Long-Term Outcomes of Repeat Hepatic Resection in Patients with Recurrent Hepatocellular Carcinoma and Analysis of Recurrent Types and Their Prognosis: A Single-Center Experience in China

Background

Recurrent hepatocellular carcinoma (HCC) after curative resection usually originates from intrahepatic metastasis (IM) or multicentric occurrence (MO). The long-term outcomes of repeat hepatic resection in patients with different types of recurrence have not been evaluated in a large number of patients. The surgical indications for recurrent HCC remain controversial. The purpose of this study was to investigate long-term outcomes of repeat hepatic resection and clinicopathologic factors associated with different types of recurrent HCC, and to single out principle differentiating factors between IM and MO.

Methods

82 patients who underwent repeat hepatic resection for recurrent HCC were retrospectively studied. The recurrent type was evaluated by histopathologic analysis of primary and recurrent HCC. The recurrence and survival rates as well as clinicopathologic factors associated with different types of recurrence were analyzed.

Results

45 patients (54.9%) had confirmed with IM, and 37 patients (45.1%) had with MO. The recurrence rates in the MO patients after initial or repeat resection were significantly lower than those in the IM patients (p?p?Conclusions Repeat hepatic resection resulted in much higher survival rates in the MO patients than in the IM patients. Repeat hepatic resection could be recommended for those patients in whom the recurrent HCC occurs more than 18?months after initial resection.     

Clinicopathological Features of Recurrence in Patients After 10-year Disease-free Survival Following Curative Hepatic Resection of Hepatocellular Carcinoma

Background

The present study aimed to clarify the clinicopathologic features of long-term disease-fee survival after resection of hepatocellular carcinoma (HCC).

Methods

This retrospective study identified 940 patients who underwent curative resection of HCC between 1991 and 2000 at five university hospitals. Seventy-four patients with 10 years of recurrence-free survival were identified and followed up. They were divided into two groups, 60 recurrence-free and 14 with recurrence after a 10-year recurrence-free period.

Results

Overall survival rates of recurrence and non-recurrence groups were 68 and 91 % at 16 years, and 34 and 91 % at 20 years (p = 0.02), respectively. There were five (36 %), and two deaths (3 %), respectively, after 10 recurrence-free years. A second resection for recurrence was performed in four patients (29 %), and mean survival was 15.3 years after the first hepatectomy. Although three patients in the non-recurrence group (5 %) developed esophageal and/or gastric varices, seven patients in the recurrence group (50 %) developed varices during 10 years (p < 0.0001). In multivariate analysis, preoperative and 10-year platelet count was identified as a favorable independent factor for maintained recurrence-free survival after a 10-year recurrence-free period following curative hepatic resection of HCC.

Conclusions

Recurrence of HCC may occur even after a 10-year recurrence-free period. Long-term follow-up after resection of HCC is important, and should be life-long. Patients with higher preoperative and 10-year platelet counts are more likely to have long-term survival after resection. A low platelet count, related to the degree of liver fibrosis, is a risk factor for recurrence and survival of HCC after curative resection.     

Surgical Outcomes and Clinical Characteristics of Elderly Patients Undergoing Curative Hepatectomy for Hepatocellular Carcinoma

Background

The aim of this study was to investigate the clinical characteristics and outcomes of elderly patients (≥70 years old) undergoing curative hepatectomy for hepatocellular carcinoma (HCC).

Methods

Clinicopathological data and treatment outcomes in 100 elderly patients (≥70 years old) and 120 control patients (≤70 years old) with HCC who underwent curative hepatectomy between 2000 and 2011 were retrospectively collected and compared.

Results

The overall survival rate was similar between the two groups, but the disease-free survival rate was worse in the elderly group when compared with the control group. Prognostic factors for overall and disease-free survival were the same when comparing the two groups. The elderly group had higher rate of females (p?=?0.0230), higher hepatitis C virus infection rate (p?=?0.0090), higher postoperative pulmonary complication rate (p?=?0.0484), lower rate of response to interferon (IFN) therapy (p?=?0.0203) and shorter surgical time (p?=?0.0337) when compared with the control group. The overall recurrence rate was higher in the elderly group than in the control group (p?=?0.0346), but the rate of recurrence within 2 years after the operation was similar when comparing the two groups.

Conclusion

The survival of elderly patients with HCC was similar to that of younger patients. However, the disease-free survival was worse in elderly patients than in younger patients. Aggressive antiviral therapy (e.g. IFN therapy) may be necessary to improve the disease-free survival, even in elderly patients. Additionally, clinicians should be aware of the risk of pulmonary complications in elderly patients after hepatectomy.     

Serum Antibody Titers Against Hepatitis C Virus and Postoperative Intrahepatic Recurrence of Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is the seventh most common cancer and the third leading cause of cancer deaths worldwide. Hepatitis C virus (HCV) infection is a major risk factor for HCC recurrence after curative resection. This study evaluated anti-HCV antibody (Ab) titer as a prognostic indicator of HCC recurrence after curative hepatic resection.

Methods

A total of 82 patients with HCC (anti-HCV Ab positive and hepatitis B surface antigen negative) who underwent curative hepatic resection were evaluated. Anti-HCV Ab titers were measured using a third-generation enzyme immunoassay, and patients were divided into high (n = 41) and low (n = 41) titer groups to compare their clinicopathological characteristics and disease-free survival. Univariate and multivariate analyses were conducted to identify risk factors for early or late recurrence.

Results

Multivariate analysis showed that anti-HCV Ab titer and vascular invasion were independent prognostic factors of disease-free survival [odds ratio (OR) 1.9, p = 0.03, and OR 1.8, p = 0.04, respectively]. Subgroup analysis identified only vascular invasion as an independent prognostic factor for early recurrences that were considered residual intrahepatic metastases. Subgroup analysis identified anti-HCV Ab titer and fibrosis grade as independent prognostic factors of late recurrences that were considered to be metachronous multicentric liver carcinogenesis (OR 4.8, p = 0.04, and OR 5.2, p = 0.03, respectively).

Discussion

Anti-HCV Ab titer is a predictive factor for HCC recurrence, especially the risk of late recurrence due to multicentric carcinogenesis. Prevention of liver carcinogenesis after hepatic resection for HCC might be appropriate for patients with high anti-HCV Ab titers.     

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.     

Clinical Significance of Lymph Node Metastasis in Patients Undergoing Partial Hepatectomy for Hepatocellular Carcinoma

Background

There are few detailed clinical reports about perihepatic lymph node (LN) assessment of hepatocellular carcinoma (HCC). The purpose of the present study was to evaluate the incidence, site, and impact on survival of LN metastasis in patients with HCC amenable to curative liver resection and routine regional lymphadenectomy.

Methods

From January 2001 to June 2004, a total of 523 HCC patients undergoing curative hepatic resection and routine regional lymphadenectomy were included in this study. The incidence, site of LN metastasis in HCC patients, and its influence on survival were analyzed.

Results

A total of 3433 lymph nodes were dissected from the 523 patients enrolled in this study and examined by pathologists. Among these patients, LN metastasis was found in 39 (7.45%) patients. Hepatic pedicle, retropancreatic space, and common hepatic artery stations were conventionally removed. The incidence of LN metastasis in the hepatic pedicle station was higher than that in the other stations (p < 0.01) The overall cumulative survival rate was significantly worse for patients with LN metastasis than for those without LN metastasis (p < 0.01). The median survival time was 28 months among the patients with LN metastasis and 53 months among those without LN metastasis. Tumors had recurred in 82.05% (32/39) of patients with LN metastasis and in 57.64% (279/484) of those without LN metastasis (p < 0.01). Regional lymphadenectomy was considerably safe with a low intraoperative complication rate (0.95%).

Conclusions

Lymph node metastasis in patients with HCC is closely related to a lower survival rate. Regional lymph node dissection should always be performed to determine the precise stage of the disease. Hepatic resection with regional lymphadenectomy is a safe procedure in patients with HCC.     

Surgical Resection versus Open-Approach Radiofrequency Ablation for Small Hepatocellular Carcinomas within Milan Criteria after Successful Transcatheter Arterial Chemoembolization

Aims

The aim of this study was to compare the effectiveness and safety of hepatic resection versus open-approach RFA (ORFA) for small hepatocellular carcinomas (HCC) within Milan criteria after successful downstaging therapy by transcatheter arterial chemoembolization.

Material and Methods

Between February 2005 and February 2008, a total of 110 patients with advanced HCC met the Milan criteria after successful downstaging therapy; 58 patients then underwent hepatic resection and 52 received ORFA. Outcomes, including short- and long-term morbidity, 1-, 3-, and 5-year mortality and HCC-free survival, were analyzed and compared between the two groups.

Results

Patients in the hepatic resection and ORFA groups showed similar baseline characteristics and downstaging protocols. The ORFA group showed less blood loss, lower hospital costs, shorter surgical time, and fewer hospital stay days (P?<?0.05). The 1-, 3-, and 5-year overall survival rates were 94.8, 86.2, and 79.3 %, respectively, with liver resection and 96.2, 82.7, and 76.9 % with ORFA (P?=?0.772). The 1-, 3-, and 5-year recurrence-free survival rates were 93.1, 81.0, and 77.6 % with resection and 94.2, 76.9, and 73.1 % with ORFA (P?=?0.705). The ORFA patients suffered fewer postoperative complications (P?=?0.09), particularly among the cases of central HCC (P?=?0.015).

Conclusion

Resection and ORFA achieved similar survival benefits in the management of HCC within Milan criteria after successful downstaging. The decreased blood loss, hospital costs, surgical time, and hospital stay days, and lower complication rates in central cases render ORFA a preferred treatment option.     

Comparing Hepatic Resection and Transarterial Chemoembolization for Barcelona Clinic Liver Cancer (BCLC) Stage B Hepatocellular Carcinoma: Change for Treatment of Choice?

Background

Compared to transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC), stage B in the Barcelona Clinic Liver Cancer (BCLC) classification, the role of hepatic resection remains unclear. The present study compared the long-term outcome of hepatic resection with TACE in the treatment of BCLC stage B HCC.

Methods

A total of 171 patients with BCLC stage B, Child’s classification A (Child A), HCC were included in this retrospective study. Of these, 93 patients underwent hepatic resection (group I) and 73 patients received TACE (group II). We evaluated the long-term outcome and therapy-related mortality in both groups. The risk factors of mortality were assessed. The survival curve was analyzed by the Kaplan–Meier method.

Results

The 1-, 2-, and 3-year overall survival rates for the two groups after hepatic resection and TACE were 83%, 62%, 49% and 39%, 5%, 2%, respectively (P < 0.0001). We did not observe significant differences in the therapy-related mortality between the two groups (P = 0.78). Treatment modality and serum albumin level were independent risk factors for survival by Cox regression analysis.

Conclusions

Our study demonstrated that hepatic resection for BCLC stage B, Child A HCC patients had better survival rates than TACE group. Thus, hepatic resection is indicated in selected patients with BCLC stage B.     

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.     

Hepatic Resection for Hepatocellular Carcinoma Patients on Hemodialysis for Uremia: A Nationwide Cohort Study

Background

The association between uremia and survival outcomes of patients undergoing hepatic resection for hepatocellular carcinoma (HCC) has not been well investigated, particularly for perioperative complications. This nationwide cohort study aimed to compare survival outcomes as well as perioperative mortality and complications between uremia-HCC patients and non-uremia-HCC patients who underwent hepatic resection.

Methods

Using Taiwan’s National Health Institute Research Database, 149 uremia-HCC patients who underwent hepatic resection between 1996 and 2008 were enrolled. The control group comprised 596 HCC patients who also received hepatic resection during the same time period. The two groups were matched for age, gender, viral hepatitis status, and underlying liver cirrhosis. Disease-free survival, overall survival, and perioperative complications were compared between the two groups.

Results

For the uremia-HCC cohort, the 1-, 5-, and 10-year overall and disease-free survival rates were 86, 52, and 38 %, as well as 77, 27, and 18 %, respectively. The survival outcomes were comparable between uremia-HCC cohort and the HCC cohort, regardless of extent of hepatic resection. As for perioperative complications, the uremia-HCC cohort had a higher risk of postoperative infections requiring invasive interventions as well as an increased risk of life-threatening heart-associated complications, compared to the HCC cohort.

Conclusions

Uremia did not influence survival outcomes between the uremia-HCC and the HCC cohorts, irrespective of extent of hepatic resection. This study urges a better perioperative care strategy to avoid potential cardiac and infectious complications in uremia-HCC patients.     

Prognosis After Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma Originating from Non-cirrhotic Liver

Background

Long-term prognosis after resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) originating from non-cirrhotic liver is not fully clarified.

Methods

A total of 183 patients who underwent curative hepatectomy for HCC without cirrhosis were classified into two groups: HBV infection group (n = 124) and non-HBV infection group (n = 59). Long-term postoperative outcomes were compared between the two groups.

Results

The 5-year postoperative overall survival (OS) and disease-free survival (DFS) were 42.6 and 39.0 %, respectively, in the HBV infection group versus 52.3 and 46.5 % in the non-HBV infection group (both p > 0.05). When patients were subdivided according to TNM stages, OS in stages II or III HCC patients was similar between the two groups. In contrast, OS and DFS were significantly worse in stage I patients with HBV infection than those in stage I patients without HBV infection (p = 0.041 and 0.038, respectively). Preoperative serum HBV DNA >4 log₁₀ copies/mL and vascular invasion were independent factors associated with poor prognosis (p = 0.034 and 0.017, respectively) for patients with HBV infection.

Conclusions

After hepatic resection for HCC in non-cirrhotic liver, patients with HBV infection with early-stage tumors had worse prognosis than patients without HBV infection, possibly due to the carcinogenetic potential of viral hepatitis in the remnant liver. Antiviral therapy should be considered after hepatectomy in patients with high HBV DNA levels.     

Predictors for Microinvasion of Small Hepatocellular Carcinoma ≤2?cm

Background

Hepatocellular carcinoma (HCC) ??2?cm in diameter is considered to have a low potential for malignancy.

Methods

A retrospective review was undertaken of 149 patients with primary solitary HCC ??2?cm who underwent initial hepatic resection between 1994 and 2010. The independent predictors of the microinvasion (MI) such as portal venous, hepatic vein, or bile duct infiltration and/or intrahepatic metastasis were identified by multivariate analysis. Prognosis of patients with HCC ??2?cm accompanied by MI was compared to that of patients with HCC ??2?cm without MI.

Results

Forty-three patients with HCC ??2?cm had MI in patients (28.9%). Three independent predictors of the MI were revealed: invasive gross type (simple nodular type with extranodular growth or confluent multinodular type), des-??-carboxy prothrombin (DCP) >100?mAU/ml, and poorly differentiated. Disease-free survival rates of patients with HCC ??2?cm with MI (3?year 44%) were significantly worse than those for HCC ??2?cm without MI (3?year 72%). This disadvantage of disease-free survival rate of patients with HCC ??2?cm with MI could be dissolved by hepatic resection with a wide tumor margin of ??5?mm (P?=?0.04).

Conclusions

Even in cases of HCC ??2?cm, patients who are suspected of having invasive gross type tumors in preoperative imaging diagnosis or who have a high DCP level (>100?mAU/ml) are at risk for MI. Therefore, in such patients, hepatic resection with a wide tumor margin should be recommended.     

Tumor Size Does Not Independently Affect Long-Term Survival after Curative Resection of Solitary Hepatocellular Carcinoma Without Macroscopic Vascular Invasion

Objective

The aim of this study was to investigate the prognostic value of tumor size alone on long-term survival and recurrence after curative resection for solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion.

Methods

A single-center cohort of 615 patients with solitary HCC (a single tumor, without macroscopic vascular invasion or distant metastasis) undergoing curative hepatic resection from 2002 to 2010 was retrospectively studied. Using 2.0, 3.0, 4.0, 5.0, 8.0, and 10.0 cm as cut-off values of tumor size, the overall survival (OS) and recurrence-free survival (RFS) rates were compared between the groups of patients with tumor size up to a certain cut-off value and the groups of patients with tumor size above that cut-off value. Thus, multiple comparisons were done. The prognostic factors of OS and RFS were evaluated using univariate and multivariate analyses.

Results

The median tumor size of all HCCs was 4.0 cm (range 0.9–22.0 cm). The in-hospital mortality rate was 1.0 %, and the overall morbidity rate was 22.3 %. The 1-, 3-, and 5-year OS rates were 96.0, 79.8, and 69.9 %, and the corresponding RFS rates were 83.6, 72.7, and 57.2 %, respectively. On univariate analyses, the 1-, 3-, and 5-year OS and RFS rates were significantly different between the individual two groups of patients as divided by the aforementioned different cut-off values of tumor sizes (all p < 0.05). However, when tumor size was put as a continuous variable into multivariate analysis, it was no longer an independent prognostic factor of OS or RFS after curative resection.

Conclusions

Tumor size did not independently affect long-term survival and recurrence after curative resection of solitary HCC without macroscopic vascular invasion. Therefore, there is no size limit that precludes hepatic resection for solitary HCC, provided the tumor is resectable.     

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.     

Could radiofrequency ablation replace liver resection for small hepatocellular carcinoma in patients with compensated cirrhosis? A 5-year follow-up

Purpose

Treating hepatocellular carcinoma involves many different specialists and requires multidisciplinary management. In light of the current discussion on the role of ablative therapy, the aim of this study is to compare patients who undergo hepatic resection to those treated with radiofrequency ablation.

Methods

The procedures have been conducted in two institutes following the same methodologies. Ninety-six patients with Child–Pugh class A cirrhosis, single or multinodular hepatocellular carcinoma (HCC) and a diameter less than or equal to 3 cm, have been included in this retrospective study: 52 patients have been treated by surgical resection and 44 by radiofrequency ablation. Patient characteristics, survival and disease-free survival have all been analysed.

Results

Disease-free survival was longer in the resection group in comparison to the radiofrequency group with a median disease-free time of 48 versus 34 months, respectively (P?=?0.04, hazard ratio?=?1.5, 95 % confidence interval?=?0.9–2.5). In the resection group, median survival was 54 months with a survival rate at 1, 3 and 5 years of 100, 98 and 46.2 %. In the radiofrequency group, median survival was 40 months with 1-, 3- and 5-year survival rate of 95.5, 68.2 and 36.4 %.

Conclusion

The current study shows that for small HCC in the presence of compensated cirrhosis, surgical resection gives better results than radiofrequency, both in terms of overall survival, as well as disease-free survival. Further evidence is required to clarify the role of ablative therapy as a curative treatment and whether it can replace surgery.     

The Significance of Classifying Microvascular Invasion in Patients with Hepatocellular Carcinoma

Background

Microvascular invasion (MVI) has been recognized as a risk factor for outcome following curative resection in hepatocellular carcinoma (HCC). Because MVI can range from few to many invaded vessels, we evaluated the significance of MVI classification in this study.

Methods

Between January 1995 and December 2010, 207 consecutive patients who underwent curative resection for HCC within Milan criteria were included in this retrospective study. Patients were classified into mild and severe MVI groups based on the number of vessels invaded. This study evaluated whether MVI classification can help to predict recurrence and survival after curative resection.

Results

Of the total 207 patients, 103 (50 %) patients had no detectable MVI, whereas 59 (28 %) had mild MVI, and 45 (22 %) had severe MVI. Recurrence-free survival rates at 2 years for patients without MVI, with mild MVI, and severe MVI were 75.9, 47.2, and 32.7 %, respectively. Patients with severe MVI experienced a high frequency of fatal recurrence, such as multiple tumors, macroscopic vascular invasion, and extrahepatic metastasis after curative resection. Multivariate analysis revealed age, number of tumors, mild MVI, and severe MVI as independent predictors of recurrence-free survival. Disease-specific survival rates at 5 years for patients without MVI, with mild MVI, and severe MVI were 91.5, 70.4, and 51.4, respectively. Multivariate analysis also revealed cirrhosis, tumor size, mild MVI, and severe MVI as independent predictors of disease-specific survival.

Conclusions

We demonstrated that MVI classification can stratify HCC patients by different patterns of recurrence and risk of survival after curative resection.     

Role of Operative Therapy in Non-cirrhotic Patients with Metastatic Hepatocellular Carcinoma

Introduction

We investigated the role of operative therapy in non-cirrhotic patients who developed metastatic hepatocellular carcinoma (HCC).

Methods

This retrospective cohort study included consecutive non-cirrhotic patients with metastatic HCC after a prior hepatectomy treated between 1990 and 2009. Patients were stratified by operative therapy (resection, ablation, transcatheter therapy). Kaplan?CMeier analyses with log-rank comparisons tested effects of operative therapy on overall survival (OS) and progression-free survival (PFS).

Results

Of 195 non-cirrhotic patients treated for HCC during the study period, 98 [median age 65, interquartile range (IQR) 53?C71; 55?% male] subsequently developed metastatic HCC (55 intrahepatic only). Median time to development of metastases after the index operation was 10?months (IQR 5?C20?months); median number of metastases was 3 (IQR 2?C7). Half of these patients (n?=?50) underwent operative treatment of metastases; 20 (40?%) underwent metastasectomy, 18 (36?%) ablation, and 12 (24?%) transcatheter therapy. Operative therapy was associated with improved OS (p?p????0.006). Nine patients (seven resection, two ablation) are disease free at a median of 50?months (IQR 24?C80?months) posttreatment.

Conclusions

Resection and ablation are associated with an improved PFS and long-term OS and should be considered in select patients with metastatic HCC.     

Effect of Body Composition on Outcomes after Hepatic Resection for Hepatocellular Carcinoma

Purpose

To evaluate the effect of body composition on outcomes after hepatic resection for patients with hepatocellular carcinoma (HCC).

Methods

We performed 190 hepatic resections for HCC and divided the patients into 2 groups on the basis of visceral fat area (VFA), assessed by computed tomographic measurement at the level of the umbilicus, into high VFA (H-VFA) (n = 106) and low VFA (L-VFA) (n = 84) groups. We compared the surgical outcomes between the two groups.

Results

L-VFA was significantly correlated with a lower body mass index, sarcopenia, lower serum albumin, and liver cirrhosis. There was no difference in the incidence of postoperative complications and mortality between the 2 groups. Patients in the L-VFA group had a significantly poorer prognosis than those in the H-VFA group in terms of both overall (P = 0.043) and recurrence-free (P = 0.001) survival. The results of multivariate analysis showed that sarcopenia rather than L-VFA was an independent and prognostic indicator after hepatic resection with HCC.

Conclusions

Body composition is an important factor affecting cancer outcomes after hepatic resection for HCC in Japan.     

Liver Resection for Metastatic Melanoma with Postoperative Tumor-Infiltrating Lymphocyte Therapy

Background

Patients with metastatic melanoma to the liver (MML) have a median survival of 4 to 6 months. This study evaluated patients who underwent liver resection with intent to receive postoperative tumor-infiltrating lymphocyte (TIL) therapy.

Methods

Retrospective analysis of a prospective database identified patients with MML who underwent liver resection from 1980 to 2008.

Results

A total of 539 patients had MML, and 39% (204 of 539) had tumor collected for TIL. A total of 17% (35 of 204) underwent liver resection for TIL. The 3-year overall survival was 53%. Lack of extrahepatic disease (P = .026), negative margin (P = .056), and single hepatic metastasis (P = .04) predicted survival after univariate analysis. Only lack of extrahepatic disease remained a significant predictor of survival after multivariate analysis (P = .043). A total of 31% (11 of 35) underwent complete resection without TIL, and 69% (24 of 35) underwent resection with synchronous intrahepatic and extrahepatic disease with intent to receive TIL. For 9 of 11 patients (2 of 11 excluded for gene therapy), 3-year survival was 80%. A total of 4 (44%) of 9 experienced recurrence, with a median disease-free survival of 1.2 years. For 24 patients (69%) with residual disease, 3-year survival was 51% (2 of 24 excluded for gene therapy). A total of 63% (15 of 24) received postoperative TIL (3-year survival 65%), and 29% (7 of 24) did not. A total of 40% (6 of 15) had disease that partially responded to TIL; the disease of 67% (4 of 6) had not progressed at median follow-up of 55 months (range, 42–197+ months). The seven patients who did not receive TIL had a median survival of 4.6 months.

Conclusions

Resection of MML with TIL should be considered because it can result in prolonged survival in a highly selected group of patients.     

Effects of Genomic Changes in Hepatitis B Virus on Postoperative Recurrence and Survival in Patients with Hepatocellular Carcinoma

Purpose

To determine whether the genomic changes in hepatitis B virus (HBV) affect the clinical outcomes of hepatocellular carcinoma (HCC) in patients with HBV-associated HCC treated with curative surgical resection.

Methods

A total of 247 patients with HBV-associated HCC were treated with curative surgical resection. They were followed regularly for a median of 30 months. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced.

Results

The genomic changes such as the G1896A at precore, the A1762T/G1764A at BCP, the C1653T and the T1753V at X gene, and pre-S2 deletion were not significantly associated with postoperative recurrence of HCC or survival of patients after curative resection. However, in univariate analysis, younger age, elevated serum α-fetoprotein level, elevated serum alanine aminotransferase level, larger tumor size, microvascular invasion, and advanced Cancer of the Liver Italian Program stage were closely associated with shorter survival after surgical resection. In multivariate analysis, only microvascular invasion revealed to be an independent risk factor of postoperative recurrence (relative risk [RR] 5.406; P < 0.001); the independent risk factors of shorter survival appeared to be infiltrative type (RR 5.110; P = 0.032), larger tumor size (RR 1.976; P = 0.047), and microvascular invasion (RR 6.118; P < 0.001).

Conclusions

The postoperative recurrence or survival period may not be affected by the genomic changes at the precore, BCP, X, and pre-S2 regions in HBV of genotype C2 in patients with HBV-associated HCC treated with curative surgical resection. Rather, it may be closely associated with tumor characteristics, such as the size and type of HCC or presence of microvascular invasion.