Chemical, molecular, and single cell analysis reveal chondroitin sulfate proteoglycan aberrancy in fibrolamellar carcinoma

Fibrolamellar carcinoma (FLC) is an aggressive liver cancer with no effective therapeutic options. The extracellular environment of FLC tumors is poorly characterized and may contribute to cancer growth and/or metastasis. To bridge this knowledge gap, we assessed pathways relevant to proteoglycans, a major component of the extracellular matrix. We first analyzed gene expression data from FLC and non-malignant liver tissue to identify changes in glycosaminoglycan (GAG) biosynthesis pathways. We then implemented a novel LC-MS/MS based method to quantify the abundance of different types of GAGs in patient tumors, followed by measurement of the levels of different GAG-associated proteins. Finally, we performed the first single-cell assay for transposon-accessible chromatin-sequencing on FLC tumors, to identify which cell types are linked to the most dominant GAG-associated protein in FLC. Our results reveal a pathologic aberrancy in chondroitin (but not heparan) sulfate proteoglycans in FLC and highlight a potential role for activated stellate cells.

Study of nosological features of morbidity and mortality of the population of Ukraine caused by malignant neoplasms

Annotation. Oncological disorders remain one of the most important medical, biological and economic problems in the world. The aim of the study is to analyze the indicators of morbidity and mortality of the population of Ukraine from oncological pathologies in their distribution by nosological forms. The study was conducted on the basis of data analysis of the National Cancer Registry of Ukraine over a ten-year period: from 2010 to 2019. Statistical methods (analysis of relative values, calculation of growth rate), structural-logical analysis and system approach are used. Statistical calculations were performed using RStudio v. 1.1.442 and R Commander v.2.4-4. The study revealed that the main form of morbidity and mortality in women are malignant neoplasms of the breast, while in men it is malignant neoplasms of the trachea, bronchi, lungs, and in children aged 0−17 − leukemia and malignant tumors of the brain. An increase in morbidity and mortality due to malignant neoplasms of the prostate in men, malignant neoplasms of the uterine body in women and malignant neoplasms of the pancreas in the general population of Ukraine has been noted. The highest degree of neglect is observed in patients diagnosed with malignant neoplasms of the stomach (32,2-38,2%), malignant neoplasms of the pancreas (30,8-37,9%), malignant pharyngeal neoplasms (27,6-39%), malignant neoplasms of the trachea, bronchi, lungs (27,3-37,9%) and malignant neoplasms of the liver (27,9-35,9%). Only one in two patients diagnosed with malignant neoplasms of the esophagus (50,2-56%), malignant neoplasms of the stomach (44,3-47,6%), malignant neoplasms of the trachea, bronchi, lungs (40,8-43,7%), one in four patients with malignant pancreatic neoplasms (25,7-28,7%) and one in five patients with malignant liver neoplasms (17,7-19,8%) received special antitumor treatment within a year of diagnosis. The highest mortality rate up to one year is characteristic of individuals with malignant neoplasms of the pancreas and malignant neoplasms of the liver: 70,2-77,8% and 69-77,7%, respectively. The results of the study are the basis for the development and improvement of measures to combat the prevalence of certain nosological forms of oncological pathologies and reduce mortality caused by a specific pathology.

CHEMOEMBOLIZATION OF THE HEPATIC ARTERY IN THE TREATMENT OF PATIENTS WITH CHEMORESISTANT METASTASES OF COLORECTAL CANCER. REVIEW

In the structure of the incidence of malignant tumors for a number of years, colorectal cancer occupies one of the leading positions, with a steady tendency to growth. The five-year survival rate of patients with metastatic liver damage in colorectal cancer does not exceed 28%. A significant breakthrough in the study of the biology of colorectal cancer has led to a deep understanding of individual processes of carcinogenesis and a personalized approach to treatment tactics. Despite this, the problem of chemoresistance remains one of the most acute. The high toxicity of systemic chemotherapy limits its use in this group of patients. In this connection, minimally invasive and at the same time effective methods of local treatment of malignant liver tumors have been introduced into clinical practice. These methods include: hepatic artery chemoinfusion, chemoembolization, oil chemoembolization and radioembolization. At present, a large world experience has already been accumulated in the application of the above-described methods of treatment. However, the question of the application of methods of interventional surgery in the treatment of patients with chemoresistant metastases is still open. The presented review reflects the results of the analysis of scientific literature on the treatment of this group of patients. The main stages of development and improvement of X-ray endovascular methods of treatment are presented.

Percutaneous Navigation under Local Anesthesia for Computed Tomography-Guided Microwave Ablation of Malignant Liver Lesions Located in the Hepatic Dome

Background and Objectives: The aim of the present study was to report the safety and efficacy of percutaneous navigation under local anesthesia for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Patients with primary and secondary malignant liver lesions located in the hepatic dome who underwent percutaneous computed tomography-guided microwave ablation using a computer-assisted navigation system under local anesthesia were prospectively evaluated. The primary objective was technical success. Materials and Methods: The sample consisted of 10 participants (16 lesions) with a mean age of 60.60 years (SD = 9.25 years) and a mean size of 20.37 ± 7.29 cm, and the mean follow-up time was 3.4 months (SD = 1.41) months. Results: Primary technical success was 93.75%. Tumor remnant was noticed at one month follow-up in a single metastatic lesion, which was re-treated with an ablation session, and no tumor remnant was depicted in the subsequent imaging follow-up (secondary technical success 100%). Grade I self-limited complications (according to the CIRSE classification system) included small pleural effusion (n = 1) and minor bleeding post antenna removal (n = 1) requiring nothing but observation. Conclusions: the findings of the present study indicate that percutaneous navigation under local anesthesia is a safe and efficacious approach for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Large randomized controlled studies are warranted to observe treatment effectiveness and compare the results with those of other options.

TP6.2.6 A meta-analysis and systematic review of Laparoscopic versus open hepatectomy for malignant liver tumours in the elderly patients

Aims To evaluate comparative outcomes of laparoscopic versus open hepatectomy for malignant liver tumours in elderly patients. Methods A systematic online search was conducted using the following databases: PubMed, Scopus, Cochrane database, The Virtual Health Library, Clinical trials.gov and Science Direct. Comparative studies comparing laparoscopic (LH) versus open hepatectomy (OH) for both primary and metastatic malignant liver tumours in the elderly were included. Total operative time (minutes), need to perform Pringle’s manoeuvre, blood loss (ml), requirement for blood transfusion intra-operatively/post-operatively, post-operative complications, R0 resection rate, specimen resection margin (mm), re-operation rate, length of hospital stay (LOS), and 90-day mortality were the evaluated outcome parameters. Results Twelve studies reporting a total number of 1762 patients who underwent laparoscopic (n = 831) or open (n = 931) hepatectomy were included. OH group was associated with a significantly higher number of post-operative complications compared to LH (P = 0.00001). Complications such as post-operative liver failure (P = 0.02), ascites formation (P = 0.002), surgical site infection (P = 0.02), blood loss (P = 0.03), blood transfusion rate (P = 0.05) and LOS (P = 0.00001) were significantly higher in the OH group when compared to LH. There was no significant difference between the two groups in terms of total operative time (P = 0.53), bile leak (P = 0.12), R0 resection rate (P = 0.36), re-operation (P = 0.70) and 90-day mortality (P = 0.11). Conclusion Laparoscopic liver resections are safe with at least equal or superior peri-operative outcomes in the elderly population. Importantly, oncological outcomes are also comparable with open surgery. This approach needs to be utilised wherever possible to provide optimal healthcare in an aging population.