Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually.However,infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants.Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene(ist)from streptomyces thermotoleran.Carrimycin has good antibacterial and antiviral effects.However,no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia(SP)after solid organ transplantation.AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment.METHODS In March 2022,ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022.When the condition was critical and difficult to control with other drugs,carrimycin was administered.These ten patients'clinical features and treatment protocols were retrospectively analyzed,and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated.RESULTS All ten patients were included in the analysis.Regarding etiological agent detection,there were three cases of fungal pneumonia,two cases of bacterial pneumonia,two cases of Pneumocystis pneumonia,and three cases of mixed infections.After treatment with carrimycin,the disease in seven patients significantly improved,the course of the disease was significantly shortened,fever was quickly controlled,chest computed tomography was significantly improved,and oxygenation was significantly improved.Finally,the patients were discharged after curing.One patient died of acute respiratory distress syndrome,and two patients discontinued treatment.CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation.Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

Pleural empyema with endobronchial mass due to Rhodococcus equi infection after renal transplantation: A case report and review of literature

BACKGROUND Kidney transplantation is the best option for patients with end-stage renal disease.However,the need for lifelong immunosuppression results in renal transplant recipients being susceptible to various infections.Rhodococcus equi(R.equi)is a rare opportunistic pathogen in humans,and there are limited reports of infection with R.equi in post-renal transplant recipients and no uniform standard of treat-ment.This article reports on the diagnosis and treatment of a renal transplant recipient infected with R.equi 21 mo postoperatively and summarizes the charac-teristics of infection with R.equi after renal transplantation,along with a detailed review of the literature.Here,we present the case of a 25-year-old man who was infected with R.equi 21 mo after renal transplantation.Although the clinical features at the time of presentation were not specific,chest computed tomography(CT)showed a large volume of pus in the right thoracic cavity and right middle lung atelectasis,and fiberoptic bronchoscopy showed an endobronchial mass in the right middle and lower lobe orifices.Bacterial culture and metagenomic next-generation sequen-cing sequencing of the pus were suggestive of R.equi infection.The immunosup-pressive drugs were immediately suspended and intravenous vancomycin and azithromycin were administered,along with adequate drainage of the abscess.The endobronchial mass was then resected.After the patient’s clinical symptoms and chest CT presentation resolved,he was switched to intravenous ciprofloxacin and azithromycin,followed by oral ciprofloxacin and azithromycin.The patient was re-hospitalized 2 wk after discharge for recurrence of R.equi infection.He recovered after another round of adequate abscess drainage and intravenous ciprofloxacin and azithromycin.CONCLUSION Infection with R.equi in renal transplant recipients is rare and complex,and the clinical presentation lacks specificity.Elaborate antibiotic therapy is required,and adequate abscess drainage and surgical excision are necessary.Given the recurrent nature of R.equi,patients need to be followed-up closely.

Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.

Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.

Diagnosis and treatment of Whipple disease after kidney transplantation:A case report

BACKGROUND Kidney transplantation is the standard treatment for end-stage renal disease.Particularly,rare and specific pathogenic infections which are asymptomatic are often difficult to diagnose,causing delayed and ineffective treatment and thus seriously affecting prognosis.Tropheryma whipplei(T.whipplei)is a Gram-positive actinomycete widely found in soil,sewage,and other external environments and is present in the population as an asymptomatic pathogen.There is relatively little documented research on T.whipplei in renal transplant patients,and there are no uniform criteria for treating this group of post-transplant patients.This article describes the treatment of a 42-year-old individual with post-transplant T.whipplei infection following kidney transplantation.CASE SUMMARY To analyze clinical features of Whipple’s disease and summarize its diagnosis and treatment effects after renal transplantation.Clinical data of a Whipple’s disease patient treated in the affiliated hospital of Guizhou Medical University were collected and assessed retrospectively.The treatment outcomes and clinical experience were then summarized via literature review.The patient was admitted to the hospital due to recurrent diarrhea for 1 mo,shortness of breath,and 1 wk of fever,after 3 years of renal transplantation.The symptoms of the digestive and respiratory systems were not significantly improved after adjusting immunosuppressive regimen and anti-diarrheal,empirical antibiotic treatments.Bronchoscopic alveolar fluid was collected for meta-genomic next-generation sequencing(mNGS).The deoxyribonucleic acid sequence of Tropheryma whipplei was detected,and Whipple’s disease was diagnosed.Meropenem,ceftriaxone,and other symptomatic treatments were given,and water-electrolyte balance was maintained.Symptoms resolved quickly,and the patient was discharged after 20 d of hospitalization.The compound sulfamethoxazole tablet was continued for 3 mo after discharge.No diarrhea,fever,and other symptoms occurred during the 6-month follow-up.CONCLUSION Whipple’s disease is rare,with no specific symptoms,which makes diagnosis difficult.Polymerase chain reaction or mNGS should be immediately performed when the disease is suspected to confirm the diagnosis.

Successful treatment of a case of COVID-19 pneumonia following kidney transplantation using paxlovid and tocilizumab

BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following kidney transplantation have been limited and no uniform treatment guidelines for these patients have yet to be established.CASE SUMMARY Here,we report the case of a 39-year-old patient recovering from kidney transplantation who contracted perioperative COVID-19 pneumonia that was successfully controlled with oral paxlovid and a single intravenous drip infusion of tocilizumab following the discontinuation of immunosuppressive drugs.CONCLUSION Given the rapid spread of severe acute respiratory syndrome coronavirus 2 infections,clinicians should be aware of the potential for more cases of COVID-19 among patients following kidney transplantation and be familiar with appropriate treatment options and likely clinical outcomes.

Progress in diagnosis and treatment of invasive aspergillosis after liver transplantation

Invasive aspergillosis is an opportunistic fungal infection disease,and the risk factors of Invasive aspergillosis after liver transplantation are increasing,which seriously affects the quality of life of patients.Invasive Aspergillus has no specific clinical manifestations and occurs most frequently in the lungs.The diagnostic methods for invasive aspergillosis are continuously updated,including serological tests,polymerase chain reaction(PCR),next-generation sequencing,Matrix-assisted laser desorption ionization time-of-flight mass spectrometry,Aspergillus GM lateral flow test,and some new markers under study have made the diagnosis of invasive aspergillosis infection more definitive.Voriconazole is the drug of choice for the treatment and prevention of invasive aspergillosis,and immunotherapy may become an adjuvant therapy or monotherapy for invasive aspergillosis with the emergence of more and more resistant strains.This article summarizes the progress in the diagnosis and treatment of invasive aspergillosis after liver transplantation,in order to provide a reference for clinical practice.

Progress of mechanical perfusion in split liver transplantation

Split liver transplantation is an essential means which expand the donor pool currently and the two livers obtained after splitting are marginal donor livers.The adoption of Static Cold Storage during allocation and preservation leads to a higher cold ischemia time,thus increasing the occurrence of related postoperative complications,which limits the further development of split-liver transplantation.Mechanical perfusion as a complement to split liver transplantation can minimize the damage to the marginal donor liver during preservation and reduce the occurrence of ischemia-reperfusion.At present,mechanical perfusion has achieved better efficacy in other types of marginal donor liver transplantation such as DCD,elderly donor liver,fatty liver,and so on.In recent years,mechanical perfusion has also shown great potential for application in split-liver transplantation,and limited clinical studies have shown outstanding therapeutic effects.Therefore,this paper will summarize the research progress and mechanisms related to the application of mechanical perfusion in split liver transplantation in order to promote the application of mechanical perfusion in split liver transplantation and reduce the damage of the organ during preservation.

Meta-analysis of the efficacy and safety of extended right liver transplantation versus whole liver transplantation

Objective:To compare the differences in postoperative survival and complications between extended right liver transplantation(ERLT)and whole liver transplantation(WLT).Methods:The Chinese and English databases were searched for clinical studies on comparing ERLT with WLT for end-stage liver disease from the date of database construction to April 15,2022.The searched literature was de-duplicated and selected according to the order of title,abstract and content,after which NOS quality evaluation was performed for literature that matched the study.Postoperative complications and survival data were extracted from the eligible literature and subjected to Meta-analysis with Review Manager 5.3,and finally data sensitivity analysis and publication bias tests were performed.Results:The complication of ERLT such as biliary complications[OR=1.77,95%CI=(1.39,2.25),P<0.00001],biliary leakage[OR=2.16,95%CI=(1.64,2.84),P<0.0001],total vascular complications[OR=2.00,95%CI=(1.48,2.70),P<0.0001],hepatic arterial thrombosis[OR=2.06,95%CI=(1.50,2.83),P<0.00001],re-Transplantation[OR=1.93,95%CI=(1.53,2.45),P<0.00001]have a higher occurrence rate compared with WLT.While the biliary stenosis[OR=0.74,95%CI=(0.48,1.15),P=0.18],hepatic portal vein thrombosis[OR=1.72,95%CI=(0.84,3.49),P=0.14],primary non-function[OR=1.27,95%CI=(0.80,2.02),P=0.32]had no statistically difference in the incidence of complications after liver transplantation.In terms of survival,ERLT had lower 1-year graft survival rate[OR=0.64,95%CI=(0.54,0.76),P<0.00001]and patient survival rate[OR=0.75,95%CI=(0.62,0.91),P=0.003]than WLT.Fortunately,there was no statistically difference in 5-year graft survival rate[OR=0.97,95%CI=(0.76,1.23),P=0.78]and 5-year patient survival rate[OR=0.94,95%CI=(0.78,1.14),P=0.54].Conclusion:ERLT is a safe and effective treatment for adult end-stage liver disease.As a surgical method with postoperative complications and survival similar to that of WLT,ERLT can increase the source of donor liver.

Development of a diagnostic nomogram for alpha-fetoproteinnegative hepatocellular carcinoma based on serological biomarkers

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related death worldwide.Serum biomarkers play an important role in the early diagnosis and prognosis of HCC.Because a certain percentage of HCC patients are negative for alpha-fetoprotein(AFP),the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC.AIM To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers.METHODS A total of 180 HCC patients were enrolled in this study.The expression levels of GP73,des-γ-carboxyprothrombin(DCP),CK18-M65,and CK18-M30 were detected by a fully automated chemiluminescence analyser.The variables were selected by logistic regression analysis.Several models were constructed using stepwise backward logistic regression.The performance of the models was compared using the C statistic,integrated discrimination improvement,net reclassification improvement,and calibration curves.The clinical utility of the nomogram was assessed using decision curve analysis(DCA).RESULTS The results showed that the expression levels of GP73,DCP,CK18-M65,and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls(P<0.001).Multivariate logistic regression analysis revealed that GP73,DCP,and CK18-M65 were independent factors for diagnosing AFP-negative HCC.By comparing the diagnostic performance of multiple models,we included GP73 and CK18-M65 as the model variables,and the model had good discrimination ability(area under the curve=0.946)and good goodness of fit.The DCA curves indicated the good clinical utility of the nomogram.CONCLUSION Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC.The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

Correction to:Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

Correction to“Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection.World J Gastroenterol 2017 June 14;23(22):4016-4038”.In this article,there is a picture that needs to be corrected.

Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation

AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat model.METHODS BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff technique.Recipients were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/BMMSCs.Liver function was examined at six time points.The levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent assay.The portal vein pressure(PVP)was detected by Power Lab ML880.The expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western blotting.ATPase in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron microscope.RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,compared with those of the NS group and BMMSCs group(P<0.05).In term of the energy metabolism of the transplanted liver,HO-1/BMMSCs repaired the damaged mitochondria,and improved the activity of mitochondrial aspartate aminotransferase(ASTm)and ATPase,compared with the other two groups(P<0.05).CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly,and recover the energy metabolism of damaged hepatocytes in rats following RLT,thus protecting the transplanted liver.

Kinetics of phytohemaglutinin-induced IFN-γ and TNF-a expression in peripheral blood mononuclear cells from patients with chronic hepatitis B after liver transplantation

AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation （OLT） before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-γ and TNF-α in culture supematants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR. RESULTS： The levels of INF-γ and TNF-α in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns （INF-γ 155.52±72.32 ng/L vs 14.76±9.88 ng/L vs 13.22±10.35 ng/L, F= 6.946, P= 0.027〈0.05; TNF-α 80.839±46.75 ng/L vs18.59±17.29 ng/L vs9.758±7.96 ng/L, F= 22.61, P = 0.0001〈0.05）. The levels of INF-γ and TNF-α were higher in groups with phytohemagglutinin （PHA） than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-γ and TNF-α could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated （HBV detected rate： 51.4%, 13.3%, 50% respectively; HBV DNA： 3.55±0.674 log（10） copies/mL vs 3.00±0.329 log（10） copies/mL vs 4.608±1.344 log（10） copies/mL, F= 7.582, P= 0.002〈0.05）. HBV DNA in serum was 4.48±1.463 log（10） copies/mL before surgery and 〈 10^3 copies/mL after OLT except for one with 5.72×10^6 copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-γ and TNF-α were lower in patients with a high HBV load than in those with a low HBV load （HBV DNA detected/undetected in PBMCs： IFN-γ 138.08±72.44 ng/L vs 164.24±72.07 ng/L, t = 1.065, P= 0.297〉0.05, TNF-α 80.75±47.30 ng/L vs 74.10±49.70 ng/L, t= 0.407, P= 0.686〉 0.05; HBV DNA positive/negative： IFN-γ 136.77±70.04 ng/L vs 175.27±71.50 ng/L, t= 1.702, P= 0.097〉0.05; TNF-α 75.37±43.02 ng/L vs 81.53±52.46 ng/L, t = 0.402, P = 0.690〉0.05）. CONCLUSION： The yielding of INF-γ and TNF-α from PBMCs is inhibited significantly by immunosuppressive agents following OLT with HBV load increased, indicating that the impaired immunity of host is associated with HBV recurrence after OLT.

High expression of protein phosphatase 2 regulatory subunit B''alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation

BACKGROUND Protein phosphatase 2 regulatory subunit B''alpha(PPP2R3A)gene has been reported in other tumors,but the influence of PPP2R3A gene expression on the occurrence,development,and prognosis of hepatocellular carcinoma(HCC)remains unclear.AIM To investigate whether the PPP2R3A gene could be used to predict tumor recurrence and survival of HCC patients after liver transplantation(LT).METHODS Diseased liver tissues of HCC patients after LT were collected as well as their clinical data and follow-up information.The immunohistochemical method was used to detect the expression of PPP2R3A protein in the tissues of 108 patients with primary liver cancer.Theχ2 test was used to analyze the relationship between PPP2R3A protein expression levels and the clinicopathological features of tumors.The Kaplan-Meier method was used to analyze overall postoperative survival.The COX proportional hazard model was used to analyze adverse prognostic factors.RESULTS Immunohistochemistry showed that the PPP2R3A protein was mainly expressed in the cytoplasm of HCC cells.Compared to corresponding peritumoral tissues,expression was higher in HCC tissues(P≤0.001).Correlation analysis showed that high PPP2R3A expression was correlated with preoperative serum alphafetoprotein(AFP)levels(P=0.003),tumor-node-metastasis-t stage(P≤0.001),and envelope invasion(P=0.001).Univariate analysis showed that overall survival(P≤0.001)and recurrence-free survival(P=0.025)of patients with high PPP2R3A expression(≥4 points)were poor compared to those with low expression(<4 points).The overall survival rates or recurrence-free survival rates at 1,2,and 3 years with high PPP2R3A expression were 73%,38%,and 23%or 31%,23%,and 23%,respectively.Multivariate analysis showed that high PPP2R3A expression(hazard ratio=2.900,95%confidence interval:1.411–5.960,P=0.004)was an independent survival risk factor of HCC patients after LT,and it was also an independent predictor of postoperative tumor recurrence.This study also showed in patients with AFP≥400 ng/mL,the overall survival(P≤0.001)and recurrencefree survival(P=0.023)of those with high PPP2R3A expression were significantly worse compared to those with low PPP2R3A expression.When PPP2R3A expression was low,the overall survival rate(P=0.461)or recurrence-free survival rate(P=0.072)after LT in patients with AFP<400 ng/mL and≥400 ng/mL was not significantly difference.The 1,2,and 3 year survival rate of patients with low PPP2R3A expression and AFP<400 ng/mL were 98%,80%,and 69%,respectively,while patients who met Hangzhou criteria had a posttransplant 1,2,and 3 years overall survival rate of 89%,66%,and 55%,respectively.CONCLUSION High expression of PPP2R3A might be a potential marker for predicting poor prognosis of HCC after LT.Combined with serum AFP levels,PPP2R3A might enhance the accuracy of predicting HCC outcome in patients after LT and supplement the efficacy of the Hangzhou criteria.

Occult pancreaticobiliary reflux is a pathogenic factor of some benign biliary diseases and gallbladder cancer

Background:Pancreaticobiliary maljunction(PBM)is a well-known high-risk factor for biliary malignant tumors because of constant pancreaticobiliary reflux(PBR).However,the impact of occult pancreaticobiliary reflux(OPR),which is characterized by high bile amylase levels in individuals with anatomically normal pancreaticobiliary junction,on biliary diseases remains unclear.The aim of this study was to assess the correlation between OPR and biliary diseases.Methods:We enrolled 94 consecutive patients with normal pancreaticobiliary junction and primary biliary diseases confirmed by magnetic resonance cholangiopancreatography.We prospectively collected patients’bile samples and measured bile amylase levels.We investigated the incidence of OPR and the difference in bile amylase levels among these patients and assessed the correlation between high bile amylase levels(HBAL)and benign or malignant biliary diseases,as well as the OPR risk factors.Results:The incidence of OPR was 36.6%in patients with benign biliary diseases,26.7%in those with cholangiocarcinoma and 62.5%in those with gallbladder cancer.The median bile amylase level tended to be higher in patients with gallbladder cancer than in those with benign biliary diseases,but there was no significant difference(165.5 IU/L vs.23.0 IU/L,P=0.212).The prevalence of an HBAL with bile amylase levels of 1000-7500 IU/L was similar in patients with gallbladder cancer and benign biliary diseases.However,the incidence of HBAL with bile amylase levels greater than 7500 IU/L was significantly higher in patients with gallbladder cancer than in those with benign biliary diseases(37.5%vs.4.2%,P=0.012).Multivariate logistic regression analysis revealed that choledocholithiasis was an independent risk factor for OPR.Conclusions:OPR can occur in benign and malignant biliary diseases,and it may be a pathogenic factor for some benign biliary diseases and a high-risk factor for gallbladder cancer.There is a correlation between choledocholithiasis and OPR.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.

Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients

BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To investigate the role of TRP genes in HCC,their association with HCC development and treatment was examined.METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database,and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum.Based on these analyses,clinically relevant TRP family genes were selected,and the association between the key TRP canonical type 1(TRPC1)gene and HCC patient prognosis was evaluated.RESULTS In total,28 TRP family genes were screened for clinical relevance,with multivariate analyses ultimately revealing three of these genes(TRPC1,TRP cation channel subfamily M member 2,and TRP cation channel subfamily M member 6)to be significantly associated with HCC patient prognosis(P<0.05).These genes were utilized to establish a TRP-related risk model.Patients were separated into low-and high-risk groups based on the expression of these genes,and high-risk patients exhibited a significantly poorer prognosis(P=0.001).Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways.TRPC1 was identified as a candidate gene in this family worthy of further study,with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes.Consistently,quantitative,immunohistochemistry,and western blot analyses revealed increased TRPC1 expression in HCC.CONCLUSION These three TRP genes help determine HCC patient prognosis,providing insight into tumor immune status and immunological composition.These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.

Might liver transplantation recipients with primary hepatocellular carcinoma benefit from GVT effect of aGVHD?

We aimed to access if acute graft-versus-host disease （aGVHD） in liver transplantation recipients of hepatocellular carcinoma （HCC） might develop a graft-versus-tumor effect （GVT） other than immunological damage which would benefit prophylaxis of tumor recurrence. Methods： Dynamic observation of 3 cases of liver transplantation recipients of HCC and cirrhosis, which developed manifestations of fever, skin rash, watery diarrhea, pancytopenia and were finally diagnosed as aGVHD. Two of which got recovered from intravenously pulse methylprednisolone, high-dose intravenous immunoglobulin, antibiotics administration simultaneously and promptly withdrawal of oral immunosuppressants. Two survivors were follow-up regularly with biological monitoring and imaging surveillance for tumor recurrence thereafter. Results： Two recipients survived healthily with stable liver graft function and normal serum AFP level and blood routine test. No sign of tumor recurrence was found in repeat imaging examinations for liver graft, lung, brain and other tissue or organs within a period of 96 months and 17 months to date, respectively. Conclusien： Despite of the fatal damage to according organs and tissue, it suggest that aGVHD in liver recipients of HCC may also develop a GVT effect and benefit prophylaxis of tumor recurrence and result in a long-term healthy recipients survival.

Intravenous prograf in maintenance treatment of intestinal obstruction complicated with hepatic function injury after renal transplantation: a case report

For renal transplant recipients, intestinal obstruction caused by incisional hernia is a rarely encountered event. Until now, there is no specific literature concerning the adjustment of immunosuppressants under such clinical condition. We present such a case who received a successful long-term single intravenous prograf administration to transitionally maintain the immunosuppression.