[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.

[Role of clustered HER2/neu amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II-III breast cancer]. / Rol' klasternoi amplifikatsii gena HER2/neu kak markera 'osoboi' chuvstvitel'nosti k neoad''iuvantnoi anti-HER2-terapii trastuzumabom pri rake molochnoi zhelezy II­III stadii.

OBJECTIVE: To evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II-III breast cancer (BC). MATERIAL AND METHODS: Treatment results were studied in 73 patients with HER2-positive Stage II-III BC, who received treatment at the N.N. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (T1-3N0-1) and 54.8% had locally advanced tumors. All the patients had grade 2-3 anaplasia; luminal HER2-positive BC was diagnosed in 41.4% of patients; hormone-negative tumors were seen in 58.9%; 91.5% of patients had Ki-67 ≥20% in 75.3% of patients, preoperative systemic therapy included anthracycline-containing regimens (4AC + 4 x paclitaxel 175 mg/m2/12 × weekly administrations of paclitaxel 80 mg/m2; trastuzumab therapy was simultaneously performed with the administration of taxanes in the standard regimen) and anthracycline-free regimen TCH ± Pertuzumab regimen in 24.7% of cases. After NACT patients underwent surgery (radical mastectomy in 78.1%, breast-sparing treatment in 21.9%) with the assessment of morphological findings. Biopsy specimens obtained before the treatment was restudied; HER2 amplification was detected using a Dako HER2 IQFISH pharmDx kit according to its instruction and the 2018 ASCO/CAP guidelines. In 87.1% of cases, the HER2-positive status corresponded to the first category of the 2018 ASCO/CAP criteria for HER2-positive BC; clustered HER2 amplification was found in 30.1% of cases. The authors analyzed the frequency of bpCR and tpCR attainment by various clinical and morphological factors, as well as the impact of a HER2 amplification level on pCR rates. RESULTS: A breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36-50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%. CONCLUSION: Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II-III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.

[Structure of microorganism species cultured from urine of urolithiasis patients].

AIM: To investigate the incidence of microorganisms of different taxonomic groups and their associations in the pelvic and bladder urine of adult urolithiasis patients. MATERIALS AND METHODS: A bacteriological method and metagenomic sequencing were used to investigate the bacterial spectrum of microflora cultured from pelvic and bladder urine sampled during surgical interventions in urolithiasis patients. RESULTS: The both microbiotas had approximately the same spectrum, but in 26.1% of patients it was inconsistent. Metagenomic analysis detected DNA of microorganisms in urine samples which were found free of microflora by the bacteriological method. CONCLUSION: The study findings showed species diversity of microorganisms cultured from pelvic and bladder urine sampled during surgical interventions in urolithiasis patients.

[Abdominal sepsis and oxidative stress].

INTRODUCTION: Oxidative stress deserves special attention in the pathogenesis of sepsis. MATERIAL AND METHODS: The study included 96 patients with abdominal sepsis caused by advanced suppurative peritonitis and destructive pancreatitis. All patients were divided into 3 groups depending on the severity of sepsis. Level of malondialdehyde (MDA) was determined to evaluate the intensity of lipid peroxidation (LPO). Proteins oxidative modification was assessed according to level of sulfhydryl groups (SH-groups) and carbonyls in proteins. State of anti-oxidant system (AOS) was defined based on activity of catalase, peroxidase, superoxide dismutase and glutathione peroxidase in erythrocytes. RESULTS AND DISCUSSION: There was no relationship between severity of multiple organ failure, MDA concentration, SH-groups and anti-oxidant enzymes levels. At the same time positive correlation between severity of multiple organ failure and carbonyls content in proteins was revealed. CONCLUSION: In surgical patients sepsis develops on background of oxidative stress. Significant reduction of SH-groups in proteins by the moment of sepsis diagnosis is an unfavorable factor for outcome. The degree of multiple organ failure in patients with abdominal sepsis correlates with oxidative injury of proteinic structures.

ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making.

Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

Involvement of cingulate cortex in the formation of defensive behavior in rats.

Changes in behavior patterns in rats during electric stimulation of the ventromedial hypothalamus (the center of defensive behavior) and cingulate cortex were studied. Electric stimulation of the frontomedial cingulate cortex reduced the latency for anxiety and escape reactions during electric stimulation of the ventromedial hypothalamus. Electrolytic destruction of the frontomedial cingulate cortex substantially increased the threshold of escape behavior during stimulation of the ventromedial hypothalamus. These findings demonstrate the involvement of the frontomedial cingulate cortex into the development of defensive (anxiety and escape) behavior in rats.

Spike activity of neurons in the lateral hypothalamus in rats during microiontophoretic application of melatonin and noradrenaline.

Microiontophoretic application of melatonin to the perineuronal space of nerve cells in the lateral hypothalamus of WAG and Fischer-344 rats led to decreases in the frequency and regularization of the spike activity of neurons, and also blocked activation of neurons and changing the patterns of adrenaline-induced spike activity. The effects of melatonin were more marked in WAG rats, which demonstrated the more active behavior in the open field test and were predicted to be more resistant to emotional stress, than in passive Fischer-344 rats, with predisposition to emotional stress. These results suggest that the mechanism of the stress-protective action of melatonin involves suppression of the spike activity of neurons in emotiogenic brain structures and changes in their sensitivity to noradrenaline.

Antidepressant properties of antibodies to serotonin, brain-specific S100 protein, and delta sleep-inducing peptide.

Potentiated antibodies to delta sleep-inducing peptide and S100 protein produced an antidepressant effect in Wistar rats. This effect was more pronounced after combined treatment with these antibodies. It can be assumed that these antibodies modulate neurobiological mechanisms of positive emotional reinforcement and, therefore, affect the resistance to depression associated with psychoemotional stress.

Apoplasmic and Protoplasmic Water Transport through the Parenchyma of the Potato Storage Organ.

Stationary volume fluxes through living and denatured parenchyma slices of the potato (Solanum tuberosum L.) storage organ were studied to estimate the hydraulic conductivity of the cell wall and to evaluate the significance of water transport through protoplasts, cell walls, and intercellular spaces. Slices were placed between liquid compartments, steady-state fluxes induced by pressure or concentration gradients of low- and high-molecular-mass osmotica were measured, and water transport pathways were distinguished on the basis of their difference in limiting pore size. The protoplasts were the dominating route for osmotically driven water transport through living slices, even in the case of a polymer osmoticum that is excluded from cell walls. The specific hydraulic conductivity of the cell wall matrix is too small to allow a significant contribution of the narrow cell wall bypass to water flow through the living tissue. This conclusion is based on (a) ultrafilter coefficients of denatured parenchyma slices, (b) the absence of a significant difference between ultrafilter coefficients of the living tissue slices for osmotica with low and high cell wall reflection coefficients, and (c) the absence of a significant interaction (solvent drag) between apoplasmic permeation of mannitol and the water flux caused by a concentration difference of excluded polyethylene glycol. Liquid-filled intercellular spaces were the dominating pathways for pressure-driven volume fluxes through the parenchyma tissue.

Gradients of turgor, osmotic pressure, and water potential in the cortex of the hypocotyl of growing ricinus seedlings : effects of the supply of water from the xylem and of solutes from the Phloem.

To evaluate the possible role of solute transport during extension growth, water and solute relations of cortex cells of the growing hypocotyl of 5-day-old castor bean seedlings (Ricinus communis L.) were determined using the cell pressure probe. Because the osmotic pressure of individual cells (pi(i)) was also determined, the water potential (psi) could be evaluated as well at the cell level. In the rapidly growing part of the hypocotyl of well-watered plants, turgor increased from 0.37 megapascal in the outer to 1.04 megapascal in the inner cortex. Thus, there were steep gradients of turgor of up to 0.7 megapascal (7 bar) over a distance of only 470 micrometer. In the more basal and rather mature region, gradients were less pronounced. Because cell turgor approximately pi(i) and psi approximately 0 across the cortex, there were also no gradients of psi across the tissue. Gradients of cell turgor and pi(i) increased when the endosperm was removed from the cotyledons, allowing for a better water supply. They were reduced by increasing the osmotic pressure of the root medium or by cutting off the cotyledons or the entire hook. If the root was excised to interrupt the main source for water, effects became more pronounced. Gradients completely disappeared and turgor fell to 0.3 megapascal in all layers within 1.5 hours. When excised hypocotyls were infiltrated with 0.5 millimolar CaCl(2) solution under pressure via the cut surface, gradients in turgor could be restored or even increased. When turgor was measured in individual cortical cells while pressurizing the xylem, rapid responses were recorded and changes of turgor exceeded that of applied pressure. Gradients could also be reestablished in excised hypocotyls by abrading the cuticle, allowing for a water supply from the wet environment. The steep gradients of turgor and osmotic pressure suggest a considerable supply of osmotic solutes from the phloem to the growing tissue. On the basis of a new theoretical approach, the data are discussed in terms of a coupling between water and solute flows and of a compartmentation of water and solutes, both of which affect water status and extension growth.

Neurochemical mechanisms of the involvement of cortical sensorimotor neurons in alimentary and orientational behavior.

The object of these experiments was the study of the features of the neurochemical mechanisms of the involvement of individual neurons of the sensorimotor cortex of the rabbit brain the orienting reaction and the goal-oriented alimentary behavior elicited by stimulation of the "hunger center" of the lateral hypothalamus using electrical current of varying intensity. It is demonstrated that the neurotransmitters acetylcholine and norepinephrine, in approximately equal percentages, reorganize the reaction of neurons at the subthreshold as much as at the threshold level of stimulation. The microiontophoretic application to cortical sensorimotor neurons of the protein synthesis blocker, cycloheximide, also elicits alterations in their reactions to threshold and subthreshold stimulation of the lateral hypothalamus which are apparently linked to the suppression of synthesis of neuropeptides specific to both behaviors. It is proposed that the orienting, and especially the alimentary, motivational reactions are achieved by the activation of the synthesis of specific peptide molecules in the cortical sensorimotor neurons, which in fact may induce a change in their sensitivity to neurotransmitters.