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.     

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.     

Impact of Intrahepatic Hepatitis B DNA and Covalently Closed Circular DNA on Survival After Hepatectomy in HBV-Associated Hepatocellular Carcinoma Patients

Background

Chronic hepatitis B virus (HBV) infection induces persistent but ineffective immune activation that contributes to necroinflammation, fibrosis, and risk of hepatocellular carcinoma (HCC). This study aims to determine the relationship of intrahepatic total HBV (ih HBV) DNA and covalently closed circular DNA (cccDNA) with necroinflammation and fibrosis, and their impact on prognosis after resection in HBV HCC patients.

Methods

Data are from 111 patients treated with primary liver resection for HBV HCC at Mount Sinai, New York (1991–2008). ih HBV DNA and cccDNA were quantitated by real-time PCR. Necroinflammation was graded according to histologic activity index (HAI), and liver fibrosis was staged by the modified Ishak method.

Results

A total of 106 (95 %) and 89 patients (80 %) had detectable ih HBV DNA and cccDNA, respectively, while 43 % had detectable serum HBV DNA. cccDNA made up a small proportion of ih HBV DNA (median cccDNA/ih HBV DNA ratio = 0.022). Higher levels of ih HBV DNA were associated with higher HAI and serum alanine aminotransferase (ALT), while a lower ratio of cccDNA/ih HBV DNA was associated with higher HAI, ALT, and Ishak fibrosis stage. ih HBV and cccDNA were not associated with survival, but the lowest quintile of cccDNA/ih HBV DNA ratio (<0.0024) was independently associated with poor overall survival.

Conclusions

A lower cccDNA/ih HBV DNA ratio was associated with greater necroinflammation and liver fibrosis, and was independently associated with poor overall survival. Thus, intracellular virus loads and relative proportions of virus DNA reflect histologic damage in the liver and influence the clinical outcome of HBV HCC patients.     

A Prospective Randomized Controlled Trial to Compare Pringle Manoeuvre with Hemi-hepatic Vascular Inflow Occlusion in Liver Resection for Hepatocellular Carcinoma with Cirrhosis

Background

The duration of hepatic vascular inflow occlusion and the amount of intraoperative blood loss have significant negative impacts on postoperative morbidity, mortality and long-term survival outcomes of patients who receive partial hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis.

Aim

This study aimed to compare the perioperative outcomes of partial hepatectomy for HCC superimposed on hepatitis B-related cirrhosis using two different occlusion techniques.

Methods

A randomized controlled trial was carried out to evaluate the impact of two different vascular inflow occlusion techniques. The postoperative short-term results were compared.

Results

During the study period, 252 patients received partial hepatectomy for HCC with cirrhosis. Of these patients, 120 were randomized equally into two groups: the Pringle manoeuvre group (n?=?60) and the hemi-hepatic vascular inflow occlusion group (n?=?60). The number of patients who had poor liver function on postoperative day 5 with ISLGS grade B or worse was 24 and 13, respectively (P?=?0.030). The postoperative complication rate was significantly higher in the Pringle manoeuvre group (40 versus 22 %, P?=?0.030). However, the Pringle manoeuvre group had significantly shorter operating time (116 versus 136 min, P?=?0.012) although there was no significant difference in intraoperative blood loss between the two groups [200 ml (range 10–5,000 ml) versus 300 ml (range 100–1,000 ml); P?=?0.511]. There was no perioperative mortality.

Conclusions

The results indicated that for patients with HCC with cirrhosis, hemi-hepatic vascular inflow occlusion was a better inflow occlusion method than Pringle manoeuvre.     

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.     

Diabetes Mellitus and Increased Postoperative Risk of Acute Renal Failure After Hepatectomy for Hepatocellular Carcinoma: A Nationwide Population-Based Study

Background

This study aimed to determine the effects of diabetes mellitus (DM) on the risk of surgical mortality and morbidity in patients undergoing hepatectomy for hepatocellular carcinoma (HCC).

Methods

We identified 2,962 DM patients who underwent a hepatectomy for HCC from 2000 to 2010. The non-DM control cohort consisted of 2,962 patients who also received a hepatectomy during the same period. Age, sex, comorbidities, and year of admission were all matched between the 2 cohorts.

Results

The prevalence of preoperative coexisting medical conditions was comparable between the DM and non-DM cohorts, except the percentage of patients undergoing major hepatectomy (lobectomy; 18.1 % in the DM cohort vs. 20.4 % in the non-DM cohort; p = 0.02).The hazard ratio (HR) of 30-day postoperative mortality in the DM patients after hepatectomy was 1.17 [95 % confidence interval (CI) 0.75–1.84] after adjustment. The DM cohort exhibited a significantly higher risk of postoperative septicemia (adjusted hazard ratio, 1.45; 95 % CI 1.06–2.00) and acute renal failure (adjusted hazard ratio, 1.70; 95 % CI 1.01–2.84) compared with that of the non-DM cohort, but this higher risk was not associated with the increased risk of other major morbidities, including pneumonia, stroke, and myocardial infarction. Further analysis showed that major hepatectomy (lobectomy) in DM patients carried higher risks of septicemia and acute renal failure. In multiple regression models, preoperative diabetes-related comorbidities were not significantly associated with 30-day postoperative mortality.

Conclusions

DM is associated with a significantly high risk of septicemia and acute renal failure, but not with other major complications or mortality, after hepatectomy for HCC.     

Inferior Right Hepatic Vein-preserving Major Right Hepatectomy for Hepatocellular Carcinoma in Patients with Significant Fibrosis or Cirrhosis

Background

Liver resection represents a most effective treatment for hepatocellular carcinoma (HCC). The extent of hepatectomy for HCC involves maintaining a tricky balance between radical resection of tumors and preservation of sufficient liver parenchyma. Generally, removal of the right hepatic vein often involves resection of the whole posterior right lobe, which may prevent patients with impaired liver function from maintaining a functional reserve and could also limit the future liver remnant from curative hepatectomy. As a common anatomic variation, preservation of the inferior right hepatic vein (IRHV) may enable preservation of liver segment 6, even when the right hepatic vein has to be removed. In the present study, we report our experience with IRHV-preserving major right hepatectomy.

Methods

From February 2009 to December 2011, eight trisegmentectomies 5-7-8 and two segmentectomies 4-5-7-8 were performed with the IRHV-sparing technique on patients with HCC and significant fibrosis or cirrhosis. Data including demographic information, preoperative evaluations, postoperative outcomes, and follow-up results were collected and evaluated.

Results

All patients survived and recovered from hepatectomy. The incidence of complications was higher in cirrhotic patients. The 1-year overall survival rate was 80 %, and the 1-year disease free survival rate was 60 %.

Conclusions

IRHV-preserving major right hepatectomy increases the resectability of HCC. Intraoperative ultrasonography is recommended to facilitate protection of the IRHV. This technique is safe with careful preoperative evaluation and meticulous perioperative care. The short-term outcome of IRHV-preserving liver resections is satisfactory.     

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.     

Infection with Hepatitis C Virus is an Adverse Prognostic Factor after Liver Resection for Early-stage Hepatocellular Carcinoma

Introduction

Recent data support liver resection (LR) as first-line approach in patients with preserved liver function who have resectable/transplantable hepatocellular carcinoma (HCC). This study was designed to evaluate the outcome of LR in patients with transplantable HCC.

Methods

Between 1998 and 2009, 75 patients (65 men, mean age 61 ± 11 years) with HCC eligible for liver transplantation (LT) underwent LR. The underlying hepatic disease was related to hepatitis C (HCV) in 30 (40 %) patients, hepatitis B (HBV) in 15 (20 %) patients, alcohol abuse in 26 patients (36 %) and other in 10 patients (13 %). Fifty-five (73 %) patients had cirrhosis. Intermittent clamping of the hepatic pedicle was used in 41 (55 %) patients. Treatment of recurrence by salvage LT was performed in 6 (8 %) patients.

Results

Operative morbidity and mortality rates were 37 and 5  % respectively. At 1, 3, and 5 years, overall (OS) and disease-free (DFS) survival rates were 81, 69,55 and 56, 31, and 21 %, respectively. On multivariate analysis, HCV infection was the only independent factor associated with decreased OS (p = 0.02). On multivariate analysis, HCV infection (p = 0.05) and intermittent hepatic pedicle clamping (p = 0.003) were associated with decreased DFS. The 1-, 3-, and 5-year OS and DFS rates in patients with HCV-related HCC were 69, 53, 38 and 50, 18, and 9% respectively.

Conclusions

Overall and disease-free survival after liver resection in patients with HCV-related HCC and preserved liver function is poor. Primary LT should be offered to these patients.     

Impact of laparoscopic liver resection for hepatocellular carcinoma with F4-liver cirrhosis

Background

Although the utility of laparoscopic liver resection for hepatocellular carcinoma (HCC) has been recognized in recent years, the impact of the laparoscopic liver resection for HCC with complete liver cirrhosis (F4) is still unknown.

Methods

Retrospective analysis of 56 patients who underwent partial hepatectomy for HCC (3 cm or smaller in a diameter) and had complete liver cirrhosis (F4) diagnosed histologically was performed. Of the 56 patients, partial hepatectomy was performed under laparotomy in 28 patients (laparotomy group) or under laparoscopy in 28 patients (laparoscopy group). Perioperative outcome was analyzed in the two groups.

Results

There were no significant differences in the results of the preoperative liver function tests and the operation time between the two groups. The intraoperative blood loss was lower in the laparoscopy group than the laparotomy group (p = 0.0003). The incidence of the postoperative complications was significantly higher in the laparotomy group (20/36 patients) than in the laparoscopy group (3/28 patients, p < 0.0001). The incidences of surgical site infection, especially incisional infection, and intractable ascites were significantly higher in the laparotomy group than in the laparoscopy group (p = 0.0095, p < 0.0001, respectively). The proportions of patients who were classified into Clavien’s grade I and IIIa were higher in the laparotomy group than in the laparoscopy group (p = 0.0043, p = 0.051, respectively). The duration of the postoperative hospital stay was significantly shorter in the laparoscopy group than in the laparotomy group (p < 0.0001).

Conclusions

The postoperative morbidity, such as surgical site infection and intractable ascites, decreased by the induction of laparoscopic liver resection in patients with liver cirrhosis. As the results, the necessity of invasive treatment for postoperative complications decreased and the duration of the postoperative stay was shortened.     

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.     

Preoperative Aspartate Aminotransferase to Platelet Ratio is an Independent Prognostic Factor for Hepatitis B-Induced Hepatocellular Carcinoma After Hepatic Resection

Background

There is conflicting evidence concerning platelet status and hepatocellular carcinoma (HCC) prognosis. We evaluated the prognostic value of platelet-based indices, including platelet count, platelet/lymphocyte ratio (PLR), and aspartate aminotransferase to platelet ratio index (APRI) in HCC after hepatic resection.

Methods

We retrospectively reviewed 332 patients with HCC treated with hepatectomy between 2006 and 2009. Preoperative platelet count, as well as demographic, clinical, and pathologic data, were analyzed.

Results

Both disease-free survival (DFS) and overall survival (OS) were significantly improved for patients with low platelet count, PLR, and APRI compared to patients with elevated values. On multivariate analysis, APRI, tumor size ≥5 cm, noncapsulation, and multiple tumors were all associated with both poor DFS and OS. The 1-, 3-, and 5-year DFS rates were 52, 36, and 32 % for patients with APRI <0.62 and were 35, 22, and 19 % for patients with APRI ≥0.62. Correspondingly, the 1-, 3-, and 5-year OS rates were 77, 51, and 42, and 63, 35, and 29 % for both groups. Both DFS and OS of patients with APRI <0.62 were significantly better compared to patients with an elevated APRI (P = 0.009 and 0.002, respectively). Patients with elevated APRI tended to have cirrhosis, hepatitis B virus (HBV) infection, surgical margin <1 cm, and noncapsulated tumors.

Conclusions

Elevated platelets based inflammatory indices, especially APRI, was associated with adverse characteristic features and poor prognosis in HCC, especially for patients with HBV infection or cirrhosis. Antiplatelet treatment may represent a potential therapy for HBV-induced HCC recurrence.     

Accuracy of preoperative automatic measurement of the liver volume by CT-scan combined to a 3D virtual surgical planning software (3DVSP)

Background

Liver volumetry is a critical component of safe hepatic surgery, in order to minimize the risk of postoperative liver failure. Liver volumes can be calculated routinely using the time-consuming gold standard method of manual volumetry. The current work sought to evaluate an alternative automatic technique based on a novel 3D virtual planning software, and to compare it to the manual technique.

Methods

A prospective study of patients undergoing liver resection was conducted. Every patient had a pre and 2-day postoperative CT-scan. For each patient, total, remnant and resected volumes were calculated manually and automatically. Planes of resection were verified by a hepatobiliary surgeon and compared with postoperative volumes. Paired t-tests and correlation coefficients were calculated.

Results

A major hepatectomy was carried out in 36/43 patients. The automatic TLV (1,759 mL) and the manual TLV (1,832 mL) were significantly different (p < 0.001), but extremely highly correlated (r = 0.989). The percentages of preoperative RLV (manual 58.5 %, automatic 58.9 %) were similar, with an excellent correlation of 0.917. The preoperative RLV were matched with the 2-day postoperative RLV showing a significant difference (p = 0.0301). The resected volumes using both techniques (871 and 832 mL) were compared with the resected specimen volume (670 mL), showing a significant difference (p < 0.001) but a high degree of correlation (r = 0.874).

Conclusion

The 3D virtual surgical planning software is accurate and reliable in determining the total liver and future remnant liver volumes. This technique demonstrates a good correlation with the manual technique. Future work will be required to confirm these findings and to evaluate the clinical value of the three-dimensional planning platform.     

The Impact of Posthepatectomy Liver Failure on the Recurrence of Hepatocellular Carcinoma

Background

Patients with hepatocellular carcinoma (HCC) who underwent hepatectomy often developed an intrahepatic recurrence, even though it was a curative one. The relationship between surgery-induced liver damage and the recurrence of HCC has not been described. This study evaluated whether posthepatectomy liver failure, as defined by the International Study Group of Liver Surgery, affected the recurrence of HCC.

Methods

We performed a retrospective cohort study of 488 patients with HCC who underwent hepatectomy between 2004 and 2012 at Kyoto University Hospital. Early posthepatectomy liver failure (EPLF) was defined as liver failure occurring between postoperative days 5 and 10. The patients were divided into an EPLF group and a non-EPLF group. Disease-free survival (DFS) was compared between these groups. The influences of host-related, surgery-related, and tumor-related factors on patient outcomes were evaluated using multivariate analyses.

Results

The EPLF group and the non-EPLF group contained 153 and 335 patients, respectively. The probability of DFS was significantly increased in the non-EPLF group (median: 574 days) compared to the EPLF group (median: 348 days) (hazard ratio, HR [95 % confidence interval, CI] 1.61 [1.29–2.00]). The multivariate analysis revealed that EPLF was an independent factor for DFS (HR [95 % CI] 1.43 [1.13–1.81]), besides the factors previously described, including fibrosis (1.32 [1.05–1.67]), stage (1.85 [1.34–2.51]), tumor differentiation (1.46 [1.11–1.89]), and des-γ-carboxyprothrombin (1.39 [1.10–1.74]).

Conclusions

EPLF was associated with postoperative HCC recurrence. The prevention of EPLF might improve the prognosis of patients with HCC.     

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.     

Improved Long-Term Survival after Major Resection for Hepatocellular Carcinoma: A Multicenter Analysis Based on a New Definition of Major Hepatectomy

Background

Advances in the surgical management of hepatocellular carcinoma (HCC) have expanded the indications for curative hepatectomy, including more extensive liver resections. The purpose of this study was to examine long-term survival trends for patients treated with major hepatectomy for HCC.

Patients and Methods

Clinicopathologic data for 1,115 patients with HCC who underwent hepatectomy between 1981 and 2008 at five hepatobiliary centers in France, China, and the USA were assessed. In addition to other performance metrics, outcomes were evaluated using resection of ≥4 liver segments as a novel definition of major hepatectomy.

Results

Major hepatectomy was performed in 539 patients. In the major hepatectomy group, median tumor size was 10 cm (range: 1–27 cm) and 22 % of the patients had bilateral lesions. The TNM Stage distribution included 29 % Stage I, 31 % Stage II, 38 % Stage III, and 2 % Stage IV. The postoperative histologic examination indicated that chronic liver disease was present in 35 % of the patients and tumor microvascular invasion was identified in 60 % of the patients. The 90-day postoperative mortality rate was 4 %. After a median follow-up time of 63 months, the 5-year overall survival rate was 40 %. Patients treated with right hepatectomy (n?=?332) and those requiring extended hepatectomy (n?=?207) had similar 90-day postoperative mortality rates (4 % and 4 %, respectively, p?=?0.976) and 5-year overall survival rates (42 % and 36 %, respectively, p?=?0.523). Postoperative mortality and overall survival rates after major hepatectomy were similar among the participating countries (p?>?0.1) and improved over time with 5-year survival rates of 30 %, 40 %, and 51 % for the years 1981–1989, 1990–1999, and the most recent era of 2000–2008, respectively (p?=?0.004). In multivariate analysis, factors that were significantly associated with worse survivals included AFP level >1,000 ng/mL, tumor size >5 cm, presence of major vascular invasion, presence of extrahepatic metastases, positive surgical margins, and earlier time period in which the major hepatectomy was performed.

Conclusions

This multinational, long-term HCC survival analysis indicates that expansion of surgical indications to include major hepatectomy is justified by the significant improvement in outcomes over the past three decades observed in both the East and the West.     

Recent trends in hepatectomy for elderly patients with hepatocellular carcinoma

Purpose

The incidence of hepatocellular carcinoma (HCC) in the elderly population has recently been increasing. In this study, we focused on a recent 10-year survey, and compared the clinicopathological features and postoperative outcomes of HCC in elderly (≥75 years of age) and younger patients (<75 years of age).

Methods

A total of 255 patients who underwent hepatectomy for HCC from 2001 to 2010 at Wakayama Medical University Hospital were reviewed. The clinical characteristics were compared between the elderly and younger patients. The risk factors for postoperative complications and prognostic factors were identified using the multivariate analyses.

Results

A total of 66 patients were classified as elderly patients. The incidence of HCC without viral liver disorders was significantly high in the elderly group than in the younger group. The independent risk factors [odds (95 % confidence intervals)] for postoperative complications were an ASA score of 3 [2.57 (1.20–5.49)] and the length of the operation [1.41 (1.09–1.81)]. The survival was similar between the two groups, and the only independent prognostic factor for survival in the elderly patients was vessel invasion.

Conclusions

HCC derived from non-viral liver disorders was dominant in the elderly patients. Aging itself was not a risk factor for postoperative complications or the survival outcome.     

Effect of Dosage and Type of Hepatitis B Immunoglobulin on Hepatitis Antibody Levels in Liver Transplant Recipients

Background

The current study aimed to evaluate the effect of dosage and type (intramuscular [IM] vs intravenous [IV]) of hepatitis B immunoglobulin (HBIG) on hepatitis antibody level in liver transplant recipients.

Clinicopathological and Prognostic Significance of Preoperative Serum Zinc Status in Patients with Hepatocellular Carcinoma After Initial Hepatectomy

Background

The purpose of this study was to determine the relationship between serum zinc (Zn) level and clinicopathological profiles in patients with hepatocellular carcinoma (HCC). Furthermore, we investigate the influence of serum Zn level on the long-term prognosis after hepatectomy.

Methods

A retrospective analysis was conducted of 310 patients who underwent initial hepatectomy for HCC. The correlation between serum Zn level and preoperative liver functional indicator, pathological features, including the degree of hepatic fibrosis, and perioperative outcome were evaluated. The patients were divided into two groups (serum Zn ≤ 65 mg/dL; n = 71 and Zn > 65 mg/dL; n = 239), and their long-term prognosis were compared.

Results

There were strong correlations between preoperative serum Zn level and serum albumin (r = 0.47, P < 0.0001), branched-chain amino acids (r = 0.28, P < 0.0001), and hyaluronic acid level (r = ?0.33, P < 0.0001). The patients with low Zn group were characterized as hepatitis C virus (HCV) infection, impaired liver function, background hepatic fibrosis, and pathological vascular invasion. The disease-free and overall survivals in the low Zn group were significantly lower than those in the high Zn group, especially in subgroup with HCV-related liver disease (P = 0.041 and 0.0004, respectively). Multivariate analyses showed that serum Zn level was an independent prognostic factor for overall survival (hazard ratio 1.79, P = 0.038).

Conclusions

Serum Zn level reflects liver function and is useful for predicting the hepatic fibrosis before surgery. The prognosis of patients with HCC was found to be associated with preoperative serum Zn level, especially in patients with HCV-related chronic liver disease.     

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.