Head and Neck

Head and Neck

Scoring system for selective tracheostomy in head and neck surgery with free flap reconstruction

04-12-2019 – Tian‐yi Cai, Wen‐bo Zhang, Yao Yu, Yang Wang, Chi Mao, Chuan‐bin Guo, Guang‐yan Yu, Xin Peng

Abstract
Background
Selective tracheostomy is an effective but invasive airway management method for patients undergoing head and neck free flap reconstruction. Studies have shown that not all patients need tracheostomy. Several systems evaluating the need for tracheostomy have been proposed, but none is used clinically.
Methods
A total of 533 cases underwent head and neck free flap reconstruction at Peking University School of Stomatology were reviewed for system development. Another 131 cases undergone the same surgery were included for system verification. Patients demographic and surgical‐related information were analyzed.
Result
A total of 321 cases in the development cohort and 68 cases in the system cohort underwent tracheostomy. The score was estimated: score = ∑(|log2OR|). Patients scoring >3 required tracheostomy, those scoring <2 should avoid tracheostomy, and those scoring 2 or 3 need further evaluation.
Conclusion
This scoring system can help determine the need for selective tracheostomy in patients undergoing head and neck free flap reconstruction.

Induction chemotherapy followed by radiotherapy for N3 head and neck squamous cell carcinoma

04-12-2019 – Chengrun Du, Pierre Blanchard, Caroline Even, Angela Boros, Philippe Gorphe, Ingrid Breuskin, Neus Baste‐Rotllan, France Nguyen, Amandine Ruffier, François Bidault, Camélia Billard, François Janot, Haitham Mirghani, Stephane Temam, Yungan Tao

Abstract
Background
The treatment outcomes for N3 HNSCC treated with induction chemotherapy (ICT) followed by definitive radiation were reported to clarify the role of ICT and potential prognostic factors.
Methods
A retrospective study was conducted on 120 patients with N3 (≥6 cm) HNSCC, who were treated with ICT as initial treatment. Survival outcomes and potential prognostic factors were reported.
Results
The response rate to ICT was 68.3%. There was a statistically significant difference between responders and non‐responders in terms of 5‐year OS (35.1% vs 13.3%, P < .001) and PFS (29.4% vs 7.4%, P < .001). Good response to ICT (P < .001) and upfront neck dissection (UFND) before radiotherapy (P = .016) were factors predicting for better OS. However, UFND before radiotherapy was not associated with improved outcomes among responders.
Conclusions
This study suggests that ICT could be one treatment option for N3 HNSCC. Among responders to ICT, UFND before radiotherapy could be avoided.

Long‐term opioid use in curative‐intent radiotherapy: One‐Year outcomes in head/neck cancer patients

30-11-2019 – Leif‐Erik D. Schumacher, Zoukaa B. Sargi, Melissa Masforroll, Deukwoo Kwon, Wei Zhao, Maria A. Rueda‐Lara, Laura M. Freedman, Nagy Elsayyad, Stuart E. Samuels, Matthew C. Abramowitz, Michael A. Samuels

Journal Article

Abstract
Background
No study has determined the incidence of long‐term opioid use, or risk factors for long‐term use, ≥1 year after radiotherapy.
Methods
Medical records of 276 head/neck cancer patients were retrospectively assessed for persistent opioid use 1‐year after curative‐intent radiotherapy. Numerous potential risk factors were assessed and the physicians documented reasons for continued use were qualitatively categorized as suspected opioid use disorder (OUD) or as medically indicated for control of ongoing pain.
Results
Of note, 20 of 276 patients continued using opioids long‐term. High maximum opioid dose and the use of opioids and/or psychotropics/non‐opioid analgesics at the radiation oncology intake visit were associated with this outcome. Three patients continued due to suspected OUD and 17 due to medical indications.
Conclusion
Of note, 7.2% of patients developed long‐term opioid use, which was associated with high maximum opioid dose and early initiation of opioids and/or psychotropics/non‐opioid analgesics. Physicians cited medical indications as the primary reason for continued use.

Prophylactic arterial ligation following transoral robotic surgery: A systematic review and meta‐analysis

28-11-2019 – Craig A. Bollig, David R. Gilley, Jumah Ahmad, Jeffrey B. Jorgensen

Journal Article, Review

Abstract
Prophylactic arterial ligation has been proposed to reduce the severity of postoperative hemorrhage following transoral robotic surgery (TORS). Previous studies have shown a trend toward a reduction in major and severe bleeding. Search strategies were implemented in multiple databases and completed in August 2018. Inclusion and exclusion criteria were designed to capture studies examining adults undergoing TORS for oropharyngeal cancer. Four retrospective studies were selected appropriate for analysis by two reviewers who independently extracted data. PRISMA guidelines were followed. A random‐effects model was used for meta‐analysis. Meta‐analysis of 619 patients in four retrospective reviews showed that the pooled RR of major and severe bleeding events was significantly lower in prophylactically ligated patients (RR, 0.28; 95% CI, 0.08‐0.92; I2 = 0). Prophylactic arterial ligation of external carotid artery branches is associated with a decreased risk of major and severe bleeding events, although confounding factors remain incompletely analyzed.

Lymphatic mapping with SPECT‐CT for evaluation of contralateral drainage in lateralized oropharyngeal cancers using an awake injection technique

28-11-2019 – Carissa M. Thomas, Mohemmed N. Khan, Ravi Mohan, Aaron Hendler, Ali Hosni, Douglas B. Chepeha, David P. Goldstein, Richard M Cooper, John R. Almeida

Journal Article

Abstract
Background
Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is currently based on clinical risk factors. We propose lymphatic mapping with single photon emission computed tomography (SPECT‐CT) for tumor‐specific delineation of lymphatic drainage to guide treatment.
Methods
Retrospective review of lymphatic drainage patterns in c
T1‐2 OPSCC and contralateral c
N0 neck with a nonoperative, awake injection of 99 m‐Tc sulfur colloid and SPECT‐CT.
Results
Ten patients were reviewed. Primary sites included tonsil (n = 8, 80%) and tongue base (n = 2, 20%). All patients tolerated awake injections with no complications. Nine patients (90%) demonstrated satisfactory migration of radiotracer to neck node(s) with seven (78%) to the ipsilateral lateral neck, one (11%) to the ipsilateral lateral neck and retropharynx, and one (11%) to bilateral lateral neck nodes.
Conclusions
Characterization of lymphatic drainage in OPSCC is feasible using a nonoperative injection technique and SPECT‐CT. Drainage to the contralateral neck is rare, warranting further study to tailor treatment appropriately.

Potential pitfalls in incorporating plasma Epstein‐Barr virus DNA in the management of nasopharyngeal carcinoma

28-11-2019 – Edwin C. Y. Wong, Jessica L. C. Hung, Wai T. Ng

Journal Article

Abstract
Background
This study identifies potential pitfalls in incorporating plasma Epstein‐Barr virus (EBV) DNA into the management of nasopharyngeal carcinoma (NPC).
Methods
A total of 208 NPC patients without distant metastasis who received radical treatment and had measurements of EBV DNA at baseline, 8 weeks and 26 weeks postradiotherapy were analyzed. Prognostic and predictive values at each time‐point were compared.
Results
Risk stratification by pretreatment level failed to identify a poor prognostic group. Detectable EBV DNA at 8 weeks and 26 weeks postradiotherapy were both associated with significantly poorer 5‐year disease‐free survival (HR 0.30, P < .001 and HR 0.03, P < .001, respectively) and overall survival (HR 0.27, P = .009 and HR 0.03, P < .001, respectively). Eighty percentage had detectable EBV DNA at recurrence (53.3% for local only, 100% for regional only, and 100% for distant failure).
Conclusions
Posttreatment EBV DNA, particularly at 26 weeks post‐radiotherapy, has high prognostic and predictive values. Surveillance endoscopy/imaging are recommended for the detection of local recurrence.

Alcohol‐related head and neck cancer: Summary of the literature

27-11-2019 – Allison Marziliano, Sewit Teckie, Michael A. Diefenbach

Journal Article, Review

Abstract
Alcohol drinking is a risk factor for the development of head‐and‐neck malignancies, including oral, pharyngeal, and laryngeal cancers, and coupled with tobacco use, accounts for 75% of oral cancers. We summarized the literature on alcohol‐related head and neck cancer (HNC) and identified gaps that represent areas for future investigation. Research indicates that alcohol consumption has not only been linked to the development of primary HNCs, but also to secondary cancers with continued alcohol intake, cancer recurrences, and other poor health outcomes. Given this evidence, several organizations have called for reduction or avoidance of alcohol, particularly in HNC survivors. Despite these strong recommendations, evidence suggests that HNC survivors continue to use alcohol. There is a need to forge collaborations among clinicians, researchers, and social workers, to address this problem of alcohol consumption in the growing population of HNC survivors.

Anatomical subsite modifies survival in oropharyngeal squamous cell carcinoma: National Cancer Database study

27-11-2019 – Tristan Tham, Seungjun Ahn, Douglas Frank, Dennis Kraus, Peter Costantino

Journal Article

Abstract
Background
Oropharyngeal squamous cell carcinomas (OPSCC) can occur in either tonsillar related areas (TRA) or nontonsillar areas (n
TRA). 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.
Methods
This NCDB study was conducted by stratifying the HPV‐positive oropharyngeal cancer cohort into two primary groups, TRA and n
TRA. Kaplan Meier survival analysis was stratified according to HPV status, and further analysis was conducted using multivariable Cox regression.
Results
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 n
TRA HR: 0.76, 95% CI: 0.67‐0.86, P < .0001).
Conclusion
In this large cohort, OPSCC subsite was found to be an independent prognostic factor for survival.

Radiation treatment of soft palate squamous cell carcinoma

27-11-2019 – Cooper T. Rapp, Bhishamjit S. Chera, Christopher G. Morris, Robert J. Amdur, Jessica M. Kirwan, William M. Mendenhall

Journal Article

Abstract
Background
To report our institutions experience treating soft palate squamous cell carcinoma with radiotherapy alone or combined with adjuvant chemotherapy and/or neck dissection for residual disease.
Methods
We analyzed 159 patients treated curatively between 1963 and 2016. Median follow‐up was 4 years.
Results
The 5‐year local control rates were T1, 90%; T2, 90%; T3, 70%; and T4, 59%. The 5‐year cause‐specific survival (CSS) rate was nearly identical for patients with stage I‐III disease (88%, 86%, and 88%, respectively) compared to stage IVA/B (58%). Five‐year overall survival was similar between patients with stage I‐III disease (50%, 57%, and 54%, respectively) and approximately double that of patients with stage IVA/B disease (26%). Thirteen patients (8%) had severe complications related to radiotherapy.
Conclusions
The likelihood of cure after definitive radiotherapy is relatively high in patients with stage I‐III disease with soft palate carcinoma. Patients with stage IVA/B disease have a lower cure rate but with a 5‐year CSS exceeding 50%.

Complications of tissue expansion in the head and neck

27-11-2019 – Jayson L. Azzi, Chloe Thabet, Alain J. Azzi, Mirko S. Gilardino

Journal Article, Review

Abstract
Background
The authors aim to present a comprehensive review detailing the present state of evidence with regard to complications following tissue expansion in the head and neck.
Methods
A systematic literature search was conducted to identify all studies reporting complications of tissue expansion in the head and neck between 2000 and 2019. Subgroup comparisons based on expander locations and planes were conducted.
Results
A total of 7058 patients were included. Tissue expansion was associated with an overall complication rate of 8.73% (616/7058). The most common complications were extrusion (207/7009; 3.0%) and hematoma (200/7009; 2.9%). Overall complications were highest in the scalp (65/238; 27.3%) and lowest in the mastoid (347/5688; 6.1%). Complications were more common with expansion in the non‐subcutaneous plane (63/590; 10.7%).
Conclusion
In the absence of large clinical trials, systematic reviews such as these can help inform clinical guidelines and provide practitioners with an evidence‐based reference to improve informed consent.

Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

27-11-2019 – Nader Sadeghi, Sarah Khalife, Marco A. Mascarella, Agnihotram V. Ramanakumar, Keith Richardson, Arjun S. Joshi, Nathaniel Bouganim, Reza Taheri, Andrew Fuson, Robert Siegel

Journal Article

Abstract
Background
A paradigm shift has led to de‐escalation trials for the treatment of HPV‐positive oropharynx cancer (OPC). The objective of this study was to assess the ability of tumor volume reduction on imaging to predict pathological response to neoadjuvant chemotherapy in patients with HPV‐positive OPC.
Methods
A prospective observational study of 54 patients with HPV‐positive OPC enrolled in a clinical trial of neoadjuvant chemotherapy followed by surgery was performed. Patients underwent three cycles of induction chemotherapy (cisplatin/docetaxel); prechemotherapy and postchemotherapy imaging were obtained. Receiver operating characteristic curves and logistic regression analyses were used.
Results
The complete pathologic response (p
CR) rate at primary and nodal sites were 72% and 57%, respectively. Tumor volume reduction of ≥90% following induction chemotherapy predicted p
CR of the primary tumor.
Conclusions
Neoadjuvant chemotherapy followed by definitive transoral surgery is a new paradigm worthy of further investigation and MRI is a reliable modality to assess preoperative response.

Reply to “Possible risk of iatrogenic lymphedema after harvest of posterior tibial artery perforator flap”

26-11-2019 – Jun Liu, Di Deng, Fei Chen

Letter

Possible risk of iatrogenic lymphedema after harvest of posterior tibial artery perforator flap

26-11-2019 – Reiko Tsukuura, Takashi Kageyama, Hayahito Sakai, Yuma Fuse, Kanako Tsuihiji

Letter

Impact of active smoking on outcomes in HPV+ oropharyngeal cancer

26-11-2019 – Roy Xiao, Yvonne Pham, Matthew C. Ward, Narcissa Houston, Chandana A. Reddy, Nikhil P. Joshi, John F. Greskovich, Neil M. Woody, Deborah J. Chute, Eric D. Lamarre, Brandon L. Prendes, Robert R. Lorenz, Joseph Scharpf, Brian B. Burkey, Jessica L. Geiger, David J. Adelstein, Shlomo A. Koyfman

Journal Article

Abstract
Background
The role of smoking among patients with human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is unclear.
Methods
A retrospective cohort study of patients with HPV(+) OPSCC from 2001 to 2015 at a tertiary‐care institution was conducted. The primary outcome was overall survival (OS).
Results
Among 484 included patients, 94 (19.4%) were active smokers, 226 (46.7%) were former smokers, and 164 (33.9%) never smoked. Among active smokers, 82 patients (87.2%) had a ≥10 pack‐year and 69 (73.4%) had a ≥20 pack‐year smoking history. After adjusting for covariates, active smoking was a significant predictor of inferior OS (HR 2.28, P < .001) and PFS (HR 2.26, P < .001). When including pack‐years as the covariate, ≥20 pack‐years predicted a decreased effect‐size for inferior OS and PFS.
Conclusions
For patients with HPV(+) OPSCC, active smoking at diagnosis is the most powerful covariate capturing smoking history to predict OS and PFS.

Impact of PD‐L1 expression and human papillomavirus status in anti‐PD1/PDL1 immunotherapy for head and neck squamous cell carcinoma—Systematic review and meta‐analysis

24-11-2019 – Jaimin J. Patel, Dylan A. Levy, Shaun A. Nguyen, Hannah M. Knochelmann, Terry A. Day

Journal Article, Review

Abstract
Programmed cell death‐1 (PD‐1) pathway inhibition in head and neck squamous cell carcinoma (HNSCC) has demonstrated inconsistent efficacy regarding human papillomavirus (HPV) status and PD‐L1 expression. This study compared outcomes in HNSCC in the context of PD‐L1 and HPV expression. Outcomes: PD‐L1 and HPV expression; overall survival (OS), and tumor response (ORR). 1088 patients received PD‐1/L1 inhibitors. Four methodologies were identified in determining PD‐L1 expression, most commonly using the Dako PD‐L1 IHC 22C3 pharma
Dx assay. Using a 1% threshold, ORR was greater for PD‐L1 expressers vs non‐expressers (18.9%, CI 16.1‐21.8 v 8.8% CI 5.3‐13.7, P = 0.009), as was OS at 6 months (60.6%, CI 49.2‐71.4 v 49.0%, CI 39.1‐59.0, P = 0.04) but not at 12 or 18 months. No advantages were identified for HPV expressers. Patients expressing PD‐L1 may have a better tumor response and OS. No impact on survival or response was observed based on HPV status.

Mapping the University of Washington Quality of life questionnaire onto EQ‐5D and HUI‐3 indices in patients with head and neck cancer

24-11-2019 – Robert F. Stephens, Christopher W. Noel, Jie (Susie) Su, Wei Xu, Murray Krahn, Eric Monteiro, David P. Goldstein, Meredith Giuliani, Aaron R. Hansen, John R. Almeida

Journal Article

Abstract
Background
There is no mechanism to predict health utility (HU) values from the University of Washington Quality of Life Questionnaire (UWQoL) scores. We sought to develop a mapping algorithm capable of using UWQoL data to approximate HU scores.
Methods
Outpatients with head and neck cancer completed the UWQoL, EQ‐5D, and the Health Utilities Index‐Mark 3 (HUI‐3). Results of the UWQoL were mapped onto both EQ‐5D and HUI‐3 scores using ordinary least‐squares regression models. Two‐part models were explored. The predictive power of the model was assessed using 10‐fold cross‐validation.
Results
A total of 209 patients were recruited. The reduced model converting UWQoL data into EQ‐5D scores performed best (adjusted R2 = 0.628, root mean square error = 0.076). Both models demonstrated construct validity by discriminating between clinical indices of disease severity.
Conclusions
The abovementioned algorithms enable researchers to perform health economic evaluations with existing UWQoL data in cases where prospectively collected HU values are not available.

Next‐generation sequencing in salivary gland carcinoma: Targetable alterations lead to a therapeutic advantage—Multicenter experience

24-11-2019 – Assaf Moore, Yael Bar, Corinne Maurice‐Dror, Inna Ospovat, Michal Sarfaty, Yasmin Korzets, Hadar Goldvaser, Noa Gordon, Salem Billan, Orit Gutfeld, Aron Popovtzer

Journal Article

Abstract
Background
Salivary gland cancers (SGCs) are rare. The approach to metastatic patients is histology‐dependent. There is little evidence on whether next‐generation sequencing (NGS) findings translate to tumor control in SGCs.
Methods
We analyzed all patients with histologically confirmed SGC who underwent NGS.
Results
Twenty‐seven patients were identified, 14 (51.8%) had targetable findings in NGS: 5 ERBB2 amplifications, 3 PIK3CA mutations, 2 RUNX1 mutations, 1 TRIM33‐RET fusion, 1 FGFR3‐TACC3 fusion, 1 microsatellite instability‐high, and 2 high mutational burden. Ten patients were treated accordingly. Median progression‐free survival for targeted treatment was 8.4 months. Of five patients who achieved durable responses of 8.4 to 31.3 months, two are ongoing. The overall median survival was not reached for patients receiving targeted treatment and was 40.4 months for patients treated conventionally (P = .18).
Conclusions
In the absence of a well‐established therapeutic approach, NGS may detect clinically significant genetic alterations and benefit patients with advanced SGC.

A critical appraisal of the clinical applicability and risk of bias of the predictive models for mortality and recurrence in patients with oropharyngeal cancer: Systematic review

24-11-2019 – Antonio Palazón‐Bru, Emma Mares‐García, David López‐Bru, Enrique Mares‐Arambul, David M. Folgado‐de la Rosa, María de los Ángeles Carbonell‐Torregrosa, Vicente F. Gil‐Guillén

Journal Article, Review

Abstract
The use of predictive models is becoming widespread. However, these models should be developed appropriately (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies CHARMS and Prediction model Risk Of Bias ASsessment Tool PROBAST statements). Concerning mortality/recurrence in oropharyngeal cancer, we are not aware of any systematic reviews of the predictive models. We carried out a systematic review of the MEDLINE/EMBASE databases of those predictive models. In these models, we analyzed the 11 domains of the CHARMS statement and the risk of bias and applicability, using the PROBAST tool. Six papers were finally included in the systematic review and all of them presented high risk of bias and several limitations in the statistical analysis. The applicability was satisfactory in five out of six studies. None of the models could be considered ready for use in clinical practice.

“The diagnostic value of cytology in parotid Warthins tumors: international multicenter series”

24-11-2019 – Daniele Borsetto, Jonathan M. Fussey, Diego Cazzador, Joel Smith, Andrea Ciorba, Stefano Pelucchi, Sara Donà, Paolo Boscolo‐Rizzo, Michele Tomasoni, Davide Lombardi, Piero Nicolai, Elisabetta Zanoletti, Roberta Colangeli, Enzo Emanuelli, Max S. Osborne, Syed F. Ahsan, Margherita Tofanelli, Giancarlo Tirelli, Katherine McNamara, Leonard Liew, Katherine Harrison, Ambrogio Fassina, Samantha Sarcognato, Neil Sharma, Kanishka Rao, Paul Pracy, Paul Nankivell

Journal Article

Abstract
Introduction
Warthins tumor (WT) is a common benign salivary gland neoplasm with a negligible risk of malignant transformation. However, there is a risk of malignant tumors being misdiagnosed as WT on cytology and inappropriately managed conservatively.
Methods
Patients from nine centers in Italy and the United Kingdom undergoing parotid surgery for cytologically diagnosed WT were included in this multicenter retrospective series. Definitive histology was compared with preoperative cytological diagnoses. Surgical complications were recorded.
Results
A total of 496 tumors were identified. In 88.9%, the final histological diagnosis was WT. In 21 cases (4.2%) a malignant neoplasm was diagnosed, which had been incorrectly labeled as WT on cytology.
Conclusions
The risk of undiagnosed malignancy should be balanced against surgical risks when considering the management of WT. Although nonsurgical management remains an appropriate option, there may be a rationale for serial clinical or radiological evaluation if surgical excision is not performed.

Clinical utility of 177Lu‐DOTATATE PRRT in somatostatin receptor‐positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity

22-11-2019 – Rahul V. Parghane, Chinna Naik, Sanjay Talole, Anuja Desmukh, Devendra Chaukar, Sharmila Banerjee, Sandip Basu

Journal Article

Abstract
Background
The primary aim of this study was to evaluate the therapeutic efficacy and outcome of 177Lu‐DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor‐positive metastatic medullary thyroid carcinoma (MTC), including progression‐free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients.
Methods
A total of 43 somatostatin receptor‐positive metastatic MTC patients, treated with 177Lu‐DOTATATE PRRT in a large tertiary care center, were included in this analysis. After receiving the therapy, post‐treatment response evaluation was undertaken for symptomatic and biochemical responses (serum calcitonin) and imaging responses with 68Ga‐DOTATATE, 18F‐FDG PET‐CT, Ce
CT (PERCIST and RECIST 1.1 criteria). Calcitonin doubling time (Ctn
DT) was calculated by the American Thyroid Association calculator. The adverse events were graded according to the NCI‐CTCAE v5.0 criteria. The observed Kaplan‐Meier curves for both PFS and OS since first PRRT were compared with Ctn
DT (more than 24 months vs less than 24 months) by log‐rank (Mantel‐Cox) test. The prognostic variables were investigated for their association with Ctn
DT and response to PRRT using Cox proportional‐hazards model.
RESULTSThe median OS was 26 months (95% CI 16.6‐35.3 months) and the median PFS 24 months (95%.
CI: 15.1‐32.9 months). Following 177Lu‐DOTATATE PRRT, the observed median PFS and OS was longer in patients who had Ctn
DT more than 24 months compared to those with Ctn
DT less than 24 months (median PFS not yet reached vs 10 months and median OS 60 months vs 20 months). Assessing from the time‐point of first 177Lu‐DOTATATE PRRT cycle, the patients with Ctn
DT more than 24 months had a significantly longer PFS (P < .001) and OS (P < .001) compared to those with less than 24 months. Less than 5 lesions, FDG uptake in lesions (SUVmax of <5) and patients alive at the time of analysis were the significant variables for association with Ctn
DT (more than 24 months). Out of 43 patients, 26 were responders (61%) and 17 nonresponders (39%) based upon PERCIST criteria, and 27 were responders (62%) while 16 patients were nonresponders (38%) based upon RECIST 1.1 criteria. The univariate analysis showed significant association between responses to PRRT with following prognostic variables: (a) size of lesions (<2 cm) and (b) FDG uptake in lesions (SUVmax of <5). PRRT was well tolerated in all patients without any major grade 3 or 4 toxicity.
Conclusion
The results demonstrated that, 177Lu‐DOTATATE is a potentially efficacious and safe therapeutic option in SSTR avid metastatic MTC patients.

The effect of jaw exercises on anxiety and depression in patients with head and neck cancer receiving radiotherapy: Prospective 2‐year follow‐up study

22-11-2019 – Susan Aghajanzadeh, Therese Karlsson, Lisa Tuomi, Caterina Finizia

Journal Article

Abstract
Background
This nonrandomized matched study investigates jaw exercise effect on anxiety/depressive symptoms in head and neck cancer patients with trismus during 2 years postradiotherapy.
Methods
Fifty patients with trismus postradiotherapy were included in a 10‐week jaw‐training intervention. A matched control group was included (N = 50). Maximum interincisal opening (MIO) ≤ 35 mm was used as the trismus criterion. Patients were assessed using MIO and Hospital Anxiety Depression Scale preintervention, postintervention, and at 2‐year follow‐up.
Results
A significant difference was found in depressive symptoms between the intervention group and control group (4% vs 33%) at 2‐year follow‐up, with more control group patients reporting possible depression. In the intervention group, significantly fewer patients had possible/probable depressive symptoms at follow‐up (4%) compared to preintervention (34%). No change was seen within the control group.
Conclusion
Structured jaw exercise in patients with postradiation trismus had positive effects on MIO and depressive symptoms but does not seem to have any significant effects on anxiety symptoms.

The risk of second primary tumors in head and neck cancer: A systematic review

21-11-2019 – Andrés Coca‐Pelaz, Juan P. Rodrigo, Carlos Suárez, Iain J. Nixon, Antti Mäkitie, Alvaro Sanabria, Miquel Quer, Primož Strojan, Carol R. Bradford, Luiz P. Kowalski, Ashok R. Shaha, Remco Bree, Dana M. Hartl, Alessandra Rinaldo, Robert P. Takes, Alfio Ferlito

Journal Article

Abstract
Background
Second primary tumors (SPTs) are a common cause of reduced life expectancy in patients treated for head and neck cancer (HNC). This phenomenon forms an area to be addressed during posttreatment follow‐up.
Methods
We conducted a systematic review of literature following PRISMA guidelines, from 1979 to 2019, to investigate incidence of SPTs, synchronous, and metachronous, in HNC population.
Results
Our review includes data of 456 130 patients from 61 articles. With a minimum follow‐up of 22 months, mean incidence of SPTs was 13.2% (95% CI: 11.56‐14.84): 5.3% (95% CI: 4.24‐6.36) for synchronous SPTs and 9.4% (95% CI: 7.9‐10.9) for metachronous SPTs. The most frequent site for SPTs was head and neck area, followed by the lungs and esophagus.
Conclusion
Although with wide variations between studies, the rate of SPTs in HNC patients is high. Given the impact in the prognosis, we must develop strategies for the early diagnosis of SPTs.

Association between immunohistochemical expression of matrix metalloproteinases and metastasis in oral squamous cell carcinoma: Systematic review and meta‐analysis

21-11-2019 – Andressa F. P. Miguel, Fernanda W. Mello, Gilberto Melo, Elena R. C. Rivero

Journal Article, Review

Abstract
Background
The aim of this systematic review (SR) was to summarize and critically appraise available evidence on the association of the immunohistochemical expression of matrix metalloproteinases (MMPs) with the occurrence of lymph node/distant metastasis of oral squamous cell carcinoma (OSCC).
Methods
Searches were conducted in five main electronic and three gray literature databases.
Results
From 2128 records identified, 50 were included for qualitative analysis. A total of 12 MMPs were identified (‐1, ‐2, ‐3, ‐7, ‐8, ‐9, ‐10, ‐11, ‐13, ‐25, ‐26, and MT1‐MMP). Most included studies reported a positive association of MMP‐1, ‐2, ‐3, ‐7, ‐9, and MT1‐MMP with lymph node metastasis. MMP‐8, ‐25, and ‐26 were not associated with lymph node metastasis.
Conclusions
According to this SR, MMP‐1, ‐2, ‐3, ‐7, ‐9, and MT1‐MMP seem to play an important role in lymph node metastasis of OSCC.

Cervical‐transoral robotic nasopharyngectomy: A preclinical study

21-11-2019 – Philippe Gorphe, Hubert Stein, Antoine Moya‐Plana

Journal Article

Abstract
Background
We performed a preclinical study to assess the feasibility of the cervical‐transoral robotic pharyngectomy procedure in surgery for nasopharyngeal cancer, where deep margins and vascular safety are key issues.
Materials and methods
Four cadaveric dissections were performed with the da Vinci Xi system. The first step was a robotic parapharyngeal dissection along the internal carotid artery (ICA). The second step was a type 3 transoral robotic nasopharyngectomy.
Results
In each procedure, a comprehensive dissection of the parapharyngeal space was performed along the ICA up to the foramen lacerum. A type 3 nasopharyngectomy was performed transorally with an “en‐bloc” removal of the parapharyngeal space, and with complete removal of the eustachian tube up to its bony part.
Conclusion
A comprehensive cervical‐transoral robotic type 3 nasopharyngectomy with “en‐bloc” removal of the parapharyngeal space and the eustachian tube proved to be technically feasible in a preclinical study.

Prognostic capacity of Systemic Inflammation Response Index (SIRI) in patients with head and neck squamous cell carcinoma

21-11-2019 – Cristina Valero, Laura Pardo, Aina Sansa, Jacinto Garcia Lorenzo, Montserrat López, Miquel Quer, Xavier León

Journal Article

Abstract
Background
Inflammation and immune evasion are associated with carcinogenesis. Systemic Inflammation Response Index (SIRI) has been proposed as a pretreatment peripheral blood biomarker. The aim of this study is to analyze its prognostic capacity in head and neck squamous cell carcinomas (HNSCC).
Methods
We performed a retrospective study in 824 patients with HNSCC. SIRI was calculated by neutrophils*monocytes/lymphocytes. Using a recursive‐partitioning analysis considering disease‐specific survival (DSS) as dependent variable, three categories were defined according to SIRI value.
Results
Males, patients with history of toxic consumption, oropharyngeal or hypopharyngeal tumors, and advanced tumors had a significantly higher SIRI value. As SIRI increased, a significant decrease in DSS was observed. In a multivariable analysis, SIRI was an independent predictor of DSS. Moreover, SIRI was a significant predictor of local, regional, and distant recurrence‐free survival.
Conclusions
SIRI has independent prognostic capacity in HNSCC. Patients with higher SIRI have a significant decrease in DSS.

Management of unilateral head and neck carcinoma of unknown primary: Retrospective analysis of the impact of postoperative radiotherapy target volumes

18-11-2019 – Fabien Podeur, Pascal Pommier, Carole Crozes, Elodie Monchet, Jean Ton Van, Pierre‐Eric Roux, Marc Poupart, Philippe Zrounba, Morbize Julieron, Sophie Deneuve

Journal Article

Abstract
Background
We compared the outcome of postoperative unilateral cervical nodes radiotherapy (UL‐RT) vs bilateral cervical nodes plus total mucosal irradiation (COMP‐RT) in the management of head and neck carcinoma of unknown primary (HNCUP).
Methods
HNCUP, defined by the absence of primary despite a PET‐CT combined with a panendoscopy, were treated with curative intent by initial ipsilateral neck dissection. Sixty‐nine patients with unilateral HNCUP were included: 23 received UL‐RT while 46 received COMP‐RT. Carcinologic outcomes and long‐term quality of life (QOL) according to the QOL Questionnaire for Head and Neck 35 were assessed.
Results
Within 6.3 years of median follow‐up, there was no significant difference in primary tumor emergence rate (P = .68), cervical node recurrence rate (P = .34), or overall survival (P = .33) between UL‐RT and COMP‐RT groups. A trend toward QOL improvement was observed in the UL‐RT group.
Conclusion
UL‐RT seems to provide similar outcomes as COMP‐RT in unilateral HNCUP management.

SMARCB1 (INI‐1) and NUT immunoexpression in a large series of head and neck carcinomas in a Brazilian reference center

15-11-2019 – Rodrigo Neves‐Silva, Luciana Y. Almeida, Heitor A. Silveira, Carla B. N. Colturato, Andressa Duarte, Tulio M. Ferrisse, Evânio V. Silva, Bárbara F. Vanzolin, Andreia Bufalino, Alfredo Ribeiro‐Silva, Jorge E. León

Journal Article

Abstract
Background
SMARCB1 (INI‐1)‐deficient carcinomas and NUT carcinomas are aggressive neoplasms, often affecting the sinonasal region. Not uncommonly, their diagnoses are made retrospectively.
Methods
Through SMARCB1 (INI‐1) and NUT immunomarkers, 643 head and neck carcinomas were assessed retrospectively. Moreover, SMARCB1 (INI‐1)‐deficient and NUT carcinomas were additionally evaluated by immunohistochemistry, as well as in situ hybridization analysis for HPV and EBV.
Results
Four SMARCB1 (INI‐1)‐deficient carcinomas (located in lower lip, soft palate, hypopharynx and vocal cord, this latter high‐risk HPV positive) and three NUT carcinomas (all located in oropharynx) were detected, previously diagnosed as nonkeratinizing or moderately differentiated squamous cell carcinoma. All cases showed squamous differentiation. NUT carcinomas than SMARCB1 (INI‐1)‐deficient carcinomas showed low overall survival rate.
Conclusion
The current cases expand the clinicopathological spectrum of SMARCB1 (INI‐1)‐deficient carcinomas and NUT carcinomas. Notably, the diagnosis of these cases is easily reached through immunohistochemistry, with impact on their accurate classification, treatment, and prognosis.

Rational choice of neck dissection in clinically N0 patients with supraglottic cancer

14-11-2019 – Ye Zhang, Siyuan Xu, Wensheng Liu, Xiaolei Wang, Kai Wang, Shaoyan Liu, Zhengang Xu, Jie Liu

Journal Article

Abstract
Background
The mainstay treatment of the neck for clinically negative neck (c
N0) supraglottic laryngeal carcinoma (SGLC) is neck dissection. However, the optimal extent remains controversial. This studys purpose is to determine whether ipsilateral level II‐III neck dissection is appropriate for c
N0SGLC patients.
Methods
The records of 220 consecutive untreated c
N0SGLC patients were retrospectively reviewed. Relevant factors related to occult and contralateral neck metastasis were analyzed and the distribution of metastasis was described.
Results
Seventy‐seven and 143 patients underwent unilateral and bilateral neck dissection, respectively. The rate of occult neck metastases was 21.4%. The histologic differentiation was an independent risk factor for occult neck metastasis. In the bilateral neck dissection group, the incidence of contralateral neck metastasis of patients with noncentral tumors was 0.7%. Moreover, only 1.7% of patients had positive nodes at level IV, and no isolated nodal metastases existed in level IV.
Conclusion
Ipsilateral level II‐III neck dissection is feasible for patients with noncentral c
N0SGLC.

Issue Information

14-11-2019 –

Editorial‐Airway Team Dynamics and Risk Reduction

14-11-2019 – Christopher H. Rassekh

Editorial

Surgical consensus guidelines on sentinel node biopsy in patients with oral cancer

14-11-2019 – Mark McGurk

Letter

Letter to the editor‐in‐chief of Head and Neck

14-11-2019 – Domenico Rubello, Girolamo Tartaglione, Renato Valdes Olmos, Francesco Giammarile

Letter

Prognostic implications of human papillomavirus status and p16 expression in laryngeal squamous cell carcinoma

14-11-2019 – Yingying Zhu, Xin Xia, Neil Gross, Kristina R. Dahlstrom, Liming Gao, Zhiyong Liang, Zhiqiang Gao, Peng Wei, Chuan Liu, Guojun Li, Yuncheng Li, Xingming Chen

Journal Article

Abstract
Background
The purpose of this study was to investigate significance of HPV16 DNA/p16 for survival of patients with laryngeal squamous cell carcinoma (LSCC).
Methods
HPV16 DNA and p16 status in 812 LSCC patients were determined. The survival was performed using Kaplan‐Meier estimates and Cox model.
Results
Compared with HPV negativity, adjusted HRs for HPV16 positivity were 0.57, 95% CI, 0.38 to 0.87; 0.60, 0.40 to 0.88; and 0.65, 0.46 to 0.94 for disease‐specific survival (DSS), recurrence‐free survival (RFS), and overall survival (OS), respectively. Additionally, for p16 expression, a
HRs were 0.68, 95% CI, 0.48 to 0.96; 0.72, 0.52 to 0.98; and 0.73, 0.54 to 0.99 for DSS, RFS, and OS, respectively. Finally, for combined analysis, patients with both HPV16‐positivity/p16‐positivity had much better prognosis than those with either negativity. Such above survivals are more significantly better in never smokers.
Conclusion
Our findings suggest that HPV16/p16 may affect survival outcomes of LSCC patients, particularly in never smokers.

Phenotypic association of presence of a somatic GNAQ mutation with port‐wine stain distribution in capillary malformation

14-11-2019 – Kyeong‐Tae Lee, Jong Eun Park, Yeseul Eom, Ha Seong Lim, Chang‐Seok Ki, So Young Lim

Journal Article

Abstract
Background
A somatic mutation of GNAQ (c.548G>A, p.
Arg183Gln) plays a key role in capillary malformation development. The present study aimed to evaluate clinical manifestations of port‐win stain (PWS) associated with this genetic mutation.
Methods
Skin tissue was obtained from 70 patients with capillary malformation who had been treated with excision for lesions. Droplet digital polymerase chain reaction was used to quantify the abundance of cells with the GNAQ mutation.
Results
The GNAQ mutation was found in 50 patients. Patients with lesions involving upper facial region, which included forehead, eyebrow, and upper eyelid, showed a significantly higher rate of positive GNAQ mutation than those not involving it. Cases with facial PWS involving all three facial regions (upper, middle, and lower) showed significantly higher positive rate of GNAQ mutation compared to those involving one or two.
Conclusions
Presence of the somatic mutation GNAQ p.
Arg183Gln might be associated with clinical manifestations of PWS.

Understanding the natural history of papillary thyroid cancer: Case series

14-11-2019 – Jonathan K. Lin, Lori C. Sakoda, Jeanne Darbinian, Whitney Chiao, Nathaniel Calixto, Deepak Gurushanthaiah, Kevin H. Wang, Megan Durr

Journal Article

Abstract
Background
Papillary thyroid cancer (PTC) incidence continues to rise. We describe the natural history of untreated PTC patients.
Methods
Retrospective case series of 31 untreated PTC patients.
Results
We identified 31 untreated patients from the Kaiser Permanente Cancer Registry with PTC from 1973 to 2010. Patients were categorized as low risk (n = 16), high risk (n = 12), or low risk but medically contraindicated for surgery (n = 3). At diagnosis, 7 (58.3%) in the high‐risk group had cervical lymph node metastases and 5 (41.7%) had distant metastases, compared to none in the low‐risk group. Among the latter, three (18.8%) patients developed tumor growth >3 mm and one (6.3%) developed regional lymph node metastases without distant metastases. The 10‐year overall survival was 71% and 35% for the low‐risk and high‐risk groups, respectively.
Conclusions
Patients with low‐risk untreated PTC were less likely to develop new regional or distant metastases and had better overall survival than patients with high‐risk untreated PTC.
Level of Evidence4

Transoral robotic thyroidectomy on two human cadavers using the Intuitive da Vinci single port robotic surgical system and CO2 insufflation: Preclinical feasibility study

14-11-2019 – Dawon Park, Mohammad Shaear, Yu‐Hsien Chen, Jonathon O. Russell, Hoon Yub Kim, Ralph P. Tufano

Journal Article

Abstract
Background
Transoral vestibular approach endoscopic thyroidectomy has gained popularity worldwide because it avoids a cutaneous incision. Some surgeons have expressed reservations about operating with only 2 instruments in the endoscopic technique, and some therefore utilize an axillary incision as an adjunct to facilitate dissection. The Intuitive da Vinci single port robotic system offers the potential to overcome this limitation without an axillary incision.
Methods
In this study, the Intuitive da Vinci single port robotic surgical system was used to perform transoral thyroidectomy on 2 human cadavers.
Results
A total thyroidectomy was performed in 2 cadavers using the da Vinci single port (SP) robot via transoral vestibular technique. The dissections were performed with removal of the thyroid gland and preservation of the recurrent laryngeal nerves and parathyroid glands.
Conclusion
In our evaluation, transoral vestibular approach robotic thyroidectomy using the Intuitive da Vinci SP system facilitated dissection without the need for an axillary incision.

Evaluation of oncologic outcomes in head and neck cancer patients ≥80u2009years old based on adherence to NCCN guideline for postoperative adjuvant treatment

14-11-2019 – Dylan Roden, Kelly Daniels, James Metkus, Richard Goldman, Amanda Walsh, Jennifer Johnson, James Hamilton, William Keane, Andrew Chapman, Voichita Bar‐Ad, Larissa Sweeny, Joseph Curry, David Cognetti, Adam Luginbuhl

Journal Article

Abstract
Background
There is a paucity of literature characterizing outcomes in older adult patients with head and neck cancer (HNC). This study aims to describe patients from this group, their adherence to National Comprehensive Cancer Network (NCCN) adjuvant treatment guidelines, and the impact of guideline adherence on overall survival (OS).
Methods
In this retrospective cohort study, we reviewed all patients ≥80 years old with HNC who underwent surgery with curative intent from 2008 to 2016. Adherence to NCCN guidelines was determined in blinded fashion, and quality metrics and OS were compared.
Results
One hundred fifty‐nine patients met inclusion criteria. The majority of patients (n = 94, 59%) underwent treatment in accordance with NCCN recommendations while 65 (41%) deviated from NCCN guidelines. The two cohorts did not demonstrate a difference in 2‐year OS (62% vs 66%, P = .50).
Conclusion
Older adult patient outcomes were not different when treatment deviated from NCCN guidelines.

Factors predisposing to the development of orocutaneous fistula following surgery for oral cancer: Experience from a tertiary cancer center

14-11-2019 – “Farhana Girkar, Shivakumar Thiagarajan, Akshat Malik, Shikhar Sawhney, Anuja Deshmukh, Devendra Chaukar, Anil DCruz”

Journal Article

Abstract
Background
Orocutaneous fistula (OCF) is one of the frequently encountered postoperative complications following surgery for oral cancer, leading to prolonged hospital stay and delay in the initiation of adjuvant therapy.
Methods
We included all patients with oral cancer operated between January 2016 to December 2017 and at risk to develop an OCF. We assessed the incidence of OCF, its management, and factors predisposing to its development.
Results
Of 587 eligible patients, 9% developed OCF. On univariate and multivariate analysis, patients undergoing bilateral neck dissection or with surgical site infection (SSI) (P < .001) were at maximum risk. On univariate analysis, the incidence was higher following resections for tongue‐floor of mouth sub site (P = .002), irrespective of the type of flap used for reconstruction. Majority (57%) required surgical intervention for management.
Conclusion
The presence of SSI and performing bilateral neck dissection posed the maximum risk for developing OCF in patients undergoing surgery for oral cancer.

Transcripto‐based network analysis reveals a model of gene activation in tongue squamous cell carcinomas

14-11-2019 – Hao Zeng, Hui Li, Yunuo Zhao, Linyan Chen, Xuelei Ma

Journal Article

Abstract
Background
Tongue squamous cell carcinoma (TSCC) is the most common malignant tumor derived from the oral cavity, yet its specific molecular mechanisms have not been fully clarified. The aim of this study was to evaluate the association between potential genes and clinical features through constructing gene co‐expression networks.
Methods
The weighted gene co‐expression network analysis was used to construct gene co‐expression networks and to identify candidate key modules and hub genes. The gene expression profiles of GSE31056 obtained from the Gene Expression Omnibus (GEO) database was used to construct co‐expression networks.
Results
Five hub genes (FAP, AGTRAP, PLOD1, POSTN, and TSHZ3) were identified and validated at transcriptional levels. Moreover, the protein levels of these five hub genes were also found significantly higher in tumor tissues. Among them, FAP was most associated with immune infiltration.
Conclusions
These five candidate biomarkers and therapeutic targets are worthy of further investigation and discussion.

Young and elderly oral squamous cell carcinoma patients present similar angiogenic profile and predominance of M2 macrophages: Comparative immunohistochemical study

14-11-2019 – Lucas R. Teixeira, Luciana Y. Almeida, Rodrigo N. Silva, Ana T. M. Mesquita, Carla B. N. Colturato, Heitor A. Silveira, Andressa Duarte, Alfredo Ribeiro‐Silva, Jorge E. León

Journal Article

Abstract
Background
M2 macrophages are often detected in oral squamous cell carcinoma (OSCC), which, influenced by hypoxic conditions, appear to have high angiogenesis‐inducing capacity. However, the effects of immunosenescence on tumor‐associated macrophages (TAMs) and angiogenesis in OSCC are unknown.
Methods
Fifty‐seven OSCCs were divided into 3 groups (I: <40 years n = 17; II: 40‐65 years n = 20; III: >65 years n = 20). Immunohistochemistry for CD68 and CD163 (TAMs), and CD34 and D2‐40 for microvessel density (MVD), microvessel area (MVA), and total vascular area (TVA) were performed.
Results
All groups showed similar clinicopathological and immunohistochemical findings. Similar CD68 and CD163 expression, confirmed a M2 phenotype. MVD, MVA, and TVA were similar, however, with significant predominance of blood vessels. No significant correlation between macrophage and angiogenic markers was observed.
Conclusions
A similar TAM and angiogenesis profile suggests the participation of other mechanisms, instead immunosenescence, in young and elderly OSCC patients.

Free flap salvage from venous thrombosis by creation of a venocutaneous fistula: Case report and review of the literature

14-11-2019 – Rishabh Sethia, Zahir Allarakhia, Sidharth Puram, Stephen Kang, Enver Ozer, Amit Agrawal, Ricardo Carrau, James Rocco, Matthew Old

Case Reports

Abstract
Background
Venous congestion is the most frequently reported complication of free flap tissue transfer in head and neck patient with cancer. Numerous methods are utilized and prompt correction is necessary to prevent flap failure.
Methods
A 77‐year‐old woman underwent oral cavity resection and neck dissection for squamous cell carcinoma followed by radial forearm free flap for reconstruction. Three days later, the flap became congested and surgical exploration revealed extensive venous thrombosis throughout the free flap venous system and internal jugular vein. The flap vein was evacuated and flowing, and a venocutaneous fistula was created thereafter.
Results
Venocutaneous fistula resulted in flap decongestion and successful salvage. The patient was discharged from the hospital with no further flap or surgical complications.
Conclusion
When anatomical revision of the venous anastomosis is not feasible in a venous‐congested free flap, the creation of a venocutaneous fistula should be considered as a viable option for salvage.

Rapid head and neck tissue identification in thyroid and parathyroid surgery using optical coherence tomography

14-11-2019 – Nathan Yang, Caroline Boudoux, Etienne De Montigny, Anastasios Maniakas, Olga Gologan, Wendy‐Julie Madore, Sharmila Khullar, Louis Guertin, Apostolos Christopoulos, Eric Bissada, Tareck Ayad

Journal Article

Abstract
Background
Optical coherence tomography (OCT) is a noninvasive imaging modality that may reproduce the microarchitecture of tissues in real‐time. This study examines whether OCT can render distinct images of thyroid, parathyroid glands, adipose tissue, and lymph nodes in both healthy and pathological states.
Methods
Twenty‐seven patients undergoing thyroidectomy, parathyroidectomy, and/or neck dissection for thyroid cancer were recruited prospectively for imaging prior to histopathological analysis.
Results
Based on 122 imaged specimens, qualitative OCT descriptions were derived for healthy thyroid, parathyroid gland, adipose tissue, and lymph node. The frequencies at which distinguishing features were present for each tissue type were 88%, 83%, 100%, and 82%. OCT appearance of pathological specimens were also described.
Conclusions
Healthy neck tissues have distinct OCT appearances, which could facilitate parathyroid identification during thyroidectomies. However, images of parathyroid adenomas could be confused with those of lymph nodes, and benign and malignant thyroid nodules could not be differentiated.

Determination of legal responsibility in shared airway management between anesthesiology and otolaryngology

14-11-2019 – Henry C. Ideker, Jatin S. Julakanti, Nishat A. Momin, Mohamad R. Chaaban

Journal Article

Abstract
Background
Malpractice litigation remains an important point of contention in the United States. Airway management often sees multidisciplinary teams of anesthesiologists and otolaryngologists. This report analyzes lawsuits affecting both teams in airway management.
Methods
The Westlaw legal database (West Publishing Co., St. Paul, MN) was used to search for malpractice cases involving failed airway management, where both anesthesiology and otolaryngology were involved.
Results
Among the 28 cases analyzed, otolaryngology and anesthesiology were most commonly sued together (46.4%). When sued together, defendants were less likely to win and average award amounts ($4, 558 716) were higher. These cases most commonly occurred in the operating room (78.6%), involved a difficult/improper intubation (39.3%), alleged a failure to follow standard of care (57%), and resulted in death (60.7%).
Conclusion
These cases primarily cited failure to follow standard of care and communication failures. Efforts should be directed toward multidisciplinary airway management protocols and effective communication.

Paranasal sinus invasion suggested T4 classification of patients of nasopharyngeal carcinoma: A two‐center retrospective investigation

14-11-2019 – Liqing Wu, Shuiqing Zhuo, Weike Zeng, Shaobo Liang, Shunxin Wang, Chunyan Cui, Jian Zhou, Guangyin Ruan, Shuoyu Xu, Lifei Wang, Ling Huang, Lizhi Liu, Haojiang Li

Journal Article

Abstract
Background
To investigate the prognostic significance of paranasal sinus invasion in nasopharyngeal carcinoma (NPC) patients.
Methods
Patients with NPC after intensity‐modulated radiotherapy from 2010 to 2013 were identified (n = 1225). Clinical features and magnetic resonance images were analyzed.
Results
Paranasal sinus invasion was identified in 182/1225 patients (14.9%). Multivariate analysis showed that paranasal sinus invasion was an independent factor for overall survival, progression‐free survival, distant metastasis‐free survival, and local recurrence‐free survival (P < .05 for all). T3 NPC patients with paranasal sinus invasion had a poorer prognosis than those without (P < .05), and there was no significant survival difference compared with T4 patients, regardless of involvement of inner structures (P > .05 for all). Upgrading NPC with paranasal sinus invasion to T4 disease achieved better predictive abilities.
Conclusions
Paranasal sinus invasion is an independent prognostic factor for NPC. It may be appropriate to upgrade the T classification.

Neoadjuvant chemotherapy improves survival compared with concurrent chemoradiation alone in nasopharyngeal carcinoma patients with N3 disease

14-11-2019 – James E. Han, Sun K. Yi, Steven Wang, Audrey Erman, Shethal Bearelly, Simran Sindhu, Jared R. Robbins, Julie Bauman, Charles C. Hsu

Journal Article

Abstract
Background
Neoadjuvant chemotherapy (NAC) trials in endemic regions of nasopharyngeal carcinoma (NPC) found improved survival, but studies are lacking in nonendemic regions. We assessed whether adding NAC to concurrent chemoradiation (CRT) improves overall survival (OS), especially in high‐risk nonendemic patients.
Methods
Definitively treated NPC patients (n = 5424) from the National Cancer Database were analyzed for predictors of NAC and NAC effects on OS with multivariate Cox proportional hazards analysis (multivariate analysis MVA). Propensity score matched (1:2) survival analysis of NAC (n = 968) and CRT alone (n = 1914) was also performed. Effects on OS were stratified by risk group.
Results
On MVA, NAC‐improved OS among the total cohort (hazard ratio HR 0.89, P = .049), particularly among stratified keratinizing histology (HR 0.82, P = .015) and N3 disease (HR 0.73, P = .046). Among propensity matched patients, NAC improved OS in patients with N3 disease (n = 336; HR 0.71, P = .046).
Conclusions
NAC may improve OS among nonendemic NPC patients at higher risk of distant micrometastases, particularly N3 disease and those with unfavorable histology.

Inhibition of tropomyosine receptor kinase B on the migration of human Schwann cell and dispersion of oral tongue squamous cell carcinoma in vitro

14-11-2019 – Liliana Ein, Olena Bracho, Christine Mei, Jaimin Patel, Thomas Boyle, Paula Monje, Cristina Fernandez‐Valle, Esperanza Bas, Giovana Thomas, Donald Weed, Zoukaa Sargi, Christine Dinh

Journal Article

Abstract
Background
Schwann cells (SC) may play an important role in perineural invasion (PNI) by promoting cancer cell dispersion. Brain‐derived neurotrophic factor (BDNF) may contribute to these cellular events by activating tropomyosine receptor kinase B (Trk
B). This study examines the effect of Trk
B inhibition on SC migration and oral cancer cell dispersion in vitro.
Methods
Human tongue squamous cell carcinoma (SCC‐9) and human SCs were cocultured in three different conditioned mediums: control, BDNF, and Trk
B inhibitor. Cell migration, cancer cell dispersion, and SC dedifferentiation were measured on time‐lapse and immunofluorescence images.
Results
Cancer cell migration exceeded SC migration in all conditions. Trk
B inhibition promoted SC dedifferentiation and significantly increased SC migration, when compared to BDNF conditions. Trk
B inhibition also reduced cancer cell dispersion, when compared to control and BDNF‐treated cultures.
Conclusion
SCs may have importance in the pathophysiology of PNI. Trk
B inhibition may be a potential avenue for therapeutic intervention.

Postoperative radiation therapy vs observation for pN1 oral cavity squamous cell carcinoma

14-11-2019 – Krish Suresh, John D. Cramer

Journal Article

Abstract
Background
American Society of Clinical Oncology guidelines recommend that the decision to give postoperative radiotherapy (PORT) for p
N1 oral cavity squamous cell carcinoma (OCSCC) without other adverse features be based on the adequacy of the neck dissection (<18 or ≥18 nodes).
Methods
We conducted a cohort study of the National Cancer Database examining how PORT affects survival. We stratified analyses by the adequacy of the neck dissection and lymph node (LN) size.
Results
Our cohort comprised 1909 patients (898 received PORT). PORT conferred a survival benefit in the overall cohort (adjusted hazard ratio 0.82, 95% CI 0.72‐0.94). There was similar benefit in patients receiving inadequate and adequate neck dissections. Patients with >10 mm LN metastasis derived greater benefit compared with patients with smaller metastases.
Conclusions
In p
N1 OCSCC without other adverse features, the size of the LN metastases may predict benefit from PORT, whereas the adequacy of the neck dissection may not.

ERRATUM

14-11-2019 –

Published Erratum

Adjuvant therapies in the management of medication‐related osteonecrosis of the jaws: Systematic review

14-11-2019 – Elen Souza Tolentino, Tamara F. Castro, Felipe C. Michellon, Ana C. C. Passoni, Lorena J. A. Ortega, Lilian C. V. Iwaki, Mariliani C. Silva

Journal Article, Review

Abstract
Background
We investigated the efficacy of hyperbaric oxygen (HBO), low‐intensity laser (LIL), and platelet‐rich plasma (PRP) in the management of medication‐related osteonecrosis of the jaws (MRONJ).
Methods
A literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Two examiners independently assessed eligibility and risk of bias and extracted data.
Results
There was improvement in 75.6% of the 41 patients submitted to HBO, with positive effects on pain relief and decreased size and number of lesions at a faster rate, with better effects when the drug was discontinued. For LIL, 158 (64.2%) of the 246 patients/sites improved the symptoms and 98 (39.8%) healed completely. Fourteen (17.3%) of the 81 patients treated with PRP significantly improved the symptoms and 65 (80.2%) completely healed.
Conclusions
These therapies served as safe and effective adjuvant modalities for MRONJ treatment. The lack of randomized clinical trials evidences the need for more high‐quality investigations on the subject.

Reproductive factors and thyroid cancer risk: Meta‐analysis

14-11-2019 – Arathy S. Mannathazhathu, Preethi S. George, Sreekala Sudhakaran, Durga Vasudevan, Jagathnath Krishna KM, Christopher Booth, Aleyamma Mathew

Journal Article, Review

Abstract
Background
Assessed pooled risk on reproductive factors and oral contraceptives (OC) on thyroid cancer (TC) using published studies (1996‐2017).
Methods
Summary odds ratio (OR) for case‐control studies (n = 10) and risk ratio (RR) for cohort studies (n = 9) was done.
Results
OR was 1.43 (95% CI: 1.16‐1.77) for age at menarche >14 years, 1.49 (95% CI: 1.19‐1.86) for parity >2, 1.38 (95% CI: 1.18‐1.61) for miscarriage/abortion, and 2.05 (95% CI: 1.39‐3.01) for artificial menopause. A protective effect (ORs: 0.85; 95% CI: 0.72‐0.99) on TC was observed for prolonged use of OCs. RR was 1.17 (95% CI: 0.90‐1.57) for age at menarche >14 years, 1.10 (95% CI: 0.94‐1.27) for parity >2, 1.20 (95% CI: 1.03‐1.40) for miscarriage/abortion, and 2.16 (95% CI: 1.41‐3.31) for artificial menopause and protective effect (RR: 0.78; 95% CI: 0.65‐0.92) for prolonged use of OCs.
Conclusions
This meta‐analysis supports an association due to changes in female hormones during menstrual cycle and pregnancy with the risk of TC and explains female preponderance.

Ameloblastic carcinoma: Clinicopathological analysis of 18 cases and a systematic review

14-11-2019 – Ling Deng, Rui Wang, Mingzhong Yang, Wei Li, Ling Zou

Journal Article, Review

Abstract
Objectives
Exploring the clinicopathological features of ameloblastic carcinoma (AC) and reviewing the literature to improve the diagnosis and treatment of the disease.
Materials and Methods
Clinical data and pathological features of 18 cases of AC were retrospectively analyzed. A systematic review was carried out by searching PubMed and Medline databases using the Me
SH terms “ameloblastic” and “carcinoma.”Results
In the systematic analysis, 125 cases of AC from 81 eligible original studies and 18 cases of AC from this research were included. The male‐to‐female ratio was 2.58:1, and the mandible‐to‐maxilla ratio was 1.80:1. Mean age of patients was 45.3 years. Thirty‐seven cases of recurrence and 27 cases of metastasis were recorded.
Conclusion
AC is a rare neoplasm of the odontogenic epithelium. A systematic review indicates that diagnoses at the early phase and a close periodic assessment for recurrence and metastasis are necessary.

TRPV1 regulates inflammatory process in the tongue of surgically induced xerostomia mouse

13-11-2019 – Min H. Yoo, Yun‐Hee Rhee, JaeYun Jung, Sang‐Joon Lee, Jung‐Hwan Moon, Ji‐Hun Mo, Phil‐Sang Chung

Journal Article

Abstract
Background
The aim of study is to investigate the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) on xerostomia‐induced inflammatory response in vivo.
Methods
Parotid, submandibular, and lingual gland were removed for xerostomia induction. The expression of inflammatory cytokines, TRPV1, NFk
B, and MAPK in xerostomia was evaluated and compared in both TRPV1 wild and knockout mice.
Results
The level of interleukin‐6 (IL‐6) and IL‐17, neutrophil/CD4 T‐cell infiltration, phosphorylation of extracellular signal‐regulated kinase (ERK) and c‐Jun N terminal kinase, TRPV1, and the localization of NFk
B were elevated in xerostomia‐induced TRPV1 wild‐type mice. In contrast, inflammatory cytokines and MAPK were decreased in xerostomia‐induced TRPV1 knockout mice. TRPV1 antagonist treatment also reduced tongue ulceration, neutrophil/CD4+ T‐cell expression, IL‐6, and IL‐17 in TRPV1 wild‐type mice.
Conclusion
TRPV1 had a crucial role in modulating inflammation in xerostomia and targeting TRPV1 might be a promising therapeutic strategy for xerostomia.

Reply to the letter of the editor: Is tailored management better than salvage in laryngeal squamous cell carcinomas?

12-11-2019 – Ximena Mimica, Martin Hanson, Marc A. Cohen

Letter

Is tailored management better than salvage in laryngeal squamous cell carcinomas

12-11-2019 – Bhargaw Ilapakruty, Vishal U. S. Rao

Letter

Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy

11-11-2019 – Li Wang, Liuqing Yang, Shichao Han, Jinming Zhu, Yuting Li, Zeming Wang, You‐Hong Fan, Eric Lin, Ruiping Zhang, Narayan Sahoo, Yupeng Li, Xiaodong Zhang, Xiaochun Wang, Tengfei Li, Xiaorong R. Zhu, Hongtu Zhu, John V. Heymach, Jeffrey N. Myers, Steven J. Frank

Journal Article

Abstract
Background
Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear.
Methods
Proteomics analyses of protein expression profiles by reverse‐phase protein arrays were done for two human papillomavirus HPV‐negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested.
Results
Compared with PRT, XRT tended to induce lower expression of DNA damage repair—and cell cycle arrest‐related proteins and higher expression of cell survival‐ and proliferation‐related proteins.
Conclusions
Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT.

Evaluation of 18F‐FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma

09-11-2019 – Felipe Galiza Barbosa, Oliver Riesterer, Stephanie Tanadini‐Lang, Sonja Stieb, Gabriela Studer, Martin Pruschy, Gerhard F. Huber, Martin W. Huellner, Paul Stolzmann, Patrick Veit‐Haibach

Journal Article

Abstract
Background
To determine whether 18F‐PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18F‐PET/CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy.
Methods
A total of 54 patients with head and neck cancer were prospectively enrolled in this single‐center, randomized study from 03/2012‐04/2015. Patients underwent FDG‐PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow‐up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS).
Results
Thirty‐two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P > .05) during clinical follow‐up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P > .05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P < .01).
Conclusions
Early response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no prognostic value concerning PFS and cannot identify high risk patients for consolidation therapy. Imaging responders showed a significantly longer PFS compared to nonresponders and therefore PET/CT might serve as a prognostic biomarker.
Trial registration
Clinical Trials.gov identifier: NCT01435252.

Laryngeal Cancer, Rogério A. Dedivitis, Giorgio Peretti, Ehab Hanna, Claudio R. Cernea, Thieme Medical Publishers, Inc, New York, NY, 2019, 183 pages, $139.99 USD

05-11-2019 – Timothy Blood

Clinical characteristics and prognostic factors of malignant tumors involving pterygopalatine fossa

04-11-2019 – Hyun‐Jae Woo, Peter H. Hwang, Michael J. Kaplan, Garret Choby

Journal Article

Abstract
Background
To identify the clinical characteristics and prognostic factors of malignancies involving the pterygopalatine fossa (PPF).
Methods
Fifty‐seven patients who underwent curative surgery for malignant tumor involving PPF were reviewed.
Results
The rates for three‐year local control (LC), five‐year disease‐free survival (DFS) and five‐year overall survival (OS) were 55.4%, 34.5%, and 52.7%, respectively. Perineural invasion (PNI) of the maxillary nerve with facial numbness (symptomatic V2 PNI) (P = .04) and cranial involvement (P = .03) were predictors for poor OS. Symptomatic V2 PNI was also a significant predictor for poor LC (P = .05) and DFS (P = .03). Within the subgroup analysis of patients with pathologically confirmed V2 PNI, asymptomatic V2 PNI patients had significantly better LC (71.2% vs 31.8%, P = .05) and DFS (43.8% vs 17.3%, P = .05) compared to symptomatic patients.
Conclusion
Malignant tumors involving the PPF have diverse pathologies and a poor prognosis. Symptomatic V2 PNI may be an independent poor prognostic factor.

Safety and efficacy of transoral robotic and endoscopic thyroidectomy: The first 100 cases

04-11-2019 – Kyung Tae, Yong Bae Ji, Chang Myeon Song, Jeong Seon Park, Jung Hwan Park, Dong Sun Kim

Journal Article

Abstract
Background
The aim of this study was to evaluate the safety and efficacy of transoral robotic and endoscopic thyroidectomy.
Methods
We analyzed and compared the first 100 cases of transoral robotic (71 cases) and endoscopic (29 cases) thyroidectomy with 207 cases of conventional transcervical thyroidectomy.
Results
Transoral thyroidectomy was completed successfully in all patients, except for three who were converted to the robotic facelift or transcervical approach. The mean operative time of the transoral procedure was significantly longer than that of the conventional procedure. Perioperative complications such as hypoparathyroidism, vocal cord palsy, hematoma, and seroma did not differ between the two groups. However, there were some unusual complications such as CO2 embolism, surgical site infection, skin trauma, burn, and ecchymosis in transoral thyroidectomy. Postoperative cosmesis was significantly better in the transoral group.
Conclusion
Transoral robotic and endoscopic thyroidectomy is feasible and comparable to conventional transcervical thyroidectomy in highly selected patients.

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo‐radiotherapy

04-11-2019 – Pierluigi Bonomo, Cinzia Talamonti, Isacco Desideri, Livia Marrazzo, Donato Pezzulla, Andrea Rampini, Silvia Bertocci, Roberta De Majo, Chiara Gasperi, Assunta Simona Curion, Luciana Lastrucci, Luca Dominici, Stefania Pallotta, Lorenzo Livi, Saverio Caini

Journal Article

Abstract
Background
We investigated whether the pattern of intensity‐modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD).
Methods
A frequency‐matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models.
Results
The incidence of G3/G4 RD was 41.1% in 90 patients included (50% vs 36.6% in the cetuximab and cisplatin cohorts, respectively). In multivariate analysis, PS ≥ 1 and weight loss at RT completion >10 kg were the only factors that retained significance. The best dosimetric predictive accuracy was provided by 19.9 cc and 5.8 cc of skin ring 2 mm V50 and V60, respectively (AUC: 0.61 for both).
Conclusion
Along with clinical factors, the pattern of dose distribution to a ring structure localized 2 mm below the patients surface may help predict the development of severe RD.

The surgical treatment of cerebrospinal fistula: Qualitative and quantitative analysis of indications and results

04-11-2019 – Alessandra Iavarone, Paolo Luparello, Maria Silvia Lazio, Lara Valentina Comini, Federica Martelli, Oliviero De Luca, Giovanni Paolo Santoro, Roberto Santoro, Giammarco Alderotti, Giuditta Mannelli

Journal Article, Review

Abstract
Cerebrospinal fistula might occur in different ways. CSF closure techniques have undergone significant evolution that has led to the consolidation of the transnasal endoscopic approach. Despite the existence of multiple publications, meaningful information is still lacking in clinical practice and the literature about the ideal method, material, and timing for repair of CSF. The purpose of this review was to summarize the success rate of endoscopic CSF leak repair as well as whether specific techniques or materials influence the primary success rate through a review of the latest advancements in endoscopic CSF management published in the past 10 years. The principles of multilayer reconstructions and the routine use of vascularized flaps in expanded endonasal surgery have reduced postoperative CSF leaks failure rates between 5% and 10% (4% in this meta‐analysis). Effective endoscopic anterior skull base (ASB) closure may be achieved by multiple reconstructive techniques, which should be tailored case by case according to the patient and defect conditions.

Smart flap of sternocleidomastoid muscle in anterior cervical spine surgery: Surgical anatomical dissection technique

01-11-2019 – Fabrizio Cuzzocrea, Matteo Ghiara, Roberto Vanelli, Marta Medetti, Ambrogio Alberto Lombardini, Francesco Benazzo, Simone Mauramati, Chiara Mossinelli, Irene Herman, Marco Benazzo

Journal Article

Abstract
The use of sternocleidomastoid muscle flap has firstly been described in 1909. In spine surgery, it is usually reserved in the cases of revision after anterior cervical spine procedures. The aim of this article is to introduce its usage as prophylactic measure in cases at high risk of iatrogenic fistula formation. The procedure consists of three main steps: sternocleidomastoid isolation, flap design and harvesting, and flap fixation. The use of a surgical anchor allows a better adherence to the plate preventing hematoma formation. The use of SCM smart flap in primary anterior cervical spine surgery as a prophylactic method could be considered a safe and feasible procedure in patients with a high risk of iatrogenic fistulas.

American College of Surgeons National Surgical Quality Improvement Program assessment of risk factors for 30‐day unplanned readmission in patients undergoing head and neck surgery requiring free tissue reconstruction

31-10-2019 – Orly M. Coblens, Jason A. Brant, William W. Thomas, John P. Fischer, Jason G. Newman, Steven B. Cannady

Journal Article

Abstract
Background
Unplanned readmissions have become a metric for measuring quality of care. We analyzed the factors associated with 30‐day unplanned readmission (30d
UR) following head and neck cancer resections that included free tissue reconstruction (FTR).
Methods
The 2012‐2014 ACS‐National Surgical Quality Improvement Program (NSQIP) data set was queried. Univariate and multivariate logistic regression analyses were performed.
Results
Out of 1114 cases, 121 had a 30d
UR. The most common reasons were wound complications, including incisional infections, hematoma, and hemorrhage. A significant independent risk factor for 30d
UR included a clean/contaminated wound class (odds ratio OR, 2.27; 95% confidence interval CI, 1.20‐4.76). Patients receiving an osseous FTR had lower readmission rates (OR, 0.51; CI, 0.27‐0.91). Discharge destination had no statistical significance.
Conclusions
Based on the NSQIP data set, 10.9% of patients receiving an FTR for head and neck malignancy had a 30d
UR. Although large, population‐based data sets have limitations, these results elucidate that these patients are at an increased risk for unplanned readmissions, which can guide patient expectations and discharge planning.

Minimally invasive surgery for laryngopharyngeal cancer: Multicenter feasibility study of a combination strategy involving transoral surgery and real‐time indocyanine green fluorescence‐navigated sentinel node navigation surgery

31-10-2019 – Koji Araki, Masayuki Tomifuji, Akihiro Shiotani, Shigeru Hirano, Junkichi Yokoyama, Kiyoaki Tsukahara, Akihiro Homma, Seichi Yoshimoto, Yasuhisa Hasegawa

Journal Article

Abstract
Background
Sentinel node navigation surgery using indocyanine green (ICG‐SNNS) can be performed in the operation room. The combination of minimally invasive transoral surgery (TOS) with ICG‐SNNS can provide functional preservation options for both primary lesions and lymph node (LN) metastasis. This multicenter feasibility study of this strategy was conducted in Japan.
Methods
Patients with clinical T1 or T2, N0 oropharyngeal, hypopharyngeal, or supraglottic cancer were enrolled. The identification rate of sentinel nodes, delayed cervical LN metastasis in 2 years, and survival rate were assessed.
Results
Twenty‐two patients (10 oropharynx, 8 hypopharynx, 4 supraglottic cancer) were enrolled. The identification rate was 100%. One case had delayed nodal metastasis. The accuracy was 95.5%, sensitivity was 75%, and specificity was 100%. The 5‐year disease‐specific survival was 100%, overall survival was 72.3%, and disease‐free survival was 60.5%.
Conclusions
The combination of TOS with ICG‐SNNS is feasible as a minimally invasive strategy and has favorable oncological outcomes.

Preliminary clinical experience with the 4 K3‐dimensional microvideoscope (VITOM 3D) system for free flap head and neck reconstruction

30-10-2019 – Armando De Virgilio, Giuseppe Mercante, Francesca Gaino, Phil Yiu, Tiziana Mondello, Luca Malvezzi, Giovanni Colombo, Raul Pellini, Giuseppe Spriano

Journal Article

Abstract
Background
To demonstrate the use of a 4 K 3‐dimensional microvideoscope (VITOM 3D) system for free flap head and neck reconstruction.
Methods
Clinical human study of free flap harvesting and microvascular anastomosis in patients undergoing reconstruction after ablative surgery for head and neck carcinoma. The video shows the harvesting of a chimeric myofascial/fascio‐cutaneous anterolateral thigh free flap and microvascular anastomosis using different techniques.
Results
The VITOM 3D exoscope system provided sufficient access, reach, and visualization to perform successfully free flap harvesting and microvascular anastomosis. Using the 3D glasses, both surgeons and nurses can have the same visualization throughout the entire procedure. We performed 10 arterial and venous anastomosis without significant complications.
Conclusions
This study demonstrates the technical feasibility of free flap harvesting and microvascular anastomosis using the 4 K3‐Dimensional Microvideoscope (VITOM 3D) System.

Prognostic significance of MTOR expression in HPV positive and negative head and neck cancers treated by chemoradiation

27-10-2019 – Thomas G. Wilson, Alaa Hanna, Johnathon Recknagel, Barbara L. Pruetz, Andrew M. Baschnagel, George D. Wilson

Journal Article

Abstract
Background
The mechanistic target of rapamycin (MTOR) plays a key role in regulating cell growth and metabolism and is commonly overexpressed in head and neck cancer (HNSCC). This study investigated the association of MTOR with clinical outcome in human papilloma virus (HPV) positive and negative HNSCC patients treated by chemoradiation.
Methods
A tissue microarray (TMA) consisting of cores from 109 HNSCC patients treated by definitive chemoradiation was constructed and stained with antibodies against p16 and MTOR and expression correlated with clinicopathological features and clinical outcome.
Results
MTOR varied widely between tumor cores and was not associated with HPV status or clinicopathological features. There was a positive correlation with pre‐treatment FDG uptake.(P = .01). In HPV negative patients, MTOR predicted for shorter locoregional control (P = .02), diseases free survival (P = .02), and overall survival (P = .04). MTOR expression was not associated with outcome in HPV positive patients.
Conclusions
Prognostic significance of MTOR expression depends on HPV status.

Assessment of shoulder function following scapular free flap

27-10-2019 – Krupal B. Patel, Tsu‐Hui (Hubert) Low, Allison Partridge, Anthony C. Nichols, S. Danielle MacNeil, John Yoo, Kevin Fung

Journal Article

Abstract
Background
The scapular system free flap has been increasing in popularity to reconstruct short segment mandibular bony defects. It is important to assess donor site morbidities systematically.
Methods
Prospective cohort study using objective measures of range of motion (ROM) and shoulder strength were measured. Subjective disability was evaluated with validated questionnaires—Neck Disability Impairment Index and Shoulder Pain and Disability Index.
Results
Twenty‐six patients were recruited—19 with scapular tip and 7 with lateral border scapular free flap. Decreased ROM on the operated side was noted for shoulder abduction, shoulder flexion, and external rotation. No significant difference was noted for shoulder extension. Strength was reduced for shoulder flexion, shoulder abduction, and external rotation. Subjective measurements did not indicate significant shoulder function disruption.
Conclusion
Patients with scapular free flap reconstruction did not experience significant shoulder morbidity. Measures of shoulder ROM and power were objectively affected; however, subjective measures of shoulder disability were not significantly affected.

Degree of technical difficulty of thyroidectomy for autoimmune thyroid disease

25-10-2019 – Robert Saadi, Alyssa Brandt, Yesul Kim, Elizabeth Cottrill, Brian Saunders, Eric Schaefer, David Goldenberg

Journal Article

Abstract
Background
Our goal was to elucidate the differences in degree of technical difficulty of thyroidectomy in patients with autoimmune thyroid diseases.
Methods
Charts of adult patients who had undergone thyroidectomy were reviewed. Patients with Hashimotos Thyroiditis (HT) or Graves Disease (GD) were individually compared to a control group of patients with early stage malignancy or goiter.
Results
The HT (n = 65) group was significantly more likely to have friable (P = .001) and fibrotic (P < .001) thyroids, longer operative times (P = .02), and a 22‐modifier (P = .005). The GD (n = 169) group was significantly more likely to have friable (P < .001), vascular (P < .001), fibrotic (P = .038), and heavy (P = .002) thyroids, longer operative times (P = .03), increased length of stay (P = .01) and a 22‐modifier (P = .01).
Conclusion
Our experience at an institution with a high‐volume thyroid practice demonstrates that patients with autoimmune thyroid disease have consistent qualitative changes of the thyroid and significantly increased operative times and surgical difficulty.

The relations of dosimetric parameters with long‐term outcomes and late toxicities in advanced T‐stage nasopharyngeal carcinoma with IMRT

24-10-2019 – Xiaoxia Gou, Baofeng Duan, Huashan Shi, Lei Qin, Jianghong Xiao, Nianyong Chen

Journal Article

Abstract
Background
Balancing the dose requirements between targets and normal tissue is a challenge in radiation of nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the dosimetric parameters and clinical outcomes in NPC.
Methods
We presented a retrospective review of patients with T3‐4 NPC treated by intensity‐modulated radiation therapy (IMRT). Patient characteristics, dosimetric parameters, and the follow‐up data for survival and late toxicities were analyzed.
Results
The 5‐year overall survival, local relapse‐free survival, and distant metastasis‐free survival were 83.0%, 90.1%, and 82.4%, respectively. Multivariate analysis revealed that the volume of involved lymph node was an independent prognostic factor. The volume of primary tumor and the maximal dose were significant factors affecting temporal lobe injury.
Conclusions
IMRT provided satisfactory local control for advanced T‐stage NPC, with acceptable late toxicities. The dose constraint criteria of selected critical structures can be appropriately loosen.

Association between pathological invasion patterns and late lymph node metastases in patients with surgically treated clinical No early oral tongue carcinoma

24-10-2019 – Yukiko Hori, Akira Kubota, Tomoyuki Yokose, Madoka Furukawa, Takeshi Matsushita, Nobuhiko Oridate

Journal Article

Abstract
Background
This study evaluated the combination of tumor budding and depth (BD model) and worst pattern of invasion (WPOI) as histopathological prognostic factors in clinical N0 early oral tongue carcinoma.
Methods
Data from 62 patients were retrospectively analyzed. Associations between histopathological factors (differentiation, stage, lymphatic invasion, blood vessel invasion, WPOI, and BD model) and regional control (RC) or disease‐free survival (DFS) were evaluated.
Results
The five‐year RC and DFS rates were 74% and 65%, respectively. Univariate analysis identified blood vessel invasion, lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, and BD model, as predictive factors for RC. Univariate analysis identified lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, as predictive factors for DFS.
Conclusion
The pathological invasion patterns should be considered when determining the follow‐up plan for patients with clinical N0 early oral tongue carcinoma.

Efficacy of EPA‐enriched supplement compared with standard formula on body weight changes in malnourished patients with head and neck cancer undergone surgery: a randomized study

24-10-2019 – Kitti Jantharapattana, Orachat Orapipatpong

Journal Article

Abstract
Background
Eicosapentaenoic acid (EPA) containing nutritional supplement can reverse weight loss and increase lean body mass in a perioperative period of patients with head and neck cancer. To study effects of an EPA‐enriched supplement compared with a conventional supplement in malnourished patients with head and neck cancer following surgery is primary objective.
Methods
The patients were randomized into EPA‐enriched and standard formula group. The supplements were prescribed 7 days preoperative through 14 days postoperative. Body weight and composition including serum parameters were measured from 7 days preoperative until 4 months postoperative. The hospitalized courses were recorded.
Results
Thirty‐one patients in each group consumed EPA‐enriched and standard formula supplements. There was no significant body weight or composition changes perioperative. No significant differences in the hospitalized days and postoperative complications was observed.
Conclusions
Body weight changes in malnourished patients with head and neck cancer following surgery were not influenced by EPA additives to perioperative nutritional supplements.

Radiation‐induced nausea and vomiting in head and neck cancer: Is it something worth considering in the intensity modulated radiotherapy era? “A narrative review”

21-10-2019 – Fabiola Paiar, Agostino Cristaudo, Alessandra Gonnelli, Noemi Giannini, Paola Cocuzza, Sabrina Montrone, Luca Bruschini, Francesco Pasqualetti, Stefano Ursino, Pierluigi Bonomo

Journal Article, Review

Abstract
Radiation therapy is one of the cornerstones in the treatment of head and neck squamous cell carcinomas (HNSCC), alone or in combination with chemotherapy or surgery. Technological advances which occurred over the last few decades have increased the efficacy of radiotherapy (RT), particularly, intensity‐modulated RT (IMRT). IMRT can deliver treatments on complex tumoral targets with dose escalation while sparing organs at risk; anyway IMRT deposits dose in unpredictable patterns outside of the target volume with the purpose of improving conformality. Radiation‐induced nausea and vomiting (RINV) is a frequent albeit neglected side effect of RT that can lead to delays in treatment with serious consequences on cure rates. According to several guidelines (MASCC 2016, NCCN 2018), RT for HNSCC has traditionally been regarded as a low emetic risk treatment. Nevertheless, several works suggest that IMRT could increase RINV. Further studies are needed to define the exact incidence and the detailed pathophysiology of RINV in patients with HNSCC treated with state of art IMRT techniques, with and without concurrent chemotherapy.

Impact of human papillomavirus status on survival and recurrence in a geographic region with a low prevalence of HPV‐related cancer: A retrospective cohort study

21-10-2019 – Rafael De Cicco, Rosilene Melo Menezes, Ulisses R. Nicolau, Clovis A. L. Pinto, Luisa L. Villa, Luiz P. Kowalski

Journal Article

Abstract
Background
Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with better tumor‐response rates and survival outcomes. However, in some geographic regions, the impact of HPV infection on prognosis remains unclear. The aim of this study was to describe the patterns of recurrence and survival among patients treated for OPSCC in a geographic region with a reported low prevalence of HPV‐related OPSCC.
Methods
We retrospectively evaluated 215 patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to IV OPSCC who were treated with upfront surgery or radiation therapy with or without chemotherapy in a tertiary Cancer Center in Brazil. The collected data included demographic information, HPV status, tobacco and alcohol consumption, and pathologic and treatment variables. The patterns of recurrence were recorded according to HPV status. Disease‐specific survival and recurrence‐free survival were calculated.
Results
One hundred twenty‐seven (59.1%) patients were diagnosed with HPV‐positive OPSCC. According to the AJCC eighth edition, 34 (15.8%), 71 (33%), 47 (21.9%), and 60 (27.9%) patients had stage I, II, III, and IV disease, respectively. Surgery was performed in 109 (50.7%) cases, and upfront chemoradiation regimens were provided in 104 (48.4%, P = .69) patients. Overall, the 5‐year cancer‐specific survival was 73.5% and 68.1% for patients positive and negative to HPV, respectively. Tobacco status was considered the only independent prognostic factor for survival. Furthermore, HPV status was not associated with differences in recurrence rates (P = .68). While all distant relapses were found to be lung metastases in the HPV‐negative group, we observed unusual sites of distant metastases in the HPV‐positive group.
Conclusions
HPV status was not associated with higher rates of survival among the investigated population. Moreover, smoking status was considered the only independent prognostic factor for survival. Furthermore, patients with HPV‐positive tumors were more likely than patients with HPV‐negative OPSCC to have unusual distant metastases.

Prospective evaluation of oral premalignant lesions using a multimodal imaging system: a pilot study

17-10-2019 – Eric C. Yang, Imran S. Vohra, Hawraa Badaoui, Richard A. Schwarz, Katelin D. Cherry, Justin Jacob, Jessica Rodriguez, Michelle D. Williams, Nadarajah Vigneswaran, Ann M. Gillenwater, Rebecca R. Richards‐Kortum

Journal Article

Abstract
Background
Multimodal optical imaging, incorporating reflectance and fluorescence modalities, is a promising tool to detect oral premalignant lesions in real‐time.
Methods
Images were acquired from 171 sites in 66 patient visits for clinical evaluation of oral lesions. An automated algorithm was used to classify lesions as high‐ or low‐risk for neoplasia. Biopsies were acquired at clinically indicated sites and those classified as high‐risk by imaging, at the surgeons discretion.
Results
Twenty sites were biopsied based on clinical examination or imaging. Of these, 12 were indicated clinically and by imaging; 58% were moderate dysplasia or worse. Four biopsies were indicated by imaging evaluation only; 75% were moderate dysplasia or worse. Finally, four biopsies were indicated by clinical evaluation only; 75% were moderate dysplasia or worse.
Conclusion
Multimodal imaging identified more cases of high‐grade dysplasia than clinical evaluation, and can improve detection of high grade precancer in patients with oral lesions.

Closure of radial forearm free flap donor site: A comparative study between keystone flap and skin graft

17-10-2019 – Pauline Potet, Guillaune De Bonnecaze, Emilien Chabrillac, Agnès Dupret‐Bories, Sébastien Vergez, Benoit Chaput

Journal Article

Abstract
Background
The aim was to investigate the feasibility of radial forearm free flap (RFFF) donor site closure by keystone flap (KF) and compare its outcomes to those of skin graft (SG) closure.
Methods
One hundred and one patients who underwent RFFF for head and neck reconstruction were included (35 KF closure and 65 SG closure). Duration of wound healing and donor site complications was collected. After a minimal follow‐up of 1 year, patients were questioned about functional and esthetic impairment.
Results
Coverage of donor site by KF was successful in all cases. The duration of wound healing was longer after SG than after KF (32 days vs 18 days, P < .001). Healing complications, esthetic and functional results were not statistically different.
Conclusion
Forearm donor site closure by KF is a feasible alternative to the traditional SG. Its main advantages are the reduced wound healing time and the avoidance of a second donor site.

The infraclavicular pedicled flap in head and neck reconstruction: applications and outcomes

16-10-2019 – Charles Alain, Pierre‐Hugues Fortier, Mathieu Belzile

Journal Article

Abstract
Background
An infraclavicular pedicled flap (ICPF) was recently described in the literature. This anatomical region is attractive for the restoration of head and neck oncological defects. This paper is a review of our experience with this versatile flap.
Methods
A retrospective study was conducted by reviewing the records of all the patients operated in a tertiary‐care center between August 2013 and January 2019 whose surgery involved an ICPF.
Results
Forty‐four patients received an ICPF for various indications, including large vessel coverage in neck/parotid recontouring (34.1%), postlaryngectomy reconstruction (34.1%), and fistula closure (25.0%). All flaps survived. Thirteen patients experienced a postoperative complication (29.5%), six of whom (13.9%) required a repeat procedure under general anesthesia.
Conclusion
ICPF is suitable for several indications and is a useful adjunctive tool in head and neck reconstruction. It proved to have a high survival rate, with complication rates similar to other regional flaps.

Dose volume effects of re‐irradiation for locally recurrent nasopharyngeal carcinoma

16-10-2019 – Wai‐Tong Ng, Michael CH Lee, Nelson TC Fung, Edwin CY Wong, Alice KW Cheung, James CH Chow, Kwok‐Hung Au, Darren MC Poon, Jessica WY Lai, Chi‐Leung Chiang, Horace CW Choi, Tin‐Ching Chau, Victor HF Lee, Anne WM Lee

Journal Article

Abstract
Background
This study analyzed the dose volume effects of re‐irradiation for locally recurrent nasopharyngeal carcinoma (NPC) and attempts to determine the optimal dose for the best survival.
Methods
Ninety‐one patients were studied. The local control, fatal complication, and overall survival were analyzed against the dose (in Equivalent Dose at 2 Gy/fractions) and recurrent gross tumor volume (GTV).
Results
The local control and fatal complication rate appear to increase with prescribed dose. The overall survival peaks at around 60 Gy10. Local control decreases significantly with increasing GTV (P < .001) while overall survival shows similar trend (P = .06). No correlation was observed between the fatal complication rate and GTV volume. The dose response of local control appears to be stronger for smaller tumors.
Conclusion
GTV volume plays a significant role in local control. A 60 Gy10 appears to be optimal for the best survival outcome; higher doses might be considered for small tumors.

Utility of negative‐pressure wound therapy for orocutaneous and pharyngocutaneous fistula following head and neck surgery

16-10-2019 – Yusuke Inatomi, Hideki Kadota, Sei Yoshida, Kenichi Kamizono, Ryo Shimamoto, Seita Fukushima, Kayo Miyashita, Mioko Matsuo, Ryuji Yasumatsu, Shunichiro Tanaka, Junichi Fukushima

Journal Article

Abstract
Background
Because of the difficulty of airtight sealing and risk of salivary contamination, negative‐pressure wound therapy (NPWT) has rarely been applied for postoperative fistula following head and neck surgery; thus, its utility remains unclear.
Methods
We applied NPWT in 34 patients who developed orocutaneous and pharyngocutaneous fistula after head and neck surgery. Here we retrospectively analyzed the utility of NPWT for managing those fistulas.
Results
Thirty‐two patients (94.1%) underwent NPWT as scheduled without adverse events. In 28 patients (82.4%), fistula closure was completed only by NPWT, and the mean period to fistula closure was 30.4 days. The mean period to closure did not differ significantly between fistulas with (21.7 days) and without (39.1 days) previous irradiation.
Conclusions
Airtight sealing can be maintained and postoperative fistula can be closed by NPWT with a high success rate, even after previous irradiation. NPWT is an effective and minimally invasive treatment for postoperative fistula.

Method of detection of thyroid nodules: correlation with frequency of fine‐needle aspiration and malignancy rate

15-10-2019 – Gary D. Rothberger, Melissa Cohen, Priya Sahay, Paula T. Szczepanczyk, Shahidul Islam

Journal Article

Abstract
Background
Thyroid nodules are commonly found by screening, and the clinical implications are unclear.
Methods
We retrospectively studied 460 patients who were evaluated for thyroid nodules. Medical records were queried to determine how the nodules were detected. We compared the rates of fine needle aspiration (FNA) and malignancy between nodules detected clinically, incidentally on imaging, or by screening.
Results
Nodules were detected clinically in 184 patients (40%), incidentally in 121 patients (26%), and by screening in 155 patients (34%). The rates of FNA and malignancy were lower for patients with nodules detected by screening (28% and 1%, respectively), compared to patients with clinically apparent nodules (75% and 15%) and patients with incidental nodules (69% and 8% P < .001).
Conclusion
Thyroid nodules detected via screening has a lower rate of FNA and is less likely to be diagnosed as a malignancy compared to nodules detected clinically or incidentally on imaging. Thyroid ultrasound examinations should be reserved for nodules that are clinically apparent or to evaluate nodules found incidentally on imaging.

Outcomes for elderly patients 75u2009years and older treated with curative intent radiotherapy for mucosal squamous cell carcinomas of the head and neck

08-10-2019 – Patrick J. Horsley, Lakmalie Perera, Michael J. Veness, Mark J. Stevens, Thomas N. Eade, Michael Back, Chris Brown, Dasantha T. Jayamanne

Journal Article

Abstract
Background
Elderly patients with mucosal squamous cell carcinomas of the head and neck (m
HNSCC) represent a challenging clinical dilemma.
Methods
A retrospective review was performed of patients ≥75 years, treated with curative‐intent radiotherapy for m
HNSCC in two quaternary Sydney hospitals between 2007 and 2017.
Results
Ninety‐five patients met inclusion criteria. The median age was 79 years (75‐94). Patients received radiotherapy alone (n = 24), concurrent chemoradiotherapy (n = 22), surgery and adjuvant radiotherapy (n = 45), or surgery with adjuvant chemoradiotherapy (n = 4). Median follow‐up was 4.5 years, median overall survival (OS) was 3.8 years, and 2‐year and 5‐year OS were 56% and 43%, respectively. Eastern Cooperative Oncology Group performance status of ≥2 (P < .001) was a statistically significant predictor of reduced OS. Thirty‐four patients (36%) required hospitalization, 5 (5%) did not complete radiotherapy, and 9 (9%) were feeding tube dependent beyond 6 months.
Conclusions
Appropriately selected elderly patients can achieve durable outcomes from curative intent radiotherapy with acceptable treatment toxicity.

Intraoperative and postanesthesia care unit fluid administration as risk factors for postoperative complications in patients with head and neck cancer undergoing free tissue transfer

08-10-2019 – Bryan J. Dooley, Daniella Karassawa Zanoni, Marlena R. Mcgill, Mahmoud I. Awad, Jatin P. Shah, Richard J. Wong, Clara Broad, Babak J. Mehrara, Ian Ganly, Snehal G. Patel

Journal Article

Abstract
Background
This study aims to evaluate the impact of perioperative fluid administration, defined as fluid delivered intraoperatively and in the postanesthesia care unit, on postoperative outcomes.
Methods
Medical records of 102 patients with oral cavity squamous cell carcinoma undergoing free flap reconstruction between January 2011 and December 2015 were reviewed. The primary endpoint was development of a postoperative complication according to the Clavien‐Dindo classification. Perioperative factors recorded were Washington University Head and Neck Comorbidity Index, operating time, vasopressor use, blood loss, intraoperative fluid, and perioperative fluid.
Results
Greater perioperative fluid administration was independently associated with surgical complications, flap complications, overall incidence of any complication, and increased length of stay. Greater intraoperative fluid administration was independently associated with higher rates of surgical complications. Intraoperative delivery of vasopressors was not associated with flap or surgical complications.
Conclusion
Receiving less perioperative fluid was associated with fewer complications and decreased length of stay.

Isthmusectomy in selected patients with well‐differentiated thyroid carcinoma

07-10-2019 – Hakyoung Park, Victoria Harries, Marlena R. McGill, Ian Ganly, Jatin P. Shah

Journal Article

Abstract
Background
Isthmusectomy in the treatment of well‐differentiated thyroid carcinoma (WDTC) is controversial. In this study, we analyze the outcomes of WDTC managed by isthmusectomy alone.
Methods
Forty‐three patients treated with isthmusectomy alone were identified from an institutional database of 6259 surgically treated patients with WDTC. Patient and tumor characteristics were analyzed. Disease‐specific survival (DSS) and recurrence‐free survival (RFS) were calculated using the Kaplan‐Meier method.
Results
The p
T classification was T1 for 41 and T2 for two patients. All were clinical N0, but 10 pts were p
N1a. Using the American Thyroid Association risk stratification system, 9 patients were low‐risk and 22 were intermediate‐risk. One patient developed local recurrence, and two developed regional lymph node metastases; the 5‐ and 10‐year DSS was 100.0%. The 5‐ and 10‐year RFS was 93.1%.
Conclusions
Isthmusectomy alone is an acceptable procedure in selected patients with low‐ and intermediate‐risk WDTC limited to the isthmus.

Malignant development in patients with oral potentially malignant disorders detected through nationwide screening: Outcomes of 5‐year follow‐up at a single hospital

07-10-2019 – Wei‐Fan Chiang, Shyun‐Yeu Liu, Jen‐Fen Lin, Sheng‐Fu Chiu, Shin‐Bin Gou, Chang‐Ta Chiou, Chi‐Hua Chang

Journal Article

Abstract
Background
Although survival rate and quality of life are improved if patients with oral carcinoma can be detected early, however, such lesions are usually asymptomatic; therefore, it is hard to raise awareness. Screening has proved to be cost‐effective for early detection.
Methods
Sixty‐two patients with oral carcinomas and 555 patients with oral potentially malignant disorders (OPMDs) who were detected through screening were examined the relationship between clinicopathological features and follow‐up outcomes.
Results
The 5‐year cumulative cancer‐free interval rate was 94.1%, and the annual malignant transformation rate was 1.16%. The rate of interval carcinoma development from Candida hyperplasia, oral submucous fibrosis, homogeneous leukoplakia, non‐homogenous leukoplakia, and verrucous hyperplasia, was 13.6%, 5.7%, 4.6%, 12.1%, and 21.3%, respectively. Significant independent risk factors for interval carcinoma development were heavy betel quid chewing, verrucous hyperplasia, and surgery refusal.
Conclusions
Well‐designed risk assessment, treatment, and surveillance program could lead to earlier cancer detection and thereby reduce mortality and morbidity.