Establishment and validation of a predictive model for peripherally inserted central catheter-related thrombosis in patients with liver cancer

BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population.Several risk factors have been identified for the development of PICC-related thrombosis,including cancer type,stage,comorbidities,and catheter characteristics.Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis.AIM To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer,construct a predictive model,and validate it.METHODS Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected.Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected,and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls.A total of 255 samples were collected and used as the training set,and 77 cases were collected as the validation set in a 7:3 ratio.General patient information,case data,catheterization data,coagulation indicators,and Autar Thrombosis Risk Assessment Scale scores were analyzed.Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors,and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed statistically significant differences(P<0.05)in age,sex,Karnofsky performance status score(KPS),bedridden time,activities of daily living impairment,parenteral nutrition,catheter duration,distant metastasis,and bone marrow suppression between the thrombosis group and the non-thrombosis group.Other aspects had no statistically significant differences(P>0.05).Multivariate regression analysis showed that age≥60 years,KPS score≤50 points,parenteral nutrition,stage III to IV,distant metastasis,bone marrow suppression,and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer(P<0.05).Catheter duration of 1-6 months and catheter duration>6 months were protective factors for PICC-related thrombosis(P<0.05).The predictive model for PICC-related thrombosis was obtained as follows:P predictive probability=[exp(Logit P)]/[1+exp(Logit P)],where Logit P=age×1.907+KPS score×2.045+parenteral nutrition×9.467+catheter duration×0.506+tumor-node-metastasis(TNM)staging×2.844+distant metastasis×2.065+bone marrow suppression×2.082+activities of daily living impairment×13.926.ROC curve analysis showed an area under the curve(AUC)of 0.827(95%CI:0.724-0.929,P<0.001),with a corresponding optimal cut-off value of 0.612,sensitivity of 0.755,and specificity of 0.857.Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence(P>0.05).ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets,respectively.CONCLUSION Age,KPS score,parenteral nutrition,TNM staging,distant metastasis,bone marrow suppression,and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer,while catheter duration is a protective factor for the disease.The predictive model has an AUC of 0.827,indicating high predictive accuracy and clinical value.

Exosomal microRNAs in hepatocellular carcinoma,expanding research field

In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.

A special growth manner of intrahepatic biliary cystadenoma

We report a case of a 56-year-old woman with intrahepatic biliary cystadenoma(IBC)accompanying a tumor embolus in the extrahepatic bile duct,who was admitted to our department on October 13,2008.Imaging showed an asymmetry dilation of the biliary tree,different bile signals in the biliary tree,a multiloculated lesion and an extrahepatic bile duct lesion with internal septation.A regular left hemihepatectomy en bloc was performed with resection of the entire tumor,during which a tumor embolus protruding into the extrahepatic bile duct and originating from biliary duct of segment 4 was revealed.Microscopically,the multiloculated tumor was confirmed to be a biliary cystadenoma with an epithelial lining composed of biliary-type cuboidal cells and surrounded by an ovarian-like stroma.An aggressive en bloc resection was recommended for the multiloculated lesion.Imaging workup,clinicians and surgeons need to be aware of this different presentation.

Negative short-term impact of intraoperative biliary lavage in patients with hepatolithiasis

AIM: To evaluate short-term outcomes following intraoperative biliary lavage for hepatolithiasis.METHODS: A total of 932 patients who were admitted to the West China Medical Center of Sichuan University between January 2010 and January 2014 and underwent bile duct exploration and lithotomy were retrospectively included in our study. The patients were divided into the lavage group and the control group. Related pre-, intra-, and postoperative factors were recorded, analyzed, and compared between the two groups in order to verify the effects of biliary lavage on the short-term outcome of patients with hepatolithiasis. RESULTS: Amongst the patients who were included, 678 patients with hepatolithiasis were included in the lavage group, and the other 254 patients were enrolled in the control group. Data analyses revealed that preoperative baseline and related intraoperative variables were not significantly different. However, patients who underwent intraoperative biliary lavage had prolonged postoperative hospital stays(6.67 d vs 7.82 d, P = 0.024), higher hospitalization fees(RMB 28437.1 vs RMB 32264.2, P = 0.043), higher positive rates of bacterial cultures from blood(13.3% vs 25.8%, P = 0.001) and bile(23.6% vs 40.7%, P= 0.001) samples, and increased usage of advanced antibiotics(26.3% vs 38.2%, P = 0.001). In addition, in the lavage group, more patients had fever(> 37.5℃, 81.4% vs 91.1%, P = 0.001) and hyperthermia(> 38.5℃,39.7% vs 54.9%, P = 0.001), and higher white blood cell counts within 7 d after the operation compared to the control group.CONCLUSION: Intraoperative biliary lavage might increase the risk of postoperative infection, while not significantly increasing gallstone removal rate.

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.

Studies on the Mechanism of Arsenic Trioxide-Induced Apoptosis in HepG_2 Human Hepatocellular Carcinoma Cells

OBJECTIVE To study the anti-tumor effect of arsenic trioxide on the HepG2 human hepatocellular carcinoma cell line, and to explore its mechanism of action. METHODS The MTT assay was used to determine the inhibitory effect of As2O3 on HepG2 cells at various As2O3 concentrations. The expression of p-JNK, caspase-3 and PARP was detected by Western blots. RESULTS As2O3 markedly inhibited the growth of the HepG2 cells and induced apoptosis. The results of Western blot analysis showed that the As2O3-induced apoptosis was accompanied by caspase-3 and PARP activation. p-JNK was detected at 10 min following As2O3 treatment, and preceded to peak at 20 min, and decreased by 30 min. The total protein content did not obviously change. The activation of JNK occurred prior to cell apoptosis. SP600125, a JNK inhibitor, suppressed the As2O3-induced activation of caspase-3 and PARP cleavage. CONCLUSION As2O3 inhibits the proliferation of human HepG2 hepatocellular carcinoma cells by inducing apoptosis in vitro. As2O3-induced apoptosis is accessed through the caspase-3 pathway. The JNK signal-transduction pathway and caspase-3 are involved upstream in the As2O3 induced HepG2 apoptotic response.

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma:A single-institution experience in China

AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival(OS) and disease-free survival(DFS) were evaluated by univariate and multivariate analyses.RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio(HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease(HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation(HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion(HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins(HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease(HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation(HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion(HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins(HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio(OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter(OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures(OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage(OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion(OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumorfree margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin.

Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer

AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA) 199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre-and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non- recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma:An analysis of 42 cases

AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis(XGC) clinically.METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our hospital, among which 42 were misdiagnosed as gallbladder carcinoma(GBC) based on preoperative radiographs and/or intra-operative findings. The clinical characteristics, preoperative imaging, intra-operative findings, frozen section(FS) analysis and surgical procedure data of these patients were collected and analyzed.RESULTS: The most common clinical syndrome in these 42 patients was chronic cholecystitis, followed by acute cholecystitis. Seven(17%) cases presented with mild jaundice without choledocholithiasis. Thirtyfive(83%) cases presented with heterogeneous enhancement within thickened gallbladder walls on imaging, and 29(69%) cases presented with abnormal enhancement in hepatic parenchyma neighboring the gallbladder, which indicated hepatic infiltration. Intra-operatively, adhesions to adjacent organs were observed in 40(95.2%) cases, including the duodenum, colon and stomach. Thirty cases underwent FS analysis and the remainder did not. The accuracy rate of FS was 93%, and that of surgeon's macroscopic diagnosis was 50%. Six cases were misidentified as GBC by surgeon's macroscopic examination and underwent aggressive surgical treatment. No statistical difference was encountered in the incidence of postoperative complications between total cholecystectomy and subtotal cholecystectomy groups(21% vs 20%, P > 0.05).CONCLUSION: Neither clinical manifestations and laboratory tests nor radiological methods provide apractical and effective standard in the differential diagnosis between XGC and GBC.

Prognostic value of lymphovascular invasion in Bismuth-Corlette type Ⅳ hilar cholangiocarcinoma

AIM To assess the prognostic value of lymphovascular invasion(LVI)in Bismuth-Corlette typeⅣhilar cholangiocarcinoma(HC)patients. METHODS A retrospective analysis was performed on 142consecutively recruited typeⅣHC patients undergoing radical resection with at least 5 years of followup.Survival analysis was performed by the KaplanMeier method,and the association between the clinicopathologic variables and survival was evaluated by log-rank test.Multivariate analysis was adopted to identify the independent prognostic factors for overall survival(OS)and disease-free survival(DFS).Multiple logistic regression analysis was performed to determine the association between LVI and potential variables. RESULTS LVI was confirmed histopathologically in 29(20.4%)patients.Multivariate analysis showed that positive resection margin(HR=6.255,95%CI:3.485-11.229,P<0.001),N1 stage(HR=2.902,95%CI:1.132-7.439,P=0.027),tumor size>30 mm(HR=1.942,95%CI:1.176-3.209,P=0.010)and LVI positivity(HR=2.799,95%CI:1.588-4.935,P<0.001)were adverse prognostic factors for DFS.The independent risk factors for OS were positive resection margin(HR=6.776,95%CI:3.988-11.479,P<0.001),N1 stage(HR=2.827,95%CI:1.243-6.429,P=0.013),tumor size>30 mm(HR=1.739,95%CI:1.101-2.745,P=0.018)and LVI positivity(HR=2.908,95%CI:1.712-4.938,P<0.001).LVI was associated with N1 stage and tumor size>30 mm.Multiple logistic regression analysis indicated that N1 stage(HR=3.312,95%CI:1.338-8.198,P=0.026)and tumor size>30 mm(HR=3.258,95%CI:1.288-8.236,P=0.013)were associated with LVI. CONCLUSION LVI is associated with N1 stage and tumor size>30mm and adversely influences DFS and OS in typeⅣHC patients.

Radical nerve dissection for the carcinoma of head of pancreas: report of 30 cases

Objective： To explore the clinical value of the radical nerve dissection （RND） for the carcinoma of head of pancreas （CHP）. Methods： The clinical and pathological data of 30 CHP patients who underwent RND in our hospital were retrospectively analyzed, with an attempt to explore the safety and short-term efficacy of this procedure. Results： Among these 30 patients, the operative time was （351±61） rain, the intra-operative blood loss was 350 （range, 300-600） mL, and the grades B and C pancreatic fistula was 23.33%. During the follow-up （range, 2-30 months; median： 17 months）, the 1-year survival rate was 63.33% and the 1-year disease-free survival rate was 56.67%. Among the 23 patients （76.66%） with positive extra-pancreatic perineural invasion （PNI）, the 1-year case- fatality rate was 34.78%, which was not significantly different from that （28.57%） of patients with negative PNI （P=0.760）. Conclusions： Our results suggested potential advantages of RND in the fields of surgery-associated risk and prognosis compared with the Whipple operation in the treatment of CHP. Due to the low sample size of this study, further well-designed research of large sample size is needed.

Replication-incompetent Adenovirus Vector-mediated MDA-7/IL-24 Selectively Induces Growth Suppression and Apoptosis of Hepatoma Cell Line SMMC-7721

In order to investigate the effect of replication-incompetent adenovirus vector expressing MDA-7/IL-24 on tumor growth and apoptosis of human hepatocellular carcinoma （HCC） cell line SMMC-7721 and normal liver cell line L02, the recombinant replication-incompetent Ad.mda-7 virus vector was constructed and infected into the HCC cell line SMMC-7721 and normal liver cell line L02. RT-PCR was performed to examine the expression of MDA-7 mRNA. The concentrations of MDA-7/IL-4 in culture superuatants were determined by using ELISA. MTT and Hoechst staining assay were applied to observe the inhibitory and killing effects of MDA-7 on the HCC cells. By using flow cytometry, the apoptosis, cell cycle and proliferation of SMMC-7721 and L02 cells were measured. The results showed recombinant replication-incompetent virus expressing MDA-7/IL-24 was constructed successfully, and RT-PCR revealed that it could mediate the high expression of the exogenous gene MDA-7/IL-24 in SMMC-7721 and L02 cells. The expression of MDA-7/IL-24 proteins in the culture superuatant was detectable by ELISA. Ad.mda-7 infection induced apoptosis and growth suppression in SMMC-7721 cells and an increased percentage of HCC cells in the GyM phase of the cell cycle, but not in L02 cells. It was concluded that mda-7/IL-24 gene, mediated with replication-incompetent adenovirus vector, could selectively induce growth suppression and apoptosis in HCC cell line SMMC-7721 but without any toxic side-effect on normal liver line L02.

Safety and efficacy of microwave ablation for periductal hepatocellular carcinoma with intraductal cooling of the central bile ducts through a percutaneous transhepatic cholangial drainage tube

Background and aims:Biliary thermal injury caused by microwave ablation(MWA)for a hepatocellular carcinoma(HCC)close to the central bile ducts always results in severe complications and leads to mortality.Some studies have demonstrated that intraductal cooling of the biliary tract with chilled saline during thermal ablation can successfully prevent these complications.In this study,we present a novel bile duct cooling technique through a percutaneous transhepatic cholangial drainage(PTCD)tube for preventing biliary thermal injury caused by MWA,and compare the feasibility and safety of the intraductal cooling technique when performed with a PTCD tube and with an endoscopic nasobiliary drainage(ENBD)tube.Methods:Participants were randomly assigned to undergo MWA of HCC with intraductal chilled saline perfusion through a PTCD tube or an ENBD tube.The main study outcomes were bile duct complications related to MWA and local tumor recurrence,p value<0.05 was considered to indicate a statistically significant difference.Results:A total of 23 patients with an HCC(23 nodules)close to a central bile duct were enrolled in this study.Of these patients,12 had a PTCD tube and 11 had an ENBD tube placed into the hepatic duct close to the lesions.There were no PTCD-and ENBD-related mortality cases.There was no complication related to the PTCD procedure;however,3 patients(27.27%)developed acute pancreatitis and 1 patient(9.09%)had hemorrhage in the ENBD group(p=0.037).One patient(8.33%)in the PTCD group had bile leakage and 2 patients(18.18%)in the ENBD group developed a biloma.Within 5 years,1 patient in the PTCD group and 2 patients in the ENBD group had local recurrence.There was no significant difference in local recurrence,nonlocal hepatic recurrence,mortality rate,or median cumulative overall survival between the 2 groups.Conclusions:The intraductal cooling technique using a PTCD tube is a feasible and effective method for preventing bile duct thermal injury caused by MWA for an HCC close to the central bile ducts.It does not increase local recurrence and may be safer than intraductal cooling through an ENBD tube.

Role of hydrogen sulfide in portal hypertension and esophagogastric junction vascular disease

AIM: To investigate the association between endogenous hydrogen sulfide (H2S) and portal hypertension as well as its effect on vascular smooth muscle cells.

Common bile duct injury by fibrin glue: Report of a rare complication

Fibrin glue is widely used in clinical practice and plays an important role in reducing postoperative complications.We report a case of a 65-year-old man, whose common bile duct was injured by fibrin glue, with a history of failed laparoscopic cholecystectomy and open operation for uncontrolled laparoscopic bleeding.In view of thepersistent liver dysfunction, xanthochromia and skin itching, the patient was admitted to us for further management.Ultrasound, computed tomography, and magnetic resonance cholangiopancreatography(MRCP) revealed multiple stones in the common bile duct, and liver function tests confirmed the presence of obstructive jaundice and liver damage.Endoscopic retrograde cholangiopancreatography was unsuccessfully performed to remove choledocholithiasis, but a small amount of tissue was removed and pathologically confirmed as calcified biliary mucosa.This was followed by open surgery for suspicious cholangiocarcinoma.There was no evidence of cholangiocarcinoma, but the common bile duct wall had a defect of 8 mm × 10 mm at Calot's triangle.A hard, grid-like foreign body was removed, which proved to be solid fibrin glue.Subsequently, the residual choledocholithiasis was removed by a choledochoscopic procedure, and the common bile duct deletion was repaired by liver round ligament with T-tube drainage.Six months later, endoscopy was performed through the T-tube fistula and showed a well-repaired bile duct wall.Eight months later, MRCP confirmed no bile duct stenosis.A review of reported cases showed that fibrin glue is widely used in surgery, but it can also cause organ damage.Its mechanism may be related to discharge reactions.

Histological examination of frozen sections for patients with acute cholecystitis during cholecystectomy

BACKGROUND： Unexpected gallbladder cancer may present with acute cholecystitis-like manifestat/ons. Some authors rec- ommended that frozen section analysis should be performed during laparoscopic cholecystectomy for all cases of acute cholecystitis. Others advocate selective use of frozen section analysis based on gross examination of the specimen by the surgeon. The aim of the present study was to evaluate whether surgeons could effectively identify suspected gallbladder with macroscopic examination alone. If not, is routine frozen sec- tion analysis worth advocating？

Construction of a risk score prognosis model based on hepatocellular carcinoma microenvironment

BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leading to poor prognosis.However,the effects of genes involved in TME on the prognosis of HCC patients remain unclear.Here,we investigated the HCC microenvironment to identify prognostic genes for HCC.AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm.Additionally,a risk score model was established based on Differentially Expressed Genes(DEGs)between high and lowimmune/stromal score patients.RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients.The patients were divided into high-or low-risk groups.The genes(Disabled homolog 2,Musculin,C-X-C motif chemokine ligand 8,Galectin 3,B-cell-activating transcription factor,Killer cell lectin like receptor B1,Endoglin and adenomatosis polyposis coli tumor suppressor)involved in our risk score model were considered to be potential immunotherapy targets,and they may provide better performance in combination.Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway,respectively,related to the immune-related genes in the DEGs between high-and low-risk groups.The receiver operating characteristic(ROC)curve analysis confirmed the good potency of the risk score prognostic model.Moreover,we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database.A nomogram was established to predict the overall survival of HCC patients.CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.

Individualized nomogram improves diagnostic accuracy of stage Ⅰ-Ⅱ gallbladder cancer in chronic cholecystitis patients with gallbladder wall thickening

BACKGROUND： Early diagnosis of gallbladder cancer（GBC） can remarkably improve the prognosis of patients. This study aimed to develop a nomogram for individualized diagnosis of stage Ⅰ-Ⅱ GBC in chronic cholecystitis patients with gallbladder wall thickening.METHODS： The nomogram was developed using logistic regression analyses based on a retrospective cohort consisting of 89 consecutive patients with stage Ⅰ-Ⅱ GBC and 1240 patients with gallbladder wall thickening treated at one biliary surgery center in Shanghai between January 2009 and December 2011. The accuracy of the nomogram was validated by discrimination, calibration and a prospective cohort treated at another center between January 2012 and December 2014（n=928）.RESULTS： Factors included in the nomogram were advanced age, hazardous alcohol consumption, long-standing diagnosed gallstones, atrophic gallbladder, gallbladder wall calcification, intraluminal polypoid lesion, higher wall thickness ratio and mucosal line disruption. The nomogram had concordance indices of 0.889 and 0.856 for the two cohorts, respectively. Internal and external calibration curves fitted well. The area under the receiver-operating characteristic curves of the nomogram was higher than that of multidetector row computed tomography in diagnosis of stage Ⅰ-Ⅱ GBC（P〈0.001）.CONCLUSION： The proposed nomogram improves individualized diagnosis of stage Ⅰ-Ⅱ GBC in chronic cholecystitis patients with gallbladder wall thickening, especially for those the imaging features alone do not allow to confirm the diagnosis.

Xanthogranulomatous cholecystitis misdiagnosed as gallbladder carcinoma: retrospective analysis of 10 cases

Objective: To investigate the reasons for misdiagnosing xanthogranulomatous cholecystitis (XGC) as gallbladder carcinoma, and to provide differential points between these two diseases. Methods: Thirty-three patients with the final diag- nosis of XGC in our hospital over a period of 10 years (1996–2005) were reviewed, among which 10 (6 males and 4 females) were misdiagnosed as having gallbladder carcinoma either preoperatively or intraoperatively. Results: 10 misdiagnosed cases were examined preoperatively by B-ultrasound (BUS) and computed tomography (CT). BUS and CT revealed 5 cases of gallbladder carcinoma and 1 of chronic cholecystitis; 2 cases were diagnosed as gallbladder carcinoma on BUS but chronic cholecystitis on CT; other 2 cases were diagnosed as chronic cholecystitis on BUS but as gallbladder carcinoma on CT. Intra- operatively, thickening of the gallbladder wall was found in all of the patients; xanthogranulomatous tissue was found invading into other tissues including gallbladder bed and omentum majus. Intraoperative frozen section investigation was performed on 1 patient revealing that no tumor cell was found. Open cholecystectomy + partial hepatic wedge resection were performed on 3 patients; cholecystectomy + partial hepatic wedge resection + regional lymphadenectomy in the liver duodenum ligament on 6 patients; cholecystectomy + cholecystoenterostomy + colocolic anastomosis after partial resection of transverse colon on 1 patient. Postoperative pathological findings revealed XGC in all these patients. Conclusion: XGC is an uncommon variant of chronic cholecystitis of which clinical and imaging presentations closely resemble gallbladder carcinoma. Thus differentiation is essential by means of intraoperative frozen section investigation to ensure optimal surgical treatment since XGC has its pathological distinctions, which are not that of a precancerous change.

Protective Effects of Hydrogen Sulfide on Portal Hypertensive Vasculopathy in Rabbits by Activating AKT-NF-κB Pathway

The role of hydrogen sulfide（H;S） in portal hypertension（PH）-induced esophagus-gastric junction vascular lesions in rabbits was observed. The rabbit PH models were established. The animals were randomly divided into the following groups: normal, PH, PH+sodium hydrosulfide（PH+S）, PH+propargylglycine（PH+PPG）. The plasma H;S levels, apoptosis of esophageal-gastric junction vascular smooth muscle cells, and the expression of nuclear transcription factor-κB（NF-κB）, p-AKT, IκBa and Bcl-2 were detected. The cystathionine γ lyase（cystathionine-gamma-splitting enzyme, CSE） in the junction vascular tissue was measured. The results showed that the plasma H;S levels and the CSE expression levels had statistically significant difference among different groups（P<0.05）. As compared with PH group, plasma H;S levels were declined obviously（11.9±4.2 vs. 20.6±4.5, P<0.05）, and CSE expression levels in the junction vascular tissue were notably reduced（1.7±0.6 vs. 2.8±0.8, P<0.05）, apoptosis rate of vascular smooth muscle cells per unit area was significantly decreased（0.10±0.15 vs. 0.24±0.07, P<0.05）, and the expression levels of p-AKT and NF-κB were significantly decreased（2.31±0.33 vs. 3.04±0.38, P<0.05; 0.33±0.17 vs. 0.51±0.23, P<0.05）, however, IκBa and Bcl-2 expression increased obviously（5.57±0.17 vs. 3.67±0.13, P<0.05; 0.79±0.29 vs. 0.44±0.36, P<0.05） in PH+PPG group. As compared with PH group, H;S levels were notably increased（32.7±7.3 vs. 20.6±4.5, P<0.05）, the CSE levels in the junction vascular tissue were significantly increased（6.3±0.7 vs. 2.8±0.8, P<0.05）, apoptosis rate of vascular smooth muscle cells per unit area was significantly increased（0.35±0.14 vs. 0.24±0.07, P<0.05）, and the expression levels of p-AKT and NF-κB were significantly increased（4.29±0.49 vs. 3.04±0.38, P<0.05; 0.77±0.27 vs. 0.51±0.23, P<0.05）, yet IκBa and Bcl-2 expression decreased significantly（3.23±0.24 vs. 3.67±0.13, P<0.05; 0.31±0.23 vs. 0.48±0.34, P<0.05） in PH+S group. It is concluded that esophagus-gastric junction vascular lesions happen under PH, and apoptosis of smooth muscle cells is declined. H;S can activate NF-κB by the p-AKT pathway, leading to the down-regulation of Bcl-2, eventually stimulating apoptosis of vascular smooth muscle cells, easing PH. H;S/CSE system may play an important role in remission of PH via the AKT-NF-κB pathway.