Diabetes Mellitus and Hearing Loss: A Complex Relationship.

Background and Objectives: Discussion is open about the relationship between diabetes (DM) and hearing loss (HL). There is a lot of evidence in the literature suggesting a causal link between these conditions, beyond being considered simple comorbidities. The difficulty in identifying populations free from confounding factors makes it difficult to reach definitive conclusions on the pathophysiological mechanisms at play. Nonetheless, there is numerous evidence that demonstrates how the population affected by DM is more affected by sensorineural HL (SNHL) and exhibit a higher prevalence of idiopathic sudden sensorineural HL (ISSNHL). Materials and Methods: Articles reporting potentially relevant information were reviewed, and the most significant results are discussed in this article. Starting from the possible mechanisms relating to auditory impairment in the diabetic condition, this article summarizes the studies on auditory evaluation in subjects with DM1 and DM2 and addresses the relationship between DM and ISSNHL. Results: DM is considered a risk factor for SNHL, although some studies have reported no relationship when the associations were adjusted for age, gender, and hypertension. Macro and microvascular insults that cause decreased blood flow, oxygen exchange, and ion transport are major complications of hypertension and DM and can have a direct effect on the sensory and support cells of the cochlea. Conclusions: Given the difficulty of carrying out studies on populations without confounding factors, new laboratory studies are strongly required to clarify which specific physiopathological mechanisms underlie the diabetic damage caused to the hearing organs and how pharmacological management may contribute to counteracting the pathophysiological effects of the diabetic condition on the auditory system.

Symptoms and clinical features in patients affected by endolymphatic sac tumor: a systematic review and meta-analysis.

PURPOSE: Most ELST data in the literature are case studies or limited to small cohorts (< 16 patients). We evaluated the main clinical signs observed at endolymphatic sac tumor (ELST) diagnosis in patients with or without Von Hippel-Lindau disease. METHODS: We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science. We included studies with at least 1 patient, of any age, affected by sporadic or VHL-related ELSTs reporting levels of hearing loss and facial nerve function and a comprehensive description of presenting symptoms at ELST diagnosis. We combined data for proportional meta-analysis. p values of 0.05 were considered statistically significant. Methodological quality was evaluated. Analyses were performed with MedCalc 14.8.1 software. RESULTS: A total of 26 studies, including 113 patients and 118 cases of ELSTs were included. Pooled proportion rates (95% CI) of overall hearing loss was 88.7%, (82.4-93.4), severe hearing loss was 21.6% (12.8-32.1) profound hearing loss was 39.8% (28.7-51.5), vertigo/imbalance was 42.0% (33.8-50.5), tinnitus was 61.8% (53.4-69.8) and facial nerve palsy was 30.6% (23.2-38.9). Generally, symptoms were homogeneous or moderately heterogeneous among included studies. CONCLUSION: This is the first systematic review of clinical presentations at ELST diagnosis. The most serious clinical events include profound hearing loss and facial impairment. Fluctuating hearing loss, tinnitus and vertigo are frequently reported and may confound correct and prompt ELST diagnosis.

Orbital wall decompression in the management of Graves' orbitopathy: a systematic review with meta-analysis.

PURPOSE: To systematically review outcomes of orbital bony wall decompression for Grave's orbitopathy according to the surgical approach. METHODS: A systematic search for studies published in "Ovid MEDLINE", "Web of Science" and "Embase" of patients with surgical treatment of Grave's orbitopathy was performed. The overall postoperative change in Hertel exophthalmometry was calculated by random-effect meta-analysis model with 95% confidence interval (CI). RESULTS: A total of 33 studies, including 1686 patients and 2946 procedures, were included. The weighted mean Hertel value overall reduction was - 4.56 mm (95% CI - 5.05 to - 4.07 mm). According to surgical techniques the reduction was - 4.36 mm (95% CI - 5.22 to - 3.50) for infero-medial technique, - 4.88 mm (- 5.68 to - 4.08) for medial-lateral technique, - 4.32 mm (- 4.80to - 3.84) for lateral technique, - 5.45 mm (- 6.16 to - 4.74) for three-wall technique and - 3.47 mm (- 5.81 to - 1.12) for medial technique. The overall rate of new-onset of primary gaze diplopia was reported in 23 studies. The included procedures were 653 and results were heterogeneous (heterogeneity: Q = 78.8 df = 22, I2 = 72.09%, p < 0.01). The pooled proportion (95% CI) rate of new-onset of primary gaze diplopia was 12% (7-16). CONCLUSION: Our metanalysis highlights that orbital bony wall decompression represents an effective surgical procedure. The three wall approach was associated with the best results in terms of exophthalmos reduction. Data suggest that an exclusive lateral approach may help to avoid the new-onset of primary gaze diplopia during the postoperative period.

Fine needle aspiration cytology for parotid neoplasms: risk of malignancy through inconclusive results and lower grade tumors.

PURPOSE: Fine needle aspiration cytology (FNAC) is a commonly performed procedure for parotid masses, although its accuracy in detecting malignancies widely varies through different series. We evaluated our single-center cohort of parotidectomies to highlight possible limitations of preoperative FNAC. METHODS: Seven hundred and eighteen consecutive patients submitted to parotid surgery at San Raffaele Scientific Institute (Milan) were retrospectively evaluated (2002-2018). Five hundred and fifty four FNAC were analyzed. FNAC accuracy was assessed with and without inclusion of "inconclusive" results. The peculiar role of lower grade primary parotid cancers was investigated. RESULTS: FNAC reports were "diagnostic" in 502 cases (90.4%) and "inconclusive" in 52 (9.6%). Histopathology revealed 488 benign lesions (88.1%) and 66 malignancies (11.9%). FNAC sensitivity, specificity, PPV, NPV and accuracy in detecting malignancies were 59%, 99%, 89%, 95%, and 95%, respectively. Sensitivity fell to 48%, when "inconclusive" FNAC was computed. Within 66 parotid cancers, FNAC could discriminate malignancy in 32 cases (48.5%), provide proper grading in 21 (31.8%), and precise histopathological diagnosis in 15 (22.7%). Malignancy was more likely in patients with "inconclusive" FNAC than in those with "diagnostic" cytologies (23.1% vs 10.8%, p = 0.003). Low-intermediate-grade primary parotid cancers were associated to a higher rate of FNAC failure in comparison with high-grade ones (86.4% vs 19.0%; p < 0.001). CONCLUSION: FNAC is an important tool for preoperative assessment of parotid masses, though its sensitivity in detecting malignancy remains poor. "Inconclusive" FNAC results could further jeopardize FNAC accuracy and should elicit resorting to additional tests, especially when a lower grade parotid cancer is suspected.

Low skeletal muscle mass as predictor of postoperative complications and decreased overall survival in locally advanced head and neck squamous cell carcinoma: the role of ultrasound of rectus femoris muscle.

PURPOSE: Skeletal muscle mass (SMM) depletion and sarcopenia as predictors of postoperative complications and poorer overall survival (OS) have been validated in many surgical fields through cross-sectional imaging (CT, MRI), with potential limitations. We evaluated it in a stage III-IV head and neck squamous cell carcinoma (HNSCC) surgical cohort through ultrasound (US) of rectus femoris muscle (RF), a quick, cheap, repeatable alternative. METHODS: Patients submitted to surgical treatment with curative purpose were recruited and prospectively evaluated through clinical, biometric, biochemical, surgical, pathological and functional prognosticators and with preoperative US of RF with regards to 30-day complications and OS. RESULTS: Forty-seven patients completed the study. RF cross-sectional area (RF-CSA) was used to identify patients with low SMM (CSA ≤ 0.97 cm2: 18/47, 38.3%). RF-CSA was lower in complicated cases (0.95 ± 0.48 vs 1.41 ± 0.49 cm2; p = 0.003), remaining the only independent predictor of postoperative complications at multivariate analysis, with a model including ASA score and modified Frailty index (OR 9.84; p = 0.004). SMM depletion significantly impaired OS (13.6 ± 2.9 vs 26.3 ± 2.1 months; p = 0.017), being its only independent prognosticator at multivariate Cox regression analysis (OR 4.42; p = 0.033). CONCLUSION: RF-CSA, evaluated with US, seems a reliable method for identification of patients with low SMM in a stage III-IV HNSCC cohort, defining a subset at high-risk of 30-day complications and poorer OS.

Prognostic aspects in the treatment of juvenile nasopharyngeal carcinoma: a systematic review.

To systematically review and discuss the published data about treatments and outcomes for children and adolescents affected by nasopharyngeal carcinoma. In April 2015, an appropriate string was run on PubMed to retrieve all relevant articles. A cross-check was performed by two of the authors on abstracts and full-text articles found using the selected inclusion and exclusion criteria. A meta-analysis concerning the rate of reported disease-free survival and overall survival was performed. Fifteen studies were identified comprising a total of 865 subjects affected by nasopharyngeal carcinoma. According to the American Joint Committee for Cancer Staging system, the majority of tumors were classified as Stage IV (57.3 %). All included patients underwent radiotherapy, while 687 (79.4 %) received also some regimen of chemotherapy. On the basis of our statistical analysis, the mean (95 % CI) rate of disease-free survival was 66 % (95 % CI 56-76). The mean (95 % CI) rate of the overall survival resulted 68 % (95 % CI 58-78). On the basis of our analysis, it may be affirmed that the prognosis of juvenile nasopharyngeal carcinoma is still unsatisfactory. New reports on homogeneous populations are needed to better define the most influencing prognostic factors and to evaluate the introduction of possible alternative therapeutic protocols.

Therapeutic modalities and oncologic outcomes in the treatment of T1b glottic squamous cell carcinoma: a systematic review.

T1a and T1b glottic squamous cell carcinoma (SCC) are often analyzed together by authors who investigate the oncologic outcomes achieved after different therapeutic options. Nevertheless, T1b definitely represents a more advanced tumor stage compared to T1a glottic SCC. The objective of this review was first to analyze the overall success rates in the treatment of patients affected by T1b glottic SCC. Moreover, a subgroup analysis was planned to specifically compare the outcomes obtained with radiotherapy (RT), transoral laser microsurgery (TLM) and open partial laryngectomies (OPL). An electronic library search of the relevant English literature was performed. Potentially eligible articles were reviewed. Qualified articles were selected and evaluated. Fifty-two studies comprising 2360 patients were included. The overall rate of disease-free survival (DFS) was 85% (95% CI 83-87). The overall rate of overall survival was 85% (95% CI 80-88) while the rate of disease-specific survival (DSS) was found to be 96% (95% CI 90-98). Statistical data concerning outcomes for each therapeutic modality showed an higher DFS rate for subjects treated with RT and OPL, respectively, 87% (95% CI 0.85-0.89) and 83% (95% CI 0.78-0.89), when compared to those who underwent TLM 77% (95% CI 0.69-0.83). In conclusion, our results showed a high level of overall DSS (96%) for patients affected by T1b glottic SCC. Regarding the specific therapeutic options, our subgroup analysis showed as patients treated with TLM present a higher rate of oncological recurrence in comparison to those who underwent RT or OPL. Nevertheless, on the basis of our data it was also noted that no significant differences subsist in terms of survival rates among the three different treatments. Moreover, the absence of a comparative analysis useful to confirm these conclusions must be considered.

Surgical Management of Endolymphatic Sac Tumor: A Systematic Review and Meta-Analysis.

The aim of our study was to report rates of facial nerve palsy and residual tumor following surgical intervention and subsequent tumor recurrence in patients with endolymphatic sac tumors. A systematic literature review of preoperative assessment and surgical management is also included. Studies including patient/s affected by sporadic or von Hippel-Lindau disease related endolymphatic sac tumors, reporting levels of facial nerve function, residual and recurrence pathology following a surgical procedure, were considered. Data were combined for proportional meta-analysis, and the selected studies' methodological quality was also evaluated. Overall 34 papers, including 202 subjects (209 cases of endolymphatic sac tumors) were analyzed. Pooled proportion rate (95% CI) of overall facial nerve palsy was 39.7% (28.2-51.9) and residual tumor was 16.5% (10.3-23.7) after surgical procedure. Pooled proportion rate (95% CI) of tumor recurrence was 14.0% (9.7-19.3) during a mean follow-up period of 49.7 months (8-136). Our results showed that preoperative facial nerve function is impaired in almost 30% of patients with endolymphatic sac tumors. Surgical management of endolymphatic sac tumor may cause a worsening of facial nerve function in a low percentage of treated subjects. Residual and/or recurrence of endolymphatic sac tumors are not rare events, and follow-up strategies should be designed accordingly.

Skeletal Muscle Depletion and Major Postoperative Complications in Locally-Advanced Head and Neck Cancer: A Comparison between Ultrasound of Rectus Femoris Muscle and Neck Cross-Sectional Imaging.

Skeletal muscle mass (SMM) depletion has been validated in many surgical fields as independent predictor of complications through cross-sectional imaging. We evaluated SMM depletion in a stage III-IV head and neck cancer cohort, comparing the accuracy of CT/MRI at C3 level with ultrasound (US) of rectus femoris muscle (RF) in terms of prediction of major complications. Patients submitted to surgery were recruited from 2016 to 2021. SMM was estimated on CT/MRI by calculating the sum of the cross-sectional area (CSA) of the sternocleidomastoid and paravertebral muscles at C3 level and its height-indexed value (cervical skeletal muscle index, CSMI) and on US by computing the CSA of RF. Specific thresholds were defined for both US and CT/MRI according to ROC curve in terms of best prediction of 30-day major complications to detect sarcopenic subjects (40-53%). Sixty-five patients completed the study. At univariate analysis, major complications were associated to lower RF CSA, lower CSA at C3 level and lower CSMI, together with previous radiotherapy, higher ASA score and higher modified frailty index (mFI). At multivariate analysis RF CSA (OR 7.07, p = 0.004), CSA at C3 level (OR 6.74, p = 0.005) and CSMI (OR 4.02, p = 0.025) were confirmed as independent predictors in three different models including radiotherapy, ASA score and mFI. This analysis proved the value of SMM depletion as predictor of major complications in a head and neck cancer cohort, either defined on cross-sectional imaging at C3 or on US of RF.

The importance of the patient's perspective in function-sparing parotid surgery for benign neoplasms: clinical reappraisal.

OBJECTIVE: Function-sparing surgery is the cornerstone for the treatment of benign parotid neoplasms. We assessed the incidences and determinants of the main postoperative complications, reappraising their influence on the patient's quality of life (QoL). METHODS: Patients who underwent parotid surgery for benign neoplasms were reviewed (2016-2019). Parotidectomy Outcome Inventory-8 (POI-8) and condition-specific questionnaires were used to investigate the patient's perspective. RESULTS: We enrolled 211 patients. Preservation of the posterior branch of the great auricular nerve (GAN) seemed to reduce early dysfunction (87% vs 96%, p = 0.053), but not the late one. Deep lobe dissection and resection of more than one parotid segment favoured first bite syndrome (FBS) and Frey's syndrome (FS), respectively (16% vs 3%, p = 0.003; 37% vs 15%, p = 0.003). Neither GAN impairment, FBS, nor FS influenced patient QoL. Facial weakness affected 19 patients (9%), being more likely after total parotidectomy (23% vs 7%, p = 0.034). According to POI-8, QoL was mainly jeopardised by fear of revision surgery, especially in females (p = 0.005) and those experiencing early complications (p = 0.004). CONCLUSIONS: Reappraisal of the patient's perspective after functional parotid surgery is fundamental to tailor preoperative counselling.

High-risk early-stage oral tongue squamous cell carcinoma, when free margins are not enough: Critical review.

Oral tongue squamous cell carcinoma (OTSCC) is a quite peculiar disease from an anatomical and biological standpoint. An increasing amount of literature highlights the existence of a small subset of T1-T2N0 OTSCC, properly resected on a margin-dependent basis, which conversely proved higher than expected rates of loco-regional/distant failure and disease-specific mortality. These specific high-risk tumors might not have a margin-dependent disease and could possibly benefit from a more aggressive upfront loco-regional treatment, especially addressing the so-called T-N tract. Widespread adoption of a histopathological risk model would allow early recognition of these high-risk diseases and, consequently, intensification of the traditional treatment strategies in that specific niche. We reviewed the available knowledge trying to shed light on the potential determinants of the dismal prognosis of these high-risk OTSCC, with special reference to the role of overlooked T-N tract involvement and possible alternatives in terms of elective neck management and risk stratification.

The prognostic value of anterior commissure involvement in T1 glottic cancer: A systematic review and meta-analysis.

OBJECTIVE: The anterior commissure is considered a laryngeal subsite, but it is not taken into account in the current T-staging system. The impact of anterior commissure involvement (ACI) on the oncologic outcomes of T1 glottic tumors has not been well defined and remains controversial. The aim of this study was to assess the influence of ACI in the prognosis of T1 glottic tumors. METHODS: A systematic review and meta-analysis of observational studies was performed by including studies published up to July 2019. Studies were selected if they had investigated the local control rate (LCR) at 5 years of clinical stage I (T1 and N0) glottic squamous cell carcinoma with and without ACI. The difference in LCR at 5 years between T1 glottic tumors without and with ACI was evaluated. RESULTS: The meta-analysis showed that the difference in LCR at 5 years between T1 glottic tumors without and with ACI is 12% (95% confidence interval: 8%-16%, p < 0,0001, I2 = 34.81%). CONCLUSIONS: Our study pointed out that the anterior commissure involvement is a negative prognostic factor in LCR at 5 years for T1 glottic tumors. Our results suggest the need to consider ACI in the T staging of glottic tumors. Laryngoscope, 130:1932-1940, 2020.

Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature.

Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.

Long-term Swallowing Function, Pulmonary Complications, and Quality of Life after Supracricoid Laryngectomy.

OBJECTIVES: Long-term effects of supracricoid laryngectomies are nowadays under discussion. The purpose of this study was to detect the prevalence of chronic aspiration and incidence of pulmonary complications, to investigate possible influencing factors, and to analyze dysphagia-related quality of life in a cohort of patients who recovered swallowing function after undergoing supracricoid laryngectomies. STUDY DESIGN: Retrospective observational study. SETTING: San Raffaele Hospital, Vita-Salute University, Milan, Italy. METHODS: A cohort of 39 patients who recovered swallowing function free of disease after a minimum 3-year follow-up period was retrospectively investigated between October and December 2017-clinically with the Pearson's Scale and M. D. Anderson Dysphagia Inventory and instrumentally with fiberoptic endoscopic evaluation of swallowing. RESULTS: Chronic aspiration was demonstrated in a significant portion of patients (clinically in 33.3% and instrumentally in 35.9%). Aspiration was influenced by advanced age at surgery (P = .020). Type of surgical procedure, resection of 1 arytenoid cartilage, postoperative rehabilitation with a speech-language therapist, radiotherapy, age at consultation, and length of follow-up did not influence the prevalence of aspiration. Pulmonary complications affected 5 patients; incidence of pulmonary complications was related to aspiration and was favored by poor laryngeal sensation/cough reflex. Aspiration significantly affected quality of life. CONCLUSIONS: Chronic aspiration is frequent and affects patients' quality of life. However, incidence of pulmonary complications is low; therefore, oral feeding should not be contraindicated for aspirating patients. Preservation of laryngeal sensation and cough reflex is mandatory to prevent pulmonary complications.

Diagnosis and Treatment of Laryngeal Schwannoma: A Systematic Review.

Objective This review summarizes the clinical features, diagnostic workup, and surgical treatment of laryngeal schwannoma with the aim of providing guidance for the management of this rare disease. The collated data allowed the statistical testing of several hypotheses, including the efficacy of endoscopic vs open surgical intervention and the usefulness of preoperative biopsy. Data Sources PubMed, Google Scholar, Cochrane, and SCOPUS. Review Methods Basic epidemiological and clinical presentation data were collated together with details of diagnostic image modality, lesion attributes, and the use of preoperative biopsy. Surgical approach to intervention and outcome was also collated and simple statistical analyses applied. Results The 60 original articles selected provided a combined cohort of 74 patients for review. The combined data revealed that schwannoma with pedunculated morphology were always safely removed by endoscopic resection regardless of size and should be treated as a separate entity. Of the nonpedunculated schwannoma, larger tumors were more likely to undergo an open approach, which in turn was associated with higher rates of tracheotomy and postoperative vocal fold paralysis. The small cohort did not reveal a significant association between surgery type and persistent disease. Interestingly, the data revealed a significant association between the use of incisional biopsy and persistent disease. Cases exhibiting extralaryngeal extension of the lesion were shown to exclusively belong to patients with neurofibromatosis/schwannomatosis syndromes. Conclusions Taken together, these findings suggest that incisional biopsy should be avoided, and given the benign nature of the pathology, the least invasive radical approach should be employed.

Rupture of the extracranial carotid artery caused by misdiagnosed infected pseudoaneurysm during deep cervical abscess drainage: A case report.

Infected aneurysms or pseudoaneurysms of the extracranial carotid artery are extremely rare, but they can lead to lethal complications. In some cases, infected pseudoaneurysms can be masked by the excessive inflammation of surrounding tissues. Here we describe the case of a 69-year-old woman with several comorbidities, who presented with a rapidly enlarging left neck bulge. CT was suggestive of an abscess involving the left common carotid artery. Colour Doppler ultrasound did not document intralesional flow. Abscess drainage under ultrasonographic assistance was attempted unsuccessfully, with collection of creamy, purple material. Surgical drainage of the abscess was, therefore, decided. As soon as necrotic tissue debridement was started, a massive haemorrhage originating from the common carotid artery invaded the surgical field. The carotid artery was then repaired with a bovine pericardial patch and covered with a pectoralis major muscle flap. The patient recovered without any neurological consequences. Revision of CT imaging revealed a very small misdiagnosed infected pseudoaneurysm. With better preoperative surgical planning and a good suspicion index, such a life-threatening emergency could have been avoided.

MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival. STUDY DESIGN: Retrospective cohort study. METHODS: Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. RESULTS: A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. CONCLUSIONS: A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences. LEVEL OF EVIDENCE: NA.