High Expression of Patched Homolog-1 Messenger RNA and Glioma-Associated Oncogene-1 Messenger RNA of Sonic Hedgehog Signaling Pathway Indicates a Risk of Postresection Recurrence of Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) has a high recurrence rate after resection. Abnormal activation of the sonic hedgehog (SHH) signaling pathway contributing to the carcinogenesis of some organs had been reported. We hypothesize that activation of SHH pathway contributes to the recurrence of HCC after surgical resection.

Methods

In a prospective study, from January 2006 to June 2010, a total of 50 consecutive patients with HCC after curative resection were enrolled. The ratio of the expression of messenger RNA (mRNA) of SHH, patched homolog-1 (PTCH-1) and glioma-associated oncogene-1 (GLI-1) between HCC tissues and the paired noncancerous liver tissues were measured. Both the clinicopathologic characteristics and these ratios were compared between those with recurrence and those without recurrence. They were also compared between those with and without survival.

Results

There was a statistically significant correlation among the ratios of PTCH-1 mRNA and serum AFP level (p = 0.045), tumor size (p = 0.001), vascular permeation (p = 0.043) and tumor, node, metastasis staging system (TNM) stage (p = 0.003). A borderline significant correlation was found among ratios of GLI-1 mRNA and tumor size (p = 0.062) and TNM stage (p = 0.051). There was no such significant correlation between SHH mRNA and any parameter. Both the ratios of PTCH-1 mRNA and GLI-1 mRNA significantly adversely affected recurrence (p = 0.003 and 0.005, respectively) and survival (p < 0.001 and <0.001, respectively).

Conclusions

Expression of PTCH-1 mRNA and GLI-1 mRNA in HCC tissues is a potential biomarker to predict postresection disease recurrence.     

HBV DNA and HBsAg Levels as Risk Predictors of Early and Late Recurrence after Curative Resection of HBV-related Hepatocellular Carcinoma

Background

Recent studies have shown that high hepatitis B virus (HBV) load is associated with increased risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). The aim of our study was to investigate the predictive role of HBV DNA and hepatitis B surface antigen (HBsAg) levels in early and late recurrence of HCC after curative resection in patients with HBV-related HCC.

Methods

From January 2008 to December 2010, a total of 248 patients underwent curative resection for HBV-related early-stage HCC (solitary tumor; < 5 cm in diameter or multinodular tumor; number of tumors ≤3 and diameter < 3 cm). We analyzed the predictive factors including HBV DNA and HBsAg levels for early recurrence (within 2 years) and late recurrence (after 2 years) of HCC after curative resection.

Results

The median follow-up duration was 33.3 months. Cumulative recurrence rates after resection at 1, 3, and 5 years were 16.6, 34.0, and 46.7 %, respectively. The multivariate analysis showed that risk factors for early recurrence were the presence of microvascular invasion (hazard ratio [HR] 3.86; p < 0.001), preoperative HBV DNA levels ≥ 20,000 IU/mL (HR 2.77; p < 0.001), and des-γ-carboxy prothrombin level ≥ 40 mAU/mL (HR 1.76; p = 0.045). Although, the risk factors for late recurrence by multivariate analysis were preoperative HBsAg levels ≥ 4,000 IU/mL (HR 2.80; p = 0.023) and age at resection ≥ 50 years (HR 3.22; p = 0.032).

Conclusion

The HBV DNA levels were associated with early recurrence, whereas HBsAg levels were associated with late recurrence after curative resection in HBV-related HCC.     

Prognostic Significance of Preoperative Peripheral Blood Monocyte Ratio in Patients with Hepatocellular Carcinoma

Background

Leukocyte subsets in peripheral blood, which include neutrophils, lymphocytes, and monocytes, have not been well established as prognostic factors in patients with hepatocellular carcinoma (HCC).

Methods

Consecutive patients who underwent curative hepatic resection for HCC at the National Cancer Center, Republic of Korea, from 2001 to 2008 were enrolled in this retrospective study. Clinicopathologic factors, cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed with respect to preoperative lymphocyte subsets, especially monocyte ratio.

Results

The 603 patients had a median follow-up of 40.0 months and a 5-year overall survival rate of 67.7 %. In univariate analysis of survivals, preoperative lymphocyte ratio ≤35 % and monocyte ratio >7 % were significantly poor prognostic factors. In multivariate analysis, preoperative monocyte ratio >7 %, satellite nodule, and microvascular invasion were independent risk factors for CSS and DFS (hazard ratio of monocyte ratio >7 % = 1.77, p = 0.02 and 1.57, p = 0.006, respectively). Considering monocyte ratio with preoperative α-fetoprotein level, patients with both abnormal α-fetoprotein levels (>12 ng/mL) and monocyte ratio >7 % showed significantly worse CSS and DFS than other groups (p < 0.001). Cirrhotic patients with monocyte ratio >7 % showed significantly poor CSS and DFS compared with non-cirrhotic patients (p = 0.033 and <0.001, respectively).

Conclusions

A preoperative monocyte ratio >7 % of peripheral blood is an independent risk factor for CSS and DFS after hepatic resection for HCC. Preoperative monocyte ratio might be considered as a novel biomarker for HCC.     

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.     

Risk Factors for Early Recurrence of Single Lesion Hepatocellular Carcinoma After Curative Resection

Background and objectives

Hepatic resection is established as the treatment for HCC. However, patients sometimes experience early recurrence of HCC (ER HCC) after curative resection.

Methods

A retrospective analysis was conducted for 193 patients with single HCC who underwent curative liver resection in our medical center between April 2000 and March 2013. We divided the cohort into two groups; early recurrence group (ER G) which experienced recurrence within 6 months after resection, and non-early recurrence group (NER G). Risk factors for ER HCC were analyzed.

Results

Thirty-nine out of 193 (20.2 %) patients had ER HCC. Univariate analysis showed Glasgow prognostic score (GPS, p = 0.036), neutrophil to lymphocyte ratio (NLR, p = 0.001), level of PIVKA-II (p = 0.0001), level of AFP (p = 0.0001), amounts of blood loss (p = 0.001), operating time (p = 0.002), tumor size (p = 0.0001), stage III and IV (p = 0.0001), and microvascular invasions (portal vein: p = 0.0001 and hepatic vein: p = 0.001) to be associated with ER HCC. By multivariate analysis, there were significant differences in high NLR (p = 0.029) and high AFP (p = 0.0001) in patients with ER HCC.

Conclusions

Preoperative high AFP (more than 250 ng/ml) and high NLR (more than 1.829) were independent risk factors for ER HCC.

     

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.     

Above 5 cm,Size Does Not Matter Anymore in Patients with Hepatocellular Carcinoma

Background

Solitary hepatocellular carcinoma (HCC) is a good candidate for surgical resection. However, the significance of the size of the tumor in solitary HCC remains unclear.

Objective

The aim of this study was to evaluate the impact of tumor size on overall and recurrence-free survival of patients with solitary HCC.

Materials

We retrospectively reviewed 616 patients with histologically confirmed solitary HCC who underwent curative surgical resection between 1994 and 2010. The characteristics and prognosis of patients with HCC were analyzed stratified by tumor size.

Results

A total of 403 patients (65 %) had tumors <5 cm, 172 (28 %) had tumors between 5 and 10 cm, and 41 (7 %) had tumors >10 cm. The incidence of microvascular invasion, satellite nodules, and advanced tumor grade significantly increased with tumor size. The 5-year overall and recurrence-free survival rates of HCC <5 cm were 69.6 % and 32 %, respectively, which were significantly better than those of HCC between 5 and 10 cm (58 % and 26 %, respectively) and HCC >10 cm (53 % and 24 %, respectively). On multivariate analysis, cirrhosis (p = 0.0307), Child–Pugh B (p = 0.0159), indocyanine green retention rate at 15 min >10 % (p = 0.0071), microvascular invasion (p < 0.0001), and satellite nodules (p = 0.0009) were independent predictors of poor survival, whereas tumor size >5 cm was not.

Conclusion

Although recurrence rates are high, surgical resection for solitary HCC offers good overall survival. Tumor size was not a prognostic factor. Solitary large HCC >10 cm would be a good candidate for hepatectomy as well as solitary HCC between 5 and 10 cm.     

Combination of Osteopontin with Peritumoral Infiltrating Macrophages is Associated with Poor Prognosis of Early-Stage Hepatocellular Carcinoma after Curative Resection

Background

Crosstalk between a tumor and the microenvironment plays a key role in tumor progression and metastasis. This study was performed to elucidate the prognostic significance of combining tumor-secreted osteopontin (OPN) with microenvironment-associated peritumoral macrophages (PTMs) in hepatocellular carcinoma (HCC), especially for those with early-stage disease.

Methods

Tissue microarray-based immunohistochemistry was used to investigate OPN and PTMs expression in two independent cohorts consisting of 374 patients with HCC who underwent radical resection. The prognostic value for the two factors alone or in combination was investigated in these patients.

Results

OPN combined with PTMs was an independent prognostic factor for both overall survival (OS; p < 0.0001) and time to recurrence (TTR; p = 0.003) from the learning cohort (n = 96). Their combined value for prognosis was validated in early-stage HCCs using another independent cohort (n = 278; OS, p < 0.001; TTR, p = 0.001). This combination remained significant in HCCs with low α-fetoprotein levels in both cohorts, and was predictive for early recurrence/death risk (<2 years) compared with a single marker. Only OPN+HCCs had a significant correlation of PTMs levels with OS (p = 0.01) or TTR (p = 0.011).

Conclusions

Tumor OPN combined with PTMs is a promising predictor of tumor recurrence and survival in patients with HCC, especially for those with early-stage disease. The interplay of OPN and PTMs represents a new insight into tumor progression and therapeutic targets for HCC.     

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.     

Thermal Ablation Versus Repeated Hepatic Resection for Recurrent Intrahepatic Cholangiocarcinoma

Background

Repeated hepatic resection (HR) and thermal ablation therapy (TAT) are increasingly being used to treat recurrent intrahepatic cholangiocarcinoma (RICC). This study compared the efficacy and safety of these procedures for RICC treatment.

Methods

Patients were studied retrospectively after curative resection of RICCs by repeated HR (n = 32) or TAT (n = 77). Treatment effectiveness and prognosis were compared between the two treatment groups.

Results

The repeated HR and TAT groups did not differ in their overall survival (OS; p = 0.996) or disease-free survival (DFS; p = 0.692) rates. However, among patients with recurrent tumors >3 cm in diameter, patients in the repeated HR group had a higher OS rate than patients in the TAT group (p = 0.037). The number of recurrent tumors and the recurrence interval were significant prognostic factors for OS. The major complications incidence rate was greater in the repeated HR group than in the TAT group (p < 0.001).

Conclusions

Repeated HR and TAT are both effective treatments for RICC with similar overall efficacies. TAT should be preferred in any cases when the RICC is ≤3 cm in diameter and technically feasible. However, for large tumors (>3 cm), repeated HR may be a better choice.     

Hepatectomy for Huge Hepatocellular Carcinoma: Single Institute’s Experience

Background

The surgical resection of huge hepatocellular carcinoma (HCC) is still controversial. This study was designed to introduce our experience of liver resection for huge HCC and evaluate the safety and outcomes of hepatectomy for huge HCC.

Methods

A total of 258 hepatic resections for the patients with huge HCC were analysed retrospectively from December 2002 to December 2011. The operative outcomes were compared with 293 patients with HCC >5.0 cm but <10.0 cm in diameter. Prognostic factors for long-term survival were evaluated by univariate and multivariate analyses.

Results

The 1-, 3-, 5-year overall survival rates after liver resection were 84, 62, and 33 %. Overall survival and disease-free survival in huge HCC group and HCC >5.0 cm but <10.0 cm group were similar (P = 0.751, P = 0.493). Solitary huge HCC group has significantly a more longer overall and disease-free survival time than nodular huge HCC (P = 0.026, P = 0.022). Univariate and multivariate analysis revealed that the types of tumour, vascular invasion, and UICC stage were independent prognostic factors for overall survival (P = 0.047, P = 0.037, P = 0.033).

Conclusions

Hepatic resection can be performed safely for huge HCC with a low mortality and favorable survival outcomes. Solitary huge HCC has the better surgical outcomes than nodular huge HCC.     

Early Recurrence After Liver Resection for Colorectal Metastases: Risk Factors,Prognosis, and Treatment. A LiverMetSurvey-Based Study of 6,025 Patients

Purpose

The aims of this study were to assess the risk of early recurrence after liver resection for colorectal metastases (CRLM) and its prognostic value; identify early recurrence predictive factors; clarify the effect of perioperative chemotherapy on its occurrence; and elucidate the best early recurrence management.

Methods

Patients of the LiverMetSurvey registry who underwent complete liver resection (R0/R1) between 1998 and 2009 were reviewed. Early recurrence was defined as any recurrence that occurred within 6 months after resection.

Results

A total of 6,025 patients were included; 2,734 (45.4 %) had recurrence, including 639 (10.6 %) early recurrences. Early recurrence was mainly hepatic (59.5 vs. 54.4 % for late recurrences; p = 0.023). Independent risk factors of early recurrence were: T3–4 primary tumor (p = 0.0002); synchronous CRLM (p = 0.0001); >3 CRLM (p < 0.0001); 0-mm margin liver resection (p = 0.003); and associated intraoperative radiofrequency ablation (p = 0.0005). Response to preoperative chemotherapy (complete/partial) and administration of adjuvant chemotherapy reduced early recurrence risk (p = 0.003 and p < 0.0001, respectively). Intraoperative ultrasonography reduced hepatic early recurrence rate (p = 0.025). Early recurrence negatively affected prognosis: 5-year survival 26.9 versus 49.4 % for the late recurrence group (p < 0.0001, median follow-up 34.4 months). Overall, 234 (36.6 %) patients with early recurrence underwent re-resection. These patients had survival rates higher than non-re-resected patients (5-year survival 47.2 vs. 8.9 %; p < 0.0001) and similar to re-resected patients for late recurrence (48.7 %). Chemotherapy before early recurrence resection improved later survival (5-year survival 61.5 vs. 43.7 %; p = 0.028).

Conclusions

Early recurrence risk is enhanced for extensive disease after poor preoperative disease control and inadequate surgical treatment, but is reduced after adjuvant chemotherapy. Although early recurrence negatively affects prognosis, re-resection may restore better survival. Chemotherapy before early recurrence resection is advocated.     

Total Tumor Volume Is a Better Marker of Tumor Burden in Hepatocellular Carcinoma Defined by the Milan Criteria

Background

The Milan criteria are used to define small hepatocellular carcinoma (HCC) and to select patients for curative treatments. Total tumor volume (TTV) is an alternative parameter for tumor burden. We aimed to evaluate whether TTV is a feasible prognostic marker in HCC patients with upper boundary TTV of 65.5 cm³, which is equivalent to a single 5 cm tumor nodule defined by the Milan criteria.

Methods

A total of 774 HCC patients with TTV <65.5 cm³ receiving surgical resection, liver transplantation, or radiofrequency ablation (RFA) as the primary treatment were retrospectively analyzed.

Results

Of these patients, 50 (6.5 %) did not fulfill the Milan criteria. Patients beyond the Milan criteria more often had larger tumor size and TTV, as well as more tumor nodules (p values all <0.01). There was no significant survival difference between patients within and beyond the Milan criteria (p = 0.205). Patients with TTV >15 cm³ had a significantly poorer survival than patients with TTV <15 cm³ (p = 0.007). There was no survival difference between patients receiving surgical treatments versus RFA (p = 0.932). In the Cox proportional hazards model, TTV >15 cm³ [risk ratio (RR): 1.474, p = 0.005], serum bilirubin ≥1.5 mg/dL (RR: 1.663, p = 0.003), serum sodium <135 mmol/L (RR: 2.016, p = 0.01), and α-fetoprotein (AFP) ≥100 ng/mL (RR: 1.37, p = 0.033) were independent predictors of poor prognosis.

Conclusions

Total tumor volume, is an independent and better prognostic marker than the Milan criteria to indicate tumor burden in HCC patients who had tumor volume defined by the Milan criteria and underwent curative therapies.     

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.     

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.     

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.     

Adjuvant Hepatic Arterial Infusion Chemotherapy after Hepatic Resection of Hepatocellular Carcinoma With Macroscopic Vascular Invasion

Background

The prognosis of hepatocellular carcinoma (HCC) with macroscopic vascular invasion is extremely poor even after hepatic resection. We aimed to clarify the efficacy of adjuvant hepatic arterial infusion chemotherapy (HAI) for HCC with vascular invasion.

Methods

A total of 73 HCC patients with macroscopic vascular invasion were divided into two groups: 38 with hepatectomy with HAI (HAI group) and 35 with hepatectomy alone (non-HAI group). From 1997 to 2007, HAI was performed via an implanted injection port. The treatment comprised three courses of weekly infusion of HAI, which comprised cisplatin (10 mg daily on days 1–5) followed by 5-fluorouracil (5-FU; 250 mg daily on days 1–5) infusion. From 2007, cisplatin (60 mg/m²), 5-FU (600 mg/m²), and a mixture of mitomycin C (3 mg/m²) and degradable starch microspheres were administered for two courses.

Results

Overall, 92 % of patients completed adjuvant HAI. In the HAI and non-HAI groups, the 5-year disease-free survival (DFS) rates were 33.1 % and 11.8 %, respectively (p = 0.029), and the 5-year overall survival (OS) rates were 46.7 % and 32.7 %, respectively (p = 0.318). Among the patients with Vp3/4 or Vv3 (n = 32) in the HAI group, the 3-year DFS and OS rates were 33.7 % and 56.8 %, respectively (p = 0.049). Those in the non-HAI group were 8.3 % and 12.0 %, respectively (p = 0.023). Cox proportional multivariate analysis for DFS revealed that HAI was an independent favorable prognostic factor in all 73 patients (hazard ratio 0.536; p = 0.029).

Conclusions

Adjuvant HAI for HCC patients with vascular invasion might reduce the risk of recurrence.     

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.     

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.     

Impact of Viral Hepatitis on Outcomes after Liver Resection for Hepatocellular Carcinoma: Results from a North American Center

Background

Hepatitis B (HBV) and hepatitis C (HCV) are well-recognized risk factors for hepatocellular carcinoma (HCC). The characteristics and clinical outcomes of HCC arising from these conditions may differ. This study was conducted to compare the outcomes of HCC associated with HBV and HCV after liver resection.

Methods

Of 386 liver resections for HCC performed between July 1992 and April 2011, 181 patients had HBV and 74 patients had HCV. Patients with HBV/HCV coinfections (n = 20), non-HBV/HCV etiology (n = 94), and postoperative death within 3 months (n = 17) were excluded. Patient, tumor characteristics, and perioperative and oncologic outcomes were compared between patients with HBV and HCV.

Results

The patients with HBV had better overall survival (OS) than patients with HCV (68 vs. 59 months, p = 0.03); however, there was no difference in recurrence-free survival (RFS) between the groups (44 vs. 45 months, p = 0.1). The factors predictive of OS based on multivariate analyses included: vascular invasion [p < 0.01, hazard ratio (HR) = 3.4], Child-Pugh Score (p < 0.01, HR = 4.8), and underlying liver disease (HCV vs HBV) (p = 0.01, HR = 1.9). Vascular invasion and tumor number (p < 0.01, HR = 2.3 and p < 0.01, HR = 2.1) were independent predictors of RFS.

Conclusions

OS but not RFS after liver resection for HCC is better in patients with HBV than HCV. This survival advantage for HBV patients may be due to differences in tumor biology and outcomes after disease recurrence.