Nuclear factor-KB decoy oligodeoxynucleotides attenuates ischemia/reperfusion injury in rat liver graft

AIM: To evaluate the protective effect of NF-κB decoy oligodeoxynucleotides (ODNs) on ischemia/reperfusion (I/R) injury in rat liver graft. METHODS: Orthotopic syngeneic rat liver transplantation was performed with 3 h of cold preservation of liver graft in University of Wisconsin solution containing phosphorothioated double-stranded NF-κB decoy ODNs or scrambled ODNs. NF-κB decoy ODNs or scrambled ODNs were injected intravenously into donor and recipient rats 6 and 1 h before operation, respectively. Recipients were killed 0 to 16 h after liver graft reperfusion. NF-κB activity in the liver graft was analyzed by electrophoretic mobility shift assay (EMSA). Hepatic mRNA expression of TNF-α, IFN-γ and intercellular adhesion molecule-1 (ICAM-1) were determined by semiquantitative RT-PCR. Serum levels of TNF-α and IFN-γ were measured by enzyme-linked immunosorbent assays (ELISA). Serum level of alanine transaminase (ALT) was measured using a diagnostic kit. Liver graft myeloperoxidase (MPO) content was assessed. RESULTS: NF-κB activation in liver graft was induced in a time-dependent manner, and NF-κB remained activated for 16 h after graft reperfusion. NF-κB activation in liver graft was significant at 2 to 8 h and slightly decreased at 16 h after graft reperfusion. Administration of NF-κB decoy ODNs significantly suppressed NF-κB activation as well as mRNA expression of TNF-α, IFN-γ and ICAM-1 in the liver graft. The hepatic NF-κB DNA binding activity [presented as integral optical density (IOD) value] in the NF-κB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (2.16±0.78 vs 36.78 ±6.35 and 3.06±0.84 vs 47.62± 8.71 for IOD value after 4 and 8 h of reperfusion, respectively, P<0.001). The hepatic mRNA expression level of TNF-α, IFN-γ and ICAM-1 [presented as percent of p-actin mRNA (%)] in the NF-κB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (8.31 ±3.48 vs 46.37±10.65 and 7.46± 3.72 vs 74.82±12.25 for hepatic TNF-a mRNA, 5.58±2.16 vs 50.46±9.35 and 6.47±2.53 vs 69.72±13.41 for hepatic IFN-y mRNA, 6.79 ±2.83 vs 46.23±8.74 and 5.28±2.46 vs 67.44±10.12 for hepatic ICAM-1 mRNA expression after 4 and 8 h of reperfusion, respectively, P<0.001). Administration of NF-κB decoy ODNs almost completely abolished the increase of serum level of TNF-α and IFN-γ induced by hepatic ischemia/reperfusion, the serum level (pg/mL) of TNF-α and IFN-γ in the NF-kB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (42.7±13.6 vs 176.7±15.8 and 48.4±15.1 vs 216.8±17.6 for TNF-α level, 31.5±12.1 vs 102.1±14.5 and 40.2±13.5 vs 118.6±16.7 for IFN-γ level after 4 and 8 h of reperfusion, respectively, P<0.001). Liver graft neutrophil recruitment indicated by MPO content and hepatocellular injury indicated by serum ALT level were significantly reduced by NF-κB decoy ODNs, the hepatic MPO content (A655) and serum ALT level (IU/L) in the NF-κB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (0.17±0.07 vs 1.12 ±0.25 and 0.46±0.17 vs 1.46±0.32 for hepatic MPO content, 71.7±33.2 vs 286.1±49.6 and 84.3±39.7 vs 467.8±62.3 for ALT level after 4 and 8 h of reperfusion, respectively, P< 0.001). CONCLUSION: The data suggest that NF-κB decoy ODNs protects against I/R injury in liver graft by suppressing NF-κB activation and subsequent expression of proinflammatory mediators.

Outcomes of laparoscopic bile duct exploration for choledocholithiasis with small common bile duct

BACKGROUND Laparoscopic cholecystectomy(LC)combined with laparoscopic common bile duct(CBD)exploration(LCBDE)is one of the main treatments for choledocholithiasis with CBD diameter of larger than 10 mm.However,for patients with small CBD(CBD diameter≤8 mm),endoscopic sphincterotomy remains the preferred treatment at present,but it also has some drawbacks associated with a series of complications,such as pancreatitis,hemorrhage,cholangitis,and duodenal perforation.To date,few studies have been reported that support the feasibility and safety of LCBDE for choledocholithiasis with small CBD.AIM To investigate the feasibility and safety of LCBDE for choledocholithiasis with small CBD.METHODS A total of 257 patients without acute cholangitis who underwent LC+LCBDE for cholecystolithiasis from January 2013 to December 2018 in one institution were reviewed.The clinical data were retrospectively collected and analyzed.According to whether the diameter of CBD was larger than 8 mm,257 patients were divided into large CBD group(n=146)and small CBD group(n=111).Propensity score matching(1:1)was performed to adjust for clinical differences.The demographics,intraoperative data,short-term outcomes,and long-term follow-up outcomes for the patients were recorded and compared.RESULTS In total,257 patients who underwent successful LC+LCBDE were enrolled in the study,146 had large CBD and 111 had small CBD.The median follow-up period was 39(14-86)mo.For small CBD patients,the median CBD diameter was 0.6 cm(0.2-2.0 cm),the mean operating time was 107.2±28.3 min,and the postoperative bile leak rate,rate of residual CBD stones(CBDS),CBDS recurrence rate,and CBD stenosis rate were 5.41%(6/111),3.60%(4/111),1.80%(2/111),and 0%(0/111),respectively;the mean postoperative hospital stay was 7.4±3.6 d.For large CBD patients,the median common bile duct diameter was 1.0 cm(0.3-3.0 cm),the mean operating time was 115.7±32.0 min,and the postoperative bile leak rate,rate of residual CBDS,CBDS recurrence rate,and CBD stenosis rate were 5.41%(9/146),1.37%(2/146),6.85%(10/146),and 0%(0/146),respectively;the mean postoperative hospital stay was 7.7±2.7 d.After propensity score matching,184 patients remained,and all preoperative covariates except diameter of CBD stones were balanced.Postoperative bile leak occurred in 11 patients overall(5.98%),and no difference was found between the small CBD group(4.35%,4/92)and the large CBD group(7.61%,7/92).The incidence of CBDS recurrence did not differ significantly between the small CBD group(2.17%,2/92)and the large CBD group(6.52%,6/92).CONCLUSION LC+LCBDE is safe and feasible for choledocholithiasis patients with small CBD and did not increase the postoperative bile leak rate compared with choledocholithiasis patients with large CBD.

Adenocarcinoma arising from intrahepatic heterotopic pancreas: A case report and literature review

Heterotopic pancreas is mostly found incidentally, and adenocarcinoma arising from heterotopic pancreas appears to be extremely rare. A case of a 46-year-old woman with adenocarcinoma arising from intrahepatic heterotopic pancreas is reported herein. Computed tomography demonstrated a mass located in the bile duct of the left hepatic lobe. Pathological examination revealed a moderately differentiated adenocarcinoma arising from intrahepatic heterotopic pancreas with nerve infiltration. This may be the first reported case of adenocarcinoma arising from intrahepatic heterotopic pancreas.

Adenomas of the common bile duct in familial adenomatous polyposis

Familial adenomatous polyposis(FAP)or Gardner’s syndrome is often accompanied by adenomas of the stomach and duodenum.We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis.Only 8 cases of adenomas or adenocarcinoma ofthe common bile duct have been reported in the literature in patients with FAP or Gardner’s syndrome.Those patients presented with acute cholangitis or pancreatitis.Local excision or Whipple procedure may be the reasonable surgical option.