How to Manage Advanced Differentiated Thyroid Cancer: Step-by-Step Analysis from Two Italian Tertiary Referral Centers.

BACKGROUND: Differentiated thyroid carcinoma (DTC) has an excellent prognosis; however, advanced disease is associated with a worse prognosis and is relatively common. Surgery followed by RAI treatment remains the mainstream treatment for a large majority of patients with high- and intermediate-risk DTC, but its benefits should be carefully weighed against the potential for harm. The aim of this paper is to critically review the experience in treating advanced DTC at two tertiary referral centers in Italy. METHODS: Retrospective analysis of 300 patients who underwent surgery for ADTC over 30 years. RESULTS: The complication rate was 50.33%. A total of 135 patients (45%) remained at regular follow-up, 118 (87.4%) were alive, while 17 (12.6%) were deceased. The mean overall survival at 12 years was 84.8% with a mean of 238 months. Eleven patients (8.1%) experienced a relapse after a median of 13 months. CONCLUSIONS: ADTC patients adequately treated can achieve prolonged survival even in the case of metastasis or disease relapse. Patients with ADTC should be referred to high-volume centers with the availability of an extended multidisciplinary team to receive tailored treatment.

Artificial intelligence, machine learning, and deep learning in rhinology: a systematic review.

PURPOSE: This PRISMA-compliant systematic review aims to analyze the existing applications of artificial intelligence (AI), machine learning, and deep learning for rhinological purposes and compare works in terms of data pool size, AI systems, input and outputs, and model reliability. METHODS: MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov databases. Search criteria were designed to include all studies published until December 2021 presenting or employing AI for rhinological applications. We selected all original studies specifying AI models reliability. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for data pool size, AI tools used, input and outputs, and model reliability. RESULTS: Among 1378 unique citations, 39 studies were deemed eligible. Most studies (n = 29) were technical papers. Input included compiled data, verbal data, and 2D images, while outputs were in most cases dichotomous or selected among nominal classes. The most frequently employed AI tools were support vector machine for compiled data and convolutional neural network for 2D images. Model reliability was variable, but in most cases was reported to be between 80% and 100%. CONCLUSIONS: AI has vast potential in rhinology, but an inherent lack of accessible code sources does not allow for sharing results and advancing research without reconstructing models from scratch. While data pools do not necessarily represent a problem for model construction, presently available tools appear limited in allowing employment of raw clinical data, thus demanding immense interpretive work prior to the analytic process.

Implementation of Routine Endoscopy with Narrow Band Imaging in the Evaluation of Oral and Upper Airways Lesions in Oral Chronic Graft-Versus-Host Disease: A Preliminary Study.

(1) Background: The aim of our study is to investigate the main oral lesion patterns in patients with oral graft-versus-host disease and to describe and validate the use of endoscopy enhanced with narrow-band imaging (NBI) as a personalized, reliable and user-friendly tool for the early detection of oral potentially diseases. (2) Methods: We retrospectively evaluated the medical records of 20 patients with chronic GVHD and with oral manifestations, who were referred to our "Interdisciplinary Center for Oropharyngeal Pathology (CIPO)" from January 2017 to July 2022. (3) Results: Data on GVHD, oral localization and NBI endoscopic evaluation are collected. A total of six mucositis, one mucosal erythematous change, ten lichenoid-like changes, eight erosive lesions, one leukoplakia, two erythroplakia and two case of blisters were observed. Two vascular abnormalities were seen with NBI, leading to one excisional biopsy. The patient was diagnosed with squamous cell carcinoma. (4) Conclusion: Our study is the first to highlight the relevance of the routine use of endoscopy with NBI in patients with oral chronic GVHD. We highlighted its role as a reliable, reproducible, easy-to-use and tailor-made tool in the follow-up of those patients and to allow an earlier identification of aberrant neoangiogenesis related to oral potentially malignant disorders and oral cancer.

Advanced Differentiated Thyroid Cancer: A Complex Condition Needing a Tailored Approach.

Differentiated thyroid cancers (DTCs) are slow-growing malignant tumours, including papillary and follicular carcinomas. Overall, prognosis is good, although it tends to worsen when local invasion occurs with bulky cervical nodes, or in the case of distant metastases. Surgery represents the main treatment for DTCs. However, radical excision is challenging and significant morbidity and functional loss can follow the treatment of the more advanced forms. Literature on advanced thyroid tumours, both differentiated and undifferentiated, does not provide clear and specific guidelines. This emerges the need for a tailored and multidisciplinary approach. In the present study, we report our single-centre experience of 111 advanced (local, regional, and distant) DTCs, investigating the rate of radical excision, peri-procedural and post-procedural complications, quality of life, persistence, recurrence rates, and survival rates. Results are critically appraised and compared to the existing published evidence review.

Conversion rates in robotic thyroid surgery: A systematic review and meta-analysis.

OBJECTIVE: To define the conversion risk to open procedure during robot-assisted thyroid surgery (RATS) identifying potential specific subclasses of procedures or accesses at higher conversion risk. METHODS: In a PRISMA-compliant framework, all original prospective studies providing RATS conversion rates from multiple databases were pooled in a random-effects meta-analysis. Conversion rates were compared between different typologies of thyroid surgery and robotic access. RESULTS: 13 studies were deemed eligible. Four conversions from two studies were reported out of 398 procedures. No significant heterogeneity was observed (Cochran's Q p = 0.932; I2 = 0%). The pooled conversion rate was 1% (95% confidence interval, 0.1%-2%). The ANOVA-Q test failed to show significant differences when comparing type of thyroid surgery or robotic access (respectively p = 0.766 and p = 0.457). CONCLUSION: While the conversion rate appears consistently low across studies, prospective data collection and systematic reporting of procedural complications are required for framing high-risk procedures and accesses.

Evidence of SARS-CoV-2 in nasal brushings and olfactory mucosa biopsies of COVID-19 patients.

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.

Adenoidectomy for middle ear disease in cleft palate children: a systematic review.

PURPOSE: Cleft palate children have a higher incidence of otitis media with effusion, more frequent recurrent acute otitis media episodes, and worse conductive hearing losses than non-cleft children. Nevertheless, data on adenoidectomy for middle ear disease in this patient group are scarce, since many feared worsening of velopharyngeal insufficiency after the procedure. This review aims at collecting the available evidence on this subject, to frame possible further areas of research and interventions. METHODS: A PRISMA-compliant systematic review was performed. Multiple databases were searched with criteria designed to include all studies focusing on the role of adenoidectomy in treating middle ear disease in cleft palate children. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for clinical indications and outcomes. RESULTS: Among 321 unique citations, 3 studies published between 1964 and 1972 (2 case series and a retrospective cohort study) were deemed eligible, with 136 treated patients. The outcomes were positive in all three articles in terms of conductive hearing loss improvement, recurrent otitis media episodes reduction, and effusive otitis media resolution. CONCLUSION: Despite promising results, research on adenoidectomy in treating middle ear disease in the cleft population has stopped in the mid-Seventies. No data are, therefore, available on the role of modern conservative adenoidectomy techniques (endoscopic and/or partial) in this context. Prospective studies are required to define the role of adenoidectomy in cleft children, most interestingly in specific subgroups such as patients requiring re-tympanostomy, given their known risk of otologic sequelae.

Management and Outcome of Parathyroid Carcinoma-Induced Primary Hyperparathyroidism: A Single-Centre Experience.

BACKGROUND: Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to its rarity, treatment is challenging. METHODS: A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. We identified and individually described the patients affected with PC. Then, we split all patients treated for PHPT into four groups based on the cause: PC, adenoma, atypical adenoma, and hyperplasia. Patients' demographics, preoperative evaluation results, intraoperative findings, and outcomes for the PC group were compared with groups of PHPT due to benign causes. RESULTS: Eight cases of PC were identified, five males and three females. Seven cases presented with symptoms of hypercalcemia and one with a neck mass. Five underwent en bloc resections and three local excisions. Histopathological features showed capsular invasion in four patients, capsular and soft tissue invasion in three patients, and vascular invasion in one case. No patients had distant metastasis. One patient was classed as high risk based on the Schulte classification system. All patients treated for PC were alive and disease-free at a mean follow-up of 38.4 months. When compared with other PHPT patients, PC patients were more frequently male and had higher preoperative blood calcium and PTH and lower phosphate levels, larger and heavier parathyroids excised, lower postoperative calcium, and a higher rate of postoperative hypoparathyroidism. CONCLUSION: Our study highlights some aspects valuable to suspect PC and differentiate PHPT-PC from benign causes of PHPT preoperatively. Preoperative suspicion of malignancy is essential to guarantee the best course of treatment for patients. Although limited for size and follow-up, the excellent outcome of our series seems to support the value of both surgery extension and risk class according to the Schulte classification as possible prognostic factors for recurrence.

Evaluation of Wisconsin and CaPTHUS Indices Usefulness for Predicting Monoglandular and Multiglandular Disease in Patients with Primary Hyperparathyroidism through the Analysis of a Single-Center Experience.

BACKGROUND: The main challenge for treating primary hyperparathyroidism (PHPT) is to understand if it is caused by a single adenoma (80-85% of the cases) or by a multiglandular disease (15-20%), both preoperatively and intraoperatively. For this reason, some preoperative scores were proposed in the literature, to perform focused parathyroidectomy, avoiding intraoperative parathormone assay (ioPTH). The most known are the CaPTHUS test and the Wisconsin index. We applied them to our experience. METHODS: A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. Only patients affected with benign PHPT and neck ultrasound performed at our institution were included. Both patients for whom preoperative imaging agreed with the localization of a single diseased parathyroid and those with only ultrasound or scintigraphy positive for parathyroid localization underwent Mini-Invasive Video-assisted parathyroidectomy. In all cases, ioPTH assay was performed. The conversion to bilateral neck exploration was decided based on the drop in ioPTH. CaPTHUS score and the Wisconsin index (Win) were applied to the series. CaPTHUS score ≥3 and Win index >1600, according to the original studies of the literature, were considered at high probability of monoglandular disease. Outcomes in these two groups were examined. RESULTS: 236 patients were eligible for the study. The pathology resulted in multiglandular disease in 24 patients (10.2%). Among these, 18 (75.0%) obtained a CaPTHUS score ≥3, and 20 (83.3%) had a Win index>1600. Intraoperative PTH allowed to identify multiglandular disease in 16 of 18 cases with CaPTHUS ≥3 and in 18 of 20 cases with win >1600, who could have been lost, based only on the results of these 2 tests. CONCLUSION: Based on our experience, CaPTHUS test and Wisconsin index were not so useful in predicting multiglandular disease as ioPTH.

Through The Back Door: Expiratory Accumulation of SARS-Cov-2 in the Olfactory Mucosa as Mechanism for CNS Penetration.

Introduction: SARS-CoV-2 is a respiratory virus supposed to enter the organism through aerosol or fomite transmission to the nose, eyes and oropharynx. It is responsible for various clinical symptoms, including hyposmia and other neurological ones. Current literature suggests the olfactory mucosa as a port of entry to the CNS, but how the virus reaches the olfactory groove is still unknown. Because the first neurological symptoms of invasion (hyposmia) do not correspond to first signs of infection, the hypothesis of direct contact through airborne droplets during primary infection and therefore during inspiration is not plausible. The aim of this study is to evaluate if a secondary spread to the olfactory groove in a retrograde manner during expiration could be more probable. Methods: Four three-dimensional virtual models were obtained from actual CT scans and used to simulate expiratory droplets. The volume mesh consists of 25 million of cells, the simulated condition is a steady expiration, driving a flow rate of 270 ml/s, for a duration of 0.6 seconds. The droplet diameter is of 5 µm. Results: The analysis of the simulations shows the virus to have a high probability to be deployed in the rhinopharynx, on the tail of medium and upper turbinates. The possibility for droplets to access the olfactory mucosa during the expiratory phase is lower than other nasal areas, but consistent. Discussion: The data obtained from these simulations demonstrates the virus can be deployed in the olfactory groove during expiration. Even if the total amount in a single act is scarce, it must be considered it is repeated tens of thousands of times a day, and the source of contamination continuously acts on a timescale of several days. The present results also imply CNS penetration of SARS-CoV-2 through olfactory mucosa might be considered a complication and, consequently, prevention strategies should be considered in diseased patients.

Sinonasal teratocarcinosarcoma treated with surgery and proton beam therapy: clinical, histological aspects and differential diagnosis of a new case.

Sinonasal teratocarcinosarcoma is a rare aggressive malignant tumor with a primary setting involving the nasal cavity followed by the ethmoid sinus and maxillary sinus. It accounts for approximately 3% of all head and neck cancers and less than 1% of all tumors. Nasal obstruction, recurrent epistaxis and headache represent the typical clinical presentation. Imaging shows the presence of a mass in the nasal cavity. The treatment usually consists of surgery and adjuvant intensity modulated radiotherapy. The rarity and the variability of the histological features make its diagnosis particularly difficult.In this paper, we report a case of sinonasal teratocarcinosarcoma in a 62-year-old male treated with a multidisciplinary approach. As an alternative to intensity modulated radiotherapy, we proposed proton beam therapy for the first time. The patient benefited from the new and personalized protocol that provided excellent results and few adverse effects. At 45 months follow-up there is no evidence of relapse and the patient is in good health.

Adenoidal Disease and Chronic Rhinosinusitis in Children-Is there a Link?

Adenoid hypertrophy (AH) is an extremely common condition in the pediatric and adolescent populations that can lead to various medical conditions, including acute rhinosusitis, with a percentage of these progressing to chronic rhinosinusitis (CRS). The relationship between AH and pediatric CRS has been extensively studied over the past few years and clinical consensus on the treatment has now been reached, allowing this treatment to become the preferred clinical practice. The purpose of this study is to review existing literature and data on the relationship between AH and CRS and the options for treatment. A systematic literature review was performed using a search line for "(Adenoiditis or Adenoid Hypertrophy) and Sinusitis and (Pediatric or Children)". At the end of the evaluation, 36 complete texts were analyzed, 17 of which were considered eligible for the final study, dating from 1997 to 2018. The total population of children assessed in the various studies was of 2371. The studies were categorized as surgical-observational, microbiological, genetic-immunological, and radiological. The analysis of the studies confirms the relationship between AH and CRS and supports the existing consensus on medical and surgical therapy. Furthermore, these studies underline the necessity to adapt medical and surgical treatment considering age, comorbidities including asthma and, if present, the Computed Tomography (CT) score.

Odontogenic rhinosinusitis and sinonasal complications of dental disease or treatment: prospective validation of a classification and treatment protocol.

PURPOSE: Odontogenic sinusitis and sinonasal complications of dental disease or treatment (SCDDT) represent a heterogeneous group of conditions that often require multidisciplinary care. The present study aims to prospectively validate a classification and treatment protocol for SCDDT patients. METHODS: One hundred twenty-eight consecutive patients (73 females and 45 males, mean age 52.4 years) affected by SCDDT not responding to dental and medical therapy were classified and surgically treated according to the proposed protocol. The protocol classified patients into three aetiology-based groups (preimplantologic, implantologic, and related to traditional dental diseases and procedures, respectively). The groups were further divided into classes according to the presence of oro-antral communications and/or dislocated dental hardware. Each condition was treated according to the class-related, protocol-defined treatment, by either a transnasal or combined transnasal/transoral approach. All patients were successfully classified according to our protocol. None of the proposed classes were redundant, and no condition fell outside the definitions. RESULTS: The surgical treatment protocol proved to be adequate and effective, in that 125 of the 128 patients completely recovered after surgical treatment. CONCLUSIONS: The term SCDDT and the consequent classification proposed by the authors appear, therefore, to be nosologically correct. Furthermore, the protocol-related proposed treatment appears to be clinically sound, with a success rate nearing 98%.