Treatment of intestinal failure: intestinal transplantation

Over the past 15 years, intestinal transplantation for the treatment of intestinal failure has changed from a desperate last-ditch effort into a standard therapy for which a good outcome is expected. Patient survival after intestinal transplantation has improved in the past 3-5 years and now approaches that of other solid organ allograft recipients, including liver and kidney, and is similar to survival on permanent therapy with parenteral nutrition. Complications are more common and often more severe during the initial hospitalization period after intestinal transplantation than they are after transplantation of other solid organs. After intestinal transplantation the initial hospitalization period is, therefore, usually 3-8 weeks long. Nearly all patients discharged after intestinal transplantation have good allograft function and have been weaned from total parenteral nutrition. The cost of the initial hospitalization period is one to two times the cost of permanent total parenteral nutrition for 1 year, which means that, in most cases, intestinal transplantation is cost-saving within 2 years of transplantation. In addition, quality of life after intestinal transplantation, as determined by standardized quality of life measures, is good or normal.     

Intestinal transplantation: a review

Parenteral nutrition is a life-saving therapy for patients with intestinal failure. Intestinal transplantation is now recognized as a treatment for patients who develop complications of parenteral nutrition and in whom attempts at intestinal rehabilitation have failed. Patients with parenteral nutrition related liver disease will require a liver graft typically part of a multivisceral transplant. Isolated intestinal transplants are more commonly performed in adults while multivisceral transplants are most commonly performed in infants. Isolated intestinal transplants have the best short-term outcome, with over 80?% survival at 1?year. Patients requiring multivisceral transplants have a high rate of attrition with a 1?year survival less than 70?%. Prognostic factors for a poor outcome include patient hospitalization at the time of transplant and donor age greater than 40?years while systemic sepsis and acute rejection are the major determinant of early postoperative outcome. For patients surviving the first year the outcome of transplantation of the liver in addition to intestine affords some survival advantage though long-term outcome does not yet match other abdominal organs. Outcomes for intestinal retransplantation are poor as a result of immunology and patient debility. Overall intestinal transplantation continues to develop and is a clear indication with cost and quality of life advantages in patients with intestinal failure that do not remain stable on parenteral nutrition.     

Reduced E-Cadherin Expression and Enlargement of Cancer Nuclei Strongly Correlate with Hematogenic Metastasis in Colorectal Adenocarcinoma

Background: Small-bowel transplantation is an alternative to home parenteral nutrition (HPN) in patients with gut failure. Our aim was to report the indication, diagnosis, morbidity, mortality, and intestinal adaptation in the total cohort of Danish patients receiving HPN at any time during the 5 years between 1 January 1991 and 31 December 1995. The data were analysed against the option of transplantation. Results: HPN was given to 129 patients; 59 (46%) had inflammatory bowel disease (15% died), 26 (20%) had cured cancers (42% died), and 44 (34%) had other diseases (dysmotility, surgical complications, infarcts, and so forth; 27% died). Of these, 60% were new in the HPN program, but only 19% received HPN all 5 years; 31% had terminated HPN, 19% permanently, and 25% died. Only four deaths were HPN-related. In December 1995, 73 patients were receiving HPN in Denmark, for a prevalence of 13.9 per million, which is the highest in Europe but 10-fold lower than in the United States. Conclusions: Gut failure was the only indication for HPN in Denmark. Weight loss without gut failure, such as disseminated cancer and acquired immunodeficiency syndrome, was not an indication for HPN. Survival after small-bowel transplantation should be assessed against a sizeable mortality among candidates receiving HPN, and this depends on diagnosis and age. In an HPN population comparable with the Danish, a quarter is likely to die within a period of 5 years, a quarter will terminate HPN, and the others survive with HPN. Small-bowel transplantation can be a lifesaving procedure in the small fraction of foreseeable HPN-related deaths, mainly caused by liver failure. Transplantation will not improve survival in most adult HPN patients, and only an improved quality of life after transplantation justifies this procedure in most HPN patients.     

Role of home parenteral nutrition in chronic radiation enteritis

OBJECTIVES: The management of chronic radiation enteritis (CRE) is difficult and often controversial. The aim of the study was to compare long-term outcome of patients with radiation-induced intestinal obstruction treated either surgically or with intestinal rest and home parenteral nutrition (HPN). METHODS: Thirty patients, with mechanical bowel obstruction due to CRE, were retrospectively included in the study and divided in two groups according to the first treatment approach. Seventeen patients underwent surgery (S group) and 13 patients were supported with HPN (HPN group). Survival, nutrition autonomy, number of surgeries, related complications and persistence of symptoms were evaluated in the two groups. Associations between factors and treatment group were assessed by means of the Wilcoxon rank sum test for continuous variables and the Fisher exact test for categorical variables. Overall survival was calculated using the Kaplan-Meier method. RESULTS: The two groups were similar in terms of age, dose of radiation therapy, time of occurrence and degree of signs and symptoms. 7/13 patients in the HPN group resolved the obstruction without surgery. 10/17 patients of the S group developed intestinal failure which required HPN. Nutrition autonomy was achieved in 100% and 58.8% of HPN and S group respectively (p = 0.01). The overall five-year survival was 90.0% and 68.4% respectively in the HPN and S group (p = 0.0231). CONCLUSIONS: Both HPN and surgery are often necessary in patients with chronic radiation-induced intestinal obstruction. However, the long term nutrition autonomy and survival seem to be better in patients initially treated with intestinal rest and HPN.     

Understanding short bowel syndrome: Current status and future perspectives

Short bowel syndrome (SBS) is a rare malabsorptive disorder as a result of the loss of bowel mass mostly secondary to surgical resection of the small intestine. Other causes are vascular diseases, neoplasms or inflammatory bowel disease. The spectrum of the disease is widely variable from single micronutrient malabsorption to complete intestinal failure, depending on the remaining length of the small intestine, the anatomical portion of intestine and the function of the remnant bowel. Over the last years, the management of affected patients has remarkably improved with the increase in patients’ quality of life and survival, mainly thanks to advances in home-based parenteral nutrition (PN). In the last ten years new treatment strategies have become available together with increasing experience and the encouraging results with new drugs, such as teduglutide, have added a new dimension to the management of SBS.This review aims to summarize the knowledge available in the current literature on SBS epidemiology, pathophysiology, and its surgical (including intestinal lengthening procedures and intestinal transplantation) and medical management with emphasis on the recent advances.Moreover, this review attempts to provide the new understanding and recent approaches to SBS complications such as sepsis, catheter thrombosis, and intestinal failure-associated liver disease.     

Problems and organization of a home parenteral nutrition service

Home parenteral nutrition services have revolutionized the treatment, and improved the survival, of patients with prolonged or permanent intestinal failure. Without such a programme, these patients either would be condemned to continuous in-patient parenteral nutrition or to death. The indications for HPN in the UK remain predominantly intestinal failure resulting from inflammatory bowel disease, and major small bowl resection. Nearly 50% of patients receiving HPN will ultimately have normal intestinal function restored and thus be able to return to enteral feeding. This knowledge is reflected in the selection criteria for instituting HPN. The use of HPN in patients with malignant disease poses significant ethical questions. The success of HPN is dependent upon the organization of nutritional units to allow centralization of HPN programmes and to provide the necessary support to patients. It is clear that not all patients will benefit from HPN, and it is only by careful assessment of patients, based on the experience of specialized nutritional units, that a rational HPN service can be provided.     

Outcome of patients with radiation enteritis treated with home parenteral nutrition

OBJECTIVES: Intestinal failure requiring either surgery or home parenteral nutrition (HPN) develops in approximately 5% of patients treated with radiation. The aim of the study was to determine survival, duration of HPN, and complications associated with HPN in patients with intestinal failure after radiation therapy. METHODS: Fifty-four patients with radiation enteritis who received HPN were studied (39 women and 15 men with a mean age of 57.9 yr). Retrospective data were collected from the patients' medical records dated between 1975 and 1999. The probability of survival was calculated by the Kaplan-Meier method. RESULTS: HPN was initiated a median of 20 months (range = 2-432) from the start of radiation therapy. The mean number of intestinal operations for radiation-related complications was 2.2/patient (range = 0-6). The causes of intestinal failure resulting from radiation therapy were intestinal obstruction (27 patients), short bowel (17), malabsorption (five), fistula (three), and dysmotility (two). The mean duration of HPN was 20.4 months (range = 2-108). At last follow-up, 37 patients (68%) were dead, most as a result of recurrent cancer. One patient died of catheter sepsis, and no other deaths were directly related to HPN. The overall estimated 5-yr probability of survival on HPN calculated by Kaplan-Meier analysis was 64%. CONCLUSIONS: HPN is a reasonable treatment option in patients with intestinal failure as a result of radiation enteritis. Survival and complications associated with HPN in patients with radiation enteritis seem to be similar to those in other HPN-treated groups.     

Safety and efficacy of home parenteral nutrition for chronic intestinal failure: a 16-year experience at a single centre

BACKGROUND: Comparisons between safety and efficacy of home parenteral nutrition and of intestinal transplantation for treatment of chronic intestinal failure derived from observational studies. AIMS: To present the 16-year experience of home parenteral nutrition by the Chronic Intestinal Failure Centre of Bologna University. PATIENTS: A total of 40 adult patients were enrolled between 1986 and 2001. METHODS: Safety indices: survival and cause of death, catheter-related bloodstream infection, deep vein thrombosis, liver disease. Efficacy indices: nutritional and rehabilitation status, quality of life (SF36 instrument), re-hospitalisation rate. Statistics: Kaplan-Maier analysis and Cox model for survival probability and risk factors; logistic regression for catheter-related bloodstream infection risk factors. RESULTS: Survival rates at 1, 3 and 5 years were 97, 82 and 67% respectively. Survival was higher in patients < or = 40 years. One death was home parenteral nutrition-related. Incidence of catheter-related bloodstream infection: 0.30/year home parenteral nutrition, was lower in patients treated by a specialized nursing protocol. Incidence of deep vein thrombosis was 0.05/year home parenteral nutrition. Hepatosteatosis occurred in 55%. Body weight remained stable or increased in 80%. Rehabilitation was total or partial in 74%. Re-hospitalisation rate was 0.70/year home parenteral nutrition. Quality of life scored significantly lower than in healthy populations in six out of eight domains. CONCLUSIONS: Home parenteral nutrition is a safe and efficacious therapy for chronic intestinal failure. Survival compares favourably with survival after intestinal transplantation.     

Candidates for intestinal transplantation: a multicenter survey in Europe

OBJECTIVES: Epidemiology of candidacy for intestinal transplantation (ITx) and timing for referral for ITx are unknown. Patient candidacy and physician attitudes toward ITx were investigated among centers that participated in previous European surveys on home parenteral nutrition (HPN). METHODS: Patients on HPN for benign intestinal failure (IF) were evaluated by a structured questionnaire. Candidacy was assessed by USA Medicare and American Transplantation Society criteria, categorized as: (1) life-threatening HPN complications; (2) high risk of death because of the gastrointestinal disease; (3) IF with high morbidity or patient HPN refusal. Physicians judged candidacy as immediate or potential. RESULTS: Forty-one centers from nine countries enrolled 688 adults (> 18 yr) and 166 pediatric patients; 70% of patients were from five countries which collected 60-100% of their HPN patients. Candidacy was 15.7% in adults and 34.3% in pediatrics (HPN failure, 62.1% and 28.1%; gastrointestinal disease, 25.9% and 59.6%; high morbidity IF or HPN refusal, 12.0% and 12.3%, respectively). Immediate candidacy was required for 14.8% of adult and 15.8% of pediatric candidates (< 50% of candidates because of HPN-related liver failure). Among centers, the candidacy rate ranged 0-100% and was negatively associated with the number of patients enrolled in the survey (R = -0.463, p = 0.002). Among the major contributing countries, candidacy ranged 0.3-0.8/million inhabitants for adults and 0.9-2/million inhabitants < or = 18 yr for pediatric candidates. CONCLUSIONS: The rate of candidacy and the indications for ITx candidacy differed greatly among age groups and HPN centers; within countries candidacy was more homogeneous; physicians had a generally reserved attitude toward ITx.     

Parenteral approaches in malabsorption: Home parenteral nutrition

Severe malabsorption of fluids and nutrients leads to intestinal failure (IF) where intravenous supplementation of nutrients and fluids is necessary to maintain health and/or growth. Long-term treatment of IF implies the start of intravenous support in the outpatient setting (home parenteral nutrition, HPN). Although HPN has proven lifesaving for many patients for more than four decades this strategy remains associated with complications that compromise the quality of life. Many problems relate to the presence of the venous access device and concern infections or vascular occlusion due to thrombosis. Patient training remains key to prevent these complications. Also metabolic problems may arise that involve liver function or composition or bone mineralization. While intestinal transplantation remains inferior to HPN as alternative treatment strategy in terms of survival, promising developments include the introduction of hormones that promote intestinal adaptation, mixed lipid emulsions that decrease liver problems and catheter lock solutions that prevent infections.     

Long-term survival and parenteral nutrition dependence in adult patients with the short bowel syndrome.

BACKGROUND & AIMS: The short bowel syndrome (SBS) may be associated with either transient or permanent intestinal failure, presently treated by parenteral nutrition (PN). Survival and PN-dependence probabilities, taking into account both small bowel remnant length and the type of the digestive circuit of anastomosis, are not known in adult SBS patients. The aim of this study was to assess such prognostic factors. METHODS: A total of 124 consecutive adults with nonmalignant SBS were enrolled from 1980 to 1992 at 2 home PN centers. They were analyzed for survival and PN-dependence probabilities using the Cox model and for PN dependence using linear discriminant analysis. Data were updated in April 1996. RESULTS: Survival and PN-dependence probabilities were 86% and 49% and 75% and 45% at 2 and 5 years, respectively. In multivariate analysis, survival was related negatively to end-enterostomy, to small bowel length of <50 cm, and to arterial infarction as a cause of SBS, but not to PN dependence. The latter was related negatively to postduodenal small bowel lengths of <50 and 50-99 cm and to absence of terminal ileum and/or colon in continuity. Cutoff values of small bowel lengths separating transient and permanent intestinal failure were 100, 65, and 30 cm in end-enterostomy, jejunocolic, and jejunoileocolic type of anastomosis, respectively. CONCLUSIONS: In adult SBS patients, small bowel length of <100 cm is highly predictive of permanent intestinal failure. Presence of terminal ileum and/or colon in continuity enhances both weaning off PN and survival probabilities. After 2 years of PN, probability of permanent intestinal failure is 94%. These rates may lead to selection of other treatments, especially intestinal transplantation, instead of PN, for permanent intestinal failure caused by SBS.     

Management of intestinal failure in inflammatory bowel disease: Small intestinal transplantation or home parenteral nutrition?

Inflammatory bowel disease and Crohn’s disease in particular,is a common cause of intestinal failure.Current therapeutic options include home parenteral nutrition and intestinal transplantation.For most patients,home intravenous therapy including parenteral nutrition,with a good probability of long-term survival,is the favoured choice.However,in selected patients,with specific features that may shorten survival or complicate home parenteral nutrition,intestinal transplantation presents a viable alternative.We present survival,complications,quality of life and economic considerations that currently influence individualised decision-making between home parenteral nutrition and intestinal transplantation.     

Liver and small bowel transplantation: therapeutic alternatives for the treatment of liver disease and intestinal failure

Intestinal transplantation is an established life-saving therapy for parenteral nutrition dependent patients suffering from severe complications of parenteral nutrition. Improvements in outcomes over the last decade have occurred with refinements in surgical technique, better immunosuppressive regimens, and clinical experience. The long-term results of intestinal transplantation are not well known and morbidity remains an important obstacle to wider application of this procedure to patients with short bowel syndrome (SBS). This article reviews the indications for intestinal transplantation, the evaluation of potential candidates, therapeutic considerations, postoperative management and common complications experienced by the recipients.     

Intestinal rehabilitation and the short bowel syndrome: part 1

The management of patients with intestinal failure due to short bowel syndrome (SBS) is complex, requiring a comprehensive approach that frequently necessitates long-term, if not life-long, use of parenteral nutrition (PN). Despite tremendous advances in the provision of PN over the past three decades, which have allowed significant improvements in the survival and quality of life of these patients, this mode of nutritional support carries with it significant risks to the patient, is very costly and, ultimately, does not attempt to improve the function of the remaining bowel. Intestinal rehabilitation refers to the process of restoring enteral autonomy and, thus, allowing freedom from parenteral nutrition, usually by means of dietary, medical, and, occasionally, surgical strategies. While recent investigations have focused on the use of trophic substances to increase the absorptive function of the remaining gut, whether intestinal rehabilitation occurs as a consequence of enhanced bowel adaptation or is simply a result of an optimized, comprehensive approach to the care of these patients remains unclear. In Part 1 of this review, an overview of SBS and pathophysiological considerations related to the remaining bowel anatomy in these patients will be provided. Additionally, a review of intestinal adaptation and factors that may enhance the adaptive process, focusing on evidence derived from animal studies, will also be discussed. In Part 2, relevant data on the development of intestinal adaptation in studies involving humans will be reviewed as will the general management of SBS. Lastly, the potential benefits of a multidisciplinary intestinal rehabilitation program in the care of these patients will also be discussed.     

Quality of life of patients on long-term total parenteral nutrition at home

Quality of life and quality-adjusted survival were measured for a cohort of 73 patients maintained on long-term parenteral nutrition at home (HPN) for periods ranging from six months to 12 years. Quality-adjusted survival was also modeled (although not directly observed) for this cohort under alternative therapeutic strategies (e.g., parenteral nutrition in hospital as needed). Using three utility assessment techniques (category scaling, time-tradeoff, direct questioning of objectives), quality of life was measured through interviews with 37 patients. The quality of life of the patients interviewed was good (mean value 0.73 where 0 represents death and 1.0 represents perfect health); for those who had experienced a period of chronic malnutrition before HPN, quality of life had improved. For the entire cohort, the estimate of quality-adjusted survival was four times greater with HPN than with the alternative therapeutic strategies (p less than 0.001). In comparison with alternative strategies, HPN significantly improves the quality of life of patients unable to sustain themselves with oral alimentation. Quality of life (utility) techniques can be used to evaluate the effectiveness of interventions for patients with chronic diseases.     

Home parenteral nutrition in adults: the current use of an experienced method.

Home parenteral nutrition (HPN) is now commonly used in industrialized countries. In Europe, the mean incidence of newly enrolled cases is about 3 patients per 10(6) inhabitants, per year. The use of HPN is much larger in North America. Cancer has become the largest single indication of HPN over the world. The complications are either related to the central catheter (sepsis, thrombosis, migration) or metabolic (liver abnormalities, bone disorder, deficiencies). Complications rate may be lowered by an adequate nutritional regimen, a good teaching of the patients and the presence of a nutritional team in specialized centres. The survival probability for patients with benign diseases is about 65% at 5 years. The mortality rate related to HPN itself is less than 10%. For patients with benign diseases, weaning of HPN is observed in 40 to 70% of the cases. Sixty percent of the patients have a very good quality of life. HPN must be used selectively in cancer patients.     

Intestinal failure

Abstract The recognition of intestinal failure (IF) as a distinct clinical entity over the past 20 years has primarily come about through the emergence of increasingly successful treatment based on use of intravenous nutrition delivered both in hospital and at home. Intestinal failure has many and varied causes, and may be complete or partial, acute and short lived, or chronic and permanent. If the latter, lifetime dependence on parenteral nutrition will usually be indicated and where possible patients are trained in the techniques of home parenteral nutrition (HPN). The success of HPN is itself primarily dependent on meticulous catheter care protocols. Sufficient numbers of such patients have now been entered into randomized controlled trials for there to be an evidence base for this aspect of IF treatment. The balanced delivery of nutrients, especially when an enteral component is included, can prevent many of the complications, such as liver and bone disease, recorded as being associated with prolonged total parenteral nutrition. However, nutritional balance is difficult to achieve in the presence of total gut resection, multiple intestinal fistulas or persisting sepsis. Surgical approaches involving bowel lengthening and reversed loops are indicated in selected patients. They have limited success and carry with them the risk of further loss of precious residual bowel. Greatest promise is held out by intestinal transplantation, but the problems associated with the powerful immunosuppression required reduce the value of this treatment. Specialized referral units for patients with severe and persistent IF can produce a high percentage of clinically effective and cost-effective outcomes.     

Short Bowel Syndrome: A Review of Management Options

Extensive resection of the intestinal tract frequently results in inadequate digestion and/or absorption of nutrients, a condition known as short bowel syndrome (SBS). This challenging condition demands a dedicated multidisciplinary team effort to overcome the morbidity and mortality in these patients. With advances in critical care management, more and more patients survive the immediate morbidity of massive intestinal resection to present with SBS. Several therapies, including parenteral nutrition (PN), bowel rehabilitation and surgical procedures to reconstruct bowel have been used in these patients. Novel dietary approaches, pharmacotherapy and timely surgical interventions have all added to the improved outcome in these patients. However, these treatments only partially correct the underlying problem of reduced bowel function and have limited success resulting in 30% to 50% mortality rates. However, increasing experience and encouraging results of intestinal transplantation has added a new dimension to the management of SBS. Literature available on SBS is exhaustive but inconclusive. We conducted a review of scientific literature and electronic media with search terms ''short bowel syndrome, advances in SBS and SBS’ and attempted to give a comprehensive account on this topic with emphasis on the recent advances in its management.     

Short bowel syndrome

Opinion statement Treatment of short bowel syndrome (SBS) is often a difficult endeavor due to the high variability among patients with SBS in regard to remaining anatomical structure and functional capacity. Research efforts to substantiate the use of existing therapies in the treatment of SBS are ongoing, with newer developments yet to be fully explored. Current therapy for SBS begins with the implementation of a modified diet based on the presence or absence of the colon. Patients with difficulty ingesting enough nutrients and fluids for weight maintenance and fluid balance may benefit from nocturnal enteral nutrition and hydration. Those with inadequate absorptive capacity despite maximization of oral and enteral intake will need parenteral nutrition (PN) or hydration. Medications, including antisecretory agents, antidiarrheals, pancreatic enzymes, bile acid sequestrants, and antibiotics, often are useful in abating symptoms commonly associated with SBS. Growth factors, including recombinant human growth hormone and glucagon-like peptide 2, may be trialed to stimulate intestinal adaptation and enhance absorption in PN-dependent SBS patients. The gradual refinement of surgical procedures for SBS, including small bowel transplantation, has led to improved outcomes, and early referral of SBS patients to centers of excellence will optimize care.     

Classification, epidemiology and aetiology

Intestinal failure and its most important cause, short-bowel syndrome (SBS), are rare clinical entities leading to a vast complex of symptoms and complications with significant morbidity and mortality. Both conditions occur as the result of a massive reduction in enteral nutrient absorptive capacity. Disease manifestation is based on aetiological and anatomical characteristics such as remaining intestinal length and the presence of a functionally intact colon.Congenital and perinatal conditions, for example, intestinal atresia, necrotizing enterocolitis (NEC) and intestinal volvulus are the most important causes in children. The aetiology in adults is based on diseases inducing loss of intestinal function or loss of intestinal surface area after extensive surgical resections. The most frequent causes are mesenteric infarction, radiation enteritis and Crohn's disease. Knowledge of the epidemiology of intestinal failure and SBS is limited, being mainly based on the extrapolated figures of home parenteral nutrition centres and single-centre studies. At present, the incidence of SBS is estimated to be 2-5 per million.