[Surgical treatment and prognostic factors in perihilar tumors]. / Khirurgicheskoe lechenie i faktory prognoza pri perikhilyarnoi opukholi.

OBJECTIVE: To study the results of surgical treatment in patients with perihilar tumors. MATERIAL AND METHODS: We analyzed 98 patients with perihilar tumors who underwent surgery. RESULTS: We prefer percutaneous transhepatic biliary drainage (n=58) for jaundice. Retrograde interventions were performed in 18 cases (20.5%), complications grade III-IV were more common (p=0.037) in the last group. Postoperative mortality was 12%. Complications developed in 81 patients (82.7%), grade ≥3 - in 39 (39.8%) cases. Portal vein resection (n=26) increased the incidence of complications grade ≥III (p=0.035) and portal vein thrombosis (p=0.0001). Chemotherapy after surgery was performed in 47 patients (48.0%), photodynamic therapy - in 7 (7.1%) patients. A 5-year overall survival was 28.1%, the median survival - 29 months. R2 resection and/or M1 stage (n=12) significantly worsened the prognosis and overall survival (16.5 vs. 31 months, p=0.0055). Lymph node (LN) lesion, microscopic status (R0 vs. R1) of resection margin, technique of decompression and isolated resection of extrahepatic bile ducts did not affect the prognosis, and we combined appropriate patients (n=72) for analysis. SI resection and excision of ≥6 lymph nodes were independent positive factors for disease-free survival (p=0.042 and p=0.007, respectively). Blood transfusion and high preoperative neutrophil-lymphocyte index (NLI ≥2.15) worsened overall (p=0.009 and p=0.002, respectively) and disease-free survival (p=0.002 and 0.007, respectively). The absence of adjuvant therapy worsened disease-free survival alone (p=0.024). CONCLUSION: SI liver resection, adequate lymph node dissection and adjuvant therapy should be used for perihilar tumors. Isolated resection of extrahepatic bile ducts is permissible in some cases. Blood transfusion and NLI ≥2.15 are independent negative prognostic factors.

[Intestinal microbiome as a predictor of the anti-PD-1 therapy success: metagenomic data analysis]. / Mikrobiom kishechnika kak prediktor uspekha anti-PD1 terapii: analiz metagenomnykh dannykh.

Anti-PD-1 immunotherapy has a large impact on cancer treatment but the rate of positive treatment outcomes is 40-45% and depends on many factors. One of the factors affecting the outcome of immunotherapy is the gut microbiota composition. This effect has been demonstrated both in model objects and in clinical patients groups. However, in order to identify clear causal relationships between microbiota and anti-PD1 immunotherapy response, it is necessary to expand the number of patients and experimental samples. This work presents an analysis of metagenomic data obtained using whole-genome sequencing of stool samples from melanoma patients (n=45) with different responses to anti-PD1 therapy. The analysis of the differential representation of microbial species has shown a difference in the composition of the microbiota between the experimental groups. Results of this study indicate existence of a strong link between the composition of the gut microbiota and the outcome of anti-PD1 therapy. Expansion of similar research may help develop additional predictive tools for the outcome of anti-PD1 cancer immunotherapy, as well as increase its effectiveness.

[Cholangiocellular cancer: the state of the problem and ways to improve the results of surgical treatment]. / Kholangiotselliuliarnyi rak: sostoianie problemy i puti uluchsheniia khirurgicheskogo lecheniia.

AIM: To improve the outcomes in patients with resectable biliary cancer. MATERIAL AND METHODS: There were 263 procedures for cholangiocellular carcinoma (CCC) for the period 1998­2017. Adjuvant chemotherapy was performed in 102 (38.8%) patients. Extensiveliver resections (78.9%) prevailed for intrahepatic cholangiocellular carcinoma (n=128), 6 (4.7%) patients required vascular resection. Seventy-seven pancreatoduodenectomies were performed for common bile duct cancer, portal vein resection was done in 8 (10.4%) patients. In case of Klatskin tumor (n=58) liver resection combined with bile duct resection (n=52) prevailed. Portal vein resection was done in 16 (27.6%) patients. RESULTS: Postoperative morbidity in patients with intrahepatic CCC was revealed in 68 (53.1%) cases, mortality ­ in 5 (3.9%) cases. Among patients with Klatskin tumor morbidity was revealed in 51 (87.9%) cases, mortality ­ in 6 (10.3%) cases. In patients with common bile duct cancer morbidity was revealed in 53 (68.8%) cases, mortality ­ in 4 (5.2%) cases. In whole cohort median overall survival was 30 months. R0-resection was associated with better long-term results (median 37 months) compared with R1­R2 resection (20 months; p=0.01). Lymph node involvement is associated with significantly worse prognosis (p=0.016), however 5-year survival is observed (25.6%). Adjuvant chemotherapy in R0-resection significantly improved long-term results: median was 46 months (vs. 30 in group without chemotherapy; p=0.02). In intrahepatic CCC patients multiple lesions or mechanical jaundice did not aggravate long-term results. CONCLUSION: R0-resection including lymphadenectomy, resection of adjacent organs and vessels is advisable for CCC. Isolated bile duct resection should be used as an exception. Adjuvant therapy improved long-term results. Multiple lymph node lesion or bile duct infiltration are not contraindications to surgery in intrahepatic CCC patients.

[Impact of СD8/FoxP3 T lymphocyte ratio in the peritumoral area of primary cutaneous melanoma on the prognosis of the disease]. / Vliyanie sootnosheniya CD8/FoxP3 T-limfotsitov v peritumoral'noi zone pervichnoi melanomy kozhi na prognoz techeniya zabolevaniya.

UNLABELLED: Cutaneous melanoma (CM) is a malignant tumor characterized by typical histological features, one of which is tumor-infiltrating lymphocytes (TIL) that reflect the state of local immunity and determines the course of the disease. AIM: to study a correlation of the ratio of CD8/Foxp3 T lymphocyte subpopulations infiltrating primary cutaneous melanoma (PCM) with the clinical and morphological factors and prognosis of the disease. MATERIAL AND METHODS: The CD8+ and FoxP3+ T-lymphocyte subpopulations infiltrating PCM were investigated in 180 cases by immunohistochemical staining with anti-CD8 and anti-FoxP3 antibodies. RESULTS: The predominant type of TIL was CD8+ cytotoxic T lymphocytes (80.1 cells in the field of vision); FoxP3+ T lymphocytes averaged 34.9 cells in the field of vision. There was a statistically significant correlation of a high ratio of CD8/FoxP3 T cells with disease stage, ulceration and regression segments in PCM, a low disease progression rate, and higher 5-year overall and relapse-free survival. CONCLUSION: The findings may be used in researches and in the practical work of pathologists and clinicians.

[Treatment of advanced ovarian cancer: results of the Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin RORC from 1993-2010].

The aim of this study was to analyse the outcome of ovarian cancer depending on the type of surgical debulking, the strategy of treatment of recurrent cancer, and other clinical factors. We performed retrospective analysis of patients with stage IC-IV ovarian cancer treated at the Department of Clinical Pharmacology and Chemotherapy in 1993-2010. A total of 353 patients were included. The medians of progression-free and overall survival were 11.3 and 40.8 months respectively. The results of the treatment depended on the mode of surgical debulking, histological type and stage of the tumour, regimen of front-line chemotherapy. The main prognostic factor in recurrent ovarian cancer was the number of potentially effective anticancer agents used during the treatment.

A prognostic model in patients treated for metastatic gastric cancer with second-line chemotherapy.

BACKGROUND: This retrospective study was carried out to evaluate the prognostic significance of clinical factors in patients treated for metastatic gastric cancer with second-line chemotherapy. PATIENTS AND METHODS: We evaluated the prognostic significance of various clinical factors in 126 patients, who were treated with second-line chemotherapy. RESULTS: Median progression-free and overall survival (OS) for second-line chemotherapy were 3.3 and 5.3 months, respectively, with an overall response rate of 11.1%. Multivariate analysis identified three independent prognostic factors: performance status: Eastern Cooperative Oncology Group zero to one [hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.7-5.4], hemoglobin (Hb) level: >/=10 g/dl (HR 2.2, 95% CI 2.1-2.4) and time-to-progression (TTP) under first-line therapy: >/=5 months (HR 0.5, 95% CI 0.3-0.8). From the obtained data, a prognostic index was constructed, dividing the patients into three risk groups: good (n = 40), intermediate (n = 36) and poor risk group (n = 56). The median survival for good, intermediate and poor risk groups were 13.5, 6.0 and 2.9 months, respectively, whereas the 1-year OS rates were 50.2%, 14.2% and 2.6%, respectively (P = 0.00001). CONCLUSIONS: With inadequate data from randomized controlled trials at the moment, our report indicates that second-line chemotherapy is effective and beneficial in patients with good performance status, higher Hb level along with higher TTP under first-line therapy.

[A novel marker of multiple drug resistance BCRP]. / Novyi marker mnozhestvennoi lekarstvennoi rezistentnosti--BCRP.

Data on a new marker of multidrug resistance from the group of ABC-transporters--BCRP (breast cancer resistance protein) and in particular the data on the general characteristics of BCRP, spectrum of substrates for this transporter, data on the role of BCRP in human organism, pathways of inhibiting BCRP-dependent transport by pharmacological agents are presented. The data on BCRP expression in human normal tissues and tumor cells are considered in detail. Possible reasons of results inconsistency in evaluation of BCRP expression in different tumors and prognostic significance of BCRP in prediction of sensitivity to chemotherapy and aggressiveness of disease process are discussed.