Fast-Tracking of Publication Times of Otolaryngology Papers During the COVID-19 Pandemic

Introduction The outbreak of COVID-19 has produced an unprecedented number of trials and articles

The Immune Interplay between Thyroid Papillary Carcinoma and Hepatic Fibrosis.

A high prevalence of thyroid papillary cancer was reported in hepatitis-C-virus (HCV) positive patients. However, the mechanistic role of hepatic-fibrosis in thyroid malignancy progressions is still unclear.We aimed to study the immune-modulatory interactions between thyroid papillary carcinoma and hepatic-fibrosis.Hepatic-fibrosis was induced in nude-nu-male mice by intra-peritoneal administration of carbon-tetrachloride. To induce thyroid-tumor, a thyroid papillary carcinoma cell line (NPA) was injected subcutaneously in the backs. Fibrotic profile was estimated by α-smooth-muscle-actin (αSMA) expression in liver tissue extracts using western-blots and RT-PCR. Intra-hepatic NK cells were isolated and stained for NK activity (CD107a) by flow cytometry. Liver histopathology (H&E staining), thyroid tumor mass and serum alanine aminotransferase (ALT), serum vascular endothelial growth factor (VEGF) and free-T4 levels were also assessed.Ex-vivo: NPA cells were co-cultured with intra-hepatic NK cells isolated from fibrotic mice with/without the tumor were analyzed for CFSE-proliferations. Both tumor groups (with/without hepatic-fibrosis) excreted higher serum free T4 levels. Hepatic-fibrosis increased tumor weight and size and serum free-T4 levels. In addition, tumor induction increased liver injury (both hepatic-fibrosis, necro-inflammation and serum ALT levels). In addition, tumor-bearing animals with hepatic-fibrosis had increased NK activity. NPA tumor-bearing animals increased fibrosis in spite of increased NK activity; probably due to a direct effect through increased serum free-T4 excretions. Serum VEGF levels were significantly increased in the fibrotic- bearing tumor groups compared to the non-fibrotic groups. In-vitro, NK cells from fibrotic tumor-bearing animals reduced proliferation of NPA cells. This decrease is attributed to increase NK cells activity in the fibrotic animals with the NPA tumors.Our results propose that NK cells although were stimulated in advanced fibrosis with tumor, they lost their anti-tumor and anti-fibrotic activity probably due to secretions of T4 and VEFG and may explain increased risk of thyroid tumors in chronic HCV patients

The Prognostic Value and Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test in Cutaneous Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Background: The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for identifying patients at high risk of cSCC. This meta-analysis aimed to assess the prognostic significance of a 40-gene expression profile (40-GEP) both independently and integrated with clinicopathologic risk factors and established staging systems (American Joint Committee on Cancer, eighth edition (AJCC8) and Brigham and Women’s Hospital (BWH)). Methods: Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar, were systematically searched to identify cohort studies and randomized controlled trials on evaluations of the prediction value of 40-GEP in cSCC patients up to January 2023. The metastatic risk analysis of a given 40-GEP class combined with tumor stage and/or other clinicopathologic risk factors was based upon log hazard ratios (HRs) and their standard error (SE). Heterogeneity and subgroup analyses were performed, and data quality was assessed. Results: A total of 1019 patients from three cohort studies were included in this meta-analysis. The overall three-year metastatic-free survival rates were 92.4%, 78.9%, and 45.4% for class 1 (low risk), class 2A (Intermediate risk), and class 2B (high risk) 40-GEP, respectively, indicating a significant variation in survival rates between the risk classification groups. The pooled positive predictive value was significantly higher in class 2B when compared to AJCC8 or BWH. The subgroup analyses demonstrated significant superiority of integrating 40-GEP with clinicopathologic risk factors or AJCC8/BWH, especially for class 2B patients. Conclusions: The integration of 40-GEP with staging systems can improve the identification of cSCC patients at high risk of metastasis, potentially leading to improved care and outcomes, especially in the high-risk class 2B group

Obstetrical Outcomes of Head and Neck (Nonthyroid) Cancers: A 27-Year Retrospective Series and Literature Review

Abstract Objective To describe the clinical presentation and obstetrical outcomes of nonthyroid head and neck cancers (HNCs), and to review literature on this rare condition in pregnancy. Study Design Pregnant women with nonthyroid HNC were identified retrospectively from 1990 to 2017. Maternal, neonatal, pregnancy, and demographic data were collected. A review of the literature from January 1980 to May 2018 was performed. Results Over the 27-year time period, 16 women with history of nonthyroid HNC were identified (9 diagnosed during and 7 diagnosed before current pregnancy). The cases were analyzed in detail and the most updated review of management of each type of HNC was provided. Conclusions HNCs are rare with diagnosis and management challenges during pregnancy. In this series, the cases diagnosed and managed previously to pregnancy presented better perinatal outcomes than the cases presented during pregnancy. The maternal outcomes appeared similar for HNC diagnosed before or after pregnancy

Hepatic fibrosis increase NPA tumor weight and size.

<p>In vivo S.C injection of NPA cells model was performed as described in M&M. In this model; S.C NPA-cells tumor was induced in fibrotic and naïve (no fibrosis) animals. S.C tumors were explanted at the end of 6 weeks post S.C injection, and evaluated for tumor weight and volume. (A) and (B) show the external appearance of the tumor in the animal’s back. Tumor weight (C) and volume (D) was increased significantly from (0.13±0.06gr) and (0.28±0.18ml) in the fibrotic group to (0.05±0.025 gr) and (0.09±0.01ml) in the non-fibrotic group; p-value = 0.02 and 0.04, respectively.</p

VEGF serum levels.

<p>Quantikine Mouse VEGF immunoassay serum levels was significantly increased in the fibrotic group bearing tumor as compared to tumor alone (p = 0.01) or fibrosis alone groups (p = 0.04). No statistical significant differences were found in VEGF serum levels between the fibrotic and non-fibrotic group with tumor induction.</p

NPA Tumor inductions increase the severity of CCl4 related hepatic injury.

<p>CCl4-hepatic injury was evaluated by hematoxylin and eosin (H&E) staining of necro-inflammatory liver lesions and ALT serum levels. Immunohistochemical staining with H&E (5X magnification) for the four major animal groups showed necro-inflammatory lesions and cell infiltrations that were increased in the fibrotic mice receiving the NPA-tumor cells (D) as compared to fibrotic alone (C). Arrows indicate the area with lymphocyte infiltrations. No inflammatory infiltrates were seen in H&E staining of (A) naïve WT and (B) naïve mice receiving the NPA-tumor cells. (E) Serum ALT levels were in line with histological findings and showed increase from (60±25/L) in fibrotic animals without tumor to (85.5 ± 20.5 U/L) in animals with tumor and hepatic fibrosis; p-value = 0.021.</p

In vitro co-culture of lymphocytes with NPA cell line.

<p>Adhered-NPA cells post co-culture with NK cells from different animal groups were analyzed for proliferation by CFSE using flow cytometry. (A) Direct co-culture of NPA cells with spleen NKs from fibrotic mice with tumor significantly decreased NPA tumor cell proliferation compared to the fibrotic mice without tumor, indicating highly stimulated NK cells effects; p-value = 0.001. (B) A representative histogram of the NPA cells following incubations with NK cells of fibrosis and tumor mice. The histogram shows CSFE-proliferations changes in day 3 and day 5 as compared to day 0 of CSFE staining. Proliferations fold changes were calculated by divided day 0 to day 5.</p

Accuracy and reproducibility of virtual cutting guides and 3D-navigation for osteotomies of the mandible and maxilla.

BACKGROUND:We set out to determine the accuracy of 3D-navigated mandibular and maxillary osteotomies with the ultimate aim to integrate virtual cutting guides and 3D-navigation into ablative and reconstructive head and neck surgery. METHODS:Four surgeons (two attending, two clinical fellows) completed 224 unnavigated and 224 3D-navigated osteotomies on anatomical models according to preoperative 3D plans. The osteotomized bones were scanned and analyzed. RESULTS:Median distance from the virtual plan was 2.1 mm unnavigated (IQR 2.6 mm, ≥3 mm in 33%) and 1.2 mm 3D-navigated (IQR 1.1 mm, ≥3 mm in 6%) (P<0.0001); median pitch was 4.5° unnavigated (IQR 7.1°) and 3.5° 3D-navigated (IQR 4.0°) (P<0.0001); median roll was 7.4° unnavigated (IQR 8.5°) and 2.6° 3D-navigated (IQR 3.8°) (P<0.0001). CONCLUSION:3D-rendering enables osteotomy navigation. 3 mm is an appropriate planning distance. The next steps are translating virtual cutting guides to free bone flap reconstruction and clinical use