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1、682CHAPTER 29HISTORY Disease processes that lead to an inability to sustain oneself via normal enteral nutrition remain a therapeutic challenge to patients and physicians alike. The terms short gut syndrome and short bowel syndrome are often used to describe patients who are dependent on total paren
2、teral nutrition (TPN) because of sig- nificant loss of bowel length from a variety of causes, ranging from congenital malformations to traumatic injury to ischemic loss. Prior to the availability of TPN, short bowel syndrome was almost always fatal and, even with current therapies, extremely short r
3、emnant bowel length, less than 50 cm of jejunoileum in adults, is associated with a 43% 5-year mortality.1 However, the term short bowel syndrome excludes a subset of patients who may have a normal or near-normal intestinal length. Inflammatory illnesses such as Crohns disease, motility disorders su
4、ch as intes- tinal pseudo-obstruction, and diseases of the enterocytes such as intestinal epithelial dysplasia share the same devastating conse- quence of being unable to sustain oneself via enteral means. For this reason, the term intestinal failure represents a more accurate and fully inclusive te
5、rm when describing patients who are unable to tolerate enteral feedings. Dudrick and associates seminal work2 in the laboratory showing that puppies could achieve near-normal growth pat- terns while exclusively sustained via hyperalimentation was one of the most significant medical breakthroughs of
6、the century. Long-term TPN support increased patient survival, but also introduced a new set of problems, including potentially life- threatening infections and technical difficulties for maintaining access. As more patients were sustained for longer periods with TPN, cholestasis leading to liver fa
7、ilure was increasingly recog- nized as a potentially fatal complication.3 Until recently, transplantation or death appeared to be inevitable once a patient developed parenteral nutritionassociated liver disease (PNALD). However, a new investigational fish oilbased lipid formulation has been reported
8、 to prevent or even reverse TPN- induced cholestasis,4 and may be the next major breakthrough in this field. Early investigational models of intestinal transplantation were being developed long before the advent of TPN, but were doomed to failure because of a lack of understanding of immu- nology. T
9、he first investigation of intestinal transplantation as novel therapy for intestinal failure is attributed to Alexis Carrel in 1905.5 Approximately 50 years later, in 1959, after the earli- est successful kidney transplantation in Boston, Lillehei and colleagues6 at the University of Minnesota publi
10、shed their suc- cessful work transplanting intestines using a canine model. Starzl and associates7 in Pittsburgh reported transplanting a cluster of organs, including the intestine, in dogs in 1960. The first published human intestinal transplantation was performed by Lillehei and coworkers8 in 1967
11、, but the patient unfortu- nately did not survive because of thromboembolic complica- tions. Over the next few years, there were several other unsuccessful attempts in humans,9 primarily because of the inability to control rejection, resulting in overwhelming infec- tions. Given the apparent success
12、 of parenteral nutritional support, there was diminished enthusiasm for further clinical trials of intestinal transplantation. The advent of cyclosporine immunosuppression in the early 1980s coincided with descriptions of life-threatening com- plications associated with long-term TPN and led to rene
13、wed interest in the field of intestinal transplantation. Cohen and coworkers10 in Toronto reported the first isolated intestinal transplantation using cyclosporine in 1985 but, unfortunately, the 26-year-old recipient died on postoperative day 9. Over the next 5 years, several successful intestinal
14、transplants procedures were performed by Deltz,11 Starzl,12 and colleagues, resulting in patient survival ranging from 6 months to longer than 20 years.13 In the early 1990s, substantial improvements in control of rejec- tion accompanied the introduction of tacrolimus immunosup- pression, and indivi
15、dual centers were able to demonstrate consistent successes.14,15 In the United States, over 1800 intesti- nal transplantation were performed through the end of 2009, based on Organ Procurement and Transplantation Network (OPTN) data (http:/optn.transplant.hrsa.gov).history nontransplantation therapi
16、es for short bowel syndrome indications for intestinal transplantation evaluation anatomic considerations immunosuppression monitoring and rejection complications outcomes conclusionsSMALL BOWEL TRANSPLANTATIONAbigail E. Martin and Debra L. SudanSmall Bowel TranSplanTaTion Chapter 29 683SECTION IV TranSplanTaTion anD immUnoloGYNONTRANSPLANTATION THERAPIES FOR SHORT BOWEL SYNDROME Although nontransplantation surgery is not the focus o
