Wei-Chen Lee

Hepatic Resection and Prognosis for Patients With Hepatocellular Carcinoma Larger Than 10 cm: Two Decades of Experience at Chang Gung Memorial Hospital

AbstractBackground: Although screening programs in high-risk populations have facilitated the detection of small hepatocellular carcinoma (HCC), some HCC patients continue to present with advanced, large tumors. However, reports of hepatic resection for HCC larger than 10 cm (L-HCC) are limited. This study aims to determine the clinicopathologic factors that influence the prognosis of hepatic resection for L-HCC. Methods: The clinical features of 211 L-HCC patients undergoing hepatic resection were reviewed. Clinical features and factors influencing the outcome of 985 patients with HCC smaller than 10 cm (S-HCC) were used for comparison. Results: Of 1196 surgically resected HCCs, 211 (17.6%) were L-HCC. Multivariate logistic regression analysis showed that the presence of dull abdominal pain, a low indocyanine green retention rate value, a high percentage of alfa fetoprotein (AFP) >400 ng/mL, major hepatectomy, absence of tumor capsule formation, satellite lesions, and vascular invasion were the seven main independent factors differentiating L-HCC from S-HCC patients. Significantly worse overall survival was noted in L-HCC patients, especially those with tumor rupture, satellite lesions, AFP >400 ng/mL, and blood loss of >1 L during surgery. Conclusions: Hepatic resection, when feasible, is safe and is the preferred treatment for L-HCC patients. However, overall and disease-free survival for L-HCC are worse than for S-HCC. Disease-free survival for L-HCC patients undergoing hepatic resection is significantly influenced by a high value of alkaline phosphatase and by AFP. Overall survival for L-HCC patients undergoing hepatic resection is significantly influenced by a high value of AFP, blood loss, tumor rupture, and satellite lesions.

Minor versus major hepatic resection for small hepatocellular carcinoma (HCC) in cirrhotic patients: A 20-year experience

BACKGROUND The choice between minor versus major resection or anatomic versus nonantatomic resection for small (<5 cm) solitary hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. The aim of our study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) after minor or major hepatic resection for small solitary HCC in cirrhotic patients. METHODS Between January 1983 and December 2002, patients with solitary HCC of < or = 5 cm in size who had histologically proven liver cirrhosis and microscopically tumor-free margin were included. These selected patients underwent either minor (< or = 2 segments) or major (> or = 3 segments) hepatectomy. RESULTS In 373 patients, 259 underwent minor and 114 underwent major hepatectomy. Patients in the minor resection group had more severe underlying liver disease (P = .005). Therefore, only 29.3% received anatomic resection in the minor resection group in comparison with 72.8% in the major hepatectomy group (P = .0001). No difference was found in postoperative morbidity (P = .105), mortality (P =.222), intrahepatic recurrence (P = .742), and 5-year DFS and OS (31.6% vs 31.8%, P = .932 and 50.7% vs 44.0%, P = .114) in both groups. The type of operative resection was not found to be a significant factor affecting survival in univariate analysis, but the preoperative liver function (alanine aminotransferase [AST] or alanine aminotransferase [ALT], serum albumin, or Child-Pugh status), tumor characteristics (alpha-feto protein, size, and presence of daughter nodules), and blood transfusion were found to be independent factors that affect the DFS and OS in a multivariate analysis. CONCLUSION The severity of cirrhosis and tumor characteristics depicts long-term survival rather than the type of resection in HCC.

Hepatitis B virus–DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma

Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma (HCC). However, the postoperative prognostic value of the virological factors assayed directly from liver tissue has never been investigated. To address this issue, 185 liver samples obtained from the noncancerous part of surgically removed HBV‐associated HCC tissues were subjected to virological analysis. Assayed factors included the amount of HBV‐DNA in the liver tissues; genotype; and the presence of the HBV precore stop codon G1896A mutation, basal core promoter A1762T/G1764A mutation, and pre‐S deletions/stop codon mutation. All virological factors and clinicopathological factors were subjected to Cox proportional hazard model analysis to estimate postoperative survival. It was found that an HBV‐DNA level >3.0 × 107 copies/g of liver tissue and the presence of the basal core promoter mutation independently predicted disease‐free (adjusted hazard ratio 1.641 [95% confidence interval (CI) 1.010‐2.667] and 2.075 [95% CI 1.203‐3.579], respectively) and overall (adjusted hazard ratio 2.807 [95% CI 1.000‐7.880] and 5.697 [95% CI 1.678‐19.342], respectively) survival. Kaplan‐Meier survival analysis indicated that in‐frame, short stretch (<100 bp) pre‐S deletions, but not large fragment (>100 bp) pre‐S deletions, were significantly associated with poorer disease‐free (P = 0.005) and overall (P = 0.020) survival. A hot deletion region located between codons 107 and 141 of the pre‐S sequence was identified for the short stretch pre‐S deletion mutants. Conclusion: The amount of HBV‐DNA in liver tissue and the presence of the basal core promoter mutation were two independent predictors for postoperative survival in HCC. A short stretch pre‐S deletion located between codons 107 and 141 was strongly associated with a poorer postoperative prognosis. (Hepatology 2010)

Hepatic Resection for Hepatocellular Carcinoma with Obstructive Jaundice due to Biliary Tumor Thrombi

ABSTRACTHepatocellular carcinoma (HCC) with obstructive jaundice due to biliary tumor thrombi is uncommon, and few studies have examined the outcome of hepatectomy for HCC with this unusual entity. This study examined the clinicopathologic factors influencing the outcomes of 17 HCC patients with obstructive jaundice due to biliary tumor thrombi undergoing hepatectomy. The clinical features of 17 HCC patients with obstructive jaundice due to biliary tumor thrombi (group A) undergoing hepatectomy from 1986 to 1998 were reviewed. The clinical features and factors influencing the outcome of 555 HCC patients without biliary tumor thrombi (group B) undergoing hepatectomy were used for comparison. Of 572 patients with surgically resected HCCs, 17 (3.0%) were classified into group A. Right upper quadrant pain, physical signs of jaundice, low albumin level, elevated bilirubin level, small tumor size, more vascular invasion, and tumor rupture were characteristic of group A patients. Multivariate stepwise logistic regression analysis revealed no independently significant factor differentiating group A patients from group B patients. The disease-free survival was similar between the group A and B patients, although group B patients exhibited significantly better overall survival (p = 0.014). Vascular invasion may adversely influence overall survival in group A patients undergoing hepatic resection (p = 0.0709). When feasible, hepatic resection is the preferred treatment for HCC patients with obstructive jaundice due to biliary tumor thrombi. It can achieve a disease-free survival comparable to that of HCC patients without biliary tumor thrombi. However, HCC patients with biliary tumor thrombi had significantly worse overall survival than did those without biliary tumor thrombi, especially those with concomitant vascular invasion.

Right hepatectomy by the anterior method with liver hanging versus conventional approach for large hepatocellular carcinomas

The aim was to compare short‐term results of right hepatectomy using the anterior approach (AA) and liver hanging manoeuvre with the conventional approach (CA) for large hepatocellular carcinoma (HCC).

CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus infection

BackgroundCD133 was detected in several types of cancers including hepatocellular carcinoma (HCC), which raised the possibility of stem cell origin in a subset of cancers. However, reappearance of embryonic markers in de-differentiated malignant cells was commonly observed. It remained to be elucidated whether CD133-positive HCCs were indeed of stem cell origin or they were just a group of poorly differentiated cells acquiring an embryonic marker. The aim of this study was to investigate the significance of CD133 expression in HCC in an area endemic for hepatitis B virus (HBV) infection to gain insights on this issue.Methods154 HCC patients receiving total removal of HCCs were included. 104 of them (67.5%) were positive for HBV infection. The cancerous and adjacent non-cancerous liver tissues were subjected for Western blot and immunohistochemistry analysis for CD133 expression. The data were correlated with clinical parameters, patient survivals, and p53 expression.ResultsOf 154 patients, 24 (15.6%) had CD133 expression in HCC. Univariate and multivariate logistic regression analysis revealed that CD133 expression was negatively correlated with the presence of hepatitis B surface antigen (HBsAg). The unadjusted and adjusted odds ratios were 0.337 (95%CI 0.126 - 0.890) and 0.084 (95%CI 0.010 - 0.707), respectively. On the other hand, p53 expression was positively associated with the presence of HBsAg in univariate analysis. The unadjusted odds ratio was 4.203 (95%CI 1.110 - 18.673). Survival analysis indicated that both CD133 and p53 expression in HCC predicted poor disease-free survival (P = 0.009 and 0.001, respectively), whereas only CD133 expression predicted poor overall survival (P = 0.001). Cox proportional hazard model showed that p53 and CD133 expression were two independent predictors for disease-free survival. The hazard ratios were 1.697 (95% CI 1.318 - 2.185) and 2.559 (95% CI 1.519 - 4.313), respectively (P < 0.001 for both).ConclusionIn area where HBV infection accounts for the major attributive risk of HCC, CD133 expression in HCC was negatively associated with the presence of HBsAg, implicating a non-viral origin of CD133-positive HCC. Additionally, CD133 expression predicted poor disease-free survival independently of p53 expression, arguing for two distinguishable hepatocarcinogenesis pathways.

Surgical resection of centrally located large hepatocellular carcinoma.

BACKGROUND Centrally located large hepatocellular carcinoma (HCC) is a difficult issue in surgery. These HCCs can be treated by hemi-/extended or central hepatectomies. The aim of this study was to analyze the results of hemi-/extended and central hepatectomies. METHODS One hundred and four patients with centrally-located large tumors were retrospectively reviewed. Patients were divided into group 1 (n = 41) with hemi-/extended hepatectomies, and group 2 (n = 63) with central hepatectomies. Characteristics were analyzed between groups and survival rates were calculated. RESULTS Parenchyma resection was limited in group 2. The resection margin in 92.6% of group 2 patients was < 1 cm, compared with 78.9% of group 1 patients (p = 0.056). The 1- and 5-year disease-free survival rates were 50% and 38.9% for group 1, and 50% and 15% for group 2 (p = 0.279). The 1-, 5-year overall survival rates were 89.5% and 66.2% for group 1 and 87.5% and 53.1% for group 2 (p = 0.786). Cirrhosis, the preoperative aspartate aminotransferase (AST) level and lower resected liver weight were independent factors impairing survival. CONCLUSION Hemi-/extended and central hepatectomies have comparable complication rates and long-term survival rates for patients with centrally located large HCC. Cirrhosis, the AST level and resected liver weight were independent factors determining long-term survival.

Predictors of long-term disease-free survival after resection of hepatocellular carcinoma: two decades of experience at Chang Gung Memorial Hospital.

AbstractBackground: Hepatocellular carcinoma (HCC) is a common disease in Taiwan. A high incidence of recurrence after hepatectomy is the most important cause of unsatisfactory results after resection of HCC. This study aimed to determine the clinicopathologic factors for predicting survival >5 years without recurrence in HCC patients treated with hepatectomy. Methods: The clinical features of 46 patients with surgically resected HCC who survived >5 years without recurrence (group A) were reviewed. Also, comparison was made with the clinical features and factors influencing the outcome of 1046 cases of resected HCC who survived <5 years both with and without recurrence and for >5 years with recurrence (group B). Results: Of 1092 cases of surgically resected HCC, 46 (4.5%) survived >5 years without recurrence. Univariate analysis revealed that absence of vascular invasion, satellite lesions, low histological grading of HCC, a lower rate of underlying liver cirrhosis, wider resection margins, and an uneventful postoperative course were frequent in group A patients compared with group B patients. Moreover, multivariate stepwise logistic regression analysis identified an absence of satellite lesions and an uneventful postoperative course as the two main independently significant predictors of HCC patients undergoing hepatectomy with long-term disease-free survival. The 1-, 3-, 5-, and 10-year survival rates of group A patients were 100%, 100%, 100%, and 84.1%, whereas those of group B patients were 73.5%, 47.9%, 29.0%, and 21.2%, respectively. Conclusions: An absence of satellite lesions and an uneventful postoperative course are the two main independent predictors for long-term disease-free survival in HCC patients undergoing hepatic resection.

Surgical management of giant hepatic hemangiomas: complications and review of the literature.

BACKGROUND Hepatic hemangiomas are the most common benign hepatic tumors, and they are usually asymptomatic with normal liver function. When hepatic hemangiomas reach 4 cm, we define them as giant hemangiomas. Treatment options for giant hemangiomas are observation, surgical resection, and transcatheter arterial embolization. The aim of this study was to identify the risk factors for surgical complications. METHODS In this study, the records of 61 patients with giant hepatic hemangiomas treated with surgical resection at Chang Gung Memorial Hospital, Linkou were retrospectively reviewed. Data on clinical variables including symptoms, the size, number, and location of the tumors, preoperative liver function tests, operative method, operation time, and operative blood loss were collected and analyzed. RESULTS There were 8 patients (13.1%, 95% confidence interval 5.8% to 24.2%) with complications after resection or enucleation. Postoperative complications were associated with large tumor size (p = 0.021) and tumors that were symptomatic (p = 0.017). In addition, complications were associated with greater use of intraoperative inflow control (p = 0.053), longer operative time (p = 0.001), and greater intraoperative blood loss (p = 0.022). Most complications could be treated conservatively, but invasive interventions such as endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangial drainage were required for management of grade III complications. CONCLUSIONS Most giant hepatic hemangiomas can be treated with enucleation or resection. Important factors associated with complications were large tumor size, the presence of symptoms, surgical bleeding, and prolonged surgery. Most complications were grade I and could be treated conservatively. Both resection and enucleation were relatively safe with an acceptable complication rate (13.1%) and no mortality in our study.

Outcomes of resection for colorectal cancer hepatic metastases stratified by evolving eras of treatment

Background and purposeThe outcomes and management of colorectal cancer (CRC) hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment.MethodsWe conducted a retrospective review of 279 patients who underwent liver resection (LR) for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1) and post-2003 (era 2) were examined.ResultsOf the patients included in the study, 210 (75.3%) had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 vs. 69.5% in era 2; p = 0.008). Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% vs. 2.2% for 5-year survival; p < 0.0001).ConclusionThe incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.