Prospective,single-center cohort studyanalyzing the efficacy of complete laparoscopic resection on recurrent hepatocellular carcinoma

Background:Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma(HCC).However,few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy.The present prospective study compared the clinical efficacy of laparoscopic surgery with conventional open surgery in HCC patients with postoperative tumor recurrence.Methods:We conducted a prospective study of 64 patients,all of whom had undergone open surgery once before,who were diagnosed with recurrent HCC between June 2014 and November 2014.The laparoscopic group(n = 31)underwent laparoscopic hepatectomy,and the control group(n = 33) underwent conventional open surgery.Operation time,intraoperative blood loss,surgical margins,postoperative pain scores,postoperative time until the patient could walk,anal exsufflation time,length of hospital stay,and inpatient costs were compared between the two groups.The patients were followed up for 1 year after surgery,and relapse-free survival was compared between the two groups.Results:All surgeries were successfully completed.No conversion to open surgery occurred in the laparoscopic group,and no serious postoperative complications occurred in either group.No significant difference in inpatient costs was found between the laparoscopic group and the control group(P = 0.079),but significant differences between the two groups were observed for operation time(116.7 ± 37.5 vs.148.2 ± 46.7 min,P = 0.031),intraoperative blood loss(117.5 ± 35.5 vs.265.9 ± 70.3 mL,P = 0.012),postoperative time until the patient could walk(1.6 ± 0.6vs.2.2 ± 0.8 days,P < 0.05),anal exsufflation time(2.1 ± 0.3 vs.2.8 ± 0.7 days,P = 0.041),visual analogue scale pain score(P < 0.05),postoperative hepatic function(P < 0.05),and length of hospital stay(4.5 ± 1.3 vs.6.0 ± 1.2 days,P = 0.014).During the 1-year postoperative follow-up period,6 patients in each group had recurrent HCC on the side of the initial operation,but no significant difference between groups was observed in the recurrence rate or relapse-free survival.In the laparoscopic group,operation time,postoperative time until the patient could walk,anal exsufflation time,and inpatient costs were not different(P > 0.05) between the patients with contralateral HCC recurrence(n=18) and those with ipsilateral HCC recurrence(n = 13).However,intraoperative blood loss was significantly less(97.7 ± 14.0 vs.186.3 ± 125.6 mL,P = 0.012) and the hospital stay was significantly shorter(4.2 ± 0.7 vs.6.1 ± 1.7 days,P = 0.021) for the patients with contralateral recurrence than for those with ipsilateral recurrence.Conclusions:For the patients who previously underwent conventional open surgical resection of HCC,complete laparoscopic resection was safe and effective for recurrent HCC and resulted in a shorter operation time,less intraoperative blood loss,and a faster postoperative recovery than conventional open surgery.Laparoscopic resection was especially advantageous for the patients with contralateral HCC recurrence.

Impact of oral anti-hepatitis B therapy on the survival of patients with hepatocellular carcinoma initially treated with chemoembolization

Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.

Left jackknife position:a novel position for laparoscopic hepatectomy

Background: Laparoscopic hepatectomy for hepatocellular carcinoma(HCC) located in segment Ⅵ, Ⅶ, or Ⅷ of the liver is usually difficult because of poor operative exposure, due to the unique anatomical structure. In this study, we evaluated the practice of laparoscopic hepatectomy with the left jackknife position for patients with HCC located in segment Ⅵ, Ⅶ, or Ⅷ.Methods: A total of 10 patients were enrolled to undergo laparoscopic hepatectomy with the left jackknife position.Tumors located in segment Ⅵ, Ⅶ, or Ⅷ were assessed by preoperative dynamic computed tomography or magnetic resonance imaging. Operation time, intraoperative blood loss, postoperative fasting time, postoperative drainage time, major postoperative complications, and duration of postoperative hospital stay were recorded.Results: All surgeries were successfully completed. None of the patients required conversion to open surgery during the procedure, and no serious postoperative complications were observed.The median tumor size was 31 mm(range 23-41 mm) in diameter, the mean operation time was 166 ± 38 min, the mean intraoperative blood loss was220 ± 135 mL, and the median postoperative hospital stay was 4 days(range 2-7 days).Conclusions: For HCC located in segment Ⅵ, Ⅶ, or Ⅷ, laparoscopic hepatectomy with this novel position—the left jackknife position—is safe and effective during tumor resection by exposing a sufficient operating field.Trial registration ClinicalTrials.gov ID:

Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) patients.METHODS We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival(OS) outcomes.RESULTS The expression of nuclear IDO1 was significantly correlated with body mass index(P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1(P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio(HR) = 2.044, 95% confidence interval(CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2(HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2(HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1(P = 0.041), nuclear/cytoplasmic IDO1(HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2(HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC(HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients(HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC.

左侧折刀体位在腹腔镜肝切除术中的新应用

背景与目的由于独特的解剖结构和手术显露不佳,通过腹腔镜肝切除术治疗位于肝脏Ⅵ、Ⅶ或Ⅷ段的肝细胞癌(hepatocellular carcinoma,HCC)通常是比较困难的。在本研究中,我们评价了左侧折刀体位腹腔镜肝切除术对治疗位于Ⅵ、Ⅶ或Ⅷ段的HCC患者的临床疗效。方法共10例患者进行了左侧折刀体位腹腔镜肝切除术。通过术前动态计算机断层扫描或磁共振成像来评估位于Ⅵ、Ⅶ或Ⅷ段的肿瘤。记录了手术时间、术中出血量、术后开始进食时间、术后引流时间、术后主要并发症及术后住院时间。结果所有手术均顺利完成。在手术过程中没有患者需要转为开腹手术,且术后无严重并发症发生。肿瘤直径的中位数为31 mm(23–41 mm),平均手术时间为166±38 min,术中平均出血量为220±135 mL,术后住院时间中位数为4 d(2–7 d)。结论左侧折刀体位在肿瘤切除术中可以展示出足够的术野显露,在这种新的体位下对位于Ⅵ、Ⅶ或Ⅷ段的HCC进行腹腔镜肝切除术是安全有效的。

预测肝细胞癌腹腔镜肝切除术后复发风险的列线图模型

背景与目的肝细胞癌(hepatocellular carcinoma,HCC)患者手术切除术后5年复发率很高(60%)。腹腔镜肝切除术(laparoscopic hepatectomy,LH)不断发展,但鲜有研究对LH与传统手术方法治疗HCC的疗效进行比较。本研究旨在建立一种预测HCC患者LH后复发风险的列线图模型。方法收集432例病理确诊为HCC并首次接受LH治疗且手术切缘>1cm的患者的临床资料。评估了其临床病理特征对无复发生存期(recurrence-free survival,RFS)的影响,在此基础上,使用训练队列(n=324)建立了列线图,并在现有的验证队列(n=108)中进行了内部验证。结果乙型肝炎表面抗原[风险比(hazard ratio,HR),1.838;P=0.044]、肿瘤数目(HR,1.774;P=0.003)、癌栓(HR,2.356;P=0.003)、癌细胞分化程度(HR,0.745;P=0.080)和肿瘤微血管浸润(HR,1.673;P=0.007)是训练队列中RFS的独立预后因素,并用于建立列线图。采用列线图预测RFS的C-index为0.786,高于第8版美国癌症联合会TNM分期系统(C-index,0.698)和巴塞罗那临床肝癌分期系统(C-index,0.632)。校准曲线也证明了列线图预测结果与实际生存一致性较高。受试者工作特征曲线分析表明,与其他系统相比,该列线图对RFS的预测效果更佳,具有更高的阈值概率,这在验证队列中也得到了证实。结论我们建立和验证了可将HCC患者首次接受LH后复发风险量化的列线图,该列线图可应用于临床,辅助医生对患者制订个性化术后监测方案。

Integrated genetic and epigenetic analysis reveals DNA repair alterations in multifocal hepatocellular carcinoma

Dear Editor,Hepatocellular carcinoma(HCC)ranks the fourth most lethal cancer worldwide and over 50%of cases are diagnosed as multifocal HCC(mHCC)with dismal prognosis.1 mHCC displays more complicated intratumor heterogeneity(ITH)and clonal evolution course which decreases the efficacy of clinical treatments.

A nomogram predicting the recurrence of hepatocellular carcinoma in patients after laparoscopic hepatectomy

Background:Patients with hepatocellular carcinoma(HCC)undergoing surgical resection still have a high 5-year recurrence rate(~60%).With the development of laparoscopic hepatectomy(LH),few studies have compared the efficacy between LH and traditional surgical approach on HCC.The objective of this study was to establish a nomo-gram to evaluate the risk of recurrence in HCC patients who underwent LH.Methods:The clinical data of 432 patients,pathologically diagnosed with HCC,underwent LH as initial treatment and had surgical margin>1 cm were collected.The significance of their clinicopathological features to recurrence-free survival(RFS)was assessed,based on which a nomogram was constructed using a training cohort(n=324)and was internally validated using a temporal validation cohort(n=108).Results:Hepatitis B surface antigen(hazard ratio[HR],1.838;P=0.044),tumor number(HR,1.774;P=0.003),tumor thrombus(HR,2.356;P=0.003),cancer cell differentiation(HR,0.745;P=0.080),and microvascular tumor invasion(HR,1.673;P=0.007)were found to be independent risk factors for RFS in the training cohort,and were used for con-structing the nomogram.The C-index for RFS prediction in the training cohort using the nomogram was 0.786,which was higher than that of the 8th edition of the American Joint Committee on Cancer TNM classification(C-index,0.698)and the Barcelona Clinic Liver Cancer staging system(C-index,0.632).A high consistency between the nomogram prediction and actual observation was also demonstrated by a calibration curve.An improved predictive benefit in RFS and higher threshold probability of the nomogram were determined by receiver operating characteristic curve analysis,which was also confirmed in the validation cohort compared to other systems.Conclusions:We constructed and validated a nomogram able to quantify the risk of recurrence after initial LH for HCC patients,which can be clinically implemented in assisting the planification of individual postoperative surveil-lance protocols.

Tescalcin is an unfavorable prognosis factor that regulats cell proliferation and survival in hepatocellular carcinoma patients

Background:Hepatocellular carcinoma(HCC)is a major health problem and a primary cause of cancer-related death worldwide.Although great advances have achieved recently by large-scale high-throughput analysis,the precise molecular mechanism underlying HCC progression remains to be clearly elucidated.We investigated the relationship between Tescalcin(TESC),a candidate oncogene,and clinicopathological features of HCC patients and explored the role of TECS in HCC development.Methods:To identify new genes involved in HCC development,we analyzed The Cancer Genome Atlas liver cancer database,and TESC was selected for further investigation.HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance.TESC was knocked down by using short-hairpin RNAs.Cell proliferation was analyzed by WST-1 assay and cell counting.Cell apoptosis was tested by fluorescence-activated cell sorting.A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC.Affymetrix microarray was used to identify its molecular mechanism.Results:TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues.High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray.Large tumor(>5 cm)and elevated total bilirubin were associated with high TESC expression(both P<0.050).In multivariate analysis,TESC was identified as an independent prognostic factor for short overall survival of HCC patients.TESC knockdown impaired HCC cell growth in vitro and in vivo.TESC knockdown significantly increased cell apoptosis in HCC cell lines.Furthermore,Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways.Conclusion:TESC was identified as an independent prognostic factor for short overall survival of HCC patients,and was critical for HCC cell proliferation and survival.

IPO Pricing Efficiency in China： A ChiNext Board Focus

This paper examines what determines the offer price for a ChiNext IPO and discusses how we can improve the current ＂Chinese-style＂ bookbuilding process. We establish that the ChiNext IPO underwriter relies upon the institutional investors to discover the issuer＇s intrinsic value （in the form of a preliminary price）, and that the same underwriter adjusts the preliminary price to establish the final offer price, based on its assessment of the institutional investors＇ motivations. Since the underwriter does not have discretionary power in new share allocation, this ＂Chinese-style＂ bookbuilding process contains certain pitfalls from an information asymmetry standpoint. The institutional investors mainly use ＂simple and direct＂ variables that do not adequately reflect the issuer＇s true intrinsic value to develop the preliminary price, while the underwriter adjusts that price downward to establish the offer price to clear the market, as a measure to counter a perceived free-rider issue among the institutional investors. This process, in effect, contributes to initial IPO underpricing and causes principal-agent conflicts between the underwriter and the issuer. We argue that such a pricing inefficiency could be improved by an innovative ＂bookbuilding plus price discretionary auction＂ process, which is a combination of the modified OpenlPO and Taiwan-style auctioned IPO approaches.