Horizons of development of immunotherapy for malignant liver tumors

Primary liver tumors are one of the most common types of malignant neoplasms. Surgical excision is still the most effective treatment in the early stages of the disease, however in most cases early diagnosis is difficult. Moreover, even if the treatment is carried out according to a radical program, the risk of relapse remains extremely high. In this regard, the search for new strategies for the treatment of liver malignancies that differ from traditional methods of treatment is not terminated. One of such promising approaches is immunotherapy. The present review is devoted to the current understanding of the mechanisms of action and the available clinical experience in the use of immunotherapy approaches in the treatment of liver malignancies. Combining different types of immunotherapy or combining immunotherapy with traditional therapeutic approaches can facilitate a synergistic effect and contribute to the development of personalized medicine.

Stereotactic and Robotic Minimally Invasive Thermal Ablation of Malignant Liver Tumors: A Systematic Review and Meta-Analysis

BackgroundStereotactic navigation techniques aim to enhance treatment precision and safety in minimally invasive thermal ablation of liver tumors. We qualitatively reviewed and quantitatively summarized the available literature on procedural and clinical outcomes after stereotactic navigated ablation of malignant liver tumors.MethodsA systematic literature search was performed on procedural and clinical outcomes when using stereotactic or robotic navigation for laparoscopic or percutaneous thermal ablation. The online databases Medline, Embase, and Cochrane Library were searched. Endpoints included targeting accuracy, procedural efficiency, and treatment efficacy outcomes. Meta-analysis including subgroup analyses was performed.ResultsThirty-four studies (two randomized controlled trials, three prospective cohort studies, 29 case series) were qualitatively analyzed, and 22 studies were included for meta-analysis. Weighted average lateral targeting error was 3.7 mm (CI 3.2, 4.2), with all four comparative studies showing enhanced targeting accuracy compared to free-hand targeting. Weighted average overall complications, major complications, and mortality were 11.4% (6.7, 16.1), 3.4% (2.1, 5.1), and 0.8% (0.5, 1.3). Pooled estimates of primary technique efficacy were 94% (89, 97) if assessed at 1–6 weeks and 90% (87, 93) if assessed at 6–12 weeks post ablation, with remaining between-study heterogeneity. Primary technique efficacy was significantly enhanced in stereotactic vs. free-hand targeting, with odds ratio (OR) of 1.9 (1.2, 3.2) (n = 6 studies).ConclusionsAdvances in stereotactic navigation technologies allow highly precise and safe tumor targeting, leading to enhanced primary treatment efficacy. The use of varying definitions and terminology of safety and efficacy limits comparability among studies, highlighting the crucial need for further standardization of follow-up definitions.

Clinical outcome of hepatic resection for malignant liver tumors in elderly patients

Background: Aging hinders the liver capacity to restitute its volume and function after partial hepatectomy. Concomitant hepatic parenchyma disorders and major resections may increase the susceptibility of elderly patients to worse postoperative outcome.Methods: Prospectively collected medical records of adult patients who underwent elective partial hepatectomy for malignant liver tumors at Sohag University Hospital (June 2014–May 2020) were analyzed. A group of elderly (≥65 years) were compared with a matched control group of non-elderly (<65 years) patients as regards posthepatectomy liver failure (PHLF) and overall complications, including mortality. Markers associated with PHLF and postoperative death were investigated.Results: Forty-eight patients were enrolled, 24 per group. 34 were males (71%). All patients had primary hepatic malignancy or metastatic tumors. Hepatocellular carcinoma (HCC) was the most common indication for liver resection in both groups (32 patients, 66.6%). Elderly patients exhibited significantly higher grades of overall postoperative complications (p<0.05). PHLF was significantly increased in the elderly group, in evident connection with significant persistence of higher bilirubin levels and reduced prothrombin concentration (p<0.05) until 5th postoperative day. Subgroup analysis showed that major resections and cirrhosis correlated with increased morbidity among elderly compared with younger patients. Postoperative mortality occurred in 3 elderly cirrhotic patients, who failed to recover normal platelet count postoperatively.Conclusions: In elderly patients, major liver resection for malignant tumors is associated with worse outcome, particularly in those with coexisting cirrhosis. Predictors include early postoperative thrombocytopenia and persistent hyperbilirubinemia and coagulopathy.

Tumor Solid Stress: Assessment with MR Elastography under Compression of Patient-Derived Hepatocellular Carcinomas and Cholangiocarcinomas Xenografted in Mice

Malignant tumors have abnormal biomechanical characteristics, including high viscoelasticity, solid stress, and interstitial fluid pressure. Magnetic resonance (MR) elastography is increasingly used to non-invasively assess tissue viscoelasticity. However, solid stress and interstitial fluid pressure measurements are performed with invasive methods. We studied the feasibility and potential role of MR elastography at basal state and under controlled compression in assessing altered biomechanical features of malignant liver tumors. MR elastography was performed in mice with patient-derived, subcutaneously xenografted hepatocellular carcinomas or cholangiocarcinomas to measure the basal viscoelasticity and the compression stiffening rate, which corresponds to the slope of elasticity versus applied compression. MR elastography measurements were correlated with invasive pressure measurements and digital histological readings. Significant differences in MR elastography parameters, pressure, and histological measurements were observed between tumor models. In multivariate analysis, collagen content and interstitial fluid pressure were determinants of basal viscoelasticity, whereas solid stress, in addition to collagen content, cellularity, and tumor type, was an independent determinant of compression stiffening rate. Compression stiffening rate had high AUC (0.87 ± 0.08) for determining elevated solid stress, whereas basal elasticity had high AUC for tumor collagen content (AUC: 0.86 ± 0.08). Our results suggest that MR elastography compression stiffening rate, in contrast to basal viscoelasticity, is a potential marker of solid stress in malignant liver tumors.