Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival

AIM: To evaluate outcomes of radiofrequency ablation(RFA) therapy for early hepatocellular carcinoma(HCC) and identify survival- and recurrence-related factors. METHODS: Consecutive patients diagnosed with early HCC by computed tomography(CT) or magnetic resonance imaging(MRI)(single nodule of ≤ 5 cm, or multi-(up to 3) nodules of ≤ 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Cancer do Estado de S o Paulo, Brazil were enrolled in the study. RFA of the liver tumors(with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response(absence of enhancing tissue at the tumor site) or incomplete response(enhancing tissue remaining at the tumor site). Overall survival and diseasefree survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed during the study period on 34 patients(age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo(range, 1-33). The study population showed predominance of male sex(76%), less severe liver disease(Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor(65%). The maximum tumor diameters ranged from 10 to 50 mm(median, 26 mm). The initial(immediately post-procedure) rate of RFAinduced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule(vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema(resolved with intervention) and intestinal perforation(led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis(HR = 15; 95%CI: 3-76 mo; P = 0.001). The 1-and 2-year cumulative disease-free survival rates were 65% and 36%, respectively. CONCLUSION: RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.

Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

AIM: To evaluate the impact of hepatitis C virus (HCV) infection with genotype 1 or 3 and the presence or absence of liver cirrhosis (LC) in the early viral kinetics response to treatment. METHODS: Naive patients (n = 46) treated with interferon-α (IFN-α) and ribavirin and followed up with frequent early HCV-RNA determinations were analysed. Patients were infected with genotype 1 (n = 28, 7 with LC) or 3 (n = 18, 5 with LC). RESULTS: The fi rst phase decline was larger in geno- type 3 patients than in genotype 1 patients (1.72 vs 0.95 log IU/mL, P < 0.001). The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients (0.87 vs 0.15 log/wk, P < 0.001). Differences were found in both cirrhotic and non-cirrhotic patients. Genotype 1 cirrhotic patients had a slower 2nd phase slope than non-cirrhotic patients (0.06 vs 0.18 log/wk, P < 0.02). None of genotype 1 cirrhotic patients had a 1st phase decline larger than 1 log (non-cirrhotic patients: 55%, P < 0.02). A similar trend toward a slower 2nd phase slope was observed in genotype 3 cirrhotic pa- tients but the 1st phase slope decline was not different. Sustained viral response was higher in genotype 3 pa- tients than in genotype 1 patients (72% vs 14%, P < 0.001) and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients (19% vs 0%). A secondphase decline slower than 0.3 log/wk was predictive of non-response in all groups. CONCLUSION: Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1st phase slope decline in genotype 1 patients.

Pro-atherosclerotic markers and cardiovascular risk factors one year after liver transplantation

AIM:To investigate pro-atherosclerotic markers(endothelial dysfunction and inflammation)in patients one year after liver transplantation.METHODS:Forty-four consecutive liver transplant(LT)outpatients who were admitted between August2009 and July 2010,were followed-up by for 1 year,exhibited no evidences of infection or rejection,all of them underwent tacrolimus-based immunosuppressive regimens were consecutively enrolled.Inflammatory cytokines(TNFα,IFNγ,IL-8,and IL-10),endothelial biomarkers(sVCAM-1,sICAM-1,MPO,adiponectin,PAI-1,SAP,SAA,E-selectin,and MMP-9),high sensitive C-reactive protein,and Framingham risk score(FRS)were assessed.The anthropometric data,aminotransferases,metabolic syndrome features,glucose and lipid profiles,and insulin resistance data were also collected.The LT recipients were compared to 22 biopsy-proven non-alcoholic steatohepatitis(NASH)patients and 20healthy controls(non-obese,non-diabetics,and nondyslipidemic).RESULTS:The LT recipients had significantly younger ages and lower body mass indices,aminotransferases,fasting glucose and insulin levels,glucose homeostasis model and metabolic syndrome features than the NASH patients.Classic cardiovascular risk markers,such as Hs-CRP and FRS[2.0(1.0-8.75)],were lower in the LT patients compared to those observed in the NASH patients(P=0.009).In contrast,the LT recipients and NASH patients had similar inflammatory and endothelial serum markers compared to the controls(pg/mL):lower IL-10 levels(32.3 and 32.3 vs 62.5,respectively,P=0.019)and higher IFNγ(626.1 and 411.9 vs 67.9,respectively,P<0.001),E-selectin(48.5 and 90.03vs 35.7,respectively,P<0.001),sVCAM-1(1820.6and 1692.4 vs 1167.2,respectively,P<0.001),and sICAM-1(230.3 and 259.7 vs 152.9,respectively,P=0.015)levels.CONCLUSION:Non-obese LT recipients have similar pro-atherosclerotic serum profiles after a short 1-year follow-up period compared to NASH patients,suggesting a high risk of atherosclerosis in this population.

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura(ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack oftuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas.

Use of Initial Modified RECIST Tumor Response Evaluation Criteria for Predicting Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization with Drug-Eluting Beads

Introduction: Transarterial chemoembolization (TACE) reduces tumor growth and increases survival in patients with hepatocellular carcinoma (HCC). Drug-eluting beads (DEB) deliver slow-release chemotherapy and reduce systemic toxicity during TACE. This study correlated initial tumor response according to modified RECIST (mRECIST) criteria and 1-year survival in patients with HCC treated with TACE-DEB, and identified predictors of tumor response. Methods: Fifty-two patients with HCC received TACE-DEB loaded with doxorubicin 75 mg during a 6-month period. Tumor response was evaluated 1 month after the procedure according to mRECIST criteria. Results: Most patients were cirrhotic and etiology of liver disease was hepatitis C in 26/52 (50%). Similar numbers of patients had Barcelona Clinic Liver Cancer (BCLC) A and BCLC B disease. Most patients had one nodule (66%). Complete response (CR) was achieved in 12/52 (23%), partial response in 19/52 (37%), stable disease in 4/52 (8%) and progressive disease in 17/52 (32%). Largest HCC ≤58 mm and BCLC stage A were associated with CR. The 1-year survival was 74%, with survival rates of 95% and 56% in the BCLC A and B groups, respectively. Variables reflecting tumor extension were associated with better survival. CR according to mRECIST criteria was a predictor of better 1-year survival (100% vs. 64%, P < 0.05). Conclusion: BCLC A and CR according to mRECIST criteria predict improved 1-year survival in patients with HCC treated with TACE-DEB. Further studies are needed to evaluate other predictors of survival and to determine if tumor response predicts long-term survival.

Branch retinal vein thrombosis and visual loss probably associated with pegylated interferon therapy of chronic hepatitis C

有干扰素治疗的眼科的复杂并发症通常温和、可逆，不要求治疗的退却。我们报导把视觉损失可能与干扰素治疗联系了的一个病人的一个案例。长期的丙肝病毒感染(遗传型 1a ) 在一个 33 年的老无征状的人被诊断。他的过去的病历是不显蓍的，以前的平淡的眼科学检查是正常的。Pegylated 干扰素高山哈并且 ribavirin 被开始。三个星期以后，他报导了视觉的无痛苦的减小。眼科学检查显示出广泛的视网膜内出血和棉花羊毛点，与劣等的分支 retinal 静脉血栓联系了。抗病毒的治疗立即被中止，但是一年以后，他坚持严重地减少的视敏度。这个案例在 pegylated 干扰素治疗期间说明无法预言、严重的复杂并发症的可能性。

Surgical treatment of fibrolamellar hepatocellular carcinoma:an underestimated malignant tumor?

BACKGROUND： Fibrolamellar hepatocellular carcinoma （FLHCC） is a rare disease with an indolent behavior. Its prognosis is better than that of patients with hepatocellular carcinoma. The authors present their experience with resection of FLHCC. METHODS： Twenty-one patients with FLHCC were treated at our institution between 1990 and 2012. Of these patients, 14 were subjected to resection of the tumor. Patient demographics, medical history, results of imaging studies and laboratory tests, surgical data, and pathologic findings were evaluated. RESULTS： The median age of the patients at the diagnosis of the tumor was 20 years and 14 patients were female. None of the patients had tumor-associated chronic liver disease or cirrhosis. The mean tumor size was 12.8 cm （range 6-19） and 18 patients had a single liver nodule. Fourteen patients were subjected to hepatectomy and six of them had lymph node metastases resected. Pathologic evaluation revealed that 5 （35.7%） patients had major vascular invasion. Tumor recurrence was seen in 8 patients （66.7%）, during a follow-up. The median survival time for patients who were subjected to resection was 36 months. The 5-year overall survival rate and disease free survival rate were 28.0% and 8.5%, respectively. Univariate analysis showed that vascular invasion was the only variable associated with the disease free survival rate.CONCLUSIONS： Despite an aggressive treatment, patients with FLHCC presented unexpected low survival rates. It seems that an underestimated malignant behavior is attributed to this disease, and that the forms of adjuvant treatment should be urgently evaluated.

Hepatocellular Carcinoma: The Final Moments of Life

Hepatocellular carcinoma (HCC) is a wide world prevalent hepatic disease, being the third greater cancer related death cause and most of the patients are not eligible for liver transplant. Palliative care is an option for, in average, half of hepatocellular carcinoma diagnosed patients and only recently the molecular targeted drug, Sorafenib, has been introduced among the therapeutic options for these patients. The physical pain comes frequently associated with progression disease (metastasis). Patients may be very fragile, with immobility, loss of interest in food and beverage intake, as well as weakness and drowsiness. Therefore, it is important that health professionals start planning care with patients and their relatives, before the end-stage disease. Informing the patient about therapeutic options guarantee a doctor patient relationship improvement and more belief on the health team.