Kelvin K. Ng

External Drainage of Pancreatic Duct With a Stent to Reduce Leakage Rate of Pancreaticojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial

Objective:Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy. External drainage of pancreatic duct with a stent has been shown to reduce pancreatic fistula rate of pancreaticojejunostomy in a few retrospective or prospective nonrandomized studies, but no randomized controlled trial has been reported thus far. This single-center prospective randomized trial compared the results of pancreaticoduodenectomy with external drainage stent versus no stent for pancreaticojejunal anastomosis. Methods:A total of 120 patients undergoing pancreaticoduodenectomy with end-to-side pancreaticojejunal anastomosis were randomized to have either an external stent inserted across the anastomosis to drain the pancreatic duct (n = 60) or no stent (n = 60). Duct-to-mucosa anastomosis was performed in all cases. Results:The 2 groups were comparable in demographic data, underlying pathologies, pancreatic consistency, and duct diameter. Stented group had a significantly lower pancreatic fistula rate compared with nonstented group (6.7% vs. 20%, P = 0.032). Radiologic or surgical intervention for pancreatic fistula was required in 1 patient in the stented group and 4 patients in the nonstented group. There were no significant differences in overall morbidity (31.7% vs. 38.3%, P = 0.444) and hospital mortality (1.7% vs. 5%, P = 0.309). Two patients in the nonstented group and none in the stented group died of pancreatic fistula. Hospital stay was significantly shorter in the stented group (mean 17 vs. 23 days, P = 0.039). On multivariate analysis, no stenting and pancreatic duct diameter <3 mm were significant risk factors of pancreatic fistula. Conclusion:External drainage of pancreatic duct with a stent reduced leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy.

Continuous Improvement of Survival Outcomes of Resection of Hepatocellular Carcinoma: A 20-Year Experience

Objective:To investigate the trend of the posthepatectomy survival outcomes of hepatocellular carcinoma (HCC) patients by analysis of a prospective cohort of 1198 patients over a 20-year period. Background:The hospital mortality rate of hepatectomy for HCC has improved but the long-term survival rate remains unsatisfactory. We reported an improvement of survival results 10 years ago. It was not known whether there has been further improvement of results in recent years. Methods:The patients were categorized into two 10-year periods: period 1, before 1999 (group 1, n = 390) and period 2, after 1999 (group 2, n = 808). Patients in group 2 were managed according to a modified protocol and technique established in previous years. Results:The patients in group 2 were older and had a higher incidence of comorbid illness and cirrhosis. They had a lower hospital mortality rate (3.1% vs 6.2%, P = 0.012) and longer 5-year overall survival (54.8% vs 42.1%, P < 0.001) and disease-free survival rates (34.8% vs 24%, P = 0.0024). An improvement in the overall survival rate was observed in patients with cirrhosis, those undergoing major hepatectomy, and those with tumors of tumor-node-metastasis stages II, IIIA, and IVA. A significant increase in the survival rates was also seen in patients whose tumors were considered transplantable by the Milan criteria (72.5% vs 62.7%, P = 0.0237). Multivariate analysis showed a significantly more favorable patient survival for hepatectomy in period 2. Conclusions:A continuous improvement of survival outcomes after hepatectomy for HCC was achieved in the past 20 years even in patients with advanced diseases. Hepatectomy remains the treatment of choice for resectable HCC in a predominantly hepatitis B virus-based Asian population.

Is Hepatic Resection for Large or Multinodular Hepatocellular Carcinoma Justified? Results From a Multi-Institutional Database

BackgroundThe role of surgical resection in patients with large or multinodular hepatocellular carcinoma (HCC) remains unclear. This study evaluated the long-term outcome of patients with hepatic resection for large (>5 cm in diameter) or multinodular (more than three nodules) HCC by using a multi-institutional database.MethodsThe perioperative and long-term outcomes of 404 patients with small HCC (<5 cm in diameter; group 1) were compared with those of 380 patients with large or multinodular HCC (group 2). The prognostic factors in the latter group were analyzed.ResultsThe postoperative complication rate (27% vs. 23%; P = .16) and hospital mortality rate (2.4% vs. 2.7%; P = .82) were similar between groups. The overall survival rates were significantly higher in group 1 than group 2 (1 year, 88% vs. 74%; 3 years, 76% vs. 50%; 5 years, 58% vs. 39%; P < .001). Among patients in group 2, five independent prognostic factors were identified to be associated with a worse overall survival: namely, symptomatic disease, presence of cirrhosis, multinodular tumor, microvascular tumor invasion, and positive histological margin.ConclusionsHepatic resection can be safely performed in patients with large or multinodular HCC, with an overall 5-year survival rate of 39%. Symptomatic disease, the presence of cirrhosis, a multinodular tumor, microvascular invasion, and a positive histological margin are independently associated with a less favorable survival outcome.

Learning curve for radiofrequency ablation of liver tumors: prospective analysis of initial 100 patients in a tertiary institution.

Objective:This study aims to evaluate the effect of operator experience on the treatment outcomes of radiofrequency ablation (RFA) for malignant liver tumors. Summary Background Data:RFA is gaining popularity as the ablative therapy of choice for liver tumors. It is generally considered a simple and safe technique, and little attention has been paid to the importance of operator experience in this treatment. A learning curve in this treatment modality has not been documented before. Patients and Methods:The clinical data and treatment outcomes of the initial 100 patients undergoing RFA for liver tumors (hepatocellular carcinoma, n = 84; metastasis, n = 15; cholangiocarcinoma n = 1) were collected prospectively. All patients were managed by a single team of surgeons and interventional radiologists. The data of the first 50 patients (group I) and the second 50 patients (group II) were compared. Results:RFA was performed by percutaneous (group I, n = 22; group II, n = 19), open (group I, n = 26; group II, n = 30) or laparoscopic (group I, n = 2; group II, n = 1) approach. In group I, 30 patients (60%) had a solitary tumor and 20 (40%) had multiple tumors; in group II, 35 patients (70%) had a solitary tumor and 15 (30%) had multiple tumors (P = 0.295). The size of the largest tumor was comparable between groups I and II (median, 2.8 cm in both groups; P = 0.508). Group II had significantly shorter hospital stay (median, 4.0 versus 5.5 days; P = 0.048), lower morbidity rate (4% versus 16%; P = 0.046) and higher complete ablation rate (100% versus 85.7%; P = 0.006) than group I. There was 1 hospital death (2%) in group I and 0 in group II. By multivariate analysis, treatment period (group I versus group II) was an independent significant factor affecting the morbidity rate and complete ablation rate. Conclusions:A low complication rate and a high complete ablation rate could be achieved with the accumulated experience from the first 50 cases of RFA for liver tumors by a specialized team. This study demonstrates that there is a significant learning curve in RFA for liver tumors.

Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population

The current study was a phase 2 open–label study to evaluate the efficacy and tolerability of single‐agent sorafenib in the treatment of advanced HCC patients in a hepatitis B–endemic Asian population.

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.

Changing paradigm in the management of hepatocellular carcinoma improves the survival benefit of early detection by screening.

Objective:To evaluate the impact of improved surgical management of hepatocellular carcinoma (HCC) on the survival of patients with screened HCC. Summary Background Data:It is unclear whether the advent of new treatment modalities such as liver transplantation and radiofrequency ablation (RFA) in recent years have improved the long-term survival in patients with HCC detected by screening. Methods:A prospective database of 1366 patients with known chronic hepatitis B or C virus infection diagnosed with HCC either by screening or symptomatic presentation from January 1991 to December 2004 was reviewed. The long-term survival of HCC patients in the screened and symptomatic groups was compared. The management and survival of patients in two 7-year periods (1991–1997 vs. 1998–2004) were further compared. Results:Long-term survival was significantly better in the screened group than in the symptomatic group (median survival 61.9 vs. 11.5 months, P < 0.001). The proportion of patients with curative treatment increased from 50.5% in the first period to 67.8% in the second period in the screened group, but there was no significant change in the symptomatic group. Improved long-term survival was observed in patients with HCC detected by screening and treated in the second period compared with the first period (median survival 68.5 vs. 38.7 months, P = 0.022), but no significant improvement was observed for symptomatic patients. Conclusion:Survival of patients with HCC detected by screening has improved in recent years due to increased chance of curative treatment with the advent of liver transplantation and RFA.

High-Intensity Focused Ultrasound for Hepatocellular Carcinoma A Single-Center Experience

Objective: This study aims to evaluate the outcome of patients with hepatocellular carcinoma (HCC) treated by high-intensity focused ultrasound (HIFU) in a single tertiary referral center. Background: HIFU is the latest developed local ablation technique for unresectable HCC. The initial experience on its efficacy is promising, but the survival benefit of patients undergoing HIFU for HCC is poorly defined. Methods: From October 2006 to December 2008, 49 patients received HIFU for unresectable HCC. Each patient underwent a single session of HIFU with a curative intent. Treatment efficacy and survival outcome were evaluated. Clinicopathologic factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis. Results: The median size of the treated tumors was 2.2 cm, ranging from 0.9 to 8 cm. The majority of patients had single tumors (n = 41, 83.6%). Thirty-one patients (63.2%) had artificial right pleural effusion during HIFU treatment to reduce damage to the lung and diaphragm. The hospital mortality rate was 2% (n = 1) and the complication rate was 8.1% (n = 4). The primary technique effectiveness rate was 79.5% (39 of 49 patients). It increased from 66.6% in the initial series to 89.2% in the last 28 patients. Tumor size (≥3.0 cm) was the significant risk factor affecting the complete ablation rate. The 1- and 3-year overall survival rates were 87.7% and 62.4%, respectively. Child-Pugh liver function grading was the significant prognostic factor influencing the overall survival rate. Conclusions: HIFU is an effective treatment modality for unresectable HCC with a high technique effectiveness rate and favorable survival outcome.

Thermal ablative therapy for malignant liver tumors: A critical appraisal

Abstract  The management of primary and secondary malignant liver tumors poses a great challenge to clinicians. Although surgical resection is the gold‐standard treatment, most patients have unresectable malignant liver tumors. Over the past decade, various modalities of loco‐regional therapy have gained much interest. Among them, thermal ablative therapy, including cryotherapy, microwave coagulation, interstitial laser therapy, and radiofrequency ablation (RFA), have been proven to be safe and effective. Despite the effective tumor eradication achieved within cryotherapy, the underlying freeze/thaw mechanism has resulted in serious complications that include bleeding from liver cracking and the ‘cryoshock’ phenomenon. Thermal ablation using microwave and laser therapy for malignant liver tumors is curative and is associated with minimal complications. However, this treatment modality is effective only for tumors <3 cm diameter. Radiofrequency ablation seems to be the most promising form of thermal ablative therapy in terms of a lower complication rate and a larger volume of ablation. However, its use is restricted by the difficulty encountered when using imaging studies to monitor the areas of ablation during and after the procedure. Moreover, the techniques of RFA need to be refined in order to achieve the same oncological radicality of malignant liver tumors as achieved by surgical resection. As each of the loco‐regional therapies has its own advantages and limitations, a multidisciplinary approach using a combination of therapies will be the future trend for the management of malignant liver tumors.

Can positron emission tomography with the dual tracers [11C]acetate and [18F]fludeoxyglucose predict microvascular invasion in hepatocellular carcinoma?

Microvascular invasion is a poor prognostic indicator of the recurrence of hepatocellular carcinoma (HCC) after surgical treatment. Positron emission tomography (PET) with [18F]fludeoxyglucose ([18F]FDG) as a tracer has been employed to predict the prognosis before surgery for various kinds of tumors, but it has not been found to be sensitive enough for HCC. Thus, [11C]acetate has been adopted as an additional tracer. This study was designed to evaluate the ability of dual‐tracer PET ([18F]FDG and [11C]acetate) to predict microvascular invasion before liver resection or transplantation. Fifty‐eight HCC patients who were preoperatively examined with whole‐body dual‐tracer PET were studied. Twenty‐five patients were [18F]FDG‐positive, and 56 were [11C]acetate‐positive. The sensitivity of [18F]FDG in detecting primary HCC was 43%, and the sensitivity of [11C]acetate was 93%. Twenty‐nine patients had HCC with microvascular invasion according to the final pathological examination. The sensitivity, specificity, positive predictive value, and negative predictive value of [18F]FDG PET in predicting microvascular invasion were 55.2%, 69%, 64%, and 60.6%, respectively; the corresponding rates for [11C]acetate PET were 93.1%, 0%, 48.2%, and 0%. The factors associated with HCC recurrence, which included multifocal involvement, a large tumor size, microsatellite lesions, poor HCC differentiation, and an advanced stage of disease, were analyzed and compared with positive PET results. A tumor size greater than 5 cm was significantly associated with positive [18F]FDG PET results; [11C]acetate was not associated with poor prognostic indicators. Preoperative [18F]FDG PET may predict microvascular invasion. The addition of [11C]acetate improves the overall sensitivity of PET, but it has no incremental value in predicting microvascular invasion. Liver Transpl 17:1218–1225, 2011.