Overview of Short Bowel Syndrome

Short bowel syndrome (SBS) is a rare disease in which patients are incapable of maintaining proper nutrition and hydration through normal oral intake alone because of a reduction in functional intestinal area. SBS often results from intestinal resection but can also be caused by other conditions that decrease absorptive capacity in the absence of resection, including radiation enteritis, chronic intestinal pseudo-obstruction, and congenital villus atrophy.1,2 The first recorded massive intestinal resection took place in 1880. Despite the loss of 205 cm of bowel, the patient survived and retained intestinal function.3 In 1935, Haymond published a report describing the outcomes of 257 patients with intestinal resections >200 cm, summarized from the literature.4 Haymond's reported overall survival rate of 66.5% was likely inflated as a result of the bias for reporting positive results. The study concluded that 33% of intestinal length could be removed without serious consequences, and removal of 50% of the intestinal length represented the “upper limit of safety.” The development of effective long-term parenteral nutrition (PN) in the late 1960s was an enormous advancement for patients with SBS and intestinal failure.5 This innovation, for the first time, permitted the extended survival of patients with massive intestinal resection. In the current millennium, we have entered a new era of enhanced bowel rehabilitation, pharmacologic therapies, and transplantation, which together have the potential to further increase survival and life quality for patients with SBS. This supplement brings together multiple articles from leaders in the field summarizing the recent research on the phenotype, etiology, and management of SBS in adult patients. The first article, by Palle B. Jeppesen,6 provides an overview of the demographics, physiology, and clinical features of SBS. This article presents available data on the incidence and prevalence of SBS, while emphasizing that the actual size of this population is unknown because of the lack of a large-scale patient database. The heterogeneity of patients with SBS, which stems from differences in demographic characteristics, disease etiology, and length and location of the resected bowel, is highlighted. In addition, the article discusses common complications of SBS and adverse events associated with PN support. Survival rates among patients with SBS and risk factors associated with increased mortality in this population are also presented. Because of the high degree of interpatient diversity in the SBS population, it is concluded that individualized patient management is critical to reducing adverse events and mortality and maximizing life quality. Although Haymond4 considered remnant bowel length the primary determinant of postresection outcome, it is now clear that the specific anatomy and health, and not just the length, of the remnant bowel play important roles in the degree of postresection intestinal function. The second article in this supplement, by Kelly A. Tappenden,7 reviews the physiology of the healthy intestinal tract and the impact of resection on digestion and absorption. The article discusses the 3 primary types of intestinal resections and the common ramifications of each. This article emphasizes the enhanced adaptive capacity of the ileum vs the jejunum and highlights the importance of the colon in fluid and energy recovery. The humoral and neural mediators of nutrient processing and their disruption by resection are also discussed. Finally, the pathophysiologic impacts of SBS outside of the gastrointestinal tract are described, including effects on the renal, hepatobiliary, and skeletal systems. Following bowel resection, the remaining intestinal tissue undergoes a process of adaptation, during which the absorptive capacity of the remnant tissue increases. The third supplement article, also by Dr Tappenden,8 presents an overview of the structural and functional changes that occur during intestinal adaptation and discusses the role of enteral nutrients, anatomic features, hormones, and growth factors in mediating adaptation. Much of the evidence that forms the basis of our understanding of intestinal adaptation is derived from animal studies; it is noted that the extent, mechanisms, and timing of intestinal adaptation in humans have yet to be fully determined. SBS management strategies that enhance endogenous adaptation, including enteral nutrition and trophic pharmacologic therapies, have the potential to improve enteral autonomy for affected patients. Since its development in the late 1960s, home PN has become a mainstay of treatment for patients with SBS who are unable to meet their nutrition needs through oral intake alone. The fourth supplement article, by Marion F. Winkler and Carol E. Smith,9 describes the impact of this important therapy on quality of life for both the patient and the caregiver. The authors discuss the physical effects of PN, including the risk of catheter-related complications, liver disease, and metabolic bone disease. In addition, the technological adjustments and psychosocial burdens experienced by this patient population are explored. Despite these challenges, many patients who are dependent on PN are able to adapt to the changes associated with this chronic therapy.10 Interventions that may enhance the resilience and quality of life of PN-dependent patients, such as patient education and participation in support groups, are also highlighted. Patients with SBS experience a variety of symptoms, often including severe diarrhea. In the fifth article in this supplement, Vanessa J. Kumpf11 describes the multifactorial etiology underlying SBS-associated diarrhea and the available pharmacologic management strategies. An algorithm for treatment selection and clinical recommendations for implementation of antidiarrheal therapies are provided. Because SBS-associated diarrhea may have several causes, multiple medications may be necessary for effective management. This article emphasizes a stepwise approach to the treatment of diarrhea, with slow escalation of dosages or incremental increases in the numbers of medications to maximize effectiveness while minimizing adverse events. Considering the debilitating nature of chronic severe diarrhea, successful symptom mitigation can have a substantial positive impact on the lives of affected patients. Rather than simply alleviate SBS-associated symptoms, newer trophic therapies aim to enhance the absorptive capacity of the remnant bowel by augmenting the endogenous process of intestinal adaptation. In the sixth article of this supplement, Dr Jeppesen12 outlines the available phase III trial data for the 2 currently approved pharmacologic therapies for patients with SBS who are dependent on PN: teduglutide, a glucagon-like peptide-2 analogue, and somatropin, a recombinant version of human growth hormone.1314–15 Both treatments are associated with a reduction in PN volume requirements, teduglutide as a stand-alone therapy and somatropin in conjunction with an optimized diet. These treatments are associated with distinct sets of risks and adverse event profiles. Furthermore, the 2 therapies differ in terms of treatment regimens and schedules; somatropin is restricted to a 4-week course, whereas teduglutide treatment is not limited in duration and has been administered to patients for up to 30 months in clinical trials.16 No head-to-head studies have been conducted to evaluate the comparative effectiveness or safety of these 2 therapies. Therefore, treatment decisions for patients with SBS must be individualized, taking into account the patient's medical history and disease phenotype in each case. In addition to pharmacologic therapy, surgery is another available approach to restore and enhance intestinal function for patients with SBS. In the seventh supplement article, Kishore R. Iyer17 highlights the role of the surgeon in preventing intestinal failure during the initial surgeries by maximizing bowel preservation and recruiting distal unused bowel, when feasible, once the patient has stabilized. The article also reviews the surgical options available to increase absorptive surface area, including longitudinal intestinal lengthening and tapering (Bianchi procedure), serial transverse enteroplasty, and segmental reversal of the small bowel. The choice of procedure depends on multiple factors, including remnant bowel anatomy, patient symptoms, and, in some cases, surgeon preference. Finally, the indications for intestinal transplantation and combined liver-intestine transplantation are discussed, and the available outcomes data for patients who have undergone these surgeries are presented. Particular emphasis is placed on the importance of early patient referral to transplantation to avoid the need for combined liver-intestine transplantation and to potentially improve outcomes. The final article, by Laura E. Matarese, Palle B. Jeppesen, and Stephen J. D. O'Keefe,18 underscores the importance of interdisciplinary cooperation among clinicians and other care providers in managing patients with a complex, multifaceted disease such as SBS. Interdisciplinary teams include a dietitian, gastroenterologist, surgeon, clinical pharmacist, clinical nurse specialist, and other specialists as needed. Intestinal rehabilitation programs are described, being composed of patient education initiatives, nutrition and fluid optimization, administration of pharmacologic treatments and adjunctive medications, supportive care, and surgery when necessary. These programs often reside in specialized intestinal rehabilitation centers (IRCs), major medical centers with experienced interdisciplinary teams that allow for centralized, integrated management of SBS. The authors strongly advocate referral of patients to IRCs when feasible, along with regular, effective communication between the IRC and local healthcare providers. Implementation of these strategies has the potential to yield sizable benefits for patients with SBS in terms of increased enteral autonomy, improved symptom management, enhanced life quality, and, one would hypothesize, improved survival rates. Patients with SBS, with or without intestinal failure, comprise a small population with complex pathophysiology and require expert care. The articles in this important supplemental issue of JPEN provide a broad overview of the current state of affairs. Many patients are not receiving management at a level consistent with the current state of the art. This is true, in part, because such a level of care is only reproducibly available at a limited number of intestinal rehabilitation or bowel transplant centers extant in the United States. Intestinal Rehabilitation Centers of Excellence, a concept with which our European colleagues have marched ahead, should be defined within our national context and developed in all major U.S. population centers. Beyond this, it remains common practice for community practitioners, who will likely never accumulate adequate experience, to manage these patients from within drivable distances of more qualified multidisciplinary programs. Clearly, the optimal flow of care management begs redistribution. Great progress has been made over the few decades since the work of Dudrick and colleagues5 brought us into the era of effective intravenous nutrition support. However, medical complications continue to adversely affect patients with SBS, due both to inadequate availability of countermeasures (for such target organs as the kidneys, liver, and bones) and those of an iatrogenic nature (such as PN-related infections, vascular access setbacks, and intestinal transplant failure). The optimal management of SBS-associated serious phenomena, such as bacterial overgrowth, and the optimal use of medical nutrition therapies, such as glutamine and short-chain fatty acid sources, remain incompletely defined. There is much potential to improve life expectancy for patients with SBS. Progress is needed in optimizing dietary management, psychosocial support, metabolic management, pharmacologic therapies, and surgery (both utilization of existing bowel and improved transplant outcomes). It is uplifting that, after a gap of 10 years, a second agent has been approved by the U.S. Food and Drug Administration to assist in improving intestinal absorption in patients with intestinal failure. With the addition of teduglutide, the pharmacologic part of our biologic toolkit has doubled. It has been noted that the adaptive response to bowel resection includes a symphony of known humoral and luminal factors, as well as several yet to be discovered. Animal studies have already shown that synergistic benefit is obtainable when multiple biologic agents working through complementary mechanisms are used in combination. There is a need to discover factors that have specific trophic effects on the bowel, such as increasing villus length, crypt depth, the number of microvilli per epithelial cell, and not only the number of epithelial cells but transport capacity per epithelial cell. With discoveries to come from the ever-accelerating field of human genomic research, there's no doubt pharmacotherapy will continue to be an exciting area of development. Additional funding is needed to improve existing tools and develop new ones. Existing Centers of Excellence in Intestinal Rehabilitation should be recognized and, in underserved regions of the United States, should be developed. Our patients should be supported more optimally through the use of existing therapies while we continue to find newer and better countermeasures for their benefit. The road ahead is becoming clearer. By aggregating the experience gained by caring for patients with SBS-associated intestinal failure in Centers of Excellence, optimal use of existing therapies can be achieved. This will lay the groundwork for the evaluation and incorporation of newer therapies in a safe, effective, and economically prudent manner. Medical writing assistance was provided by Heather Heerssen, PhD, of Complete Healthcare Communications, Inc (Chadds Ford, PA) under the direction of the author.