Endoscopic ultrasonography-guided drainage for patients with symptomatic obstruction and enlargement of the pancreatic duct

AIM: To evaluate the use of translumenal pancreatography with placement of endoscopic ultrasonography(EUS)-guided drainage of the pancreatic duct.METHODS: This study enrolled all consecutive patients between June 2002 and April 2014 who underwent EUSguided pancreatography and subsequent placement of a drain and had symptomatic retention of fluid in the pancreatic duct after one or more previous unsuccessful attempts at endoscopic retrograde cannulation of the pancreatic duct. In all,94 patients underwent 111 interventions with one of three different approaches:(1) EUS-endoscopic retrograde drainage with a rendezvous technique;(2) EUS-guided drainage of the pancreatic duct; and(3) EUS-guided,internal,antegrade drainage of the pancreatic duct.RESULTS: The mean duration of the interventions was 21 min(range,15-69 min). Mean patient age was 54 years(range,28-87 years); the M:F sex ratio was 60:34. The technical success rate was 100%,achieving puncture of the pancreatic duct including pancreatography in 94/94 patients. In patients requiring drainage,initial placement of a drain wassuccessful in 47/83 patients(56.6%). Of these,26 patients underwent transgastric/transbulbar positioning of a stent for retrograde drainage; plastic prostheses were used in 11 and metal stents in 12. A ring drain(antegrade internal drainage) was placed in three of these 26 patients because of anastomotic stenosis after a previous surgical intervention. The remaining 21 patients with successful drain placement had transpapillary drains using the rendezvous technique; the majority(n = 19) received plastic prostheses,and only two received metal stents(covered self-expanding metal stents). The median follow-up time in the 21 patients with transpapillary drainage was 28 mo(range,1-79 mo),while that of the 26 patients with successful transgastric/transduodenal drainage was 9.5 mo(range,1-82 mo). Clinical success,as indicated by reduced or absence of further pain after the EUS-guided intervention was achieved in 68/83 patients(81.9%),including several who improved without drainage,but with manipulation of the access route.CONCLUSION: EUS-guided drainage of the pancreatic duct is a safe,feasible alternative to endoscopic retrograde drainage when the papilla cannot be reached endoscopically or catheterized.

Depletion of CD25^+CD4^+T cells (Tregs) enhances the HBV-specific CD8^+ T cell response primed by DNA immunization

AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining. RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBV specific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n - 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells. CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunotherapeutic strategies to control HBV infection by inducing virus-specific cytotoxic T lymphocyte responses in chronically infected subjects.

Transjugular intrahepatic portosystemic shunt in liver transplant recipients

AIM： To evaluate the efficacy of transjugular intrahepatic portosystemic shunts （TIPSs） after liver transplantation （LT）. METHODS： Between November 1996 and December 2005, 10 patients with severe recurrent hepatitis C virus infection （n = 4）, ductopenic rejection （n = 5） or portal vein thrombosis （n = 1） were included in this analysis. Eleven TIPSs （one patient underwent two TIPS procedures） were placed for management of therapy-refractory ascites （n = 7）, hydrothorax （n = 2） or bleeding from colonic varices （n = 1）. The median time interval between LT and TIPS placement was 15 （4-158） mo. RESULTS： TIPS placement was successful in all patients. The mean portosystemic pressure gradient was reduced from 12.5 to 8.7 mmHg. Complete and partial remission could be achieved in 43% and 29% of patients with ascites. Both patients with hydrothorax did not respond to TIPS. No recurrent bleeding was seen in the patient with colonic varices. Nine of 10 patients died during the study period. Only one of two patients, who underwent retransplantation after the TIPS procedure, survived. The median survival period after TIPS placement was 3.3 （range 0.4-20） too. The majority of patients died from sepsis with multiorgan failure. CONCLUSION： Indications for TIPS and technical performance in LT patients correspond to those in non-transplanted patients. At least partial control of therapy-refractory ascites and variceal bleeding could be achieved in most patients. Nevertheless, survival rates were disappointing, most probably because of the advanced stages of liver disease at the time of TIPS placement and the high risk of sepsis as a consequence of immunosuppression.