Tt Cheung

Risk factors and prognostic factors of local recurrence after radiofrequency ablation of hepatocellular carcinoma.

BACKGROUND Local recurrence rates after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) vary from 2% to 36% in the literature. Limited data were available about the prognostic significance of local recurrence. STUDY DESIGN Between April 2001 and March 2006, 273 patients with 357 hepatocellular carcinoma nodules underwent RFA, with radiologically complete tumor ablation after a single session of RFA. The risk factors of local recurrence and its impact on overall survival of patients were analyzed. RESULTS With a median followup period of 24 months, local recurrence occurred in 35 patients (12.8%). By multivariate analysis, tumor size > 2.5 cm was the only independent risk factor for local recurrence. There was no notable difference in overall survival between patients with and without local recurrence. By multivariate analysis, local recurrence more than 12 months after RFA and complete response after additional treatment of local recurrence were associated with better overall survival in patients with local recurrence. CONCLUSIONS This study demonstrated that tumor size > 2.5 cm was the main risk factor for local recurrence after RFA of hepatocellular carcinoma. Our data suggested that additional aggressive treatment of local recurrence aimed at complete tumor response improves overall survival of patients. Late local recurrence was also associated with better prognosis, suggesting different tumor biology between early and late local recurrent tumors after RFA.

Oral Nucleoside/Nucleotide Analogs Without Hepatitis B Immune Globulin After Liver Transplantation for Hepatitis B

OBJECTIVES:The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone.METHODS:A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up.RESULTS:Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients.CONCLUSIONS:Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.

Liver transplantation for hepatocellular carcinoma: the Hong Kong experience

Orthotopic liver transplantation (OLT) is the best treatment option for selected patients with hepatocellular carcinoma (HCC) with the background of cirrhosis since this treatment modality can cure both diseases at once. Over the years, the applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a shortage of deceased donor liver grafts is a universal problem having to be faced in all transplant centers. Living-donor liver transplant (LDLT) has therefore been developed to counteract organ shortage and the high prevalence of HCC. The application of LDLT for HCC is a complex process involving donor voluntarism, selection criteria for the recipient and justification with respect to long-term survival in comparison to the result of deceased donor liver transplant. This article reviews the authors’ experience with OLT for HCC patients in Hong Kong, with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism has a significant impact on the application of LDLT. “Fast-track” LDLT in the setting of recurrence following curative treatment carries a high risk of recurrence even though the tumor stage fulfills the standard criteria. Although the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still the main treatment option for patients with transplantable HCC in Hong Kong, and a reasonable survival outcome can be achieved in selected patients with extended indications. It is particularly true that LDLT provides the only hope for patients with advanced HCC under the constricting problem of organ shortage.

Efficacy and Tolerability of Low-Dose Thalidomide as First-Line Systemic Treatment of Patients with Advanced Hepatocellular Carcinoma

Objective: The systemic treatment of advanced hepatocellular carcinoma (HCC) has produced disappointing results thus far. HCC is a hypervascular tumor with over-expression of angiogenic factors such as vascular endothelial growth factor. Thalidomide is an anti-neoplastic agent with anti-angiogenic and other mechanisms of action. We aim to evaluate the efficacy and toxicity of low-dose (100 mg) thalidomide as the first-line treatment of advanced HCC. Methods: Between August 2003 and March 2007, 45 patients who had received thalidomide 100 mg daily as first-line treatment of advanced HCC were reviewed retrospectively. Advanced HCC was defined as either metastatic or not amenable to surgical or locoregional therapies. Diagnosis of HCC was based on clinical, biochemical and radiological grounds. Survival was analyzed by the Kaplan-Meier method. Results: Thirty-eight patients were evaluable for response and toxicity. Two (5%) patients had partial response and 8 (21%) had stable disease. The overall median survival of patients in this cohort was 3.2 months (95% CI: 2.8–3.7 months). The common toxicities were somnolence (13%), peripheral neuropathy (11%) and ankle edema (8%), with no grade 3 or 4 toxicities and treatment-related deaths. Conclusion: Our study shows that a single agent, low-dose thalidomide has a modest clinical activity with good tolerability in treating advanced HCC patients.

Use of Liver Stiffness Measurement for Liver Resection Surgery: Correlation with Indocyanine Green Clearance Testing and Post-Operative Outcome

Background Liver stiffness measurement (LSM) using transient elastography has recently become available for the assessment of liver fibrosis. Whether LSM can predict the functional liver reserve in patients undergoing liver resection is not certain. Aim To correlate liver stiffness measurement (LSM) with indocyanine green (ICG) clearance test and liver biochemistry, and to determine its usefulness in predicting postoperative outcomes in patients undergoing liver resection. Patients and Methods Transient elastography and ICG clearance test were performed pre-operatively in 44 patients with hepatocellular carcinoma. The LSM and ICG retention rate at 15 minutes (R15) were correlated with pre-operative factors and post-operative outcomes. Results There was significant correlation between ICG R15 and LSM. In patients with LSM ≥11 kPa vs <11 kPa, there was significantly higher ICG R15 (17.1% vs 10.0% respectively, p = 0.025). For patients with ICG R15≥10% compared to those <10%, there was significantly higher LSM (12.0 vs 7.6 kPa respectively, p = 0.015). Twenty-eight patients proceeded to resection. There was a significant correlation between LSM and the peak INR after liver resection (r = 0.426, p = 0.024). There was a significant correlation between ICG R15 and the post-operative peak AST level (r = −0.414, p = 0.029) and peak ALT level (r = −0.568, p = 0.002). The operative time was a significant independent factor associated with post-operative complications and peak INR. Conclusion LSM correlated well with ICG R15 in patients undergoing liver resection, and predicted early post-operative complications. Addition of LSM to ICG R15 testing may provide better prognostic information for patients undergoing resection.

Long‐term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: Results up to 8 years

Long‐term antiviral prophylaxis is required to prevent hepatitis B recurrence for patients with chronic hepatitis B after liver transplantation. We determined the long‐term outcome of 265 consecutive chronic hepatitis B liver transplant recipients treated with entecavir monotherapy without hepatitis B immune globulin. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow‐up. The median duration of follow‐up was 59 months. The cumulative rates of hepatitis B surface antigen (HBsAg) seroclearance were 90% and 95% at 1 and 5 years, respectively. At 1, 3, 5, and 8 years, 85%, 88%, 87.0%, and 92% were negative for HBsAg, respectively, and 95%, 99%, 100%, and 100% had undetectable hepatitis B virus (HBV) DNA, respectively. Fourteen patients remained persistently positive for HBsAg, all of whom had undetectable HBV DNA. There was no significant difference in liver stiffness for those who remained HBsAg‐positive compared to those who achieved HBsAg seroclearance (5.5 versus 5.2 kPa, respectively; P = 0.52). The overall 9‐year survival was 85%. There were 37 deaths during the follow‐up period, of which none were due to hepatitis B recurrence. Conclusion: Long‐term entecavir monotherapy is highly effective at preventing HBV reactivation after liver transplantation for chronic hepatitis B, with a durable HBsAg seroclearance rate of 92%, an undetectable HBV DNA rate of 100% at 8 years, and excellent long‐term survival of 85% at 9 years. (Hepatology 2017;66:1036‐1044).

Outcomes including liver histology after liver transplantation for chronic hepatitis B using oral antiviral therapy alone

The outcomes of hepatitis B virus (HBV)–related hepatitis after liver transplantation (LT) without hepatitis B immune globulin (HBIG) is not well documented. This study aims to determine the outcomes of chronic hepatitis B (CHB) patients using an HBIG‐free regimen. All biopsies performed 3 months or more after LT in consecutive CHB patients transplanted from 2003 to 2012 were reviewed. None of the patients received HBIG. Results of all liver histologies were reviewed to determine the cause of graft dysfunction. Of the 435 patients transplanted during this period, 263 liver biopsies were performed in 144 patients. Thirty‐six patients were positive for hepatitis B surface antigen (HBsAg) with undetectable HBV DNA at the time of biopsy, and none had histological evidence of HBV infection. Of the 263 biopsies, 44 (17%) had evidence of fibrosis. There was a significantly higher rate of fibrosis in those with large duct obstruction compared to those without (51% versus 9%, respectively; P < 0.001). Of the 291 patients without a liver biopsy during the same period, 43 were HBsAg+. Seven patients had evidence of virological rebound, of whom 6 had evidence of rtM204V/I mutation and 1 had recurrence of hepatocellular carcinoma with low‐level rebound and wild‐type virus. In conclusion, for patients without virological rebound, positive serum HBsAg was not associated with histological evidence of HBV‐related hepatitis after LT. To prevent virological rebound, nucleos(t)ide analogues with higher barriers to resistance should be used. Liver Transpl 21:1504‐1510, 2015.

Safety and Efficacy of Radiofrequency Ablation for Periductal Hepatocellular Carcinoma with Intraductal Cooling of the Central Bile Duct

R R al app our c cs) w exp mors g of t d atic i was a neeepatocellular carcinoma (HCC) is among the three m ommon causes of cancer death worldwide, accounting bout 315,000 deaths annually. 1 Radiofrequency ablation RFA) is a recently developed technique for ablation of umors. It is well-tolerated in patients with unresect CC, with a low morbidity rate ranging from 0% to nd a perioperative mor tality rate of 0% to 2%. 2-7 A recent andomized controlled trial also showed that percutane FA was as effective as hepatic resection in terms of o nd disease-free sur vival in treatment of solitar y resec CC 5 cm. RFA is based on the interaction of alternating ele urrent with living tissue. At high-frequency setting, urrent causes agitation of ions in the adjacent tissues, rating frictional heat. 9 For tumors located close to entral bile ducts, heat generated by RFA damages the ucts, causing stenosis and bile duct dilation. 10,11 In one tudy describing the complications of RFA of liver tum iliar y complications represented 1% of the complicat n 3,670 patients. 12 Some authors suggested that RF hould not be used in tumors closer than 15 to 20 he central bile ducts. 10,12 Elias and colleagues repor ted eries of 13 patients with liver tumors treated with RFA ntraductal cooling of the central bile ducts aimed at enting biliar y complications. The majority of patien his series had colorectal liver metastases and only on ient suffered from HCC. The only biliar y complicatio hat series was seen in the patient with HCC, prese ith segmental stenosis of the bile ducts near the s FA 6 months after the procedure.

Advanced Pancreatic Cancer: Flourishing Novel Approaches in the Era of Biological Therapy

The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance.

Randomized clinical trial of hepatic resection versus radiofrequency ablation for early-stage hepatocellular carcinoma.

Hepatic resection and radiofrequency ablation (RFA) are treatment options for early‐stage hepatocellular carcinoma (HCC). Whether tumour recurrence and long‐term survival favour either treatment has not been established. This randomized trial aimed to test the hypothesis that RFA is superior to hepatic resection in terms of lower tumour recurrence rate and better long‐term survival.