Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival.
To examine ...patterns of tumor factors in large HCC patients.
A database of large HCC patients was examined.
A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio ≥2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin >3.5 g/dL and the absence of both PVT and multifocality had the best survival rate, while all combinations that included the presence of PVT had poor survival and hazard ratios. We identified four clinical phenotypes, each with a distinct median survival: patients with or without PVT or multifocality plus serum albumin ≥3.5 (g/dL), with each subgroup displaying high (≥100 IU/mL) or low (<100 IU/mL) blood AFP levels. Across a range of MTDs, we identified only two significant trends, blood AFP and platelets.
Patients with large HCCs have distinct phenotypes and survival, as identified by the combination of PVT, multifocality, and blood albumin levels.
Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers ...(sartans) are still lacking. Aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. Data on 215 patients were reviewed. The study population was classified into three groups: 113 (52.5%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 59 (27.4%) patients treated with angiotensin-converting enzyme inhibitors (group 2) and 43 (20.1%) patients treated with sartans (group 3). Survival outcomes were analyzed using Kaplan-Meier analysis and compared with log-rank test. In the whole study population, 85.6% of patients were in Child-Pugh A-class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10-40 mm) and alpha-fetoprotein was 25 (1.1-2100) IU/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (42-51) in group 1, 51 months (42-88) in group 2, and 63 months (51-84) in group 3 (
= 0.15). Child-Pugh stage and Model for End-staging Liver Disease (MELD) score resulted as significant predictors of overall survival in multivariate analysis. Median time to recurrence was 33 months (24-35) in group 1, 41 (23-72) in group 2 and 51 months (42-88) in group 3 (
= 0.001). Number of nodules and anti-angiotensin treatment were confirmed as significant predictors of time to recurrence in multivariate analysis. Sartans significantly improved time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients but did not improve overall survival.
Diarrhea is a recurrent symptom in patients with neuroendocrine tumors (NETs) and can represent different etiologies; thus, differential diagnosis is challenging. This paper distinguishes the ...different causes of chronic diarrhea in patients with gastroenteropancreatic NETs, with the aim to identify the most appropriate therapeutic approach. Underlying causes of diarrhea can be multifactorial, including not only diarrhea that is related to specific hormonal hypersecretory syndromes, but also diarrhea that is secondary to the following: extensive surgery which can cause pancreatic exocrine insufficiency or short bowel syndrome, treatment with somatostatin analogs or other antineoplastic agents, and bile acid malabsorption. After initial management of diarrhea with general treatments (dietary modification, use of antidiarrheals), a proper differential diagnosis is necessary to treat patients with specific etiology-driven therapeutic approaches, such as somatostatin analogs, pancreatic enzyme replacement therapy, and tryptophan hydroxylase inhibitors. In conclusion, NETs should be considered in the differential diagnosis of patients suffering from chronic diarrhea, after the exclusion of more common etiologies. Furthermore, physicians should keep in mind that several different etiologies might be responsible for diarrhea occurrence in NET patients. A prompt diagnosis of the actual cause of diarrhea is necessary to guide the treatment and a multidisciplinary approach is mandatory.
AIM： To prospectively long term clinical impact evaluate the short and of selective transarterial chemoembolization （TACE） on fiver function in patients with hepatocellular carcinoma （HCC）. To assess ...side effects in relation to treatments. To analyze the overall survival and HCC progression free survival probability. METHODS： One hundred and seventeen cirrhotic patients with HCC were enrolled. Baseline liver function included Child-Pugh score and serum levels of alanine- aminotransferase （ALT）, prothrombin time （PT） and bilirubin. According to Cancer Liver Italian Program （CLIP） and Barcelona Clinic Liver Cancer （BCLC） staging systems, 71 patients were eligible for TACE; 32 had previously received treatment for HCC. No significant differences in liver function were observed between previously treated and not treated patients. TACE was performed by selective catheterization of the arteries nourishing the lesions. While hospitalized, patients underwent clinical, hematologic and ultrasonographic assessments. One month after TACE a CT scan was performed to assess tumor response. A second TACE was performed ＂on demand＂ Liver function tests were checked in all patients every four months. RESULTS： After first TACE, the mean Child-Pugh score increased from a mean baseline 5.62 ±1.12 to 6.11 ±1.57 at discharge time （P 〈 0.0001）, decreasing after four months to 5.81 ± 0.73 （not significant）. ALT, PT and bilirubin significantly （P 〈 0.0001） increased 24 h after TACE and progressively decreased until discharge. After the second TACE, variations in Child-Pugh score, ALT, PT and bilirubin were comparable to that described after the first TACE. No major complications were observed. The mean follow-up was 14.7 ＋ 6.3 mo （median： 16 mo）. Only one patient died. No other patient experienced important long term worsening of clinical status. The overall survival probability at twenty-four months was 98.18% with a correspondent HCC progression free survival probability of 69%. CONCLUSION： Selective TACE may produce significant, but transitory increases in ALT values, with no major impact on liver function and Child-Pugh score. Preservation of liver function is achievable also in patients previously treated with other therapeutic modalities and in patients undergoing multiple TACE cycles. Liver function can remain stable in the long-term, with optimal medium term survival. This result can be achieved through rigorous patient selection on the basis of tumour characteristics and clinical conditions.
Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We ...retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. Results: The median OS of the enrolled patients was 41 months. According to LRT χ 2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10–1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. Conclusion: An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.
The development of new treatment options for hepatocellular carcinoma has changed not only the way in which cancer is treated, but also how it is diagnosed, especially the assessment of tumor ...response. The traditional radiologic methods, which are mainly based on the evaluation of changes in tumor size, are considered to be insufficiently sensitive and unreliable for determining tumor progression when targeted therapies such as sorafenib are involved. Several lines of research are currently focusing on the development of new assessment tools that try to combine morphological and vascular functional data in order to obtain an accurate measurement of tumor characteristics, such as volume, density or vascularization. This article presents some of the new instruments that have reported positive results.
Hepatocellular carcinoma (HCC) is the fifth most common neoplasia in the world. In the past, treatment of advanced HCC with conventional antineoplastic drugs did not result in satisfactory outcomes: ...recently, in this patient population the oral multikinase inhibitor sorafenib has been able to induce a statistically significant improvement of overall survival. Similarly to other anti-angiogenic drugs employed in other tumour types, also sorafenib seldom induces the dimensional tumour shrinking usually observed with conventional cytotoxic drugs: data gathered from studies carried out with sorafenib and other competitors under development do not report any complete response in HCV-induced HCC.
An 84-year old man with a long-lasting history of chronic HCV hepatitis was referred to our Institution for an ultrasonography investigation of a focal hepatic lesion. To better characterize the liver disease and clearly define the diagnosis of the focal hepatic lesion, the patient was hospitalized in our department. Laboratory and instrumental investigations confirmed the clinical picture of HCV-related liver cirrhosis and identified a hepatic lesion of about 6 cm featuring infiltrating HCC with thrombosis of the portal trunk. Due to the advanced stage of the disease, therapy with sorafenib 400 mg bid was started. Right from one month after the treatment was started, a reduction of alpha-fetoprotein level was observed which, by the third month, turned down within the normal limits. In addition the CT scan showed 50% reduction of the neoplastic lesion along with canalization of the portal trunk. At the sixth month the normalization of the alpha-fetoprotein level at the lower limit of normality was confirmed and the MRI showed complete disappearance of the neoplasia. In addition a reduction of a metallo-proteinase serum level was observed. At the twelfth month a further MRI confirmed complete response had been maintained. At present the patient is in a follow-up program to evaluate the duration of the complete response.
This case is worth mentioning since, to the best of our knowledge, it represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related HCC.
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