Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial.

BACKGROUND: Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. METHODS: This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment. RESULTS: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. CONCLUSION: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.

Endoscopic subperichondrial transseptal transsphenoidal approach is safe and efficient for non-extended pituitary surgery.

PURPOSE: To report the results of a series of patients undergoing the endoscopic subperichondrial transseptal (STRAS) approach for pituitary surgery and to evaluate the efficiency and the safety of this approach. METHODS: This is a single-centre retrospective study including all patients undergoing pituitary lesion resection through the STRAS approach from January 2002 to December 2017 by a multidisciplinary surgical team (ENT and neurosurgeon). Demographic data, tumour type, complication rate and pre- and post-operative visual, endocrine and tumour status were retrospectively analysed. RESULTS: 119 patients were included in the study, 80 (67%) presenting macroadenoma, 24 (20%) microadenoma (20%) and 6 (5%) giant adenoma. 61 (51%) patients had secreting adenoma and 51 (42%) patient had non-functioning adenoma. The STRAS approach allowed a good visualization of intrasphenoidal and intrasellar anatomical landmarks in all cases and no patient needed turbinate resection. No patient died or had neurological deficit. Endocrine remission or control was achieved in 90.5% of hormone-secreting microadenomas and in 84.2% of hormone-secreting macroadenomas. Gross-total resection was achieved for 39 patients (48.8%) of the 80 macroadenomas. Nasal complication rate was very low, with no septal perforation and two epistaxis (1.7%) medically treated. CONCLUSION: The STRAS approach is an elegant approach to the sphenoid sinus that enables a good exposure of the intrasphenoidal anatomical landmarks with a maximal preservation of the nasal mucosa. This approach allows an intrasellar work with great comfort and safety for the surgeon using a two-hand or a four-hand technique.

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.

Feasibility and Efficacy of an Addiction Treatment Program in Patients With Upper Aerodigestive Tract Cancer.

BACKGROUND: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. METHOD: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. RESULTS: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). CONCLUSION: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

Necrosis of the intranasal structures and soft palate as a result of heroin snorting: a case series.

BACKGROUND: The link between nasal inhalation of cocaine and nasal and palatal necrosis is well documented. In contrast, few data are available concerning nasal mucosa necrosis related to heroin snorting. The authors report here the retrospective analysis of 24 cases of orofacial lesions in patients with nasal heroin usage, collected between 2006 and 2012. CASES: The cases concern 17 males and 7 females (median age 29.5 (range: 24-42)) with chronic consumption of intranasal heroin (from 2 months to more than 10 years). Six patients had a history of cocaine abuse. The median daily amount of heroin consumption was 5 g (range: 0.5-10). The complications were nasal perforation (11 cases), nasal ulceration or erythema (5 cases), nasal septum necrosis (5 cases), pharyngeal ulceration (3 cases), and palate damages (5 cases). The most common clinical signs and symptoms were nasal pain, purulent sputum, dysphagia, and rhinitis. Maintenance therapy with methadone (19 cases) or buprenorphine (3 cases) was initiated. In 8 cases, the injury improved. DISCUSSION: The potential of heroin to induce destructive orofacial lesions should be considered when nasal damages are observed in patients with drug abuse. A multidisciplinary approach seems to be the most effective means of managing such patients.

Laser-Assisted Lithotripsy With Sialendoscopy: Systematic Review of YO-IFOS Head and Neck Study Group.

INTRODUCTION: Sialolithiasis is the most common cause of symptomatic obstructive sialadenitis. Sialendoscopy represent a minimally invasive technique that has evolved significantly in the last 2 decades, with high success rates in managing sialolithiasis and allowing gland preservation. Lithotripsy assisted or not by laser represents the fragmentation of stone or lithiasis within the salivary duct followed immediately by removal of the fragmented pieces. Material and Methods: A systematic review investigating the role of laser-assisted lithotripsy with sialendoscopy (LAS) in the treatment of sialolithiasis was performed. RESULTS: Sixteen papers meet inclusion criteria. The mean maximum diameter of lithiasis was 7.11 mm (min: 2 mm/max: 17 mm; standard deviation [SD]: 2.33; 95% CI = 1.573-4.463). Success rate described ranging from 71% to 100% with a mean of 87.3% (SD: 7.21; 95% CI: 5.326-11.158) and the gland preservation rate was 97%. Considering only "non retrievable-non floating stones" studies that include both parotid and submandibular stones: Eight clinical retrospectives, nonrandomized studies and 1 prospective, nonrandomized study report results from parotid and submandibular gland lithiasis. According to this, the most common gland involved was the submandibular gland (n = 153; 65.1%), in comparison to the parotid gland (n = 82; 34.8%). CONCLUSION: The current evidence supports LAS as a conservative, efficient, safe, and gland-preserving alternative technique, in experienced hands, for management of mid-size sialolith removal from major salivary glands, when the indication is appropriate.

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 mum. 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 cN(0) patients with oral and oropharyngeal squamous cell carcinoma seems to be a promising approach.

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 surgeon's experience; the main objective is a complete resection. The endoscopic endonasal approach is the most frequent procedure.

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. DESIGN: Cohort study. PATIENTS: Forty-seven patients were referred for RPA (1981-2003). Among them, 32 (18 unmonitored and 14 monitored) patients displayed no preoperative facial palsy, and histologic analyses revealed evidence of recurrence. The operation time and the extent and duration of postoperative facial nerve palsy were examined in both groups (monitored vs. unmonitored). Both groups had a similar clinical appearance distribution. RESULTS: Facial nerve paralysis was estimated using the House-Brackmann grading scale. CFNM reduced the intensity of facial nerve paralysis independently of the kind of surgery performed. The complete deficit rates were 0% for the monitored group and 5.6% for the unmonitored group. Postoperative facial nerve paralysis was significantly lower (P = .01) in the monitored group than in the unmonitored group. CFNM improved the duration of facial paralysis (P = .001) in the monitored group. The operation time was significantly lower in the monitored group than in the unmonitored group (P = .001). CONCLUSIONS: Routine use of CFNM during RPA surgery improves the surgical outcome. The facial nerve deficit can be reduced, and the recovery of facial nerve function is faster.

[How can the diagnostic value of head and neck biopsies be increased in Wegener's granulomatosis: a clinicopathologic study of 49 biopsies in 21 patients]. / 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.

Head and neck biopsies usually have a low diagnostic value in Wegener's granulomatosis (WG). On the basis of 49 biopsies obtained from 21 WG patients at diagnosis from various sites, i.e. nose (29), paranasal sinus (7), oral cavity (4), larynx (4), conjunctiva (3) and external ear (2), we described the suggestive histological features and studied the diagnostic potential of the biopsy size, anaesthesia method (general (GA) or local (LA)), anatomic region of the biopsy, number of sections, and presenting macroscopic manifestations. Associated granulomatous inflammation (scattered giant cells, 28.5% of biopsies; poorly-formed granulomas, 28.5%), necrosis (neutrophilic microabscesses, 16.3%; geographic necrosis, 18.3%), angiitis (leukocytoclastic, 10%; necrotizing, 12%; and granulomatous, 6%) which confirmed the diagnosis were only present in 18.3% of the biopsies (28.5% of the patients). We think it is possible to propose a "WG-compatible" diagnosis when at least one of these histological features is present (24.5% of biopsies, 26% of patients in our study). We found that it was always better to perform biopsies targeted on macroscopic lesions. When there was no lesion, samples from paranasal sinuses obtained under GA had the highest diagnostic value in the head and neck region, whereas 90% of nasal systematic biopsies performed under LA were nonspecific. Moreover, we demonstrated that performing two further sections increased the sensitivity of histological examination by 7%.

Robot-assisted transaxillary thyroidectomy: surgical technique.

Robot-assisted transaxillary thyroid surgery avoids the need for a neck incision. It consists of thyroid lobectomy and isthmectomy for moderately large unilateral benign nodules. The surgical imperatives are the same as for conventional surgery, but with differences in terms of patient positioning, surgical incision, equipment, surgical technique and indications. The purpose of this article is to describe the equipment, patient positioning and surgical technique of exclusive robot-assisted transaxillary total thyroid lobectomy and isthmectomy.

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.

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 >or= 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.