ObjectiveInsulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs.DesignThe mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed.ResultsPanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate of YY1 mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additional DAXX/ATRX mutations could predict an increased relapse risk in the first 2-year period.ConclusionThese WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns and DAXX/ATRX mutations.

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Objective: Despite several nationwide cohort studies of germline BRCA1/2 mutations and several small cohort studies of somatic BRCA1/2 mutations in Chinese epithelial ovarian cancer (EOC) patients, little is known about the impact of these findings on survival outcomes in this population. In this study of 172 retrospectively recruited Chinese EOC patients, germline and somatic BRCA1/2 mutations and their value for predicting survival outcomes were evaluated. Methods: Unselected patients who visited the study center from January 1, 2011, to January 1, 2015, were recruited and asked to provide peripheral blood samples for this study if they were pathologically confirmed to have primary EOC. All patients received staging surgeries or debulking surgeries involving systemic platinum-based chemotherapy, and the patients were then followed up to December 1, 2017. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections and peripheral blood and sequenced for somatic and germline testing, respectively. The demographic and clinicopathological characteristics of the patients were collected to analyze the distribution of BRCA mutations in subgroups. Survival outcomes were compared among various BRCA mutation statuses using univariate and multivariate models. Results: In 58 (33.7%) patients, 63 variants were identified, including variants of unknown significance (VUS) in 18 patients (10.5%) and pathogenic or likely pathogenic variants in a partially overlapping set of 41 patients (23.8%). Germline BRCA mutations, somatic BRCA mutations, BRCA1 mutations in general, and BRCA2 mutations in general were found in 35 (20.3%), 7 (4.1%), 28 (16.3%), and 13 (7.6%) patients, respectively. Five recurrent mutations were identified. Personal and family cancer histories as well as hereditary breast and ovarian cancer (HBOC) criteria were associated with deleterious BRCA mutations both overall and in the germline specifically, whereas only age at diagnosis of EOC was associated with somatic BRCA mutations. In univariate and Cox regression analyses, patients with BRCA1/2 mutations in general had significant improvements in progression-free survival (PFS) and overall survival (OS). You et al. Germline and Somatic BRCA1/2 Mutations in EOC Conclusions: In Chinese EOC patients, the distributions and risk factors associated with germline and somatic BRCA1/2 mutations were similar to those previously reported in international studies. Deleterious BRCA mutations in general were associated with improved survival outcomes in this cohort.

ObjectiveTo investigate the clinical characteristics and survival outcomes of patients with malignant transformation arising from ovarian mature cystic teratoma (MT-MCT).MethodsThis retrospective study included patients with ovarian MCTs at Peking Union Medical College Hospital (PUMCH) during 1990.01-2020.12. When the pathologic histology was MT-MCT, detailed information was collected.ResultsOverall, 7229 ovarian MCT patients and 22 patients with MT-MCT were enrolled. The rate of malignant transformation of all ovarian MCTs was 0.30%. Most patients with MT-MCT were 51 (21–75) years old, and the tumor mass size was 10 (3–30) cm. The typical clinical symptoms were mainly abdominal pain and distension. The levels of tumor markers were elevated on preoperative examination. Early diagnosis could be made by ultrasonic examination, pelvic enhanced MRI and CT. Most patients underwent debulking surgery and adjuvant chemotherapy. The most common histological type to exhibit malignant transformation was squamous cell carcinoma (59.1%), followed by adenocarcinoma (13.6%), carcinoid (9.1%), and borderline tumor (18.2%). The 5-year RFS and OS rates were 54.5% and 81.8%, respectively. Patients with FIGO stage I had the best RFS (P=0.047) and OS (P=0.018), followed by those with FIGO stage II-IV.ConclusionMT-MCTs mainly occur in elderly females, are rare and have a poor prognosis. Advanced FIGO stage is a risk factor for survival. Although there is no standard treatment, cytoreductive debulking surgery and adjuvant chemotherapy could be considered. Perimenopausal and menopausal women with MCT should receive surgical treatment.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

BackgroundTo date, effect of preoperatively continued aspirin administration in off-pump coronary artery bypass grafting (CABG) is less known. We aimed to assess the effect of preoperatively continued aspirin use on early and mid-term outcomes in patients receiving off-pump CABG.MethodsFrom October 2009 to September 2013 at the Fuwai Hospital, 709 preoperative aspirin users were matched with unique 709 nonaspirin users using propensity score matching to obtain risk-adjusted outcome comparisons between the two groups. Early outcomes were in-hospital death, stroke, intra- and post-operative blood loss, reoperation for bleeding and blood product transfusion. Major adverse cardiac events (death, myocardial infarction or repeat revascularization), angina recurrence and cardiogenic readmission were considered as mid-term endpoints.ResultsThere were no significant differences among the groups in baseline characteristics after propensity score matching. The median intraoperative blood loss (600 ml versus 450 ml, P = 0.56), median postoperative blood loss (800 ml versus 790 ml, P = 0.60), blood transfusion requirements (25.1% versus 24.4%, P = 0.76) and composite outcome of in-hospital death, stroke and reoperation for bleeding (2.8% versus 1.6%, P = 0.10) were similar in aspirin and nonaspirin use group. At about 4 years follow-up, no significant difference was observed among the aspirin and nonaspirin use group in major adverse cardiac events free survival estimates (95.7% versus 91.5%, P = 0.23) and freedom from cardiogenic readmission (88.5% versus 85.3%, P = 0.77) whereas the angina recurrence free survival rates was 83.7% and 73.9% in the aspirin and nonaspirin use group respectively (P = 0.02), with odd ratio for preoperative aspirin estimated at 0.71 (95% confidence interval, 0.49-1.04, P = 0.08).ConclusionsPreoperatively continued aspirin use was not associated with increased risk of intra- and post-operative blood loss, blood transfusion requirements and composite outcome of in-hospital death, stroke and reoperation for bleeding in off-pump CABG. Preoperative aspirin use tended to decrease the hazard of mid-term angina recurrence.

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