surgery using a next-generation robot. An extended Caldwell-Luc antrostomy, measuring 3.3 cm by 4.0 cm, was performed in 15 min using a Kerrison rongeur and the robotic endoscope. A single-port, robotic system (da Vinci Sp®, Intuitive Surgical, Inc, Sunnyvale, CA, USA) was then deployed throught the extended Caldwell-Luc approach and provided sufficient reach, visualization, and maneuverability to work within the pterygopalatine fossa (PPF) and the infratemporal fossa (ITF) using three surgical instruments. The ITF dissection was easiest with two instruments using the third instrument to retract the muscles of mastication. This study demonstrates the feasibility of single-port robotic transmaxillary approaches to the lateral ITF. Using a single-port robotic system, the operating surgeon can for the first time work in the PPF and ITF using two functional arms for tumor dissection and a third to retract.

    View details for DOI 10.1002/hed.26680

    View details for Web of Science ID 000632453200001

    View details for PubMedID 33764626

  • Anatomical-based classification for transoral base of tongue resection. Head & neck De Virgilio, A., Kim, S., Wang, C., Holsinger, F. C., Magnuson, S., Lawson, G., Pellini, R., Mercante, G., Costantino, A., Spriano, G. 2021

    Abstract

    BACKGROUND: To propose a classification of transoral base of tongue (BOT) procedures able to provide uniform terminology in order to better define postoperative results.METHODS: The classification resulted from the consensus of the different authors and is based on anatomical and surgical principles.RESULTS: The classification comprises three types of BOT resections: type 1 is the resection of the entire lingual tonsil to the muscular plane; type 2 is performed by removing the entire lingual tonsil and part of BOT muscles; type 3 is performed by removing the entire lingual tonsil and the entire BOT muscles. Based on the extension of the dissection, we can use the suffix A (contralateral BOT), B (supraglottic larynx), C (lateral oropharynx), and/or D (oral tongue).CONCLUSION: The proposed classification could allow us to easily compare data from different centers.

    View details for DOI 10.1002/hed.26628

    View details for PubMedID 33580740

  • Videomics: bringing deep learning to diagnostic endoscopy. Current opinion in otolaryngology & head and neck surgery Paderno, A., Holsinger, F. C., Piazza, C. 2021

    Abstract

    PURPOSE OF REVIEW: Machine learning (ML) algorithms have augmented human judgment in various fields of clinical medicine. However, little progress has been made in applying these tools to video-endoscopy. We reviewed the field of video-analysis (herein termed 'Videomics' for the first time) as applied to diagnostic endoscopy, assessing its preliminary findings, potential, as well as limitations, and consider future developments.RECENT FINDINGS: ML has been applied to diagnostic endoscopy with different aims: blind-spot detection, automatic quality control, lesion detection, classification, and characterization. The early experience in gastrointestinal endoscopy has recently been expanded to the upper aerodigestive tract, demonstrating promising results in both clinical fields. From top to bottom, multispectral imaging (such as Narrow Band Imaging) appeared to provide significant information drawn from endoscopic images.SUMMARY: Videomics is an emerging discipline that has the potential to significantly improve human detection and characterization of clinically significant lesions during endoscopy across medical and surgical disciplines. Research teams should focus on the standardization of data collection, identification of common targets, and optimal reporting. With such a collaborative stepwise approach, Videomics is likely to soon augment clinical endoscopy, significantly impacting cancer patient outcomes.

    View details for DOI 10.1097/MOO.0000000000000697

    View details for PubMedID 33595977

  • Postoperative Observation Versus Radiotherapy for Pathologic N1 Oral Cavity Squamous Cell Carcinoma. American journal of clinical oncology Xiang, M. n., Holsinger, F. C., Gensheimer, M. F., Divi, V. n., Pollom, E. L., Colevas, A. D., Le, Q. T., Beadle, B. M. 2021; Publish Ahead of Print

    Abstract

    To investigate the benefit of postoperative radiotherapy (PORT) for low-volume (pN1) nodal disease after resection of oral cavity squamous cell carcinoma.The National Cancer Database was queried for adults with nonmetastatic squamous cell carcinoma of the oral cavity treated by surgical resection with pathologic stage T1-2 N0-2 (American Joint Committee on Cancer 7th edition) and with the maximal exclusion of standard indications for PORT. Overall survival was compared within pN1 for observation versus PORT and then compared for pN1 versus pN0 and versus pN2 stratified by receipt of observation or PORT. Multivariable Cox regression was used to adjust for potential confounders between PORT and survival, including comorbidity and age.Overall 5017 pN0, 530 pN1, and 253 pN2 patients were identified, of whom 9%, 35%, and 64% received PORT, respectively. Within the pN1 cohort, PORT was associated with improved survival versus observation (adjusted hazard ratio, 0.66; 95% confidence interval, 0.46-0.97; P=0.03). Among observed patients, the prognosis of pN1 was equivalent to pN2 and inferior to pN0; in contrast, among patients treated with PORT, the prognosis of pN1 was equivalent to pN0 and superior to pN2. Without PORT, pN1 remained an adverse risk factor relative to pN0 regardless of the depth of invasion, lymph node size, lymph node location, and extent of lymph node dissection.PORT was associated with a survival benefit compared with observation. Notably, pN1 was an adverse risk factor relative to pN0 if, and only if, patients did not receive PORT, suggesting pN1 by itself may be an indication for PORT.

    View details for DOI 10.1097/COC.0000000000000792

    View details for PubMedID 33417322

  • Safety and Feasibility of Surgery for Oropharyngeal Cancers During the SARS-CoV-2-Pandemic. Frontiers in oncology Gorphe, P., Grandbastien, B., Dietz, A., Duvvuri, U., Ferris, R. L., Golusinski, W., Holsinger, F. C., Hosal, S., Lawson, G., Mehanna, H., Paleri, V., Shaw, R., Succo, G., Leemans, C. R., Simon, C. 2021; 11: 651123

    View details for DOI 10.3389/fonc.2021.651123

    View details for PubMedID 33842364

  • Treatment Breaks During Definitive Head/Neck Radiotherapy: Survival Impact and Predisposing Factors Xiang, M., Gensheimer, M., Pollom, E., Holsinger, F., Colevas, A., Quynh-Thu Le, Beadle, B. ELSEVIER SCIENCE INC. 2020: E39
  • Retroauricular thyroidectomy with a single-arm robotic surgical system: Preclinical cadaveric study. Head & neck Noel, J. E., Lee, M., Tam, K., Lim, G., Holsinger, F. C., Koh, Y. W. 2020

    Abstract

    BACKGROUND: In this study, we evaluate a new flexible, single-arm robotic system in performing thyroidectomy via a retroauricular approach.METHODS: Four fresh cadavers were used. Technical details of the new system are discussed, and the comprehensive surgical procedures are described step by step.RESULTS: This single-port flexible system could be used to successfully perform retroauricular thyroidectomy. The ideal angle to dock the patient-side cart was at a 90° angle to the operating table. When the cannula tip was placed 10 to 15cm away from the skin incision, positioning and full movement of all four instruments without collisions were possible. Three flexible instruments and an endoscope made the robotic dissection more efficient.CONCLUSIONS: We describe the first preclinical evaluation of an innovative, flexible, single-arm robotic surgical system for retroauricular thyroidectomy.

    View details for DOI 10.1002/hed.26436

    View details for PubMedID 32852084

  • Correction to: Compensatory motion scaling for time-delayed robotic surgery. Surgical endoscopy Orosco, R. K., Lurie, B., Matsuzaki, T., Funk, E. K., Divi, V., Holsinger, F. C., Hong, S., Richter, F., Das, N., Yip, M. 2020

    Abstract

    This article was updated to correct Tokio Matsuzaki's name in author listing.

    View details for DOI 10.1007/s00464-020-07825-9

    View details for PubMedID 32696146

  • A novel surgeon credentialing and quality assurance process using transoral surgery for oropharyngeal cancer in ECOG-ACRIN Cancer Research Group Trial E3311. Oral oncology Ferris, R. L., Flamand, Y., Holsinger, F. C., Weinstein, G. S., Quon, H., Mehra, R., Garcia, J. J., Hinni, M. L., Gross, N. D., Sturgis, E. M., Duvvuri, U., Mendez, E., Ridge, J. A., Magnuson, J. S., Higgins, K. A., Patel, M. R., Smith, R. B., Karakla, D. W., Kupferman, M. E., Malone, J. P., Judson, B. L., Richmon, J., Boyle, J. O., Bayon, R., O'Malley, B. W., Ozer, E., Thomas, G. R., Koch, W. M., Bell, R. B., Saba, N. F., Li, S., Sigurdson, E. R., Burtness, B. 2020; 110: 104797

    Abstract

    PURPOSE: Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA.PATIENTS AND METHODS: E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections.RESULTS: 120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients.CONCLUSIONS: We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.

    View details for DOI 10.1016/j.oraloncology.2020.104797

    View details for PubMedID 32679405

  • A new endoscopic surgical approach to the larynx, hypopharynx, and neck lymphatics: The robotic-assisted extended "Sistrunk" approach (RESA). Head & neck Simon, C., Holsinger, F. C., Rheinwald, M., Kemper, J., Lambercy, K. 2020

    Abstract

    BACKGROUND: We report on the feasibility of a novel robotic-assisted extended "Sistrunk" approach (RESA) to the larynx, hypopharynx, and lateral neck lymphatics.METHODS: Studies were performed using the da Vinci Xi and SP system on three cadavers comprising of three supraglottic laryngectomies, one partial hypopharyngectomy, and four lateral level II to IV neck dissections.RESULTS: In all resections at first a central common working space overlying the hyoid bone was created. The da Vinci Xi system was used with two vestibular and two submental ports for laryngeal/hypopharyngeal resections, and an additional port through a facelift incision for level II to IV neck dissections. The da Vinci SP system was used with only one submental port.CONCLUSIONS: We describe herein a novel endoscopic robotic approach to the larynx, hypopharynx, and neck based on the traditional "Sistrunk" procedure. The technique should help improving exposure of the primary lesion and reduce access-related morbidity to the neck.

    View details for DOI 10.1002/hed.26273

    View details for PubMedID 32533578

  • Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus. The Lancet. Oncology Mehanna, H., Hardman, J. C., Shenson, J. A., Abou-Foul, A. K., Topf, M. C., AlFalasi, M., Chan, J. Y., Chaturvedi, P., Chow, V. L., Dietz, A., Fagan, J. J., Godballe, C., Golusinski, W., Homma, A., Hosal, S., Iyer, N. G., Kerawala, C., Koh, Y. W., Konney, A., Kowalski, L. P., Kraus, D., Kuriakose, M. A., Kyrodimos, E., Lai, S. Y., Leemans, C. R., Lennon, P., Licitra, L., Lou, P., Lyons, B., Mirghani, H., Nichols, A. C., Paleri, V., Panizza, B. J., Parente Arias, P., Patel, M. R., Piazza, C., Rischin, D., Sanabria, A., Takes, R. P., Thomson, D. J., Uppaluri, R., Wang, Y., Yom, S. S., Zhu, Y., Porceddu, S. V., de Almeida, J. R., Simon, C., Holsinger, F. C. 2020

    Abstract

    The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

    View details for DOI 10.1016/S1470-2045(20)30334-X

    View details for PubMedID 32534633

  • Compensatory motion scaling for time-delayed robotic surgery. Surgical endoscopy Orosco, R. K., Lurie, B., Matsusaki, T., Funk, E. K., Divi, V., Holsinger, F. C., Hong, S., Richter, F., Das, N., Yip, M. 2020

    Abstract

    BACKGROUND: Round trip signal latency, or time delay, is an unavoidable constraint that currently stands as a major barrier to safe and efficient remote telesurgery. While there have been significant technological advancements aimed at reducing the time delay, studies evaluating methods of mitigating the negative effects of time delay are needed. Herein, we explored instrument motion scaling as a method to improve performance in time-delayed robotic surgery.METHODS: This was a robotic surgery user study using the da Vinci Research Kit system. A ring transfer task was performed under normal circumstances (no added time delay), and with 250ms, 500ms, and 750ms delay. Robotic instrument motion scaling was modulated across a range of values (- 0.15, - 0.1, 0,+0.1,+0.15), with negative values indicating less instrument displacement for a given amount of operator movement. The primary outcomes were task completion time and total errors. Three-dimensional instrument movement was compared against different motion scales using dynamic time warping to demonstrate the effects of scaling.RESULTS: Performance declined with increasing time delay. Statistically significant increases in task time and number of errors were seen at 500ms and 750ms delay (p<0.05). Total errors were positively correlated with task time on linear regression (R=0.79, p<0.001). Under 750ms delay, negative instrument motion scaling improved error rates. Negative motion scaling trended toward improving task times toward those seen in non-delayed scenarios. Improvements in instrument path motion were seen with the implementation of negative motion scaling.CONCLUSIONS: Under time-delayed conditions, negative robotic instrument motion scaling yielded fewer surgical errors with slight improvement in task time. Motion scaling is a promising method of improving the safety and efficiency of time-delayed robotic surgery and warrants further investigation.

    View details for DOI 10.1007/s00464-020-07681-7

    View details for PubMedID 32514831

  • Intraoperative identification of critical vascular landmarks of the lateral oropharynx and tongue base using transoral robotic ultrasound (TORUS) Liu, W. P., Holsinger, F., Vendra, V. AMER ASSOC CANCER RESEARCH. 2020: 66
  • Status and strategies for the management of head and neck cancer during COVID-19 pandemic: Indian Scenario. Head & neck Gupta, A., Arora, V., Nair, D., Agrawal, N., Su, Y., Holsinger, C., Chan, J. 2020

    Abstract

    In India, oral cancer is the most common head and neck cancer (HNC) in men in India, mainly due to the consumption of smoked and smokeless tobacco. During the current pandemic, delaying surgery for even 1-2months may lead to more extensive surgery or inoperability, when only supportive care can be provided. Being semi-emergent in nature, treatment for these patients is currently on hold or delayed in most centres across the country. This study was conducted to assess the impact of COVID-19 pandemic and inability of the health system to treat HNC in a timely fashion and how surgeons are coping to this emergent situation. This article highlights the situation in Indian, a country burdened with one of the highest incidence of HNC. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/hed.26227

    View details for PubMedID 32357281

  • Survival Benefit of Postoperative Radiotherapy in Pathological N1 Oral Cavity Squamous Cell Carcinoma Xiang, M., Holsinger, F. C., Gensheimer, M. F., Divi, V., Pollom, E., Colevas, A. D., Le, Q. T., Beadle, B. M. ELSEVIER SCIENCE INC. 2020: 1125
  • A THYROID GENETIC CLASSIFIER CORRECTLY PREDICTS BENIGN NODULES WITH INDETERMINATE CYTOLOGY: TWO-INDEPENDENT MULTICENTER, PROSPECTIVE VALIDATION TRIALS. Thyroid : official journal of the American Thyroid Association Zafereo, M. n., McIver, B. n., Vargas, S. n., Domínguez Ruiz-Tagle, J. M., Steward, D. n., Holsinger, F. C., Kandil, E. n., Williams, M. D., Cruz, F. n., Loyola, S. n., Solar, A. n., Roa, J. C., Leon, A. n., Droppelmann, N. n., Arias, T. n., Lobos, M. n., Kong, C. S., Busaidy, N. n., Grubbs, E. G., Graham, P. H., Stewart, J. n., Tang, A. n., Wang, J. n., Orloff, L. A., Hernríquez-Henríquez, M. n., Lagos, M. n., Wohllk, N. n., Diaz, R. E., Véliz, J. n., Horvath, E. n., Tala, H. n., Pineda, P. n., Arroyo, P. n., Vasquez, F. n., Osorio, M. n., Schacter, D. n., Franco, C. n., Medina, F. n., Traipe, E. n., Marin, L. n., Miranda, G. n., Bruce, E. n., Bracamonte Nole, M. n., Mena, N. n., Gonzalez, H. n. 2020

    Abstract

     Although most thyroid nodules with indeterminate cytology are benign, in most of the world surgery remains as the most frequent diagnostic management. We have previously reported a 10-gene thyroid genetic classifier which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology.Classifier performance was tested in two independent, ethnically diverse, prospective, multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to pathology report. A matched surgical pathology and valid classifier score was available for 270 samples.Cohorts showed significant differences including; i) clinical site patient source (academic, 43% and 97% for TGCT-1 and 2, respectively), ii) ethnic diversity, with greater proportion of Hispanic (40% vs 3%) for TGCT-1 and greater proportion of African-American (11% vs 0%) and Asian (10% vs 1%) population for TGCT-2, and iii) tumor size, (mean of 1.7 cm and 2.5 cm for TGCT-1 and -2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT 1 and 2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% (95% confidence interval CI 77-97%) and 91% (95% CI 79-98%) for TGCTs 1 and 2, respectively. One hundred and one of 114 and 61 of 70 nodules were correctly predicted as benign yielding a specificity of 89% (95% CI 82-94%) and 87% (95% CI 77-94%), respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%.Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.

    View details for DOI 10.1089/thy.2019.0490

    View details for PubMedID 31910118

  • Management of Dysphagia in The Head and Neck Cancer Patient during COVID-19 Pandemic: A Practical Strategy. Head & neck Ku, P. K., Holsinger, F. C., Chan, J. Y., Yeung, Z. C., Chan, B. Y., Tong, M. C., Starmer, H. M. 2020

    Abstract

    The global pandemic of 2019 Novel Coronavirus Disease (COVID-19) has tremendously altered routine medical service provision and imposed unprecedented challenges to the healthcare system. This impacts patients with dysphagia complications caused by head and neck cancers. As this pandemic of COVID-19 may last longer than SARS in 2003, a practical workflow for managing dysphagia is crucial to ensure a safe and efficient practice to patients and healthcare personnel. This document provides clinical practice guidelines based on available evidence to date to balance the risks of SARS-CoV-2 exposure with the risks associated with dysphagia. Critical considerations include reserving instrumental assessments for urgent cases only, optimizing the non-instrumental swallowing evaluation, appropriate use of PPE, and use of telehealth when appropriate. Despite significant limitations in clinical service provision during the pandemic of COVID-19, a safe and reasonable dysphagia care pathway can still be implemented with modifications of setup and application of newer technologies. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/hed.26224

    View details for PubMedID 32348591

  • Perceived value drives use of routine asymptomatic surveillance PET/CT by physicians who treat head and neck cancer. Head & neck Roman, B. R., Lohia, S. n., Mitra, N. n., Wang, M. B., Pou, A. M., Holsinger, F. C., Myssiorek, D. n., Goldenberg, D. n., Asch, D. A., Shea, J. A. 2020

    Abstract

    Why physicians use surveillance imaging for asymptomatic cancer survivors despite recommendations against this is not known.Physicians surveilling head and neck cancer survivors were surveyed to determine relationships among attitudes, beliefs, guideline familiarity, and self-reported surveillance positron-emission-tomography/computed-tomography use.Among 459 responses, 79% reported using PET/CT on some asymptomatic patients; 39% reported using PET/CT on more than half of patients. Among attitudes/beliefs, perceived value of surveillance imaging (O.R. 3.57, C.I. 2.42-5.27, P = <.0001) was the strongest predictor of high imaging, including beliefs about outcome (improved survival) and psychological benefits (reassurance, better communication). Twenty-four percent of physicians were unfamiliar with guideline recommendations against routine surveillance imaging. Among physicians with high perceived-value scores, those less familiar with guidelines imaged more (O.R. 3.55, C.I. 1.08-11.67, P = .037).Interventions to decrease routine surveillance PET/CT use for asymptomatic patients must overcome physicians' misperceptions of its value. Education about guidelines may modify the effect of perceived value.

    View details for DOI 10.1002/hed.26071

    View details for PubMedID 31919944

  • Effectiveness of a Home-based Head and Neck Lymphedema Management Program: A Pilot Study. The Laryngoscope Yao, T. n., Beadle, B. n., Holsinger, C. F., Starmer, H. M. 2020

    Abstract

    This study aimed to compare outcomes in patients with head and neck lymphedema receiving either a home-based lymphedema treatment program or a hybrid approach including both home-based treatment and regular clinical visits.Outcomes were assessed in patients receiving head and neck lymphedema rehabilitation. Baseline measures of neck, submental, and facial edema were obtained and repeated following treatment. A home program was recommended for all patients, and those receiving hybrid care received the same recommendations as well as a visit with the lymphedema therapist for additional treatment. Their outcomes were compared using standard statistical analysis.Fifty consecutive individuals were included, 25 in each group. Adherence to at least 50% of recommended treatment was reported in 68% of those receiving home-based treatment and 84% of those receiving hybrid care. Significant improvement was demonstrated for 66% of patients. There was no statistically significant difference between treatment groups with regard to clinically significant improvement (P = .15). Patients receiving hybrid therapy demonstrated treatment advantages regarding facial edema (P = .037). Adherence to treatment was associated with clinical improvement (P = .047).Comparable benefits were observed regardless of whether patients had a home-based or hybrid lymphedema treatment approach. These data suggest a home-based treatment approach may be appropriate for patients unable to participate in clinical sessions. However, for patients with significant facial edema, a hybrid approach may be preferable. Adherence was associated with better outcomes. Given these findings, future investigations should consider strategies to improve adherence to optimize the outcomes lymphedema treatment.3b Laryngoscope, 2020.

    View details for DOI 10.1002/lary.28549

    View details for PubMedID 32068894

  • Bleeding Complications After Transoral Robotic Surgery: A Meta-Analysis and Systematic Review. The Laryngoscope Stokes, W. n., Ramadan, J. n., Lawson, G. n., Ferris, F. R., Holsinger, F. C., Turner, M. T. 2020

    Abstract

    Postoperative hemorrhage is the most common complication of transoral robotic surgery (TORS), the severity of which can range from minor bleeding treated with observation to catastrophic hemorrhage leading to death. To date, little is known about the incidence, risk factors, and management of post-TORS hemorrhage.Systematic Review and Metanlysis.A systematic review of the published literature using the Cochrane Handbook for Systematic Reviews of Interventions was performed and examined TORS, postoperative hemorrhage, and the use of prophylactic transcervical arterial ligation (TAL).A total of 13 articles were included in the analysis. To date, there have been 332 cases of hemorrhage following a total of 5748 TORS. The pooled median post-TORS hemorrhage rate was 6.47%. The overall incidence of minor and major hemorrhage was 5.29% and 2.90%. Patients with prior radiation (relative risk [RR] = 1.46, 95% confidence interval [CI] = 1.00-2.12), large tumors (RR = 2.11, 95% CI = 1.48-2.99), and those requiring perioperative coagulation (RR = 2.25, 95% CI = 1.54-3.28) had significantly higher relative risks of hemorrhage. There was no significant difference in the relative risk of overall hemorrhage with TAL. Looking at major hemorrhage, patients undergoing TAL had a large but insignificant relative risk reduction in post-TORS hemorrhage (RR = 0.40, 95% CI = 0.15-1.07).The incidence of post-TORS hemorrhage is low (5.78%), and for major hemorrhage requiring emergent embolization, TAL, or tracheotomy to control hemorrhage it is even lower (2.90%). Large tumors, perioperative anticoagulation, and prior radiation were associated with significantly increased risk of post-TORS hemorrhage. TAL does not reduce the overall incidence of post-TORS hemorrhage but may lead to fewer severe hemorrhages.III Laryngoscope, 2020.

    View details for DOI 10.1002/lary.28580

    View details for PubMedID 32108347

  • There is no routine head and neck exam during the COVID-19 pandemic. Head & neck Chan, J. Y., Tsang, R. K., Yeung, K. W., Abdullah, V. n., Ku, P. n., Wong, E. W., Mehta, N. n., Orosco, R. K., Holsinger, F. C. 2020

    View details for DOI 10.1002/hed.26168

    View details for PubMedID 32298028

  • A Framework for Prioritizing Head and Neck Surgery during the COVID-19 Pandemic. Head & neck Topf, M. C., Shenson, J. A., Holsinger, F. C., Wald, S. H., Cianfichi, L. J., Rosenthal, E. L., Sunwoo, J. B. 2020

    Abstract

    The COVID-19 pandemic has placed an extraordinary demand on the United States healthcare system. Many institutions have cancelled elective and non-urgent procedures to conserve resources and limit exposure. While operational definitions of elective and urgent categories exist, there is a degree of surgeon judgment in designation. In the present commentary, we provide a framework for prioritizing head and neck surgery during the pandemic. Unique considerations for the head and neck patient are examined including risk to the oncology patient, outcomes following delay in head and neck cancer therapy, and risk of transmission during otolaryngologic surgery. Our case prioritization criteria consist of four categories: urgent - proceed with surgery, less urgent - consider postpone >30 days, less urgent - consider postpone 30-90 days, and case-by-case basis. Finally, we discuss our preoperative clinical pathway for transmission mitigation including defining low-risk and high-risk surgery for transmission and role of preoperative COVID-19 testing. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/hed.26184

    View details for PubMedID 32298036

  • Managing the Head and Neck Cancer Patient with Tracheostomy or Laryngectomy During the COVID-19 Pandemic. Head & neck Kligerman, M. P., Vukkadala, N. n., Tsang, R. K., Sunwoo, J. B., Holsinger, F. C., Chan, J. Y., Damrose, E. J., Kearney, A. n., Starmer, H. M. 2020

    View details for DOI 10.1002/hed.26171

    View details for PubMedID 32298035

  • Prolongation of definitive head and neck cancer radiotherapy: Survival impact and predisposing factors. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Xiang, M. n., Gensheimer, M. F., Pollom, E. L., Holsinger, F. C., Colevas, A. D., Le, Q. T., Beadle, B. M. 2020

    Abstract

    To quantify the survival impact of prolongation of definitive radiotherapy (RT) for head and neck cancer in a national, modern cohort, and to identify predictive factors for prolongation.The National Cancer Database was queried for adults with non-metastatic cancer of the nasopharynx, oropharynx, larynx, or hypopharynx diagnosed 2004-2015, treated with definitive RT to 66-70 Gy in 30-35 fractions at 2-2.2 Gy per fraction. Multivariable Cox regression and propensity score matching were used to model the survival impact of RT prolongation, adjusting for potential confounders such as age and comorbidity. Predictors of RT prolongation were identified using multivariable multinomial logistic regression.In total, 36,367 patients were identified. As a continuous variable, RT prolongation increased the relative hazard of death by 2% per day (P < .0001). In the matched cohorts, patients with short (4-8 days) or long prolongation (> 8 days) had lower absolute 4-year overall survival by 4% and 12% respectively (P < .0001), while prolongation of 1-3 days was not significantly adverse. Major predictors of increased risk of prolongation were administration of systemic therapy, baseline comorbidity, lack of private insurance, and tumor/nodal stage. Conversely, higher facility volume was significantly protective, with a 55% lower risk of long prolongation within the topmost quartile (> 11.5 patients/year).RT prolongation, especially > 8 days, is significantly deleterious. Systemic therapy and facility volume were major predictors. Early identification of patients at increased risk of treatment interruptions may facilitate implementation of preventive measures.

    View details for DOI 10.1016/j.radonc.2020.12.025

    View details for PubMedID 33383061

  • COVID-19 and the otolaryngologist - preliminary evidence-based review. The Laryngoscope Vukkadala, N. n., Qian, Z. J., Holsinger, F. C., Patel, Z. M., Rosenthal, E. n. 2020

    Abstract

    The SARS-CoV-2 virus which causes coronavirus disease 2019 (COVID-19) has rapidly swept across the world since its identification in December 2019. Otolaryngologists are at unique risk due to the close contact with mucus membranes of the upper respiratory tract and have been among the most affected healthcare workers in Wuhan, China. We present information on COVID-19 management relevant to otolaryngologists on the frontlines of this pandemic and provide preliminary guidance based on practices implemented in China and other countries and practical strategies deployed at Stanford University. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/lary.28672

    View details for PubMedID 32219846

  • Transoral thyroidectomy with a next generation flexible robotic system: A feasibility study in a cadaveric model GLAND SURGERY Chan, J. K., Koh, Y. W., Richmon, J., Kim, J., Holsinger, F., Orloff, L., Anuwong, A. 2019; 8 (6): 644-+
  • Transoral thyroidectomy with a next generation flexible robotic system: A feasibility study in a cadaveric model. Gland surgery Chan, J. Y., Koh, Y. W., Richmon, J., Kim, J., Holsinger, F. C., Orloff, L., Anuwong, A. 2019; 8 (6): 644-647

    Abstract

    Transoral endoscopic thyroidectomy provides access via the oral vestibule and gas insufflation to provide reliable remote access surgery to perform a total thyroidectomy. The da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA, USA) is a next generation flexible single port system that offers unique advantages over previous robotic rigid systems. Here we sought to evaluate the feasibility of performing transoral thyroidectomy with this next generation flexible robotic system.Cadaveric dissection with gas insufflation to test the feasibility of performing transoral thyroidectomy with the da Vinci SP.A 2 cm incision was made in the oral vestibule and the working space created with a 1cm central port and two lateral 5 mm ports. Then an extra small wound protector (Applied Medical, Rancho Santa Margarita, CA) was placed through the central incision after closure of the 5 mm ports. The robotic system was then deployed through the wound protector while insufflation was maintained at ~6 mmHg. Three instrument arms were deployed. A fenestrated bipolar was used to grasp the thyroid gland while Maryland bipolars and monopolar scissors were used to mobilize each hemi lobe of the thyroid. The recurrent laryngeal nerves were seen and preserved bilaterally. After completion of the surgery and removal of the wound protector the vestibular incision was measured to be 3 cm. Further dissection to identify the mental nerves identified each nerve to be >1 cm from the lateral extent of the central incision.In summary, it is feasible to perform a total thyroidectomy with gas insufflation utilizing this next generation flexible robotic system. Further evaluation will be needed to validate the clinical applicability of this technique.

    View details for DOI 10.21037/gs.2019.10.13

    View details for PubMedID 32042671

    View details for PubMedCentralID PMC6989906

  • Anatomical-based classification for transoral lateral oropharyngectomy. Oral oncology De Virgilio, A., Kim, S., Magnuson, J. S., Holsinger, C., Remacle, M., Lawson, G., Wang, C., Mercante, G., Malvezzi, L., Iocca, O., Di Maio, P., Ferreli, F., Pellini, R., Spriano, G. 2019; 99: 104450

    Abstract

    PURPOSE: The aim of the study is proposing a classification of different transoral lateral oropharyngectomy procedures in order to ensure better definitions of post-operative results.METHODS: The classification resulted from the consensus of the different authors and was based on anatomical-surgical principles.RESULTS: The classification comprises three types of lateral oropharyngectomy: type 1 is the resection of the palatine tonsil deep to the pharyngobasilar fascia; type 2 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle and the superior constrictor muscle; type 3 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle, the superior constrictor muscle, the buccopharyngeal fascia with extension to the pterygoid muscle and parapharyngeal space fat content. Based on the extension of the dissection we can use the suffix A (soft palate), B (posterior pharyngeal wall), C (base of tongue) and D (retromolar trigone).CONCLUSION: The proposed classification introduces a simple and easy to use categorization of transoral lateral oropharyngectomies into three classes. Resection extensions are easily described using suffixes.

    View details for DOI 10.1016/j.oraloncology.2019.104450

    View details for PubMedID 31707218

  • Augmented reality for image guidance in transoral robotic surgery. Journal of robotic surgery Chan, J. Y., Holsinger, F. C., Liu, S., Sorger, J. M., Azizian, M., Tsang, R. K. 2019

    Abstract

    With the advent of precision surgery, there have been attempts to integrate imaging with robotic systems to guide sound oncologic surgical resections while preserving critical structures. In the confined space of transoral robotic surgery (TORS), this offers great potential given the proximity of structures. In this cadaveric experiment, we describe the use of a 3D virtual model displayed in the surgeon's console with the surgical field in view, to facilitate image-guided surgery at the oropharynx where there is significant soft tissue deformation. We also utilized the 3D model that was registered to the maxillary dentition, allowing for real-time image overlay of the internal carotid artery system. This allowed for real-time visualization of the internal carotid artery system that was qualitatively accurate on cadaveric dissection. Overall, this shows that virtual models and image overlays can be useful in image-guided surgery while approaching different sites in head and neck surgery with TORS.

    View details for DOI 10.1007/s11701-019-01030-0

    View details for PubMedID 31555957

  • Editorial on "Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy". Annals of surgical oncology Chan, J. Y., Holsinger, F. C. 2019

    View details for DOI 10.1245/s10434-019-07855-1

    View details for PubMedID 31549318

  • Hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy via transoral robotic surgery LARYNGOSCOPE Nakayama, M., Holsinger, F., Orosco, R. K. 2019; 129 (9): 2065–70

    View details for DOI 10.1002/lary.27628

    View details for Web of Science ID 000481918800027

  • Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline JOURNAL OF CLINICAL ONCOLOGY Koyfman, S. A., Ismaila, N., Crook, D., D'Cruz, A., Rodriguez, C. P., Sher, D. J., Silbermins, D., Sturgis, E. M., Tsue, T. T., Weiss, J., Yom, S. S., Holsinger, F. 2019; 37 (20): 1753-+
  • Cost comparison of treatment for oropharyngeal carcinoma LARYNGOSCOPE Tam, K., Orosco, R. K., Colevas, A., Bedi, N., Starmer, H. M., Beadle, B. M., Holsinger, F. 2019; 129 (7): 1604–9

    View details for DOI 10.1002/lary.27544

    View details for Web of Science ID 000471915700026

  • Prospective clinical trial to evaluate safety and feasibility of using a single port flexible robotic system for transoral head and neck surgery. Oral oncology Chan, J. Y., Tsang, R. K., Holsinger, F. C., Tong, M. C., Ng, C. W., Chiu, P. W., Ng, S. S., Wong, E. W. 2019; 94: 101–5

    Abstract

    INTRODUCTION: The aim of this study was to determine the clinical safety and feasibility of a novel single-port flexible robot for Transoral Robotic Surgery (TORS).MATERIALS AND METHODS: This was a prospective phase II / IDEAL stage 2 clinical trial of both benign and malignant lesions of the head and neck. The primary endpoint included conversion rates and perioperative complications within 30 days following surgery. The study was registered on www.ClinicalTrials.gov (NCT03010813). The Fisher's exact test and Mann-Whitney U test were used to compare categorical, and non-parametric data for the trial. A p value <0.05 was considered to be statistically significant. Statistical analysis was performed with SPSS 20.0 (IBM Corp., Armonk, New York) RESULTS: Twenty-one patients safely underwent TORS with the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA) demonstrating the feasibility of access to the nasopharynx, oropharynx, larynx and hypopharynx. There were no conversions of the robotic surgical system. There were no serious adverse events or adverse events related to the use of the robot at 30-day follow-up for all patients.CONCLUSIONS: In a prospective Phase II clinical trial, a novel single-port flexible robotic system appears safe and feasible to use for transoral endoscopic head and neck surgery to access the nasopharynx, oropharynx, larynx and hypopharynx.

    View details for DOI 10.1016/j.oraloncology.2019.05.018

    View details for PubMedID 31178203

  • Submandibular gland resection via the trans-hairline approach: A preclinical study of a novel flexible single-port surgical system and the surgical experiences of standard multiarm robotic surgical systems HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Yang, T., Li, H., Holsinger, F., Koh, Y. 2019; 41 (7): 2231–38

    View details for DOI 10.1002/hed.25692

    View details for Web of Science ID 000471816100028

  • Transoral supraglottic laryngectomy using a next-generation single-port robotic surgical system HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Orosco, R. K., Tam, K., Nakayama, M., Holsinger, F., Spriano, G. 2019; 41 (7): 2143–47

    View details for DOI 10.1002/hed.25676

    View details for Web of Science ID 000471816100016

  • Curved Laryngopharyngoscope With Flexible Next-Generation Robotic Surgical System for Transoral Hypopharyngeal Surgery: A Preclinical Evaluation. The Annals of otology, rhinology, and laryngology Eguchi, K., Chan, J. Y., Tateya, I., Shimizu, A., Holsinger, F. C., Sugimoto, T. 2019: 3489419856391

    Abstract

    OBJECTIVES: The indication of transoral robotic surgery for hypopharyngeal cancer is limited because of poor accessibility. The aim of this study was to explore the efficacy of a curved laryngopharyngoscope used in combination with a next-generation flexible robotic surgical system for accessing and resecting the hypopharynx.METHODS: A comparative evaluation of the curved laryngopharyngoscope versus standard straight-blade retractors using the flexible robotic surgical system was conducted on 2 cadavers. End points measured included visualization, accessibility, and ease of dissection for accessing and resecting the hypopharynx.RESULTS: Visualization, accessibility, and dissection were superior with the curved laryngopharyngoscope in all subareas of the hypopharynx. The advantages of accessibility and visualization were much more evident in the cadaver with a high body mass index.CONCLUSIONS: These preclinical data suggest that using a curved laryngopharyngoscope in combination with a flexible robotic surgical system may lead to technical innovations concerning transoral surgery of the hypopharynx.

    View details for DOI 10.1177/0003489419856391

    View details for PubMedID 31220916

  • The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer HORMONES & CANCER Martinez, J. W., Vargas-Salas, S., Urra Gamboa, S., Munoz, E., Miguel Dominguez, J., Leon, A., Droppelmann, N., Solar, A., Zafereo, M., Holsinger, F., Gonzalez, H. E. 2019; 10 (2-3): 97–106
  • Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline Summary JOURNAL OF ONCOLOGY PRACTICE Koyfman, S. A., Ismaila, N., Holsinger, F. 2019; 15 (5): 273-+
  • The dawn of robotic surgery in otolaryngology-head and neck surgery JAPANESE JOURNAL OF CLINICAL ONCOLOGY Nakayama, M., Holsinger, F., Chevalier, D., Orosco, R. K. 2019; 49 (5): 404–11
  • Transoral tongue base mucosectomy for the identification of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis. Oral oncology Farooq, S., Khandavilli, S., Dretzke, J., Moore, D., Nankivell, P. C., Sharma, N., Almeida, J. R., Winter, S. C., Simon, C., Paleri, V., De, M., Siddiq, S., Holsinger, C., Ferris, R. L., Mehanna, H. 2019; 91: 97-106

    Abstract

    The use of transoral robotic surgery (TORS) and laser microsurgery (TLM) in the diagnosis and identification of the site of the unknown primary has become increasingly common. This systematic review and meta-analysis aims to assess the use and efficacy of TORS and TLM for this indication.Systematic review and meta-analysis of studies employing TORS or TLM in diagnosis of the unknown primary tumor site in patients with cervical nodal metastases of squamous cell origin. MEDLINE, EMBASE and CINHAL were searched from inception to July 2018 for all studies that used TORS and or TLM in identifying the unknown primary.251 studies were identified, of which 21 were eligible for inclusion. The primary tumour was identified by TORS/TLM in 78% of patients (433 out of 556). Tongue base mucosectomy (TBM) identified the primary in 222 of 427 cases (53%). In patients with negative physical examination, diagnostic imaging and PETCT, TBM identified the primary in 64% (95% CI 50, 79) cases. In patients who had negative CT/MRI imaging, negative PETCT and negative EUA and tonsillectomy, TBM identified a tongue base primary in 78% (95% CI 41, 92) cases. Haemorrhage, the commonest complication, was reported in 4.9% cases. Mean length of stay varied between 1.4 and 6.3 days.Tongue base mucosectomy, performed by TORS or TLM, is highly efficacious in identifying the unknown primary in the head and neck region.

    View details for DOI 10.1016/j.oraloncology.2019.02.018

    View details for PubMedID 30926070

  • Transoral tongue base mucosectomy for the identification of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis ORAL ONCOLOGY Farooq, S., Khandavilli, S., Dretzkeke, J., Moore, D., Nankivell, P. C., Sharma, N., de Almeida, J. R., Winter, S. C., Simon, C., Paleri, V., De, M., Siddiq, S., Holsinger, C., Ferris, R. L., Mehanna, H. 2019; 91: 97–106
  • Lateral pharyngotomy EUROPEAN ANNALS OF OTORHINOLARYNGOLOGY-HEAD AND NECK DISEASES Laccourreye, O., Villeneuve, A., Rubin, F., Holsinger, F. C. 2019; 136 (2): 135–40
  • The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer. Hormones & cancer Martinez, J. R., Vargas-Salas, S., Gamboa, S. U., Munoz, E., Dominguez, J. M., Leon, A., Droppelmann, N., Solar, A., Zafereo, M., Holsinger, F. C., Gonzalez, H. E. 2019

    Abstract

    The use of BRAFV600E and RET/PTC1 as biomarkers to guide the extent of surgery in patients with papillary thyroid cancer (PTC) remains controversial. We assessed the combined use of demographic data (sex and age) with mRNA expression levels and/or mutational status (BRAFV600E and RET/PTC1) to identify potential subsets of patients with aggressive histopathological features (lymph node metastases and extrathyroidal extension). In a cohort of 126 consecutive patients, BRAFV600E and RET/PTC1 mutations were found in 52 and 18%, respectively. By conditional bivariate analysis (CBVA), a 'high activity' profile of BRAF (BRAFV600E positive or high expression) and 'low activity' profile of RET (RET/PTC1 negative or low expression) was associated with extrathyroidal extension (ETE) (OR 4.48). Alternatively, a 'high activity' profile of RET (RET/PTC1 positive or high expression) and 'low activity' profile of BRAF (BRAFV600E negative or low expression) were associated with lymph node metastasis (LNM) (OR 12.80). Furthermore, in patients younger than 55years, a low expression of BRAF was associated with LNM (OR 17.65) and the presence of BRAFV600E mutation was associated with ETE (OR 2.76). Our results suggest that the analysis of demographic and molecular variables by CBVA could contribute to identify subsets of patients with aggressive histopathologic features, providing a potential guide to personalised surgical management of PTC.

    View details for PubMedID 30903583

  • Submandibular gland resection via the trans-hairline approach: A preclinical study of a novel flexible single-port surgical system and the surgical experiences of standard multiarm robotic surgical systems. Head & neck Yang, T., Li, H., Holsinger, F. C., Koh, Y. W. 2019

    Abstract

    BACKGROUND: Cosmetic outcome after submandibular gland (SMG) surgery has greatly improved since the development of robotic surgery through a trans-hairline approach. However, the bulky sizes of robotic arms and the rigid design of camera and instruments in the current multiarm robotic systems increased the surgical difficulty.METHODS: Clinical and preclinical studies demonstrated the surgical configuration and procedures of robotic trans-hairline SMG resection using a flexible, single-port, and multiarm systems.RESULTS: The surgical procedures of trans-hairline approach for SMG resection could be successfully performed using the flexible single-port (SP) robotic system in the preclinical study. The unique features include an easier docking procedure, different viewing angles, the use of the third arm, and coordination of instrument positions without a bedside assistant, which are unavailable in current multiarm robotic systems.CONCLUSIONS: This study demonstrates the feasibility and the advantages of applying the flexible, SP robotic system in SMG resection through the trans-hairline approach.

    View details for PubMedID 30896063

  • Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline Summary. Journal of oncology practice Koyfman, S. A., Ismaila, N., Holsinger, F. C. 2019: JOP1800727

    View details for PubMedID 30883257

  • Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Koyfman, S. A., Ismaila, N., Crook, D., D'Cruz, A., Rodriguez, C. P., Sher, D. J., Silbermins, D., Sturgis, E. M., Tsue, T. T., Weiss, J., Yom, S. S., Holsinger, F. C. 2019: JCO1801921

    Abstract

    PURPOSE: The aim of the current work is to provide evidence-based recommendations to practicing physicians and others on the management of the neck in patients with squamous cell carcinoma of the oral cavity and oropharynx.METHODS: ASCO convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2018. Outcomes of interest included survival, regional disease control, neck recurrence, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.RESULTS: The literature search identified 124 relevant studies to inform the evidence base for this guideline. Six clinical scenarios were devised; three for oral cavity cancer and three for oropharynx cancer, and recommendations were generated for each one.RECOMMENDATIONS: For oral cavity cancers, clinical scenarios focused on the indications for and the hallmarks of a high-quality neck dissection, indications for postoperative radiotherapy or chemoradiotherapy, and whether radiotherapy alone is sufficient elective treatment of an undissected neck compared with high-quality neck dissection. For oropharynx cancers, clinical scenarios focused on hallmarks of a high-quality neck dissection, factors that would favor operative versus nonoperative primary management, and clarifying criteria for an incomplete response to definitive chemoradiation for which salvage neck dissection would be recommended. Consensus was reached and recommendations were made for all six clinical scenarios. Additional information is available at www.asco.org/head-neck-cancer-guidelines .

    View details for PubMedID 30811281

  • The dawn of robotic surgery in otolaryngology: head and neck surgery. Japanese journal of clinical oncology Nakayama, M., Holsinger, F. C., Chevalier, D., Orosco, R. K. 2019

    Abstract

    Transoral robotic surgery (TORS) utilizing the da Vinci robotic system has opened a new era for minimally-invasive surgery (MIS) in Otolaryngology-Head and Neck Surgery. Awareness of the historical steps in developing robotic surgery (RS) and understanding its current application within our field can help open our imaginations to future of the surgical robotics. We compiled a historical perspective on the evolution of surgical robotics, the road to the da Vinci surgical system, and conducted a review of TORS regarding clinical applications and limitations, prospective clinical trials and current status in Japan. We also provided commentary on the future of surgical robotics within our field. Surgical robotics grew out of the pursuit of telerobotics and the advances in robotics for non-medical applications. Today in our field, cancers and diseases of oropharynx and supraglottis are the most common indications for RS. It has proved capable of preserving the laryngopharyngeal function without compromising oncologic outcomes, and reducing the intensity of adjuvant therapy. TORS has become a standard modality for MIS, and will continue to evolve in the future. As robotic surgical systems evolve with improved capabilities in visual augmentation, spatial navigation, miniaturization, force-feedback and cost-effectiveness, we will see further advances in the current indications, and an expansion of indications. By promoting borderless international collaborations that put 'patients first', the bright future of surgical robotics will synergistically expand to the limits of our imaginations.

    View details for PubMedID 30796834

  • Transoral supraglottic laryngectomy using a next-generation single-port robotic surgical system. Head & neck Orosco, R. K., Tam, K., Nakayama, M., Christopher, F., Spriano, G. 2019

    Abstract

    BACKGROUND: To investigate the feasibility of transoral robotic surgery (TORS) supraglottic laryngectomy (SGL) using a next-generation flexible surgical robot.METHODS: Preclinical human cadaver anatomic study of TORS SGL via en bloc resection.RESULTS: A single-port robotic surgical system (da Vinci Sp, Intuitive Surgical, Inc., Sunnyvale, California) provided sufficient access, reach, and visualization to perform TORS SGL. Access and exposure were achieved with a standard laryngo-pharyngoscope retractor. The remote center of the robotic system was located 10 cm from the maxillary alveolus. Three surgical instruments and one flexible camera could be deployed with minimal collision or restriction of arm movement.CONCLUSIONS: Routine resection supraglottic cancers through TORS have been hindered by challenging exposure and visualization and limited instrument maneuverability deep within the laryngopharyngeal complex. This preclinical feasibility study demonstrates the technical feasibility for TORS SGL using a next-generation flexible surgical robot.

    View details for PubMedID 30775823

  • Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. Journal of the National Comprehensive Cancer Network : JNCCN Xiang, M. n., Colevas, A. D., Holsinger, F. C., Le, Q. X., Beadle, B. M. 2019; 17 (9): 1065–73

    Abstract

    For definitive chemoradiotherapy (chemoRT) of head and neck squamous cell carcinoma (HNSCC), cisplatin is the preferred concurrent agent, with superiority over cetuximab for HPV-associated oropharyngeal squamous carcinoma recently shown in 2 randomized trials (RTOG 1016 and De-ESCALaTE). Patients who are not candidates for cisplatin may be treated with carboplatin instead, but its comparative efficacy is unclear. We analyzed nationwide patterns of care and cancer-specific outcomes after cisplatin- versus carboplatin-based chemoRT.Patients with locoregionally advanced (stages III-IVB according to the 6th and 7th editions of the AJCC Cancer Staging Manual) squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received definitive radiotherapy (RT) were identified in the linked SEER-Medicare database. The concurrent chemotherapy regimen was determined through corresponding Medicare claims. Death caused by HNSCC (cancer-specific mortality [CSM]) was analyzed with competing risks. Propensity score analysis and multivariable Fine-Gray regression were used to adjust for baseline differences, including age and comorbidity.We identified 807 patients who received cisplatin-based chemoRT and 342 who received carboplatin-based chemoRT. Most carboplatin recipients (68%) had combination chemotherapy, predominantly with paclitaxel. Carboplatin- and cisplatin-based chemoRT had similar incidences of death attributable to HNSCC (3-year CSM, 29% vs 26%; P=.19), which persisted in propensity score-matched analysis. In addition, no significant difference in overall survival was seen in the matched cohorts. ChemoRT with either cisplatin or carboplatin was superior to RT alone and RT with concurrent cetuximab. In the multivariable model, the adjusted hazard ratio of CSM for carboplatin relative to cisplatin was 1.01 (95% CI, 0.79-1.28; P=.94).Definitive carboplatin-based chemoRT was equivalent to cisplatin-based therapy and superior to RT alone and RT with concurrent cetuximab. In light of recent results of the RTOG 1016 and De-ESCALaTE trials, our findings suggest that carboplatin-based regimens warrant prospective investigation as an alternative to cisplatin for patients who are not cisplatin candidates.

    View details for DOI 10.6004/jnccn.2019.7297

    View details for PubMedID 31487677

  • A Next-Generation Single-Port Robotic Surgical System for Transoral Robotic Surgery: Results From Prospective Nonrandomized Clinical Trials. JAMA otolaryngology-- head & neck surgery Holsinger, F. C., Magnuson, J. S., Weinstein, G. S., Chan, J. Y., Starmer, H. M., Tsang, R. K., Wong, E. W., Rassekh, C. H., Bedi, N. n., Hong, S. S., Orosco, R. n., O'Malley, B. W., Moore, E. J. 2019

    Abstract

    Transoral endoscopic head and neck surgery now plays an important role in the multidisciplinary management of oropharyngeal carcinoma. Previous generations of robotic surgical systems used a multiport system with a rigid stereo-endoscope and 2 wristed instruments that facilitated transoral robotic surgery.To evaluate a new single-port robotic surgical system in head and neck surgery prospectively through concurrent nonrandomized clinical trials.Two prospective clinical trials were conducted from December 16, 2016, to December 26, 2017, to assess the safety, feasibility, and performance of a flexible single-port robotic surgical system in 4 institutions, including 3 in the United States and 1 in Hong Kong. A total of 47 patients with tumors of the oropharynx were enrolled and underwent surgery. All patients were classified as having American Society of Anesthesiologists class I to III status and Eastern Cooperative Oncology Group status 0 to 1. An initial cohort of 7 patients underwent staging and endoscopic procedures for benign disease. The remaining 40 patients all had malignant tumors of the oropharynx.Safety was measured by the incidence of device-related serious adverse events. Feasibility and performance were measured by the conversion rate from the use of the single-port robotic surgical system to either open surgery or the use of any other transoral technology required to complete the planned procedure. Secondary end points of swallowing function and surgical margins were also measured.All 47 patients (8 women and 39 men; mean [SD] age, 61 [8] years) safely underwent transoral resection with the single-port robotic surgical system without conversion to open surgery, laser surgery, or multiport robotic surgery. There were no intraoperative complications or device-related serious adverse events. Mean (SD) estimated intraoperative blood loss per procedure was 15.4 (23.9) mL; no patients received a transfusion. Two patients underwent a planned tracheotomy owing to medical comorbidity (previous chemoradiotherapy; obesity and severe sleep apnea). Two patients (4%) had grade III or IV postoperative hemorrhage, requiring a return to the operating room; however, both patients had medical comorbidities requiring the use of antithrombotic medication. The incidence of positive margins for patients with oropharyngeal malignancy was 3% (1 of 40). Within 30 days, 45 patients (96%) were eating by mouth and without the need for a percutaneous endoscopic gastrostomy tube.This study describes the results of phase 2 clinical testing of a next-generation, robotic surgical system using a single-port architecture. The use of the device appears to be feasible, safe, and effective for transoral robotic surgery of oropharyngeal tumors.ClinicalTrials.gov identifiers: NCT03010813 and NCT03049280.

    View details for DOI 10.1001/jamaoto.2019.2654

    View details for PubMedID 31536129

  • Reply to C. Schilling et al. Journal of oncology practice Koyfman, S. A., Ismaila, N. n., Holsinger, F. C. 2019: JOP1900434

    View details for DOI 10.1200/JOP.19.00434

    View details for PubMedID 31513479

  • Development of proficiency-based knot-tying and suturing curriculum for otolaryngology residents: A pilot study. Auris, nasus, larynx Sato, E. n., Mitani, S. n., Nishio, N. n., Kitani, T. n., Sanada, T. n., Ugumori, T. n., Christopher Holsinger, F. n., Baik, F. M., Hato, N. n. 2019

    Abstract

    Basic surgical skills such as knot-tying and suturing are important for all otolaryngologists, regardless of subspecialty. The present study was undertaken in order to assess basic surgical techniques such as knot-tying and suturing required for novice otolaryngology residents with taking the variety of subspecialties into consideration, and evaluate the impact of a proficiency-based training curriculum based on these techniques.A prospective study was performed for developing of proficiency-based knot-tying and suturing curriculum for otolaryngology residents in the third post-graduate year (PGY-3). The proficiency-based training curriculum was developed based on the tasks selected by RAND/UCLA method with expert panel, which is an iterative and anonymous survey used to establish consensus among participants. Expert panelists were selected from various divisions to reflect variety of their subspecialties. PGY-3 residents trained with the developed curriculum that included proctored pre-test, self-training to proficiency, and proctored post-test. Visual analogue scale (VAS) of trainees' overall competence in the operating room was self-assessed by each resident, before and after completing the training curriculum.Nine PGY-3 residents were enrolled as trainees. Eleven experts chosen as panelists had various subspecialty, including 2 from otology, 2 from rhinology, 2 from laryngology, 2 from head and neck surgery, and 3 from general otolaryngology. Seven tasks were selected from RAND/UCLA method and used to develop the curriculum. Trainee scores at pre-test were significantly lower than expert scores for all 7 tasks (p < 0.01) and each coefficient of variation of trainee score was larger than that of expert score (p < 0.05), supporting construct validity. The mean of composite scores between pre-test and post-test had statistical significance (68.6 ± 11.6 vs 95.9 ± 3.6, p < 0.01), documenting substantial improvement after training. Self-assessment VAS was also improved pre- to post-training (1.2 ± 0.9 vs 4.5 ± 1.4, p < 0.01). A follow-up questionnaire showed that trainees felt the educational curriculum to be beneficial.In the present study, seven basic technical skills were selected using the RAND/UCLA method and used to create a proficiency-based training curriculum. Our results indicate that this curriculum significantly improves proficiency of basic surgical skills of junior otolaryngology residents.

    View details for DOI 10.1016/j.anl.2019.11.005

    View details for PubMedID 31870599

  • Endoscopic Transoral Hybrid Supracricoid Partial Laryngectomy with Cricohyoidoepiglottopexy. The Annals of otology, rhinology, and laryngology Nakayama, M. n., Orosco, R. K., Holsinger, F. C., Spriano, G. n., Succo, G. n., De Virgilio, A. n., Oridate, N. n. 2019: 3489419885139

    Abstract

    The hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP, that is, open partial horizontal laryngectomies OPHL Type IIa) has been described using a flexible next generation robotic surgical platform for manipulation. We sought to evaluate the feasibility of performing this procedure using endoscopic transoral (EndoT) surgical techniques without robotics.Preclinical cadaveric study using two human cadavers. Hybrid SCPL-CHEP was performed with a flexible endoscope for visualization and hand-held instruments for manipulation (SILS Hook monopolar and Dissect, HAVAS LaryngoFIT malleable straight jaw instruments, and Stratafix 4-0 spiral knotless barbed suture).EndoT hybrid SCPL-CHEP was successfully performed. The hand-manipulated rigid instruments allowed for transoral incisions and mucosal suturing. We provide the procedural steps of EndoT hybrid techniques.EndoT hybrid SCPL-CHEP was technically feasible in the preclinical cadaveric laboratory setting and appeared comparable to the hybrid SCPL-CHEP via transoral robotic surgery (TORS). Selected handheld instruments and flexible endoscopy appear to facilitate minimally invasive surgery of the larynx. This novel procedure and technique warrant further clinical study for consideration of feasibility, applicability, and patient benefit.

    View details for DOI 10.1177/0003489419885139

    View details for PubMedID 31672022

  • Robotic Head and Neck Surgery. Surgical oncology clinics of North America Finegersh, A., Holsinger, F. C., Gross, N. D., Orosco, R. K. 2019; 28 (1): 115–28

    Abstract

    Robotic head and neck surgery applies minimally invasive principles to unique anatomy and natural orifices for surgical access. Expanding from a tradition of minimally invasive endoscopic otolaryngology procedures, surgical robotics has transformed head and neck surgery. However, surgeons are faced with significant challenges, and anatomic constraints impede visualization and constrain surgical maneuvers. Transoral robotic surgery (TORS) has been developed over the past decade with favorable oncologic and functional outcomes, changing the way head and neck surgeons approach both malignant and benign diseases. As new robotic platforms emerge, access will continue to improve and push the boundaries of minimally invasive approaches.

    View details for PubMedID 30414677

  • Robotic Head and Neck Surgery SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA Finegersh, A., Holsinger, F., Gross, N. D., Orosco, R. K. 2019; 28 (1): 115-+
  • Gasless transoral robotic thyroidectomy using the DaVinci SP system: Feasibility, safety, and operative technique. Oral oncology Park, Y. M., Kim, D. H., Moon, Y. M., Lim, J. Y., Choi, E. C., Kim, S. H., Holsinger, F. C., Koh, Y. W. 2019; 95: 136–42

    Abstract

    Transoral robotic thyroidectomy (TORT) is an ideal method for minimally invasive thyroidectomy, as there is less flap dissection during the procedure and no postoperative scars. However, this method also has the limitation of present DaVinci system and some technical problems related to CO2 gas insufflation that must be resolved. We investigated the feasibility and safety of gasless TORT using the latest version of the DaVinci system (SP).From October 2018 to January 2019, we performed 10 surgeries of gasless TORT using the DaVinci SP at Yonsei University Hospital.Nine patients underwent unilateral thyroid lobectomy and one patient received total thyroidectomy. All operations were successfully completed. Nine cases had papillary thyroid carcinoma, and one had benign nodules. The mean surgical time was 177 min, and the mean hospital stay was 6.3 days. There were no reports of transient or permanent vocal cord palsy, recurrence, or mortality during the follow-up period. Temporary hypoesthesia of the chin due to mental nerve injury was observed in 3 of 10 patients, but it recovered spontaneously within 1 months in all cases.Gasless TORT using the DaVinci SP system is feasible and safe for selected patients and is a potential alternative approach for scarless thyroid surgery.

    View details for DOI 10.1016/j.oraloncology.2019.06.003

    View details for PubMedID 31345381

  • Hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy via transoral robotic surgery. The Laryngoscope Nakayama, M., Holsinger, F. C., Orosco, R. K. 2018

    Abstract

    OBJECTIVES/HYPOTHESIS: To describe a hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy (hybrid SCPL-CHEP) combining limited transcervical and transoral robotic approaches.STUDY DESIGN: Preclinical cadaveric study.METHODS: Using six human cadavers in a series of three preclinical laboratories (July 2016-February 2018), we developed a novel hybrid technique for SCPL-CHEP. A flexible single-port robotic surgical system was utilized for the transoral aspects of the procedure.RESULTS: Detailed procedural steps are defined: 1) transoral: mucosal incisions under direct visualization of the laryngopharynx (tumor resection); 2) transcervical: incision and mobilization of the larynx and pexis; and 3) transoral: mucosal closure. Hybrid SCPL-CHEP was technically feasible and allowed for complete transoral mucosal reconstruction. We discuss potential clinical significance of adding this TORS approach to conventional open SCPL-CHEP.CONCLUSIONS: This hybrid technique for SCPL-CHEP provides two main advantages over the standard technique: direct visualization during tumor resection prior to laryngotomy and full closure of the laryngopharynx defect. These technical refinements might facilitate postoperative recovery and in turn make this larynx preservation procedure more accessible to patients and surgeons. A clinical trial evaluating the efficacy of hybrid SCPL-CHEP appears warranted to validate these observations.LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

    View details for PubMedID 30569529

  • Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis CANCER Xiang, M., Holsinger, F., Colevas, A., Chen, M. M., Quynh-Thu Le, Beadle, B. M. 2018; 124 (23): 4486–94

    View details for DOI 10.1002/cncr.31708

    View details for Web of Science ID 000452622400012

  • Styloglossus muscle: a critical landmark in head and neck oncology EUROPEAN ANNALS OF OTORHINOLARYNGOLOGY-HEAD AND NECK DISEASES Laccourreye, O., Orosco, R. K., Rubin, F., Holsinger, F. C. 2018; 135 (6): 421–25
  • Next-Generation Robotic Head and Neck Surgery. ORL; journal for oto-rhino-laryngology and its related specialties Orosco, R. K., Arora, A., Jeanon, J. P., Holsinger, F. C. 2018; 80 (3-4): 213–19

    Abstract

    Following the inception of transoral robotic surgery (TORS) in 2005, the field of robotic head and neck surgery has undergone refinement and innovation. Optimizing patient outcome, preserving function, and limiting morbidity are the key drivers. The next leap forward is another generation of flexible robotic surgical systems. Several such systems are under clinical and preclinical evaluation. A new single-port (Sp) robotic surgical architecture is now available integrating three fully articulating instruments and a flexible three-dimensional high-definition camera delivered through a 25-mm cannula. Preclinical feasibility studies of the Sp in human cadaver and porcine models suggest improved application compared to existing platforms for oropharyngeal and nasopharyngeal resection. With 3-handed manipulation of tissue, traction and countertraction may be used to deliver a more precise surgical dissection of head and neck anatomy than is currently possible. The single-port design permits greater access and maneuverability for the bedside surgical assistant. An alternative currently available in clinical use includes the Flex system using a robotic camera and manually controlled endoscopic instruments. The Cambridge Medical Robotics Versius system is undergoing preclinical evaluation for TORS and may offer a novel modular approach. All of these systems allow the head and neck surgeon to reach further beyond the upper aerodigestive tract with greater agility and precision, expanding the boundaries of minimal access head and neck surgery.

    View details for PubMedID 30404095

  • Cisplatin or Carboplatin-Based Chemoradiation for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck: A Population-Based Comparison Xiang, M., Holsinger, F. C., Colevas, A. D., Hara, W., Le, Q. T., Beadle, B. M. ELSEVIER SCIENCE INC. 2018: E371
  • Decreased gastrostomy tube incidence and weight loss after transoral robotic surgery for low- to intermediate-risk oropharyngeal squamous cell carcinoma HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Heah, H., Goepfert, R. P., Hutcheson, K. A., Garden, A. S., Gunn, G., Fuller, C. D., Lewin, J. S., Kupferman, M. E., Holsinger, F., Hessel, A. C., Gross, N. D. 2018; 40 (11): 2507–13

    Abstract

    Functional outcomes after treatment for oropharyngeal squamous cell carcinoma (SCC) are increasingly prioritized. The purpose of this study was to investigate the incidence of gastrostomy tube placement and weight loss in patients with oropharyngeal SCC who may be eligible for either transoral robotic surgery (TORS) or nonsurgical management.We conducted a retrospective review of previously untreated T1 to T2 and N0 to N2b oropharyngeal SCC to determine the rates of gastrostomy tube placement and weight loss according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Multivariate regression models were fit to compare these end points between groups.Two hundred twenty-three patients were included, comprised of 66 patients who underwent TORS and 157 patients who underwent (chemo)radiation. Thirty-two (48.5%) of the TORS patients received adjuvant radiation. On multivariate analysis, patients treated nonsurgically were 10.6 times and 8.1 times more likely to receive a gastrostomy tube and experience greater than CTCAE grade 1 weight loss, respectively.In selected patients with oropharyngeal SCC, TORS may help avoid critical weight loss and gastrostomy tube placement in the acute treatment period.

    View details for PubMedID 30102824

  • Detecting oropharyngeal carcinoma using multispectral, narrow-band imaging and machine learning LARYNGOSCOPE Mascharak, S., Baird, B. J., Holsinger, F. 2018; 128 (11): 2514–20

    View details for DOI 10.1002/lary.27159

    View details for Web of Science ID 000451624900021

  • Lateral pharyngotomy. European annals of otorhinolaryngology, head and neck diseases Laccourreye, O., Villeneuve, A., Rubin, F., Holsinger, F. C. 2018

    Abstract

    Based on a review of the medical literature, the authors document the key technical points, variants, technical errors to avoid and main functional results of lateral pharyngotomy for resection of cancers originating from the lateral oro and/or hypopharynx.

    View details for PubMedID 30482706

  • Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis. Cancer Xiang, M., Holsinger, F. C., Colevas, A. D., Chen, M. M., Le, Q., Beadle, B. M. 2018

    Abstract

    BACKGROUND: Cisplatin and cetuximab are both systemic therapies commonly used in combination with radiation (RT) for the definitive treatment of head and neck cancers, but their comparative efficacy is unclear.METHODS: Patients with locoregionally advanced (American Joint Committee on Cancer stage III-IVB) squamous cell carcinomas of the oropharynx, larynx, or hypopharynx were identified in the Surveillance, Epidemiology, and End Results-Medicare database. Patients received either cisplatin or cetuximab concurrent with RT, as determined by Medicare claims. The primary study outcome was head and neck cancer-specific mortality (CSM) analyzed with competing risks. Filtering, propensity score matching, and multivariable Fine-Gray regression were used to adjust for differences between the cisplatin and cetuximab cohorts, including age, comorbidity, and cycles of systemic therapy received.RESULTS: The total cohort consisted of 1395 patients, of whom 786 (56%) received cisplatin and 609 (44%) received cetuximab; the median follow-up was 3.5 years in the patients who remained alive. In the cetuximab cohort, CSM was significantly higher than in the cisplatin cohort (39% vs 25% at 3 years; P < .0001). In the matched cohorts (n = 414), the adjusted hazard ratio of CSM for cetuximab was 1.65 (95% confidence interval, 1.30-2.09; P < .0001) relative to cisplatin, corresponding to an absolute difference of approximately 10% in both CSM and overall survival at 3 years. Cetuximab was associated with less dysphagia, more dermatitis, and a similar incidence of mucositis.CONCLUSIONS: In this sizeable, national patient population, treatment with cetuximab was associated with significantly higher CSM than cisplatin. These results suggest that cisplatin may be the preferred chemotherapeutic agent in this setting. Cancer 2018;124:000-000.

    View details for PubMedID 30332498

  • The styloglossus muscle: A critical landmark in onclogy and mandibular preservation surgery for squamous cell carcinoma of the lateral oropharynx. European annals of otorhinolaryngology, head and neck diseases Laccourreye, O., Orosco, R. K., Rubin, F., Holsinger, F. C. 2018

    Abstract

    GOAL: To document the role of the styloglossus muscle (SG) in the oncologic staging and mandibular preservation surgery for squamous cell carcinoma of the lateral oropharynx (SCCLO).METHOD: Based on a search conducted within the Pubmed, Embase, and Cochrane databases, using the key words SG muscle, parapharyngeal space and oropharynx, the authors discuss the embryology, physiology, anatomy and radiology of this muscle as well as its role in the oncologic staging and mandibular preservation surgery of SCCLO.RESULTS: The most specific radiologic exam to evaluate the involvement of SG muscle in SCCLO is magnetic resonance imaging (MRI). Radiologic invasion of the SG muscle, at the time of MRI, leads to reclassify as T4a many tumors considered as T1-3 at the time of clinical and/or on computerized tomography evaluation. This must lead to extreme care when comparing oncologic results from series published prior and after the MRI era. When transoral resection of the SG muscle is advocated for SCCLO, one must know that this maneuver brings numerous arterial and venous structures within the operative field. If difficulties to achieve safe margins of resection and/or to control bleeding are encountered, a simple trans cervical maneuver described herein is most useful.CONCLUSION: The importance of the SG muscle should be emphasized as a touchstone for staging and surgeon's guide to mandibular preservation surgery of SCCLO. The various approaches allowing the control of this muscle and its vascular environment must be taught at the time of initial training.

    View details for PubMedID 30341015

  • Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence CANCER RESEARCH Gao, R. W., Teraphongphom, N. T., van den Berg, N. S., Martin, B. A., Oberhelman, N. J., Divi, V., Kaplan, M. J., Hong, S. S., Lu, G., Ertsey, R., Tummers, W. J., Gomez, A. J., Holsinger, F., Kong, C. S., Colevas, A. D., Warram, J. M., Rosenthal, E. L. 2018; 78 (17): 5144–54
  • Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence. Cancer research Gao, R. W., Teraphongphom, N. T., van den Berg, N. S., Martin, B. A., Oberhelman, N. J., Divi, V., Kaplan, M. J., Hong, S. S., Lu, G., Ertsey, R., Tummers, W. S., Gomez, A. J., Holsinger, F. C., Kong, C. S., Colevas, A. D., Warram, J. M., Rosenthal, E. L. 2018

    Abstract

    For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor-mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. 21 adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 (n=3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A (n=5) received 0.5mg/kg, cohort 2B (n=7) received 1mg/kg, and cohort 3 (n=6) received 50 mg. Patients were followed 30 days post-infusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. In situ imaging demonstrated tumor-to-background ratio (TBR) of 2-3, compared to ex vivo specimen imaging TBR of 5-6. We obtained clear differentiation between tumor and normal tissue, with a three-fold signal difference between positive and negative specimens (p<0.05). We achieved high correlation of fluorescence intensity with tumor location with sensitivities and specificities >89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy which are otherwise less amenable to image guidance.

    View details for PubMedID 29967260

  • Recent progress of retroauricular robotic thyroidectomy with the new surgical robotic system LARYNGOSCOPE Byeon, H., Holsinger, F., Duvvuri, U., Kim, D., Park, J., Chang, E., Kim, S., Koh, Y. 2018; 128 (7): 1730–37

    View details for DOI 10.1002/lary.26938

    View details for Web of Science ID 000440007000053

  • Recent progress of retroauricular robotic thyroidectomy with the new surgical robotic system. The Laryngoscope Byeon, H. K., Holsinger, F. C., Duvvuri, U., Kim, D. H., Park, J. H., Chang, E., Kim, S. H., Koh, Y. W. 2018; 128 (7): 1730-1737

    Abstract

    Previously, we have reported the feasibility of retroauricular (RA) robotic thyroidectomy. Despite its promising surgical outcomes, there were certain intrinsic mechanical limitations inherent to the da Vinci Si System (Intuitive Surgical, Sunnyvale, California, U.S.A.). Since the advent of an upgraded model, the Xi System (Intuitive Surgical), we have actively incorporated the new model into performing RA thyroidectomy. Here, we intend to verify the feasibility of RA robotic thyroidectomy using the new da Vinci Xi System (Intuitive Surgical) with comparison of the former Si-applied surgery (Intuitive Surgical).Comparative analysis.There were total 165 consecutive patients who received RA robotic thyroidectomy from January 2013 to February 2016. The patients were divided into two groups: Si group (n = 125) and Xi group (n = 40). Perioperative and treatment outcomes were compared and analyzed.Compared with the previous system, new da Vinci Xi system (Intuitive Surgical) enabled insertion of an extra third robotic instrumental arm. Unlike the previous robotic surgical technique, the robotic dissection could be initiated immediately after the establishment of working space and the resulting total operation time could be significantly decreased. There was no difference in the surgical completeness, as confirmed by postoperative thyroglobulin levels. Additionally, flexed EndoWrist (Intuitive Surgical) instruments equipped with the Erbe (Erbe USA Inc., Marietta, Georgia, U.S.A.) system could be mounted, which further facilitated the operation. There were no significant differences in postoperative complications between the two groups.The RA robotic thyroidectomy with the new Xi System (Intuitive Surgical) can greatly facilitate the robotic surgery with comparable or improved surgical outcomes. Its application is expected to open up a new era of robotic neck surgery.4. Laryngoscope, 128:1730-1737, 2018.

    View details for DOI 10.1002/lary.26938

    View details for PubMedID 29068059

  • Comparative Effectiveness of Cetuximab or Cisplatin With Concomitant Radiation for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck: A Population-Based Analysis Xiang, M., Holsinger, F. C., Chen, M. M., Colevas, A. D., Beadle, B. M. ELSEVIER SCIENCE INC. 2018: 1322
  • Detecting oropharyngeal carcinoma using multispectral, narrow-band imaging and machine learning. The Laryngoscope Mascharak, S., Baird, B. J., Holsinger, F. C. 2018

    Abstract

    OBJECTIVE: To determine if multispectral narrow-band imaging (mNBI) can be used for automated, quantitative detection of oropharyngeal carcinoma (OPC).STUDY DESIGN: Prospective cohort study.METHODS: Multispectral narrow-band imaging and white light endoscopy (WLE) were used to examine the lymphoepithelial tissues of the oropharynx in a preliminary cohort of 30 patients (20 with biopsy-proven OPC, 10 healthy). Low-level image features from five patients were then extracted to train naive Bayesian classifiers for healthy and malignant tissue.RESULTS: Tumors were classified by color features with 65.9% accuracy, 66.8% sensitivity, and 64.9% specificity under mNBI. In contrast, tumors were classified with 52.3% accuracy (P=0.0108), 44.8% sensitivity (P=0.0793), and 59.9% specificity (P=0.312) under WLE. Receiver operating characteristic analysis yielded areas under the curve (AUC) of 72.3% and 54.6% for classification under mNBI and WLE, respectively (P=0.00168). For classification by both color and texture features, AUC under mNBI increased (80.1%, P=0.00230) but did not improve under WLE (below 55% for both models, P=0.180). Cross-validation with five folds yielded an AUC above 80% for both mNBI models and below 55% for both WLE models (P=0.0000410 and 0.000116).CONCLUSION: Compared to WLE, mNBI significantly enhanced the performance of a naive Bayesian classifier trained on low-level image features of oropharyngeal mucosa. These findings suggest that automated clinical detection of OPC might be used to enhance surgical vision, improve early diagnosis, and allow for high-throughput screening.LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

    View details for PubMedID 29577322

  • Flexible next-generation robotic surgical system for transoral endoscopic hypopharyngectomy: A comparative preclinical study HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Tateya, I., Koh, Y., Tsang, R. K., Hong, S. S., Uozumi, R., Kishimoto, Y., Sugimoto, T., Holsinger, F. 2018; 40 (1): 16–23

    View details for DOI 10.1002/hed.24868

    View details for Web of Science ID 000418261100005

  • Transoral Robotic Surgery: Advances and Applications HEAD AND NECK CANCERS: EVIDENCE-BASED TREATMENT Turner, M. T., Holsinger, F., Ferris, R. L., Argiris, A., Ferris, R. L., Rosenthal, D. I. 2018: 119–39
  • De-intensified adjuvant (chemo) radiotherapy versus standard adjuvant chemoradiotherapy post transoral minimally invasive surgery for resectable HPV-positive oropharyngeal carcinoma COCHRANE DATABASE OF SYSTEMATIC REVIEWS Howard, J., Dwivedi, R. C., Masterson, L., Kothari, P., Quon, H., Holsinger, F. 2018: CD012939

    Abstract

    More than 400,000 cases of oropharyngeal squamous cell cancer (OPSCC) are diagnosed every year worldwide and this is rising. Much of the increase has been attributed to human papillomavirus (HPV). HPV-positive OPSCC patients are often younger and have significantly improved survival relative to HPV-negative patients. Traditional management of OPSCC has been with radiotherapy with or without chemotherapy, as this was shown to have similar survival to open surgery but with significantly lower morbidity. Techniques have evolved, however, with the development of computerised planning and intensity-modulated radiotherapy, and of minimally invasive surgical techniques. Acute and late toxicities associated with chemoradiotherapy are a significant burden for OPSCC patients and with an ever-younger cohort, any strategies that could decrease treatment-associated morbidity should be investigated.To assess the effects of de-intensified adjuvant (chemo)radiotherapy in comparison to standard adjuvant (chemo)radiotherapy in patients treated with minimally invasive transoral surgery (transoral robotic surgery or transoral laser microsurgery) for resectable HPV-positive oropharyngeal squamous cell carcinoma.The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 26 April 2018.Randomised controlled trials (RCTs) in patients with carcinoma of the oropharynx (as defined by the World Health Organization classification C09, C10). Cancers included were primary HPV-positive squamous cell tumours originating from the oropharyngeal mucosa. Tumours were classified as T1-4a with or without nodal spread and with no evidence of distant metastatic spread. The intervention was minimally invasive transoral surgery followed by de-intensified adjuvant therapy (either omission of chemotherapy or reduced-dose radiotherapy). The comparator was minimally invasive transoral surgery followed by standard concurrent chemoradiotherapy or standard-dose radiotherapy. The treatments received were of curative intent and patients had not undergone any prior intervention, other than diagnostic biopsy.We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related survival was to be studied where possible) and disease-free survival, measured at one, two, three and five years. Our secondary outcomes included assessment of swallowing ability and voice, measured at one, six, 12 and 24 months. We planned to use GRADE to assess the quality of evidence for each outcome.We did not identify any completed RCTs that met our inclusion criteria. However, three eligible studies are in progress:ADEPT is a phase III trial comparing postoperative radiotherapy with or without cisplatin in HPV-positive T1-4a OPSCC patients. Included patients must have received minimally invasive surgery and demonstrated extra-capsular spread from disease in the neck.ECOG-E3311 is a phase II trial of treatment for HPV-positive locally advanced OPSCC (stages III-IVa + IVb without distant metastasis). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy.PATHOS is a phase III trial of treatment for HPV-positive OPSCC (T1-3, N0-2b). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy. High-risk patients are randomised to radiotherapy with or without concurrent cisplatin.This review highlights the current lack of high-quality randomised controlled trials studying treatment de-escalation after minimally invasive surgery in patients with HPV-positive OPSCC. However, trials that will meet the inclusion criteria for this review are in progress with results expected between 2021 and 2023.

    View details for DOI 10.1002/14651858.CD012939.pub2

    View details for Web of Science ID 000455302700020

    View details for PubMedID 30550641

  • Next-Generation Robotic Head and Neck Surgery ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY HEAD AND NECK SURGERY Orosco, R. K., Arora, A., Jeanon, J., Holsinger, F. 2018; 80 (3-4): 213–19

    View details for DOI 10.1159/000490599

    View details for Web of Science ID 000451810100011

  • Non-HPV-Associated Oropharyngeal Cancer HEAD AND NECK CANCERS: EVIDENCE-BASED TREATMENT Turner, M. T., Saraswathula, A., Holsinger, F., Argiris, A., Ferris, R. L., Rosenthal, D. I. 2018: 253–70
  • Flexible next-generation robotic surgical system for transoral endoscopic hypopharyngectomy: A comparative preclinical study. Head & neck Tateya, I., Koh, Y. W., Tsang, R. K., Hong, S. S., Uozumi, R., Kishimoto, Y., Sugimoto, T., Holsinger, F. C. 2018; 40 (1): 16-23

    Abstract

    The purpose of this cadaveric study was to determine the efficacy of a flexible, next-generation robotic surgical system for transoral robotic hypopharyngectomy.A comparative evaluation study of the flexible versus rigid robotic surgical systems for the hypopharynx was conducted using 3 cadavers. Endpoints for assessment were visualization of the hypopharynx, access to the hypopharynx, and difficulty of dissection. Hypopharyngectomy was performed on 3 other cadavers using the da Vinci Sp surgical system.Access to the apex of the pyriform sinus and the esophageal inlet was easier with the da Vinci Sp than with the da Vinci Si. Dissection with the da Vinci Sp was easier in all areas of the hypopharynx than with the da Vinci Si. Robotic hypopharyngectomy was successfully completed on all cadavers using the da Vinci Sp surgical system.Preclinical testing in human cadavers suggests that flexible robotic surgery may facilitate successful transoral hypopharyngectomy.

    View details for DOI 10.1002/hed.24868

    View details for PubMedID 29130568

  • Thyroid cancer risk in airline cockpit and cabin crew: a meta-analysis. Cancers of the head & neck Liu, G. S., Cook, A. n., Richardson, M. n., Vail, D. n., Holsinger, F. C., Oakley-Girvan, I. n. 2018; 3: 7

    Abstract

    Airline crew are exposed to ionizing radiation as part of their occupation and have a documented increased risk of melanoma and cataracts. However, whether their occupation predisposes them to an increased risk of thyroid cancer is not established. The purpose of this systematic review and meta-analysis was to assess the risk of thyroid cancer in airline cockpit and cabin crew compared with the general population.The MEDLINE database accessed via PubMed and Cochrane Database were searched. We included cohort studies reporting the standardized incidence ratio (SIR) or standardized mortality ratio (SMR) of thyroid cancers in any flight-based occupation.Of the 1777 citations retrieved in PubMed, eight studies with a total of 243,088 aircrew members and over 3,334,114 person-years of follow-up were included in this meta-analysis. No relevant studies were identified on Cochrane Database. The overall summary SIR of participants in any flight-based occupation was 1.11 (95% CI, 0.79-1.57; p = 0.613; 6 records). The summary SIR for cockpit crew was 1.21 (95% CI, 0.75-1.95; p = 0.383; 4 records) and the summary SIR for cabin crew was 1.00 (95% CI, 0.60-1.66; p = 0.646; 2 records). The overall summary standardized mortality ratio for airline crew was 1.19 (95% CI, 0.59-2.39; p = 0.773; 2 records).Airline crew were not found to have a significantly elevated risk of thyroid cancer incidence or mortality relative to the general population. Future research should capitalize on the growing occupational cohort dataset and employ innovative methods to quantify lifetime radiation exposure to further assess thyroid cancer risk in airline crew.

    View details for PubMedID 31093360

  • Improved transoral dissection of the tongue base with a next-generation robotic surgical system LARYNGOSCOPE Chen, M. M., Orosco, R. K., Lim, G., Holsinger, F. 2018; 128 (1): 78–83

    Abstract

    To describe the application of a novel, flexible, single-port robotic surgical system for transoral tongue base resection, and compare it to the current multiport, rigid-arm robotic surgical system.Preclinical anatomic study using four human cadavers.Transoral resection of the tongue base using the da Vinci Sp and the Si robotic surgical systems. A standardized operative procedure is outlined, and operative parameters were compared between robotic systems.Successful completion of tongue base resection was achieved in all cadavers using both the Sp and the Si systems. The optimal entry guide and instrument position for the Sp system was with the cannula rotated 180° from the standard position so that the camera was in the most inferior (caudal) channel. In the optimal configuration, no instrument exchanges were needed with the Sp system, but use of the Si system required one instrument exchange.This is the first preclinical anatomic study of robotic tongue base resection that compares a novel single-port robotic system to the current multiarm system. Surgical workflow was more streamlined with the da Vinci Sp system, and the new capabilities of simultaneous dissection, traction, and counter traction allowed for improved dissection and vessel control.NA. Laryngoscope, 128:78-83, 2018.

    View details for PubMedID 28681924

  • Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of Clinical Oncology Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline JOURNAL OF CLINICAL ONCOLOGY Quon, H., Vapiwala, N., Forastiere, A., Kennedy, E. B., Adelstein, D. J., Boykin, H., Califano, J. A., Holsinger, F., Nussenbaum, B., Rosenthal, D. I., Siu, L. L., Waldron, J. N. 2017; 35 (36): 4078-+
  • Transoral lateral oropharyngectomy EUROPEAN ANNALS OF OTORHINOLARYNGOLOGY-HEAD AND NECK DISEASES Rubin, F., Laccourreye, O., Weinstein, G. S., Holsinger, F. C. 2017; 134 (6): 419–22

    Abstract

    Based on a review of the indexed scientific medical literature, the authors document the key technical points, the errors to avoid, the limitations, indications and main oncologic and functional results when performing transoral lateral oropharyngectomy in cancer originating from the tonsillar region.

    View details for PubMedID 28669807

  • A flexible next-generation robotic system for transoral robotic nasopharyngectomy: A comparative preclinical study Tsang, R., Holsinger, C. AMER ASSOC CANCER RESEARCH. 2017
  • Early results of a safety and feasibility clinical trial of a novel single-port flexible robot for transoral robotic surgery EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Chan, J. K., Wong, E. Y., Tsang, R. K., Holsinger, F., Tong, M. F., Chiu, P. Y., Ng, S. M. 2017; 274 (11): 3993–96

    Abstract

    The aim of this study was to describe the early results of a phase 1 safety and feasibility clinical trial of the first clinical use of a novel robot for transoral robotic surgery (TORS)-the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA, USA). Study design of this study is prospective clinical trial. The methods used in this study are prospective innovation, development, exploration, assessment, and long-term study phase 1 clinical trial. Early results of six patients underwent TORS with the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA, USA) demonstrate access the nasopharynx, oropharynx, larynx, and hypopharynx. There were no conversions of the robotic surgical system. There were no serious adverse events or adverse events related to the use of the robot at 30-day follow-up for all six patients. The early results of this safety and feasibility trial of the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA, USA) clearly demonstrate that the device is safe and that it is feasible in performing TORS to access the nasopharynx, oropharynx, larynx, and hypopharynx.

    View details for PubMedID 28871410

    View details for PubMedCentralID PMC5633617

  • Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of Clinical Oncology Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Quon, H., Vapiwala, N., Forastiere, A., Kennedy, E. B., Adelstein, D. J., Boykin, H., Califano, J. A., Holsinger, F. C., Nussenbaum, B., Rosenthal, D. I., Siu, L. L., Waldron, J. N. 2017: JCO2017738633

    Abstract

    Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy in oropharyngeal squamous cell carcinoma (OPSCC) that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. After applying standard critical appraisal policy and endorsement procedures, ASCO chose to endorse the ASTRO guideline. Methods The ASTRO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. The ASCO guideline approval body, the Clinical Practice Guidelines Committee, approved the final endorsement. Results The ASCO Expert Panel determined that the ASTRO guideline recommendations, published in July 2017, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the ASTRO guideline and added minor qualifying statements. Recommendations Recommendations for the addition of systemic therapy to definitive radiotherapy in the treatment of OPSCC, postoperative radiotherapy with and without systemic therapy following primary surgery of OPSCC, induction chemotherapy in the treatment of OPSCC, and the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC are outlined for a variety of disease stages and clinical scenarios. ASCO Endorsement Panel qualifying statements and minor modifications were made to the ASTRO recommendations. The staging system that is referenced in these guidelines is the American Joint Committee on Cancer Staging Manual, 7th edition. Additional information is available at: www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .

    View details for PubMedID 29064744

  • Is transoral robotic surgery a safe and effective multilevel treatment for obstructive sleep apnoea in obese patients following failure of conventional treatment(s)? ANNALS OF MEDICINE AND SURGERY Garas, G., Kythreotou, A., Georgalas, C., Arora, A., Kotecha, B., Holsinger, F. C., Grant, D. G., Tolley, N. 2017; 19: 55–61

    Abstract

    A best evidence topic was written according to a structured protocol. The question addressed was whether TransOral Robotic Surgery (TORS) is a safe and effective multilevel treatment for Obstructive Sleep Apnoea (OSA) in obese patients following failure of conventional treatment(s). A total of 39 papers were identified using the reported searches of which 5 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Existing treatments for OSA - primarily CPAP - though highly effective are poorly tolerated resulting in an adherence often lower than 50%. As such, surgery is regaining momentum, especially in those patients failing non-surgical treatment (CPAP or oral appliances). TORS represents the latest addition to the armamentarium of Otorhinolaryngologists - Head and Neck Surgeons for the management of OSA. The superior visualisation and ergonomics render TORS ideal for the multilevel treatment of OSA. However, not all patients are suitable candidates for TORS and its suitability is questionable in obese patients. In view of the global obesity pandemic, this is an important question that requires addressing promptly. Despite the drop in success rates with increasing BMI, the success rate of TORS in non-morbidly obese patients (BMI = 30-35kgm-2) exceeds 50%. A 50% success rate may at first seem low, but it is important to realize that this is a patient cohort suffering from a life-threatening disease and no option left other than a tracheostomy. As such, TORS represents an important treatment in non-morbidly obese OSA patients following failure of conventional treatment(s).

    View details for DOI 10.1016/j.amsu.2017.06.014

    View details for Web of Science ID 000411637200011

    View details for PubMedID 28649379

    View details for PubMedCentralID PMC5470525

  • The impact of developing a speech and swallow rehab program: Improving patient satisfaction and multidisciplinary care. Laryngoscope Starmer, H. M., Ayoub, N., Byward, C., Kizner, J., Le, Q., Hara, W., Holsinger, F. C. 2017

    Abstract

    The objective of this study was to evaluate the impact of developing an integrated head and neck cancer speech and swallowing rehabilitation program on physician/team focus on functional outcomes.Prospective cross-sectional design.Surveys regarding physician behavior and patient satisfaction with speech and swallowing were administered in an academic oncology practice prior to and 1 year following establishment of a dedicated head and neck speech and swallowing rehabilitation program. Participants included new and established head and neck cancer patients recruited consecutively. The primary outcome was physician behavior regarding speech and swallowing outcomes (as measured by discussion of function, providing suggestions regarding function, and referral to speech-language pathology services).A total of 199 surveys were returned at the first time point and 271 at the second. Demographic variables were comparable between the two groups. The later cohort was more likely to report team discussion and suggestions regarding speech and swallowing function than the former (P < .001, 95% confidence interval [CI]: -0.775 to -0.265; P < .001, 95% CI: -0.928 to -0.035, respectively). Although there was no significant difference between the groups in regard to satisfaction with speech (P = .07), more favorable satisfaction with swallowing was reported by the later cohort (P = .028, 95% CI: -0.531 to -0.029).Integration of speech and swallowing rehabilitation into head and neck cancer programs is associated with increased physician focus on functional outcomes and greater patient satisfaction in regard to swallowing function. We advocate for standard integration of such services into the multidisciplinary head and neck cancer care team.4. Laryngoscope, 2017.

    View details for DOI 10.1002/lary.26695

    View details for PubMedID 28561453

  • Remote Access Robotic Facelift Thyroidectomy: A Multi-institutional Experience WORLD JOURNAL OF SURGERY Duke, W. S., Holsinger, F. C., Kandil, E., Richmon, J. D., Singer, M. C., Terris, D. J. 2017; 41 (1): 116-121

    Abstract

    Robotic facelift thyroidectomy (RFT) was developed as a new surgical approach to the thyroid gland using a remote incision site. Early favorable results led to this confirmatory multi-institutional experience.Prospectively collected data on consecutive patients undergoing RFT in five North American academic endocrine surgical practices were compiled. Surgical indications, operative times, final pathology, nodule size, complications, and postoperative management (drain use and length of hospital stay) were evaluated.A total of 102 RFT procedures were undertaken in 90 patients. All but one of the patients (98.9 %) were female, and the mean age was 41.9 ± 13.1 years (range 12-69 years). The indication for surgery was nodular disease in 91.2 % of cases; 8.8 % were completion procedures performed for a diagnosis of cancer. The mean size of the largest nodule was 1.9 cm (range 0-5.6 cm). The mean total operative time for a thyroid lobectomy was 162 min (range 82-265 min). No permanent complications occurred. There were 4 cases (3.9 %) of transient recurrent laryngeal nerve weakness, no cases of hypocalcemia, and 3 (2.9 %) hematomas. There were no conversions to an anterior cervical approach. The majority of patients were managed on an outpatient basis (61.8 %) and without a drain (65.7 %).RFT is technically feasible and safe in selected patients. RFT can continue to be offered to carefully selected patients as a way to avoid a visible cervical scar. Future prospective studies to compare this novel approach to other remote access approaches are warranted.

    View details for DOI 10.1007/s00268-016-3738-0

    View details for Web of Science ID 000392147000018

  • Transoral endoscopic head and neck surgery (eHNS) for minor salivary gland tumors of the oropharynx. Cancers of the head & neck Schoppy, D. W., Kupferman, M. E., Hessel, A. C., Bell, D. M., Garland, E. M., Damrose, E. J., Holsinger, F. C. 2017; 2: 5

    Abstract

    Transoral endoscopic head and neck surgery (eHNS), including transoral laser microsurgery (TLM) and transoral robotic surgery (TORS), provides access to subsites in the head and neck that have traditionally been difficult to approach. Minor salivary gland tumors, while relatively uncommon, are frequently malignant and can occur at sites in the oropharynx accessible by transoral eHNS. Presented here is the largest review to date of patients with minor salivary gland tumors of the oropharynx managed with transoral eHNS as primary or salvage therapy.A retrospective chart review was performed, including data from 20 patients with minor salivary gland tumors of the oropharynx managed with transoral eHNS at 2 tertiary, academic medical centers. Details of tumor pathology, margin analysis, adjuvant therapy, and an assessment of oncologic outcome were included.The base of tongue was the most common tumor site (75%). Adenoid cystic carcinoma (ACC) accounted for most cases (35%), and negative margins were obtained in most (95%) through an endoscopic-only approach. Overall, 50% of patients received post-operative radiation therapy. Postoperative complications were limited, with one patient (5%) returning to the OR for control of post-operative oropharyngeal bleeding. On average follow-up of 36 months, 90% of patients were alive with no evidence of recurrence.In this experience, transoral eHNS provided a safe and consistent surgical approach to management of minor salivary gland malignancies, with low complication rates and good locoregional control. Thus, transoral eHNS may play a valuable role in the multi-disciplinary management of these malignancies.None/not applicable.

    View details for DOI 10.1186/s41199-017-0024-2

    View details for PubMedID 31093352

    View details for PubMedCentralID PMC6460795

  • Lymph Node Count From Neck Dissection Predicts Mortality in Head and Neck Cancer JOURNAL OF CLINICAL ONCOLOGY Divi, V., Chen, M. M., Nussenbaum, B., Rhoads, K. F., Sirjani, D. B., Holsinger, F. C., Shah, J. L., Hara, W. 2016; 34 (32): 3892-?

    Abstract

    Multiple smaller studies have demonstrated an association between overall survival and lymph node (LN) count from neck dissection in patients with head and neck cancer. This is a large cohort study to examine these associations by using a national cancer database.The National Cancer Database was used to identify patients who underwent upfront nodal dissection for mucosal head and neck squamous cell carcinoma between 2004 and 2013. Patients were stratified by LN count into those with < 18 nodes and those with ≥ 18 nodes on the basis of prior work. A multivariable Cox proportional hazards regression model was constructed to predict hazard of mortality. Stratified models predicted hazard of mortality both for patients who were both node negative and node positive.There were 45,113 patients with ≥ 18 LNs and 18,865 patients with < 18 LNs examined. The < 18 LN group, compared with the ≥ 18 LN group, had more favorable tumor characteristics, with a lower proportion of T3 and T4 lesions (27.9% v 39.8%), fewer patients with positive nodes (46.6% v 60.5%), and lower rates of extracapsular extension (9.3% v 15.1%). Risk-adjusted Cox models predicting hazard of mortality by LN count showed an 18% increased hazard of death for patients with < 18 nodes examined (hazard ratio [HR] 1.18; 95% CI, 1.13 to 1.22). When stratified by clinical nodal stage, there was an increased hazard of death in both groups (node negative: HR, 1.24; 95% CI, 1.17 to 1.32; node positive: HR, 1.12; 95% CI, 1.05 to 1.19).The results of our study demonstrate a significant overall survival advantage in both patients who are clinically node negative and node positive when ≥ 18 LNs are examined after neck dissection, which suggests that LN count is a potential quality metric for neck dissection.

    View details for DOI 10.1200/JCO.2016.67.3863

    View details for PubMedID 27480149

  • Remote Access Robotic Facelift Thyroidectomy: A Multi-institutional Experience. World journal of surgery Duke, W. S., Holsinger, F. C., Kandil, E., Richmon, J. D., Singer, M. C., Terris, D. J. 2016: -?

    Abstract

    Robotic facelift thyroidectomy (RFT) was developed as a new surgical approach to the thyroid gland using a remote incision site. Early favorable results led to this confirmatory multi-institutional experience.Prospectively collected data on consecutive patients undergoing RFT in five North American academic endocrine surgical practices were compiled. Surgical indications, operative times, final pathology, nodule size, complications, and postoperative management (drain use and length of hospital stay) were evaluated.A total of 102 RFT procedures were undertaken in 90 patients. All but one of the patients (98.9 %) were female, and the mean age was 41.9 ± 13.1 years (range 12-69 years). The indication for surgery was nodular disease in 91.2 % of cases; 8.8 % were completion procedures performed for a diagnosis of cancer. The mean size of the largest nodule was 1.9 cm (range 0-5.6 cm). The mean total operative time for a thyroid lobectomy was 162 min (range 82-265 min). No permanent complications occurred. There were 4 cases (3.9 %) of transient recurrent laryngeal nerve weakness, no cases of hypocalcemia, and 3 (2.9 %) hematomas. There were no conversions to an anterior cervical approach. The majority of patients were managed on an outpatient basis (61.8 %) and without a drain (65.7 %).RFT is technically feasible and safe in selected patients. RFT can continue to be offered to carefully selected patients as a way to avoid a visible cervical scar. Future prospective studies to compare this novel approach to other remote access approaches are warranted.

    View details for PubMedID 27738835

  • Transoral Endoscopic Nasopharyngectomy With a Flexible Next-Generation Robotic Surgical System LARYNGOSCOPE Tsang, R. K., Holsinger, F. C. 2016; 126 (10): 2257-2262

    Abstract

    To determine the feasibility of transoral endoscopic nasopharyngectomy without division of the soft plate using a flexible, next-generation robotic surgical system.Preclinical anatomic study using four human cadavers.Transoral resection of the nasopharyngeal wall with en-bloc resection of the cartilaginous Eustachian tube and dissection of the parapharyngeal fat space.The first flexible robotic surgical system has recently been described. We performed a series of laboratory experiments to determine whether this flexible system could be used to perform transoral robotic nasopharyngectomy. This novel system allowed docking of the patient-side cart at the side of the operating table. The cannula tip was placed approximately 12 cm from the edge of the retractor pointing superiorly toward the nasopharynx (NP). Retraction of the soft palate anteriorly and tonsillar pillars laterally with stay sutures expanded the velopharyngeal inlet, providing adequate space to deploy all four instruments (three surgical instruments and a camera) into the NP for dissection. All instruments could be deployed into the NP, without collision or restriction of joint movement in this cadaver model. Using this position and docking location, the new flexible surgical robot provided sufficient access, reach, and visualization to complete robotic nasopharyngectomy with en-bloc resection of the cartilaginous Eustachian tube.This feasibility study showed that transoral endoscopic nasopharyngectomy could be performed without compromising the integrity of the soft palate using a novel flexible robotic surgical system.N/A. Laryngoscope, 2016.

    View details for DOI 10.1002/lary.25970

    View details for Web of Science ID 000386930800018

    View details for PubMedID 27312523

  • Design and rationale of a prospective, multi-institutional registry for patients with sinonasal malignancy. Laryngoscope Beswick, D. M., Holsinger, F. C., Kaplan, M. J., Fischbein, N. J., Hara, W., Colevas, A. D., Le, Q., Berry, G. J., Hwang, P. H. 2016; 126 (9): 1977-1980

    Abstract

    Assessment of patients with sinonasal malignancy is challenging due to the low disease incidence and diverse histopathology. The current literature is composed mainly of retrospective studies with heterogeneous cohorts, and the rarity of cases limits our understanding of disease characteristics and treatment outcomes. We describe the development of a prospective, multi-institutional registry that utilizes cloud-based computing to evaluate treatment outcomes in patients with sinonasal cancer.A web-based, secure database was built to prospectively capture longitudinal outcomes and quality-of-life (QoL) data in patients diagnosed with sinonasal malignancy. Demographics, tumor staging, and treatment outcomes data are being collected. The Sinonasal Outcome Test-22 and University of Washington Quality of Life Questionnaire are administered at presentation and at recurring intervals. To date, seven institutions are participating nationally.This prospective, multi-institutional registry will provide novel oncological and QoL outcomes on patients with sinonasal malignancy to inform management decisions and disease prognostication. The application of cloud-based computing facilitates secure multi-institutional collaboration and may serve as a model for future registry development for the study of rare diseases in otolaryngology.2C. Laryngoscope, 2016.

    View details for DOI 10.1002/lary.25996

    View details for PubMedID 27283472

  • Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes (NRG Oncology RTOG 9501 and RTOG 0234). Cancer Divi, V., Harris, J., Harari, P. M., Cooper, J. S., McHugh, J., Bell, D., Sturgis, E. M., Cmelak, A. J., Suntharalingam, M., Raben, D., Kim, H., Spencer, S. A., Laramore, G. E., Trotti, A., Foote, R. L., Schultz, C., Thorstad, W. L., Zhang, Q. E., Le, Q. T., Holsinger, F. C. 2016

    Abstract

    Prospective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study was to investigate the association between lymph node counts from neck dissection, local-regional recurrence, and overall survival.The number of lymph nodes counted from neck dissection in patients treated in 2 NRG Oncology trials (Radiation Therapy Oncology Group [RTOG] 9501 and RTOG 0234) was evaluated for its prognostic impact on overall survival with a multivariate Cox model adjusted for demographic, tumor, and lymph node data and stratified by the postoperative treatment group.Five hundred seventy-two patients were analyzed at a median follow-up of 8 years. Ninety-eight percent of the patients were pathologically N+. The median numbers of lymph nodes recorded on the left and right sides were 24 and 25, respectively. The identification of fewer than 18 nodes was associated with worse overall survival in comparison with 18 or more nodes (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09-1.74; P = .007). The difference appeared to be driven by local-regional failure (HR, 1.46; 95% CI, 1.02-2.08; P = .04) but not by distant metastases (HR, 1.08; 95% CI, 0.77-1.53; P = .65). When the analysis was limited to NRG Oncology RTOG 0234 patients, adding the p16 status to the model did not affect the HR for dissected nodes, and the effect of nodes did not differ with the p16 status.The removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local-regional failure, and this should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma. Cancer 2016. © 2016 American Cancer Society.

    View details for DOI 10.1002/cncr.30204

    View details for PubMedID 27419843

  • Ameloblastoma: a clinical review and trends in management EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY McClary, A. C., West, R. B., McClary, A. C., Pollack, J. R., Fischbein, N. J., Holsinger, C. F., Sunwoo, J., Colevas, A. D., Sirjani, D. 2016; 273 (7): 1649-1661

    Abstract

    Ameloblastoma is a rare odontogenic neoplasm of the mandible and maxilla, with multiple histologic variants, and high recurrence rates if improperly treated. The current mainstay of treatment is wide local excision with appropriate margins and immediate reconstruction. Here we review the ameloblastoma literature, using the available evidence to highlight the change in management over the past several decades. In addition, we explore the recent molecular characterization of these tumors which may point towards new potential avenues of personalized treatment.

    View details for DOI 10.1007/s00405-015-3631-8

    View details for PubMedID 25926124

  • Consultation via telemedicine and access to operative care for patients with head and neck cancer in a Veterans Health Administration population HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Beswick, D. M., Vashi, A., Song, Y., Pham, R., Holsinger, F. C., Rayl, J. D., Walker, B., Chardos, J., Yuan, A., Benadam-Lenrow, E., Davis, D., Sung, C. K., Divi, V., Sirjani, D. B. 2016; 38 (6): 925-929

    Abstract

    The purpose of this study was to evaluate a telemedicine model that utilizes an audiovisual teleconference as a preoperative visit.Veterans Health Administration (VHA) patients with head and neck cancer at 2 remote locations were provided access to the Palo Alto Veterans Affairs (PAVA) Health Care System otolaryngology department via the telemedicine protocol: tissue diagnosis and imaging at the patient site; data review at PAVA; and a preoperative teleconference connecting the patient to PAVA. Operative care occurred at PAVA. Follow-up care was provided remotely via teleconference.Fifteen patients were evaluated. Eleven underwent surgery, 4 with high-grade neoplasms (carcinoma). Average time from referral to operation was 28 days (range, 17-36 days) and 72 (range, 31-108 days), respectively, for high-grade and low-grade groups. The average patient was spared 28 hours traveling time and $900/patient was saved on travel-related costs.A telemedicine model enables timely access to surgical care and permits considerable savings among select VHA patients with head and neck cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: 925-929, 2016.

    View details for DOI 10.1002/hed.24386

    View details for PubMedID 26899939

  • Clar as Mud? Origins of the head mirror: A historical note HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Laccourreye, O., Werner, A., McGill, I., Holsinger, F. C. 2016; 38 (6): 930-932

    Abstract

    In Europe, the name "Clar" immediately evokes to any otorhinolaryngologist the classic head mirror that remains a symbol of our profession. Yet, the origin of Clar has never been investigated. In this clinical and historical review, based on an Internet and PubMed database search together with perusal of Fischer's Biographical Lexikon, the authors seek to elucidate this medical enigma. The data presented suggest that Clar was not a physician but rather a term picked by the company that designed the mirror by the end of the 19th century to underscore the bright and sharp view provided by this then innovative medical device. © 2015 Wiley Periodicals, Inc. Head Neck 38: 930-932, 2016.

    View details for DOI 10.1002/hed.24093

    View details for Web of Science ID 000379939900022

    View details for PubMedID 25919889

  • Number of positive nodes is superior to the lymph node ratio and American Joint Committee on Cancer N staging for the prognosis of surgically treated head and neck squamous cell carcinomas CANCER Roberts, T. J., Colevas, A. D., Hara, W., Holsinger, F. C., Oakley-Girvan, I., Divi, V. 2016; 122 (9): 1388-1397

    Abstract

    Recent changes in head and neck cancer epidemiology have created a need for improved lymph node prognostics. This article compares the prognostic value of the number of positive nodes (pN) with the value of the lymph node ratio (LNR) and American Joint Committee on Cancer (AJCC) N staging in surgical patients.The Surveillance, Epidemiology, and End Results database was used to identify cases of head and neck squamous cell carcinomas from 2004 to 2012. The sample was grouped by the AJCC N stage, LNR, and pN and was analyzed with Kaplan-Meier and multivariate Cox proportional hazards models. The sample was also analyzed by the site of the primary tumor.This study identified 12,437 patients. Kaplan-Meier survival curves showed superior prognostic ability for LNR and pN staging in comparison with AJCC staging. Patients with a pN value > 5 had the worst overall survival (5-year survival rate, 16%). Patients with oropharyngeal tumors had better outcomes for all groupings, and a pN value > 5 for oropharyngeal cancers was associated with decreased survival. Multivariate regressions demonstrated larger hazard ratios (HRs) and a lower Akaike information criterion for the pN model versus the AJCC stage and LNR models. The HRs were 1.78 (95% confidence interval, 1.62-1.95) for a pN value of 1, 2.53 (95% confidence interval, 2.32-2.75) for a pN value of 2 to 5, and 4.64 (95% confidence interval, 4.18-5.14) for a pN value > 5.The pN models demonstrated superior prognostic value in comparison with the LNR and AJCC N staging. Future modifications of the nodal staging system should be based on the pN with a separate system for oropharyngeal cancers. Future trials should consider examining adjuvant treatment escalation in patients with >5 lymph nodes. Cancer 2016;122:1388-1397. © 2016 American Cancer Society.

    View details for DOI 10.1002/cncr.29932

    View details for Web of Science ID 000374706500010

    View details for PubMedID 26969807

  • Concordance of oral HPV prevalence between patients with oropharyngeal cancer and their partners INFECTIOUS AGENTS AND CANCER Tsao, A. S., Papadimitrakopoulou, V., Lin, H., Guo, M., Lee, J. J., Holsinger, F. C., Hong, W. K., Sturgis, E. M. 2016; 11

    Abstract

    Human papilloma virus (HPV) is a known causative factor in oropharyngeal squamous cell cancer (OPC). In this prospective study, we sought to define the risk of HPV transmission between OPC patients and their sexual partners by performing HPV genotyping on oral cytology brushings.Newly diagnosed OPC patients and their sexual partners underwent oral mouth swabs and answered a risk factor questionnaire. Patient tumor samples and oral swabs from both the patient and partner were assessed for HPV status and genotyped using Easy-Chip HPV Blot PCR.We enrolled 227 patient-partner pairs and obtained sufficient analyzable DNA from both members in 198 pairs. Of 144 patients with available OPC tumor tissue, 128 (89 %) had HPV-positive tumors by either in situ hybridization or p16 immunohistochemical analysis (104 or 121, respectively). In total, there were 28 patients and 30 partners who were HPV positive by oral swab. The prevalence rate of oral HPV in partners was 15 %. There were 39 patient-partner pairs who had one or both members returning positive for HPV in the oral swab, and 49 % of these pairs were concordant for their HPV-genotype. Female partners had a higher oral HPV prevalence (16 %) than did male partners (11 %). Patients who were non-white were also found to have a higher oral prevalence of HPV (p = 0.032) by mouth swab.Partners of OPC patients may have a higher prevalence of oral HPV and should be studied prospectively to understand their OPC risk. Additional future research is needed to identify oral HPV persistence in partners to OPC patients and to determine the optimal sampling methods and technologies to screen patients at high risk for HPV-related disease.

    View details for DOI 10.1186/s13027-016-0066-9

    View details for Web of Science ID 000374861500001

    View details for PubMedID 27123042

    View details for PubMedCentralID PMC4847345

  • A flexible, single-arm robotic surgical system for transoral resection of the tonsil and lateral pharyngeal wall: Next-generation robotic head and neck surgery LARYNGOSCOPE Holsinger, F. C. 2016; 126 (4): 864-869

    Abstract

    To describe the application of a novel flexible robotic surgical system to transoral endoscopic head and neck surgery of the tonsillar fossa and lateral oropharyngeal wall.Preclinical anatomic study using three human cadavers.Transoral resection of the lateral oropharyngeal wall with mucosal and muscular resection of the tonsillar fossa.This single-port flexible robotic system could be used to successfully perform transoral resection of this region. The optimal angle to dock the patient-side cart was at a 90-degree angle to the operating room table. The placement of the remote center of the robotic instrument arm was evaluated in three positions. When the cannula tip was placed at 10 to 15 cm, all instruments could be deployed past the first and second joggle joint settings, without collision or restriction of arm movement. Using this position and docking location, all four arms were deployed inside the oral cavity without collision or restriction of movement in all three cadavers. The Da Vinci SP (Intuitive Surgical, Inc., Sunnyvale, CA) provided sufficient access, reach, and visualization in order to complete a transoral lateral oropharyngectomy.The first preclinical feasibility study of a novel, flexible, single-arm robotic surgical system is presented for its use in transoral endoscopic head and neck surgery.N/A.

    View details for DOI 10.1002/lary.25724

    View details for Web of Science ID 000373382100022

  • A flexible, single-arm robotic surgical system for transoral resection of the tonsil and lateral pharyngeal wall: Next-generation robotic head and neck surgery. The Laryngoscope Holsinger, F. C. 2016; 126 (4): 864-9

    Abstract

    To describe the application of a novel flexible robotic surgical system to transoral endoscopic head and neck surgery of the tonsillar fossa and lateral oropharyngeal wall.Preclinical anatomic study using three human cadavers.Transoral resection of the lateral oropharyngeal wall with mucosal and muscular resection of the tonsillar fossa.This single-port flexible robotic system could be used to successfully perform transoral resection of this region. The optimal angle to dock the patient-side cart was at a 90-degree angle to the operating room table. The placement of the remote center of the robotic instrument arm was evaluated in three positions. When the cannula tip was placed at 10 to 15 cm, all instruments could be deployed past the first and second joggle joint settings, without collision or restriction of arm movement. Using this position and docking location, all four arms were deployed inside the oral cavity without collision or restriction of movement in all three cadavers. The Da Vinci SP (Intuitive Surgical, Inc., Sunnyvale, CA) provided sufficient access, reach, and visualization in order to complete a transoral lateral oropharyngectomy.The first preclinical feasibility study of a novel, flexible, single-arm robotic surgical system is presented for its use in transoral endoscopic head and neck surgery.N/A.

    View details for DOI 10.1002/lary.25724

    View details for PubMedID 26509920

  • Robotics in otolaryngology and head and neck surgery: Recommendations for training and credentialing A Report of the 2015 AHNS Education Committee, AAO-HNS Robotic Task Force and AAO-HNS Sleep Disorders Committee HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Gross, N. D., Holsinger, F. C., Magnuson, J. S., Duvvuri, U., Genden, E. M., Ghanem, T. A., Yaremchuk, K. L., Goldenberg, D., Miller, M. C., Moore, E. J., Morris, L. G., Netterville, J., Weinstein, G. S., Richmon, J. 2016; 38: E151-E158

    Abstract

    Training and credentialing for robotic surgery in otolaryngology - head and neck surgery is currently not standardized, but rather relies heavily on industry guidance. This manuscript represents a comprehensive review of this increasingly important topic and outlines clear recommendations to better standardize the practice. The recommendations provided can be used as a reference by individuals and institutions alike, and are expected to evolve over time. © 2016 Wiley Periodicals, Inc. Head Neck 38: E151-E158.

    View details for DOI 10.1002/hed.24207

    View details for PubMedID 26950771

  • Prognostic Value of Lymph Node Status Is Greater Than Lymph Node Ratio and AJCC N Staging for Head and Neck Squamous Cell Carcinomas Roberts, T., Colevas, A. D., Hara, W., Holsinger, F. C., Oakley-Girvan, I., Divi, V. ELSEVIER SCIENCE INC. 2016: 911–12
  • Endoscopic retroauricular thyroidectomy: preliminary results SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Byeon, H. K., Holsinger, F. C., Tufano, R. P., Park, J. H., Sim, N. S., Kim, W. S., Choi, E. C., Koh, Y. W. 2016; 30 (1): 355-365

    Abstract

    We sought to seek the potential role of endoscopic thyroidectomy with the retroauricular (RA) approach prior to future comparative study with the robotic RA thyroidectomy. Therefore, this study aims to verify the surgical feasibility of endoscopic RA thyroidectomy.Eighteen patients who underwent endoscopic RA thyroidectomy for clinically suspicious papillary thyroid carcinoma or benign lesions from January to December 2013 were retrospectively reviewed and analyzed.All endoscopic operations via RA or modified facelift approach were successfully performed, without any significant intraoperative complications or conversion to open surgery. Based on patient-reported outcome questionnaires, all patients were satisfied with their postoperative surgical scars.Endoscopic RA thyroidectomy is technically feasible and safe with satisfactory cosmetic results for patients where indicated.

    View details for DOI 10.1007/s00464-015-4202-1

    View details for Web of Science ID 000369334600048

    View details for PubMedID 25875088

  • Robotic Reconstructive Surgery RECONSTRUCTIVE PLASTIC SURGERY OF THE HEAD AND NECK: CURRENT TECHNIQUES AND FLAP ATLAS Ibrahim, A., Sarhane, K. A., Holsinger, F., Selber, J. C., Hanasono, M., Robb, G., Skoracki, R., Yu, P. 2016: 220–29
  • Design and rationale of a prospective multi-institutional registry for patients with sinosodal malignancy The Laryngoscope Beswick, D. M., Holsinger, F. C., Kaplan, M. J., Fischbein, N. J., Hara, W. Y., Colevas, A. D., Le, Q. T., Berry, G. J., Hwang, P. H. 2016

    Abstract

    Assessment of patients with sinonasal malignancy is challenging due to the low disease incidence and diverse histopathology. The current literature is composed mainly of retrospective studies with heterogeneous cohorts, and the rarity of cases limits our understanding of disease characteristics and treatment outcomes. We describe the development of a prospective, multi-institutional registry that utilizes cloud-based computing to evaluate treatment outcomes in patients with sinonasal cancer.A web-based, secure database was built to prospectively capture longitudinal outcomes and quality-of-life (QoL) data in patients diagnosed with sinonasal malignancy. Demographics, tumor staging, and treatment outcomes data are being collected. The Sinonasal Outcome Test-22 and University of Washington Quality of Life Questionnaire are administered at presentation and at recurring intervals. To date, seven institutions are participating nationally.This prospective, multi-institutional registry will provide novel oncological and QoL outcomes on patients with sinonasal malignancy to inform management decisions and disease prognostication. The application of cloud-based computing facilitates secure multi-institutional collaboration and may serve as a model for future registry development for the study of rare diseases in otolaryngology.2C. Laryngoscope, 2016.

    View details for DOI 10.1002/lary.25996

  • Development of prognostic signatures for intermediate-risk papillary thyroid cancer. BMC cancer Brennan, K., Holsinger, C., Dosiou, C., Sunwoo, J. B., Akatsu, H., Haile, R., Gevaert, O. 2016; 16 (1): 736-?

    Abstract

    The incidence of Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, has risen rapidly worldwide. PTC usually has an excellent prognosis. However, the rising incidence of PTC, due at least partially to widespread use of neck imaging studies with increased detection of small cancers, has created a clinical issue of overdiagnosis, and consequential overtreatment. We investigated how molecular data can be used to develop a prognostics signature for PTC.The Cancer Genome Atlas (TCGA) recently reported on the genomic landscape of a large cohort of PTC cases. In order to decrease unnecessary morbidity associated with over diagnosing PTC patient with good prognosis, we used TCGA data to develop a gene expression signature to distinguish between patients with good and poor prognosis. We selected a set of clinical phenotypes to define an 'extreme poor' prognosis group and an 'extreme good' prognosis group and developed a gene signature that characterized these.We discovered a gene expression signature that distinguished the extreme good from extreme poor prognosis patients. Next, we applied this signature to the remaining intermediate risk patients, and show that they can be classified in clinically meaningful risk groups, characterized by established prognostic disease phenotypes. Analysis of the genes in the signature shows many known and novel genes involved in PTC prognosis.This work demonstrates that using a selection of clinical phenotypes and treatment variables, it is possible to develop a statistically useful and biologically meaningful gene signature of PTC prognosis, which may be developed as a biomarker to help prevent overdiagnosis.

    View details for DOI 10.1186/s12885-016-2771-6

    View details for PubMedID 27633254

  • De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer. Cancers of the head & neck An, Y. n., Holsinger, F. C., Husain, Z. A. 2016; 1: 18

    Abstract

    Current adjuvant treatment guidelines for oropharyngeal squamous cell carcinoma treated with primary surgery are based on studies that predate the human papillomavirus (HPV) era. HPV-associated oropharynx carcinoma (HPV-OPC) has a much more favorable prognosis compared to HPV-unassociated cancer and is increasingly considered to be a distinct disease entity due to its unique etiology, presentation, and behavior. Currently, there is significant interest in adjuvant treatment de-intensification of HPV-OPC patients in order to reduce treatment-related toxicity while maintaining excellent clinical outcomes. Here, we review the evidence and rationale underlying the ongoing prospective trials of adjuvant treatment de-intensification for HPV-OPC patients.

    View details for DOI 10.1186/s41199-016-0016-7

    View details for PubMedID 31093347

    View details for PubMedCentralID PMC6460758

  • Origins of the binocular head mirror: The mystery of Dr. Clar, clarified. International journal of pediatric otorhinolaryngology Mudry, A., Holsinger, C., Rameau, A. 2016; 80: 101-105

    Abstract

    The origin of Dr. Clar's forehead mirror remains a mystery. The aim of this study is to track the roots of this eponym anew to find a definitive answer.Historical, notably by the analysis of the reports of medical meetings and the content of instrument trade catalogs of the corresponding epoch.Konrad or Conrad Clar (1844-1904) was an Austrian balneologist and geologist particularly interested in laryngological examination. He notably invented a lighting apparatus in 1874, his famous forehead mirror in 1886, and a handgrip for laryngological instruments in 1901.Konrad Clar is the man behind the eponymous Dr. Clar's mirror. This study allowed to definitively confirm this statement.

    View details for DOI 10.1016/j.ijporl.2015.11.017

    View details for PubMedID 26746620

  • Morbidity and Mortality Associated With Robotic Head and Neck Surgery: An Inquiry of the Food and Drug Administration Manufacturer and User Facility Device Experience Database. JAMA otolaryngology-- head & neck surgery Chen, M. M., Holsinger, F. C. 2016; 142 (4): 405–6

    View details for PubMedID 26939860

  • Oncologic Outcomes After Transoral Robotic Surgery A Multi-institutional Study JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY de Almeida, J. R., Li, R., Magnuson, J. S., Smith, R. V., Moore, E., Lawson, G., Remacle, M., Ganly, I., Kraus, D. H., Teng, M. S., Miles, B. A., White, H., Duvvuri, U., Ferris, R. L., Mehta, V., Kiyosaki, K., Damrose, E. J., Wang, S. J., Kupferman, M. E., Koh, Y., Genden, E. M., Holsinger, F. C. 2015; 141 (12): 1043-1051

    Abstract

    Large patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer.To review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality.A retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions.Select patients received radiation therapy and/or chemotherapy before or after TORS.Locoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors.Of the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2- year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis.This large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers.

    View details for DOI 10.1001/jamaoto.2015.1508

    View details for PubMedID 26402479

  • Real-time navigation in transoral robotic nasopharyngectomy utilizing on table fluoroscopy and image overlay software: a cadaveric feasibility study. Journal of robotic surgery Tsang, R. K., Sorger, J. M., Azizian, M., Holsinger, C. F. 2015; 9 (4): 311-314

    Abstract

    Inability to integrate surgical navigation systems into current surgical robot is one of the reasons for the lack of development of robotic endoscopic skull base surgery. We describe an experiment to adapt current technologies for real-time navigation during transoral robotic nasopharyngectomy. A cone-beam CT was performed with a robotic C-arm after the injecting contrast into common carotid artery. 3D reconstruction of the skull images with the internal carotid artery (ICA) highlighted red was projected on the console. Robotic nasopharyngectomy was then performed. Fluoroscopy was performed with the C-arm. Fluoroscopic image was then overlaid on the reconstructed skull image. The relationship of the robotic instruments with the bony landmarks and ICA could then been viewed in real-time, acting as a surgical navigation system. Navigation during robotic skull base surgery is feasible with available technologies and can increase the safety of robotic skull base surgery.

    View details for DOI 10.1007/s11701-015-0532-1

    View details for PubMedID 26530843

  • Transoral Endoscopic Head and Neck Surgery The Contemporary Treatment of Head and Neck Cancer HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Lim, G. C., Holsinger, F. C., Li, R. J. 2015; 29 (6): 1075-?

    Abstract

    Traditional open surgical approaches are indicated for treatment of select tumor subsites of head and neck cancer, but can also result in major cosmetic and functional morbidity. Transoral surgical approaches have been used for head and neck cancer since the 1960s, with their application continuing to evolve with the changing landscape of this disease and recent innovations in surgical instrumentation. The potential to further reduce treatment morbidity with transoral surgery, while optimizing oncologic outcomes, continues to be investigated. This review examines current literature evaluating oncologic and quality-of-life outcomes achieved through transoral head and neck surgery.

    View details for DOI 10.1016/j.hoc.2015.08.001

    View details for Web of Science ID 000366063400008

    View details for PubMedID 26568549

  • Transoral Endoscopic Head and Neck Surgery and Its Role Within the Multidisciplinary Treatment Paradigm of Oropharynx Cancer: Robotics, Lasers, and Clinical Trials JOURNAL OF CLINICAL ONCOLOGY Holsinger, F. C., Ferris, R. L. 2015; 33 (29): 3285-?

    Abstract

    Transoral endoscopic head and neck surgery is a new approach for the treatment of oropharyngeal tumors. Using either a robotic system and/or laser, surgeons gain access through the mouth via minimally invasive technique and thus have improved visualization of the tumors of the oropharynx, without disfiguring incisions. This transoral route of access minimizes long-term speech and swallowing dysfunction. Surgeons view this approach as a considerable technologic advance, analogous to the evolution in radiation therapy from conventional two- and three-dimensional conformal techniques to intensity-modulated techniques. Although the use of radiation with or without chemotherapy to treat oropharyngeal cancer (OPC) is supported by evidence from prospective clinical trials, there are no prospective data supporting the use of this new surgical approach for OPC. Here, we review the fundamentals of transoral endoscopic head and neck surgery, with robotics and laser technology, and discuss ongoing clinical trials for patients with OPC.

    View details for DOI 10.1200/JCO.2015.62.3157

    View details for Web of Science ID 000366474000009

    View details for PubMedID 26351337

    View details for PubMedCentralID PMC4586168

  • Salvage Conservation Laryngeal Surgery After Radiation Therapy Failure OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Chen, M. M., Holsinger, F. C., Laccourreye, O. 2015; 48 (4): 667-?

    Abstract

    Conservation laryngeal surgery (CLS) includes time-honored approaches such as the vertical partial laryngectomy and the open horizontal supraglottic laryngectomy, as well as the supracricoid partial laryngectomy and transoral laser microsurgery. Carefully selected patients can undergo transoral endoscopic or open CLS for early to intermediate stage recurrent tumors of the glottic and supraglottic larynx. Patient factors, such as comorbid pulmonary disease, are essential in selecting patients for CLS, especially after previous radiation therapy. This article reviews the preoperative indications and postoperative management of salvage CLS after radiation therapy for laryngeal cancer.

    View details for DOI 10.1016/j.otc.2015.04.011

    View details for PubMedID 26233791

  • Surgical trials in head and neck oncology: Renaissance and revolution? Head & neck Shaw, R. J., Holsinger, F. C., Paleri, V., Evans, M., Tudur-Smith, C., Ferris, R. L. 2015; 37 (7): 927-930

    View details for DOI 10.1002/hed.23846

    View details for PubMedID 25043823

  • Supracricoid partial laryngectomy with cricohyoidoepiglottopexy: Surgical technique illustrated in the anatomy laboratory HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Holsinger, F. C., Tomeh, C., Moore, M. W., Yan, W., Chen, C., Laccourreye, O. 2015; 37 (6): 906-908

    Abstract

    Despite its first introduction by Majer and Rieder in 1959 and its widespread implementation by French surgeons, supracricoid partial laryngectomy (SCPL) only started to be discussed in the English literature in the early 1990s. The procedure has been employed for decades as a partial laryngectomy that preserves laryngeal function, namely speaking, swallowing, and breathing. SCPL is similar to an extended supraglottic laryngectomy; however, while the glottis remains intact with a supraglottic laryngectomy, a neolarynx is recreated in SCPL using the fundamental elements of the cricoarytenoid unit. In SCPL with cricohyoidoepiglottopexy (CHEP), a pexy is created between the cricoid cartilage below and the preserved epiglottis and hyoid bone above. Remarkably, but reliably, this reconstruction recreates the airway and improves swallowing to the point where even one arytenoid can be sacrificed. Head Neck, 2014.

    View details for DOI 10.1002/hed.23921

    View details for Web of Science ID 000355012000023

    View details for PubMedID 25354982

  • Squamous Cell Carcinoma of Parotid Gland Associated with Concurrent Lymphoepithelial Cysts and Lymphoepithelial Lesion: Case Report and Proposed Histogenesis HEAD & NECK PATHOLOGY Zhou, J. H., Holsinger, F. 2015; 9 (2): 305–8

    Abstract

    Lymphoepithelial cyst and lymphoepithelial lesion have similar histologic features and an affinity for the parotid gland. Though considered as different entities, both conditions arise from heterotopic salivary epithelial rests or inclusions in intra- or peri-parotid lymph nodes. We present a case of squamous cell carcinoma of parotid gland associated with concurrent lymphoepithelial cyst and lymphoepithelial lesion in a patient who was not infected with human immunodeficiency virus. We propose that lymphoepithelial cyst and lymphoepithelial lesion have a similar histogenesis.

    View details for DOI 10.1007/s12105-014-0571-3

    View details for Web of Science ID 000214612900017

    View details for PubMedID 25284597

    View details for PubMedCentralID PMC4424203

  • Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes, NRG Oncology/RTOG 9501-0234. Divi, V., Harris, J., Harari, P. M., Cooper, J., McHugh, J. B., Bell, D., Sturgis, E. M., Cmelak, A., Suntharalingam, M., Raben, D., Kim, H. E., Spencer, S., Laramore, G. E., Trotti, A., Foote, R., Schultz, C. J., Thorstad, W. L., Zhang, Q., Quynh-Thu Le, Holsinger, F. AMER SOC CLINICAL ONCOLOGY. 2015
  • Survival benefit for adjuvant radiation therapy in minor salivary gland cancers. Oral oncology Zeidan, Y. H., Pekelis, L., An, Y., Holsinger, F. C., Kong, C. S., Chang, D. T., Le, Q. 2015; 51 (5): 438-445

    Abstract

    The goal of the current study is to investigate the role of adjuvant radiation therapy (adjuvant RT) in minor salivary gland tumors (mSGT) using an established national database.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients treated with or without adjuvant RT for mSGT from 1988 to 2008. Regression analyses were performed to identify factors associated with improved overall survival (OS).Most tumors were located within the oral cavity (75%) followed by nasal cavity/paranasal sinuses (15%). Multivariate Cox analysis showed that adjuvant RT was associated with better OS compared to surgery alone. Using logistic regression analysis, we provide a novel web based tool for predicting survival impact of adjuvant RT in patients with mSGT.Adjuvant RT is associated with improved survival in patients with mSGT and adverse clinicopathologic factors such as advanced T/N category, adenoid cystic histology, high grade, and nasopharynx location.

    View details for DOI 10.1016/j.oraloncology.2015.02.096

    View details for PubMedID 25771077

  • Late radiation-associated dysphagia with lower cranial neuropathy in long-term oropharyngeal cancer survivors: Video case reports HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Hutcheson, K. A., Yuk, M. M., Holsinger, F. C., Gunn, G. B., Lewin, J. S. 2015; 37 (4): E56-E62

    Abstract

    Background: Lower cranial neuropathies are a late effect of radiotherapy, typically reported in nasopharynx cancer survivors. Limited data examine these neuropathies after oropharyngeal cancer, particularly as it relates to late radiation-associated dysphagia (late-RAD). Methods: Two cases were examined over 4 to 6 years. Late-RAD was assessed per MBSImp™©, PAS, PSSHN, and MDADI. Neuropathies were examined via clinical examination and laryngeal videostroboscopy, and compared with trajectories of late-RAD. Results: Media-enriched case reports describe the course of late-RAD and neuropathies in two cases after definitive radiotherapy ± EGFR-inhibitor for oropharynx cancer. Late-RAD was characterized by severe physiologic impairments per MBSImp™© and decreased swallowing-related QOL per MDADI. Trajectories of late-RAD paralleled the progression or stability of neuropathies. Conclusions: Late-RAD with lower cranial neuropathies resulted in profound and persistent functional impairment. Rarely reported, late radiation-associated lower cranial neuropathies may be a major contributor to new-onset or progressive dysphagia in long-term oropharyngeal cancer survivors. Head Neck, 2014.

    View details for DOI 10.1002/hed.23840

    View details for Web of Science ID 000351690800003

    View details for PubMedID 25043608

  • Is robotic parathyroidectomy a feasible and safe alternative to targeted open parathyroidectomy for the treatment of primary hyperparathyroidism? International journal of surgery Garas, G., Holsinger, F. C., Grant, D. G., Athanasiou, T., Arora, A., Tolley, N. 2015; 15: 55-60

    Abstract

    A best evidence topic was written according to a structured protocol. The question addressed was whether robotic parathyroidectomy (RP) is a feasible and safe alternative to targeted open parathyroidectomy for the treatment of primary hyperparathyroidism (pHPT). A total of 36 papers were identified using the reported searches of which 5 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Targeted parathyroidectomy constitutes the co-gold-standard procedure for pHPT with results equivalent to bilateral cervical exploration. This has led to the proliferation of minimally invasive parathyroidectomy (MIP) techniques for pre-operatively localised adenomas. None has been shown to be overwhelmingly superior. RP constitutes the most recent addition. RP overcomes the limitations of conventional endoscopic surgery and simultaneously avoids a neck scar by concealing it in the axilla or infraclavicular area. The evidence from the present review shows that RP is feasible and leads to a superior cosmetic result compared to targeted open parathyroidectomy (TOP) with an equivalent safety profile. As with every surgical technique, appropriate patient selection is crucial. Long-term data are currently awaited on RP especially in view of its high cost and long operative time compared to TOP and other MIP techniques. Hence, RP offers a viable but costly alternative to other forms of MIP in patients where even the smallest and most cosmetic neck scar is not an option.

    View details for DOI 10.1016/j.ijsu.2015.01.019

    View details for PubMedID 25638734

  • Functional outcomes after TORS for oropharyngeal cancer: a systematic review EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Hutcheson, K. A., Holsinger, F. C., Kupferman, M. E., Lewin, J. S. 2015; 272 (2): 463-471

    Abstract

    Summarize functional outcomes after transoral robotic surgery (TORS) ± adjuvant therapy for oropharyngeal cancer (OPC). A systematic review was conducted. The MEDLINE database was searched (MeSH terms: TORS, pharyngeal neoplasms, oropharyngeal neoplasms). Peer-reviewed human subject papers published through December 2013 were included. Exclusion criteria were as follows: (1) case report design (n < 10), (2) review article, or (3) technical, animal, or cadaver studies. Functional outcomes extracted included feeding tube dependence, swallow examination findings, speech ratings, velopharyngeal insufficiency, pneumonia, and oral intake measures. Twelve papers comprising 441 patients with OPC treated with TORS ± adjuvant therapy were included. Feeding tube rates were the most commonly reported functional outcome. Excluding prophylactic placement, 18-39 % of patients required gastrostomy placement, typically during adjuvant therapy. Chronic gastrostomy dependence ranged from 0 to 7 % (mean follow-up 11-26 months), regardless of disease stage. Composite MD Anderson Dysphagia Inventory (MDADI) scores ranged from 65.2 to 78 (89 patients, 3 series, mean follow-up 12-13 months). Videofluoroscopic swallowing studies were not systematically reported. Incidence of postoperative pneumonia was 0-7 %. Predictors of swallowing function included baseline function, T-stage, N-stage, tongue base primary tumors, and adjuvant chemoradiation. Rates of transient hypernasality were 4-9 %. A single study suggested dose-dependent effects of adjuvant therapy (none, radiation alone, chemoradiation) on diet scores at 6 and 12 months. Crude end points of functional recovery after TORS ± adjuvant therapy suggest promising swallowing outcomes, depending on the functional measure reported.

    View details for DOI 10.1007/s00405-014-2985-7

    View details for Web of Science ID 000347823800030

    View details for PubMedID 24643851

    View details for PubMedCentralID PMC4169348

  • Robotic Transoral Periosteal Thyroidectomy (TOPOT): Experience in Two Cadavers JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Lee, H. Y., Richmon, J. D., Walvekar, R. R., Holsinger, C., Kim, H. Y. 2015; 25 (2): 139-142

    Abstract

    Transoral techniques for endoscopic thyroidectomy have recently been reported, including a robotic transoral technique to access the thyroid gland. Herein, we developed a robotic transoral periosteal thyroidectomy technique.The da Vinci(®) Surgical System (Intuitive Surgical, Sunnyvale, CA) robot was used in two human cadavers to perform robotic transoral periosteal thyroidectomies. In the first cadaver, the anterior neck was exposed below the platysmal muscle. The anatomical spaces and surgical planes were observed with four ports by a periosteal approach. In the second cadaver, robotic transoral periosteal thyroidectomy was performed using three ports.A total thyroidectomy and central neck dissection were performed in two cadavers using the da Vinci robot with the transoral periosteal approach. Complete thyroidectomy and central neck dissection were possible without injury to the recurrent laryngeal nerve.Robotic transoral periosteal thyroidectomy provides superior access to the thyroid and central neck compartment. Transoral thyroidectomy using four ports is a feasible and safe method.

    View details for DOI 10.1089/lap.2014.0543

    View details for Web of Science ID 000349324100010

    View details for PubMedID 25629368

  • Guideline Familiarity Predicts Variation in Self-Reported Use of Routine Surveillance PET/CT by Physicians Who Treat Head and Neck Cancer. Journal of the National Comprehensive Cancer Network Roman, B. R., Patel, S. G., Wang, M. B., Pou, A. M., Holsinger, F. C., Myssiorek, D., Goldenberg, D., Swisher-McClure, S., Lin, A., Shah, J. P., Shea, J. A. 2015; 13 (1): 69-77

    Abstract

    Use of routine surveillance testing beyond guideline recommended levels is common in many oncologic disciplines, including head and neck cancer. The impact of guideline familiarity and other physician characteristics on surveillance imaging use are not well understood.A cross-sectional national survey was performed of physicians responsible for surveillance of patients with head and neck squamous cell carcinoma (HNSCC). The primary outcome was self-reported use of routine surveillance PET/CT in asymptomatic patients. A secondary outcome was familiarity with guideline recommendations. Using multivariable regression, the impact of guideline familiarity and other physician characteristics on PET/CT use was examined.Of the 502 responders, 79% endorsed ever using PET/CT scans for routine surveillance imaging, and 39% were high imaging users (used PET/CT scans on more than half of their asymptomatic patients); 76% were familiar with the NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers recommending against routine surveillance PET/CT scans. Although guideline familiarity was associated with being a low imaging user or a never-user, among those who were familiar with guidelines, 31% were nonetheless high imaging users and 73% endorsed ever using PET/CT scans. In multivariable analysis controlling for physician characteristics, guideline familiarity was the strongest predictor of PET/CT use.Familiarity with the NCCN Guidelines predicts self-reported routine surveillance PET/CT use among physicians who treat patients with HNSCC. However, given the observed variation and high levels of imaging even among physicians who are familiar with the guidelines, further research should examine the reasons physicians choose to use surveillance PET/CT scans.

    View details for PubMedID 25583771

  • The Care of the HPV-Negative Head and Neck Cancer Patient: Presentation, Prognosis, Treatment HPV AND HEAD AND NECK CANCERS Cmelak, A. J., Rettig, E., Holsinger, F., Fakhry, C., DSouza, G. 2015: 111–27
  • Feasibility of robot-assisted neck dissection followed by transoral robotic surgery BRITISH JOURNAL OF ORAL & MAXILLOFACIAL SURGERY Byeon, H. K., Holsinger, F. C., Kim, D. H., Kim, J. W., Park, J. H., Koh, Y. W., Choi, E. C. 2015; 53 (1): 68-73

    Abstract

    Our aim was to evaluate the feasibility of robot-assisted neck dissection (RAND) followed by transoral robotic surgery (TORS) in treatment of cancers of the head and neck, which is expected to improve cosmesis and function. We studied 37 patients with biopsy-confirmed cNO or cN+ tumours of the oropharynx (n=22), hypopharynx (n=8), larynx (n=6), and oral cavity (n=1) who were treated by RAND then TORS from May 2010 to December 2012. Patients' characteristics and clinical details were recorded, together with operative complications and functional variables such as management of the airway and nasogastric or enterogastric feeding. All endoscopic TORS and RAND were successful, with no serious intraoperative complications or need to convert to open operation. All patients were satisfied with the cosmesis according to the answers given to a questionnaire. RAND followed by TORS in some cancers of the head and neck are feasible and showed a clear cosmetic benefit, although the longer operating time is a drawback. Studies of more patients with longer follow-up are required to evaluate long-term oncological and functional outcomes in more detail.

    View details for DOI 10.1016/j.bjoms.2014.09.024

    View details for Web of Science ID 000346570500015

    View details for PubMedID 25453254

  • Robotic Total Thyroidectomy with Modified Radical Neck Dissection via Unilateral Retroauricular Approach ANNALS OF SURGICAL ONCOLOGY Byeon, H. K., Holsinger, F. C., Tufano, R. P., Chung, H. J., Kim, W. S., Koh, Y. W., Choi, E. C. 2014; 21 (12): 3872-3875

    Abstract

    Traditionally, total thyroidectomy was performed through an open transcervical incision; in cases where there was evident nodal metastasis, the conventional surgical approach was to extend the incision into a large single transverse incision to complete the required neck dissection. However, recent innovation in the surgical technique of thyroidectomy has offered the opportunity to reduce the patient's burden from these prominent surgical scars in the neck. Minimally invasive surgical techniques have been developed and applied by many institutions worldwide, and more recently, various techniques of remote access surgery have been suggested and actively applied.1-6 Since the advent of robotic surgical systems, some have adopted the concept of remote access surgery into developing various robotic thyroidectomy techniques. The more former and widely acknowledged robotic thyroidectomy technique uses a transaxillary (TA) approach, which has been developed by Chung et al. in Korea.7,8 This particular technique has some limitations in the sense that accessing the lymph nodes of the central compartment is troublesome. Terris et al. realized some shortcomings of robotic TA thyroidectomy, especially in their patients in the United States, and developed and reported the feasibility of robotic facelift thyroidectomy.9-13 In cases of thyroid carcinomas with lateral neck node metastases, most abandoned the concept of minimally invasive or remote access surgery and safely adopted conventional open surgical methods to remove the tumor burden. However, Chung et al. have attempted to perform concomitant modified radical neck dissection (MRND) after robotic thyroidectomy through the same TA port.14 This type of robot-assisted neck dissection (RAND) had some inherent limitations, due to fact that lymph nodes of the upper neck were difficult to remove. Over the past few years, we have developed a RAND via modified facelift (MFL) or retroauricular (RA) approach and reported the feasibility and safety of this technique.15, 16 Since then, we have actively applied such RAND techniques in various head and neck cancers. In our country, almost all cases of robotic total thyroidectomy utilize the TA approach. According to the reports made by Terris et al., robotic facelift thyroidectomy technique has been solely applied for ipsilateral hemithyroidectomy. For total thyroidectomy, Terris et al. performed the robotic surgery with bilateral RA incisions. Here, we intend to introduce our novel surgical method after successfully attempting simultaneous robotic total thyroidectomy and RAND via a single RA approach without an axillary incision. To our knowledge, this is the first to report in the medical literature.We present four cases of our surgical experience since the beginning of 2013. All patients received robotic total thyroidectomy with MRND via single RA port without axillary incision after approval from the institutional review board at Severance Hospital, Yonsei University College of Medicine. The inclusion criteria for this operation were as follows: (1) patients with malignant carcinomas of the thyroid gland with evident cervical lymph node metastasis on preoperative imaging studies which are indicated for surgery; (2) patients with no previous history of treatment for thyroid carcinoma. The exclusion criteria were as follows: (1) patients with recurred thyroid tumors; (2) patients with thyroid carcinomas that showed gross invasion to local structures or extensive extrathyroidal capsular spread; (3) patients with clinically evident neck nodal metastasis with extracapsular spread; (4) patients with past history of neck surgery of any kind. In order to assess the extent of disease, neck ultrasonography with fine needle aspiration, neck CT or MRI and PET-CT were performed as preoperative evaluation. All patients were given full information of the possible treatment options for their thyroid cancer comprising of open transcervical approach and robotic surgery via RA approach, including the advantages and disadvantages of each treatment choice and provided written, informed consents before the surgery. General clinical information of the patients is outlined in Table 1. The skin incision for the operation was designed just like the approach for robotic facelift thyroidectomy by Terris et al. and RAND, which has been first reported by our institution.11 (,) 16 The operation was performed by the following sequence. Initially, the skin-subplatysmal flap was elevated after making the skin incision to create sufficient working space. During this process, the elevated skin flap was retracted and maintained by retractors held by the assistant. After application of the self-retaining retractor (Sangdosa Inc., Seoul), neck dissection of the upper neck levels was performed under gross vision. Next, RAND through the RA incision was conducted followed by ipsilateral thyroidectomy with central compartment neck dissection (CCND) via the same approach. Finally, contralateral thyroidectomy with CCND was performed via the single RA port. During these steps, the operator is aided by the bedside assistant with long-suction tips to manipulate and direct the dissected specimen to maintain optimal surgical view or to suck out the fume created by the thermocoagulation from the Harmonic shears. The da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced via the RA port with a facedown 30° dual-channel endoscopic arm placed in the center, and two instrument arms equipped at either side with 5-mm Maryland forceps and Harmonic curved shears. During the step of robotic contralateral thyroidectomy, a ProGrasp forceps was utilized at times, instead of 5-mm Maryland forceps. The rest of the surgery was completed with the robotic system (see Video for demonstration of operation for patient 2). Table 1 Clinical characteristics of the patients Patient Sex/age (yr) BMI Side(a) Approach Pathology(b) Tumor size(c) (cm) CCND(d) MRND(d) Drain removal day Drainage amount (ml) Hospital stay (days) 1 F/38 23.8 L RA PC 0.7 2/5 8/23 8 788 11 2 F/18 18.3 L RA PC 0.8 2/8 7/35 6 398 9 3 F/44 23.1 L RA PC 0.9 5/12 5/27 6 607 9 4 F/26 32.9 L RA PC 1.4 3/14 9/48 7 476 15 BMI body mass index, RA retroauricular approach, PC papillary carcinoma, CCND central compartment neck dissection, MRND modified radical neck dissection (a)Side refers to the site of main lesion (b)Pathology refers to the primary tumor within the thyroid gland (c)Tumor size refers to the diameter of the largest tumor in the thyroid gland (d)For each type of lymph node dissection, the number of positive nodes/total number of retrieved nodes is statedFor all of the patients, robotic total thyroidectomy with MRND (levels II, III, IV, V) via unilateral RA approach was successfully completed without any significant intraoperative complications or conversion to open or other approach methods. The total operation time was defined as the time from initial skin incision to removal of the final specimen, which was an average 306.1 ± 11.1 min (Table 2). This included the time for skin flap elevation and neck dissection under gross vision (87 ± 2.8 min), setting up the robotic system for RAND (6.8 ± 2.4 min), console time using the robotic system for RAND (59.3 ± 2.2 min), flap elevation for thyroidectomy (11.3 ± 2.5 min), robotic arms docking for ipsilateral thyroidectomy (6.3 ± 2.5 min), console time for ipsilateral thyroidectomy (61.3 ± 2.1 min), robotic arms docking for contralateral thyroidectomy (6.3 ± 2.5 min), and console time for contralateral thyroidectomy (61.8 ± 2.1 min). The working space created from RA incision was sufficient, and manipulations of the robotic instruments through this approach were technically feasible and safe without any mutual collisions throughout the entire operation. It also allowed for an excellent magnified surgical view enabling visualization of important local anatomical structures. There was no postoperative vocal cord palsy due to recurrent laryngeal nerve injury. However, two patients developed transient hypoparathyroidism, which resolved in the end without the need for calcium or vitamin D supplementation after certain period of medical management (Table 3). Also, there was no incidence of postoperative hemorrhage or hematoma formation, although a single patient developed a postoperative seroma on postoperative day 9, which was managed conservatively without the need for further surgical intervention. On average, the wound catheter was removed 6.8 ± 1 days after surgery and the patient was discharged from the hospital at an average 11 ± 2.8 days from admission (Table 1). Final surgical pathology confirmed the diagnosis of papillary carcinoma for every patient. The total number of cervical nodes retrieved from CCND and MRND was 9.8 ± 4 and 33.1 ± 11 respectively, and the number of positive metastatic nodes was 3 ± 1.4 and 7.3 ± 1.7 respectively (Table 1). In three patients (patients 2, 3, and 4), the presence of one parathyroid gland was each verified in the pathology specimen. All four patients have received high-dose (150 mCi) radioiodine ablation (RAI) therapy after the operation and are being followed up (average 11.3 months, range 9-13 months) on a regular basis with no evidence of recurrence (post-RAI, most recent, nonsuppressed thyroglobulin range 0.1-0.4 ng/ml, antithyroglobulin antibody range 13.7-147.5 IU/ml). (ABSTRACT TRUNCATED)

    View details for DOI 10.1245/s10434-014-3896-y

    View details for Web of Science ID 000343085600030

    View details for PubMedID 25227305

  • CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma. Oncotarget Murillo-Sauca, O., Chung, M. K., Shin, J. H., Karamboulas, C., Kwok, S., Jung, Y. H., Oakley, R., Tysome, J. R., Farnebo, L. O., Kaplan, M. J., Sirjani, D., Divi, V., Holsinger, F. C., Tomeh, C., Nichols, A., Le, Q. T., Colevas, A. D., Kong, C. S., Uppaluri, R., Lewis, J. S., Ailles, L. E., Sunwoo, J. B. 2014; 5 (16): 6854-6866

    Abstract

    Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.

    View details for PubMedID 25149537

  • Late radiation-associated dysphagia (late-RAD) with lower cranial neuropathy after oropharyngeal radiotherapy: A preliminary dosimetric comparison. Oral oncology Awan, M. J., Mohamed, A. S., Lewin, J. S., Baron, C. A., Gunn, G. B., Rosenthal, D. I., Holsinger, F. C., Schwartz, D. L., Fuller, C. D., Hutcheson, K. A. 2014; 50 (8): 746-752

    Abstract

    Late radiation-associated dysphagia (late-RAD) is a rare delayed toxicity, in oropharyngeal cancer (OPC) survivors. Prevention of late-RAD is paramount because the functional impairment can be profound and refractory to standard therapies. The objective of this analysis is to identify candidate dosimetric predictors of late-RAD and associated lower cranial neuropathies after radiotherapy (RT) or chemo-RT (CRT) for OPC.An unmatched retrospective case-control analysis was conducted. Late-RAD cases were identified among OPC patients treated with definitive RT or CRT. Controls were selected with minimum of 6years without symptoms of late-RAD. Dysphagia-aspiration related structures (DARS) and regions of interest containing cranial nerve paths (RCCNPs) were retrospectively contoured. Dose volume histograms were calculated. Non-parametric bivariate associations were analyzed with Bonferroni correction and multiple logistic regression models were fit.Thirty-eight patients were included (12 late-RAD cases, 26 controls). Median latency to late-RAD was 5.8years (range: 4.5-11.3years). Lower cranial neuropathies were present in 10 of 12 late-RAD cases. Mean superior pharyngeal constrictor (SPC) dose was higher in cases relative to controls (median: 70.5 vs. 61.6Gy). Mean SPC dose significantly predicted late-RAD (p=0.036) and related cranial neuropathies (p=0.019). RCCNPs did not significantly predict late-RAD or cranial neuropathies.SPC dose may predict for late-RAD and related lower cranial neuropathies. These data, and those of previous studies that have associated SPC dose with classical dysphagia endpoints, suggest impetus to constrain dose to the SPCs when possible.

    View details for DOI 10.1016/j.oraloncology.2014.05.003

    View details for PubMedID 24906528

  • Management of the Neck in Thyroid Cancer OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Schoppy, D. W., Holsinger, F. C. 2014; 47 (4): 545-?

    Abstract

    The management of regional lymph nodes in thyroid carcinoma is guided by preoperative evaluation, histologic subtype, and often a consideration of data for potential benefit and morbidity of a neck dissection. The goal of lymphadenectomy is complete surgical resection of grossly evident metastatic disease and the removal of regional lymph node groups at highest risk for microscopic disease. Surgery should achieve disease eradication but preserve voice, airway, swallowing, and parathyroid function. This article discusses recommendations for addressing cervical lymph nodes in thyroid carcinoma, discusses current literature regarding the common histologic subtype (papillary carcinoma), and details our operative approach.

    View details for DOI 10.1016/j.otc.2014.04.004

    View details for Web of Science ID 000340440800009

    View details for PubMedID 25041957

  • Robotic Surgery of the Head and Neck Preface OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Gross, N. D., Holsinger, F. C. 2014; 47 (3): IX-X

    View details for DOI 10.1016/j.otc.2014.03.005

    View details for PubMedID 24882802

  • Robotic Thyroidectomy OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Holsinger, F. C., Chung, W. Y. 2014; 47 (3): 373-?

    Abstract

    Robotic thyroidectomy is ideal for patients with indeterminate, likely benign lesions less than 3 cm, and a body mass index less than 35 kg/mg(2). Proper arm position and padding are important to facilitate exposure and development of the working space from axilla to thyroid bed. The working space is developed using headlight and retractors without robotic assistance, establishing exposure of the thyroid bed from a 5-cm incision in the axilla. Three robotic instruments and a stereoscopic endoscope provide excellent visualization of the associated thyroid neurovasculature anatomy.

    View details for DOI 10.1016/j.otc.2014.03.001

    View details for Web of Science ID 000337982400003

    View details for PubMedID 24882795

  • Measuring the Extent of Total Thyroidectomy for Differentiated Thyroid Carcinoma Using Radioactive Iodine Imaging Relationship With Serum Thyroglobulin and Clinical Outcomes JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Holsinger, F. C., Ramaswamy, U., Cabanillas, M. E., Lang, J., Lin, H. Y., Busaidy, N. L., Grubbs, E., Rahim, S., Sturgis, E. M., Lee, J. E., Weber, R. S., Clayman, G. L., Rohren, E. M. 2014; 140 (5): 410-415

    Abstract

    IMPORTANCE Despite performing total thyroidectomy (TT), postoperative radioactive iodine (RAI) imaging often demonstrates the presence of residual thyroid tissue within the operative bed. OBJECTIVE To measure the extent of TT using postoperative RAI imaging and assessing serum thyroglobulin (Tg) level for patients with differentiated thyroid carcinoma (DTC). DESIGN, SETTING, AND PARTICIPANTS We evaluated 245 patients undergoing TT for clinically staged cT1-3N0M0 DTC, who underwent diagnostic postoperative RAI imaging. INTERVENTIONS Total thyroidectomy. MAIN OUTCOMES AND MEASURES On the basis of quantitative measurements, RAI uptake (RAIU) in the thyroid bed of 0.2% of administered activity was selected as the cutpoint to determine the presence or absence of thyroid remnant. RESULTS By postoperative RAI imaging, TT in 106 patients (43%) resulted in RAIU of less than 0.2%. In the remaining 139 patients (57%), there was measurable iodine-avid thyroid tissue and/or tumor in the thyroid bed (n = 117 [84%]), the neck (n = 4 [3%]), or both (n = 18 [13%]). For the entire study population, mean 24-hour RAIU was 0.62%. Stimulated serum Tg levels were obtained in 232 of 245 patients (95%). Measurable stimulated Tg level (≥1 ng/mL) (to convert to micrograms per liter, multiply by 1) was found in 26 of 102 patients (25%) without thyroid remnant and in 87of 133 patients (65%) with thyroid remnant (P < .001). CONCLUSIONS AND RELEVANCE A goal of postthyroidectomy RAIU of less than 0.2% helps maximize the likelihood of an unmeasurable postoperative Tg level, potentially simplifying follow-up evaluation and reducing the use of postoperative RAI in order to facilitate surveillance.

    View details for DOI 10.1001/jamaoto.2014.264

    View details for Web of Science ID 000335960800004

    View details for PubMedID 24700275

  • Intestinal-type adenocarcinoma of the larynx: Report of a rare aggressive phenotype and discussion of histogenesis HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Bell, D., Holsinger, F. C., Ordonez, N., El-Naggar, A. K. 2014; 36 (5): E44-E47

    Abstract

    Primary laryngeal adenocarcinomas are uncommon and typically of salivary or seromucinous glands origin. Similarly, metastatic adenocarcinoma, including intestinal origin to the larynx, is a rare occurrence.We present a case of a 63-year-old woman with odynophagia and an epiglottic mass of 2 months' duration. Physical examination revealed a large mass involving the entire epiglottis with extension to the preepiglottic space anteriorly and to the right lateral wall of the oropharyngeal/hypopharyngeal junction.Induction chemotherapy was initiated, and, after 4 cycles with no noticeable response, the patient underwent total laryngectomy and bilateral levels II to IV neck dissection. The final pathology diagnosis was primary intestinal-type adenocarcinoma of the larynx.We present a primary high-stage intestinal-type adenocarcinoma of the larynx and discuss its putative origin and the clinicopathologic characteristics.

    View details for DOI 10.1002/hed.23474

    View details for Web of Science ID 000334423500001

    View details for PubMedID 24038722

  • Long- term functional and survival outcomes after induction chemotherapy and risk- based definitive therapy for locally advanced squamous cell carcinoma of the head and neck HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Hutcheson, K. A., Lewin, J. S., Holsinger, F. C., Steinhaus, G., Lisec, A., Barringer, D. A., Lin, H. Y., Villalobos, S., Garden, A. S., Papadimitrakopoulou, V., Kies, M. S. 2014; 36 (4): 474-480

    Abstract

    BACKGROUND: The purpose of this study was to evaluate long-term outcomes after induction chemotherapy followed by "risk-based" local therapy for locally-advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Forty-seven patients (stage IV; ≥N2b) were enrolled in a phase II trial. Baseline and 24-month functional measures included modified barium swallow (MBS) studies, oropharyngeal swallow efficiency (OPSE), and the MD Anderson Dysphagia Inventory (MDADI). Functional status was assessed at 5 years. RESULTS: Five-year overall survival (OS) was 89% (95% confidence interval [CI], 81% to 99%). A nonsignificant 13% average reduction in swallowing efficiency (OPSE) was observed at 24 months relative to baseline (p = .191). MDADI scores approximated baseline at 24 months. Among 42 long-term survivors (median, 5.9 years), 3 patients (7.1%) had chronic dysphagia. The rate of final gastrostomy dependence was 4.8% (2 of 42). CONCLUSION: Sequential chemoradiotherapy achieved favorable outcomes among patients with locally advanced SCCHN, mainly of oropharyngeal origin. MBS and MDADI scores found modest swallowing deterioration at 2 years, and chronic aspiration was uncommon in long-term survivors. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.

    View details for DOI 10.1002/hed.23330

    View details for Web of Science ID 000332700600006

    View details for PubMedID 23780650

  • Surgical innovation, industry partnership, and the enemy within HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Lee, W. T., Rocke, D., Holsinger, F. C. 2014; 36 (4): 461-465

    View details for DOI 10.1002/hed.23476

    View details for Web of Science ID 000332700600003

    View details for PubMedID 23996465

  • Laryngeal cancer. Current opinion in otolaryngology & head and neck surgery Tomeh, C., Holsinger, F. C. 2014; 22 (2): 147-153

    Abstract

    Treatment of laryngeal carcinoma continues to evolve, and whereas there was a transition from total laryngectomy to chemoradiation in response to the Veterans Affairs study and Radiation Therapy Oncology Group (RTOG) 91-11, recent data suggest the role of partial laryngectomy must be revisited.Recent data have shown that laryngeal preservation does not equate with laryngeal function. Data are accumulating in support of operative management of advanced laryngeal carcinoma away from chemoradiation for select patients. In particular, supracricoid laryngectomy may be a viable option for intermediate and selected advanced laryngeal carcinoma while maintaining laryngeal function.The evolution of treatment for advanced laryngeal carcinoma is focusing treatment on maintaining locoregional control while also maintaining a functional larynx.

    View details for DOI 10.1097/MOO.0000000000000032

    View details for PubMedID 24504224

  • Endoscopic supraomohyoid neck dissection via a retroauricular or modified facelift approach: Preliminary results HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Byeon, H. K., Holsinger, F. C., Koh, Y. W., Ban, M. J., Ha, J. G., Park, J. J., Kim, D., Choi, E. C. 2014; 36 (3): 425-430

    Abstract

    BACKGROUND: Based on our previous experiences with endoscopic or robotic neck surgery utilizing the retroauricular (RA) or modified facelift (MFL) approach, we realized the value of verifying the feasibility of endoscopic supraomohyoid neck dissection (SOND). Therefore, the purpose of this study was to evaluate the potential role of endoscopic SOND. METHODS: Six patients who underwent elective endoscopic SOND of the ipsilateral neck for biopsy proven head and neck cancer from January 2011 to February 2012 were analyzed. RESULTS: All endoscopic operations via RA or MFL were successfully performed without any significant intraoperative complications or conversion to open surgery. Based on patient-reported outcome questionnaires, all patients were satisfied with the cosmetic surgical outcomes. CONCLUSION: Endoscopic selective neck dissection via an RA or an MFL approach is technically feasible and safe with satisfactory cosmetic results for patients with clinically node-negative early-stage head and neck cancer. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.

    View details for Web of Science ID 000331404400018

    View details for PubMedID 23728878

  • Transoral Robotic Reconstructive Surgery SEMINARS IN PLASTIC SURGERY Selber, J. C., Sarhane, K. A., Ibrahim, A. E., Holsinger, F. C. 2014; 28 (1): 35-38

    Abstract

    Transoral robotic surgery (TORS) has emerged as a technique that allows head and neck surgeons to safely resect large and complex oropharyngeal tumors without dividing the mandible or performing a lip-split incision. These resections provide a reconstructive challenge because the cylinder of the oropharynx remains closed and both physical access and visualization of oropharyngeal anatomy is severely restricted. Transoral robotic reconstruction (TORRS) of such defects allows the reconstructive surgeon to inset free flaps or perform adjacent tissue transfer while seeing what the resecting surgeon sees. Early experience with this technique has proved feasible and effective. Robotic reconstruction has many distinct advantages over conventional surgery, and offers patients a less morbid surgical course. In this review, we discuss the clinical applicability of transoral robotic surgery in head and neck reconstruction, highlighting the benefits and limitations of such an approach, and outlining the guidelines for its utilization.

    View details for DOI 10.1055/s-0034-1368166

    View details for Web of Science ID 000360545000008

    View details for PubMedCentralID PMC3948381

  • Transoral robotic reconstructive surgery. Seminars in plastic surgery Selber, J. C., Sarhane, K. A., Ibrahim, A. E., Holsinger, F. C. 2014; 28 (1): 35-8

    Abstract

    Transoral robotic surgery (TORS) has emerged as a technique that allows head and neck surgeons to safely resect large and complex oropharyngeal tumors without dividing the mandible or performing a lip-split incision. These resections provide a reconstructive challenge because the cylinder of the oropharynx remains closed and both physical access and visualization of oropharyngeal anatomy is severely restricted. Transoral robotic reconstruction (TORRS) of such defects allows the reconstructive surgeon to inset free flaps or perform adjacent tissue transfer while seeing what the resecting surgeon sees. Early experience with this technique has proved feasible and effective. Robotic reconstruction has many distinct advantages over conventional surgery, and offers patients a less morbid surgical course. In this review, we discuss the clinical applicability of transoral robotic surgery in head and neck reconstruction, highlighting the benefits and limitations of such an approach, and outlining the guidelines for its utilization.

    View details for DOI 10.1055/s-0034-1368166

    View details for PubMedID 24872777

    View details for PubMedCentralID PMC3948381

  • Corniculate Reconstruction After Arytenoid Resection in Supracricoid Laryngectomy LARYNGOSCOPE Loyo, M., Laccourreye, O., Weinstein, G. S., Holsinger, F. C. 2014; 124 (2): 472-475

    View details for DOI 10.1002/lary.24139

    View details for Web of Science ID 000329929900031

    View details for PubMedID 24130109

  • Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx. Part II: When and why. Laryngoscope Laccourreye, O., Benito, J., Garcia, D., Menard, M., Bonfils, P., Holsinger, C. 2013; 123 (11): 2718-2722

    Abstract

    OBJECTIVES/HYPOTHESIS: To analyze local failure following lateral pharyngotomy for selected untreated invasive squamous cell carcinoma (SCC) of the lateral oropharynx. STUDY DESIGN: Retrospective review from a university teaching hospital. METHODS: Inception cohort of 91 patients who underwent lateral pharyngotomy for an isolated and previously untreated selected invasive carcinoma of the lateral oropharynx classified as T1 (26), T2 (47), T3 (11), and T4 (7). Induction chemotherapy, neck dissection, and postoperative radiation therapy were used in 91.2%, 94.5%, and 53.5% of patients. RESULTS: The 5-year Kaplan-Meier estimate of local failure was 16.6% for T1, 19% for T2, 38.6% for T3, and 16.7% for T4 lesions (P = .46). In a logistic regression model, only positive margins of resection statistically increased (P = .01) the risk for local failure. In patients with safe margins of resection, the 5-year Kaplan-Meier estimate of local failure was 5.6% for T1 lesions, 10.7% for T2 lesions, 23.8% for T3 lesions, and 20% for T4 lesions (P = .4). Local failure had a significant impact on increased nodal failure (P = .001) and on reduced survival (P < .0001). CONCLUSION: The lateral pharyngotomy approach should be viewed as a valuable oncologic alternative to both mandibulotomy and chemoradiation in patients with selected SCC of the lateral oropharynx. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.

    View details for DOI 10.1002/lary.24246

    View details for PubMedID 23775844

  • Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx--part I: how. Laryngoscope Laccourreye, O., Benito, J., Menard, M., Garcia, D., Malinvaud, D., Holsinger, C. 2013; 123 (11): 2712-2717

    Abstract

    To revisit the surgical technique of lateral pharyngotomy in patients with selected, isolated, and untreated invasive squamous cell carcinoma of the lateral oropharynx. To describe postoperative management, complications, and functional outcomes.Retrospective review from a French university teaching hospital.Ninety-one patients consecutively underwent lateral pharyngotomy for selected T1–T4 squamous cell carcinoma of the lateral oropharynx.Of the patients, 73.6% and 98.9% experienced an uncomplicated surgical and medical postoperative course, respectively. There were no intraoperative deaths, but a single patient died in the immediate postoperative period from carotid rupture following salivary oropharyngeal fistula. The most common significant complications were severe postoperative swallowing impairment, pneumonia from aspiration, and salivary oropharyngeal fistula noted in 6.5%, 4.3%, and 4.3% of cases, respectively. In univariate analysis, none of the variables under analysis was related to the various significant complications noted and/or to immediate postoperative death. No patient had a permanent tracheotomy, whereas one had a permanent gastrostomy. Of the patients in whom a full course of radiation therapy was delivered postoperatively, 13.6% developed a major complication.From a functional point of view, lateral pharyngotomy is a safe, reliable surgery with few major complications and might be considered a valuable alternative to chemoradiation and/or mandibulotomy for selected tumors of the lateral oropharynx.

    View details for PubMedID 24325020

  • Robotic Surgery for Primary Head and Neck Squamous Cell Carcinoma of Unknown Site JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Patel, S. A., Magnuson, J. S., Holsinger, F. C., Karni, R. J., Richmon, J. D., Gross, N. D., Bhrany, A. D., Ferrell, J. K., Ford, S. E., Kennedy, A. A., Mendez, E. 2013; 139 (11): 1203-1211

    Abstract

    Identification of the primary site in head and neck squamous cell carcinoma (HNSCC) is crucial because it improves the patient's prognosis and minimizes morbidity from treatment.To determine the efficacy of transoral robotic surgery (TORS) in identifying unknown primary sites of head and neck squamous cell carcinoma.Retrospective, multi-institutional case series from January 1, 2010, to February 28, 2013, in which data were pooled from the following 6 institutions: University of Washington Medical Center, The University of Texas MD Anderson Cancer Center, University of Alabama-Birmingham Hospital, The University of Texas Medical School at Houston, Johns Hopkins Hospital, and Oregon Health Sciences University. All patients diagnosed as having HNSCC of an unknown primary site who underwent TORS to identify the primary site were included in the study. We excluded those with recurrent disease, a history of radiation therapy to the head and neck, or evidence of a primary tumor site based on previous biopsy results.Identification of the primary tumor site.Forty-seven patients were eligible for the study. The tumor site was identified by TORS in 34 of 47 patients (72.3%). The primary site was located in the base of tongue for 20 patients (58.8%) and the palatine tonsil for 13 patients (38.2%), with 1 patient having a primary site in both the base of tongue and the palatine tonsil. Suspicious physical examination findings were present in 23 of 47 patients (48.9%), with positive and negative predictive values of 56.5% and 25.0%, respectively. Of those who underwent any imaging, 16 patients had suspicious findings, with positive and negative predictive values of 50.0% and 16.7%, respectively. In 18 of 47 patients (38.3%), both preoperative radiographic and physical examination failed to suggest a primary site. Of these 18 patients, 13 (72.2%) were identified after undergoing TORS.We demonstrate that TORS is a useful approach to identify and treat the primary site in patients with HNSCC who present with an unknown primary site.

    View details for DOI 10.1001/jamaoto.2013.5189

    View details for PubMedID 24136446

  • Lateral Pharyngotomy for Selected Invasive Squamous Cell Carcinoma of the Lateral Oropharynx-Part I: How LARYNGOSCOPE Laccourreye, O., Benito, J., Menard, M., Garcia, D., Malinvaud, D., Holsinger, C. 2013; 123 (11): 2712-2717

    View details for DOI 10.1002/lary.24161

    View details for Web of Science ID 000326231200034

  • Salvage Surgery for Recurrent Cancers of the Oropharynx Comparing TORS With Standard Open Surgical Approaches JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY White, H., Ford, S., Bush, B., Holsinger, F. C., Moore, E., Ghanem, T., Carroll, W., Rosenthal, E., Magnuson, J. S. 2013; 139 (8): 773-778

    Abstract

    Surgical salvage may be the only viable treatment option for recurrent tumors of the oropharynx. To our knowledge, there have been no published reports directly comparing the oncologic and functional outcomes of patients with recurrent oropharyngeal squamous cell carcinoma (SCC) treated with transoral robotic-assisted surgery (TORS) with those treated with traditional open surgical approaches.To compare the oncologic and functional outcomes of patients with recurrent oropharyngeal SCC treated with TORS with those treated with traditional open surgical approaches.Retrospective multi-institutional case-control study; study dates, March 2003 through October 2011.Four tertiary care institutions (University of Alabama at Birmingham; M. D. Anderson Cancer Center, Houston, Texas; Mayo Clinic, Rochester, Minnesota; and Henry Ford Hospital, Detroit, Michigan). PARTICIPANTS Sixty-four patients who underwent salvage TORS for recurrent oropharyngeal SCC were matched by TNM stage to 64 patients who underwent open salvage resection. INTERVENTION OR EXPOSURE: Salvage TORS for recurrent SCC of the oropharynx.Patient demographics, operative data, functional, and oncologic outcomes were recorded and compared with a similarly TNM-matched patient group that underwent salvage surgical resection by traditional open surgical approaches. RESULTS Patients treated with TORS were found to have a significantly lower incidence of tracheostomy use (n = 14 vs n = 50; P < .001), feeding tube use (n = 23 vs n = 48; P < .001), shorter overall hospital stays (3.8 days vs 8.0 days; P < .001), decreased operative time (111 minutes vs 350 minutes; P < .001), less blood loss (49 mL vs 331 mL; P < .001), and significantly decreased incidence of positive margins (n = 6 vs n = 19; P = .007). The 2-year recurrence-free survival rate was significantly higher in the TORS group than in the open approach group (74% and 43%, respectively) (P = .01).This study demonstrates that TORS offers an alternative surgical approach to recurrent tumors of the oropharynx with acceptable oncologic outcomes and better functional outcomes than traditional open surgical approaches. This adds to the growing amount of clinical evidence to support the use of TORS in selected patients with recurrent oropharyngeal SCC as a feasible and oncologically sound method of treatment.

    View details for DOI 10.1001/jamaoto.2013.3866

    View details for Web of Science ID 000323545800003

    View details for PubMedID 23949352

  • Conventional transoral surgery for stage III squamous cell carcinoma of the tonsillar region HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Laccourreye, O., Malinvaud, D., Alzahrani, H., Menard, M., Garcia, D., Bonfils, P., Holsinger, F. C. 2013; 35 (5): 653-659

    Abstract

    The purpose of this study was to review the results of conventional transoral resection and neck dissection for stage I to II squamous carcinoma of the tonsillar region.We conducted a retrospective review of 65 patients (stage I, 21 patients; stage II, 44 patients). Induction chemotherapy and postoperative radiation therapy (RT) were administered in 76.9% and 12.3%, respectively, of these cases.The postoperative course was uneventful in 96.9% of patients. Five-year actuarial estimates for local recurrence, nodal recurrence, distant metastasis, and survival were 0% to 7.6%, 0% to 7.8%, 0% to 7.3%, and 70.8% to 71.5% for patients with T1 to T2 carcinoma, respectively. Contralateral and retropharyngeal recurrence occurred in only 1 patient.Conventional transoral resection with ipsilateral neck dissection provides an alternative approach for patients with stage I to II squamous cell carcinoma (SCC) of the tonsillar region. A primary surgical approach spares the use of radiotherapy to eliminate late effects and to permit its use for subsequent management of metachronous head and neck second primary cancer.

    View details for DOI 10.1002/hed.23018

    View details for Web of Science ID 000317304000014

    View details for PubMedID 22605677

  • Robot-Assisted Selective Neck Dissection of Levels II to V via a Modified Facelift or Retroauricular Approach OTOLARYNGOLOGY-HEAD AND NECK SURGERY Park, Y. M., Holsinger, F. C., Kim, W. S., Park, S. C., Lee, E. J., Choi, E. C., Koh, Y. W. 2013; 148 (5): 778-785

    Abstract

    We performed robot-assisted selective neck dissection via a modified facelift or retroauricular approach without creating an apparent scar around the neck to remove neck node of levels II to V after transoral robotic surgery of a primary lesion in patients with laryngopharyngeal carcinoma. Patient data were prospectively analyzed to verify the feasibility and efficacy of robot-assisted neck dissection in the treatment of cN0 laryngopharyngeal carcinoma.Prospective case series.University tertiary care facility.Between March 2011 and March 2012, 7 patients were enrolled in the study. Before study initiation, the Institutional Review Board of Yonsei University approved the protocol, and informed consent was obtained from all patients.Robot-assisted neck dissection was successfully performed in all patients. Five patients underwent selective neck dissection including levels II to IV, and 2 patients underwent selective neck dissection including levels II to V. The average number of lymph nodes retrieved was 25.1. Occult nodal metastasis was found in 1 (14%) neck specimen. During the follow-up period (mean of 13.5 months), all patients were alive without locoregional recurrence. All patients were extremely satisfied with their cosmetic results.Robot-assisted selective neck dissection is a feasible and safe technique to manage the neck in cN0 laryngopharyngeal carcinoma patients. It may be especially helpful for patients undergoing transoral robotic surgery since no apparent scar around the neck remains. Long-term results with respect to oncologic safety and functional outcomes are required to establish the validity of robot-assisted neck dissection.

    View details for DOI 10.1177/0194599813478934

    View details for Web of Science ID 000318363500011

    View details for PubMedID 23429040

  • Biomarker-Directed Therapy of Squamous Carcinomas of the Head and Neck: Targeting PI3K/PTEN/mTOR Pathway JOURNAL OF CLINICAL ONCOLOGY Holsinger, F. C., Piha-Paul, S. A., Janku, F., Hong, D. S., Atkins, J. T., Tsimberidou, A. M., Kurzrock, R. 2013; 31 (9): E137-E140

    View details for DOI 10.1200/JCO.2012.43.2716

    View details for Web of Science ID 000316187600006

    View details for PubMedID 23358976

  • A 13-Gene Signature Prognostic of HPV-Negative OSCC: Discovery and External Validation CLINICAL CANCER RESEARCH Lohavanichbutr, P., Mendez, E., Holsinger, F. C., Rue, T. C., Zhang, Y., Houck, J., Upton, M. P., Futran, N., Schwartz, S. M., Wang, P., Chen, C. 2013; 19 (5): 1197-1203

    Abstract

    To identify a prognostic gene signature for patients with human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCC).Two gene expression datasets were used: a training dataset from the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA; n = 97) and a validation dataset from the MD Anderson Cancer Center (MDACC, Houston, TX; n = 71). We applied L1/L2-penalized Cox regression models to the FHCRC data on the 131-gene signature previously identified to be prognostic in patients with OSCCs to identify a prognostic model specific for patients with high-risk HPV-negative OSCCs. The models were tested with the MDACC dataset using a receiver operating characteristic (ROC) analysis.A 13-gene model was identified as the best predictor of HPV-negative OSCC-specific survival in the training dataset. The risk score for each patient in the validation dataset was calculated from this model and dichotomized at the median. The estimated 2-year mortality (± SE) of patients with high-risk scores was 47.1% (± 9.24%) compared with 6.35% (± 4.42) for patients with low-risk scores. ROC analyses showed that the areas under the curve for the age, gender, and treatment modality-adjusted models with risk score [0.78; 95% confidence interval (CI), 0.74-0.86] and risk score plus tumor stage (0.79; 95% CI, 0.75-0.87) were substantially higher than for the model with tumor stage (0.54; 95% CI, 0.48-0.62).We identified and validated a 13-gene signature that is considerably better than tumor stage in predicting survival of patients with HPV-negative OSCCs. Further evaluation of this gene signature as a prognostic marker in other populations of patients with HPV-negative OSCC is warranted.

    View details for DOI 10.1158/1078-0432.CCR-12-2647

    View details for Web of Science ID 000315740200027

    View details for PubMedID 23319825

  • Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Adelstein, D. J., Ridge, J. A., Brizel, D. M., Holsinger, F. C., Haughey, B. H., O'Sullivan, B., Genden, E. M., Beitler, J. J., Weinstein, G. S., Quon, H., Chepeha, D. B., Ferris, R. L., Weber, R. S., Movsas, B., Waldron, J., Lowe, V., Ramsey, S., Manola, J., Yueh, B., Carey, T. E., Bekelman, J. E., Konski, A. A., Moore, E., Forastiere, A., Schuller, D. E., Lynn, J., Ullmann, C. D. 2012; 34 (12): 1681-1703

    Abstract

    Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.

    View details for DOI 10.1002/hed.23136

    View details for Web of Science ID 000311291900001

    View details for PubMedID 23015475

  • Late dysphagia after radiotherapy-based treatment of head and neck cancer CANCER Hutcheson, K. A., Lewin, J. S., Barringer, D. A., Lisec, A., Gunn, G. B., Moore, M. W., Holsinger, F. C. 2012; 118 (23): 5793-5799

    Abstract

    Changing trends in head and neck cancer (HNC) merit an understanding of the late effects of therapy, but few studies examine dysphagia beyond 2 years of treatment.A case series was examined to describe the pathophysiology and outcomes in dysphagic HNC survivors referred for modified barium swallow (MBS) studies ≥ 5 years after definitive radiotherapy or chemoradiotherapy (January 2001 through May 2011). Functional measures included the penetration-aspiration scale (PAS), performance status scale-head and neck (PSS-HN), National Institutes of Health Swallowing Safety Scale (NIH-SSS), and MBS impairment profile (MBSImp).Twenty-nine patients previously treated with radiotherapy (38%) or chemoradiotherapy (62%) were included (median years posttreatment, 9; range, 5-19). The majority (86%) had oropharyngeal cancer; 52% were never-smokers. Seventy-five percent had T2 or T3 tumors; 52% were N+. The median age at diagnosis was 55 (range, 38-72). Abnormal late examination findings included: dysarthria/dysphonia (76%), cranial neuropathy (48%), trismus (38%), and radionecrosis (10%). MBS studies confirmed pharyngeal residue and aspiration in all dysphagic cases owing to physiologic impairment (median PAS, 8; median NIH-SSS, 10; median MBSImp, 18), whereas stricture was confirmed endoscopically in 7 (24%). Twenty-five (86%) developed pneumonia, half requiring hospitalization. Swallow postures/strategies helped 69% of cases, but no patient achieved durable improvement across functional measures at last follow-up. Ultimately, 19 (66%) were gastrostomy-dependent.Although functional organ preservation is commonly achieved, severe dysphagia represents a challenging late effect that may develop or progress years after radiation-based therapy for HNC. These data suggest that novel approaches are needed to minimize and better address this complication that is commonly refractory to many standard dysphagia therapies.

    View details for DOI 10.1002/cncr.27631

    View details for Web of Science ID 000311306000010

    View details for PubMedID 23640737

  • Oropharynx Cancer CURRENT PROBLEMS IN CANCER Skinner, H. D., Holsinger, F. C., Beadle, B. M. 2012; 36 (6): 334-415
  • Functional and Oncological Outcomes of Primary Versus Salvage Transoral Laser Microsurgery for Supraglottic Carcinoma ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Hutcheson, K. A., Jantharapattana, K., Barringer, D. A., Lewin, J. S., Holsinger, F. C. 2012; 121 (10): 664-670

    Abstract

    We evaluated the functional and oncological outcomes of transoral laser microsurgery (TLM) in patients with previously untreated supraglottic carcinoma compared with the outcomes in salvage cases after radiation-based treatment.We conducted a retrospective case-control study at a single academic tertiary care institution. The functional outcomes were stratified by prior irradiation and were assessed at baseline, less than 1 week after operation, and at last follow-up.Five patients underwent TLM for previously untreated disease, and 5 previously irradiated patients underwent salvage TLM for local failure. No patient required tracheostomy. There was no local recurrence after TLM as primary therapy, and none of those patients required radiotherapy. One salvage patient developed local recurrence. The duration of feeding tube dependence (p = 0.049) and the rates of chronic aspiration (more than 1 month after operation; p = 0.048) were significantly higher in the salvage TLM cases than in the previously untreated cases. The median scores on the PSS-HN Understandability of Speech were 75 ("usually understandable") in the salvage group and 100 ("always understandable") in the previously untreated group.Both local control and function were better in the previously untreated patients than in the salvage patients. Our findings provide support for the use of TLM as a primary treatment modality for selected supraglottic carcinomas, but also suggest a potential for functional recovery in both previously untreated and salvage cases.

    View details for Web of Science ID 000310110500008

    View details for PubMedID 23130541

  • Gene Expression in Uninvolved Oral Mucosa of OSCC Patients Facilitates Identification of Markers Predictive of OSCC Outcomes PLOS ONE Lohavanichbutr, P., Houck, J., Doody, D. R., Wang, P., Mendez, E., Futran, N., Upton, M. P., Holsinger, F. C., Schwartz, S. M., Chen, C. 2012; 7 (9)

    Abstract

    Oral and oropharyngeal squamous cell carcinomas (OSCC) are among the most common cancers worldwide, with approximately 60% 5-yr survival rate. To identify potential markers for disease progression, we used Affymetrix U133 plus 2.0 arrays to examine the gene expression profiles of 167 primary tumor samples from OSCC patients, 58 uninvolved oral mucosae from OSCC patients and 45 normal oral mucosae from patients without oral cancer, all enrolled at one of the three University of Washington-affiliated medical centers between 2003 to 2008. We found 2,596 probe sets differentially expressed between 167 tumor samples and 45 normal samples. Among 2,596 probe sets, 71 were significantly and consistently up- or down-regulated in the comparison between normal samples and uninvolved oral samples and between uninvolved oral samples and tumor samples. Cox regression analyses showed that 20 of the 71 probe sets were significantly associated with progression-free survival. The risk score for each patient was calculated from coefficients of a Cox model incorporating these 20 probe sets. The hazard ratio (HR) associated with each unit change in the risk score adjusting for age, gender, tumor stage, and high-risk HPV status was 2.7 (95% CI: 2.0-3.8, p = 8.8E-10). The risk scores in an independent dataset of 74 OSCC patients from the MD Anderson Cancer Center was also significantly associated with progression-free survival independent of age, gender, and tumor stage (HR 1.6, 95% CI: 1.1-2.2, p = 0.008). Gene Set Enrichment Analysis showed that the most prominent biological pathway represented by the 71 probe sets was the Integrin cell surface interactions pathway. In conclusion, we identified 71 probe sets in which dysregulation occurred in both uninvolved oral mucosal and cancer samples. Dysregulation of 20 of the 71 probe sets was associated with progression-free survival and was validated in an independent dataset.

    View details for DOI 10.1371/journal.pone.0046575

    View details for Web of Science ID 000309973900186

    View details for PubMedID 23029552

  • Trade-Off Between Survival and Laryngeal Preservation in Advanced Laryngeal Cancer: The Otorhinolaryngology Patient's Perspective ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Laccourreye, O., Malinvaud, D., Holsinger, F. C., Consoli, S., Menard, M., Bonfils, P. 2012; 121 (9): 570-575

    Abstract

    We performed a prospective study to evaluate, from the patient's perspective, the trade-off between speech and survival that individuals face when given a diagnosis of advanced-stage laryngeal cancer amenable to either total laryngectomy or a laryngeal preservation protocol using chemotherapy and radiotherapy.Volunteers (309) consecutively seen at the otorhinolaryngology clinic of a university teaching hospital in France completed an anonymous questionnaire designed to determine their position if they faced the diagnosis of an advanced-stage laryngeal cancer. Univariate analysis was performed for potential statistical relationships with various variables.We found that 12.9% of patients were unable to determine their position regarding the two treatment options offered, and this group had a significant statistical relationship with four variables (age, education, professional status, and history of cancer among relatives). We found that 24.6% of patients made survival their main consideration and would not consider any trade-off. Among the 62.5% who considered the trade-off, the percentage of cure that patients were ready to lose in order to preserve their larynx varied from 5% to 100% (mean, 33%; SD, 23%). Aside from the undecided group, none of the variables analyzed was related either to the decision as to whether to consider a trade-off or to the percentage of c re that patients agreed to trade to preserve their larynx.In patients with advanced-stage laryngeal cancer, treatment should be initiated only after careful evaluation of the patient's attitude toward both laryngeal preservation and survival.

    View details for Web of Science ID 000308851800002

    View details for PubMedID 23012894

  • Reconstruction after Robotic Head and Neck Surgery: When and Why JOURNAL OF RECONSTRUCTIVE MICROSURGERY Longfield, E. A., Holsinger, F. C., Selber, J. C. 2012; 28 (7): 445-449

    Abstract

    The advancement of robotically assisted surgery during the last decade has seen a revolution in the approach to surgical oncologic resection, moving toward reducing patient morbidity without compromising oncologic outcomes. In no field has this been more dramatic than in the application of transoral robotic surgery (TORS), using the da Vinci surgical system for resecting tumors of the head and neck. This organ-preserving technique allows the surgeon to remove tumors of the upper aerodigestive tract without external incisions and potentially spare the patient adjuvant treatment. The introduction of TORS improves upon current transoral techniques to the oropharynx and supraglottis. The traditional conception of TORS is that it would be used for smaller tumors and defects would be permitted to heal by secondary intention; however, as head and neck surgeons pursue larger tumors robotically, robotic-assisted reconstruction has entered the paradigm. Given the relative infancy of these procedures, clear guidelines for when reconstruction is warranted do not exist. The current literature, thus far, has focused on feasibility, safety, and implement of the robot in reconstruction. We reviewed the current literature pertinent to TORS reconstruction focusing on patient selection, tumor size, and location. Furthermore, we briefly review our own experience of 20 TORS procedures involving robotic-assisted reconstructions. Finally, we provide an algorithmic approach to determining the need for reconstruction in a given patient. This focuses on four key criteria: tumor location, tumor extent, prior treatment, and patient-specific factors.

    View details for DOI 10.1055/s-0032-1306376

    View details for Web of Science ID 000307630200003

    View details for PubMedID 22399257

  • Robotic Harvest of the Latissimus Dorsi Muscle: Laboratory and Clinical Experience JOURNAL OF RECONSTRUCTIVE MICROSURGERY Selber, J. C., Baumann, D. P., Holsinger, C. F. 2012; 28 (7): 457-464

    Abstract

    Minimally invasive harvest of the latissimus dorsi (LD) muscle is a desirable goal because of both the wide utility of this muscle and the length of incision required to harvest it. In this study, robotic harvest of the LD muscle was evaluated in a cadaver model and clinical series. Ten LD flaps were robotically harvested in eight cadavers. Positioning, port placement, procedural steps, instrumentation, and technical obstacles were all critically analyzed and reported. After modifying the technique based on experience gained in the cadaver study, eight LD muscles were robotically harvested and transferred in eight patients. Access included a short axillary incision and two additional port sites along the anterior border of the muscle. Insufflation was used to maintain the optical cavity. Indications included pedicled flaps for implant-based breast reconstruction and free flaps for scalp reconstruction. All flaps were successfully transferred without converting to open technique. In the clinical series, average time for setup and port placement was 23 minutes, and average robotic time was 1 hour and 51 minutes. There were no major complications. Robotic harvest of the LD is feasible and effective and permits full muscle harvest without a visible incision.

    View details for DOI 10.1055/s-0032-1315789

    View details for Web of Science ID 000307630200005

    View details for PubMedID 22744894

  • Transoral robotic surgery: A multicenter study to assess feasibility, safety, and surgical margins LARYNGOSCOPE Weinstein, G. S., O'Malley, B. W., Magnuson, J. S., Carroll, W. R., Olsen, K. D., Daio, L., Moore, E. J., Holsinger, F. C. 2012; 122 (8): 1701-1707

    Abstract

    Our objective was to determine the safety, feasibility, and the adequacy of surgical margins for transoral robotic surgery (TORS), by reviewing the early results from independent institutional review board-approved clinical trials in three separate institutions.Pooled Data from Independent Prospective Clinical Trials.One hundred ninety-two patients were initially screened, but inadequate exposure did not permit TORS in 13 (6.7%). For two additional patients, TORS was begun but intraoperatively converted to an open procedure. Thus, the intent-to-treat population was 177 patients (average age, 59 years; 81% male), predominantly comprised of tumors arising in the oropharynx (139, 78%) and larynx (26, 15%). TORS was performed for 161 (91%) patients with malignant disease: 153 (95%) with squamous cell carcinoma (T1 [50, 32.7%], T2 [74, 48.4%], T3 [21, 13.7%], T4 [8, 5.2%]), six patients (3.72%) with salivary gland tumors, and two patients with carcinoma in situ. The average follow-up was 345 days.There was no intraoperative mortality or death in the immediate postoperative period. Average estimated blood loss was 83 mL; no patient required transfusion. The rate of positive margins was 4.3%. Twenty-nine patients (16%) experienced 34 serious adverse events that required hospitalization or intervention (grade 3) or were considered life threatening (grade 4, 2.3%). Tracheostomy was performed in 12.4% of all patients (22/177), but only 2.3% had a tracheostomy at last follow-up. For all patients undergoing TORS without previous therapy, the percutaneous endoscopic gastrostomy dependency rate was 5.0%. The average hospital stay was 4.2 days.Based on this multicenter study, TORS appears to be safe, feasible, and as such play an important role in the multidisciplinary management of head and neck cancer.

    View details for DOI 10.1002/lary.23294

    View details for Web of Science ID 000306894500012

    View details for PubMedID 22752997

  • Osteosarcoma of the jaw in children and young adults HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Huh, W. W., Holsinger, F. C., Levy, A., Palla, F. S., Anderson, P. M. 2012; 34 (7): 981-984

    Abstract

    Pediatric jaw osteosarcoma is uncommon, and data are scarce regarding clinical presentation, prognostic factors, and outcome.A single-institution medical record review from 1983 to 2008 for 12 patients age ≤ 21 years was undertaken for this study.Median diagnosis age was 16.3 years (range, 6.3-21.9). Nine patients had mandible tumors. Osteoblastic subtype was most common (4 patients). Most tumors were large (ie, T2; n = 8) and high-grade (n = 8). Treatment characteristics were varied. Median follow-up was 27.1 months (range, 8-252 months). Five patients had tumor necrosis <80% after chemotherapy. No deaths were observed.Jaw osteosarcoma outcome is better compared to extremity osteosarcoma, but further study is required regarding clinical prognostic factors.

    View details for DOI 10.1002/hed.21850

    View details for Web of Science ID 000305513100011

    View details for PubMedID 21853501

  • Robotic Latissimus Dorsi Muscle Harvest: A Case Series PLASTIC AND RECONSTRUCTIVE SURGERY Selber, J. C., Baumann, D. P., Holsinger, F. C. 2012; 129 (6): 1305-1312

    Abstract

    The latissimus dorsi muscle is a workhorse of reconstructive surgery. Traditional harvest technique requires a long, posterior donor-site incision. Endoscopic harvest is limited by technical challenges. Robotic technology permits a simpler, minimally invasive harvest technique.Seven consecutive robotic latissimus dorsi muscle harvests were performed by a single surgeon. Two were used as free flaps for scalp reconstruction and the remaining five as pedicled flaps for breast reconstruction; three were for immediate, implant-based reconstruction with nipple-areola complex-sparing mastectomies, and two were for radiated breasts when the expander was exchanged for an implant. Harvest technique employed a short, axillary incision for pedicle dissection and two to three additional ports for robotic instrumentation.All seven muscle flaps were harvested without converting to an open technique. Both free flaps were successfully transferred. All pedicled flaps resulted in successful breast reconstructions. Flap harvest complications included a single, temporary radial nerve palsy in the contralateral extremity, likely from positioning. There were no donor-site hematomas, seromas, or cutaneous thermal injuries. Robotic harvest time decreased from over 2 hours to about an hour over the study period.Robotic harvest of the latissimus dorsi is a novel and effective method of muscle harvest. It offers technical advantages over endoscopic harvest and aesthetic advantages over the open technique.Therapeutic, IV.

    View details for DOI 10.1097/PRS.0b013e31824ecc0b

    View details for Web of Science ID 000304648500043

    View details for PubMedID 22634647

  • Robotic transaxillary thyroidectomy with gasless approach in a girl with goitre INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY Kandil, E., Noureldine, S., Khalek, M. A., Aslam, R., Ekaidi, I., Steiner, R., Holsinger, F. C. 2012; 8 (2): 210-214

    Abstract

    Robotic-assisted transaxillary thyroidectomy is a minimally invasive approach for the removal of the thyroid through the axilla. This technique eliminates a visible scar and affords excellent optics of the cervical anatomy. We sought to describe the technique and outcome for transaxillary gasless subtotal thyroidectomy in the paediatric population.A 13 year-old female with an enlarged goitre underwent a transaxillary robot-assisted gasless subtotal thyroidectomy in an academic institution. The main outcome measures were feasibility of the robotic approach, patient and gland characteristics, operative time and complications.There was no conversion to laparoscopic or open surgery. The robotic docking time was 110 min and total operative time was 150 min. The patient tolerated the procedure well. Estimated blood loss was 10 ml. The patient was discharged within 24 h. There were no perioperative or postoperative complications. In addition there was no evidence of postoperative vocal cord palsy or paresis.This initial experience demonstrates that this technique can be a feasible, safe and effective method for subtotal thyroidectomy in the paediatric population. The use of robotic technology for endoscopic thyroid surgery could overcome the limitations of conventional endoscopic surgeries in the surgical management of thyroid disease.

    View details for DOI 10.1002/rcs.455

    View details for Web of Science ID 000304470500012

    View details for PubMedID 22454366

  • Functional Organ Preservation for Laryngeal Cancer: Past, Present and Future JAPANESE JOURNAL OF CLINICAL ONCOLOGY Nakayama, M., Laccourreye, O., Holsinger, F. C., Okamoto, M., Hayakawa, K. 2012; 42 (3): 155-160

    Abstract

    Management of laryngeal cancer has focused on improving survival while preserving function. Over the past 20 years, the trends have shifted from surgery to chemoradiotherapy and presently we are facing various challenges. It is imperative to re-examine what has happened and what can be done.Review of the literature along with our experience in the management of functional organ preservation for laryngeal cancer.There was an increasing use of chemoradiotherapy with a decreasing use of surgery. Inappropriate patient selection along with inability to properly apply salvage surgeries have been presumed to be responsible for survival deterioration in laryngeal cancer. Reports concerning late adverse events after chemoradiotherapy are also increasing. Reconfirmation of the multidisciplinary team approach is imperative. Transoral laser microsurgery can be used for early laryngeal cancer and, in some experienced institutes, for advanced-stage cancers. Supracricoid laryngectomy demonstrated satisfactory oncologic and functional outcomes, based on our experience.Treatment selection for larynx preservation should not merely be decided by guidelines but considering each patient's individual condition. Head and neck surgeons are encouraged to take reasonable risks in performing salvage larynx preservation surgery when it is the only option to save a functioning larynx.

    View details for DOI 10.1093/jjco/hyr190

    View details for Web of Science ID 000301067700001

    View details for PubMedID 22223858

  • Transoral robotic-assisted thyroidectomy with central neck dissection: preclinical cadaver feasibility study and proposed surgical technique. Journal of robotic surgery Richmon, J. D., Holsinger, F. C., Kandil, E., Moore, M. W., Garcia, J. A., Tufano, R. P. 2011; 5 (4): 279-282

    Abstract

    Recently, a transoral robotic-assisted technique to access the thyroid gland has been introduced. Despite the advantages this approach may have over other minimally invasive and robotic-assisted techniques, we found that the placement of the camera through the floor of mouth led to restricted freedom of movement. We describe our modification to this technique to overcome this problem. In a study using two fresh human cadavers, the camera port of the da Vinci robot was placed in the midline oral vestibule instead of the floor of the mouth. A transoral thyroidectomy and central neck dissection was successfully performed. Our modification led to an unfettered view of the central neck and allowed for a total thyroidectomy and central neck dissection. Our modification of transoral robotic-assisted thyroidectomy provides superior access to the central compartment of the neck over other robotic-assisted thyroidectomy techniques. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11701-011-0287-2) contains supplementary material, which is available to authorized users.

    View details for DOI 10.1007/s11701-011-0287-2

    View details for PubMedID 22162981

  • Initial experience using robot- assisted transaxillary thyroidectomy for Graves' disease JOURNAL OF VISCERAL SURGERY Kandil, E., Noureldine, S., Khalek, M. A., Alrasheedi, S., Aslam, R., Friedlander, P., Holsinger, F. C., Bellows, C. F. 2011; 148 (6): E447-E451

    Abstract

    Graves' disease is the most common form of hyperthyroidism and surgery to remove the thyroid gland is a common treatment option for many of these patients. Interestingly, due to the enlarged gland size, their high vascularity, and the difficulty to control bleeding, many authors feel that Graves' disease remains a contraindication to current endoscopic techniques. We hypothesize that performing robotic subtotal thyroidectomy in Graves' disease settings could overcome the limitations of conventional endoscopic surgeries in the surgical management of this challenging thyroid disease.Prospective study in an academic hospital.Sixty-seven patients had robotic transaxillary thyroidectomy within a year. Of these, five cases (7%) were done for Graves' disease. There were three females and two males (mean age, 36 years). There were no conversions to laparoscopic or open surgery. The mean (SD) thyroid volume was 16.6 (3.2) ml. The mean (SD) operative time was 159 (17.8)min and docking time was 81 (20)min. Mean blood loss was 18 mL. All patients were discharged home in 24h. There were no perioperative or postoperative complications. There was no evidence of postoperative vocal cord palsy or paresis.We showed that robotic transaxillary thyroidectomy is feasible and can be safe and effective in patients with Graves' disease. To our knowledge, this is the first article describing this approach for Graves' disease. These findings, however, warrant additional investigation within future prospective clinical trials.

    View details for DOI 10.1016/j.jviscsurg.2011.10.002

    View details for Web of Science ID 000298150100008

    View details for PubMedID 22118896

  • Retropharyngeal lymphadenectomy with transoral robotic surgery for papillary thyroid cancer. Journal of robotic surgery Moore, M. W., Jantharapattana, K., Williams, M. D., Grant, D. G., Selber, J. C., Holsinger, F. C. 2011; 5 (3): 221-?

    Abstract

    Retropharyngeal metastasis of papillary thyroid carcinoma is a rare but well recognized phenomenon. Traditional open surgical approaches to nodal metastasis located in the retropharyngeal space are particularly morbid considering the relatively indolent nature of some thyroid cancers. Minimally invasive surgical approaches offer a useful alternative that is both low in morbidity and high in levels of patient acceptance. To assess feasibility and safety, we report a case series of robotic lymphadenectomy in two patients with thyroid cancer metastatic to the retropharyngeal space. Two patients, ages 66 and 73, with unilateral recurrent papillary carcinoma of the retropharyngeal lymph nodes had previously undergone thyroidectomy, neck dissection, and radioactive iodine ablation prior to retropharyngeal resection. Retropharyngeal lymphadenectomy via transoral robotic surgery was performed for both patients: for the first, the oropharyngeal wound was left to heal by secondary intention, while for the other patient, simple pharyngeal flap closure was performed. Retropharyngeal lymph node dissections were successfully carried out using a transoral robotic retropharyngotomy with the da Vinci surgical robotic system. Both patients tolerated the procedure well. One patient did developed temporary dysphagia which resolved with conservative measures, not requiring a feeding tube. We report the first two cases of transoral robot-assisted resection of thyroid cancer metastatic to the retropharyngeal lymph nodes. The technique is feasible, minimally invasive, and appears to be as safe as conventional surgical methods in achieving the goals of management of regionally metastatic disease.

    View details for DOI 10.1007/s11701-011-0269-4

    View details for PubMedID 27637712

  • ASPIRATION AFTER SUPRACRICOID PARTIAL LARYNGECTOMY: INCIDENCE, RISK FACTORS, MANAGEMENT, AND OUTCOMES HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Benito, J., Holsinger, F. C., Perez-Martin, A., Garcia, D., Weinstein, G. S., Laccourreye, O. 2011; 33 (5): 679-685

    Abstract

    The aim of this study was to evaluate the incidence, risk factors, management, and outcome of postoperative aspiration in patients managed with a supracricoid partial laryngectomy (SCPL) for selected invasive squamous carcinoma of the larynx.In all, 457 patients underwent SCPL at an academic, tertiary referral care center, 1975-2000. The incidence of aspiration defined in accord with Pearson's scale was recorded. Univariate and multivariate analyses were performed for potential statistical relation with various variables. The management and outcome of aspiration are presented.Normal swallowing without aspiration was noted in 259 patients (58.9%). Grades 1, 2, and 3 aspiration occurred in 87, 48, and 53 patients (19%, 10.5%, and 11.6%), respectively. A significant relationship was noted between aspiration and increased age, performing cricohyoidopexy, not repositioning the pyriform sinuses, and resecting an arytenoid cartilage. A prediction model, based on multinomial logistic regression, found that the probability that severe aspiration cases (grade 2-3) exceeded the subclinical ones (grade 0-1) occurred only when a cricohyoidopexy with partial or total arytenoid resection was performed in patients >70 years of age (p = .0000001). Management of aspiration required a temporary gastrostomy, a permanent gastrostomy, and a completion total laryngectomy in 65, 3, and 7 of 188 patients (34.5%, 1.6%, and 3.7%, respectively) who aspirated, and 65, 3, and 7 of 457 of the entire population (14.2%, 0.6%, and 1.5%, respectively). Aspiration-related death was not encountered in the current series.Aspiration after SCPL is a common but rarely severe event, with a low incidence for permanent gastrostomy or completion laryngectomy. Aspiration can be minimized with careful patient selection and precise surgical technique.

    View details for DOI 10.1002/hed.21521

    View details for Web of Science ID 000289379200012

    View details for PubMedID 20737502

  • Robot assisted transaxillary surgery (RATS) for the removal of thyroid and parathyroid glands SURGERY Landry, C. S., Grubbs, E. G., Morris, G. S., Turner, N. S., Holsinger, F. C., Lee, J. E., Perrier, N. D. 2011; 149 (4): 549-555

    Abstract

    Robotic assisted transaxillary surgery (RATS) is a minimally invasive approach for the removal of the thyroid and/or parathyroid glands through the axilla. This anatomically directed technique, popularized by Chung, eliminates a visible scar and affords excellent high definition optics of the cervical anatomy. We report an initial series of single access RATS in the U.S.The prospective endocrine surgery database at a tertiary care center was used to capture all patients who underwent RATS between October 2009 and March 2010. All procedures were performed using a single transaxillary incision.Fourteen operations were performed on 13 patients. Indications for RATS were indeterminate thyroid nodules in 11 patients, the need for completion thyroidectomy in 1 patient, and primary hyperparathyroidism in 2 patients. For patients who underwent robotic assisted thyroid lobectomy, the median thyroid nodule size was 2.1 cm (range, 0.8-2.8 cm), and the median body mass index was 25.33 (range, 21.3-34.4). Mean and median total operative times for robotic assisted thyroid lobectomies were 142 minutes and 137 minutes respectively (range, 113-192 minutes). Operative time for the 2 patients who underwent robotic assisted parathyroidectomy was 115 and 102 minutes. Minor complications occurred in 4 patients (28.5%), with no significant perioperative morbidity or mortality.RATS is feasible. We believe that further study of the RATS technique for removing thyroid lobes and parathyroid glands is warranted. This initial series suggests that careful, continued investigation is necessary prior to routine implementation into clinical practice across the U.S.

    View details for DOI 10.1016/j.surg.2010.08.014

    View details for Web of Science ID 000289017500011

    View details for PubMedID 20947113

  • Sinonasal and nasopharyngeal applications of the hand-held CO2 laser fiber INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Agarwal, G., Kupferman, M. E., Holsinger, F. C., Hanna, E. Y. 2011; 1 (2): 109-112

    Abstract

    Carbon dioxide (CO(2)) laser provides precision and excellent hemostasis, leading to healing with minimal discomfort and complications. In spite of the advantages, the application of CO(2) laser has been limited in the sinonasal region due to the difficulty in delivering laser energy to the deep, narrow, and confined spaces. The availability of flexible laser fibers and custom-designed hand pieces has rectified these limitations but, until this date, there are no data on their safety and efficacy profile.We conducted a retrospective chart review of patients who underwent sinonasal and nasopharyngeal surgery with a hand-held CO(2) laser at M.D. Anderson Cancer center between 2007 and 2009.Out of 12 patients, 3 patients had postradiotherapy adhesions, 2 patients had a recurrent sinonasal mucoepidermoid carcinoma and 1 patient each had a ganglioneuroblastoma of the nasopharynx involving the basisphenoid and clivus, recurrent spindle cell melanoma of the nasopharynx, juvenile nasopharyngeal angiofibroma, papilloma of the nasal cavity, pituitary adenoma, spindle cell lipoma of the nasopharynx, and intranasal Rosai-Dorfman disease. The CO(2) laser, along with conventional endoscopic techniques and instruments, was used at 6-12 W continuous mode, to excise the disease. Median blood loss was 88 mL with no laser-related complication in any patient.In sinonasal and nasopharyngeal regions, use of hand-held CO(2) laser fiber provides precision, excellent hemostasis and minimizes tissue manipulation thereby reducing risk to the underlying structures. Thus, it can be an important tool for rhinologists and skull-base surgeons, especially for revision and postradiotherapy cases.

    View details for DOI 10.1002/alr.20017

    View details for Web of Science ID 000308912300006

    View details for PubMedID 22287328

  • Initial experience with transoral robotic surgery using the da VinciA (R) surgical system HNO Simon, C., El-Baba, B., Albrecht, T., Holsinger, F. C., Plinkert, P. K. 2011; 59 (3): 261-265

    Abstract

    Transoral robotic surgery (TORS) can be considered an extension of transoral microscopic laser surgery. The microscope is replaced by an endoscope that provides the surgeon with a three-dimensional view of the surgical field. The surgeon operates from a console that controls the arms of the patient cart. These arms hold miniaturized surgical instruments that are transorally inserted into the patient, enabling tumor resection. Exposure is ensured by various mouth gags. The use of various endoscopes (0°, 30°), a work radius of 540° for instruments, and a zoom function provides significant advantages over the common transoral laser techniques. With this article we report our first experience with this technique and believe that it may provide significant advantages. However, thorough clinical testing in Germany is required before conclusions can be drawn.

    View details for DOI 10.1007/s00106-010-2254-z

    View details for Web of Science ID 000288556100007

    View details for PubMedID 21424364

  • Robotic Thyroid Surgery: An Initial Experience with North American Patients LARYNGOSCOPE Kuppersmith, R. B., Holsinger, F. C. 2011; 121 (3): 521-526

    Abstract

    To review the initial experience of gasless transaxillary robot-assisted endoscopic thyroid surgery in a series of patients and describe modifications of the technique for the North American patients, selection criteria, and other issues related to this technology.Retrospective review of the first 31 consecutive cases at a single institution.Thirty-one patients underwent robotic thyroid surgery. Twenty thyroid lobectomies and 11 total thyroidectomies were performed. Improvements in the length of time to perform components of the procedure were noted from the early group of cases to later group of cases. No major or permanent complications occurred.Robotic thyroid surgery is feasible in North American patients and can be safely performed. The procedure has potential complications and a definite learning curve exists for both surgeons and operating room staff. Training methods need to be validated to ensure safe adoption. More studies need to be performed to further evaluate the relative benefits of this technique.

    View details for DOI 10.1002/lary.21347

    View details for Web of Science ID 000287789400014

    View details for PubMedID 21344427

  • CRTC1/MAML2 fusion transcript in central mucoepidermoid carcinoma of mandible-diagnostic and histogenetic implications ANNALS OF DIAGNOSTIC PATHOLOGY Bell, D., Holsinger, C. F., El-Naggar, A. K. 2010; 14 (6): 396-401

    Abstract

    Intraosseous salivary gland carcinomas are extremely rare, comprising only 2% to 3% of all mucoepidermoid carcinomas (MECs) reported. The t(11;19) translocation and its CRTC1/MAML1 fusion transcript have been identified in MEC at different sites and are believed to be associated with the development of a subset of these tumors. However, the status of the fusion transcript has not been reported in intraosseous MEC. Here, we report 3 examples of central MEC of the mandible, including a case with a history of primary retromolar MEC. Reverse transcriptase-polymerase chain reaction and DNA sequencing analyses of the microdissected components of these tumors were used for the detection and verification of the fusion transcript. We identified, for the first time, the t(11;19) fusion gene transcript in central MEC, including in the previous primary retromolar MEC. No fusion transcript was detected in the second primary noncentral MEC or in another central MEC. The results indicate that central MEC can manifest the fusion transcript. This finding may have diagnostic and histogenetic roles in the future analysis of this entity.

    View details for DOI 10.1016/j.anndiagpath.2010.05.009

    View details for Web of Science ID 000284673200002

    View details for PubMedID 21074686

  • Prereferral Head and Neck Cancer Treatment Compliance With National Comprehensive Cancer Network Treatment Guidelines ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Lewis, C. M., Hessel, A. C., Roberts, D. B., Guo, Y. Z., Holsinger, F. C., Ginsberg, L. E., El-Naggar, A. K., Weber, R. S. 2010; 136 (12): 1205-1211

    Abstract

    to evaluate the prereferral treatment of patients referred to our tertiary care center with recurrent or persistent head and neck cancer for compliance with National Comprehensive Cancer Network (NCCN) guidelines.a prospective recruitment and retrospective chart review.the study included new patients identified at multidisciplinary treatment planning conference from October 1, 2008, to February 1, 2009, who had received prior treatment at an outside institution and presented to our department with recurrent or persistent disease.all facets of prior care were examined, including the time from initial symptoms to diagnosis and whether their prereferral treatment was compliant with or deviated from NCCN guidelines for head and neck cancer.a total of 566 consecutive new patients were identified, of whom 107 (18.9%) had persistent or recurrent disease. The average time from first presentation with initial symptoms to diagnosis among patients who presented with persistent disease was 23.8 weeks. Nearly half of the patients who presented with persistent or recurrent disease had either endocrine (21.5%) or cutaneous (24.2%) primary cancers, with the rest of the cases being distributed among 10 other sites. Of the patients who presented with recurrent or persistent disease, 43.0% had prereferral care that was noncompliant with NCCN guidelines. Of these patients, 58.7% had inadequate surgical management, 15.2% were treated for the wrong diagnosis, 10.9% received inadequate adjuvant therapy, 4.4% received inadequate radiotherapy, and 10.9% refused indicated recommended treatment.significant deviation from NCCN guidelines for head and neck cancer treatment was observed in the cohort of study patients. The failure to administer adjuvant therapy when indicated by NCCN guidelines is particularly concerning. Economic and noneconomic costs, including lost wages, cost of "do-over" therapy, and potentially diminished survival, are substantial. Measures to ensure that patients receive therapy according to guidelines should be a national priority.

    View details for Web of Science ID 000285323000006

    View details for PubMedID 21173369

  • CANDIDATE DOSIMETRIC PREDICTORS OF LONG-TERM SWALLOWING DYSFUNCTION AFTER OROPHARYNGEAL INTENSITY-MODULATED RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Schwartz, D. L., Hutcheson, K., Barringer, D., Tucker, S. L., Kies, M., Holsinger, F. C., Ang, K. K., Morrison, W. H., Rosenthal, D. I., Garden, A. S., Dong, L., Lewin, J. S. 2010; 78 (5): 1356-1365

    Abstract

    To investigate long-term swallowing function in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT), and to identify novel dose-limiting criteria predictive for dysphagia.Thirty-one patients with Stage IV oropharyngeal squamous carcinoma enrolled on a Phase II trial were prospectively evaluated by modified barium swallow studies at baseline, and 6, 12, and 24 months post-IMRT treatment. Candidate dysphagia-associated organs at risk were retrospectively contoured into original treatment plans. Twenty-one (68%) cases were base of tongue and 10 (32%) were tonsil. Stage distribution was T1 (12 patients), T2 (10), T3 (4), T4 (2), and TX (3), and N2 (24), N3 (5), and NX (2). Median age was 52.8 years (range, 42-78 years). Thirteen patients (42%) received concurrent chemotherapy during IMRT. Thirteen (42%) were former smokers. Mean dose to glottic larynx for the cohort was limited to 18 Gy (range, 6-39 Gy) by matching IMRT to conventional low-neck fields.Dose-volume constraints (V30 < 65% and V35 < 35% for anterior oral cavity and V55 < 80% and V65 < 30% for high superior pharyngeal constrictors) predictive for objective swallowing dysfunction were identified by univariate and multivariate analyses. Aspiration and feeding tube dependence were observed in only 1 patient at 24 months.In the context of glottic laryngeal shielding, we describe candidate oral cavity and superior pharyngeal constrictor organs at risk and dose-volume constraints associated with preserved long-term swallowing function; these constraints are currently undergoing prospective validation. Strict protection of the glottic larynx via beam-split IMRT techniques promises to make chronic aspiration an uncommon outcome.

    View details for DOI 10.1016/j.ijrobp.2009.10.002

    View details for Web of Science ID 000284987800010

    View details for PubMedID 20646872

  • Differential diagnosis of pediatric tumors of the nasal cavity and paranasal sinuses: A 45-year multi-institutional review ENT-EAR NOSE & THROAT JOURNAL Holsinger, F. C., Hafemeister, A. C., Hicks, M. J., Sulek, M., Huh, W. W., Friedman, E. M. 2010; 89 (11): 534-?

    Abstract

    We conducted a retrospective case-series review to identify the various diagnoses of neoplasms of the nasal cavity and paranasal sinuses in a pediatric population. Our study group was made up of 54 children-23 boys and 31 girls, aged 8 months to 16 years (mean: 9 yr). All patients had been diagnosed with a tumor of the nasal cavity or paranasal sinuses between Jan. 1, 1955, and Dec. 31, 1999, at one of four university-based, tertiary care referral centers. We compiled data on tumoral characteristics (location, size, and histopathology), morbidity and mortality, and rates of recurrence. Lesions included adnexal neoplasm, ameloblastic fibro-odontoma, basal cell carcinoma, benign fibrous histiocytoma, blue nevus, chondrosarcoma, compound nevus, epithelioma adenoides cysticum, esthesioneuroblastoma, Ewing sarcoma, fibrosarcoma, giant cell granuloma, granulocytic sarcoma, hemangioma, hemangiopericytoma, Langerhans cell histiocytosis, lymphangioma, lymphoma, melanoma, neuroblastoma, neurofibroma, ossifying osteofibroma, osteochondroma, osteosarcoma, port wine stain, rhabdomyosarcoma, Spitz nevus, and xanthogranuloma. To the best of our knowledge, this is the largest such study of its kind to date. We believe that the large size of this study and the data on disease incidence will allow clinicians to be better informed of the differential diagnosis of neoplasms of the nasal cavity and paranasal sinuses in the pediatric population.

    View details for Web of Science ID 000284921400007

    View details for PubMedID 21086277

  • A Shifting Paradigm for Patients with Head and Neck Cancer: Transoral Robotic Surgery (TORS) ONCOLOGY-NEW YORK Bhayani, M. K., Holsinger, F. C., Lai, S. Y. 2010; 24 (11): 1010-1015

    Abstract

    The evolution of surgical oncologic technology has moved toward reducing patient morbidity without compromising oncologic resection. In head and neck surgery, organ-preserving techniques have paved the way for the development of transoral techniques that remove tumors of the upper aerodigestive tract without external incisions and potentially spare the patient adjuvant treatment. The introduction of transoral robotic surgery (TORS) improves upon current transoral techniques to the oropharynx and supraglottis. This review will report on the evolution of robotic-assisted surgery: We will cover its applications in head and neck surgery by examining early oncologic and functional outcomes, training of surgeons, costs, and future directions.

    View details for Web of Science ID 000293341200006

    View details for PubMedID 21155450

  • SIMPLE CAROTID-SPARING INTENSITY-MODULATED RADIOTHERAPY TECHNIQUE AND PRELIMINARY EXPERIENCE FOR T1-2 GLOTTIC CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rosenthal, D. I., Fuller, C. D., Barker, J. L., Mason, B., Garcia, J. A., Lewin, J. S., Holsinger, F. C., Stasney, C. R., Frank, S. J., Schwartz, D. L., Morrison, W. H., Garden, A. S., Ang, K. K. 2010; 77 (2): 455-461

    Abstract

    To investigate the dosimetry and feasibility of carotid-sparing intensity-modulated radiotherapy (IMRT) for early glottic cancer and to report preliminary clinical experience.Digital Imaging and Communications in Medicine radiotherapy (DICOM-RT) datasets from 6 T1-2 conventionally treated glottic cancer patients were used to create both conventional IMRT plans. We developed a simplified IMRT planning algorithm with three fields and limited segments. Conventional and IMRT plans were compared using generalized equivalent uniform dose and dose-volume parameters for in-field carotid arteries, target volumes, and organs at risk. We have treated 11 patients with this simplified IMRT technique.Intensity-modulated radiotherapy consistently reduced radiation dose to the carotid arteries (p < 0.05) while maintaining the clinical target volume coverage. With conventional planning, median carotid V35, V50, and V63 were 100%, 100%, and 69.0%, respectively. With IMRT planning these decreased to 2%, 0%, and 0%, respectively (p < 0.01). Radiation planning and treatment times were similar for conventional radiotherapy and IMRT. Treatment results have been excellent thus far.Intensity-modulated radiotherapy significantly reduced unnecessary radiation dose to the carotid arteries compared with conventional lateral fields while maintaining clinical target volume coverage. Further experience and longer follow-up will be required to demonstrate outcomes for cancer control and carotid artery effects.

    View details for DOI 10.1016/j.ijrobp.2009.04.061

    View details for Web of Science ID 000278167500019

    View details for PubMedID 19679406

  • Serum Signature of Hypoxia-Regulated Factors Is Associated with Progression after Induction Therapy in Head and Neck Squamous Cell Cancer MOLECULAR CANCER THERAPEUTICS Byers, L. A., Holsinger, F. C., Kies, M. S., William, W. N., El-Naggar, A. K., Lee, J. J., Hu, J., Lopez, A., Tran, H. T., Yan, S., Du, Z., Ang, K. K., Glisson, B. S., Raso, M. G., Wistuba, I. I., Myers, J. N., Hong, W., Papadimitrakopoulou, V., Lippman, S. M., Heymach, J. V. 2010; 9 (6): 1755-1763

    Abstract

    Tumor hypoxia regulates many cytokines and angiogenic factors (CAF) and is associated with worse prognosis in head and neck squamous cell cancer (HNSCC). Serum CAF profiling may provide information regarding the biology of the host and tumor, prognosis, and response to therapy. We investigated 38 CAFs in HNSCC patients receiving induction therapy on a phase II trial of carboplatin, paclitaxel, and cetuximab. CAFs were measured by multiplex bead assay and enzyme-linked immunosorbent assay in 32 patients. Baseline and postinduction CAF levels were correlated with disease progression (PD) and human papilloma virus (HPV) status by Wilcoxon rank sum test. Baseline levels of eight hypoxia-regulated CAFs (the "high-risk signature" including vascular endothelial growth factor, interleukins 4 and 8, osteopontin, growth-related oncogene-alpha, eotaxin, granulocyte-colony stimulating factor, and stromal cell-derived factor-1alpha) were associated with subsequent PD. Elevation in >or=6 of 8 factors was strongly associated with shorter time to progression (P = 0.001) and was 73% specific and 100% sensitive for PD. Increasing growth-related oncogene-alpha from baseline to week 6 was also associated with PD. Progression-free and overall survival were shorter in patients with HPV-negative tumors (P = 0.012 and 0.046, respectively), but no individual CAF was associated with HPV status. However, among 14 HPV-negative patients, the high-risk CAF signature was seen in all 6 patients with PD, but only 2 of 14 without PD. In conclusion, serum CAF profiling, particularly in HPV-negative patients, may be useful for identifying those at highest risk for recurrence.

    View details for DOI 10.1158/1535-7163.MCT-09-1047

    View details for Web of Science ID 000278569200027

    View details for PubMedID 20530716

  • CURRENT CONCEPTS AND NEW HORIZONS IN CONSERVATION LARYNGEAL SURGERY: AN IMPORTANT PART OF MULTIDISCIPLINARY CARE HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Holsinger, F. C., Nussenbaum, B., Nakayama, M., Saraiya, S., Sewnaik, A., Ark, N., Ferris, R. L., Tufano, R. P., McWhorter, A. J. 2010; 32 (5): 656-665

    Abstract

    New surgical techniques in conservation laryngeal surgery (CLS) have emerged over the past 20 years and now offer a viable "organ-preservation" approach for patients with laryngeal cancer. We review traditional and new CLS procedures and summarize the functional and oncologic outcomes of CLS in both primary and salvage settings.We searched the literature by accessing Medline for articles from 1991 to 2007 on primary or salvage surgery (open and transoral) for laryngeal neoplasms.Our review of the literature suggests that proper selection of patients for CLS can yield long-term local control rates equal to or better than those obtained using radiation-based approaches. We believe that CLS should be directly compared with radiation or chemoradiation to further refine the indications for each kind of treatment in cases of primary and recurrent/refractory laryngeal cancer.

    View details for DOI 10.1002/hed.21208

    View details for Web of Science ID 000277347100015

    View details for PubMedID 19672871

  • The Emergence of Endoscopic Head and Neck Surgery CURRENT ONCOLOGY REPORTS Holsinger, F. C., Sweeney, A. D., Jantharapattana, K., Salem, A., Weber, R. S., Chung, W. Y., Lewis, C. M., Grant, D. G. 2010; 12 (3): 216-222

    Abstract

    Endoscopic and minimally invasive techniques represent a natural evolution for the discipline of head and neck surgery. Endoscopic head and neck surgery (eHNS) encompasses transoral laser microsurgery, transoral robotic surgery, as well as video-assisted and robotic surgery of the neck and thyroid. In the next 5 years, with robotic surgery and laser technology as a common platform, we foresee the development and widespread use of eHNS procedures, via transoral and transaxillary approaches.

    View details for DOI 10.1007/s11912-010-0097-0

    View details for Web of Science ID 000287499800011

    View details for PubMedID 20425082

  • TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma ONCOGENE Kupferman, M. E., Jiffar, T., El-Naggar, A., Yilmaz, T., Zhou, G., Xie, T., Feng, L., Wang, J., Holsinger, F. C., Yu, D., Myers, J. N. 2010; 29 (14): 2047-2059

    Abstract

    Head and neck squamous cell carcinoma (HNSCC) remains a significant public health problem, accounting for over 5% of all cancer-related deaths, and these deaths primarily result from metastatic disease. The molecular processes involved in HNSCC pathogenesis and progression are poorly understood, and here we present experimental evidence for a direct role of the cell surface receptor tyrosine kinase, TrkB, in HNSCC tumor progression. Using immunohistochemical analysis and transcriptional profiling of archival HNSCC tumor specimens, we found that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are expresses in greater than 50% of human HNSCC tumors, but not in normal upper aerodigestive tract (UADT) epithelia. Studies with HNSCC cell lines reveal that in vitro stimulation with BDNF, the ligand for TrkB, upregulates the migration and invasion of HNSCC cells, and both transient and stable suppressions of TrkB result in significant abrogation of constitutive and ligand-mediated migration and invasion. Furthermore, enforced overexpression of TrkB results in altered expression of molecular mediators of epithelial-to-mesenchymal transition (EMT), including downregulation of E-cadherin and upregulation of Twist. Using an in vivo mouse model of HNSCC, we were able to show that downregulation of TrkB suppresses tumor growth. These results directly implicate TrkB in EMT and the invasive behavior of HNSCC, and correlate with the in vivo overexpression of TrkB in human HNSCC. Taken together, these data suggest that the TrkB receptor may be a critical component in the multi-step tumor progression of HNSCC, and may be an attractive target for much needed new therapies for this disease.

    View details for DOI 10.1038/onc.2009.486

    View details for Web of Science ID 000276402800004

    View details for PubMedID 20101235

  • Robotic Thyroidectomy: Operative Technique Using a Transaxillary Endoscopic Approach Without CO2 Insufflation OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Holsinger, F. C., Terris, D. J., Kuppersmith, R. B. 2010; 43 (2): 381-?

    Abstract

    In the last 20 years, there has been a significant increase in the diagnosis of benign and malignant thyroid tumors. With improved ultrasound technology and better access to sonographic imaging, many tumors are identified at earlier stages. Consequently, there has been an evolution in surgical technique, moving toward minimally invasive approaches. This article describes the technique of robotic thyroidectomy via transaxillary endoscopic approach without CO(2) insufflation.

    View details for DOI 10.1016/j.otc.2010.01.007

    View details for Web of Science ID 000279254100013

    View details for PubMedID 20510721

  • Transoral Robotic Free Flap Reconstruction of Oropharyngeal Defects: A Preclinical Investigation Pan American Robotic Oncology Symposium Selber, J. C., Robb, G., Serletti, J. M., Weinstein, G., Weber, R., Holsinger, F. C. LIPPINCOTT WILLIAMS & WILKINS. 2010: 896–900

    View details for DOI 10.1097/PRS.0b013e3181cb6568

    View details for Web of Science ID 000275714700017

    View details for PubMedID 20195117

  • Induction Chemotherapy and Cetuximab for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Results From a Phase II Prospective Trial JOURNAL OF CLINICAL ONCOLOGY Kies, M. S., Holsinger, F. C., Lee, J. J., William, W. N., Glisson, B. S., Lin, H. Y., Lewin, J. S., Ginsberg, L. E., Gillaspy, K. A., Massarelli, E., Byers, L., Lippman, S. M., Hong, W. K., El-Naggar, A. K., Garden, A. S., Papadimitrakopoulou, V. 2010; 28 (1): 8-14

    Abstract

    PURPOSE To determine the potential efficacy of combining cetuximab with chemotherapy in patients with advanced nodal disease, we conducted a phase II trial with induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m(2) and carboplatin (area under the curve = 2) with cetuximab 400 mg/m(2) in week 1 and then 250 mg/m(2) (PCC). PATIENTS AND METHODS Forty-seven previously untreated patients (41 with oropharynx primaries; 33 men, 14 women; median age, 53 years; performance status of 0 or 1) with squamous cell carcinoma of the head and neck (SCCHN; T1-4, N2b/c/3) were treated and evaluated for clinical and radiographic response. After ICT, patients underwent risk-based local therapy, which consisted of either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis. Results After induction PCC, nine patients (19%) achieved a complete response, and 36 patients (77%) achieved a partial response. The most common grade 3 or 4 toxicity was skin rash (45%), followed by neutropenia (21%) without fever. At a median follow-up time of 33 months, locoregional or systemic disease progression was observed in six patients. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 87% (95% CI, 78% to 97%) and 91% (95% CI, 84% to 99%), respectively. Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P = .012) and OS (P = .046). CONCLUSION ICT with weekly PCC followed by risk-based local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV-positive tumors have an excellent prognosis.

    View details for DOI 10.1200/JCO.2009.23.0425

    View details for Web of Science ID 000273103900004

    View details for PubMedID 19917840

  • Robotic Axillary Thyroidectomy: Multi-Institutional Clinical Experience with the daVinci Seybt, M., Kuppersmith, R. B., Holsinger, C., Terris, D. J. WILEY-BLACKWELL. 2010: S182–S182

    View details for DOI 10.1002/lary.21646

    View details for Web of Science ID 000286438600058

    View details for PubMedID 21225780

  • Secondary Tracheoesophageal Puncture With In-Office Transnasal Esophagoscopy ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LeBert, B., McWhorter, A. J., Kunduk, M., Walvekar, R. R., Lewin, J. S., Hutcheson, K. A., Barringer, D. A., Hessel, A. C., Holsinger, F. C. 2009; 135 (12): 1190-1194

    Abstract

    To evaluate the outcomes of voice restoration using office-based transnasal esophagoscopy (TNE) to guide placement of the secondary tracheoesophageal puncture (TEP).Retrospective chart review.Two tertiary care medical centers.The study included 39 patients who underwent the TNE-TEP procedure from January 2004 to December 2008.Clinical, demographic, and TE speech-related data were recorded to examine the ease, efficiency, complications, and speech-related outcomes.Among 39 patients identified, the average age was 65 years (age range, 47-83 years), with 32 male (82%) and 7 female (16%) patients. Twenty-five patients (64%) underwent total laryngectomy; 8 (21%) underwent total laryngectomy with partial pharyngectomy; and 14 (36%) underwent microvascular flap reconstruction. The overall success rate of secondary TNE-assisted TEP placement was 97% (n = 38), with 1 unsuccessful attempt. There was no statistically significant correlation found between patients having undergone radiation therapy (either before or after oncologic resection) or a cricopharyngeal myotomy and successful TEP placement, type of reconstruction used to close the pharyngeal defect when compared with the difficulty in the placement of the TEP, development of complications associated with TEP placement, use of the TEP prosthesis, or speech intelligibility at the last follow-up visit. Thirty-one patients (79%) were still using their TEP prosthesis for speech at the last follow-up visit. Of the patients reviewed, 28 (72%) had understandable TE speech.In-office TNE-assisted TEP placement can safely be performed, with excellent speech outcomes. Reconstruction with musculocutaneous or microvascular free-tissue transfer did not limit our ability to place secondary TEPs with TNE.

    View details for Web of Science ID 000272626200001

    View details for PubMedID 20026814

  • Advanced approaches for thyroid surgery OTOLARYNGOLOGY-HEAD AND NECK SURGERY Kuppersmith, R. B., Salem, A., Holsinger, F. C. 2009; 141 (3): 340-342

    Abstract

    Over the past several years, new surgical approaches to the thyroid have been described, and efforts to further refine thyroid surgery continue. These new approaches can be classified by the anatomic location that access is obtained and whether CO(2) insufflation is necessary for the procedure to be performed. While these new approaches provide the potential for exciting innovation, more work should be done to refine some of these techniques and study the implications of adopting them from the perspective of patient outcomes and cost.

    View details for DOI 10.1016/j.otohns.2009.05.029

    View details for Web of Science ID 000269604300007

    View details for PubMedID 19716010

  • Transantral robotic access to the pituitary gland OTOLARYNGOLOGY-HEAD AND NECK SURGERY Kupferman, M., DeMonte, F., Holsinger, F. C., Hanna, E. 2009; 141 (3): 413-415

    View details for DOI 10.1016/j.otohns.2009.05.028

    View details for Web of Science ID 000269604300020

    View details for PubMedID 19716023

  • Platin-Based Exclusive Chemotherapy for Selected Patients With Squamous Cell Carcinoma of the Larynx and Pharynx 43rd Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Holsinger, F. C., Lin, H. Y., Bassot, V., Laccourreye, O. WILEY-BLACKWELL. 2009: 3909–18

    Abstract

    The current study was conducted to determine the long-term outcomes of patients with squamous cell carcinoma of the larynx and pharynx who were treated with platin-based exclusive chemotherapy (EC) after they achieved a complete clinical response (CCR) to induction chemotherapy.One hundred forty-two who achieved a CCR after platin-based induction chemotherapy were treated exclusively with additional chemotherapy, and 98.6% were followed for a minimum of 3 years or until death. Thirty-five patients had >10 years of follow-up.The survival rates at 1 year and 5 years were 95.8% and 61.2%, respectively. The main causes of death were metachronous second primary tumors (n = 27) and intercurrent disease (n = 21). Death related to EC was not encountered, and only 2 patients (1.4%) had grade 4 toxicity. In multivariate analysis, primary tumor arising outside the glottic larynx (P = .0001) and a Charlson comorbidity index >1 (P = .0001) were associated with a statistically significant reduction in survival. The 1-year and 5-year Kaplan-Meier local control estimates were 76.1% and 50.7%, respectively. Salvage treatment resulted in an observed final local control rate of 93% that varied from 97.2% in patients who had glottic cancer to 88.7% in patients who had tumor originating from other sites (P = .097). Combined chemotherapy with cisplatin and 5-fluorouracil (PF) allowed for the successful modulation of local therapy in 54.9% of patients.For selected patients, EC may provide long-term, durable disease control. For patients who developed recurrent disease after EC, this approach did not diminish survival and maintained function in the majority of patients. Future work should be directed toward select markers of response to PF chemotherapy with which to identify those patients who are suited optimally for this approach.

    View details for DOI 10.1002/cncr.24477

    View details for Web of Science ID 000269230700016

    View details for PubMedID 19551883

  • Extended Lateral Pharyngotomy for Selected Squamous Cell Carcinomas of the Lateral Tongue Base ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Laccourreye, O., Seccia, V., Menard, M., Garcia, D., Vacher, C., Holsinger, F. C. 2009; 118 (6): 428-434

    Abstract

    In a retrospective review of an inception cohort of 26 patients with an isolated, previously untreated, moderately to well-differentiated invasive squamous cell carcinoma of the lateral tongue base, consecutively managed with an extended lateral pharyngotomy approach at a single tertiary referral care center, the authors review the key surgical points, highlight the potential technical pitfalls, and document the complications and long-term functional and oncological outcomes in terms of survival and local control.The adjunctive measures included induction chemotherapy, ipsilateral neck dissection, and postoperative radiotherapy, used in 96.1%, 96.1%, and 38.5% of patients, respectively. All patients but 2 were followed for at least 5 years or until death (maximum, 158 months).The significant postoperative complications included pharyngocutaneous fistula in 3 patients (11.5%) and hemorrhage requiring reoperation, partial flap necrosis, and pneumonia from aspiration in 1 patient (3.8%) each. In univariate analysis, no significant statistical relationship was noted between the significant postoperative complications noted and the variables under analysis. Overall, successful oral alimentation was achieved in 100% of patients by the first postoperative month without gastrostomy, tracheotomy, or completion total laryngectomy. There were no intraoperative or perioperative deaths. The main causes of death were metachronous second primary tumor, intercurrent disease, and distant metastasis, resulting in 84.6%, 64%, and 46.9% 1-, 3-, and 5-year Kaplan-Meier actuarial survival estimates, respectively. Two patients (7.6%) had local recurrence, resulting in 100%, 86.7%, and 86.7% 1-, 3-, and 5-year Kaplan-Meier actuarial local control estimates, respectively. As a function of T stage, the 3- and 5-year actuarial local control estimates were 100%, 87.5%, and 90.9% in patients with tumors classified as T1, T2, and T3-T4a, respectively.Such results suggest that extended lateral pharyngotomy should be integrated among the various conservative treatment options available to patients with selected carcinomas of the lateral tongue base.

    View details for Web of Science ID 000266952500005

    View details for PubMedID 19663374

  • Durable Long-Term Remission With Chemotherapy Alone for Stage II to IV Laryngeal Cancer JOURNAL OF CLINICAL ONCOLOGY Holsinger, F. C., Kies, M. S., Diaz, E. M., Gillenwater, A. M., Lewin, J. S., Ginsberg, L. E., Glisson, B. S., Garden, A. S., Ark, N., Lin, H. Y., Lee, J. J., El-Naggar, A. K., Hong, W. K., Shin, D. M., Khuri, F. R. 2009; 27 (12): 1976-1982

    Abstract

    For patients with stage II to IV laryngeal cancer, radiation therapy (RT) either alone or with concurrent chemotherapy provides the highest rate of organ preservation but can be associated with functional impairment. Thus, we studied the use of induction chemotherapy with or without conservation laryngeal surgery (CLS). Our objectives were to study the sensitivity of laryngeal cancer to platinum-based chemotherapy alone and to highlight the efficacy of CLS in this setting.Thirty-one previously untreated patients with laryngeal cancer (T2-4, N0-1, M0), who were resectable with CLS, were enrolled. Patients received three to four cycles of paclitaxel, ifosfamide, and cisplatin (TIP) chemotherapy, and response was assessed histologically. Patients with partial response (PR) proceeded to CLS. Patients achieving pathologic complete response (pCR) received an additional three cycles of TIP and no other treatment.Thirty patients were assessable for response. With TIP chemotherapy alone, 11 patients (37%) achieved pCR, 10 of whom (33%) remain alive with durable disease remission and no evidence of recurrence over a median follow-up time of 5 years. Nineteen patients (63%) treated with TIP alone achieved PR. The overall laryngeal preservation (LP) rate was 83%, and only five patients (16%) required postoperative RT. No patient required a gastrostomy tube or tracheotomy.Chemotherapy alone in selected patients with T2-4, N0-1 laryngeal cancer can provide durable disease remission at 5 years. For patients with PR, CLS provides a high rate of LP. This prospective study suggests that chemotherapy alone may cure selected patients with laryngeal cancer, warranting further prospective investigation.

    View details for DOI 10.1200/JCO.2008.17.6396

    View details for Web of Science ID 000266194700012

    View details for PubMedID 19289628

  • Clinicopathological Analyses of Fifty Supracricoid Laryngectomized Specimens: Evidence Base Supporting Minimal Margins ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES Nakayama, M., Holsinger, C., Okamoto, M., Seino, Y., Miyamoto, S., Takeda, M., Yokobori, S., Masaki, T., Hayashi, S. 2009; 71 (6): 305-311

    Abstract

    Supracricoid laryngectomy (SCL) is a reliable laryngeal preservation surgery. However, close surgical margins are often inevitable. Based on clinicopathological analyses of supracricoid laryngectomized specimens, we evaluated the evidence base supporting minimal margins.The distance between tumor edge and resected margin was measured macro- and microscopically at the anterior, posterior, superior and inferior edges, using 50 surgical specimens. The margins were correlated with pathological T staging and the prognoses.The anterior and posterior margins were the shortest, and the superior margin was the longest. The inferior margin was the only edge at which a positive margin was encountered. Cancer extending 10 mm below the glottal free edge significantly decreased the inferior margin.The surgical potential of SCL with cricohyoidoepiglottopexy was confirmed to be able to cope with tumor extensions showing margins of a few millimeters at the anterior, posterior and superior ends. Accurate assessment and management at the inferior margin is the key to stable local control.

    View details for DOI 10.1159/000261836

    View details for Web of Science ID 000273777100002

    View details for PubMedID 19940534

  • Maxillary osteosarcoma associated with a dental implant - Report of a case and review of the literature regarding implant-related sarcomas JOURNAL OF THE AMERICAN DENTAL ASSOCIATION McGuff, H. S., Heim-Hall, J., Holsinger, F. C., Jones, A. A., O'Dell, D. S., Hafemeister, A. C. 2008; 139 (8): 1052-1059

    Abstract

    The development of malignant neoplasms has been reported as a rare complication of the use of implanted biomaterials. The majority of these cases have been sarcomas related to orthopedic hardware. The authors present the first reported case of a sarcoma arising in association with a dental implant.A 38-year-old woman developed a low-grade chondroblastic osteosarcoma of the right maxilla 11 months after receiving a titanium dental implant. She was treated with systemic chemotherapy and then a maxillary resection. As of this publication, 47 months later, she is alive and disease-free.The use of endosseous implants has been associated with a low risk for the development of cancer. As the use of dental implants continues to expand, dentists need to be aware of this rare but devastating complication.

    View details for Web of Science ID 000258430500015

    View details for PubMedID 18682619

  • Outcomes after radiotherapy for basaloid squamous cell carcinoma of the head and neck - A case-control study 17th Annual Meeting of the French-Society-of-Radiation-Oncology Thariat, J., Ahamad, A., El-Naggar, A. K., Williams, M. D., Holsinger, F. C., Glisson, B. S., Allen, P. K., Morrison, W. H., Weber, R. S., Ang, K. K., Garden, A. S. WILEY-BLACKWELL. 2008: 2698–2709

    Abstract

    Basaloid squamous cell carcinoma (BSCC) is an uncommon, high-grade variant of squamous cell carcinoma (SCC) of the head and neck. Its poorer prognosis compared with common SCC remains controversial. The authors investigated the outcomes of patients with BSCC who received radiotherapy and compared them with the outcomes of patients with SCC.From 1994 to 2004, 1007 patients received radiotherapy for head and neck carcinoma with lymph node involvement. The histologic types consisted of 51 BSCC, 431 poorly differentiated SCC (PSCC), and 525 well or moderately differentiated SCC (WMSCC). A case-control analysis was performed with BSCC matched against both PSCC and WMSCC to compare disease-control and survival rates.Patients with BSCC received treatment modalities similar to those received by patients with SCC: They received induction chemotherapy (12%) or concurrent chemotherapy (33%), and a median radiation dose of 70 Gray. Posttreatment viable tumor was present in 44%, 13%, and 28% of neck dissection specimens from patients with BSCC, PSCC, and WMSCC, respectively. The 5-year disease-free survival rates (63%, 77%, and 76%, respectively) and overall survival rates (85%, 70%, and 71%, respectively) demonstrated no statistically significant differences for BSCC, PSCC, or WMSCC, respectively.In this study, a poorer prognosis could not be demonstrated for irradiated patients with BSCC compared with either PSCC or WMSCC. All patients in this study had positive lymph node status, and the majority of patients (84%) had oropharyngeal cancer. The BSCC cohort did have a relatively high rate of viable tumor in their posttreatment neck dissections, and they had a relatively high rate of distant disease. On the basis of the high rate of lung metastases and the possibility of efficient salvage, the authors recommend obtaining a chest computed tomography scan during initial staging and follow-up.

    View details for DOI 10.1002/cncr.23486

    View details for Web of Science ID 000256580200011

    View details for PubMedID 18429002

  • Horizontal supraglottic partial laryngectomy for selected squamous carcinoma of the vallecula HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Laccourreye, L., Garcia, D., Menard, M., Brasnu, D., Laccourreye, O., Holsinger, F. C. 2008; 30 (6): 756-764

    Abstract

    Our aim was to determine the incidence of local control in patients with selected squamous carcinoma of the vallecula treated with horizontal supraglottic laryngectomy; to analyze the consequences of local recurrence in terms of nodal recurrence, distant metastasis, survival, causes of death, overall local control, and laryngeal preservation; and to identify any clinical factors predictive of these outcomes.This was a retrospective nonrandomized case series in a university teaching hospital. An inception cohort of 95 previously untreated patients were followed until death or for a minimum of 5 years. According to the 2002 Union Internationale Contre le Cancer (UICC) staging classification system, the tumor was classified as T1, T2, and T3 in 13, 60, and 22 patients, respectively, while disease in 67 patients was considered to be in stages III to IV. All patients underwent a horizontal partial supraglottic partial laryngectomy. Ninety-four patients had an associated neck dissection. An induction chemotherapy regimen was used in 91 patients; postoperative radiation therapy was given for 49 patients. The main outcome measures were local recurrence, nodal recurrence, distant metastasis, and survival.The 1-, 3-, and the 5-year actuarial survival estimates were 86.3%, 64.2%, and 47.4%, respectively. Overall, the main causes of death were as follows: metachronous second primary tumor (47.2% of patients), intercurrent disease (16.7%), distant metastasis (15.3%), local recurrence (6.3%), and nodal recurrence, (4.2%). The 1-, 3-, and 5-year actuarial local recurrence rates were 4.5%, 11%, and 11%, respectively. Nine patients developed a local recurrence; 3 were successfully salvaged. Using multivariate analysis, no single variable was found to increase the risk for local recurrence. The overall laryngeal preservation rate and local control rate were 89.5% (85/95) and 93.4% (89/95), respectively. Local recurrence was associated with a significant increase in nodal recurrence (p <.04) and distant metastasis (p = .03).Based on this experience, horizontal partial supraglottic laryngectomy appears to be a valid approach for functional organ-preservation in patients with selected T1-T3 SCC of the vallecula.

    View details for DOI 10.1002/hed.20780

    View details for Web of Science ID 000256537900010

    View details for PubMedID 18286490

  • Functional analysis of swallowing outcomes after supracricoid partial laryngectomy HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Lewin, J. S., Hutcheson, K. A., Barringer, D. A., May, A. H., Roberts, D. B., Holsinger, C., Diaz, E. M. 2008; 30 (5): 559-566

    Abstract

    In this study, we analyzed swallowing recovery after supracricoid partial laryngectomy (SCPL).We retrospectively reviewed 27 patients treated with SCPL (September 1997 to March 2005). We evaluated recovery course, nutritional outcomes, and swallowing using objective analysis. Modified barium swallow (MBS) study results identified swallowing physiology and therapeutic effectiveness.Average length of hospitalization was 7.7+/-9.2 days; time to decannulation was 5.3+/-8.2 weeks. The most common complications included pneumonia and subcutaneous emphysema (26%). Twenty-two patients had MBS studies, in which initially, all patients aspirated due to neoglottic incompetency, and impaired base of tongue and laryngeal movements. Although aspiration rates did not change significantly over time, use of appropriately selected swallowing strategies effectively protected the airway (p= .0365). Ultimately, 81% of patients returned to complete oral intake with median tube removal at 9.4 weeks.SCPL produces severe dysphagia initially. Our findings suggest that objective swallowing assessment is important for return to oral nutrition after SCPL.

    View details for DOI 10.1002/hed.20738

    View details for Web of Science ID 000255578300001

    View details for PubMedID 18098304

  • Recent advances in thyroid cancer. In brief. Current problems in surgery Grubbs, E. G., Rich, T. A., Li, G., Sturgis, E. M., Younes, M. N., Myers, J. N., Edeiken-Monroe, B., Fornage, B. D., Monroe, D. P., Staerkel, G. A., Williams, M. D., Waguespack, S. G., Hu, M. I., Cote, G., Gagel, R. F., Cohen, J., Weber, R. S., Anaya, D. A., Holsinger, F. C., Perrier, N. D., Clayman, G. L., Evans, D. B. 2008; 45 (3): 149-151

    View details for DOI 10.1067/j.cpsurg.2007.12.008

    View details for PubMedID 18346476

  • Swing of the Pendulum: Optimizing Functional Outcomes in Larynx Cancer CURRENT ONCOLOGY REPORTS Holsinger, F. C. 2008; 10 (2): 170-175

    Abstract

    For years, total laryngectomy was the only treatment option for patients with intermediate to advanced laryngeal cancer. Over the past two decades, great progress has been made in the management of this disease, with multimodality approaches aimed at laryngeal preservation reshaping the treatment landscape. In the era of chemoradiation, greater focus and attention are now directed toward functional laryngeal preservation--not simply "organ preservation." The continued development and integration of new treatment approaches, including organ preservation surgery (eg, transoral minimally invasive surgery of the head and neck, supracricoid partial laryngectomy), intensity-modulated radiotherapy, and targeted molecular therapies, offer the potential to improve clinical outcomes, function, and quality of life. Incorporation of these new approaches advances the concept of personalized medicine, with treatment strategies tailored to the circumstances and future of each patient.

    View details for Web of Science ID 000207842200012

    View details for PubMedID 18377831

  • Recent advances in thyroid cancer CURRENT PROBLEMS IN SURGERY Anonymous 2008; 45 (3): 156-?

    View details for DOI 10.1067/j.cpsurg.2007.12.010

    View details for Web of Science ID 000254483800002

    View details for PubMedID 18346477

  • Videos in clinical medicine. Examination of the larynx and pharynx. New England journal of medicine Holsinger, F. C., Kies, M. S., Weinstock, Y. E., Lewin, J. S., Hajibashi, S., Nolen, D. D., Weber, R., Laccourreye, O. 2008; 358 (3)

    View details for DOI 10.1056/NEJMvcm0706392

    View details for PubMedID 18199857

  • Management of locally invasive well-differentiated thyroid cancer SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA Ark, N., Zemo, S., Nolen, D., Holsinger, E. C., Weber, R. S. 2008; 17 (1): 145-?

    Abstract

    Thyroid carcinoma invasion of the aerodigestive tract and recurrent laryngeal nerve (RLN) are important factors with increase in morbidity and mortality. Primary treatment is surgery; the decision about the extent of surgery is difficult, because preserving function is as essential as removal of the tumor. This article discusses the literature relating to the assessment of disease, surgical management, and adjuvant therapy for invasive thyroid cancer of the aerodigestive tract and RLN and makes suggestions based on the authors' experience.

    View details for DOI 10.1016/j.soc.2007.10.009

    View details for Web of Science ID 000252980700009

    View details for PubMedID 18177804

  • Robotic endoscopic surgery of the skull base Annual Meeting of the American-Head-and-Neck-Society Hanna, E. Y., Holsinger, C., DeMonte, F., Kupferman, M. AMER MEDICAL ASSOC. 2007: 1209–14

    Abstract

    To describe a novel robotic surgical approach that allows adequate endoscopic access for resection of tumors involving the anterior and central skull base and allows 2-handed, tremor-free, endoscopic dissection and precise suturing of dural defects.Transnasal endoscopic approaches are being increasingly used for surgical access and resection of tumors of the anterior and central skull base. One major disadvantage of this approach is the inability to provide watertight dural closure and reconstruction, which limits its safety and widespread adoption in surgery of intracranial skull base tumors. Other disadvantages include limited depth perception and several ergonomic constraints. Four human cadaver specimens were used for this study. The surgical approach starts with bilateral sublabial incisions and wide anterior maxillary antrostomies (Caldwell-Luc). Transantral access to the nasal cavity is gained through bilateral wide middle meatal antrostomies. A posterior nasal septectomy facilitates bilateral access by joining both nasal cavities into 1 surgical field. The da Vinci Surgical System is then "docked" by introducing the camera arm port through the nostril and the right and left surgical arm ports through the respective anterior and middle antrostomies, into the nasal cavity. A 5-mm dual-channel endoscope coupled with a dual charge-coupled device camera is inserted in the camera port and allows for 3-dimensional visualization of the surgical field at the surgeon's console. Using the robotic surgical arms, the surgeon may perform endoscopic anterior or posterior ethmoidectomy, sphenoidotomy, or resection of the middle or superior turbinates depending on the extent of needed surgical exposure. In addition, resection of the cribriform plate is performed robotically with sharp dissection of the skull base. The dural defect is then repaired with a 6-0 nylon suture.Adequate access to the anterior and central skull base, including the cribriform plate, fovea ethmoidalis, medial orbits, planum sphenoidale, sella turcica, suprasellar and parasellar regions, nasopharynx, pterygopalatine fossa, and clivus, was obtained in all cadaveric dissections. The 3-dimensional visualization obtained by the dual-channel endoscope at the surgeon's console provided excellent depth perception. The most significant advantage was the ability of the surgeon to perform 2-handed tremor-free endoscopic closure of dural defects.Transantral robotic surgery provides adequate endoscopic access to the anterior and central skull base. To our knowledge, this is the first study to report the feasibility and advantages of robotic-assisted endoscopic surgery of the skull base. This novel approach also allows for 3-dimensional, 2-handed, tremor-free endoscopic dissection and precise closure of dural defects. These advantages may expand the indications of minimally invasive endoscopic approaches to the skull base.

    View details for Web of Science ID 000251684900004

    View details for PubMedID 18086961

  • The effect of dental artifacts, contrast media, and experience on Interobserver contouring variations in head and neck anatomy 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology O'Daniel, J. C., Rosenthal, D. I., Garden, A. S., Barker, J. L., Ahamad, A., Ang, K. K., Asper, J. A., Blanco, A. I., De Crevoisier, R., Holsinger, C., Patel, C. B., Schwartz, D. L., Wang, H., Dong, L. LIPPINCOTT WILLIAMS & WILKINS. 2007: 191–98

    Abstract

    To investigate interobserver variability in the delineation of head-and-neck (H&N) anatomic structures on CT images, including the effects of image artifacts and observer experience.Nine observers (7 radiation oncologists, 1 surgeon, and 1 physician assistant) with varying levels of H&N delineation experience independently contoured H&N gross tumor volumes and critical structures on radiation therapy treatment planning CT images alongside reference diagnostic CT images for 4 patients with oropharynx cancer. Image artifacts from dental fillings partially obstructed 3 images. Differences in the structure volumes, center-of-volume positions, and boundary positions (1 SD) were measured. In-house software created three-dimensional overlap distributions, including all observers. The effects of dental artifacts and observer experience on contouring precision were investigated, and the need for contrast media was assessed.In the absence of artifacts, all 9 participants achieved reasonable precision (1 SD < or =3 mm all boundaries). The structures obscured by dental image artifacts had larger variations when measured by the 3 metrics (1 SD = 8 mm cranial/caudal boundary). Experience improved the interobserver consistency of contouring for structures obscured by artifacts (1 SD = 2 mm cranial/caudal boundary).Interobserver contouring variability for anatomic H&N structures, specifically oropharyngeal gross tumor volumes and parotid glands, was acceptable in the absence of artifacts. Dental artifacts increased the contouring variability, but experienced participants achieved reasonable precision even with artifacts present. With a staging contrast CT image as a reference, delineation on a noncontrast treatment planning CT image can achieve acceptable precision.

    View details for DOI 10.1097/01.coc.0000256704.58956.45

    View details for Web of Science ID 000245637100014

    View details for PubMedID 17414470

  • Primary adrenal natural killer/T-cell nasal type lymphoma: First case report in adults 87th Annual Meeting of the Endocrine-Society Thompson, M. A., Habra, M. A., Routbort, M. J., Holsinger, F. C., Perrier, N. D., Waguespack, S. G., Rodriguez, M. A. WILEY-LISS. 2007: 299–303

    Abstract

    We report the first case of a primary adrenal natural killer (NK)/T-cell nasal type lymphoma in adults. The patient presented with an enlarging left adrenal mass and the initial concern was for adrenocortical carcinoma. Surgical resection revealed NK/T-cell lymphoma. Rapid recurrence in the contralateral adrenal gland was treated with a single cycle of chemotherapy before he died due to infectious complications and progressive disease. This case demonstrates the aggressive presentation of a novel subset of primary adrenal lymphoma that should be considered in the differential diagnosis of a rapidly enlarging adrenal mass.

    View details for DOI 10.1002/ajh.20811

    View details for Web of Science ID 000245464400010

    View details for PubMedID 17094095

  • Swing of the surgical pendulum: A return to surgery for treatment of head and neck cancer in the 21st century? 1st Multidisciplinary Head and Neck Cancer Symposium Holsinger, F. C., Weber, R. S. ELSEVIER SCIENCE INC. 2007: S129–S131

    Abstract

    Treatment for head and neck cancer has evolved significantly during the past 100 years. Beginning with Bilroth's total laryngectomy on New Year's Day in 1873, "radical" surgery remained the only accepted treatment for head and neck cancer when optimal local and regional control was the goal. Bigger was still better when it came to managing the primary tumor and the neck. The "commando" procedure and radical neck dissection were the hallmarks of this first generation of treatments of head-and-neck cancer. With the advent of microvascular reconstructive techniques, larger and more comprehensive resections could be performed. Despite these large resections and their "mutilating" sequelae, overall survival did not improve. Even for intermediate-stage disease in head-and-neck cancer, the 5-year survival rate did not improve >50%. Many concluded that more than the scalpel was needed for optimal local and regional control, especially for intermediate- and advanced-stage disease. Most important, the multidisciplinary teams must identify and correlate biomarkers in the tumor and host that predict for a response to therapy and for optimal functional recovery. As the pendulum swings back, a scientific approach using tissue biomarkers for the response to treatment in the setting of multidisciplinary trials must emerge as the new paradigm. In the postgenomic era, treatment decisions should be made based on functional and oncologic parameters-not just to avoid perceived morbidity.

    View details for DOI 10.1016/j.ijrobp.2007.05.044

    View details for Web of Science ID 000249999000037

    View details for PubMedID 17848281

  • Laryngeal preservation in the era of chemoradiation: limitations of the current AJCC staging system. Head & neck Holsinger, F. C., Diaz, E. M. 2006; 28 (12): 1058-1060

    View details for PubMedID 17099907

  • Sternocleidomastoid myofascial flap for reconstruction after composite resection of invasive squamous cell carcinoma of the tonsillar region: Technique and outcome LARYNGOSCOPE Laccourreye, O., Menard, M., Behm, E., Garcia, D., Cauchois, R., Holsinger, F. C. 2006; 116 (11): 2001-2006

    Abstract

    To present the surgical technique and determine the efficacy of sternocleidomastoid myofascial (SCMF) flap reconstruction after composite resection with intent to cure.Retrospective review of 73 consecutive patients with a previously isolated and untreated moderately to well-differentiated invasive squamous cell carcinoma of the tonsillar region and a minimum of 3 years follow-up, managed at a tertiary referral care center during the years 1970 to 2002, with an ipsilateral superiorly based SCMF flap after composite resection.The surgical procedure is presented in detail. Potential technical pitfalls are highlighted. Survival, mortality, and morbidity are documented. Univariate analysis for potential correlation between the incidence for postoperative flap complications and various variables is also performed.The 1, 3, and 5 year Kaplan-Meier actuarial survival estimates were 82.2%, 64.4%, and 49.3%, respectively. Death never appeared to be related to the completion of the SCMF flap. Thirty-three (45.2%) patients had some kind of significant postoperative surgical complication, and nine (12.3%) patients had some kind of significant postoperative medical complication. The most common significant postoperative complication was partial SCMF flap necrosis and pharyngocutaneous fistula noted in 30.1% and 10.9% of patients, respectively. Complete SCMF flap necrosis was never encountered. No patient developed carotid artery rupture or died as a result of the SCMF flap, and none required additional surgery. In univariate analysis, no significant statistical relation was noted between the significant postoperative surgical complications related to the use of the SCMF flap and the variables under analysis.The superiorly based SCMF flap appears to be simple to perform and useful for reconstruction of defects after composite resection.

    View details for DOI 10.1097/01.mlg.0000236845.51421.03

    View details for Web of Science ID 000241806300013

    View details for PubMedID 17075422

  • Resection of selected invasive squamous cell carcinoma of the pyriform sinus by means of the lateral pharyngotomy approach: The partial lateral pharyngectomy HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Holsinger, F. C., Motamed, M., Garcia, D., Brasnu, D., Menard, M., Laccourreye, O. 2006; 28 (8): 705-711

    Abstract

    Although the lateral pharyngotomy is a well-known surgical procedure, to our knowledge, no published reports have described the results achieved with a lateral pharyngectomy approach in patients with isolated and previously untreated selected invasive squamous cell carcinoma of the lateral wall of the pyriform sinus.The medical files and operative charts of 30 patients with an isolated, and previously untreated, squamous cell carcinoma of the pyriform sinus, treated for cure by lateral partial pharyngectomy and primary closure, as well as postoperative radiotherapy (n = 22), and preoperative chemotherapy (n = 8), were retrospectively studied. Sixteen tumors were classified as T1 and 14 as T2. All patients but one were followed until death.Three patients (9%) died in the immediate postoperative period (two from medical complications and one from a surgery-related complication). Overall, 29 patients died, resulting in a 77.7%, 40%, 23.3%, and 15% 1-, 3-, 5- and 10-year Kaplan-Meier actuarial survival estimate, respectively. Only one patient had a serious postoperative complication develop. All patients were decannulated. No patients required a gastrostomy and/or completion total laryngectomy for functional reasons. Local recurrence occurred in four patients (13%). The 3-and 5-year Kaplan-Meier actuarial local control estimates were 88.5% and 79.6%, respectively. The use of a platin-based induction chemotherapy (p = .05) regimen was the only variable that was significantly statistically related to local recurrence. Overall, a 93.3% laryngeal preservation rate was achieved.Partial pharyngectomy by means of the lateral pharyngotomy combined with postoperative radiation therapy is an efficient and function-sparing approach to control selected invasive squamous cell carcinomas of the lateral wall of the pyriform sinus.

    View details for DOI 10.1002/hed.20375

    View details for Web of Science ID 000239179900006

    View details for PubMedID 16786602

  • Use of the photonic band gap fiber assembly CO2 laser system in head and neck surgical oncology LARYNGOSCOPE Holsinger, F. C., Prichard, C. N., Shapira, G., Weisberg, O., Torres, D. S., Anastassiou, C., Harel, E., Fink, Y., Weber, R. S. 2006; 116 (7): 1288-1290
  • Elective neck dissection during salvage laryngectomy 106th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery Yao, M., Roebuck, J. C., Holsinger, F. C., Myers, J. N. W B SAUNDERS CO-ELSEVIER INC. 2005: 388–92

    Abstract

    To evaluate the rate of occult metastases detected with elective neck dissection during salvage laryngectomy for radiation failures.Retrospective review of 63 patients failing radiation therapy treated with salvage surgery between 1970 and 1999. Charts were reviewed for tumor stage, neck treatment, complications, surgical time, and survival. Median follow-up for patients with glottic and supraglottic cancers was 7.8 and 4.5 years, respectively.Thirty-one of 41 glottic cancer patients received elective neck dissections. Three (10%) of 31 had occult metastases. Recurrent staged rT3 and greater tumors showed a 20% rate of occult metastases. No survival advantage was noted between patients treated with elective neck dissection and those followed expectantly (P = .87). Cartilage invasion and perineural invasion in the larynx were associated with a higher risk of occult metastases (P < .05). Ten of 22 supraglottic cancer patients received elective neck dissections. Two (20%) of 10 had occult metastases, and a statistically significant survival advantage was not noted (P = .49).We recommend bilateral neck dissection at the time of laryngectomy for recurrent staged rT3/4 tumors and all patients with recurrent supraglottic cancers because of the higher rate of occult metastases.

    View details for DOI 10.1016/j.amjoto.2005.05.002

    View details for Web of Science ID 000233473000005

    View details for PubMedID 16275407

  • Technical refinements in the supracricoid partial laryngectomy to optimize functional outcomes JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Holsinger, F. C., Laccourreye, O., Weinstein, G. S., Diaz, E. M., McWhorter, A. J. 2005; 201 (5): 809-820
  • Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck Meeting of the Southern Section of the Triological-Society Moore, B. A., Weber, R. S., Prieto, V., El-Naggar, A., Holsinger, F. C., Zhou, X., Lee, J. J., Lippman, S., Clayman, G. L. JOHN WILEY & SONS INC. 2005: 1561–67

    Abstract

    Cutaneous squamous cell carcinoma (CSCC) has been reported to metastasize to parotid and cervical lymph nodes. Few prospective investigations of associated clinical and histopathologic findings and their effect on patient outcomes exist. We seek to identify risk factors for nodal metastases in CSCC and determine the impact of lymphatic spread on survival and recurrence.Subset analysis of a prospective, longitudinal database of patients with CSCC at a comprehensive cancer center.Eligible patients with nonmelanoma skin cancer were consecutively enrolled in a prospective database from July 1996 through June 2001; this cohort was then followed to the key endpoints of recurrence and mortality.Two hundred ten patients were enrolled, and 193 patients with CSCC of the head and neck are included in this analysis. The incidence of nodal metastases in this population was 20.7% at study entry. Median follow-up was 20 months in patients with lymph node metastases and 24 months in patients without metastases. Nodal metastases were significantly associated with recurrent lesions (P = .002) and the following histopathologic features: lymphovascular invasion (P < .0001), inflammation (P = .010), poorly differentiated histology (P = .001), invasion into the subcutaneous tissues (P = .0001), perineural invasion (P = .005), and larger size (P = .0007). Metastases to the cervical nodes were not clinically apparent in 42% of patients with parotid metastases. Combination surgery and radiation therapy resulted in regional control rates of 95%, although local recurrence and distant metastases, along with second primary tumors, were the most frequent recurrent events. Kaplan-Meier survival analysis demonstrates a decrease in overall survival (P = .005), disease-free survival (P = .015), disease-specific survival (P = 0002), and time to recurrence (P = .012) in patients with nodal metastases compared with controls.Lymph node metastases from CSCC are common in our population and are associated with diminished survival. The presence of nodal spread occurs with other adverse histopathologic findings, and we recommend surgery and postoperative radiation therapy to control regional disease in the presence of nodal metastases and perineural invasion. New approaches in early identification of nodal metastases, treatment, and prevention of local recurrences and second primary malignancies are warranted.

    View details for DOI 10.1097/01.mlg.0000173202.56739.9f

    View details for Web of Science ID 000232047100007

    View details for PubMedID 16148695

  • Thyroplasty type I with Montgomery implant among native French language speakers with unilateral laryngeal nerve paralysis LARYNGOSCOPE Laccourreye, O., El Sharkawy, L., Holsinger, F. C., Hans, S., Menard, M., Brasnu, D. 2005; 115 (8): 1411-1417

    Abstract

    To document the long-term results achieved with the Montgomery implant in 96 French speakers with a unilateral laryngeal nerve paralysis (ULNP).Retrospective series, inception cohort of 96 patients.Data regarding morbidity and functional results were obtained at regular visits to our clinic. All patients were followed for a minimum of 6 months or until death. Forty-two patients had a minimum of 12 months of follow-up. Early in the study, 36 patients were prospectively recorded under similar conditions before placement of the Montgomery implant and at 1, 3, 6, and 12 months postoperatively.None of the 96 patients died in the immediate postoperative period. The perioperative course was unremarkable in 94.8% of cases. Perioperative problems included failure to obtain a satisfactory phonatory result in three patients, difficulty to stabilize the implant posteriorly in one patient, and fracture of the inferior rim of the thyroid cartilage window in another patient. The primary immediate postoperative problem (within the first postoperative month) was laryngeal dyspnea, noted in four patients. According to the patient's subjective assessment, speech and voice was always improved in the immediate postoperative period. However, three patients had secondary degradation of speech and voice. Revision surgery under local anesthesia resulted in a 97.9% ultimate speech and voice success rate. According to the patient's subjective assessment, adequate swallowing in the immediate postoperative period was achieved in 94.2% of cases that had swallowing problems preoperatively. A significant statistical increase in the duration parameters (phonation time, phrase grouping, speech rate) together with a statistical significant decrease in both the jitter and shimmer values was noted when comparing the preoperative and the postoperative values at 1 month. Analysis of the evolution of the speech and voice parameters at 1, 3, 6, and 12 months postoperatively showed a significant decrease in the fundamental frequency and noise-to-harmonic ratio values but did not demonstrate any significant differences for the other speech and voice parameters.From the reported data, we conclude that the type I thyroplasty with Montgomery implant insertion is a safe and reproducible method to treat ULNP. Furthermore, this system achieves very good and stable phonatory results. Finally, the use of this technique and implant system appears safe in patients from various cultures with ULNP from a variety of causes and severe comorbidity. Over the past decade at our department, this procedure progressively replaced the use of the intracordal injection of autologous fat injection that was initially advocated in patients with ULNP.

    View details for DOI 10.1097/01.mlg.0000168059.12949.a6

    View details for Web of Science ID 000231033400014

    View details for PubMedID 16094114

  • Organ-preservation laryngeal surgery in the era of chemoradiation CURRENT PROBLEMS IN CANCER Moore, B. A., Holsinger, F. C., Diaz, E. M., Weber, R. S. 2005; 29 (4): 169-179
  • Supracricoid partial laryngectomy: An organ-preservation surgery for laryngeal malignancy CURRENT PROBLEMS IN CANCER Holsinger, C., Weinstein, G. S., Laccourreye, O. 2005; 29 (4): 190-200
  • Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region - II. An analysis of the incidence, related variables, and consequences of local recurrence 6th International Conference on Head and Neck Cancer Laccourreye, O., Hans, S., Menard, M., Garcia, D., Brasnu, D., Holsinger, C. AMER MEDICAL ASSOC. 2005: 592–99

    Abstract

    To determine the incidence of local and regional failure, distant metastasis, and overall survival following transoral lateral oropharyngectomy (TLO) and to determine factors associated with local recurrence.Retrospective case series throughout 20 years; mean follow-up of 10 years.Academic center.A total of 166 previously untreated patients with squamous cell carcinoma of the tonsil.A total of 131 (81.9%) of the 166 patients received preoperative induction chemotherapy. Fifty-one patients (30.7%) underwent postoperative radiation therapy.Local and regional recurrence, distant metastasis, second primary tumors, and survival.The 1- and 5-year Kaplan-Meier local control estimates were 91.2% and 82.1%, respectively. The 1- and 5-year Kaplan-Meier local control estimates were 98.3% and 89.0% for T1, 88.9% and 81.7% for T2, and 78.9% and 62.7% for T3 lesions, respectively (P = .02). In univariate analysis, 7 variables were significantly associated with an increased risk of local failure: increasing T classification; positive margins of resection; poor clinical response to induction chemotherapy; tumor spread to the posterior pillar, posterior pharyngeal wall, and contralateral soft palate; and invasion of the junction between the tonsil and soft palate. In a logistic regression model, spread to the posterior pillar was the only variable statistically associated with local failure (P = .02). The 1-, 3-, and 5-year Kaplan-Meier survival estimates were 87.9%, 67.2%, and 57.7%, respectively. The Kaplan-Meier survival estimate was significantly reduced (P = .009) in patients with local failure.Selected tonsillar squamous cell carcinoma can be managed with TLO with local control comparable to radiotherapy. Patient selection is critical and TLO is best suited for patients with anterior T1 to T2 squamous cell carcinoma of the tonsil, without posterior anatomic spread.

    View details for Web of Science ID 000230409300010

    View details for PubMedID 16027281

  • Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region - I. Technique, complications, and functional results 6th International Conference on Head and Neck Cancer Holsinger, F. C., McWhorter, A. J., Menard, M., Garcia, D., Laccourreye, O. AMER MEDICAL ASSOC. 2005: 583–91

    Abstract

    To describe the surgical technique for transoral lateral oropharyngectomy (TLO) and its safety, postoperative management, complications, and functional outcomes.A 20-year retrospective case series review. Mean follow-up was 10 years. All but 10 patients were followed up until the fifth postoperative year or death.Academic, tertiary referral center.A total of 191 patients who underwent TLO for selected invasive squamous cell carcinoma of the tonsil and/or tonsillar fossa.Ten patients had received preoperative radiation therapy. Induction chemotherapy was used in 153 patients (80.3%). An associated neck dissection was performed in 148 patients (77.5%). Postoperative radiation therapy was administered to 52 patients (28.7%).Overall survival rate, intraoperative mortality, and perioperative mortality were determined. The need for and length of nasogastric tube feeding and tracheotomy were calculated. The incidence of significant postoperative surgical and medical complications was recorded.No intraoperative mortality occurred, but 5 patients (2.6%) died in the immediate postoperative period, 3 from medical complications and 2 from unknown causes. In this series, the internal carotid artery was never injured, and no cutaneous-oropharyngeal fistulas were apparent. The incidence of significant surgical complications from the oropharynx was 6.3%. Nasopharyngeal reflux and severe rhinolalia were the most common complications, occurring in 9 patients. Increasing tobacco use was statistically correlated with an increase in postoperative pneumonia from aspiration (P = .05) but no surgical complications. Seven patients (3.7%) had a temporary tracheotomy for a mean of 5 days. One hundred twelve patients (58.6%) had a nasogastric tube inserted for a mean of 6 days. No patients had a permanent gastrostomy or tracheotomy tube. The mean duration of hospitalization was 9 days. The duration of hospitalization was statistically correlated with the need for nasogastric tube placement and its duration (P<.001) or tracheotomy (P<.001).From a functional standpoint, the TLO is a safe surgical approach for treating selected carcinoma of the tonsillar fossa. It is a reliable technique that should be considered for treatment of appropriate squamous cell carcinoma of the tonsil.

    View details for Web of Science ID 000230409300009

    View details for PubMedID 16027280

  • Foreword. Current problems in cancer Weber, R. S., Holsinger, F. C. 2005; 29 (4): 168-?

    View details for PubMedID 16143164

  • Mortality risk from squamous cell skin cancer JOURNAL OF CLINICAL ONCOLOGY Clayman, G. L., Lee, J. J., Holsinger, F. C., Zhou, X., Duvic, M., El-Naggar, A. K., Prieto, V. G., Altamirano, E., Tucker, S. L., Strom, S. S., Kripke, M. L., Lippman, S. M. 2005; 23 (4): 759-765

    Abstract

    To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality.Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality.We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions > or = 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor.Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.

    View details for DOI 10.1200/JCO.2005.02.155

    View details for Web of Science ID 000226738900015

    View details for PubMedID 15681519

  • A simple method to expose the surgical field when performing a thyroplasty OTOLARYNGOLOGY-HEAD AND NECK SURGERY Laccourreye, O., Holsinger, F. C. 2005; 132 (1): 108-109

    View details for DOI 10.1016/j.otohns.2004.09.036

    View details for Web of Science ID 000226216300019

    View details for PubMedID 15632919

  • Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer CLINICAL CANCER RESEARCH Schiff, B. A., McMurphy, A. B., Jasser, S. A., Younes, M. N., Doan, D., Yigitbasi, O. G., Kim, S. W., Zhou, G., Mandal, M., Bekele, B. N., Holsinger, F. C., Sherman, S. I., Yeung, S. C., El-Naggar, A. K., Myers, J. N. 2004; 10 (24): 8594-8602

    Abstract

    No effective treatment options currently are available to patients with anaplastic thyroid cancer (ATC), resulting in high mortality rates. Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy.The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC. We assessed the potential of the EGFR inhibitor gefitinib ("Iressa," ZD1839) to inhibit EGFR activation in vitro and in vivo, inhibit ATC cellular proliferation, induce apoptosis, and reduce the growth of ATC cells in vivo when administered alone and in combination with paclitaxel.EGFR was overexpressed in ATC cell lines in vitro and in vivo and in human ATC specimens. Activation of EGFR by EGF was blocked by the addition of gefitinib. In vitro studies showed that gefitinib greatly inhibited cellular proliferation and induced apoptosis in ATC cell lines and slowed tumor growth in a nude mouse model of thyroid carcinoma cells injected subcutaneously.ATC cells consistently overexpress EGFR, rendering this receptor a potential target for molecular therapy. Gefitinib effectively blocks activation of EGFR by EGF, inhibits ATC cellular proliferation, and induces apoptosis in vitro. Our in vivo results show that gefitinib has significant antitumor activity against ATC in a subcutaneous nude mouse tumor model and therefore is a potential candidate for human clinical trials.

    View details for Web of Science ID 000225957800061

    View details for PubMedID 15623643

  • Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography ORAL ONCOLOGY Curino, A., Patel, V., Nielsen, B. S., Iskander, A. J., Ensley, J. F., Yoo, G. H., Holsinger, F. C., Myers, J. N., El-Nagaar, A., Kellman, R. M., Shillitoe, E. J., Molinolo, A. A., Gutkind, J. S., Bugge, T. H. 2004; 40 (10): 1026-1032

    Abstract

    Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 microg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

    View details for DOI 10.1016/j.oraloncology.2004.05.011

    View details for Web of Science ID 000225147700009

    View details for PubMedID 15509494

  • Acquisition of anoikis resistance is a critical step in the progression of oral tongue cancer ORAL ONCOLOGY Swan, E. A., Jasser, S. A., Holsinger, F. C., Doan, D., Bucana, C., Myers, J. N. 2003; 39 (7): 648-655

    Abstract

    We hypothesized that acquisition of resistance to anoikis is a critical step in oral cancer progression. To test this hypothesis, we compared a panel of cell lines derived from human oral tissues across the spectrum of tumor progression from oral keratinocytes (HOK-16B), invasive oral squamous cell carcinoma (Tu167), and finally metastatic carcinoma (TxCS-1, MDA1986) for their sensitivity to detachment from the extracellular matrix. The relationship between stage of tumor progression and anoikis resistance was demonstrated by the apoptotic fractions after 48 h in suspension culture which were 93.33, 61.6, 34.5, and 3.71%, respectively. To further demonstrate that anoikis resistance is important for tumor progression, we selected a highly anoikis resistant cell line, JMAR, by serial passage of the Tu167 cell line in suspension culture. Initially, the JMAR line, and clones derived from it, were characterized for anoikis resistance in vitro, and after 72 h in suspension culture the rates of anoikis in the Tu167 and JMAR lines were found to be 73 and 26%, respectively. The degree of anoikis resistance was found to correlate with survival of nude mice orthotopically injected with 5x10(5) Tu167 or JMAR cells. The JMAR mice had a median survival of 17 days versus over 30 days in mice implanted with the Tu167 line. Finally, we found that in vivo selection in the orthotopic model for a regionally metastatic cell line by implantation of Tu167 into the tongues of nude mice and harvesting and culturing cervical lymph nodes led to production of a cell line, Tu167LN1, which was found to be anoikis-resistant. This cell line had an apoptotic cell fraction of 16.2% (+/-3.14%) after 48 h in suspension culture.

    View details for DOI 10.1016/S1368-8375(03)00049-6

    View details for Web of Science ID 000185296300003

    View details for PubMedID 12907203

  • Epidermal growth factor receptor blockade potentiates apoptosis mediated by paclitaxel and leads to prolonged survival in a murine model of oral cancer CLINICAL CANCER RESEARCH Holsinger, F. C., Doan, D. D., Jasser, S. A., Swan, E. A., Greenberg, J. S., Schiff, B. A., Bekele, B. N., Younes, M. N., BUCANA, C. D., FIDLER, I. J., Myers, J. N. 2003; 9 (8): 3183-3189

    Abstract

    Because survival for patients with oral cancer has not improved over the past 25 years, new approaches for treatment are needed. Targeted molecular therapy against epidermal growth factor receptor (EGFR) has shown promise as an adjuvant therapy in preliminary studies in several solid tumors, including head and neck cancer. The objective of this study was to determine the efficacy of paclitaxel and PKI166, a novel inhibitor of EGFR, against oral cavity cancer. Experimental Design and Results: JMAR human oral cancer cells were pretreated for 1 h with PKI166 and then stimulated with epidermal growth factor. EGFR-specific tyrosine kinase autophosphorylation measured by Western immunoblotting was inhibited by PKI166 in a dose-dependent fashion at all doses tested (0.01-1 micro M). Next, the induction of apoptosis in JMAR cells treated with paclitaxel (0.001 to 0.1 micro M) with or without PKI166 (0, 1, or 2 micro M) was determined using a propidium iodide assay. The addition of 2.0 micro M PKI166 significantly increased tumor cell death, shifting the amount of paclitaxel needed to induce apoptosis in 50% of cells from 0.1 to 0.001 micro M. These in vitro findings were confirmed using an orthotopic model of oral cancer. JMAR oral cancer cells were implanted into the tongues of nude mice. After lingual tumors developed, mice were randomized into four groups (n = 10): (a) oral PKI166 (100 mg/kg); (b) i.p. paclitaxel (200 micro g/wk); (c) PKI166 and paclitaxel; or (d) placebo. Mice treated with PKI166/paclitaxel demonstrated a significant increase in survival (P = 0.028). After necropsy, all tongue tumors were evaluated for apoptosis by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. A greater apoptotic fraction of tumor cells was found in tumors of mice treated with paclitaxel and PKI166 as compared with the other treatment groups (136.4 versus 37.8; P = 0.016).Combination therapy with paclitaxel and PKI166 prolongs survival in an orthotopic preclinical model of tongue cancer by increasing programmed cell death of oral cancer.

    View details for Web of Science ID 000184680200042

    View details for PubMedID 12912971

  • Squamous cell carcinoma of the buccal mucosa: One institution's experience with 119 previously untreated patients 5th International Conference on Head and Neck Surgery Diaz, E. M., Holsinger, F. C., Zuniga, E. R., Roberts, D. B., Sorensen, D. M. JOHN WILEY & SONS INC. 2003: 267–73

    Abstract

    Squamous cell carcinoma (SCC) of the buccal mucosa is a rare, but especially aggressive, form of oral cavity cancer, associated with a high rate of locoregional recurrence and poor survival. We reviewed our institution's experience with 119 consecutive, previously untreated patients with buccal SCC.We reviewed the charts of 250 patients who were seen at The University of Texas M. D. Anderson Cancer Center between January, 1974, and December, 1993. Of these, 119 were untreated and were subsequently treated exclusively at our institution. Patients who were previously treated elsewhere or whose lesions arose in other sites and only secondarily involved the buccal mucosa were excluded.Patients with T1- or T2-sized tumors had only a 78% and 66% 5-year survival, respectively. Muscle invasion, Stensen's duct involvement, and extracapsular spread of involved lymph nodes were all associated with decreased survival (p <.05). Surgical salvage for patients with locoregional recurrence after radiation therapy was rarely successful.SCC of the buccal mucosa is a highly aggressive form of oral cavity cancer, with a tendency to recur locoregionally. Patients with buccal mucosa SCC have a worse stage-for-stage survival rate than do patients with other oral cavity sites.

    View details for DOI 10.1002/hed.10221

    View details for Web of Science ID 000181798000002

    View details for PubMedID 12658730

  • Targeted molecular therapy for oral cancer with epidermal growth factor receptor blockade - A preliminary report 5th International Conference on Head and Neck Cancer of the International-Society-of-Head-Neck-Cancer Myers, J. N., Holsinger, F. C., Bekele, B. N., Li, E., Jasser, S. A., Killion, J. J., FIDLER, I. J. AMER MEDICAL ASSOC. 2002: 875–79

    Abstract

    Overexpression of epidermal growth factor receptor (EGF-R) is associated with increased malignant potential and correlates with poor clinical outcome in head and neck cancer. Therefore, inhibition of the EGF-R pathway provides an ideal target for molecular therapy. We examined in vitro and in vivo effects of PKI166, an orally administered EGF-R inhibitor, on 2 human squamous cell carcinoma of the oral cavity cell lines, Tu159 and MDA1986.Basic science, laboratory investigation.For Western blotting, Tu159 and MDA1986 cells were pretreated for 1 hour and then stimulated with EGF. The EGF-R-specific tyrosine kinase autophosphorylation was inhibited completely by PKI166 at all doses tested (1-10 micro g/mL). By means of a tetrazolium-based viable cell assay, PKI166 was shown to arrest the growth of Tu159 and MDA1986 cells. The inhibitory concentration (50%), calculated from regression lines on the linear portion of the growth inhibition graphs, was 0.18 micro M (R = 0.98) for Tu159 cells and 0.23 micro M (R = 0.97) for MDA1986 cells. Nude mice were inoculated subcutaneously with 1 x 10(6) Tu159 tumor cells and observed for 7 days. Next, daily doses of PKI166 (0, 10, or 50 mg/kg) were delivered by orogastric lavage for 28 days and the animals were observed for tumor growth. PKI166 significantly reduced tumor growth in mice treated for 1 month with oral PKI166 in a dose-dependent fashion.Targeted molecular therapy with EGF-R blockade arrests the growth of oral cancer in vitro and reduces its proliferation in an experimental xenograft animal model.

    View details for Web of Science ID 000177346300001

    View details for PubMedID 12162763

  • Central mucoepidermoid carcinoma of the mandible - Tumorigenesis within a keratocyst ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Holsinger, F. C., Owens, J. M., Raymond, A. K., Myers, J. N. 2002; 128 (6): 718-720

    View details for Web of Science ID 000176264300017

    View details for PubMedID 12049571

  • An orthotopic nude mouse model of oral tongue squamous cell carcinoma CLINICAL CANCER RESEARCH Myers, J. N., Holsinger, F. C., Jasser, S. A., Bekele, B. N., FIDLER, I. J. 2002; 8 (1): 293-298

    Abstract

    Despite advances in our understanding, prevention, and treatment of head and neck squamous cell carcinoma (SCC), the 5-year survival rates for patients remain low. This poor prognosis for head and neck SCC and SCC of the oral tongue (SCCOT) in particular reflects a limited understanding of the mechanisms of local and regional metastasis, which accounts for a majority of deaths. To analyze the molecular and cellular mechanisms of metastasis, we have developed an orthotopic nude mouse model of SCCOT.Nude mice were injected submucosally in the tongue or subcutis with human squamous cell carcinoma of the oral cavity cell lines Tu159, Tu167, and MDA1986. The mice were necropsied and examined for the presence of primary tumors, and regional and systemic metastases.For all three of the squamous cell carcinoma of the oral cavity cell lines, tumors developed more readily in the orthotopic site, the tongue, than in the ectopic subcutis. MDA1986 cells were highly tumorigenic, particularly at the orthotopic site, with as few as 5 x 10(3) cells producing tumors in all of the mice. In contrast, s.c. tumor formation required at least 1 x 10(5) cells. The tumorigenicity observed between those mice given submucosal inoculation and those mice given s.c. inoculation (P < 0.0001). Regional metastases initially occurred in <10% of mice. To generate tumor lines of increased metastatic potential, regional metastases were isolated from cervical lymph nodes after the development of orthotopic tongue tumors. Serial passage of these lymph nodes resulted in a cell line more metastatic than its parental line. When injected into the tongues of mice, these cells metastasized to regional lymph nodes in 30% of mice and to the lungs in 20%.In this orthotopic murine model, oral tongue cancer recapitulates the behavior of human SCCOT, allowing for detailed studies of its biology and therapy.

    View details for Web of Science ID 000173519700042

    View details for PubMedID 11801572

  • Hearing preservation in conservation surgery for vestibular schwannoma AMERICAN JOURNAL OF OTOLOGY Holsinger, F. C., Coker, N. J., Jenkins, H. A. 2000; 21 (5): 695-700

    Abstract

    To evaluate preservation of hearing in the resection of vestibular schwannomas.A retrospective case review.Tertiary-care medical center.Forty-seven patients (25 men, 22 women) were studied; mean age was 46 years, mean tumor diameter 9.8 mm (range 3-30 mm.)All patients underwent resection of vestibular schwannomas by the middle cranial fossa (MCF) or the retrosigmoid (RS) approach.Hearing preservation was classified by the criteria outlined by the American Academy of Otolaryngology-Head Neck Surgery. Hearing was assessed preoperatively and postoperatively at 1 month and 1 year. Facial function was graded according to the House-Brackmann scale. Minimum follow-up was 18 months.Hearing was preserved in 69% of patients who underwent the MCF approach but in only 33% of patients for whom the RS approach was used. The RS approach was used for larger tumors (mean diameter 15 mm) and the MCF procedure for smaller tumors (mean diameter 9 mm). One hundred percent of patients had facial function H/B grade II or better, regardless of approach.Hearing function can be reliably preserved in a high percentage of selected patients undergoing resection of vestibular schwannoma.

    View details for Web of Science ID 000089111500020

    View details for PubMedID 10993461

  • Computer based physician education OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Jewett, B. S., Holsinger, C., Kuppersmith, R. B., Buenting, J. E. 1998; 31 (2): 301-?

    Abstract

    Physicians are turning to computers with increasing frequency to access patients' records and laboratory values, to communicate with colleagues, and to keep current with the developments in their field. This article reviews the impact of the computers on the education of medical students and on continuing education for residents and practicing physicians. Furthermore, it emphasizes the importance and need for educating physicians about computers and the basic principles behind their development.

    View details for Web of Science ID 000073494600006

    View details for PubMedID 9518438

  • The use of e-mail by otolaryngologists ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Kuppersmith, R. B., Holsinger, C., Jenkins, H. A. 1996; 122 (9): 921-922

    Abstract

    Electronic mail (e-mail) is an extremely powerful form of communication and the most frequently used application on the Internet. While e-mail is not the appropriate mode of communication for every situation, there are many instances where its use is invaluable.

    View details for Web of Science ID A1996VG38600001

    View details for PubMedID 8797553

  • SUCCESSFUL TREATMENT OF INVASIVE BRONCHIAL ASPERGILLOSIS AFTER SINGLE-LUNG TRANSPLANTATION CLINICAL INFECTIOUS DISEASES BIGGS, V. J., Dummer, S., Holsinger, F. C., Loyd, J. E., Christman, B. W., Frist, W. H. 1994; 18 (1): 123-124

    View details for Web of Science ID A1994MX20500026

    View details for PubMedID 8054428