Stefania De Lorenzo

The role of metronomic capecitabine for treatment of recurrent hepatocellular carcinoma after liver transplantation

The management of recurrent hepatocellular carcinoma untreatable with surgical options is based on systemic therapy with sorafenib. Due to the high rates of adverse events connected to the therapy with sorafenib, metronomic capecitabine seems a promising strategy for these patients. We analyzed the data of 38 patients with hepatocellular carcinoma recurrent after liver transplantation performed at our center. We compared the outcome of 17 patients receiving metronomic capecitabine versus 20 patients experiencing best supportive care and versus the data of the literature about treatment with sorafenib. In the group treated with metronomic capecitabine we observed an increased survival after tumor recurrence at the univariate and multivariate analysis compared to the group of best supportive care (median 22 months vs. 7 months, p < 0.01). Data from the literature on the use of sorafenib showed outcomes like our study group, with similar patient and tumoral features. The episodes of acute rejection and the tumor stage at the recurrence showed a correlation with patient survival at the univariate analysis. The metronomic capecitabine for hepatocellular cancer recurrent after liver transplantation seems effective without important adverse events and comparable results to sorafenib.

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial

The search for systemic therapies for hepatocellular carcinoma has been characterized by difficulties and failures. Despite recent progresses, many issues are still to be settled. In particular, the development of drugs inhibiting different neoplastic pathways remains a priority for patients intolerant or resistant to antiangiogenic drugs. This task may be daunting, as previous failures extensively demonstrated. We aimed to identify the future perspective of postsorafenib trials analyzing the strengths and the critical points of past and currently undergoing studies, in the light of the most recent evidences in the field. We identified various points (including stratification, biomarkers, end points, radiologic criteria of response, treatment beyond radiologic progression) that should be considered by future trials to reduce the risks of failure.

Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients

BACKGROUND The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. METHODS Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. RESULTS Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24-0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI 0.34-2.68; three to four cycles: HR 0.99, 95% CI 0.34-2.90; five to six cycles: HR 0.27, 95% CI 0.10-0.77). CONCLUSION hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. IMPLICATIONS FOR PRACTICE Gemcitabine is becoming an increasingly used adjuvant modality in cholangiocarcinoma (CC), but limited data are available on predictive biomarkers of response. In this study, patients receiving more than four cycles of adjuvant gemcitabine and harboring Human equilibrative nucleoside transporter 1 (hENT-1, the major transporter involved in gemcitabine intracellular uptake) on tumor cell membrane had a longer disease-free survival compared with patients negative or positive for hENT-1 only in the cytoplasm of tumor cells. Overall these results may lay the basis for further prospective randomized trials based on a larger population of patients and may prove useful for tailoring appropriate gemcitabine-based chemotherapy for CC patients in the adjuvant setting.

Oral oxycodone/naloxone for pain control in cirrhosis: Observational study in patients with symptomatic metastatic hepatocellular carcinoma

Pain management in cirrhosis is a clinical challenge. Most analgesics are metabolized in the liver and cirrhosis may deeply alter their concentration, favouring the appearance of side effects. We aimed to assess the efficacy and safety of oral prolonged‐release association of oxycodone/naloxone tablets (OXN) in the treatment of moderate/severe cancer pain in cirrhotic patients with metastatic hepatocellular carcinoma (HCC).

Fulminant hepatitis in a patient with hepatocellular carcinoma related to nonalcoholic steatohepatitis treated with sorafenib.

Background Endometriosis and infertility have been shown to be related to one another. The mechanisms that explain this phenomenon are not fully understood. One of the possible mechanisms of infertility in endometriosis patients is failure of implantation of the embryo in the endometrium. This may be caused by high levels of methylation of HOXA10 gene in patients with endometriosis, resulting a decrease in the expression of genes that play a role in this endometrial receptivity. Objective To determine the methylation profile of HOXA10 gene on eutopic endometrium in endometriosis patients with infertility. Methods This is a cross-sectional study conducted at Cipto Mangunkusumo General Hospital from July 2015 to July 2016. The subjects of research were cystic ovarian endometriosis patients with infertility, confirmed histopathologically and non-endometriosis-fertile patients. The methylation status of HOXA 10 gene in both groups was examined and compared. Statistical analysis is Mann-Whitney U-test, a two-tailed p value less than 0.05 was considered significant. Results There were six endometriosis patients and six controls. Six samples on endometriosis group showed the following percentage rate of methylation: 63.29%, 55.28%, 33.92%, 43.27%, 77.20% and 65.94%. Meanwhile, four samples in the control group did not undergo methylation at all and two other samples methylated at low levels equal to 15.24% and 16.48%. Methylation status between these two groups is statistically different with p 0.03. Conclusions In patients with endometriosis-associated infertility, HOXA10 gene in eutopic endometrium has a higher methylation level.We describe a case of acute liver failure in a patient with advanced hepatocellular carcinoma related to nonalcoholic steatohepatitis during sorafenib treatment. A 74-year-old man with diabetes mellitus and hypertension was diagnosed with hepatocellular carcinoma associated with fatty liver. Three weeks after sorafenib therapy, at Eastern Cooperative Oncology Group performance status 3, he developed jaundice, general weakness, flapping tremor, nausea, and anorexia. Sorafenib was stopped: laboratory tests showed a relevant elevation of transaminases suggesting diagnosis of acute hepatitis. During hospital admission, the patient died of liver failure. Sorafenib is the first successful target therapy effective for advanced hepatocellular carcinoma. The most common adverse events are fatigue, hand-foot skin reaction, skin rash/desquamation, diarrhea, and hypertension, whereas liver dysfunction is uncommon. To our knowledge, this is the first patient reported in the literature with hepatocellular carcinoma related to nonalcoholic steatohepatitis who died of rapid worsening of liver function during sorafenib treatment.

Aspirin for cholangiocarcinoma prevention: new targets to shift the dogma from ascertained risk to possible prevention (Reply to: Risk Factors for Cholangiocarcinoma: Aspirin‐use and the Risk of Cholangiocarcinoma)

HBV infection. A 78-year cycle with a 1-year interval is specified for the Markov model. Given that most infants and children with perinatal HBV infection maintain immune tolerance, the researchers start the Markov process at age 20 years. Considering the hypothetical 2010 birth cohort of 4 million infants and approximately 190 million quality-adjusted life-years (QALYs) for each strategy, there is an obvious discrepancy between the average 47.5 QALYs and the 78 years of life expectancy, probably attributed to exemption of the first 20 years’ QALYs for the entire cohort. We suggest that these common QALYs should be included in the total rewards, while the final incremental costeffectiveness ratio (ICER) results remain the same. Second, the researchers summarize the parameter values and their ranges for the decision tree and Markov model in Table 1. Two baseline parameters, that is, cost for hepatitis B surface antigen screening test and HepB vaccination, are lacking. Actually, these costs contributed substantially to the total cost and should be listed in the article, as in other reports. Third, using one-way sensitivity analyses, the researchers demonstrate that the antiviral prophylaxis remains cost-effective over wide ranges of time-varying and district-specific factors. However, the results in Table 4 might be misleading because the ranges of output ICERs are not consistent with the interpretation within the text. For example, bigger reduction in perinatal HBV transmission (20%-80%) from maternal antiviral therapy makes antiviral prophylaxis a more cost-effective program (ICER

Adjuvant treatment in biliary tract cancer

97,749/QALY—cost saving, rather than cost saving—

Metronomic capecitabine vs. best supportive care in Child-Pugh B hepatocellular carcinoma: a proof of concept

97,749/QALY), compared with the current strategy. Similarly, the ranges of

Brain Metastases from Biliary Tract Cancer: A Monocentric Retrospective Analysis of 450 Patients

2,886-

Intestinal Microbiota, Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma: The Potential Role of Dysbiosis in the Hepatocarcinogenesis

15,552/QALY,