Dr. Holsinger is Professor and Chief of Head and Neck Surgery at Stanford University.

His research focuses on surgical innovation and clinical trials through NCI-funded cooperative groups. 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. He leads an investigative device exemption trial to evaluate the safety and efficacy of anext-generation flexible robotic surgical system.

In 2014, he began a prospective clinical trial to evaluate multispectral imaging of patients with oropharyngeal cancer, in an effort to discern tumor from tumor. Currently, he leads a study to evaluate hyper-spectral imaging to improve surgical vision.

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.

Dr. Holsinger’s surgical practice focuses on the surgical management of benign and malignant diseases of the 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.

At the Cancer Center, Dr. Holsinger has led an effort to improve the quality of multidisciplinary tumor boards in H&N, but also across the Cancer Center, beginning with the founding of the H&N Multidisciplinary Cancer Care Clinical Program in 2014.

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.

Dr. Holsinger has authored or co-authored numerous articles and abstracts, which have appeared in publications such as the New England Journal of Medicine, Journal of the American College of Surgeons, the Journal of Clinical Oncology, Clinical Cancer Research, Head & Neck, Laryngoscope, and the Archives of Otolaryngology—Head and Neck Surgery.

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

Clinical Focus

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

Academic Appointments

Administrative Appointments

  • Director, Head and Neck Cancer Care Program, Stanford Cancer Center (2013 - 2017)
  • Member, Stanford Cancer Institute (2013 - Present)

Professional Education

  • Fellowship:MD Anderson Cancer Center (2003) TX
  • Board Certification: Otolaryngology, American Board of 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

  • Clinical Validation of ThyroidPrint: A Gene Expression Signature for Diagnosis of Indeterminate Thyroid Nodules 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.

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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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2018-19 Courses

All Publications

  • 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 DOI 10.1200/JOP.18.00727

    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


    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 .

    View details for DOI 10.1200/JCO.18.01921

    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


    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 DOI 10.1093/jjco/hyz020

    View details for PubMedID 30796834

  • 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


    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 DOI 10.1016/j.soc.2018.07.008

    View details for PubMedID 30414677

  • 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


    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 DOI 10.1159/000490599

    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


    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 DOI 10.1002/hed.25382

    View details for Web of Science ID 000454204600025

    View details for PubMedID 30102824

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


    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 DOI 10.1016/j.anorl.2018.10.011

    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


    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 DOI 10.1002/cncr.31708

    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


    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 DOI 10.1016/j.anorl.2017.11.012

    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. S., Gomez, A. J., Holsinger, F. C., Kong, C. S., Colevas, A. D., Warram, J. M., Rosenthal, E. L. 2018


    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 DOI 10.1158/0008-5472.CAN-18-0878

    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

  • 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


    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 DOI 10.1002/lary.27159

    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

  • 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


    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;; 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

  • 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


    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 DOI 10.1002/lary.26704

    View details for Web of Science ID 000418424600021

    View details for PubMedID 28681924

  • 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


    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 DOI 10.1016/j.anorl.2017.06.002

    View details for Web of Science ID 000417560900011

    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


    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 DOI 10.1007/s00405-017-4729-y

    View details for Web of Science ID 000412652600022

    View details for PubMedID 28871410

    View details for PubMedCentralID PMC5633617

  • 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


    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


    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


    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

  • 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-?


    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 Web of Science ID 000388926900012

    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: -?


    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


    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


    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


    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

  • 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


    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 Web of Science ID 000379939900021

    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


    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


    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


    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


    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

  • 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


    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 Web of Science ID 000375116400002

    View details for PubMedID 26950771

    View details for PubMedCentralID PMC4927077

  • 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


    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

  • 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


    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 DOI 10.1001/jamaoto.2015.3673

    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


    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 Web of Science ID 000367146400003

    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


    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-?


    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-?


    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-?


    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 Web of Science ID 000360324700011

    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


    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


    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


    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


    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


    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


    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

  • 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


    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


    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


    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


    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

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


    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

  • 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


    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

  • 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 Web of Science ID 000337982400001

    View details for PubMedID 24882802

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


    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


    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


    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


    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


    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


    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


    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

  • 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


    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

  • 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


    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 Web of Science ID 000328944900019

    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


    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

  • 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


    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


    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


    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


    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


    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


    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


    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)


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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-?


    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



    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


    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


    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


    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


    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


    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


    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



    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-?


    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


    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


    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


    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



    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


    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


    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-?


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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-?


    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


    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


    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


    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


    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


    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


    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


    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


    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


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

    View details for PubMedID 16143164

  • 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


    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


    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

  • 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


    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


    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


    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


    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


    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


    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


    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


    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


    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-?


    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


    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


    View details for Web of Science ID A1994MX20500026

    View details for PubMedID 8054428