Surgical Resection Versus Radiofrequency Ablation in the Treatment of Small Unifocal Hepatocellular Carcinoma

Background  Hepatocellular carcinoma (HCC) has a high worldwide prevalence and mortality. While surgical resection and transplantation offers curative potential, donor availability and patient liver status and comorbidities may disallow either. Interventional radiological techniques such as radiofrequency ablation (RFA) may offer acceptable overall and disease-free survival rates. Materials and Methods  Sixty-eight cirrhotic patients matched for age, sex, tumor size, and Child–Pugh grade with small (1–5 cm) unifocal HCC were studied retrospectively to find determinants of overall and disease-free survival in those treated with surgical resection and RFA between 1991 and 2003. Results  Multivariate analysis using Cox proportional regression modeling showed that overall survival was related to tumor recurrence (p = 0.010), tumor diameter (p = 0.002), and treatment modality (p = 0.014); overall p = 0.008. Recurrence was independently related to the use of RFA over surgery (p = 0.023) on multivariate analysis; overall p = 0.034. Conclusion  Surgical resection offers longer disease-free survival and potentially longer overall survival than RFA in patients with small unifocal HCC.     

Percutaneous Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma After Hepatectomy: Long-term Results and Prognostic Factors

Background We evaluated the long-term survival results and safety of percutaneous radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) after hepatectomy, and assessed the prognostic factors that can influence its long-term therapeutic results. Methods One hundred and two patients, who had 119 recurrent HCC in their livers, underwent ultrasound-guided percutaneous RFA. All the patients had a history of hepatic resection as a first-line treatment modality for HCC. The mean diameter of the recurrent tumors was 2.0 cm (range, 0.8–5.0 cm). We evaluated the effectiveness rates, local tumor progression rates, survival rates, and complications. We also assessed the prognostic factors of the survival rates by using Cox proportional hazard models. Results The primary effectiveness rate was 93.3% (111 of 119). The cumulative rates of local tumor progression at 1, 3, and 5 years were 6.0, 8.6, and 11.9%, respectively. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 93.9, 83.7, 65.7, 56.6, and 51.6%, respectively. Patients with a lower serum α-fetoprotein (AFP) level (≤100 μg/L) before RFA or with small resected tumors (≤5 cm) demonstrated better survival results (P < .05). There was only one major complication (liver abscess, 1.0% per treatment) during the follow-up period. There were no procedure-related deaths. Conclusions Percutaneous RFA is an effective and safe treatment modality for intrahepatic recurrent HCC after hepatectomy. Serum AFP level before RFA and resected tumor size were significant prognostic predictors of long-term survival.     

Resection Versus Laparoscopic Radiofrequency Thermal Ablation Of Solitary Colorectal Liver Metastasis

Purpose  There is scant data in the literature regarding radiofrequency thermal ablation (RFA) versus resection of colorectal liver metastases. The aim of this study is to compare the clinical profile and survival of patients with solitary colorectal liver metastasis undergoing resection versus laparoscopic RFA. Methods  Between 1996 and 2007, 158 patients underwent RFA (n = 68) and open liver resection (n = 90) of solitary liver metastasis from colorectal cancer. Patients were evaluated in a multidisciplinary fashion and allocated to a treatment type. Data were collected prospectively for the RFA patients and retrospectively for the resection patients. Results  Although the groups were matched for age, gender, chemotherapy exposure and tumor size, RFA patients tended to have a higher ASA score and presence of extra-hepatic disease (EHD) at the time of treatment. The main indication for referral to RFA included technical reasons (n = 25), patient comorbidities (n = 24), extra-hepatic disease (n = 10) and patient decision (n = 9). There were no peri-operative mortalities in either group. The complication rate was 2.9% (n = 2) for RFA and 31.1% (n = 28) for resection. The overall Kaplan–Meier median actuarial survival from the date of surgery was 24 months for RFA patients with EHD, 34 months for RFA patients without EHD and 57 months for resection patients (p < 0.0001). The 5-year actual survival was 30% for RFA patients and 40% for resection patients (p = 0.35). Conclusions  This study shows that, although patients in both groups had a solitary liver metastasis, other factors including medical comorbidities, technically challenging tumor locations and extra-hepatic disease were different, prompting selection of therapy. With a simultaneous ablation program, higher risk patients have been channeled to RFA, leaving a highly selected group of patients for resection with a very favorable survival. RFA still achieved long-term survival in patients who were otherwise not candidates for resection.     

Radiofrequency Ablation Versus Surgical Resection for the Treatment of Hepatocellular Carcinoma in Cirrhosis

Background and Aims Percutaneous radiofrequency ablation (RFA) demonstrated good results for the treatment of hepatocellular carcinoma (HCC) in cirrhotic patients; it is still not clear whether the overall survival and disease-free survival after RFA are comparable with surgical resection. The aims of this study are to compare the overall survival and disease-free survival in two groups of cirrhotic patients with HCC submitted to surgery or RFA. Methods Two hundred cirrhotic patients with HCCs smaller than 6 cm were included in this retrospective study: 109 underwent RFA and 91 underwent surgical resection at a single Division of Surgery of University of Verona. Results Median follow-up time was 27 months. Overall survival was significantly longer in the resection group in comparison with the RFA group with a median survival of 57 and 28 months, respectively (P = 0.01). In Child–Pugh class B patients and in patients with multiple HCC, survival was not significantly different between the two groups. In patients with HCC smaller than 3 cm, the overall survival and disease-free survival for RFA and resection were not significantly different in univariate and multivariate analysis. Whereas in patients with HCC greater than 3 cm, surgery showed improvement in outcome in both univariate and multivariate analysis. Conclusions Surgical resection significantly improves the overall survival and disease-free survival in comparison with RFA. In a selected group of patients (Child–Pugh class B, multiple HCC, or in HCC ≤3 cm), the results between the two treatments did not show significant differences.     

Prognosis and Results After Resection of Very Large (≥10 cm) Hepatocellular Carcinoma

Introduction Few potentially curative treatment options exist besides resection for patients with very large (≥10 cm) hepatocellular carcinoma (HCC). We sought to examine the outcomes and risk factors for recurrence after resection of ≥10 cm HCC. Methods Perioperative and long-term outcomes were examined for 189 consecutive patients from 1993 to 2004 who underwent potentially curative resection of HCC ≥10 cm (n = 24; 13%) vs. those with HCC <10 cm (n = 165; 87%). Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan–Meier analysis and patient, tumor, and treatment characteristics were compared using univariate and multivariate analysis. Results Median follow-up was 34 months. Tumors ≥10 cm were more likely to be symptomatic, of poorer grade, and have vascular invasion (p < 0.05). Twelve patients (50%) underwent an extended resection of more than four hepatic segments or resection of adjacent organs for oncologic clearance (diaphragm-2, inferior vena cava (IVC)-2, median sternotomy-1). Postoperative complications were more common after resection of >10 cm HCC (12/24, 50% vs. 35/165, 21%; p = 0.04). Median DFS was significantly shorter in patients with large HCC (≥10 cm) group compared to patients with smaller HCC (8.4 vs. 38 months; p = 0.001), but overall survival was not different between the two groups (5-year survival 54% vs. 53%; p = 0.43). Seventeen patients (71%) with very large HCC developed recurrences (12 intrahepatic, five systemic); eight of these patients (47%) underwent additional therapy (resection-4, TACE-3, RFA-1). Pathological positive margins and vascular invasion were significant determinants of DFS in tumors ≥10 cm (p < 0.05), but only vascular invasion was an independent risk factor for recurrence after multivariate analysis (HR 0.17; 95% CI: 0.04–0.8). Median OS after recurrence was 24 months. Conclusion Surgical resection is the optimal therapy for very large (≥10 cm) HCC. Although recurrences are common after resection of these tumors, overall survival was not significantly different from patients after resection of smaller HCC in this series. Presented at the 2006 American Hepato-Pancreatico-Biliary Congress, Miami, FL, March 9–12, 2006.     

Incomplete Ablation After Radiofrequency Ablation of Hepatocellular Carcinoma: Analysis of Risk Factors and Prognostic Factors

Background Complete ablation rates after a single session of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) vary from 48% to 97%. Limited data are available regarding risk factors and prognostic significance of incomplete ablation. Methods Between April 2001 and March 2006, 298 patients underwent RFA of 393 HCC nodules with an intent of complete ablation after a single session. Risk factors for incomplete ablation and its effect on overall survival were analyzed. Results Two hundred seventy-three (91.6%) underwent complete tumor ablation, whereas the other 25 (8.4%) underwent incomplete tumor ablation after a single session of RFA. By multivariate analysis, tumor size >3 cm (P = .049) was found to be the only independent risk factor for incomplete ablation. There was no statistically significant difference in overall survival between patients with complete and incomplete ablation. By univariate analysis, no previous transarterial chemoembolization (TACE), preoperative serum alfa-fetoprotein ≤100 μg/mL, and complete response after further treatment of incomplete ablation were associated with better overall survival in patients with incomplete ablation. Conclusions This study demonstrated that incomplete ablation after RFA of HCC was associated with tumor size >3 cm. Our data also suggest that aggressive further treatment of tumors with incomplete ablation aiming at complete tumor response improves overall survival.     

Long-term Outcomes and Prognostic Factors of Elderly Patients with Hepatocellular Carcinoma Undergoing Hepatectomy

Objective  The present study aimed to evaluate the long-term outcomes and prognostic factors of elderly patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. Material and Methods  From January 1983 to December 2006, 2,283 patients with HCC received hepatectomy in Sun Yat-sen University Cancer Center. The clinicopathological data and treatment outcomes of 67 elderly HCC patients (elderly group, ≥70 years of age) and 268 patients (control group, <70 years of age) who were selected randomly from the 2216 younger patients were compared retrospectively. Results  The elderly HCC patients had lower hepatitis B surface antigen-positive rate (P < 0.001), lower rate of marked α-fetoprotein elevation (P = 0.004), higher infection rate of hepatitis C virus (P = 0.010), more preoperative comorbidities (P < 0.001), higher rate of tumor encapsulation (P = 0.040), and better overall survival rate (P = 0.017); whereas there were no significant differences between these two groups in other factors, including gender ratio, liver function, accompanying cirrhosis, pathological tumor–node–metastasis (pTNM) staging, satellite nodules, vascular invasion, tumor rupture, resection margin, intraoperative blood loss, incidence of postoperative complications, hospital mortality, and disease-free survival rate. Multivariate analysis showed that pTNM staging was an independent prognostic factor of long-term survival in elderly patients with HCC. Conclusion  HCC in the elderly was less HBV-associated, less advanced, and less aggressive. Hepatectomy for selected elderly patients with HCC possibly have a better curative effect compared with younger patients. For the elderly patients without preoperative comorbidities or with controlled comorbidities, hepatectomy is a safe and effective treatment. pTNM staging is the only independent predictor of postoperative overall survival in elderly HCC patients.     

Does Microvascular Invasion Affect Outcomes After Liver Transplantation for HCC? A Histopathological Analysis of 155 Consecutive Explants

Macroscopic vascular invasion (macroVI) is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). Whether microvascular invasion (microVI) is associated with the same adverse prognosis is unclear. One hundred and fifty-five consecutive patients with confirmed HCC after LT from March 1991 to 2004 at our institution were reviewed. Patients had to satisfy Milan criteria to be accepted for LT. They were followed with surveillance images every 3 months while on the waiting list. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan–Meier analysis. Demographic, tumor, and histopathologic characteristics were tested for their prognostic significance. Median follow-up after LT was 30 months. Overall graft survival rates were 87, 74, and 65% at 1, 3, and 5 years, respectively. All recurrences (22/155, 14%) developed within 4 years after LT with an overall 5-year DFS of 79%. Vascular invasion, either microVI or macroVI, was more likely in patients with multicentric HCC (n ≥ 3, p < 0.001) and larger tumor size >4 cm (p = 0.04). Tumor size >5 cm (p = 0.04), advanced pathological TMN stage (p = 0.007), microVI (p = 0.001), and macroVI (p < 0.001) predicted poor tumor-free survival on univariate analysis, but only macroVI was significant in multivariate analysis (hazard ratio 54.2, 95% confidence interval 11, 266). Furthermore, only macroVI was a significant predictor of mortality after LT (p = 0.01). Macrovascular invasion is strongly associated with high rates of recurrence and diminished survival after LT whereas microVI is not an independent risk factor. Presented at the 2005 American Transplant Congress, Seattle, WA, May 20–23, 2005.     

Radiofrequency Ablation vs. Resection for Hepatic Colorectal Metastasis: Therapeutically Equivalent?

Introduction  The role of ablation for hepatic colorectal metastases (HCM) continues to evolve as ablation technology changes and systemic chemotherapy improves. Our aim was to evaluate the therapeutic efficacy of radiofrequency ablation (RFA) of HCM compared to surgical resection. Methods  A retrospective review of our 1,105 patient prospective hepatic database from August 1995 to July 2007 identified 192 patients with only hepatic resection or only ablation for HCM. Results  Patients who underwent RFA were similar to resection patients based on a similar Fong score (1.8 vs. 2.1 p = 0.28), presence of extrahepatic disease (15% vs. 9% p = 0.19), mean number of hepatic lesions (2.8 vs. 2.1 p = 0.14), and prior chemotherapy (67% vs. 60% p = 0.33). Median time to recurrence was shorter with ablation than resection (12.2 vs. 31.1 months; p < 0.001). Recurrence at the ablation–resection site was more common with ablation than resection occurring 17% vs. 2% (p ≤ 0.001) of the time, respectively. Distant recurrence in the liver was also more common with ablation occurring in 33% of patients vs. 14% for resection (p = 0.002). Conclusions  Surgical resection is associated with a lower chance of recurrence and a longer disease-free interval than RFA and should remain the treatment of choice in resectable HCM.     

Prognostic Impact of Sarcomatous Change of Hepatocellular Carcinoma in Patients Undergoing Liver Resection and Liver Transplantation

Sarcomatous change has been rarely observed in hepatocellular carcinoma (HCC), but it is usually associated with very aggressive tumor behavior and widespread metastasis. To assess the impact of sarcomatous changes, we analyzed the outcomes of 15 patients with sarcomatous HCC after resection (n = 11) or liver transplantation (LT) (n = 4). No imaging findings characteristic of sarcomatous changes were observed. According to modified pathological tumor-node metastasis staging, the HCC lesions were classified as stage II in five patients, stage III in six, stage IVa2 in two, and stage IVb in one. The Milan criteria were met in 7 of 15 patients, including 3 of 4 in the LT group. R0 resection was achieved in 9 of 11 resected patients, and their 3-year overall and disease-free survival rates were both 18.2%. In the LT group, 3-year overall and disease-free survival rates were 37.5 and 25%, respectively. In patients within the Milan criteria, 2-year overall survival rate was 25% after resection and 33% after LT, showing no prognostic difference. Extrahepatic metastasis as initial recurrence was detected in 80% after resection and 66.7% after LT. In conclusion, we found that the prognosis of patients with sarcomatous HCC was very unfavorable after either resection or LT and that, except for liver biopsy, no diagnostic method could distinguish between sarcomatous and ordinary HCC. Vigorous postoperative systemic surveillance may be helpful for timely detection and treatment of localized metastases.     

High Serum Vascular Endothelial Growth Factor Levels Predict Poor Prognosis after Radiofrequency Ablation of Hepatocellular Carcinoma: Importance of Tumor Biomarker in Ablative Therapies

Background Radiofrequency ablation (RFA) is a recently developed treatment for hepatocellular carcinoma (HCC). Thus far, the prognostic impact of tumor biomarkers has not been evaluated in this treatment. High serum level of vascular endothelial growth factor (VEGF) has been shown to predict microscopic vascular invasion and metastasis in HCC. This study investigated the prognostic significance of pre-treatment serum VEGF level in patients with HCC undergoing RFA treatment. Methods Serum VEGF levels were measured using enzyme-linked immunosorbent assay in 120 patients with HCC undergoing RFA, and in 15 healthy controls. Serum VEGF levels were correlated with clinicopathological features of the HCC patients. The prognostic significance of serum VEGF levels was assessed by univariate and multivariate analyses. Results The median serum VEGF level in the HCC patients was 240 pg/mL (range 17–1162), significantly higher than that of healthy controls (p = .024). The serum VEGF levels were significantly correlated with platelet counts (r = .487, p < .001) but not other clinicopathological features. Patients with serum VEGF level > 240 pg/mL had worse overall and recurrence-free survival compared with those with serum VEGF level > 240 pg/mL (p = .005 and .002, respectively). By multivariate analysis, serum VEGF level was a significant prognostic factor of both overall and recurrence-free survival. Conclusions High pre-treatment serum VEGF levels predict poor prognosis after RFA of HCC. This study highlights the importance of tumor biomarker as a prognostic predictor in ablative therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.     

Anastomotic Leakage is Associated with Poor Long-Term Outcome in Patients After Curative Colorectal Resection for Malignancy

The impact of anastomotic leakage on long-term outcomes after curative surgery for colorectal cancer has not been well documented. This study aimed to investigate the effect of anastomotic leakage on survival and tumor recurrence in patients who underwent curative resection for colorectal cancer. Prospectively collected data of the 1,580 patients (904 men) of a median age of 70 years (range: 24–94), who underwent potentially curative resection for colorectal cancer between 1996 and 2004, were reviewed. Cancer-specific survival and disease recurrence were analyzed using Kaplan Meier method, and variables were compared with log rank test. Cox regression model was used in multivariate analysis. The cancer was situated in the colon and the rectum in 933 and 647 patients, respectively. Anastomotic leakage occurred in 60 patients (clinical leakage: n = 48; radiological leak: n = 12). The leakage rate was significantly higher in patients with surgery for rectal cancer (6.3 vs 2.0%, p < 0.001). The 5-year cancer-specific survivals were 56.9% in those with leakage and 75.9% in those without leakage (p = 0.012). The 5-year systemic recurrence rates were 48.4 and 22.6% in patients with and without anastomotic leak, respectively (p = 0.001), whereas the 5-year local recurrence rates were 12.9 and 5.7%, respectively (p = 0.009). Anastomotic leakage remained an independent factor associated with a worse cancer-specific survival (p = 0.043, hazard ratio: 1.63, 95% CI: 1.02–2.60) and a higher systemic recurrence rate (hazard ratio: 1.94, 95% CI: 1.23–3.06, p = 0.004) on multivariate analysis. In rectal cancer, anastomotic leakage was an independent factor for a higher local recurrence rate (hazard ratio: 2.55, 95% CI: 1.07–6.06, p = 0.034). In conclusion, anastomotic leakage is associated with a poor survival and a higher tumor recurrence rate after curative resection of colorectal cancer. Efforts should be undertaken to avoid this complication to improve the long-term outcome. This work was presented in the plenary session of the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract at the Digestive Disease Week in Los Angeles on 22 May 2006.     

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.     

Intraoperative Radiofrequency Ablation for Hepatocellular Carcinoma: Long-Term Results in a Large Series

Background  Intraoperative radiofrequency (RF) ablation with or without surgical resection currently plays one of important roles in modern hepatocellular carcinoma (HCC) therapy. We evaluated long-term follow-up results including prognostic factors of intraoperative RF ablation for HCC that was difficult to treat percutaneously. Methods  A total of 133 patients (male, 22 female, mean age 55.8 years) underwent intraoperative RF ablations for 200 HCCs (follow-up period 3.0–79.7 months, median 22.3 months). Hepatic resection was also performed in 29 patients. Reasons for the intraoperative procedure included no safe electrode path (n = 59), excessive tumor burden (n = 41), nonvisualization of the HCC on ultrasonography (n = 20), and risk of collateral thermal damage to adjacent organs (n = 13). We evaluated the technique effectiveness rate at 1 month computed tomography (CT), cumulative local tumor progression rate, cumulative disease-free and overall survival rates, and complications. We also sought significant prognostic factors for overall survival. Results  The technique effectiveness at 1 month was 94.7% (126/133). The cumulative local tumor progression rates at 1 and 3 years were 4.9% and 8.8%, respectively. The cumulative disease-free and overall survival rates at 1, 3 and 5 years were 51.8%, 21.3%, and 16.0% and 92.3%, 72.6%, and 46.5%, respectively. Major complications occurred in nine patients (6.8%). Procedure-related mortality was 1.5% (2/133). The patients treated for recurrent HCC (P = 0.003) or with high serum alpha-fetoprotein levels (P = 0.009) had poor survival by multivariate analysis. Conclusion  The results of this study showed that intraoperative radiofrequency ablation with or without hepatic resection is a safe and effective treatment for hepatocellular carcinoma in patients who are not candidates for the percutaneous approach.     

Endoscopic hepatic resection and endoscopic radiofrequency ablation as initial treatments for hepatocellular carcinoma within the Milan criteria

The indication of endoscopic (laparoscopic and thoracoscopic) hepatic resection (HR) has been expanded in the past decade because of its low invasiveness. However, the indications of endoscopic HR and radiofrequency ablation (RFA) have not yet been determined. Among the 906 patients hospitalized for the initial treatment of hepatocellular carcinoma (HCC) between 2000 and 2017, 77 underwent endoscopic partial HR (E-pHR), and 94 underwent endoscopic RFA (E-RFA). We compared the short- and long-term outcomes between the E-pHR and E-RFA groups. The patients in the E-RFA group were characterized primarily by an impaired liver function. Among the patients with liver damage B or C, the overall survival (OS) in the E-pHR group was significantly worse than in the E-RFA group (3-year OS: 36% vs. 82%, p = 0.003). E-RFA may be recommended for the initial treatment of HCC in patients with a severely impaired liver function. However, E-pHR should be avoided as the initial treatment of HCC in such patients.     

Clinicopathologic Characteristics of Hepatocellular Carcinoma with Bile Duct Invasion

To clarify the characteristics of hepatocellular carcinoma (HCC) with bile duct invasion, we retrospectively analyzed clinical features and surgical outcome of HCC with bile duct invasion (b⁺ group, n = 15) compared to those without bile duct invasion (b⁻ group, n = 256). In the b⁺ group, four patients (27%) showed obstructive jaundice, and a diagnosis of bile duct invasion was obtained preoperatively in seven patients (47%). The levels of serum bilirubin and carbohydrate antigen 19–9 were significantly higher in the b⁺ group. Macroscopically, confluent multinodular type and infiltrative type were predominant in the b⁺ group (P = 0.002). Microscopically, capsule infiltration (P = 0.040) and intrahepatic metastasis (P = 0.013) were predominant in the b⁺ group. Portal vein invasion was associated significantly with the b⁺ group (P = 0.004); however, the frequency of hepatic vein invasion was similar (P = 0.096). The median survival after resection was significantly shorter in the b⁺ group than in the b⁻ group (11.4 vs. 56.1 months, P = 0.002), and eight of 11 intrahepatic recurrences in the b⁺ group occurred within 3 months after surgery. HCC with bile duct invasion has an infiltrative nature and a high risk of intrahepatic recurrence, resulting in poor prognosis.     

Combined Hepatectomy and Radiofrequency Ablation for Multifocal Hepatocellular Carcinomas: Long-term Follow-up Results and Prognostic Factors

Background For multifocal hepatocellular carcinomas (HCCs) that are untreatable with resection only, locoregional therapies added to hepatectomy have been introduced. However, some preliminary reports have documented average survival results and relatively high complication rates. We evaluated the long-term survival results and safety of combined hepatectomy and radiofrequency ablation (RFA) in patients with HCCs and assessed the prognostic factors affecting their survival. Methods A total of 53 patients who had 148 HCCs in their livers underwent hepatectomy combined with ultrasound-guided intraoperative RFA. The mean diameter of the 82 resected tumors was 4.8 cm (range 1.3–21.0 cm) and that of 66 ablated tumors was 1.5 cm (range 0.8–3.5 cm). We evaluated the primary effectiveness rates, survival rates, and complications. In addition, we assessed the prognostic factors associated with the survival rates using Cox proportional hazard models. Results The primary effectiveness rate of RFA was 98% (65 of 66). Local tumor progression was observed in two (3%) ablation zones of 65 tumors with complete primary effectiveness. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 87, 83, 80, 68, and 55%, respectively. Patients with smaller resected tumors (≤5 cm) demonstrated better survival results (P = 0.004). No procedure-related deaths occurred. We observed hepatectomy-related complications in 4 patients (8%, 4 of 53) and an RFA-related complication in 1 patient (2%, 1 of 53). Conclusions Combined hepatectomy and RFA is an effective and safe treatment modality for multifocal HCCs. Resected tumor size was a significant prognostic predictor of long-term survival.     

Long-term Follow-up Outcome of Patients Undergoing Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma

The long-term outcome of radiofrequency thermal ablation (RFA) for unresectable hepatocellular carcinoma (HCC) has not been reported. This study was performed to evaluate the long-term survival of patients with unresectable HCC after RFA and to identify possible factors that might affect survival. In this prospective study, 65 patients with unresectable HCC who underwent RFA were followed. A total of 84 RFA operations were performed percutaneously (n = 49), laparoscopically (n = 20), or by open surgery (n = 15), to ablate 191 tumors. Twenty-two patients died within 16 months; otherwise, the follow-up period was at least 16 months, up to 71 months, with median 20.0 months and mean (± standard deviation) 24.8 ± 18.4 months for all patients. Local tumor recurrence developed in 12 of 191 tumors (6.3%) in 11 of 84 operations (13.1%), or 11 of 65 patients (16.9%). New liver and/or extrahepatic recurrence developed in 48 operations (57.1%). The overall median, mean, and 5-year survivals were 40.0 months, 33.7 ± 2.9 months, and 39.9%. The disease-free survivals were 16.0 month, 32.9 ± 3.0 months, and 27.9%. Factors that had a significant effect on survival outcome after RFA were TNM cancer stage and the operative approach method employed for RFA. Age, gender, race, etiology, alpha-fetoprotein, previous or subsequent treatment, and liver function (Child-Pugh class) did not affect survival. For patients with unresectable HCC, RFA is an effective and repeatable local treatment that can afford long-term survival, although often with disease recurrence.     

Clonality Analysis for Multicentric Origin and Intrahepatic Metastasis in Recurrent and Primary Hepatocellular Carcinoma

Aims  To clarify the incidence of multicentric occurrence (MO) and intrahepatic metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus in China and to identify the differences between them. Methods  Histopathologic and genetic features of primary and recurrent tumors in 160 cases with HCC were analyzed. The two groups, the origin of which was definitely determinable as of multicentric occurrence or as of intrahepatic metastasis, were analyzed for their disease-free survival and clinicopathological differences. Results  According to histopathological findings, 27.5% and 59.4% patients were considered to be MO and IM, respectively. By comparing the genetic information of loss of heterozygosity and microsatellite instability for 10 different markers between primary and recurrent tumor, 30.0% and 63.8% patients with recurrent HCC were considered to be MO and IM, respectively. In total, 126 cases with unanimous conclusions from the histopathological and genetic method were selected and divided into the MO group (37 cases) and the IM group (89 cases). Analysis of stepwise regression identified that recurrence time, grading, portal vein invasion, tumor number, and Child’s stage were the most important discriminating factors between MO and IM (p < 0.05). As for their prognosis, Kaplan–Meier and log rank test showed that the disease-free survival in the MO group was significantly better than in the IM group (p = 0.002). Conclusions  Combined analysis of histopathological and genetic analysis may reflect more exactly the nature of recurrent HCC. The incidence of MO in China is lower than in other countries—30% compared to up to 50% in Japan [Morimoto et al., Journal of Hepatology 39:215–221, 2003; Yamamoto et al., Hepatology 29;1446–1452, 1999]. Recurrence time, tumor grading, portal vein invasion, tumor number, and Child’s stage are the most important discriminating factors between MO and IM. The prognosis (disease-free survival) of patients with MO compared to IM is significantly better.     

Impact of Intermittent Pringle Maneuver on Long-Term Survival After Hepatectomy for Hepatocellular Carcinoma: Result from Two Combined Randomized Controlled Trials

Hepatectomy remains an important curative treatment for hepatocellular carcinoma (HCC). Intermittent Pringle maneuver (IPM) is commonly applied during hepatectomy for control of bleeding. Whether the ischemia/reperfusion injury brought by IPM adversely affects the operative outcomes is controversial. This study aims to examine whether the application of IPM during hepatectomy affects the long-term outcomes. Two randomized controlled trials (RCT) have been carried out previously to evaluate the short-term outcomes of IPM. The present study represented a post hoc analysis on the HCC patients from the first RCT and all patients from the second RCT, and the long-term outcomes were evaluated. There were 88 patients each in the IPM group and the no-Pringle-maneuver (NPM) group. The patient demographics, type and extent of liver resection and histopathological findings were comparable between the two groups. The 1-, 3-, 5-year overall survival in the IPM and NPM groups was 92.0%, 82.0%, 72.1% and 93.2%, 68.8%, 58.1%, respectively (P = 0.030). The 1-, 3-, 5-year disease-free survival in the IPM and NPM groups was 73.6%, 56.2%, 49.7% and 71.6%, 49.4%, 40.3%, respectively (P = 0.366). On multivariable analysis, IPM was a favorable factor for overall survival (P = 0.035). Subgroup analysis showed that a clamp time of 16–30 min (P = 0.024) and cirrhotic patients with IPM (P = 0.009) had better overall survival. IPM provided a better overall survival after hepatectomy for patients with HCC. Such survival benefit was noted in cirrhotic patients, and the beneficial duration of clamp was 16–30 min. NCT00730743 and NCT01759901 (http://www.clinicaltrials.gov).