Surgical approaches and intestinal transplantation

The surgical treatment of short-bowel syndrome has been traditionally based on the correction of mechanical obstruction, which is responsible for bacterial overgrowth syndrome, or on intestinal expansion procedures.Since the introduction of clinical intestinal transplantation by Lillehei in 1964, there have been remarkable advances in the immunosuppressive regimens to control rejection and in preservation techniques, monitoring and critical care. Newer and more powerful immunosuppressants have helped to transform intestinal transplantation into a clinical reality—transplantation can now be a life-saving procedure for patients with intestinal failure. It is currently indicated in the event of life-threatening complications of an underlying disease or from total parenteral nutrition (TPN). Rehabilitation in successful cases is excellent.     

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.     

Cytomegalovirus prophylaxis with ganciclovir and cytomegalovirus immune globulin in liver and intestinal transplantation

Liver and intestinal transplant recipients at the University of Miami receive an intensive regimen of cytomegalovirus (CMV) prophylactic therapy consisting of a combination of CMV immune globulin intravenous (CMV-IGIV, CytoGam®) and ganciclovir. The 5-year experience with this regimen in liver transplant patients showed effective CMV prophylaxis in this patient population. The importance of an effective prophylactic strategy was underscored by higher observed rates of chronic rejection and post-transplant lymphoproliferative disorder (PTLD) in CMV-infected patients. The use of CMV-positive donors for intestinal transplants did not increase the incidence of CMV disease. Intestinal transplant recipients had improved survival rates, reflecting an aggressive policy of monitoring, immunosuppression, and CytoGam® plus ganciclovir prophylaxis.     

Intestinal failure: A new era in clinical management

Only 50 years ago intestinal failure was considered incompatible with life. Since then, developments in parenteral nutrition, and, more recently, small intestinal transplantation, have provided new therapeutic options with the potential to offer long-term survival with a good quality of life. Current medical and surgical strategies are aimed at enhancing intestinal adaptation, improving absorption to achieve nutritional independence, and minimizing the complications of parenteral nutrition therapy. An integrated, multidisciplinary approach to the management of patients with intestinal failure, closely linked to a transplantation program to facilitate early referral, is recognized as a key factor in optimizing patient outcomes.     

Fifteen years’ experience of intestinal and multivisceral transplantation in the Nordic countries

Abstract

Objective. Intestinal and multivisceral transplantation have gained acceptance as treatment modalities for patients with: intestinal failure and life-threatening complications of parenteral nutrition (PN), rare cases of vascular abdominal catastrophes and selected cases of low-grade neoplastic tumors such as neuroendocrine pancreatic tumors and desmoids involving the mesenteric root. The aim was to describe the survival and nutritional outcome in the transplanted Nordic patients and the complications attributed to this procedure. Method. The authors included all Nordic patients transplanted between January 1998 and December 2013. Information on patients transplanted outside the Nordic region was collected through questionnaires. Results. A total of 34 patients received different types of intestinal allografts. Currently, there are two Nordic transplant centers (n = 29) performing these procedures (Gothenburg, Sweden n = 24, Helsinki, Finland n = 5). The remaining five patients were transplanted in the USA (n = 3) and the UK (n = 2). Most patients were transplanted for life-threatening failure of PN (70%) caused primarily by intestinal motility diseases (59%). Allograft rejection was the most common complication and occurred in 79% of the patients followed by post-transplantation lymphoproliferative disorders (21%) and graft-versus-host disease (18%). The 1- and 5-year survival was 79% and 65% respectively for the whole cohort and nutritional autonomy was achieved in 73% of the adults and 57% of the children at 1 year after transplantation. Conclusion. This collective Nordic experience confirms that intestinal transplantation is a complex procedure with many complications, yet with the possibility to provide long-term survival in selected conditions previously considered untreatable.     

Chronic intestinal failure and short bowel syndrome in Crohn’s disease

Chronic intestinal failure (CIF) is a rare but feared complication of Crohn’s disease. Depending on the remaining length of the small intestine, the affected intestinal segment, and the residual bowel function, CIF can result in a wide spectrum of symptoms, from single micronutrient malabsorption to complete intestinal failure. Management of CIF has improved significantly in recent years. Advances in home-based parenteral nutrition, in particular, have translated into increased survival and improved quality of life. Nevertheless, 60% of patients are permanently reliant on parenteral nutrition. Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy. The outcomes of patients with CIF could be greatly improved by more effective prevention, understanding, and treatment. In complex cases, the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation, nutritional support, and an improved quality of life. Here, we summarize current literature on CIF and short bowel syndrome, encompassing epidemiology, pathophysiology, and advances in surgical and medical management, and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.     

Intestinal transplantation: current status

Intestine transplant is indicated for patients with intestinal failure who are unable to be weaned from parenteral nutrition (PN). Long-term PN, although life sustaining in many patients, can be associated with life-threatening complications including PN-associated liver disease (PNALD). Most patients are not considered for intestine transplant until they have developed severe PNALD and also need a liver transplant. Overall outcomes with intestinal transplantation are steadily improving, and current 1-year patient survivals for intestine-only transplants are now similar to those for liver transplant. Intestinal transplantation should be considered earlier in intestinal failure patients who are at high risk for developing PNALD and other life-threatening complications.     

Mortality and economics in short bowel syndrome

The incidence of patients with short-bowel syndrome (SBS) has increased over the years due to progress of intensive care medicine and parenteral nutrition techniques. These techniques have significantly improved the prognosis of neonates, children and adults who have lost major parts of their intestinal tract. Long-term survival is possible and does not depend primarily on the length of the remaining bowel but on complications such as parenteral nutrition-associated cholestasis, recurrent septicaemia, central venous catheter infections, and the motility of the remaining intestine. Thus, the overall related mortality in infants with SBS ranges from 15 to 25%, and in adults from 15 to 47%, depending on the age of the patients, the underlying disease, and the duration on total parenteral nutrition. Home parenteral nutrition (HPN) significantly decreases the complication rate and improves the psychological situation of the patient. Additionally, HPN reduces in-hospital cost significantly. Nevertheless, the annual costs/patient are between $100000 and $150000. The mortality rate of SBS patients on HPN is about 30% after 5 years, which is still lower than the 5-year survival rate of intestinal grafts, and it is about equal to patients' survival after intestinal transplantation. However, the overall costs of a successful intestinal transplantation are already lower after 2 years when compared with the cost of a prolonged HPN programme.     

Expanding Indications for Liver Transplant: Tumor and Patient Factors

During the past few decades, liver transplant has developed from a high-mortality procedure to an almost routine procedure with good survival outcomes. The development of living donor liver transplant has increased the availability of liver grafts, and the scope of indications for liver transplant has been expanding ever since. The aim of this review is to provide an overview of such an expansion of scope. Various criteria have been proposed to expand the eligibility of patients with hepatocellular carcinoma exceeding the Milan criteria for liver transplant. Furthermore, liver transplant is increasingly performed as a treatment modality for cholangiocarcinoma, neuroendocrine liver metastasis and colorectal liver metastasis. The number of elderly patients receiving liver transplant is on the rise. Combined organ transplantation has also been adopted to treat patients with multiple organ failure. Going forward, further development of preoperative noninvasive predictors in tumor, patient and even donor factors is needed to identify patients at risk of poor outcomes and hence optimize patient management.     

Intestinal transplantation in children with chronic intestinal pseudo-obstruction

BACKGROUND: Children with chronic intestinal pseudo-obstruction (CIPO) often require total parenteral nutrition (TPN) which puts them at risk of liver failure and recurrent line infections. Intestinal transplantation has become a therapeutic option for TPN dependent children with intestinal failure who are failing management with TPN. AIMS: To investigate the outcome of children with CIPO referred for intestinal transplantation. METHODS: A retrospective review was carried out of records and diagnostic studies from 27 patients with CIPO referred for intestinal transplantation. RESULTS: Five children were not listed for transplantation: two because of parental decision, two because of suspicion of Munchausen syndrome by proxy, and one because he tolerated enteral nutrition. Six are still TPN dependent and awaiting transplantation. Eight children died awaiting transplantation. Eight children underwent transplantation. Three died (two months, seven months, and four years after transplant). Five children are alive with a median follow up of 2.6 years (range two months to six years). All transplanted children were able to tolerate full enteral feedings. The postoperative course was complicated by dumping syndrome, Munchausen syndrome by proxy, narcotic withdrawal, and uncovering of achalasia. Conclusion-Intestinal transplantation may be a life saving procedure in children with CIPO. Early referral and thorough pretransplant evaluation are keys to successful transplantation.     

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.     

Heart transplantation for congenital heart disease in the first year of life

Successful infant heart transplantation has now been performed for over 25 years. Assessment of long term outcomes is now possible. We report clinical outcomes for322 patients who received their heart transplant during infancy. Actuarial graft survival for newborn recipients is 59% at 25 years. Survival has improved in the most recent era. Cardiac allograft vasculopathy is the most important late cause of death with an actuarial incidence at 25 years of 35%. Post-transplant lymphoma is estimated to occur in 20% of infant recipients by25 years. Chronic kidney disease grade 3 or worse is present in 31% of survivors. The epidemiology of infant heart transplantation has changed through the years as the results for staged repair improved and donor resources remained stagnant. Most centers now employ staged repair for hypoplastic left heart syndrome and similar extreme forms of congenital heart disease. Techniques for staged repair, including the hybrid procedure, are described. The lack of donors is described with particular note regarding decreased donors due to newer programs for appropriate infant sleep positioning and infant car seats. ABO incompatible donors are a newer resource for maximizing donor resources, as is donation after circulatory determination of death and techniques to properly utilize more donors by expanding the criteria for what is an acceptable donor. An immunological advantage for the youngest recipients has long been postulated, and evaluation of this phenomenon may provide clues to the development of accommodation and/or tolerance.     

Stem cell transplantation for indolent lymphoma: a reappraisal

Allogeneic transplantation is established as a curative treatment for follicular lymphoma, but with considerable short and long-term morbidity and mortality. Data and controversies regarding conditioning regimen, donor source, GVHD prophylaxis, post transplant interventions and approaches to predict and reduce morbidity and mortality are reviewed. Total body irradiation is very effective but toxic and reduced intensity conditioning is often preferred though associated with somewhat higher rates of recurrence. The risk of chronic GVHD and its late sequelae can be markedly reduced by in-vivo T-cell depletion using alemtuzumab but also leads to somewhat higher incidence of disease recurrence. When using such treatment strategies, one can consider prophylactic or preemptive donor lymphocyte infusions or low toxicity medical treatment such as rituximab. Overall the long term outcomes, particularly survival and current progression free survival of patients undergoing allogeneic transplantation for indolent lymphoma have steadily improved and transplant can now often safely be considered up to the sixth decade of life. Outcomes of unrelated donor transplantation approach those of HLA-identical sibling transplant and even mismatched umbilical cord transplant can be considered in selected patients. The assessment of risks and benefits is aided by the use of various novel tools.     

Isospora belli infection after isolated intestinal transplant

F. Gruz, C. Fuxman, A. Errea, M. Tokumoto, A. Fernandez, J. Velasquez, C. Nagel, A. Ruf, E. Mauriño, F. Nachman, M. Rumbo, G. Gondolesi. Isospora belli infection after isolated intestinal transplant.
Transpl Infect Dis 2010: 12: 69–72. All rights reserved
Abstract: Isospora belli is a protozoan that only affects humans, after ingestion of Isospora 's oocysts. Immunocompetent patients usually do not develop the infection. Immunocompromised hosts may have profuse diarrhea with other gastrointestinal symptoms. Treatment is based on trimethoprim-sulfamethoxazole. In 2006 we performed an isolated intestinal transplantation in a patient with ultra-short bowel syndrome. Neither rejection nor clinical problems occurred after transplant, but signs of intestinal inflammation were seen in every protocol biopsy starting at the first month post transplant. Almost 3 months after the procedure, the patient was re-admitted with diarrhea. I. belli infection was diagnosed by detection of the oocysts in stool samples. Antibiotic treatment with trimethoprim–sulfamethoxazole was initiated with excellent outcome and without relapses. To the best of our knowledge, this is the first case of isosporosis in a small bowel recipient.     

Intestinal pseudoobstruction secondary to amyloidosis responsive to cisapride

Summary A case of chronic intestinal pseudoobstruction secondary to systemic amyloidosis in a patient with multiple myeloma is described. Gastrointestinal symptoms and indices of nutrition improved markedly after commencing treatment with cisapride, which may have been responsible for relatively prolonged survival compared with similar reported cases.     

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.     

Strongyloides hyperinfection syndrome after intestinal transplantation

Abstract: Strongyloides stercoralis is a helminth with the ability to autoinfect the human host and persist asymptomatically for several years. Immunosuppression can accelerate autoinfection and result in Strongyloides hyperinfection syndrome (SHS), which is associated with significant morbidity and mortality. Immunosuppressed solid organ transplant recipients, particularly in the setting of rejection, are at increased risk for reactivation of latent infections, such as Strongyloides . We describe a case of SHS in an intestinal transplant recipient; we hypothesize that she acquired the infection from the donor. We also review the current literature and address both prophylaxis and treatment of strongyloidiasis in the solid organ transplant patient.     

Adult heart transplant: indications and outcomes

Cardiac transplantation is the treatment of choice for many patients with end-stage heart failure (HF) who remain symptomatic despite optimal medical therapy. For carefully selected patients, heart transplantation offers markedly improved survival and quality of life. Risk stratification of the large group of patients with end-stage HF is essential for identifying patients who are most likely to benefit, particularly as the number of suitable donors is insufficient to meet demand. The indications for heart transplant and review components of the pre-transplant evaluation, including the role for exercise testing and risk scores such as the Heart Failure Survival Score (HFSS) and Seattle Heart Failure Model (SHFM) are summarized. Common contraindications are also discussed. Outcomes, including survival and common complications such as coronary allograft vasculopathy are reviewed.     

Small bowel transplantation

Thirty-seven patients were listed for small bowel transplantation; 16 were transplanted and 15 died while waiting for a donor. Cyclosporine (N=6) or tacrolimus (N=10) were used for immune suppression. Graft rejection rates were lower in the combined liver/small bowel grafts than the isolated intestinal transplants (1/7 vs 5/7;P<0.01) All of the cyclosporine group have died; the median survival was 25.7 months with two patients living more than five years. The tacrolimus group had fewer infections and a shorter hospital stay. All but two are alive with a median survival of 13 months. Seven of eight long-term survivors are off intravenous feedings. We conclude that small bowel transplantation is a life-saving option for patients with intestinal failure who cannot be maintained on total parenteral nutrition.     

Intestinal transplantation

Intestinal transplantation has now emerged as a lifesaving therapeutic option and standard of care for patients with irreversible intestinal failure. Improvement in survival over the years has justified expansion of the indications for intestinal transplantation beyond the original indications approved by Center for Medicare and Medicaid services. Management of patients with intestinal failure is complex and requires a multidisciplinary approach to accurately select candidates who would benefit from rehabilitation versus transplantation. Significant strides have been made in patient and graft survival with several advancements in the perioperative management through timely referral, improved patient selection, refinement in the surgical techniques and better understanding of the immunopathology of intestinal transplantation. The therapeutic efficacy of the procedure is well evident from continuous improvements in functional status, quality of life and cost-effectiveness of the procedure. This current review summarizes various aspects including current practices and evidence based recommendations of intestinal transplantation.