Somatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel. Mutations were detected most frequently in the CDH1 (13/47) and TP53 (12/47) genes. As expected, somatic CDH1 mutations were positively correlated with distant metastases (p = 0.019) and tumours with signet ring cells (p = 0.043). These findings confirm the association of the CDH1 mutations with diffuse GC type. TP53 mutations were found to be significantly associated with a decrease in overall survival in patients with Lauren diffuse-type tumours (p = 0.0085), T3-T4 tumours (p = 0.037), and stage III-IV tumours (p = 0.013). Our results confirm that the detection of mutations in the main driver genes may have a significant prognostic value for GC patients and provide an independent GC-related set of clinical and molecular genetic data.Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide after lung cancer and breast cancer. The incidence of GC is particularly high in East Asia, including China, Japan and Korea, and in South America 1 . Based on the Lauren classification, GC is divided into two main types, namely, intestinal and diffuse, which have different epidemiological, morphological and clinical features. Intestinal GC commonly appears in elderly patients with multifocal atrophic gastritis, which is accompanied by intestinal metaplasia or dysplasia. Diffuse GC is more common in younger patients, and its association with atrophic gastritis or intestinal metaplasia is not obvious. Clinical differences between these two types reflect different mechanisms of the development and molecular pathogenesis of tumours 2 . However, Lauren's classification is not closely associated with treatment and prognosis, necessitating the development of a classification combining clinical, morphological, and molecular features of GC in response to certain therapeutic modalities.Comprehensive studies, including analyses of the genome, epigenome, proteome and transcriptome, offered an entirely different view on the tumour, moving it out of a single plane and into a multidimensional spatial image. The ability to determine the tumour-specific spectrum of genetic and epigenetic changes enables us to expand our understanding of the molecular pathogenesis of the tumour and to obtain information about the potential of targeted therapies. Mutational profiling is one way to classify tumours depending on the mutation spectrum into specific molecular subtypes that differ from the standard morphological classification. The results of recent studies, such as TCGA Validation of mutations detected by next-generation sequencing. Validation of th...

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Background Laparoscopic surgery has justified its efficacy in the treatment of early gastric cancer. There are limited data indicating the eligibility of laparoscopic interventions in locally advanced gastric cancer. Publications describing the safety of laparoscopic techniques in the treatment of local and metastatic gastric cancer complicated by bleeding and stenosis are scarce. Methods The study included patients with histologically confirmed locally advanced and disseminated gastric cancer and complicated with bleeding and/or stenosis who underwent gastrectomy with vital indications between February 2012 and August 2018. Surgical and oncologic outcomes after laparoscopic surgery (laparoscopic surgery) and open surgery (OS) were compared. Results In total, 127 patients (LS, n = 52; OS, n = 75) were analyzed. Baseline characteristics were similar between the groups. Forty-four total gastrectomies with resection of the abdominal part of the esophagus, 63 distal subtotal (43 Billroth-I and 20 Billroth-II), and 19 proximal gastrectomies were performed. The median duration of surgery was significantly longer in the LS group, 253 min (interquartile range [IQR], 200–295) versus 210 min (IQR, 165–220) (p < 0.001), while median intraoperative blood loss in the LS group was significantly less, 180 ml (IQR, 146—214) versus 320 ml (IQR, 290–350), (p < 0.001). Early postoperative complications occurred in 35% in the LS group and in 45 % of patients in the OS group (p = 0.227). There was no difference in postoperative mortality rates between the groups (3 [6 %] versus 5 (7 %), p = 1.00). Median intensive care unit stay and median postoperative hospital stay were significantly shorter after laparoscopy, 2 (IQR, 1–2) versus 4 (IQR, 3–4) days, and 8 (IQR, 7–9) versus 10 (IQR, 8–12) days, both p < 0.001. After laparoscopy, patients started adjuvant chemotherapy significantly earlier than those after open surgery, 20 vs. 28 days (p < 0.001). However, overall survival rates were similar between the group. Three-year overall survival was 24% in the LS group and 27% in the OS groups. Conclusions Despite the technical complexity, in patients with complicated locally advanced and metastatic gastric cancer, laparoscopic gastrectomies were associated with longer operation time, reduced intraoperative blood loss, shorter reconvalescence, and similar morbidity, mortality rates and long-term oncologic outcomes compared to conventional open surgery.

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority (n = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority (n = 41), in histone modifier genes, among which mutations were most commonly found in KMT2D and KMT2C. Somatic mutations in KMT2D, KMT2C, ARID1A and CHD7 were mutually exclusive (p = 0.038). Mutations in ARID1A were associated with distant metastases (p = 0.03). The overall survival of patients in the group with metastases and in the group with tumors with signet ring cells was significantly reduced in the presence of mutations in epigenetic regulation genes (p = 0.036 and p = 0.041, respectively). Separately, somatic mutations in chromatin remodeling genes correlate with low survival rate of patients without distant metastasis (p = 0.045) and in the presence of signet ring cells (p = 0.0014). Our results suggest that mutations in epigenetic regulation genes may be valuable clinical markers and deserve further exploration in independent cohorts.

Российская ФедерацияЦель. Улучшение результатов лечения пациентов, страдающих циррозом печени, путем внутрипече-ночного введения криопреципитата, стимулирующего регенерацию органа.Материал и методы. В исследование включено 72 пациента, страдающих циррозом печени вирусной (НСV и НВV) и токсической этиологии. Цирроз печени класса А и В по Child-Pugh до введения криопреципитата был у 32 (44%) пациентов, класса С -у 40 (56%). Криопреципитат вводили чрескожно в печень пункционным методом под ультразвуковым контролем. Оценивали динамику клинико-лабораторных показателей, параметры порталь-ного кровотока у всех пациентов, изменения в морфологической картине биопсийного материала печени у 42 (58%) и показатели иммунного статуса у 38 (53%) пациентов до и после введения криопреципитата.Результаты. После стимуляции регенерации печени криопреципитатом у большинства пациентов от-мечено уменьшение выраженности клинических и лабораторных проявлений цирроза печени как через 3, так и через 6 и 12 месяцев после введения криопреципитата. Цирроз печени класса С через год регистрировался у 7 пациентов (до стимуляции -у 40). Через 12 месяцев у 65 (90%) достоверно уменьшился диаметр воротной и селезеночной вен. У 11 (15%) пациентов снизился индекс застоя, у 18 (25%) -сплено-портальный индекс. У 40 (95%) из 42 больных при морфологическом исследовании биоптата печени спустя год после проведенного лечения была выявлена положительная динамика (снижение воспалительно-клеточной инфильтрации, дистро-фических изменений, у 29 (69%) -уменьшение выраженности ступенчатого некроза гепатоцитов.Заключение. Введение криопреципитата в печень под ультразвуковым контролем является безопас-ным, так как позволяет избежать травмирования крупных внутрипеченочных сосудов. Криопреципитат оказывает стимулирующее действие на регенерацию печени, что улучшает ее функциональную активность и позволяет продлить время до трансплантации печени. Ключевые слова: цирроз печени, портальная гипертензия, хирургическое лечение, регенерация печени, малоинвазивная хирургия, криопреципитат, функциональная активностьObjectives. To improve the results of treating patients with liver cirrhosis by intrahepatic injection of cryoprecipitate, stimulating regeneration of cirrhotic liver.Methods. The study included 72 patients who suffered from hepatitis B virus (HBV) and hepatitis C virus (HCV) and toxic liver cirrhosis. 32 (44%) patients had liver cirrhosis grading Child-Pugh class B, and 40 (56%) patientsclass C. Cryoprecipitate injected percutaneously into the liver by puncture method under ultrasound guidance. Dynamics of clinical and laboratory parameters, portal blood flow in all patients, morphological changes in the liver biopsy were evaluated in 42 (58%) patients and immunological parameters › -in 38 (53%) patients before and after administration of cryoprecipitate.Results. The improvements of clinical and laboratory parameters were registered in 3, 6, and 12 months after the administration of cryoprecipitate in most patients. After a year 7 patients had Child-Pugh class C live...