Child-Pugh A Hepatitis B-Related Cirrhotic Patients with a Single Hepatocellular Carcinoma Up to 5 cm: Liver Transplantation vs. Resection

Objective

This study aims to analyze the outcomes of patients with Child-Pugh A class cirrhosis and a single hepatocellular carcinoma (HCC) up to 5 cm in diameter who underwent liver transplantation vs. resection.

Methods

During 2007 to 2012, 282 Child-Pugh A cirrhotic patients with a single HCC up to 5 cm in diameter either underwent liver resection (N?=?243) or received liver transplantation (N?=?39) at our center. Patient and tumor characteristics and outcomes were analyzed.

Results

Patients who underwent liver transplantation had a better recurrence-free survival (RFS) vs. those who underwent liver resection. However, the 5-year survival rates after these two treatments were comparable. Similar results were observed when we analyzed patients with a HCC less than 3 cm, and for patients with portal hypertension. In the multivariate analysis, tumor differentiation, difference of primary treatment, and presence of microvascular invasion were associated with postoperative recurrence. However, only differentiation negatively impacted overall survival after operation.

Conclusion

Although more recurrences were observed in Child A cirrhotic patients with a single HCC up to 5 cm after liver resection, liver resection offers a similar 5-year survival to liver transplantation, even for patients with portal hypertension.     

Improved Results of a Surgical Resection for the Recurrence of Hepatocellular Carcinoma After Living Donor Liver Transplantation

Purpose

This study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence.

Methods

A total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered.

Results

The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (n = 9), and nonsurgical therapy group (n = 7). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence.

Conclusions

Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available.     

Early Viral Suppression Predicts Good Postoperative Survivals in Patients with Hepatocellular Carcinoma with a High Baseline HBV-DNA Load

Purpose

To correlate early HBV-DNA suppression by antiviral treatment with posthepatectomy long-term survivals in patients with HBV-related hepatocellular carcinoma (HCC).

Methods

A retrospective study was conducted on patients with a baseline HBV-DNA load of >2,000 IU/ml. The cumulative rates of HBV-DNA undetectability at weeks 24 and 48, as well as long-term tumor recurrence and overall survivals were determined.

Results

Of 1,040 patients with a high baseline HBV-DNA load, 865 patients received antiviral treatment. At a median follow-up of 42 months, 616 patients (59.2 %) had developed HCC recurrence and 482 patients (46.3 %) had died. The median time to recurrence was 25 months. In patients who received antiviral treatment, the cumulative rates of HBV-DNA undetectability (<200 IU/ml) were 54.3 and 88.1 % at weeks 24 and 48, respectively. There was no significant difference between the two groups of patients who received antiviral treatment or not for disease-free survival. On multivariate analyses, tumor size >5 cm, blood transfusion, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak inflammation score were significant risk factors of HCC recurrence. Also, tumor size >5 cm, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak fibrosis score were significant factors associated with poor postoperative overall survival. On the other hand, an undetectable HBV-DNA level before week 24 was a significant protective factor of disease-free survival and overall survival.

Conclusions

Early HBV-DNA suppression with antiviral treatment improved prognosis of patients with HBV-related HCC.     

Locoregional Therapy-Induced Tumor Necrosis as a Predictor of Recurrence after Liver Transplant in Patients with Hepatocellular Carcinoma

Background

Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy.

Methods

We conducted a hospital-based retrospective analysis of 100 patients with HCC who received a liver transplant, 86 of whom had received pretransplant locoregional therapy. We evaluated various patient- and tumor-related parameters to determine the risk factors for recurrence. Furthermore, we grouped patients by the degree of tumor necrosis after locoregional therapy and identified the factors that were associated with a favorable tumor response.

Results

Initial tumor extent beyond the University of San Francisco (UCSF) criteria, microvascular invasion, and attainment of less than 90% tumor necrosis after locoregional therapy were independent risk factors for tumor recurrence. In addition, there was a significant correlation between the tumor necrosis percentage and disease-specific survival rate. Among patients whose tumors initially exceeded the UCSF criteria, those with extensive locoregional therapy-induced tumor necrosis had lower recurrence rates. All recurrences after transplant occurred within 3 years, and recurrence rates in patients with extensive tumor necrosis at 1, 2, and 3 years were 3%, 6%, and 10%, respectively. Female gender and a solitary tumor were independently associated with extensive tumor necrosis.

Conclusions

In HCC patients who are transplant candidates and undergo pretransplant locoregional therapy, the degree of induced tumor necrosis affects both tumor recurrence and survival rate.     

Postoperative Serum Osteopontin Level is a Novel Monitor for Treatment Response and Tumor Recurrence after Resection of Hepatitis B–related Hepatocellular Carcinoma

Background

Presurgery serum osteopontin (OPN) level has been demonstrated to correlate to tumor recurrence and survival of hepatocellular carcinoma (HCC) patients. This study investigated the postoperative dynamic changes of serum OPN level and its clinical significance in HCC patients.

Methods

Presurgery serum OPN levels were measured by enzyme-linked immunosorbent assay in cohort A of 179 HCC patients and were compared with the multiple controls including different kinds of liver diseases and healthy individuals. In cohort B of 110 patients with resectable HCCs, besides preoperative assays, serum OPN was monitored at 1 week, 1, and ≥2 months after operation.

Results

The baseline presurgery serum OPN of HCC patients was significantly higher than that of the patients with the other kinds of liver diseases (p < 0.0001). The prognostic values of presurgery serum OPN level in HCC patients were further confirmed. The postsurgery OPN levels were significantly elevated within 1 week after HCC resection, then decreased at 1 month and reached the nadir later than 2 months after operations. It increased again at the time of tumor recurrence, then declined after the second removal of recurrent HCCs. Moreover, postoperative OPN in α-fetoprotein-negative and -positive HCC patients had the same changing pattern; it only correlated to liver function and C-reactive protein level.

Conclusions

After a transient fluctuation, serum OPN levels significantly decrease after curative resection of HCCs. Postoperative serum OPN could serve as a surrogate serologic biomarker for monitoring treatment response and tumor recurrence after HCC resection, including α-fetoprotein-negative ones.     

Impact of Spontaneous Hepatocellular Carcinoma Rupture on Recurrence Pattern and Long-term Surgical Outcomes after Partial Hepatectomy

Background

The clinical significance of spontaneous hepatocellular carcinoma (HCC) rupture association with recurrence pattern and long-term surgical outcomes remains under debate. We investigated the impact of spontaneous HCC rupture on recurrence pattern and long-term surgical outcomes after partial hepatectomy.

Methods

From 2000 to 2012, 119 patients with diagnosed ruptured HCC were reviewed. To compare outcomes between staged hepatectomy in spontaneously ruptured HCC and hepatectomy in non-ruptured HCC, we performed propensity score-matching to adjust for significant differences in patient characteristics. Overall survival, disease-free survival, and recurrence pattern were compared between the matched groups.

Results

Forty-four patients with newly diagnosed ruptured HCC and Child A class were initially treated with transcatheter arterial embolization for hemostasis. Three patients underwent emergency laparotomy, 18 underwent staged hepatectomy, and 23 received transarterial chemoembolization (TACE) alone after transcatheter arterial embolization. Among the 23 patients treated with TACE alone, 10 had resectable tumors. The staged hepatectomy group shows significantly higher overall survival with TACE alone than the resectable tumor group (P < 0.001). After propensity score-matching, overall survival, disease-free survival, and recurrence pattern were not significantly different between the ruptured HCC with staged hepatectomy group and the non-ruptured HCC with hepatectomy group. Peritoneal recurrence rates were similar at 14.3 % versus 10.0 %, respectively (P = 0.632).

Conclusions

Patients with spontaneously ruptured HCC with staged hepatectomy show comparable long-term survival and recurrence pattern as patients with non-ruptured HCC having similar tumor characteristics and liver functional status. Thus, spontaneous HCC rupture may not increase peritoneal recurrence and decrease long-term survival after partial hepatectomy.     

Liver Transplantation in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: The Influence of Viral Characteristics on Clinical Outcome

Background

Hepatitis B virus (HBV) relapse and/or hepatocellular carcinoma (HCC) recurrence remains a major concern for patients who undergo liver transplantation (LT) because of HBV-related HCC. This study investigates the correlation between HBV relapse and HCC recurrence and it explores factors that affect patient outcomes after LT.

Methods

Between September 2002 and August 2009, 78 consecutive patients who underwent LT because of HBV-related HCC were enrolled in this study. Serum samples obtained before LT were assayed both for virological factors associated with HBV DNA and for genotypic characteristics of the virus. All patient clinicopathological features and virological factors were assessed further by univariate and multivariate analyses to determine prognostic factors.

Results

During a median follow-up period of 29.4 months, 13 (16.6 %) patients experienced HCC recurrence and 18 (23.1 %) patients experienced HBV relapse. HBV relapse exhibited a close association with HCC recurrence (p = 0.004) and led to unfavorable overall survival after LT. Multivariate analysis of prognostic factors showed that the basal core promoter (BCP) mutation independently predicted a shorter survival period free from HBV relapse (p = 0.036). Moreover, with the exception of unfavorable tumor characteristics, the BCP mutation was found to be an important prognostic factor that affected HCC recurrence after LT (p = 0.042).

Conclusions

In this study, the HBV–BCP mutation was identified as an important predictor of post-LT clinical outcomes in patients with HBV-related HCC. Therefore, we recommend that aggressive antiviral treatment may be considered for patients associated with this risk factor.     

Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study

Purposes

The long-term outcomes of branched-chain amino acids (BCAA) administration after hepatic resection in patients with hepatocellular carcinoma (HCC) remain unclear. This study assessed the effect of oral supplementation with BCAA on the development of liver tumorigenesis after hepatic resection in HCC patients.

Methods

Fifty-six patients were randomly assigned to receive either BCAA supplementation (Livact group, n = 26) or a conventional diet (Control group, n = 30). Twenty-six patients in the BCAA group were treated orally for 2 weeks before and 6 months after hepatic resection. Postoperative tumor recurrence was continuously evaluated in all patients by measuring various clinical parameters.

Results

There was no significant difference in the overall survival rate between the two patient groups; however, the recurrence rate at 30 months after surgery was significantly better in the Livact group in comparison to the Control group. Interestingly, the tumor markers, such as AFP and PIVKA-II, significantly decreased at 36 months after liver resection in the Livact group in comparison to the Control group.

Conclusions

Oral supplementation of BCAA reduces early recurrence after hepatic resection in patients with HCC. This treatment regimen offers potential benefits for clinical use in such patients, even in cases with a well-preserved preoperative liver function.     

Predictor for Histological Microvascular Invasion of Hepatocellular Carcinoma: A Lesson from 229 Consecutive Cases of Curative Liver Resection

Background

Microscopic vascular invasion is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. To predict microscopic portal venous invasion, the following two questions were examined retrospectively: Is it possible to detect microvascular invasion preoperatively? What are the characteristics of a group of early HCC recurrences even with no microvascular invasion?

Methods

Study 1 included 229 patients with HCC who underwent curative liver resection between 1991 and 2008; 127 had HCC without microscopic portal venous invasion, and 52 had HCC with microscopic portal venous invasion (MPVI). These two distinct groups were analyzed with regard to various clinicopathologic factors. Subsequently, we specifically investigated if HCCs <5 cm with vascular invasion (n = 32) have some characteristics that would allow detection of latent microvascular invasion. Study 2 included 127 HCC patients without MVPI; 42 had a recurrence within 2 years, and 85 patients were recurrence-free for at least 2 years. These two distinct groups were analyzed with regard to various clinicopathologic factors.

Results

HCC diameter of >5 cm, the macroscopic appearance of HCC, and high levels of preoperative des-γ-carboxyprothrombin are significant prognostic factors in identifying microvascular invasion of HCC. The strongest predictor of early recurrence (within 2 years) was the serum α-fetoprotein level in patients without clear microvascular invasion.

Conclusions

Tumor size, macroscopic appearance, and high tumor marker levels are important elements in identifying the group of patients with a low HCC recurrence rate after curative liver resection.     

Single HCC in Cirrhotic Patients: Liver Resection or Liver Transplantation? Long-term Outcome According to an Intention-to-treat Basis

Background

Compensated cirrhotic patients with single hepatocellular carcinoma (HCC) ≤5 cm may benefit from both liver resection (LR) and liver transplantation (LT); however, the better 10-year actuarial survival of the two treatments remains unclear. We aimed to assess the long-term outcome of cirrhotic patients with single HCC ≤5 cm treated either with LR or LT on an intention-to-treat basis.

Methods

A total of 217 cirrhotic patients with single HCC ≤5 cm were evaluated at our department: 95 were treated with LR (LR group), and 122 were included on the waiting list for LT (LT group). Patients in the LR group were divided into very early HCC (tumor size ≤2 cm) and early HCC (tumor size >2 cm). Median follow-up was 5.3 (range 0.1–18) years.

Results

Tumor recurrence was 72 % in the LR group versus 16 % in the LT group (p < 0.001). 1-, 5-, and 10-year cumulative risk of recurrence was 18, 69, and 83 % in the LR group versus 4, 18, and 20 % in the LT group (p < 0.001). Ten-year actuarial survival was 33 % in the LR group versus 49 % in the LT group (p = 0.002). At HCC recurrence, 27.3 % were included on the waiting list for salvage transplantation (very early HCC group) versus 15.1 % (early HCC group) (p = 0.2). After salvage transplantation, HCC recurrence was 0 % (very early HCC group) versus 40 % (early HCC group) (p = 0.2). No significant differences were observed in 1-, 5-, and 10-year actuarial survival between the very early HCC group and the LT group (95, 55, and 50 % vs. 82, 62, and 50 %).

Conclusions

LR should be the treatment of choice for cirrhotic patients with very early HCC.     

High risk of lung metastasis after resection of hepatocellular carcinoma more than 7 cm in diameter

Purpose

The relationship between the tumor size and organs of recurrence was analyzed to identify a high-risk group for the extrahepatic recurrence of hepatocellular carcinoma (HCC) after resection.

Methods

A total of 544 patients with HCC underwent primary surgical resection for HCC between 2001 and 2010. Of these, 293 patients had a solitary tumor but no macroscopic vascular invasion. The prognostic factors for the overall survival and relapse-free survival were analyzed among these 293 patients. The recurrent organs and frequency of recurrence were also examined.

Results

The analysis of the 293 patients showed that both the overall and relapse-free survival rates of the patients with a large tumor (>7 cm in diameter) were significantly worse than those of the patients with a tumor <7 cm. The incidence of lung metastasis was remarkably high in the group of patients with tumors more than 7 cm (24.0 %), in comparison to those with tumors <7 cm. A multivariate analysis revealed that the tumor size was the only independent risk factor for lung metastasis.

Conclusions

The patients with large HCC tumors more than 7 cm in diameter were at high-risk for a poor prognosis due to a high percentage of lung metastasis, even if there was no macroscopic vascular invasion.     

Complete Necrosis After Transarterial Chemoembolization Could Predict Prolonged Survival in Patients with Recurrent Intrahepatic Hepatocellular Carcinoma After Curative Resection

Background

We explored the predictors of response to transarterial chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular carcinoma (HCC) after hepatectomy and investigated the survival of these patients according to the response to TACE.

Methods

We analyzed data from 199 consecutive HCC patients who underwent curative liver resection and who later received repeat TACE for intrahepatic HCC recurrence.

Results

Of 199 patients, 139 (69.8%) achieved complete necrosis (CN) of HCC after repeated TACE (mean TACE session number, 1.3) and the other 60 (30.2%) (non-CN group) did not achieve CN. At hepatectomy, the CN group showed significantly smaller proportions of tumor capsular invasion, microvascular invasion, and pathologic tumor–node–metastasis stage III or IV HCCs. At first TACE, the CN group showed a significantly greater proportion of patients with time to recurrence ≥ 1 year, Child–Pugh class A, serum alpha-fetoprotein (AFP) levels < 200 ng/mL, tumor size < 3 cm, solitary tumors, and nodular tumor types; portal vein invasion were less common than seen in the non-CN group. After multivariate analysis, tumor size < 3 cm and a single tumor at first TACE were independently related to attainment of CN after TACE. Median survival after first TACE was significantly longer in the CN group (48.9 versus 17.0 months). In a Cox regression model, CN after TACE was an independent predictor of favorable survival outcome after first TACE.

Conclusions

CN after repeat TACE for postresection intrahepatic recurrence was attained more commonly in patients with smaller tumor size and lower tumor number at first TACE and favored longer survival in recurrent patients.     

γ-Glutamyltranspeptidase is a Prognostic Marker of Survival and Recurrence in Radiofrequency-Ablation Treatment of Hepatocellular Carcinoma

Purpose

Serum γ-glutamyltranspeptidase (GGT) level, which is often elevated in hepatocellular carcinoma (HCC), has now been found to be an oxidative stress marker which correlates with inflammation in the extracellular hepatic microenvironment. The aim of this study was to investigate the prognostic significance of GGT serum levels in patients undergoing radiofrequency ablation (RFA) therapy for the treatment of HCC.

Methods

This retrospective study included 254 patients with small liver cancer (tumor of ≤5 cm in diameter and nodule of ≤3 cm) who had been treated with RFA. Baseline serum GGT was examined before therapy, and overall survival (OS) and recurrence-free survival were evaluated by the Kaplan–Meier method. Univariate and multivariate analyses were used to analyze the significance of GGT and other serum markers as prognostic factors.

Results

After a median follow-up of 27 months, 51 patients had died and 123 had hepatic recurrence. After treatment with RFA, HCC patients with elevated GGT had a shorter OS versus those with normal GGT level (p = 0.001); they also had higher recurrence (p = 0.001). On multivariate analysis, albumin (p = 0.003), GGT (p = 0.035), and tumor size (p = 0.027) were independent risk factors for survival, and GGT (p = 0.010) and tumor size (p = 0.026) were significant risk factors for recurrence.

Conclusions

Serum GGT is a convenient prognostic biomarker related to OS and recurrence in HCC patients undergoing RFA treatment.     

Milan Criteria, Multi-nodularity, and Microvascular Invasion Predict the Recurrence Patterns of Hepatocellular Carcinoma After Resection

Aims

This study aims to evaluate the risk factors for tumor recurrence beyond the Milan criteria (MC) for patients with hepatocellular carcinoma (HCC) after surgical resection (SR) in which salvage liver transplantation is relatively contraindicated.

Methods

A total of 447 patients who underwent SR for HCC were enrolled consecutively. Among them, 248 and 199 patients were within the Milan criteria and beyond the Milan criteria (BMC group), respectively. Overall survival, recurrence, and disease-free survival were analyzed by multivariate analysis.

Results

After a median follow-up of 34.4 months, 130 patients died. Microvascular invasion, higher Edmondson stage of tumor cell differentiation, BMC group, and no anti-viral therapy were associated with poor overall survival. Multi-nodularity, higher Edmondson stage, BMC group, and no anti-viral therapy were independent risk factors for tumor recurrence, while BMC group and no anti-viral therapy were independent risk factors for disease-free survival. The Milan criteria, multi-nodularity, and microvascular invasion were used to stratify the patients into low-, medium-, and high-risk groups for tumor recurrence outside the MC and showed statistical significance (low vs. medium, p?=?0.011; low vs. high, p?<?0.001; medium vs. high, p?=?0.009).

Conclusions

The combination of the MC, multi-nodularity, and microvascular invasion predict the post-operative recurrence of HCC and may provide a roadmap for further treatment.     

Protein Induced by Vitamin K Antagonist-II (PIVKA-II) Is a Reliable Prognostic Factor in Small Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) <2 cm in diameter has a favorable prognosis. Therefore surgical resection of small HCC is associated with good outcomes. However, the predisposing factors of prognosis following resection of HCC remain ill-defined. The aims of the present study were to identify the clinicopathologic characteristics and outcomes of patients with small HCC and analyze the predisposing factors for tumor recurrence after surgery.

Methods

We retrospectively reviewed 180 patients with small HCC who underwent hepatectomy between 2006 and 2010. Independent predictors of tumor recurrence were identified with Cox regression analysis.

Results

The 1-year, 3-year, and 5-year disease-free survival rates and overall survival rates were 83.7, 68.0, 65.3, and 98.9, 96.5, 92.7 %, respectively. Multivariate analysis reported that protein induced by the vitamin K antagonist-II (PIVKA-II) ≥200 mAU/mL, alkaline phosphatase (ALP) ≥80 IU/mL, and microvascular invasion were important predisposing factors for tumor recurrence. Elevated serum PIVKA-II level was associated with microvascular invasion in small HCC, which was a powerful predisposing factor.

Conclusions

Although small HCC is generally associated with a good prognosis, serum PIVKA-II level ≥200 mAU/mL, ALP ≥ 80 IU/L, and microvascular invasion were predisposing factors for tumor recurrence. These factors can be used to stratify patients with respect to recurrence after resection. Elevated PIVKA-II was closely associated with microvascular invasion in small HCC. These data emphasize the importance of PIVKA-II in small HCC.     

Feasibility of Laparoscopic Re-resection for Patients with Recurrent Hepatocellular Carcinoma

Background

Repeated resection via an open approach is an effective treatment for post-operative recurrent hepatocellular carcinoma (HCC). However, there are limited data on the application of laparoscopic approach for recurrent HCC in patients with prior liver resections. The aim of this study was to review our experience of laparoscopic re-resection in patients with postoperative tumor recurrence.

Materials and methods

A total of 11 patients received laparoscopic re-resections for postoperative tumor recurrence in our center. Data were reviewed for demographics, tumor characteristics, and perioperative outcomes. Case-match analysis with the open approach was performed in a 1:2 ratio.

Results

Six patients had their first liver resection carried out via the open approach and the remaining five patients received the laparoscopic approach. The recurrent tumor size was 20 mm (12–50 mm) and ten patients had a solitary recurrence. Two patients had laparoscopic left lateral sectionectomy and the remaining nine patients had sub-segmentectomies. There was no significant difference in patient characteristics, preoperative liver function, and tumor features between the laparoscopic and open groups. Perioperative blood loss was significantly reduced in the laparoscopic group (100 vs. 314 mL; p = 0.014) but the morbidity rate (18.2 vs. 4.5 %; p = 0.199) and length of hospitalization were comparable (6 vs. 5 days; p = 0.831). The 3-year overall survival rates for the laparoscopic and open groups were 60.0 and 89.3 %, respectively (p = 0.279).

Conclusion

Our study showed that laparoscopic re-resection for recurrent HCC was feasible with satisfactory postoperative and oncological outcomes, even in patients with previous major liver resections.     

Efficacy and survival analysis of percutaneous radiofrequency versus microwave ablation for hepatocellular carcinoma: an egyptian multidisciplinary clinic experience

Background

Hepatocellular carcinoma (HCC) is a primary tumor of the liver with poor prognosis. For early stage HCC, treatment options include surgical resection, liver transplantation, and percutaneous ablation. Percutaneous ablative techniques (radiofrequency and microwave techniques) emerged as best therapeutic options for nonsurgical patients.

Aims

We aimed to determine the safety and efficacy of radiofrequency and microwave procedures for ablation of early stage HCC lesions and prospectively follow up our patients for survival analysis.

Patients and methods

One Hundred and 11 patients with early HCC are managed in our multidisciplinary clinic using either radiofrequency or microwave ablation. Patients are assessed for efficacy and safety. Complete ablation rate, local recurrence, and overall survival analysis are compared between both procedures.

Results

Radiofrequency ablation group (n = 45) and microwave ablation group (n = 66) were nearly comparable as regards the tumor and patients characteristics. Complete ablation was achieved in 94.2 and 96.1 % of patients managed by radiofrequency and microwave ablation techniques, respectively (p value 0.6) with a low rate of minor complications (11.1 and 3.2, respectively) including subcapsular hematoma, thigh burn, abdominal wall skin burn, and pleural effusion. Ablation rates did not differ between ablated lesions ≤3 and 3–5 cm. A lower incidence of local recurrence was observed in microwave group (3.9 vs. 13.5 % in radiofrequency group, p value 0.04). No difference between both groups as regards de novo lesions, portal vein thrombosis, and abdominal lymphadenopathy. The overall actuarial probability of survival was 91.6 % at 1 year and 86.1 % at 2 years with a higher survival rates noticed in microwave group but still without significant difference (p value 0.49).

Conclusion

Radiofrequency and microwave ablations led to safe and equivalent ablation and survival rates (with superiority for microwave ablation as regards the incidence of local recurrence).     

Prediction of Disease-free Survival in Hepatocellular Carcinoma by Gene Expression Profiling

Background

Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. The molecular prognostic model that could be applied to the HCC patient population in general is needed for effectively predicting disease-free survival (DFS).

Methods

A cohort of 286 HCC patients from South Korea and a second cohort of 83 patients from Hong Kong, China, were used as training and validation sets, respectively. RNA extracted from both tumor and adjacent nontumor liver tissues was subjected to microarray gene expression profiling. DFS was the primary clinical end point. Gradient lasso algorithm was used to build prognostic signatures.

Results

High-quality gene expression profiles were obtained from 240 tumors and 193 adjacent nontumor liver tissues from the training set. Sets of 30 and 23 gene-based DFS signatures were developed from gene expression profiles of tumor and adjacent nontumor liver, respectively. DFS gene signature of tumor was significantly associated with DFS in an independent validation set of 83 tumors (P = 0.002). DFS gene signature of nontumor liver was not significantly associated with DFS in the validation set (P = 0.827). Multivariate analysis in the validation set showed that DFS gene signature of tumor was an independent predictor of shorter DFS (P = 0.018).

Conclusions

We developed and validated survival gene signatures of tumor to successfully predict the length of DFS in HCC patients after surgical resection.     

Prognosis of Hepatocellular Carcinoma Patients Who Achieved Long-Term Recurrence-Free Survival After Curative Therapy: Impact of the ALBI Grade

Background/Aims

Some patients experience very late recurrence of HCC more than 5 years after initial therapy. We aimed to clarify the predictive factors for very late recurrence of HCC in such cases.

Methods

Among 807 HCC patients undergoing surgical resection or ablative therapy with curative intent, the patients who survived for 5 years without any recurrence were reviewed. The prognosis and possible predictive factors for late recurrence were analyzed retrospectively.

Results

A total of 184 patients survived for more than 5 years without recurrence. Among them, 61 patients experienced recurrence, at a median of 6 years after initial therapy. In univariate analysis, the pre-treatment aspartate aminotransferase, alanine aminotransferase, Child-Pugh class, and ALBI grade were not related to recurrence, but those at 5 years after treatment were significantly related to recurrence. By multivariate analysis, an ALBI grade of 2–3 at 5 years was an independent risk factor for recurrence (P?<?0.0001). Moreover, variation of the ALBI grade over the 5 years after the initial treatment was significantly related to recurrence-free survival.

Conclusions

The ALBI grade is an effective index of the variation in liver function after curative therapy and may be a useful prognostic factor for the long-term recurrence-free survival of HCC patients.

     

Recurrence Patterns and Prognostic Factors in Patients with Hepatocellular Carcinoma in Noncirrhotic Liver: A Multi-Institutional Analysis

Background

Hepatocellular carcinoma (HCC) primarily affects patients with a cirrhotic liver. Reports on the characteristics of patients with HCC in noncirrhotic liver, as well as predictors of recurrence and survival, are scarce.

Methods

Between 1992 and 2011, 334 patients treated for HCC in noncirrhotic liver were identified from three major hepatobiliary centers. Clinicopathological characteristics were analyzed and independent predictors of recurrence and overall survival were identified using Cox proportional hazards models.

Results

Median patient age was 58 years and 77 % were male. Most patients had a solitary (81 %) and poorly or undifferentiated tumor (56 %); median size was 6.5 cm. The majority of patients (96 %) underwent liver resection (microscopically negative margins in 94 %), whereas a few had transarterial chemoembolization or transplantation (4 %). Median recurrence-free survival (RFS) was 2.5 years, and 1- and 5-year RFS was 71.1, and 35 %, respectively. Elevated alkaline phosphatase levels [hazards ratio (HR) = 1.82], poor tumor differentiation (HR = 1.4), macrovascular invasion (HR = 2.18), and the presence of satellite lesions (HR = 1.9), or intrahepatic metastases (HR = 2.59) were independently associated with shorter RFS; in contrast, an intact tumor capsule independently prolonged RFS (HR = 0.46). Median overall survival was 5.9 years, and 1- and 5-year overall survival was 86.9, and 54.5 %, respectively. Tumor size ≥5 cm (HR = 2.27), macrovascular (HR = 2.72) or adjacent organ invasion (HR = 3.34), and satellite lesions (HR = 2.18) were independently associated with shorter overall survival, whereas an intact tumor capsule showed a protective effect (HR = 0.51).

Conclusions

Following resection of HCC in the setting of no cirrhosis, more than one-half of patients were alive after 5 years. However, even among patients with no cirrhosis, recurrence was common. Factors associated with RFS and overall survival included tumor characteristics, such as tumor capsule, satellite lesions, and vascular invasion.