Automated Assessment of the Area of Infiltration by CD8+ Cells in Gastric Carcinoma and Areas of Normal Mucosa as a Significant Prognostic Factor.

In 139 patients with verified gastric cancer, the infiltration of the postoperative material with CD8+ cells was analyzed. Automated morphometric analysis of immunostained slides was performed separately in different specimen sites (tumor center, invasive edge, and peritumoral mucosa). The mean area of infiltrating CD8+ cells in the tumor center and in the invasive edge was not predictive, while in the peritumoral mucosa it provided a new negative predictive factor (hazard ratio 2.10; confidence interval 0.87-4.92, Cox regression) reliably associated with the TNM stage (hazard ratio 1.91; confidence interval 0.91-4.61, Cox regression).

[Mucins expression in gastric cancer: connection of MUC status with clinical, morphological and prognostic characteristics of the tumor]. / Ekspressiya mutsinov v rake zheludka: svyaz' MUC-statusa s kliniko-morfologicheskimi i prognosticheskimi kharakteristikami opukholi.

OBJECTIVE: Clarification of the prognostic value and relationship of MUC-phenotypes of gastric cancer with clinical and morphological parameters. MATERIAL AND METHODS: Surgical material from 310 patients with a verified diagnosis of gastric cancer was studied. Samples were immunohistochemically stained with antibodies to MUC2, CD10, MUC5AC. The results were compared with clinical and morphological characteristics of gastric cancer and patient survival data. RESULTS: The MUC-null and MUC-mix groups significantly differ in the prevalence of subtotal/total tumors from the MUC-I group (p=0.022 and p=0.007, respectively), where there are significantly fewer such tumors. Tubular tumors were more common in the MUC-null group compared to the MUC-G (p=0.026) and MUC-mix (p=0.006) groups, and there were fewer cases with the presence of "signet-ring" cells in the MUC-null group (p=0.000). When studying the discohesive histological type, the literature data on smaller tumor sizes and a lower frequency of lymph node metastasis for MUC-G status were not confirmed, but a more frequent proximal localization of MUC-I tumors was found (p=0.003). No statistically significant differences in survival were found in the analysis of the total sample. Differences in survival were found only in discohesive cancers, where the best survival was recorded for the MUC-null group, and the worst for the MUC-mix group (p=0.022). MUC status is not an independent predictor of gastric cancer (HR=1.662, p=0.093). CONCLUSION: Between tumors with different MUC statuses, there were differences in localization and belonging to individual histological types. Significant differences in survival were found only for discohesive cancers with MUC-null and MUC-mix statuses. Separation of gastric cancers according to MUC status may have only limited predictive value in selected histological forms of cancer.

[Prognostic significance of PD-L1 expression as a potential predictor of survival in gastric cancer]. / Prognosticheskaya znachimost' ekspressii PD-L1 kak potentsial'nogo prediktora vyzhivaemosti pri rake zheludka.

BACKGROUND: Currently, PD-L1 expression in patients with tumors of various localizations is being actively studied. Studies on the expression of PD-L1 detected by clones SP142 and SP263 in gastric cancer (for the drugs atezolizumab and durvalumab, respectively) are rare in the literature. The prognostic role of PD-L1 expression in patients who were not treated with immune checkpoint inhibitors has also not been investigated. OBJECTIVE: To determine the expression level of PD-L1 (clones SP263 and SP142, Roche Ventana) in gastric cancer specimens and evaluate its effect on overall survival in patients who did not receive adjuvant therapy with immune checkpoint inhibitors. MATERIAL AND METHODS: The study included 131 patients with a verified diagnosis of gastric cancer. The material obtained from 127 patients was stained with antibodies to PD-L1 SP263, and from 126 patients - with antibodies to PD-L1 SP142. A multivariate Cox regression model with Wald's step-by-step exclusion algorithm was used to evaluate predictors of survival. RESULTS: The total five-year survival rate of patients in the PD-L1-negative tumor group was significantly lower than the total five-year survival rate of patients in the PD-L1-positive tumor group, which was 50.0% and 40.0% also for both clones (p=0.027). An increase in the expression of PD-L1 clone SP263, determined by both the CPS and TPS method, reduces the chances of death by 1.35 times (p=0.02) and 1.61 times (p=0.004), respectively. An increase in the expression of PD-L1 clone SP142, determined by the CPS method, reduces the chances of death by 1.54 times (p=0.005). CONCLUSION: The survival rate of patients in the group of PD-L1-positive tumors is significantly higher than in patients in the group of PD-L1-negative tumors. Elevated PD-L1 expression, as assessed by the SP263 and SP142 clones, is an important prognostic marker that predicts a higher chance of overall survival for patients, even though these patients are not receiving immune checkpoint inhibitors adjuvant therapy.

[Microsatellite instability in gastric cancer is a predictor of a favorable prognosis]. / Mikrosatellitnaya nestabil'nost' v rake zheludka ­ prediktor blagopriyatnogo prognoza.

OBJECTIVE: Evaluation of the frequency of microsatellite instability in gastric adenocarcinomas in patients of the Russian Federation, determination of the relationship of microsatellite instability with clinical and morphological characteristics and the impact on the prognosis. MATERIAL AND METHODS: We used samples of surgical material from 310 patients with a verified diagnosis of gastric cancer. The age of the patients ranged from 22 to 85 years (mean 63 years). The median follow-up of patients was 83 months. Each sample was immunohistochemically stained with antibodies to microsatellite instability markers MLH1, MSH2, MSH6, and PMS2. The results were compared with the main clinical and morphological characteristics of gastric cancer and data on patient survival. RESULTS: The frequency of detection of MMR-negative tumors in the Russian population is 8.1% of all patients with gastric cancer. It was found that patients with MMR-negative gastric carcinomas are older (mean age 69 years, p=0.008). In this group predominates distal localization of tumors, type 2 according to R. Bormann classification (p=0.010), tubular histological type (p=0.010), intestinal subtype according to P. Lauren classification (p=0.003). There were no significant differences between MMR-negative and MMR-positive tumors in terms of other clinical and morphological parameters (including the stage of the tumor process). The overall median survival of patients with MMR-negative tumors was 76%, which significantly (p=0.013) exceeds that in the group of MMR-positive tumors (36%). It was found that despite significant differences in survival, MMR-status is not an significant prognostic factor in gastric cancer (HR=0.983). CONCLUSION: The established differences in patient survival make it possible to distinguish a group of MMR-negative tumors into a separate pathogenetic subtype of gastric cancer (MSI subtype) based on immunohistochemical studies. This subtype occurs predominantly in elderly patients with tubular gastric adenocarcinomas and is characterized by a favorable prognosis.

[PD-L1 expression in EBV-associated gastric carcinomas]. / Ekspressiya PD-L1 v EBV-assotsiirovannom rake zheludka.

OBJECTIVE: Assessment of the incidence of PD-L1 expression in EBV-associated gastric adenocarcinomas, as well as clarification of the clinical and morphological characteristics and median survival of patients with PD-L1-positive EBV-associated gastric cancer. MATERIAL AND METHODS: Samples of surgical material from 127 patients with stomach cancer were studied. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). Expression of PD-L1 was assessed immunohistochemically (PD-L1 SP263, PD-L1 SP142). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer and median survival of patients. RESULTS: The detection rate of PD-L1 SP263 and PD-L1 SP142 in EBV-associated gastric adenocarcinoma in our sample was 100% and 76.9% respectively, thus, PD-L1 expression (SP263, SP142) is significantly more frequently detected in EBV-associated gastric carcinomas. It was found that patients with positive expression of PD-L1 in EBV-associated gastric carcinomas are younger (mean age 56.3 years for SP263 and 55.6 years for SP142), belonging to male gender. In addition, this group is dominated by proximal localization of tumors, ulcerative form of growth, tubular histological type, intermediate subtype according to P. Lauren. These characteristics do not depend on the antibody clone: positive expression of SP142 and SP 263 was detected in the same patients with a few exceptions. The overall median survival of patients with positive PD-L1 status SP263 in EBV-associated gastric carcinomas was 35 months, for patients with positive PD-L1 status SP142 - 25 months. Median survival of SP142 PD-L1 positive patients is higher than overall median survival of PD-L1 negative patients in EBV-associated gastric carcinomas. It was found that PD-L1 status in EBV-associated gastric cancer is not a significant prognostic factor. CONCLUSION: A single PD-L1 status does not significantly affect the prognosis in patients with gastric cancer, including those in the group of EBV-associated carcinomas, and can only be considered in conjunction with 'classic' clinical and morphological characteristics, primarily with the stage of the tumor process, since they determine the prognostic properties of the tumor.

[Study of gastric adenocarcinomas association with the Epstein-Barr virus-encoded small RNAs]. / Issledovanie assotsiatsii adenokartsinom zheludka s malymi virusnymi RNK virusa Epshteina­Barr.

OBJECTIVE: Assessment of the incidence of EBV-associated gastric adenocarcinomas in a sample of Russian patients, as well as clarification of the clinical and morphological characteristics and median survival of patients with EBV-associated gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 282 patients with a verified diagnosis of gastric cancer. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer. RESULTS: The detection rate of EBV-associated gastric adenocarcinoma in our sample was 9.57%. EBER-positive tumors much more often (p=0.021) belong to the intermediate type according to the P. Lauren classification (66.67%) in comparison with EBER-negative tumors (38.82%). EBER-positive tumors significantly more often (p=0.035) belong to high-grade tumors - 75.00% in comparison with EBER-negative tumors (52.13%). The overall median survival of all patients with EBER-positive tumors (53.5 months) was higher compared to the overall median survival of all patients with EBER-negative tumors - 36.5 months (p=0.5379). The median survival of patients with EBER-positive stage III tumors (30.0 months) was also higher compared to that for patients with EBER-negative tumors - 20.0 months (p=0.5622). It was found that a single EBER status is not a significant prognostic factor (HR=1.0143; CI: 0.9897-1.0196). CONCLUSION: Separately taken EBER-status is not a significant independent prognostic factor and can be considered only in conjunction with the «classical¼ clinical and morphological characteristics, primarily with the stage of the tumor process, since it is they that determine the prognostic properties of the tumor.

[Persistence of Epstein-Barr virus antigens in gastric cancer: characteristic of inflammatory cellular reactions in tumor]. / Persistentsiya antigenov virusa Epshteina­Barr pri rake zheludka: kharakteristika vospalitel'nykh kletochnykh reaktsii v opukholi.

THE AIM OF THE STUDY: Is to establish the relationship between the persistence of viral antigens of the Epstein-Barr virus (EBV) and the cellular composition of the immune microenvironment of tumor tissue and the mucous membrane of peritumoral area in gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 55 patients with a verified diagnosis of gastric cancer. The expression of CD4, CD8, CD68, CD1a and LMP-1 was assessed. The results were assessed by the morphometric method. We selected three fields of view (magnification x200) in tumor tissue and in peritumoral areas separately and counted an absolute number of cells with positive staining with further calculation of the average number of cells and the median. RESULTS: LMP-1-negative tumors with LMP-1 expression in epithelium of peritumoral area were characterized by the highest density of CD4+ lymphocyte infiltration in the central part of the tumor; the highest density of CD8+ lymphocyte infiltration in the mucous membrane of peritumoral area (p=0.0190); the highest density of infiltration by macrophages in the mucous membrane of peritumoral area (p=0.2492); the highest density of infiltration by CD1a+ cells in the mucous membrane of peritumoral area (p=0.1503). The highest density of infiltration with CD1a+ cells was characteristic for LMP-1-positive and LMP-1-negative tumors (p=0.0813). The persistence of the LMP-1 viral antigen in the glandular epithelium of the peritumoral area in our sample does not have a statistically significant effect on the prognosis of the disease (RR=1.7718; p=0.0885) but there is a tendency towards a negative predictive value. CONCLUSION: High density of infiltration of glandular epithelium of peritumoral area with the expression of LMP-1 by CD4+ and CD8+ lymphocytes is most likely associated with the activation of the cellular immune response and may be one of the signs of the persistence of viral antigens. It was shown for the first time that the phenomenon of persistence of the LMP-1 viral antigen is characterized by a trend towards negative predictive value for patients with gastric cancer.

[Resection of retroperitoneal leiomyosarcoma followed by replacement of cavarenal segment of inferior vena cava]. / Udalenie zabryushinnoi leiomiosarkomy s rezektsiei i protezirovaniem kavarenal'nogo segmenta nizhnei poloi veny Klinicheskoe nablyudenie.

The authors reported a rare clinical case of successful surgical treatment of young female with retroperitoneal leiomyosarcoma followed by lesion of the cavarenal segment of inferior vena cava, left renal vein. Clinical and morphological features of disease, postoperative outcomes and prognostic factors in patients with retroperitoneal leiomyosarcoma are discussed.

[Anaesthesia and intensive care during intraoperative intraperitoneal hyperthermic chemotherapy in patients with gastric cancer (literature review and own clinical experience)].

UNLABELLED: Despite a steady decline in the incidence in recent decades, gastric cancer remains one of the most frequent causes of death from cancer in the world. By the time of diagnosis the tumor process is locally advanced or generalized in nearly 70% of patients that reduces the possibility of radical surgical treatment. Peritoneal carcinomatosis is a one of the main causes of treatment failure. There patients need complex treatment with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) to improve the quality and duration of life. Today in Russia, surgeries with IHIC are performed in a very limited number of oncology hospitals, thus there is no unified approach to the perioperative management of these patients. DESIGN: Since November 2010 in our institution we started a prospective clinical study of the use of intraoperative hyperthermic intraperitoneal chemotherapy in patients with locally advanced or metastatic gastric cancer. MATERIALS AND METHODS: The study included 30 patients (18 men and 12 women) who underwent transabdominal gastrectomy with extended lymphadenectomy D2, supplemented principled cholecystectomy and oophorectomy (in women). Mean age was 48.5 ± 5.3 years. Technique involved the use of regional anesthesia com- ponent and inhalation anesthetic sevoflurane. Preoperative preparation included enteral nutrition (based on 25-30 kcal/ kg/day), liver protection (intravenous remaxol infusion of 500 ml/day for 3 days prior to surgery), antisecretory and antifermental therapy (omeprazole 40 mg/day, 100 mg octreotide for 2 h before surgey, aprotinin sulfate 30000 after induction of anesthesia), antioxidant and immunomodulatory therapy (galavit, cytoflavin, ceruloplasmin vitamin C), anticoagulant prophylaxis (enoxaparin sodium 40 mg on the evening before surgery). RESULTS: Analysis of the world and our own clinical experience with intraoperative hyperthermic intraperitoneal chemotherapy in a comprehensive plan of treatment of patients with gastric cancer showed that the this aggressive, but highly effective technique can be requires not only careful patient selection according to the criteria, but also the use of special methods to protective therapy at all stages of the surgical treatment. Application of pathogenetic ways of protection from thermal injury, timely control and correction of homeostasis caused by the toxic effects of chemotherapy and burn peritoneum, early enteral nutrition and the use of organ-therapy reduce the risk of complications and achieve better results of treatment in cancer patients.

[ENDOCYTOSCOPY--NOVEL ENDOSCOPIC DIAGNOSTICS APPROACH: PRINCIPLES AND PROCEDURE].

Endocytoscopy is one of the most novel endoscopic diagnostic procedures, providing optical magnification up to 1150 times of gastrointestinal and respiratory tract mucosa. Such approach allows real-time tissue and cellular structure visualization. Endocytoscopy, along with confocal laser endomicroscopy, can be considered as "optical biopsy" in vivo. Of course, endocytoscopy currently is experimental diagnostic method, all available endocytoscopes are prototypes. According to published data, endocytoscopy can be used in precancerous conditions and early intramucosal cancer diagnostics in esophagus, stomach, colon and bronchial tree. Different types of endocytoscopes are used for examinations: some of them are baby-scopes, with fixed magnification 570-1150 times, introduced into accessory channel of the therapeutic parent-endoscope, others--are integrated type, providing scalable magnification from 80 to 380 times. As for traditional pathology ex vivo, for endocytoscopy mucosal cell nuclei stain is needed. For vital staining during endocytoscopy methylene blue, toluidine blue and crystal violet in different concentrations are more often used. In cases of squamous-cell dysplasia or cancer, it is recommended to use 1% methylene blue solution, whereas in intestinal type metaplasia, dysplastic changes and cancer (Barrett's esophagus, P. Correa precancerous cascade, colon adenomas), 1% toluidine blue is preferred. With endocytoscopy, after vital staining, we can visualize and estimate mucosa tissue and cell characteristics: papillae, crypt and gland shapes and sizes, their integrity (tissue markers); cell nuclei size and shape, polarity and nuclear dye intensity (cell markers).

[ENDOCYTOSCOPY--NEW TYPE OF ENDOSCOPIC EXAMINATION OF LOWER GASTROINTESTINAL AND RESPIRATORY TRACT].

Majority of published data describing endocytoscopic examination of upper gastrointestinal tract mucosa, but in recent publications, it is reported, that endocytoscopy is suitable for small bowel, colon, respiratory tract and even peritoneum "optical biopsy". In number of articles possibilities of celiac sprue diagnostics with endocytoscopy is discussed, but small-bowel endocytoscopy is limited, due to absence of endocytoscopes, compatible with enteroscopes. More widely endocytoscopy is used in colon, mostly in lateral-spreading adenomas diagnostics. Prof. S-E. Kudo developed endocytoscopic classification of colonic mucosa changes, used for differential diagnostics and lesion mapping, describing hyperplasia, adenomas with different grades of intraepithelial neoplasia, non-invasive and invasive cancer. Some authors reported about good possibilities of endocytoscopy in inflammatory bowel disease diagnostics. Most of data, related to respiratory tract endocytoscopic examination, focused on precancerous conditions and early pharyngeal and lung cancer, and the preliminary results are promising, but, unfortunately, for now, endocytoscopy in bronchial tree is limited, due to lack of thin endocytoscopes. According to some article data, it is possible to use endocytoscopy not only in gastrointestinal and respiratory tract, but also in optical confirmation of peritoneal tumor dissemination in gastric and ovarian cancer patients, and--in bladder mucosa examination.