[Comparative immunohistochemistry study of different antibodies clones for detection of breast cancer markers (estrogen receptor, progesterone receptor, HER2/neu, Ki-67)]. / Sravnitel'noe issledovanie antitel razlichnykh klonov dlya vyyavleniya markerov raka molochnoi zhelezy (retseptorov estrogenov, progesterona, HER2/neu, Ki-67) immunogistokhimicheskim metodom.

OBJECTIVE: A comparative study of detection of breast cancer markers (estrogen receptors, progesterone receptors, HER2/neu, Ki-67) by immunohistochemical method with antibodies produced by PrimeBioMed (Russia) and antibodies produced by Roche Ventana (USA). MATERIAL AND METHODS: Surgical specimens and biopsies from 37 patients with invasive breast cancer were used. Sections were stained with antibodies of clones ER SP1 and GM030, PR 1E2 and PBM-5B8, HER2/neu 4B5 and PBM-46A6, Ki-67 30-9 and GM010. RESULTS: There was a high positive and significant correlation between the immunohistochemistry results and antibodies of the clones ER-SP1 and GM030, PR1E2 and PBM-5B8, HER2/neu4B5 and PBM-46A6, Ki-67 30-9 and GM010. CONCLUSION: The study showed the possibility of using antibodies of clones GM030, HER2/neu 4B5, PBM-46A6, GM010 (PrimeBioMed) on the Ventana Bench Marck Ultra automatic immunostainer using the detection system UltraView Universal DAB Detection Kit.

[Prognostic significance of PD-L1 expression as a potential predictor of survival in gastric cancer]. / Prognosticheskaya znachimost' ekspressii PD-L1 kak potentsial'nogo prediktora vyzhivaemosti pri rake zheludka.

BACKGROUND: Currently, PD-L1 expression in patients with tumors of various localizations is being actively studied. Studies on the expression of PD-L1 detected by clones SP142 and SP263 in gastric cancer (for the drugs atezolizumab and durvalumab, respectively) are rare in the literature. The prognostic role of PD-L1 expression in patients who were not treated with immune checkpoint inhibitors has also not been investigated. OBJECTIVE: To determine the expression level of PD-L1 (clones SP263 and SP142, Roche Ventana) in gastric cancer specimens and evaluate its effect on overall survival in patients who did not receive adjuvant therapy with immune checkpoint inhibitors. MATERIAL AND METHODS: The study included 131 patients with a verified diagnosis of gastric cancer. The material obtained from 127 patients was stained with antibodies to PD-L1 SP263, and from 126 patients - with antibodies to PD-L1 SP142. A multivariate Cox regression model with Wald's step-by-step exclusion algorithm was used to evaluate predictors of survival. RESULTS: The total five-year survival rate of patients in the PD-L1-negative tumor group was significantly lower than the total five-year survival rate of patients in the PD-L1-positive tumor group, which was 50.0% and 40.0% also for both clones (p=0.027). An increase in the expression of PD-L1 clone SP263, determined by both the CPS and TPS method, reduces the chances of death by 1.35 times (p=0.02) and 1.61 times (p=0.004), respectively. An increase in the expression of PD-L1 clone SP142, determined by the CPS method, reduces the chances of death by 1.54 times (p=0.005). CONCLUSION: The survival rate of patients in the group of PD-L1-positive tumors is significantly higher than in patients in the group of PD-L1-negative tumors. Elevated PD-L1 expression, as assessed by the SP263 and SP142 clones, is an important prognostic marker that predicts a higher chance of overall survival for patients, even though these patients are not receiving immune checkpoint inhibitors adjuvant therapy.

[Features of encrustation of ureteral stents in patients with calcium oxalate and urinary acid stones].

INTRODUCTION: Stent encrustation is one of the most difficult problems that can lead to difficulties in stent removal, while ureteral obstruction can lead to renal failure. Despite the search for various preventive measures, it still remains unresolved. AIM: To study the effect of Blemaren on stent encrustation in patients with calcium-containing and uric acid stones after ureteroscopy with lithotripsy. MATERIALS AND METHODS: A total of 60 patients with ureteral stones who underwent ureteroscopy with lithotripsy in A.V. Vishnevsky National Medical Research Center of Surgery from January to August 2022, were included in the study. In all cases ureteral stents 6 Ch were placed at the end of the procedure. Patients with uric acid and calcium oxalate stones (n=48) were randomized into two groups: in the main group (n=20), they were prescribed Blemaren up to the stent removal. In the control group (n=28), patients did not receive additional therapy. To determine the severity of incrustation, we used our own classification, where the percentage of lithogenic deposits relative to the lumen of the stent was calculated. Visual assessment and microscopic examination of the removed stents were performed on days 30+/-4.1 and 60+/-7.3. RESULTS: In patients of both groups, the severity of encrustation on the 30th day after stent placement was low (up to 30%). There were no significant differences between the groups (p=0.421). The main changes were detected 60 days after stent placement. Microscopic study revealed significant differences between two groups. In patients who did not receive Blemaren, microscopic signs of encrustation of the proximal curl of the stent occurred 2.5 times more often than in the main group (p=0.001). CONCLUSIONS: 1. The number of encrusted stents in patients with calcium oxalate and uric acid stones who did not receive Blemaren significantly increases after two months. 2. Upper urinary tract drainage with a stent for a period of more than 2 months is possible if clinically necessary, however, preventive measures to reduce the risk of encrustation should be applied.

Alanine response to low energy synchrotron x-ray radiation.

Objective. The radiation response of alanine is very well characterized in the MV photon energy range where it can be used to determine the dose delivered with an accuracy better than 1%, making it suitable as a secondary standard detector in cancer radiation therapy. This is not the case in the very low energy keV x-ray range where the alanine response is affected by large uncertainties and is strongly dependent on the x-ray beam energy. This motivated the study undertaken here.Approach. Alanine pellets with a nominal thickness of 0.5 mm and diameter of 5 mm were irradiated with monoenergetic x-rays at the Diamond Light Source synchrotron, to quantify their response in the 8-20 keV range relative to60Co radiation. The absorbed dose to graphite was measured with a small portable graphite calorimeter, and the DOSRZnrc code in the EGSnrc Monte Carlo package was used to calculate conversion factors between the measured dose to graphite and the absorbed dose to water delivered to the alanine pellets. GafChromic EBT3 films were used to measure the beam profile for modelling in the MC simulations.Main results. The relative responses measured in this energy range were found to range from 0.616 to 0.643, with a combined relative expanded uncertainty of 3.4%-3.5% (k= 2), where the majority of the uncertainty originated from the uncertainty in the alanine readout, due to the small size of the pellets used.Significance. The measured values were in good agreement with previously published data in the overlapping region of x-ray energies, while this work extended the dataset to lower energies. By measuring the response to monoenergetic x-rays, the response to a more complex broad-spectrum x-ray source can be inferred if the spectrum is known, meaning that this work supports the establishment of alanine as a secondary standard dosimeter for low-energy x-ray sources.

[Mortality in acute appendicitis in Russia]. / Letal'nost' pri ostrom appenditsite v Rossii.

OBJECTIVE: To analyze the causes of mortality in patients with acute appendicitis in Russia. MATERIAL AND METHODS: We retrospectively studied mortality in patients with acute appendicitis in the Russian Federation in 2020. We surveyed the hospitals with mortality reported in the electronic database of annual reports to the chief surgeon of the Ministry of Health of the Russian Federation. RESULTS: There were 259 deaths among 150.393 patients with acute appendicitis aged ≥18 years (in-hospital mortality 0.17%). We obtained data about 95.8% (n=248) of lethal cases including 86.3% (n=214) complicated and 13.7% (n=34) uncomplicated forms of disease. Two patients died without surgery (0.8%). Among the deceased, 58.2% (n=145) were men and 41.8% (n=103) were women. Mean patient age was 66.2 years [0.95% CI 64.2-68.1]. The main cause of death in complicated appendicitis was late presentation (after 4.9 days [0.95% CI 4.3-5.4]) that resulted peritonitis and sepsis in 71.5% (n=153) of patients. Cardiovascular diseases were noted in 23.4% (n=50) of cases. A new coronavirus infection was detected in 7.0% (n=15) of patients. However, COVID-19 as a direct cause of death was recognized in 2.8% (n=6) of cases. Other reasons accounted for 2.3% (n=5). In uncomplicated appendicitis, cardiovascular diseases were the main cause of mortality (73.5%, n=25). Peritonitis and sepsis were found in 11.8% (n=4) of cases, COVID-19 - in 5.9% (n=2). Other causes accounted for 8.8% (n=3). Diagnostic, tactical, technical problems and their combination were revealed in 54.4% of lethal outcomes. CONCLUSION: Mortality from acute appendicitis in the Russian Federation is low, comparable with international data, and mainly associated with delayed treatment and complicated course of disease. However, the impact of diagnostic, tactical and technical errors on the outcome of acute appendicitis is significant.

[PD-L1 expression in EBV-associated gastric carcinomas]. / Ekspressiya PD-L1 v EBV-assotsiirovannom rake zheludka.

OBJECTIVE: Assessment of the incidence of PD-L1 expression in EBV-associated gastric adenocarcinomas, as well as clarification of the clinical and morphological characteristics and median survival of patients with PD-L1-positive EBV-associated gastric cancer. MATERIAL AND METHODS: Samples of surgical material from 127 patients with stomach cancer were studied. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). Expression of PD-L1 was assessed immunohistochemically (PD-L1 SP263, PD-L1 SP142). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer and median survival of patients. RESULTS: The detection rate of PD-L1 SP263 and PD-L1 SP142 in EBV-associated gastric adenocarcinoma in our sample was 100% and 76.9% respectively, thus, PD-L1 expression (SP263, SP142) is significantly more frequently detected in EBV-associated gastric carcinomas. It was found that patients with positive expression of PD-L1 in EBV-associated gastric carcinomas are younger (mean age 56.3 years for SP263 and 55.6 years for SP142), belonging to male gender. In addition, this group is dominated by proximal localization of tumors, ulcerative form of growth, tubular histological type, intermediate subtype according to P. Lauren. These characteristics do not depend on the antibody clone: positive expression of SP142 and SP 263 was detected in the same patients with a few exceptions. The overall median survival of patients with positive PD-L1 status SP263 in EBV-associated gastric carcinomas was 35 months, for patients with positive PD-L1 status SP142 - 25 months. Median survival of SP142 PD-L1 positive patients is higher than overall median survival of PD-L1 negative patients in EBV-associated gastric carcinomas. It was found that PD-L1 status in EBV-associated gastric cancer is not a significant prognostic factor. CONCLUSION: A single PD-L1 status does not significantly affect the prognosis in patients with gastric cancer, including those in the group of EBV-associated carcinomas, and can only be considered in conjunction with 'classic' clinical and morphological characteristics, primarily with the stage of the tumor process, since they determine the prognostic properties of the tumor.

[Study of gastric adenocarcinomas association with the Epstein-Barr virus-encoded small RNAs]. / Issledovanie assotsiatsii adenokartsinom zheludka s malymi virusnymi RNK virusa Epshteina­Barr.

OBJECTIVE: Assessment of the incidence of EBV-associated gastric adenocarcinomas in a sample of Russian patients, as well as clarification of the clinical and morphological characteristics and median survival of patients with EBV-associated gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 282 patients with a verified diagnosis of gastric cancer. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer. RESULTS: The detection rate of EBV-associated gastric adenocarcinoma in our sample was 9.57%. EBER-positive tumors much more often (p=0.021) belong to the intermediate type according to the P. Lauren classification (66.67%) in comparison with EBER-negative tumors (38.82%). EBER-positive tumors significantly more often (p=0.035) belong to high-grade tumors - 75.00% in comparison with EBER-negative tumors (52.13%). The overall median survival of all patients with EBER-positive tumors (53.5 months) was higher compared to the overall median survival of all patients with EBER-negative tumors - 36.5 months (p=0.5379). The median survival of patients with EBER-positive stage III tumors (30.0 months) was also higher compared to that for patients with EBER-negative tumors - 20.0 months (p=0.5622). It was found that a single EBER status is not a significant prognostic factor (HR=1.0143; CI: 0.9897-1.0196). CONCLUSION: Separately taken EBER-status is not a significant independent prognostic factor and can be considered only in conjunction with the «classical¼ clinical and morphological characteristics, primarily with the stage of the tumor process, since it is they that determine the prognostic properties of the tumor.

Surveying the Challenges to Improve Linear Accelerator-based Radiation Therapy in Africa: a Unique Collaborative Platform of All 28 African Countries Offering Such Treatment.

Radiation therapy is a critical component for curative and palliative treatment of cancer and is used in more than half of all patients with cancer. Yet there is a global shortage of access to this treatment, especially in Sub-Saharan Africa, where there is a shortage of technical staff as well as equipment. Linear accelerators (LINACs) offer state-of-the-art treatment, but this technology is expensive to acquire, operate and service, especially for low- and middle-income countries (LMICs), and often their harsh environment negatively affects the performance of LINACs, causing downtime. A global initiative was launched in 2016 to address the technology and system barriers to providing radiation therapy in LMICs through the development of a novel LINAC-based radiation therapy system designed for their challenging environments. As the LINAC prototype design phase progressed, it was recognised that additional information was needed from LMICs on the performance of LINAC components, on variables that may influence machine performance and their association, if any, with equipment downtime. Thus, a survey was developed to collect these data from all countries in Africa that have LINAC-based radiation therapy facilities. In order to understand the extent to which these performance factors are the same or different in high-income countries, facilities in Canada, Switzerland, the UK and the USA were invited to participate in the survey, as was Jordan, a middle-income country. Throughout this process, LMIC representatives have provided input on technology challenges in their respective countries. This report presents the method used to conduct this multilevel study of the macro- and microenvironments, the organisation of departments, the technology, the training and the service models that will provide input into the design of a LINAC prototype for a LINAC-based radiation therapy system that will improve access to radiation therapy and thus improve cancer treatment outcomes. It is important to note that new technology should be introduced in a contextual manner so as not to disrupt existing health systems inadvertently, especially with regards to existing staffing, infrastructure and socioeconomic issues. A detailed analysis of data is underway and will be presented in a follow-up report. Selected preliminary results of the study are the observation that LINAC-based facilities in LMICs experience downtime associated with failures in multileaf collimators and vacuum pumps, as well as power instability. Also, that there is a strong association of gross national product per capita with the number of LINACs per population.

[Effect of morphological state of pancreatic parenchyma on the long-term outcome of surgery for chronic pancreatitis]. / Vliyanie morfologicheskogo sostoyaniya parenkhimy podzheludochnoi zhelezy na otdalennye rezul'taty khirurgicheskogo lecheniya khronicheskogo pankreatita.

OBJECTIVE: To determine the effect of baseline morphological state of the pancreas on the long-term outcomes of duodenum-preserving pancreatic head resection (DPPHR). MATERIAL AND METHODS: The study included 104 patients with chronic pancreatitis (CP), who underwent DPPHR in 2014-2019. Pain syndrome, exocrine and endocrine pancreatic insufficiency and quality of life (QoL) were assessed in long-term postoperative period. Patients were stratified depending on CT enhancement of pancreatic parenchyma as an indicator of fibrosis and amount of preserved acinar cells in resected pancreatic tissue. RESULTS. S: Ignificant relief of pain syndrome in long-term period was observed in patients with higher density of pancreatic tissue in venous phase of CT compared to delayed phase. Moreover, these patients needed less additional enzyme intake and had higher QoL. Exocrine insufficiency depended on the number of preserved acinar cells. The percentage of preserved acinar cells also affects the QoL of patients with CP. There were no correlations between endocrine insufficiency and CT-findings, as well as the number of preserved acinar cells. CONCLUSION: Higher CT-density of pancreatic parenchyma in venous phase indicates a lesser degree of fibrosis. It is a favorable prognostic factor for postoperative pain relief and preservation of exocrine function. The percentage of preserved acinar cells in the resected pancreatic tissue is a reliable predictor of exocrine insufficiency.

[Computed tomography in determining the differentiation of ductal adenocarcinoma of pancreatic head]. / Vozmozhnosti komp'yuternoi tomografii v opredelenii stepeni differentsirovki protokovoi adenokartsinomy golovki podzheludochnoi zhelezy.

OBJECTIVE: To evaluate the features of «hypervascular rim¼, tumor dimensions and density as prognostic factors of differentiation of pancreatic head adenocarcinoma. MATERIAL AND METHODS: Pancreatoduodenectomy was performed in 311 patients with pancreatic head adenocarcinoma for the period 2013-2019. A retrospective study included 81 patients who met the following criteria: available data of morphological and immunohistological examination indicating tumor grade from Grade 1 to Grade 3, as well as available preoperative CT images in four phases (native, arterial, portal and delayed). Tumor dimensions, density of the pancreas, adenocarcinoma and abdominal aorta by the phases of contrast enhancement were analyzed in all patients. Moreover, we estimated coefficient of relative enhancement change. Perifocal hypervascular enhancement was assessed in arterial and portal phases. Contrast-enhanced MRI was performed in 15 out of 81 patients. MR images were analyzed regarding a hypervascular rim, and the last one was compared with CT images. RESULTS: There was no significant difference in density values between different tumor grades. Coefficient of relative enhancement change >1 was observed in 63.64% of highly-differentiated tumors. REC ≤1 was found in 85.11% of tumors grade 2 and 82.6% of tumors grade 3 (p=0.005). According to Chi-square test, there was a correlation between tumor differentiation and hypervascular rim (p=0.03). Moderate and low differentiation was observed in 96.42% of tumors with perifocal enhancement. Hypervascular rim was absent in 81.82% of tumors grade 1. Adenocarcinoma grade 2 was found in 85.71% of cases with unclear perifocal enhancement. CONCLUSION: Preoperative contrast-enhanced CT is valuable to assume the tumor grade in patients with pancreatic head adenocarcinoma due to assessment of hypervascular rim and REC.

Evaluating very high energy electron RBE from nanodosimetric pBR322 plasmid DNA damage.

This paper presents the first plasmid DNA irradiations carried out with Very High Energy Electrons (VHEE) over 100-200 MeV at the CLEAR user facility at CERN to determine the Relative Biological Effectiveness (RBE) of VHEE. DNA damage yields were measured in dry and aqueous environments to determine that ~ 99% of total DNA breaks were caused by indirect effects, consistent with other published measurements for protons and photons. Double-Strand Break (DSB) yield was used as the biological endpoint for RBE calculation, with values found to be consistent with established radiotherapy modalities. Similarities in physical damage between VHEE and conventional modalities gives confidence that biological effects of VHEE will also be similar-key for clinical implementation. Damage yields were used as a baseline for track structure simulations of VHEE plasmid irradiation using GEANT4-DNA. Current models for DSB yield have shown reasonable agreement with experimental values. The growing interest in FLASH radiotherapy motivated a study into DSB yield variation with dose rate following VHEE irradiation. No significant variations were observed between conventional and FLASH dose rate irradiations, indicating that no FLASH effect is seen under these conditions.

Assessment of Clinical Decision Support System Efficiency in Spinal Neurosurgery for Personalized Minimally Invasive Technologies Used on Lumbar Spine.

The aim of the study was to assess clinical decision support system (CDSS) in spinal surgery for personalized minimally invasive technologies on lumbar spine. Materials and Methods: The prospective study involved 59 patients operated on using CDSS based on a personalized surgical algorithm considering patient-specific parameters of lumbar segments. Among them, 11 patients underwent total disk replacement (TDR), 25 and 23 patients had minimally invasive (MI-TLIF) and open (O-TLIF) dorsal rigid stabilization, respectively, according to an original technology. The comparative analysis was carried out using retrospective findings of 196 patients operated on involving TDR (n=42), MI-TLIF (n=79), and O-TLIF (n=75). The efficiency of CDSS medical algorithms was assessed by pain syndrome in the lumbar spine and lower limbs, as well as by patients' functional status on discharge according to ODI, 3 and 6 months after the operation. Results: The comparison by gender characteristics and anthropometric data revealed no significant intergroup differences among the groups under study (p>0.05). Intergroup analysis of functional status by ODI, pain intensity in lower limbs and lumbar spine showed better clinical outcomes in patients operated using CDSS compared to a retrospective group (p<0.05): 6 months after TDR and O-TLIF, and 3 months after MI-TLIF. Conclusion: The study findings demonstrated high efficiency of CDSS developed for personalized surgical treatment of patients with degenerative lumbar spine diseases taking into consideration individual biometric parameters of lumbar segments.

Effect of Silicon Dioxide Nanoparticles on Syrian Hamsters Infected by Opisthorchis felineus: 1H MRS Study of the Brain.

In recent years, silicon dioxide nanoparticles have been widely used in medicine and the pharmaceutical industry, however, their effect on the brain has hardly been studied. We assessed the effects of long-term consumption of 5-nm amorphous silicon dioxide nanoparticles (SiO2-NPs) by Syrian hamsters infected with the trematodes Opisthorchis felineus on the hippocampus and frontal cortex. Spectroscopic determination of brain neurometabolites, performed using a horizontal Magnetic Resonance Imaging system at 11.7 Tesla magnetic field, has shown that the ratio of the excitatory neurotransmitters (glutamate + glutamine + aspartate) to the inhibitory ones (GABA + glycine) was higher in the animals infected with O. felineus. However, pre-consumption of the SiO2-NPs solution prevented this imbalance. In addition, the protective effect of SiO2-NPs on the level of myo-inositol and glycine was found. It is concluded that the use of SiO2-NPs can neutralize the negative effects of infectious factors on the brain.

[Miocarditis in Patients with COVID-19 Confirmed by Immunohistochemical].

Aim      Despite the regular heart damage in patients with coronavirus pneumonia caused by SARS-Cov-2, a possibility of developing lymphocytic myocarditis as a part of COVID-19 remains unsubstantiated. The aim of this study was to demonstrate a possibility of lymphocytic myocarditis and to study its morphological features in patients with the novel coronavirus infection (COVID-19) with a severe course.Material and methods   Postmortem data were studied for 5 elderly patients (74.8±4.4 years; 3 men and 2 women) with the novel coronavirus infection and bilateral, severe polysegmental pneumonia (stage 3-4 by computed tomography). COVID-19 was diagnosed based on the typical clinical presentation and positive polymerase chain reaction test in nasopharyngeal swabs. All patients were treated in different hospitals repurposed for the treatment of patients with COVID-19. A standard histological study was performed with hematoxylin and eosin, toluidine blue, and van Gieson staining. Serial paraffin slices were studied immunohistochemically with antibodies to CD3, СD68, CD20, perforin, and toll-like receptors (TLR) 4 and 9.Results In none of the cases, myocarditis was suspected clinically, added to the diagnosis or indicated as a possible cause of death. IHD and acute myocardial infarction were mentioned as error diagnoses not confirmed by the postmortem examination. The morphological examination of the heart identified signs of lymphocytic myocarditis consistent with Dallas criteria for this diagnosis. Myocardial infiltrate was characterized in detail, and a combined inflammatory damage of endocardium and pericardium was described. The immunohistochemical study with cell infiltrate typing confirmed the presence of CD3-positive Т lymphocytes and the increased expression of TLR-4. A picture of coronaritis, including that with microvascular thrombosis, was found in all cases.Conclusion      A possibility for development of lymphocytic viral myocarditis in COVID-19 was confirmed morphologically and immunohistochemically. Specific features of myocarditis in COVID-19 include the presence of coronaritis and a possible combination of myocarditis with lymphocytic endo- and pericarditis.

[Massive localized lymphedema of anterior abdominal wall]. / Massivnaya lokalizovannaya limfedema perednei bryushnoi stenki.

Massive localized lymphedema (MLL) is a rare disease observed in people with morbid obesity. MLL is easily confused with soft tissue sarcoma. Therefore, MLL is sometimes called as pseudosarcoma in the literature. MLL was initially described by G. Farshid and S. Weiss in 1998. However, etiology of MLL is still unknown despite certain relationships with injuries, operations and hypothyroidism. Since the term «MLL¼ was introduced only 20 years ago, there are no reliable statistical data on the prevalence of MLL. According to the World Health Organization data (2016), 13% of the adult world population are obese. Therefore, the risk of MLL is increased in these people. Thigh is the most common site of lesion. Abdominal wall lesion is rare and can cause diagnostic difficulties due to large dimensions and appearance. We report a 50-year-old obese woman with MLL of anterior abdominal wall. She experienced discomfort while walking and sleeping due to giant MLL of anterior abdominal wall that significantly reduced quality of life. Removal of MLL (weight 22160 g) was followed by favorable cosmetic and functional outcome. Analysis of differences between MLL and soft tissue sarcoma in the era of «obesity epidemic¼ is valuable for correct diagnosis and treatment of this rare complication. This report is the first case of MLL, registered in Russia. In our opinion, this is associated with insufficient awareness of physicians about this complication of obesity. We hope our observation will help clinicians to identify and treat this complication.

[Predicting of pancreatic fistula after pancreatoduodenectomy]. / Prognozirovanie vozniknoveniya pankreaticheskogo svishcha posle pankreatoduodenal'noi rezektsii.

OBJECTIVE: Identifying the opportunity of objective prognosis of pancreatic fistula emergence after pancreatoduodenectomy. MATERIAL AND METHODS: In the department of abdominal surgery in 2016-2019, 177 pancreatoduodenectomies for pancreatobiliary tumors were performed. 4 risk factors were identified: type of tumor, preoperative CT with an accumulation coefficient in the pancreas of more than 1, soft pancreas, the number of functioning acinar structures identified during intraoperative histological examination. Statistical data processing and predictive modeling were performed using a binary logistic regression model. RESULTS: Clinically significant pancreatic fistula was developed in 47 (26,6%) patients. Risk indicators for the occurrence of pancreatic fistula depending on the presence or absence of risk factors were obtained. Groups of patients were identified that require various preventive and therapeutic measures aimed to treat postoperative pancreatitis and its consequences. CONCLUSION: Predicting the pancreatic fistula emergence allows to take timely preventive and therapeutic measures, both minimal and aggressive (early extracorporeal detoxification, pancreatectomy), which may lead to complications. Well-reasoned pancreatectomy and extracorporeal detoxification is a surgeon's defense in an insured case or legal conflict.

[Duodenopancreatectomy for pancreatic tumors - pros and cons]. / Duodenopankreatéktomiia pri opukholiakh podzheludochnoi zhelezy - PRO ET CONTRA.

AIM: To optimize surgical treatment of multiple and advanced pancreatic tumors. MATERIAL AND METHODS: There were 852 patients with various pancreatic tumors for the period 2011 - September 2019. Duodenopancreatectomy (DPE) was performed in 18 patients. Locally advanced ductal adenocarcinoma was diagnosed in 10 patients, acinar cell carcinoma - in 1 patient, multiple neuroendocrine tumors - in 4 cases, intraductal papillary mucinous tumor - in 2 patients, multiple metastases of renal cell carcinoma - in 1 patient. This procedure was avoided in 9 patients who underwent alternative operations: pancreatoduodenectomy (PDE) with pancreatic body resection for intraductal papillary mucinous tumor - 5 cases, two-stage (2) and one-stage (1) distal pancreatectomy and PDE for multiple neuroendocrine tumors - 2 patients, simultaneous pancreatic head resection and distal pancreatectomy for multiple metastases of renal cell carcinoma - 1 patient. RESULTS: Postoperative complications occurred in 14 patients after DPE (77.8%) and in 5 patients after alternative operations (55.5%). Alternative procedures in patients with neuroendocrine tumors, intraductal papillary mucinous tumors and metastases of renal cell carcinoma ensured radical surgical treatment. These patients did not need for insulin replacement therapy and enzyme drugs. CONCLUSION: Strict adherence to oncological canons and differentiated approach in patients with multiple neuroendocrine tumors, metastases of renal cell carcinoma and intraductal papillary mucinous tumors are essential to avoid DPE in some cases in favor of alternative operations.

[Novel Genes Associated with the Development of Carotid Paragangliomas].

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors of the head and neck. "Germline" and somatic mutations in a number of genes were shown to be associated with the development of CPGLs; however, molecular mechanisms of the tumor pathogenesis have not been fully understood. In the work, we have used whole exome sequencing data of 52 CPGLs obtained earlier. Using MutSigCV, the search for genes with high mutation rate was performed. Thirty four genes (MADCAM1, SARM1, ZFPM1, CTDSP2, DSPP, POTED, ANP32B, FRG2B, BAGE3, CCDC89, ACOT2, KRTAP10-1, ATXN1, GXYLT1, MUC2, AQP7, TMPRSS13, KRTAP4-3, PRR21, PSPH, PLBD1, ZNF595, IGSF3, PRR16, FAM157A, KCNJ12, HYDIN, IGFBP2, KIAA1671, DISC1, MUC6, XKR3, HRNR, and MUC4) potentially associated with the CPGL initiation and progression were revealed. The involvement of these genes in the pathogenesis of CPGLs was first shown, and possible mechanisms of their participation in that were discussed.

[The expression of moesin, p21-activated kinase 4 (PAK 4), matrix metalloproteinases (MMP 2, MMP 9), and CD34 in the eutopic and ectopic endometrium in adenomyosis]. / Ékspressiia moézina, p21-aktivirovannoi kinazy 4 (PAK 4), matriksnykh metalloproteinaz (MMR 2, MMR 9) i CD34v éutopicheskom i éktopicheskom éndometrii pri adenomioze.

OBJECTIVE: To investigate the expression of moesin, p21-activated kinase 4 (PAK 4), matrix metalloproteinases (MMP 2, MMP 9), and CD34 in the eutopic and ectopic endometrium in different forms of adenomyosis. MATERIAL AND METHODS: Fifty uteri removed for diffuse adenomyosis and for adenomyomas were examined in reproductive-aged (n=25) and premenopausal (n=25) women. A comparison group included 20 uteri removed for intramural and subserosal fibroids in reproductive-aged and premenopausal women. The investigators performed histological and immunohistochemical (using antibodies to moesin, PAK 4, MMP 2, MMP 9, and CD34) examinations of the eutopic and ectopic endometrium. RESULTS: Different forms of adenomyosis were characterized by the irregular border of the endometrium and myometrium due to that there were multiple foci of ingrowth of the basal layer of the endometrium through the terminal plate into the myometrium. In both diffuse adenomyosis and adenomyomas, the basal layer of the eutopic and ectopic endometrium differed many (3-8.5) times, showing the higher expression of the enzymes in the epithelial and stromal cells, which affected their invasive activity (moesin, PAK 4, MMP 2 and MMP 9), and the increased number of CD34 cells in its stroma. At the same time, there were no statistically significant differences in their expression in the basal layer of the eutopic and ectopic endometrium in diffuse adenomyosis and adenomyomas. CONCLUSION: The findings favor the theory of the pathogenesis of adenomyosis due to the invasion of the eutopic endometrium into the myometrium.