Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous...Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic dysfunction.Our center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”donors.We detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.展开更多
Background:Hepatocellular carcinoma(HCC)is the most common type of liver cancer.Recently,developments in radiotherapy technology have led to radiotherapy becoming one of the main therapeutics of HCC.Therefore,a suitab...Background:Hepatocellular carcinoma(HCC)is the most common type of liver cancer.Recently,developments in radiotherapy technology have led to radiotherapy becoming one of the main therapeutics of HCC.Therefore,a suitable animal model for radiotherapy of the orthotopic HCC mouse model is urgently needed.Methods:In the present study,Hepa1-6 cells were injected into the liver of C57BL/6 mice in situ to mimic the pathological characteristics of the original HCC.Tumor formation was monitored by applying magnetic resonance imaging techniques and verified by H&E histopathological staining,AFP staining,and Ki67 staining.A single dose of 10 Gy X-ray was applied to simulate clinical radiotherapy plans using image-guided radiotherapy(IGRT)equipment.The efficiency of radiotherapy was then assessed by examining tumor size and weight one week after radiation.Cleaved-caspase3 staining and TUNEL were used to assess apoptosis in tumor tissues.Results:Intrahepatic tumor development was detected in the liver according using MRI.A high-density shadow could be seen 10 days after cell injection,which indicated the formation of HCC in vivo.The tumors grew steadily bigger,and underwent precision radiotherapy 20 days after injection.The typical pathological characteristics of HCC,such as large,deeply stained nuclei and irregular cell size,were visible with H&E staining.After radiotherapy,significantly higher expression of the immunohistochemical markers Ki67 and AFP were detected in tumor tissue than in the nearby normal tissue.Compared with the control group,the tumor volume(p=0.05)and weight(p<0.05)of the irradiated group were significantly reduced.In addition,a higher frequency of apoptosis was identified in irradiated HCC tumor tissue using the TUNEL and cleaved-caspase3 staining assay.Conclusions:In a well-established orthotopic HCC model,MRI was utilized to monitor the formation of tumors,and IGRT was used to simulate clinical radiotherapy.The present study could provide a suitable preclinical system for HCC radiotherapyrelated studies.展开更多
Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over ti...Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.展开更多
Background:As mammography X-ray imaging technologies advance and provide elevated contrast in soft tissues,a need has developed for reliable imaging phantoms for use in system design and component calibration.In advan...Background:As mammography X-ray imaging technologies advance and provide elevated contrast in soft tissues,a need has developed for reliable imaging phantoms for use in system design and component calibration.In advanced imaging modalities such as refraction-based methods,it is critical that developed phantoms capture the biological details seen in clinical precancerous and cancerous cases while minimizing artifacts that may be caused due to phantom production.This work presents the fabrication of a breast tissue imaging phantom from cadaveric breast tissue suitable for use in both transmission and refraction-enhanced imaging systems.Methods:Human cancer cell tumors were grown orthotopically in nude athymic mice and implanted into the fixed tissue while maintaining the native tumor/adipose tissue interface.Results:The resulting human–murine tissue hybrid phantom was mounted on a clear acrylic housing for absorption and refraction X-ray imaging.Digital breast tomosynthesis was also performed.Conclusion:Both attenuation-based imaging and refraction-based imaging of the phantom are presented to confirm the suitability of this phantom's use in both imaging modalities.展开更多
AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hep...AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.展开更多
BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global health issue, and the prognosis of patients with HBV-associated fulminant hepatic failure is extremely poor. The application of antiviral th...BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global health issue, and the prognosis of patients with HBV-associated fulminant hepatic failure is extremely poor. The application of antiviral therapies has led to significant improvements in patient outcomes. This article aimed to review the current strategies in antiviral treatment of HBV-associated fulminant hepatic failure. DATA SOURCES: Literature search was conducted using PubMed on the related subjects. Part of the data was from the most recent work of the authors' laboratory. RESULTS: Hepatitis B immunoglobulin in prevention of recurrent HBV infection after orthotopic liver transplantation (OLT) has been proven effective. However, its cost is high, and significant side effects have been found to induce viral mutations. Lamivudine has a potent suppression for HBV replication and an excellent safety profile in decompensated cirrhotic patients, but its major drawback is the high rate of drug-resistance. Adefovir is effective for lamivudine-resistance strains in the post-OLT situation, and its drug-resistance rate is relatively low. Combination therapies such as hepatitis B immunoglobulin combined with lamivudine and lamivudine combined with adefovir have been widely adopted for prophylaxis against HBV recurrence of infection after OLT. Entecavir, telbivudine, tenofovir and other newer agents have been widely used in antiviral therapy. CONCLUSIONS: The prognosis of HBV-associated fulminant hepatic failure is being transformed by developments in antiviral therapy. However, it should be noticed that HBV is controlled but never eliminated, and drug-resistance still remains a major issue. Hopefully, newer strategies may help to solve these problems.展开更多
Although vascular complications(VCs) following orthotopic liver transplantation(OLT) seldom occur, they are the most feared complications with a high incidence of both graft loss and mortality, as they compromise the ...Although vascular complications(VCs) following orthotopic liver transplantation(OLT) seldom occur, they are the most feared complications with a high incidence of both graft loss and mortality, as they compromise the blood flow of the transplant(either inflow or outflow). Diagnosis and therapeutic management of VCs constitute a major challenge in terms of increasing the success rate of liver transplantation. While surgical treatment used to be considered the first choice for management, advances in endovascular intervention have increased to make this a viable therapeutic option. Considering VC as a rare but a major and dreadful issue in OLT history, and in view of the continuing and rapid progress in recent years, an update on these uncommon conditions seemed necessary. In this sense, this review comprehensively discusses the important features(epidemiological, clinical, paraclinical, prognostic and therapeutic) of VCs following OLT.展开更多
BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is consider...BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.展开更多
AIM:To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points.METHODS:Human gastric cancer SGC-7901 cell suspensions w...AIM:To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points.METHODS:Human gastric cancer SGC-7901 cell suspensions were injected subcutaneously into a nude mouse to develop solid tumors,and the tumor tissue pieces were implanted under the serous coat.The nude mice were then euthanized in group every two weeks to observe the primary tumor growth and metastases.RESULTS:Within 2-4 wk,there were no obvious chang-es about the primary tumor in stomach.At the sixth week,the primary tumor began to grow fast,resulting in incrassation of the gastric wall and stenosis of the gastric cavity,and metastases into the liver and lymph nodes were detected.The tumor,which compressed the adjacent organs,gradually became bigger and bigger followed by stenosis or vanishment of the gastric cavity from 8 to 12 wk.There were massive metastases,and the rate of metastasis was 58%in lymph nodes,78%in liver,39%in kidney,and 81%in peritoneum or septum.CONCLUSION:A gastric cancer model is established,which can simulate the clinical tumor behavior and provide experimental carrier for clinical trials of gastric cancer treatment.展开更多
Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Biliary strictures are classifi ed as anastomotic or non-anastomotic strictures according to location and are defi ...Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Biliary strictures are classifi ed as anastomotic or non-anastomotic strictures according to location and are defi ned by distinct clinical behaviors. Anastomotic strictures are localized and short. The outcome of endoscopic treatment for anastomotic strictures is excellent. Nonanastomotic strictures often result from ischemic and immunological events, occur earlier and are usually multiple and longer. They are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and need for retransplantation. Living donor OLT patients present a unique set of challenges arising from technical factors, and stricture risk for both recipients and donors. Endoscopic treatment of living donor OLT patients is less promising. Current endoscopic strategies for biliary strictures after OLT include repeated balloon dilations and placement of multiple side-by-side plastic stents. Lifelong surveillance is required in all types of strictures. Despite improvements in incidence and long term outcomes with endoscopic management, and a reduced need for surgical treatment, the impact of strictures on patients after OLT is signifi cant. Future considerations include new endoscopic technologies and improved stents, which could potentially allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. This review focuses on the role of endoscopy in biliary strictures, one of the most common biliary complications after OLT.展开更多
Biliary complications are signifi cant causes of morbidity and mortality after orthotopic liver transplantation (OLT). The estimated incidence of biliary complications after OLT ranges between 10%-25%,however,these nu...Biliary complications are signifi cant causes of morbidity and mortality after orthotopic liver transplantation (OLT). The estimated incidence of biliary complications after OLT ranges between 10%-25%,however,these numbers continue to decline due to improvement in surgical techniques. The most common biliary complications are strictures (both anastomotic and non-anastomotic) and bile leaks. Most of these problems can be appropriately managed with endoscopic retrograde colangiography (ERC). Other complications such as bile duct stones,bile casts,sphincter of Oddi dysfunction,and hemobilia,are less frequent and also can be managed with ERC. This article will review the risk factors,diagnosis,and endoscopic management of the most common biliary complications after OLT.展开更多
Viral-mediated gene transfer of thymidine kinase ofherpes simplex virus (HSV-tk) has been used to confercytotoxic sensitivity to ganciclovir (GCV) in a variety oftnmor cells. HSV-tk converts GCV into a phosphorylatedc...Viral-mediated gene transfer of thymidine kinase ofherpes simplex virus (HSV-tk) has been used to confercytotoxic sensitivity to ganciclovir (GCV) in a variety oftnmor cells. HSV-tk converts GCV into a phosphorylatedcompound which is toxic for dividing cells by blockingDNA synthesis. Our previous study has shown展开更多
The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgic...The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgical and medical treatment.The recurrence rate involves 2 phases:an early phase and a late phase.The early phase usually occurs within 2 years after resection;it is mainly related to local invasion and intrahepatic metastases and,therefore,to the intrinsic biology of the tumor.On the other hand,the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment.Since recent studies have reported that early and late recurrences may have different risk factors,it is clinically important to recognize these factors in the individual patient as soon as possible.The aim of this review was,therefore,to identify predicting factors for the recurrence of hepatocellularcarcinoma,by means of invasive and non-invasive methods,according to the different therapeutic strategies available.In particular the role of emerging techniques(e.g.,transient elastography)and biological features of hepatocellular carcinoma in predicting recurrence have been discussed.In particular,invasive methods were differentiated from non-invasive ones for research purposes,taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.展开更多
Orthotopic liver transplantation ( OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have co...Orthotopic liver transplantation ( OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have contributed to the current success of OLT, but surgical complications, especially involving the biliary reconstruction, remain a morbid problem. Biliary complications after OLT include leaks and strictures. Strictures may be anastoinotic or intrahepatic and diffuse, as seen in cases of hepatic artery thrombosis. Current efforts to expand the limited donor pool include the use of non-heart beating donors. The organ procurement process in these donors entails an increased period of warm ischemia and results with non-heart beating donor grafts have been mixed. It is now appreciated that there is an increased incidence of subsequent diffuse biliary stricturing or ' ischemic cholangiopathy' in recipients of these organs. Animal models of this phenomenon and potential therapeutic strategies targeted at ischemic cholangiopathy are being developed with potential applicability to non-heart beating donation and will be the focus of this review.展开更多
AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune, rapamycin) in a consecutive cohort of 248 liver allograft recipients. METHODS: Thirty-six liver ...AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune, rapamycin) in a consecutive cohort of 248 liver allograft recipients. METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL- based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insuffidency caused by caldneurin inhibitor (CNI) were assigned to group C (n = 7) after OLT. RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 too) after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/ or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable. CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.展开更多
Cholangiocarcinoma is a malignant tumor of the biliary system that can be classified into intrahepatic(i CCA),perihiliar(ph CCA) and distal. Initial experiences with orthotopic liver transplantation(OLT) for patientsw...Cholangiocarcinoma is a malignant tumor of the biliary system that can be classified into intrahepatic(i CCA),perihiliar(ph CCA) and distal. Initial experiences with orthotopic liver transplantation(OLT) for patientswith i CCA and ph CCA had very poor results and this treatment strategy was abandoned. In the last decade,thanks to a strict selection process and a neoadjuvant chemoradiation protocol,the results of OLT for patients with non-resectable phC CA have been shown to be excellent and this strategy has been extended worldwide in selected transplant centers. Intrahepatic cholangiocarcinoma is a growing disease in most countries and can be diagnosed both in cirrhotic and in non-cirrhotic livers. Even though OLT is contraindicated in most centers,recent investigations analyzing patients that were transplanted with a misdiagnosis of HCC and were found to have an iC CA have shown encouraging results. There is some information suggesting that patients with early stages of the disease could benefit from OLT. In this review we analyze the current stateof-the-art of OLT for cholangiocarcinoma as well as the new insights and future perspectives.展开更多
Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasi...Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.展开更多
Orthotopic liver transplantation(OLT)represents a major treatment for end-stage chronic liver disease,as well as selected cases of hepatocellular carcinoma and acute liver failure.The ever-increasing development of im...Orthotopic liver transplantation(OLT)represents a major treatment for end-stage chronic liver disease,as well as selected cases of hepatocellular carcinoma and acute liver failure.The ever-increasing development of imaging modalities significantly contributed,over the last decades,to the management of recipients both in the pre-operative and post-operative period,thus impacting on graft and patients survival.When properly used,imaging modalities such as ultrasound,multidetector computed tomography,magnetic resonance imaging(MRI)and procedures of direct cholangiography are capable to provide rapid and reliable recognition and treatment of vascular and biliary complications occurring after OLT.Less defined is the role for imaging in assessing primary graft dysfunction(including rejection)or chronic allograft disease after OLT,e.g.,hepatitis C virus(HCV)recurrence.This paper:(1)describes specific characteristic of the above imaging modalities and the rationale for their use in clinical practice;(2)illustrates main imaging findings related to post-OLTcomplications in adult patients;and(3)reviews future perspectives emerging in the surveillance of recipients with HCV recurrence,with special emphasis on MRI.展开更多
BACKGROUND: Recipients of liver transplantation could have postoperative structural injury and declined absorptive function in the gastrointestinal tract. Glutamine (Gln) is a special nutrient of small intestinal muco...BACKGROUND: Recipients of liver transplantation could have postoperative structural injury and declined absorptive function in the gastrointestinal tract. Glutamine (Gln) is a special nutrient of small intestinal mucosa and of various kinds of cells proliferating rapidly. But Gln could form a kind of poisonous pyroglutamic acid in water solution, which is the limitation of Gln in clinical practice. Glycyl-glutamine (Gly-Gln) is highly soluble and can be hydro-lyzed to release glutamine. This study was undertaken to observe the effect of Gly-Gln dipeptide by enteral feeding on the intestinal structure and absorptive function after allogenetic liver transplantation in rats. METHODS: Twelve male inbred Lewis rats were selected randomly as donors, and 24 male inbred BN rats as recipients of allogenetic liver transplantation. The recipients were also randomly divided into two groups; control group (ALA group, n = 12 ) and experimental group ( GLN group , n =12). In each group, 6 normal BN rats were sampled as the normal parameter on the 3rd preoperative day. The 6 recipients in the control group received alanine 0. 6 g/kg daily for 3 days before operation and 7 days after operation by gastric perfusion, and the 6 recipients in the experimental group were given Gly-Gln 0.6 g/kg daily the same way. The 12 BN recipients underwent 3-day fasting (free access to water with 0. 23% sodium chloride) and ortho-topic liver transplantation in aseptic conditions and were given subcutaneous injection of CsA 2 mg/kg daily after the operation. The 12 BN recipients were sampled on the 8th postoperative day. All of the 24 BN rats were subjected to examination of mucosal structure, activities of Na + -K + - ATP and disaccharidase, and D-xylose absorption test. RESULTS: The 12 BN recipients were alive after liver transplantation. On the 3rd preoperative day, mucosal structure , activities of Na + -K -ATP and disaccharidase and D-xylose absorption in the two groups were not significantly different. On the 8th postoperative day, the parameters of the two groups were markedly changed compared with those on the 3rd preoperative day. However, the parameters of GLN group were remarkably higher than those of ALA group. CONCLUSION: Enteral feeding of Gly-Gln could improve the structure and absorptive function of the small intestine after liver transplantation in rats.展开更多
文摘Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic dysfunction.Our center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”donors.We detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.
基金Key R&D Program of China,Grant/Award Number:2022YFC2503700 and 2022YFC2503703National Natural Science Foundation of China,Grant/Award Number:81773226,82103483 and U1967220Shanghai Sailing Program,Grant/Award Number:20YF1459700。
文摘Background:Hepatocellular carcinoma(HCC)is the most common type of liver cancer.Recently,developments in radiotherapy technology have led to radiotherapy becoming one of the main therapeutics of HCC.Therefore,a suitable animal model for radiotherapy of the orthotopic HCC mouse model is urgently needed.Methods:In the present study,Hepa1-6 cells were injected into the liver of C57BL/6 mice in situ to mimic the pathological characteristics of the original HCC.Tumor formation was monitored by applying magnetic resonance imaging techniques and verified by H&E histopathological staining,AFP staining,and Ki67 staining.A single dose of 10 Gy X-ray was applied to simulate clinical radiotherapy plans using image-guided radiotherapy(IGRT)equipment.The efficiency of radiotherapy was then assessed by examining tumor size and weight one week after radiation.Cleaved-caspase3 staining and TUNEL were used to assess apoptosis in tumor tissues.Results:Intrahepatic tumor development was detected in the liver according using MRI.A high-density shadow could be seen 10 days after cell injection,which indicated the formation of HCC in vivo.The tumors grew steadily bigger,and underwent precision radiotherapy 20 days after injection.The typical pathological characteristics of HCC,such as large,deeply stained nuclei and irregular cell size,were visible with H&E staining.After radiotherapy,significantly higher expression of the immunohistochemical markers Ki67 and AFP were detected in tumor tissue than in the nearby normal tissue.Compared with the control group,the tumor volume(p=0.05)and weight(p<0.05)of the irradiated group were significantly reduced.In addition,a higher frequency of apoptosis was identified in irradiated HCC tumor tissue using the TUNEL and cleaved-caspase3 staining assay.Conclusions:In a well-established orthotopic HCC model,MRI was utilized to monitor the formation of tumors,and IGRT was used to simulate clinical radiotherapy.The present study could provide a suitable preclinical system for HCC radiotherapyrelated studies.
基金supported by a grant from the Bundesminis-terium für Bildung und Forschung (01ZX1903A)。
文摘Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.
基金National Institutes of Health,Grant/Award Number:EB023969 and HL154687。
文摘Background:As mammography X-ray imaging technologies advance and provide elevated contrast in soft tissues,a need has developed for reliable imaging phantoms for use in system design and component calibration.In advanced imaging modalities such as refraction-based methods,it is critical that developed phantoms capture the biological details seen in clinical precancerous and cancerous cases while minimizing artifacts that may be caused due to phantom production.This work presents the fabrication of a breast tissue imaging phantom from cadaveric breast tissue suitable for use in both transmission and refraction-enhanced imaging systems.Methods:Human cancer cell tumors were grown orthotopically in nude athymic mice and implanted into the fixed tissue while maintaining the native tumor/adipose tissue interface.Results:The resulting human–murine tissue hybrid phantom was mounted on a clear acrylic housing for absorption and refraction X-ray imaging.Digital breast tomosynthesis was also performed.Conclusion:Both attenuation-based imaging and refraction-based imaging of the phantom are presented to confirm the suitability of this phantom's use in both imaging modalities.
文摘AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.
基金supported by grants from the National Basic Research Program of China(973 Program)(No.2007CB512900)National Natural Science Foundation of China(No.30470964)
文摘BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global health issue, and the prognosis of patients with HBV-associated fulminant hepatic failure is extremely poor. The application of antiviral therapies has led to significant improvements in patient outcomes. This article aimed to review the current strategies in antiviral treatment of HBV-associated fulminant hepatic failure. DATA SOURCES: Literature search was conducted using PubMed on the related subjects. Part of the data was from the most recent work of the authors' laboratory. RESULTS: Hepatitis B immunoglobulin in prevention of recurrent HBV infection after orthotopic liver transplantation (OLT) has been proven effective. However, its cost is high, and significant side effects have been found to induce viral mutations. Lamivudine has a potent suppression for HBV replication and an excellent safety profile in decompensated cirrhotic patients, but its major drawback is the high rate of drug-resistance. Adefovir is effective for lamivudine-resistance strains in the post-OLT situation, and its drug-resistance rate is relatively low. Combination therapies such as hepatitis B immunoglobulin combined with lamivudine and lamivudine combined with adefovir have been widely adopted for prophylaxis against HBV recurrence of infection after OLT. Entecavir, telbivudine, tenofovir and other newer agents have been widely used in antiviral therapy. CONCLUSIONS: The prognosis of HBV-associated fulminant hepatic failure is being transformed by developments in antiviral therapy. However, it should be noticed that HBV is controlled but never eliminated, and drug-resistance still remains a major issue. Hopefully, newer strategies may help to solve these problems.
文摘Although vascular complications(VCs) following orthotopic liver transplantation(OLT) seldom occur, they are the most feared complications with a high incidence of both graft loss and mortality, as they compromise the blood flow of the transplant(either inflow or outflow). Diagnosis and therapeutic management of VCs constitute a major challenge in terms of increasing the success rate of liver transplantation. While surgical treatment used to be considered the first choice for management, advances in endovascular intervention have increased to make this a viable therapeutic option. Considering VC as a rare but a major and dreadful issue in OLT history, and in view of the continuing and rapid progress in recent years, an update on these uncommon conditions seemed necessary. In this sense, this review comprehensively discusses the important features(epidemiological, clinical, paraclinical, prognostic and therapeutic) of VCs following OLT.
基金supported by grants from the Health Bureau(H200770)Technology Bureau(BS2005038)of Jiangsu Province,China
文摘BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.
基金Supported by the Natural Science Foundation of China,No. 30830040
文摘AIM:To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points.METHODS:Human gastric cancer SGC-7901 cell suspensions were injected subcutaneously into a nude mouse to develop solid tumors,and the tumor tissue pieces were implanted under the serous coat.The nude mice were then euthanized in group every two weeks to observe the primary tumor growth and metastases.RESULTS:Within 2-4 wk,there were no obvious chang-es about the primary tumor in stomach.At the sixth week,the primary tumor began to grow fast,resulting in incrassation of the gastric wall and stenosis of the gastric cavity,and metastases into the liver and lymph nodes were detected.The tumor,which compressed the adjacent organs,gradually became bigger and bigger followed by stenosis or vanishment of the gastric cavity from 8 to 12 wk.There were massive metastases,and the rate of metastasis was 58%in lymph nodes,78%in liver,39%in kidney,and 81%in peritoneum or septum.CONCLUSION:A gastric cancer model is established,which can simulate the clinical tumor behavior and provide experimental carrier for clinical trials of gastric cancer treatment.
文摘Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Biliary strictures are classifi ed as anastomotic or non-anastomotic strictures according to location and are defi ned by distinct clinical behaviors. Anastomotic strictures are localized and short. The outcome of endoscopic treatment for anastomotic strictures is excellent. Nonanastomotic strictures often result from ischemic and immunological events, occur earlier and are usually multiple and longer. They are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and need for retransplantation. Living donor OLT patients present a unique set of challenges arising from technical factors, and stricture risk for both recipients and donors. Endoscopic treatment of living donor OLT patients is less promising. Current endoscopic strategies for biliary strictures after OLT include repeated balloon dilations and placement of multiple side-by-side plastic stents. Lifelong surveillance is required in all types of strictures. Despite improvements in incidence and long term outcomes with endoscopic management, and a reduced need for surgical treatment, the impact of strictures on patients after OLT is signifi cant. Future considerations include new endoscopic technologies and improved stents, which could potentially allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. This review focuses on the role of endoscopy in biliary strictures, one of the most common biliary complications after OLT.
文摘Biliary complications are signifi cant causes of morbidity and mortality after orthotopic liver transplantation (OLT). The estimated incidence of biliary complications after OLT ranges between 10%-25%,however,these numbers continue to decline due to improvement in surgical techniques. The most common biliary complications are strictures (both anastomotic and non-anastomotic) and bile leaks. Most of these problems can be appropriately managed with endoscopic retrograde colangiography (ERC). Other complications such as bile duct stones,bile casts,sphincter of Oddi dysfunction,and hemobilia,are less frequent and also can be managed with ERC. This article will review the risk factors,diagnosis,and endoscopic management of the most common biliary complications after OLT.
文摘Viral-mediated gene transfer of thymidine kinase ofherpes simplex virus (HSV-tk) has been used to confercytotoxic sensitivity to ganciclovir (GCV) in a variety oftnmor cells. HSV-tk converts GCV into a phosphorylatedcompound which is toxic for dividing cells by blockingDNA synthesis. Our previous study has shown
文摘The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgical and medical treatment.The recurrence rate involves 2 phases:an early phase and a late phase.The early phase usually occurs within 2 years after resection;it is mainly related to local invasion and intrahepatic metastases and,therefore,to the intrinsic biology of the tumor.On the other hand,the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment.Since recent studies have reported that early and late recurrences may have different risk factors,it is clinically important to recognize these factors in the individual patient as soon as possible.The aim of this review was,therefore,to identify predicting factors for the recurrence of hepatocellularcarcinoma,by means of invasive and non-invasive methods,according to the different therapeutic strategies available.In particular the role of emerging techniques(e.g.,transient elastography)and biological features of hepatocellular carcinoma in predicting recurrence have been discussed.In particular,invasive methods were differentiated from non-invasive ones for research purposes,taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.
文摘Orthotopic liver transplantation ( OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have contributed to the current success of OLT, but surgical complications, especially involving the biliary reconstruction, remain a morbid problem. Biliary complications after OLT include leaks and strictures. Strictures may be anastoinotic or intrahepatic and diffuse, as seen in cases of hepatic artery thrombosis. Current efforts to expand the limited donor pool include the use of non-heart beating donors. The organ procurement process in these donors entails an increased period of warm ischemia and results with non-heart beating donor grafts have been mixed. It is now appreciated that there is an increased incidence of subsequent diffuse biliary stricturing or ' ischemic cholangiopathy' in recipients of these organs. Animal models of this phenomenon and potential therapeutic strategies targeted at ischemic cholangiopathy are being developed with potential applicability to non-heart beating donation and will be the focus of this review.
基金Supported by the key project grant of the Science and Technological Committee of Shanghai Municipality, No.024001119the Foundation for "New Star of Medicine" of Shanghai Health Bureau, No. 1999-59
文摘AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune, rapamycin) in a consecutive cohort of 248 liver allograft recipients. METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL- based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insuffidency caused by caldneurin inhibitor (CNI) were assigned to group C (n = 7) after OLT. RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 too) after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/ or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable. CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.
文摘Cholangiocarcinoma is a malignant tumor of the biliary system that can be classified into intrahepatic(i CCA),perihiliar(ph CCA) and distal. Initial experiences with orthotopic liver transplantation(OLT) for patientswith i CCA and ph CCA had very poor results and this treatment strategy was abandoned. In the last decade,thanks to a strict selection process and a neoadjuvant chemoradiation protocol,the results of OLT for patients with non-resectable phC CA have been shown to be excellent and this strategy has been extended worldwide in selected transplant centers. Intrahepatic cholangiocarcinoma is a growing disease in most countries and can be diagnosed both in cirrhotic and in non-cirrhotic livers. Even though OLT is contraindicated in most centers,recent investigations analyzing patients that were transplanted with a misdiagnosis of HCC and were found to have an iC CA have shown encouraging results. There is some information suggesting that patients with early stages of the disease could benefit from OLT. In this review we analyze the current stateof-the-art of OLT for cholangiocarcinoma as well as the new insights and future perspectives.
文摘Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.
文摘Orthotopic liver transplantation(OLT)represents a major treatment for end-stage chronic liver disease,as well as selected cases of hepatocellular carcinoma and acute liver failure.The ever-increasing development of imaging modalities significantly contributed,over the last decades,to the management of recipients both in the pre-operative and post-operative period,thus impacting on graft and patients survival.When properly used,imaging modalities such as ultrasound,multidetector computed tomography,magnetic resonance imaging(MRI)and procedures of direct cholangiography are capable to provide rapid and reliable recognition and treatment of vascular and biliary complications occurring after OLT.Less defined is the role for imaging in assessing primary graft dysfunction(including rejection)or chronic allograft disease after OLT,e.g.,hepatitis C virus(HCV)recurrence.This paper:(1)describes specific characteristic of the above imaging modalities and the rationale for their use in clinical practice;(2)illustrates main imaging findings related to post-OLTcomplications in adult patients;and(3)reviews future perspectives emerging in the surveillance of recipients with HCV recurrence,with special emphasis on MRI.
文摘BACKGROUND: Recipients of liver transplantation could have postoperative structural injury and declined absorptive function in the gastrointestinal tract. Glutamine (Gln) is a special nutrient of small intestinal mucosa and of various kinds of cells proliferating rapidly. But Gln could form a kind of poisonous pyroglutamic acid in water solution, which is the limitation of Gln in clinical practice. Glycyl-glutamine (Gly-Gln) is highly soluble and can be hydro-lyzed to release glutamine. This study was undertaken to observe the effect of Gly-Gln dipeptide by enteral feeding on the intestinal structure and absorptive function after allogenetic liver transplantation in rats. METHODS: Twelve male inbred Lewis rats were selected randomly as donors, and 24 male inbred BN rats as recipients of allogenetic liver transplantation. The recipients were also randomly divided into two groups; control group (ALA group, n = 12 ) and experimental group ( GLN group , n =12). In each group, 6 normal BN rats were sampled as the normal parameter on the 3rd preoperative day. The 6 recipients in the control group received alanine 0. 6 g/kg daily for 3 days before operation and 7 days after operation by gastric perfusion, and the 6 recipients in the experimental group were given Gly-Gln 0.6 g/kg daily the same way. The 12 BN recipients underwent 3-day fasting (free access to water with 0. 23% sodium chloride) and ortho-topic liver transplantation in aseptic conditions and were given subcutaneous injection of CsA 2 mg/kg daily after the operation. The 12 BN recipients were sampled on the 8th postoperative day. All of the 24 BN rats were subjected to examination of mucosal structure, activities of Na + -K + - ATP and disaccharidase, and D-xylose absorption test. RESULTS: The 12 BN recipients were alive after liver transplantation. On the 3rd preoperative day, mucosal structure , activities of Na + -K -ATP and disaccharidase and D-xylose absorption in the two groups were not significantly different. On the 8th postoperative day, the parameters of the two groups were markedly changed compared with those on the 3rd preoperative day. However, the parameters of GLN group were remarkably higher than those of ALA group. CONCLUSION: Enteral feeding of Gly-Gln could improve the structure and absorptive function of the small intestine after liver transplantation in rats.