Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease‐free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non‐TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27–72% vs. non‐TACE 23–52%; complete TACE 0–28% vs. non‐TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non‐randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.     

Systematic hepatectomy for small hepatocellular carcinoma in Korea

Background/Purpose

Systematic hepatectomy for small hepatocellular carcinoma (HCC) is a widely preferred modality, but evidence concerning its benefits is lacking. The aim of this study was to document hepatic resection for small HCC in Korea, and to determine whether patient survival or the pattern of tumor recurrence was influenced by the methods used.

Methods

Ten major hospitals that perform hepatectomy for HCC in Korea were surveyed for surgeons' opinions concerning systematic hepatectomy and current trends in hepatic resection for small HCC. An analysis was also performed of 119 patients who underwent curative hepatectomy for small HCC (size < 5?cm) between January 2000 and December 2002 at Seoul National University Hospital. Seventy-four of these 119 patients underwent anatomical resection (AR) and 45 had a nonanatomical resection (NAR). Recurrence-free survival, recurrence pattern, overall survival rates, and the risk factors for recurrence were analyzed.

Results

In the survey, eight of ten surgeons preferred systematic hepatectomy and considered it to aid prognosis. No significant difference was found between the AR and NAR groups in terms of the clinicopathologic findings, except that the presence of underlying hepatic cirrhosis was more prevalent in the NAR group. The postoperative morbidity rate was higher in the NAR group (33.3% vs 27.0%), but this difference was not statistically significant. The respective 1- and 3-year recurrence-free survival rates were 78.1% and 49.7% in the AR group, and 68.9% and 46.5% in the NAR group (P > 0.05). The corresponding 1- and 3-year overall survival rates were 88.8% and 80.8% in the AR group and 91.0% and 71.4% in the NAR group (P > 0.05).

Conclusions

Although systematic hepatectomy seems to be superior to nonanatomical hepatectomy from the oncological and anatomical aspects, this superiority is not reflected by the recurrence patterns or the survival and recurrence rates of the two procedures. Postoperative recurrence appears, rather, to be related to the underlying liver condition.     

Prognostic determinants for survival after resection/ablation of a large hepatocellular carcinoma

Background:

Liver resection of large hepatocellular carcinomas (HCC), measuring at least 10 cm remains a controversial debate. Multiple studies on HCCs treated with surgical resection and/or ablation had shown variable results with 5-year survival rates ranging from 0% to 54.0%. The aim of this study was to evaluate the survival of patients with HCCs measuring at least 10 cm and to identify the potential prognostic variables affecting the outcome.

Methods:

Retrospective analysis was performed on the prospectively updated HCC database. A total of 44 patients with tumours measuring 10 cm or more were ‘curatively’ treated with surgical resection with or without ablation. Patient demographics, clinical, surgical, pathology and survival data were collected and analysed.

Results:

Thirty-one patients received surgical resection alone. Thirteen other patients were treated with a combination of surgical resection and ablation. The median follow-up duration was 14.5 months. The overall median survival at 1, 3 and 5 years were 66.4%, 38.1% and 27.8%, respectively. The median time to tumour recurrence was 10.7 months and the 1, 3 and 5-year disease-free survival were 49.6%, 23.9% and 19.1%, respectively.Univariate analysis demonstrated cirrhosis, microvascular invasion, poor tumour differentiation and ethnicity to adversely affect survival. For overall survival, only cirrhosis, poor tumour differentiation and ethnicity were significant on multivariate analysis. Portal vein tumour thrombus, microvascular invasion and ethnicity were identified on univariate analysis to significantly affect disease-free survival.

Conclusion:

Surgical treatment offers good survival to patients with large HCCs (≥10 cm). Both cirrhosis and poor tumour differentiation are independent variables prognostic of adverse survival.     

Determinants of long-term survival following hepatectomy for hepatocellular carcinoma,with special reference to patients surviving more than 10 years

To elucidate the determinants of survival and the clinicopathologic features of long-term survivors of resections for HCC, we reviewed 539 patients who had had hepatectomy alone or hepatectomy together with hepatic arterial ligation or ethanol injection for the treatment of hepatocellular carcinoma (HCC) at our department between 1973 and December 1992. Of these patients, 30% (79/264) survived for more than 5 years and 11% (10/87) for more than 10 years. All the long-term survivors had received curative resections. The 5- and 10-year survivors accounted for 58% (79/136) and 29% (10/35) of those with curative resections, respectively. Crucial determinants for long-term survival were the absence of portal invasion and satellite nodules, a diploid pattern of DNA content, and a curative resection. A curative resection for diploid HCCs led to much better survival rates (73%) at 5 years than such a resection for aneuploid HCCs (35%), and than for non-curative resections for aneuploid HCCs (0%). The history and tumor background of the ten patients who survived for more than 10 years were characterized by good reserve liver function, warranting a wider resection, predominance of female sex, single nodular growth, and the absence of poorly differentiated cells, in addition to the favorable conditions described above. Three of the ten patients developed a new lesion; these were successfully treated by re-resection or repeated arterial embolization, since they were confined to the remnant liver and showed single nodular growth without extranodular spread. This analysis indicates that hepatectomy is the option of first choice for HCC patients with the potential for cure and good reserve liver function.     

Hepatic resection for large hepatocellular carcinoma in the era of UCSF criteria

Background:

Treating patients with hepatocellular carcinoma (HCC) remains a challenge, especially when the disease presents at an advanced stage. The aim of this retrospective study was to determine the efficacy of liver resection in patients who fulfil or exceed University of California San Francisco (UCSF) criteria by assessing longterm outcome.

Methods:

Between 2002 and 2008, 59 patients with large HCC (>5 cm) underwent hepatectomy. Thirty-two of these patients fulfilled UCSF criteria for transplantation (group A) and 27 did not (group B). Disease-free survival and overall survival rates were compared between the two groups after resection and were critically evaluated with regard to patient eligibility for transplant.

Results:

In all patients major or extended hepatectomies were performed. There was no perioperative mortality. Morbidity consisted of biliary fistula, abscess, pleural effusion and pneumonia and was significantly higher in patient group B. Disease-free survival rates at 1, 3 and 5 years were 66%, 37% and 34% in group A and 56%, 29% and 26% in group B, respectively (P < 0.01). Survival rates at 1, 3 and 5 years were 73%, 39% and 35% in group A and 64%, 35% and 29% in group B, respectively (P= 0.04). The recurrence rate was higher in group B (P= 0.002).

Conclusions:

Surgical resection, if feasible, is suggested in patients with large HCC and can be performed with acceptable overall and disease-free survival and morbidity rates. In patients eligible for transplantation, resection may also have a place in the management strategy when waiting list time is prolonged for reasons of organ shortage or when the candidate has low priority as a result of a low MELD (model for end-stage liver disease) score.     

Current status of laparoscopic hepatectomy for the treatment of hepatocellular carcinoma: A systematic literature review

Background:Laparoscopic hepatectomy (LH) was first introduced in the 1990s and has now become widely accepted for the treatment of hepatocellular carcinoma (HCC). Laparoscopic liver resection (LLR) is considered a safe and effective approach for liver disease. However, the role of laparoscopic hepatectomy in HCC with cirrhosis remains controversial and needs to be further assessed, and the present literature review aimed to review the surgical and oncological outcomes of Laparoscopic hepatectomy (LH). According to Hong and colleagues laparoscopic resection for liver cirrhosis is a very safe and feasible procedure for both ideal cases and select patients with high risk factors [29]. The presence of only 1 of these factors does not represent an absolute contraindication for LH.Methods and results:We selected 23 studies involving about 1363 HCC patients treated with LH. 364 (27%) patients experienced major resections. The mean operative time was 244.9 minutes, the mean blood loss was 308.1 mL and blood transfusions were required in only 4.9% of patients. There were only 2 (0.21%) postoperative deaths and overall morbidity was 9.9%. Tumor recurrence ranged from 6 to 25 months. The 1-year, 3-year, and 5-year disease free Survival (DFS) rates ranged from 71.9% to 99%, 50.3% to 91.2%, and 19% to 82% respectively. Overall survival rates ranged from 88% to 100%, 73.4% to 94.5%, and 52.6% to 94.5% respectively.Conclusions:In our summery LH is lower risk and safer than conventional open liver surgery and is just as efficacious. Also, the LH approach decreased blood-loss, operation time, postoperative morbidity and had a lower conversion rate compared to other procedures whether open or robotic. Finally, LH may serve as a promising alternative to open procedures.     

Assessment of safety in hepatic resection for hepatocellular carcinoma focusing on indirect hyperbilirubinemia

Background/purpose

The indications for hepatic resection for hepatocellular carcinoma (HCC) patients with total bilirubin (T-Bil) equal to or higher than 1.2 mg/dl remain controversial. The aim of this study was to investigate the safety of hepatic resection for HCC patients who showed high T-Bil (≥1.2 mg/dl) with low direct bilirubin (D-Bil ≤ 0.5 mg/dl).

Methods

Thirty-four HCC patients showing high T-Bil with low D-Bil were treated with mono- to tri-segmentectomy between January 2000 and December 2010. The perioperative clinical parameters and prognosis of the high T-Bil/low D-Bil patients were compared with those of 253 HCC patients showing normal T-Bil. In addition, complication rates of the patients with high T-Bil/high D-Bil (n = 4) were analyzed.

Results

The prothrombin time activity, indocyanine green clearance test, asialo-scintigraphy, and platelet count were similar in the two groups. The mean serum albumin in high T-Bil/low D-Bil patients was significantly higher than that of normal T-Bil patients (4.2 ± 0.5 vs. 4.0 ± 0.4 g/dl, P = 0.004). There were no significant differences in operation time, intraoperative bleeding, red cell concentrate transfusion rate, postoperative complication rate, and disease-free and overall survivals between the two groups. Postoperative hyperbilirubinemia (T-Bil >5 mg/dl) with ascites was observed in one of four high T-Bil/high D-Bil patients (25 %).

Conclusions

Mono- to tri-segmentectomy can be performed in patients with low D-Bil (≤0.5 mg/dl) similarly to patients with low T-Bil (<1.2 mg/dl), even in HCC patients showing high T-Bil (≥1.2 mg/dl).     

Predictive factors for long‐term survival in patients with clinically significant portal hypertension following resection of hepatocellular carcinoma

Background: Hepatic resection for hepatocellular carcinoma (HCC) is not currently recommended for patients with clinically significant portal hypertension (PHT); however, recent studies have shown similar post‐operative outcomes between patients with and without clinically significant PHT. Aim: To clarify the post‐operative prognostic relevance of clinically significant PHT in Child–Pugh A cirrhotic patients. Methods: A total of 100 Child–Pugh A cirrhotic patients who underwent curative resection of HCC were eligible for this analysis. Patients were divided into two groups: PHT group (n=47) and non‐PHT group (n=53). Results: Clinicopathological variables showed no significant differences except for prothrombine time. Liver‐related complications were significantly higher in the PHT group (P=0.015), and the 5‐year overall survival rate was significantly higher in the non‐PHT group (78.7 vs. 37.9%, P<0.001). The proportion of patients who died because of complications of cirrhosis was significantly higher in the PHT group (P=0.001). Multivariate analysis indicated that the presence of clinically significant PHT was the most powerful adverse prognostic factor for overall survival. Multivariate analysis of the 47 patients with clinically significant PHT indicated that gross vascular invasion and non‐single nodular type were poor prognostic factors. The 5‐year survival rate of patients with single nodular type and without gross vascular invasion (n=17) was 78.4%. Conclusions: In Child–Pugh A cirrhotic patients, the presence of clinically significant PHT was significantly associated with post‐operative hepatic decompensation and poor prognosis after resection of HCC. However, in patients with clinically significant PHT, those with single nodular tumours lacking gross vascular invasion may be good surgical candidates.     

Prolonged survival after repeat resection of pulmonary metastasis from hepatocellular carcinoma

We report a patient in whom two pulmonary resections were performed for lung metastasis after hepatic resection of hepatocellular carcinoma (HCC). A 56‐year‐old Japanese man with an 8‐year history of chronic liver disease was admitted with elevated serum alpha‐fetoprotein (AFP) and a liver tumor that had been detected by ultrasonography. Computed tomography showed a 6‐cm tumor in the medial segment of the liver, and partial resection of the medial segment was performed. Thirty‐six months after the first operation, pulmonary resection was performed for a solitary metastasis in the left lung. Fifty‐one months after the second operation, a solitary metastatic tumor was detected in the right lung, without any evidence of recurrence or other metastatic foci, and thoracoscopic partial resection of the right lung was performed as the third operation. The patient is alive 36 months after the second pulmonary resection, has a normal AFP value, and shows no signs of recurrent or metastatic foci. Repeat pulmonary resection for metastasis from HCC resulted in long‐term survival in this patient.     

A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma

Background

A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma.

Methods

Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses.

Results

Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10.

Conclusions

Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.     

Current status of hepatic resection for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. For this disease, a variety of therapeutic measures have been applied, including hepatic resections, total hepatectomy followed by allografting, transarterial chemoembolization, and percutaneous tumor ablative therapy by ethanol, microwave coagulation, and radiofrequency ablation. This article focuses on the current status of hepatic resections for HCC.     

Single-center experience on actual mid-term (≥5 years) and long-term (≥10 years) survival outcome in patients with hepatocellular carcinoma after curative hepatectomy: A bimodal distribution

Analysis for actual mid-term (≥5 years) and long-term (≥10 years) survivors with hepatocellular carcinoma (HCC) following curative hepatectomy are rarely reported in the literature.This retrospective study aims to study the mid- and long-term survival outcome and associated prognostic factors following curative hepatectomy for HCC in a tertiary referral center.The clinical data of 325 patients who underwent curative hepatectomy for HCC were reviewed. They were stratified into 3 groups for comparison (Group 1, overall survival <5 years; Group 2, overall survival ≥5, and <10 years; Group 3, overall survival ≥10 years). Favorable independent prognostic factors for mid- and long-term survival were analyzed.A bimodal distribution of actual survival outcome was observed, with short-term (<5 years) survival of 52.7% (n = 171), mid-term survival of 18.1% (n = 59), and long-term survival of 29.2% (n = 95). Absence of microvascular invasion (OR 3.690, 95% CI: 1.562–8.695) was independent good prognostic factor for mid-term survival. Regarding long-term overall survival, young age (OR 1.050, 95% CI: 0.920–0.986), ASA grade ≤2 (OR 3.746, 95% CI: 1.325–10.587), high albumin level (OR 1.008, 95% CI: 0.920–0.986), solitary tumor (OR 3.289, 95% CI: 1.149–7.625) and absence of microvascular invasion (OR 4.926, 95% CI: 2.192–11.111) were independent good prognostic factors.Curative hepatectomy results in bimodal actual survival outcome with favorable long-term survival rate of 29.2%. Favorable independent prognostic factors (age, ASA grade, albumin level, tumor number, and microvascular invasion) are identified for overall survival.     

Repeated liver resection for recurrent hepatocellular carcinoma

Background and Aim: Tumor recurrence after liver resection occurs in the majority of patients with hepatocellular carcinoma (HCC). This study was conducted to clarify the safety and effectiveness of repeated liver resection as a curative option for intrahepatic HCC recurrence. Methods: Between July 1990 and January 2009, 483 patients underwent 514 curative hepatic resections for HCC in our institution. Among this collective, 27 patients underwent 31 repeated resections due to recurrent HCC (27 s resections, three third resections and one forth resection). The outcome of these patients was retrospectively reviewed using a prospective database. Results: Perioperative morbidity and mortality was 11% (three of 27) and 0%. Six patients showed multiple liver lesions, 23 underwent minor liver resections (fewer than three segments) and five patients underwent major resections (three or more segments). The majority of the patients showed no signs of chronic liver disease (16 of 27). The median tumor free margin was 1.5 mm (range: 0 to 20 mm). The median tumor diameter was 40 mm (range: 10 to 165 mm). Tumor dedifferentiations at time of tumor recurrence were not observed. The 1‐, 3‐ and 5‐year overall survival rates after second liver resection were 96%, 70% and 42%. Conclusions: Repeated liver resection is a valid and safe curative therapy option for recurrent HCC and results in significant prolongation of survival in comparison to interventional treatment strategies in selected patients. However, due to impaired liver function, multifocal intrahepatic or extrahepatic recurrence repeated resection is only feasible in a minority of patients.