William Stein

Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance

Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post‐transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single‐dose of Thymoglobulin (rATG) or Campath‐1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic‐guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.

Surgical and medical approach to patients requiring total small bowel resection: Managing the “no gut syndrome”

Background. Total resection of the jejunum and ileum, a rarely performed procedure, is indicated after mesenteric vascular events, trauma, or resection of abdominal neoplasms. We describe our recent experience with the operative and medical management of patients with “no gut syndrome.” Methods. We retrospectively reviewed 341 adult patients who were referred to our center between January 2013 and December 2016. Results. Thirteen patients with a mean age of 42.5 years (range 17 to 66 years) underwent near total enterectomy. Indications for small bowel resection were vascular event (n = 5), intraabdominal fibroid/desmoid (n = 4), and trauma (n = 4). Foregut secretions were managed with duodenocolostomy (n = 5), tube decompression (n = 5), and end duodenostomy (n = 2). Duodenal stump was stapled off in 4 cases. One patient underwent a spleen‐preserving duodenopancreatectomy combined with total enterectomy. Biliary secretions were managed with choledochocolostomy. All patients were discharged on full total parenteral nutrition infused over a 10‐ to 16‐hour period. Average total parenteral nutrition volume and caloric requirement were 2,800 mL/day (range 2,000 to 4,000) and 1,774 Kcal/day (range 1,443 to 2,290), respectively. Patients who underwent duodenocolonic anastomosis received smaller TPN volume (33.8 vs 49.8 mL/kg). Ten patients (77%) required supplemental intravenous fluid. There were no intraoperative or perioperative deaths. One patient was lost to follow‐up 2 months after operation. After a 20‐month median follow‐up (range 4 to 48 months), 9 patients are still alive (75%). All patients with duodenocolostomy remain alive (median follow‐up 36.4 months). Three patients underwent uneventful isolated small bowel transplantation, and another 4 are being evaluated or are already listed for visceral transplantation. Conclusion. In summary, resection of the entire small bowel is feasible and can be a lifesaving procedure for a select group of patients. Long‐term survival can be achieved in specialized centers. In addition, reestablishment of gastrointestinal tract continuity after total enterectomy appears to be the best option for postoperative fluid and electrolyte management.