In this issue of EJSO, Gu and colleagues (Beijing, China) propose a novel classification of carotid body tumors (CBTs) designated PUMCH (Peking Union Medical College Hospital) [ [1] Gu G. Wu X. Ji L. Liu Z. Li F. Liu B. et al. Proposed modification of the Shamblin's classification of carotid body tumors: a single-center experience of 116 tumors. Eur J Surg Oncol. 2021 Mar; ([This issue]) Abstract Full Text Full Text PDF Scopus (2) Google Scholar ]. This combines vertical and horizontal tumor extent into a sophisticated model, which seemingly outperforms the traditional but inadequate Shamblins' classification. Corroboration of these data promises potential to optimize surgical risk stratification and preoperative preparation of surgeons and patients. Proposed modification to the Shamblin's classification of carotid body tumors: A single-center retrospective experience of 116 tumorsEuropean Journal of Surgical OncologyVol. 47Issue 8PreviewCarotid body tumors (CBTs) are rare head and neck neoplasms, we aimed to propose a modification to the Shamblin's classification of CBTs. Full-Text PDF Assessing the complexity of a carotid body tumor resectionEuropean Journal of Surgical OncologyVol. 47Issue 8PreviewSurgical resection of paragangliomas of the neck and especially Carotid Body Tumors (CBT) can be challenging. The tumors are fixated in the arterial wall of the carotid artery and cranial nerves as the vagal nerve and hypoglossal nerve are adjacent to and might even be fixated in the tumor. Since the majority of CBT are benign and slow growing tumors, a good assessment of the risk of complications related to resection of the tumor is of the utmost importance. Only by comparison of the risks and benefits of removal of the tumor can a proper tradeoff be made between wait and scan policy and surgery [1]. Full-Text PDF

In this issue of EJSO, Zhou and Qin (China) [ [1] Zhou B and Qin J. High-risk factors for lymph node metastasis in contralateral central compartment in unilateral papillary thyroid carcinoma（cT1N0). European Journal of Surgical Oncology. [This issue]. Google Scholar ] and Back et al. (South Korea) [ [2] Back K, Choe J-H, Kim JS, Kim J-H. Contralateral central lymph node metastasis in papillary thyroid carcinoma with ipsilateral lateral neck metastasis. European Journal of Surgical Oncology. [This issue]. Google Scholar ] discuss a novel angle to the debate of elective central neck dissection for papillary thyroid carcinoma (PTC). Both studies explore the viability of complication reduction through unilateral central neck dissection in patients with PTC by analyzing prognostic factors that may guide a selective approach. Occult contralateral central neck metastasis in papillary thyroid carcinoma with preoperatively documented ipsilateral lateral neck metastasisEuropean Journal of Surgical OncologyVol. 47Issue 6PreviewThis study was conducted to evaluate risk factors and long-term prognosis of contralateral central neck metastasis (CCNM) in papillary thyroid cancer (PTC) patients with ipsilateral lateral neck metastasis. We present clinical evidence to aid in surgical decision-making regarding the extent of central neck dissection (CND), focusing on separation between ipsilateral and contralateral sides. Full-Text PDF High-risk factors for lymph node metastasis in contralateral central compartment in unilateral papillary thyroid carcinoma（cT1N0）European Journal of Surgical OncologyVol. 47Issue 4PreviewThe incidence of papillary thyroid carcinoma (PTC) increases yearly. Central lymph node metastasis (CLNM) is common in PTC. Many studies have addressed ipsilateral CLNM; however, few studies have evaluated contralateral CLNM. The purpose of this study is to investigate the high-risk factors of lymph node metastasis in the contralateral central compartment of cT1 stage in PTC. Full-Text PDF

The vast majority of differentiated thyroid cancers (DTC) are characterized by an innocuous nature, excellent patient survival, and limited treatment requirement. However, a significant proportion of affected patients is prone to receiving overtreatment, due to undertreatment concerns associated with the difficulty to differentiate them from a small minority affected by aggressive DTC. Identification of prognostic factors and development of staging systems has helped to reduce the proportion of overtreatment in DTC. However, the absolute number of overtreated patients continues to increase, as a result of an on-going incidence surge in early DTC associated with the increased application and sensitivity of modern diagnostic tools. In the present paper, we describe how DTC treatment can be optimized by thoughtful evidence-based balancing of oncologic safety against treatment associated morbidity.

The vast majority of differentiated thyroid cancers (DTC) are characterized by an innocuous nature, excellent patient survival, and limited treatment requirement. However, a significant proportion of affected patients is prone to receiving overtreatment, due to undertreatment concerns associated with the difficulty to differentiate them from a small minority affected by aggressive DTC. Identification of prognostic factors and development of staging systems has helped to reduce the proportion of overtreatment in DTC. However, the absolute number of overtreated patients continues to increase, as a result of an on-going incidence surge in early DTC associated with the increased application and sensitivity of modern diagnostic tools. In the present paper, we describe how DTC treatment can be optimized by thoughtful evidence-based balancing of oncologic safety against treatment associated morbidity.

Mutations in Fanconi Anemia or Homologous Recombination (FA/HR) genes can cause DNA repair defects and could therefore impact cancer treatment response and patient outcome. Their functional impact and clinical relevance in head and neck squamous cell carcinoma (HNSCC) is unknown. We therefore questioned whether functional FA/HR defects occurred in HNSCC and whether they are associated with FA/HR variants. We assayed a panel of 29 patient-derived HNSCC cell lines and found that a considerable fraction is hypersensitive to the crosslinker Mitomycin C and PARP inhibitors, a functional measure of FA/HR defects. DNA sequencing showed that these hypersensitivities are associated with the presence of bi-allelic rare germline and somatic FA/HR gene variants. We next questioned whether such variants are associated with prognosis and treatment response in HNSCC patients. DNA sequencing of 77 advanced stage HNSCC tumors revealed a 19% incidence of such variants. Importantly, these variants were associated with a poor prognosis (p = 0.027; HR = 2.6, 1.1–6.0) but favorable response to high cumulative cisplatin dose. We show how an integrated in vitro functional repair and genomic analysis can improve the prognostic value of genetic biomarkers. We conclude that repair defects are marked and frequent in HNSCC and are associated with clinical outcome.

Differentiated thyroid cancer is characteristically associated with an innocuous clinical course, but a minority of cases may manifest surprisingly aggressive behaviour. Such aggressive DTC are directly responsible for the majority of thyroid cancer related deaths. Moreover, they contribute indirectly to increased DTC-related morbidity, because our inability to differentiate these tumours from innocuous DTC at an early stage fuels a significant degree of DTC overtreatment around the globe. In the present paper we describe how improved understanding of the clinicopathological thyroid tumour progression model and optimization of clinical staging systems continues to improve our ability to diagnose and treat aggressive DTC. Early recognition of aggressive DTC allows instillation of an aggressive management strategy which is based upon surgical-oncologic completeness, and minimization of treatment-related sequelae through continued development of reconstructive options and focussed delivery of adjuvant treatments.

ABSTRACT High-risk head and neck squamous cell carcinoma (HNSCC) includes an ill-defined collection of tumors that share an extremely poor outcome after seemingly appropriate multimodality treatment. Accumulating evidence suggests that extracapsular nodal spread and suboptimal surgical margins may be markers of high-risk HNSCC, but their utility is limited by ambiguous pathological criteria and unsatisfactory establishment of independent prognostic value. Inaccurate definition of high-risk HNSCC continues to obscure the scientific basis of treatment intensification protocols that have been proposed for high-risk HNSCC. Recent studies propose a more objective definition of clinically relevant extracapsular nodal spread (ECS) and surgical margins, which may contribute to improved staging and treatment selection. How to cite this article Wreesmann VB. Role of Extracapsular Nodal Spread and Surgical Margin Status in defining High-risk Head and Neck Squamous Cell Carcinoma and its Treatment Intensity. Int J Head Neck Surg 2017;8(2):76-83.

Background: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. Methods: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. Results: Using age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. Conclusions: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.

Age 45 years is used as a cutoff in the staging of well-differentiated thyroid cancer (WDTC) as it represents the median age of most datasets. The aim of this study was to determine a statistically optimized age threshold using a large dataset of patients treated at a comprehensive cancer center.Overall, 1807 patients with a median follow-up of 109 months were included in the study. Recursive partitioning was used to determine which American Joint Committee on Cancer (AJCC) variables were most predictive of disease-specific death, and whether a different cutoff for age would be found. From the resulting tree, a new age cutoff was picked and patients were restaged using this new cutoff.The 10-year disease-specific survival (DSS) by Union for International Cancer Control (AJCC/UICC) stage was 99.6, 100, 96, and 81 % for stages I-IV, respectively. Using recursive partitioning, the presence of distant metastasis was the most powerful predictor of DSS. For M0 patients, age was the next most powerful predictor, with a cutoff of 56 years. For M1 patients, a cutoff at 54 years was most predictive. Having reviewed the analysis, age 55 years was selected as a more robust age cutoff than 45 years. The 10-year DSS by new stage (using age 55 years as the cutoff) was 99.2, 98, 100, and 74 % for stages I-IV, respectively.A change in age cutoff in the AJCC/UICC staging for WDTC to 55 years would improve the accuracy of the system and appropriately prevent low-risk patients being overstaged and overtreated.

ABSTRACT Background An objective definition of clinically relevant extracapsular nodal spread (ECS) in head and neck squamous cell carcinoma (SCC) is unavailable. Methods Pathologic review of 245 pathologically positive oral cavity SCC neck dissection specimens was performed. The presence/absence of ECS, its extent (in millimeters), and multiple nodal and primary tumor risk factors were related to disease‐specific survival (DSS) at a follow‐up of 73 months. Results ECS was detected in 109 patients (44%). DSS was significantly better for patients without ECS than patients with ECS. Time‐dependent receiver operator curve (ROC) analysis identified a prognostic cutoff for ECS extent at 1.7 mm. In multivariate analyses, DSS was significantly lower for patients with major ECS compared with patients with minor ECS, but not significantly different between patients with minor ECS and patients without ECS. Conclusion ECS is clinically relevant in oral cavity SCC when it has extended more than 1.7 mm beyond the nodal capsule. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E1192–E1199, 2016

BACKGROUNDVascular invasion (VI) is an important predictor of distant metastasis and possible radioactive iodine (RAI) benefit in follicular, Hürthle cell, and poorly differentiated thyroid carcinomas, but its role in well-differentiated papillary thyroid cancer (WDTC) remains unclear.METHODSArchived pathological material of all differentiated thyroid carcinoma patients undergoing primary surgical treatment at Memorial Sloan-Kettering Cancer Center between 1986 and 2003 was reviewed by two dedicated thyroid pathologists. Only WDTCs were included in the present study. Standard statistical methods were used to assess the relationship between VI and outcomes of interest, including 10-year disease-specific survival (DSS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS).RESULTSVI was present in 47 of 698 WDTC (6.7%). VI was significantly associated with tumor size >4.0 cm, extrathyroidal extension, distant metastasis, and RAI treatment. On univariate analysis, VI was predictive of decreased 10-year DRFS, but not DSS or RRFS. On multivariate analysis, VI was not an independent predictor of DRFS. Univariate survival analysis of 422 RAI-naïve WDTC showed that both size >4 cm and VI were predictors of outcome, but only size remained independently predictive on multivariate analysis.CONCLUSIONThe presence of VI is not an independent predictor of outcome in WDTC.

Head and neck squamous cell carcinoma (HNSCC) mainly affects patients between the fifth and seventh decade of life but is increasingly seen in young patients (<40 years old). Controversy exists in the literature regarding outcomes for younger patients with HNSCC.

Epidemiologic analyses have shown disproportional increases of head and neck squamous cell carcinoma (HNSCC) incidence in a younger age group (younger than 45 years old), compared to patients above 45 years old. Although this group is small (5%), it includes a significant subset of the HNSCC patient population, and is characterized by a distinct clinical and etiological phenotype. HNSCC in young patients often presents without significant exposure to alcohol and tobacco and primarily affects the oropharynx and oral cavity. Exposure to human papilloma virus (HPV) has been identified as a major contributor to the pathogenesis of oropharyngeal carcinomas, and explains part of the observed incidence variation. Specific hereditary influences, including genetic predispositions accounting for an increased mutagen sensibility and inherited syndromes like Fanconi Anemia and Bloom's syndrome, have been identified as causative factors in a subgroup of young-onset HNSCC, but their cumulative influence remains at present likely underestimated. Circumstantial evidence suggests that young-onset HNSCC patients have a clinically different phenotype compared to older patients, however, the true impact of young age on HNSCC clinical behavior will remain difficult to determine unless multi-institutional databases will be combined. The rising incidence of young–onset HNSCC mandates intensification of research endeavors into its etiology, clinical phenotype and optimal management.

Despite successful efforts to control tobacco and alcohol consumption in the western world, several developed countries report rising oropharyngeal squamous cell carcinoma (OPSCC) incidence figures, specifically in young individuals. Similar to anogenital cancers, a significant proportion of OPSCC (up to 60%) is caused by sexually acquired HPV infection and the rise in OPSCC has been attributed to changing sexual behaviours in the Western World. Accordingly, patients with HPV-positive OPSCC report divergent sexual histories and absence of classical risk factors as tobacco and alcohol exposure compared to patients with HPV-negative OPSCC. The profile of HPV-positive OPSCC differs from HPV-negative OPSCC in several other significant aspects, including a unique molecular biologic tumor characteristics and improved clinical behaviour. Thus, a further increase in HPV-positive OPSCC will impact significantly upon clinical management of OPSCC, unless it is halted by adequate preventive measures aimed at reduction of HPV-associated disease. HPV vaccination has been recently offered to young females in an attempt to reduce HPV-induced cervical cancer and may ultimately result in a decline of OPSCC incidence as well. Until then, close collaboration between otolaryngologists/head and neck surgeons and anogenital/genitourinary specialists is warranted to optimize clinical management of HPV-induced malignancy and improve detection of second primary tumor development.

Background. Tracheoesophageal fistula (TEF) is a rare but serious complication associated with high mortality rates. Traditional management of TEF includes primary closure with or without interposition of regional tissue flaps but is associated with a significant recurrence risk, especially in case of larger fistulas. Application of microvascular free flap reconstruction is an emerging alternative in the surgical management of large TEFs, but may be limited by issues of flap bulkiness and requirement for neoepithelialization across the large inner flap surface.Methods and Results. Here, we report prefabrication of a bilaminar radial forearm free flap to successfully close a large recurrent TEF that occurred years after tracheoesophageal puncture-based voice rehabilitation in a laryngectomized patient.Conclusion. The bilaminar radial forearm free flap may prove to be an important adjunct to the closure of large TEFs. (c) 2008 Wiley Periodicals, Inc. Head Neck 31: 838-842, 2009

Thyroid cancer constitutes a progressive continuum of disease ranging from indolent well-differentiated carcinomas to aggressive poorly differentiated carcinomas and universally fatal anaplastic carcinomas. The wide divergence in clinical behavior is poorly predicted for by current clinicopathological factors. Moreover, therapeutic armentarium against aggressive thyroid cancers remains limited. Recent studies have identified a range of molecular alterations in thyroid cancers. Clinical implications of the molecular alterations include their utility in diagnostic evaluation, staging and targeted treatment. Continued molecular analysis of thyroid cancers promises to increase our understanding of its biologic behavior and is expected to have further impact on its clinical management.

Background/Aims: Much of our understanding of human cancer has come from studies of the hereditary cancer predisposition syndromes. Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA crosslinking agents, progressive bone marrow failure, and cancer predisposition to solid malignancies, especially head and neck squamous cell carcinoma (HNSCC). Since FA pathway-deficient cells are hypersensitive to DNA crosslinking chemotherapy agents, the presence of somatic FA gene inactivation in sporadic cancers may be of clinical interest. This study sought to determine the frequency of FA gene downregulation in sporadic HNSCC. Methods: The expression of the FA genes FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCJ, FANCL and FANCM in 11 HNSCC cell lines and 49 tongue carcinoma samples was studied with quantitative real-time polymerase chain reaction. Results: Downregulation of at least one FA gene was observed in 3 of 11 HNSCC cell lines and 66% of tongue carcinoma samples. FANCB, FANCF, FANCJ and FANCM were most commonly affected by downregulation, whereas downregulation of FANCA, FANCE and FANCD2 was rare. Conclusion: Our data suggest that downregulation of FA genes is common in sporadic HNSCC. The clinical implications of this finding merit further study.