The Postresection Alpha-Fetoprotein in Cirrhotic Patients with Hepatocellular Carcinoma. An Independent Predictor of Outcome

Background

The postresection alpha-fetoprotein (AFP) in cirrhotic patients with hepatocellular carcinoma (HCC) may predict overall survival (OS) and recurrence beyond Milan criteria (MC) among the subgroup of initially transplantable patients.

Methods

All patients with cirrhosis resected for HCC between January 1990 and December 2010 in a single institution and presenting a serum AFP value?>?15 ng/ml at diagnosis were included. The postresection AFP was analyzed as a dichotomized variable: normalization (norm + group) or not (norm ? group) within the 90-day postresection period.

Results

Among 271 resected patients, 141 patients (52 %) had a level of serum AFP?≥?15 ng/ml at diagnosis. Five-year OS and median survival were 42 % and 52 months in group norm + versus 20 % and 23 months in the group norm ? (P?=?0.009). On multivariate analysis, the absence of AFP normalization was an independent factor of poor OS as well as microvascular invasion, and satellites nodules. Among theoretically transplantable patients, independent predictors of recurrence beyond MC were the absence of AFP normalization (risk ratio (RR) 5.02 [1.53–16.34]) and microvascular invasion (RR 4.76 [1.42–15.34]).

Conclusion

The postresection AFP has an independent prognostic value. Transplantable patients resected for HCC without 90-day AFP normalization should be discussed for early liver transplantation.     

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.     

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.     

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.     

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.     

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.     

Prognosis of Fibrolamellar Carcinoma Compared to Non-cirrhotic Conventional Hepatocellular Carcinoma

Background

Fibrolamellar carcinoma (FLC) and conventional hepatocellular carcinoma (HCC) share the same American Joint Committee on Cancer (AJCC) staging. The worse survival with HCC is attributed to the underlying cirrhosis.The aim of this study was to compare stage-matched prognosis after resection of FLC and non-cirrhotic HCC.

Methods

Outcomes after resection of 65 consecutive patients with FLC and 158 non-cirrhotic patients with HCC were compared. Patients were staged according to the 7th edition AJCC staging.

Results

The AJCC stage distributions for FLC and HCC demonstrated a predominance of stage IV disease in FLC and stage I in HCC (FLC stage I—23 %, II—15 %, III—15 %, IV—46 % vs. HCC stage I—42 %, II—32 %, III—20 %, IV—6 %, p?<?0.001). Among stage IV FLC patients, 81 % had isolated nodal metastases, which did not affect overall survival (OS) or recurrence-free survival (RFS). In FLC, OS was significantly affected by the number of tumors and vascular invasion (p?<?0.05). Recurrent disease developed in 56 (86 %) FLC patients and was treated with repeat surgical resection in 25 (45 %) patients. Vascular invasion was associated with recurrent FLC, with 3-year RFS rates of 9 % and 35 %, with and without vascular invasion (p?=?0.034). With respect to RFS, the AJCC staging did not stratify FLC patients, compared to non-cirrhotic HCC.

Conclusions

When compared to non-cirrhotic HCC, patients with FLC are not adequately stratified by AJCC staging with respect to RFS. Our results support classifying lymph node metastases in FLC as regional disease, rather than systemic disease. Important prognostic factors in FLC are the number of tumors and vascular invasion.

     

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.     

Assessment of ISGLS Definition of Posthepatectomy Liver Failure and Its Effect on Outcome in Patients with Hepatocellular Carcinoma

Background

Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients.

Methods

We retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. The median follow-up period after hepatectomy was 35.2 months.

Results

Thirty-nine (18.6 %) patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at 1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and 45.1/57.8 %, respectively (P?=?0.002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and 15.7/20.3 %, respectively (P?=?0.003). Multivariate analysis revealed that PHLF was significantly associated with both OS (P?=?0.047) and RFS (P?=?0.019). Extent of resection (P?<?0.001), intraoperative blood loss (P?=?0.002), and fibrosis stage (P?=?0.040) were identified as independent risk factors for developing PHLF.

Conclusion

The ISGLS definition of PHLF was associated with OS and RFS in HCC patients, and long-term survival will be improved by reducing the incidence of PHLF.     

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.     

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

Background

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

Methods

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

Results

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

Conclusions

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

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.     

Systematic Review and Meta-Analysis of Adjuvant I131 Lipiodol after Excision of Hepatocellular Carcinoma

Background

Curative resection for hepatocellular carcinoma (HCC) has an 80 % recurrence at 5 years. Survival could be prolonged with adjuvant iodine¹³¹ lipiodol. This systematic review and meta-analysis was designed to assess the survival benefit of this treatment in patients with resected HCC compared with surgery alone.

Methods

Studies were identified through a systematic search of MEDLINE, EMBASE, PubMed, and Cochrane databases in June 2013. Three case-control series and two randomized, controlled trials (RCT) were included. Two of these studies had a second publication that analyzed long-term follow-up. Two reviewers extracted data with respect to disease-free and overall survival (OS). The data from the seven studies was then subject to meta-analysis.

Results

Age, sex, liver function, tumor size, encapsulation, microvascular invasion, multifocality, and the rate of major hepatic resection were similar in the two groups. Peto odds ratio for disease-free survival was 0.47 (95 % confidence interval (CI) 0.37–0.59, I ² = 10 %) and for OS was 0.5 (95 % CI 0.39–0.64, I ² = 37 %), in favor of treatment.

Conclusions

This study is limited by its comparison of two RCTs with three case-control studies. Most patients also had preserved liver function, and there was a generally low rate of microvascular invasion. Nonetheless, there is strong evidence for the use of adjuvant I¹³¹ lipiodol, to prolong disease-free and OS, up to 5 years after resection.     

Discrepancy Between Recurrence-Free Survival and Overall Survival in Patients with Resectable Colorectal Liver Metastases: A Potential Surrogate Endpoint for Time to Surgical Failure

Background

Recurrence-free survival (RFS) may not be a surrogate for overall survival (OS) in patients with resectable colorectal liver metastases (CLM). We investigated whether a new composite tool—time to surgical failure (TSF)—is a suitable endpoint.

Methods

The medical records of consecutive patients who underwent curative resection for CLM at our center over a 17-year period were reviewed. Patients with liver-limited tumors (n = 371) who had not received previous treatment for metastasis were eligible for analysis. TSF was defined as the time until unresectable relapse or death. The correlations between TSF and OS, and between RFS and OS, were assessed for all the eligible patients.

Results

The median OS, TSF, and RFS were 5.7, 2.7, and 0.7 years, respectively, and the 5-year OS, TSF, and RFS rates were 52.6, 39.8, and 23.7 %, respectively, for all patients. The rates of first, second, and third relapse were 75.5, 77.6, and 70.8 %, respectively, and repeat resections were performed in 54.3 % (first relapses), 40.7 % (second relapses), and 47.1 % (third relapses) of patients. The concordance proportions of TSF and RFS for OS events were 0.83 and 0.65, respectively. The correlation between TSF and OS was stronger than that between RFS and OS in terms of the predicted probabilities.

Conclusions

The correlation between TSF and OS was stronger than that between RFS and OS after curative hepatic resection. TSF could be a suitable endpoint for CLM overall management.     

Adjuvant Hepatic Intra-arterial Iodine-131-Lipiodol Following Curative Resection of Hepatocellular Carcinoma: A Prospective Randomized Trial

Background

The purpose of the present study was to determine whether intrahepatic injection of ¹³¹I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC).

Methods

From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4–6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan–Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong.

Results

The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46–1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51–1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by ¹³¹I-lipiodol and hepatic artery dissection during angiography.

Conclusions

The randomized trial provides insufficient evidence to recommend the routine use of ¹³¹I-lipiodol in these patients.     

Recurrence of Hepatocellular Carcinoma in Noncirrhotic Liver After Hepatectomy

Background

Hepatocellular carcinoma in noncirrhotic liver (HCCNC) is rare. This tumor has a particular epidemiology and presentation, and it requires specific treatment, compared with HCC in cirrhotic liver. The aims of this study were to determine the survival and recurrence rates, prognostic factors, and optimum treatment of HCCNC and to propose a follow-up protocol for patients who have undergone surgery for HCCNC.

Methods

This study included 131 patients who underwent surgical treatment for HCCNC from January 1992 to December 2010. Survival and recurrence rates were evaluated, and the prognostic factors and characteristics of recurrence were analyzed. Pathologic characteristics of the tumors and the nontumoral liver were examined.

Results

The mean survival time was 67.9 months. The 5- and 10-year overall survival rates were 72.9 and 36.7 %, respectively. In all, 54 patients (41.2 %) developed recurrence at a median interval of 30.96 months. Of these recurrences, 31.5 % occurred during the first year, and 24.1 % occurred more than 5 years after surgery. Macro- or microvascular invasion and tumor size >5 cm were significantly associated with a poor survival rate. The predictive factors for recurrence were multiple tumors, tumor diameter >5 cm, and satellite nodules. Patients who underwent surgical treatment for recurrence had a significantly longer survival time than those who did not (p < 0.0292).

Conclusions

Recurrence is the most common cause of death after hepatectomy for HCC, and patients should undergo careful, long-term follow-up. Early detection and treatment of recurrence with curative intent should improve the prognosis of these patients.     

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

Background

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

Methods

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

Results

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

Conclusions

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

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.     

The oncological outcomes of segmentectomy in clinical-T1b lung adenocarcinoma with a solid-dominant appearance on thin-section computed tomography

Purpose

We investigated the surgical outcomes of clinical-T1b lung adenocarcinomas patients whose tumors had a solid-dominant radiological appearance and who were treated with segmentectomy or lobectomy.

Methods

We examined 154 surgically resected clinical-T1b lung adenocarcinomas with a “solid-dominant” appearance on thin-section computed tomography (CT). The preoperative thin-section CT images of all cases were reviewed. “Solid-dominant” was defined as 0.5≤ consolidation/tumor ratio (CTR) <1.0.

Results

Pathological nodal metastasis, lymphatic invasion, vascular invasion, and pleural invasion were found in 7 (4.5 %), 27 (18 %), 21 (14 %), and 15 (10 %) patients with clinical-T1b solid-dominant lung adenocarcinoma, respectively. Lobectomy and segmentectomy were performed in 123 (80 %) and 31 (20 %) cases, respectively. The 3-year overall survival (OS) and relapse-free survival (RFS) of patients with clinical-T1b solid-dominant lung adenocarcinoma were 95.5 and 92.4 %, respectively. The 3-year RFS and OS did not differ significantly between the patients who underwent lobectomy or segmentectomy (3-year RFS, 92.3 vs. 93.4 %, p = 0.8713; 3-year OS, 95.3 vs. 96.6 %, p = 0.7603). Segmentectomy was not found to be a prognostic factor for RFS (p = 0.8714), or OS (p = 0.7613).

Conclusions

Segmentectomy can achieve acceptable oncological outcomes (both in terms of OS and RFS), which are similar to those achieved with standard lobectomy, in patients with clinical-T1b solid-dominant lung adenocarcinoma.