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.     

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.

     

Antiviral Therapy Decreases Recurrence of Hepatitis B Virus-related Hepatocellular Carcinoma after Curative Resection: A Meta-analysis

Background

The long-term outcome after curative resection of hepatocellular carcinoma (HCC) remains unsatisfactory because of the high incidence of recurrence. The present study was intended to assess the impact of hepatitis B virus (HBV) DNA level and nucleos(t)ide analog therapy on posthepatectomy recurrence of HBV-related HCC.

Methods

Eligible studies were identified through a computerized literature search. The pooled relative risk ratio (RR) with 95 % confidence interval (CI) was calculated using Review Manager 5.1 Software.

Results

Twenty studies with a total of 8,204 participants were included for this meta-analysis. Pooled analysis showed that high viral load was significantly associated with risk of recurrence (RR: 1.85, 95 % CI: 1.41–2.42; P < 0.001), poorer disease-free survival (DFS) (RR: 1.96, 95 % CI: 1.62–2.38; P < 0.001), and poorer overall survival (OS) (RR: 1.47, 95 % CI: 1.22–1.77; P < 0.001) of HBV-related HCC after surgical resection. Nucleos(t)ide analog therapy significantly decreased the recurrence risk (RR: 0.69, 95 % CI: 0.59–0.80; P < 0.001) and improved both DFS (RR: 0.70, 95 % CI: 0.58–0.83; P < 0.001) and OS (RR: 0.46, 95 % CI: 0.32–0.68; P < 0.001).

Conclusions

High DNA level is associated with posthepatectomy recurrence of HBV-related HCC. Nucleos(t)ide analog therapy improves the prognosis of HBV-related HCC after resection.     

Prognostic Factors and Optimal Treatment Strategy for Intrahepatic Nodular Recurrence After Curative Resection of Hepatocellular Carcinoma

Background Intrahepatic recurrence is a major problem after curative resection of hepatocellular carcinoma. However, the most effective treatments for patients with intrahepatic recurrence still remain unclear. In addition, the selection of various treatment modalities such as repeat resection, local ablation therapy, and transarterial chemoembolization is only applicable to patients with intrahepatic nodular recurrence. Methods Of 353 patients who underwent curative resection, 97 patients with intrahepatic nodular recurrence were retrospectively studied. The prognostic factors for survival after recurrence and treatment modalities were analyzed. The patients were divided into two groups, a control group and a progression group, according to their response to initial treatment for recurrent tumors. Results The 1-, 3-, and 5-year overall survival rates after recurrence in patients with intrahepatic nodular recurrence were 91.0%, 71.0%, and 37.5%, respectively. Multivariate analysis revealed that early recurrence (≤12 months), Child-Pugh class B or C at diagnosis of recurrence, and serum albumin level of ≤3.5 g/dL at diagnosis of recurrence were poor prognostic factors for survival after recurrence. With regard to the response to the initial treatment, time to recurrence of ≤12 months was found to be the only statistically significant risk factor for progression of disease in multivariate analysis. Conclusions Time to recurrence, which usually corresponds with the cellular origin of recurrence, seems to be more important when determining the prognosis of patients with recurrent disease and treatment response than treatment modality. Therefore, different treatment methods should be selected according to the time to recurrence of intrahepatic nodular recurrence.     

Prospective Case-controlled Trial of Adjuvant Chemotherapy after Resection of Hepatocellular Carcinoma

Recurrence of hepatocellular carcinoma (HCC) after curative hepatic resection is frequent and is an important factor adversely influencing long-term survival. The role of postoperative chemotherapy in the reduction of tumor recurrence rate is still controversial. During the period of 1992–1995 a series of 49 patients who underwent curative resection of HCC and had at least one risk factor of tumor recurrence were followed in this prospective study. Patients were allocated to adjuvant chemotherapy and control groups. Twenty-four patients received a combination of low dose intravenous epirubicin (20 mg/m²) and mitomycin (5 mg) monthly for seven courses starting 5 to 6 weeks after surgery. Twenty-five patients had no adjuvant treatment. The disease-free and overall survivals were compared for the two groups. A total of 154 courses of chemotherapy were given to the 24 patients. The chemotherapy-related side effects were mild and tolerable with no mortality. At a median follow-up of 39 months (range 9–71 months), 9 patients in the adjuvant chemotherapy group and 16 patients in the control group developed tumor recurrence. The respective 1-, 2-, 3-, and 5-year disease-free survival rates were 75%, 67%, 63%, and 63% for patients in the adjuvant chemotherapy group and 68%, 42%, 37%, and 32% for patients in the control group (p= 0.0575). The 1-, 2-, 3-, and 5-year overall survival rates were 100%, 96%, 77%, and 72% in the adjuvant chemotherapy group and 92%, 67%, 63%, and 51% in the control group (p= 0.0746). In conclusion, postoperative adjuvant chemotherapy using the present regimen has a tendency to reduce tumor recurrence rate and may improve long-term survival for high risk patients.     

Analysis of the Risk Factors of Untransplantable Recurrence After Primary Curative Resection for Patients with Hepatocellular Carcinoma

Purpose

To determine the prognostic factors that predict recurrence of hepatocellular carcinoma (HCC) exceeding the University of California at San Francisco (UCSF) criteria after primary resection.

Methods

HCC patients who underwent curative liver resections between 2001 and 2007 and who were within the UCSF criteria (n = 716) were examined. Independent prognostic factors were examined by the Cox proportional hazard model.

Results

A total of 285 patients (39.8 %) developed recurrences. Of the patients who developed recurrences, 180 had HCC still within the UCSF criteria (63.2 %), and 105 developed HCC beyond this criteria (36.8 %). Among the population with primary transplantable HCC, patients with larger primary tumor sizes, serum α-fetoprotein (AFP) levels over 400 ng/mL, satellite nodules, vascular invasion, or undifferentiated HCC had a risk of untransplantable recurrence, as shown by univariate analysis. In multivariate analysis, undifferentiated HCC and vascular invasion were identified as the significant predictors with adjusted hazard ratios of 9.25 [95 % confidence interval (CI) 2.13–40.21] and 2.19 (95 % CI 1.34–3.58), respectively. When only preoperative factors were considered in multivariate analysis, primary tumor size and serum AFP levels over 400 ng/mL were identified as significant predictors with adjusted hazard ratios of 1.24 (95 % CI 1.07–1.45) and 1.72 (95 % CI 1.05–2.82), respectively.

Conclusions

For primary HCC patients within the UCSF criteria, larger tumor sizes and AFP levels over 400 ng/mL were associated with postresection recurrence of HCC exceeding the UCSF criteria. Because these are clearly markers for aggressive tumor biology, whether early primary transplant will alter the aggressive tumor behaviors warrant further investigation.     

Testimony Therapy With Ritual: A Pilot Randomized Controlled Trial*

Testimony therapy can provide low‐cost, brief, simple, and culturally adaptable psychosocial services in low‐income countries (Agger, Raghuvanshi, Khan, Polatin, & Laursen, 2009). Nonetheless, there have been no well‐controlled studies of testimony therapy. We report the analyses of a randomized controlled trial designed to assess the effectiveness of testimony therapy plus a culturally adapted ceremony in reducing mental health symptoms among Khmer Rouge torture survivors from across Cambodia. Using multilevel modeling, we compared symptoms of posttraumatic stress disorder, anxiety, and depression between a treatment (n = 45) and a control group (n = 43) at baseline, 3 months, and 6 months. We found that testimony therapy plus ceremony significantly reduced symptoms of posttraumatic stress disorder (d = 0.49), anxiety (d = 0.44), and depression (d = 0.53).     

Clinical Features of Hepatocellular Carcinoma Developing Extrahepatic Recurrences After Curative Resection

BACKGROUND: Few details of the clinical features of hepatocellular carcinoma (HCC) developing extrahepatic recurrence after a curative resection have been published. The purpose of this study was to clarify the clinicopathologic findings of patients with HCC who experienced extrahepatic metastases. METHODS: Clinicopathologic data were available for 119 patients who underwent an R0 resection for HCC. Twenty-three patients who developed extrahepatic metastases during the follow-up period were compared with the patients who remained free from recurrence for at least 5 years after resection (n = 21) or with only intrahepatic recurrences (n = 75). RESULTS: Patients with extrahepatic recurrences were more likely to have their tumor macro- or microscopically invading the tumor capsule (P < 0.001) and hepatic vein (P = 0.003), a high AFP concentration (P = 0.014), and advanced TNM stage (P = 0.006) than the other patients. As for treatment-related variables, inflow vessel occlusion during hepatectomy was less frequently associated with extrahepatic recurrences than if it were not performed (P < 0.001). By multivariate analysis, absence of tumor invasion to the capsule (relative risk [RR] = 0.080; P = 0.023) or to the hepatic vein (RR = 0.108; P = 0.014) and a hepatectomy in which inflow vessel occlusions were performed (RR = 0.161; P = 0.004) were selected as independent factors for reducing extrahepatic recurrences after a hepatectomy. CONCLUSION: In HCC patients, the control of intrahepatic recurrences and extrahepatic recurrences after a hepatectomy is important to improve the prognosis. Inflow occlusion during the hepatectomy may reduce HCC metastases to extrahepatic sites.     

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.     

Survival Benefit of Transplantation for Recurrence of Hepatocellular Carcinoma After Liver Resection

Background

Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non–transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies.

Methods

We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list.

Results

The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P = .84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P = .3), whereas 5-year ITT survival of DW patients was significantly higher (P < .01) than that of 105 beyond-Milan HCC patients resected only.

Conclusions

LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group.     

A Prognostic Model and Treatment Strategy for Intrahepatic Recurrence of Hepatocellular Carcinoma after Curative Resection

Background  

The aim of this study was to evaluate the prognostic factors for intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resection.     

Adjuvant I-131 Lipiodol After Resection or Radiofrequency Ablation for Hepatocellular Carcinoma

Background and objectives

High rates of recurrence have been observed after curative treatment for hepatocellular carcinoma (HCC). The main aim of this study was to establish the influence of adjuvant transarterial radioembolization-based I-131 lipiodol on survival and recurrence.

Methods

Between 2004 and 2010, 38 patients were treated with adjuvant I-131 lipiodol therapy, at a dosage of 2220 MBq, within 4 months after surgery. This treated cohort was compared to a control cohort consisting of 42 consecutive patients operated prior to the time the I-131 lipiodol treatment became available.

Results

Recurrence-free survival in the control and in the I-131 lipiodol cohort was 12.6 and 18.7 months, respectively (HR = 1.871, p = 0.025). At 2 and 5 years, the cumulative incidence of a first recurrence or death was, respectively, 50 % and 61 % in the treated cohort versus 69 % and 74 % in the control cohort. Median overall survival was 55 and 29 months, respectively (p = 0.051). Among patients with a recurrence at 2 years, more patients had already experienced such recurrence at 1 year in the control cohort (70 % vs 33 %, p = 0.014).

Conclusions

Adjuvant I-131 lipiodol improves disease-free survival in patients with HCC.

     

Risk Factors Influencing Recurrence, Patterns of Recurrence, and the Efficacy of Adjuvant Therapy After Radical Resection for Gallbladder Carcinoma

Backgrounds

Gallbladder carcinoma (GBC) is an aggressive neoplasm, and resection is the only curative modality. Recurrence frequently occurs after the curative resection of advanced GBC. Adjuvant treatment, particularly radiotherapy, is recommended and is used without any evidence of a beneficial effect. The aim of this study was to characterize patterns of recurrence and to identify the factors that influence recurrence and the efficacy of adjuvant therapy after the curative resection of GBC.

Methods

The records of patients that underwent surgical resection with curative intent for gallbladder carcinoma from October 1994 and August 2007 were retrospectively reviewed. Recurrence patterns, times to recurrence, and survival rates were analyzed. Sites of recurrence were identified retrospectively and categorized as locoregional or distant.

Results

One hundred sixty-six patients underwent surgical resection with curative intent for gallbladder adenocarcinoma. The 5-year recurrence rates of stages IA, IB, IIA, and IIB patients were 0%, 24.3%, 44.9%, and 58.3%, retrospectively. Positivity for lymph node metastases was found to have predictive significance for disease-free survival (p?=?0.009). Regional lymph node recurrence (27.7%) was observed most frequently. There was no significant disease-free survival rates between the no adjuvant therapy and the adjuvant therapy groups.

Conclusions

The regional lymph nodes and the liver were found to be the most common sites of recurrence after curative resection. Lymph node metastases were identified as an independent predictor of tumor recurrence by multivariate analysis. Based on the disease-free survivals observed in this study, the authors find it would be difficult to advocate the routine use of adjuvant radiotherapy and/or chemotherapy     

Multimodal Treatment for Lymph Node Recurrence of Esophageal Carcinoma After Curative Resection

Background  Although esophagectomy with extended lymph node dissection can improve survival of patients with esophageal carcinoma, lymph node metastasis has remained one of the main recurrence patterns. The aim of this study was to evaluate the outcome of intensive treatment for recurrent lymph node metastasis. Methods  Recurrent lymph node metastasis was detected in 68 patients with thoracic esophageal carcinoma after curative esophagectomy (R0, International Union Against Cancer criteria). Multimodal treatment was performed in 41 patients: 19 patients underwent lymphadenectomy with adjuvant therapy, and 22 received definitive chemoradiotherapy and repeated chemotherapy. The remaining 27 patients (40%) received chemotherapy or best supportive care. Results  Survival of the lymphadenectomy and the chemoradiotherapy groups was significantly better than that of the patients who received chemotherapy or best supportive care (P < .0001). Fifteen patients (79%) underwent curative lymph node dissection (R0) in the lymphadenectomy group. Complete response, partial response, and stable disease were obtained in 8 (37%), 10 (45%), and 4 (18%) patients who received chemoradiotherapy, respectively. There was no statistically significant difference in survival between the lymphadenectomy and the chemoradiotherapy groups. Although the location of lymph node metastasis did not influence survival significantly, seven patients with nodes around the abdominal aorta did not survive longer than 3 years. The most common repeat recurrence pattern was organ metastasis after the treatment. Multivariate analysis showed that the number of metastatic nodes and tumor marker were independent prognostic factors. Conclusion  Multimodal treatment including lymphadenectomy and chemoradiotherapy could improve survival of the patients with lymph node recurrence of esophageal carcinoma after curative resection.     

Appropriate Treatment Strategy for Intrahepatic Recurrence After Curative Hepatectomy for Hepatocellular Carcinoma

Introduction  

The aim of this study is to evaluate the appropriate treatment for intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC).     

The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

Background

The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors. However, it is not clear which of the two plays the predominant role in tumor invasion and progression. In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients.

Materials and Methods

MMP-9 and MMP-2 expression in HCC cell lines and in vitro HCC invasion model were detected by quantitative RT-PCR and immunofluorescence. The expression levels of MMP-9 and MMP-2 were assessed by immunohistochemistry in HCC tissue microarrays from HCC patients (study set) who underwent curative resection. The clinicopathological data were retrospectively analyzed. The results were further verified in an independent cohort of 92 HCC patients (validation set).

Results

Univariate analysis demonstrated that high expression of MMP-9 was associated with both time to recurrence (TTR, P = .015) and overall survival (OS, P = .024), whereas high expression of MMP-2 was only correlated with TTR (P = .041). Multivariate analysis confirmed that MMP-9 expression was an independent predictor of TTR and OS. The coindex of MMP-9 and preoperative serum AFP levels was significantly correlated with TTR and OS (P = .036 and P = .040), but the coindex of MMP-2 and AFP did not show prognostic significance for either TTR or OS (P = .067 and P = .053). The prognostic value of MMP-9 overexpression was validated in the independent data set.

Conclusion

MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.

     

The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

Background

The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors. However, it is not clear which of the two plays the predominant role in tumor invasion and progression. In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients.

Materials and Methods

MMP-9 and MMP-2 expression in HCC cell lines and in vitro HCC invasion model were detected by quantitative RT-PCR and immunofluorescence. The expression levels of MMP-9 and MMP-2 were assessed by immunohistochemistry in HCC tissue microarrays from HCC patients (study set) who underwent curative resection. The clinicopathological data were retrospectively analyzed. The results were further verified in an independent cohort of 92 HCC patients (validation set).

Results

Univariate analysis demonstrated that high expression of MMP-9 was associated with both time to recurrence (TTR, P = .015) and overall survival (OS, P = .024), whereas high expression of MMP-2 was only correlated with TTR (P = .041). Multivariate analysis confirmed that MMP-9 expression was an independent predictor of TTR and OS. The coindex of MMP-9 and preoperative serum AFP levels was significantly correlated with TTR and OS (P = .036 and P = .040), but the coindex of MMP-2 and AFP did not show prognostic significance for either TTR or OS (P = .067 and P = .053). The prognostic value of MMP-9 overexpression was validated in the independent data set.

Conclusion

MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.

     

Safety of Liver Resection for Hepatocellular Carcinoma After Sorafenib Therapy: A Multicenter Case-Matched Study

Background

Liver resection can be considered in some hepatocellular carcinoma (HCC) patients who received sorafenib. The lack of clinical data about safety of resection after sorafenib treatment led us to assess its potential impact on perioperative course in a multicentric study.

Methods

From 2008 to 2011, a total of 23 HCC patients who underwent liver resection after treatment with sorafenib (sorafenib group) were compared with 46 HCC patients (control group) matched for age, gender, underlying liver disease, tumor characteristics and type of resection. Patients received sorafenib for a median duration of 1 (range 0.2–11) months and drug was interrupted at least 7 days before surgery. End points were intraoperative (operative time, vascular clamping, blood loss and transfusion), and postoperative outcomes focusing on recovery of liver function.

Results

In the sorafenib group, HCC was developed on F4 cirrhosis in 48 % and the rate of major resection was 44 %. Surgical procedure duration (280 vs. 240 min), transfusion rate (26 vs. 15 %), blood loss (400 vs. 300 mL) and vascular clamping (70 vs. 74 %) were similar in the two groups. Mortality was zero in the sorafenib group and one (2.1 %) in the control group (p = 1.000). The incidence of postoperative complications was 44 % in the sorafenib group and 59 % in the control group (p = 0.307). Recovery of liver function was similar in the two groups in terms of prothrombin time (90 vs. 81 %, p = 0.429) and bilirubin level (16 vs. 24 μmol/L, p = 102) at postoperative day 5.

Conclusions

No adverse effect of preoperative administration of sorafenib was observed during and immediately after liver resection for HCC.     

High Hepatitis B Viral Load Predicts Recurrence of Small Hepatocellular Carcinoma after Curative Resection

A retrospective cohort study was conducted to identify risk factors for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. A total of 317 patients who had received curative resection of pathologically proven small HCC (≤3 cm in diameter) were analyzed to ascertain the factors affecting recurrence. The median follow-up period was 33.7 months. Cumulative recurrence rates at 1, 3, and 5 years after resection were 23.5%, 49.5%, and 65.5%, respectively. Male sex, alpha-fetoprotein (AFP) ≥400 ng/mL, HBV DNA level ≥4 log₁₀ copies/mL, prolonged prothrombin time, tumor size ≥2 cm, microvascular invasion, absence of capsular formation, moderate/poor tumor differentiation, and absence of postoperative interferon-alpha (IFN-α) treatment were associated with increased cumulative risk of HCC recurrence. By multivariate analysis, HBV DNA level ≥4 log₁₀ copies/mL (P < 0.001, hazard ratio (HR) 2.110), AFP ≥400 ng/mL (P = 0.011, HR 1.574), microvascular invasion (P < 0.001, HR 1.767), and postoperative IFN-α treatment (P = 0.022, HR 0.562) remained to be independently associated with HCC recurrence. Those contributing to late recurrence (>2 years) were older age and HBV DNA level ≥4 log₁₀ copies/mL. Patients with persistent HBV DNA level ≥4 log₁₀ copies/mL at resection and follow-up had the highest recurrence risk (P < 0.001, HR 4.129). HBV DNA level ≥4 log₁₀ copies/mL at the time of resection was the most important risk factor for recurrence. Postoperative IFN-α treatment significantly decreased the recurrence risk after resection.