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 u...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.展开更多
BACKGROUND The prognosis of intrahepatic cholangiocarcinoma(ICC) with lymph node metastasis is poor.The feasibility of surgery is not certain,which is a contraindication according to the National Comprehensive Cancer ...BACKGROUND The prognosis of intrahepatic cholangiocarcinoma(ICC) with lymph node metastasis is poor.The feasibility of surgery is not certain,which is a contraindication according to the National Comprehensive Cancer Network guidelines.The role of immunotherapy as a neoadjuvant therapy for ICC is not clear.We herein describe a case of ICC with lymph node metastasis that was successfully treated with neoadjuvant therapy.CASE SUMMARY A 60-year-old man with a liver tumor was admitted to our hospital.Enhanced computed tomography and magnetic resonance imaging revealed a spaceoccupying lesion in the right lobe of the liver.Multiple subfoci were found around the tumor,and the right posterior branch of the portal vein was invaded.Liver biopsy indicated poorly differentiated cholangiocytes.According to the American Joint Committee on Cancer disease stage classification,ICC with hilar lymph node metastasis(stage ⅢB) and para-aortic lymph node metastasis was suspected.A report showed that two patients with stage ⅢB ICC achieved a complete response(CR) 13 mo and 16 mo after chemotherapy with a PD-1 monoclonal antibody.After multidisciplinary consultation,the patient was given neoadjuvant therapy,surgical resection and lymph node dissection,and postoperative adjuvant therapy.After three rounds of PD-1 immunotherapy(camrelizumab) and two rounds of gemcitabine combined with cisplatin regimen chemotherapy,the tumor size was reduced.Therefore,a partial response was achieved.Exploratory laparotomy found that the lymph nodes of Group 16 were negative,and the tumor could be surgically removed.Therefore,the patient underwent right hemihepatectomy plus lymph node dissection.The patient received six rounds of chemotherapy and five rounds of PD-1 treatment postoperatively.After 8 mo of follow-up,no recurrence was found,and a CR was achieved.CONCLUSION Neoadjuvant therapy combined with surgical resection is useful for advanced-stage ICC.This is the first report of successful treatment of stage ⅢB ICC using neoadjuvant therapy with a PD-1 inhibitor.展开更多
Objective： The outcome of surgical treatment of patients with intrahepatic cholangiocarcinoma （ICC） is poor. This study was designed to analyze prognostic factors after surgical procedure for ICCs. Methods： A retr...Objective： The outcome of surgical treatment of patients with intrahepatic cholangiocarcinoma （ICC） is poor. This study was designed to analyze prognostic factors after surgical procedure for ICCs. Methods： A retrospective clinical analysis was made in 183 cases of ICC, admitted to Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, from December 1996 to July 2003. Fifteen clinicopathologic factors that could possibly influence survival were selected. A multivariate analysis of these individuals was performed using the Cox Proportional Hazards Model. Results： The accumulative 1-, 3-and 5-year survival rates of the patients were 51.3%, 21.6% and 11.8% respectively. The statistical analysis showed that surgical procedure, lymph node metastasis, serum level of CA19-9 and pathological differentiation grade affected postoperative survival significantly, but transfusion, postoperative radiotherapy and chemotherapy, diameter of tumor, serum level of AFP, cirrhosis, preoperative total serum bilirubin level （TBIL）, ratio of albumin to globulin （A/G）, sex and age were not significant factors influencing postoperative survival. Conclusion： Major hepatectomy with systematic lymph node dissection may be recommended for the surgical treatment of ICC. Aggressive treatment and prevention on postoperative intrahepatic recurrence and lymph node metastasis are important strategy to improve the survival for ICC.展开更多
BACKGROUND: Pyogenic hepatic abscess may mimic primary or secondary carcinoma of the liver on contrast-enhanced computed tomography(CECT). The present study was to explore the usefulness of the analysis of multislice-...BACKGROUND: Pyogenic hepatic abscess may mimic primary or secondary carcinoma of the liver on contrast-enhanced computed tomography(CECT). The present study was to explore the usefulness of the analysis of multislice-based texture acquired from CECT in the differentiation between pyogenic hepatic abscesses and malignant mimickers.METHODS: This retrospective study included 25 abscesses in 20 patients and 33 tumors in 26 subjects who underwent CECT. To make comparison, we also enrolled 19 patients with hepatic single simple cyst. The images from CECT were analyzed using a Laplacian of Gaussian band-pass filter(5 filter levels with sigma weighting ranging from 1.0 to 2.5). We also quantified the uniformity, entropy, kurtosis and skewness of the multislice-based texture at different sigma weightings. Statistical significance for these parameters was tested with oneway ANOVA followed by Tukey honestly significant difference(HSD) test. Diagnostic performance was evaluated using the receiver operating characteristic(ROC) curve analysis.RESULTS: There were significant differences in entropy and uniformity at all sigma weightings(P〈0.001) among hepatic abscesses, malignant mimickers and simple cysts. The significant difference in kurtosis and skewness was shown at sigma 1.8 and 2.0 weightings(P=0.002-0.006). Tukey HSD testshowed that the abscesses had a significantly higher entropy and lower uniformity compared with malignant mimickers(P=0.000-0.004). Entropy(at a sigma 2.0 weighting) had the largest area under the ROC curve(0.888) in differentiating abscesses from malignant mimickers, with a sensitivity of 81.8% and a specificity of 88.0% when the cutoff value was set to 3.64.CONCLUSION: Multislice-based texture analysis may be useful for differentiating pyogenic hepatic abscesses from malignant mimickers.展开更多
Combined hepatocellular-cholangiocarcinoma（CHC） is a mixed tumor containing elements of both hepatocellular carcinoma（HCC） and cholangiocarcinoma（CC）. Its remarkable histological heterogeneity has been linked to...Combined hepatocellular-cholangiocarcinoma（CHC） is a mixed tumor containing elements of both hepatocellular carcinoma（HCC） and cholangiocarcinoma（CC）. Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell（HPC） origin. However, detailed histological or phenotypic description is rarely documented. In the present study, we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining, focusing on HPC associated phenotypic observation of intermediate area of the tumor. It was found that tumor cells showed remarkable heterogeneity in intermediate area. Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei, arranging in solid nests mostly. By Keratin 7（K7） staining, it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the ＂transitional＂ cells. Then, these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization. In conclusion, the HPC associated trait in CHC can be interpreted by HPC origin or gain of ＂stemness＂ by dedifferentiation. It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.展开更多
To study the effect of HBx gene on the apoptosis of the cell lines （L02, HepG2） and the interaction between HBx and X-linked inhibitor of apoptosis protein （XIAP）, the apoptosis of pcDNA3. I-HBx transiently transf...To study the effect of HBx gene on the apoptosis of the cell lines （L02, HepG2） and the interaction between HBx and X-linked inhibitor of apoptosis protein （XIAP）, the apoptosis of pcDNA3. I-HBx transiently transfected cell lines （L02, HepG2） was detected by flow cytometry and the mRNA expression of XIAP was assayed by real-time RT-PCR. Our study showed （1） the morphology of L02/pcDNA3. I-HBx was changed and the appearance of the cells mimicked that of HepG2 cells; （2） HBx gene could be detected in L02/pcDNA3. I-HBx and HepG2/pcDNA3.1-HBx; （3） the apoptosis rate of L02/pcDNA 3. I-HBx was higher than that of L02 cells （P〈0.01） and the apoptosis rate of HepG2/pcDNA3. I-HBx was lower than that of HepG2 cells （P〈0.05）; （4） the XIAP expression in L02 was about 3 times that in L02/pcDNA3. I-HBx cells （P〈0.01）, and the expression of XIAP in HepG2/pcDNA3. I-HBx was about 4 times that in HepG2 （P〈0.01）. It is concluded that HBx gene may promote the apoptosis of normal hepatocytes and inhibit the apoptosis of cells of hepatic carcinoma by regulating the expression of XIAP.展开更多
BACKGROUND Shwachman-Diamond syndrome(SDS)is a rare genetic disorder that affects multiple organs,primarily the liver.Most patients are diagnosed during infancy or early childhood.As they grow older,the majority of af...BACKGROUND Shwachman-Diamond syndrome(SDS)is a rare genetic disorder that affects multiple organs,primarily the liver.Most patients are diagnosed during infancy or early childhood.As they grow older,the majority of affected children may experience spontaneous remission,and cases of cirrhosis in adults are rarely reported.CASE SUMMARY A 36-year-old male patient presented with massive ascites.Laboratory tests revealed pancytopenia and a serum-ascites albumin gradient greater than 1.1 g/dL.An abdominal computed tomography scan demonstrated cirrhosis,splenomegaly,pancreatic fat infiltration,and a substantial accumulation of peritoneal fluid.Gastroscopy identified esophageal varices.Liver stiffness measurement indicated a value of 32.7 kPa.Based on the results of auxiliary examinations,common causes of cirrhosis were excluded,and a mutation in the Shwachman-Bodian-Diamond syndrome gene was ultimately identified through whole-exome sequencing.The patient was diagnosed with cirrhosis secondary to SDS.Following the correction of hypoalbuminemia and administration of diuretics,the patient's ascites resolved.CONCLUSION Patients with liver cirrhosis who also exhibit pancreatic fat infiltration and pancytopenia necessitate further exon testing to exclude the possibility of SDS.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantati...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.展开更多
BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),wh...BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),which constitute a cellfree therapeutic approach,have garnered extensive attention in alleviating HIRI.However,the potential of hucMSC-exos in mitigating apoptosis and their underlying mechanisms remain largely unknown.AIM To investigate the effects of hucMSC-exos on apoptosis after HIRI and explore the underlying mechanisms.METHODS The therapeutic effects of hucMSC-exos on HIRI and hypoxia/reoxygenation injury in L02 cells were investigated.RNA sequencing was used to detect differentially expressed genes in L02 cells after hucMSC-exo treatment,and the expression of apoptosis markers in L02 cells was analyzed.MicroRNA(miRNA)sequencing was performed to analyse the miRNA expression profiles of hucMSCexos and L02 cells after hucMSC-exo treatment.Through a miRNA-mRNA integrated analysis,candidate miRNAs and their regulated target genes were identified.We subsequently studied the roles of these candidate miRNAs in mouse HIRI and L02 cell hypoxia/reoxygenation injury.RESULTSFluorescence confocal microscopy revealed that hucMSC-exos effectively homed to the liver and were taken up byhepatocytes, likely due to the presence of anti-very late antigen-4 and anti-lymphocyte function-associated antigen-1 on the surface of hucMSC-exos. HucMSC-exos alleviate hepatocyte damage by inhibiting apoptosis. Specifically,let-7i-5p within hucMSC-exos inhibited the expression of the factor-related apoptosis ligand protein in L02 cells,leading to the upregulation of B-cell lymphoma-2 and the downregulation of B-cell lymphoma-2-associated Xprotein and cysteinyl aspartate specific proteinase-3, thereby inhibiting L02 cell apoptosis and enhancing cellproliferation activity. The overexpression of let-7i-5p effectively enhanced the antiapoptotic effects of hucMSC-exosboth in vitro and in vivo.CONCLUSIONOur findings indicate that hucMSC-exos alleviate HIRI by inhibiting apoptosis. We demonstrated that hucMSCexostarget apoptosis in L02 cells and mediate the let-7i-5p/factor-related apoptosis ligand pathway, therebyameliorating HIRI. This study provides new insights into the role of hucMSC-exos in hepatocyte apoptosis andhighlights the potential of hucMSC-exos as a therapeutic strategy for HIRI.展开更多
BACKGROUND Ulcerative colitis(UC)is a complex inflammatory bowel disease,and its etiology and pathogenesis remain incompletely elucidated.AIM To analyze the effects of Saccharomyces boulardii in combination with sulfa...BACKGROUND Ulcerative colitis(UC)is a complex inflammatory bowel disease,and its etiology and pathogenesis remain incompletely elucidated.AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted.All patients met complete inclusion and exclusion criteria.Based on the treatment interventions received,they were divided into a control group(n=63)and an observation group(n=64).Both groups of patients received routine treatment upon admission.The control group received sulfasalazine in addition to routine interventions,while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment.The clinical efficacy,improvement in symptoms,modified Baron endoscopic scores,quality of life“inflammatory bowel disease questionnaire(IBDQ)”,levels of intestinal microbial indicators(such as Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli),intestinal mucosal barrier function indicators[diamine oxidase(DAO),lipopolysaccharide(LPS),D-lactic acid(D-LA)],and adverse reaction occurrences were compared between the two groups.RESULTS(1)Clinical efficacy:The total effective rate in the control group was 79.37%,while in the observation group,it was 93.75%,significantly higher than that of the control group(P<0.05);(2)Improvement in symptoms:The observation group showed significantly lower relief time for abdominal pain,diarrhea,rectal bleeding,fever symptoms,and mucosal healing time compared to the control group(P<0.05);(3)Baron endoscopic scores and IBDQ scores:Before treatment,there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups(P>0.05).However,after treatment,the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group(P<0.05);(4)Levels of intestinal microbial indicators:Before treatment,there was no significant difference in the levels of Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli between the two groups(P>0.05).After treatment,the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group,while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group(P<0.05);(5)Levels of intestinal mucosal barrier function indicators:Before treatment,there was no significant difference in the levels of DAO,LPS,and D-LA between the two groups(P>0.05).However,after treatment,the levels of DAO,LPS,and D-LA in the observation group were significantly lower than those in the control group(P<0.05);and(6)Occurrence of adverse reactions:The incidence of adverse reactions in the control group was 9.52%,while in the observation group,it was 10.94%.There was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness.Compared to sole sulfasalazine intervention,the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients,alleviates intestinal mucosal inflammation,and improves the quality of life.Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function.Moreover,the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients,indicating a higher level of medication safety and advocating for its clinical promotion and application.展开更多
Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their pr...Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their prognostic biomarker potential.Methods:Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)Cox regression.The expression levels of CYB5D2 and TGF-βin HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blotting(WB)assays.Effects of CYB5D2 overexpression on cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)marker regulation were assessed in vitro,while in vivo tumorigenicity was evaluated using a xenograft model of HCC in nude mice.Results:In this study,WGCNA identified the turquoise module as significantly associated with HCC,containing 452 DEGs.LASSO Cox regression analysis revealed 9 key prognostic genes,with CYB5D2 being underexpressed in HCC cells and tissues.TGF-βwas negatively correlated with CYB5D2 expression,resulting in poor patient prognosis.Functional assays demonstrated that CYB5D2 overexpression inhibited proliferation,migration,and invasion of HCC cell lines,and altered EMT marker expression.Furthermore,the addition of TGF-βpartially reversed the suppressive effects caused by CYB5D2 overexpression.In vivo,CYB5D2 overexpression significantly reduced tumor growth,indicating its potential as a therapeutic target for HCC.Conclusion:The tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-βoffered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.展开更多
Background:Currently,there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreatobiliary su...Background:Currently,there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreatobiliary surgery subsequent to experiencing breakthrough infection of coronavirus disease 2019(COVID-19).This study aimed to find factors predicting postoperative complications and construct an innovative nomogram to pinpoint patients who were susceptible to developing severe complications following breakthrough infection of COVID-19 after undergoing elective hepato-pancreato-biliary surgery.Methods:This multicenter retrospective cohort study included consecutive patients who underwent elective hepato-pancreato-biliary surgeries between January 3 and April 1,2023 from four hospitals in China.All of these patients had experienced breakthrough infection of COVID-19 prior to their surgeries.Additionally,two groups of patients without preoperative COVID-19 infection were included as comparative controls.Surgical complications were meticulously documented and evaluated using the comprehensive complication index(CCI),which ranged from 0(uneventful course)to 100(death).A CCI value of 20.9 was identified as the threshold for defining severe complications.Results:Among 2636 patients who were included in this study,873 were included in the reference group I,941 in the reference group II,389 in the internal cohort,and 433 in the external validation cohort.Multivariate logistic regression analysis revealed that completing a full course of COVID-19 vaccination>6 months before surgery,undergoing surgery within 4 weeks of diagnosis of COVID-19 breakthrough infection,operation duration of 4 h or longer,cancer-related surgery,and major surgical procedures were significantly linked to a CCI>20.9.A nomogram model was constructed utilizing CCI>20.9 in the training cohort[area under the curve(AUC):0.919,95%confidence interval(CI):0.881–0.957],the internal validation cohort(AUC:0.910,95%CI:0.847–0.973),and the external validation cohort(AUC:0.841,95%CI:0.799–0.883).The calibration curve for the probability of CCI>20.9 demonstrated good agreement between the predictions made by the nomogram and the actual observations.Conclusions:The developed model holds significant potential in aiding clinicians with clinical decisionmaking and risk stratification for patients who have experienced breakthrough infection of COVID-19 prior to undergoing elective hepato-pancreato-biliary surgery.展开更多
Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruc...Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruction of blood vessels after resection is of paramount importance.When direct vascular reconstruction is not feasible,the application of vascular grafts becomes necessary to restore vascular continuity and function.Commonly employed vascular grafts in clinical practice include allogeneic graft vessels(AGVs),autologous vessels,and artificial vessels.Among these,AGVs offer distinct advantages particularly in its complex structures and satisfying histocompatibility,making it a valuable option for vascular reconstruction.展开更多
According to the 2024 global cancer data from GLOBOCAN,liver cancer ranks the 6th most common malignancy and the 3rd leading cause of cancer-related mortality worldwide[1].Among these cases,hepatocellular carcinoma(HC...According to the 2024 global cancer data from GLOBOCAN,liver cancer ranks the 6th most common malignancy and the 3rd leading cause of cancer-related mortality worldwide[1].Among these cases,hepatocellular carcinoma(HCC)accounts for approximately 85%−90%[2,3].Its incidence and mortality rates remain persistently high worldwide.However,China has the highest incidence and mortality rates of the disease in the world[4].And the majority of patients are diagnosed at intermediate or advanced stages.Thus,identifying novel tumor biomarkers for early detection and implementing precision therapy has long been a key focus of research.展开更多
BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the ...BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the efficacy of a traditional herbal medicine （THM） regimen and transarterial chemoembolization （TACE） in preventing recurrence in post-resection patients with small HCC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a multicenter, open- label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE. MAIN OUTCOME MEASURES： Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure. RESULTS： Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 （P = 0.048）. Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively （P = 0.026）. Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar. CONCLUSION： In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.展开更多
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).
AIM: To compare clinical outcomes between surgical resection (RES) and nonsurgical-RES (nRES) ablation therapies for small hepatocellular carcinoma (HCC).
Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC...Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.展开更多
The effect of portal vein tumor thrombus(PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosi...The effect of portal vein tumor thrombus(PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosis and treatment of PVTT remain challenging. Therefore, this study aimed to summarize the progress in these areas. A computerized literature search in Medline and EMBASE was performed with the following combinations of search terms: "hepatocellular carcinoma" AND "portal vein tumor thrombus." Although several signal transduction or molecular pathways related to PVTT have been identified, the exact mechanisms of PVTT are still largely unknown. Many biomarkers have been reported to detect microvascular invasion, but none have proved to be clinically useful because of their low accuracy rates. Sorafenib is the only recommended therapeutic strategy in Western countries. However, more treatment options are recommended in Eastern countries, including surgery, radiotherapy(RT), transhepatic arterial chemoembolization(TACE), transarterial radioembolization(TARE), and sorafenib. Therefore, we established a staging system based on the extent of portal vein invasion. Our staging system effectively predicts the long-term survival of PVTT patients. Currently, several clinical trials had shown that surgery is effective and safe in some PVTT patients. RT,TARE, and TACE can also be performed safely in patients with good liver function. However, only a few comparative clinical trials had compared the effectiveness of these treatments. Therefore, more randomized controlled trials examining the extent of PVTT should be conducted in the future.展开更多
AIM:To investigate the prognostic factors after resection for hepatitis B virus(HBV)-associated intrahepatic cholangiocarcinoma(ICC) and to assess the impact of different extents of lymphadenectomy on patient survival...AIM:To investigate the prognostic factors after resection for hepatitis B virus(HBV)-associated intrahepatic cholangiocarcinoma(ICC) and to assess the impact of different extents of lymphadenectomy on patient survival.METHODS:A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed.The patients were classified into groups according to the extent of lymphadenectomy(no lymph node dissection,sampling lymph node dissection and regional lymph node dissection).Clinicopathological characteristics and survival were reviewed retrospectively.RESULTS:The cumulative 1-,3-,and 5-year survival rates were found to be 60 %,18 %,and 13 %,respectively.Multivariate analysis revealed that liver cirrhosis(HR = 1.875,95%CI:1.197-3.278,P = 0.008) and multiple tumors(HR = 2.653,95%CI:1.562-4.508,P < 0.001) were independent prognostic factors for survival.Recurrence occurred in 70 patients.The 1-,3-,and 5-year disease-free survival rates were 36%,3% and 0%,respectively.Liver cirrhosis(HR = 1.919,P = 0.012),advanced TNM stage(stage Ⅲ/Ⅳ)(HR = 2.027,P < 0.001),and vascular invasion(HR = 3.779,P = 0.02) were independent prognostic factors for disease-free survival.Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection.Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status.CONCLUSION:The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC,and routine lymph nodedissection is not recommended,particularly for those without lymph node metastasis.展开更多
文摘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.
基金Supported by The National 13th Five-Year Science and Technology Plan Major Projects of China,No. 2017ZX10203205-006-001 and No. 2017ZX10203205-001-003。
文摘BACKGROUND The prognosis of intrahepatic cholangiocarcinoma(ICC) with lymph node metastasis is poor.The feasibility of surgery is not certain,which is a contraindication according to the National Comprehensive Cancer Network guidelines.The role of immunotherapy as a neoadjuvant therapy for ICC is not clear.We herein describe a case of ICC with lymph node metastasis that was successfully treated with neoadjuvant therapy.CASE SUMMARY A 60-year-old man with a liver tumor was admitted to our hospital.Enhanced computed tomography and magnetic resonance imaging revealed a spaceoccupying lesion in the right lobe of the liver.Multiple subfoci were found around the tumor,and the right posterior branch of the portal vein was invaded.Liver biopsy indicated poorly differentiated cholangiocytes.According to the American Joint Committee on Cancer disease stage classification,ICC with hilar lymph node metastasis(stage ⅢB) and para-aortic lymph node metastasis was suspected.A report showed that two patients with stage ⅢB ICC achieved a complete response(CR) 13 mo and 16 mo after chemotherapy with a PD-1 monoclonal antibody.After multidisciplinary consultation,the patient was given neoadjuvant therapy,surgical resection and lymph node dissection,and postoperative adjuvant therapy.After three rounds of PD-1 immunotherapy(camrelizumab) and two rounds of gemcitabine combined with cisplatin regimen chemotherapy,the tumor size was reduced.Therefore,a partial response was achieved.Exploratory laparotomy found that the lymph nodes of Group 16 were negative,and the tumor could be surgically removed.Therefore,the patient underwent right hemihepatectomy plus lymph node dissection.The patient received six rounds of chemotherapy and five rounds of PD-1 treatment postoperatively.After 8 mo of follow-up,no recurrence was found,and a CR was achieved.CONCLUSION Neoadjuvant therapy combined with surgical resection is useful for advanced-stage ICC.This is the first report of successful treatment of stage ⅢB ICC using neoadjuvant therapy with a PD-1 inhibitor.
文摘Objective： The outcome of surgical treatment of patients with intrahepatic cholangiocarcinoma （ICC） is poor. This study was designed to analyze prognostic factors after surgical procedure for ICCs. Methods： A retrospective clinical analysis was made in 183 cases of ICC, admitted to Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, from December 1996 to July 2003. Fifteen clinicopathologic factors that could possibly influence survival were selected. A multivariate analysis of these individuals was performed using the Cox Proportional Hazards Model. Results： The accumulative 1-, 3-and 5-year survival rates of the patients were 51.3%, 21.6% and 11.8% respectively. The statistical analysis showed that surgical procedure, lymph node metastasis, serum level of CA19-9 and pathological differentiation grade affected postoperative survival significantly, but transfusion, postoperative radiotherapy and chemotherapy, diameter of tumor, serum level of AFP, cirrhosis, preoperative total serum bilirubin level （TBIL）, ratio of albumin to globulin （A/G）, sex and age were not significant factors influencing postoperative survival. Conclusion： Major hepatectomy with systematic lymph node dissection may be recommended for the surgical treatment of ICC. Aggressive treatment and prevention on postoperative intrahepatic recurrence and lymph node metastasis are important strategy to improve the survival for ICC.
基金supported by grants from Medical Engineering Cross Research Foundation of Shanghai Jiaotong University(YG2013MS37 and YG2012MS16)the National Natural Science Foundation of China(81201172,81371660 and 81371622)
文摘BACKGROUND: Pyogenic hepatic abscess may mimic primary or secondary carcinoma of the liver on contrast-enhanced computed tomography(CECT). The present study was to explore the usefulness of the analysis of multislice-based texture acquired from CECT in the differentiation between pyogenic hepatic abscesses and malignant mimickers.METHODS: This retrospective study included 25 abscesses in 20 patients and 33 tumors in 26 subjects who underwent CECT. To make comparison, we also enrolled 19 patients with hepatic single simple cyst. The images from CECT were analyzed using a Laplacian of Gaussian band-pass filter(5 filter levels with sigma weighting ranging from 1.0 to 2.5). We also quantified the uniformity, entropy, kurtosis and skewness of the multislice-based texture at different sigma weightings. Statistical significance for these parameters was tested with oneway ANOVA followed by Tukey honestly significant difference(HSD) test. Diagnostic performance was evaluated using the receiver operating characteristic(ROC) curve analysis.RESULTS: There were significant differences in entropy and uniformity at all sigma weightings(P〈0.001) among hepatic abscesses, malignant mimickers and simple cysts. The significant difference in kurtosis and skewness was shown at sigma 1.8 and 2.0 weightings(P=0.002-0.006). Tukey HSD testshowed that the abscesses had a significantly higher entropy and lower uniformity compared with malignant mimickers(P=0.000-0.004). Entropy(at a sigma 2.0 weighting) had the largest area under the ROC curve(0.888) in differentiating abscesses from malignant mimickers, with a sensitivity of 81.8% and a specificity of 88.0% when the cutoff value was set to 3.64.CONCLUSION: Multislice-based texture analysis may be useful for differentiating pyogenic hepatic abscesses from malignant mimickers.
基金supported by grants from National Natural Science Foundation of China(No.81302130)Military Medical Scientific Youth Cultivation Project(No.13QNP054)
文摘Combined hepatocellular-cholangiocarcinoma（CHC） is a mixed tumor containing elements of both hepatocellular carcinoma（HCC） and cholangiocarcinoma（CC）. Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell（HPC） origin. However, detailed histological or phenotypic description is rarely documented. In the present study, we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining, focusing on HPC associated phenotypic observation of intermediate area of the tumor. It was found that tumor cells showed remarkable heterogeneity in intermediate area. Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei, arranging in solid nests mostly. By Keratin 7（K7） staining, it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the ＂transitional＂ cells. Then, these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization. In conclusion, the HPC associated trait in CHC can be interpreted by HPC origin or gain of ＂stemness＂ by dedifferentiation. It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.
文摘To study the effect of HBx gene on the apoptosis of the cell lines （L02, HepG2） and the interaction between HBx and X-linked inhibitor of apoptosis protein （XIAP）, the apoptosis of pcDNA3. I-HBx transiently transfected cell lines （L02, HepG2） was detected by flow cytometry and the mRNA expression of XIAP was assayed by real-time RT-PCR. Our study showed （1） the morphology of L02/pcDNA3. I-HBx was changed and the appearance of the cells mimicked that of HepG2 cells; （2） HBx gene could be detected in L02/pcDNA3. I-HBx and HepG2/pcDNA3.1-HBx; （3） the apoptosis rate of L02/pcDNA 3. I-HBx was higher than that of L02 cells （P〈0.01） and the apoptosis rate of HepG2/pcDNA3. I-HBx was lower than that of HepG2 cells （P〈0.05）; （4） the XIAP expression in L02 was about 3 times that in L02/pcDNA3. I-HBx cells （P〈0.01）, and the expression of XIAP in HepG2/pcDNA3. I-HBx was about 4 times that in HepG2 （P〈0.01）. It is concluded that HBx gene may promote the apoptosis of normal hepatocytes and inhibit the apoptosis of cells of hepatic carcinoma by regulating the expression of XIAP.
文摘BACKGROUND Shwachman-Diamond syndrome(SDS)is a rare genetic disorder that affects multiple organs,primarily the liver.Most patients are diagnosed during infancy or early childhood.As they grow older,the majority of affected children may experience spontaneous remission,and cases of cirrhosis in adults are rarely reported.CASE SUMMARY A 36-year-old male patient presented with massive ascites.Laboratory tests revealed pancytopenia and a serum-ascites albumin gradient greater than 1.1 g/dL.An abdominal computed tomography scan demonstrated cirrhosis,splenomegaly,pancreatic fat infiltration,and a substantial accumulation of peritoneal fluid.Gastroscopy identified esophageal varices.Liver stiffness measurement indicated a value of 32.7 kPa.Based on the results of auxiliary examinations,common causes of cirrhosis were excluded,and a mutation in the Shwachman-Bodian-Diamond syndrome gene was ultimately identified through whole-exome sequencing.The patient was diagnosed with cirrhosis secondary to SDS.Following the correction of hypoalbuminemia and administration of diuretics,the patient's ascites resolved.CONCLUSION Patients with liver cirrhosis who also exhibit pancreatic fat infiltration and pancytopenia necessitate further exon testing to exclude the possibility of SDS.
基金Supported by the National Natural Science Foundation of China,No.82270634Third Affiliated Hospital of Naval Medical University,No.tf2024yzyy01.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.
基金Supported by Natural Science Foundation Project of Yunnan Province,No.202302AA310025 and No.202449CE340016Health Research Project of Yunnan Province,No.300068.
文摘BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),which constitute a cellfree therapeutic approach,have garnered extensive attention in alleviating HIRI.However,the potential of hucMSC-exos in mitigating apoptosis and their underlying mechanisms remain largely unknown.AIM To investigate the effects of hucMSC-exos on apoptosis after HIRI and explore the underlying mechanisms.METHODS The therapeutic effects of hucMSC-exos on HIRI and hypoxia/reoxygenation injury in L02 cells were investigated.RNA sequencing was used to detect differentially expressed genes in L02 cells after hucMSC-exo treatment,and the expression of apoptosis markers in L02 cells was analyzed.MicroRNA(miRNA)sequencing was performed to analyse the miRNA expression profiles of hucMSCexos and L02 cells after hucMSC-exo treatment.Through a miRNA-mRNA integrated analysis,candidate miRNAs and their regulated target genes were identified.We subsequently studied the roles of these candidate miRNAs in mouse HIRI and L02 cell hypoxia/reoxygenation injury.RESULTSFluorescence confocal microscopy revealed that hucMSC-exos effectively homed to the liver and were taken up byhepatocytes, likely due to the presence of anti-very late antigen-4 and anti-lymphocyte function-associated antigen-1 on the surface of hucMSC-exos. HucMSC-exos alleviate hepatocyte damage by inhibiting apoptosis. Specifically,let-7i-5p within hucMSC-exos inhibited the expression of the factor-related apoptosis ligand protein in L02 cells,leading to the upregulation of B-cell lymphoma-2 and the downregulation of B-cell lymphoma-2-associated Xprotein and cysteinyl aspartate specific proteinase-3, thereby inhibiting L02 cell apoptosis and enhancing cellproliferation activity. The overexpression of let-7i-5p effectively enhanced the antiapoptotic effects of hucMSC-exosboth in vitro and in vivo.CONCLUSIONOur findings indicate that hucMSC-exos alleviate HIRI by inhibiting apoptosis. We demonstrated that hucMSCexostarget apoptosis in L02 cells and mediate the let-7i-5p/factor-related apoptosis ligand pathway, therebyameliorating HIRI. This study provides new insights into the role of hucMSC-exos in hepatocyte apoptosis andhighlights the potential of hucMSC-exos as a therapeutic strategy for HIRI.
文摘BACKGROUND Ulcerative colitis(UC)is a complex inflammatory bowel disease,and its etiology and pathogenesis remain incompletely elucidated.AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted.All patients met complete inclusion and exclusion criteria.Based on the treatment interventions received,they were divided into a control group(n=63)and an observation group(n=64).Both groups of patients received routine treatment upon admission.The control group received sulfasalazine in addition to routine interventions,while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment.The clinical efficacy,improvement in symptoms,modified Baron endoscopic scores,quality of life“inflammatory bowel disease questionnaire(IBDQ)”,levels of intestinal microbial indicators(such as Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli),intestinal mucosal barrier function indicators[diamine oxidase(DAO),lipopolysaccharide(LPS),D-lactic acid(D-LA)],and adverse reaction occurrences were compared between the two groups.RESULTS(1)Clinical efficacy:The total effective rate in the control group was 79.37%,while in the observation group,it was 93.75%,significantly higher than that of the control group(P<0.05);(2)Improvement in symptoms:The observation group showed significantly lower relief time for abdominal pain,diarrhea,rectal bleeding,fever symptoms,and mucosal healing time compared to the control group(P<0.05);(3)Baron endoscopic scores and IBDQ scores:Before treatment,there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups(P>0.05).However,after treatment,the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group(P<0.05);(4)Levels of intestinal microbial indicators:Before treatment,there was no significant difference in the levels of Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli between the two groups(P>0.05).After treatment,the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group,while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group(P<0.05);(5)Levels of intestinal mucosal barrier function indicators:Before treatment,there was no significant difference in the levels of DAO,LPS,and D-LA between the two groups(P>0.05).However,after treatment,the levels of DAO,LPS,and D-LA in the observation group were significantly lower than those in the control group(P<0.05);and(6)Occurrence of adverse reactions:The incidence of adverse reactions in the control group was 9.52%,while in the observation group,it was 10.94%.There was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness.Compared to sole sulfasalazine intervention,the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients,alleviates intestinal mucosal inflammation,and improves the quality of life.Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function.Moreover,the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients,indicating a higher level of medication safety and advocating for its clinical promotion and application.
基金National Natural Science Foundation of China Youth Training Project(2021GZR003)Medical-Engineering Interdisciplinary Research Youth Training Project(2022YGJC001).
文摘Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their prognostic biomarker potential.Methods:Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)Cox regression.The expression levels of CYB5D2 and TGF-βin HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blotting(WB)assays.Effects of CYB5D2 overexpression on cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)marker regulation were assessed in vitro,while in vivo tumorigenicity was evaluated using a xenograft model of HCC in nude mice.Results:In this study,WGCNA identified the turquoise module as significantly associated with HCC,containing 452 DEGs.LASSO Cox regression analysis revealed 9 key prognostic genes,with CYB5D2 being underexpressed in HCC cells and tissues.TGF-βwas negatively correlated with CYB5D2 expression,resulting in poor patient prognosis.Functional assays demonstrated that CYB5D2 overexpression inhibited proliferation,migration,and invasion of HCC cell lines,and altered EMT marker expression.Furthermore,the addition of TGF-βpartially reversed the suppressive effects caused by CYB5D2 overexpression.In vivo,CYB5D2 overexpression significantly reduced tumor growth,indicating its potential as a therapeutic target for HCC.Conclusion:The tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-βoffered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.
基金supported by grants from the Science Fund for Creative Research Groups of the National Natural Science Founda-tion of China(81521091 and 82073031)the National Natural Sci-ence Foundation of China(92269204)Clinical Research Plan of SHDC(SHDC2020CR5007 and SHDC22020213)。
文摘Background:Currently,there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreatobiliary surgery subsequent to experiencing breakthrough infection of coronavirus disease 2019(COVID-19).This study aimed to find factors predicting postoperative complications and construct an innovative nomogram to pinpoint patients who were susceptible to developing severe complications following breakthrough infection of COVID-19 after undergoing elective hepato-pancreato-biliary surgery.Methods:This multicenter retrospective cohort study included consecutive patients who underwent elective hepato-pancreato-biliary surgeries between January 3 and April 1,2023 from four hospitals in China.All of these patients had experienced breakthrough infection of COVID-19 prior to their surgeries.Additionally,two groups of patients without preoperative COVID-19 infection were included as comparative controls.Surgical complications were meticulously documented and evaluated using the comprehensive complication index(CCI),which ranged from 0(uneventful course)to 100(death).A CCI value of 20.9 was identified as the threshold for defining severe complications.Results:Among 2636 patients who were included in this study,873 were included in the reference group I,941 in the reference group II,389 in the internal cohort,and 433 in the external validation cohort.Multivariate logistic regression analysis revealed that completing a full course of COVID-19 vaccination>6 months before surgery,undergoing surgery within 4 weeks of diagnosis of COVID-19 breakthrough infection,operation duration of 4 h or longer,cancer-related surgery,and major surgical procedures were significantly linked to a CCI>20.9.A nomogram model was constructed utilizing CCI>20.9 in the training cohort[area under the curve(AUC):0.919,95%confidence interval(CI):0.881–0.957],the internal validation cohort(AUC:0.910,95%CI:0.847–0.973),and the external validation cohort(AUC:0.841,95%CI:0.799–0.883).The calibration curve for the probability of CCI>20.9 demonstrated good agreement between the predictions made by the nomogram and the actual observations.Conclusions:The developed model holds significant potential in aiding clinicians with clinical decisionmaking and risk stratification for patients who have experienced breakthrough infection of COVID-19 prior to undergoing elective hepato-pancreato-biliary surgery.
基金supported by grants from the Research and Demonstration Application of Clinical Diagnostic and Treatment Techniques in the Capital(Z211100002921025)Capital’s Funds for Health Improvement and Research(CFH2020-2-2036)。
文摘Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruction of blood vessels after resection is of paramount importance.When direct vascular reconstruction is not feasible,the application of vascular grafts becomes necessary to restore vascular continuity and function.Commonly employed vascular grafts in clinical practice include allogeneic graft vessels(AGVs),autologous vessels,and artificial vessels.Among these,AGVs offer distinct advantages particularly in its complex structures and satisfying histocompatibility,making it a valuable option for vascular reconstruction.
基金supported by a grant from the Central Level Public Welfare Research Institutes Basic Research Expenses of Chinese Academy of Medical Sciences(No.2023-RW320-05)。
文摘According to the 2024 global cancer data from GLOBOCAN,liver cancer ranks the 6th most common malignancy and the 3rd leading cause of cancer-related mortality worldwide[1].Among these cases,hepatocellular carcinoma(HCC)accounts for approximately 85%−90%[2,3].Its incidence and mortality rates remain persistently high worldwide.However,China has the highest incidence and mortality rates of the disease in the world[4].And the majority of patients are diagnosed at intermediate or advanced stages.Thus,identifying novel tumor biomarkers for early detection and implementing precision therapy has long been a key focus of research.
基金Supported by a grant from the Ministry of Science and Technology of China (National Key Technology Research & Development Program, No. 2006BAI 04A06)
文摘BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the efficacy of a traditional herbal medicine （THM） regimen and transarterial chemoembolization （TACE） in preventing recurrence in post-resection patients with small HCC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a multicenter, open- label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE. MAIN OUTCOME MEASURES： Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure. RESULTS： Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 （P = 0.048）. Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively （P = 0.026）. Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar. CONCLUSION： In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.
基金Supported by Grants of National Science and Technology Major Project Foundation,No.2008ZX10002-025Scientific Research Fund Projects of Shanghai Health Bureau,No.2009Y066
文摘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).
基金Supported by National Key Basic Research Program of China-973 Program,No.2012CB526706International Science and Technology Cooperation Program of the Ministry of Science and Technology,No.2011DFA32980+1 种基金The Innovation Program of Shanghai Municipal Education Commission,No.2013ZZ060the National Natural Science Foundation of China,No.NSFC81271694
文摘AIM: To compare clinical outcomes between surgical resection (RES) and nonsurgical-RES (nRES) ablation therapies for small hepatocellular carcinoma (HCC).
基金supported in part by the National Natural Sci-ence Foundation of China(81472284 and 81672699)Shanghai Pujiang Program(16PJD004)
文摘Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.
基金supported by grants from the Science Fund for Creative Research Groups (Grant No. 81221061)The State Key Project on Diseases of China (Grant No. 2012zx10002016016003)+9 种基金The China National Funds for Distinguished Young Scientists (Grant No. 81125018)Chang Jiang Scholars Program (2013) of Chinese Ministry of EducationThe National Key Basic Research Program (Grant No. 2015CB554000)National Natural Science Foundation of China (Grant No. 81101831, 81101511, and 81472282)The New Excellent Talents Program of Shanghai Municipal Health Bureau (Grant No. XBR2011025)Shanghai Science and Technology Committee (Grant No. 134119a0200)Shanghai Science and Technology Development Funds (Grant No. 14QA1405000)中央人民政府 Innovation Alliance for Liver Cancer Diagnosis and Treatment (Grant 2012)General Program from Shanghai Municipal Health Bureau (Grant No. 20124301)Shanghai Rising-star Program from Shanghai Science and Technology Committee (Grant No.13QA 1404900)
文摘The effect of portal vein tumor thrombus(PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosis and treatment of PVTT remain challenging. Therefore, this study aimed to summarize the progress in these areas. A computerized literature search in Medline and EMBASE was performed with the following combinations of search terms: "hepatocellular carcinoma" AND "portal vein tumor thrombus." Although several signal transduction or molecular pathways related to PVTT have been identified, the exact mechanisms of PVTT are still largely unknown. Many biomarkers have been reported to detect microvascular invasion, but none have proved to be clinically useful because of their low accuracy rates. Sorafenib is the only recommended therapeutic strategy in Western countries. However, more treatment options are recommended in Eastern countries, including surgery, radiotherapy(RT), transhepatic arterial chemoembolization(TACE), transarterial radioembolization(TARE), and sorafenib. Therefore, we established a staging system based on the extent of portal vein invasion. Our staging system effectively predicts the long-term survival of PVTT patients. Currently, several clinical trials had shown that surgery is effective and safe in some PVTT patients. RT,TARE, and TACE can also be performed safely in patients with good liver function. However, only a few comparative clinical trials had compared the effectiveness of these treatments. Therefore, more randomized controlled trials examining the extent of PVTT should be conducted in the future.
基金Supported by National Natural Science Foundation of China,No.81402523
文摘AIM:To investigate the prognostic factors after resection for hepatitis B virus(HBV)-associated intrahepatic cholangiocarcinoma(ICC) and to assess the impact of different extents of lymphadenectomy on patient survival.METHODS:A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed.The patients were classified into groups according to the extent of lymphadenectomy(no lymph node dissection,sampling lymph node dissection and regional lymph node dissection).Clinicopathological characteristics and survival were reviewed retrospectively.RESULTS:The cumulative 1-,3-,and 5-year survival rates were found to be 60 %,18 %,and 13 %,respectively.Multivariate analysis revealed that liver cirrhosis(HR = 1.875,95%CI:1.197-3.278,P = 0.008) and multiple tumors(HR = 2.653,95%CI:1.562-4.508,P < 0.001) were independent prognostic factors for survival.Recurrence occurred in 70 patients.The 1-,3-,and 5-year disease-free survival rates were 36%,3% and 0%,respectively.Liver cirrhosis(HR = 1.919,P = 0.012),advanced TNM stage(stage Ⅲ/Ⅳ)(HR = 2.027,P < 0.001),and vascular invasion(HR = 3.779,P = 0.02) were independent prognostic factors for disease-free survival.Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection.Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status.CONCLUSION:The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC,and routine lymph nodedissection is not recommended,particularly for those without lymph node metastasis.
