Objective To summarize the development of gallbladder carcinoma related resistance genes and targeted therapy. Methods Domestic and international publications online involving resistance genes and targeted therapy of gallbladder carcinoma in recent years were collected and reviewed. Results Recent studies had shown that chemotherapy drug resistance of gallbladder carcinoma mainly involved lysosome protein transmembrane β4 （LAPTM4B） gene， NF-E2-related factor 2 （Nrf2） gene， and cancer stem cells （CSCs）. While the latest gene targets of treatment for gallbladder carcinoma mainly involved LAPTM4B， Nemo-like kinase （NLK）， tissue factor way inhibitor-2 （TFPI-2）， vascular endothelial growth factor-D （VEGF-D）， epidermal growth factor receptor （EGFR）， and melanoma differentiation-associated gene 7/interleukin 24 （mda-7/IL-24） gene. Conclusion The research involving resistance genes and targeted therapy of gallbladder carcinoma has make a certain progress， which broaden the concept of traditional treatment of gallbladder carcinoma.
【Abstract】ObjectiveTo explore the relationship between anomalous pancreaticobiliary ductal junction(APBDJ) and gallbladder carcinoma. MethodsThe current related literatures were reviewed.ResultsAPBDJ was associated with gallbladder carcinoma development. A proposed mechanism was free reflux of pancreatic juice into the gallbladder and molecular alterations of gallbladder epithelial cells.ConclusionAPBDJ is a high risk factor for gallbladder carcinoma. Prophylactic cholecystectomy is recommended for patients with APBDJ.
Objective To study the expression of p16 and Rb gene in primary gallbladder carcinoma (PGC). MethodsFiftysix cases of PGC and 26 of gallbladder benign lesions were observed by immunohistochemistry (SP). ResultsThe positive rates of p16 and Rb protein in PGC were 46.3% and 71.4% respectively. No association of Rb expression with histological grade, histological type, invasion, metastasis and prognosis was found. There were close correlation between p16 expression and invasion, metastasis as well as prognosis. The inverse correlation of p16 and Rb gene expression in PGC was confirmed. Conclusion The loss of p16 or Rb gene protein is an important molecular event in PGC,and closely related to the block in the negative regulatory pathway of all cell cycle. The detection of p16 protein may be useful in evaluating biological characteristics and prognosis in PGC.
Objective To study the expressions of human ether-a-go-go related gene (HERG) in CD1 mice gallbladder and interstitial cells of Cajal (ICC) and explore their possible implications. Methods The expression of HERG protein in gallbladder tissue slices obtained from CD1 mice was detected by immunohistochemistry method. The expression of HERG mRNA in gallbladder tissue was detected by reverse transcription (RT)-PCR. The production of HERG protein was confirmed in the CD1 mice gallbladder by Western blot. Enzymatically dispersed cells were identified as ICC using the specific ICC marker c-kit antibody, and the double positive cells of c-kit and HERG were observed by laser passing confocal microscope. Results HERG was present in the CD1 mice gallbladder tissues for the yellow or buffy positive reaction. At the same time, the expression of mRNA specific for the HERG gene and production of HERG protein in the CD1 mice gallbladder tissues were indicated by RT-PCR and Western blot analysis, respectively. Using double labeling of anti-c-kit and anti-HERG, the double positive cells of c-kit and HERG were observed in the CD1 mice ICC by laser passing confocal microscope. Conclusion The study demonstrates that HERG is present in the CD1 mice gallbladder tissues and ICC, which is likely related to the pacemaking activity of ICC.
【Abstract】Objective To study the regulatory ability of peroxisome proliferatoractivated receptor γ(PPARγ) ligands to the inflammatory response in human gallbladder epithelial cells. Methods Culture human gallbladder epithelial cells and identify them . Cells were treated for 24 hours with 0, 10 μmol/L, 20 μmol/L, 30 μmol/L, 50 μmol/L and 100 μmol/L of Ciglitazone during cellular growth peak(5th day), then stimulated them with hIL-1β 5 ng/ml for 2 hours and measured the concentration of IL-6、IL-8 and TNF-α in cellular supernatants by riadioimmunoassay. Results Contrasted with control group, the expression of IL-6 and IL-8 in each test group were inhibited （P＜0.001）. The IL-6 and IL-8 levels were gradually dropped and corelated with the dosage of Cigtitazone, and manifested dosagedependence (P＜0.001). The concentration of TNF-α could not be measured. Conclusion PPARγ ligands can inhibit the expression of IL-6 and IL-8 in human gallbladder epithelial cells and probably produce effect in the regulation of cholecystic inflammation.
ObjectiveTo investigate and compare the advantages and disadvantages of laparoscopic cholecystolithotomy and laparoscopic cholecystectomy for patients with gallbladder stone. MethodsThe eligible patients with gallbladder stones hospitalized in our department between January 2007 and December 2011 were included, and all of them received either laparoscopic cholecystolithotomy (observation group) or laparoscopic cholecystectomy (control group) minimally-invasive surgery. The operation time, bleeding volume, enterokinesia recovery time, hospital stay, post-operative complication and follow-up results were compared between the two groups. ResultsA total of 148 patients were included, with 68 patients in the observation group and 80 patients in the control group. In this cohort, the success rate of surgery for the observation group and the control group was 100.0% (68/68) and 98.8% (79/80), respectively; and the success rate of complete stone removal was 100% for both two groups. B-ultrasound examination after 2 weeks of treatment showed that gallbladder wall was normal and gallbladder contraction rate was more than 30% for all patients with laparoscopic cholecystolithotomy. The operation time was (49.6±5.2) minutes for the observation group and (50.5±6.2) minutes for the control group, and bleeding volume was (9.5±1.4) mL for the observation group and (50.2±8.1) mL for the control group; the difference in bleeding volume was significant between the two groups (P<0.05). The difference in enterokinesia recovery time[(33.9±2.2) and (34.4±2.6) minutes] or hospital stay[(3.4±1.0) and (3.6±1.2) days] between the observation group and the control group was not significant (both P >0.05). The post-operative complications of bleeding, bile leakage and wound infection were not observed in both two groups, and all patients were followed up for 6 to 12 months with no stone recurrence; and only 2.7% of patients (1/37) had stone recurrence after 3-year follow-up. ConclusionBoth laparoscopic cholecystolithotomy and laparoscopic cholecystectomy procedures are safe and efficient. However, laparoscopic cholecystolithotomy not only reserves gallbladder but also has superiority of less bleeding volume.
Objective To study the relation between retinoblastoma (Rb) gene expression and biological characteristics of gallbladder carcinoma. Methods The expression of Rb protein in tissues of 41 cases of gallbladder carcinoma, 7 cases of gallbladder papilloma, and 14 cases of cholecystitis were detected by immunohistochemical staining of SP with polyclonal antibody. Results The rate of positive staining was 58.7% in gallbladder carcinoma which was significantly lower than that in cholecystitis and gallbladder papilloma (100%). There was a significant difference of Rb protein expression among the low, moderate and high differentiations and so was between S5, S4, S1, S2 and S3 stage (Ｐ＜0.05). Conclusion It sugests that expression or non-expression of Rb gene is closely related to the malignant potential invasiveness and prognosis of gallbladder carcinoma.
Objective To explore the operative managements of ectopic gallbladder during laparoscopic cholecystectomy (LC).Methods Twenty one cases of ectopic gallbladder undergone LC in this hospital were analyzed regarding the perioperative management, principle, and technique of operation.Results There were 2 cases of situs transversus, 1 case with gallbladder under right posterior lobe of liver, 2 under left lateral lobe of liver and 16 in the liver. All 21 cases of ectopic gallbladder had undergone LC successfully, and no complications were found during and after operation. Conclusion Anatomic ectopia of gallbladder tosses a challenging problem to laparoscopic surgeon. It is safe for surgeons to recognise actual anatomical anomaly and to manage them appropriately.
Objective To evaluate the sclerosing effects of several chemical sclerosants on the gallbadder mucosa in vivo. Methods Twentyeight rabbits were randomly divided into： Normal saline was used as contrast agent, and 95% ethanol, 5% tetracycline and compound phenol as sclerosants respectively. The cystic duct was ligated and cholecystostomy was performed for each animal. Sclerosants and contrast agent were injected into the gallbladder through a tube respectively and were kept in the gallbladder for 15 minutes. Animals were killed two weeks later; the gallbladder, bile duct and adjacent liver tissue were obtained for histopathological examination. Results With the naked eye, normal saline and 5% tetracycline made the cavity of the gallbladder unchanged; 95% ethanol made two gallbladder cavities occluded, two smaller, and three unchanged; and compound phenol made four gallbladder cavities occluded, and three smaller. In histopathological observations, 95% ethanol and compound phenol could make seven rabbits’ gallbladder mucosa completely destroyed (7/7); compared with normal saline (1/7), there was significant difference (P＜0.01). Five percent tetracycline had some effect of ablating the gallbladder mucosa (5/7), but compared with normal saline, there was no difference (Pgt;0.05). Conclusion Ninety-five percent ethanol can be clinically applied as an effective and safe sclerosant.
Objective To explore the value of expression of carcinomaassociated antigens in early diagnosis and predicting prognosis in gallbladder carcinoma. MethodsThe expression of carcinoembryonic antigen (CEA), carbohydrate antigen (CA50), Ecadherin (ECD) and proliferating cell nuclear antigen (PCNA) in 10 cases of cholecystitis, 10 cases of gallbladder adenomas and 50 cases of gallbladder carcinomas were detected by immunohistochemistry. ResultsThe positive rate of CEA, CA50 and PCNA labeling index (LI) in gallbladder carcinomas were significantly higher than that of gallbladder adenomas and cholecystitis (P＜0.05 and P＜0.01). The positive rate of ECD in gallbladder carcinomas, especially with metastasis, was significantly lower than that of gallbladder adenomas and cholecystitis (P＜0.05). The 3year survival rate was significantly lower in gallbladder carcinomas with CEA and PCNA overexpression (P＜0.05), the 3year survival rate in patients with ECD positive tumors was higher than that of those with negative tumors (P＜0.05). Conclusion The detection of CEA, CA50 and PCNA is useful for early diagnosis of malignant change in gallbladder adenomas and gallbladder carcinomas. Therefore, the CEA, PCNA and ECD might be useful for predicting prognosis of gallbladder carcinomas.