Harrisludvigsen8819

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5-63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients' outcomes. Copyright © 2020 Katarzyna Pogoda et al.Carcinoid syndrome (CS) develops in patients with hormone-producing neuroendocrine neoplasms (NENs) when hormones reach a significant level in the systemic circulation. The classical symptoms of carcinoid syndrome are flushing, diarrhoea, abdominal pain, and wheezing. Neuroendocrine neoplasms can produce multiple hormones 5-hydroxytryptamine (serotonin) is the most well-known one, but histamine, catecholamines, and brady/tachykinins are also released. Serotonin overproduction can lead to symptoms and also stimulates fibrosis formation which can result in development of carcinoid syndrome-associated complications such as carcinoid heart disease (CaHD) and mesenteric fibrosis. Transforming growth factor beta (TGF-β) is one of the main factors in developing fibrosis, but platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF2), and connective tissue growth factor (CTGF or CCN2) are also related to fibrosis development. Treatment of CS focuses on reducing serotonin levels with somatostatin analogues (SSA's). Telotristat ethyl and peptide receptor radionuclide therapy (PRRT) have recently become available for patients with symptoms despite being established on SSA's. Screening for CaHD is advised, and early intervention prolongs survival. Mesenteric fibrosis is often present and associated with poorer survival, but the role for prophylactic surgery of this is unclear. Depression, anxiety, and cognitive impairment are frequently present symptoms in patients with CS but not always part of their care plan. The role of antidepressants, mainly SSRIs, is debatable, but recent retrospective studies show evidence for safe use in patients with CS. Carcinoid crisis is a life-threatening complication of CS which can appear spontaneously but mostly described during surgery, anaesthesia, chemotherapy, PRRT, and radiological procedures and may be prevented by octreotide administration. Copyright © 2020 Dominique Clement et al.Background This study aimed to investigate factors associated with the development of ileostomy complications in rectal cancer patients, including those who received neoadjuvant treatment. Methods This retrospective trial included 133 consecutive patients who underwent surgery for rectal cancer with temporary diverting ileostomy. Patients' demographic characteristics as well as the pre- and postclosure outcomes and complications were analyzed. Results In logistic regression analysis, longer duration of ileostomy emerged as a significant independent predictor of any complication during ileostomy. The respective odds ratios for 3-6 months and >6 months vs. less then 3 months of ileostomy duration were as follows OR, 4.5 (95% CI, 1.2-16.7), p=0.023; and OR, 15.2 (95% CI, 3.1-75.2), p=0.001. An additional stepwise model also identified hypertension as a significant predictor. In stepwise logistic regression model, adjuvant chemoradiotherapy emerged as significant independent predictor of "any ileostomy-related complication after ileostomy closure" OR, 4.5 (2.0-10.2), p less then 0.001. Conclusion Duration of ileostomy appears to be the main determinant of ileostomy-related complications. Patients who had received neoadjuvant or adjuvant therapy had longer ileostomy duration, which may be attributed to the concerns of the surgeon or to the complications themselves. Copyright © 2020 Nadir Adnan Hacim et al.Background Although surgery for hepatocellular carcinoma (HCC) complicated with inferior vena cava tumor thrombus (IVCTT) may improve survival for some patients, prognostic markers remain elusive because of its rarity. We constructed a prognostic nomogram which predicts individualized survival benefit of curative-intent surgery for HCC patients with IVCTT. Methods According to abdominothoracic anatomy of inferior vena cava (IVC), IVCTT can be divided into 3 types inferior diaphragmic (ID), superior diaphragmic (SD), and intracardiac type (IC). Data of 64 HCC patients with IVCTT who underwent curative-intent surgery between 2008 and 2015 in four centers in China were analyzed retrospectively. Univariate and multivariate Cox regression analyses were conducted to select variables for the construction of a prognostic nomogram. Predictive accuracy and discriminative ability were examined by concordance index (C-index) and calibration curve. Results Of 64 patients in the IVCTT classification, 37 (57.8%) were classified as ID type, 15 (23.4%) as SD type, and 12 (18.8%) as IC type. The 1-, 2-, 3-, and 5-year disease-specific survival (DSS) rates for patients in ID, SD, and IC groups were 94.4%, 55.6%, 71.4%, and 30.0%; 27.8%, 21.4%, 7.1%, and 0%; and 8.3%, 0%, 0%, and 0%, respectively. Independent factors included in the nomogram were ECOG performance status, AFP level ≥ 400 μg/L, tumor size ≥ 10 cm, portal vein tumor thrombosis, and IVCTT classification. The C-index of the nomogram was 0.812 (95% CI 0.761-0.873). The calibration plot for DSS probability showed excellent agreement between the prediction by nomogram and actual observation. Conclusions Curative-intent surgery should be carefully evaluated and suggested according to our novel IVCTT classification. We have developed a visual web-based nomogram model to predict oncological prognosis of curative-intent surgery for HCC patients with IVCTT. Copyright © 2020 Yannan Bai et al.Introduction The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. Objective Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. Methods We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. check details Results From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490-15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). Conclusions FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules. Copyright © 2020 Bernardo Marques et al.A battery of OECD- and GLP-compliant toxicological studies was performed to assess the safety of a highly purified germanium sesquioxide, an organic form of the naturally occurring, nonessential trace element germanium. Germanium dioxide and germanium lactate citrate (inorganic germaniums) have been shown to induce renal toxicity, whereas germanium sesquioxide (an organic germanium) has been shown to have a more favorable safety profile. However, past toxicity studies on germanium sesquioxide compounds have not clearly stated the purity of the tested compounds. In the studies reported herein, there was no evidence of mutagenicity in a bacterial reverse mutation test or an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/day. In a 90-day repeated-dose oral toxicity study in HanWIST rats conducted at doses of 0, 500, 1000, and 2000 mg/kg bw/day by gavage, there were no mortalities, treatment-related adverse effects, or target organs identified. The no-observed-adverse-effect-level (NOAEL) was determined to be 2000 mg/kg bw/day. Copyright © 2020 Robin A. Reddeman et al.Hi-C data is important for studying chromatin three-dimensional structure. However, the resolution of most existing Hi-C data is generally coarse due to sequencing cost. Therefore, it will be helpful if we can predict high-resolution Hi-C data from low-coverage sequencing data. Here we developed a novel and simple computational method based on deep learning named super-resolution Hi-C (SRHiC) to enhance the resolution of Hi-C data. We verified SRHiC on Hi-C data in human cell line. We also evaluated the generalization power of SRHiC by enhancing Hi-C data resolution in other human and mouse cell types. Results showed that SRHiC outperforms the state-of-the-art methods in accuracy of prediction. Copyright © 2020 Li and Dai.Mutations in the retinol dehydrogenase 12 (RDH12) gene are primarily associated with Leber congenital amaurosis (LCA) type 13, a severe early onset autosomal recessive retinal dystrophy. Only one family with a heterozygous variant, associated with mild retinitis pigmentosa (RP), has been reported. We report a novel heterozygous variant [(c.759del; p.(Phe254Leufs∗24)], resulting in a frameshift and premature termination identified in two unrelated individuals with familial autosomal dominant RP. Both heterozygous variants are associated with a late onset RP phenotype, suggesting a possible genotype-phenotype correlation. Copyright © 2020 Sarkar, Dubis, Downes and Moosajee.