A Method for the Production of Recombinant VSVs with Confirmation of Biological Activity.

The design of new effective cancer treatment methods is a promising and important research field in translational medicine. Oncolytic viruses can induce immunogenic cell death by activating the body's immune system to recognize tumor cells. This work presents the results for optimizing the production of recombinant vesicular stomatitis viruses (rVSVs). To ensure the assembly of viral particles, we developed the HEK293TN-T7 cell line, which stably expresses DNA-dependent RNA polymerase 7 for viral genome transcription, and obtained helper plasmids encoding viral genes under the control of the CAG promoter. The oncolytic activity of the purified virus preparation was assessed in a murine model of B16F10Red melanoma cells expressing a red fluorescent protein. The presented method makes it possible to obtain purified viral preparations with a high titer and oncolytic activity. The amplification of viral particles in a HEK293 suspension culture allows for rapid scalability. Therefore, the developed approach can be used to obtain other recombinant VSV-based oncolytic viruses for tumor immunotherapy.

Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial.

BACKGROUND: DESTINY-Breast03 is a randomized, multicenter, open-label, phase III study of trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. A statistically significant improvement in progression-free survival (PFS) versus T-DM1 was reported in the primary analysis. Here, we report exploratory efficacy data in patients with and without brain metastases (BMs) at baseline. PATIENTS AND METHODS: Patients were randomly assigned 1 : 1 to receive T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg. Patients with clinically inactive/asymptomatic BMs were eligible. Lesions were measured as per modified RECIST, version 1.1. Outcomes included PFS by blinded independent central review (BICR), objective response rate (ORR), and intracranial ORR as per BICR. RESULTS: As of 21 May 2021, 43/261 patients randomized to T-DXd and 39/263 patients randomized to T-DM1 had BMs at baseline, as per investigator assessment. Among patients with baseline BMs, 20/43 in the T-DXd arm and 19/39 in the T-DM1 arm had not received prior local BM treatment. For patients with BMs, median PFS was 15.0 months [95% confidence interval (CI) 12.5-22.2 months] for T-DXd versus 3.0 months (95% CI 2.8-5.8 months) for T-DM1; hazard ratio (HR) 0.25 (95% CI 0.13-0.45). For patients without BMs, median PFS was not reached (95% CI 22.4 months-not estimable) for T-DXd versus 7.1 months (95% CI 5.6-9.7 months) for T-DM1; HR 0.30 (95% CI 0.22-0.40). Confirmed systemic ORR was 67.4% for T-DXd versus 20.5% for T-DM1 and 82.1% for T-DXd versus 36.6% for T-DM1 for patients with and without BMs, respectively. Intracranial ORR was 65.7% with T-DXd versus 34.3% with T-DM1. CONCLUSIONS: Patients with HER2-positive mBC whose disease progressed after trastuzumab and a taxane achieved a substantial benefit from treatment with T-DXd compared with T-DM1, including those with baseline BMs.

[The first experience of small intestinal autotransplantation for advanced digestive cancer]. / Pervyi opyt autotransplantatsii tonkoi kishki pri mestno-rasprostranennykh opukholyakh zheludochno-kishechnogo trakta.

Usually, gastrointestinal tumors (GIT) invading great vessels are acknowledged to be irresectable. Along with that, we can expect positive oncological results only when there is combination treatment with radical surgery (R0 resection). In this article we share the first experience of small intestinal autotransplantation as a method of radical surgery in locally advanced GIT. We conducted the analysis of outcomes of three patients (with pancreas cancer (n=2) and neuroendocrine tumor of caecum (n=1), with neoplastic process involving to superior mesenteric artery and vein. We analyzed intraoperative aspects and algorithm of small intestinal autotransplantation. Long-term outcomes with 1.5-13 months of observing time are presented. On the basis of conducted analysis the authors suggest the possibility of small intestinal autotransplantation in referral centers with strict personalized approach and multidisciplinary surgical team.

[Delayed esophagojejunostomy as a damage control principle]. / Otsrochennyi ezofagoeyunoanastomoz kak printsip «Damage Control¼.

The authors describe 2 patients with rare gastric diseases and indications for gastrectomy with delayed esophagojejunostomy for objective causes. In one case, they could not determine extent of resection, and other patient had hemorrhagic shock. Damage control principle was applied in both cases.

[Simultaneous surgery for upper gastrointestinal cancer and cardiovascular diseases]. / Simul'tannye operatsii pri rake zheludka, pishchevoda i serdechno-sosudistykh zabolevaniyakh.

OBJECTIVE: To analyze the immediate and long-term results of simultaneous surgical treatment in patients with upper gastrointestinal cancer and cardiovascular diseases. MATERIAL AND METHODS: There were 9 patients with upper gastrointestinal cancer and cardiovascular diseases who underwent simultaneous surgical treatment. We assessed safety and efficacy of this approach. Mean age of patients was 65.7±5.7 years. Coronary artery disease was diagnosed in 3 patients, aortic valve disease - 1 patient, abdominal aortic aneurysm - 2; 4 patients suffered from isolated mitral valve disease, stenosis of the left vertebral artery, internal and external carotid arteries and Leriche syndrome. RESULTS: Considering immediate and long-term postoperative results, we can emphasize advisability of simultaneous surgeries in appropriate patients.

Properties and Activity of Peptide Derivatives of ACE2 Cellular Receptor and Their Interaction with SARS-CoV-2 S Protein Receptor-Binding Domain.

The aim of this work was to design and characterize peptides based on the α-helices h1 and h2 of the ACE2 receptor, forming the interaction interface between the receptor-binding domain (RBD) of the SARS-CoV-2 S protein and the cellular ACE2 receptor. Monomeric and heterodimeric peptides connected by disulfide bonds at different positions were synthesized. Solubility, RBD-binding affinity, and peptide helicity were experimentally measured, and molecular dynamics simulation was performed in various solvents. It was established that the preservation of the helical conformation is a necessary condition for the binding of peptides to RBD. The peptides have a low degree of helicity and low affinity for RBD in water. Dimeric peptides have a higher degree of helicity than monomeric ones, probably due to the mutual influence of helices. The degree of helicity of the peptides in trifluoroethanol is the highest; however, for in vitro studies, the most suitable solvent is a water-ethanol mixture.

First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study.

BACKGROUND: Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. METHODS: TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1-5 and 8-12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1-14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. RESULTS: At 1 September 2020, median OS was 22.3 months (95% CI: 18.0-23.7) with TT-B and 17.7 months (95% CI: 12.6-19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55-1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. CONCLUSIONS: TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy. CLINICAL TRIAL INFORMATION: NCT02743221 (clinicaltrials.gov).

Peptide Inhibitors of the Interaction of the SARS-CoV-2 Receptor-Binding Domain with the ACE2 Cell Receptor.

Computer simulation has been used to identify peptides that mimic the natural target of the SARS-CoV-2 coronavirus spike (S) protein, the angiotensin-converting enzyme type 2 (ACE2) cell receptor. Based on the structure of the complex of the protein S receptor-binding domain (RBD) and ACE2, the design of chimeric molecules consisting of two 22-23-mer peptides linked to each other by disulfide bonds was carried out. The chimeric molecule X1 was a disulfide dimer, in which terminal cysteine residues in the precursor molecules h1 and h2 were connected by the S-S bond. In the chimeric molecule X2, the disulfide bond was located in the middle of each precursor peptide molecule. The precursors h1 and h2 mimic amino acid sequences of α1- and α2-helices of the ACE2 extracellular peptidase domain, respectively, keeping intact most of the amino acid residues involved in the interaction with RBD. The aim of the work was to evaluate the binding efficiency of chimeric molecules and their constituent peptides with RBD (particularly in dependence of the middle and terminal methods of fixing the initial peptides h1 and h2). The proposed polypeptides and chimeric molecules were synthesized by chemical methods, purified to 95-97% purity, and characterized by HPLC and MALDI-TOF mass spectrometry. Binding of these peptides to the SARS-CoV-2 RBD was evaluated by microthermophoresis with recombinant domains corresponding in sequence to the original Chinese (GenBank ID NC_045512.2) and the British (B. 1.1.7, GISAID EPI_ISL_683466) variants. The original RBD of the Chinese variant bound to three synthesized peptides: linear h2 and both chimeric variants. Chimeric peptides were also bound to the RBD of the British variant. The antiviral activity of the proposed peptides was evaluated in Vero cell line.

[Effect of an antioxidant on vascular wall cell apoptosis markers after reconstructive operations]. / Vliianie antioksidanta na markery apoptoza kletok sosudistoi stenki posle rekonstruktivnykh operatsii.

AIM: This study was aimed at determining Bcl-2 and Bax proteins expression before and after reconstructive-repairing operations in patients with atherosclerosis obliterans of lower extremities and at assessing the effect of an antioxidant (vitamin E at a dose of 100 mg once daily for 1 month after surgery) on the dynamics of changes of Bcl-2 and Bax proteins in the postoperative period. PATIENTS AND METHODS: The study included a total of 60 patients with stage III-IV lower limb atherosclerosis obliterans. All patients underwent reconstructive-repairing operations on the arteries of the aortofemoral segment. After surgery the patients were divided into two groups. Group A included 30 patients who during 1 month received additionally to basic therapy vitamin E at a daily dose of 100 mg. Group B was composed of 30 patients receiving basic therapy alone according to the National guidelines of managing patients with peripheral artery disease. All patients before, on POD 1, and 1 month after surgery were subjected to venous blood test aimed at determining Bcl-2 and Bax apoptosis proteins expression by means of enzyme-linked immunosorbent assay. RESULTS: In patients of groups A and B, the baseline level of Bcl-2 protein (4.75 and 4.2 ng/ml, respectively) was comparable with that in apparently healthy volunteers (5.3 ng/ml). The baseline levels of Bax protein in patients of the operated groups (26.9 and 26.0 ng/ml, respectively) were increased compared with the values in healthy volunteers (16.5 ng/ml). On POD 1 there was increased expression of Bax protein in Group A and B patients to 39.4 and 30.2 ng/ml, respectively. One month after surgery, Group B patients demonstrated a decrease in the Bcl-2 values below the baseline level - 1.1 ng/ml (p=0.003), with the Bax level continuing to increase - 36 ng/ml (p=0.004). In turn, Group A patients after 1 month were found to have increased levels of the Bcl-2 protein - 5.75 ng/ml, with the Bax level returning to the baseline values - 27.4 ng/ml. CONCLUSION: In stage III and IV lower limb obliterating atherosclerosis, the level of the Bax proapoptoric protein was higher than that in healthy volunteers. On POD 1, there occurred increased expression of the pro-apoptotic protein Bax and activation of apoptosis markers. On the background of using vitamin E at a dose of 100 mg once daily for 1 month, there was a decrease in level of the Bax propapoptotic protein (p=0.003) and an increase in level of the anti-apoptotic Bcl-2 protein level (p=0.0007).

[Peptide inhibitors of the interaction of the SARS-CoV-2 receptor-binding domain with the ACE2 cell receptor]. / Peptidnye ingibitory vzaimodeistviia retseptor-sviazyvaiushchego domena virusa SARS-CoV-2 s kletochnym retseptorom ASE2.

Computer simulation has been used to identify peptides that mimic the natural target of the SARS-CoV-2 coronavirus spike (S) protein, the angiotensin converting enzyme type 2 (ACE2) cell receptor. Based on the structure of the complex of the protein S receptor-binding domain (RBD) and ACE2, the design of chimeric molecules consisting of two 22-23-mer peptides linked to each other by disulfide bonds was carried out. The chimeric molecule X1 was a disulfide dimer, in which edge cysteine residues in the precursor molecules h1 and h2 were connected by the S-S bond. In the chimeric molecule X2, the disulfide bond was located in the middle of the molecule of each of the precursor peptides. The precursors h1 and h2 modelled amino acid sequences of α1- and α2-helices of the extracellular peptidase domain of ACE2, respectively, keeping intact most of the amino acid residues involved in the interaction with RBD. The aim of the work was to evaluate the binding efficiency of chimeric molecules and their RBD-peptides (particularly in dependence of the middle and edge methods of fixing the initial peptides h1 and h2). The proposed polypeptides and chimeric molecules were synthesized by chemical methods, purified (to 95-97% purity), and characterized by HPLC and MALDI-TOF mass spectrometry. The binding of the peptides to the SARS-CoV-2 RBD was evaluated by microthermophoresis with recombinant domains corresponding in sequence to the original Chinese (GenBank ID NC_045512.2) and the British (B. 1.1.7, GISAID EPI_ISL_683466) variants. Binding to the original RBD of the Chinese variant was detected in three synthesized peptides: linear h2 and both chimeric variants. Chimeric peptides were also bound to the RBD of the British variant with micromolar constants. The antiviral activity of the proposed peptides in Vero cell culture was also evaluated.

[A comparative analysis of clinical efficiency of laser and radiofrequency denervation in patients with primary trigeminal neuralgia]. / Sravnitel'nyi analiz klinicheskoi effektivnosti primeneniya lazernoi i radiochastotnoi denervatsii u patsientov s pervichnoi nevralgiei troinichnogo nerva.

OBJECTIVE: To compare the clinical efficacy of laser and radiofrequency denervation in patients with primary trigeminal neuralgia. MATERIAL AND METHODS: The study included 50 patients with primary trigeminal neuralgia who were operated on by laser (group I, n=25) or radiofrequency denervation (group II, n=25) in the period from 2018 to 2019. To assess the clinical efficacy, we analyzed the dynamics of the pain syndrome level according to the scale of facial pain and the quality of life according to the Short Form Medical Outcomes Study (SF-36), as well as patient satisfaction with the operation according to the Macnab scale, the presence of postoperative surgical complications and adverse effects of anesthesia. RESULTS: In the postoperative period, according to the scale of facial pain, a decrease in its intensity was noted in both study groups (p<0.001). Comparative analysis showed a comparable level of pain in the early postoperative period: at discharge (p=0.43) and 6 months after surgery (p=0.07). At the same time, after 12 months, lower scores on the scale of facial pain were noted in patients of group I (p=0.02). According to SF-36, a significant improvement in the physical and psychological components of health was determined in group I (p<0.001) and group II (p<0.05). Comparison of SF-36 scores in the long-term postoperative period revealed the best indicators in group I (p=0.02 and p=0.01, respectively). Comparative analysis verified a greater subjective satisfaction with the operation in group I, compared with group II (p<0.001). A comparable number of adverse effects of anesthesia was determined in both groups. Comparative analysis revealed a significantly greater number of postoperative surgical complications in group II (p=0.0017). CONCLUSION: Laser denervation and radiofrequency denervation are highly effective methods of minimally invasive treatment of primary trigeminal neuralgia.

[The place of arterial allograft in reconstructive surgery of the main arteries of the lower extremities]. / Mesto arterial'nykh allograftov v rekonstruktivnoi khirurgii magistral'nykh arterii nizhnikh konechnostei.

Critical limb ischemia, especially in the absence of autologous vein, prosthetic and native vascular infections are isolated diseases for which there currently doesn't have best surgical treatment. Vascular allografts may be the treatment of choice for these patients. In this analysis, we tried to reflect the directions of development of vascular allotransplantation, global trends related to indications for their use, methods of conservation, degradation and endothelial dysfunction. At the present time there doesn't have meta-analyzes on the efficiency of using arterial allografts or other options for implantation (synthetic graft, xenografts) for critical limb ischemia and graft and native infections. Now it is wrong to recommend using them always. Further studies of their performance are necessary. In addition, development of graft control techniques is also needed when rejection develops. Currently, there are no special diagnostic markers, the assessment of which could save patients with immune-mediated dilatation and dysfunction of allografts.

[Functional rehabilitation of patients after endovitreal surgery of rhegmatogenous retinal detachment with complete retinal attachment]. / Otsenka rezul'tatov primeneniya novogo farmakoterapevticheskogo podkhoda v funktsional'noi reabilitatsii patsientov posle endovitreal'noi khirurgii regmatogennoi otsloiki setchatki s polozhitel'nym anatomicheskim rezul'tatom.

Rhegmatogenous retinal detachment (RRD) is one of the most severe eye diseases typically occurring in people of working age. The annual rates of primary vision disability in patients with RRD is 2-9%. PURPOSE: To increase the functional effectiveness of endovitreal surgery in patients with RRD by including Cytoflavin in the system of postoperative rehabilitation. MATERIAL AND METHODS: The study involved 68 patients with RRD aged 37 to 65 years. Patients underwent vitrectomy using the 25 Gauge technology with endolaser coagulation of rupture zones and silicone oil tamponade in the vitreous cavity. Three months after the surgery, silicone oil was removed from the vitreous cavity. Patients were divided into 2 groups: the main - 34 people who received Cytoflavin in addition to standard therapy, and the control - 34 people receiving only standard postoperative treatment. The time course of the treatment's functional effectiveness was analyzed using best corrected visual acuity (BCVA) and macular photosensitivity. Laser Doppler flowmetry (LDF) was used to register the microcirculation and microcirculation efficiency indices. Morphological signs of macular ischemia were registered by optical coherence tomography angiography (OCT-A). RESULTS: Patients of the main group showed higher level of restoration of macular function compared with the control group. The increase in functional activity of the macular area correlated with postoperative dynamics of restoration of central retinal thickness. Analysis of LDF and OCT-A indices showed that improvement of visual functions in patients treated with Cytoflavin is directly related to restoration of chorioretinal blood flow. CONCLUSION: The use of Cytoflavin in patients after endovitreal surgery of RRD led to improvement of BCVA by an average of 2.6 times and photosensitivity of the macula by 2 times. The visual functions of patients improved after using Cytoflavin due to its positive effect on chorioretinal microcirculation and the density of macular capillary plexuses.

[Successful treatment of an aortoduodenal fistula after operation on the abdominal portion of the aorta]. / Uspeshnoe lechenie aorto-duodenal'noi fistuly posle operatsii na briushnom otdele aorty.

Gastrointestinal haemorrhage is a common cause of emergency admission of patients to surgical hospitals. Within the structure of nosological entities, not unreasonably referred to the rarest causes of gastrointestinal bleeding is the formation of an aortointestinal fistula whose early diagnosis is of paramount importance. The clinical picture may be different but it is mostly represented by gastrointestinal haemorrhage. The incidence of gastrointestinal fistulas following a surgical intervention ranges from 0.6 to 2.3%. Unless timely diagnosed and with incorrect therapeutic decision-making, the mortality rate amounts to 90%. In this article we present a clinical case report regarding successful treatment of a patient presenting with a secondary aortoduodenal fistula occurring 5 years after previously performed aortofemoral bypass grafting and complicated by relapsing intestinal bleeding and acute ischaemia of the right lower extremity.

Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study.

BACKGROUND: We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. PATIENTS AND METHODS: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (N = 77) or C-B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. RESULTS: Median (range) duration of treatment was 7.8 (6.0-9.7) months and 6.2 (4.1-9.1) months in the TT-B and C-B groups, respectively. Median (range) PFS was 9.2 (7.6-11.6) and 7.8 (5.5-10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT-B had more grade ≥3 neutropenia (47% versus 5% with C-B). Patients receiving C-B had more grade ≥3 hand-foot syndrome (12% versus 0% with TT-B) and grade ≥3 diarrhea (8% versus 1% with TT-B), consistent with the known safety profiles of these agents. CONCLUSION: TT-B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. CLINICAL TRIAL INFORMATION: NCT02743221 (ClinicalTrials.gov).

[Laparoscopic and robot-assisted procedures in patients with gastrointestinal stromal tumors (GIST) of stomach]. / Laparoskopicheskie i robot-assistirovannye operatsii u bol'nykh gastrointestinal'noi stromal'noi opukhol'iu zheludka.

OBJECTIVE: To analyze the results of minimally invasive surgical procedures in patients with gastric GIST. MATERIAL AND METHODS: The study included 30 patients aged 52.2±9.8 years. ASA grade II (44%), III (26%) and I (23%) were predominant. Lesion of stomach body was noted in 17 (56%) patients, antrum - in 8 (27%), fundus - in 2 (7%) and cardia - in 3 (10%) patients. GIST was located on the anterior wall of stomach in 56% of patients. Exophytic growth was observed in 16 (53%) patients, endophytic - in 12 (40%), transmural growth - in 2 (7%) cases. T2 grade of tumor was noted in 67% of cases (TNM 8). All patients underwent laparoscopic or robot-assisted ('daVinci Si') partial resection of the stomach. RESULTS: Radical resection (R0) without injury of pseudocapsule of tumor was made in all patients. Laparoscopic procedures were performed in 25 (83%) patients, robot-assisted - in 5 (17%). Early postoperative complications (Clavien-Dindo II) were observed in 3 patients. Spindle cell structure of tumors (93%) with low mitotic activity (63%) prevailed. Tumor stage I was observed in 56% of patients. Patients with high mitotic tumor index (44%) were directed to targeted therapy. Recurrence and/or metastasis in long-term period were absent in 26 (87%) patients. CONCLUSION: Laparoscopic surgery for gastric GIST is safe and characterized by the absence of significant postoperative complications and long-term recurrence-free period. The use of robotic surgical system is effective and justified for anatomically difficult localization of GIST.

[Choice of surgical approach to insulin-producing pancreatic tumors]. / Vybor metoda khirurgicheskogo lecheniia insulinprodutsiruiushchikh opukholei podzheludochnoi zhelezy.

AIM: To determine the optimal surgical approach to insulin-producing pancreatic tumors via an analysis of early postoperative results. MATERIAL AND METHODS: There were 134 patients with insulin-producing pancreatic tumors followed by organic hyperinsulinism who have undergone surgery in the faculty-based surgical clinic of the Sechenov First Moscow State Medical University for the period 1990-2017. Patients were divided into three groups depending on type of surgical intervention. Surgical procedure was determined after comprehensive preoperative and intraoperative examination including intraoperative ultrasound. RESULTS: Incidence of postoperative complications was 32.8%. Ten (7.5%) patients required redo surgical interventions. Overall postoperative mortality was 4.5%. The best immediate results were observed in patients undergoing distal pancreatectomy. There was a correlation between incidence of early postoperative complications and tumor location depth in the enucleation group. CONCLUSION: Enucleation is advisable for insulinoma of pancreatic head or uncinated process, as well as superficial tumors of the left half of the pancreas. Distal pancreatectomy is indicated for deep tumors of the left half of the pancreas. Indications for pancreatoduodenectomy are individual.

[Prevention of thromboembolic and hemorrhagic events in patients with atrial fibrillation undergoing elective surgery]. / Profilaktika tromboémbolicheskikh i gemorragicheskikh oslozhnenii u patsientov s fibrilliatsiei predserdii pri provedenii planovogo khirurgicheskogo lecheniia.

OBJECTIVE: To compare incidence of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF) undergoing elective surgery on different schemes of perioperative anticoagulant therapy (ACT). MATERIAL AND METHODS: There were 86 patients (56 (65.1%) men and 30 (34.9%) women, mean age was 69 (64; 78) years) with non-valvular AF who underwent elective interventions. Forty (46.5%) patients underwent abdominal surgery, 34 (39.5%) - cardiovascular procedures, 12 (14.0%) patients underwent surgery for malignant diseases. We have analyzed incidence of thromboembolic and hemorrhagic events and compliance of perioperative ACT modes with current international guidelines. RESULTS: Thromboembolic and hemorrhagic events developed in 14 (16.3%) patients. Thromboembolic complications were noted in 6 (7.0%) patients, hemorrhagic events - in 8 (9.3%) cases. Maximum complication rate was observed in case of bridge-therapy (n=12, 20.0%). Cancellation of ACT was followed by 2 (9.5%) complications, bridge-therapy - by 4 (6.7%) thromboembolic complications. Hemorrhagic events were 2 times more common in case of this therapy (n=8, 13.3%). It was found that ESC guidelines for perioperative ACT were applied in less than half of patients (41, 47.7% patients with AF undergoing elective surgery). Half of complications (8 out of 16) occurred if unapproved modes of ACT were used (including 7 cases of bridge-therapy was not necessary). The causes of these complications were inadequate assessment of perioperative risk of thromboembolic and hemorrhagic events; unreasonable administration of bridge therapy. CONCLUSION: An unambiguous clinical effect of bridge therapy has not been confirmed in patients with high risk of thromboembolic complications. Cancer patients have higher risk of complications compared with others. These events occur mainly due to non-compliance with clinical guidelines and insufficient prevention of thromboembolic events.

[Effect of genetic polymorphisms on functioning of a permanent vascular access in patients on dialysis]. / Vliianie geneticheskikh polimorfizmov na funktsionirovanie postoiannogo sosudistogo dostupa u patsientov na dialize.

Thromboses and stenoses of permanent vascular access appear to be a serious hazard for patients with end-stage kidney disease on programmed haemodialysis. Relapses of these pathological conditions are the cause of repeated hospitalization, secondary surgical interventions and may eventually lead to impossibility of carrying out procedures of haemodialysis. Often, vascular access dysfunction occurs for no apparent reason, thus underlying the importance of studies aimed at revealing additional factors of intravascular thrombogenesis and neointimal formation in a vascular access, including the works dedicated to studying genetic predictors of the development of the above-mentioned complications. The authors examined herein the role of polymorphisms of the genes of endothelin-1 (END-1), nitric oxide synthase-3 (NOS-3), angiotensinogen-2 (AGT-2), angiotensinogen-1 (AGT-1), angiotensinogen 2 receptor type 1 (AGTR1), mitochondrial superoxide dismutase-2 (SOD-2), catalase (CAT) superoxide dismutase-1 (SOD-1) and angiotensin converting enzyme (ACE) in the functional state of permanent vascular access in patients on dialysis. The obtained results demonstrated direct cause-and-effect relationships between polymorphisms lys-198 asn in the END-1 gene, C60T, T58C in the SOD-2 gene and the function of vascular access. The presence of END-1 gene lys-198 asn polymorphism in a homozygous state (allele 1) was associated with a high risk of an unsatisfactory condition of permanent vascular access (p=0.019).