Hepatic Oncology最新文献

Rap proteins regulate liver physiopathology. For example, Rap2B promotes hepatocarcinoma (HCC) growth, while Rap1 might play a dual role. The RapGEF, Epac1, activates Rap upon cAMP binding, regulating metabolism, survival, and liver regeneration. A liver specific Epac2 isoform lacking cAMP-binding domain also activates Rap1, promoting fibrosis in alcoholic liver disease. C3G (RapGEF1) is also present in the liver, but mainly as shorter isoforms. Its function in the liver remains unknown. Information from different public genetic databases revealed that C3G mRNA levels increase in HCC, although they decrease in metastatic stages. In addition, several mutations in RapGEF1 gene are present, associated with a reduced patient survival. Based on this, C3G might represent a new HCC diagnostic and prognostic marker, and a therapeutic target.

Hepatocellular adenomas are rare benign liver tumors usually developing in young women using oral contraception. The two main complications are hemorrhage (10-20%) and malignant transformation into hepatocellular carcinoma (<5%). A molecular classification has been recently updated in six major subgroups, linked to risk factors, histology, imaging and clinical features: adenomas inactivated for HNF1A, inflammatory adenomas, β-catenin-activated adenomas mutated in exon 3, β-catenin-activated adenomas mutated in exon 7-8, sonic hedgehog adenomas, and unclassified adenomas. Indeed, β-catenin-mutated adenomas in exon 3 are associated with malignant transformation, and sonic hedgehog adenomas with bleeding. This new nosology of hepatocellular adenomas will help to stratify patients according to risk of complications and will guide therapeutics in the future.

Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited systemic therapies available. Immunotherapy is a fast-moving field that is quickly evolving as a treatment for HCC with three recent clinical trials published treating HCC with immune checkpoint inhibitors with promising results. Checkpoint inhibition may lead to a unique adverse event profile with the potential to cause immune-related adverse events by unbalancing the immune system. Here, we report a case of a 61-year-old male with advanced HCC who developed a shellfish allergy after completing three cycles of combination of tremelimumab and durvalumab therapy.

Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.

Cellular senescence is a stress-induced cell-cycle arrest program that prevents malignant transformation of senescent cells following oncogenic pathway activation and DNA damage. Senescent cells are metabolically active and secrete cytokines and chemokines that shape the function and composition of their microenvironment. These cytokines can recruit immune cells such as lymphocytes and myeloid cells that depending on the context can either promote or inhibit liver tumor development and progression. Accordingly, pharmacologically targeting of secreted cytokines or reprogramming the expression of these cytokines in senescent cells represents a promising approach to skew senescence-associated immune responses toward cancer cell killing.

Early detection of hepatocellular carcinoma (HCC) leads to improved survival; however, current early detection strategies for HCC surveillance are ineffective. Thus, there has been interest in developing biomarkers to aid in the early detection HCC. In this review, we discuss the five phases of biomarker discovery that are necessary for clinical implementation. We also describe the most promising investigational biomarkers and their phase of discovery. We review several promising technologies for the early detection of HCC, including miRNA, metabolomics and proteomics. Promisingly, there are samples from multiple longitudinal cohorts of patients with cirrhosis in the USA that are being collected in order to validate candidate biomarkers for HCC. A biomarker-based strategy has the potential to become the primary surveillance method for HCC detection.

Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract. Complete surgical resection can be curative, but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis. Most deaths are attributable to local disease progression rather than distant metastases, supporting the use of locoregional therapies. There is evidence that locoregional therapies can provide local tumor control resulting in increased survival while avoiding some of the side effects of systemic treatments, increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments. This review considers the evidence for locoregional therapies in cholangiocarcinoma, which can be classified into endoscopic, vascular, percutaneous and radiation oncological therapies. Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospective data, but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice.

Sorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed.

Surgical resection remains the primary curative treatment option for patients with colorectal liver metastases. While the majority of patients will develop tumor relapse within or outside of the liver after hepatic metastasectomy, a subset of these patients may be amenable to salvage surgical resection. However, outcomes for this approach are not well defined. In this article, we summarize the current evidence for the incidence, feasibility and outcomes of salvage resection for recurrence after initial resection of colorectal liver metastases.

Aim: Compare radioembolization (Y90) and chemoembolization (CE) for the treatment of unresectable intrahepatic cholangiocarcinoma (UICC).

Materials & methods: Institutional Review Board-approved, retrospective search was performed. Forty patients with UICC were treated with either Y90 (n = 25, 39 treatments) or CE (n = 15, 35 treatments). Comparative analysis was performed using Student's t and fisher-exact tests. Multivariable-logistic regression was also performed.

Results: Median ages were 60 and 64 years for CE and Y90 groups, respectively (p = 0.798). Patient variables including age, Eastern Cooperative Oncology Group score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery were similar between groups. Adverse events were similar in both groups (CE 20%, Y90 26%; p > 0.9). Overall response rate (CE 6%, Y90 4%; p > 0.9) and disease control rate (CE 46%, Y90 48%; p > 0.9) were statistically similar. Multilogistic regression did not identify any variables that correlated with disease control rate, including Eastern Cooperative Oncology Group score and tumor burden.

Conclusion: Our observation shows that CE and Y90 display similar toxicity and disease control in the treatment of UICC.