Ex vivo liver resection and autotransplantation as alternative to allotransplantation for end-stage hepatic alveolar echinococcosis.

BACKGROUND & AIMS: Radical resection is the best treatment for patients with advanced hepatic alveolar echinococcosis (AE). Liver transplantation is considered for selected advanced cases; however, a shortage of organ donors and the risk of postoperative recurrence are major challenges. The aim of this study was to assess the clinical outcomes of ex vivo liver resection and autotransplantation for end-stage AE. METHODS: In this prospective study, 69 consecutive patients with end-stage hepatic AE were treated with ex vivo resection and liver autotransplantation between January 2010 and February 2017. The feasibility, safety and long-term clinical outcome of this technique were assessed. RESULTS: Ex vivo extended hepatectomy with autotransplantation was successful in all patients without intraoperative mortality. The median weight of the graft and AE lesion were 850 (370-1,600) g and 1,650 (375-5,000) g, respectively. The median duration of the operation and anhepatic phase were 15.9 (8-24) h and 360 (104-879) min, respectively. Six patients did not need any blood transfusion. Complications higher than IIIa according to Clavien classification were observed in 10 patients. The 30-day-mortality and overall mortality (>90 days) were 7.24% (5/69) and 11.5% (8/69), respectively. The mean hospital stay was 34.5 (12-128) days. Patients were followed-up systematically for a median of 22.5 months (14-89) without recurrence. CONCLUSION: This is the largest series assessing ex vivo liver resection and autotransplantation in end-stage hepatic AE. This technique could be an effective alternative to liver transplantation in patients with end-stage hepatic AE, with the advantage that it does not require an organ nor immunosuppressive agents. LAY SUMMARY: Ex vivo liver resection and autotransplantation were performed in a large series of patients with end-stage hepatic alveolar echinococcosis. The results showed that this surgical option was feasible, with acceptable postoperative mortality, but 100% disease-free survival in survivors. Careful patient selection, as well as precise assessment for size and quality of the remnant liver are key to successful surgery.

Supine lithotomy versus prone position in minimally invasive percutaneous nephrolithotomy for upper urinary tract calculi.

OBJECTIVE: To compare operative time, safety and effectiveness of minimally invasive percutaneous nephrolithotomy (MPCNL) in the supine lithotomy versus prone position. METHODS: Between January 2008 and December 2010, a total of 109 consecutive patients with upper urinary tract calculi were enrolled and randomly divided into group A (53 patients, supine lithotomy position) and group B (56 patients, prone position). The MPCNL procedures were performed under the guidance of real-time grayscale ultrasound system. The preoperative characteristics, intraoperative and postoperative parameters were analyzed and compared. RESULTS: All patients were successfully operated. There was no significant difference between the two groups in stone-free rate (group A 90.1 vs. group B 87.5%, p = 0.45), mean blood loss, number of access tracts, calyx puncture, mean hospital stay (group A 6 ± 1.1 vs. group B 6 ± 1.5 days, p = 0.38) and complications. But the operative time was significantly shortened in supine lithotomy position (group A 56 ± 15 vs. group B 86 ± 23 min, p < 0.001). CONCLUSIONS: The effectiveness and safety of the supine lithotomy position for MPCNL were similar to the prone position. However, the supine lithotomy position has an important advantage of reducing the operative time. The supine lithotomy position could be a good choice to perform MPCNL.

[Efficacy and safety of sorafenib in the prevention and treatment of hepatocellular carcinoma recurrences after liver transplantation].

OBJECTIVE: To evaluate the efficacy and safety of sorafenib in the prevention and treatment of hepatocellular carcinoma (HCC) relapse after liver transplantation. METHODS: A retrospective cohort study was performed to assess the efficacy and safety of sorafenib for HCC. Forty-four patients who underwent liver transplant for HCC beyond Milan criteria form July 2007 to May 2010 were included study group (sorafenib, n = 22) and control group (without sorafenib, n = 22). The primary endpoints of the study were disease-free survival (DFS), overall survival (OS). Secondary outcomes included the rates of acute rejection and graft survival. RESULTS: The clinical data of 44 patients were completely collected. There were significantly differences between sorafenib group and control group in 1-year DFS (81.8% (n = 18) vs 63.6% (n = 14), P < 0.05) and OS (90.9% (n = 20) vs 72.7% (n = 16), P < 0.05) respectively. The acute rejection rates in Sorafenib were 13.6% (3/22), compared with 18.2% (4/22) in control group (P = 0.524) and 1-year graft survival in Sorafenib group were 86.4% (19/22), compared with 72.7% (16/22) in control group (P = 0.086). The overall incidence of treatment-related adverse events was 68.1% (n = 15) in sorafenib group and 31.8% (n = 7) in the control group (P < 0.01). Adverse events that were reported for patients receiving sorafenib were predominantly grade 1 or 2 in severity including diarrhea (45.5%, n = 10), liver dysfunction (40.9%, n = 9), hand-foot skin reaction (31.8%, n = 7) and pains of head and four limbs (22.7%, n = 5). Two patients with grade 3 adverse events in study group were stopped continuing to use the sorafenib. Three patients with the dose of 400 mg twice daily and 17 patients with the dose reduction of sorafenib continued to the study endpoint. CONCLUSION: Patients with HCC undergoing liver transplantation could get the benefits of Sorafenib in reducing the incidence of tumor recurrence and extending disease-free and overall survival time.

[A study of the efficacy and safety of using hepatitis B surface antigen-positive donors for liver transplantation].

OBJECTIVE: To evaluate the outcomes of liver transplant recipients who received liver allografts from hepatitis B surface antigen (HBsAg)-positive donors. METHODS: The medical records of 23 male patients (median age, 42.5 years; range: 29-61) who received HBsAg-(+) liver allografts in our organ transplant center were retrospectively analyzed. All patients had confirmed diagnosis of end-stage liver disease (ESLD) secondary to hepatitis B virus (HBV) infection, including 13 HBsAg(+)/HBeAg(-)/HBcAb(+) cases and 10 HBsAg(+)/HBeAb(+)/HBcAb(+) cases. After transplantation, all patients were administered oral entecavir and intravenous anti-hepatitis B immunoglobulin (HBIG) (2000 IU/d during the first week), along with a steroid-free immune suppression regimen. HBV-related antigen and antibody and HBV DNA were detected on post-transplantation days 1, 7, 14, 21, and 30. The liver allografts were monitored by ultrasound imaging. After discharge, monthly follow-up recorded liver function, renal function, acute rejection, infections, vascular complications, biliary complications, HBV recurrence, cancer recurrence, and patient survival. RESULTS: Two of the recipients died from severe perioperative pneumonia. The remaining 21 recipients were followed-up for 10 to 38 months, and all 21 patients remained HBsAg(+). One recipient developed biliary ischemia and required a second liver transplantation at five months after the primary transplantation. Three recipients (all primary) died from tumor recurrence at 9, 14, and 18 months post-transplantation, respectively. All other recipients survived and had acceptably low HBV DNA copy levels. Color Doppler imaging showed good graft function and normal texture. The patient and graft survival rates were 78.3% (18/23) and 73.9% (17/23), respectively. The recurrence rate of HBV infection was 100% (23/23). In surviving patients, no liver function abnormality, graft loss, or death was found to be related to the recurrence of HBV infection. CONCLUSION: Liver transplantation using HBsAg(+) liver grafts was safe for patients with ESLD secondary to HBV infection.

[Clinical characteristics, diagnosis and treatment of digestive tract leakage after orthotopic liver transplantation].

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of digestive tract leakage after orthotopic liver transplantation (OLT). METHODS: Sixty-one recipients had digestive tract leakage in early stage after OLT among 1173 cases from January 2000 to December 2010. There were 55 male and 6 female patients, aging from 36 to 61 years, with a median of 45 years. Digestive tract leakage included bile leakage (46 cases), gastric leakage (5 cases), duodenal leakage (1 case), jejunal leakage (4 cases), ileal leakage (1 case) and colon transversum leakage (4 cases). Ten of recipients with gastrointestinal leakage had 1 to 3 times of abdominal surgery before OLT. Abdominal drainage was used in 28 cases with bile leakage, and additionally, endoscopic retrograde cholangiopancreatography, endoscopic nasobiliary drainage and stenting were performed for 8 of them, and surgical neoplasty for another 18 patients with bile leakage. Simple surgical neoplasty of perforation was performed for 13 patients with gastrointestinal leakage, and diverticulectomy and neoplasty for 1 case with duodenal leakage, and partial jejunostomy for one severe jejunal leakage. Nutritional support was administered for all of cases. RESULTS: The incidence rate of digestive tract leakage in early stage after OLT was 5.20% (61/1173). Intra-operative iatrogenic injury of gastrointestinal tract was occurred in 6 cases with gastrointestinal leakage. After treatment, 11 cases died of multiple organ failure resulted from severe infection, with mortality of 18.0% (11/61), including 4 cases with bile leakage, with the mortality of 8.6% (4/46), and 7 cases with gastrointestinal tract leakage, with the mortality of 46.6% (7/15). The remanent 50 cases through comprehensive treatment with a span of 1 to 3 months recovered and discharged healthily. No digestive tract leakage reoccurred in the follow-up of 6 to 84 months. CONCLUSIONS: The morbidity of digestive tract leakage in early stage after OLT is low, but its mortality is high, especially for gastrointestinal tract leakage. High dose corticosteroids therapy, history of abdominal operation and intra-operative iatrogenic injury may be high risk factor. Comprehensive treatment is crucial for improving prognosis.

[Diagnosis and treatment of primary hepatic angiosarcoma: a report of 7 cases with a literature review].

OBJECTIVE: To explore the clinical features, diagnosis, treatment and prognosis of primary hepatic angiosarcoma (PHA). METHODS: The clinical data of 7 PHA patients admitted to our hospital from December 2004 to December 2010 were retrospectively analyzed and the relevant literatures reviewed. RESULTS: Seven cases (5 males and 2 females) were diagnosed as PHA among 1027 (0.68%) patients with primary hepatic malignant tumors. Their mean age was 43.3 years old (range: 33 - 74). Four cases were of solitary lesion and three of multiple lesions. No specific clinical features were observed. The PHA lesions were easily misdiagnosed as benign or hepatic metastatic tumors. Contrast enhanced ultrasound (CEUS) showed the lesions with characteristic manifestations. And the positron emission tomography (PET-CT) could confirm the hepatic lesions as malignant tumors. The survival time for two untreated cases was 3 & 5 months, for two cases with liver transplantation (LTx) 3 & 8 months and for two cases treated with surgical resection & targeted therapy was 14 & 19 months respectively. One case was lost to follow-up at 6 months after hepatic resection. CONCLUSION: PHA is a clinically rare and highly malignant tumor with a rapid progression and a poor prognosis. Both CEUS and PET-CT are helpful for its differential and confirmative diagnosis. LTx should be considered as a contraindication for PHA. Hepatic resection has proven to be beneficial for PHA patients with solitary lesion. Surgical resection plus targeted medicines may improve their survival.

[Clinical efficacies of ABO-incompatible adult liver transplantation].

OBJECTIVE: To evaluate the efficacy and safety of ABO-incompatible liver transplantation in adult patients with fulminant hepatitis B. METHODS: The clinical data of 97 cases of adult liver transplantation for fulminant hepatitis B were retrospectively analyzed. The patients were grouped as ABO-identical (ABO-Id, n = 58), ABO-compatible (ABO-C, n = 19) and ABO-incompatible (ABO-In, n = 20). The rates of rejection, infection, biliary tract complications, vascular complications, and patient and graft survivals were compared among 3 groups. RESULTS: The 3-month, 1-year and 3-year graft survival rates were 87.9%/77.6%/65.3% in ABO-Id group, 84.2%/73.7%/66.5% in ABO-C group and 50.0%/35.0%/33.3% in ABO-In group respectively. There were significant differences between ABO-Id and ABO-In (P < 0.05). The incidences of rejection, infection, vascular complications and biliary tract complications were 8.6%, 20.7%, 3.4% and 6.9% in ABO-Id group, 35%, 60%, 20% and 30% in ABO-In group (P < 0.05) and 10.5%, 26.3%, 5.3% and 10.5% respectively in ABO-C group (P > 0.05). CONCLUSION: ABO-C liver transplantation is an important therapeutic option in adult patients with acute liver failure awaiting an emergency procedure. ABO-In transplantation can be used only for life-rescuing in patients with fulminant hepatitis since it is associated with a higher risk of rejection, infection, vascular thrombosis, ischemic bile duct complications and poor patient and graft survival.

[A 17-year study of bloodstream Escherichia coli infection after liver transplantation: resistance rate, risk factor and mortality].

OBJECTIVE: To explore the resistance rate, risk factors and mortality of Escherichia coli bloodstream infections (BSI) after liver transplantation. METHODS: From January 1993 to May 2010, a retrospective analysis of Escherichia coli in liver transplants were conducted. RESULTS: A total of 88 BSI occurred in 83/695 patients and Escherichia coli (n = 23) was most commonly found. Carbapenem and piperacillin-tazobactam were the most consistently active against Escherichia coli while the resistance rate to enterococcus for ciprofloxacin, gentamycin, ampicillin-clavulanic acid was over 60%. Univariate analysis identified the following variables as risk factors for Escherichia coli bacteremia: cholangioenterostomy (P < 0.001) and ductal complications (P < 0.001). Escherichia coli bloodstream infection could increase the mortality at 15 days after bloodstream infection. No significant difference in mortality occurred at 30 days and 1 year after enterococcal bacteremia. CONCLUSION: Escherichia coli after liver transplantation is resistant to agents but commonly active to carbapenem and piperacillin-tazobactam. The risk factor associated with Escherichia coli bloodstream infections are cholangioenterostomy and ductal complications. Escherichia coli bloodstream infection can increase the mortality at 15 days after bloodstream infection.

A tolerogenic semimature dendritic cells induce effector T-cell hyporesponsiveness by activation of antigen-specific CD4+CD25+ T regulatory cells that promotes skin allograft survival in mice.

Semimature dendritic cells (smDCs) can induce autoimmune tolerance by activation of host antigen-specific CD4(+)CD25(+) regulatory T (Treg) cells. We hypothesized that donor smDCs injected into recipients would induce effector T-cell hyporesponsiveness by activating CD4(+)CD25(+)Treg cells, and promote skin allograft survival. Myeloid smDCs were derived from C57BL/6J mice (donors) in vitro. BALB/c mice (recipients) were injected with smDCs to generate antigen-specific CD4(+)CD25(+)Treg cells in vivo. Allograft survival was prolonged when BALB/c recipients received either C57BL/6J smDCs prior to grafting or C57BL/6J smDC-derived CD4(+)CD25(+)Treg cells post-grafting, and skin flaps from these grafts showed the highest IL-10 production regardless of rapamycin treatments. Our findings confirm that smDCs constitute an independent subgroup of DCs that play a key role for inducing CD4(+)CD25(+)Treg cells to express high IL-10 levels, which induce hyporesponsiveness of effector T cells. Pre-treating recipients with donor smDCs may have potential for transplant tolerance induction.

[A 17-year study of bloodstream infection after liver transplantation: resistance rate, risk factor and mortality of enterococcal bloodstream infections].

OBJECTIVE: To explore the resistance rate, risk factor and mortality of enterococcal bloodstream infections (BSI) after liver transplantation. METHODS: From January 1993 to May 2010, a retrospective analysis of enterococcus in liver transplants were conducted. RESULTS: Fifty-eight BSI occurred in 53 of 695 patients. And a total of 30 enterococci were isolated. Linezolid and glycopeptide antibiotics were the most consistently active against the Enterococcus. The resistance rates to Enterococcus for erythromycin, clindamycin, imipenem, ciprofloxacin, gentamycin and ampicillin-clavulanic acid were all over 70%. The univariate analysis identified the following variables as the risk factors for enterococcal bacteremia: retransplantation (P=0.03) and biliary duct complications (P=0.02). Enterococcal bloodstream infection increased the mortality at Day 15. No significant difference was found in the mortality rate at Day 30 and 1 year after enterococcal bacteremia. CONCLUSION: Enterococcus after liver transplantation is resistant to multiple agents but active to linezolid and glycopeptide antibiotics. The risk factors commonly associated with enterococcal BSI are retransplantation and biliary duct complications. Enterococcal BSI can increase the mortality at Day 15 after liver transplantation.

[A survival analysis of patients with early-stage hepatocellular carcinoma fulfilling Milan criteria and undergoing hepatectomy].

OBJECTIVE: To summarize the experience of hepatectomy in patients with hepatocellular carcinoma fulfilling the Milan criteria and analyze the clinicopathological factors for patient survival and tumor recurrence. METHODS: The clinicopathological data of 104 patients with early-stage hepatocellular carcinoma fulfilling the Milan criteria and underwent hepatectomy at Peking Union Medical College Hospital between April 2003 and June 2009 were retrospectively analyzed. RESULTS: The median follow-up was 24 months. There were 54 recurrent cases. The 1-, 3- and 5-year cumulative disease-free survival rate were 63.0%, 32.6% and 22.4% respectively. Neither univariate analysis nor multivariate analysis indicated any factor significantly correlated with recurrence (P>0.05). The cumulative overall survival rate at 1, 3 and 5 years were 88.8%, 68.1% and 68.1% respectively. Univariate analysis revealed that blood transfusion (P=0.000), involvement of hepatic capsule (P=0.000) and postoperative transarterial chemotherapy (P=0.049) were significantly correlated with survival. And multivariate analysis indicated that blood transfusion (P=0.001) and involvement of hepatic capsule (P=0.000) were independent prognostic factors for survival. CONCLUSION: For the patients with early-stage hepatocellular carcinoma and compensated liver function fulfilling the Milan criteria, hepatectomy serves as the preferred treatment strategy.

[Application of steroids minimization immunosuppressive regimen in liver transplantation].

OBJECTIVE: To investigate the safety and feasibility of steroids minimization immunosuppressive regimen in liver transplantation. METHODS: One hundred and sixteen patients in line with the selecting criteria from January 2005 to June 2008 were divided into three groups according to the withdrawal of steroids: 40 cases in 3 months withdrawal group, 40 cases in 7 d withdrawal group and the other 36 cases in 24 h withdrawal group. The difference of recipients' survival, infection, acute rejection and steroids resistant acute rejection, wound healing, recurrence of HBV and hepatocellular cell (HCC), new on-set of diabetes, hyperlipidemia and hypertension between the three groups were compared. RESULTS: The difference of recipients' survival, acute rejection including steroids resistant acute rejection, recurrence of HBV and HCC, hyperlipidemia between the three groups were not significant (P > 0.05), the incidence of wound un-healing and hypertension in 24 h withdrawal group was significantly lower than that in the other 2 groups (P < 0.05), the incidence of infection and new on-set diabetes in 24 h withdrawal group and 7 d withdrawal group was significantly lower than that in 3 months withdrawal group (P < 0.05). CONCLUSION: Steroids minimization immunosuppressive strategy is safe and feasible in liver transplantation field, it will significantly reduce the steroids related complications without increasing the risk of rejection.

Ethanol ablation of hepatocellular carcinoma Up to 5.0 cm by using a multipronged injection needle with high-dose strategy.

PURPOSE: To investigate whether ethanol ablation by using a multipronged needle delivery system (multipronged ethanol ablation) could eradicate hepatocellular carcinoma (HCC) up to 5.0 cm in diameter with a single-session high-dose strategy. MATERIALS AND METHODS: The hospital ethics committee approved the prospective study, and each patient provided written informed consent. One hundred forty-one patients (125 men, 16 women; mean age, 53 years; range, 27-76 years) with 164 primary or recurrent HCC ranging from 1.3 to 5.0 cm in diameter (mean, 2.9 cm +/- 0.9) were treated with high-dose multipronged ethanol ablation. Patients were unsuitable for surgery, declined surgery and radiofrequency ablation, or had tumors located at unfavorable sites. Primary technique effectiveness (PTE) (complete ablation within two sessions), local tumor progression (LTP), and complications after the treatment were observed. Twenty risk factors of local effectiveness and complications were analyzed by means of univariate and multivariate analysis. RESULTS: Mean number of treatment sessions was 1.1. The mean volume of ethanol per tumor was 31 mL (range, 8-68 mL). PTE was achieved in 134 (95%) of 141 patients and was significantly associated with tumor pattern (capsulated vs noncapsulated, P = .018). After a mean follow-up period of 25 months, LTP was observed in 16 (12%) of 134 patients, and in nine (56%) patients, LTP occurred in tumors 3.1-5.0 cm in diameter. Alanine aminotransferase level (P = .023) was the independent risk factor for LTP. Three (2%) of 141 patients had major complications. CONCLUSION: Multipronged ethanol ablation with a high-dose strategy can be used to treat HCC up to 5.0 cm in diameter effectively and safely, often in a single session.

Pancreatic head carcinoma: clinical analysis of 189 cases.

BACKGROUND: Pancreatic cancer is a lethal disease with an increasing incidence. We retrospectively reviewed the clinical data on diagnosis and treatment of pancreatic head carcinoma, and analyzed the factors affecting prognosis of the disease. METHODS: The data of 189 patients with pancreatic head carcinoma treated from September 1, 1995 to August 31, 2005 were reviewed retrospectively. Ninety-four patients treated from September 1, 2000 to August 31, 2005 were followed up in April 2008. The median survival time (MST) and 1- to 5- year cumulative survival rates of the patients were calculated by the life table method and the Kaplan-Meier method. Cox regression was used to screen out significant risk factors. RESULTS: 96.9% of the patients were more than 40 years old, and the male/female ratio was 1.63. The detection rate of transabdominal ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), and serum tumor marker CA19-9 were 82.0%, 93.1%, 94.7% and 79.8%, respectively. The MST of patients with pancreatic head carcinoma was 360+/-60 days. The 1- to 5-year cumulative survival rates were 50.0%, 19.2%, 12.1%, 9.4% and 4.7%, respectively. However, patients with unresectable tumor survived for a shorter time (183+/-18 days). Their 1- to 2-year cumulative survival rates were 28.3% and 0.0%. Cox regression analysis showed that in pancreatic head carcinoma, the independent predictors for prognosis included tumor size, invasion of the superior mesenteric vessel, and radical resection. The MST of patients with pancreatic head carcinoma after radical resection was 510 days, significantly longer than that of patients undergoing non-specific treatment and palliative therapy (225 days). In addition, patients with slight jaundice survived for the longest time (533+/-51 days), compared with patients with severe jaundice (236+/-43 days) and without jaundice (392+/-109 days). CONCLUSIONS: Pancreatic head carcinoma is easily misdiagnosed, and is usually found to be advanced when tumor size is too large (above 4 cm in diameter) with local spread or metastatic disease. In these cases, surgical resection is usually not feasible, and its prognosis is usually very poor. Therefore, careful attention should be paid to these high-risk patients, especially, males, more than 40 years old, and presenting slight jaundice. Then imaging examination (US, CT and EUS) and serum tumor marker examination (CA19-9) are used to detect this disease earlier, and perform curative resection earlier. In this way, it is possible to cure the patients with a longer survival time and better quality of life.

[Two-dose steroid combined with two-dose daclizumab and tacrolimus regimen in liver transplant recipients].

OBJECTIVE: To investigate the efficiency and safety of two-dose steroid combined with two-dose daclizumab and tacrolimus (FK506) regimen in liver transplant recipients. METHODS: There were 74 patients who treated in the First Affiliated Hospital of Sun Yat-Sen University from September 2006 to March 2008. Expect for 7 patients who didn't measure up, 67 adult liver transplant recipients were randomized into two groups: conventional protocol group (n = 35) in which steroid was withdrawn in 3 months after operation, and two-dose steroid group (n = 32). Comparison of rejection, infection (bacteria, fungal and cytomegalovirus) and metabolic complications rates were studied between two groups. RESULTS: There were significant differences between two groups in the rate of early postoperation hyperglycemia, the average dosage of insulin consumption among hyperglycemia recipients as well as the rate of diabetes mellitus, hypertension and infection during the follow-up period (P < 0.05). The rate of hypertension in early postoperation period, hyperlipemia and rejection rate during the follow-up period were similar in two groups (P > 0.05). CONCLUSIONS: Two-dose steroid combined with two-dose daclizumab and tacrolimus would be a safe and efficient immunosuppression strategy without increase the acute rejection rate hazard, that could reduce post-transplant infection and other complications from side-effect of long-term usage of steroid.

Identification and expression analysis of novel LAGE-1 alleles with single nucleotide polymorphisms in cancer patients.

OBJECTIVE: The purpose of this study is to identify single nucleotide polymorphisms (SNPs) in the coding region alleles of the X chromosomal LAGE-1 gene, and investigate the frequency of such SNPs in both cancer patients and healthy controls, and thus determine the potential significance of these SNPs with respect to cancer vaccine therapy. METHODS: In this study, different mRNAs transcribed from the LAGE-1 gene were identified by RT-PCR from healthy donors and cancer patients samples. RESULTS: A new LAGE-1 allele containing three coding region SNPs (69A/G, 317C/G, and 397T/G) were identified. The allele is highly expressed as the LAGE-1a mRNA variant AY679089 in some of the cancer patients. The three SNPs altered the LAGE-1 gene sequence to that of NYESO-1 at both the nucleotide and amino acid level. CONCLUSION: There is a high frequency of the LAGE-1 gene allele with SNPs in coding regions in cancer patients. There was a clear relationship between the variant AY679089 and gastric cancer. The SNPs may lead to accelerated progress of poorly differentiated gastric cancer. The SNPs found in these alleles may also alter the immunological characteristics of LAGE-1a and should be taken into account if this antigen is adopted as a cancer vaccine component.

Graft-verse-host disease after liver transplantation: a report of two cases and review of literature.

Graft-verse-host disease (GVHD) is an uncommon fatal complication following liver transplantation (LTx). In mainland China, only six cases have been reported with a morbidity rate up to 1%-2%. Definitive diagnosis was achieved by molecular techniques (HLA typing or PCR-STR) in only two cases and the remaining cases were diagnosed based on typical clinical features with exclusion of other possible causes. All patients died of septic shock or multiple organ failure even after administration of increased corticosteroids and supportive therapy, and reduced immunosuppressive agents. In our center, two cases of GVHD were found among 128 (1.56%) patients. One case was diagnosed by detecting lymphocyte macrochimerism through DNA-STR. Both of them died even after aggressive treatment. In China, the incidence of GVHD is similar to that reported by foreign centers except for an extremely bad prognosis. Rapid diagnosis is crucial for a better prognosis. In China, only 37.5% of cases are diagnosed by molecular methods. We recommend detecting lymphocyte macrochimerism through DNA-STR to get a rapid diagnosis, and interleukin 2-receptor antibody (basiliximab or daclizumab) therapy seems to be a good choice for the disease.

Induction of specific cytolytic T lymphocytes using fusions of hepatocellular carcinoma (HCC) patient-derived dendritic cells and allogeneic HCC cell line.

BACKGROUND/AIMS: To assess the ability of hepatocellular carcinoma (HCC) patient-derived dendritic cells (DCs) fused with allogeneic HCC cell line to activate autologous lymphocytes to generate specific cytotoxic T lymphocytes (CTL) in vitro. METHODOLOGY: DCs were obtained by culturing adherent peripheral blood mononuclear cells (PBMC) from HCC patients in the presence of 100 microg/L recombinant human granulocyte/ macrophage- colony stimulating factor (rhGM-CSF) and 20 microg/L interleukin-4 (rhIL-4) for 1 week in vitro. DCs were fused with allogeneic HCC cell line HepG2 cells using polythyleneglycol (PEG), and the fusion cells were designated as DCs/HepG2. By labeling DCs and HepG2 with green and red fluoresceins, respectively, the cellular fusion was examined under fluorescence microscope. The ability of DCs/HepG2 to stimulate proliferation and differentiation of autologous lymphocytes was assessed by MTT method, and the specific killing efficacy of DCs/HepG2-induced CTL against HepG2 was evaluated. RESULTS: HCC patient-derived DCs expressed a certain level of CD1a, HLA-DR, CD54, CD80 and CD86. Fluorescence microscopic examination demonstrated that co-incubation of DCs and HepG2 in the presence of PEG lead to generation of DCs/HepG2. In the mixed lymphocyte reaction assay, DCs/HepG2 had a significantly greater ability to activate proliferation of autologous lymphocytes, as compared with DCs alone, DCs plus HepG2, HepG2 alone and medium control (P<0.05). The DCs/HepG2-activated CTL showed a potent specific killing efficacy against HepG2 cells. CONCLUSIONS: Fusions of HCC patient-derived DCs and allogeneic HCC cell line could efficiently stimulate autologous lymphocytes to generate tumor-specific CTL in vitro. It might represent a promising approach of immunotherapy for HCC.