ObjectiveTo determine the nuclear factor kappa B (NFkB) activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NFkB activation with severity of biliary tract infection and clinical outcome.MethodsTwenty patients with ACST were divided into survivor group (14 cases) and nonsurvivor group (6 cases). Other 10 patients undergoing elective gastrectomy or inguinal hernia repair were selected as control group. Peripheral blood samples were taken 24 hours after operation, PBMC was separated and nuclear proteins were isolated from PBMC, and NFkB was determined with electrophoretic mobility shift assay (EMSA). The levels of TNFα, IL6 and IL10 in plasma were determined by using an enzymelinked immunoassay (ELISA). ResultsThe NFkB activity was 5.02±1.03, 2.98±0.51 and 1.02±0.34 respectively in three groups. It was increased in all patients with ACST, versus the control group (P＜0.05), and the patients of nonsurvivor group had higher levels of NFkB activation than those of survivor group (P＜0.05). The levels of TNFα and IL6 were (496.28±52.35) ng/L and (578.13±67.72) ng/L in nonsurvivor group; (284.47±39.41) ng/L and (318.67±34.92) ng/L in survivor group; (89.43±10.39) ng/L and (101.27±13.47) ng/L in control group. All patients with ACST had increased levels of TNFα and IL6, which were many fold greater than that of control group, and there was an evidence of significantly higher levels in nonsurvivor group than in survivor group (P＜0.05). All patients had also increased levels of IL10 as compared to control group (P＜0.05), but the IL10 concentrations in plasma were not significantly higher in nonsurvivors than that of in those survivors (Pgt;0.05). ConclusionNFkB activation in PBMCs in patients with ACST
ObjectiveTo elucidate the mechanism of multiple organs dysfunction (MOD) during acute obstructive cholangitis (AOC). MethodsThe reports about MOD and AOC in recent 10 years were collected and reviewed.ResultsApplicable animal models of AOC were established. During AOC, the decrease of Kupffer cells (KCs) phagocytic function and clearance function, hepatocyte mitochondrion damage, the effect of KCs on protein synthesis of hepatocytes and activation of KCs by endotoxin played an important role in the pathogenesis of MOD. ConclusionThe mechanism of pathogenesis of MOD during AOC is complicated and the changes of KCs functions is one of major factors.
Objective To explore the diagnostic and treating scheme of primary sclerotic cholangitis. Methods 24 cases of primary sclerotic cholangitis identified by radiological and pathological examinations from 1972 to 1998 were analysed retrospectively. According to Thompson, 1 case was classified as type Ⅰ, 5 cases were type Ⅱ, 10 cases were type Ⅲ and 8 cases were type Ⅳ. The operation were as follows,resection of gallbladder plus T tube drainage in 8 cases, plus Roux-en-Y anastomosis of bile duct and jejunum in 12 cases, plus U tube stent and drainage in 4 cases. Results The total mortality rate was 25% (6/24) in 2～18 years follow-up after operation. Conclusion Early diagnosis and operation may resolve the drainage of bile into the jejunum. When serious lesions and worse liver functions exist, liver transplantation should be considered.
To study the lipid peroxidation injury and the protecting effect of vitamin E emulsion on liver function following acute cholangitis. During the operation and 24 hours after operation, vitamin E emulsion or placebo emulsion was infused via mesenteric vein in rats suffering acute cholangitis. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and adenosine triphosphate (ATP) in the liver tissue and serum were measured at 48hrs after operation. Results: As compared with the placebo emulsion group, MDA and mGOT contents in the liver tissue and serum decreased significantly, but SOD activity increased dramatically in the VE emulsion group. ATP content in the infected lobe was much higher than those in the placebo emulsion group. Conclusion: Intravenous infusion of large dose of vitamin E emulsion may reduce the lipid peroxidation reaction in acute cholangitis, and have protecting effect.
A acute partial obstructive hepatocholangitis model by selective ligation and injection of E coli into left hepatic bile duct was successfully founded in rat. Using parameters including mortality, mitochondrial glutamic oxalacetic transaminase and ornithine carbamoytransferase activity, pathological observation and blood culture of bacteria, we evaluated the model. The authors emphasize that this models is superior to the wole-bile-duct-challenged cholangitis model, which is characterized by liver injury.
Objective To determine whether local delivery of c-myc shRNA could inhibit hyperplasia and lithogenic potentiality in a rat model of chronic proliferative cholangitis (CPC) via specific blockade of the c-myc expression. Methods The CPC animal model (CPC group) was established via retrograde insertion of a 5-0 nylon thread into the common bile duct through Vater’s papilla. Three kinds of c-myc shRNAs were then respectively injected in c-myc shRNA group, which were included shRNA-1, shRNA-2, and shRNA-3, respectively. Negative control group and sham operation group were established for comparison. Subsequently, histopathological changes of bile duct wall were observed by HE, Massion, and PAS/AB staining; c-myc protein was detected by immunohistochemistry method; 5-bromodeoxyuridine (BrdU) protein was tested by immumofluorescence method; c-myc, Mucin 3, and Procollagen Ⅰ mRNAs were detected by real time PCR; Ki-67 protein was determined by Western blot; Activity of β-glucuronidase was measured by modified Fisherman method. Results ①Compared with the CPC and negative control groups, biliary tract mucosa epithelium (HE staining), submucosal acid mucinous gland (mid-blue staining, PAS/AB staining), and degree of over-hyperplasia of collagen fiber in bile duct wall (blue staining, Massion staining) were weaker in the c-myc shRNA group. ②The expressions of c-myc mRNA, Mucin 3 mRNA, Procollagen Ⅰ mRNA, Ki-67 protein, and β-G activity in the c-myc shRNA group were lower than those of the CPC and negative control groups (Plt;0.05), but higher than those of the sham operation group (Plt;0.05). Conclusion c-myc shRNA treatment could effectively inhibit the hyperplastic behavior and lithogenic potential of CPC, which might help to prevent the biliary restenosis and stone recurrence.
Objective To observe the effect of gefitinib on expression of epidermal growth factor receptor (EGFR) in bile duct epithelial cells, and the feasibility of inhibiting hyperplasia of bile duct epithelial cells with gefitinib. Methods Sixty-one patients with hepatolithiasis having to be in hospital for surgery from the First People’s Hospital of Shuangliu county were selected, with 25-65 years old, average 46.92 years. The patients were randomly divided into therapy group and control group. There were 30 cases in therapy group, in which fine duct was placed on lesion bile duct during operation, and through whom gefitinib solution was perfused after operation. There were 31 cases in control group with only T tube drainage after operation. The bile duct sample was obtained respectively during the operation and 6 weeks and 12 weeks after operation. The histology and expression change of EGFR were observed by HE staining, immunohistochemistry and RT-PCR method respectively. Results There were no significant differences in pathohistology changes of bile duct and the EGFR protein and mRNA expression between therapy group and control group during operation. The hyperplasia of epithelium mucosae and submucosal gland in the therapy group were obviously decreased as compared with those in control group, the EGFR mRNA and protein expression in therapy group were weaker than those of control group （Plt;0.05） 6 weeks and 12 weeks after gefitinib treatment. Conclusion EGFR is overexpressed in the chronic proliferative cholangitis, and continuously local application of gefitinib after operation can specifically interrupt the activation and expression of EFGR and then effectively inhibit the hyperplasia of bile duct epithelial cells.
Objective To evaluate the relationship between endothelin (ET) in bile and peripheral blood with systemic and hepatobiliary injury in patients with acute cholangitis of severe type (ACST). Methods ET, ALT and total bilirubin in bile and peripheral veinous blood of 25 patients with acute cholangitis of severe type (ACST) were detected during operation, one week and two weeks after operation. Results The contents of ET, ALT and total bilirubin were significantly lower on 7-day and 14-day after operations as compared with that during operations (Ｐ＜0.05 and Ｐ＜0.01). The concentration of ET in peripheral veinous blood paralleled with that in bile. Conclusion This suggests that ET is tightly related with the pathologic process of ACST. So, in patients with ACST, the dynamic measurement of ET in peripheral veinous blood can be an index for judging the degree of pathological damage either to the hepatobiliary or systemic systems.
Objective To study the neural mechanism of hypotension or shock state in acute cholangitis in severe type (ACST) and its value of clinical application. Methods A technique of blocking abdominal splanchnic nervi via right adipose capsule of kidney was carried out on 28 patients by injecting 1% lidocaine before urgent operation. Results After blocking the relevant nervi, hypotension or shock state in 23 patients were improved significantly (Ｐ＜0.05). The death rate was lower (14.3%) after having performed biliary decompressions with laparotomy. Conclusion Patients′ hypotension or shock state at the early phase of ACST is the result of neural reflex in which the splanchnic nervi is its afferent pathway. Blocking the relevant nervi before urgent operation, the valuable opportunity of emergency treatment can be obtainded and the complication and death rate are reduced significantly.
Objective To investigate the alternatives of different endoscopic drainages for acute cholangitis of severe type (ACST) in elderly patients with chronic respiratory disease. Methods The clinical data of 74 cases of ACST in elderly patients with chronic respiratory disease undergoing 3 kinds of drainages, endoscopic retrograde double biliary stent drainage (D-ERBD), endoscopic retrograde single biliary stent drainage (S-ERBD), or endoscopic nasobiliary drainage (ENBD) in the First Hospital of Lanzhou University from October 2005 to October 2015 were collected to analyze prospectively. Results Compared with preoperative, the white blood cell (WBC), direct bilirubin (DBIL), temperature, and abdominal pain NRS evaluation in 48 h after operation in 3 groups all decreased, the difference was statistically significant (P＜0.05). Compared among 3 groups, there were no significant difference among the incidences of postoperative hyperamylasemia, pancreatitis and gastrointestinal hemorrhage (P＞0.05). The group of ENBD was more likely to develop pulmonary infection and achieve a secondary treatment than other 2 groups (P＜0.05). Totally 5 patients died in 3 groups, with a mortality of 6.76%, but the mortality rates were similar among the 3 groups (P＞0.05). The deaths were predominantly caused by multiple organ failure (MOF), 4 cases of which were caused by respiratory failure related to respiratory infection. Conclusion The alternative of endoscopic retrograde double biliary stent drainage (D-ERBD) can not only alleviate cholangitis rapidly, but it can reduce the incidence of aspiration pneumonia.