Laura E. Matarese

Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges.

Objective:To assess the evolution of visceral transplantation in the milieu of surgical technical modifications, new immunosuppressive protocols, and other management strategies. Summary Background Data:With the clinical feasibility of intestinal and multivisceral transplantation in 1990, multifaceted innovative tactics were required to improve outcome and increase procedural practicality. Methods:Divided into 3 eras, 453 patients received 500 visceral transplants. The primary used immunosuppression was tacrolimus-steroid-only during Era I (5/90–5/94), adjunct induction with multiple drug therapy during Era II (1/95–6/01), and recipient pretreatment with tacrolimus monotherapy during Era III (7/01–11/08). During Era II/III, donor bone marrow was given (n = 79), intestine was ex vivo irradiated (n = 44), and Epstein-Barr-Virus (EBV)/cytomegalovirus (CMV) loads were monitored. Results:Actuarial patient survival was 85% at 1-year, 61% at 5-years, 42% at 10-years, and 35% at 15-years with respective graft survival of 80%, 50%, 33%, and 29%. With a 10% retransplantation rate, second/third graft survival was 69% at 1-year and 47% at 5-years. The best outcome was with intestine-liver allografts. Era III rabbit antithymocyte globulin or alemtuzumab pretreatment-based strategy was associated with significant (P < 0.0001) improvement in outcome with 1- and 5-year patient survival of 92% and 70%. Conclusion:Survival has greatly improved over time as management strategies evolved. The current results clearly justify elevating the procedure level to that of other abdominal organs with the privilege to permanently reside in a respected place in the surgical armamentarium. Meanwhile, innovative tactics are still required to conquer long-term hazards of chronic rejection of liver-free allografts and infection of multivisceral recipients.

Nutrition and Quality of Life Following Small Intestinal Transplantation

BACKGROUND:The outcome from small bowel transplantation (SBTx) has improved progressively over the past decade raising questions as to whether indications should be broadened from those currently followed based on “TPN (total parenteral nutrition) failure.”OBJECTIVE AND METHODS:To assess current outcome, we studied the effect of transplantation on nutritional autonomy, organ function, and quality of life (QoL) measured by a validated self-administered questionnaire containing 26 domains and 130 questions, for a minimum of 12 months in a cohort of 46 consecutively transplanted patients between June 2003 and July 2004. The majority of transplanted patients (76%) had intestinal failure because of extreme short bowel, the remainder having either chronic pseudo-obstruction or porto-mesenteric vein thrombosis (PMVT). All but the PMVT patients were dependent on home TPN (HPN) (median 2, range 0–25 yr) and had developed serious recurrent infective complications with (25%) or without central vein thrombosis and liver failure. Sixty-one percent received a liver in addition to a small intestine.RESULTS:Follow-up was for a mean of 21 (range 12–36) months. Five patients died, two with chronic graft rejection. All the remaining patients have graft survival with an average of 1.2 (range 0–5) episodes of acute rejection. All patients were weaned from TPN by a median of 18 days (range 1–117 days) and from tube feeding by day 69 (range 22–272 days). There was a significant improvement in overall assessment of QoL and in 13 of 26 of the specific domains examined.CONCLUSION:Our results confirm the claim that a new era has dawned for SBTx, such that, with continued progress, it can potentially become an alternative to HPN for the management of permanent intestinal failure, rather than a last-chance treatment for “TPN failure.”

Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks.

Background. Early experience with intestinal and multivisceral transplantation was plagued with high risk of rejection and posttransplant lymphoproliferative disorders (PTLD). To improve outcome, innovative management and immunosuppressant strategies were sequentially evolved. Methods. With initiation of the program in 1990, serial monitoring of Epstein-Barr-Viral load was introduced in 1994 with adoption of preemptive antiviral therapy. In 1995, cyclophosphamide or daclizumab induction was added to the tacrolimus-steroid-based multiple drug immunosuppressions. Such a conventional approach was replaced in 2001 with a novel immunosuppressive protocol consisting of recipient pretreatment with a single dose of rabbit antithymocyte globulin or alemtuzumab and posttransplant tacrolimus monotherapy. Results. With a total of 395 consecutive primary recipients, de novo malignancy(s) developed in 61 (15%) patients, with PTLD in 52 (13%), and nonlymphoid cancer (NLC) in 13 (3.2%). Malignancy was donor driven in 3 (4.6%) recipients and associated with graft-versus-host disease in 7 (11.4%). Children were at a significantly higher risk (P<0.001) of PTLD, and adults were more vulnerable (P=0.01) to NLC. With multivariate analyses, type of immunosuppression, recipient age, splenectomy, and treatment of rejection were significant PTLD risk factors. Conclusions. Despite pretransplant lymphoid depletion, preemptive antiviral therapy and minimization of posttransplant immunosuppression significantly reduced PTLD morbidity (P=0.0001) and mortality (P=0.001) with no impact on NLC. Patient survival was also improved (P=0.0001) with 91% at 1 year and 75% at 5 years.

Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial.

BACKGROUND Hospitalized, malnourished older adults have a high risk of readmission and mortality. OBJECTIVE Evaluation of a high-protein oral nutritional supplement (HP-HMB) containing beta-hydroxy-beta-methylbutyrate on postdischarge outcomes of nonelective readmission and mortality in malnourished, hospitalized older adults. DESIGN Multicenter, randomized, placebo-controlled, double-blind trial. SETTING Inpatient and posthospital discharge. PATIENTS Older (≥65 years), malnourished (Subjective Global Assessment [SGA] class B or C) adults hospitalized for congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. INTERVENTIONS Standard-of-care plus HP-HMB (n = 328) or a placebo supplement (n = 324), 2 servings/day. MEASUREMENTS Primary composite endpoint was 90-day postdischarge incidence of death or nonelective readmission. Other endpoints included 30- and 60-day postdischarge incidence of death or readmission, length of stay (LOS), SGA class, body weight, and activities of daily living (ADL). RESULTS The primary composite endpoint was similar between HP-HMB (26.8%) and placebo (31.1%). No between-group differences were observed for 90-day readmission rate, but 90-day mortality was significantly lower with HP-HMB relative to placebo (4.8% vs. 9.7%; relative risk 0.49, 95% confidence interval [CI], 0.27 to 0.90; p = 0.018). The number-needed-to-treat to prevent 1 death was 20.3 (95% CI: 10.9, 121.4). Compared with placebo, HP-HMB resulted in improved odds of better nutritional status (SGA class, OR, 2.04, 95% CI: 1.28, 3.25, p = 0.009) at day 90, and an increase in body weight at day 30 (p = 0.035). LOS and ADL were similar between treatments. LIMITATIONS Limited generalizability; patients represent a selected hospitalized population. CONCLUSIONS Although no effects were observed for the primary composite endpoint, compared with placebo HP-HMB decreased mortality and improved indices of nutritional status during the 90-day observation period. CLINICAL TRIAL REGISTRATION www.ClinicalTrials.govNCT01626742.

Short Bowel Syndrome: Clinical Guidelines for Nutrition Management

Intestinal failure is a condition in which inadequate digestion or absorption of fluid, electrolytes, and nutrients leads to dehydration or malnutrition. The most common cause of intestinal failure is short bowel syndrome (SBS) defined as <200 cm of functional small intestine. SBS may result from congenital abnormalities or from surgical resection. For the past 3 decades, patients with severe SBS were managed with home parenteral nutrition (HPN). With the emergence of new therapies, the clinician now has multiple options to treat these patients. These include intestinal rehabilitation regimens whereby patients are treated with specialized oral diets, soluble fiber, oral rehydration solutions (ORS), and trophic factors to enhance absorption. There are also a variety of surgical techniques available to preserve intestinal length. Small bowel and multivisceral transplantation has evolved during the last decade to be a valid therapeutic option for those patients who cannot be rehabilitated or who fail HPN. These are interrelated services designed to offer the patient the best therapeutic options to meet their individual needs. This article reviews the principles associated with the nutrition management of this very complex and diverse group of patients.

Nutrition and Fluid Optimization for Patients With Short Bowel Syndrome

Short bowel syndrome (SBS) is characterized by nutrient malabsorption and occurs following surgical resection, congenital defect, or disease of the bowel. The severity of SBS depends on the length and anatomy of the bowel resected and the health of the remaining tissue. During the 2 years following resection, the remnant bowel undergoes an adaptation process that increases its absorptive capacity. Oral diet and enteral nutrition (EN) enhance intestinal adaptation; although patients require parenteral nutrition (PN) and/or intravenous (IV) fluids in the immediate postresection period, diet and EN should be reintroduced as soon as possible. The SBS diet should include complex carbohydrates; simple sugars should be avoided. Optimal fat intake varies based on patient anatomy; patients with end-jejunostomies can tolerate a higher proportion of calories from dietary fat than patients with a remnant colon. Patients with SBS are prone to deficiencies in vitamins, minerals, and essential fatty acids; serum levels should be periodically monitored and supplements provided as needed. Prebiotic or probiotic therapy may be beneficial for patients with SBS, although further research is needed to determine optimal protocols. Patients with SBS, particularly those without a colon, are at high risk of dehydration; oral rehydration solutions sipped throughout the day can help maintain hydration. One of the primary goals of SBS therapy is to reduce or eliminate dependence on PN/IV; optimization of EN and hydration substantially increases the probability of successful PN/IV weaning.

Dietary and Medical Management of Short Bowel Syndrome In Adult Patients

Resection of the small bowel can lead to malabsorption of fluid, electrolytes, minerals, and other essential nutrients, resulting in malnutrition and dehydration. Individualized and tailored nutritional management for patients with short bowel syndrome (SBS) helps to optimize intestinal absorption, leading to nutritional independence such that a patient can resume as normal a lifestyle as possible. Parenteral nutrition (PN), used to supply the required nutrients following resection, is associated with a number of complications affecting patient morbidity and mortality. Attempts should be made to wean patients from PN to an oral diet as soon as possible. Dietary management is complex and needs to be individualized for each patient on the basis of his or her specific gastrointestinal anatomy, underlying disease, and lifestyle. In addition to nutrient intake, management of SBS also requires appropriate oral rehydration, vitamin and mineral supplementation, and pharmacotherapy. Several medications provide a useful adjunctive function to dietary intervention, including antidiarrheal agents, H2 antagonists and proton pump inhibitors, pancreatic enzymes, somatostatin analogs, antimicrobials, and trophic factors.

A.S.P.E.N. Position Paper Parenteral Nutrition Glutamine Supplementation

The parenteral multivitamin preparations that are commercially available in the United States (U.S.) meet the requirements for most patients who receive parenteral nutrition (PN). However, a separate parenteral vitamin D preparation (cholecalciferol or ergocalciferol) should be made available for treatment of patients with vitamin D deficiency unresponsive to oral vitamin D supplementation. Carnitine is commercially available and should be routinely added to neonatal PN formulations. Choline should also be routinely added to adult and pediatric PN formulations; however, a commercially available parenteral product needs to be developed. The parenteral multi–trace element (TE) preparations that are commercially available in the U.S. require significant modifications. Single-entity trace element products can be used to meet individual patient needs when the multiple-element products are inappropriate (see Summary/A.S.P.E.N. Recommendations section for details of these proposed modifications).

Therapeutic Efficacy of Intestinal and Multivisceral Transplantation: Survival and Nutrition Outcome

The clinical introduction of intestinal transplantation has added a new dimension and offered a valid therapeutic option for patients with irreversible intestinal failure. In the year 2000, the Center for Medicare & Medicaid Services (CMS) recognized intestinal, combined liver-intestinal, and multivisceral transplantation as the standard of care for patients with irreversible intestinal and parenteral nutrition (PN) failure. Accordingly, the indications for the procedure are currently limited to those who develop life-threatening PN complications. However, a recent improvement in survival similar to other solid organ transplant recipients should justify lifting the current restricted criteria, and the procedure should be considered before the development of PN failure. Equally important is the awareness of the recent evolution in nutrition management and outcome after transplantation. Early and progressive enteral feeding using a complex polymeric formula is safe and effective after successful transplantation. Full nutrition autonomy is universally achievable among most intestinal and multivisceral recipients, with enjoyment of unrestricted oral diet. Such a therapeutic benefit is commonly maintained among long-term survivors, with full rehabilitation and restoration of quality of life.

Short Bowel Syndrome in Adults The Need for an Interdisciplinary Approach and Coordinated Care

Short bowel syndrome (SBS) is a heterogeneous disorder with broad variation in disease severity arising from different types of intestinal resection. The spectrum of malabsorption ranges from intestinal insufficiency to intestinal failure. Individualized patient strategies involving modifications of dietary macro- and micronutrients, fluid, and pharmacologic options are required to maximize health and quality-of-life outcomes and to minimize complications and SBS-associated mortality. Intestinal rehabilitation (IR) is an established but evolving approach to improving patient outcomes by decreasing long-term dependency on parenteral support (PS) for nutrition and fluid requirements. Specialized IR programs employ team-based interdisciplinary approaches to coordinate individualized patient care and treatment management through centralized facilities. Such facilities are often specialized intestinal care centers (ICCs) established at large medical centers. A multifaceted IR program offers the comprehensive interrelated services required by patients with SBS-associated intestinal failure throughout the course of disease. Components of interdisciplinary IR programs should include medical services offering diagnostics and monitoring, pharmacologic management, and symptom and complication control; nutrition services, including dietary modifications and interventions; and supportive psychosocial and educational services. A model of care centered on the IR concept means that long-term patient management, including decisions on long-term PS, is overseen by a member of the specialized care center. Rational, seamless, and timely communication among the patients network of home-based and ICC healthcare providers is crucial to the success of any IR program. This paradigm shift to specialized IR programs will likely result in improvements across the patient care continuum.