Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease in Japanese and Korean patients: the OPERA study

Background/Aims@#PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). @*Methods@#OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. @*Results@#In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. @*Conclusions@#In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)

Surgery vs. endoscopy competitive or complementary tools for management of post cholecystectomy problems, 10 years experience in major referral center

A prospective work to study and evaluate surgical and endoscopic techniques used in management of post cholecystectomy problems. In the period from Mars 2000 to October 2009, a random sample of 630 patients [366 females and 264 males] were collected from general surgery department, and gastro-intestinal endoscopy unit, Assuit University hospitals, and managed accordingly using surgery in 143 patients, and endoscopy in 482 patients [plus percutaneous techniques in 25 patients]. Endoscopy was very successful. as an initial treatment of 457 patients [73%], as being less invasive, low morbidity and mortality, competitive to surgery in treatment of missed stone [88%], mild to moderate biliary leakage [82%], and biliary stricture [74%].Its success increased by addition of percutaneous techniques in 4%, 2.8% and 8.3% for missed stone, leakage, and stricture respectively. But endoscopy was somewhat complementary to surgery in major leakage, and massive stricture, and surgery was resold to in 15%, and 17% of cases. Surgery remain as the treatment of choice in complex problems, and endoscopy play a complementary role in such cases of transaction, ligation, combined problems of stones, stricture, and leakage [< 40%], compared to 60% for surgery. Bilio-enteric anastomosis was the procedure of choice, done in 86 cases, with stent splintage in unhealthy, or small sized ducts. And stricture complication was encountered in 6% of cases treated by perculaneous rout in 4, and redo surgery in1 case. The learning curve seems influential in both endoscopy and surgery. The cumulative experience increase the success rate of endoscopy from initial 50% to 95% nowadays, also surgery improved with decreased morbidity and mortality as complications encountered was seen in initial experience and decreased with time. Endoscopy was competitive to surgery in simple problems and advised to be the initial treatment choice, but complementary in major leak, ligation, transection, and complex problems, where surgery plays the main role in treatment with its invasiveness, high morbidity and morbidity. Cumulative experience influence endoscopic and surgical treatment of such problems and it is mandatory with other facility and equipment for management of such challenging cases

Multidisciplinary approaches for management of post-cholecystectomy problems, [surgery, endoscopy, and percutaneous approaches]

This prospective study was undertaken to study and evaluate different techniques used in management of post cholecystectomy problems namely surgery, endoscopy, and percutaneous manipulation. In the period March 2005 to April 2006, a randomly selected sample of 210 patients with post cholecystectomy problems [122 females and 88 males] were collected from surgery department, and managed accordingly using surgery [40 attempts], endoscopy [207 attempts], or percutaneous approaches [34 attempts]. Endoscopic [ERCP] management was done as a therapeutic approach with 183 cases, or diagnostic cholangiogram only with 24 cases. Those cases treated included stone extraction in 81 cases, stricture or injuries [55 cases] treated by dilatation and stenting, and bile leakage [35 case] treated by sphincterotomy and/or stenting. Percutaneous approaches were done with 34 cases by diagnostic PTC prior surgery in 19 cases, percutaneous internal biliary stenting in 2 cases of stricture, and combined with endoscopy in 13 cases. Surgery was done in 40 cases either urgent in 10 cases with biliary peritonitis 4.8% of cases], or planned in 30 cases [14.3% of cases]. The techniques were peritoneal lavage in 7 cases prior proper approach, choledocholithotomy in 8 cases, undo ligation and T shaped tube drainage in 5 cases, repair of CBD laceration splinted by T tube in 3 cases, choledocho-ducodenostomy in 1 case, and choledocho-jejunostomy as Roux-en Y loop in 18 cases. Endoscopic approaches proved efficacy, safety, and cost effectiveness not only in diagnosis and evaluation, but was also considered the main stay of treatment, especially when combined with percutaneous approaches that help in avoiding failure in some problematic cases. However surgery remains the gold standard, effective in treatment not only that failed to be treated by the less invasive approaches, but in some cases that is mandatory to be explored as biliary peritonitis

use of plastic shield to protect anastomotic line internally in primary colonic anastomosis without preparation in traumatic colonic injury in Assuit

In this study, 12 patients were chosen, all of them complaining of traumatic colon injury of variable degrees [grade II-VI]. The ages of the patients were variable and the injury was caused by either penetrating injuries [five cases] or blunt injuries [seven cases]. The proposed technique for management is primary colon repair with the implantation of an intra-colonic bypass tube that was formed from condom catheter sleeve after good debridement or resection of the colon, if viability is questioned. It was the only procedure in four cases or combined with other surgical procedures [as splenectomy, or repair of a liver tear], in eight cases; it was a relatively safe and easy technique and the operative time was greatly reduced [90 minutes] as compared with other options for treatment as proximal colostomy of an intra-operative lavage [120 and 180 minutes, respectively]. Moreover, the mortality rate was 0% in this work and all cases were operated smoothly without any problem