[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.

Studying the Possibilities of Using 2-Halogen-Substituted Acetamides As Acyl Donors in Penicillin Acylase-Catalyzed Reactions.

The possibility of using amides of halogen-substituted acetic acids as acyl donors in penicillin acylase-catalyzed reactions has been investigated, and the ability of this group of compounds to inactivate enzymes in the course of the catalytic conversion has been established. The strongest inactivating effect was demonstrated by iodoacetamide and bromoacetamide. However, the negative contribution of this side activity can be minimized by decreasing the temperature, when the rate of acyl donor conversion by penicillin acylases is still high enough, but the impact of enzyme inactivation becomes less significant. The catalytic activity of penicillin acylase from Alcaligenes faecalis in the conversion of 2-haloacetamides was significantly (5-8 times) higher than that of penicillin acylase from Escherichia coli.

Publisher Correction: Wave kinetics of random fibre lasers.

This corrects the article DOI: 10.1038/ncomms7214.

[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.

Wave kinetics of random fibre lasers.

Traditional wave kinetics describes the slow evolution of systems with many degrees of freedom to equilibrium via numerous weak non-linear interactions and fails for very important class of dissipative (active) optical systems with cyclic gain and losses, such as lasers with non-linear intracavity dynamics. Here we introduce a conceptually new class of cyclic wave systems, characterized by non-uniform double-scale dynamics with strong periodic changes of the energy spectrum and slow evolution from cycle to cycle to a statistically steady state. Taking a practically important example-random fibre laser-we show that a model describing such a system is close to integrable non-linear Schrödinger equation and needs a new formalism of wave kinetics, developed here. We derive a non-linear kinetic theory of the laser spectrum, generalizing the seminal linear model of Schawlow and Townes. Experimental results agree with our theory. The work has implications for describing kinetics of cyclical systems beyond photonics.

[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.

[Statistical models of longevity, aging and degradation in demography, gerontology and oncology].

Several interesting papers related with the problems of mathematical modelling in connection with a study of aging and longevity have been published recently in "Advances of Gerontology"; see, for example, [1-4, 10, 11]. Following the main idea of these papers we consider here some approaches for construction of statistical models used today in survival analysis and reliability, and which can be used in demography, gerontology and carcinogenesis studies. We expose the so called dynamic regression models, which are well adapted for studies of survival in dynamic environments.

[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.

Flexible regression models for dynamic prediction of survival in elderly in presence of cancer or other chronic diseases.

We consider degradation and failure time models with multiple failure modes adapted for the statistical analysis of survival in the elderly in presence of chronic diseases such as cancer, but also other conditions like dementia, Alzheimer, diabetes, etc... These models can be applied in gerontology, general medicine, biology and demography for the analysis of longevity and survival of highly complex biological systems as any human is.

Accelerated degradation model and its applications to statistical analysis of the role played by dementia and sex in the loss of functional autonomy in elderly patients.

The paper considers the statistical analysis of aging and degradation processes in the elderly. The role played by dementia and sex in the loss of functional autonomy in elderly patients, in terms of progression and recovery, through several stages of increasing disability is analysed. The conjoint accelerated degradation model for statistical analysis of survival and degradation data is discussed.

Increased risk of developing atrophic gastritis in patients infected with CagA+ Helicobacter pylori.

BACKGROUND: To clarify the possible role of CagA positive (CagA+) Helicobacter pylori strains in the development of atrophic gastritis, the prevalence of antibodies to H. pylori and CagA (120 kD protein) was studied among subjects with atrophic and non-atrophic gastritis. METHODS: The study population was randomly selected among 12,252 Finnish men who were screened for atrophic corpus gastritis with serum pepsinogen I-assay (S-PGI). S-PGI level was used as a selection criterion. Group A consisted of 295 subjects with S-PGI <25 microg/l (low), group B of 320 subjects with S-PGI 25-100 microg/l (normal) and group C of 338 subjects with S-PGI >100 microg/l (high). Antibodies to H. pylori were measured with EIA and immunoblot analysis and antibodies to CagA with immunoblot analysis. Endoscopical and histological examinations were performed for 203 patients from group A. RESULTS: The prevalence of antibodies to H. pylori was significantly lower in group B than in groups A or C (P < 0.0001, chi-squared test). There was a significant association between the prevalence of antibodies to CagA and the lowered level of S-PGI (P < 0.0001, Jonckheere-Terpstra trend test). There was also a linear decrease in the prevalence of antibodies to CagA as the atrophic corpus gastritis became more severe (P < 0.0001, linear-by-linear trend test). CONCLUSION: The presence of antibodies to CagA seems to be associated with development of atrophic corpus gastritis.

Estimation in degradation models with explanatory variables.

Influence of covariates on degradation is modelled. Models which include dependence of the intensity of the process of traumatic events on the degradation level are also discussed. Estimation of reliability and degradation characteristics from data with covariates is considered in dynamic environments.

A probabilistic description of radioactive contamination: a multivariate model.

A multivariate discrete probability model is used to facilitate the description of gamma-ray spectroscopic data obtained from radioactively contaminated territory, east of the former Semipalatinsk nuclear test site in Kazakhstan. Two possible estimators of probabilities of interest have been considered: maximum likelihood and unbiased estimators. We show that unbiased estimators are much easier to compute. The model was used in two variants: (i) several radionuclides in spatially independent measurements, (ii) a single radionuclide in spatially dependent measurements. We show that, in both cases, it is important to take into account the correlation for the accurate evaluation of probabilities of interest.