Tristan Tham, MD

All Publications

• Impact of Dysplasia on Inverted Papilloma Recurrence: A Systematic Review and Meta-Analysis. International forum of allergy & rhinology Giannaris, P., Tham, T., Giannaris, E., Wohlars, K., Kim, A., Plann-Curley, B., Lee, H., Pollack, A. Z., Chaskes, M. B., Fastenberg, J. H., Tong, C. C. 2026

  Abstract

  Sinonasal inverted papilloma (SNIP) is a benign but locally aggressive tumor that has demonstrated a propensity to recur. Multiple anatomic and surgical factors have been proposed to influence recurrence; dysplasia has recently emerged as a predictor, yet its prognostic significance remains unclear. Clarifying its role may improve postoperative risk stratification.A systematic review and meta-analysis were performed following PRISMA guidelines and registered with PROSPERO (CRD420251140223). PubMed, Embase, Scopus, and Web of Science were queried for studies reporting recurrence outcomes stratified by dysplasia status. Studies with extractable recurrence data for dysplasia and non-dysplasia SNIP were included. Fixed-effects meta-analysis was performed using the inverse variance method to calculate pooled odds ratios (OR) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 and Cochran's Q statistics.Thirteen studies comprising 1893 patients were included. Based on reported data, mean age ranged from 48.3 to 58.0 years. The cohort was predominantly male (1172/1720; 68.1%). Of 283 patients with dysplasia, 104 experienced recurrence (36.7%), compared with 302 of 1346 patients without dysplasia (22.4%). Dysplasia was significantly associated with increased recurrence risk (pooled OR 3.42; 95% CI, 2.45-4.78; p < 0.001) with low-moderate heterogeneity (I2 = 20.33%). Mean follow-up was 39.8 months. Findings were robust on leave-one-out sensitivity analysis and trim-and-fill adjustment (adjusted OR 3.05; 95% CI 2.21-4.22).Dysplasia is a significant independent predictor of recurrence in SNIP, conferring 3.4 times increased odds of recurrence. Standardized dysplasia reporting and risk stratification protocols are needed to optimize surveillance strategies in SNIP patients.

  View details for DOI 10.1002/alr.70215

  View details for PubMedID 42383302

• A Novel Risk Stratification Tool for Sinonasal Inverted Papilloma Recurrence: Multi-Institutional Nomogram Incorporating Dysplasia Severity. International forum of allergy & rhinology Tham, T., Giannaris, P., Kokabee, M., Kim, A., Wilensky, J., Tsang, C., Wang, B. Y., Panara, K., Kuan, E. C., Papagiannopoulos, P., Tajudeen, B., Eide, J. G., Craig, J. R., Kshirsagar, R. S., Christian, Z., Locke, T. B., Fastenberg, J. H., Chaskes, M. B., Pollack, A. Z., Har-El, G., Cui, S., Guerrero, D., Ahn, S., Oh, E. J., Kennedy, D. W., Workman, A. D., Kohanski, M. A., Douglas, J., Adappa, N. D., Palmer, J. N., Tong, C. C. 2026

  Abstract

  High-risk dysplasia and multifocal attachment independently predict inverted papilloma recurrence. Novel nomogram generates individualized 3-, 6-, and 9-year recurrence risk estimates. Risk-stratified surveillance may optimize postoperative monitoring intensity and intervals.

  View details for DOI 10.1002/alr.70102

  View details for PubMedID 41508928

• Is the Risk of Clinically Significant Hemorrhage Following Tonsillectomy Greater in Adults Than Children? The Laryngoscope Tham, T., Megwalu, U. C. 2025

  View details for DOI 10.1002/lary.70120

  View details for PubMedID 40923521

• Functional and radiological sinonasal outcomes of CFTR modulators for sinus disease in cystic fibrosis: A meta-analysis. International forum of allergy & rhinology Tham, T., Li, F. A., Schneider, J. R., Saleem, M. I., Werner, M. T., Chaskes, M. B., Tong, C. C., Fastenberg, J. H. 2024

  Abstract

  Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease.English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements.Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I2 = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I2 = 67%, p = 0.030).CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve.

  View details for DOI 10.1002/alr.23439

  View details for PubMedID 39212072

• Machine Learning Methods in Classification of Prolonged Radiation Therapy in Oropharyngeal Cancer: National Cancer Database. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Ahn, S., Oh, E. J., Saleem, M. I., Tham, T. 2024

  Abstract

  To investigate the accuracy of machine learning (ML) algorithms in stratifying risk of prolonged radiation treatment duration (RTD), defined as greater than 50 days, for patients with oropharyngeal squamous cell carcinoma (OPSCC).Retrospective cohort study.National Cancer Database (NCDB).The NCDB was queried between 2004 to 2016 for patients with OPSCC treated with radiation therapy (RT) or chemoradiation as primary treatment. To predict risk of prolonged RTD, 8 different ML algorithms were compared against traditional logistic regression using various performance metrics. Data was split into a distribution of 70% for training and 30% for testing.A total of 3152 patients were included (1928 prolonged RT, 1224 not prolonged RT). As a whole, based on performance metrics, random forest (RF) was found to most accurately predict prolonged RTD compared to both other ML methods and traditional logistic regression.Our assessment of various ML techniques showed that RF was superior to traditional logistic regression at classifying OPSCC patients at risk of prolonged RTD. Application of such algorithms may have potential to identify high risk patients and enable early interventions to improve survival.

  View details for DOI 10.1002/ohn.926

  View details for PubMedID 39082895

• Impact of Treatment Parameters on Racial Survival Differences in Oropharyngeal Cancer: National Cancer Database Study. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Zhu, D., Wong, A., Oh, E. J., Ahn, S., Wotman, M., Sahai, T., Bottalico, D., Frank, D., Tham, T. 2022; 166 (6): 1134-1143

  Abstract

  To investigate how differences in treatment parameters account for survival differences between races of patients with oropharyngeal squamous cell carcinoma (OPSCC).Retrospective cohort study.National Cancer Database.Data of patients with OPSCC undergoing radiation therapy (RT) or concurrent chemoradiation therapy as primary treatment were obtained from the National Cancer Database from 2004 to 2016. We analyzed 4 treatment-related time intervals to determine their impact on survival between races when controlling for human papilloma virus (HPV) status. Cox proportional hazards models, stepwise logistic regressions, covariate adjustments, and propensity score matching were performed.A total of 3152 patients were identified (2877 White, 275 Black). In HPV- cases, Black patients with prolonged radiation duration had a significantly worse overall survival as compared with White patients (hazard ratio, 1.77; 95% CI, 1.03-3.05; P = .039). In a logistic regression model, the only covariate that was significantly associated with prolonged RT was facility type. When further adjusted for facility type, the survival difference between Black and White patients with HPV- status and prolonged RT times was no longer significant (hazard ratio, 1.55; 95% CI, 0.90-2.69; P = .116).There is a significant disparity in overall survival between Black and White patients with HPV- OPSCC when RT duration is prolonged. Clinicians should be aware of the negative impact of prolonged RT, especially in Black patients, so that they can attempt to decrease treatment-related time intervals. Facility type was also found to affect the outcomes of patients with OPSCC, and efforts should be made to improve patient access to well-equipped, high-volume facilities.

  View details for DOI 10.1177/01945998211035056

  View details for PubMedID 34399637

• The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Tong, J. Y., Wong, A., Zhu, D., Fastenberg, J. H., Tham, T. 2020; 163 (1): 3-11

  Abstract

  To determine the pooled global prevalence of olfactory and gustatory dysfunction in patients with the 2019 novel coronavirus (COVID-19).Literature searches of PubMed, Embase, and Scopus were conducted on April 19, 2020, to include articles written in English that reported the prevalence of olfactory or gustatory dysfunction in COVID-19 patients.Search strategies developed for each database contained keywords such as anosmia, dysgeusia, and COVID-19. Resulting articles were imported into a systematic review software and underwent screening. Data from articles that met inclusion criteria were extracted and analyzed. Meta-analysis using pooled prevalence estimates in a random-effects model were calculated.Ten studies were analyzed for olfactory dysfunction (n = 1627), demonstrating 52.73% (95% CI, 29.64%-75.23%) prevalence among patients with COVID-19. Nine studies were analyzed for gustatory dysfunction (n = 1390), demonstrating 43.93% (95% CI, 20.46%-68.95%) prevalence. Subgroup analyses were conducted for studies evaluating olfactory dysfunction using nonvalidated and validated instruments and demonstrated 36.64% (95% CI, 18.31%-57.24%) and 86.60% (95% CI, 72.95%-95.95%) prevalence, respectively.Olfactory and gustatory dysfunction are common symptoms in patients with COVID-19 and may represent early symptoms in the clinical course of infection. Increased awareness of this fact may encourage earlier diagnosis and treatment, as well as heighten vigilance for viral transmission. To our knowledge, this is the first meta-analysis to report on the prevalence of these symptoms in COVID-19 patients.

  View details for DOI 10.1177/0194599820926473

  View details for PubMedID 32369429

• Intra-arterial cetuximab for the treatment of recurrent unresectable head and neck squamous cell carcinoma†. Journal of experimental therapeutics & oncology Tham, T., White, T. G., Chakraborty, S., Lall, R. R., Ortiz, R., Langer, D. J., Shatzkes, D., Filippi, C. G., Kraus, D., Boockvar, J. A., Costantino, P. D. 2016; 11 (4): 293-301

  Abstract

  Management of recurrent head and neck squamous cell carcinoma is a common and challenging clinical problem in head and neck oncology.Here we present the first reported case of super-selective intra-arterial (SSIA) microcatheter based local delivery of cetuximab for head and neck cancer. This technical report describes the techniques used to deliver the SSIA dose of cetuximab, as well as the patient outcome.This technical report is part of an ongoing Phase I Clinical Trial.The New York Head and Neck Institute (NYHNI) is a full-service otolaryngology and neurosurgery department at Lenox Hill Hospital, part of the Northwell Health System. The NYHNI serves a diverse patient population with a wide range of head and neck diseases in a tertiary hospital setting.SSIA Cetuximab.A patient presents to our clinic with recurrent unresectable squamous cell carcinoma of the nasopharynx. He is recruited into the first cohort of a phase I clinical trial to assess the safety of SSIA cetuximab, dose starting at 100mg/m2. Adjuvant chemo-radiation therapy is also given.Safety, as measured by toxicity of SSIA cetuximab.SSIA Cetuximab has been demonstrated to be a safe and feasible procedure in this technical report.This case illustrates technical feasibility and a very preliminary assessment of the safety of a novel delivery of a biologic agent for squamous cell carcinoma of the head and neck, which is part of an ongoing phase I clinical trial.NCT02438995.

  View details for PubMedID 27849340

• Sinonasal Inverted Papilloma and Clinical Significance of Dysplasia: A Multi-Institutional Study LARYNGOSCOPE Kim, A. H., Tham, T., Giannaris, P. S., Kokabee, M., Wilensky, J., Tsang, C., Wang, B. Y., Panara, K., Kuan, E. C., Papagiannopoulos, P., Tajudeen, B., Eide, J. G., Craig, J. R., Kshirsagar, R. S., Christian, Z., Locke, T. B., Fastenberg, J. H., Chaskes, M. B., Pollack, A. Z., Har-el, G., Cui, S., Guerrero, D., Ahn, S., Oh, E., Workman, A. D., Kohanski, M. A., Douglas, J., Robertson, E. S., Jalaly, J., Adappa, N. D., Palmer, J. N., Tong, C. C. L. 2025

  Abstract

  Sinonasal inverted papilloma (SNIP) is a benign sinonasal tumor with a tendency to recur and potential for malignant transformation. Dysplasia may be present, ranging from mild to severe. We aim to evaluate the effect of dysplasia on tumor behavior and patient outcomes.Retrospective chart review of SNIP cases from 2002 to 2023 treated by fellowship-trained Rhinologists at seven institutions. Clinical data were extracted, and tumors were histologically confirmed.Four hundred and forty-eight patients were eligible for analysis. The mean age was 58 years with an average postoperative surveillance of 27 months. Most patients had tumors without dysplasia (74.3%), followed by severe (10.5%), mild (10.0%), and moderate (5.1%) dysplasia. The overall recurrence rate was 11.6%. Unifocal attachment was most prevalent in tumors without dysplasia. Among patients with multifocal attachment, recurrence was highest in those with severe dysplasia (38.1%) compared to no dysplasia (17.2%). Unifocal attachment was associated with improved recurrence-free survival in all three histology types (without, mild, and moderate dysplasia).In the largest study to date examining the effect of dysplasia on patient outcomes, we found that SNIP that has severe dysplasia to be high risk for recurrence while the other three types of dysplasia to be of lower risk. We therefore propose a two-tiered grading system to improve consensus among pathologists and to guide patient counseling. In the treatment of SNIP, high-risk dysplasia is more often associated with multifocal attachment pattern and remains the most challenging to treat.

  View details for DOI 10.1002/lary.70263

  View details for Web of Science ID 001619990900001

  View details for PubMedID 41273225

• Frontal Sinus Inverted Papilloma: Surgical Challenges and Outcomes of a Multi-Institutional Cohort. The Laryngoscope Tham, T., Kim, A. H., Wilensky, J., Tsang, C., Giannaris, P. S., Wang, B. Y., Panara, K., Christian, Z., Kuan, E. C., Papagiannopoulos, P., Tajudeen, B., Eide, J. G., Craig, J. R., Kshirsagar, R. S., Locke, T. B., Ahn, S., Oh, E. J., Fastenberg, J. H., Chaskes, M. B., Pollack, A. Z., Har-El, G., Workman, A. D., Kohanski, M. A., Douglas, J., Adappa, N. D., Palmer, J. N., Tong, C. C. 2025

  Abstract

  Inverted papilloma (IP) is typically a benign sinonasal tumor with a propensity to recur. The surgical treatment of IP arising from the frontal sinus is complicated by proximity to the orbit and skull base. The objective of this study is to describe the surgical challenges when managing this disease and report treatment outcomes in a multicenter cohort.A retrospective review was performed on frontal sinus IP resected from 1993 to 2023. Demographic and clinicopathologic data, complications, surgical approach, and outcomes were analyzed.Ninety-eight patients (60 males, 38 females) were identified. Mean age was 59 years, with a median follow-up of 44 months. Histopathologic evaluation identified 13 lesions with carcinoma in situ or invasive carcinoma (13.3%). Bilateral involvement was found in 28 patients (28.6%). Overall, 17 patients (17.3%) had recurrent disease with a median recurrence time of 29.2 months. Fourteen patients (14.3%) underwent staged procedures, with a median time to the second procedure of 7.7 months. Twenty-three patients (23.5%) presented with skull base dehiscence on perioperative imaging. Skull base dehiscence had a significant effect on intraoperative cerebrospinal fluid leak (OR 9.1, 95% CI 3.0-27.4 p < 0.001).Frontal sinus IP is commonly attached at the skull base and associated with skull base dehiscence, CSF leak, and often requires operative repair and staged procedures. Complete tumor removal can be challenging and may necessitate a combined open and endoscopic approach. Careful surgical planning and close follow-up in the postoperative period are essential for disease control.Level 4.

  View details for DOI 10.1002/lary.70103

  View details for PubMedID 40899433

• Synchronous yet distinct HPV-associated sinonasal carcinomas on an immune-dysfunctional background. Journal of surgical case reports Thomas, J., Giannaris, P., Lee, K., Gomez Marti, J. L., Tham, T., Pollack, A. Z., Westra, W. H., Opher, E., Tong, C. C. 2025; 2025 (9): rjaf693

  Abstract

  Human papillomavirus (HPV)-associated multiphenotypic sinonasal carcinoma (HMSC) is a relatively new classification of head and neck carcinomas that displays histological combinations of multiple different neoplasms. Despite their high-grade appearance, the disease course is often indolent. Here, we report a unique case of HMSC in which a patient with a prior history of sarcoidosis presented with two histologically, and anatomically distinct tumors in the sinonasal tract. One of the tumors was denoted as HMSC, and the other resembled a nonkeratinizing squamous cell carcinoma. Importantly, these two tumors were both found to be driven by the same high-risk HPV strain, HPV45, which has not been reported previously in HMSC. In this patient, it is important to note that the concomitant diagnosis of malignancy and sarcoidosis makes disease monitoring challenging, given the ability of sarcoidotic nodules to mimic the metabolic characteristics of tumors on PET scans.

  View details for DOI 10.1093/jscr/rjaf693

  View details for PubMedID 40904594

  View details for PubMedCentralID PMC12401870

• Leveraging two-phase data for improved prediction of survival outcomes with application to nasopharyngeal cancer. Biometrics Oh, E. J., Ahn, S., Tham, T., Qian, M. 2025; 81 (2)

  Abstract

  Accurate survival predicting models are essential for improving targeted cancer therapies and clinical care among cancer patients. In this article, we investigate and develop a method to improve predictions of survival in cancer by leveraging two-phase data with expert knowledge and prognostic index. Our work is motivated by two-phase data in nasopharyngeal cancer (NPC), where traditional covariates are readily available for all subjects, but the primary viral factor, human papillomavirus (HPV), is substantially missing. To address this challenge, we propose an expert-guided method that incorporates prognostic index based on the observed covariates and clinical importance of key factors. The proposed method makes efficient use of available data, not simply discarding patients with unknown HPV status. We apply the proposed method and evaluate it against other existing approaches through a series of simulation studies and real data example of NPC patients. Under various settings, the proposed method consistently outperforms competing methods in terms of c-index, calibration slope, and integrated Brier score. By efficiently leveraging two-phase data, the model provides a more accurate and reliable predictive ability of survival models.

  View details for DOI 10.1093/biomtc/ujaf080

  View details for PubMedID 40568759

• Methodology of cfHPV-DNA Detection in Head and Neck Cancer: A Systematic Review and Meta-analysis OTOLARYNGOLOGY-HEAD AND NECK SURGERY Thomas, J., Mazzara, E., Guller, M., Landsberger, H., Tham, T., Cooper, D., Pereira, L., Kamdar, D., Frank, D., Miles, B., Mandal, R. 2024

  Abstract

  We aim to compare the diagnostic accuracy of the different methodologies used in the detection of cell-free human papillomavirus (HPV) DNA in HPV-associated head and neck squamous cell carcinoma detection using bivariate analysis methods.Pubmed, Embase, and Scopus were queried using a broad search strategy to search for relevant studies.Test characteristics were extracted from 33 studies following literature screening, and underwent analyses utilizing a bivariate approach. Summary statistics were identified for each type of methodology, and forest plots and summary receiver operating characteristic curves were constructed. Bias was estimated using Deek's Funnel Plot and the QUADAS-2 tool.In terms of diagnostic accuracy, digital droplet polymerase chain reaction (ddPCR) based testing exhibited the highest diagnostics odds ratio at 138 (59.5, 318), followed closely by next-generation sequencing (NGS) at 120 (39.7, 362), then by polymerase chain reaction (PCR) at 31.4 (14.4, 68.6), and quantitative PCR at 8.74 (4.63, 16.5).NGS and ddPCR are comparable in overall diagnostic accuracy, bringing into question their relative roles in diagnosis and screening. Cost-effective ddPCR assays may serve as useful diagnostic and screening tests in the clinic with their low false positive rates and high sensitivity. However, NGS assays also offer high sensitivity and companion metrics, suggesting they may have a more precise role in disease monitoring. Importantly, assay development and benchmarking need further standardization to improve comparison between assays. Finally, saliva-based testing needs to be further investigated using NGS and ddPCR to further understand its limitations in disease detection and monitoring.

  View details for DOI 10.1002/ohn.1056

  View details for Web of Science ID 001368356100001

  View details for PubMedID 39624913

• Selective Laser Trabeculoplasty Outcomes in Phakic and Pseudophakic Patients: A Meta-Analysis. Journal of current ophthalmology Kumbhani, R., Wong, A., Zhu, A., Shah, P., Tham, T., Anwar, F., Zhu, D. 2024; 36 (3): 242-251

  Abstract

  To perform a meta-analysis to compare the efficacy of selective laser trabeculoplasty (SLT) in phakic and pseudophakic eyes.Scopus, Embase, PubMed, and gray literature were searched for studies comparing SLT outcomes in phakic and pseudophakic patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). The mean change in intraocular pressure was compared using a standardized mean difference (SMD) meta-analysis (RevMan 5.4.1). Begg's funnel plots and Egger's test were used to assess publication bias.Eleven studies with 1058 eyes (323 pseudophakic and 735 phakic) were identified. There was no statistically significant difference in the observed efficacy of SLT between pseudophakic and phakic eyes (SMD = -0.10; 95% confidence interval = -0.24, 0.03; P = 0.14). There was no publication bias or heterogeneity (I 2 = 0%; P = 0.66) detected. Subgroup analysis of studies stratified by length of follow-up in months (6, 12, and 24 or greater) revealed no significant difference in SLT efficacy at the different time points (P = 0.86, P = 0.59, and P = 0.16, respectively).Our pooled and subgroup analysis revealed no significant difference in SLT response between the two populations. Our results support SLT as a viable treatment option for patients with OAG or OHT regardless of pseudophakic status.

  View details for DOI 10.4103/joco.joco_285_23

  View details for PubMedID 40557409

  View details for PubMedCentralID PMC12184856

• Outcomes of Chandelier-Assisted Scleral Buckling in Rhegmatogenous Retinal Detachments: Systematic Review and Meta-analysis. Journal of vitreoretinal diseases Zhu, D., Wong, A., Jiao, G., Zhang, C., Yakobashvili, D., Zhu, E., Tham, T., Lieberman, R. 2024; 8 (2): 158-167

  Abstract

  Purpose: To examine the outcomes of chandelier endoillumination-assisted scleral buckling (chandelier scleral buckling) for rhegmatogenous retinal detachments (RRDs) and compare them with those of standard scleral buckling using indirect ophthalmoscopy. Methods: A literature search was performed on April 15, 2023. Outcomes analyzed included the primary anatomic success rates, surgical duration, and complication rates. A meta-analysis of proportions estimated the pooled success rate of chandelier scleral buckling. In addition, meta-analyses compared the success rates between pseudophakic eyes and phakic eyes having chandelier scleral buckling and compared success rates and surgical duration between standard scleral buckling and chandelier scleral buckling. Results: Thirty studies with 1133 eyes were included. The pooled primary anatomic success rate of chandelier scleral buckling was 91.7% (95% CI, 89.6%-93.6%). In studies comparing success rates between the 2 techniques, there was no significant difference (risk ratio, 1.01; 95% CI, 0.94-1.08; P = .80). The surgical times were significantly shorter with chandelier scleral buckling than with standard scleral buckling (mean difference, -18.83; 95% CI, -30.88 to -6.79; P = .002). There was no significant difference in the success rate between pseudophakic eyes and phakic eyes (risk ratio, 0.99; 95% CI, 0.91-1.08; P = .89). No cases of endophthalmitis were reported. Conclusions: Chandelier endoillumination-assisted scleral buckling may be a promising technique given its high rate of primary anatomic success for RRDs and success rates similar to those of standard scleral buckling. There was no significant difference in the efficacy of chandelier scleral buckling between pseudophakic eyes and phakic eyes.

  View details for DOI 10.1177/24741264231224956

  View details for PubMedID 38465358

  View details for PubMedCentralID PMC10924592

• Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy. Head & neck Guller, M., Cooper, D. J., Alkhatib, H., Suru, A., Blancaflor, A., Maroun, C. A., Tham, T., Allen, H., Mazzara, E., Thomas, J., Amin, N., Wu, E., Eisele, D. W., Fakhry, C., Pardoll, D., Seiwert, T. Y., Zhu, G., Mandal, R. 2023; 45 (11): 2789-2797

  Abstract

  To explore the impact of pre-existing comorbidities on immunotherapy response, overall and progression-free survival, and immune-related adverse events (irAEs) of patients with advanced head and neck cancer (HNC) treated with immunotherapy.Ninety-three patients treated with immunotherapy were identified and stratified into comorbidity absent or present (CCI < 1 and CCI ≥ 1, respectively) cohorts, and clinical outcomes were compared between these two groups.Patients with no comorbidities had longer overall survival (aHR = 2.74, 95% CI [1.18, 6.40], p = 0.02) and progression-free survival (aHR = 2.07, 95% CI [1.03, 4.16], p = 0.04) and a higher tumor response rate (32% in CCI < 1 vs. 14% in CC ≥ 1, p = 0.05). Risk for irAEs was higher in the comorbidity absent group (p = 0.05).Comorbidity should be considered as a significant prognostic factor in clinical decision-making for patients with advanced HNC undergoing immunotherapy.

  View details for DOI 10.1002/hed.27502

  View details for PubMedID 37682116

  View details for PubMedCentralID PMC10634321

• Preoperative Embolization Techniques in the Treatment of Juvenile Nasopharyngeal Angiofibroma: A Systematic Review. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Kothari, D. S., Linker, L. A., Tham, T., Maroda, A. J., McElfresh, J. M., Fastenberg, J. H., Hachem, R. A., Elijovich, L., Michael, L. M., Rangarajan, S. V. 2023; 169 (3): 454-466

  Abstract

  Preoperative embolization has proven beneficial in the surgical treatment of juvenile nasopharyngeal angiofibromas (JNA). However, the consensus for the best embolization practices remains unclear. This systematic review seeks to characterize the reporting of embolization protocols throughout the literature and to compare differences in surgical outcomes.PubMed, Embase, and Scopus.Studies investigating embolization in the treatment of JNA from 2002 to 2021 were selected from defined inclusion criteria. All studies underwent a 2-stage blinded screening, extraction, and appraisal process. Embolization material, time to surgery, and embolization route were compared. Embolization complications, surgical complications, and rate of recurrence were pooled.Of 854 studies, 14 retrospective studies with 415 patients met the criteria for inclusion. A total of 354 patients underwent preoperative embolization. A total of 330 patients (93.2%) underwent transarterial embolization (TAE) and 24 patients had a combination of direct puncture embolization and TAE. Polyvinyl alcohol particles were the most used embolization material (n = 264, 80.0%). The most common reported time to surgery was 24 to 48 hours (n = 8, 57.1%). Pooled results showed an embolization complication proportion of 3.16% (95% confidence interval [CI]: 0.96-6.60) (n = 354), a surgical complication proportion of 4.96% (95% CI: 1.90-9.37) (n = 415), and a recurrence proportion of 6.30% (95% CI: 3.01-10.69) (n = 415).The current data on JNA embolization parameters and their effect on surgical outcomes remains too heterogenous to provide expert recommendations. Future studies should use uniform reporting to allow for more robust comparisons of embolization parameters, which, in turn, may lead to optimized patient outcomes.

  View details for DOI 10.1002/ohn.303

  View details for PubMedID 36808756

• Accuracy of Surgeon Predictions in Rhinoplasty Outcomes Using Computer Imaging: A Quantitative Analysis of Dorsal Height. Facial plastic surgery & aesthetic medicine Harounian, J., Tham, T., Dodhia, S., Pearlman, S. 2023; 25 (2): 186-188

  View details for DOI 10.1089/fpsam.2022.0020

  View details for PubMedID 35506909

• Incidence of Head and Neck Cancers before and after 9/11 in New York City and New York State. ORL; journal for oto-rhino-laryngology and its related specialties Machado, R., Tham, T., Zhu, D., Wong, A., Hiltzik, D., Roche, A. 2022; 84 (4): 324-335

  Abstract

  The incidence of cancers in New York State (NYS) before and after 9/11 including lung, colorectal, and renal cancers has been previously described. To date, the incidence of head and neck cancers (HNCs) before and after 9/11 has not been described.Cancers involving the oral cavity and oropharynx; the nose, nasal cavity, nasopharynx, and middle ear; larynx; and thyroid were identified using the New York State Cancer Registry (NYSCR). Age-adjusted incidence and rates per 100,000 residents from 1987 to 2015 were analyzed using joinpoint regression. Trends in incidence using annual percent changes are presented.The overall rate of HNC increased slightly by 0.7% (p < 0.001) from 1987 to 2003 in NYS. From 2003 to 2008, the rate increased by 5.73% (p < 0.001), and from 2008 to 2015, the rate increased by 1.68% (p < 0.001). The rate of thyroid cancer increased by 6.79% (p < 0.001) from 1987 to 2003, by 9.99% (p < 0.001) from 2003 to 2009, and by 2.41% (p = 0.001) from 2009 to 2015. The rate of thyroid cancer was higher in women at all time points. In a subset analysis of HNCs excluding thyroid cancer, the rate decreased by 2.02% (p < 0.001) from 1991 to 2001, followed by a nonsignificant increase of 0.1% (p = 0.515) from 2001 to 2015. The rate of oropharyngeal (OP) cancer significantly increased from 1999 to 2015 (2.65%; p < 0.001). The rate of oral cavity cancer significantly decreased from 1987 to 2003 (1.97%; p < 0.001), with no significant change after 2003. The rate of laryngeal cancer decreased significantly by 2.43% (p < 0.001) from 1987 to 2015, as did the rate of nasal cavity/nasopharyngeal cancer (0.33%; p = 0.03).In NYS, OP cancer and thyroid cancer rates increased significantly during the study period. The rate of thyroid cancer was higher in women. The rate of combined HNC increased significantly after 9/11 compared to before 9/11; however, in a subset analysis of all HNC patients excluding thyroid cancer, the rate decreased significantly prior to 9/11 and then nonsignificantly increased afterward. This suggests that the increase in thyroid cancer accounts for the increase in combined HNC in NYS. The impact of 9/11 on rates of HNC requires further research.

  View details for DOI 10.1159/000519840

  View details for PubMedID 34959232

• Management of Extruded Porous High-density Polyethylene Implant in the Internal Nasal Valve. Plastic and reconstructive surgery. Global open Diaz, A. M., Tham, T., Saleem, M. I., Ponder, B., Georgolios, A. 2022; 10 (11): e4647

  Abstract

  Porous high-density polyethylene (PHDPE) has been used since the 1990s as an alternative to autologous grafts. Implant extrusion is a rare but well-known complication of PHDPE and other alloplastic implants. This article discusses the case of PHDPE implant extrusion in a 69-year-old man with unsuccessful previous alar batten graft placement for internal nasal valve insufficiency. We detail the surgical techniques engaged in removing the implant from the internal nasal valve, postoperative results, and care, and present a histologic study of the removed implants.

  View details for DOI 10.1097/GOX.0000000000004647

  View details for PubMedID 36438463

  View details for PubMedCentralID PMC9682612

• Clinical Outcomes in Dorsal Preservation Rhinoplasty: A Meta-Analysis. Facial plastic surgery & aesthetic medicine Tham, T., Bhuiya, S., Wong, A., Zhu, D., Romo, T., Georgolios, A. 2022; 24 (3): 187-194

  Abstract

  Background: Dorsal preservation rhinoplasty (PR-D) attempts to preserve as much of the native nasal anatomy as possible when performing a hump reduction, but clinical outcomes are unclear. Objective: In patients undergoing PR-D rhinoplasty, this article investigates the rates of complications and revisions. Methods: This meta-analysis was prospectively registered on the PROSPERO database. The Pubmed, Embase, and Scopus databases were searched. Pooled incidence was calculated in a meta-analysis within a random-effects model. Results: Twenty-two studies representing a cohort of 5660 patients were included in this study. Postoperative hump recurrence rates (4.18%, 95% confidence interval [CI]: 2.41-6.40%), rates of revision rhinoplasty (3.48%, 95% CI: 1.77-5.74%), rates of postoperative nasal deviation (1.13%, 95% CI 0.37-2.28%), and rates of infection (1.89%, 95% CI: 0.35-4.62%) were all found to be low. Conclusion: PR-D has low rates of revision surgery, residual or recurrent hump, postoperative nasal deviation, and postoperative infection.

  View details for DOI 10.1089/fpsam.2021.0312

  View details for PubMedID 35172105

• Recurrent, oral cavity tumor-like exophytic lesions mimicking neoplastic disease in a patient with history of human papillomavirus-mediated squamous cell carcinoma. SAGE open medical case reports Hawthorne, M., Tham, T., Ponder, B., Georgolios, A. 2021; 9: 2050313X211065884

  Abstract

  Reactive hyperplasia is a phenomenon responsible for exophytic lesions in the oral cavity, and may appear to be suspicious, especially in patients who have a significant history of malignancy. Here, we present a case of reactive hyperplasia mimicking recurrence in a patient who was previously treated for tonsillar carcinoma. Physicians who commonly see patients with oral lesions, particularly oral surgeons and otolaryngologists, should be cognizant of the unusual presentation of these lesions as they may mimic the physical characteristics of recurrence.

  View details for DOI 10.1177/2050313X211065884

  View details for PubMedID 34925843

  View details for PubMedCentralID PMC8679042

• The prognostic impact of depression or depressive symptoms on patients with head and neck cancer: A systematic review and meta-analysis. Head & neck Van der Elst, S., Bardash, Y., Wotman, M., Kraus, D., Tham, T. 2021; 43 (11): 3608-3617

  Abstract

  This systematic review and meta-analysis sought to assess the extent to which pretreatment depression or depressive symptoms are related to prognosis in patients with head and neck cancer (HNC).Medline, EMbase, Scopus, and The Cochrane Library databases were searched. A meta-analysis was done to generate a forest plot and pooled hazard ratio (HR) with 95% CI for overall survival (OS). RevMan 5.3 and Meta Essentials were used for statistical analysis.Based on seven studies involving 1743 patients, the results showed that HNC patients with pretreatment depression or depressive symptoms had worse OS than patients without depression or depressive symptoms, with an HR of 1.33, 95% CI 1.16-1.52, p = <0.0001. There is heterogeneity in the pooled summary effect (I2  = 80%, p < 0.0001).Pretreatment depression or depressive symptoms may indicate worse OS in patients with HNC. The pooled analysis demonstrated a statistically significant effect. These results were limited by mild heterogeneity.

  View details for DOI 10.1002/hed.26868

  View details for PubMedID 34525238

• The jaw-dropping costs of oral cavity cancer malpractice. Head & neck Wong, A., Zhu, D., Tong, J. Y., Ko, A., Tham, T., Kraus, D. 2021; 43 (10): 2869-2875

  Abstract

  Medical litigation is different than it was 20 years ago due to changes in health care. This study provides an updated analysis of oral cavity malpractice litigation from the past two decades (2000-2010 and 2011-2019).Verdict reviews from the Westlaw database were analyzed from January 2000 to August 2019. Data were collected and analyzed with the Statistical Package for the Social Sciences.Sixty-five lawsuits were evaluated across 24 states. Failure to diagnose was the most common allegation in both decades. Adjusting for inflation, the average amount awarded from 2000 to 2010 was $1 721 068 and $3 925 504 from 2011 to 2019.There has been a significant rise in allegations of failure to biopsy and failure to refer (p < 0.05). In addition, while award amounts appear different between decades, the difference is not statistically significant (p = 0.248). Education should focus on early diagnosis, biopsy, and referral to physicians who routinely care for this patient population.

  View details for DOI 10.1002/hed.26764

  View details for PubMedID 34050580

• The impact of the COVID-19 pandemic on otolaryngologic emergency department visits at two major NYC hospital systems AMERICAN JOURNAL OF OTOLARYNGOLOGY Patel, V. M., Kominsky, E., Tham, T., Bottalico, D., Setzen, M., Ferastraoaru, D., Akbar, N., Fastenberg, J. H. 2021; 42 (5): 103123

  Abstract

  Since the COVID-19 pandemic began, emergency departments (ED) across the country have seen a significant decrease in patient visits. We aim to evaluate the impact of COVID-19 on ED visits for acute otolaryngologic complaints in New York City, one of the first epicenters of the pandemic in the US.We conducted a retrospective study of patients who presented to the ED with a primary diagnosis of an acute otolaryngologic complaint between March 1 and May 31 in 2019 and 2020. This was a multicenter study, including two tertiary care hospital systems encompassing Manhattan, Bronx, Queens, and Long Island.A total of 10,162 patients were identified. Significantly fewer patients presented to the ED for acute otolaryngologic complaints in 2020 (7332 vs 2830, p < 0.001). The rate of total otolaryngology-related ED visits was decreased by a factor of 0.635 (95% CI 0.6079 to 0.6634). In a subgroup analysis of each individual diagnosis, there was a significant decrease in rate of ED visits for 13 out of 18 diagnoses, including for life-threatening conditions, such as anaphylaxis. There was no significant difference based on which borough in New York City. Pediatric patients (age 0-17) were more significantly impacted by the pandemic compared to other age groups.The COVID-19 pandemic has led to a reduction in the utilization of ED for acute otolaryngologic complaints, including those requiring emergent management, and an even more significant reduction in the pediatric population. Healthcare providers should encourage patients to seek appropriate care, particularly for those illnesses with significant associated morbidity and mortality.

  View details for DOI 10.1016/j.amjoto.2021.103123

  View details for Web of Science ID 000690739600001

  View details for PubMedID 34186437

  View details for PubMedCentralID PMC8214322

• Response to Alfonso Santamaría-Gadea and Colleagues. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Tong, J. Y., Wong, A., Zhu, D., Fastenberg, J. H., Tham, T. 2021; 164 (2): 456-457

  View details for DOI 10.1177/0194599820951135

  View details for PubMedID 32777977

• Radiologically Defined Sarcopenia Affects Survival in Head and Neck Cancer: A Meta-Analysis. The Laryngoscope Wong, A., Zhu, D., Kraus, D., Tham, T. 2021; 131 (2): 333-341

  Abstract

  To determine whether radiologically defined sarcopenia at the C3 or L3 level as measured by computed tomography or magnetic resonance imaging is prognostic of overall survival (OS) in head and neck cancers (HNCs).Literature searches of PubMed, Embase, and Scopus were conducted on July 12, 2019, to include articles written in the English language with no constraints on publication date. To be included in the analysis, articles had to report the prognostic impact of skeletal muscle mass measured radiologically at the C3 or L3 vertebral level in HNC patients; hazard ratios (HRs) for OS; 95% confidence intervals (CIs); be from a clinical trial, cohort, or case-control study; and have English full-text availability. Articles were reviewed in consensus by two reviewers, with disagreements reviewed by a third reviewer. Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology Checklist guidelines were used for reporting. Study quality assessment was performed using Quality In Prognosis Studies tool. The random-effects DerSimonian and Laird method was used for meta-analysis.Ten articles, nine retrospective and one prospective, were included in this meta-analysis (n = 2,181 patients). Significant differences were found in OS for HNC patients with sarcopenia (HR = 1.98; 95% CI: 1.64-2.39; P < .00001). No heterogeneity was detected in either the overall or subgroup analyses.Radiologically defined sarcopenia is a negative predictor of OS in patients with HNC. Early detection of sarcopenia in cancer patients may help guide nutritional and adjuvant support to improve treatment outcomes.NA Laryngoscope, 131:333-341, 2021.

  View details for DOI 10.1002/lary.28616

  View details for PubMedID 32220072

• The Prognostic Role of Programmed Death-Ligand 1 in Nasopharyngeal Carcinoma. The Laryngoscope Wotman, M., Herman, S. W., Costantino, P., Tham, T. 2020; 130 (11): 2598-2606

  Abstract

  Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that may be a useful prognostic biomarker in nasopharyngeal cancer (NPC). The purpose of this systematic review and meta-analysis was to investigate the relationship between PD-L1 expression and survival in NPC.PubMed, Cochrane, Embase, Scopus, and Web of Science were searched from inception to present. A predefined inclusion and exclusion criteria were used to select articles. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled for overall survival (OS), disease-free survival (DFS), and disease metastasis-free survival (DMFS).Eleven studies published from 2014 to 2018 were included, with 1,356 total participants. PD-L1 expression was not associated with OS (HR = 1.10, 95% CI: 0.79-1.55), DFS (HR = 1.66, 95% CI: 0.68-4.03), or DMFS (HR = 1.18, 95% CI: 0.44-3.20).The prognostic role of PD-L1 in NPC remains unsubstantiated. Future research is needed. Laryngoscope, 130:2598-2606, 2020.

  View details for DOI 10.1002/lary.28523

  View details for PubMedID 32112431

• Improving post-CRT neck assessment in patients with HPV-associated OPSCC (Review). Molecular and clinical oncology Wotman, M., Ghaly, M., Massaro, L., Tham, T., Seetharamu, N., Kamdar, D., Frank, D., Kraus, D., Teckie, S. 2020; 13 (4): 24

  Abstract

  The positive predictive value (PPV) of 12-week post-therapy FDG-PET/CT is low in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) after treatment with definitive chemoradiation (CRT). Moreover, the diagnostic performance of post-CRT fine needle aspiration (FNA) in detecting persistent disease is unknown in this population. Given these important shortcomings in post-CRT treatment assessment, head and neck oncologists are limited in appropriately selecting patients for consolidative neck dissection, which results in over-treatment of a favorable risk population. Using the PubMed database, we performed a literature review of published series in HPV-associated OPSCC to investigate potential strategies for improvement of post-CRT neck assessment. Several different approaches were found, including continued surveillance with PET/CT, delayed timing of restaging PET/CT, initial response evaluation with multimodality or alternative imaging, and detection of circulating HPV DNA. At present, the optimal approach to post-CRT treatment assessment is unclear; further investigation and incorporation of new technologies and surveillance protocols will be highly beneficial for patients with HPV-associated OPSCC.

  View details for DOI 10.3892/mco.2020.2094

  View details for PubMedID 32765872

  View details for PubMedCentralID PMC7403806

• Author Reply to: "Comment on 'The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis'". Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Tong, J. Y., Wong, A., Zhu, D., Fastenberg, J. H., Tham, T. 2020; 163 (4): 853

  View details for DOI 10.1177/0194599820934760

  View details for PubMedID 32539660

• The paralyzing legal costs of facial nerve injury in head and neck tumors. American journal of otolaryngology Zhu, D., Wong, A., Tham, T., Kraus, D. 2020; 41 (6): 102693

  Abstract

  Facial nerve paralysis from head and neck tumors can result from disease progression or iatrogenic causes, leading to litigation. The aim of this study was to investigate lawsuits regarding facial paralysis as a consequence of these tumors to understand and better educate physicians behind the reasons for litigation.Jury verdict reviews were obtained from the Westlaw database from 1985 to 2018. Gathered data, including verdicts, litigation reasons, defendant specialties, and amounts awarded, were analyzed via Statistical Package for the Social Sciences.Of the 26 lawsuits analyzed, the leading reason for litigation was failure to diagnose (53.8%), followed by iatrogenic injury (34.6%). The average award was $2,704,470. Otolaryngologists were the most common defendants. Defendants that included an otolaryngologist had shorter delays of diagnosis compared to those that did not (p < 0.05).Failure to diagnose parotid injury was the leading cause of litigation. In instances where the jury found for the plaintiff, the amount was material. There were equivalent incidences of cases in favor of plaintiffs and defendants.

  View details for DOI 10.1016/j.amjoto.2020.102693

  View details for PubMedID 32866849

• The effect of race in head and neck cancer: A meta-analysis controlling for socioeconomic status. American journal of otolaryngology Russo, D. P., Tham, T., Bardash, Y., Kraus, D. 2020; 41 (6): 102624

  Abstract

  To investigate the association between race and ethnicity and prognosis in head and neck cancers (HNC), while controlling for socioeconomic status (SES).Medline, Scopus, EMBASE, and the Cochrane Library were used to identify studies for inclusion, from database inception till March 5th 2019. Studies that analyzed the role of race and ethnicity in overall survival (OS) for malignancies of the head and neck were included in this study. For inclusion, the study needed to report a multivariate analysis controlling for some proxy of SES (for example household income or employment status). Pooled estimates were generated using a random effects model. Subgroup analysis by tumor sub-site, meta-regression, and sensitivity analyses were also performed. RevMan 5.3, Meta Essentials, and OpenMeta[Analyst] were used for statistical analysis.Ten studies from 2004 to 2019 with a total of 108,990 patients were included for analysis in this study. After controlling for SES, tumor stage, and treatment variables, blacks were found to have a poorer survival compared to whites (HR = 1.27, 95%CI: 1.18-1.36, p < 0.00001). Subgroup analysis by sub-site and sensitivity analysis agreed with the primary result. No differences in survival across sub-sites were observed. Meta-regression did not identify any factors associated with the pooled estimate.In HNC, blacks have poorer OS compared to whites even after controlling for socioeconomic factors.

  View details for DOI 10.1016/j.amjoto.2020.102624

  View details for PubMedID 32663732

• MLKL-dependent epithelial-to-mesenchymal transition in nasopharyngeal carcinoma: a novel finding and avenues for future research. Annals of translational medicine Tham, T. 2020; 8 (5): 153

  View details for DOI 10.21037/atm.2020.01.83

  View details for PubMedID 32309302

  View details for PubMedCentralID PMC7154460

• Anatomical subsite modifies survival in oropharyngeal squamous cell carcinoma: National Cancer Database study. Head & neck Tham, T., Ahn, S., Frank, D., Kraus, D., Costantino, P. 2020; 42 (3): 434-445

  Abstract

  Oropharyngeal squamous cell carcinomas (OPSCC) can occur in either tonsillar related areas (TRA) or nontonsillar areas (nTRA). The prognostic differences between these sites are unclear. This study investigated this question using the National Cancer Database (NCDB), controlling for other confounders including human papillomavirus (HPV) status.This NCDB study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA. Kaplan Meier survival analysis was stratified according to HPV status, and further analysis was conducted using multivariable Cox regression.A total of 23 297 patients were included in this study. In the multivariable cox regression analysis, OPSCC subsite was found to be an independent prognostic factor for survival (TRA vs nTRA HR: 0.76, 95% CI: 0.67-0.86, P < .0001).In this large cohort, OPSCC subsite was found to be an independent prognostic factor for survival.

  View details for DOI 10.1002/hed.26019

  View details for PubMedID 31773842

• Investigating the role of octamer binding transcription Factor-4 (Oct-4) in oral cavity squamous cell carcinoma: A systematic review and meta-analysis. American journal of otolaryngology Gliagias, V., Wotman, M., Herman, S. W., Costantino, P., Kraus, D., Tham, T. 2019; 40 (2): 282-288

  View details for DOI 10.1016/j.amjoto.2018.12.011

  View details for PubMedID 30595225

• Survival impact of treatment-related time intervals in nasopharyngeal carcinoma in the United States. The Laryngoscope Tham, T., Ahn, S., Teckie, S., Roche, A., Frank, D., Kraus, D., Costantino, P. 2019; 129 (11): 2514-2520

  Abstract

  To determine if delayed or prolonged treatment-related time intervals (TRTIs) was associated with survival in patients with nasopharyngeal carcinoma (NPC) undergoing curative-intent concurrent chemoradiation (CCRT). The TRTIs investigated were duration of radiation treatment (RTd), time to radiation start (TTR), and time to chemotherapy start (TTC).Observational cohort study using the National Cancer Database (NCDB). In this observational cohort study, 3,893 eligible patients with NPC were identified from the NCDB. Patients received CCRT of at least 66 grays and radiation treatment time of at least 40 days. Separate univariable Cox regression model was used to analyze overall survival (OS) as a function of TRTIs, as well as for Charlson/Deyo Score, tumor classification, node classification, histological type, ethnicity, age, sex, and facility type. Upon finding significance at P < 0.05, the multivariable Cox regression analysis with backward elimination was performed to yield the final prediction model. Results were considered statistically significant when P < 0.05.Radiation treatment was significantly associated with OS in the univariable analysis (hazard ratio: 1.006, 95% confidence interval = 1.004-1.008, P < 0.001). However, RTd was not related to OS in the multivariable analysis (P = 0.19). The TTR and TTC variables were not associated with OS in the univariable analysis (P = 0.88 and P = 0.88, respectively).TRTIs were not independently associated with OS in this cohort of NPC patients in the NCDB. Future research into the association of TRTI with other disease outcomes, such as disease-free survival and locoregional control, is needed.NA. Laryngoscope, 129:2514-2520, 2019.

  View details for DOI 10.1002/lary.27818

  View details for PubMedID 30702156

• Systemic immune response in squamous cell carcinoma of the head and neck: a comparative concordance index analysis. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Tham, T., Wotman, M., Chung, C., Ahn, S., Dupuis, H., Gliagias, V., Movsesova, T., Kraus, D., Costantino, P. 2019; 276 (10): 2913-2922

  Abstract

  The objective of this study was to investigate the prognostic role of three inflammatory markers: the neutrophil to lymphocyte ratio (NLR), the lymphocyte to monocyte ratio (LMR), and the platelet to lymphocyte ratio (PLR) as prognostic indicators in squamous cell carcinoma of the head and neck (HNSCC).Patients with HNSCC treated with primary surgery, with or without adjuvant radiochemotherapy were enrolled. The preoperative NLR, LMR, and PLR were recorded. Confounding variables were also recorded: age, sex, BMI, comorbidities, performance status, AJCC T and N stage and HPV status. Endpoints were overall survival (OS) and event-free survival (EFS). Survival analysis was performed using Kaplan-Meier analysis, and multivariable analysis was performed using Cox proportional hazards regression. Survival models were evaluated using Harrell's concordance index (c-index).NLR (p = 0.2413), PLR (p = 0.1593), and LMR (p = 0.0552) were not significantly associated with OS in the multivariable analysis. With regard to EFS, low LMR (HR = 2.95, 95% CI 1.54-5.65, p = 0.001), high PLR (HR = 2.68, 95% CI 1.42-5.09, p = 0.003), and high NLR (HR = 3.37, 95% CI 1.7-6.69, p < 0.001) were associated with EFS. The multivariable c-index was highest for LMR (0.762), followed by NLR (0.761) and PLR (0.739).The LMR, PLR, and NLR were not associated with OS, but were associated with EFS in HNSCC. These markers are easily obtainable, and in the age of individualized patient care and precision medicine, they might represent further risk stratification tools for HNSCC patients.

  View details for DOI 10.1007/s00405-019-05554-x

  View details for PubMedID 31312922

• Platelet-Lymphocyte Ratio as a Predictor of Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis. Oncology research and treatment Bardash, Y., Olson, C., Herman, W., Khaymovich, J., Costantino, P., Tham, T. 2019; 42 (12): 665-677

  Abstract

  The aim of this systematic review and meta-analysis was to investigate the prognostic utility of the platelet-to-lymphocyte ratio (PLR) in head and neck cancer. Medline (via PubMed), EMBASE, Scopus, and the Cochrane Library databases were searched from their inception to May 2017 for relevant literature. A systematic review and meta-analysis were performed to generate the pooled hazard ratios (HR) for overall survival (OS) and disease-specific survival (DSS). The study was conducted in accordance with the Cochrane Handbook and PRISMA guidelines. Risk of bias was assessed using the QUIPS tool. The logarithm of the HR with standard error was used as the primary summary statistic. Heterogeneity was assessed using Cochran's Q and Higgins' I2. A total of 13 studies were included in the final analysis, combining data from 4,541 patients. The results demonstrated that an elevated PLR was significantly associated with poorer OS [HR 1.85, 95% CI 1.35-2.52, p < 0.00001] and DSS [HR 1.57, 95% CI 1.25-1.97, p < 0.0001]. Significant heterogeneity was detected for the pooled end points. Subgroup analysis demonstrated reduction of heterogeneity by controlling for sample size and cutoff value. 95% prediction intervals showed wide ranges crossing the null threshold.

  View details for DOI 10.1159/000502750

  View details for PubMedID 31550732

• Personalized prognostication in head and neck cancer: A systematic review of nomograms according to the AJCC precision medicine core (PMC) criteria. Head & neck Tham, T., Machado, R., Herman, S. W., Kraus, D., Costantino, P., Roche, A. 2019; 41 (8): 2811-2822

  Abstract

  The American Joint Committee on Cancer (AJCC) Precision Medicine Core (PMC) has recognized the need for more personalized probabilistic predictions above the "TNM" staging system and has recently released a checklist of inclusion and exclusion criteria for evaluating prognostic models.A systematic review of articles in which nomograms were created for head and neck cancer (HNC) was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The AJCC PMC criteria were used to score the individual studies.Forty-four studies were included in the final qualitative analysis. The mean number of inclusion criteria met was 9.3 out of 13, and the mean number of exclusion criteria met was 2.1 out of 3. Studies were generally of high quality, but no single study fulfilled all of the AJCC PMC criteria.This is the first study to utilize the AJCC checklist to comprehensively evaluate the published prognostic nomograms in HNC. Future studies should attempt to adhere to the AJCC PMC criteria. Recommendations for future research are given.The AJCC recently released a set of criteria to grade the quality of prognostic cancer models. In this study, we grade all published nomograms for head and neck cancer according to the new guidelines.

  View details for DOI 10.1002/hed.25778

  View details for PubMedID 31012188

• HPV status in patients with nasopharyngeal carcinoma in the United States: A SEER database study. American journal of otolaryngology Wotman, M., Oh, E. J., Ahn, S., Kraus, D., Costantino, P., Tham, T. 2019; 40 (5): 705-710

  Abstract

  To investigate the etiologic and prognostic role of Human Papilloma Virus (HPV) in Nasopharyngeal Carcinoma (NPC).Patients diagnosed with NPC were identified with the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to investigate the effect of clinicopathologic predictors on HPV positivity in NPC. Survival analyses were performed with Kaplan-Meier curves and Cox regression models.180/517 patients (34.8%) with known HPV testing were positive for HPV-associated NPC. East Asians and individuals over 25 were less likely to have HPV-associated NPC, while controlling for AJCC-7 stage and AJCC-7 M stage. According to the survival analysis, cause-specific survival (CSS) did not differ significantly by HPV status throughout the study period, but did differ significantly by HPV ethnicity group.The clinical implications of HPV in NPC are further elucidated but require more investigation.IV.

  View details for DOI 10.1016/j.amjoto.2019.06.007

  View details for PubMedID 31277887

• Management of the neck after definitive chemoradiation in patients with HPV-associated oropharyngeal cancer: An institutional experience. American journal of otolaryngology Wotman, M., Ghaly, M., Massaro, L., Tham, T., Seetharamu, N., Kamdar, D., Frank, D., Kraus, D., Teckie, S. 2019; 40 (5): 684-690

  Abstract

  To investigate the multidisciplinary management of patients with Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and an incomplete nodal response on restaging PET/CT after definitive chemoradiation (CRT).A retrospective chart review was performed of patients diagnosed with node-positive HPV-associated OPSCC from 2012 to 2017, who underwent definitive upfront CRT, and had an incomplete response on post-therapy PET/CT according to NCCN criteria. Post-CRT PET/CT results, management decisions, and clinical outcomes were recorded.Seventy-four patients with node-positive HPV-associated OPSCC were identified; 20 patients with incomplete neck response on PET/CT according to NCCN criteria were included in the final case series. Median follow-up time was 33 months. Patients were managed as follows: 8 underwent observation and surveillance imaging, 6 underwent ultrasound-guided fine needle aspiration (FNA), and 6 had immediate neck dissection. All the observed patients were disease-free at most recent follow-up. None of the patients who underwent immediate neck dissection had residual neck disease on pathological examination; two patients in this group ultimately developed metastatic disease. Among the 6 who underwent FNA, 1 individual had positive pathology, along with residual primary disease, for which the patient underwent salvage surgery. The 5 remaining individuals had negative FNA results, were subsequently observed, and remained free of disease.This institutional experience supports the notion of a high threshold for neck dissection in this low-risk population; only 1 of 20 patients with suspicious PET/CT findings had residual disease in the neck. Moreover, these patients should be managed by a multidisciplinary tumor board (MTB) since current algorithms do not universally include HPV status. Finally, the use of restaging PET/CT to guide management of the neck can be improved with changes in terminology and consideration of FDG-avidity at the primary site and on pre-therapy scans.

  View details for DOI 10.1016/j.amjoto.2019.06.003

  View details for PubMedID 31229365

• The prognostic effect of anatomic subsite in HPV-positive oropharyngeal squamous cell carcinoma. American journal of otolaryngology Tham, T., Wotman, M., Roche, A., Kraus, D., Costantino, P. 2019; 40 (4): 567-572

  Abstract

  Since most HPV-associated disease occurs in the tonsillar-related areas (TRA) - palatine and lingual tonsils, the effect of HPV on survival in non-tonsillar oropharyngeal subsites (nTRA) is not well established. The objective of this study was to use a large population-based cohort to investigate the survival impact of HPV in nTRA subsites versus TRA subsites.This SEER database study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA.HPV-positive squamous cell cancer was significantly more common in TRAs (73%) compared to nTRAs (31.2%, p < 0.001). After controlling for age, treatment, stage, race, and income, patients with HPV-positive disease in nTRAs had a worse cause-specific survival (CSS) than individuals with HPV-positive disease in TRAs (HR = 2.16, 95% CI 1.20-3.86, p = 0.01).Patients with HPV-positive OPSCC in nTRAs had poorer survival outcomes compared to patients with HPV-positive OPSCC in TRAs.

  View details for DOI 10.1016/j.amjoto.2019.05.006

  View details for PubMedID 31113681

• Evaluation of Time to Surgery and Its Effect on Prognosis in Head and Neck Cancer. Oncology research and treatment Tham, T., Leung, E., Khaymovich, J., Mitha, S., Olson, C., Wotman, M., Teegala, S., Coury, J., Costantino, P. 2019; 42 (7-8): 387-395

  Abstract

  Recently, time to treatment initiation has been observed to be increasing specifically for head and neck cancer. It is acknowledged that the pattern of increase is reflective of the use of sophisticated diagnostic and therapeutic techniques but was also determined to affect survival.Our study sought to further investigate time to surgery (TTS) for surgically treated patients to see whether TTS would influence patient survival.TTS was defined as the time from the earliest pathological report or scan, whichever was earlier, to surgery. The endpoints were overall survival (OS) and event-free survival (EFS).A total of 294 patients with head and neck cancer were included. Patients were organized into TTS quartiles of 0-14 days (quartile 1), 15-29 days (quartile 2), 30-49 days (quartile 3), and ≥50 days (quartile 4). The median follow-up time was 651 days, and the median TTS was 32 days. Using a univariable analysis of Cox regression, TTS was not significantly associated with OS or EFS. Kaplan-Meier curves were not significant for OS (p = 0.8904) and EFS (p = 0.9556).In this cohort study, we could not conclude that TTS was associated with OS or EFS.

  View details for DOI 10.1159/000500207

  View details for PubMedID 31079104

• Comparison of venous thromboembolism risk stratification models in a high risk otolaryngology patient cohort. Journal of perioperative practice Tham, T., Costantino, P. 2019; 29 (5): 129-134

  Abstract

  Our objective was to compare the venous thromboembolism outcomes in two of the most commonly utilised venous thromboembolism assessment tools, the Caprini system and the University of Michigan system, in a high risk head and neck surgery population. Currently, there is a lack of data reporting the validation of well known scoring systems in this patient population. Established risk factors for venous thromboembolism were included in the data collection process. We retrospectively evaluated all patients with the Caprini Risk Assessment and the University of Michigan Health System (UMHS) Scores. Out of all the risk factors, only length of surgery was found to be associated with venous thromboembolism. The mean Caprini scores in those with and without venous thromboembolism were 8.00 ± 3.00 and 6.86 ± 1.45, respectively. The mean UMHS scores in those with and without venous thromboembolism were 6.85 ± 1.28 and 6.54 ± 1.20, respectively. Both scoring systems were not found to be associated with venous thromboembolism.

  View details for DOI 10.1177/1750458919826794

  View details for PubMedID 30672371

• Evaluation of the prognostic utility of the combination of platelet count with mean platelet volume as a prognostic indicator in head and neck cancer. Molecular and clinical oncology Tham, T., Leung, E., Olson, C., Wotman, M., Khaymovich, J., Coury, J., Teegala, S., Costantino, P. 2019; 10 (4): 457-462

  Abstract

  The combination of platelet count to mean platelet volume (COP-MPV) has been recently reported as a prognostic indicator of oral cavity cancer and other cancer sites. The aim of the present study was to validate the utility of the COP-MPV as a prognostic indicator in all head and neck cancer (HNC) sites. The clinicopathological characteristics of the COP-MPV with HNC were also investigated. This is a retrospective cohort study that recruited consecutively treated patients at a tertiary level academic hospital. Clinicopathological characteristics were recorded, including the COP-MPV scores. Survival was analyzed using Kaplan-Meier analysis, as well as multivariate Cox Proportional Hazards regression. COP-MPV was not associated with the survival outcome in univariate or multivariate analysis. In the multivariate model, tumor differentiation, tumor stage, nodal stage, surgical margins and hemoglobin were revealed to be significantly associated with survival. The results demonstrated that the COP-MPV is not a suitable prognostic factor for HNC.

  View details for DOI 10.3892/mco.2019.1813

  View details for PubMedID 30931118

  View details for PubMedCentralID PMC6425510

• Anaphylactoid hypersensitivity reaction from intra-arterial cetuximab: Clinical considerations and management. SAGE open medical case reports Bardash, Y., Tham, T., Olson, C., Khaymovich, J., Costantino, P. 2019; 7: 2050313X18823447

  Abstract

  Intra-arterial infusion of drugs shows promising results in terms of safety and efficacy. Intra-arterial cetuximab, a monoclonal antibody treatment, is currently being tested for its use in head and neck cancers. We present the case of a 45-year-old Asian male who developed an anaphylactoid hypersensitivity reaction, manifesting itself in the form of bronchospasm, tachycardia, and hypotension, during intra-arterial infusion of cetuximab. The symptoms were quickly diagnosed, and the patient was treated accordingly. Despite the safety profile of cetuximab and the decreased risk of systemic effects with intra-arterial infusion versus intravenous infusion, severe hypersensitivity reactions are still a risk in intra-arterial cetuximab infusions. Consequently, proper planning and care must be taken to prophylactically prevent and in the case of a reaction, treat the reaction accordingly. The case presented herein is, to the best of our knowledge, the first recorded moderate-to-severe infusion reaction in a patient receiving intra-arterial cetuximab treatment for head and neck cancer.

  View details for DOI 10.1177/2050313X18823447

  View details for PubMedID 30728973

  View details for PubMedCentralID PMC6350015

• Human papillomavirus and World Health Organization type III nasopharyngeal carcinoma: Multicenter study from an endemic area in Southern China. Cancer Tham, T. 2019; 125 (1): 161

  View details for DOI 10.1002/cncr.31819

  View details for PubMedID 30343533

• Neuroradiological and Neuropathological Changes After 177Lu-Octreotate Peptide Receptor Radionuclide Therapy of Refractory Esthesioneuroblastoma. Operative neurosurgery (Hagerstown, Md.) Schneider, J. R., Shatzkes, D. R., Scharf, S. C., Tham, T. M., Kulason, K. O., Buteau, F. A., Del Prete, M., Chakraborty, S., Anderson, T. A., Asiry, S., Beauregard, J. M., Langer, D. J., Costantino, P. D., Boockvar, J. A. 2018; 15 (6): 100-109

  Abstract

  Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB.A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease.We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.

  View details for DOI 10.1093/ons/opy028

  View details for PubMedID 29554305

• Efficacy of a non-invasive middle ear aeration device in children with recurrent otitis media: A randomized controlled trial protocol. Contemporary clinical trials communications Tham, T., Rahman, L., Costantino, P. 2018; 12: 92-97

  Abstract

  Acute otitis media (AOM) represents a significant disease burden in the pediatric population. Besides vaccinations, there are no robust measures of reducing incidence of AOM in this age-group. This is a randomized controlled clinical trial evaluating the efficacy of a non-invasive middle ear aeration device, the EarPopper device (EP). We aim to investigate the reduction of episodes AOM in children with recurrent otitis media. The control arm will be observational. The intervention arm will have the EP used. The primary endpoint is incidence of AOM. The secondary endpoints are hazard ratio of time to AOM, proportion without AOM and antibiotics use, quality of life (OMO-22 Form), and adherence to treatment. Sample size is a minimum of 150 patients. The inclusion criteria is ages 4-11, with history of recurrent Acute Otitis Media (AOM).

  View details for DOI 10.1016/j.conctc.2018.09.008

  View details for PubMedID 30320237

  View details for PubMedCentralID PMC6180339

• Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: A systematic review and meta-analysis. Head & neck Tham, T., Bardash, Y., Herman, S. W., Costantino, P. D. 2018; 40 (11): 2546-2557

  Abstract

  The purposes of this systematic review and meta-analysis were to investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and prognosis in head and neck cancer.A systematic review and meta-analysis were done to investigate the role of NLR in overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and progression-free survival (PFS).For qualitative analysis, 33 cohorts with over 10 072 patients were included. For quantitative analysis, 15 studies were included with 5562 patients. The pooled data demonstrated that an elevated NLR significantly predicted poorer OS and DSS.An elevated pretreatment NLR is a prognostic marker for head and neck cancer. It represents a simple and easily obtained marker that could be used to stratify groups of high-risk patients who might benefit from adjuvant therapy.

  View details for DOI 10.1002/hed.25324

  View details for PubMedID 29761587

• Evaluation of the prognostic utility of the hemoglobin-to-red cell distribution width ratio in head and neck cancer. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Tham, T., Olson, C., Wotman, M., Teegala, S., Khaymovich, J., Coury, J., Costantino, P. 2018; 275 (11): 2869-2878

  Abstract

  Hemoglobin is a known prognostic marker in many cancers, including head and neck cancer (HNC). There is some evidence that the red cell distribution width, which is an index of variation in size of red blood cells (RBCs), might be associated with prognosis as well. Recently, a novel prognostic biomarker has been reported-the ratio of the hemoglobin-to-red cell distribution width (Hb/RDW). Our objective was to evaluate the prognostic utility of the pretreatment Hb/RDW in HNC, controlled with known prognostic indices.Retrospective cohort study in a tertiary academic hospital setting. Patients diagnosed with HNC treated with curative-intent surgery were eligible. Metastatic disease was excluded. The variables collected were age, sex, BMI, alcohol/tobacco exposure, performance scores, ACE-27, tumor characteristics, adjuvant treatment, and lab values. The primary endpoints were event-free survival (EFS) and overall survival (OS). OS was defined as time from start of treatment to death from any cause, and EFS was defined as time from start of treatment to any progression, recurrence, or death from any cause. Univariate and multivariate survival analysis was performed on the primary endpoints.A total of 205 patients were enrolled from 2010 to 2016. In multivariate analysis, the factors independently associated with EFS were BMI (p = 0.0364), advanced T stage (p = 0.001), and low Hb/RDW ratio (p = 0.017). The factors independently associated with OS were ECOG score (p = 0.042), advanced T stage (p < 0.0001), positive nodes (p = 0.0195), and Hemoglobin (0.0134).A low Hb/RDW ratio was associated with poorer EFS (HR = 2.02, 95% CI 1.13-3.61, p = 0.017), but was not associated with OS. This is the first study reporting the prognostic utility of Hb:RDW in head and neck cancer.

  View details for DOI 10.1007/s00405-018-5144-8

  View details for PubMedID 30251123

• Analysis of bone healing with a novel bone wax substitute compared with bone wax in a porcine bone defect model. Future science OA Tham, T., Roberts, K., Shanahan, J., Burban, J., Costantino, P. 2018; 4 (8): FSO326

  Abstract

  This pilot study describes a novel composite of hydroxyapatite and biodegradable polylactic acid with wax-like handling properties (BoneSeal®). The goal was to compare quantitative measures of bone healing between BoneSeal versus Bone wax.BoneSeal and Bone wax were introduced into separate defects of a single porcine specimen. After 6 weeks, the defect sites were harvested for analysis.Both groups had similar hemostatic action. The amount of new bone was significantly greater at 6 weeks in the BoneSeal group (38.05%) versus the Bone wax group (11.88%), p = 0.028.In this pilot study, BoneSeal had higher amounts of new bone formation compared with Bone wax.

  View details for DOI 10.4155/fsoa-2018-0004

  View details for PubMedID 30271614

  View details for PubMedCentralID PMC6153452

• Is human papillomavirus and p16 expression associated with survival outcomes in nasopharyngeal cancer?: A systematic review and meta-analysis. American journal of otolaryngology Tham, T., Teegala, S., Bardash, Y., Herman, S. W., Costantino, P. 2018; 39 (6): 764-770

  Abstract

  Human papillomavirus (HPV) is a known prognostic indicator in oropharyngeal cancer. Not much is known about the prognostic role of HPV in Nasopharyngeal cancer (NPC). Here, we performed a systematic review and meta-analysis of the literature to investigate if HPV status was a prognostic factor for NPC.PubMed (via the web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled Hazard Ratios (HR) for Overall Survival (OS).A total of 7 studies from 2014 to 2018, reporting data on 2646 patients (range 43-1328) were included in this meta-analysis. The pooled data showed that HPV/p16 status was not associated with OS in NPC with HR of 0.77 (95% CI: 0.55-1.09, p = 0.14). The test for heterogeneity showed little to no heterogeneity of results (I2 = 4%, p = 0.38). Subgroup analysis showed that in large sample sizes, HPV was significantly associated with survival.Despite the finding in the pooled HR, we could not draw a definitive conclusion as to the prognostic significance of HPV in NPC. Recommendations for future research are given.

  View details for DOI 10.1016/j.amjoto.2018.07.005

  View details for PubMedID 30029797

• The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Tham, T., Olson, C., Khaymovich, J., Herman, S. W., Costantino, P. D. 2018; 275 (7): 1663-1670

  Abstract

  The aim of this systematic review and meta-analysis was to investigate the relationship between the pre-treatment lymphocyte-to-monocyte ratio (LMR) and prognosis in HNC.PubMed (via the Web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS).Our analysis included the results of 4260 patients in seven cohorts. The pooled data demonstrated that an elevated LMR was associated with significantly improved OS (HR 0.5; 95% CI 0.44-0.57), and DFS (HR 0.70; 95% CI 0.62-0.80). Of note, there was no detectable heterogeneity in either OS (I2 = 0%) or DFS (I2 = 0%).An elevated LMR may be an indicator of favorable prognosis in HNC. However, our results should be interpreted with some degree of caution due to the retrospective nature of cohort studies. Further research with high-quality prospective studies is needed to confirm the effect of LMR in HNC prognosis.

  View details for DOI 10.1007/s00405-018-4972-x

  View details for PubMedID 29651542

• Venous Thromboembolism Risk in Head and Neck Cancer: Significance of the Preoperative Platelet-to-Lymphocyte Ratio. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Tham, T., Rahman, L., Persaud, C., Olson, C., Costantino, P. 2018; 159 (1): 85-91

  Abstract

  Objective We aimed to investigate the association between the preoperative platelet-to-lymphocyte ratio (PLR) and venous thromboembolism (VTE) in patients with head and neck cancer (HNC) undergoing major surgery. Study Design Retrospective cohort study. Setting Academic tertiary hospital from 2011 to 2017. Subjects and Methods Patients with confirmed HNC undergoing major surgery were included in this study. The preoperative PLR was recorded for all patients. Known VTE risk factors, including Caprini score, age, sex, smoking, body mass index, prior VTE, and anticoagulation, were also recorded. Risk factors were screened in univariate analysis using Wilcoxon's rank sum test and χ2 test (Bonferroni corrected). Significant covariates were included in a multivariate regression model. Bootstrap techniques were used to obtain credible confidence intervals (CIs). Results There were 306 patients enrolled with 7 cases of VTE (6 deep vein thromboses and 1 pulmonary embolism. On univariate analysis, length of stay ( P = .0026), length of surgery ( P = .0029), and PLR ( P = .0002) were found to have significant associations with VTE. A receiver operator characteristic (ROC) curve was constructed that yielded an area under the ROC of 0.905 (95% CI, 0.82-0.98). Using an optimized cutoff, the multivariate model showed that length of surgery (β 95% CI, 0.0001-0.0006; P = .0056) and PLR (β 95% CI, 5.3256-5.3868; P < .0001) were significant independent predictors of VTE. Conclusion This exploratory pilot study has shown that PLR offers a potentially accurate risk stratification measure as an adjunct to current tools in VTE risk prediction, without additional cost to health systems.

  View details for DOI 10.1177/0194599818756851

  View details for PubMedID 29406795

• The red cell distribution width as a prognostic indicator in upper aerodigestive tract (UADT) cancer: A systematic review and meta-analysis. American journal of otolaryngology Tham, T., Bardash, Y., Teegala, S., Herman, W. S., Costantino, P. D. 2018; 39 (4): 453-458

  Abstract

  The aim of this systematic review and meta-analysis was to investigate the relationship between the Red Cell Distribution Width (RDW) and prognosis in upper aerodigestive tract (UADT) cancer.PubMed (via the web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled hazard ratios (HR) for overall survival (OS), disease specific survival (DSS), and recurrence free survival (RFS).Our analysis included the results of 4200 patients in 8 cohorts. The pooled data demonstrated that an elevated RDW was associated with significantly poorer OS (HR: 1.44, 95% CI: 1.13-1.83), RFS (HR: 1.43, 95%CI: 1.13-1.82). The DSS result had high heterogeneity and 95% CI was not pooled.An elevated RDW may be an indicator of poor prognosis in UADT cancers in certain populations. Further research is needed to confirm this effect.

  View details for DOI 10.1016/j.amjoto.2018.04.013

  View details for PubMedID 29699714

• The Temporalis Muscle Flap for Palate Reconstruction: Case Series and Review of the Literature. International archives of otorhinolaryngology Brennan, T., Tham, T. M., Costantino, P. 2017; 21 (3): 259-264

  Abstract

  Introduction  The temporalis myofascial (TM) is an important reconstructive flap in palate reconstruction. Past studies have shown the temporalis myofascial flap to be safe as well as effective. Free flap reconstruction of palate defects is also a popular method used by contemporary surgeons. We aim to reaffirm the temporalis myofascial flap as a viable alternative to free flaps for palate reconstruction. Objective  We report our results using the temporalis flap for palate reconstruction in one of the largest case series reported. Our literature review is the first to describe complication rates of palate reconstruction using the TM flap. Methods  Retrospective chart review and review of the literature. Results  Fifteen patients underwent palate reconstruction with the TM flap. There were no cases of facial nerve injury. Five (33%) of these patients underwent secondary cranioplasty to address temporal hollowing after the TM flap. Three out of fifteen (20%) had flap related complications. Fourteen (93%) of the palate defects were successfully reconstructed, with the remaining case pending a secondary procedure to close the defect. Ultimately, all of the flaps (100%) survived. Conclusion  The TM flap is a viable method of palate defect closure with a high defect closure rate and flap survival rate. TM flaps are versatile in repairing palate defects of all sizes, in all regions of the palate. Cosmetic deformity created from TM flap harvest may be addressed using cranioplasty implant placement, either primarily or during a second stage procedure.

  View details for DOI 10.1055/s-0037-1598653

  View details for PubMedID 28680495

  View details for PubMedCentralID PMC5495588

• The Laparoscopically Harvested Omental Free Flap: A Compelling Option for Craniofacial and Cranial Base Reconstruction. Journal of neurological surgery. Part B, Skull base Costantino, P. D., Shamouelian, D., Tham, T., Andrews, R., Dec, W. 2017; 78 (2): 191-196

  Abstract

  Background Management of craniofacial and cranial base tumors is a challenge due to the anatomic intricacies associated with the calvarium, the pathological diversity of lesions that present, and the potential complications. Clinical outcomes in laparoscopically harvested omentum free flaps for cranial base and craniofacial reconstruction are presented in this paper, in the largest case series to date. Methods A retrospective single-center experience for over 10 years with laparoscopically harvested omentum flaps used to reconstruct craniofacial and cranial base defects. Results A total of 13 patients underwent craniofacial or cranial base reconstruction using laparoscopically harvested omentum free flaps. The mean patient age was 48 years. The anterior skull base represented the most common site of reconstruction. A total of 12 of the flaps survived (92%), with one flap failure due to infection. All patients demonstrated satisfactory aesthetic and functional outcomes. There were no perioperative or intra-abdominal complications. Conclusions The laparoscopically harvested omentum free flap is a safe and effective tool in the armamentarium of the reconstructive surgeon. It is the ideal option to treat complex, three-dimensional subcutaneous defects, such as those encountered in craniofacial and cranial base reconstruction. Its unique angiogenic and immunologic capacity makes it an excellent flap for the previously irradiated and/or infected wound bed.

  View details for DOI 10.1055/s-0036-1597138

  View details for PubMedID 28321385

  View details for PubMedCentralID PMC5357238

• Erratum: The Laparoscopically Harvested Omental Free Flap: A Compelling Option for Craniofacial and Cranial Base Reconstruction. Journal of neurological surgery. Part B, Skull base Costantino, P. D., Shamouelian, D., Tham, T., Andrews, R., Dec, W. 2017; 78 (2): e5

  Abstract

  [This corrects the article DOI: 10.1055/s-0036-1597138.].

  View details for DOI 10.1055/s-0037-1604035

  View details for PubMedID 30464880

  View details for PubMedCentralID PMC6246108

• The Laparoscopically Harvested Omental Free Flap: A Compelling Option for Craniofacial and Cranial Base Reconstruction (vol 78, pg 191, 2017) JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE Costantino, P. D., Shamouelian, D., Tham, T., Andrews, R., Dec, W. 2017; 78 (2): E5

  View details for DOI 10.1055/s-0037-1604035

  View details for Web of Science ID 000450746500003

• Multiportal Combined Transorbital and Transnasal Endoscopic Resection of Fibrous Dysplasia. Journal of neurological surgery reports Tham, T., Costantino, P., Bruni, M., Langer, D., Boockvar, J., Singh, P. 2015; 76 (2): e291-6

  Abstract

  Introduction Historically, access to the anterior skull base was achieved with open procedures. The paradigms to this approach were challenged with the advent of minimally disruptive endoscopic surgical techniques and supporting technology. The next step in the evolution of minimally disruptive surgery was the combination of multiportal endoscopic surgery. Results The patient was an 18-year-old man who presented with right-sided proptosis. Further diagnostic tests revealed a fibrous dysplasia (FD) occupying the skull base and orbit. The lesion was successfully resected. Conclusions The location of the tumor in this case was challenging, in which surgeons at some centers would have opted to have performed as an open procedure instead of endoscopically. The combined transnasal/transorbital approach is an uncommonly used technique that we have used to remove this tumor successfully. The patient also had a unique disease (FD) in a unique location that was treated without complications. This case report highlights how surgeons may use an expanded armamentarium in dealing with complex pathologies.

  View details for DOI 10.1055/s-0035-1566126

  View details for PubMedID 26623245

  View details for PubMedCentralID PMC4648726

• Probable Immunoglobulin Subtype-G4-Related Disease in the Head and Neck from Foreign Body Injection: A Case Report. Journal of neurological surgery reports Highstein, M. J., Mallen, J., Tham, T., Brennan, T., Boubour, A., Opher, E., Wolf, V., Singh, P., Costantino, P. 2015; 76 (2): e265-9

  Abstract

  Introduction Immunoglobulin subtype G4-related disease (IgG4-RD) is a fibroinflammatory disease of unknown etiology, with manifestations involving nearly every organ system. Its association with foreign bodies is not established. Here, we present a novel case of IgG4-RD in response to foreign body injection. Case Description A 58-year-old woman presented with history of persistent left facial pain, xerophthalmia, blurred vision, and trismus. The patient's medical history was significant for left-sided temporomandibular joint (TMJ) reconstruction with silicone injection into the joint. Magnetic resonance imaging revealed a lesion in the left skull base. Biopsies demonstrated the cardinal histopathological features of IgG4-RD. The patient was treated with a tapering dose of prednisolone followed by rituximab, resulting in tumor shrinkage and resolution of her symptoms. Discussion This is the first reported case of IgG4-RD potentially precipitated by a foreign body, in this case injected silicone into the TMJ. The pathogenesis and etiology of IgG4-RD is still not fully elucidated, but allergic and reactive inflammatory reactions have been implicated in the disease process. This case report should raise the idea of reactive foreign bodies as a causative agent for IgG4-RD.

  View details for DOI 10.1055/s-0035-1564602

  View details for PubMedID 26623239

  View details for PubMedCentralID PMC4648737