Effects of cytoreductive surgery combined with hyperthermic perfusion chemotherapy on prognosis of patients with advanced gallbladder cancer

BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.

Heparin is an effective treatment for preventing liver failure after hepatectomy

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver resection.Heparin,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver failure.AIM To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.METHODS The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were not.The statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU mortality.Logistic regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two groups.RESULTS In this study,1388 patients who underwent liver cancer hepatectomy were analyzed.PSM yielded 213 matched pairs from the heparin-treated and control groups.Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples.Further analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU mortality.CONCLUSION Liver failure is an important hazard following hepatic surgery.During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure.This indicates that heparin may provide a hopeful option for controlling PHLF.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Machine learning approach to predict acute kidney injury after liver surgery

BACKGROUND Acute kidney injury(AKI)after surgery appears to increase the risk of death in patients with liver cancer.In recent years,machine learning algorithms have been shown to offer higher discriminative efficiency than classical statistical analysis.AIM To develop prediction models for AKI after liver cancer resection using machine learning techniques.METHODS We screened a total of 2450 patients who had undergone primary hepatocellular carcinoma resection at Changzheng Hospital,Shanghai City,China,from January 1,2015 to August 31,2020.The AKI definition used was consistent with the Kidney Disease:Improving Global Outcomes.We included in our analysis preoperative data such as demographic characteristics,laboratory findings,comorbidities,and medication,as well as perioperative data such as duration of surgery.Computerized algorithms used for model development included logistic regression(LR),support vector machine(SVM),random forest(RF),extreme gradient boosting(XGboost),and decision tree(DT).Feature importance was also ranked according to its contribution to model development.RESULTS AKI events occurred in 296 patients(12.1%)within 7 d after surgery.Among the original models based on machine learning techniques,the RF algorithm had optimal discrimination with an area under the curve value of 0.92,compared to 0.87 for XGBoost,0.90 for DT,0.90 for SVM,and 0.85 for LR.The RF algorithm also had the highest concordance-index(0.86)and the lowest Brier score(0.076).The variable that contributed the most in the RF algorithm was age,followed by cholesterol,and surgery time.CONCLUSION Machine learning algorithms are highly effective in discriminating patients at high risk of developing AKI.The successful application of machine learning models may help guide clinical decisions and help improve the long-term prognosis of patients.

Propensity score analyses of long-term outcomes of perivascular hepatocellular carcinoma: Radiofrequency ablation vs. surgery

To the Editor:WereadwithgreatinterestthearticlebyDr.Leeetal.[1],which compared the long-term outcomes of patients with perivascular hepatocellular carcinoma (HCC) after radiofrequency ablation(RFA) and surgical resection (SR) as first-line treatment. By using propensity score matching (PSM) analyses, the authors concluded that SR provided better long-term tumor control and overall survival than RFA for patients with small periportal tumors. Herein,

Endovascular treatment of delayed arterial hemorrhage after radical operation for hilar cholangiocarcinoma

Radical operation for hilar cholangiocarcinoma(HCCA)is the most effective treatment,but high rates of severe postoperative complication and death remain concerns due to the complexity of biliary and vascular anatomy of the hepatobiliary region.De-layed arterial hemorrhage(DAH)occurring>24 h postoperatively usually causes life-threatening bleeding,and relaparotomy for DAH would be difficult and hazardous because of postoperative adhe-sions and critical general condition.As endovascular technique is less invasive and has improved over the recent decades,clini-cians have begun to prefer endovascular treatment(EVT)to surgi-cal treatment of DAH after hepatobiliary pancreatic surgery.How-ever,to our knowledge,a relatively large series of patients dealing with the outcomes of EVT of DAH after surgery for HCCA has not been reported.Herein,we analyzed the technical and clinical out-comes of EVT in 17 patients to evaluate the efficacy and safety of EVT.

Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy

Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical practice.However,almost half of the patients have tumor recurrence,and there is no reliable prognostic prediction tool.Besides,it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it.It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus,to improve the outcomes of these patients.The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival(RFS)and overall survival(OS)in patients with singular nodular HCC by integrating the clinical data and radiological features.Methods:We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital(EHBH).They all met the surgical indications and underwent radical resection.We randomly divided the patients into the training cohort(n=132)and the validation cohort(n=79).We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS.By analyzing the receiver operating characteristic(ROC)curve,the discrimination accuracy of the models was compared with that of the traditional predictive models.Results:Our RFS model was based on HBV-DNA score,cirrhosis,tumor diameter and tumor capsule in imaging.RFS nomogram had fine calibration and discrimination capabilities,with a C-index of 0.74(95%CI:0.68-0.80).The OS nomogram,based on cirrhosis,tumor diameter and tumor capsule in imaging,had fine calibration and discrimination capabilities,with a C-index of 0.81(95%CI:0.74-0.87).The area under the receiver operating characteristic curve(AUC)of our model was larger than that of traditional liver cancer staging system,Korea model and Nomograms in Hepatectomy Patients with Hepatitis B VirusRelated Hepatocellular Carcinoma,indicating better discrimination capability.According to the models,we fitted the linear prediction equations.These results were validated in the validation cohort.Conclusions:Compared with previous radiography model,the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC.Our models may preoperatively identify patients with high risk of recurrence.These patients may benefit from neoadjuvant therapy which may improve the patients’outcomes.

Establishment of image-guided radiotherapy of orthotopic hepatocellular carcinoma mouse model

Background:Hepatocellular carcinoma(HCC)is the most common type of liver cancer.Recently,developments in radiotherapy technology have led to radiotherapy becoming one of the main therapeutics of HCC.Therefore,a suitable animal model for radiotherapy of the orthotopic HCC mouse model is urgently needed.Methods:In the present study,Hepa1-6 cells were injected into the liver of C57BL/6 mice in situ to mimic the pathological characteristics of the original HCC.Tumor formation was monitored by applying magnetic resonance imaging techniques and verified by H&E histopathological staining,AFP staining,and Ki67 staining.A single dose of 10 Gy X-ray was applied to simulate clinical radiotherapy plans using image-guided radiotherapy(IGRT)equipment.The efficiency of radiotherapy was then assessed by examining tumor size and weight one week after radiation.Cleaved-caspase3 staining and TUNEL were used to assess apoptosis in tumor tissues.Results:Intrahepatic tumor development was detected in the liver according using MRI.A high-density shadow could be seen 10 days after cell injection,which indicated the formation of HCC in vivo.The tumors grew steadily bigger,and underwent precision radiotherapy 20 days after injection.The typical pathological characteristics of HCC,such as large,deeply stained nuclei and irregular cell size,were visible with H&E staining.After radiotherapy,significantly higher expression of the immunohistochemical markers Ki67 and AFP were detected in tumor tissue than in the nearby normal tissue.Compared with the control group,the tumor volume(p=0.05)and weight(p<0.05)of the irradiated group were significantly reduced.In addition,a higher frequency of apoptosis was identified in irradiated HCC tumor tissue using the TUNEL and cleaved-caspase3 staining assay.Conclusions:In a well-established orthotopic HCC model,MRI was utilized to monitor the formation of tumors,and IGRT was used to simulate clinical radiotherapy.The present study could provide a suitable preclinical system for HCC radiotherapyrelated studies.

肝胆肿瘤中肿瘤特异性CircRNA衍生抗原肽的鉴定

基于肿瘤抗原的免疫治疗的应用受到验证免疫原性肽稀缺性的阻碍。本研究旨在研究环状RNA(circRNA)在肝胆肿瘤类器官中作为肿瘤抗原肽新来源的潜力。使用RNA测序(RNA-seq)和基于算法的评分工具,预测3950个翻译的肿瘤特异性环状RNA在27个类器官中产生18971个抗原肽。从抗原格局来看,11个氨基酸长度(mer)肽和人白细胞抗原(HLA)-A结合肽具有最高的免疫原性相关评分。在分析的3/5类器官中,有13个预测抗原肽通过质谱(MS)免疫肽组学被直接确认为HLA-A、HLA-B和HLA-C(HLA-ABC)结合肽。在流式细胞术和酶联免疫吸附试验(ELISA)中,由HLA-ABC分子呈递的circRNA衍生的肿瘤特异性肽刺激CD8(CD8)T细胞,显示CD107a干扰素γ(IFNγ)共表达和IFNγ分泌增加。免疫原性环状RNA衍生肽诱导的靶向类器官的细胞毒性T细胞活性在杀伤实验中得到验证。值得注意的是,来自circTBC1D15的抗原肽YGFNEILKK不仅被认为是类器官的HLA-ABC呈递肽,而且还显著降低了肿瘤类器官的存活率。本研究的发现强调了产生肿瘤抗原的一个关键亚群,这对靶向肿瘤特异性circRNA具有重要意义。

Portal vein embolization for closure of marked arterioportal shunt of hepatocellular carcinoma to enable radioembolization:A case report

BACKGROUND Marked arterioportal shunt(APS)can be a contraindication for transarterial radioembolization(TARE)because of the risk of radiation-induced liver toxicity or pneumonitis.To date,the best method to close marked APS to reduce intrahepatic shunt(IHS)and hepatopulmonary shunt(HPS)before TARE has not been elucidated.CASE SUMMARY This case report describes a novel strategy of embolization of the portal venous outlet to reduce IHS and HPS caused by marked APS before TARE in a patient with advanced hepatocellular carcinoma(HCC).The patient had a significant intratumoral shunt from the tumor artery to the portal vein and had already been suspected based on pre-interventional magnetic resonance angiography,and digital subtraction angiography(DSA)confirmed the shunt.Selective right portal vein embolization(PVE)was performed to close the APS outlet and DSA confirmed complete closure.Technetium-99m macroaggregated albumin was administered and single photon emission computed tomography revealed a low HPS with 8.4%.Successful TARE was subsequently performed.No major procedurerelated complication occurred.CONCLUSION Closure of APS with PVE during mapping angiography of advanced-stage HCC to enable reduction of HPS and subsequent TARE is feasible.

Preoperative prediction of microvascular invasion in hepatocellular carcinoma using ultrasound features including elasticity

BACKGROUND Microvascular invasion(MVI)is an important predictor of poor prognosis in patients with hepatocellular carcinoma(HCC).Accurate preoperative prediction of MVI in HCC would provide useful information to guide the choice of therapeutic strategy.Shear wave elastography(SWE)plays an important role in hepatic imaging,but its value in the preoperative prediction of MVI in HCC has not yet been proven.AIM To explore the value of conventional ultrasound features and SWE in the preoperative prediction of MVI in HCC.METHODS Patients with a postoperative pathological diagnosis of HCC and a definite diagnosis of MVI were enrolled in this study.Conventional ultrasound features and SWE features such as maximal elasticity(Emax)of HCCs and Emax of the periphery of HCCs were acquired before surgery.These features were compared between MVI-positive HCCs and MVI-negative HCCs and between mild MVI HCCs and severe MVI HCCs.RESULTS This study included 86 MVI-negative HCCs and 102 MVI-positive HCCs,including 54 with mild MVI and 48 with severe MVI.Maximal tumor diameters,surrounding liver tissue,color Doppler flow,Emax of HCCs,and Emax of the periphery of HCCs were significantly different between MVI-positive HCCs and MVI-negative HCCs.In addition,Emax of the periphery of HCCs was significantly different between mild MVI HCCs and severe MVI HCCs.Higher Emax of the periphery of HCCs and larger maximal diameters were independent risk factors for MVI,with odds ratios of 2.820 and 1.021,respectively.CONCLUSION HCC size and stiffness of the periphery of HCC are useful ultrasound criteria for predicting positive MVI.Preoperative ultrasound and SWE can provide useful information for the prediction of MVI in HCCs.

Optimal interventional treatment for liver cancer:HAIC,TACE or iTACE?

Primary liver cancer is a common and lethal malignancy in China.Transcatheter arterial chemoembolization(TACE)is globally recognized as the preferred treatment modality for the non-surgical resection of hepatocellular carcinoma(HCC),while transcatheter arterial infusion(TAI)is another effective interventional treatment for HCC.In recent years,hepatic arterial infusion chemotherapy(HAIC)has gained increasing attention as an application-regulated modality for TAI.Owing to the current debate in the medical community regarding the use of HAIC and TACE for the treatment of HCC,the application of both approaches should be considered at a higher level,with a broader perspective and a more normative aspect.Accordingly,we aimed to define the rational combination of liver cancer TAI/HAIC with TACE as infusion transcatheter chemoembolization(iTACE),which suggests that the two interventions are not superior but lead to a mutually beneficial situation.In this review,we sought to discuss the development,specification,application,challenge and innovation,debate,and union of TAI/HAIC and TACE,and the clinical application and latest research on iTACE.We aimed to introduce new concepts of iTACE and expect new breakthroughs in the treatment of liver cancer owing to the combined use of the two major interventional tools.

Controlled low central venous pressure reduces blood loss and transfusion requirements in hepatectomy

AIM:To evaluate the effect of low central venous pressure(LCVP)on blood loss and blood transfusion in patients undergoing hepatectomy.METHODS:Electronic databases and bibliography lists were searched for potential articles.A meta-analysis of all randomized controlled trials(RCTs)investigating LCVP in hepatectomy was performed.The following three outcomes were analyzed:blood loss,blood transfusion and duration of operation.RESULTS:Five RCTs including 283 patients were assessed.Meta-analysis showed that blood loss in the LCVP group was significantly less than that in the control group(MD=-391.95,95%CI:-559.35--224.56,P<0.00001).In addition,blood transfusion in the LCVP group was also significantly less than that in the control group(MD=-246.87,95%CI:-427.06--66.69,P=0.007).The duration of operation in the LCVP group was significantly shorter than that in the control group(MD=-18.89,95%CI:-35.18--2.59,P=0.02).Most studies found no significant difference in renal and liver function between the two groups.CONCLUSION:Controlled LCVP is a simple and effective technique to reduce blood loss and blood transfusion during liver resection,and appears to have no detrimental effects on liver and renal function.

Prealbumin is predictive for postoperative liver insufficiency in patients undergoing liver resection

AIM:To investigate the risk factors for postoperative liver insufficiency in patients with Child-Pugh class A liver function undergoing liver resection.METHODS:A total of 427 consecutive patients undergoing partial hepatectomy from October 2007 to April 2011 at a single center(Department of Hepatic SurgeryⅠ,Eastern Hepatobiliary Surgery Hospital,Shanghai,China) were included in the study.All the patients had preoperative liver function of Child-Pugh class A and were diagnosed as having primary liver cancer by postoperative histopathology.Surgery was performed by the same team and hepatic resection was carried out by a clamp crushing method.A clamp/unclamp time of 15 min/5 min was adopted for hepatic inflow occlusion.Patients' records of demographic variables,intraoperative parameters,pathological findings and laboratory test results were reviewed.Postoperative liver insufficiency and failure were defined as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak,clinically apparent ascites,prolonged coagulopathy requiring frozen fresh plasma,and/or hepatic encephalopathy.The incidence of postoperative liver insufficiency or liver failure was observed and the attributing risk factors were analyzed.A multivariate analysis was conducted to determine the independent predictive factors.RESULTS:Among the 427 patients,there were 362 males and 65 females,with a mean age of 51.1 ± 10.4 years.Most patients(86.4%) had a background of viral hepatitis and 234(54.8%) patients had liver cirrhosis.Indications for partial hepatectomy included hepatocellular carcinoma(391 patients),intrahepatic cholangiocarcinoma(31 patients) and a combination of both(5 patients).Hepatic resections of ≤ 3 and ≥ 4 liver segments were performed in 358(83.8%) and 69(16.2%) patients,respectively.Seventeen(4.0%) patients developed liver insufficiency after hepatectomy,of whom 10 patients manifested as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak,6 patients had clinically apparent ascites and prolonged coagulopathy,1 patient had hepatic encephalopathy and died on day 21 after surgery.On univariate analysis,age ≥ 60 years and prealbumin < 170 mg/dL were found to be significantly correlated with postoperative liver insufficiency(P = 0.045 and P = 0.009,respectively).There was no statistical difference in postoperative liver insufficiency between patients with or without hepatitis,liver cirrhosis and esophagogastric varices.Intraoperative parameters(type of resection,inflow blood occlusion time,blood loss and blood transfusion) and laboratory test results were not associated with postoperative liver insufficiency either.Age ≥ 60 years and prealbumin < 170 mg/dL were selected on multivariate analysis,and only prealbumin < 170 mg/dL remained predictive(hazard ratio,3.192;95%CI:1.185-8.601,P = 0.022).CONCLUSION:Prealbumin serum level is a predictive factor for postoperative liver insufficiency in patients with liver function of Child-Pugh class A undergoing hepatectomy.Since prealbumin is a good marker of nutritional status,the improved nutritional status may decrease the incidence of liver insufficiency.

Predictors and clinical outcomes for spontaneous rupture of hepatocellular carcinoma

AIM:To determine the risk factors for hepatocellular carcinoma(HCC) rupture,and report the management and long-term survival results of patients with spontaneous rupture of HCC.METHODS:Among 4209 patients with HCC who were diagnosed at Eastern Hepatobiliary Surgery Hospital from April 2002 to November 2006,200(4.8%) patients with ruptured HCC(case group) were studied retrospectively in term of their clinical characteristics and prognostic factors.The one-stage therapeutic approach to manage ruptured HCC consisted of initial management by conservative treatment,transarterial embolization(TACE) or hepatic resection.Results of various treatments in the case group were evaluated and compared with the control group(202 patients) without ruptured HCC during the same study period.Continuous data were expressed as mean ± SD or me-dian(range) where appropriate and compared using the unpaired t test.Categorical variables were compared using the Chi-square test with Yates correction or the Fisher exact test where appropriate.The overall survival rate in each group was determined using the Kaplan-Meier method and a log-rank test.RESULTS:Compared with the control group,more patients in the case group had underlying diseases of hypertension(7.5% vs 3.0%,P =0.041) and liver cirrhosis(87.5% vs 56.4%,P < 0.001),tumor size >5 cm(83.0% vs 57.4%,P < 0.001),tumor protrusion from the liver surface(66.0% vs 44.6%,P < 0.001),vascular thrombus(30.5% vs 8.9%,P < 0.001) and extrahepatic invasion(36.5% vs 12.4%,P < 0.001).On multivariate logistic regression analysis,underlying diseases of hypertension(P = 0.002) and liver cirrhosis(P < 0.001),tumor size > 5 cm(P < 0.001),vascular thrombus(P = 0.002) and extrahepatic invasion(P < 0.001) were predictive for spontaneous rupture of HCC.Among the 200 patients with spontaneous rupture of HCC,105 patients underwent hepatic resection,33 received TACE,and 62 were managed with conservative treatment.The median survival time(MST) of all patients with spontaneous rupture of HCC was 6 mo(range,1-72 mo),and the overall survival at 1,3 and 5 years were 32.5%,10% and 4%,respectively.The MST was 12 mo(range,1-72 mo) in the surgical group,4 mo(range,1-30 mo) in the TACE group and 1 mo(range,1-19 mo) in the conservative group.Ninety-eight patients in the control group underwent hepatic resection,and the MST and median diseasefree survival time were 46 mo(range,6-93 mo) and 23 mo(range,3-39 mo) respectively,which were much longer than that of patients with spontaneous rupture of HCC undergoing hepatic resection(P < 0.001).The 1-,3-,and 5-year overall survival rates and the 1-,3-and 5-year disease-free survival rates in patients with ruptured HCC undergoing hepatectomy were 57.1%,19.0% and 7.6%,27.6%,14.3% and 3.8%,respectively,compared with those of 77.1%,59.8% and 41.2%,57.1%,40.6% and 32.9% in 98 patients with-CONCLUSION:Prolonged survival can be achieved in selected patients undergoing one-stage hepatectomy,although the survival results were inferior to those of the patients without ruptured HCC.

Routine lymph node dissection may be not suitable for all intrahepatic cholangiocarcinoma patients: Results of a monocentric series

AIM:To investigate the indications for lymph node dissection(LND)in intrahepatic cholangiocarcinoma patients.METHODS:A retrospective analysis was conducted on 124 intrahepatic cholangiocarcinoma(ICC)patients who had undergone surgical resection of ICC from January 2006 to December 2007.Curative resection was attempted for all patients unless there were metastases to lymph nodes(LNs)beyond the hepatoduodenal ligament.Prophylactic LND was performed in patients in whom any enlarged LNs had been suspicious for metastases.The patients were classified according to the LND and LN metastases.Clinicopathologic,operative,and long-term survival data were collected retrospectively.The impact on survival of LND during primary resection was analyzed.RESULTS:Of 53 patients who had undergone hepatic resection with curative intent combined with regional LND,11 had lymph nodes metastases.Whether or not patients without lymph node involvement had undergone LND made no significant difference to their survival(P=0.822).Five patients with multiple tumors and involvement of lymph nodes underwent hepatic resection with LND;their survival curve did not differ significantly from that of the palliative resection group(P=0.744).However,there were significant differences in survival between patients with lymph node involvement and a solitary tumor who underwent hepatic resection with LND and the palliative resection group(median survival time 12 mo vs 6.0 mo,P=0.013).CONCLUSION:ICC patients without lymph node involvement and patients with multiple tumors and lymph node metastases may not benefit from aggressive lymphadenectomy.Routine LND should be considered with discretion.

Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma

AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003.Of these,429(8.1%)patients were diagnosed with ICC,and their clinicopathological, surgical,and survival characteristics were analyzed. RESULTS:Upper abdominal discomfort or pain(65.0%), no symptoms(12.1%),and hypodynamia(8.2%)were the major causes for medical attention.Laboratory tests showed 198(46.4%)patients were HBsAg positive, 90(21.3%)hadα-fetoprotein>20μg/L,50(11.9%) carcinoembryonic antigen>10μg/L,and 242(57.5%) carbohydrate antigen 19-9(CA19-9)>37 U/mL.Survival data was available for 329(76.7%)patients and their mean survival time was 12.4 mo.The overall survival of the patients with R0,R1 resection and punching exploration were 18.3,6.6 and 5.6 mo,respectively. Additionally,CA19-9>37 U/mL was associated with lymph node metastases,but inversely associated withcirrhosis.Multivariate analysis indicated that radical resection,lymph node metastases,macroscopic tumor thrombi and size,and CA19-9 were associated with prognosis. CONCLUSION:Surgical radical resection is still the most effective means to cure ICC.Certain laboratory tests(such as CA19-9)can effectively predict the survival of the patients with ICC.

Cloning and expression of MXR7 gene in human HCC tissue

AIM To clone and identify the whole cDNA ofMXR7 gene and to find out its expression inhuman HCC,and normal tissues.METHODS The DNA primers were designed andsynthesized according to the whole cDNAsequence of MXR? gene.The cDNA of humanHCC was taken as the template while the cDNA ofMXR7 gene was synthesized by polymerasechain reaction（PCR）.Recombinant DNAconforming to reading frame was constructed byconnecting purified PCR product of the cDNA ofMXR? gene with expression vector pGEX-5X-1 offusion protein.The plasmid MXRT/pGEX-5X-1was identified by sequencing.Using 32p labeledMXR? cDNA as probe,MXR7 mRNA expressionwas detected by Northern blot analysis in 12different human normal tissues,7 preoperativelyuntreated non-liver tumor tissues,30preoperatively untreated HCC,theparacancerous liver tissues and 12 normal livertissues samples.RESULTS Restriction enzyme and sequenceanalysis confirmed that the insertion sequence invector pGEX-5X-1 was the same as the cDNAsequence of MXR7 gene.Northern blot analysisshowed no expression of MXR? mRNA in 12 kindsof normal human tissues including liver,7 tumortissues in other sites and 12 normal livertissues,the frequencies of MXR7 mRNA expression in HCC and paracancerous livertissues were 76.6% and 13.3%,respectively.The frequency of MXR7 mRNA expression in HCCwithout elevation of serum AFP and in HCC【5cm was 90%（9/10）and 83.3%（5/6）,respectively.CONCLUSION MXR7 mRNA is highly expressedin human HCC,which is specific and occurs at anearly stage of HCC,suggesting MXR7 mRNA canbe a tumor biomarker for HCC.The detection ofMXR7 mRNA expression in the biopsied livertissue is helpful in discovering early subclinicalliver cancer in those with negative serum AFP.

Endoscopic sphincterotomy plus large-balloon dilation vs endoscopic sphincterotomy for choledocholithiasis:A meta-analysis

AIM:To perform a meta-analysis of large-balloon dilation(LBD)plus endoscopic sphincterotomy(EST)vs EST alone for removal of bile duct stones.METHODS:Databases including PubMed,EMBASE,the Cochrane Library,the Science Citation Index,and important meeting abstracts were searched and evaluated by two reviewers independently.The main outcome measures included:complete stone removal,stone removal in the first session,use of mechanical lithotripsy,procedure time,and procedure-related complications.A fixed-effects model weighted by the Mantel-Haenszel method was used for pooling the odds ratio(OR)when heterogeneity was not significant among the studies.When a Q test or I2statistic indicated substantial heterogeneity,a random-effects model weighted by the DerSimonian-Laird method was used.RESULTS:Six randomized controlled trials involving835 patients were analyzed.There was no significant heterogeneity for most results;we analyzed these using a fixed-effects model.Meta-analysis showed EST plus LBD caused fewer overall complications than EST alone(OR=0.53,95%CI:0.33-0.85,P=0.008);sub-category analysis indicated a significantly lower risk of perforation in the EST plus LBD group(Peto OR=0.14,95%CI:0.20-0.98,P=0.05).Use of mechanical lithotripsy in the EST plus LBD group decreased significantly(OR=0.26,95%CI:0.08-0.82,P=0.02),especially in patients with a stone size larger than 15 mm(OR=0.15,95%CI:0.03-0.68,P=0.01).There were no significant differences between the two groups regarding complete stone removal,stone removal in the first session,post-endoscopic retrograde cholangiopancreatography pancreatitis,bleeding,infection of biliary tract,and procedure time.CONCLUSION:EST plus LBD is an effective approach for the removal of large bile duct stones,causing fewer complications than EST alone.