Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Nasal Vestibulitis and Vestibular Furunculosis: a systematic review about two common nasal infections and considerations about correct diagnosis and management.

Background: Nasal vestibulitis (NV) and nasal vestibular furunculosis (NVF) are two infectious processes of the nasal vestibule, sharing common etiology, the same risk of complications, and similar treatment while remaining two different pathological entities. Methods: We performed a comprehensive literature research on NV and NVF in PubMed, Cochrane, and Google Scholar databases, with the aim to review the evidence on these two conditions and discuss the therapeutic approaches. Results: We identified a total of 248 records; according to our inclusion/exclusion criteria, 27 of them, published over a period of 59 years (1962-2021), were included in this review. Conclusion: NV and NVF are reported to be common conditions, with well-known etiological agents and risk factors. The diagnosis is clinical and topical antibiotics are the mainstay of treatment. Complications appear to be infrequent. Further studies are necessary to clarify the pathogenetic mechanisms and the exact prevalence of both conditions.

Role of molecular genetics in the clinical management of cholangiocarcinoma.

The incidence of cholangiocarcinoma (CCA) has steadily increased during the past 20 years, and mortality is increasing. The majority of patients with CCA have advanced or metastatic disease at diagnosis, and treatment options for unresectable disease are limited, resulting in poor prognosis. However, recent identification of targetable genomic alterations has expanded treatment options for eligible patients. Given the importance of early and accurate diagnosis in optimizing patient outcomes, this review discusses best practices in CCA diagnosis, with a focus on categorizing molecular genetics and available targeted therapies. Imaging and staging of CCAs are discussed, as well as recommended biopsy collection techniques, and molecular and genomic profiling methodologies, which have become increasingly important as molecular biomarker data accumulate. Approved agents targeting actionable genomic alterations specifically in patients with CCA include ivosidenib for tumors harboring IDH1 mutations, and infigratinib and pemigatinib for those with FGFR2 fusions. Other agents currently under development in this indication have shown promising results, which are presented here.

Integrative molecular analysis of combined small-cell lung carcinomas identifies major subtypes with different therapeutic opportunities.

BACKGROUND: Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. MATERIALS AND METHODS: Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. RESULTS: All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. CONCLUSIONS: These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).

Evaluation of Discomfort in Nasopharyngeal Swab Specimen Collection for SARS-CoV-2 Diagnosis.

BACKGROUND: The rapid spread of COVID-19 worldwide has impo-sed the need to identify a test that quickly recognizes affected subjects, both symptomatic and asymptomatic. The most reliable option has been proven to be the RT-PCR, which allows to detect virus RNA on a specimen from a high viral load site, such as nasopharynx. Nasopha-ryngeal sample collection is possible by means of a nasopharyngeal swab (NPS) and is a practical and relatively non-invasive technique, but rather bothersome for the recipient. AIM: The aim of the present study is to evaluate the discomfort evoked during NPS. MATERIALS AND METHODS: We surveyed 429 patients receiving NPS before hospitalization or other procedures non related to COVID-19. For each one we noted the discomfort level felt during the swab using a 11-point numeric rating scale (NRS) for pain and the total time needed for the procedure to be taken. Sex, age, smoking status and positive history of previous swab have been taken into account. RESULTS: We found that, among the variables, sex had a statistically significant impact on the perceived discomfort of nasal swab, with females experiencing slightly more discomfort. CONCLUSIONS: NPS is largely a none-to-minimum discomfort in-ducing procedure. The differences in perceived discomfort could be explained based on anatomical features, and should remark the need for a tailored and anatomy-oriented approach in each patient.

Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study.

BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.

Clinical presentation, genotype-phenotype correlations, and outcome of pancreatic neuroendocrine tumors in Von Hippel-Lindau syndrome.

PURPOSE: Data regarding the clinical management and follow-up of pancreatic neuroendocrine tumors (PanNETs) associated with Von Hippel-Lindau (VHL) syndrome are limited. This study aimed to assess clinical presentation, genotype-phenotype correlations, treatment and prognosis of PanNETs in a series of VHL syndrome patients. METHODS: Retrospective analysis of data of patients observed between 2005 and 2020. RESULTS: Seventeen patients, including 12 probands and 5 relatives (mean age 30.8 ± 18.4; 7 males), were recruited. PanNETs were found in 13/17 patients (77.5%) at a median age of 37 years: 4/13 (30.7%) at the time of VHL diagnosis and 9 (69.3%) during follow up. Six (46.1%) PanNET patients underwent surgery, whereas seven were conservatively treated (mean tumor diameter: 40 ± 10.9 vs. 15 ± 5.3 mm respectively). Four patients (30.7%) had lymph node metastases and a mean tumor diameter significantly larger than the nonmetastatic PanNETs (44.2 ± 9.3 vs. 17.4 ± 7 mm, p = 0.00049, respectively). Five (83.3%) operated patients had stable disease after a median follow up of 3 years whereas one patient showed liver metastases. Six (85.7%) non-resected PanNETs were stable after a median follow-up of 2 years, whereas one patient developed a new small PanNET and a slight increase in diameter of a pre-existing PanNET. No correlation was found between the type of germline mutation and malignant behavior of PanNETs. CONCLUSIONS: PanNETs are a common disease of the VHL syndrome and can be the presenting feature. Tumor size rather than genetic mutation is a prognostic factor of malignancy.

ESMO recommendations on the standard methods to detect RET fusions and mutations in daily practice and clinical research.

Aberrant activation of RET is a critical driver of growth and proliferation in diverse solid tumours. Multikinase inhibitors (MKIs) showing anti-RET activities have been tested in RET-altered tumours with variable results. The low target specificity with consequent increase in side-effects and off-target toxicities resulting in dose reduction and drug discontinuation are some of the major issues with MKIs. To overcome these issues, new selective RET inhibitors such as pralsetinib (BLU-667) and selpercatinib (LOXO-292) have been developed in clinical trials, with selpercatinib recently approved by the Food and Drug Administration (FDA). The results of these trials showed marked and durable antitumour activity and manageable toxicity profiles in patients with RET-altered tumours. The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) launched a collaborative project to review the available methods for the detection of RET gene alterations, their potential applications and strategies for the implementation of a rational approach for the detection of RET fusion genes and mutations in human malignancies. We present here recommendations for the routine clinical detection of targetable RET rearrangements and mutations.

Is Laparoscopic CME Right Hemicolectomy an Optimal Indication for NET of the Right Colon and Terminal Ileum?

PURPOSE: Since lymphadenectomy is crucial in midgut neuroendocrine tumor (NET) surgery, we adopted laparoscopic CME right hemicolectomy (LRH-CME) for the treatment of right colon and terminal ileum NETs. In this report, we present a series of nine cases of terminal midgut NETs (TM-NETs) treated by LRH-CME with a video demonstrating oncological principles and the surgical technique. METHODS: From September 2014 to November 2019, nine patients affected by TM-NETs underwent LRH-CME at the Unit of General and Hepatobiliary Surgery, University of Verona Hospital Trust, ENETS Center of Excellence. Clinicopathological data, post-operative and oncological outcomes were prospectively collected and analyzed. RESULTS: Tumors were in ileocecal valve or terminal ileum (5 cases), right colon (3 cases), and appendix (one case). Surgery had a curative intent (R0 resection) in 7 cases. Surgical debulking was required in 2 metastatic cases. Mean surgical time was 212 + 41 min and blood loss 47 + 24 mL. No postoperative mortality was observed. Post-operative course was uneventful in all except one case (Clavien-Dindo III). Median number of harvested lymph nodes was 21 (range, 11-31) and eight out of 9 patients were node positive (median 3, range 0-6). At a median follow-up of 18 months (range, 6-50), none of the patients suffered from mesenteric locoregional recurrence and all R0 resected patients were disease-free. CONCLUSIONS: Terminal midgut NETs represent an optimal indication for LRH-CME which increases the chance of complete resection and allows optimal lymphadenectomy. In expert hands, laparoscopic approach should be favored in consideration of good short-term outcomes.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

Impact of COVID-19 on otolaryngology in Italy: a commentary from the COVID-19 task force of the Young Otolaryngologists of the Italian Society of Otolaryngology.

OBJECTIVE: The ongoing pandemic of coronavirus disease 2019 is having a dramatic effect on most medical disciplines. Otolaryngology Head and Neck Surgery is one of the most engaged disciplines, and otolaryngology specialists are facing a radical change of their role and daily activities that will have severe impact on the return to the ordinary. In this paper, the COVID-19 Task Force of the Young Otolaryngologists of the Italian Society of Otolaryngology comment on the changes that occurred for otolaryngology in Italy during the pandemic. Changes include organizational rearrangement of Otolaryngology Units, with merges and closures that affected a significant portion of them; reallocation of otolaryngology personnel, mainly to COVID-19 wards; reduction of elective clinical and surgical activity, that was mainly limited to oncology and emergency procedures; and execution of screening procedures for SARS-CoV-2 among healthcare providers and patients in otolaryngology units in Italy.

Dietary Restriction for The Treatment of Meniere's Disease.

Meniere's disease (MD) is an idiopathic inner ear disorder characterized by spontaneous recurrent vertigo, fluctuating sensorineural hearing loss (SNHL), aural fullness and tinnitus. Endolymphatic hydrops (EH) of the inner ear is currently considered the pathophysiological mechanisms that underlies typical symptoms of MD. MD diagnosis is based on the criteria of the Baràny Society. There are many therapeutic options for MD, but none is considered effective by the scientific community. The first-line treatment commonly includes dietary modification, as low salt diet and reduction of alcohol and caffeine daily intake. Although some studies showed a positive effect of these dietary restrictions, even in the prevention of recurrences, currently there is no uniform consensus on their usefulness. New dietary approach, such SPC-flakes, are being evaluated: further assessments will be needed to validate their use in clinical practice.

Pleomorphic Adenoma of the Parotid Gland and Ipsilateral Thyroid Incidentaloma: Report of A Rare Case With Review of Literature.

BACKGROUND: Pleomorphic adenomas are benign tumors of the salivary glands that mainly affect the lower pole of the superficial lobe of the parotid gland. The term "pleomorphic" refers to the epithelial and connective origin of the mass. The clinical presentation is typically that of asymptomatic swelling which increases in volume. Therapy consists in surgical removal of the tumor mass by parotidectomy with nerve preservation. CASE DETAILS: This clinical case describes an interesting case of pleomorphic adenoma of the parotid gland in a 62-year-old patient. The patient presented with a long history of an asymptomatic mildly worsening swelling of the left parotid region. The peculiarity of the clinical case is the dimension of the adenoma (9x5x9 cm) and the presence of a thyroid incidentaloma (TI), consisting of a thyroid multinodular goiter composed of nodules, the largest of which measured 8 cm in diameter. This mass dislocated the laryngotracheal axis, compressed the larynx and caused the reduction of the respiratory space, making orotracheal intubation difficult and determining the need to perform a tracheotomy. CONCLUSION: Benign pleomorphic adenomas can potentially reach large sizes if untreated. Socio-economic problems may be the reason for late diagnosis.

Sub-Clinical Effects of Chronic Noise Exposure on Vestibular System.

AIM: to investigate the effect of chronic noise exposure on vestibular function of subjects without clinical evidence of vestibular disorders and with documented cochlear damage from noise. SUBJECTS AND METHODS: 25 patients with chronic noise-induced hearing loss (NIHL) and without vestibular complaints (group A) and 25 matched controls with sensorineural hearing loss without noise exposure (group B), underwent audiological and vestibular test including caloric and cervical vestibular-evoked myogenic potentials tests (cVEMPs). RESULTS: In subjects chronically exposed to noise, similarly to that of the auditory threshold, an increase in the evocation threshold of VEMPs has been documented, statistically significant (p<0,05) and independent of the performance of the auditory threshold. p1-n1 amplitude values showed a significant difference between group A and group B. No significant difference for p1-n1 latencies between the two groups was found. CONCLUSION: We have documented the possibility of vestibular lesion, along with cochlear damage, related to chronic acoustic trauma.

Acinic cell carcinoma of the parotid gland: from pathogenesis to management: a literature review.

PURPOSE: Acinic cell carcinoma (ACCs) is uncommon malignant epithelial neoplasm of the salivary glands; the most common presentation is a well-defined painless solid mass. Diagnosis of ACCs is frequently complicated, due to its similarity with benign tumors. METHODS: A review of the literature available on ACCs was carried out. Studies were sourced from PubMed with searching of relevant headings and sub-headings and cross-referencing. RESULTS: There are no clear characteristics of ACCs found on CT, MRI and ultrasound imaging. The management of the ACC, a rare malignancy of the parotid gland, is often difficult and controversial. Radical surgery is the best treatment option. The role of radiotherapy remains controversial: the precise indications and oncologic effects of adjuvant radiotherapy in ACC of the parotid gland are not well known. There is insufficient literature regarding the chemotherapy for metastatic ACC. CONCLUSION: Knowledge about ACC, a rare malignancy of parotid gland, has changed over the past few decades. More clinical randomized works would be needed, both to assess the real effectiveness of radio and chemotherapy and to have an unanimous consensus about their indications.

Meningoencephalitis Associated with SARS-Coronavirus-2.

The aim of this work is to clarify the incidence of meningitis/encephalitis in SARS-CoV-2 patients. We conducted an initial search in PubMed using the Medical Subject Headings (MeSH) terms "meningitis," and "encephalitis,", and "COVID-19" to affirm the need for a review on the topic of the relationship between meningitis/encephalitis and SARS-CoV-2 infection. We included case series, case reports and review articles of COVID-19 patients with these neurological symptoms. Through PubMed database we identified 110 records. After removal of duplicates, we screened 70 record, and 43 were excluded because they focused on different SARS-CoV-2 neurological complications. For eligibility, we assessed 27 full-text articles which met inclusion criteria. Seven articles were excluded, and twenty studies were included in the narrative review, in which encephalitis and/or meningitis case reports/case series were reported. Neurological manifestations of COVID-19 are not rare, especially meningoencephalitis; the hypoxic/metabolic changes produced by the inflammatory response against the virus cytokine storm can lead to encephalopathy, and the presence of comorbidities and other neurological diseases, such as Alzheimer's disease, predispose to these metabolic changes. Further study are needed to investigate the biological mechanisms of neurological complications of COVID-19.

Pharmacological, Surgical and Diagnostic Innovations in Meniere's Disease: A Review.

PURPOSE: To investigate literature about pharmacological, surgical, and diagnostic innovations for Meniere's Disease (MD). SUMMARY: Meniere's disease is an inner ear disorder characterized by the presence of endolymphatic hydrops in the inner ear and symptomatology of recurrent and debilitating vertigo attacks, tinnitus, aural fullness, and fluctuating sensorineural hearing loss. Although many therapeutic options for MD have been proposed during years, no consensus has been reached by the scientific community. In the last decade, many therapeutic options have been proposed, as intratympanic steroid, intratympanic gentamicin, and intravenous glycerol. Recently, the role of the antisecretory factor in the diet of MD patients have been investigated. Surgery is recommended for intractable MD; some authors proposed new approaches including transcanal endoscopic infracochlear vestibular neurectomy, new marsupiliazation technique in sac surgery, and tenotomy of the stapedius and tensor tympani muscles.