Extent of Lung Involvement and Serum Cryptococcal Antigen Test in Non-Human Immunodeficiency Virus Adult Patients with Pulmonary Cryptococcosis / 中华医学杂志(英文版)

<p><b>Background</b>Serum cryptococcal antigen (CrAg) test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus (HIV) adult patients with pulmonary cryptococcosis and its clinical features.</p><p><b>Methods</b>One hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative (CrAg- group). It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio (OR) was used to measure correlation. Student's t- test was obtained to analyze continuous variable.</p><p><b>Results</b>No difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups (P > 0.05 in all). Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg- group (χ = 40.34, P < 0.001; OR = 39.87).</p><p><b>Conclusions</b>Among patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation.</p>

Routine use of a transanastomotic stent is unnecessary for hepatojejunostomy in liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The use of transanastomotic stents for Roux-en-Y hepatojejunostomy (RYHJ) in liver transplantation (LT) remains controversial. The aim of this retrospective study was to assess the role of transanastomotic stent for RYHJ in LT.</p><p><b>METHODS</b>RYHJ for biliary reconstruction in LT was performed in 52 patients. Twenty-five patients had bile duct reconstruction by RYHJ with transanastomotic stents (S group), while 27 patients underwent the same procedure without transanastomotic stents (non-S group). The two groups were compared in terms of post-LT biliary complications and survival.</p><p><b>RESULTS</b>The incidences of bile leakage, anastomotic stricture, non-anastomotic stricture, biliary sludge/lithiasis and biliary infection were 12% (3/25), 9.5% (2/21), 23.5% (4/17), 11.8% (2/17), and 24% (6/25), respectively in the S group, and 0, 0, 20.0% (5/25), 10.0% (2/20), and 16.7% (4/24), respectively in the non-S group. One and three year survival rates were 48.0% (12/25) and 34.0% (8/23), respectively, in the S group and 57.7% (15/26) and 38.9% (7/18), respectively, in the non-S group. There was no significant difference between the two groups in terms of the incidence of various biliary complications and survival (P > 0.05).</p><p><b>CONCLUSION</b>The routine use of transanastomotic stents is not necessary for RYHJ for biliary reconstruction in LT.</p>

Symptomatic osteonecrosis of the femoral head after adult orthotopic liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China.</p><p><b>METHODS</b>A retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported.</p><p><b>RESULTS</b>The incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up.</p><p><b>CONCLUSIONS</b>The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.</p>

Prognostic factors for late mortality after liver transplantation for benign end-stage liver disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are increasing numbers of patients who survive more than one year after liver transplantation. Many studies have focused on the early mortality of these patients. However, the factors affecting long-term survival are not fully understood. This study aims to evaluate prognostic factors predicting long-term survival and to explore measures for improving the survival outcomes of patients who underwent liver transplantation for benign end-stage liver diseases.</p><p><b>METHODS</b>The causes of late death after liver transplantation and potential prognostic factors were retrospectively analyzed for 221 consecutive patients who underwent liver transplantation from October 2003 to June 2008. Twenty-seven variables were assessed using the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step-down Cox proportional hazard regression analysis to identify the independent prognostic factors influencing the recipients' long-term survival.</p><p><b>RESULTS</b>Twenty-eight recipients died one year after liver transplantation. The major causes of late mortality were infectious complications, biliary complications, and Hepatitis B virus recurrence/reinfection. After Cox analysis, the five remaining co-variables were: age, ABO blood group, cold ischemia time, post-infection region, and biliary complications.</p><p><b>CONCLUSIONS</b>The major causes of late mortality were infection, biliary complications and Hepatitis B virus recurrence/reinfection. Five variables (Age, ABO blood group, cold ischemia time, infection, and biliary complications) had significant impacts on patient survival.</p>

Clinical analysis between "early" versus "late" liver retransplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To compare early and late orthotopic liver retransplantation (re-OLT) for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT.</p><p><b>METHODS</b>The clinical data of 36 re-OLTs from January 2004 to July 2009 were analyzed retrospectively, consisting of the first group with 17 cases of early re-OLT and the second group with 19 cases of late re-OLT. The average ages were (45 ± 13) years and (48 ± 10) years, and the time intervals were (49 ± 54) days and (514 ± 342) days in early re-OLT group and late re-OLT group, respectively.</p><p><b>RESULTS</b>Biliary tract complications were the main indications for early re-OLT and late re-OLT. Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration and perioperative mortality except the MELD score. Outcome was fatal for 8 patients in early re-OLT and 10 patients in late re-OLT. Three deaths were due to severe sepsis-related disease, 3 deaths due to multiple organ failure in early re-OLT and 4 deaths due to severe sepsis-related disease, 3 deaths due to recurrence of HCC in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 52.9% and 41.2%, respectively, for patients in early re-OLT, and 63.2% and 52.6%, respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups (P > 0.05).</p><p><b>CONCLUSIONS</b>The similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, experienced surgical procedures and effective perioperative anti-infection strategy contribute to the improvement of the overall survival rate of the patients after re-OLT.</p>

Efficient derivation of functional hepatocytes from mouse induced pluripotent stem cells by a combination of cytokines and sodium butyrate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatocyte transplantation has been proposed as an alternative to whole-organ transplantation to support many forms of hepatic insufficiency. Unfortunately, the lack of donor livers makes it difficult to obtain enough viable human hepatocytes for hepatocyte-based therapies. Therefore, it is urgent to find new ways to provide ample hepatocytes. Induced pluripotent stem (iPS) cells, a breakthrough in stem cell research, may terminate these hinders for cell transplantation. For the promise of iPS cells to be realized in liver diseases, it is necessary to determine if and how efficient they can be differentiated into functional hepatocytes.</p><p><b>METHODS</b>In this study, we directly compared the hepatic-differentiation capacity of mouse iPS cells and embryonic stem (ES) cells with three different induction approaches: conditions via embryonic body (EB) formation plus cytokines, conditions by combination of dimethyl sulfoxide and sodium butyrate and chemically defined, serum free monolayer conditions. Among these three induction conditions, more homogenous populations can be promoted under chemically defined, serum free conditions. The cells generated under these conditions exhibited hepatic functions in vitro, including glycogen storage, indocynine green (ICG) uptake and release as well as urea secretion. Although efficient hepatocytes differentiation from mouse iPS cells were observed, mouse iPS cells showed relatively lower hepatic induction efficiency compared with mouse ES cells.</p><p><b>RESULTS</b>Mouse iPS cells would be efficiently differentiated into functional hepatocytes in vitro, which may be helpful in facilitating the development of hepatocytes for transplantation and for research on drug discovery.</p><p><b>CONCLUSION</b>We demonstrate that mouse iPS cells retain full potential for fetal liver development and describe procedures that facilitates the efficient generation of highly differentiated human hepatocyte-like cells from iPS cells in vitro.</p>

The relationship between hepatocellular carcinoma recurrence and hepatitis B virus recurrence after liver transplantation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between hepatocellular carcinoma (HCC) recurrence and hepatitis B virus (HBV) recurrence.</p><p><b>METHODS</b>The clinical data of 340 patients underwent liver transplantation due to HBV related end-stage liver disease and received long-term follow up in our hospital from Jan 2004 to Dec 2008 were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list and nucleoside analogues combined low-dose HBIG therapy during and after transplantation. Patients were regularly followed up at the outpatient, monitoring the HBV recurrence and survival. Multivariate Cox regression analysis was used to evaluate the risk factors for hepatitis recurrence.</p><p><b>RESULTS</b>33 patients suffered from HBV recurrence post transplantation. The 1-, 3- and 5- year recurrence rates were 7.0%, 10% and 13% respectively. The median HBV recurrence time was 5 months (1-21 months). COX regression analysis revealed that risk factors for HBV recurrence were HCC (HR = 2.98; 95% CI 1.08-8.25; P < 0.05) and pre-transplantation HBV-DNA load over 5 log10 copies/ml (HR = 3.99; 95% CI 1.85-8.62; P < 0.01). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which were 27.9% and 8.7% (HR = 4.58;95% CI 1.88-11.12; P < 0.01) respectively. 12 patients suffered from both HCC and HBV recurrence. Spearman correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times (r = 0.583, P < 0.05).</p><p><b>CONCLUSIONS</b>Post transplantation HCC recurrence is a risk factor for HBV recurrence.</p>

Solid-phase synthesis and in vitro activity research of tumor-targeting cell-penetrating peptide / 南方医科大学学报

<p><b>OBJECTIVE</b>To synthesize a tumor-targeting cell-penetrating peptide (CPP) and evaluate its biological activity and cytotoxicity in vitro.</p><p><b>METHODS</b>With fluorenylmethyloxycarbonyl (Fmoc) as the protective group of α-amino acid, the tumor-targeting CPP were synthesized with stepwise amino acid extension using solid-phase synthesis method. 5-carboxytetramethylrhodamine was added for fluorescence labeling in the presence of the coupling agents HATU and DMF. The purity of the CPP was measured by high-performance liquid chromatography and its molecular weight measured by mass spectrometry. Fluorescence microscope was used to assess the cell-penetrating activity?of the CPP in hepatocellular carcinoma cell lines SMMC-7721 and normal hepatocellular cell lines LO2. The growth activity of CPP-treated SMMC-7721 cells was measured by MTT assay.</p><p><b>RESULTS</b>With a purity of 96.05% and a relative molecular mass of 3504.9, the synthesized CPP showed no translocation activity in normal hepatocellular cell lines LO2, but showed strong ability to translocate into SMMC-7721 cells without affecting the biological activity of the cells.</p><p><b>CONCLUSION</b>Using Fmoc solid-phase synthesis method, we have successfully synthesized the CPP with tumor-targeting activity.</p>

The clinical application of 320-slice Computed Tomography (CT) hepatic artery images in patients with liver transplantation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical significance of 320-slice CT hepatic artery images in patients with liver transplantation.</p><p><b>METHODS</b>A total of 58 patients underwent CT scanning by 320-slice scanner after liver transplantation. They were divided into 2 groups according to the concentration of contrast media as follows: Group A (27 cases, 350 mgI/ml iopromide), Group B (31 cases, 370 mgI/ml iopromide). Contrast medium was infused at 6 ml/s, with a total dose of 50 ml. Images were generated by dynamic volume scanning and were processed by 4D digital subtraction angiography (DSA) imaging software. The time-density curve (TDC) of the hepatic artery was delineated. The time to peak, peak contrast enhancement were recorded. The physiological parameters such as body weight and height were analyzed.</p><p><b>RESULTS</b>(1) There were no differences in clinical parameters such as age, sex, height, weight, or BMI between groups. The time to peak of hepatic artery of group A and B was (19.71+/-3.11) s and (20.06+/-3.67) s, and had no significant difference. The maximum peak enhancement of hepatic artery in groups B was higher than that group A (P < 0.05). (2) 4D DSA revealed hepatic artery pseudo-aneurysm (n = 2), and hepatic artery mild stenosis (n = 13), moderate stenosis (n = 5), severe stenosis (n = 9) and occlusion (n = 1), segmental moderate and severe stenosis (n = 4), and compensatory circulation with hepatic artery severe stenosis and occlusion (n = 6). hepatoportal arteriovenous fistulas (HPAVF, n = 12), donor-recipient hepatic artery mismatch (n = 3). Hepatic arterial branch are decreased and opened in 15 cases and 8 cases.</p><p><b>CONCLUSION</b>320-slice CT hepatic artery images is safe, noninvasive, and accurate technique to evaluate hepatic arterial complications after liver transplantation.</p>

Risk factors predicting late mortality after liver transplantation for benign end-stage liver disease / 中华外科杂志

<p><b>OBJECTIVES</b>To find out the risk factors predicting long-term survival, and to explore the measures for further improving the survival outcome of whom underwent liver transplantation (LT) for benign end-stage liver disease.</p><p><b>METHODS</b>The common causes of late death after LT and risk factors were retrospectively analyzed in 221 consecutive patients, who underwent LT from October 2003 to June 2007 and survived more than one year. Twenty-six potential risk factors were assessed by the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step down Cox proportional hazard regression analysis to screen the independent risk factors influencing the recipient's long-term survival.</p><p><b>RESULTS</b>There were 28 recipients died one year later after LT during the follow-up period. The major causes of late mortality were related to infectious complications 5.0% (11/221), biliary complications 3.6% (8/221) and HBV recurrence/reinfection 1.4% (3/221). After Cox proportional hazard regression analysis, 5 covariables finally retained in the formula were: age (RR = 2.325, P = 0.009), ABO blood group (RR = 2.206, P = 0.015), cold ischemia time (RR = 3.001, P = 0.000), post-infection region (RR = 1.665, P = 0.007) and biliary complications (RR = 2.655, P = 0.004).</p><p><b>CONCLUSION</b>Age (≥ 60 years), ABO blood group (incompatible), cold ischemia time (> 12 h), infectious complications (lung infection) and biliary complications (diffuse biliary stricture) significantly impact patient's survival time.</p>

Inhibition of rejection in murine islet xenografts by CTLA4Ig and CD40LIg gene transfer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Costimulatory signals play a vital role in T cell activation. Blockade of costimulatory pathway by CTLA4Ig or CD40LIg have enhanced graft survival in experimental transplantation models yet mechanisms remain undetermined. We investigated the effects of CTLA4Ig and CD40LIg gene transfer on islet xenografts rejection in rats.</p><p><b>METHODS</b>Human islets were infected with recombinant adenoviruses containing CTLA4Ig and CD40LIg genes and implanted beneath the kidney capsule of diabetic rats. Levels of blood sugar, morphological changes, and survival of grafts were recorded. Expressions of CTLA4Ig, CD40LIg and insulin were detected by immunohistochemical staining and cytokines levels were quantified by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Blood glucose levels in transplant rats decreased to normal level on the 2nd day post transplantation. The mean blood glucose in the control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig + CD40LIg cotransfected group increased on days 8, 24, 21, 68, post transplantation respectively. The grafts in control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig + CD40LIg cotransfected group survived for (8 ± 1), (29 ± 4), (27 ± 3), and (74 ± 10) days, respectively. Survival in CTLA4Ig + CD40LIg cotransfected group was significantly longer. Survivals of CTLA4Ig transfected group and CD40LIg transfected group were significantly longer than control group. In control animals, serum interleukin-2 and tumor necrosis factor α concentration significantly increased within seven days post transplantation. Haematoxylin eosin staining of grafts showed live islets in situ of transplant rats without inflammatory cell infiltration. Immunohistochemical staining confirmed the expression of insulin at islets in all experimental groups.</p><p><b>CONCLUSIONS</b>Transfer of CTLA4Ig and CD40LIg genes, especially the cotransfer of both, inhibits rejection of murine islet xenografts. Downregulated expressions of Th1 cells related cytokines might be related to the beneficial effects.</p>

Application of aging donors in rat liver transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the application of donor livers from aging rats, and discuss the age limit of the donor rats liver transplantation.</p><p><b>METHODS</b>Arterialized, two-cuff technique orthotopic liver transplantation was performed in male Wistar rats. All the recipient rats were 5 months old, and the ages of the donor rats were 5 (group A), 17 (group B), 20 (group C), 23 (group D), and 26 (group E) months (n=12). The postoperative function recovery and pathological changes of the liver grafts were evaluated by serum alanine aminotransferase (ALT) detection and histopathological examination, and the 3-month survival rate of the rats was observed.</p><p><b>RESULTS</b>Aging liver grafts in groups B, C, and D caused early elevation of ALT peak level and aggravation of liver tissue damage, and the liver graft recovery was delayed until postoperative day 7. Mild liver fibrosis, reduced hepatocytes and pigment deposition were observed in the liver grafts before the transplantation. Compared with the other groups, the rats in group E showed significantly increased ALT levels after the transplantation (P<0.05), with failure of liver graft function recovery and significantly reduced 3-month survival rate (0%, Plt;0.05).</p><p><b>CONCLUSION</b>The donor age of the rats is a crucial factor to affect the outcome of the liver grafts. Grafts obtained from rats younger than 23 months allow better functional recovery of the liver.</p>

Effects of sirolimus on the growth of transplanted hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice.</p><p><b>METHODS</b>HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus (FK506). The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected by immunohistology, microvessel density (MVD) was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay.</p><p><b>RESULTS</b>The tumor weight was (352+/-38) mg, (683+/-53) mg and (675+/-45) mg in SRL, FK506 and control group respectively. The tumor weight was significantly decreased in SRL group (P < 0.01), and there was no difference between FK506 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group (P < 0.05), and it was not significantly different between FK506 group and control group (P > 0.05). Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group (P < 0.01).</p><p><b>CONCLUSION</b>SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.</p>

Prospective evaluation of postoperative outcome after liver transplantation in hepatopulmonary syndrome patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Only a few reviews of small case series and individual case reports including a relatively small number of adult patients undergoing liver transplantation for hepatopulmonary syndrome (HPS) are available, and there has been no prospective evaluation of the long-term outcome of HPS patients after orthotopic liver transplantation (OLT). The aim of this study was to determine the frequency of HPS in OLT patients with chronic end-stage liver-disease, and the short-term and long-term postoperative outcome of HPS patients after OLT.</p><p><b>METHODS</b>This prospective study included 31 HPS and 30 control, non-HPS patients. The preoperative conditions were similar between the two groups. Twenty-six of 31 HPS patients and all of the non-HPS patients underwent OLT. Standardized methods, such as arterial blood gas at room air and 99m-technetium macroaggregated albumin ((99m)Tc MAA) lung and brain perfusion scanning were performed for the diagnosis of HPS. Patients were followed after OLT.</p><p><b>RESULTS</b>The incidence of HPS in OLT patients was 9.3% (26/279). Hypoxemia in HPS was obviously improved with a normalized shunt of (99m)Tc MAA in the lungs after OLT. The immediate postoperative survival rate (within 28 days after OLT) of HPS was 76.9% (20/26). The one year survival was 61.5% (16/26) and four-year survival was 57.7% (15/26); much higher than HPS patients without OLT (0). But high postoperative morbidity and mortality were observed in HPS patients whose death occurred within 3 months of OLT due to complications summarized in this study.</p><p><b>CONCLUSIONS</b>Liver transplantation was an effective treatment for HPS. But the postoperative mortality rate following OLT in HPS patients was still much higher than that of patients without HPS.</p>

Transplantation of human thioredoxin gene-modified hepatocytes for treatment of acute liver failure in rat model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mostly because of the limited number and proliferative ability of the transplanted hepatocytes, hepatocyte transplantation offers only temporary support to the hepatic function with rather poor functional replacement of the damaged liver parenchyma. This study aimed to observe the therapeutic effect of human thioredoxin (hTrx) gene-modified hepatocytes on experimental acute liver failure in rats.</p><p><b>METHODS</b>hTrx cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR) from human osteosarcoma 143 (TK-) cells to construct the recombinant retrovirus vector pLEGFP/hTrx, which was packaged into PA317 cells to collect the recombinant retrovirus containing hTrx gene. After titration and characterization, the recombinant retrovirus was applied to primary cultured rat hepatocyte for infection to generate hTrx gene-modified rat hepatocytes, whose viability and antioxidative capacity were examined by immunohistochemistry and MTT assay, respectively. In a Sprague-Dawley (SD) rat model of acute liver failure, the modified hepatocytes were injected into the spleen, and the hepatic function and survival rate of the recipient rats were evaluated at different time points after the transplantation.</p><p><b>RESULTS</b>NIH3T3 cells infected by the recombinant retrovirus were capable of expressing bioactive hTrx in the form of fusion proteins. Immunohistochemistry demonstrated normal function of the hTrx gene-modified hepatocytes, which possessed strong antioxidative capacity as shown by MTT assay. Transplantation of the modified hepatocytes in rats with acute liver failure resulted in significantly lowered serum alanine aminotransferase (ALT) and total bilirubin (TBIL) levels (P < 0.05). The hepatocytes exhibited long-term survival and efficient proliferation after transplantation. Fourteen days after the operation, the rat models receiving hTrx gene-modified hepatocytes had significantly higher survival rate than those without the transplantation.</p><p><b>CONCLUSION</b>hTrx gene-modified hepatocyte transplantation can effectively alleviate acute liver failure in rats.</p>

Diagnostic value of multislice spiral CT and MRI in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the manifestation and diagnostic value of multislice spiral CT (MSCT) and MRI imaging in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The clinical data of 161 consecutive HCC patients who underwent orthotopic liver transplantation were retrospectively reviewed. Twenty-nine HCC patients were classified by pTNM according to the "Pittsburgh criteria". MSCT and MRI findings of tumor recurrence after liver transplantation were evaluated retrospectively in 29 stage II-IVb HCC patients. The recurrence site and relapse interval between liver transplantation and recurrence were analyzed.</p><p><b>RESULTS</b>Lung tumor recurrence were found in 21 cases, presented as cotton-like lesions in a diameter of 2 - 3 cm, with a clear margin and homogeneous density. Pleural tumor recurrence was detected in 4 cases. Liver tumor recurrence were found in 9 cases, which can be divided into four subtypes: multinodular in 4 cases, diffuse lesion in 2 cases, huge mass in 2 cases, and uninodular in 1 case. Two cases showed tumor thrombus in the inferior vena cava and portal vein. Lymph node tumor recurrence was found in 9 cases, presented as multiple nodules at hepatic hilum, lesser peritoneal sac, posterior mediastinum, retroperitoneum, or around pancreatic head, and accompanied with merging and necrosis in one case. Bone tumor recurrence were found as osteolytic destruction in 4 cases, and accompanied with adjacent soft-tissue mass in 2 cases. The recurrence sites of the 29 cases were as following: lung (21 cases, 72.4%), liver (9 cases, 31.0%), lymph nodes (9 cases, 31.0%), bone (4 cases, 13.8%) and other sites (3 cases, 10.3%). Lung tumor recurrence was found in all the 10 stage IVb patients with tumor recurrence after liver transplantation, significantly more frequent than that in stage IVa patients (P = 0.023). After liver transplantation, all 25 patients with stage III approximately IVb HCC developed recurrence within one year, but in the 4 cases with stage II HCC at one year later (P = 0.009).</p><p><b>CONCLUSION</b>The results of our study show that in hepatocellular carcinoma patients after liver transplantation, the lung and pleura are the most frequent site of recurrence, followed by liver, lymph node and bone as the second and third sites. The Stage IVb hepatocellular carcinoma should be regarded as a contradiction for liver transplantation due to rapid recurrence. Tumor recurrence occurs later in stage II HCC than in stage III approximately IVb patients. MSCT and MRI are of significant importance in diagnosis and formulating operation plan in HCC patients with recurrence after liver transplantation.</p>

Effects of Rapamycin on angiogenesis and tumor progression in human hepatocellular carcinoma implantation mice / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effects of Rapamycin (RPM) on angiogenesis and tumor progression in human hepatocellular carcinoma (HCC) implantation mice.</p><p><b>METHODS</b>Tumor tissues of HCC were implanted into the liver of nude mice. Then, nude mice were treated with RPM and cyclosporine A (CsA). Real-time PCR was used to detect the mRNA expression of vascular endothelial growth factor (VEGF). Immunohistochemical stain and image analysis were used to detect the protein expression of VEGF and proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) was counted by endothelial cells immunostained by anti-CD34 antibody. The concentration of VEGF in the peripheral blood was detected by ELISA.</p><p><b>RESULTS</b>(1) The tumor weights were (372 +/- 35) mg, (769 +/- 39) mg and (751 +/- 42) mg in RPM, CsA and control group respectively. The tumor weight was significantly decreased in RPM group and no difference in CsA group compared with control group. (2) The expression of VEGF mRNA, VEGF and PCNA protein in tumor tissues and concentration of VEGF in the peripheral blood were remarkably down-regulated in RPM group compared with control group (P < 0.05) and were not remarkably different in CsA group from in control (P > 0.05).(3) Comparing with the control, the tumor MVD was remarkably decreased in RPM group (P < 0.05), and no difference in CsA group (P > 0.05).</p><p><b>CONCLUSION</b>RPM can inhibit angiogenesis and tumor progression of HCC by down-regulated the gene and protein expression of VEGF and inhibited the growth of tumor.</p>

Relationship of extrahepatic metastasis of primary hepatocellular carcinoma between circulative tumor cells in the blood of hepatoma patients / 中华外科杂志

<p><b>OBJECTIVE</b>To study the relationship between extrahepatic metastasis of primary hepatocellular carcinoma and circulative tumor cells in the blood of hepatoma patients.</p><p><b>METHODS</b>The immunomagnetic bead technique was employed to enrich and separate the hepatoma cells in the peripheral blood of preoperative and postoperative hepatoma patients. The relationship between postoperative extrahepatic metastasis and hepatoma cells in peripheral blood cancer cells were analyzed. The circulative tumor cells in the peripheral blood of hepatoma patients were enriched and separated by immunomagnetic bead technique. They were identified as hepatoma cells by AFP immunohistochemistry. Among 30 cases of hepatoma patients, the positive rate of hepatoma cells in the peripheral blood of preoperation and postoperation were 53.3% and 83.3% respectively. There was difference significantly in positive cases before operation and after operation (P<0.05).</p><p><b>CONCLUSIONS</b>Extrahepatic metastasis of primary hepatocellular carcinoma is obviously correlated to the positive tumor cells and the concentration in the peripheral blood of preoperative patients.</p>

Model for end-stage liver disease-sodium predicts prognosis in patients with chronic severe hepatitis B / 中华外科杂志

<p><b>OBJECTIVES</b>To study the practical use of the serum sodium incorporated model for end-stage liver disease (MELD-Na) on clinic and to assess its validity by the concordance-statistic in predicting the prognosis of the patients with chronic severe hepatitis B.</p><p><b>METHODS</b>Adult patients with a diagnosis of chronic severe hepatitis B between January 2007 and December 2007 in a single center were analyzed. The serum sodium, MELD, MELD-Na, and Delta MELD-Na (Delta MELD=MELD score at 14 days after medical treatment-MELD score at admission) scores of 426 patients with chronic severe hepatitis B were calculated. The 3-month mortality in patients was measured, and the validity of the models was determined by means of the concordance-statistic.</p><p><b>RESULTS</b>The area under the receiver-operating characteristic curves of Na, MELD and MELD-Na for the occurrence of death in 3 month were 0.718, 0.875 and 0.922. The 3-month mortality of the MELD-Na scores group <25, 25-30, >30-35, >35- <40 and > or = 40 were 2.0%, 5.4%, 35.4%, 53.8% and 86.9% respectively. There was a significant difference of 3-month mortality between the five groups (P<0.05). The 3-month mortality of Delta MELD-Na> 0 group was 65.9%, and the Delta MELD-Na < or = 0 group was 15.8%. There was a significant difference of 3-month mortality between the two groups (P<0.05).</p><p><b>CONCLUSIONS</b>MELD-Na score is a valid model to predict 3-month mortality in patients with chronic severe hepatitis B. Delta MELD-Na is clinically useful parameters for predicting the therapeutic effect of chronic severe hepatitis B.</p>

Risk factors predicting the prognosis of orthotopic liver transplantation in hepatopulmonary syndrome / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the effect of orthotopic liver transplantation (OLT) on hepatopulmonary syndrome (HPS) and investigate risk factors predicting the prognosis of OLT.</p><p><b>METHODS</b>Twenty-six cases of HPS and 30 cases of non-HPS were analyzed treated from April 2004 to January 2006. Survival rates after OLT were compared and risk factors predicting the prognosis of OLT in HPS were researched by univariant and COX analysis.</p><p><b>RESULTS</b>The 28 days survival rate in HPS after OLT was 76.9% (20/26), half a year survival rate and one year survival rate were both 61.5% (16/26). Whereas the one year survival rate of patients without HPS was 100%(P < 0.05). By univariant analysis, shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs, PaO2 and PaO2/FiO2 in room air before operation were relative to the prognosis of peri-operative period and half a year outcome after OLT in HPS (P < 0.05). Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs (OR = 1.182, P = 0.001), and mechanical ventilation time (OR = 1.003, P = 0.053) after OLT were independent risk factors predicting the prognosis of OLT in HPS by COX analysis. Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs > or = 28.4%, or PaO2 < or = 56 mm Hg (1 mm Hg = 0.133 kPa) before OLT predicted the poor outcome of OLT in HPS. The sensitivity were 83.3% and 85.0% respectively, and the specificity were 95.0% and 83.3% respectively.</p><p><b>CONCLUSIONS</b>OLT is an effective treatment for HPS.Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs before OLT and mechanical ventilation time after OLT were independent risk factors for the prognosis of OLT in HPS.</p>