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Δευτέρα 16 Νοεμβρίου 2020

Vestibular Schwannoma: What We Know and Where We are Heading

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Abstract

Vestibular schwannoma (VS) is a Schwann cell-derived tumour arising from the vestibulocochlear nerve. Although benign, it represents a threat to intracranial structures due to mass effect and carries a small risk of malignant transformation. VS therefore represents an important healthcare burden. We review the literature regarding pathogenesis, risk factors, and diagnosis of VS. The current and future potential management strategies are also discussed. A narrative review of all relevant papers known to the authors was conducted. The majority of VS remain clinically stable and do not require interventional procedures. Nevertheless, various surgical techniques exist for removing VS, the most common of which are translabyrinthine and retrosigmoid approaches. Due to surgical risks such as hearing loss, facial nerve dysfunction, post-operative headache, and cerebrospinal fluid leakage, a "watch and rescan" approach is adopted for most patients. Radiotherapy is a use ful alternative and has been shown to have a similar response for growth restriction. Due to the heterogeneous nature of VS, there is a lack of consensus regarding management of tumours that are too large for conservative management but too small to indicate surgery. Emerging biologic therapies, such as Bevacizumab, Everolimus, and Lapatinib, as well as anti-inflammatories like aspirin are promising potential treatments; however, long-term evidence of their efficacy is required. The knowledge base regarding VS continues to improve. With increased understanding of the pathogenesis of these tumors, we believe future work should focus on pharmacologic intervention. Biologic therapies aimed toward improved patient outcomes are particularly promising.

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Nasal Chondromesenchymal Hamartoma

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Abstract

Nasal chondromesenchymal hamartoma (NCMH) is a rare, benign lesion of the sinonasal tract. It usually presents as a polypoid mass in infants and older children. Imaging studies and endoscopy are required to delineate the extent of the lesion and aid in its excision. This unusual lesion is composed of proliferating mesenchymal and cartilaginous elements. Recently, a genetic association between NCMH and DICER1 mutation has been established. It is important for pathologists to be familiar with this entity to avoid misdiagnosis since the lesion is benign and surgical excision is curative.

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YAP1-NUTM1 Gene Fusion in Porocarcinoma of the External Auditory Canal

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Abstract

Gene fusions involving the NUTM1 gene (NUT) represent defining genetic markers of a highly aggressive carcinoma type with predilection for the midline structures of children and young adults, hence the original description as NUT midline carcinoma. Recent studies have increasingly documented involvement of the NUTM1 gene in the pathogenesis of other entities as well. We herein describe two cases of auditory canal carcinomas with features of porocarcinoma, both harboring a newly described YAP1-NUTM1 gene fusion. Patients were males aged 28 and 82 years who presented with slowly growing lesions in the external auditory canal. Histologic examination showed monomorphic basaloid and squamoid cells arranged into organoid solid aggregates, nests, ducts, small cysts, and focal pseudocribriform pattern with variable mitotic activity, infiltrative growth, and focal squamous differentiation, particularly in the most superficial part of the tumor. Immunohistochemistry revealed consistent reactivity for CK5, p63 and SOX10 and diffuse aberrant expression of TP53. CK7 expression was limited to a few luminal ductal cells. The androgen receptor and S100 were negative. Next generation sequencing (TruSight RNA fusion panel, Illumina) revealed the same YAP1-NUTM1 gene fusion in both tumors, which was subsequently confirmed by NUT-FISH and the monoclonal anti-NUT antibody. These cases represent a novel contribution to the spectrum of NUT-rearranged head and neck malignancies. This adnexal carcinoma variant should not be confused with the highly lethal NUT carcinoma based on NUT immunoreactivity alone.

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Anaplastic Large Cell Lymphoma with Oral Manifestation: A Series of Four Cases and Literature Review

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Abstract

The aim of this study was to describe the clinicopathological and immunohistochemical features of four cases of anaplastic large cell lymphoma (ALCL) diagnosed through oral manifestations. Clinical data were collected from charts of a single oral pathology laboratory over a 5-year period (2014–2019) and all cases were evaluated by conventional hematoxylin and eosin staining and an extended immunohistochemical panel comprising CD45, CD20, CD3, CD4, CD7, CD30, CD99, CD138, cytokeratin AE1/AE3, EMA, ALK, MUM-1 and Ki-67. The study included 3 male (75%) and 1 female (25%) patients, with a median age of 44 years. The most common intraoral affected site was the alveolar ridge (50%). Clinically, all cases were characterized as an ulcerated bleeding mass. Microscopically, proliferation of anaplastic large lymphoid cells with medium to large-sized, abundant amphophilic to eosinophilic cytoplasm and eccentric nuclei were observed. All cases were positive for CD30, while two cases strongly express ALK. Two patients died of the disease. Careful correlation of clinical, morphological and immunohistochemical data are necessary to establish the diagnosis of oral manifestation of ALCL since its microscopical features may mimic other malignant tumors. Clinicians and pathologists should consider ALCL in the differential diagnosis when evaluating oral ulcerated swellings exhibiting large lymphoid cells in patients with lymphadenopathy.

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COVID-19: Vaccine's Efficacy Near 95% / 1M Pediatric Cases

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Check out the latest COVID-19 news: Vaccine's efficacy & shelf-life: Moderna's candidate vaccine against SARS-CoV-2, known as mRNA-1273, has shown 94.5...
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Patisiran in hereditary transthyretin-mediated amyloidosis

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The clinical course of hereditary transthyretin-mediated amyloidosis has substantially changed in the past 10 years.1 Several clinical studies have widened the therapeutic landscape for the condition, including transthyretin (TTR) stabilisers and TTR gene silencers. The use of liver transplantation, which, until a few years ago, represented the only therapeutic choice, is now declining.1 Furthermore, new monoclonal antibodies targeting TTR deposits could be tested in future clinical trials.1
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Patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

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In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.
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Nothing to be ashamed of: sex robots for older adults with disabilities

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This paper spotlights ways in which sexual capacities relate to central human capabilities, such as the ability to generate a personally meaningful story of one's life; be physically, mentally and emotionally healthy; experience bodily integrity; affiliate and bond with others; feel and express a range of human emotions; and choose a plan of life. It sets forth a dignity-based argument for affording older people access to sex robots as part of reasonable efforts to support their central human capabilities at a flo or level. The argument develops stepwise: (1) first, I dispel ageism and negative stereotypes about later-life sexuality, showing their deep historical roots in medicine and science; (2) second, I set forth a positive argument, grounded in capability accounts of justice, for deploying sex robots for older people with disabilities; (3) finally, after responding to objections, I conclude that sex robots are a reasonable way to support later-life sexuality for persons with disabilities. While often depicted as a product for younger, able-bodied people, this paper is a bid for reimagining sex robots as a product for older, disabled people.

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Chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers

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Objective

Epidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome and EGFR copy number (CN) in pretreatment tissue and plasma cell-free DNA (cfDNA) of patients enrolled in a randomised first-line phase III clinical trial of chemotherapy or chemotherapy plus the anti-EGFR monoclonal antibody panitumumab in aGEA (NCT00824785).

Design

EGFR CN by eith er fluorescence in situ hybridisation (n=114) or digital-droplet PCR in tissues (n=250) and plasma cfDNAs (n=354) was available for 474 (86%) patients in the intention-to-treat (ITT) population. Tissue and plasma low-pass whole-genome sequencing was used to screen for coamplifications in receptor tyrosine kinases. Interaction between chemotherapy and EGFR inhibitors was modelled in patient-derived organoids (PDOs) from aGEA patients.

Results

EGFR amplification in cfDNA correlated with poor survival in the ITT population and similar trends were observed when the analysis was conducted in tissue and plasma by treatment arm. EGFR inhibition in combination with chemotherapy did not correlate with improved survival, even in patients with significant EGFR CN gains. Addition of anti-EGFR inhibitors to the chemotherapy agent epirubicin in PDOs, resulted in a paradoxical increase in viability and accelerated progression through the cell cycle, associated with p21 and cycli n B1 downregulation and cyclin E1 upregulation, selectively in organoids from EGFR-amplified aGEA.

Conclusion

EGFR CN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials.

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LSG vs MGB-OAGB: 5-Year Follow-up Data and Comparative Outcome of the Two Procedures over Long Term—Results of a Randomised Control Trial

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Abstract

Background

Bariatric surgery is a durable and effective way for the management of obesity and resolution of related comorbidities. The aim of this study is to evaluate the outcome of laparoscopic sleeve gastrectomy (LSG) and one-anastomosis gastric bypass (OAGB) over long term in a South Asian population.

Materials and Methods

This is a prospective randomised trial comparing the outcome of 100 and 101 LSG and OAGB patients respectively after 5-year follow-up. This study is in continuity with previous published papers with 1- and 3-year follow-up. 71 LSG and 73 OAGB patients followed at 5 years. The results of these patients were analysed and compared in terms of %EWL, comorbidity resolution and quality of life (QoL) at 5 years. Bariatric analysis reporting and outcome system (BAROS) was used to assess the outcome of patients.

Results

At 5-year follow-up, both LSG and OAGB patients performed well and patients had significant improvement in BMI (kg/m2). The mean preoperative BMI of LSG and OAGB patients was 44.89 ± 7.94 and 45.32 ± 8.24, and their mean BMI at 5 years was 33.41 ± 6.02, 30.80 ± 3.40 respectively. At 5 years, %EWL was 55.95 ± 27.01 and 65.28 ± 13.98 for LSG and OAGB patients respectively. The QoL score of LSG and OAGB patients was 1.86 ± 0.56 and 2.35 ± 0.41 while comorbidity score was 1.84 ± 0.68 and 2.24 ± 0.62 respectively at 5 years.

Conclusions

Both LSG and OAGB are effective bariatric procedures over long term with respect to weight loss, comorbidity resolution and improvement in QoL. OAGB is significantly better than LSG in all the three parameters at 5 years.

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18F-Fluorocholine PET/CT is a highly sensitive but poorly specific tool for identifying malignancy in thyroid nodules with indeterminate cytology: The Chocolate study.

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18F-Fluorocholine PET/CT is a highly sensitive but poorly specific tool for identifying malignancy in thyroid nodules with indeterminate cytology: The Chocolate study.

Thyroid. 2020 Nov 12;:

Authors: Ciappuccini R, Licaj I, Lasne-Cardon A, Babin E, de Raucourt D, Blanchard D, Bastit V, Saguet-Rysanek V, Lequesne J, Peyronnet D, Grellard JM, Clarisse B, Bardet S

Abstract
Background Refining the risk of malignancy in patients presenting thyroid nodules with indeterminate cytology (IC) is a critical challenge. We investigated the performances of 18F-Fluorocholine (FCH) PET/CT to predict malignancy. Methods Between May 2016 and March 2019, 107 patients presenting a thyroid nodule ≥15 mm with IC and eligible for surgery were prospectively included (ClinicalTrials.gov identifier: NCT02784223). Head-and-neck PET/CT acquisitions were performed 20 min and 60 min after injection of 1.5 MBq/kg of FCH. PET/CT acquisition was scored positive when maximal standardized uptake value in the IC nodule was higher than in the thyroid background. Pathology was the gold standard. Results At pathology, 19 (18%) nodules were malignant, 87 were benign and one was a non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) of FCH PET/ CT in detecting cancer or NIFTP were respectively 90%, 50%, 55%, 29% and 96% at 20 min and 85%, 49%, 67%, 28%, and 94% at 60 min. Higher specificity (58% vs 33%, p=0.01) was observed in non-oncocytic (n=72) than in oncocytic IC nodules (n=35). The pre-PET/CT probability of cancer or NIFTP in Bethesda III-IV nodules was 11% and the post-PET/CT probability was 19% in PET-positives and 0% in PET-negatives. A posteriori, 42% of surgeries were unnecessary after PET/CT and 81% before (p<0.001), resulting in a hypothetical 48% reduction (95% CI, 32-64). Conclusions FCH PET/CT offers high NPV to reliably exclude cancer in PET-negative IC nodules but suffers from low PPV, particularly in those with oncocytic cytology.

PMID: 33183159 [PubMed - as supplied by publisher]

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Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology.

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Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology.

Thyroid. 2020 Nov 12;:

Authors: McNally R, Jones JH, Shaikh MG, Donaldson M, Blakey K, Cheetham T

Abstract
BACKGROUND: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis is unknown. If transient environmental factors can impact on thyroid gland development then clustering of cases in time and / or space may occur and this would be more likely in thyroid dysgenesis than dyshormonogenesis.
METHODS: The newborn screening programme for CHT in Scotland is linked to a central database that includes case details such as post-code. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space-time clustering analysis (using a method based on K-functions, with nearest neighbor thresholds) of CHT in Scotland 1979-2015. We also looked for evidence of overall changes associated with sex and area-based birth density.
RESULTS: Of 531 cases with CHT during the study period, 290 had been categorized as dysgenesis (229) or dyshormonogenesis (61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology but there was no seasonality. There was no evidence of overall space-time clustering (p = 0.06), but there was evidence of clustering in babies with dysgenesis (p = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space-time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases (p < 0.001). Clustering of these cases was restricted to females, but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of dyshormonogenesis.
CONCLUSIONS: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid dysgenesis in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors.

PMID: 33183175 [PubMed - as supplied by publisher]

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