Biopsy from the base and edge of gastric ulcer healing or complete healing may lead to detection of gastric cancer earlier: an 8 years endoscopic follow-up study.

BACKGROUND/AIMS: To assess the incidence of gastric cancer development in gastric benign ulcer patients and to evaluate the value of biopsy by taking specimens from both the base and edges of ulcers in contrast to the traditional biopsy which takes specimens from the edges of ulcers only. METHODOLOGY: An endoscopic followup of more than 1 year was conducted on 456 gastric ulcer patients in our hospital for a duration over 8 years. We collected clinical, endoscopic and pathological data and obtained at least 6 biopsies from both the edges and the bases of ulcers healing or complete healing, respectively and assessed H. pylori infection. RESULTS: Gastric cancers developed in 11 (2.41%) of 456 GU patients. In the experimental group, 3 cases that were diagnosed by histology showed adenocarcinoma with specimens taken from the ulcer bases and in the other 5 cases the specimens were taken from the ulcer edges. The detection rate of gastric cancer from gastric ulcer between experimental group and control group was statistically significant (4.57% vs. 1.07%, p<0.05). CONCLUSIONS: Gastric ulcer may develop into gastric cancer over a certain period of time in patients infected with H. pylori. Biopsies from ulcer bases and edges at the second or subsequent endoscopies may lead to defection of gastric cancer earlier and more effectively than the biopsies which take specimens from the edges of ulcers only.

Clinical significance of changes in the Th17/Treg ratio in autoimmune liver disease.

AIM: To investigate the levels, ratios, and clinical significance of T helper 17 (Th17) cells and regulatory T (Treg) cells in the peripheral blood of patients with autoimmune liver disease (AILD). METHODS: Forty-two AILD patients were included in the experimental group (group E), and 11 healthy subjects were recruited as the control group (group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes. Furthermore, a range of biochemical indices was measured simultaneously in the blood of group E patients. RESULTS: The percentage of Th17 cells and the Th17/Treg ratio were higher in group E than in group C (P < 0.01), whereas the percentage of Tregs was lower in the group E patients (P < 0.05). Patients in group E who were admitted with AILD in the active stage showed significantly higher Th17 percentages and Th17/Treg ratios than those measured in patients with AILD in remission (P < 0.05). In addition, among patients with AILD in the active stage, individuals that remained unhealed after hospitalization showed significantly higher baseline values of the Th17 percentage and the Th17/Treg ratio than those detected in patients who improved after treatment (P < 0.05). The results suggested that imbalance in the Th17/Treg ratio plays an important role in the pathogenesis and development of AILD. CONCLUSION: A high Th17/Treg ratio appears to predict poor short-term prognosis in patients with AILD in the active stage.

Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients.

OBJECTIVE: To evaluate the serum Prostaglandin E2 (PGE2) level in Acute-on-chronic liver failure (ACLF) and determine its predicative value for infection. METHODS: From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values to predict infection. RESULTS: Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB (P < 0.0001). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication (P < 0.0001). ROC analysis showed that serum PGE2 (area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/mL. CONCLUSIONS: Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.

Hybrid artificial liver support system for treatment of severe liver failure.

AIM: To construct a novel hybrid artificial liver support system (HALSS) and to evaluate its efficacy in patients with severe liver failure. METHODS: Hepatocytes were isolated from suckling pig by the modified Seglen's method. Isolated hepatocytes were cultured in a spinner flask for 24 h to form spheroids before use and the functions of spheroids were detected. HALSS consisted of a plasma separator, a hemo-adsorba and a bioreactor with hepatocytes spheroids in its extra-fiber space. HALSS was applied to 10 patients with severe liver failure. The general condition and the biochemical indexes of the patients were studied just before and after the treatment. RESULTS: The number of cells per liver was about 2-4 x 10(10) (mean, 3.1+/-1.5 x 10(10)). The cell viabilities were more than 95%. After 24 h of spheroid culture, most hepatocytes formed spheroids. The levels of albumin and urea in the medium of spheroid culture were higher than those in supernatant of petri dish culture (P = 0.0015 and 0.0001, respectively). The capacity of albumin production and urea synthesis remained stable for more than one wk and declined rapidly after two weeks in vitro. In HALSS group, the duration of HALSS treatment was 6-10 h each time. All patients tolerated the treatment well without any fatal adverse reaction. After HALSS treatment, the general condition, psychic state, encephalopathy and hepatic function of the patients were improved. The survival rate of the HALSS group, Plasmapheresis group and control group was 30% (3/10), 20% (2/10) and 0% (0/10), respectively (P = 0.024). Two weeks after treatment, Tbil and ALT decreased and the PTA level elevated in HALSS group and pasmapheresis group (P value: 0.015 vs 0.020, 0.009 vs 0.012 and 0.032 vs 0.041, respectively). But there was no significant change of blood albumin concentration before and after treatment in HALSS group and Plasmapheresis group. CONCLUSION: The HALSS established by us is effective in supporting liver function of patients with severe liver failure.

Characterization and enrichment of hepatic progenitor cells in adult rat liver.

AIM: To detect the markers of oval cells in adult rat liver and to enrich them for further analysis of characterization in vitro. METHODS: Rat model for hepatic oval cell proliferation was established with 2-acetylaminofluorene and two third partial hepatectomy (2-AAF/PH). Paraffin embedded rat liver sections from model (11 d after hepatectomy) and control groups were stained with HE and OV6, cytokeratin19 (CK19), albumin, alpha fetoprotein (AFP), connexin43, and c-kit antibodies by immunohistochemistry. Oval cell proliferation was measured with BrdU incorporation test. C-kit positive oval cells were enriched by using magnetic activated cell sorting (MACS). The sorted oval cells were cultured in a low density to observe colony formation and to examine their characterization in vitro by immunocytochemistry and RT-PCR. RESULTS: A 2-AAF/PH model was successfully established to activate the oval cell compartment in rat liver. BrdU incorporation test of oval cell was positive. The hepatic oval cells coexpressed oval cell specific marker OV6, hepatocyte-marker albumin and cholangiocyte-marker CK19. They also expressed AFP and connexin 43. C-kit, one hematopoietic stem cell receptor, was expressed in hepatic oval cells at high levels. By using c-kit antibody in conjunction with MACS, we developed a rapid oval cell isolation protocol. The sorted cells formed colony when cultured in vitro. Cells in the colony expressed albumin or CK19 or coexpressed both and BrdU incorporation test was positive. RT-PCR on colony showed expression of albumin and CK19 gene. CONCLUSION: Hepatic oval cells in the 2-AAF/PH model had the properties of hepatic stem/progenitor cells. Using MACS, we established a method to isolate oval cells. The sorted hepatic oval cells can form colony in vitro which expresses different combinations of phenotypic markers and genes from both hepatocytes and cholangiocyte lineage.

[Effects of growth factors and extracellular matrix on proliferation and differentiation of fetal liver progenitor cell in vitro].

OBJECTIVE: Liver development needs a number of growth factors and components of the extracellular matrix. The study is to explore how growth factors and extracellular matrix regulate proliferation and differentiation of fetal liver progenitor cell. METHODS: We demonstrate isolation of hepatic progenitor/stem cells from ED 14.5 SD rat liver, which contains a large number of hepatoblasts. Proliferation assay-3H thymidine incorporation was used to detect the effect of growth factors on proliferation of hepatic progenitor cell. Growth factor and extracellular matrix were added and stem cell clone formation was counted. Mark of bile duct and hepatocyte were detected with double-marker immunocytochemistry. RESULTS: Progenitor liver cells displayed clonogenic capacity, expressed markers of hepatocytes and bile duct cells and G-6-P. HGF, EGF can accelerate DNA synthesis and stem cell clone formation of hepatic progenitor cell. Extracellular matrix collagen I, collagen IV or laminin were essential for formation of stem cell clone. Single cell culture needed HGF, EGF, extracellular matrix and supernatant of mix cell (which contained fetal parenchymal cells, mesenchymal cells and hematopoietic cells) culture. CONCLUSION: Growth factors especially HGF and EGF play crucial role in proliferation and differentiation of liver progenitor cell. Some factors secreted from mesenchymal cell and hematopoietic cells may be involved.

Reduction of fibrosis in dibutyltin dichloride-induced chronic pancreatitis using rat umbilical mesenchymal stem cells from Wharton's jelly.

OBJECTIVES: The objective of this study was to investigate the effects of rat umbilical cord mesenchymal stem cells (UCMSCs) from Wharton's jelly on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and subsequent pancreatic fibrosis in rats. METHODS: A rat model of CP induced by DBTC was used. Male Sprague-Dawley rats were randomly divided into 4 groups: the control, DBTC, DBTC + UCMSCs, and control + UCMSC groups. Umbilical cord mesenchymal stem cells were administered intravenously on day 5 after the administration of DBTC. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression levels of inflammatory cytokines and chemokines in the pancreatic tissues of different groups were evaluated using quantitative real-time polymerase chain reaction. The activation of pancreatic stellate cells was estimated by immunochemistry and Western blot analysis of α-smooth muscle actin. RESULTS: Umbilical cord mesenchymal stem cells were detected in inflamed pancreatic tissues. Umbilical cord mesenchymal stem cell treatment improved the histological scores and alleviated the fibrosis of pancreas samples, The expression of cytokines in the DBTC + UCMSC group was significantly lower than that in the DBTC group. Also, pancreatic stellate cell activation was inhibited by UCMSC treatment. CONCLUSIONS: Xenogeneic transplantation of UCMSCs is a novel approach for the treatment of CP and subsequent fibrosis. Umbilical cord mesenchymal stem cells may be a promising therapeutic intervention for human CP in the future.