[Indocyanine green in liver tumor resection]. / Primenenie ICG na etapakh planirovaniya i realizatsii rezektsii pecheni po povodu opukholei.

Primary liver cancer and colorectal cancer liver metastases are among the leading causes of cancer-related mortality worldwide. Surgery is one of the main methods of treatment to achieve the best results in overall and recurrence-free survival. The main objectives in this surgery are preoperative planning, assessment of functional viability of liver parenchyma and total resection with low complication rate. Post-resection liver failure is one of the most formidable and often fatal complication following functional failure of liver remnant. Thus, preoperative assessment of liver functional reserves is a necessary step for adequate selection of patients and safe surgery. Passive liver tests, such as biochemical parameters or clinical scales, do not accurately reflect the actual functional component of liver parenchyma. The most accurate method is dynamic quantitative test of liver, such as indocyanine green clearance. The authors discuss the practical aspects of preoperative assessment of liver functional reserves using indocyanine green, as well as the concept and technical foundations of fluorescent imaging in hepatobiliary surgery.

[Isolated endovascular liver chemoperfusion for liver metastases of uveal melanoma]. / Sposob izolirovannoi endovaskulyarnoi khimioperfuzii pecheni pri metastazakh uveal'noi melanomy v pechen'.

Isolated hepatic perfusion is one of the possible approaches for unresectable liver metastases of uveal melanoma. This technique is rare in modern oncology because of extremely difficult technique and high risk of intra- and postoperative complications. Thus, minimizing surgical trauma and increasing safety and reproducibility of this technique are important. There were 36 procedures of isolated «open¼ hepatic perfusion. The authors describe the first experience of endovascular hepatic perfusion. Advantages and clinical prospects of this method are shown.

[Laparoscopic surgery in patients with locally advanced rectal cancer - short-term outcomes]. / Laparoskopicheskie operatsii v lechenii bol'nykh mestno-rasprostranennym rakom priamoi kishki - neposredstvennye rezul'taty.

AIM: To optimize the indications for laparoscopic surgery in patients with locally advanced and prognostically unfavorable rectal cancer after neoadjuvant chemoradiotherapy. MATERIAL AND METHODS: 226 patients with locally advanced rectal cancer underwent combination therapy in A.F. Tsyba Medical Radiological Research Centre in 2003-2016. The patients were divided into two subgroups, depending on the surgical approach. The main group included 55 patients who underwent laparoscopic resections, and the control group included 171 patients - for conventional approach. RESULTS: In the subgroup of patients who underwent laparoscopic resections 42 (76.3%) organ preservation surgery were performed more often in comparison with the control subgroup 74 (43,2%) (p<0.0001). There were no significant differences in the incidence of intraoperative complications in both subgroups. The incidence of postoperative complications was lower in the laparoscopic approach group in comparison with the control group 12 (21.8%) patients and 62 (36.3%), respectively (p=0.0493). Data for local recurrence and dissemination of the process after surgery was not received. CONCLUSION: According to the main clinical and morphological features, laparoscopic resections may be an alternative, and in many cases even superior approach in comparison with the conventional surgery.

[Pancreatoduodenectomy: learning curve within single multi-field center]. / Pankreatoduodenal'naia rezektsiia: krivaia obucheniia na primere odnogo mnogoprofil'nogo tsentra.

AIM: To analyze learning curve by using of immediate results of pancreatoduodenectomy at multi-field oncology institute. MATERIAL AND METHODS: For the period 2010-2016 at Abdominal Oncology Department of Herzen Moscow Oncology Research Institute 120 pancreatoduodenal resections were consistently performed. All patients were divided into two groups: the first 60 procedures (group A) and subsequent 60 operations (group B). Herewith, first 60 operations were performed within the first 4.5 years of study period, the next 60 operations - within remaining 2.5 years. RESULTS: Learning curves showed significantly variable intraoperative blood loss (1100 ml and 725 ml), surgery time (589 min and 513 min) and postoperative hospital-stay (15 days and 13 days) in group A followed by gradual improvement of these values in group B. Incidence of negative resection margin (R0) was also significantly improved in the last 60 operations (70 and 92%, respectively). CONCLUSION: Despite pancreatoduodenectomy is one of the most difficult surgical interventions in abdominal surgery learning curve will differ from one surgeon to another.

Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study.

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR(4) (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10,000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal.

CD133+ human colorectal adenocarcinoma cells are resistant to staining with fluorescent dyes used for analysis of ABC transporter activities.

Flow cytometry measurement of the expression of surface marker CD133 simultaneously with the analysis of fluorescent dye exclusion was performed in order to develop new methods for detection of cancer stem cell populations in tumor tissue samples from patients with colorectal adenocarcinoma. No correlation was found between the count of CD133(+) cancer cells and the volume of the "population" formed from cells actively pumping off the fluorescent dye. On the other hand, the fluorescence distribution plot showed predominant location of CD133(+) cancer cells among cells stained with neither DyeCycle Violet DNA-binding dye, nor rhodamine 123 mitochondrial dye. These cells did not show the properties of the classical "side population", because they did not shift to the area of stained cell after treatment with ionic channel blocker verapamil.

Total mesorectal excision with water-jet dissection in patients with rectal cancer: surgical and morphological aspects.

AIM: This publication will describe our own experience of using the ERBEJET2(®) water-jet dissector during surgical interventions for rectal cancer. METHOD: We utilized the water-jet dissection technique to obtain tissue specimens in 10 patients with rectal cancer. All patients thus underwent nerve-sparing low anterior resection of the rectum along with para-aortic lymphadenectomy. No intraoperative complications were registered. The postoperative period went uncomplicated in all patients. No dysuria was observed. Obtained tissue specimens were examined morphologically. Macroscopic examination included assessments of the preservation of the rectal fascia propria and the amount of cellular tissue along the anterior, posterior, and lateral surfaces of the rectum. We performed microscopy of the circumferential resection margin to characterize the surgical clearance and the intensity and depth of damage to the mesorectal tissue. On morphological examination, the quality of mesorectal excision was found to be good (Grade 3) in all 10 patients. RESULTS: As the results of our study demonstrate, the depth of lateral tissue damage is minimal with the water-jet dissector. CONCLUSION: Water-jet dissectors have their own place in the long list of armamentarium used in surgical interventions performed for rectal cancer and contribute to improving oncological and functional outcomes of surgical treatment in this patient population.

[Prophylaxis of hepatic insufficiency after major hepatic resections].

UNLABELLED: The article deals with a problem of prophylaxis of hepatic insufficiency in oncological patients after liver resections. MATERIALS AND METHODS: We analyzed data of effectiveness and safety of the use of Remaxol in oncological patients with hepatic metastasis of colorectal cancer--dynamics of indicators of cytolysis and cholestasis, hepatic protein synthesis, exchange of pigments, pro- and antioxidant system and the level of endogen intoxication in postoperative period. RESULTS: Use of Remaxol allows decreasing the duration of postoperative rehabilitation and intensive care unit staying.

Subpopulation of colorectal adenocarcinoma cells co-expressing CD133 and cancer stem cells markers of other tumors.

Co-expression of colorectal adenocarcinoma cancer stem cells marker CD133 and a set of surface molecules described in published reports as possible cancer stem cell markers of other solid tumors was analyzed by flow cytometry. Minor cell populations expressing CD29, CD34, CD90, and CD117 against the background of CD133 expression were detected in cancer cells suspensions from the patients with colorectal adenocarcinoma. Our findings suggest that these markers can be used as additional markers of cancer stem cells of human colorectal adenocarcinoma.

[Probiotics as an items of increasing the effectiveness of treatment of community-acquired pneumonia in adolescents].

The aim of the work was to evaluate the efficiency of microbial probiotics Vitaflor and metabolic probiotic Aktoflor-C in complex treatment of community-acquired pneumonia in adolescents in a hospital. The observation involved 38 children aged 11 to 18 years with radiologically verified community-acquired pneumonia, including 23 boys and 15 girls. Patients were divided in 3 groups. Patients in group 1 (n = 13) simultaneously with the antibiotic therapy received per os Vitaflor probiotic containing symbiotic strains of Lactobacillus acidophilus; patients in group 2 (n = 10) along with antibiotic therapy received per os metabolic probiotic Aktoflor-C, containing low molecular weight exometabolites bacteria; patient of the comparison group (n = 15) received antibiotic therapy only. The effectiveness of the used treatment schemes was assessed on the dynamics of the gut state microbiot acoarding to an extended bacteriological examination of faecal flora, level of saliva IgA secretory (before and after treatment), the dynamics of SF-36 quality of life 1 month after discharge from hospital. Was conducted a study of economic efficiency of different modes of therapy. Results showed that adolescents with community-acquired pneumonia during standard antibiotic therapy indicated development of dysbiotic bowel disturbances in the form of reliable oppression of the bifidobacteria and laktoflora. Dysbiosis of the microbial associations are not conducive to proper implementation of immune and nutritional functions of the intestine that shows the imperfection of rehabilitation of patients with pneumonia according to the evaluation of SF-36 quality of life. Pharmacoeconomic analysis revealed the benefits of probiotic metabolic type "Aktoflor" used in addition to standard therapy of community-acquired pneumonia in adolescents.

Detection of minor subpopulations of colorectal adenocarcinoma cells expressing cancer stem cell markers.

The expression of puitative surface molecular markers of cancer stem cells on human colorectal adenocarcinoma cells was analyzed by flow cytofluorometry. Cell subpopulations expressing markers of epithelial and malignant cells and stem cell markers were identified. Four minor subpopulations with CD24(+)/CD133(+), CD44(+)/CD133(+), CD90(+)/CD71(+), or CD90(+)/CD24(+) phenotypes meeting this requirement were detected; presumably, those were cancer stem cell subpopulations. These results extend our knowledge on heterogeneity of human colorectal adenocarcinoma cell population and outline new trends of research of cancer stem cell phenotype in these tumors.

[Coumarin-induced necrosis--a rare complication of oral anticoagulant therapy]. / Necroza cumarinica--complicatie rara a terapiei anticoagulante orale.

Coumarin-induced skin necrosis represents a clinical entity that occurs very rarely, with an approximate incidence of 0.01-0.1% at patients following oral anticoagulant therapy. Most of the cases become clinical manifest between the 3rd and 6th of anticoagulant treatment (there were reports of late onset of skin necrosis after 15 years of anticoagulant therapy) and the most involved areas include breast, buttocks and thighs microcirculation-rich areas. Early symptoms include paresthesia and sensation of tension associated with an erythematous flush in the affected area. Lesions are well demarcated, painful, initially erythematous or hemorrhagic, with the onset of skin necrosis in the end stage. Early lesions can be reversible with the discontinuation of anticoagulant therapy, but skin necrosis can reoccur even without any other coumarin based treatment. We report the case of a 55-year-old female who presented with coumarin-induced skin necrosis affecting the right breast and the right deltoid area.

Differential diagnosis between chronic granulocytic leukemia, polycythaemia vera and essential thrombocythemia using micro-and ultrastructural measurement data performed at the level of megakaryocyte.

The common features of chronic myeloproliferative disorders (CMDs) make the differential diagnosis on clinical or paraclinical basis to become more difficult, and validate the requirements for new methods of detailed diagnosis. Besides the cytogenetic methods, the megakaryocyte (MK) morphology is a valuable element of diagnosis included in the recent "en vogue" criteria. The purpose of this paper is to compare different morphological parameters in MKs from patients diagnosed with three CMDs and to establish a differential diagnosis of these disorders. Studies were performed on smears of bone marrow blood - for light microscope analysis -, and bone marrow biopsies - for transmission electron microscope (TEM) analysis - collected from six patients, two diagnosed with chronic granulocytic leukemia (CGL), two with polycythaemia vera (PV), and other two with essential thrombocythemia (ET). On the light microscope images, we observed important differences between the sizes of MKs and of MKs nuclei in CGL, PV, and ET. On the TEM images, we also noted important differences concerning the size and the aspect of nuclei, aspect of mitochondria, the amount and distribution of RER, Golgi apparatus and demarcation membrane system; the most important are the differences recorded in the number, distribution and sizes of vacuoles, alpha-granules and of the dense bodies. This study provides evidence that there are significant morphological differences between the cellular structures in the MKs from the patients with diagnosed with different CMDs, and thus sustains the utilization of this approach for establishing the differential diagnosis of CMDs.

[Choice of probiotic for rational therapy of infection caused by Klebsiella in children].

AIM: To choose lactobacilli-contained probiotic for complex treatment of acute enteric infection caused by Klebsiella in infants. MATERIALS AND METHODS: On the basis of bacteriological analysis the group consisting of 40 infants with acute enteric infection caused by Klebsiella was formed. Efficacy of three probiotic preparations--lactobacterin, vitaflor, and biobacton--was assessed depending on biological features of causative agents and contents of lactobacilli and bifidobacteria in obligate gut microflora. Intraspecies antagonistic characteristics of manufacturing strains of lactobacilli against 9 clinical isolates of K. pneumoniae and 8 strains of indigenous lactoflora, as well as interspecies antagonism between Klebsiella and probiotic and indigenous strains of lactoflora were studied. RESULTS: It was shown that complex therapy of Klebsiella infection in infants using vitaflor or biobacton promoted elimination of K. pneumoniae and restoration of indigenous microflora which became apparent in significant increase of titer of lactobacilli. In vitro maximal antagonism to K. pneumoniae was noted for vitaflor, lactobacterin and heteroenzyme autostrains of ill children's lactoflora. Contrantagonism to lactoflora was typical for slowly growing strains of Klebsiella. CONCLUSION: It is therapeutically rational to use vitaflor, which promotes rapid elimination of infectious agent, in initial phase of acute infection caused by Klebsiella, and biobacton, which increases the titers of indigenous lactoflora, in phase of convalescence.

Anemia--a complication of antiviral treatment in chronic viral hepatitis C.

Anemia is an important and frequent secondary effect of the treatment with pegylated interferon and ribavirin in patients with chronic viral C hepatitis. Ribavirin produces more often hemolytic anemia, while pegylated interferon may determine medullary suppression. The level of hemoglobin beneath 10 g/dL is considered by most authors as being the reference level for anemia secondary to the antiviral treatment. Beneath this hemoglobin value it is recommended to reduce or to stop the treatment with ribavirin, to administer recombinant human erythropoietin or blood transfusion, based on the severity of the anemia. The growth rate of the serum erythropoietin in the first few weeks of treatment is correlated with the necessity of decreasing the doses or even to stop the treatment with ribavirin. The SVR (sustained viral response) rate of the patients is reduced when the ribavirin doses are reduced due to anemia.

In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems in different models of gastrointestinal injury.

1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and non-enzyme defence systems were investigated in models of stomach and colon damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of the parameters affected by indomethacin. 3. Treatment of rats with ethanol for 0.5 h led to a decrease in glutathione levels as well as activities of glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl failed to abolish the TNBS-induced changes in the followed-up parameters in colon mucosa and liver, but additional alterations (as with tolmetin) were not observed. 5. The beneficial profile of AMG in the various experimental models of free radical-induced damage investigated in this study suggests the possibility that this drug might possess antioxidant activity.

In vitro effects of alloxan/copper combinations on lipid peroxidation, protein oxidation and antioxidant enzymes.

The in vitro effects of alloxan and the product of its reduction dialuric acid (alone or in combination with copper ions) on lipid peroxidation, carbonyl content, GSH level and antioxidant enzyme activities in rat liver and kidney have been studied. The effects of Cu2+/alloxan and Cu2+/dialuric acid were compared with those of Fe3+/alloxan and Fe3+/dialuric acid. Unlike alloxan, dialuric acid increased liver and kidney lipid peroxidation; similar effects were registered in the presence of Fe3+. In the presence of Cu2+/dialuric acid, the lipid peroxidation was strongly inhibited and vice versa--the liver protein oxidation was increased. Alloxan and dialuric acid, as well as their combinations with Fe3+ had no effect on the total GSH level. Both substances did not affect the Cu2+-induced changes in GSH level, glucose-6-phosphate dehydrogenase and gluthatione reductase activities. In contrast, Cu2+ had no effect on dialuric-acid induced changes in gluthatione peroxidase and superoxide dismutase activities. The present in vitro results, concerning the metal dependence of the effects of alloxan and dialuric acid, are a premise for in vivo study of alloxan effects in metal-loaded animals.

[Regulatory functions of bacterial exometabolites].

This review deals with the issue of growth autoregulation and survival in bacterial cultures under starvation conditions. Based on our results and on published data, the conclusion has been drawn that low-molecular products of metabolism (carboxylic acids, amino acids, and other metabolites) perform regulatory functions. The same compounds also control the ecological relationship between microorganisms at the interspecific level, and affect their antagonistic activity. It is suggested that complexes of bacterial metabolites can be used for controlling the composition of various microbiocenosis, including those of humans.