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

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

Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

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.

Impact of hypoxic preconditioning on apoptosis and its possible mechanism in orthotopic liver autotransplantation in rats

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.

Serial observations on an orthotopic gastric cancer model constructed using improved implantation technique

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.

Management of biliary complications after orthotopic liver transplantation:The role of endoscopy

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.

Highly Sensitive MoS_2–Indocyanine Green Hybrid for Photoacoustic Imaging of Orthotopic Brain Glioma at Deep Site

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS_2–ICG hybrid with indocyanine green(ICG) conjugated to the surface of MoS_2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS_2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS_2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS_2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS_2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.

Multi-factor analysis of initial poor graft function after orthotopic liver transplantation

BACKGROUND: In the early period of orthotopic liver transplantation (OLT), initial poor graft function (IPGF) is one of the complications which leads to primary graft non-function (PGNF) in serious cases. This study set out to establish the clinical risk factors resulting in IPGF after OLT. METHODS: Eighty cases of OLT were analyzed. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) above 1500 IU/L within 72 hours after OLT, while those in the non-IPGF group had values below 1500 IU/L. Recipient-associated factors before OLT analyzed were age, sex, primary liver disease and Child-Pugh classification; factors analyzed within the peri-operative period were non-heart beating time (NHBT), cold ischemia time (CIT), rewarming ischemic time (RWIT), liver biopsy at the end of cold ischemia; and factors analyzed within 72 hours after OLT were ALT and/or AST values. A logistic regression model was applied to filter the possible factors resulting in IPGF. RESULTS: Donor NHBT, CIT and RWIT were significantly longer in the IPGF group than in the non-IPGF group; in the logistic regression model, NHBT was the risk factor leading to IPGF (P < 0.05), while CIT and RWIT were possible risk factors. In one case in the IPGF group, PGNF appeared with moderate hepatic steatosis. CONCLUSIONS: Longer NHBT is an important risk factor leading to IPGF, while serious steatosis in the donor liver, CIT and RWIT are potential risk factors.

Characterization of gastric cancer models from different cell lines orthotopically constructed using improved implantation techniques

AIM:To develop orthotopic gastric cancer mouse models from different cell lines and characterize the tumor features to assist further in preclinical trials and clinical treatment strategies.METHODS:Human gastric cancer SGC-7901 and BGC823 cell suspensions were injected subcutaneously into nude mice to develop solid tumors,and tumor tissue pieces were then implanted under the serous coat of the stomach.An autopsy was performed on all animals of the SGC-7901 and BGC-823 models to observe the primary tumor growth and metastases using pathological and immunohistochemical methods.RESULTS:Both models showed large tumors in situ resulting in pressure and infiltration of the adjacent organs.The gastric cavity became smaller,along with stenosis of the cardia or pylorus.There were biological and statistical differences between the two models.The metastasis rate in involved organs (lymph nodes,kidney,spleen,testis) was significantly higher in the BGC-823 model compared to the SGC-7901 model (P < 0.05 or P < 0.01).The median survival of the BGC-823 model was shorter than that of SGC-7901 (23 d vs 84 d,P < 0.05).Histopathologically,the primary tumor and metastatic lesions of the two models showed obvious atypia and mucus in the cytoplasm.Compared with the SGC-7901 model,BGC-823 appeared more poorly differentiated (absence of adenoid structure),had a smaller volume,and richer capillary structure.Immunohistochemical staining revealed cytokeratin 20 and epithelial membrane antigen expression was positive in the SGC-7901 tumors,while negative in BGC-823 ones.CONCLUSION:Models using the SGC-7901 and BGC-823 cell lines were established which could function in gastric cancer research on carcinogenesis mechanism and drug discovery.The two models showed different tumor behavior and the latter was more malignant than the former.

Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice

AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.

T-tube vs no T-tube for biliary tract reconstruction in adult orthotopic liver transplantation:An updated systematic review and metaanalysis

BACKGROUND Whether to use a T-tube for biliary anastomosis during orthotopic liver transplantation(OLT)remains a debatable question.Some surgeons chose to use a T-tube because they believed that it reduces the incidence of biliary strictures.Advances in surgical techniques during the last decades have significantly decreased the overall incidence of postoperative biliary complications.Whether using a T-tube during OLT is still associated with the reduced incidence of biliary strictures needs to be re-evaluated.AIM To provide an updated systematic review and meta-analysis on using a T-tube during adult OLT.METHODS In the electronic databases MEDLINE,PubMed,Scopus,ClinicalTrials.gov,the Cochrane Library,the Cochrane Hepato-Biliary Group Controlled Trails Register,and the Cochrane Central Register of Controlled Trials,we identified 17 studies(eight randomized controlled trials and nine comparative studies)from January 1995 to October 2020.The data of the studies before and after 2010 were separately extracted.We chose the overall biliary complications,bile leaks or fistulas,biliary strictures(anastomotic or non-anastomotic),and cholangitis as outcomes.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated to describe the results of the outcomes.Furthermore,the test for overall effect(Z)was used to test the difference between OR and 1,where P≤0.05 indicated a significant difference between OR value and 1.RESULTS A total of 1053 subjects before 2010 and 1346 subjects after 2010 were included in this meta-analysis.The pooled results showed that using a T-tube reduced the incidence of postoperative biliary strictures in studies before 2010(P=0.012,OR=0.62,95%CI:0.42-0.90),while the same benefit was not seen in studies after 2010(P=0.60,OR=0.76,95%CI:0.27-2.12).No significant difference in the incidence of overall biliary complications(P=0.37,OR=1.41,95%CI:0.66-2.98),bile leaks(P=0.89,OR=1.04,95%CI:0.63-1.70),and cholangitis(P=0.27,OR=2.00,95%CI:0.59-6.84)was observed between using and not using a T-tube before 2010.However,using a T-tube appeared to increase the incidence of overall biliary complications(P=0.049,OR=1.49,95%CI:1.00-2.22),bile leaks(P=0.048,OR=1.91,95%CI:1.01-3.64),and cholangitis(P=0.02,OR=7.21,95%CI:1.37-38.00)after 2010.A random-effects model was used in biliary strictures(after 2010),overall biliary complications(before 2010),and cholangitis(before 2010)due to their heterogeneity(I2=62.3%,85.4%,and 53.6%,respectively).In the sensitivity analysis(only RCTs included),bile leak(P=0.66)lost the significance after 2010 and a random-effects model was used in overall biliary complications(before 2010),cholangitis(before 2010),bile leaks(after 2010),and biliary strictures(after 2010)because of their heterogeneity(I2=92.2%,65.6%,50.9%,and 80.3%,respectively).CONCLUSION In conclusion,the evidence gathered in our updated meta-analysis showed that the studies published in the last decade did not provide enough evidence to support the routine use of T-tube in adults during OLT.

Liver biochemistry profile,significance and endoscopic management of biliary tract complications post orthotopic liver transplantation

AIM： To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation （OLT） biliary complications and to study their profile before and after endoscopic therapy.METHODS： Patients who developed biliary complications were analysed in detail for the clinical information, laboratory tests, treatment offered, response to it, follow up and outcomes. The profile of liver enzymes was determined. The safety, efficacy and outcomes of endoscopic retrograde cholangiography （ERC） were also analysed. RESULTS： 40 patients required ERC for 70 biliary complications. GGT was found to be 〉 3 times （388.1 ± 70.9 U/mL vs 168.5 4± 34.2 U/L, P = 0.007） and SAP 〉 2 times （345.1 ± 59.1 U/L vs 152.7 ± 21.4 U/L, P = 0.003） the immediate post OLT values. Most frequent complication was isolated anastomotic res in 28 （40%）. Sustained success was achieved in 26 （81%） patients. CONCLUSION： Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early, non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.

Placement of removable metal biliary stent in post-orthotopic liver transplantation anastomotic stricture

Postoperative biliary strictures are the most common cause of benign biliary stricture in Western countries, secondary to either operative injury or bile duct anastomotic stricture following orthotopic liver transplantation(OLT).Surgery or endoscopic interventions are the mainstay of treatment for benign biliary strictures.We aim to report the outcome of 2 patients with refractory anastomotic biliary stricture post-OLT,who had successful temporary placement of a prototype removable covered self-expandable metal stent(RCSEMS).These 2 patients(both men,aged 44 and 53 years)were given temporary placement of a prototype RCSEMS (8.5 Fr gauge delivery system,8 mm×40 mm stent dimensions)in the common bile duct across the biliary stricture.There was no morbidity associated with stent placement and removal in these 2 cases.Clinical parameters improved after the RCSEMS placement.Longterm biliary patency was achieved in both the patients. No further biliary intervention was required within 14 and 18 mo follow-up after stent removal.

Totally intracorporeal robot-assisted urinary diversion for bladder cancer(part 2).Review and detailed characterization of the existing intracorporeal orthotopic ileal neobladder

Objective:To review the most used intracorporeal orthotopic ileal neobladder(ICONB)after radical cystectomy for bladder cancer and create a unified compendium of the different alternatives,including new consistent images.Methods:We performed a non-systematic review of the literature with the keywords“bladder cancer”,“urinary diversion”,“radical cystectomy”,and“neobladder”.Results:Forty studies were included in the analysis.The most frequent type of ICONB was the modified Studer“U”neobladder(70%)followed by the Hautmann“W”modified neobladder(7.5%),the“Y”neobladder(5%),and the Padua neobladder(5%).The operative time to perform a urinary diversion ranged from 124 to 553 min.The total estimated blood loss ranged from 200 to 900 mL.The rate of positive surgical margins ranged from 0%to 8.1%.Early minor and major complication rates ranged from 0%to 100%and from 0%to 33%,respectively.Late minor and major complication rates ranged from 0%to 70%and from 0%to 25%,respectively.Conclusion:The most frequent types of ICONB are Studer“U”neobladder,Hautmann“W”neobladder,“Y”neobladder,and the Padua neobladder.Randomized studies comparing the performance of the different types of ICONB,the performance in an intra or extracorporeal manner,or the performance of an ICONB versus ICIC are lacking in the literature.To this day,there are not sufficient quality data to determine the supremacy of one technique.This manuscript represents a compendium of the most used ICONB with detailed descriptions of the technical aspects,operative and perioperative outcomes,and new consistent images of each technique.

Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study

Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation(OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk(i.e., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT(i.e., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage,which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.

Radiofrequency ablation of recurrent cholangiocarcinoma after orthotopic liver transplantation—a case report

AIM: To report the use of radiofrequency ablation in the treatment of recurrenct cholangiocarcinoma in the transplanted liver.METHODS: A lady who underwent orthotopic liver transplantation (OLT) for intrahepatic cholangiocarcinoma recurrence of tumour 13 mo after tralsplantation inspite of adjuvant chemotherapy. Her recurrent tumour was treated with radiofrequency ablation.RESULTS: She survived for 18 mo following the recurrence of her tumour.CONCLUSION: Radiofrequency ablation can be used safely in the transplanted liver to treat recurrent tumour.

Establishment of an orthotopic pancreatic cancer mouse model: Cells suspended and injected in Matrigel

AIM: To establish an orthotopic mouse model of pancreatic cancer that mimics the pathological features of exocrine pancreatic adenocarcinoma.

Orthotopic liver transplantation as a rescue operation for recurrent hepatocellular carcinoma after partial hepatectomy

AIM: To compare post-orthotopic liver transplantation (OLT) survival between patients with recurrent hepatocellular carcinoma (HCC) after partial hepatectomy and those who received de novo OLT for HCC and to assess the risk factors associated with post-OLT mortality. METHODS: From July 2003 to August 2005, 77 consecutive HCC patients underwent OLT, including 15 patients with recurrent HCC after partial hepatectomy for tumor resection (the rescue OLT group) and 62 patients with de novo OLT for HCC (the de novo OLT group). Thirty-three demographic, clinical, histological, laboratory, intra-operative and post-operative variables were analyzed. Survival was calculated by the Kaplan- Meier method. Univariable and multivariable analyses were also performed. RESULTS: The median age of the patients was 49.0 years. The median follow-up was 20 mo. Three patients (20.0%) in the rescue OLT group and 15 patients (24.2%) in the de novo OLT group died during the follow-up period (P = 0.73). The 30-day mortality of OLT was 6.7% for the rescue OLT group vs 1.6% for the de novo OLT group (P = 0.27). Cox proportional hazards model showed that pre-OLT hyperbilirubinemia, the requirement of post-OLT transfusion, the size of the tumor, and family history of HCC were significantly associated with a higher hazard for mortality. CONCLUSION: There are no significant differences in survival/mortality rates between OLT as de novo therapy and OLT as a rescue therapy for patients with hcc. Pre-OLT hyperbilirubinemia, post-OLT requirement of transfusion, large tumor size and family history of HCC are associated with a poor survival outcome.

Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

Objective： To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation （OLT） in humans. Methods： Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four （TOF） stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain Tl/Tc ratio of 2%-10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results： Rocuronium requirement, which were （0.468±0.167）mg/（kg·h） during the paleohepatic phase, decreased significantly during the anhepatic phase to （0.303±0.134）mg/（kg·h） and returned to the initial values at the neohepatic period （（0.429±0.130） mg/（kg·h））; whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. Conclusions： This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT.

Orthotopic liver transplantation in treatment of 77patients with end-stage hepatic disease

Objective: To summarize the experience of human or-thotopic liver transplantation(OLTx) in treatment ofpatients with end-stage hepatic disease and their peri-operative management.Methods: A retrospective analysis was made on OLTxperformed in 77 patients from April 1993 to September2001 in our department included combined liver-kid-ney transplantation (6 patients) and living related livertransplantation (2). Among them, 76 were adults and1 was infant (67 males and 10 females) . The donors in-cluded 7S non-heart beating donors and 2 living re-lated donors. Veno-venous bypass was used only in 45cases during the operation. Immunosuppressive agentsconsisted of cyclosporine, cellcept, ALG corticosteroidsand FK506.Results: The one-year survival rates of grafts and re-cipients with benign hepatic disease were 75%. Therecipients this year are surviving with good function ofgrafts.Conclusion: Liver transplantation is the best therapeu-tic method for a large number of patients with end-stage hepatic disease in China.

Early prevention and treatment of biliary tract complications after orthotopic liver transplantation

OBJECTIVE: To investigate the prevention and treatment of biliary complications after orthotopic liver transplantation (OLT). METHODS: OLT was performed in 18 patients with end-stage liver disease, including 6 patients with primary liver cancer. Except 1 patient was infused only through the portal vein, others were infused through the portal vein and hepatic artery of the donor. The biliary tract was reconstructed using choledochocholedostomic anastomosis in 17 patients, and using Roux-en-Y choledochojejunostomic anastomosis in 1 patient. RESULTS: Four patients with biliary complication were found. In one patient, biliary leakage was found around the T-tube on day 14 postoperatively, and disappeared after re-opening of the tube. In one patient undergoing Roux-en-Y choledochojejunostomic anastomosis, biliary leakage was found on day 12 postoperatively and reoperation was performed. The T-tube was removed from the anastomosis after reoperation, and abdominal infection was controlled, but high fever recurred on day 49 postoperatively. The patient died on day 52 postoperatively. Autopsy revealed biliary leakage and biliary tract necrosis. In another patient, biliary leakage was found on day 3 after operation, and was treated by adequate drainage. Four months after operation, biliary sludge in the common tract was found and treated successfully with oral chemolysis. But biliary sludge or stone recur on one and half year after OLT. Spincterotomy and basket extraction were performed via endoscopic retrograde cholangiopancreatography, and the biliary sludge or stone was cleared out. In case 4, biliary drainage tube cholangiogram showed anastomotic stenosis one month after operation. Three months later, biliary sludge or stone was found beyond anastomotic stenosis. After oral chemolysis (ursodeoxycholic acid) and irrigation with heparinized saline solution via the biliary drainage tube, the biliary sludge disappeared. CONCLUSIONS: To reduce the incidence of biliary complications, adequate infusion of the hepatic artery, complete slushing of the biliary tract, and reduction of injury to the blood supply of the donor biliary tract are essential. Most biliary complications can be treated successfully by non-operative treatment or minimally invasive operation.