Airway management during transoral robotic surgery for head and neck cancers: a French GETTEC group survey.

PURPOSE: The aim of the survey was to define the indications for preventive tracheostomy in transoral robotic surgery (TORS) for head and neck cancers. METHODS: From October 2019 to January 2020, an online questionnaire was e-mailed to French surgical ENT teams with considerable experience of the TORS procedure (Gettec group). A descriptive analysis of the answers was performed. RESULTS: Eighteen French surgical teams answered the questionnaire. For 77.8% of the surgical teams, a past history of radiotherapy with residual edema was an indication for prophylactic tracheostomy, and for 88.9%, > 75 mg of antiplatelet medication or anticoagulation treatment was an indication. CONCLUSION: Early preventive tracheostomy during TORS can protect airway from uncommon but potentially life-threatening complications, such as transoral hemorrhage or airway edema. We recommend it in high-risk situations, such as a past history of radiotherapy or antiplatelet therapy associated with large resections. Further studies are needed to establish evidence-based recommendations.

Microscopic Origin of Nonlocal Rheology in Dense Granular Materials.

We study the microscopic origin of nonlocality in dense granular media. Discrete element simulations reveal that macroscopic shear results from a balance between microscopic elementary rearrangements occurring in opposite directions. The effective macroscopic fluidity of the material is controlled by these velocity fluctuations, which are responsible for nonlocal effects in quasistatic regions. We define a new micromechanically based unified constitutive law describing both quasistatic and inertial regimes, valid for different system configurations.

Fortuitous discovery of non-fluorocholine-fixing papillary carcinoma of vesicular variant of the thyroid.

PURPOSE: Characterization of thyroid nodules is crucial to propose surgical intervention for histological verification. Cervical ultrasound potentially combined with fine needle aspiration is recommended, and fluorocholine positron emission tomography (FCH-PET), commonly used in prostatic cancers, has been evaluated in the diagnosis of thyroid cancers in recent publications. METHODS: We present two cases of patients with multinodular thyroid and primary hyperparathyroidism. The preoperative assessment consisted of an ultrasound, a MIBI scintigraphy and an FCH-PET in favor of a parathyroid adenoma. RESULTS: The imaging examinations pointed to a diagnosis of a parathyroid adenoma. In both cases, papillary thyroid carcinoma, missed by FCH-PET, was discovered incidentally at a distance from the parathyroid adenoma during the surgical procedure. CONCLUSIONS: These are the first descriptions of thyroid papillary carcinoma without preoperative FCH-PET identification. These clinical cases are contrary to recent publications showing a benefit of this examination in the diagnosis of thyroid cancers.

Oropharyngeal cancer: First relapse description and prognostic factor of salvage treatment according to p16 status, a GETTEC multicentric study.

INTRODUCTION: Although Human Papilloma Virus (HPV)-driven oropharyngeal cancer (OPC) prognosis is significantly better than that of other head and neck cancers, up to 25% of cases will recur within 5 years. Data on the pattern of disease recurrence and efficiency of salvage treatment are still sparse. MATERIAL AND METHOD: Observational study of all recurrent OPCs diagnosed, following a curative intent treatment, in seven French centers from 2009 to 2014. p16 Immunohistochemistry was used to determine HPV status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival was examined using Kaplan-Meier and multivariate Cox regression modeling. RESULTS: 350 recurrent OPC patients (246 p16-negative and 104 p16-positive patients). The site of recurrence was more frequently locoregional for p16-negative patients (65.4% versus 52.9% in p16-positive patients) and metastatic for p16-positive patients (47.1% versus 34.6% in p16-patients, p = 0.03). Time from diagnosis to recurrence did not differ between p16-positive and p16-negative patients (12 and 9.6 months, respectively, p-value = 0.2), as the main site of distant metastasis (all p-values ≥0.10). Overall and relapse-free survival following the first recurrence did not differ according to p16 status (p-values from log-rank 0.30 and 0.40, respectively). In multivariate analysis, prognosis factors for overall survival in p16-negative patients were distant metastasis (HR 2.11, 95% CI 1.30-3.43) and concurrent local and regional recurrences (HR 2.20, 95% CI 1.24-3.88). CONCLUSION: With the exception of the initial site of recurrence, the pattern of disease relapse and the efficiency of salvage treatment are not different between p16-positive and negative OPCs.

Upfront surgery or definitive radiotherapy for p16+ oropharyngeal cancer. A GETTEC multicentric study.

BACKGROUND: The aim of this study was to assess the impact of the initial therapeutic strategy on oncologic outcomes in patients with HPV-positive OPSCC. METHODS: All p16-positive OPSCCs treated from 2009 to 2014 in 7 centers were retrospectively included and classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Univariate, multivariate propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). RESULTS: 382 patients were included (surgical group: 144; non-surgical group: 238). Five-year OS, DSS and RFS were 89.2, 96.8 and 83.9% in the surgical group and 84.2, 87.1 and 70.4% in the non-surgical group, respectively. These differences were statistically significant for DSS and RFS after multivariate analysis, but only for RFS after propensity score matching analysis. CONCLUSION: In p16+ OPSCC patients, upfront surgery results in higher RFS than definitive radiotherapy ± chemotherapy but does not impact OS.

Metachronous second primary neoplasia in oropharyngeal cancer patients: Impact of tumor HPV status. A GETTEC multicentric study.

INTRODUCTION: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival. MATERIAL AND METHODS: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis. RESULTS: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group. CONCLUSION: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.

Upfront surgery or definitive radiotherapy for patients with p16-negative oropharyngeal squamous cell carcinoma. A GETTEC multicentric study.

INTRODUCTION: Therapeutic management of oropharyngeal squamous cell carcinomas (OPSCC) is still debated. Since the role of HPV was demonstrated, few studies have focused on HPV-negative OPSCC. The aim of our study was to assess the impact of therapeutic strategy (surgical vs. non-surgical) on oncologic outcomes in patients with HPV-negative OPSCC. MATERIAL AND METHOD: All p16-negative OPSCCs treated from 2009 to 2014 in 7 tertiary-care centers were included in this retrospective study and were classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Patients not eligible for surgery (unresectable tumor, poor general-health status) were excluded. Univariate, multivariate and propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). RESULTS: Four hundred seventy-four (474) patients were included in the study (surgical group: 196; non-surgical group: 278). Five-year OS, DSS and RFS were 76.5, 81.3 and 61.3%, respectively, in the surgical group and 49.9, 61.8 and 43.4%, respectively, in the non-surgical group. The favorable impact of primary surgical treatment on oncologic outcomes was statistically significant after multivariate analysis. This effect was more marked for locally-advanced than for early-stage tumors. Propensity score matching analysis confirmed the prognostic impact of primary surgical treatment for RFS. CONCLUSION: Therapeutic strategy is an independent prognostic factor in patients with p16-negative OPSCC and primary surgical treatment is associated with improved OS, DSS and RFS. These results suggest that surgical strategy is a reliable option for advanced stage OPSCC.

Synchronous primary neoplasia in patients with oropharyngeal cancer: Impact of tumor HPV status. A GETTEC multicentric study.

INTRODUCTION: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk of synchronous primary neoplasia (SPN) which could impact their management. The aims of this study were to evaluate the risk and distribution of SPN in OPSCC patients according to their HPV (p16) status, the predictive factors of SPN and the impact of SPN on therapeutic strategy and oncologic outcomes. MATERIAL AND METHODS: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. Univariate analyses were conducted using Chi-2 and Fisher exact tests. For multivariate analyses, all variables associated with a p ≤ 0.10 in univariate analysis were included in logistic regression models. RESULTS: Among the 1291 patients included in this study, 75 (5.8%) displayed a SPN which was preferentially located in the upper aerodigestive tract, lung and esophagus. Comorbidity level (p = 0.03), alcohol (p = 0.005) and tobacco (p = 0.01) consumptions, and p16 tumor status (p < 0.0001) were significant predictors of SPN. In multivariate analysis, p16+ status was significantly associated with a lower risk of SPN (OR = 0.251, IC95% [0.133;0.474]). Patients with a SPN were more frequently referred for non-curative treatment (p = 0.02). In patients treated with curative intent, there was no impact of SPN on the therapeutic strategy (surgical vs. non-surgical treatment). We observed no overall survival differences between patients with or without SPN. CONCLUSION: P16 tumor status is the main predictive factor of SPN in OPSCC patients. This study provides crucial results which should help adapt the initial work-up and the global management of OPSCC patients.

Reference gene selection for head and neck squamous cell carcinoma gene expression studies.

BACKGROUND: It is no longer adequate to choose reference genes blindly. We present the first study that defines the suitability of 12 reference genes commonly used in cancer studies (ACT, ALAS, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPL27, RPS29, SHAD and TBP) for the normalization of quantitative expression data in the field of head and neck squamous cell carcinoma (HNSCC). RESULTS: Raw expression levels were measured by RT-qPCR in HNSCC and normal matched mucosa of 46 patients. We analyzed the expression stability using geNorm and NormFinder and compared the expression levels between subgroups. In HNSCC and/or normal mucosa, the four best normalization genes were ALAS, GAPDH, RPS18 and SHAD and the most stable combination of two genes was GAPDH-SHAD. We recommend using KALPHA-TBP for the study of T1T2 tumors, RPL27-SHAD for T3T4 tumors, KALPHA-SHAD for N0 tumors, and ALAS-TBP for N+ tumors. ACT, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPS29, SHAD and TBP were slightly misregulated (<1.7-fold) between tumor and normal mucosa but can be used for normalization, depending on the resolution required for the assay. CONCLUSION: In the field of HNSCC, this study will guide researchers in selecting the most appropriate reference genes from among 12 potentially suitable reference genes, depending on the specific setting of their experiments.

Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse.

BACKGROUND: Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse. METHODS: For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases. RESULTS: Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%. CONCLUSION: IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva.

Endoscopic treatment of sinonasal papilloma: a 12 year review.

CONCLUSION: Endoscopic surgical management is recommended as a viable treatment option for sinonasal papilloma, with comparable results to those treated by an external approach. An external approach is still indicated in cases where the papilloma is not accessible endoscopically, or where there is extrasinus invasion. Long-term follow-up is essential for recurrence detection. OBJECTIVES: The goal of this study was to highlight our experience with endoscopic surgery for the management of sinonasal papilloma. PATIENTS AND METHODS: A retrospective study of all patients who underwent endoscopic surgery for the treatment of sinonasal papilloma over a 12 year period at the Gui de Chauliac Hospital, Montpellier, France. RESULTS: A total of 55 patients were included in this study; 32 patients (58%) were treated exclusively by an endoscopic approach and 23 (42%) were treated by a combined approach. Minimal follow-up was 3 years. The overall recurrence rate was 7%. All recurrences occurred at the initial site and the average delay between surgery and recurrence was 30 months (14 months to 4 years).

Parathyroid Hormone Assays following Total Thyroidectomy: Is There a Predictive Value?

OBJECTIVES: Parathyroid hormone (PTH) is a risk marker for hypoparathyroidism (hypoPTH). This study aimed to determine the predictive values of early PTH assays carried out at the moment of skin closure (PTH SC), to establish a treatment algorithm, identifying two threshold values. We assessed the reproducibility of this approach with two different immunoassay kits (hypoPTH) after total thyroidectomy, but its practical application is not consensual. STUDY DESIGN: We conducted a prospective descriptive study, including all patients who underwent a total thyroidectomy between March 2012 and November 2013. Postoperative PTH SC levels, corrected calcium on postoperative days, and occurrence of hypoPTH symptoms were collected. RESULTS: Of 257 patients, the rate of hypoPTH was 20%. Threshold values to obtain a 100% positive predictive value to identify patients for whom hypoPTH was absolutely certain were: PTH SC <7 ng/L for the Roche kit and PTH SC <4 ng/L for the Beckman-Coulter kit. Threshold values to obtain a 100% negative predictive value to identify patients for whom the absence of hypoPTH was absolutely certain were: PTH SC ≥19 ng/L for the Roche kit and PTH SC ≥9 ng/L the Beckman-Coulter kit. CONCLUSIONS: A single serum PTH sampled at skin closure is a reliable test to predict hypoPTH after a total thyroidectomy. The use of a threshold based on a 100% negative predictive value enables patients with no risk of hypoPTH to be safely discharged within the first 24 h postoperatively without unnecessary calcium and vitamin treatment. This medication can be given promptly to patients at risk of hypoPTH to limit the occurrence of hypocalcaemia.

Experimental study of the solid-liquid interface in a yield-stress fluid flow upstream of a step.

We present an experimental study investigating the transition zone between a liquid-like unyielded region and a solid-like yielded region in a yield-stress fluid. The configuration consists of a rectangular closed-channel flow disturbed by the presence of a step. Upstream of the step, a solid-liquid interface between a dead zone and a flow zone appears. In this study, we use a model fluid, namely polymer micro-gel Carbopol, which exhibits Herschel-Bulkley viscoplastic rheology. Exploiting the fluid transparency, the flow is monitored by particle image velocimetry using an internal visualization technique. The main outcome of this study is to show that, except in a thin transition layer close to the solid-liquid interface, the flow behaves as an apparent Poiseuille flow with an apparent slip condition at the base. The slip frontier is found to be almost independent of the flow rate while the corresponding slip velocity increases with the flow rate.

Transoral robotic surgery for the treatment of T1-T2 carcinoma of the larynx: preliminary study.

OBJECTIVES/HYPOTHESIS: To determine the feasibility and the preliminary oncological results of transoral robotic surgery (TORS) for the treatment of early stage laryngeal tumors. STUDY DESIGN: Retrospective single center study. METHODS: We reviewed the medical records of 23 patients who underwent TORS for the treatment of T1 or T2 laryngeal squamous cell carcinoma between August 2009 and March 2012. RESULTS: Laryngeal tumors were involving the glottis (13 cases) and the supraglottis (10 cases). They were classified T1 N0 in 16 cases, T2 N0 in four cases, and T2 N+ in three cases. The median TORS operative time was 60 minutes (ranging from 30 to 118 minutes). The median hospitalization time was 7.5 days. Histopathological examination of the resected tumors confirmed 14 cases in which the margins were clear, four cases in which the surgical margins were close (less than 1 mm), one case in which the margins were microscopically positive, and in four cases margins status were not able to be recorded. A tracheostomy was carried out for three patients, and 11 patients got a nasogastric feeding tube postoperatively. The local recurrence rate was 8.7% (2/ 23 cases), and in both cases the recurrence occurred in the anterior commissure area only. The overall larynx preservation rate was 95,7% (22/ 23 cases). CONCLUSION: In this preliminary study, we demonstrated that laryngeal TORS is feasible and may result in oncological results comparable with other treatment strategies, including laser CO2 surgery. This innovative approach needs to be evaluated through randomized multi-institutional trial. LEVEL OF EVIDENCE: 4.

Transaxillary robotic thyroid surgery: a preliminary European experience.

BACKGROUND: Robot-assisted endoscopic transaxillary thyroidectomy is an emerging surgical technique that needs to be evaluated in European patients. We evaluate the feasibility and preliminary results of our experience of this technique in a cohort of patients from within a single European university hospital (Nîmes, France). METHODS: We performed a retrospective review of the first 23 patients, treated consecutively between September 2010 and June 2012. RESULTS: Nine patients underwent total thyroidectomy and 14 patients lobectomies. All procedures were completed successfully with a mean total operative time of 134 min. We observed a single case of internal jugular vein injury during the console time. No instances of persistent complications were observed; however, minor postoperative events occurred in 5 patients. Pathological diagnoses included benign follicular adenoma in 18 patients, benign adenoma with lymphoid thyroiditis in 1 patient, and benign adenoma with Graves' disease in 4 patients. CONCLUSIONS: Robotic thyroid surgery is feasible in European patients and can be safely performed on selected patients. This technique has infrequent minor complications and provides a high level of satisfaction.

Robotic thyroid surgery: our experience with the infraclavicular approach.

BACKGROUND: Robot-assisted endoscopic transaxillary thyroidectomy is an emerging surgical technique. Despite promising results it presents some limitations and remains controversial in terms of usefulness and validity. We developed an alternative robotic technique using a gasless infraclavicular approach. METHODS: We tested this approach using cadaveric dissection, then we performed the technique on a series of 21 patients from October 2009 to July 2010. RESULTS: Sixteen patients underwent total thyroidectomy and 5 patients underwent lobectomies. Mean total operative time was 197 minutes. We observed postoperative complications in 4 patients. Pathologic diagnoses included: benign follicular adenoma (19 patients) and single papillary carcinoma <1 cm in diameter pT1a (2 patients). CONCLUSIONS: The infraclavicular approach for robotic thyroidectomy is feasible, but is not safe enough to be recommended, based on our experience and on the technical difficulties encountered. The use of 2 robotic arms instead of 3 is a major limitation for this technique.

Quasistatic to inertial transition in granular materials and the role of fluctuations.

On the basis of discrete element numerical simulations of a Couette cell, we revisit the rheology of granular materials in the quasistatic and inertial regimes, and discuss the origin of the transition between these two regimes. We show that quasistatic zones are the seat of a creep process whose rate is directly related to the existence and magnitude of velocity fluctuations. The mechanical behavior in the quasistatic regime is characterized by a three-variable constitutive law relating the friction coefficient (normalized stress), the inertial number (normalized shear rate), and the normalized velocity fluctuations. Importantly, this constitutive law appears to remain also valid in the inertial regime, where it can account for the one-to-one relationship observed between the friction coefficient and the inertial number. The abrupt transition between the quasistatic and inertial regimes is then related to the mode of production of the fluctuations within the material, from nonlocal and artificially sustained by the boundary conditions in the quasistatic regime, to purely local and self-sustained in the inertial regime. This quasistatic-to-inertial transition occurs at a critical inertial number or, equivalently, at a critical level of fluctuations.

The use of preoperative routine measurement of basal serum thyrocalcitonin in candidates for thyroidectomy due to nodular thyroid disorders: results from 2733 consecutive patients.

CONTEXT: The preoperative routine measurement of basal serum thyrocalcitonin (CT) in candidates for thyroidectomy due to thyroid nodules is currently a subject of debate. OBJECTIVE: The objective of this study was to evaluate the role of systematic basal serum CT measurement in improving the diagnosis and surgical treatment of medullary thyroid carcinoma (MTC) in patients undergoing thyroidectomy for nodular thyroid disorders, regardless of preoperative CT levels. DESIGN: We determined basal serum CT levels in 2733 consecutive patients before thyroid surgery and performed a pentagastrin test in patients with hypercalcitoninemia. We correlated basal and stimulated CT levels with intraoperative and definitive histopathological findings, and we analyzed the impact of these results on surgical procedures. RESULTS: Twelve MTCs were found among the 43 patients with basal serum CT level of 10 pg/ml or greater. Two MTCs were present among the 2690 patients with normal CT levels. MTC was always present in patients with a basal CT of 60 pg/ml or greater. For CT levels ranging from 10 to 59 pg/ml, MTC was diagnosed in 11% of patients. When preoperative hypercalcitoninemia was present, total thyroidectomy associated with comprehensive intraoperative histopathological analysis allowed the intraoperative diagnosis of five latent, subclinical MTCs. The pentagastrin test gave no additional diagnostic information for the management of patients with elevated preoperative basal serum CT level. CONCLUSION: Routine measurement of CT in the preoperative work-up of nodular thyroid disorders is useful. This procedure improves intraoperative diagnosis of MTC and enables adapted initial surgery, the most determinant factor of treatment success.

Gene expression profiling in head and neck squamous cell carcinoma: Clinical perspectives.

BACKGROUND: To date, more than 60 gene expression profiling (GEP) studies have been published in the field of head and neck squamous cell carcinoma (HNSCC) with variable objectives, methods, and results. METHODS: The purpose of this study was to present a state-of-the-art review of GEP in HNSCC focusing on the current advances and perspectives for clinical applications. RESULTS: Gene expression signatures have been developed to identify screening and diagnostic molecular markers, to improve tumor staging (cervical lymph node and distant metastasis prediction), to differentiate lung metastasis of HNSCC from primary lung squamous cell carcinoma, to predict tumor response to chemoradiotherapy, and to provide outcome predictors. CONCLUSION: Some transcriptional signatures that could improve HNSCC management have been identified, but further analyses are required to properly validate and to precisely evaluate their clinical relevance. After an exploratory phase, the completion of large scale projects with stringent methodology is now necessary to transfer GEP from bench to bedside.