Curative Hepatic Resection For Hepatocellular Carcinoma Research Articles

Effect of Sarcopenia on the Prognosis of Clinical Outcomes in Patients With Hepatocellular Carcinoma After Hepatic Resection.

We aimed to study the prognostic impact of sarcopenia on overall survival (OS), disease-free survival (DFS), and postoperative outcomes among patients with Hepatocellular carcinoma (HCC) who underwent curative hepatic resection. Data were collected retrospectively from patients with HCC underwent curative hepatic resection and preoperative abdominal computed tomography (CT) at our institution between January 2010 and December 2020. Sarcopenia was evaluated by the skeletal muscle mass at the inferior direction of the third-lumbar-vertebra (L3) cross-sectional area based on preoperative CT imaging using software analysis. Cutoff values for skeletal muscle index (SMI) were 43.75 and 41.10cm2/m2 for males and females. The patients were classified into sarcopenia and nonsarcopenia groups. The association between preoperative sarcopenia and clinicopathological factors, impact of sarcopenia on survival, and postoperative outcomes were analyzed. Sarcopenia was present in 39 of 83 (47.0%) patients who underwent curative hepatic resection for HCC and was significantly correlated with lower SMI, lower serum albumin levels, higher intraoperative blood loss, higher postoperative complications, and longer hospital stay. The 5-year OS was significantly lower in sarcopenic patients than in nonsarcopenic patients (58.2% vs 83.6%; P = .006), but the 5-year DFS was not significantly different between the 2 groups. Multivariate analysis revealed that sarcopenia was a significant risk factor for poor OS (HR 4.728; 95% CI, 1.458-15.329; P = .010). Sarcopenia was identified as a prognostic factor for poor OS after hepatic resection, and major postoperative complications were more frequent in sarcopenia. Early sarcopenia detection and management may improve OS and clinical outcomes in postoperative HCC.

Predictors for early recurrence beyond up-to-7 or distant metastasis after hepatocellular carcinoma resection: proposal for borderline resectable HCC.

The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5years and early recurrence (within 1year) is now recognized as having a poor prognosis and has limited treatment options. We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes. Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis. In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis.

Significance of malnutrition defined with Global Leadership Initiative on Malnutrition criteria in patients with hepatocellular carcinoma after hepatic resection.

A recent study reported the utility of the definition of malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria in many types of cancers and chronic inflammatory disease. The present retrospective study aimed to investigate the significance of malnutrition defined with GLIM criteria in patients with hepatic resection for hepatocellular carcinoma (HCC) and also to compare malnutrition using handgrip strength. We retrospectively reviewed data from 174 patients who had undergone curative hepatic resection for HCC including both skeletal muscle area and handgrip strength. Patients were divided according to malnutrition defined by GLIM or modified GLIM and clinicopathologic and short- and long-term outcomes were analyzed. The modified GLIM criteria was defined using both handgrip strength and skeletal muscle area. Malnutrition defined by GLIM criteria was diagnosed in 47 patients (26.7%) and malnutrition defined by modified GLIM criteria was diagnosed in 21 patients (11.9%). Malnutrition defined by GLIM or modified GLIM criteria was associated with poorer liver function and malignant tumor behavior, but modified GLIM criteria predicted the postoperative complication and recurrence-free survival outcome independently. In patients with poor liver function, malnutrition defined by modified GLIM criteria predicted postoperative complication and overall and recurrence-free survival. Malnutrition defined by modified GLIM criteria using both handgrip strength and skeletal muscle area can more accurately predict short- and long-term outcomes compared to malnutrition defined by the GLIM criteria. Nutritional and exercise therapy could become more important in patients with malnutrition and poor liver function.

The ratio of creatinine and cystatin C estimated glomerular filtration rates as a surrogate marker in patients with hepatocellular carcinoma undergoing hepatic resection.

The ratio of creatinine and cystatin C estimated glomerular filtration rates (eGFRcre/eGFRcys) is significantly positively correlated with sarcopenia. However, there are no published reports on the relationship between eGFRcre/eGFRcys and long-term prognosis in patients after hepatic resection for hepatocellular carcinoma (HCC). A total of 157 patients who had undergone curative hepatic resection for HCC were retrospectively reviewed. Cystatin C levels were measured in serum samples that had been frozen after collection at surgery. We aimed to investigate the significance of cystatin C in prognostic value following hepatic resection for HCC. The best cut-off eGFRcre/eGFRcys value for overall survival after hepatic resection for HCC was 1.0025. High eGFRcre/eGFRcys was significantly associated with poor liver function, low skeletal muscle mass, large tumor size, large ascitic volume, worse overall and recurrence-free survival. The eGFRcre/eGFRcys was significantly related to severe recurrence patterns (multiple liver recurrences, distant metastasis). Preoperative eGFRcre/eGFRcys can predict overall and recurrence-free survival in HCC patients undergoing hepatic resection. The eGFRcre/eGFRcys is a simple and reliable surrogate marker that indicates eligibility for hepatic resection for HCC.

The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. Conclusions: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

Clinicopathologic Features of Patients With Primary Hepatocellular Carcinoma Surviving Without Recurrence More Than 10 Years After Primary Hepatic Resection

Objective: The aim of this study was to clarify the predictive factors of recurrence-free time more than 10 years after primary hepatic resection for hepatocellular carcinoma (HCC). Summary of background data: Surgical resection is a curative treatment for HCC patients with hepatic functional reserve; however, the high recurrence rate must be addressed. Methods: The study included 595 patients who had undergone curative resection for HCC. Multivariate analysis was performed to identify factors associated with recurrence-free survival at more than 10 years. Results: Multivariate analysis revealed that tumor size ≤2 cm (P = 0.004), albumin-bilirubin (ALBI) grade 1 (P = 0.03), Fibrosis-4 (FIB-4) index ≤3.3 (P = 0.002), and histologic inflammation grade ≤1 (P = 0.03) were independent predictive factors for recurrence-free survival for more than 10 years. Predictive points were scored as follows: 2 points, tumor size ≤2 cm or FIB-4 index ≤3.3; and 1 point, ALBI grade 1 or histologic inflammation grade ≤1. Patients were divided into 3 groups according to their total points: group 1, 0 to 2 points (n = 317); group 2, 3 to 4 points (n = 239); and group 3, 5 to 6 points (n = 39). Recurrence-free survival rates among the 3 groups were significantly different (P &amp;lt; 0.0001). Conclusions: Tumor size, ALBI, FIB-4 index, and histologic inflammation grade were independent predictive factors for recurrence-free survival longer than 10 years after curative hepatic resection for HCC.

Operation start time and long-term outcome of hepatocellular carcinoma after curative hepatic resection.

PurposeThe objective of the current study was to examine the potential effects of surgery start times (morning vs. afternoon) on the long-term prognosis of patients after hepatic resection (HR) for hepatocellular carcinoma (HCC).MethodsAll eligible patients were divided into 2 groups according to the start time of surgery: group M (morning surgery, 8 AM–1 PM) and group A (afternoon surgery, 1 PM–6 PM). Clinicopathologic and surgical parameters, as well as oncologic outcomes were compared between the 2 groups.ResultsIn total, 231 patients were included in the study. There was no difference in age, body mass index, comorbidities, tumor size, tumor location, tumor stages, surgical procedures, or surgical margin between morning and afternoon surgery (all P > 0.05). In contrast, patients in group M experienced longer operation duration than those in group A (median, 240 minutes vs. 195 minutes, P = 0.004). However, no differences of overall survival were observed between morning and afternoon surgery groups in the whole cohort or stratified by surgical margin (all P > 0.05).ConclusionSurgery start times during the work day have no measurable influence on patient outcome following curative HR for HCC, indicating good self-regulation and professional judgment of surgeons for progressive fatigue during surgery.

Hepatobiliary versus Extracellular MRI Contrast Agents in Hepatocellular Carcinoma Detection: Hepatobiliary Phase Features in Relation to Disease-free Survival

Background MRI with hepatobiliary contrast material is more sensitive than MRI with extracellular contrast material in the detection of hepatocellular carcinoma (HCC). Purpose To determine whether postsurgical outcomes differ between patients who undergo MRI with hepatobiliary contrast material and those who undergo MRI with extracellular contrast material by analyzing disease-free survival (DFS) rates after curative resection of HCC. Materials and Methods From January 2014 to December 2015, 170 treatment-naïve patients who underwent contrast-enhanced preoperative liver MRI and curative hepatic resection for HCC were retrospectively included and observed until September 2018. DFS rates were compared between the two groups, which were classified based on the type of MRI contrast agent used. The MRI with hepatobiliary contrast material group was further divided into a hypointense nodule-positive group and a hypointense nodule-negative group according to the presence of residual hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) after surgery. DFS rates were calculated by using the Kaplan-Meier method and were compared among the three groups by using a log-rank test. Results Patients were included in either the MRI with extracellular contrast material group (n = 53; mean age, 60 years ± 9 [standard deviation]) or the hepatobiliary contrast material group (n = 117; mean age, 60 years ± 8; 26 patients were in the hypointense nodule-positive group). Over a median follow-up period of 34.1 months, median DFS rates did not differ between the extracellular contrast material group (35.8 months) and the hepatobiliary contrast material group (43.5 months) (P = .46). However, median DFS in the extracellular contrast material group was longer than that in the hypointense nodule-positive group (35.8 months vs 25.8 months, P < .001) and shorter than that in the hypointense nodule-negative group (35.8 months vs 48.6 months, P = .02). Conclusion Patients who undergo preoperative MRI with hepatobiliary contrast material and resection of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement may show better disease-free survival. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Motosugi in this issue.

Platelet-to-Lymphocyte Ratio and Large Tumor Size Predict Microvascular Invasion after Resection for Hepatocellular Carcinoma

Background:Recurrence after curative resection of hepatocellular carcinoma (HCC) is associated with early death and poor prognosis. Microvascular invasion (mVI) is strongly associated with disease recurrence. Although many studies have examined the relationship between various serum inflammatory indices and post-treatment prognosis, little is known about preoperative predictors of microvascular invasion in HCC.Methods:Patients who underwent curative hepatic resection for HCC at our institute from January 2006 to December 2016 were retrospectively reviewed. The associations between mVI and various potential risk factors, including tumor size, hepatitis B and C virus infection, Child–Pugh scores, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio, were analyzed. Optimal cut-off values were determined using receiver operating characteristic curves.Results:A total of 330 HCC patients were enrolled in this study, of whom 74 (22.4%) had tumors with mVI. After univariate analysis, two parameters were significantly associated with mVI after hepatic resection: platelet-to-lymphocyte ratio ≥102 (odds ratio [OR] 2.385, p = 0.001) and tumor size ≥5 cm (OR 4.29, p < 0.001). Both variables remained significant risk factors for mVI after multivariate analysis: platelet-to-lymphocyte ratio ≥102 (OR 1.831, p = 0.034) and tumor size ≥5 cm (OR 3.791, p < 0.001).Conclusions:Large tumor size (≥5 cm) and high platelet-to-lymphocyte ratio (≥102) are independent predictive factors for mVI in HCC.

Platelet-to-lymphocyte ratio and large tumor size predict microvascular invasion after resection for hepatocellular carcinoma

Background: Recurrence after curative resection of hepatocellular carcinoma (HCC) is associated with early death and poor prognosis. Microvascular invasion (mVI) is strongly associated with disease recurrence. Although many studies have examined the relationship between various serum inflammatory indices and post-treatment prognosis, little is known about preoperative predictors of microvascular invasion in HCC. Methods: Patients who underwent curative hepatic resection for HCC at our institute from January 2006 to December 2016 were retrospectively reviewed. The associations between mVI and various potential risk factors, including tumor size, hepatitis B and C virus infection, Child–Pugh scores, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio, were analyzed. Optimal cut-off values were determined using receiver operating characteristic curves. Results: A total of 330 HCC patients were enrolled in this study, of whom 74 (22.4%) had tumors with mVI. After univariate analysis, two parameters were significantly associated with mVI after hepatic resection: platelet-to-lymphocyte ratio ≥102 (odds ratio [OR] 2.385, p = 0.001) and tumor size ≥5 cm (OR 4.29, p < 0.001). Both variables remained significant risk factors for mVI after multivariate analysis: platelet-to-lymphocyte ratio ≥102 (OR 1.831, p = 0.034) and tumor size ≥5 cm (OR 3.791, p < 0.001). Conclusions: Large tumor size (≥5 cm) and high platelet-to-lymphocyte ratio (≥102) are independent predictive factors for mVI in HCC.

Impact of Sustained Virological Response to Interferon Therapy on Recurrence of Hepatitis C Virus-Related Hepatocellular Carcinoma.

Although achieving a sustained virological response (SVR) in hepatitis C virus (HCV) infection is recognized as improving liver function and reducing hepatocellular carcinoma (HCC) development, its impact on HCC recurrence is unclear. This study investigated how preoperative SVR achievement by interferon treatment affects HCC recurrence in patients undergoing hepatic resection. The study subjects were 521 patients with HCV infection who underwent initial and curative hepatic resection for HCC. To adjust for confounding factors between the SVR and non-SVR groups, propensity score-matching analysis was performed. After propensity score matching, 45 of the 49 patients in the SVR group, and an equal number of the 472 patients in the non-SVR group, were matched. The two groups had similar distributions of clinicopathological characteristics. In the matched cohort, the 3-, 5-, and 7-year recurrence-free survival rates after surgery were 56, 45, and 37%, respectively, in the SVR group, and 34, 23, and 7.2%, respectively, in the non-SVR group (p=0.033). Additionally, the 3-, 5-, and 7-year overall survival rates after surgery were 82, 80, and 75%, respectively, in the SVR group, and 78, 64, and 44%, respectively, in the non-SVR group (p=0.065). The 1- and 2-year cumulative recurrence rates in the early phase showed no significant difference between the SVR and non-SVR groups (p=0.27). however, the 3-, 5-, and 7-year cumulative recurrence rates in the late phase were 14, 32, and 43%, respectively, in the SVR group, and 33, 55, and 86%, respectively, in the non-SVR group (p=0.037). Achievement of SVR may reduce postoperative recurrence after hepatic resection.

Administration of adjuvant oral tegafur/uracil chemotherapy post hepatocellular carcinoma resection: A randomized controlled trial

Recurrence of hepatocellular carcinoma (HCC) after surgery is frequent, and is an important factor adversely influencing the long-term survival of patients. This prospective study evaluated whether adjuvant chemotherapy with oral tegafur/uracil (UFT) reduces the recurrence rate of HCC. In addition, expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were investigated in resected tumors and nontumorous tissues, and the relationship between their expression and the effectiveness of UFT was examined. A total of 117 patients who underwent curative hepatic resection for HCC were randomly allocated to UFT 400mg/d (n=24, UFT group) or surgery alone (n=56, control group). The primary endpoint was the recurrence-free survival rate, and the secondary endpoint was the overall survival rate. Expression of the DPD and TS genes were quantified with TaqMan reverse transcription-polymerase chain reaction assay using β-actin as an internal standard. The cut-off value was set at the mean value of TS and DPD expression. Among the 61 patients in the UFT group, 37 patients (60.6%) discontinued UFT within 1 month. Recurrence-free survival (p=0.16) and overall survival (p=0.29) were similar in the two groups. In the UFT group, recurrence-free survival did not differ significantly between high-TS (TS>3.6) and high-DPD (DPD>8.9; n=10), and low-TS (TS≤3.6) and low-DPD (DPD≤8.9; n=9) groups. However, there was a significant difference between the two groups in overall survival (p=0.04). Peroral UFT administration fails to prolong the recurrence-free rates and overall survival rates, in comparison with surgery alone. However, oral administration of UFT may improve the survival of HCC patients when the levels of TS and DPD mRNA are low in the tumor tissue.

CD44 expression in patients with combined hepatocellular cholangiocarcinoma.

PurposeCombined hepatocellular cholangiocarcinoma (ChC) is a rare type of primary liver cancer, which is thought to have a poorer prognosis than hepatocellular carcinoma (HCC). Cancer stem cells are associated with tumorigenesis, tumor progression, recurrence, metastasis, and poor prognosis in several malignancies including HCC. The aim of this study was to investigate the expression pattern of cancer stem cell markers in ChC and HCC, and to evaluate whether this pattern correlated to patient prognosis.MethodsThirteen patients who underwent curative hepatic resection for ChC and 13 patients who underwent curative hepatic resection for HCC (matched control cases) were included. Immunohistochemical staining for cancer stem cell markers (cytokeratin [CK]7, CK19, C-kit, cluster of differentiation [CD] 44, CD133, and epithelial cell adhesion molecule) was performed and clinical outcomes were analyzed retrospectively.ResultsThere was no significant difference in cancer stem cell marker expression between ChC and HCC. In ChC, the group that expressed CD44 showed earlier recurrence than the group that did not express CD44 (P = 0.040).ConclusionThe expression of cancer stem cell markers in ChC did not show a different pattern compared to that found in HCC. The expression of cancer stem cell marker CD44 was associated with poor prognosis in patients with ChC.

Recurrent hepatocellular carcinoma: A Western strategy that emphasizes the impact of pathologic profile of the first resection

Hepatocellular carcinoma (HCC) often recurs after curative resection, and thus the optimal treatment strategy to treat recurrences remains uncertain. We analyzed the results of different options to treat recurrent HCC and emphasized the impact of pathologic patterns of the tumor at initial resection. Between 2000 and 2014, 293 patients underwent potentially curative hepatic resection for HCC. Among them, 150 experienced a recurrence and have been treated by repeat resection (RR), radiofrequency ablation (RFA), salvage liver transplantation (SLT), transarterial chemoembolization (TACE), or conservative treatment, including systemic or targeted chemotherapy. Clinical outcomes were analyzed and compared between the treatment groups, focusing on clinical and pathologic characteristics of the tumor at initial resection. After a median follow-up of 26 months, the overall survival (OS) at 1, 3, and 5 years after recurrence was 62%, 48%, and 40%, respectively. Survival rates were greater in patients treated by a curative approach (RR, RFA, SLT) than those treated by TACE, with 5-year OS of >70% and 37%, respectively. Univariate analysis showed satellitosis and microvascular invasion (MVI) at initial resection as negative prognostic factors of survival after recurrence (P < .05). On multivariate analysis, type of treatment was the only independent factor associated with survival. A subgroup analysis showed that RR/RFA led to better survival outcomes than TACE for early stage intrahepatic recurrences in the absence of satellitosis or MVI on the primary resected tumor. Curative treatments of recurrent HCC improve patient survival. Satellitosis and MVI on the primary resected specimen may be used as selection criteria for the best treatment strategy for intrahepatic recurrences.

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

Leukocyte subsets in peripheral blood, which include neutrophils, lymphocytes, and monocytes, have not been well established as prognostic factors in patients with hepatocellular carcinoma (HCC). Consecutive patients who underwent curative hepatic resection for HCC at the National Cancer Center, Republic of Korea, from 2001 to 2008 were enrolled in this retrospective study. Clinicopathologic factors, cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed with respect to preoperative lymphocyte subsets, especially monocyte ratio. The 603 patients had a median follow-up of 40.0 months and a 5-year overall survival rate of 67.7 %. In univariate analysis of survivals, preoperative lymphocyte ratio ≤35 % and monocyte ratio >7 % were significantly poor prognostic factors. In multivariate analysis, preoperative monocyte ratio >7 %, satellite nodule, and microvascular invasion were independent risk factors for CSS and DFS (hazard ratio of monocyte ratio >7 % = 1.77, p = 0.02 and 1.57, p = 0.006, respectively). Considering monocyte ratio with preoperative α-fetoprotein level, patients with both abnormal α-fetoprotein levels (>12 ng/mL) and monocyte ratio >7 % showed significantly worse CSS and DFS than other groups (p < 0.001). Cirrhotic patients with monocyte ratio >7 % showed significantly poor CSS and DFS compared with non-cirrhotic patients (p = 0.033 and <0.001, respectively). A preoperative monocyte ratio >7 % of peripheral blood is an independent risk factor for CSS and DFS after hepatic resection for HCC. Preoperative monocyte ratio might be considered as a novel biomarker for HCC.

Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: Clinical and biological significance

Abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast-enhanced intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated by clinicopathological and gene expression analyses. We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS. Clinicopathological and gene expression analyses were performed according to CEIOUS vasculature patterns. CEIOUS images of HCC vasculatures were classified as reticular HCC or thunderbolt HCC. Thunderbolt HCC was significantly correlated with higher alpha-fetoprotein levels, tumor size, histological differentiation, portal vein invasion, and tumor-node-metastasis stage, and these patients demonstrated a significantly poorer prognosis for both recurrence-free survival (P = 0.0193) and overall survival (P = 0.0362) compared with patients who had reticular HCC. Gene expression analysis revealed that a rereplication inhibitor geminin was significantly overexpressed in thunderbolt HCCs (P = 0.00326). In vitro knockdown of geminin gene reduced significantly the proliferation of human HCC cells. Immunohistochemical analysis confirmed overexpression of geminin protein in thunderbolt HCC (P < 0.0001). Multivariate analysis revealed geminin expression to be an independent factor in predicting poor survival in HCC patients (P = 0.0170). CEIOUS vascular patterns were distinctly identifiable by gene expression profiling associated with cellular proliferation of HCC and were significantly related to HCC progression and poor prognosis. These findings might be clinically useful as a determinant factor in the postoperative treatment of HCC.

Long-term results of liver resection for hepatocellular carcinoma in noncirrhotic liver

Hepatocellular carcinoma (HCC) is among the most common malignant neoplasms worldwide. Only few data on HCC in noncirrhotic livers without viral hepatitis in Western countries are available. The purpose of this study was to define the outcomes and potential prognostic factors associated with survival after hepatic resection in patients with HCC in the absence of liver cirrhosis and hepatitis B or C infection. From January 2000 to September 2010, 148 patients without liver cirrhosis and without extrahepatic metastases underwent curative hepatic resection for HCC at the Surgical Department of the Charité, Campus Virchow Klinikum. The outcomes of these patients were retrospectively reviewed. Patients with cirrhosis or severe fibrosis, fibrolamellar HCC, and those positive for hepatitis B or C were excluded. The cumulative 1-, 3-, 5-, and 7-year survival rates were 75.4%, 54.7%, 38.9%, and 31.8%, respectively. The 1-, 3-, 5-, and 7-year disease-free survival rates were 60.3%, 38.0%, 29.1%, and 18.1%, respectively. In the multivariate analysis, cumulative survival was decreased by patient age, increased operative time, increased preoperative serum gamma-glutamyl transferase (GGT), and tumor stage. In the subgroup with unifocal neoplasms, N0 and R0 status, tumor size >10 cm, and tumor differentiation were highly predictive of lesser survival. Unfavorable survival was observed in patients with multifocal neoplasms, tumor size >10 cm, and/or poor tumor differentiation. The current TNM staging system is stratified for survival and recurrence. Extension of the current TNM staging system by grading and more exact differentiation of tumor size may increase its prognostic accuracy for predicting outcome. Preoperative increased serum GGT level could be a new poor prognostic factor.

Acoustic radiation force impulse imaging predicts postoperative ascites resulting from curative hepatic resection for hepatocellular carcinoma

Measurement of liver stiffness using Virtual Touch Tissue Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects the degree of hepatic fibrosis and reserve. This prospective study investigated how well the VTTQ value predicts the development of postoperative complications before curative hepatic resection for hepatocellular carcinoma (HCC). The study enrolled 50 consecutive patients between February 2009 and October 2010 whose preoperative VTTQ values were determined before they underwent curative hepatic resection for HCC. We assessed the relationship between postoperative complications and VTTQ values. The study included 41 (82%) patients with chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was 1.60 (m/sec), which correlated with the fibrosis stage (P = .0058). The VTTQ value was the only variable correlated with postoperative ascites that did not respond to pharmacologic treatment and required invasive management. Univariate and subsequent multivariate analyses revealed that the preoperative VTTQ value was the only independent risk factor for predicting the development of postoperative ascites (cutoff, 1.68 cm/sec; P = .007; odds ratio, 76.481). The area under the receiver operating characteristic curve for the diagnosis of postoperative ascites using VTTQ values was 0.90, whereas those using the aspartate transaminase-to-platelet ratio index and indocyanine green retention rate at 15 minutes values were 0.68 and 0.55, respectively. These data suggest that the VTTQ value is a reliable surrogate marker for predicting postoperative ascites before curative hepatic resection for HCC.

Impact of Pegylated Interferon Therapy on Outcomes of Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma After Curative Hepatic Resection

Several published reports investigating the effects of interferon (IFN) therapy on survival and tumor recurrence after curative resection of hepatocellular carcinoma (HCC) have been inconclusive. The aim of this study is to investigate the efficacy of pegylated-IFN (peg-IFN) therapy after curative hepatic resection for HCC in patients infected with hepatitis C virus (HCV). Data from 175 patients who underwent curative hepatic resection for HCC associated with HCV were retrospectively collected and analyzed; 75 patients received peg-IFN therapy after surgery, whereas 100 patients did not receive IFN therapy. To overcome biases resulting from the different distribution of covariates in the two groups, a one-to-one match was created using propensity score analysis. After matching, patient outcomes were analyzed. After one-to-one matching, patients (n = 38) who received peg-IFN therapy after surgery and patients (n = 38) who did not receive IFN therapy had the same preoperative and operative characteristics. The 3- and 5-year overall survival rates of patients who received peg-IFN therapy after hepatic resection were significantly higher than those of patients who did not receive IFN therapy (P = 0.00135). The 3- and 5-year overall survival rates were 100 and 91.7% and 76.6 and 50.6% in the peg-IFN group and non-IFN group, respectively. There was no significant difference in disease-free survival between the two matched groups (P = 0.886). Peg-IFN therapy may be effective as an adjuvant chemopreventive agent after hepatic resection in patients with HCV-related HCC.

The model of end-stage liver disease (MELD) score in predicting postoperative liver failure after hepatic resection of hepatocellular carcinoma in cirrhotic patients: The Tunisian experience

Background and study aims Hepatocellular carcinoma (HCC) is one of the most frequent cancers in the world. Factors associated with prognosis following resection remain ill defined. The model for end-stage liver disease (MELD) is considered as an index of hepatic functional reserve. This study evaluates the reliability of the MELD score in the prediction of liver failure after hepatic resection for HCC in cirrhotic patients. Patients and methods A retrospective chart review was undertaken of patients with HCC and cirrhosis undergoing hepatic resection between January 1991 and December 2007. A total of 26 cirrhotic patients underwent curative hepatic resection for HCC at our department. Patient information included demographic features, American Society of Anesthesiologists (ASA) class, aetiology of cirrhosis, laboratory test results, type of surgical procedure, duration of hospitalisation, and Child–Turcotte–Pugh and MELD scores. Results Six patients (23.1%) developed postoperative liver failure. As much as 66.66% of liver failures were seen in patients who have had major hepatectomy. Using receiver operating characteristic curve analysis, we identified that a MELD score equal to or above 9.5 is the best cut-off value for predicting postoperative liver failure. Patients were divided in two groups: MELD below 9.5 (group A) and MELD equal to or above 9.5 (group B). The highest prevalence of postoperative liver failure of 83.33% was observed in group B. MELD score ⩾9.5 and low serum sodium are strongly predictive of increased postoperative liver failure in patients with cirrhosis undergoing hepatic resection for HCC. Conclusion The presence of liver cirrhosis is an important factor that affects the prognosis of patients with hepatocellular carcinoma (HCC). Cirrhotic patients with a high MELD score are at high risk of postoperative liver failure and complications and should be referred for non-surgical treatment.