Liver resection for intermediate hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer(BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization(TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC.     

Role of surgical resection for multiple hepatocellular carcinomas

AIM:To clarify the role of surgical resection for multiple hepatocellular carcinomas(HCCs)compared to transarterial chemoembolization(TACE)and liver transplantation(LT). METHODS:Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008,160 patients who met the following criteria were retrospectively enrolled:(1) two or three radiologically diagnosed HCCs;(2)no radiologic vascular invasion;(3)Child-Pugh class A;(4) main tumor smaller than 5 cm in diameter;and(5) platelet count greater than 50 000/mm3.Long-term outcomes were compared among the following three treatment modalities:surgical resection or combined radiofrequency ablation(RFA)(n=36),TACE(n=107), and LT(n=17).The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test.To identify the patients who gained a survival benefit from surgical resection,we also investigated prognostic factors for survival following surgical resection.Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model. RESULTS:The overall survival(OS)rate was significantly higher in the surgical resection group than in the TACE group(48.1%vs 28.9%at 5 years,P<0.005). LT had the best OS rate,which was better than that of the surgical resection group,although the difference was not statistically significant(80.2%vs 48.1%at 5 years,P=0.447).The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group(88.2%vs 11.2%at 5 years, P<0.001).Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6%(20/36)in the resection group and 93.5%(100/107)in the TACE group.There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients,multisite resection was performed in 5 patients,and combined resection with RFA was performed in 8 patients. In the TACE group,only 34 patients(31.8%)were record     

Liver resection in advanced hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to assess the results of major liver resection in patients with advanced hepatocellular carcinoma in terms of safety and survival. METHODOLOGY: The subjects of this study are 19 patients that underwent 24 resections for advanced (stage IV) hepatocellular carcinoma. Eighteen of these resections were performed for primary tumor and 6 were repeat resections. Nine patients presented without cirrhosis, 5 with cirrhosis, and 5 patients had the fibrolamellar variant of hepatocellular carcinoma. RESULTS: Hospital mortality was recorded in 1 case (5%). Morbidity was noted in 7(37%) cases. All patients with fibrolamellar variant of hepatocellular carcinoma are alive at 78, 41, 24, 12 and 9 months (P = 0.008), compared with a median survival of 18 and 9 months for the noncirrhotic hepatocellular carcinoma and cirrhotic hepatocellular carcinoma groups, respectively (P = 0.24). CONCLUSIONS: We conclude that an aggressive policy of major liver resection with vascular reconstruction was justifiable in patients with advanced fibrolamellar variant of hepatocellular carcinoma and in selected patients with noncirrhotic hepatocellular carcinoma, and of doubtful value in patients with cirrhosis.     

Risk factors of long-term survival and recurrence after curative resection of hepatocellular carcinoma

BACKGROUND/AIMS: The independent risk factors contributing to long-term survival (> or = 10-year survival rate) and recurrence after curative hepatic resection for hepatocellular carcinoma (HCC) were evaluated. METHODOLOGY: The prognoses were retrospectively analyzed in 247 consecutive patients (187 men and 60 women) treated with curative hepatic resection for HCC and discharged from the hospital. Prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that pTNM stage IV, indocyanine green retention rate at 15 minutes (ICGR15) of > or = 20%, tumor size of > or = 5 cm, and positive hepatitis B surface antigen were independent risk factors of overall survival. Stage IV and ICGR15 of > or = 20% were also independent risk factors of disease-free survival. CONCLUSIONS: pTNM stage and ICGR15 may be simple and useful predictors to improve long-term survival and recurrence after curative hepatic resection for HCC.     

Anatomic versus non-anatomic resection for small single hepatocellular carcinomas

BACKGROUND/AIMS: Anatomical hepatectomy for small hepatocellular carcinomas (HCCs) is widely preferred but evidence concerning its benefits is inadequate. The aim of this study was to determine whether patient outcome is influenced by the method used to treat small single HCCs. METHODOLOGY: An analysis was performed on 168 patients who underwent curative hepatectomy for a single HCC smaller than 5cm between Jan 1998 and Dec 2001 at Seoul National University Hospital. Ninety-nine of these patients underwent anatomic resection and 69 patients non-anatomic resection. Overall survival rates, disease-free survival rates, and prognostic factors for survival and recurrence were analyzed. RESULTS: The cumulative 1-, 3- and 5-year overall survival rates were 86.9%, 73.6% and 65.5% in the anatomic resection group, and 88.4%, 63.8% and 49.7%% in the non-anatomic resection group, respectively (P = 0.032). And, the cumulative 1-, 3- and 5-year disease-free survival rates were 77.8%, 58.6% and 54.4% in the anatomic resection group and 62.3%, 42.0% and 28.6% in the non-anatomic resection group, respectively (P = 0.003). Anatomic resection was confirmed to be an independent favorable factor of disease-free survival by multivariate analysis. CONCLUSIONS: Anatomic resection for single small HCCs is superior to non-anatomic resection.     

Development and validation of a risk score to predict the overall survival following surgical resection of hepatocellular carcinoma in non-cirrhotic liver

BackgroundThe aim of this study was to develop and validate a risk score to predict overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma in non-cirrhotic liver (NC-HCC).MethodsPatients who underwent resection for NC-HCC between 2004 and 2013 were identified from the SEER database. A derivation set of 75% of this cohort was used to develop a risk score. This was then internally validated on the remaining patients, and externally validated using a cohort of patients from The HPB Unit, Birmingham, UK.ResultsA total of 3897 patients were included from the SEER database, with a median post-diagnosis survival of 59 months. In the derivation set, multivariable analyses identified male sex, increasing tumour size, the presence of multiple tumours, bilobar tumours and major vascular invasion as adverse prognostic factors. A risk score generated from these factors was significantly predictive of OS, and was used to classify patients into low, medium and high-risk groups. These groups had a five-year OS of 69%, 51% and 19% in the internal, and 73%, 50% and 45% in the external validation sets.ConclusionThe proposed risk score is useful in the selection, pre-operative consenting and counselling of patients for surgery and to allow patients to make an informed decision regarding treatment.     

Influence of age on operative mortality and long-term survival after lung resection for bronchogenic carcinoma.

The proportion of elderly patients presenting with bronchogenic carcinoma is increasing. To study the impact of age on clinical presentation, management and outcome of patients, the authors have reviewed their clinical experience over the last 20 yrs. Between 1977 and 1996, 1,079 patients underwent thoracotomy for primary lung carcinoma in the authors' institution. Patients were grouped by age at the time of surgery as <60 yrs, 60-69 yrs and > or =70 yrs. Although the mode of clinical presentation was similar between all age groups, patients <60 yrs were more prone to have advanced stage carcinoma at the time of diagnosis. The rates of exploratory thoracotomy and pneumonectomy were higher in patients <70 yrs, whereas lobectomies and lesser resections largely predominated in patients > or =70 yrs. The mortality rate following lobectomy and lesser resection increased from 1.3% in patients <60 yrs to 5.5% in patients > or =60 yrs (p=0.04) and the mortality rate following pneumonectomy increased from 6.5% in patients <60 yrs to 13.7% in patients > or =70 yrs (p=0.24). The specific long-term survival, which included only the patients who died from primary lung carcinoma, was similar in all age groups. Operative mortality and survival rates are acceptable in patients > or =70 yrs. Therefore, age in itself should not constitute a contraindication to surgical lung resection for primary lung carcinoma as long as a careful preoperative assessment is performed to appropriately select surgical candidates.     

Liver transplant mortality and morbidity following preoperative radiotherapy for hepatocellular carcinoma

BackgroundRadiotherapy (RT) can be used for tumor downstaging and as a bridge to transplantation in hepatocellular carcinoma (HCC), but its effect on surgical complications is unknown. Therefore, we investigated post-transplant mortality and acute readmission rates in HCC with and without preoperative RT using the National Cancer Database (NCDB).MethodsAfter exclusion, 11,091 transplant patients were analyzed, 165 of whom received RT prior to transplant. Multivariable binomial logistic regression analysis identified characteristics associated with use of RT, and factors associated with increased 30/90-day mortality and 30-day readmission, following propensity matching.ResultsAlthough RT (median 40 Gy in 5 fractions) was more often delivered to larger tumors and advanced stages, it resulted in 59% downstaging rate, 39% pathologic complete response rate, and a median of 4 additional months to transplantation. Crude 30/90-day mortality rates were both 1.2% with preoperative RT, compared to 2.7% and 4.4% without. The 30-day readmission rate was 5.5% with RT and 10.7% without it. Propensity matched analysis demonstrated no statistical differences in 30/90-day mortality and a lower 30-day readmission rate with preoperative RT. Age >58, stage III disease, lack of transarterial chemoembolization, and shorter time to transplant independently predicted higher 90-day mortality.ConclusionPreoperative RT for HCC did not increase postoperative mortality or length of stay following liver transplant.     

Liver transplantation for hepatocellular carcinoma- factors influencing outcome and disease-free survival

Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.     

Liver tumor promoters stimulate growth of transplanted hepatocellular carcinomas

Cell suspensions or tissue fragments from primary hepatocellular carcinomas and benign neoplastic nodules, induced by treating rats with chemical carcinogens, were transplanted by intraportal injection or subcapsular implantation in the livers of syngeneic host rats. Both nodule and carcinoma transplants produced high numbers of hepatocellular carcinomas in the hosts 2 to 5 mo after transplantation. Treatment of the host rats with liver tumor promoters (phenobarbital or 2-acetylaminofluorene) greatly stimulated tumor outgrowth, demonstrating that even established carcinoma cells can be promoter-sensitive. Tumor outgrowth was also stimulated by partial hepatectomy of the hosts, the regenerative stimulus interacting synergistically with the tumor promoters.     

Predictors of long-term survival after liver transplantation for hepatocellular carcinoma

AIMS: The aim of this study was to identify predictors of both survival and tumor-free survival of a cohort of 155 patients, with hepatocellular carcinoma (HCC) and cirrhosis, who were treated by orthotopic liver transplantation (OLT). METHODS: From January 1989 to December 2002, 603 OLTs were performed in 549 patients. HCC was diagnosed in 116 patients before OLT and in 39 at histological examination of the explanted livers. Eighty-four percent of the patients met "Milan" criteria at histology. Ninety-four patients received anticancer therapies preoperatively. RESULTS: The median follow-up was 49 months (range, 0-178). Overall, 1-, 3-, 5-, and 10-yr survival were 84%, 75%, 72%, and 62%, respectively. Survival was not affected by the patient's age or sex, etiology of liver disease, Child score at transplantation, rejection episodes, tumor number, total tumor burden, bilobar tumor, and pathologic Tumor, Nodes, Metastasis (pTNM) stages. There was no statistically significant difference in survival when patients were grouped according to the recently proposed simplified pTNM staging (5-yr survival, 80% in stage I, 69% in stage II, 50% in stage III, p= 0.3) or the United Network for Organ Sharing (UNOS) staging system for HCC. Encapsulation of the tumor and alpha-fetoprotein levels significantly affect patient survival. Five-year survival of patients with poorly differentiated (G3) HCC was significantly worse than that of patients with moderately (G2) or well-differentiated (G1) HCC (respectively, G3 44%, G2 67%, and G1 97%, p= 0.0015). Patients with micro- or macro-vascular invasion had a worse 5-yr survival than patients without vascular invasion (49%vs 77%, p= 0.04). Multivariate analysis showed that histological grade of differentiation and macroscopic vascular invasion are independent predictors of survival (HR 2.4, 95% CI 1.4-4.1, p= 0.0009 and HR 2.8, 95% CI 1.2-6.8, p= 0.022). CONCLUSION: Histological grade of differentiation and macroscopic vascular invasion, as assessed on the explanted livers, are strong predictors of both survival and tumor recurrence in patients with cirrhosis who received transplants for HCC.     

Perioperative blood transfusion and survival following curative hepatic resection for hepatocellular carcinoma

BACKGROUND/AIMS: The association between transfusion and recurrence after resection for hepatocellular carcinoma (HCC) is still under debate. The influences of perioperative blood transfusion on survival and recurrence after curative hepatic resection for HCC and prognostic factors in patients with blood transfusion were evaluated. METHODOLOGY: Curative hepatectomy was performed in 210 patients (57%) with and 158 (43%) without perioperative blood transfusion. Prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that perioperative blood transfusion was an independent predictor for recurrence in patients with serum low albumin level (< 3.5 g/dL). In transfused group, stage IV, large tumor size (> or = 5 cm), high value of ICGR15 (> or = 20%), and old age (> or = 60 year) were independent factors of poor disease-free survival. CONCLUSIONS: Perioperative blood transfusion promotes the recurrence of HCC after hepatic resection in patients with hypo-albuminemia. In transfused patients, establishment of strategy for recurrence based on pTNM staging, tumor size, ICGR15, and age may be required to improve survival.     

Combined hepatocellular and cholangiocellular carcinoma in a non-cirrhotic liver

Combined hepatocellular (HCC) and cholangiocellular carcinoma (CCC) (mixed carcinoma) is a rare subtype of primary hepatic carcinoma. We report a case of mixed carcinoma that developed in a non-cirrhotic liver, in a patient who was serologically negative for both hepatitis B and C viruses. A 65-year-old Japanese woman with a 25-year history of chronic rheumatoid arthritis had been treated with steroids and anti-inflammatory drugs, and was diagnosed by ultrasonography with an asymptomatic solitary tumor in the right lobe of the liver. On computed tomography scan and hepatic arteriography, the tumor was well enhanced by contrast medium in the early phase. Based on the findings of elevated serum alpha-feto protein (AFP, 245 ng/ml) and normal carcino-embryonic antigen (CEA, 2.6 ng/ml) levels, a preoperative diagnosis of hepatocellular carcinoma was made. Right lobectomy of the liver was performed on January 7, 1997. Histological examination showed that the resected tumor consisted of combined CCC cells and HCC cells in an intermingled form, with CCC being far more dominant than HCC. The tumor was therefore determined to be a combined carcinoma, subclassified as intermingled type. This case appears to indicate that mixed type carcinoma developed in a non-cirrhotic liver, with CCC being dominant; such a finding is extremely unusual, based on previously published reports. (Received Sept. 1, 1997; accepted Jan. 23, 1998)     

Surgical resection and survival in Western patients with hepatocellular carcinoma.

In a retrospective study the survival of 28 patients with hepatocellular carcinoma, 25 of them with underlying cirrhosis, submitted to surgical resection was compared with the survival of 28 untreated patients, matched for variables known to bear independent prognostic value and therefore sharing the same baseline prognosis. Diagnosis was made in the same time period for both groups of patients. In addition, to further evaluate the effects of tumor resection on survival, the outcome of operated patients was also compared to their expected survival. This was derived from a mathematical model which takes into account the regression coefficients of the variables previously shown to be independently related to the survival of untreated patients with hepatocellular carcinoma. The median survival for resected patients was 27.1 months, which was significantly better than untreated controls (12.4 months; p less than 0.003). Median survival for patients submitted to resection and with tumors smaller than 5 cm was 35.8 months, while the median survival for untreated cases was 14.6 months p less than 0.0005. The comparison of observed survival (82% at one year and 73% at two years) and statistically expected survival (58% and 34%, respectively) further indicated that surgical resection effectively improves prognosis in Western patients with hepatocellular carcinoma. Thus, early detection of small tumors in the population at risk appears to be justified.     

Surgical resection versus radiofrequency ablation for small hepatocellular carcinomas within the Milan criteria

Background/Purpose

It has been reported that hepatic resection may be preferable to other modalities for the treatment of small hepatocellular carcinomas (HCCs), by contributing to improved overall and disease-free survival. Ablation techniques such as radiofrequency ablation (RFA) have also been used as therapy for small HCCs; however, few studies have compared the two treatments based on long-term outcomes. The effectiveness of hepatic resection and RFA for small nodular HCCs within the Milan criteria were compared.

Methods

A retrospective cohort study was performed with 278 consecutive patients who underwent curative hepatic resection (n = 123) or initial RFA percutaneously (n = 110) or surgically (thoracoscopic-, laparoscopic-, and open-approaches; n = 45) for HCC. The selection criteria for treatment were based on uniform criteria. Mortality related to therapy and 3- and 5-year overall and disease-free survivals were analyzed.

Results

The model for endstage liver disease (MELD) scores for all patients in the series were less than 13. There were no therapy-related mortalities in either the hepatic resection or RFA groups. The incidence of death within 1 year after therapy (1.6 and 1.9%, respectively) was similar in the hepatic resection and RFA groups. The group that underwent hepatic resection showed a trend towards better survival (P = 0.06) and showed significantly better disease-free survival (P = 0.02) compared with the RFA group, although differences in liver functional reserve existed. The advantage of hepatic resection was more evident for patients with single tumors and patients with grade A liver damage. In contrast, patients with multinodular tumors survived longer when treated with RFA, regardless of the grade of liver damage. Further analysis showed that surgical RFA could potentially have survival benefits similar to those of hepatic resection for single tumors, and that surgical RFA had the highest efficacy for treating multinodular tumors.

Conclusions

In patients with small HCCs within the Milan criteria, hepatic resection should still be employed for those patients with a single tumor and well-preserved liver function. RFA should be chosen for patients with an unresectable single tumor or those with multinodular tumors, regardless of the grade of liver damage. In order to increase long-term oncological control, surgical RFA seems preferable to percutaneous RFA, if the patient’s condition allows them to tolerate surgery.