Retroperitoneal Liposarcoma: Rational Extent of Surgery Tailored to Grade of Malignancy.

This study was aimed at determining the indications for combined and organ-preserving operations. The study included 190 patients with retroperitoneal liposarcoma (RLPS). The influence of the following factors on the overall survival (OS) and recurrence-free survival (RFS) were studied: involvement of adjacent organs in the tumor, volume of surgical intervention. OS and RFS were worse in pathologically confirmed visceral invasion in the both RLPS low grade and high grade (p = 0.000). In RLPS low grade, there was no significant difference in OS and RFS between the group of patients who underwent combined surgery without confirmed visceral invasion and the group of patients who underwent organ-preserving surgery (p > 0.080). In RLPS high grade, OS and RFS were higher in the group of patients who underwent combined surgery without confirmed visceral invasion than in the group of patients who underwent organ-preserving surgery (p < 0.050). In RLPS low grade, it is advisable to perform organ-preserving operations, including nephrosaving operations. In RLPS high grade, the organ-preserving operations worsen long-term results and prognosis. Combined operations including nephrectomy are justified in RLPS high grade.

Prediction of Recurrence-Free and Overall Survival in Retroperitoneal Well-Differentiated and Dedifferentiated Liposarcoma After Surgery.

This study was aimed at creating an effective model for predicting the course of the disease in retroperitoneal well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcomas after surgery. The study included 111 patients with WDLPS and 74 patients with DDLPS. We developed a methodology for stratification of patients into prognostic groups. Overall survival (OS) and recurrence-free survival (RFS) were analyzed in accordance with it. The highest OS was achieved in the group "favorable prognosis," while the shortest OS was in the group "extremely poor prognosis" (p < 0.001). The median OS in the "favorable prognosis" group was 225 (95% CI, 174, 276) months; "intermediate prognosis" - 130 (95% CI, 115, 145) months; "poor prognosis" - 90 (95% CI, 79, 101) months; and "extremely poor prognosis" - 22 (95% CI, 15, 29) months. The highest RFS was achieved in the group "favorable prognosis," while the shortest RFS was achieved in the group "extremely poor prognosis" (p < 0.001). The median RFS in the "favorable prognosis" group was 80 (95% CI, 65, 95) months; "intermediate prognosis" - 47 (95% CI, 33, 61) months; "poor prognosis" - 26 (95% CI, 24, 28) months; "extremely poor prognosis" - 10 (95% CI, 6, 14) months. The method of predicting recurrence-free and overall survival demonstrates an adequate distribution of patients and the reliability of intergroup differences in the survival rate.

TNM classification of malignant tumors: Eighth edition for retroperitoneal liposarcoma. Ways to improve.

AIM: This study was aimed at assessing the prognostic significance of the "TNM: Classification of Malignant Tumors" eighth edition (TNM8) in the most common retroperitoneal tumors - liposarcoma. METHODS: The study included 192 patients with retroperitoneal liposarcoma (RLPS). The distribution of patients by stages and survival in accordance with the TNM8 were studied. RESULTS: In the TNM8, only the degree of malignancy of the tumor has a prognostic value. The T-category does not reflect the actual size of the RLPS and is considered as T4 in 93%, which leads to inadequate staging. During the 15-year period, there were no cases with stages II and IIIA, and the survival rate was estimated only in patients with stages I and IIIB. The tumor node metastasis (TNM) classification with new values of the T-category was proposed by us, which demonstrated a more adequate distribution of patients by stages and the reliability of intergroup differences in the survival rate. CONCLUSION: It is advisable to create a special TNM classification for RLPS, which makes up more than half of all retroperitoneal sarcomas. The TNM8 does not accurately reflect the prevalence of the tumor and the prognosis in RLPS. Revision of the T-staging is necessary to improve the accuracy of the prognosis in RLPS. The modified by us TNM classification demonstrated a more adequate distribution of patients by stages.

Isolation and Characterization of Extracellular Vesicles from Gastric Juice.

EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low. In contrast, GJ, as a local biofluid, is expected to be enriched with GC-associated EVs. However, EVs from GJ have never been applied for the screening and are underinvestigated overall. Here we show that EVs can be isolated from GJ by ultracentrifugation. TEM analysis showed high heterogeneity of GJ-derived EVs, including those with exosome-like size and morphology. In addition to morphological diversity, EVs from individual GJ samples differed in the composition of exosomal markers. We also show the presence of stomatin within GJ-derived EVs for the first time. The first conducted comparison of miRNA content in EVs from GC patients and healthy donors performed using a pilot sampling revealed the significant differences in several miRNAs (-135b-3p, -199a-3p, -451a). These results demonstrate the feasibility of the application of GJ-derived EVs for screening for miRNA GC markers.

Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients' Survival: A Pilot Study.

The identification of new prognostic markers of renal cell carcinoma (RCC) is an urgent problem in oncourology. To investigate the potential prognostic significance of tumor microbiome and stromal inflammatory markers, we studied a cohort of 66 patients with RCC (23 clear cell RCC, 19 papillary RCC and 24 chromophobe RCC). The microbiome was analyzed in tumor and normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was performed using immunohistochemistry. A significant difference in alpha diversity was demonstrated between normal kidney tissue and all types of RCC. Further, we demonstrated that the bacterial burden was higher in adjacent normal tissue than in a tumor. For the first time, we demonstrated a significant correlation between bacterial burden and the content of PU.1+ macrophages and CD66b+ neutrophils in kidney tumors. Tumors with high content of PU.1+ cells and CD66b+ cells in the stroma were characterized by a lower bacterial burden. In the tumors with high bacterial burden, the number of PU.1+ cells and CD66b+ was associated with a poor prognosis. The identified associations indicate the great prognostic potential of a combined tumor microbiome and stromal cell analysis.

Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases.

Our work aimed to differentiate 20 aberrantly methylated miRNA genes that participate at different stages of development and metastasis of ovarian carcinoma (OvCa) using methylation-specific qPCR in a representative set of clinical samples: 102 primary tumors without and with metastases (to lymph nodes, peritoneum, or distant organs) and 30 peritoneal macroscopic metastases (PMM). Thirteen miRNA genes (MIR107, MIR124-2, MIR124-3, MIR125B-1, MIR127, MIR129-2, MIR130B, MIR132, MIR193A, MIR339, MIR34B/C, MIR9-1, and MIR9-3) were hypermethylated already at the early stages of OvCa, while hypermethylation of MIR1258, MIR137, MIR203A, and MIR375 was pronounced in metastatic tumors, and MIR148A showed high methylation levels specifically in PMM. We confirmed the significant relationship between methylation and expression levels for 11 out of 12 miRNAs analyzed by qRT-PCR. Moreover, expression levels of six miRNAs were significantly decreased in metastatic tumors in comparison with nonmetastatic ones, and downregulation of miR-203a-3p was the most significant. We revealed an inverse relationship between expression levels of miR-203a-3p and those of ZEB1 and ZEB2 genes, which are EMT drivers. We also identified three miRNA genes (MIR148A, MIR9-1, and MIR193A) that likely regulate EMT-MET reversion in the colonization of PMM. According to the Kaplan-Meier analysis, hypermethylation of several examined miRNA genes was associated with poorer overall survival of OvCa patients, and high methylation levels of MIR130B and MIR9-1 were related to the greatest relative risk of death.

Blood Plasma Metabolome Profiling at Different Stages of Renal Cell Carcinoma.

Early diagnostics significantly improves the survival of patients with renal cell carcinoma (RCC), which is the prevailing type of adult kidney cancer. However, the absence of clinically obvious symptoms and effective screening strategies at the early stages result to disease progression and survival rate reducing. The study was focused on revealing of potential low molecular biomarkers for early-stage RCC. The untargeted direct injection mass spectrometry-based metabolite profiling of blood plasma samples from 51 non-cancer volunteers (control) and 78 patients with different RCC subtypes and stages (early stages of clear cell RCC (ccRCC), papillary RCC (pRCC), chromophobe RCC (chrRCC) and advanced stages of ccRCC) was performed. Comparative analysis of the blood plasma metabolites between the control and cancer groups provided the detection of metabolites associated with different tumor stages. The designed model based on the revealed metabolites demonstrated high diagnostic power and accuracy. Overall, using the metabolomics approach the study revealed the metabolites demonstrating a high value for design of plasma-based test to improve early ccRCC diagnosis.