AUTHOR AND EDITOR INFORMATION

Section 1 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Total parenteral nutrition (TPN) is the treatment of choice for patients with intestinal failure. Intestinal and multivisceral transplantation provides an alternative for patients who have life-threatening complications of TPN. Recent improvements in surgical technique, the monitoring and diagnosis of rejection, and cytomegalovirus (CMV) prophylaxis and the development of improved immunosuppression have paved the way for significant improvements in patient and graft survival rates. This article reviews the current status of intestinal and multivisceral transplantation, with emphasis on the authors' experience at the University of Miami.

History of the Procedure

Carrel performed the first experimental intestinal transplantation in 1902.¹ Half a century later, in 1959, Lillehei demonstrated successful intestinal autotransplantation after cold preservation.² Experimental multivisceral transplantation (termed polysplanchnic transplantation) was pioneered by Starzl in 1960.³ The earliest attempts at clinical intestinal transplantation were unsuccessful because of what appeared to be insurmountable barriers: graft rejection and infectious complications.^{4, 5}

The first successful intestinal transplantations occurred in the late 1980s. Grant reported successful intestinal transplantation in pigs with cyclosporine use in 1988.⁶ Starzl reported the first clinical successful multivisceral transplantation in 1987.⁷ In 1988, Goulet and Deltz independently reported the first successful isolated intestine transplantations.⁶ Grant reported the first combined liver and intestine transplantation under cyclosporine-based immunosuppression in 1990.⁸ Starzl, Todo, and Tzakis pioneered intestinal transplantation with tacrolimus in the early 1990s.^{7, 9, 10, 11, 12} As a result, the number of centers performing the procedures increased.^{13, 14}

The intestinal and multivisceral transplantation program at the University of Miami was started in 1994. Through September 2007, 278 intestinal transplantations have been performed, including 247 primary intestinal transplantations (65 isolated intestine, 32 combined liver-intestine, and 150 multivisceral transplantations) and 31 retransplantations (11 isolated intestine, 2 combined liver-intestine, and 18 multivisceral transplantations).

Problem

Short bowel syndrome is often the result of extensive intestinal resection for multiple pathophysiologies, such as volvulus, trauma, tumor, and thrombosis. An inadequate absorptive surface results in an inadequate energy intake and malabsorption of vitamin B-12 and other vitamins. Calcium and magnesium deficiencies can lead to neurologic complications such as encephalopathy, tetany, and convulsions. Intestinal failure with hyperalimentation causes liver failure. Patient with long-term hyperalimentation usually have complications, including line sepsis, thrombosed veins, and liver dysfunction.

Frequency

No database reports the exact incidence of short bowel syndrome. However, the incidence is estimated to be 1.8-2 patients per one million general population.

Etiology

The causes of intestinal failure include the following:

• Mesenteric thrombosis
• Necrotizing enterocolitis
• Gastroschisis
• Volvulus
• Desmoid tumor
• Intestinal atresia
• Trauma
• Hirschsprung disease
• Crohn disease
• Pseudoobstruction
• Microvillus inclusion disease
• Massive resection of the intestine

At the University of Miami, all patients with intestinal failure that necessitated transplantation had TPN-related complications, and most had concurrent TPN-induced liver failure. The causes of intestinal failure and the number of patients affected are as follows:

• Mesenteric thrombosis - 29
• Necrotizing enterocolitis - 32
• Gastroschisis - 36
• Volvulus - 21
• Desmoid tumor - 14
• Intestinal atresia - 17
• Trauma - 16
• Hirschsprung disease - 16
• Crohn disease - 7
• Pseudoobstruction - 13
• Megacystic microcolon -10
• Microvillus inclusion - 8
• Others - 30
• Retransplant - 31

Pathophysiology

Extensive resection of the small bowel can cause short bowel syndrome. Extensive loss of the intestinal mucosa surface results in an inadequate absorptive surface. An inadequate caloric intake and malabsorption of vitamins, including vitamin B-12, can result in severe malnutrition and neurological symptoms. Inadequate electrolyte absorption (eg, calcium, magnesium) also results in severe neurological complications, including encephalopathy, tetany, and convulsions.

Clinical

All patients who received intestinal or multivisceral transplants at the University of Miami had life-threatening TPN-related complications, such as sepsis, central vein thrombosis, and cholestatic TPN-induced liver failure.

The recipients of isolated intestinal transplants had short bowel syndrome with severe central vein thrombosis and line sepsis. Liver functions were preserved.

The recipients of liver and small bowel transplants had short bowel syndrome and cholestatic TPN-induced liver failure. Total bilirubin levels were usually higher than 20 mg/dL.

The recipients of multivisceral transplants had short bowel syndrome and cholestatic TPN-induced liver failure. In addition, they usually had a history of surgery, abdominal trauma, motility disorders, tumors, and other etiologies.

INDICATIONS

Section 3 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

The role of TPN in short bowel syndrome is established, and long-term TPN is the treatment of choice for these patients because of its well-documented long-term safety.¹⁵ A subset of patients with short bowel syndrome cannot tolerate TPN because of frequent episodes of catheter-associated sepsis, catheter-associated vascular thrombosis, or TPN-induced cholestasis. This is the subset of patients who need intestinal or multivisceral transplantation.
 
Line infection is the most common cause of fever and chills for patients with TPN. Gram-positive bacteria are the common pathogens. TPN-induced liver failure is the most common cause of jaundice in TPN therapy. If liver failure progresses, intestinal transplantation or intestinal and liver transplantation is indicated. See Etiology for the causes of intestinal failure and the experience at the University of Miami.

Liver function test findings must be carefully evaluated for derangements that suggest the need for biopsy evaluation. If significant fibrosis, macrosteatosis, or cirrhosis is present on liver biopsy findings, then liver transplantation is necessary. Evaluation of renal function is critical because of the need for long-term use of tacrolimus postoperatively.

RELEVANT ANATOMY

Section 4 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

For isolated intestinal transplantation in patients with normal anatomy, the superior mesenteric artery (SMA) of the donor is procured with the aortic cuff. The portal vein is cut above the confluence of the superior mesenteric and splenic vein. If a right replaced hepatic artery from the SMA is present, the SMA is cut distal to the takeoff of the replaced hepatic artery. The SMA of the donor is anastomosed to the recipient SMA or the abdominal aorta. The portal vein of the donor is anastomosed to the portal vein or the inferior vena cava of the recipient.

For liver and intestinal or multivisceral transplantation, the celiac trunk and SMA are procured with the abdominal aorta and thoracic aorta. The inferior vena cava is procured from the iliac vein bifurcation to above the diaphragm. The anastomosis is performed between the donor abdominal aorta and the recipient abdominal aorta in an end-to-side fashion.

CONTRAINDICATIONS

Section 5 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Transplantation is contraindicated if the recipient has active infection such as pneumonia, sepsis, or fungal infection. Because of the immunosuppressive medication used in the postoperative period, the infection must be controlled by antibiotics or antifungal therapy before transplantation.

WORKUP

Section 6 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Lab Studies

• Perform an automated cell count (ACC) and platelet (Plt) count to rule out anemia and thrombocytopenia.
• Assess electrolyte levels to look for electrolyte imbalance caused by short bowel syndrome.
• Perform liver function tests to rule out cholestatic liver failure and evaluate liver function.
• • Serum glutamic-oxaloacetic transaminase (SGOT, aspartate aminotransferase) test
  • Serum glutamic-pyruvic transaminase (SGPT, alanine aminotransferase) test
  • Alkaline phosphatase (ALKP) test
  • Glucose tolerance test (GTTP)
• Measure prothrombin time (PT) and activated partial thromboplastin time (aPTT) to rule out coagulation abnormalities and evaluate liver function.
• Perform coagulation studies to rule out the cause of thrombosis.
• • Protein C deficiency study
  • Protein A deficiency study
  • Factor deficiency study
  • Vitamin study
• Perform urinalysis to evaluate renal function and rule out infection.
• Assess creatine clearance to evaluate renal function.
• Perform a culture to rule out infection.
• Assess vitamin levels to evaluate nutrition.
• Perform an absorption test to evaluate intestinal function.

Imaging Studies

• Doppler ultrasonography of the extremities to assess the patency of the vein
• Doppler ultrasonography of the liver to assess the patency of the vessel
• CT scanning of the abdomen
• Upper GI series with small bowel follow-through
• Angiography of the abdomen
• Upper GI endoscopy
• MRI
• Magnetic resonance angiography

Other Tests

• Echocardiography
• Stress echocardiography
• Nuclear medicine studies

Diagnostic Procedures

• Biopsy of the intestine for pathological diagnosis (if indicated): If intestinal failure is functional, the diagnosis depends on the pathological findings and exclusion. Biopsy of the intestine is necessary for the final diagnosis. Perform case-by-case evaluations.

Histologic Findings

• See Diagnostic Procedures.

TREATMENT

Section 7 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Medical therapy

The role of TPN in short bowel syndrome is established, and long-term TPN is the treatment of choice for these patients because of its well-documented long-term safety.¹⁵ A subset of patients with short bowel syndrome cannot tolerate TPN because of frequent episodes of catheter-associated sepsis, catheter-associated vascular thrombosis, or TPN-induced cholestasis. These patients need intestinal or multivisceral transplantation.

Surgical therapy

Recipient characterization

At the University of Miami, a total of 278 transplantations were performed in 247 patients from December 1994 to September 2007. The number of cases per year has increased since 1994 (see Media file 6). Sex distribution was approximately equal, with 126 males (51%) and 121 females (49%). In terms of age, 154 (62%) were pediatric recipients, and 93 (38%) were adult recipients (see Media file 7). Also, 65 patients (26%) received isolated intestinal transplantation, 32 (13%) received combined liver and intestinal transplantation, and 150 (61%) received multivisceral transplantation.

Donors

The donor population consisted of 140 (57%) males and 107 (43%) females. Donor age is summarized in Media file 8. Donor selection in intestinal transplantation is critical. Donors should be in the same ABO blood group as the recipient and should have negative serology results for human immunodeficiency virus (HIV) and hepatitis viruses. CMV status of the donor has no influence on selection criteria at the University of Miami. Donor size is an important consideration because most recipients have loss of domain resulting from massive intestinal resection. Donors are usually smaller than the recipients to accommodate the small abdominal compartment that accompanies short bowel syndrome.

Preoperative details

Before organ procurement, all the teams, including the liver transplantation team, the kidney transplantation team, the pancreas transplantation team, and the intestinal transplantation team, must discuss the procedure with any organ procurement surgeons present who are unfamiliar with intestinal graft procurement. Each team present has an interest in the specific organ they are recovering, and this discussion addresses any concerns they may have.

Patients referred for intestinal transplantation are evaluated by a multidisciplinary team with representatives from the following specialties: transplant surgery, gastroenterology, nephrology, cardiology, radiology, nursing, psychology, and social work. Pertinent information for evaluation of candidates for intestinal transplantation includes a detailed medical and surgical history, radiologic mapping of GI anatomy and radiologic assessment of the patency of the 6 major routes of central venous access (eg, internal jugular, subclavian, femoral), and assessment of liver, renal, and cardiac function.

Precise information regarding previous abdominal surgery and the length of remaining intestine is critical. Liver function test results must be carefully evaluated for derangements that suggest the need for biopsy evaluation. If significant fibrosis, macrosteatosis, or cirrhosis is present on liver biopsy, then liver transplantation is necessary. Evaluation of renal function is critical because of the need for long-term use of tacrolimus postoperatively.

Intraoperative details

Donor operation

The basic principles of intestinal and multiple intra-abdominal organ procurement have evolved over the past decade, and the operative techniques have been described in detail.^{9, 16} If the intestinal graft is to be transplanted alone, the portal vein is cut above the confluence of the superior mesenteric and splenic veins, and the SMA is cut with an aortic cuff. If a right replaced hepatic artery is present, the SMA is cut distal to the takeoff of the replaced artery. In multivisceral grafts, both the celiac and superior mesenteric arteries are procured, with the thoracic and abdominal aorta proximal to the origin of the renal arteries. The graft is flushed with 4°C University of Wisconsin solution via a cannula placed in the distal aorta of the donor.

Cold ischemic time is minimized by initiating the recipient operation as soon as the donor graft is harvested. The mean cold ischemic time at the University of Miami is 480 minutes, with 13 hours being the maximum ischemic time to date. The portal vein and SMA are dissected and are prepared for isolated transplantation at the back table prior to implantation in the recipient. The composite graft, including thoracic aorta, abdominal aorta, and vena cava, is dissected and prepared for liver-intestinal or multivisceral transplantation.

Recipient operation

Three variations of transplants are performed for patients with intestinal failure (see Media files 1-4). In isolated intestinal transplantation, only the small intestine is transplanted, and the donor SMA is anastomosed to the recipient SMA or aorta, with or without an interposition graft from the donor iliac or carotid arteries. The arterial graft can be anastomosed to the supraceliac or infrarenal aorta of the recipient.

Portal venous anastomosis is performed using either portal or systemic drainage. In portal drainage, the portal vein can be anastomosed to the recipient superior mesenteric vein, to the confluence of the superior mesenteric and splenic veins, or to the side of the recipient portal vein. If access to the recipient portal system is difficult, systemic drainage can be used. In systemic drainage, the donor portal vein is anastomosed to the recipient vena cava in an end-to-side fashion. No survival advantage and no difference with regard to metabolic and immunologic consequences have been reported between portal and systemic drainage.

Combined liver and intestinal transplantation includes the liver and the intestine as a composite graft. The donor and recipient aortas are anastomosed end-to-side with an interposition aortic graft. The vena cava anastomosis is usually performed end-to-side with the recipient hepatic veins for venous outflow (piggyback technique).

Multivisceral transplantation includes the stomach, pancreas, and intestine, with or without the liver or kidney. The arterial and vena caval anastomoses are the same as for combined liver-intestinal transplantation. The proximal end of the isolated intestinal and combined liver-intestinal transplantation is anastomosed side-to-side to the distal end of the native recipient intestine. In multivisceral transplantation, the proximal anastomosis is performed between the donor stomach and the recipient esophagus. A catheter for enteral feeding is placed in the jejunum. The distal end of the transplanted intestine is exteriorized as a stoma to decompress the bowel and to monitor the graft for signs of rejection. The distal part of the intestinal graft just proximal to the ileostomy is anastomosed to recipient colon (if present).

Graft size considerations are important in intestinal transplantation. If the graft is large for the shrunken abdomen of the recipient, resection of intestine and/or liver is performed. Abdominal closure may require mesh or staged approximation. Skin flaps, muscle flaps, or synthetic mesh can be used in cases where significant size discrepancies exist.

Defects of the abdominal wall are an important surgical issue for the patient with multiple surgeries. Abdominal wall transplants have been performed for these patients. The iliac artery and vein were used for vascular anastomosis. Cadaveric fascia grafts have been used for abdominal closure.

Postoperative details

Patients require intensive hemodynamic monitoring for the first few days after surgery. Patients arrive from the operating room to the intensive care unit intubated with a central line, arterial line, Foley catheter, nasogastric tube, and an ostomy bag. If venous access permits, the patient also has a Swan-Ganz catheter. The patient remains in the intensive care unit for several days because of the need for careful fluid management due to massive third spacing that occurs in the peritoneal cavity immediately following intestinal graft reperfusion. The recipient is at risk for pulmonary edema during this early period.

Infectious prophylaxis is an important part of the postoperative care of intestinal transplant recipients. Antifungal prophylaxis with a liposomal preparation of amphotericin and broad-spectrum antibiotics is administered for the early postoperative period. Gut decontamination with amphotericin B, gentamicin, and kanamycin is administered until reasonable enteral feeding volumes are achieved. CMV was a formidable barrier to successful intestinal transplantation prior to the initiation of good prophylaxis.¹⁷ Recipients receive a prophylactic regimen consisting of intensive anti-CMV globulin (CytoGam) treatment and intravenous ganciclovir. CytoGam is administered at a dose of 100 mg/kg every other day for 30 days, followed by 150 mg/kg every 2 weeks for 3 months. No patients on this protocol have had serious problems with CMV. This protocol has allowed the use of CMV-positive donors for all recipients.

Enteral feedings are started 4-6 days after transplantation via the gastrojejunostomy tube to maintain mucosal integrity and to preserve the gut permeability barrier. Diluted Vivonex is started at a low rate and increased first in volume and then in strength until the daily energy goal for the patient is met. Oral feedings are started at 2 weeks postoperatively if intestinal function is adequate. TPN is slowly tapered and gradually discontinued once the patient can sustain total energy intake with enteral feedings.

Immunosuppression

The development of new immunosuppressive agents has been a major factor in the improvement in survival rates following intestinal and multivisceral transplantation. Tacrolimus and steroids have been the first-line immunosuppressive agents in intestinal transplantation since 1990. Tacrolimus is administered to achieve trough levels of 15-20 ng/mL via oral or intravenous routes. The interleukin (IL)–2 receptor antagonist daclizumab (Zenapax) has been used for induction immunosuppression at the University of Miami since 1998.

Sirolimus is another new immunosuppressive agent that is proving to be invaluable in intestinal and multivisceral transplantation. Sirolimus is a macrolide antibiotic that binds to FK-binding protein 12 and inhibits T-cell proliferation.¹⁸ Sirolimus is not nephrotoxic and, as such, is invaluable for patients who have poor renal function postoperatively. In addition, the authors have used sirolimus in conjunction with tacrolimus to minimize renal adverse effects caused by tacrolimus.

Recently, the authors have started using an anti-CD52 antibody alemtuzumab (Campath) as an addition to the induction immunosuppression protocol.^{19, 12} Preliminary results are satisfactory. However, determining whether alemtuzumab will have a long-lasting role in intestinal and multivisceral transplantation is not yet possible.

Monitoring for and treatment of rejection

The addition of routine early postoperative zoom video endoscopy (ZVE) has contributed to an improvement in survival rates following intestinal transplantation at the University of Miami.²⁰ Surveillance ZVE and biopsy are started on the third postoperative day and continued twice weekly for the first postoperative month. ZVE and biopsy are then performed weekly for 2-4 months postoperatively. After the fourth postoperative month, ZVE is initiated based on clinical signs of rejection. Clinical signs of rejection are increased ostomy output (>40 mL/kg/d), fever, and abdominal pain. ZVE and biopsy are initiated at any point in the postoperative course when these signs are present. ZVE is able to magnify the image of the mucosa 100 times so that individual microvilli can be observed.

The authors believe that the ZVE minimizes sampling errors because more accurate identification of the most severely injured areas of mucosa is possible. The ZVE also allows identification of rejection at a much earlier stage than conventional endoscopy; thus, the incidence of graft loss due to severe rejection has decreased greatly in the authors' series.

Since initiation of the ZVE protocol, the authors improved the timing of treatment of rejection and prevention of overimmunosuppression. Mild or moderate intestinal rejection is treated with steroids and usually resolves. If moderate rejection does not immediately respond to increased steroids, OKT3 therapy is initiated. OKT3 is effective for the treatment of moderate rejection but is only marginally effective in reversing severe rejection. Early detection of rejection to prevent severe rejection is essential to achieving long-term graft survival.

The monitoring of intestinal transplants for rejection has room for improvement. Most notably absent is the presence of a serum marker or profile for rejection. Intestinal fatty acid binding protein was extensively tested without success. Serum citrulline levels are now under examination as an early marker for graft rejection.²¹ The early results suggest that using citrulline levels to diagnose intestinal graft rejection has significant promise.

Wireless capsule endoscopy may be another option to monitor the entire small bowel tract in order to monitor acute rejection and inflammation without any delay.

Follow-up

Immunosuppression and rejection monitoring are the main issues after the transplantation.

Tacrolimus (Prograf) levels are checked daily for a month. Then, blood levels are checked twice a week for another month and then once a week depending on the blood level and condition.

Steroids are tapered slowly over several months.

Rejection monitoring by endoscopy is performed twice weekly for the first postoperative month and then weekly for postoperative months 2-4 depending on the clinical situation. After that, periodic endoscopy is performed depending on the clinical signs of rejection.

COMPLICATIONS

Section 8 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Rejection

Rejection occurs in nearly all recipients of intestinal and multivisceral transplants.²² Onset is usually manifested by high ostomy output (>40 mL/kg/d), fever, ileus, and abdominal pain. Prior to the initiation of routine surveillance with ZVE and biopsy, delays in diagnosis were frequent, and graft loss due to severe rejection was commonplace. Since the introduction of this protocol, incidence of severe rejection is very unusual. ZVE allows examination of the intestinal mucosa for villus height, shape of microvilli tips, background erythema, villous bleeding, and friability (see Media file 5). Rejection in the early stages examined by ZVE reveals villous blunting, background erythema, and mucosal friability. The authors have developed a ZVE scoring system that is undergoing evaluation for clinical use as a tool to grade rejection.

Mild and moderate rejection is treated with steroid pulses. Mild rejection only rarely does not respond to steroids, whereas moderate rejection sometimes requires a course of OKT3 to be reversed. In the authors' experience, severe rejection is irreversible, resulting in graft loss in all patients in the authors' series. Maintaining Prograf trough levels in the 15- to 20-ng/mL range during and following episodes of rejection is important. In patients whose renal function does not tolerate Prograf levels of 15-20 ng/mL, sirolimus can be added to provide further T-cell immunosuppression.

In early experimental studies, a survival advantage to transplanting the liver with the intestine was shown.²³ Clinical results have shown that the opposite is true (ie, recipients of isolated intestinal transplants fare better than those receiving liver-intestinal and multivisceral transplants).²⁴ The survival rate in isolated intestinal transplantation is better than in liver-intestinal or multivisceral transplantation at the University of Miami. Isolated liver transplantation in infants with TPN-associated liver disease has recently been considered in selected cases.²⁵.

Infection

Infection has been a primary component in the failure of clinical intestinal transplantation. Keys to minimizing infection include rigorous CMV prophylaxis, fastidious central line care, early central line removal, and routine fungal prophylaxis during periods of most intense immunosuppression. The common bacterial pathogens are Escherichia coli, Enterococcus faecium, Pseudomonas aeruginosa, Enterobacter cloacae, and Staphylococcus, Klebsiella, and Proteus species.²⁶ The most commonly encountered fungal pathogens are Candida and Aspergillus species.

Epstein Barr virus (EBV) is a common problem in clinical intestinal transplantation. Prophylaxis with CytoGam and ganciclovir has reduced the incidence of early EBV infection in intestinal transplantation. EBV transformation and the development of posttransplant lymphoproliferative disorder are particularly common in recipients of intestinal transplants. The development of anti-CD20 antibody (Rituximab) has provided a badly needed therapy for intestinal recipients with posttransplant lymphoproliferative disorder.

Adenovirus and respiratory virus are 2 viral pathogens that are encountered in pediatric recipients of intestinal transplants. Reductions in immunosuppression and ribavirin can sometimes result in patient recovery from these 2 difficult viral infections.

Surgical complications

Postoperative bleeding is the most common surgical problem in intestinal transplantation. Most of the patients have borderline liver function and bleeding tendency.

Meticulous surgical hemostasis is necessary. Vascular problems are unusual following intestinal transplantation. The authors have had 3 cases of arterial graft infection, with rupture and death in each case. Attention must be paid to aseptic procedures during the donor and recipient operations. Large-volume antibiotic irrigation is applied in the operating room in an attempt to minimize this complication. Leakage at the intestinal anastomosis has occurred twice. In one case, the patient was explored and the defective anastomosis (esophagogastrostomy) was redone. In another case, the fistula between the colon and the jejunum closed itself. The patients did well in both cases.

Renal failure

Recipients of intestinal and multivisceral transplants often have renal impairment prior to transplant and are then started on multiple nephrotoxic agents (tacrolimus, amphotericin, and vancomycin are the common ones). The addition of sirolimus to decrease Prograf dosing can have renal-sparing effects. Liposomal amphotericin may possibly minimize the nephrotoxic effects of amphotericin. If frank renal failure occurs, continuous venovenous hemodialysis or intermittent hemodialysis may be necessary until the kidneys recover. Careful attention to the use of nephrotoxic agents and close follow-up with a nephrologist are mandatory for the successful management of these critically ill patients.

OUTCOME AND PROGNOSIS

Section 9 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Patient and graft survival

The International Registry for Intestinal Transplantation reports that graft and patient survival rates have improved, with a 69% 1-year patient survival rate and a 55% graft survival rate since 1995.²² At the University of Miami, the 1-year patient survival rate is 75%, and the graft survival rate is 68% since 1994. Since 1998, the 1-year patient survival rate is 84%, and the graft survival rate is 72% (see Media file 9). In 1998, the authors introduced the ZVE and biopsy protocol and daclizumab induction therapy for all intestinal and multivisceral recipients. The authors attribute the improvement in patient and graft survival rates since 1998 to these 2 modifications in the program.

The authors are certain that earlier referral of the patients for intestinal transplantation yields improved survival results. The authors' results do show that isolated transplantation is preferable to combined liver-intestinal or multivisceral transplantation from a survival standpoint. Posttransplant prognosis is also improved when transplantation is performed prior to the onset of liver failure and prior to the exhaustion of all routes of vascular access.

Causes of death included the following:

• Sepsis after rejection
• Respiratory failure
• Sepsis
• Multiple organ failure
• Arterial graft infection
• Aspergillosis
• Posttransplantation lymphoproliferative disorder
• Intracranial bleeding
• Fungemia
• Chronic rejection
• Graft versus host disease
• Necrotizing enterocolitis
• Pancreatitis
• Pulmonary embolism
• Viral encephalitis

FUTURE AND CONTROVERSIES

Section 10 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Current state of intestinal transplantation

Most recipients of intestinal transplants are free from TPN and enjoy an excellent quality of life. Intestinal transplantation has matured into a life-saving and cost-effective therapy for patients with intestinal failure.²⁷ Rejection and infection are still the 2 most perplexing problems surrounding intestinal and multivisceral transplantation. Earlier patient referral, the development of new immunosuppressive agents, and the discovery of a serum marker for graft rejection are the keys to continued improvements in graft and patient survival rates.

Evolution and future directions

Since 1998, the authors have been changing many things, such as surgical technique, CMV prophylaxis, rejection monitoring with ZVE, new immunosuppression, and prevention of overimmunosuppression. These changes have contributed to the recent improvement in the survival rate.

Systemic drainage to the inferior vena cava has been applied, and results are satisfactory. Metabolic effect and survival rates are the same as for portal drainage. CMV-positive donors are used safely with intense CMV prophylaxis by CytoGam. Rejection monitoring with ZVE prevents the delay of the diagnosis of the rejection and overimmunosuppression. Zenapax, rapamycin, and Campath are ongoing new immunosuppression therapies. These evolutions have improved the results of intestinal transplantation since 1998. New findings from basic research may contribute to the improvement of small bowel transplantation.

Enterocytes have been studied at the University of Miami hospital. The study demonstrated the presence of host-derived (male) enterocytes in the intestinal allografts (female). The presence of male crypt cells and male enterocytes in the intestinal grafts suggested that they probably originated from circulating stem cells and that the differentiation process might have progressed from crypt cells to mature enterocytes. Generating enterocytes from a patient's own stem cells may be possible; this might assist in developing novel strategies to increase intestinal absorptive surface and repair and to engineer neointestines for patients with short bowel syndrome.

The authors' clinical study also demonstrated some promising preliminary data about serum citrulline as a marker for early acute cellular rejection after intestinal transplantation. These findings might help the rejection monitoring.

Newer immunosuppressive medications with more specific actions, further advancement of rejection monitoring, and infection control are urgently required. Continuing efforts will contribute to future success.

ACKNOWLEDGMENTS

Section 11 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

The authors gratefully acknowledge Brian Dunkin, MD, for his support involving endoscopy and patient care. The authors also acknowledge Joseph Tector, MD, for his support of this manuscript. The authors would also like to thank Debbie Weppler, RN, for her contribution of intestinal patient management and data collection.

MULTIMEDIA

Section 12 of 13  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

Media file 1:  Isolated intestine transplantation.
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Media file 2:  Liver and intestine transplantation.
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Media file 3:  Liver, intestine, and pancreas transplantation.
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Media file 4:  Multivisceral transplantation.
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Media file 5:  Endoscopic view of small-bowel graft is shown. Views A and D are normal; views B and E show moderate rejection; and views C and F indicate severe rejection.
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Media file 6:  Number of intestinal transplantations.
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Media file 7:  Intestinal transplantation in adult and pediatric patients.
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Media file 8:  Donor age.
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Media file 9:  Patient survival of isolated intestinal transplantation.
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Media file 10:  Patient survival of 3 types of intestinal transplantation.
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REFERENCES

Section 13 of 13

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Acknowledgments
• Multimedia
• References

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Article Last Updated: Jan 24, 2008