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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.

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Surgical Treatment: Evidence-Based and Problem-Oriented.

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Intestinal transplantation

, M.D. and , M.D.

Author Information

, M.D.1 and , M.D.2.

1 Department of Surgery, University of California Davis Medical Center, Sacramento,CA, U.S.A.
2 Department of Surgery, University of Minnesota, Minneapolis, MN, U.S.A.

Introduction

Intestinal transplants remain the most challenging and least frequently performed vascularized intraabdominal organ transplants. However, over the last one and a half decades, intestinal transplant outcome has significantly improved and the yearly number of transplants has steadily increased (1,2). This phenomenon can be attributed to a variety of factors that include:

1.

the refinement of surgical techniques,

2.

the introduction of more powerful immunosuppressive agents and optimization of perioperative immunosuppressive protocols,

3.

better donor and recipient selection,

4.

increasing sophistication in perioperative prophylaxis of, and monitoring for, posttransplant infections and lymphoproliferative diseases (PTLD),

5.

availability of more potent, yet less toxic antibacterial, antifungal, and antiviral agents,

6.

improvements in organ preservation, and

7.

advances in postoperative intensive care management of the high-risk intestinal transplant recipients (2,3,4,5,6,7,8,9).

To date, approximately 300 intestinal transplants have been done world-wide with long term results that are comparable to lung transplants(2).

Intestinal failure and indications for intestinal and multivisceral transplantation

Intestinal transplants are most frequently done for patients with intestinal failure who develop intractable total parenteral nutrition-related complications (2,3). The causes of intestinal failure can be subdivided into two groups:

1.

short bowel syndrome (frequently a postsurgical condition) and, resulting in a similar clinical presentation,

2.

functional disorders (e.g. impaired motility or absorptive capacity in the presence of sufficient intestinal length and surface area).

As the primary intestinal disease process progresses, considerable overlap between these two categories may develop (e.g., worsened malabsorption by bacterial small intestinal overgrowth in patients with short bowel syndrome who lost their ileocecal valve)(10).

The distribution of the primary diseases leading to intestinal failure is age-dependent. In children, these include congenital malformations (e.g., small bowel atresia, gastroschisis, aganglionosis), infections of the gastrointestinal tract (e.g., necrotizing enterocolitis), extensive bowel resections due to mesenteric ischemia (e.g., midgut volvulus), and absorptive impairment (e.g., intestinal pseudo-obstruction, microvillus inclusion disease). In adults, intestinal failure is most frequently due to short bowel syndrome after extensive resections secondary to mesenteric ischemia (e.g., following thrombosis, embolism, volvulus, trauma), inflammatory bowel disease (e.g., Crohn's disease), small bowel tumors (e.g., Gardner's syndrome), and tumors of the mesenteric root and retroperitoneum (e.g., desmoid tumor)(2).

The severity of the short bowel syndrome in these patients depends on a multitude of factors, including length and type (jejunum or ileum) of the remaining bowel, preservation of the ileocecal valve, individual variability of intestinal adaptation, as well as the presence of an intact anatomy, physiology, and function of the stomach (pylorus), pancreas, and the hepatobiliary system(10).

Unfortunately, conventional surgical alternatives for the treatment of intestinal failure (e.g., intestinal tapering and lengthening, antiperistaltic procedures, surgical creation of intestinal valves and sphincters) are not sufficiently effective to be used routinely(10). Moreover, the specific role of potential mucosal growth factors (e.g., glutamine and growth hormone) has not been definitively established(10). Hence, the majority of patients with intestinal failure is maintained on long term total parenteral nutrition.

Most pediatric and adult patients do well on total parenteral nutrition. A recent national survey in the United States reported a 3-year survival rate greater than 80% for patients on home total parenteral nutrition(11). Therefore, given the risks of intestinal transplantation, only patients who cannot be maintained on long term total parenteral nutrition and who are experiencing one or more of the following complications are currently considered as candidates for intestinal transplantation:

1.

catheter-related complications (e.g., recurrent infections and septic episodes),

2.

lack of central venous access options (e.g., following recurrent venous thromboses),

3.

total parenteral nutrition-induced liver dysfunction and liver failure, and

4.

- under rare circumstances and in the absence of complications(1),(2) or(3) – an exceptionally poor quality of life on total parenteral nutrition (2,12).

Small bowel transplants alone are offered to patients with

1.

intestinal failure that cannot be managed on total parenteral nutrition (vide supra) and/or

2.

mild to moderate liver dysfunction due to total parenteral nutrition(2).

Combined bowel-liver transplants are offered to patients with

1.

intestinal failure and advanced, irreversible liver failure due to total parenteral nutrition and

2.

intestinal failure due to a hypercoagulable state associated with enzyme deficiencies that can be corrected by a liver graft (e.g., mesenteric vascular thrombosis secondary to protein C or S deficiency)(2).

Multivisceral transplants are offered to selected patients with intraabdominal tumors that have led to local invasion, require resection of multiple abdominal organs (evisceration) for surgical cure, and show no evidence for distant metastases (2,13).

Small bowel transplants alone can be done using either cadaveric (i. e., brain dead) or living donors(14). In contrast, combined bowel-liver and multivisceral transplants rely exclusively on cadaveric organ donors.

Contraindications

Contraindications to intestinal transplantation are similar to the guidelines established for other solid organ grafts and include:

  • systemic and untreated local infections (bacterial, fungal, viral),
  • malignancies (other than the previously mentioned indications for multivisceral transplants), and
  • severe cardiac and/or pulmonary disease.

Preoperative evaluation

Recipients

  • blood group and HLA typing
  • laboratory tests: automated blood count (CBC), hepatic and renal function tests, coagulation profile
  • serologic tests: CMV, EBV, HIV, as well as hepatitis A, B, and C
  • radiographic evaluation of the entire gastrointestinal tract to determine actual bowel length and function (transit time)
  • duplex Doppler sonography of the intraabdominal vascular system (abdominal aorta, superior mesenteric artery, portal vein, superior mesenteric vein). Conventional angiography (e.g., mesentericography, splenoportography) is not routinely done and only required for selected patients
  • liver biopsy (only for recipient candidates with clinical evidence for total parenteral nutrition-induced liver dysfunction in order to assess the need for a simultaneous liver transplant)
  • assessment for the presence of infectious foci (including dental and ENT consults)
  • additional organ system-specific investigations as dictated by pathologic results of the aforementioned evaluation process (e.g., coronary angiography, pulmonary function tests, creatinine clearance).

Donors

Cadaveric (brain dead) donors

  • blood group and HLA typing
  • laboratory tests and serologies as described above
  • the donor's weight should range between 20% and 50% of the recipient's weight.

Living donors

  • thorough history and physical (including detailed family history) to exclude unspecific (e.g., cardiovascular) or specific (e.g., bowel disease) contraindications to living donation
  • blood group and HLA typing as well as laboratory and serologic tests as described for cadaveric donors
  • angiography (mesentericography) to assess the vascular supply of the small and large intestine.

Operative technique (basic steps)

Intestinal transplantation alone

Cadaveric transplantation

Donor operation

  • the intestine is usually procured from a multi organ donor
  • dissection of the supraceliac and infrarenal aorta and identification of the aortic take-off of the celiac axis and superior mesenteric artery; dissection of the superior mesenteric vein, splenic vein, and portal vein
  • after aortic cross clamping, an aortic flush with University of Wisconsin (UW) solution is performed
  • intestinal procurement without simultaneous pancreas procurement: the superior mesenteric artery is included with the bowel graft on an aortic Carrel-patch, the splenic vein is ligated near its junction with the portal vein, the superior mesenteric vein is dissected free (similar to the Whipple procedure), the portal vein is divided half way between the superior border of the pancreas and the liver)
  • intestinal procurement with simultaneous pancreas procurement: dissection of the proximal superior mesenteric artery and identification of the take-off of the inferior pancreaticoduodenal artery (which remains with the pancreas graft), division of the superior mesenteric artery distal to this take-off; division of the superior mesenteric vein proximal to its junction with the portal vein
  • the intestinal graft type determines the level of visceral transsection and the anatomy of its vascular supply: for small bowel alone-grafts, the intestine is transsected just proximal to the ileocecal valve; for small bowel-colon grafts a short segment of ascending and proximal transverse colon (with the right and middle colic artery) is procured (the inclusion of the ileocecal valve with the graft may increase the decreased transit time frequently observed in small bowel grafts); and for stomach-bowel grafts the left gastric artery on an aortic Carrel-patch must also be procured
  • donor pretreatment with mono- or polyclonal antilymphocyte antibodies, graft irradiation (directed against the abundant mesenteric lymphatic tissue), selective bowel decontamination, and preoperative bowel irrigation all have no significant impact on transplant outcome (3,5).

Recipient operation

  • intraoperative flexibility is paramount; the individual operative technique (e.g., venous drainage technique) depends on the intraabdominal vascular anatomy of the recipients who frequently have had multiple previous laparotomies
  • the graft can be drained systemically (e.g., into the infrarenal vena cava) or portally (e.g., into the superior mesenteric vein)
  • arterial revascularization is typically achieved by creating an arterial anas- tomosis to the infrarenal abdominal aorta
  • after proximal anastomosis between the graft and the recipient's gastrointestinal tract, the distal graft ileum is exteriorized and intestinal continuity is restored by creating a Bishop-Koop ileostomy (thus allowing for easy endoscopic access to the intestinal graft for monitoring and obtaining biopsies).

Living donor transplantation

Donor operation

  • taking into account the preoperative angiography results, an ileal segment of approximately 150 to 200 cm length is isolated on a vascular pedicle consisting of the ileocolic artery and vein. The ileocecal valve and the distal 20 to 25 cm of the ileum (for vitamin B12 absorption) remain with the donor, supplied by the right colic artery(14)
  • the ileocolic artery and vein are dissected at their respective take-offs (which represents the level of vascular transsection) from the superior mesenteric artery and vein
  • the graft is flushed ex situ with UW-solution
  • intestinal continuity in the donor is restored by creating an ileo-ileal anastomosis.

Recipient operation

  • the graft is revascularized by creating end-to-side anastomoses between the ileocolic artery and the recipient's infrarenal aorta as well as the ileocolic vein and the inferior vena cava(14)
  • intestinal continuity in the recipient is restored as previously described.

Combined bowel-liver transplantation

Donor operation

  • dissection of the aortic origin of the celiac axis and superior mesenteric artery, the suprarenal inferior vena cava, and the superior mesenteric vein (after division of the overlying pancreatic parenchyma)
  • division of the common bile duct (unless - as done in pediatric recipients - the head of the pancreas and duodenum are included with the graft)
  • after an in situ flush (with UW-solution) and suprarenal and supradiaphragmatic transsection of the inferior vena cava as well as proximal and distal small bowel transsection, the bowel-liver graft is procured en bloc, including a 10 cm supraceliac aortic segment in continuity with an aortic Carrel-patch bearing the celiac axis and superior mesenteric artery. Combined bowel-liver procurement precludes the simultaneous procurement of a whole pancreas graft. However, procurement of the distal pancreas (body and tail, supplied by the splenic artery and vein) for a segmental pancreatic transplant remains possible
  • the distal end of the aortic segment is oversewn.

Recipient operation

  • hepatectomy as for liver transplantation
  • end-to-side anastomosis between donor and recipient aorta, creation of the cavo-caval anastomosis (orthotopic if the recipient cava was resected, piggy-back if the recipient cava was preserved)
  • end-to-side anastomosis between the portal vein of recipient and donor
  • arterial flush of the bowel-liver graft prior to removal of the caval vascular clamps
  • intestinal reconstruction as described above (including creation of a Bishop-Koop ileostomy)
  • biliary drainage is achieved via a Roux-Y-choledocho-(bowel graft) enterostomy, unless the graft comprises the duodenum and head of the pancreas.

Postoperative management

The immediate postoperative care is delivered - as after other extrarenal intraabdominal transplants - in an intensive care setting. After anastomotic leaks have been ruled out on postoperative day 7 (radiographic contrast studies), enteral nutrition (via feeding tube, gastrostomy, or jejunostomy) is initiated. The enteral tube feedings should have low osmolarity (to prevent hyperosmolar diarrhea) and should contain medium-chain triglycerides (which are absorbed even in the [initial] absence of lymphatic drainage), easily absorbed small peptides, as well as glutamine (for enterocyte stimulation). A shortened intestinal transit time is not infrequent after intestinal transplantation and can be treated pharmacologically (e.g., with loperamide or pectin). An oral diet is initiated once enteral feedings have been administered successfully for at least seven days.

Routinely, antibacterial prophylaxis is given for the first 7 days posttransplant, antifungal prophylaxis (e.g., fluconazole) for 2 weeks, and antiviral prophylaxis (e.g., ganciclovir, acyclovir) for up to one year.

Immunosuppression

Cyclosporin A failed after its introduction in the early 1980's - in contrast to the experience with other intraabdominal extrarenal solid organ grafts (liver, pancreas) - to improve intestinal graft survival. For the latter, graft and patient survival rates did not increase significantly until tacrolimus became available during the early 1990's (1,6). Currently, the most commonly used triple protocol for induction and maintenance therapy includes tacrolimus, mycophenolate mofetil, and prednisone. For induction, some centers also give monoclonal or polyclonal antibodies for the first 7 postoperative days.

Rejection episodes are treated with corticosteroids and optimization of tacrolimus levels. For steroid-resistant rejections, a 7- to 10-day course of mono- or polyclonal antibodies is administered(5).

Posttransplant complications

Surgical complications

Surgical complications occur most frequently during the early posttransplant period and include anastomotic intestinal leaks, bleeding, and vascular graft thromboses (arterial or venous). Their treatment usually requires relaparotomy. If graft salvage is not an option (e.g., in cases of arterial thrombosis), graftectomy, followed by delayed (for bowel alone-recipients) or immediate (for bowel-liver and multivisceral recipients) retransplantation may be indicated(5).

Immunologic complications

Rejection and graft-versus-host disease

Clinical rejection symptoms (including abdominal pain and distention, tenderness on palpation, ileus, increased fecal volume and stomal output, diarrhea) are unspecific and appear often late - after rejection is already apparent on histology. Therefore, biopsy evaluation is - as for all other solid organ grafts - the gold standard for the diagnosis of intestinal rejection. Surveillance intestinal (transstomal) biopsies are obtained twice weekly for the first 2 months, then weekly for the following 4 months, and monthly thereafter. Endoscopic biopsies must be taken from all areas of the graft (because intestinal rejection can be confined to specific bowel segments) and should always include ileal specimens (because rejection is more frequently observed in the ileum than in the jejunum and colon).

Clinically relevant graft-versus-host disease is - in contrast to the findings of many experimental studies - relatively rare(5).

Posttransplant lymphoproliferative disease

The PTLD incidence in intestinal recipients (ranging from 15% in adults to up to 25% in children) is higher than in other solid organ recipients(2). Most PTLDs are EBV virus infection-associated and have a deleterious overall effect on graft and patient survival. PTLD therapy includes reduction or cessation of immunosuppression, antiviral therapy with acyclovir and ganciclovir, administration of α-interferon, and chemotherapy. However, these interventions result frequently in rejection episodes and graft losses. More recently, strategies have been focused on surveillance for, and early diagnosis of, EBV infections using molecular biology techniques (polymerase chain reaction)(5). But the impact of therapeutic interventions based on these more refined screening and diagnostic methods is presently unknown and awaits further study.

Infectious complications

Bacterial and fungal infections

Breakdown of the mucosal barrier of intestinal grafts (e.g., during rejection episodes) can cause bacterial and fungal translocation into the mesenteric lymph nodes and into the portal and systemic circulation, presenting clinically as sepsis. Thus, treatment of translocation-associated infections due to rejection includes both antimicrobial and antirejection therapy. Prophylactic interventions, such as systemic and local (selective gut decontamination) administration of antimicrobial agents have proven ineffective, leading instead to the emergence of multiresistant organisms.

Viral infections

The cytomegalovirus is the clinically most significant viral pathogen in intestinal transplant recipients(2). CMV infections still cause considerable morbidity and have been associated with increased mortality, in spite of the availability of effective antiviral therapy (e.g., ganciclovir). At highest risk are CMV-seronegative intestinal recipients of organs from CMV-positive donors. This has led to the recommendation that only seronegative donors be used for seronegative recipients - at least for bowel alone-recipients, since recipient candidates with concomitant liver failure may not survive a prolonged waiting period for a suitable seronegative donor(5).

Clinical intestinal transplant outcome

According to the most recent International Intestinal Transplant Registry summary, 273 intestinal transplants in 260 recipients (154, 59% pediatric; 106, 41% adult) were reported until 2/1997. Of these 273 cases, 113 (41%) were bowel transplants alone (with and without colon), 130 (48%) combined bowel-liver transplants, and 30 (11%) multivisceral transplants(2). Nine grafts were from living donors.

In pediatric recipients, the most common intestinal transplant indications included volvulus (28%), gastroschisis (19%), necrotizing enterocolitis (12%), pseudo-obstruction (10%), and intestinal atresia (8%). In adult recipients, the most common indications were ischemia (21%), Crohn's disease (17%), trauma (15%), desmoid tumor (13%), and other or unspecified cancers (13%).

The graft rejection incidence was 72%. Cytomegalovirus disease was noted in 23% and PTLD in 9% of all recipients.

The 1-year graft and patient survival rates for transplants done in the current era were respectively 55% and 69% for intestinal grafts, 63% and 66% for bowel-liver grafts, and 63% and 63% for multivisceral grafts. Of all intestinal recipients alive as of 1997, over 75% were off total parenteral nutrition after successfully resuming an oral diet(2).

Ongoing efforts are directed at further improving immunologic graft survival - without adding to the immunosuppressive burden of the recipient - by developing and refining clinically applicable immunomodulatory protocols (e.g., peritransplant donor bone marrow infusions) and at minimizing incidence and improving outcome of posttransplant infections and PTLD (3,4,5,15).

References

1.
Grant D. Current results of intestinal transplantation. Lancet. (1996);347:1801–1803. [PubMed: 8667925]
2.
Grant D. Intestinal transplantation: 1997 report of the International Registry. Transplantation. (1999);67:1061–1064. [PubMed: 10221494]
3.
Abu-Elmagd K, Reyes J, Todo S. et al. Clinical intestinal transplantation: new perspectives and immunologic considerations. J Am Coll Surg. (1998);186:512–527. [PMC free article: PMC2955329] [PubMed: 9583691]
4.
Tzakis A G, Nery J R, Thompson J. et al. New immunosuppressive regimens in clinical intestinal transplantation. Transplant Proc. (1997);29:683–685. [PubMed: 9123479]
5.
Reyes J, Bueno J, Kocoshis S. et al. Current status of intestinal transplantation in children. J Pediatric Surg. (1998);33:243–254. [PMC free article: PMC2966145] [PubMed: 9498395]
6.
Goulet O, Michel J L, Jobert A. et al. Small bowel transplantation alone or with the liver in children: changes by using FK506. Transplant Proc. (1998);30:1569–1570. [PubMed: 9636636]
7.
Langnas A N, Dhawan A, Antonson D L. et al. Intestinal transplantation in children. Tranplant Proc. (1996);28:2752. [PubMed: 8908040]
8.
Atkison P, Williams S, Wall W, Grant D. Results of pediatric small bowel transplantation in Canada. Transplant Proc. (1998);30:2521–2522. [PubMed: 9745468]
9.
Misiakos E P, Weppler D, Bakonyi A. et al. Clinical outcome of intestinal transplantation at the University of Miami. Transplant Proc. (1999);1999:569–571. [PubMed: 10083240]
10.
Thompson J S. Surgical considerations in the short bowel syndrome. Surg Gynecol Obstet. (1993);176:89–101. [PubMed: 8427009]
11.
Howard L, Malone M. Current status of home parenteral nutrition in the United States. Transplant Proc. (1996);28:2691–2695. [PubMed: 8908012]
12.
DiMartini A, Rovera G M, Graham T O. et al. Quality of life after small intestinal transplantation and among home parenteral nutrition patients. J Parent Ent Nutr. (1998);22:357–362. [PubMed: 9829608]
13.
Alessiani M, Tzakis A, Todo S. et al. Assessment of five-year experience with abdominal organ cluster transplantation. J Am Coll Surg. (1995);180:1–9. [PMC free article: PMC2728058] [PubMed: 8000645]
14.
Gruessner R W G, Sharp H L. Living-related intestinal transplantation. Transplantation. (1997);64:1605–1607. [PubMed: 9415566]
15.
Abu-Elmagd K M, Reyes J, Fung J J. et al. Evolution of clinical intestinal transplantation: improved outcome and cost effectiveness. Transplant Proc. (1999);31:582–584. [PMC free article: PMC2963188] [PubMed: 10083246]
Copyright © 2001, W. Zuckschwerdt Verlag GmbH.
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