彩色多普勒超声在原位肝移植的应用

目的:探讨彩色多普勒在肝移植术后并发症诊断中的应用。方法:应用彩色多普勒对28例肝移植患者术后有关并发症的超声特征进行分析。结果:28例肝移植患者中部分发生不同种类并发症,如:肝动脉血栓、门静脉血栓、急性排异、胆道并发症、肝周血肿、积液等有着不同特征的超声表现。结论:彩色多普勒超声对肝移植术后的并发症的诊断观察、指导临床治疗有着重要的意义。

肝动脉植管结扎治疗肝癌破裂出血10例

肝动脉植管结扎治疗肝癌破裂出血１０例平顶山市第一人民医院外科耿远兴，段红罡我院和第三军医大学西南医院肝胆外科中心，从１９９３年１月～１９９４年１０月，对１０例肝癌破裂出血的患者，采取肝动脉植管并结扎，以碘油－表阿霉素灌注栓塞，取得了一定的疗效，现报告...

核素肝血池显像鉴别肝良恶性占位性病变的临床价值

采用￣（９９ｍ）Ｔｃ－ＲＢＣ肝血池显像定性诊断肝脏占位性病变３４４例，对其临床价值进行了分析，结果表明，在鉴别肝脏良恶性占位性病变方面与同时检查的Ｂ超（３００例）、ＣＴ（２６１例）和ＭＲＩ（３８例）进行了比较。结果表明，在鉴别被￣（９９）ｍＴｃ－植酸钠肝显像发现的肝脏良恶性占位性病变方面肝血池显像的准确率高达９６．２％。作者提出，核素肝血池显像对肝脏占位性病变定性诊断有重要的临床价值，但认为许多学者推荐的￣（９９ｍ）Ｔｃ－ＲＢＣ肝血流相无助于进一步的鉴别诊断。此外还对核素肝血池显像１３例误诊原因进行了讨论。

Endoscopic management of biliary strictures after liver transplantation

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.

Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation:Effects on virus replication and recurrent hepatitis

AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.

Imaging in liver transplantation

The aim of this study was to illustrate the role of noninvasive imaging tools such as ultrasonography,multidetector row computed tomography,and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors,and in the detection of potential complications arising from liver transplantation.

Stromal cell derived factor-1 enhances bone marrow mononuclear cell migration in mice with acute liver failure

AIM： To evaluate the number of bone marrow mononuclear cells （BMMC） that are migrated to the liver following transplantation of murine BMMC into mice with acute liver injury.METHODS： BMMC were isolated from the bone marrow of mice in a lymphocyte separation medium and then labeled with PKH26. The labeled cells were subsequently infused into the caudal veins of BALB/c mice with hepatic injury induced by carbon tetrachloride and 2-acetylaminofluorene. Mice in experimental group were treated with stromal cell-derived factor-1 （SDF-1） which was injected intraperitoneally after trans- plantation of BMMC. Mice in control group were injected intraperitoneally with 0.1 mL of saline （0.9% NaCl） after transplantation of BMMC. After 2 wk, migration of the cells in experimental group was studied by fluorescence microscopy. The expression of proliferating cell nuclear antigen and albumin was quantified with manual methods in both groups. The serum transaminase levels at different time points were compared between the two groups.RESULTS： The labeled ＂cells＂ were found in the portal region and central veins of hepatic Iobules. The PKH26labeled cells appeared at an average frequency of 108 ± 8/high power field in the experiment group and 65 ± 8/high power field in the control group （P 〈 0.05）. The total number of positive cells was 29 ± 7/high power field in the experimental group and 13 ± 2/high power field in the control group. The albumin expression level was also higher in the experimental group than in the control group （29 ± 7 vs 13 ± 2, P 〈 0.05）. The total number of crossing points was 156 ± 5/high power field in the experimental group and 53 ± 5/high power field in the control group （P 〈 0.05）. The serum alanine aminotransferase levels in experimental and control groups were measured at different time points （120 ± 40 vs 118.50 ± 1.75, P 〉 0.05; 80.60 ± 6.50 vs 101.08 ± 5.67, P 〈 0.05; 50.74 ± 5.38 vs 80.47 ± 4.62, P 〈 0.05; 30.54 ± 2.70 vs 60.72 ± 4.37, P 〈 0.05; 30.77 ± 5.36 vs 40.47 ± 6.50, P 〈 0.05）. At the same time, the serum aspartate aminotransferase levels were measured in experimental and control groups at different time points （122.55 ± 1.46 vs 120.70 ± 4.22, P 〉 0.05; 54.26 ± 6.50 vs 98.70 ± 8.20, P 〈 0.05; 39.47 ± 5.39 vs 78.34 ± 4.50, P 〈 0.05; 28.94 ±2.70 vs 56.44 ± 4.28, P 〈 0.05; 30.77 ± 5.45 vs 42.50 ± 6.28, P 〈 0.05）.CONCLUSION： SDF-1 can promote the migration of BMMC to the liver of mice with acute liver failure.

Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation

AIM:To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation. METHODS:Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting.During a 2-h reperfusion period either saline (controls,n=8) or GSH (50 or 100 μmol/(h·kg),n=5 each) was continuously administered via the jugular vein. RESULTS:Two hours after starting reperfusion plasma ALT increased to 1 457±281 U/L (mean±SE) in controls but to only 908±187 U/L (P<0.05) in animals treated with 100 μmol GSH/(h·kg).No protection was conveyed by 50μmol GSH/(h·kg).Cytoprotection was confirmed by morphological findings on electron microscopy:GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of hepatocytes.Accordingly,postischemic bile flow increased 2-fold.Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules.Following infusion of 50μmol and 100 μmol GSH/(h·kg),plasma GSH increased to 65±7 mol/L and 97±18 mol/L,but to only 20±3 mol/L in untreated recipients. Furthermore,plasma glutathione disulfide (GSSG) increased to 7.5±1.0 mol/L in animals treated with 100μmol/(h·kg) GSH but infusion of 50μmol GSH/(h·kg) did not raise levels of untreated controls (1.8±0.5 mol/L vs 2.2±0.2 mol/L). CONCLUSION:Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver grafts.Therefore,GSH can be considered a candidate antioxidant for the Drevention of reperfusion injury after liver transplantation,in particular since it has a low toxicity in humans.

Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

AIM： To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation （OLT）. METHODS： Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system （MARS） as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality （30 d） after OLT. RESULTS： In the 50 patients, the statistically significant improvement in the biochemical parameters was observed （pre-treatment and post-treatment）. Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30d observation was： 28 kept alive and 6 patients died. CONCLUSION： Pre-operative SOFA, level of creatinine, INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly.

Glypican-3 expression and its relationship with recurrence of HCC after liver transplantation

AIM:To investigate the diagnostic value of glypican-3(GPC3) and its relationship with hepatocellular carcinoma(HCC) recurrence after liver transplantation.METHODS:HCC tissue samples(n = 31) obtained from patients who had undergone liver transplantation were analyzed.GPC3 mRNA and protein expression were analyzed by TaqMan real-time reverse transcription-polymerase chain reaction and immunohistochemistry.Correlation between the GPC3 expression and clinicopathological features was analyzed.The potential prognostic value of GPC3 was investigated by comparing recurrence-free survival between HCC patients with and without GPC3 expression.RESULTS:Using a cutoff value of 3.5 × 10-2,20 of 31 cancerous tissues had expression values of > 3.5 × 10-2,whereas 3 of 31 adjacent non-neoplastic parenchyma and 0 of 20 control liver tissues had expression values of > 3.5 × 10-2(P < 0.001).GPC3 protein was immunoexpressed in 68% of cancerous tissues,but not in adjacent non-neoplastic parenchyma and control liver tissues.Vascular invasion was significantly related to GPC3 expression(P < 0.05).Recurrence-free survival was significantly longer for patients without GPC3 mRNA overexpression(> 3.5 × 10-2) and those without vascular invasion(P < 0.05 for both).CONCLUSION:GPC3 expression may serve as a valuable diagnostic marker for HCC.GPC3 mRNA overexpression may be an adverse indicator for HCC patients after liver transplantation.

Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma:Report of an initial experience

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.

Endoscopic therapy of benign biliary strictures

Benign biliary strictures are being increasingly treated with endoscopic techniques. The benign nature of the stricture should be first confirmed in order to ensure appropriate therapy. Surgery has been the traditional treatment, but there is increasing desire for minimally invasive endoscopic therapy. At present, endoscopy has become the first line approach for the therapy of post- liver transplant anastomotic strictures and distal （Bismuth ! and I） post-operative strictures. Strictures related to chronic pancreatitis have proven more difficult to treat, and endoscopic therapy is reserved for patients who are not surgical candidates. The preferred endoscopic approach is aggressive treatment with gradual dilation of the stricture and insertion of multiple plastic stents. The use of uncovered self expandable metal stents should be discouraged due to poor long-term results. Treatment with covered metal stents or bioabsorbable stents warrants further evaluation. This area of therapeutic endoscopy provides an ongoing opportunity for fresh research and innovation.

Excessive portal flow causes graft failure in extremely small-for-size liver transplantation in pigs

AIM： To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely smallfor-size liver transplantation in pigs. METHODS： The right lateral lobe of pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were divided into two groups： graft without portocaval shunt （n = 11） and graft with portocaval shunt （n = 11）. Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated. RESULTS： In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h afcer transplantation. In the group with portocaval shunt, eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2±26.9 mL/min/100 g liver tissue and 270.5±72.9 ml./min/100 g liver tissue, respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2±27.8 ml./ min/100 g liver tissue and 42.7±32.3 mL/min/100 g liver tissue, respectively （P〈0.01）. As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed afl：er reperfusion, but these findings were not recognized in the group with portocaval shunt. CONCLUSION： These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.

Liver transplantation: Yesterday, today and tomorrow

With the advances in technical skills, management of postoperative complications and improvements in immunosuppressive drugs, liver transplantation is the standard treatment for many patients with chronic liver disease. Today, shortage of donor organs seems to be the major limiting factor for the application of liver transplantation. This review focuses on five issues that are challenging to clinical practice of liver transplantation and relevant to gastroenterologists. These include living donor liver transplantation, recurrent viral hepatitis, non-heart-beating donors, hepatocellular carcinoma, and ABO incompatible liver transplantation. Living donor and non-heart beating donor transplantations were initiated as a solution to increase the donor organ pool and it is expected that there will be an increase in the number of these donors. Recurrent hepatitis C and hepatocellular carcinoma following liver transplantation are among major problems and ongoing research in these diseases may lead to better outcomes in these recipients.

Analysis of risk factors for the interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy

AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced- stage hepatocellular carcinoma. METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups. RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine: 66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L, P < 0.01) were signifi cantly different. These were lower in the steroid-withdrawal group than in the steroid- maintenance group. CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection didnot increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased signifi cantly. This may have led to an increase in long-term survival rate.

Pediatric liver transplantation

In previous decades,pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality.Graft and patient survival have continued to improve as a result of improvements in medical,surgical and anesthetic management,organ availability,immunosuppression,and identification and treatment of postoperative complications.The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients.Newer immunosuppression regimens,including induction therapy,have had a significant impact on graft and patient survival.Future developments of pediatric liver transplantation will deal with long-term followup,with prevention of immunosuppression-related complications and promotion of as normal growth as possible.This review describes the state-of-the-art in pediatric liver transplantation.

New insights into the coagulopathy of liver disease and liver transplantation

The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrornbotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrornbopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haernostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.