C. Cartier

Continuous Facial Nerve Monitoring during Pleomorphic Adenoma Recurrence Surgery

Objectives: Surgery of recurrent pleomorphic adenoma (RPA) is known to lead to a high facial nerve complication rate. The efficacy of the continuous facial nerve monitoring (CFNM) technique remains to be proven in RPA surgery. The goal was thus to evaluate facial nerve palsy rates and the recovery period after parotidectomy for RPA using CFNM by way of continuous electromyography and to compare these rates and the operation time with those of patients who had undergone surgery without facial nerve monitoring.

Neck restaging with sentinel node biopsy in T1-T2N0 oral and oropharyngeal cancer: Why and how?

Objective: To evaluate the lack of accuracy in neck staging with the classical technique (i.e., neck dissection and routine histopathology) with the sentinel node (SN) biopsy in oral and oropharyngeal T1-T2N0 cancer. Study Design: Cross-sectional study with planned data collection. Setting: Tertiary center care. Subjects and Methods: In 50 consecutive patients, the pathological stage of sentinel node (pSN) was established after analyzing SN biopsies (n = 148) using serial sectioning and immunohistochemistry. Systematic selective neck dissection was performed. The pN stage was established with routine histopathologic analysis of both the non-SN (n = 1075) and the 148 SN biopsies. Results: The sensitivity and negative predictive value of pSN staging were 100 percent. Conversely, if one considers pSN staging procedure as the reference test for micro- and macro-metastasis diagnosis, the sensitivity of the classical pN staging procedure was 50 percent (9/1; 95% CI 26.9-73.1) and its negative predictive value was 78 percent (95% CI 61.9-88.8). Fifteen patients (30%) were upstaged, including nine cases from pN0 to pSN ≥ 1 and six cases from pN1 to pSN2. Two of the pN0-pSN1 upstaged patients died with relapsed neck disease. Conclusion: The SN biopsy technique appeared to be the best staging method in cN0 patients and provided evidence that routinely undiagnosed lymph node invasion may have clinical significance.

The Diagnostic Accuracy of Reverse Transcription-PCR Quantification of Cytokeratin mRNA in the Detection of Sentinel Lymph Node Invasion in Oral and Oropharyngeal Squamous Cell Carcinoma: A Comparison with Immunohistochemistry

Purpose: The main goal of sentinel lymph node (SLN) detection in head and neck squamous cell carcinomas is to limit neck dissections to pN+ cases only. However, intraoperative + diagnosis cannot be routinely done using the current gold standard, serial step sectioning with immunohistochemistry. Real-time quantitative reverse transcription-PCR (RT-PCR) is potentially compatible with intraoperative use, proving highly sensitive in detecting molecular markers. This study postoperatively assessed the accuracy of quantitative RT-PCR in staging patients from their SLN. Experimental Design: A combined analysis on the same SLN by serial step sectioning with immunohistochemistry and quantitative RT-PCR targeting cytokeratins 5, 14, and 17 was done in 18 consecutive patients with oral or oropharyngeal squamous cell carcinoma and 10 control subjects. Results: From 71 lymph nodes examined, mRNA levels (KRT) were linked to metastasis size for the three cytokeratins studied (Pearson correlation coefficient, r = 0.89, 0.73, and 0.77 for KRT 5, 14, and 17 respectively; P < 0.05). Histopathology-positive SLNs (macro- and micrometastases) showed higher mRNA values than negative SLNs for KRT 17 (P < 10−4) and KRT 14 (P < 10−2). KRT 5 showed nonsignificant results. KRT 17 seemed to be the most accurate marker for the diagnosis of micrometastases of a size >450 μm. Smaller micrometastases and isolated tumor cells did not provide results above the background level. Receiver operating characteristic curve analysis for KRT 17 identified a cutoff value where patient staging reached 100% specificity and sensitivity for macro- and micrometastases. Conclusion: Quantitative RT-PCR for SLN staging in cN0 patients with oral and oropharyngeal squamous cell carcinoma seems to be a promising approach.

Prognostic value of a three-grade classification in primary epithelial parotid carcinoma: Result of a histological review from a 20-year experience of total parotidectomy with neck dissection in a single institution

BACKGROUND The tumour grading of primary parotid cancers (PPCs) remains controversial. METHODS A 20-year standardised single centre treatment has been assessed retrospectively. The histological review of 155 consecutively treated parotid malignancies identified 96 suitable cases for univariate and multivariate survival analyses. RESULTS Treatment involved total parotidectomy, neck dissection and post-operative radiotherapy in, respectively, 91.7%, 83.3% and 70.4% of cases. The 5-year overall survival, disease-specific and recurrence-free survival rates were 79.4%, 83.5% and 70.8%, respectively. Univariate analysis confirmed the classical prognostic factors, i.e. age>60 years, male gender, facial palsy, hardness of the tumour, clinical stage, tumour grade, facial nerve invasion and lymph node metastases. Multivariate analysis identified a three-grade classification just after the clinical stage as the most important prognostic factor. CONCLUSION This study identifies the prognostic significance of intermediate grade tumours.

Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial

BACKGROUND Epistaxis is the most frequent and disabling manifestation of hereditary hemorrhagic telangiectasia (HHT). The efficacy of intravenous bevacizumab (an anti-vascular endothelial growth factor monoclonal antibody) for epistaxis has been shown. However, the efficacy of intranasal bevacizumab has yet to be evaluated. OBJECTIVE To evaluate the efficacy of 3 different doses of bevacizumab administered as a nasal spray in a repeated manner for the duration of nosebleeds in patients with HHT. DESIGN, SETTING, AND PARTICIPANTS Randomized, multicenter, placebo-controlled, phase 2/3 clinical trial with dose selection at an intermediate analysis and prespecified stopping rules (nonbinding stopping for futility). Patients aged 18 years or older with a diagnosis of HHT were recruited from 5 French centers from April 2014 to January 2015 with a 6-month follow-up after the end of treatment. Participants had a history of self-reported nosebleeds with a monthly duration of more than 20 minutes in at least the 3 months prior to inclusion corroborated by epistaxis grids completed during the same preinclusion period. INTERVENTIONS Eighty consecutive HHT patients were randomized and treated in the phase 2 study, with 4 parallel groups in a 1:1:1:1 ratio. One group received placebo (n = 21); the other 3 received bevacizumab nasal spray. Each bevacizumab group received a different dose of the drug (25 mg [n = 20], 50 mg [n = 20], or 75 mg [n = 19] per treatment) in 3 doses 14 days apart for a total treatment duration of 4 weeks, resulting in a total dose of 75 mg, 150 mg, and 225 mg in each treatment group. MAIN OUTCOMES AND MEASURES Mean monthly epistaxis duration for 3 consecutive months immediately after the end of the treatment. RESULTS Of the 80 patients who were randomized (mean age, 60.47 [SD, 10.61] years; 37 women [46.25%]), 75 completed the study. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 59 patients receiving bevacizumab in comparison with the placebo group (P = .57) or between the bevacizumab groups. The mean monthly epistaxis duration was 259.2 minutes (95% CI, 82.1-436.3 minutes) in the 25-mg group, 244.0 minutes (95% CI, 81.8-406.2 minutes) in the 50-mg group, 215.0 minutes (95% CI, 102.8-327.2 minutes) in the 75-mg group, and 200.4 minutes (95% CI, 109.3-291.5 minutes) in the placebo group. Toxicity was low and no severe adverse events were reported. This study was terminated prior to phase 3 for treatment futility after interim analysis on the recommendations of an independent data monitoring committee. CONCLUSIONS AND RELEVANCE In patients with HHT, a bevacizumab nasal spray treatment of 3 administrations at 14-day intervals with doses of 25 mg, 50 mg, or 75 mg per spray, compared with a placebo, did not reduce monthly epistaxis duration in the 3 consecutive months immediately after the end of treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02106520.

Pemphigus vulgaris antigen mRNA quantification for the staging of sentinel lymph nodes in head and neck cancer

Background:Molecular diagnosis has been proposed to enhance the intra-operative diagnosis of sentinel lymph node (SLN) invasion in head and neck squamous cell carcinoma (HNSCC). Although cytokeratin (CK) mRNA quantification with real-time reverse transcriptase-PCR (QRT–PCR) has produced encouraging results, the more discriminating markers remain to be identified.Methods:Pemphigus vulgaris antigen (PVA), squamous cell carcinoma antigen (SCCA), and CK17 mRNA were quantified using QRT–PCR, and the results were compared with an extensive histopathological examination of the entire SLNs on 78 SLNs harvested from 22 patients with HNSCC.Results:SCCA and CK17 quantification showed significantly higher mRNA values for macrometastases (MAs) than for either negative or isolated tumour cell (ITC) SLNs (P<0.01). Pemphigus vulgaris antigen allowed the discrimination of all MAs and micrometastases from both negative and ITC SLNs (P<0.001). For the neck staging of patients, considering metastatic vs non-metastatic status, receiver-operating characteristic curve analysis found areas under the curve of 93.8, 97.9, and 100% for CK17, SCCA, and PVA, respectively. With PVA, a cutoff value of 562 copies per 100 ng of cDNA permitted the correct distinction between patients with positive as opposed to negative neck nodes in all cases.Conclusion:PVA seems to be a highly promising marker for accurate intra-operative SLN staging in HNSCC by QRT–PCR.

Comment améliorer la rentabilité diagnostique des biopsies de la sphère oto-rhino-laryngée dans la maladie de Wegener : analyse anatomo-clinique de 49 biopsies chez 21 patients

Resume Les biopsies de la sphere oto-rhino-laryngee (ORL) et conjonctivales sont classiquement rapportees comme peu contributives dans le diagnostic de la maladie de Wegener (MW). A partir de 49 biopsies ORL ou conjonctivales (fosses nasales 29, sinus 7, cavite buccale 4, larynx 4, conjonctive 3, oreille externe 2) realisees lors du diagnostic chez 21 patients atteints de MW, nous avons decrit les lesions histologiques evocatrices et etudie la rentabilite diagnostique de ces prelevements en fonction : de la presence de lesions macroscopiques, du site anatomique biopsie, des modalites d’obtention (anesthesie generale ou locale), de leur taille et du nombre de recoupes realisees. L’association de lesions granulomateuses (cellules geantes isolees (28,5 % des biopsies), granulomes epithelioides (28,5 %)), de lesions necrosantes (micro-abces a polynucleaires neutrophiles (16,3 %), foyers de necrose du tissu conjonctif (18,3 %)) et d’une vascularite (necrosante (12 %), leucocytoclasique (10 %), granulomateuse (6 %)) permettant d’affirmer le diagnostic n’etait presente que dans 18,3 % des biopsies (28,5 % des patients). Il nous a paru licite de proposer le diagnostic « compatible avec une MW » lorsqu’une ou deux de ces lesions histologiques etaient presentes (24,5 % des biopsies, 26 % des patients). Nos resultats montrent qu’il etait toujours preferable de biopsier les lesions macroscopiques lorsqu’elles existaient. En leur absence, il valait mieux s’orienter vers un prelevement de muqueuse sinusienne sous anesthesie generale. En effet, les nombreuses biopsies systematiques des fosses nasales realisees sous AL etaient non contributives dans 90 % des cas. Enfin, nous avons montre que la realisation de deux recoupes permettait d’augmenter la sensibilite de l’examen histologique de 7 %.

Cervical lymphadenopathies signaling thyroid microcarcinoma. Case study and review of the literature.

BACKGROUND Some lateral cervical lymphadenopathies may lead to the discovery of papillary microcarcinomas (PMC) of the thyroid that are not radiologically apparent. This relatively rare clinical situation raises questions about the diagnostic approach to chronic cervical lymphadenopathy and the impact of lymph node metastasis on PMC prognosis. PURPOSE OF THE ARTICLE: To study the epidemiologic, clinical, and prognostic criteria of cases of lymphadenopathy that signaled PMC. PATIENTS AND METHODS A retrospective study of 167 consecutive cases of PMC compared with 13 cases where a cervical mass signaled other forms of PMC. RESULTS The mean age was 48.5 years, the ratio of men to women was 5:8, and the mean PMC size was 5.5mm. These data did not differently significantly from those of the other PMC cases. The preoperative imaging found fluid content in six cases, with microcalcifications in three cases. All cases were treated by modified radical neck dissection on the side with the lymphadenopathy and total thyroidectomy with central neck dissection. The lymphadenopathy included a ruptured capsule in five cases and was accompanied by central lymph node metastases in three cases. Thyroid capsule involvement was significantly more common in cases of PMC discovered due to lymphadenopathy than in other cases of PMC (69% versus 9.7%, respectively; p<0.001). The mean follow-up was 7.3 years. There were no deaths due to PMC signaled by lymphadenopathy. Two cases of lymph node recurrence after 8 and 10 years were controlled by another surgery and radioactive iodine treatment. CONCLUSION Any chronic cervical mass should suggest the possibility of thyroid origin, especially in cases with cystic content or microcalcifications in subjects with no particular risk factors. An ultrasound of the thyroid should be done, as well as a fine needle aspiration biopsy of the lymphadenopathy with a thyroglobulin assay. Treatment is the same as for any thyroid carcinoma, and results in a good oncological outcome, despite the possibility of lymph node recurrences.

Atypical presentations of sinonasal inverted papilloma: Surgical management and influence on the recurrence rate.

Background Sinonasal inverted papilloma (SNIP), classically, is a unilateral benign tumor of the nasal lateral wall. Numerous variations have been observed, depending on location, bilateral presentation, or association with nasal polyposis. Objective The aim of this work was to describe atypical presentations of SNIPs with their management specificities and to assess their influence on the recurrence rate in a large case series. Methods A retrospective single center study of 110 patients treated for SNIP. Atypical inverted papillomas were identified according to the following criteria: (1) unusual location (frontal, posterior, anterior), (2) bilateral involvement, and (3) association with nasal polyposis. Surgical management was detailed, and the influence of each atypical group on recurrence was assessed by using Kaplan-Meier survival curves and the log-rank test. Results Distribution of atypical presentations was as follows: frontal sinus localization (10.9%); posterior localization, including sphenoid sinus (9%); nasal anterior localization (3.6%); bilateral involvement (3.6%); and nasal polyposis association (10%). The surgical approach was endoscopic (74.5%), external (5.5%), or combined endoscopic and external (20%). Except for nasal anterior localization, all the groups were associated with a higher recurrence rate, without reaching statistical significance. Conclusion Recurrence rates for these atypical presentations arise from their specific surgical challenges. The choice of the surgical technique is guided by tumor location and extension, and by the surgeons experience; the main objective is a complete resection. The endoscopic endonasal approach is the most frequent procedure.

Positron emission tomography–computed tomography evaluation for recurrent differentiated thyroid carcinoma

OBJECTIVES Recurrence is observed in 15-20% of patients under surveillance following treatment of differentiated thyroid cancer (DTC). However, due to cell dedifferentiation, the recurrence may be iodine-negative, thereby compromising detection. For this reason, new methods of exploration are indispensable to enable localization of such recurrences. The purpose of this work is to review the contribution of positron emission tomography-computed tomography (PET-CT) in the exploration of iodine-negative recurrent DTC. METHOD A comprehensive review and discussion of the medical literature was carried out. RESULTS Depending on the report, the sensitivity of PET-CT ranged from 70% to 85%, with up to 90% specificity. However, the large number of false negatives, which can reach 40%, is the disadvantage of this examination. PET-CT results lead to change in the therapeutic strategy in approximately 50% of patients with isolated raised serum thyroglobulin levels, and surgical exploration of a precise anatomical area in the neck. CONCLUSION As post-treatment recurrence of a DTC can affect patient survival, a thorough diagnostic work-up is required in these cases. Where thyroglobulin levels are elevated with no uptake on 131-iodine scans, PET-CT can be a useful complementary exploration, especially for localizing the site of recurrence.