Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer.

A comprehensive analysis of the cell phenotype of the inflammatory infiltrate of the tumor stroma represents a promising area of molecular oncology. The study of not only soluble forms of various immunoregulatory molecules, but also their membrane-bound forms is also considered highly relevant. We performed a comprehensive analysis of tissue and circulating forms of the PD-1 and PD-L1 proteins, as well as macrophage and B-cell markers in the tumor stroma of gastric cancer, to assess their clinical and prognostic significance. The tumor and blood plasma samples from 63 gastric cancer patients were studied using ELISA and immunohistochemistry. Malignant gastric tumors were shown to be strongly infiltrated by B-cells, and their number was comparable to that of macrophages. For PU.1 expression, an association with tumor size was observed; i.e., larger tumors were characterized by fewer PU.1+ infiltrating cells (p = 0.005). No clinical significance was found for CD20 and CD163, but their numbers were higher at earlier stages of the disease and in the absence of metastases. It was also demonstrated that the PD-L1 content in tumor cells was not associated with the clinical and morphological characteristics of GC. At the same time, PD-L1 expression in tumor stromal cells was associated with the presence of distant metastases. The analysis of the prognostic significance of all the markers studied demonstrated that CD163 was statistically significantly associated with a poor prognosis for the disease (p = 0.019). In addition, PD-L1 expression in tumor cells tended to indicate a favorable prognosis (p = 0.122). The results obtained in this work indicate that the study of soluble and tissue markers of tumor stroma is promising in prognosticating the course of GC. The search for combinations of markers seems to be highly promising, with their comprehensive analysis capable of helping personalize advanced antitumor therapy.

[Active surgical approach for retroperitoneal liposarcoma]. / Rol' aktivnoi khirurgicheskoi taktiki pri zabryushinnoi liposarkome.

OBJECTIVE: To assess the influence of active surgical approach on the long-term postoperative outcomes in patients with retroperitoneal liposarcoma. MATERIAL AND METHODS: A retrospective study included 190 patients with retroperitoneal liposarcoma. The effect of malignancy grade, adjuvant chemotherapy, number of separate tumor nodes in primary neoplasm and the first relapse, as well as the number of previous total resections on survival rate was analyzed. RESULTS: Overall and relapse-free survival is significantly worse in patients with high-grade retroperitoneal liposarcoma (G2-3) compared to low-grade (G1) tumor (plog-rank=0.000). Multifocal growth of primary tumor (p=0.869; plog-rank=0.607) and multiple (>1) separately located nodes in abdominal cavity and retroperitoneal space at the first relapse (plog-rank=0.158 to 0.985) did not significantly impair prognosis after total resection of all types of retroperitoneal liposarcoma regardless malignancy grade. Adjuvant chemotherapy does not significantly improve relapse-free survival. Overall survival was significantly higher in patients who underwent ≥4 previous total resections compared to 1 surgical treatment for all types of retroperitoneal liposarcoma regardless malignancy grade (p=0.000; plog-rank=0.001). CONCLUSION: The only potentially radical treatment for patients with retroperitoneal liposarcoma is surgery. We reported the advantages of active surgical approach for improvement of long-term outcomes in patients with retroperitoneal liposarcoma.

[Differentiated surgical approach for retroperitoneal non-organ liposarcoma]. / Differentsirovannyi podkhod v khirurgii zabryushinnykh neorgannykh liposarkom.

OBJECTIVE: To determine the indications for combined and organ-sparing surgery depending on malignancy grade of retroperitoneal liposarcoma. MATERIAL AND METHODS: A retrospective study included 190 patients with retroperitoneal liposarcoma. Influence of malignancy grade, lesion of adjacent organs and resection/excision of adjacent organs on the overall and recurrence-free survival was studied. Moreover, we analyzed the issue of kidney-sparing surgery and nephrectomy. RESULTS: Overall and recurrence-free survival were significantly worse in high grade (G2-3) compared to low-grade tumors (G1) (p=0.0001; log-rank test). Visceral invasion was revealed in 23% of patients with low-grade (G1) tumors and 53% of patients with high-grade (G2-3) neoplasms. Visceral invasion significantly impairs overall and recurrence-free survival in both low grade (G1) and high-grade (G2-3) tumors (p=0.0001; log-rank test). In case of low grade (G1) retroperitoneal liposarcoma, overall and recurrence-free survival was similar after combined surgery without histologically confirmed visceral invasion of liposarcoma and organ-sparing surgery (p=0.006; p=0.053; log-rank test). On the contrary, high grade (G2-3) tumor was followed by significantly better overall and recurrence-free survival after combined surgery without histologically confirmed visceral invasion compared to organ-sparing surgery (p=0.006; p=0.053; log-rank test). Recurrence-free survival was similar after kidney-sparing surgery and nephrectomy among patients with low-grade (G1) tumor (p=0.456; log-rank test). In case of high-grade retroperitoneal liposarcoma (G2-3), recurrence-free survival was significantly worse after kidney-sparing surgery compared to nephrectomy (p=0.039; log-rank test). CONCLUSION: Surgery is the only potentially radical treatment of patients with retroperitoneal liposarcoma. Organ-sparing including kidney-sparing surgery is advisable for low-grade liposarcoma (G1). On the contrary, organ-sparing surgery impairs long-term results and prognosis in patients with high-grade tumors (G2-3). Combined operations including nephrectomy are justified for high-grade retroperitoneal liposarcoma (G2-3).

[Retroperitoneal dedifferentiated liposarcomas: semi-quantitative assessment of the dedifferentiated component and prognosis]. / Zabryushinnye dedifferentsirovannye liposarkomy: polukolichestvennaya otsenka dedifferentsirovannogo komponenta i prognoz.

OBJECTIVE: To evaluate the impact of malignancy grade and the proportion of the dedifferentiated component (DC) in retroperitoneal dedifferentiated liposarcomas (DDLS) on the course and prognosis of the disease. MATERIAL AND METHODS: The retrospective study enrolled 74 patients with primary retroperitoneal DDLS who underwent radical surgical treatment in the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. Histological surgery specimens from all cases of DDLS were reexamined and reclassified. According to malignancy grades and the proportion of the dedifferentiated component in the tumor, the patients were divided into the comparison groups included in the intergroup analysis of overall and relapse-free survival (OS and RFS) rates. The authors also analyzed the relationship between the proportion of the dedifferentiated component in DDLS and the frequency of adjacent organ invasion. RESULTS: Patients with a more than 15% dedifferentiated component had significantly lower OS rates than those with a less than 15% one (p=0.0001; log-rank test). The median OS in the DDLS group with a less than 15% dedifferentiated component was 91 months (95% CI, 82-100); that in the DDLS group with a more than 15% dedifferentiated component was 29 months (95% CI 17-41). The 5-year overall survival rates in the groups with less than 15% and more than 15% dedifferentiated components were 69% and 2%, respectively. The group with a more than 15% dedifferentiated component had significantly lower RFS rates than that with a less than 15% one (p=0.0001; log-rank test). In the DDLS groups with less than 15% and more than 15% dedifferentiated components, the median RFS rates were 25 months (95% CI 23-27) and 13 months (95% CI 8-18), respectively. In these groups, the 2-year RFS rates were equal to 50% and 9%, respectively. In the DDLS groups with less than 15% and more than 15% dedifferentiated components, pathologically confirmed invasion into the adjacent organs was observed in 32% and 63% of cases, respectively. There were no statistically significant differences in the OS and RFS of patients with DDLS according to tumor grade (p=0.069; p=0.102). CONCLUSION: This investigation suggests that DDLS have a more aggressive course with an increasing proportion of the dedifferentiated component in the tumor. Considering the histological variability in the dedifferentiated component, which is demonstrated in the research and scientific literature, as well as lack of a prognostic impact of histological grade, the authors believe that semi-quantitative assessment of the proportion of the dedifferentiated component in DDLS is able to serve as a simple and efficient morphological marker for the course of the disease and prognosis in retroperitoneal DDLS.

[Transanal mesorectumectomy for rectal cancer - is it optimal surgery for 'difficult' patients?] / Transanal'naia mezorektuméktomiia pri rake priamoi kishki - optimal'noe khirurgicheskoe vmeshatel'stvo dlia 'slozhnykh' patsientov?

AIM: To compare short-term outcomes after transanal total mesorectumectomy (Ta-TME) and laparoscopic (Lap-TME) procedure in 'difficult' patients. MATERIAL AND METHODS: Prospective nonrandomized trial included patients with confirmed middle-/low rectum adenocarcinoma T1-4aN0-2M0 for the period November 2013 - September 2016. We identified 20 out of 55 in TA-TME and 14 out of 54 patients in Lap-TME group as those of 'difficult' subgroup: male, BMI ≥25 кг/м2, previous chemoradiotherapy (CRT). RESULTS: Time of surgery, blood loss, conversions rate, postoperative morbidity and length of hospital-stay were similar in both groups. Hardware anastomoses were more frequent in TA-TME compared with LAP-TME group (78.9% vs. 50%, p=0.086). Specimen quality was more favorable in TA-TME group: Grade I 10% in Ta-TME group vs. 28.6% in Lap-TME group; 'positive' CRM 5% vs. 14.3%, р=0.365. Within-group analysis did not reveal any differences between 'difficult' and 'typical' patients by surgical and pathomorphological characteristics in TA-TME group in contrast to Lap-TME group. Median of follow-up was 24.6 (IR 10.6-40.2) and 23.8 (IR 12.1-39.9) months for TA-TME and Lap-TME groups, respectively. Local recurrence occurred in 1 (1.8%) 'difficult' patient after Ta-TME. Distant metastases were observed in 1 (1.8%) patient of Ta-TME and 2 (3.7%) patients of Lap-TME group. Actuarial 3-years reccurence-free survival was 95.7% for Ta-TME and 93.9% for Lap-TME group, respectively (p=0.923). CONCLUSION: TA-TME is advisable for 'difficult' patients. Further multicenter randomized trials are necessary to specify the effectiveness of TA-TME in these patients.

[Renal cell carcinoma associated with Xp11 translocation involving the gene]. / Pochechno-kletochnyi rak, assotsiirovannyi s Xp11-translokatsiei gena.

The paper describes a clinical case of the rare tumor renal cell carcinoma associated with Xp11 translocations involving the TFE3 gene in a 53-year-old male patient. It provides the detailed characteristics of current diagnostic techniques.

[Short-term outcomes of complete mesocolic excision for right colon cancer]. / Neposredstvennye rezul'taty pravostoronnei gemikoléktomii s total'noi mezokolonéktomiei i D3 limfodissektsiei pri lechenii raka pravoi poloviny obodochnoi kishki.

PURPOSE: Complete mesocolic excision (CME) appears to be a relatively new concept for colon cancer. The purpose is to evaluate the results of CME with high vascular ligation (D3 lymph node dissection) for right colon cancer. The presented study identifies possible risks and advantages of the proposed method, as well as the role of the laparoscopic approach. MATERIAL AND METHODS: The article included data from 39 patients with right colon cancer, TNM stage I-III, operated on between November 2015 and December 2016 in the oncoproctology Department of the Blokhin Cancer Research Center. The analysis of main intraoperative parameters, morbidity and mortality was carried out. RESULTS: There was no postoperative mortality. 17 (43.6%) of operations were performed by open and 22 - by laparoscopic approach. The conversion for laparoscopic approach was 1 (4.5%) in 22. The median duration of the operation was 180 (130-260) minutes for laparoscopic approach and 120 (90-280) minutes for open approach, р=0.0056. Median intraoperative blood loss was 30 (30-300) ml for laparoscopic approach, and 300 (30-500) ml for open approach (р=0.0001). The duration of lymphorrhoea, time to first bowel movement, time to start liquid and solid food intake were 5.1±2.4, 1.3±0.5, 1.26±0.4 and 3.2±0.7 days, respectively. The median number of removed lymph nodes was 35.7 (6-68), the median number of metastatic lymph nodes was 1.9 (0-16). The median number of removed apical lymph nodes was 10.3 (0-24). Metastases did not affect any of the lymph nodes of the apical group. CONCLUSION: Right mesocolic excision with D3 lymphadenectomy for right colon cancer is technically safe, and the laparoscopic approach provides all the benefits of minimally invasive surgery and excellent early treatment outcomes. Preliminary data shows no metastasis in apical lymphnodes for right colon cancer. Nonetheless, it is necessary to study the long-term results for the evaluation of oncological outcomes.

[Total mesorectal excision in rectal cancer management: laparoscopic or transanal?].

AIM: To evaluate and compare intraoperative features, early surgical outcomes, quality of excised specimen after laparoscopic and transanal total mesorectal excision (LA-TME and TA-TME). MATERIAL AND METHODS: Prospective randomized study included 45 patients with confirmed rectal adenocarcinoma (cT2-4N0-2M0) since October 2013. LA-TME and TA-TME groups consisted of 23 and 22 patients respectively. Inclusion criteria were patients with primary-operable rectal cancer and satisfactory response after neoadjuvant chemo- and radiotherapy. Both groups were comparable in stages of cancer, age and body mass index (BMI). Median length from anal edge was 6.5 cm and 7 cm in TA-TME and LA-TME groups respectively. There was significantly greater number of patients after chemo- and radiotherapy in TA-TME group (86% vs. 48%, p=0.006). RESULTS: Surgery time was 305 and 320 minutes in LA-TME and TA-TME groups recpectively, median blood loss -- less than 100 ml. Mean hospital-stay was 8.0 days in both groups. Each group had 1 conversion including laparoscopic procedure in TA-TME group. Transanal extraction of specimen was performed in 86% vs. 48% in TA-TME and LA-TME groups respectively (p=0.021). Complications (Clavien-Dindo sclale) were observed in 27% and 26% in TA-TME and LA-TME groups respectively without statistically significance. Complications IIIb, IVb and V degrees were not diagnosed in TA-TME group. Also in this group «good¼, «satisfactory¼ and «unsatisfactory¼ quality of TME was obtained in 68%, 14% and 18% of cases. At the same time in LA-TME group these values were 74%, 9% and 17% respectively (p=0.859). One of operated patients had «positive¼ lateral edge (TA-TME). Median distal edge of resection was 21 mm and 23 mm in TA-TME and LA-TME groups respectively. CONCLUSION: Preliminary data show comparable early outcomes after transanal and laparoscopic techniques. Laparotomy and associated compications are avoided in case of transanal extraction of specimen. Further researches are necessary to study functional and long-term results.

Short-term outcomes after transanal and laparoscopic total mesorectal excision for rectal cancer.

BACKGROUND: Transanal total mesorectal excision (taTME) has potential benefits of better visual control, especially in male patients with a high body mass index and low rectal cancer. However, this method has not yet been validated in clinical trials. The aim of this study was to compare the short-term outcomes of transanal and laparoscopic (lap) TME. METHODS: From October 2013 to January 2015, consecutive patients undergoing transanal or laparoscopic TME for biopsy-proven mrT1-4aN0-2M0 rectal cancer were included in a prospective database. Patients with Eastern Cooperative Oncology Group performance status 2 and higher and patients undergoing partial mesorectal excision were excluded. This analysis focused on short-term surgical outcomes. RESULTS: From October 2013 to January 2015, 22 taTME procedures and 23 laparoscopic TME procedures were performed. Patient characteristics were comparable between groups, but more patients in the taTME group underwent neoadjuvant (chemo) radiotherapy (87 vs. 48 %, p = 0.006). Median operative time was 320 min in the taTME group and 305 min in the lapTME group. There was one conversion in each group, but the transanal procedure was converted to laparoscopic resection. Transanal specimen extraction was performed in 86 versus 48 % patients in taTME and lapTME groups accordingly (p = 0.021). There was no post-operative mortality and post-operative morbidity in the taTME and lapTME groups was similar (27 vs. 26 %). One patient in the taTME group had positive circumferential resection margins. Oncologic results from resected specimens were comparable. CONCLUSIONS: Our initial experience demonstrates comparable short-term results for taTME and lap TME. Further investigation is necessary to assess long-term functional and oncologic outcomes.

Clinico-morphological analysis of the neuroendocrine neoplasms of the gastroenteropancreatic system.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are unusual and rare epithelial tumors for which the diagnosis of the grade of malignancy and prognostic assessment on the basis ofhistology represent considerable challenges for the pathologist. In this study we conducted a retrospective analysis of the cell proliferation (Ki-67 nuclear antigen) in primary and metastatic GEP NENs of 137 patients as well as the assessment of keratin 19 (CKI9) and progesterone receptors (PR) expression in pancreatic NENs of 57 patients. In 19 (27,1%) GEP NEN metastases was found I,5-4,5-fold increase of Ki-67 index compared with their primaries. Consequently, 6 (21,4%) cases of NETGI and 4 (7,0%) cases of NET G2 were up-graded Pancreatic NETs G2 with Ki-67 index >5% were significantly associated with presence of distant metastases (p =0,007) and decreased survival (p=0,03). Decreased survival also was found in the group of gastrointestinal NET G2 with Ki-67 index > 15% (p=0,005). Further analysis of immunomorphological features and proliferative activity allowed to separate a rare group of tumors - ("NET G3", characterized by decreased survival comparing to NET G2. Expression of CKI9 in pancreatic NETs was significantly associated with higher proliferative activity of primary tumor (p =0,04) and adverse outcome (p=0,003). On other hand, PR expression correlated with lower Ki-67 index (p=0,006), absence of metastases (p=0,004) and favorable outcome (p=0,000). Our results show that Ki67 index is a key parameter of morphological diagnosis of GEP NENs. Thus, the studied markers are important parameters of the morphological diagnostic of GEP NENs, which allow more accurately assess the degree of malignancy, prognosis and treatment of the disease.

[Inflammatory fibrosarcoma: a clinical morphological study of six cases].

The report describes the clinical and morphological characteristics of inflammatory fibrosarcoma (6). Tumor occurred in the mediastinum, small pelvis and liver in patients aged 12-64 yrs. It featured infiltrative growth. Primary tumor relapsed in 2 cases, distant metastases - 4. Four patients died from tumor progression within 7-14 months after diagnosis. Tumors consisted of neoplastic fibroblasts and lymphofibroblasts with polymorphous nuclei and high mitotic activity.

[Infantile myofibroma and myofibromatosis: clinical and morphologic assessment of eighteen cases].

Infantile myofibroma (myofibromatosis) (IM) is a mesenchymal tumor of soft tissues of the head, extremities and trunk. It is characterized by relapse-free infiltrative growth. It consists of neoplastic myofibroblasts at varying stage of cell differentiation which form multi-structured tumor zones. IM's morphological differentiated diagnosis is established vis-a-vis other varieties of tumor and reactive nodular structures of fibroblasts, primarily, infantile hemangiopericytomas and desmoid fibromatosis. Immunohistological and ultrastructural examination of tumor is required for making correct diagnosis of IM.

[Ectopic hormone production of beta-subunit of human chorionic gonadotropin by cells of signet ring cell carcinoma of the stomach].

The ectopic hormone production by tumor cells that have a light optical structure of typical non-endocrine cancers has long attracted the attention of investigation all over the world. Specifically, this concerns the phenomenon of the ectopic production of the beta-subunit of human chorionic gonadotropin (beta-hCG) by non-germinogenic tumors, which is, according to R.K. Iles's data, encountered in 20-40% of malignant epithelial tumors. Despite the fact that beta-hCG synthesis is traditionally regarded as the prerogative of germinogenic tumors, the world's literature contains strong evidence for latent beta-hCG gene expression and many cases of clinically evident manifestation of the effects of chorionic gonadotropin. The latter fact, if a clinician and a pathologist are unaware of the behavior of a tumor, may give rise to a diagnostic error and incorrect treatment policy.

Comparison of cholesterol and beta-sitosterol: effects on jejunal fluid secretion induced by oleate, and absorption from mixed micellar solutions.

Jejunal fluid secretion induced by perfusion with oleic acid can be reduced by the addition of cholesterol. The present study was performed to test the specificity of this effect by comparing the effects of cholesterol with that of a plant sterol, beta-sitosterol during perfusion of the jejunum in healthy volunteers. In addition, we compared the solubilities of cholesterol and beta-sitosterol in micellar solutions and their jejunal absorption rates. One millimolar beta-sitosterol was as effective as 1 mM cholesterol in reducing jejunal fluid secretion induced by 6 mM oleate (n = 7). In mixed micellar solutions consisting of 10 mM taurocholate and 6 mM oleate, solubility of beta-sitosterol is about one third of cholesterol solubility. When cholesterol was gradually replaced by beta-sitosterol in the incubation mixture, beta-sitosterol reduced cholesterol solubility to a greater extent than would be expected from an equimolar replacement of cholesterol by beta-sitosterol. Absorption of beta-sitosterol was limited by its solubility in mixed micellar solutions and both sterols were absorbed at equal rates as long as their solubility limits were not exceeded (n = 5).

[Effect of exogenous prostaglandin E2 on different stages in the formation of a humoral immune response]. / Vliianie ékzogennogo prostaglandina E2 na razlichnye étapy formirovaniia gumoral'nogo immunnogo otveta.

The influence of exogenous prostaglandin E2 on different stages of the immune response to sheep red blood cells was studied in (CBA x C57BL) F1 mouse hybrids. It was shown that prostaglandin E2 in a dose of 10(-6) M given 72 h after antigen challenge increased the number of the plaque-forming cells. Prostaglandin E2 stimulated antibody formation on being injected to mice in doses 10(-6) M--5 . 10(-4) M 24 and 2 h prior to antigen challenge. Prostaglandin E2 enhanced endogenous colony formation when injected to mice 24 and 2 h prior to sublethal irradiation. It is suggested that prostaglandins regulate different stages of the immune response.