[Landscape of KRAS, BRAF, and PIK3CA Mutations and Clinical Features of EBV-Associated and Microsatellite Unstable Gastric Cancer].

Personalization of gastric cancer (GC) treatment is an urgent problem because of the clinical heterogeneity and aggressive course of the disease. Four GC subtypes were isolated based on molecular characteristics by The Cancer Genome Atlas researchers in 2014: Epstein-Barr virus positive (EBV^(+)), microsatellite unstable (MSI), chromosomally unstable (CIN), and genomically stable (GS). There is no unified method to detect the CIN and GS subtypes today, while MSI and EBV status assessments are used routinely and are of great clinical importance. A total of 159 GC samples were tested for MSI, EBV DNA, and somatic mutations in codons 12-13 (exon 2), 61 (exon 3), and 146 (exon 4) of the KRAS gene; codons 597-601 (exon 15) of the BRAF gene; and codons 542-546 (exon 9), 1047-1049 (exon 20) of the PIK3CA gene. EBV^(+) GC was detected in 8.2% of samples; and MSI, in 13.2%. MSI and EBV+ were found to be mutually exclusive. The mean ages at GC manifestation were 54.8 and 62.1 years in patients with EBV^(+) and MSI GCs, respectively. EBV^(+) GC affected men in 92.3% of cases, 76.2% of the patients were older than 50 years of age. Diffuse and intestinal adenocarcinomas were diagnosed in 6 (46.2%) and 5 (38.5%) EBV^(+) cases, respectively. MSI GC equally affected men (n = 10, 47.6%) and women (n = 11, 52.4%). The intestinal histological type was the most prevalent (71.4%); the lesser curvature was affected in 28.6% of the cases. The E545K variant of PIK3CA was observed in one EBV^(+) GC case. A combination of clinically significant variants of KRAS and PIK3CA was found in all MSI cases. The BRAF V600E mutation, which is specific to MSI colorectal cancer, was not detected. The EBV^(+) subtype was associated with better prognosis. The five-year survival rates were 100.0 and 54.7% for MSI and EBV^(+) GCs, respectively.

[Surgical and combined treatment of patients with duodenal stromal tumors]. / Osobennosti khirurgicheskogo i kombinirovannogo lecheniya bol'nykh stromal'noi opukhol'yu dvenadtsatiperstnoi kishki.

OBJECTIVE: To evaluate the immediate and long-term results of surgical and combined treatment of patients with duodenal stromal tumors. MATERIAL AND METHODS: There were 47 patients with duodenal stromal tumors for the period 2002-2019. All patients underwent treatment at the Blokhin National Cancer Research Center. Six patients had metastatic disease, 2 ones - a rare syndrome of duodenal stromal tumor associated with neurofibromatosis type 1, other 39 patients had a localized and locally-advanced disease. Surgical treatment was performed in 37 patients (limited resections (LR) in 24 cases and gastropancreaticoduodenectomy in 13 cases).Incidence of postoperative complications was significantly lower after limited resections compared to gastropancreaticoduodenectomy (22.2% (6/24) vs. 61.5% (8/13), respectively). Severe complications (Clavien-Dindo grade 3) occurred in 4.2% (1/24) vs. 15.3% (2/13) of patients, respectively. Postoperative mortality was absent in both groups. We observed no significant differences in long-term results. Overall 5-year survival was 91% and 70% (p=0.5960), 5-year recurrence-free survival - 65 and 70% (p=0.6226), respectively. CONCLUSION: Considering similar survival rates, lower postoperative morbidity and better quality of life, limited duodenal resections are preferred for duodenal stromal tumors.

[Gastrointestinal stromal duodenal tumors: diagnostic mistakes and modern approaches to treatment]. / Gastrointestinal'nye stromal'nye opukholi dvenadtsatiperstnoi kishki: oshibki diagnostiki i sovremennye podkhody k lecheniyu.

Gastrointestinal stromal duodenal tumors are rare diseases of small intestine. Duodenal GISTs may be giant; these neoplasms can also simulate malignancies of other organs. These features result diagnostic and treatment mistakes. Neoadjuvant therapy with imatinib results tumor shrinkage and ensures organ-sparing surgery. We report duodenal GISTs in patients with primary diagnosis «retroperitoneal tumor¼, «pancreatic cyst¼ and «retroperitoneal abscess¼, who were treated at the Blokhin National Cancer Research Centre in 2019-2020.

A Group of miRNA as Candidates for Prognostic Biomarkers of Gastric Cancer Metastasis.

An association was found between reduced expression of miR-34a, miR-146a with both metastasis to regional lymph nodes (relative risk RR=10.50 and RR=5.25, respectively) and the development of distant metastases (RR=9.50 and RR=4, 40, respectively) in gastric cancer. They are excellent classifiers: AUC>0.9 for both miRNAs. The association of miR-335 expression with metastasis to the lymph nodes is much weaker, but it is also a good classifier for identifying a group with distant metastasis (RR=5.90). A correlation was found between the expression of miR-34a and miR-146a during metastasis, which is absent in non-metastatic tumors. Thus, miR-34a, miR-146a, and miR-335 miRNAs can be proposed as candidates for biomarkers of the risk of gastric cancer metastasis.

[Distal duodenectomy: a new option of surgical treatment for duodenal tumors]. / Distal'naya duodenal'naya rezektsiya: novyi sposob khirurgicheskogo lecheniya pri opukholevom porazhenii dvenadtsatiperstnoi kishki.

OBJECTIVE: To assess severity, safety and functional advisability of distal pancreatectomy using original surgical technique developed in the Blokhin National Medical Research Centre of Oncology. MATERIAL AND METHODS: There were 10 patients with duodenal malignancies who have undergone distal pancreatectomy in the Blokhin National Medical Research Centre of Oncology for the period 2006-2018. Distal pancreatectomy for primary duodenal tumors was performed in 8 patients, 2 patients underwent surgery for external invasion of the duodenum. RESULTS: Postoperative complications Clavien-Dindo grade 1 and 2 occurred in 4 (40%) patients. Surgical complication grade 2 occurred in 1 (10%) patient (pancreatic fistula with effective conservative management). There were no cases of leakage of duodenal stump and duodenojejunostomy, impaired bile flow and stenosis of anastomosis with delayed stomach emptying. CONCLUSION: Distal duodenectomyis associated with low postoperative morbidity, good functionality and quality of life. This procedure is preferred for non-epithelial and neuroendocrine tumors, as well as with secondary malignant duodenal invasion.

[Iliac arteries and aortic repair in patients with retroperitoneal sarcoma]. / Plastika podvzdoshnykh arterii i aorty u bol'nykh neorgannoi zabriushinnoi sarkomoi (s kommentariem).

AIM: To evaluate the results of surgical treatment in patients with retroperitoneal sarcoma and invasion into great vessels. MATERIAL AND METHODS: For the period 2009-2016 fourteenth patients with retroperitoneal sarcoma underwent resection and repair of great vessels at the abdominal department of N.N. Blokhin Russian Cancer Research Center. In 12 cases circular resection of infrarenal aorta, aortic bifurcation and iliac arteries followed by their replacement was made. 2 patients underwent circular resection of iliac arteries. RESULTS: Postoperative morbidity was 42.8%. There was no postoperative mortality. 10 of 14 patients are alive from 2 to 70 months after surgery. One patient died in 2 months postoperatively from unknown reasons, 3 patients died in 18, 20 and 30 months respectively due to progression of the disease. CONCLUSION: Overall survival and acceptable surgical risk underline the value of en block resection of retroperitoneal sarcoma together with involvement blood vessels.

[Combined operations by retroperitoneal liposarcomas].

Retrospective analysis of 228 patients with retroperitoneal liposarcoma, operated on in the Russian Oncology Center during 1971-2010, has been done. Of 223 performed operations, 124 were combined, i.e., required multi-organ resection. The kidney was the most frequently removed organ both in cases of primary and recurrent tumors. 10-year survival rate was 26% after combined operations and 35% after surgery, they did not need the multiorgan resection.

[Surgical treatment of relapsing metastatic stromal tumor of the gastrointestinal tract].

The study included 63 patients with relapsing metastatic stromal tumor of the gastrointestinal tract (surgery - 34, tyrosinkinase inhibitors - 29). Cytoreductive surgery is indicated in patients showing positive response to target therapy. The highest survival rates were reported in cases of surgical treatment received in conjunction with pre- and postoperative therapy with tyrosinkinase inhibitors.

[LMP1 gene polymorphism in patients with Epstein-Barr virus-negative gastric carcinomas in Russia].

The investigation was undertaken to study the molecular characteristics of Epstein-Barr virus (EBV) LMP1 gene samples amplified from the tumor and intact tissues of patients with EBV-negative forms of gastric carcinoma (GC). The genetic structure of these samples determined by their sequencing was compared with that of the gene samples isolated from the cells of oropharyngeal washing specimens from the same patients with GC, as well as peripheral blood lymphocytes of patients with infectious mononucleosis (IM) and blood donors. The findings suggest that the samples of tumor tissue LMP1 from patients with GC have higher divergence than those from patients with IM and blood donors although no specific variants of the gene for GC were found. Comparison of LMP1 sequences from tumor tissue and cells of oropharyngeal washing specimens from the same patients with EBV-negative GC revealed the common LMP1 variant in 2 cases while they differed in 3 cases. The findings are an initial step in studying the role of EBV in the carcinogenesis of EBV-negative GC that is likely to be established by investigations on representative clinical material, by applying the up-to-date technologies.