Training and competence perception differences in otolaryngology and head and neck surgery training program - an anonymous electronic national survey.

BACKGROUND: Otorhinolaryngology / Head and Neck Surgery consists of different sub-specialties, each comprising unique characteristics and challenges. Herein, we investigate the use of a uniform national electronic questionnaire for curriculum planning. MAIN OUTCOME MEASURES: (1) Analyze the residents' perception of the different sub-specialties training programs and their competence capabilities. (2) Identify sub-specialties requiring attention. (3) Investigate the characteristics associated with competence perception. METHODS: This is a national cross sectional study. An anonymous electronic questionnaire was emailed to all registered Otorhinolaryngology / Head and Neck Surgery residents. RESULTS: 63.5% registered residents responded to the questionnaire. Two sub-specialties, Rhinology and Laryngology, are located in the extremities of the residents' perceptions of competence and training (p < 0.0001), despite similar complexity perception (means 6.10 and 6.01, respectively). Rhinology is perceived as the most well-trained sub-specialty, both surgically and clinically (means 7.08 and 7.66, respectively), whereas Laryngology is bottom scaled (means 5.16 and 6.14, respectively). The same is true for perceived competence, surgical and clinical, in Rhinology (means 6.80 and 8.02, respectively) compared to Laryngology (means 5.04 and 6.75, respectively). Significant positive correlations were found between training, competence perception and workload ("golden training triangle"). CONCLUSIONS: Each ORL-HNS sub-specialty comprises different characteristics and a different learning curve, necessitating a tailored training program. Recognizing its sub-specialties distinctive features may assist in establishment of better-adapted learning curves in residency programs. Herein, we examine the use of anonymous electronic national survey. Laryngology, bottom ranked, is a prototype of a relatively new surgical discipline. Rhinology, ranked top by the residents, is an exemplar of a sub-specialty with an optimal 'educational environment'. Moreover, we have established golden training triangle, implicating, highlights the essential role of institutional and senior staff for proper residency teaching. We demonstrate and advocate the benefit of using an anonymous electronic questionnaire.

Bilateral Intratonsillar Abscesses: A Deceiving Symmetrical Oral Bulging.

BACKGROUND: Unilateral intratonsillar abscess (ITA) is an underreported, well-known complication of acute tonsillitis. The prevalence of unilateral ITA compared to peritonsillar abscess (PTA) is 1:14. However, bilateral ITA is an extremely rare entity, with only four cases reported thus far. OBJECTIVES: To describe past cases and our experience, elaborating the diagnostic challenge and the surgical treatment for bilateral ITA. METHODS: We conducted a literature search in the PubMed database using the key words intra-tonsillar abscess, tonsillar abscess, bilateral tonsillar abscess, bilateral intra-tonsillar abscess and bilateral peritonsillar abscess. Our search was limited to the years 1980 to 2020. RESULTS: We found that only four cases of bilateral ITA were previously published. All were characterized by a delay in diagnosis with a median of 10 days (4-14 days), symmetrical oral cavity appearance, enlarged bilateral kissing tonsils, and subsequent treatment by surgical drainage/paracentesis. Respiratory compromise was a concern in most cases. Our patient was treated with bilateral quinsy tonsillectomy and had a prompt recovery. CONCLUSIONS: Bilateral ITA is a rare, deceiving entity, with a diagnosis delay attributed to the symmetrical oral bulging. We present the fifth case reported and the first ever reported in a pediatric patient. We describe the assumed pathogenesis and the main characteristics among all five patients, emphasizing the important role of a high index of suspicion and appropriate imaging, guiding to proper diagnosis and treatment.

A Cohort Study of the Surgical Risks and Prediction of Complications in Surgical Tracheostomies.

BACKGROUND: Current protocols favor percutaneous tracheostomies over open procedures. We analyzed the effects of this conversion from the open approach to the percutaneous procedure in terms of relevant clinical status, complications, and mortality in surgical open tracheostomies. Relevant laboratory and clinical parameters, potentially associated with complications, were also examined. MAIN OUTCOME MEASURES: Comparison of clinical, laboratory data and outcome of surgical tracheostomy during the two eras. Investigate potential pertinent predictive parameters associated with complications. METHODS: A single center retrospective case series of consecutive patients who underwent surgical tracheostomy between the years 2006-2009 ("early era") and 2016-2020 ("late era"). RESULTS: The study included 304 patients, 160 in the "early" and 144 in the "late" era. Despite a 78% increase in patient volume in the intensive care units, there was a 55% decrease in surgical tracheostomy during the "late era". Significantly more patients with structural deformities (p < 0.001), insulin dependent diabetes mellitus (p = 0.004), extreme (high and low) body weight (p = 0.006), anemia (p < 0.001) and coagulation disorders (p < 0.001), were referred for an open tracheostomy during the "late era". The complication rate was significantly higher during the "late era" (11.7 vs. 2.5%, OR 6.09 CI 95% [1.91-19.39], p = 0.001). Diabetes mellitus (p = 0.005), anemia (p = 0.033), malnutrition (p = 0.017), thrombocytopenia (p = 0.002) and poor renal function, (p = 0.008), were all significantly associated with higher complication rates. CONCLUSIONS: Risk assessment and training programs must reflect the decrease in surgical volume of open tracheostomies and consequently reduced experience. The increase of a patient subset characterized by pertinent comorbidities should reflect this change.

Minimally Invasive Parathyroidectomy: Can Intraoperative Parathyroid Hormone Monitoring be Omitted?

BACKGROUND: Intraoperative PTH (ioPTH) monitoring has become widely accepted in the era of minimally invasive parathyroidectomy (MIP). The purpose of this study was to evaluate the need for ioPTH during parathyroidectomy in patients with positive preoperative imaging. METHODS: The charts of patients who underwent parathyroidectomy at three tertiary centers between the years 2012 and 2021 were retrospectively reviewed. Patients were defined as MIP candidates with either concordant preoperative imaging or a single positive imaging. Patients with negative or discordant imaging, concomitant thyroidectomy, or previous neck surgery were excluded. RESULTS: Of a total of 1013 patients who underwent parathyroidectomy, 535 (52.8%) were defined as MIP candidates and were included in the statistical analysis. Surgical success was achieved in all patients. A single adenoma that corresponded to the preoperative imaging was identified and resected in 517 (93.8%) patients. In only 18 (3.3%) patients, the ioPTH correctly changed the operative management where additional pathologic glands were identified and excised. Patients with additional lesions were significantly more likely to have decreased index adenoma size as indicated either by preoperative imaging or by intraoperative findings (15.5 ± 6.6 vs. 8.3 ± 2.5 mm, p < 0.001). None of the patients with an adenoma size greater than 13 mm had an additional pathologic gland. CONCLUSIONS: Our findings suggest that the routine use of ioPTH in MIP candidates may be omitted in patients with an index adenoma greater than 13 mm, even with only a single positive preoperative imaging study, without compromising surgical success.

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma.

INTRODUCTION: Immune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study's main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings. MATERIALS AND METHODS: This is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies. RESULTS: We analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (p = 0.45, p = 0.31, and p = 0.88, respectively). There was a significant (18%, 95% CI 0.65-0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity. DISCUSSION AND CONCLUSIONS: Our data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.

[HEAD AND NECK MALIGNANCIES CLASSIFICATION, THE 8TH EDITION OF THE AMERICAN JOINT COMMITTEE ON CANCER - WHAT IS NEW?]

INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging manual has become the point of reference for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. The eighth edition of the Head and Neck AJCC Cancer Staging Manual incorporates significant changes based on advances in our understanding of the etiology and certain histologic attributes of tumors. Changes were made only when there was strong evidence for inclusion, while balancing between "population-based" and a more "personalized" approach. We describe the main changes implanted into the AJCC 8th edition while analyzing the effects on treatment plans and survival metrics. 1. The most significant update, to better reflect the variety of diseases arising in the pharynx, creates a separate staging algorithm for high-risk human papillomavirus-associated cancer of the oropharynx. Therefore, pharynx carcinoma has been divided into 3 separate chapters - nasopharynx, high-risk HPV-associated (p16-positive) oropharynx, and hypopharynx and non-high risk HPV-associated (p16-negative) oropharynx. 2. Another important update incorporates extra nodal extension as a prognostic variable for regional lymph node metastases in non-viral associated head and neck tumors. 3. Significant changes to the tumor (T) categories for oral cavity are discussed, where, for every 5-mm increase in depth of invasion (DOI), categories will increase one level, demonstrating better consistent and predictive survival curves. 4. A major tumor (T) category change for nasopharyngeal squamous cell carcinoma (SCC), regarding the prevertebral and pterygoid muscles, is discussed. We go through the rationale behind the major changes while practicing the new staging system among different cases.

[LARYNGEAL MALIGNANCIES IN ISRAEL - THE DIAGNOSIS, CLASSIFICATION AND TREATMENT OF NEUROENDOCRINE TUMORS].

INTRODUCTION: The larynx is the most common site of neuroendocrine tumors in the head and neck region. Tumors are divided morphologically into epithelial-derived tumors (carcinomas) and neural-derived tumors (paragangliomas). The classification of neuroendocrine tumors has evolved over the past two decades. OBJECTIVES: To investigate the incidence and histological types of laryngeal tumors in Israel. To evaluate laryngeal neuroendocrine tumors treated at a single tertiary referral center, while describing current classification and controversies. METHODS: Retrospective investigation was conducted of laryngeal tumors treated at Hadassah University Hospital between the years 2007 and 2016. Analysis was performed of all cases diagnosed in Israel between 2005 and 2014. Previous and current classifications of laryngeal neuroendocrine tumors were reviewed. RESULTS: Two hundred and twenty new laryngeal cancers were diagnosed on average annually in Israel during the study period. Squamous cell carcinoma consisted in most cases (95%); yet, no documentation of neuroendocrine tumors was noted. Three patients, in their fifties, were treated for laryngeal neuroendocrine tumors at Hadassah. Tumors consisted of paraganglioma, typical carcinoid and small cell neuroendocrine carcinoma. Investigation, treatment, outcome, and classification are described. CONCLUSIONS: This is the first description of laryngeal neuroendocrine tumors in Israel. The lack of clarity for diagnosis, documentation and classification of this rare, heterogenic group of tumors, described worldwide, was noted in Israel as well. A multidisciplinary team, including experienced pathologists, radiologists, head and neck surgeons and oncologists, is mandatory for providing the best patient care.

Gore Iliac Branch Endoprosthesis for treatment of bilateral common iliac artery aneurysms.

OBJECTIVE: The Gore Iliac Branch Endoprosthesis (IBE; W. L. Gore & Associates, Flagstaff, Ariz) has recently been approved by the Food and Drug Administration for treatment of common iliac artery (CIA) aneurysms. Despite early excellent results in clinical trial, none of 63 patients were treated for bilateral iliac aneurysms. The goal of this study was to examine real-world experience using the Gore IBE for bilateral CIA aneurysms. METHODS: A retrospective review of an international multicenter (16 U.S., 8 European) experience using the Gore IBE to treat bilateral CIA aneurysms was performed. Cases were limited to those occurring after Food and Drug Administration approval (February 2016) in the United States and after CE mark approval (November 2013) in Europe. Demographics of the patients, presentation, anatomic characteristics, and procedural details were captured. RESULTS: There were 47 patients (45 men; mean age, 68 years; range, 41-84 years) treated with bilateral Gore IBEs (27 U.S., 20 European). Six patients (12.7%) were symptomatic and 12 (25.5%) patients were treated primarily for CIA aneurysm (aorta <5.0 cm). Mean CIA diameter was 40.3 mm. Four patients had aneurysmal internal iliac arteries (IIAs). Two of these were sealed proximally at the IIA aneurysm neck and two required coil embolization of IIA branches to achieve seal in the largest first-order branches. Technical success was achieved in 46 patients (97.9%). No type I or type III endoleaks were noted. There was no significant perioperative morbidity or mortality. IIA branch adjunctive stenting was required in four patients (one IIA distal dissection, three kinks). On follow-up imaging available for 40 patients (85.1%; mean, 6.5 months; range, 1-36 months), 12 type II endoleaks (30%) and no type I or type III endoleaks were detected. Two of 80 (2.5%) IIA branches imaged were occluded; one was intentionally sacrificed perioperatively. CONCLUSIONS: Preservation of bilateral IIAs in repair of bilateral CIA aneurysms can be performed safely with excellent technical success and short-term patency rates using the Gore IBE device. Limb and branch occlusions are rare, usually are due to kinking, and can almost always be treated successfully with stenting.

Double trouble: A cohort study of re-irradiation and laryngectomy - Severity of and risk for pharyngocutaneous fistula.

OBJECTIVES: Pharyngocutaneous fistula (PCF) is a devastating complication of laryngectomy. Different factors, principally previous irradiation, increases the risk for PCF formation. The current study objectives is to investigate the potential negative effect of re-irradiation on fistula development. Materilas and methods This is a single, referral, medical center retrospective, cohort study, conducted between the years 2011-2021. Electronic medical files, surgical notes, laboratory records and radiation plan (dose and time interval in case of re-irradiation) were examined. Main outcomes and measures Risk and predictors associated with PCF formation. Risk and severity of PCF in the setting of re-irradiation. RESULTS: Overall, 27 laryngectomized patients were investigated, of whom 21 patients had single radiation (pre or post-operative radiation) and the other 6 patients had two radiation treatments (before and after laryngectomy). The fistula rate was 33.33% (7/21) in the single radiation compared (p = 0.14) to 66.66% (4/6) in the re-irradiation group of patients (including late-onset fistulas). All single radiation PCF were self-limited, whereas, 3 out of 4 fistulas in the re-irradiation group were longstanding or permanent. In the re-irradiation group of patients, a shorter time interval between the first and second radiation treatments was demonstrated among those with fistula formation compared to patients with uneventful laryngectomy (p = 0.08). CONCLUSION: Re-irradiation and especially a brief interval between the radiation treatments is associated with a severe PCF.

Sentinel Lymph Node Identification in Cutaneous Head & Neck Cancer - Lymphoscintigraphy Late Phase.

OBJECTIVE: Sentinel node (SN) biopsy following lymphoscintography is recommended for high-risk cutaneous malignancies. Herein, we investigate different lymphoscintography phases, focusing on the importance of the late static phase and the resultant discovery of distal echelon solitary positive sentinel nodes that would otherwise have been overlooked. METHODS: In this retrospective cohort study, conducted in a tertiary referral medical center, we assessed SN localization and time from tracer injection to SN identification on lymphoscintigraphy. Findings on scan were compared with SN found in the surgical field, and with the final pathological investigation. RESULTS: Seventy-three patients, undergoing SN biopsy for head and neck skin malignancies, were investigated. Most patients were male (n = 50). The average age was 65.7 (±15.7) years and the average follow-up time was 29.1 (±22.4) months. Overall, 101 SNs were histologically investigated, demonstrating 7 positive SN. Eleven patients (15%) benefited from the late lymphoscintigraphy phase. In four studies, an SN was identified only in the late static phase, one of which was positive for the disease. In seven patients, SN was identified in the early phase with additional, different, SN on the late phase, one of which was positive for the disease. Comparing the yield (positive SNs) of early versus late phases, demonstrated the same importance (p = 0.275). CONCLUSIONS: The late lymphoscintigraphy phase has a crucial role in high-risk HN cutaneous cancer. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2164-2168, 2022.

Modified bi-weekly cetuximab-cisplatin and 5-FU/leucovorin based regimen for effective treatment of recurrent/metastatic head and neck squamous cell carcinoma to reduce chemotherapy exposure of patients.

BACKGROUND: The standard chemotherapy treatment protocol for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) requires as long as 56 days of hospitalization over six months. Where the 5-Fluorouracil (5-FU) pump is available, most treatment will be on outpatient bases, however patients will still be under chemotherapy treatment for a comparable period of time (around 50 days). AIM: A modified protocol was assessed to decrease hospitalization and/or chemotherapy treatment time without sacrificing outcomes, to potentially increase patient quality of life. METHODS AND RESULTS: A retrospective analysis (2005-2018) of recurrent/metastatic HNSCC patients with a modified treatment protocol was performed. Treatment consisted of cisplatin, cetuximab, 5-fluorouracil bolus and leucovorin administered on day 1 of a 2-week cycle, and a continuous infusion of 5-fluorouracil on days 1-2 of the cycle. Outcomes were measured by progression-free survival, overall survival, and patient hospitalization time. Analysis was done using the Kaplan-Meier survival function curve. The study cohort consisted of 27 patients. The modified treatment protocol resulted in a median progression-free survival of nine months and median overall survival of 14 months, while hospitalization time was reduced by almost 80% in the first six months of treatment. CONCLUSIONS: Modification of the cisplatin, cetuximab, 5-FU and leucovorin protocol to a bi-weekly regimen utilizing alternative drug delivery methods, significantly reduced patient hospitalization from 56 days to 12 days in the first 6 months of treatment. This was achieved without compromising treatment outcome, while significantly reducing the days patients were exposed to chemotherapy, and thus potentially improving quality of life.

Salivary Gland Heterotopia, a Clinical and Pathological TNM Staging Challenge - Carcinoma ex Pleomorphic Adenoma Arising in a Parotid Lymph node.

INTRODUCTION: Heterotopia is the presence of a particular tissue / tumor at a non-physiological / ectopic site. The study primary goals: To review the current data investigating heterotopic, normal appearing, and diseased salivary gland tumors, in lymph nodes. To describe the meticulous pathological investigation and multidisciplinary decision-making process of a heterotopic carcinoma ex pleomorphic adenoma arising in an intra-parotid lymph node. MATERIALS AND METHODS: A literature search in the "PubMed" database using key words "carcinoma ex pleomorphic adenoma", "parotid lymph node", "salivary gland" and "heterotopia" was conducted. We describe the thorough pathological investigation and clinical decision-making process, focusing TNM staging system limitations. RESULTS: A few case reports presented either normal appearing salivary tissue, benign tumors or low and high-grade salivary malignancies arising in lymph nodes. We present the investigation, controversies and treatment decision process of a 46-year-old man with CXPA in intra-parotid lymph node. CONCLUSIONS: The staging scheme does not distinguish between nodal spread and primary tumor arising in a lymph node. Multidisciplinary input regarding prognosis and follow-up plans, may consider heterotopia differently from the usual pattern of nodal spread.

The potential of somatostatin receptor 2 as a novel therapeutic target in salivary gland malignant tumors.

BACKGROUND: Treatment regimens for patients with metastatic or recurrent post-radiation, locoregional, unresectable salivary cancer are limited. An inverse correlation between somatostatin receptor 2 (SSTR2) and the proliferating marker Ki-67 in neuroendocrine tumors has enabled a treatment plan for metastatic disease, utilizing peptide receptor radionuclide therapy. Interestingly, healthy salivary glands express high levels of SSTR2. In this study, the presence of SSTR2, its correlation with Ki-67 in glandular salivary carcinomas and the clinical applicability thereof was determined. METHODS: In the retrospective part of this study, 76 adequate tumor tissue specimens obtained from patients diagnosed with primary or metastatic salivary carcinomas between 1988 and 2016, were collected for tissue array and histologically classified. Immunohistochemistry was performed to determine the presence, relative expression and potential correlation of SSTR2 and Ki-67. The clinical significance of SSTR2 expression was determined by prospectively assessing 68Ga-DOTATATE uptake using PET-CT imaging, in patients diagnosed with metastatic salivary gland malignant tumors between 2015 and 2016. RESULTS: Sixty-three primary cancer tumors and 14 metastatic tumors were tested. All tumor subtypes were found to express SSTR2 to some extent. The highest expression was seen in Mucoepidermoid carcinoma (MEC) tissues where the majority of specimens (86.4%) expressed SSTR2. A relatively strong immunohistochemical staining score for SSTR2 was observed in MEC, adenoid cystic carcinoma and polymorphous adenocarcinoma. Interestingly, an inverse correlation between SSTR2 and Ki-67 expressions was observed (44%) in MEC tissue. Uptake of 68Ga-DOTATATE was visualized using PET-CT imaging in 40% of patients, across metastatic MEC and ACC. All observations were found to be statistically significant. CONCLUSION: This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.

Furosemide administered before noise exposure can protect the ear.

OBJECTIVES: We assessed the effect of furosemide administration on noise-induced hearing loss. This drug reversibly elevates the auditory threshold by inducing a temporary reduction of the endocochlear potential and thereby suppresses the cochlear amplifier and active cochlear mechanics. METHODS: Mice were given a single injection of furosemide 30 minutes before exposure to 113 dB sound pressure level broadband noise. Control animals received saline solution. Furosemide was administered in other mice after the noise exposure. Auditory threshold shifts were assessed by recording auditory nerve brain stem evoked response (ABR) thresholds to broadband clicks. RESULTS: The mean ABR threshold in the group injected with furosemide and exposed to temporary threshold shift (TTS)-producing noise was elevated by 20.4 +/- 12.3 dB, and that in the saline control group was elevated by 35.4 +/- 18.3 dB (p < 0.02). The mean threshold elevations in the group injected with furosemide and exposed to permanent threshold shift (PTS)-producing noise and in the PTS saline control group were 15.0 +/- 10.3 dB and 27.0 +/- 12.7 dB, respectively (p < 0.01). Similar results were obtained when the PTS was assessed with an 8-kHz tone burst ABR. There was no significant difference in the PTS between mice given a single injection of furosemide and those given saline solution after the noise; this finding shows that furosemide is not acting as an antioxidant. CONCLUSIONS: It appears that reversible hearing threshold elevation as a result of furosemide administration before noise exposure can reduce the TTS and PTS. This finding provides insight into the mechanism of noise-induced hearing loss.

Reduced salicylic acid binding following noise: possible evidence for prestin disruption.

To gain insight into the mechanism of noise induced permanent threshold shift (PTS), the magnitude of the auditory threshold elevation induced by injection of salicylic acid (which competitively binds with the motor protein prestin) to animals with a pre-existing PTS was compared to that in control animals (not exposed to noise). Normal mice were exposed to a noise intensity and duration which causes a small PTS. After determining the degree of the resulting PTS two weeks following the noise, salicylic acid was injected. The salicylic acid induced an additional threshold elevation and its magnitude was compared to that in control mice which had not been noise exposed. The mean noise induced PTS in the experimental (noise exposed) group was 25.5 dB. Following the administration of salicylic acid to these animals, there was an additional (salicylic acid induced) mean threshold elevation of 17.5 dB, and this was significantly smaller than that in control (not noise exposed) mice (36.8 dB). This may be evidence for a reduced number of salicylic acid binding sites on prestin and therefore the PTS may be due to disruption of prestin by the free radicals produced during the noise exposure.

How are the inner hair cells and auditory nerve fibers activated without the mediation of the outer hair cells and the cochlear amplifier?

The present study was designed to assess whether, in the presence of a depression of the cochlear amplifier i.e. a sensorineural hearing loss (SNHL), the inner hair cells (IHCs) require the presence of a normal endocochlear potential for transduction. An SNHL was induced by injecting salicylic acid (which binds to the motor protein prestin in the outer hair cells), and then furosemide (which depresses the endocochlear potential) was injected. Furosemide did not cause an additional elevation of the threshold of the auditory nerve brainstem evoked response (ABR) over that induced by the salicylic acid injection. Exposure to noise was also used to induce a SNHL in other mice, and then furosemide was injected. Here too furosemide did not cause an additional ABR threshold elevation over that induced by the noise. These results show that the IHCs (and the auditory nerve) can be excited in the presence of a SNHL (i.e. without the cochlear amplifier) and in the absence of an endocochlear potential. Possible mechanisms of excitation in such a state are discussed.

Checkpoint inhibitors: Better outcomes among advanced cutaneous head and neck melanoma patients.

OBJECTIVE: The aim of this study was to investigate if the treatment outcomes of checkpoint inhibitors (CPI) in patients with advanced-stage skin head and neck melanoma (HNM) differs from outcomes in patients with non-HNM. DESIGN: A retrospective cohort study of patients with unresectable AJCC stage III and stage IV, who received CPI between 2010 and 2017. PARTICIPANTS: Overall, 122 unresectable AJCC stage III and metastatic stage IV melanoma adult patients were treated with CPI during the study period (consecutive patients). The HNM group of patients was comparable with limbs and trunk melanoma group except different distant metastatic (M1a/b/c/d) pattern (p = 0.025). MAIN OUTCOMES: Comparison of overall survival and clinical response to CPI in patients with advanced-stage skin melanoma of the head and neck with non-HNM. RESULTS: We analyzed 38 patients with melanoma arising in the head and neck skin regions, 33 with melanoma of limbs and 51 with trunk melanoma. Most of the head and neck patients were men (89.5%), the average age of melanoma diagnosis was 61.4±16.7 years (range 16.4-85.6). More than a third of HNM group of patients (36.8%) were 70 years and older. Overall response rate (ORR) to CPI was 50% (CR 31.6% and PR 18.4%) in the head and neck study group of patients, compared to an ORR of 36.3% and 23.5% in melanoma of the limbs and of the trunk, respectively (p = 0.03). The median overall survival of HNM group of patients was 60.2±6.3 months, CI 95% [47.7-72.7], 63% were alive at 30 months, reaching a plateau. Whereas, the median survival time of limbs and trunk melanoma were 51.2 and 53.4 months, which did not reach significance. CONCLUSIONS AND RELEVANCE: Response rate to CPI is significantly improved in patients with melanoma of the head and neck and they have a trend towards improved, long standing, overall survival.

The imperative of the Sistrunk operation: review of 160 thyroglossal tract remnant operations.

OBJECTIVE: Analysis of the pre- and postoperative features, long-term follow-up, and complications. STUDY DESIGN AND METHODS: Case series with chart review of 160 thyroglossal tract remnant excisions over a 20-year period (1988-2007). RESULTS: The mean age of diagnosis was 10.9 +/- 14.2 years with 63.8 percent male predominance. There was a prior history of thyroglossal tract remnant infections in 70 percent of patients, and 30 percent presented with cutaneous fistulas. The majority had ultrasound imaging that identified cysts mainly (66.7%) in the infrahyoid region. Preoperative fine-needle aspirations in 18 patients were benign. On pathological reevaluation, 26.5 percent had thyroid tissue inside the remnant, with one case of papillary carcinoma. After the Sistrunk operation, postoperative complications occurred in 7.5 percent including a 1.9 percent recurrence rate. CONCLUSIONS: All age groups had similar clinical presentations and outcomes. Ultrasound is a reliable and appropriate imaging modality for most patients. Surgery must effectively incorporate the tract and cyst to allow low recurrence rates (<2%). Clinically diagnosed thyroglossal tract remnant may, in fact, be other pathologies in 10 percent of cases. Nevertheless, our recommendation is a Sistrunk procedure for all midline neck lesions suspected to be a thyroglossal tract remnant.