Incidental Microscopic Bile Duct Tumor Thrombi in Hepatocellular Carcinoma after Curative Hepatectomy: A Matched Study

In patients with hepatocellular carcinoma (HCC), the presence of bile duct tumor thrombi (BDTT) in the major bile ducts indicates poor prognosis compared with that of HCC patients without BDTT. However, the prognostic significance of incidental microscopic BDTT in the peripheral bile ducts after curative liver resection is not known. We compared the outcomes of HCC patients with and without microscopic BDTT in the peripheral bile ducts who underwent hepatectomy.The electronic medical records of 31 patients with microscopic BDTT (BDTT group) were retrospectively reviewed. To compare the surgical outcomes, 62 patients (No BDTT group) were randomly chosen from the remaining HCC patients without BDTT based on age, sex, etiology of HCC, tumor size, tumor number, and modified Union for International Cancer Control T staging.The 1-year, 2-year, and 3-year disease-free survival rates and overall survival rates were 54.8%, 34.0%, 34.0% and 90.1%, 69.2%, 61.0% in the BDTT group and 66.8%, 59.2%, 42.3% and 86.4%, 84.4%, 84.4% in the No BDTT group (P = 0.089 and P = 0.014, respectively). The overall survival curve in the No BDTT group was higher than that in the BDTT group. Multivariate analysis revealed that predisposing factors for tumor recurrence after curative liver resection included increased levels of the protein induced by vitamin K antagonist-II (PIVKA-II), tumor grades 3 and 4, and the presence of BDTT.This study demonstrates that HCC prognosis is worse in patients with incidental microscopic BDTT in the peripheral bile ducts than it is in those without BDTT. The presence of BDTT should therefore be considered when evaluating a patient''s HCC prognosis after curative hepatectomy.     

Risk factors of long-term survival and recurrence after curative resection of hepatocellular carcinoma

BACKGROUND/AIMS: The independent risk factors contributing to long-term survival (> or = 10-year survival rate) and recurrence after curative hepatic resection for hepatocellular carcinoma (HCC) were evaluated. METHODOLOGY: The prognoses were retrospectively analyzed in 247 consecutive patients (187 men and 60 women) treated with curative hepatic resection for HCC and discharged from the hospital. Prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that pTNM stage IV, indocyanine green retention rate at 15 minutes (ICGR15) of > or = 20%, tumor size of > or = 5 cm, and positive hepatitis B surface antigen were independent risk factors of overall survival. Stage IV and ICGR15 of > or = 20% were also independent risk factors of disease-free survival. CONCLUSIONS: pTNM stage and ICGR15 may be simple and useful predictors to improve long-term survival and recurrence after curative hepatic resection for HCC.     

Outcomes of hepatectomy for hepatocellular carcinoma with bile duct tumour thrombus

Background

Hepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is rare. The aim of the present study was to determine the prognosis of HCC with BDTT after a hepatectomy.

Methods

A retrospective analysis was performed on all HCC patients with BDTT having a hepatectomy from 1989 to 2012. The outcomes in these patients were compared with those in the control patients matched on a 1:6 ratio.

Results

Thirty-seven HCC patients with BDTT having a hepatectomy (the BDTT group) were compared with 222 control patients. Patients in the BDTT group had poorer liver function (43.2% had Child–Pugh B disease). More patients in this group had a major hepatectomy (91.9% versus 27.5%, P = 0.001), portal vein resection (10.8% versus 1.4%, P = 0.006), en-bloc resection with adjacent structures (16.2% versus 5.4%, P = 0.041), hepaticojejunostomy (75.7% versus 1.6%, P < 0.001) and complications (51.4% versus 31.1%, P = 0.016). The two groups had similar hospital mortality (2.7% versus 5.0%, P = 0.856), 5-year overall survival (38.5% versus 34.6%, P = 0.59) and 5-year disease-free survival (21.1% versus 20.8%, P = 0.81). Multivariate analysis showed that lymphovascular permeation, tumour size and post-operative complication were significant predictors for worse survival whereas BDTT was not.

Discussion

A major hepatectomy, extrahepatic biliary resection and hepaticojejunostomy should be the standard for HCC with BDTT, and long-term survival is possible after radical surgery.     

Osteopontin,a single marker for predicting the prognosis of patients with tumor‐node‐metastasis stage I hepatocellular carcinoma after surgical resection

Background and Aim: Osteopontin (OPN) has been linked to clinical outcomes in several solid tumors. However, it has not been fully evaluated whether OPN could be used as a single marker for the prognosis of patients with hepatocellular carcinoma (HCC), particularly in patients of the tumor‐node‐metastasis (TNM) stage I. Methods: A total of 151 patients with HCC who underwent surgical resection were enrolled, including 112 patients of the TNM stage I. OPN expression was evaluated using immunohistochemistry in the tissue microarrays derived from these patients. Immunoreactivity was classified according to the percentage and intensity of staining: negative (?), weak (+) and strong (++). The impact of OPN expression on survival of patients was analyzed. Results: In total, 65.6% (99 of 151) of HCC tissues expressed OPN. Overall survival in patients of OPN (?) group was significantly higher than those of OPN (+) or OPN (++) group (P = 0.049 and P = 0.001). Interestingly, in patients of the TNM stage I, OPN expression was correlated with the early recurrence after surgical resection (P = 0.001). Multivariate analysis showed that OPN expression was an independent prognostic factor for overall survival and disease‐free survival in patients with the TNM stage I HCC (hazard ratio, 2.272, P = 0.014 and 1.982, P = 0.037). Conclusions: These results suggest that OPN is commonly expressed in HCC and is a useful marker for predicting the prognosis of patients with the TNM stage I HCC, contributing to determining which individual patient needs adjuvant therapy to prevent the early recurrence after surgical resection.     

Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Clinicopathological Analysis of Factors Predictive of Recurrence and Outcome After Surgery

Although hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is a rare entity, most patients experience tumor recurrence even after curative resection and the prognosis remains dismal. This study aimed to analyze the clinicopathological risk factors for recurrence and poor outcome after surgical treatment of HCC with BDTT.Clinicopathological data of 37 patients with HCC and BDTT who underwent surgical treatment from July 2005 to June 2012 at the authors’ hospital were reviewed retrospectively. Prognostic factors and potential risk factors for recurrence were assessed by Cox proportional hazard model and binary logistic regression model, respectively.Among the 37 patients, anatomical and nonanatomical liver resection was performed in 26 and 11 patients, respectively. The resection was considered curative in 19 patients and palliative in 18 patients. Also, 21 cases had tumor recurrence after operation and 7 cases of them were reoperated. Multivariate binary logistic regression model revealed that surgical curability was the only independent risk factor associated with postoperative tumor recurrence (P = 0.034). In addition, postoperative overall survival rates at 1, 2, and 3 years were 64.2%, 38.9%, and 24.3%, respectively. Cox multivariate analysis indicated that surgical curability and tumor recurrence were independent prognostic factors for both overall survival and recurrence-free survival (P < 0.05).Although patients with HCC and BDTT had a relatively high rate of early recurrence after surgery, relatively favorable long-term outcome after curative hepatic resection could be achieved. Therefore, extensive and curative surgical treatment should be recommended when complete resection can be achieved and liver functional reserve is satisfactory.     

The preoperative positivity for serum hepatitis B e antigen did not affect overall survival after curative resection of hepatitis B virus-related hepatocellular carcinoma

Background and Aim:  Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified.
Methods:  A total of 190 Hepatitis B surface antigen-positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease-free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (≤14 months) and late (>14 months) intrahepatic recurrence.
Results:  The 5-year disease-free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease-free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson–Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post-recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence.
Conclusions:  The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long-term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated.     

Preoperative inlfammation-based markers pre-dict early and late recurrence of hepatocellular carcinoma after curative hepatectomy

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after curative resection remains a major cause of treat-ment failure and tumor-related death. Patterns of HCC recur-rence can be categorized into early recurrence and late recur-rence which have different underlying mechanisms. In this study, we investigated if simple inlfammation-based clinical markers can distinguish patterns of recurrence after curative resection of HCC.
METHODS: A retrospective analysis of 223 patients who un-derwent curative hepatectomy for HCC was performed. Pre-operative inlfammation-based factors including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio,γ-glutamyl transferase/alanine aminotransferase ratio, aspartate amino-transferase/platelet ratio index (APRI) and prognostic nutri-tional index together with other clinicopathologic parameters were evaluated by univariate analysis and multivariate analy-sis to identify independent prognostic factors. By combining risk factors, predictive models were established to distinguish populations at high risk of early or late recurrence.
RESULTS: Age≤50 years, resection margin≤1 cm, TNM stage III-IV, NLR>2.75, APRI>0.23 and positive alpha-fetoprotein were independent adverse prognostic factors for early recur-rence. Patients with three or more risk factors were at signiif-cant higher risk of early recurrence. APRI>0.23 and positive hepatitis Be antigen (HBeAg) were independent risk factors of late recurrence, the coexistence of high APRI and positive HBeAg increased the risk of late recurrence.
CONCLUSIONS: Preoperative inlfammation-based prognostic factors predict early and late recurrence of HCC after curative resection. Different prognostic factor combinations distin-guish high-risk populations of early or late HCC recurrence.     

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP).CUP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not pubhshed. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection.METHODS: A retrospective survey was carried out in 174patients undergoing resection of HCC from January 1986 toJune 1998. Six patients who died in the hospital afteroperation and 11 patients with the recurrence of the diseasewere excluded at 1 month after hepatectomy. By the end ofJune 2001, 4 patients were lost and 153 patients with curativeresection have been followed up for at least three years.Among 153 patients, 115 developed intrahepatic recurrenceand 10 developed extrahepatic recurrence, whereas the other28 remained free of recurrence. Recurrences were classifiedinto early ( ＜ / = 3 year) and late ( ＞ 3 year) recurrence. TheCLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portalthrombosis (0-1)o By contrast, portal vein thrombosis wasdefined as the presence of tumor emboli within vascularchannel analyzed by microscopic examination in this study.Risk factors for recurrence and prognostic factors forsurvival in each group were analyzed by the chi-square test,the Kaplan-Meier estimation and the COX proportionalhazards model respectively.RESULTS: The 1-, 3-, 5-, 7-, andl0-year disease-free survivalrates after curative resection of HCC were 57.2 %、 28.3 %、23.5 %、 18.8 % and 17.8 %, respectively. Median survivaltime was 28,16,10,4,and 5 mo for CLIP score 0,1,2,3, and 4to 5, respectively. Early and late recurrence developed in109 patients and 16 patients respectively. By the chi-squaretest, tumor size, micrusatsllite, venous invasion, tumortype (uninodular, muitinodular, massive), tumor extension( ＜ / = or ＞ 50 % of liver parenchyna replaced by tumor),TNM stage,CLIP score,and resection margin were the risk factors for early recurrence,whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. in univariate survival analysis,Child-Pugh stages,resection margin,tumor size,microsatellite,venous invasion,tumor type,tumor extension,TNM stages,and CLIP score were associated with prognosis.The multivariale analysis by COX proportional hazards modes showed that the independent predictive factors of survival were resection margins and TNM stages. CONCLUSION:CLIP score has displayed a unique superiority in predictin the tumor early and late recurrence and prognosis in the patients with HCC after resection.     

Postoperative adjuvant transarterial chemoembolization improves outcomes of hepatocellular carcinoma associated with bile duct tumor thrombus: a propensity score matching analysis

BackgroundSurgical resection is the primary treatment for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT). This study was conducted to investigate the efficacy of postoperative adjuvant TACE (PA-TACE) in patients with HCC and BDTT.MethodsData from patients who underwent surgery for HCC with BDTT at two medical centers were retrospectively analyzed. The survival outcomes of patients who were treated by hepatic resection followed by PA-TACE were compared with those of patients who underwent surgery alone. Propensity score matching (PSM) analysis was performed with a 1:1 ratio.ResultsOf the 308 consecutively enrolled HCC patients with BDTT who underwent surgical resection, 134 underwent PA-TACE whereas 174 underwent surgery alone. From the initial cohort, PSM matched 106 pairs of patients. The OS and DFS rates were significantly better for the PA-TACE group than the surgery alone group (for OS: before PSM, P = 0.026; after PSM, P = 0.039; for DFS: before PSM, P = 0.010; after PSM, P = 0.013).ConclusionPA-TACE was associated with better survival outcomes than surgery alone for patients with HCC and BDTT. Prospective clinical trials are warranted to validate the beneficial effect of PA-TACE on HCC patients associated with BDTT.     

Prognostic factors in patients with middle and distal bile duct cancers

AIM:To identify the influence of the surgery type and prognostic factors in middle and distal bile duct cancers.METHODS:Between August 1990 and June 2011,data regarding the clinicopathological factors of 194patients with surgical and pathological confirmation were collected.A total of 133 patients underwent resections(R0,R1,R2;n=102,24,7),whereas 61patients underwent nonresectional surgery.Either pancreaticoduodenectomy(PD)or bile duct resection(BDR)was selected according to the sites of tumors and comorbidities of the patients after confirming resectionmargin by the frozen histology in all cases.Univariate and multivariate analyses of clinicopathologic factors were performed,utilizing the Kaplan-Meyer method and Cox hazard regression analysis.RESULTS:The overall 5-year survival rate for the 133patients who underwent resection(R0,R1,and R2)was 41.2%,whereas no patients survived longer than3 years among the 61 patient who underwent nonresectional surgeries.The 5-year survival rate of the patients who underwent a PD(n=90)was higher than the rate of those who underwent BDR(n=43),although the difference was not statistically significant(46.6%vs 30.0%P=0.105).However,PD had a higher rate of R0 resection than BDR(90.0%vs 48.8%,P<0.0001).If R0 resection was achieved,PD and BDR showed similar survival rates(49.4%vs 46.5%P=0.762).The 5-year survival rates of R0 and R1 resections were not significantly different(49.0%vs 21.0%P=0.132),but R2 resections had lower survival(0%,P=0.0001).Although positive lymph node,presence of perineural invasion,presence of lymphovascular invasion(LVI),7th AJCC-UICC tumor node metastasis(TNM)stage,and involvement of resection margin were significant prognostic factors in univariate analysis,multivariate analysis identified only TNM stage and LVI as independent prognostic factors.CONCLUSION:PD had a greater likelihood of curative resection and R1 resection might have some positive impact.The TNM stage and LVI were independent prognostic factors.     

Clinical features and prognosis of hepatocellular carcinoma in young patients from a hepatitis B-endemic area

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, the clinical features of young HCC patients have not been fully studied. In the present study, we investigated the prevalence, clinical characteristics and prognosis of young HCC patients. METHODS: A retrospective analysis was performed for HCC patients in our center using Korean cancer registry data. Among 4234 patients enrolled, there were 38 patients younger than 30 years of age (0.9%). We compared clinical characteristics and survival data of these patients (group I) with those of sex-matched, randomly selected HCC patients aged 30-59 years (group II; n = 231) and 60 years or older (group III; n = 147). RESULTS: Group I showed distinct features compared with groups II and III as follows: low frequency of smoking history, high positive rate of hepatitis B s antigen, no association with anti-hepatitis C virus antibody, high frequency of alpha-fetoprotein > or = 400 ng/mL, well-preserved liver function, larger tumor size, more advanced tumor-node-metastasis (TNM) stage and Cancer of the Liver Italian Program (CLIP) score and more frequent application of surgical resection and chemotherapy as initial treatment. The overall survival of group I was worse than that of group II, but similar to that of group III. Multivariate analysis showed that TNM stage and CLIP score, not age itself, were independent predictive factors for survival. CONCLUSIONS: The results suggest that young HCC patients tend to have a poor prognosis owing to advanced tumor stage, despite well-preserved liver function and aggressive treatment. Further studies regarding the role of HCC screening in young people may be useful, especially in hepatitis B virus carriers from high endemic areas.     

Evaluation of predictive value of CLIP, Okuda, TNM and JIS staging systems for hepatocellular carcinoma patients undergoing surgery

BACKGROUND: An accurate staging system is required to assess hepatocellular carcinoma (HCC) patients in order to benefit from hepatic resection before surgery. Cancer of the Liver Italian Program (CLIP) score was considered to be better than the Okuda staging system to predict survival. Japan Integrated Staging Score (JIS score) includes tumor, nodes, metastases (TNM) stage and Child-Pugh grade as a new staging system for HCC. The purpose of the present paper was to compare the CLIP, Okuda, TNM and JIS staging systems for HCC patients undergoing surgery. METHODS: From 1991 to 1995, 599 patients undergoing hepatic resection for HCC from four medical centers in Taiwan were evaluated. All patients were classified by Okuda, CLIP, TNM and JIS systems. Factors associated survivals were analyzed. RESULTS: There was no statistical difference in survival between CLIP 0 and 1 patients, or among CLIP 2-4 patients. The prognostic validation of the Okuda and CLIP scoring systems in discriminating survival in HCC patients undergoing surgery was not satisfied. The TNM system was successful in predicting survival for HCC patients undergoing surgery. The JIS score could also differentiate survivals for those patients except for JIS 3. By multivariate analysis, age > or =60 years old, serum albumin <3.5 g/dL, tumor size >5 cm and TNM stage were associated with survival. CONCLUSION: Both the Okuda and CLIP systems are not superior to TNM staging for HCC patients who undergo surgical resection. Whether JIS score is feasible for those patients with advanced HCC needs further evaluation.     

Surgical treatment of hepatocellular carcinoma with bile duct tumor thrombi

AIM: To study the surgical treatment effect and outcome of hepatocellular carcinoma (HCC) with bile duct tumor thrombi (BDTT). METHODS: Fifty-three consecutive HCC patients with BDTT admitted in our department from July 1984 to December 2002 were reviewed retrospectively. The clinical data, diagnostic methods, surgical procedures and outcome of these patients were collected and analyzed. RESULTS: One patient rejected surgical treatment, 6 cases underwent percutaneous transhepatic cholangial drainage (PTCD) for unresectable primary disease, and the other 46 cases underwent surgical operation. The postoperative mortality was 17.6%, and the morbidity was 32.6%. Serum total bilirubin levels of these patients with obstructive jaundice decreased gradually after surgery. The survival time of six cases who underwent PTCD ranged from 2 to 7 mo (median survival of 3.7 mo). The survival time of the patients who received surgery was as follows: 2 mo for one patient who underwent laparotomy, 5-46 mo (median survival of 23.5 mo, which was the longest survival in comparison with patients who underwent other procedures, P=0.0024) for 17 cases who underwent hepatectomy, 5-17 mo (median survival of 10.0 mo) for 5 cases who underwent HACE, 3-9 mo (median survival of 6.1 mo) for 11 cases who underwent simple thrombectomy and biliary drainage, and 3-8 mo (median survival of 4.3 mo) for four cases who underwent simple biliary drainage. CONCLUSION: Jaundice caused by BDTT in HCC patients is not a contraindication for surgery. Only curative resection can result in long-term survival. Early diagnosis and surgical treatment are the key points to prolong the survival of patients.     

Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma?

Background:The incidence of combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma(c HCC-ICC) is relatively low,and the knowledge about the prognosis of c HCC-ICC remains obscure.In the study,we aimed to screen existing primary liver cancer staging systems and shed light on the prognosis and risk factors for c HCC-ICC.Methods:We retrospectively reviewed 206 c HCC-ICC patients who received curative surgical resection from April 1999 to March 2017.The correlation of survival measures with the histological types or with tumor staging systems was determined and predictive values of tumor staging systems with c HCC-ICC prognosis were compared.Results:The histological type was not associated with overall survival(OS)(P = 0.338) or disease-free survival(DFS)(P = 0.843) of patients after curative surgical resection.BCLC,TNM for HCC,and TNM for ICC stages correlated with both OS and DFS in c HCC-ICC(all P 0.05).The predictive values of TNM for HCC and TNM for ICC stages were similar in terms of predicting postoperative OS(P = 0.798) and DFS(P = 0.191) in c HCC-ICC.TNM for HCC was superior to BCLC for predicting postoperative OS(P = 0.022) in c HCC-ICC.Conclusion:The TNM for HCC staging system should be prioritized for clinical applications in predicting c HCC-ICC prognosis.     

Hepatic resection for elderly patients with hepatocellular carcinoma: a systematic review of more than 17,000 patients

ABSTRACT

Background: With the aging population and increasing incidence of hepatic malignancies in elderly patients, establishing the safety and efficacy of hepatic resection for elderly patients with hepatocellular carcinoma (HCC) is crucial. The present systematic review investigates postoperative morbidity, hospital mortality, median survival time, overall and disease-free survival in elderly patients with undergoing hepatic resection.

Methods: Some databases were systematically searched for prospective or retrospective studies to reveal the safety and efficacy of hepatic resection for elderly patients with primary HCC.

Results: Fifty studies involving 4,169 elderly patients and 13,158 young patients with HCC were included into analyses. Elderly group patients had similar rate of median postoperative morbidity (28.2% vs. 29.6%) but higher mortality (3.0% vs. 1.2%) with young group patients. Moreover, elderly group patients had slightly lower median survival time (55 vs. 58 months), 5-years overall survival (51% vs. 56%) and 5-years disease-free survival (27% vs. 28%) than young group patients. There was an upward trend in 5-years overall and disease-free survival in either elderly or young group.

Conclusion: Though old age may increase the risk of hospital mortality for patients with HCC after hepatic resection, elderly patients can obtain acceptable long-term prognoses from hepatic resection.     

糖尿病对不同TNM分期肝细胞癌术后预后的影响

目的探讨2型糖尿病(T2DM)对肝细胞癌患者临床病理特征及其根治术后预后的影响。方法回顾性分析2009年11月至2011年6月在海军军医大学东方肝胆外科医院行根治性切除术的肝细胞癌患者的临床病理和生存资料。根据是否合并T2DM将患者分为T2DM组与无T2DM组, 比较2组患者的临床病理特征和预后情况。统计学方法采用卡方检验或Fisher确切概率法。采用Kaplan-Meier法进行单因素生存分析, 采用Cox比例风险回归模型进行多因素生存分析。结果共1 691例肝细胞癌患者入组, 其中142例(8.4%)患者合并T2DM。T2DM组患者中肝细胞癌发病年龄≥65岁的患者占比、男性占比、合并高血压病者占比、γ-谷氨酰转肽酶>61 U/L的患者占比均高于无T2DM组[24.6%(35/142)比10.4%(161/1 549)、92.3%(131/142)比85.7%(1 327/1 549)、43.7%(62/142)比12.3%(191/1 549)、58.5%(83/142)比49.4%(765/1 549)], 合并慢性肝炎病毒感染者占比、甲胎蛋白>20 μg/L的患者占...     

Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus

Aim:  Patients with high serum hepatitis B virus (HBV) DNA concentrations are at high risk of tumor recurrence after liver resection for HBV-related hepatocellular carcinoma (HCC).
Methods:  Among 24 patients with high serum HBV DNA concentrations who underwent liver resection for HBV-related HCC, postoperative lamivudine therapy was chosen by 14 (lamivudine group). The other 10 patients were controls.
Results:  Clinicopathologic findings did not differ between the groups. Tumor-free survival rate after surgery was significantly higher in the lamivudine than the control group ( P  = 0.0086). By univariate analysis, multiple tumors were also a risk factor for a short tumor-free survival. By multivariate analysis, lack of lamivudine therapy and multiple tumors were independent risk factors for a short tumor-free survival. In four patients YMDD mutant viruses were detected after beginning lamivudine administration; in two of them, adefovir dipivoxil was administered because of sustained serum alanine aminotransferase elevations.
Conclusion:  Lamivudine therapy improved tumor-free survival rate after curative resection of HBV-related HCC in patients with high serum concentrations of HBV DNA, although careful follow up proved necessary for the detection of YMDD mutant viruses.     

Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome

Background  Hepatocellular carcinoma (HCC) is uncommon in young adults. This study examined the clinical characteristics and survival outcome of young HCC patients compared with those in older patients. Methods  Data were prospectively collected from 638 patients diagnosed with HCC over a 9-year period. Patients aged ≤40 years at diagnosis of HCC were defined as young HCC patients. Their clinical characteristics and survival was compared with those aged >40 years. Results  The prevalence of young HCC was 8.6% (55/638). Young HCC patients had a significantly higher rate of hepatitis B-related disease (HBsAg positivity: 85.5% vs. 59.7%, P = 0.003), better Child-Pugh status (Child-Pugh class A: 69.1% vs. 43.9%, P = 0.002), and lower rates of cirrhosis (12.7% vs. 34.3%, P = 0.001) compared with the older group. They had more advanced disease at diagnosis, with higher α-fetoprotein levels (>12 000 μg/l: 45.4% vs. 30.5%, P = 0.026), a higher incidence of portal vein involvement (63.6% vs. 40%, P = 0.003), and a more advanced TNM stage (TNM IV: 83.6% vs. 66.4%, P = 0.018). More young patients were eligible for surgical resection (18.2% vs. 8.2%, P = 0.014). The overall survival between the two groups was similar, but when the patients were stratified for stage of disease, the median survival of young patients with early disease was superior to that of older patients (51.2 vs. 11.6 months, P = 0.025). Conclusions  HCC in young adults occurs mainly in hepatitis B carriers and is often diagnosed at an advanced stage. Their survival outcome is not different from that of older patients because the advanced disease at presentation offsets the advantages of better liver function and a higher resection rate. However, there is a distinct survival advantage for young patients diagnosed with early disease. These results support the importance of extending HCC surveillance to young hepatitis B carriers.     

Pathologic response to preoperative transarte-rial chemoembolization for resectable hepato-cellular carcinoma may not predict recurrence after liver resection

BACKGROUND: Pathologic response(PR) predicts survival after preoperative chemotherapy and resection of a malignancy. Occasionally, transarterial chemoembolization(TACE)may be selected for preoperative management of resectable hepatocellular carcinoma(HCC). This study investigated whether PR to preoperative TACE can predict recurrence after resection for resectable HCC.METHODS: We conducted analysis of 106 HCC patients who underwent TACE followed by liver resection with a curative intent. The PR was evaluated as the mean percentage of nonviable tumor area within each tumor. We divided the patients into three groups according to response rate: complete PR(CPR), major response(MJR: PR≥50%) and minor response(MNR: PR50%). The primary endpoint was disease-free survival, and the secondary endpoints were predicting factors for tumor recurrence and MJR+CPR.RESULTS: Among the 121 TACE patients, PR could be measured in 106(87.6%). The mean interval between TACE and liver resection was 33.1 days. The 5-year disease-free survival rates by PR status were as follows: 40.6% CPR, 43.7% MJR, and 49.0% MNR(P=0.815). There were also no significant differences in overall survival between the three groups. Multivariate analyses revealed that microvascular invasion and capsular invasion(hazard ratio [HR]=11.224, P=0.002 and HR=2.220P=0.043) were independent predictors of disease-free survival.Multivariate analysis of the predictors of above 50% PR revealed that only hepatitis B was an independent factor.CONCLUSION: These data could reflect that the PR after TACE for resectable HCC may not be useful for predicting recurrence of HCC after resection.     

Risk factors and surgical outcomes for spontaneous rupture of BCLC stages A and B hepatocellular carcinoma: A case-control study

AIM: To investigate the risk factors and surgical outcomes for spontaneous rupture of Barcelona Clinic Liver Cancer (BCLC) stages A and B hepatocellular carcinoma (HCC).METHODS: From April 2002 to November 2006, 92 consecutive patients with spontaneous rupture of BCLC stage A or B HCC undergoing hepatic resection were included in a case group. A control arm of 184 cases (1:2 ratio) was chosen by matching the age, sex, BCLC stage and time of admission among the 2904 consecutive patients with non-ruptured HCC undergoing hepatic resection. Histological confirmation of HCC was available for all patients and ruptured HCC was confirmed by focal discontinuity of the tumor with surrounding perihepatic hematoma observed intraoperatively. Patients with microvascular thrombus in the hepatic vein branches were excluded from the study. Clinical data and survival time were collected and analysed.RESULTS: Sixteen patients were excluded from the study based on exclusion criteria, of whom 3 were in the case group and 13 in the control group. Compared with the control group, more patients in the case group had underlying diseases of hypertension (10.1% vs 3.5%, P = 0.030) and liver cirrhosis (82.0% vs 57.9%, P < 0.001). Tumors in 67 (75.3%) patients in the case group were located in segments II, III and VI, and the figure in the control group was also 67 (39.7%) (P < 0.001). On multivariate analysis, hypertension (HR = 7.38, 95%CI: 1.91-28.58, P = 0.004), liver cirrhosis (HR = 6.04, 95%CI: 2.83-12.88, P < 0.001) and tumor location in segments II, III and VI (HR = 5.03, 95%CI: 2.70-6.37, P < 0.001) were predictive for spontaneous rupture of HCC. In the case group, the median survival time and median disease-free survival time were 12 mo (range: 1-78 mo) and 4 mo (range: 0-78 mo), respectively. The 1-, 3- and 5-year overall survival rates and disease-free survival rates were 66.3%, 23.4% and 10.1%, and 57.0%, 16.8% and 4.5%, respectively. Only radical resection remained predictive for overall survival (HR = 0.32, 95%CI: 0.08-0.61, P = 0.015) and disease-free survival (HR = 0.12, 95%CI: 0.01-0.73, P = 0.002).CONCLUSION: Tumor location, hypertension and liver cirrhosis are associated with spontaneous rupture of HCC. One-stage hepatectomy should be recommended to patients with BCLC stages A and B disease.