[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.

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.

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.

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.

[The bacterial QS-systems and prospects of creation of new metabolic probiotic preparations].

Biological functions of exometabolits of various bacterial species were analyzed from Quorum Sensing position, which showed that the functional activity of microbiocenosis is in many respects determined by the system of metabolic regulation. Possibility of changing the composition of complex microbial communities with low-molecular compounds, products of bacterial cell vital activity, is grounded from theoretical point of view. The authors adduce data on the effects of a synthetic composition on the basis of E. coli metabolites, an ingredient of colibacterin, a probiotic preparation. The preparation demonstrated a high stimulating activity towards a range of microorganisms of normal microflora, and an ability to improve the condition of intestinal epitelial cells. The results may substantiate application of metabolic probiotics for correction of intestinal microflora in man.

Arterial stenosis and atherothrombotic events in polycythemia vera and essential thrombocythemia.

UNLABELLED: Patients with polycythemia vera (PV) and essential thrombocythemia (ET) are at risk of developing arterial and venous thromboembolic complications. Given the complex interaction between blood cells and the vessel wall, it is possible that atherogenesis may also be accelerated in these patients. We used Doppler arterial ultrasound to assess the presence of arterial stenosis in a cohort of PV and ET patients. MATERIAL AND METHODS: A total of 37 patients, 29 with PV and 8 with ET, were investigated. Aside from an extensive clinical and hematological evaluation, arterial Doppler ultrasonography was performed in all patients; in 3 patients arteriography/coronarography was also performed. RESULTS: Twenty four patients (65%) had a history of atherothrombotic events including cerebral ischemic attacks (CIA) in 12 patients, ischemic heart disease (IHD) in 10 patients and peripheral occlusive arterial disease (POAD) in 12 patients. Eight patients had multiple atherothrombotic events. Twenty five patients (67%) had other atherosclerotic risk factors such as smoking, dyslipidemia, hypertension and diabetes. Significant arterial stenosis was found in 23 patients (62.1%), including 12 patients with carotid plaques, 10 with peripheral arterial stenosis, 3 with coronary stenosis, 2 with aortic plaque and 2 with common iliac artery stenosis. In 12 patients multiple arterial stenoses were found. The presence of arterial stenosis was significantly correlated with the occurrence or thrombotic events (p = 0.0003) and was also correlated with the concomitant presence of polyglobulia and thrombocytosis. Both the thrombotic risk and the probability of stenosis detection were augmented by additional risk factors such as smoking, hypertension and dyslipidemia. DISCUSSION AND CONCLUSIONS: The high incidence of arterial thrombotic events in our PV and ET patients was associated with a high incidence of stenosis detectable by arterial ultrasound. Hyperviscosity, endothelial damage due to leukocyte activation with subsequent thrombus formation, hyperhomocysteinemia and hyperexpression of activating genes such as JAK2 and STAT5 are all features characteristic of PV and ET that may contribute, along with other risk factors, to the development and progression of atherothrombosis. Cytotoxic treatment in PV and TE may be beneficial both through its antiproliferative effect on hematopoiesis and on the atherosclerotic plaques, atherogenesis being described as a proliferative disease of the vessel wall.

Expression of estrogen receptor sub-types alpha and beta in acute and chronic cardiac allograft vasculopathy.

BACKGROUND: The vasculoprotective effects of estrogen are well-established not only in women with age-related atherosclerosis, but also after experimental vascular injury and in chronic allograft vasculopathy. Evidence exists that the newly discovered estrogen receptor (ER) beta, rather than the classical ERalpha is related to the vasculoprotective effect. Here we investigate whether and to what extent the two ERs are expressed in cardiac allografts in the rat and human in native state and during acute and chronic rejection. METHODS: Rat cardiac allografts were performed from male DA (AG-B4, RT1(a)) to male WF (AG-B2, RT1(v)) strain and syngeneic transplants from DA to DA strain; human male-to-male heart allograft endomyocardial biopsies came from our biopsy files. RESULTS: Under in situ hybridization, ERbeta mRNA was prominently expressed in rat vessels and stroma, whereas ERalpha mRNA was present in low levels only. In immunohistochemistry, 2 ERbeta-specific antibodies stained rat and human vessels and stroma, whereas only a weak or no signal was obtained with 2 ERalpha-specific antibodies. Interestingly, the mRNA and protein expression levels in the rat carried only a weak correlation with the intensity of acute rejection, i.e., was not related to the intensity of inflammation. CONCLUSIONS: Our results demonstrate that ERbeta is the predominant ER in rat and human cardiac allografts, and suggest that, unless additional ERs are identified, the vasculoprotective effects of estrogen derivatives in cardiac allograft vasculopathy are mediated by ERbeta rather than by the classical ERalpha.