Intestinal Transplantation

Updated: Mar 16, 2021
Author: Oya M Andacoglu, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM 

Overview

Practice Essentials

Advances in the medical and surgical treatments of intestinal failure have led to a decrease in the number of transplants over the past decade. Patient survival has improved and morbidity associated with parenteral nutrition, including liver failure, has declined. Nevertheless, intestine transplant still plays an important role in the treatment of intestinal failure.[1] Short gut syndrome (SGS)—congenital and non-congenital—and functional gastrointestinal pathologies (eg, pseudo-obstruction) are the most common causes leading to an intestine or intestine-liver transplant.[2]

Intestine transplantation may be performed in isolation, with liver transplant, or as part of a multi-visceral transplant including any combination of liver, stomach, pancreas, and/or colon. There are notable differences in patient and transplant outcomes for intestine transplants with and without liver.[1]

Background

As with the transplantation of other organs, the history of intestinal transplantation begins with Carrel and his description of a method of performing vascular anastomosis.[3, 4] In 1959, the first canine model of intestinal transplantation was reported by Lillihei and coworkers at the University of Minnesota.[5] The first intestinal transplant in humans was performed by Deterling in Boston in 1964 (unpublished data). The first reported human intestinal transplant was performed by Lillihei and coworkers in 19677. Before 1970, eight clinical cases of small-intestine transplantation were reportedly performed worldwide; maximum graft survival time was 79 days, and all patients died of technical complications, sepsis, or rejection.

In 1988 Deltz and coworkers in Kiel, Germany, performed what is considered to be the first successful intestinal transplant.[6] Soon after, other successful outcomes were reported by the groups headed by Goulet and coworkers in Paris[7] and Grant and coworkers in London, Canada, who had established the first intestinal transplant programs.[8, 9] A total of 15 isolated small-intestine transplantations were performed from 1985-1990 using cyclosporine. 

Waitlist and Patient Profile

As of February 2021, the Organ Procurement and Transplant Network (OPTN) listed 214 patients awaiting intestinal transplantation.[10] At the end of 2019, 20.6% of candidates had been on the waiting list for less than 1 year, 15.4% for 1 to less than 2 years, 28.6% for 2 to less than 5 years, and 35.3% for 5 or more years.[1] Among candidates listed in 2018‐2019, median time to transplant was 9.7 months for intestine candidates and 6.2 months for intestine‐liver candidates.[1]

In 2019, 30.9% of patients on the intestine transplant waiting list were in medical urgency status 1 (ie, at risk of imminent death); 52.2% of patients awaiting intestine-liver transplant were in status 1. The pretransplant mortality rate on the waiting list in 2019 was higher 15.5 deaths per 100 waitlist‐years for adult candidates and 3.1 deaths per 100 waitlist‐years for pediatric candidates. Pretransplant mortality was higher for intestine‐liver candidates than for intestine transplant candidates (13.0 versus 2.9 deaths per 100 waitlist years, respectively).[1]

Non-congenital short gut syndrome (SGS) was the most common reason for transplantation in 2019, accounting for 48.8% of intestine transplants and 30.0% of intestine-liver transplants. Other etiologies included necrotizing enterocolitis, congenital SGS, pseudo-obstruction, and enteropathies.[1]

In 2019, a total of 81 intestine transplants were performed in the United States, 41 intestine without liver and 40 intestine-liver.Over the past decade, the age distribution of candidates in the waitlist for intestine and intestine-liver transplant shifted from primarily pediatric to increasing proportions of adults. Adults accounted for 41% of candidates on the list at any time during the year, with a stable proportion of those aged 18-34 years and a decrease in those aged 35 years or older. In 2012‐2014, the 1‐ and 5‐year graft survival for intestine transplants with or without a liver was 81.1% and 60.8%, respectively, for recipients aged younger than 18 years and 68.9% and 44.7% for recipients aged 18 years or older.[1]

Problem

Intestinal failure is characterized by the inability to maintain protein energy, fluid, electrolyte, or micronutrient balance due to GI disease when on a normal diet. Intestinal failure ultimately leads to malnutrition and even death if the patient does not receive parenteral nutrition or receives an intestinal transplant. 

In the United States in 2019, necrotizing enterocolitis and pseudo-obstruction were more common among candidates listed for intestine transplant, while non-congenital short gut syndrome (SGS) and enteropathies were more common among intestine-liver candidates. Congenital SGS was about equally common in intestine and intestine-liver candidates.[1] Worldwide, the leading cause of intestinal failure is SGS (68%) followed by functional bowel patholgies (15%).[11]

In children, the following are the main  causes of intestinal failure:

The following are the leading causes of intestinal failure in adults:

  • Crohn disease
  • Massive small bowel infarct due to superior mesenteric artery and/or vein thrombosis
  • Trauma
  • Desmoid tumor including the root of the mesentery
  • Volvulus
  • Pseudo-obstruction
  • Multiple gastrointestinal resections for surgical complications 
  • Radiation enteritis

Parenteral nutrition is the current standard of care for patients with intestinal failure. Nevertheless, the long-term use of parenteral nutrition is often associated with potentially life-threatening complications, including the following[12] :

  • Catheter-related sepsis
  • Catheter-related thrombosis
  • Severe dehydration
  • Metabolic derangements
  • Loss of sites for vascular access
  • Intestinal failure–associated liver disease (IFALD)

IFALD is partly caused by omega-6 fatty acids in parenteral nutrition formulas, which can be synthesized into inflammatory molecules. IFALD can range from steatohepatitis, cholestasis, or hepatic fibrosis to end-stage liver disease. Children are more likely to have cholestatic liver disease than steatohepatitis.[13] Severe liver injury has been reported in as many as 50% of patients with intestinal failure who receive parenteral nutrition for longer than 5 years; this is typically fatal. If patients have life-threatening infections, IFALD, or lose their venous access, 1 year mortality is 70% without intestinal transplantation.[14] .

As an early alternative to transplantation or total parenteral nutrition (TPN) for patients with short bowel syndrome, surgical bowel lengthening without transplant may be attempted. This requires the serial transverse enteroplasty (STEP)  or longitudinal intestinal lengthening and tailoring (LILT) procedures.[15, 16]

STEP and LILT are particularly successful in patients with decreased transit times and dilated bowel. If successful, it may reduce the amount of TPN required, or obviate its use altogether. In one study of 22 children who underwent STEP and/or LILT, 50% were weaned off parenteral nutrition and there were no surgical complications or deaths.[17]

Indications

Intestinal transplantation should be recommended for patients on TPN with associated problems listed below:

  • Impending or overt liver failure secondary to IFALD
  • Thrombosis of two or more central veins
  • Two or more episodes per year of systemic sepsis secondary to line infections, or a single episode of fungal sepsis [18]
  • Frequent episodes of severe dehydration

Additional indications for intestinal transplantation include the following:

  • Severe short bowel syndrome (gastrostomy, duodenostomy, residual small bowel [< 10 cm in infants, < 20 cm in adults])
  • Intestinal failure with frequent hospitalizations, narcotic dependency, or pseudoobstruction
  • Patient unwillingness or inability to resume long-term parenteral nutrition
  • In highly selected patients, multivisceral organ transplantation may have a role in the treatment of slow-growing abdominal cancers that are deemed non-resectable [19]

Relevant Anatomy

Isolated intestinal transplant entails ileum and jejunum transplantation. Liver-intestine transplant entails transplantation of liver, pancreas, duodenum, and intestine en bloc.  When recipient foregut is preserved, a portocaval shunt needs to be performed. Another version is multivisceral transplantation, which also includes the stomach in addition to liver, pancreas, and intestine. The need for colon graft varies, depending on the patient's underlying disease and anatomy.

Below are images representing liver-bowel and multivisceral transplantation.

Liver-small bowel graft, including the pancreas. Liver-small bowel graft, including the pancreas.
Multivisceral graft, including stomach-liver-pancr Multivisceral graft, including stomach-liver-pancreas-small bowel and right colon.

Vascular inflow and outflow varies by graft type. Isolated intestine graft is procured with the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) and these are anastomosed to either the recipient's SMA and SMV or to the aorta and vena cava. If vascular conduit is necessary, donor iliac vesels or carotid artery can be used. If liver-intestine or multivisceral transplantation is performed, graft inflow would be donor abdominal aorta, and donor thoracic aorta is used for extension. Suprahepatic vena cava would serve as outflow.

Contraindications

The contraindications to intestinal transplantation are essentially the same as those in other types of transplants. Examples include the following:

  • Severe cardiopulmonary conditions (eg, severe pulmonary hypertension, advanced cardiac failure) precluding major operation 

  • Active or uncontrolled infection or active malignancy 

  • Psychosocial factors (ie, the lack of capability to assume the responsibilities of the day-to-day management following the transplant or the absence of social support)

 

Workup

Laboratory Studies

Pretransplant workup

The evaluation of a potential recipient is done by a multidisciplinary team with members from transplant surgery, gastroenterology, nutritional services, psychiatry, social work, anesthesia, and financial services. Further consultation with other specialties may be required.

Basic laboratory studies include, but are not limited to, the following:

  • Complete blood count (CBC)
  • Coagulation profile
  • Complete metabolic panel
  • Liver function tests 
  • ABO blood group determination
  • Human leukocyte antigen (HLA) status
  • Panel reactive antibody (PRA) status
  • Screening for HIV and hepatitis B and C virus infection
  • Serologies for cytomegalovirus (CMV) and Epstein-Barr virus (EBV)

The GI tract is almost always assessed both radiologically (with contrast studies) and endoscopically. If liver disease is suspected, a liver biopsy can be performed. Since 2007, 23 points are added to patients' Pediatric End Stage Liver Disease (PELD) score if their liver disease is due to intestinal failure.[12] This is because patients with intestinal failure–associated liver disease (IFALD) have higher mortality rates on the transplant wait list.

A newer scoring system, the Pediatric Hepatology Score (PHD), has been shown to be more specific for the detection of wait list mortality than the PELD.[12] Developed in the United Kingdom, this scoring system has yet to gain wide use in the United States.[12]

Doppler ultrasonography or magnetic resonance venography should be performed to assess vascular access. Many patients will have at least one central venous stenosis or obstruction. Matsusaki et al reported no difference in recipient outcome between standard vascular access (percutaneous line via the upper body veins) and alternative vascular access (percutaneous line via the lower body veins; vascular access secured surgically, with interventional radiology, or using nonvenous sites).[20]

Patients with dysmotility disorders may require manometry of the stomach, esophagus, and rectum. Children with necrotizing enterocolitis (NEC) require a full neurologic and pulmonary workup to exclude the possibility of associated intraventricular hemorrhage and bronchopulmonary dysplasia.

Living related-donor transplantation can be discussed as an option if a potential donor is available. Most often, the terminal ileum is used.[21] It is possible to remove the graft laparoscopically to minimize cosmetic concerns.[22] The ethics of living donation are important. The risks and benefits of the procedure should be discussed, including the risk of complications from graft removal.[23]

While on the waiting list, patients are frequently reassessed, with specific attention given to any change in medical status, deterioration in liver function, or further loss of vascular access. These patients also need ongoing maintenance of their central lines to minimize line-related complications, such as infections and thrombosis.

Other Tests

Plasma Citrulline

Plasma citrulline levels have emerged as a measure for overall for intestinal health. Citrulline is made almost exclusively by enterocytes. Thus, clinicians can measure citrulline trends to assess whether a patient is indeed in intestinal failure and not recovering bowel function.[24, 25, 26] This would support a more urgent need for TPN, and possibly transplantation. A study by Lopez et al. noted that citrulline values greater than 15 micromoles/liter could predict successful withdrawal of TPN [27] . It is important to note that citrulline is excreted from the kidneys; hence renal damage can obscure interpretation of results.

Workup for cadaveric donors

Although ABO-compatible donors can be used, ABO-identical donors are preferred in most circumstances because of the risk of graft versus host disease (GVHD). Tissue typing includes but not limited to virtual crossmatch, flow and CDC cross match. 

When patients have DSA (donor specific antibody) or if they have high PRA, these patients are defined as "sensitized" and there are "desensitization" protocols to reduce the antibody load via intravenous immune globulin (IVIG),  plasmapheresis and/or  rituximab prior to transplant [28] .

The size of the donor is important. For multivisceral or intestinal transplant smaller size is desirable. In certain circumstances, segments of the intestine from a larger donor may be considered.

Intestine donors are usually young and otherwise healthy patients who suffered brain death. As with all transplants, the donor should have no significant hemodynamic instability, sepsis, history of malignancy or chronic infection, severe hypoxia, or severe acidosis, and negative serology for human immunodeficiency virus (HIV) and hepatitis B and C is preferable.

CMV and EBV serologic status of the donors and recipients should be taken in consideration. Transplantation from a serologically positive donor into a serologically negative recipient for either of these viruses can have serious consequences. In addition to the risk of a systemic CMV infection, CMV enteritis can occur, which can lead to graft loss. A new EBV infection combined with posttransplant immunosuppression puts the patient at high risk for developing a posttransplant lymphoproliferative disease (PTLD).[29]

Workup for living donors

A potential living donor also needs to be evaluated by a multidisciplinary team. As with any living donor procedure, possible complications including bleeding and death should be explained in great detail. The living donor should have a complete workup, including CBC, electrolytes, liver function tests, electrocardiogram, and chest radiography. The GI tract should be endoscopically evaluated, and, if any concerns are noted, GI contrast studies should be performed. The mesenteric vasculature should be studied to ensure that the terminal superior mesenteric artery and vein are adequate.

 

Treatment

Surgical Therapy

Procurement

The basic steps of the procurement of an isolated small bowel graft are as follows:

  • Decontamination of the donor bowel via a nasogastric tube (program specific; not universal)

  • Administration of antithymocyte globulin, muromonab, basiliximab, and/or corticosteroids to the donor (program specific; not universal); this needs to be discussed with other procuring teams (eg, cardiac team) to make sure they agree with administration of these medication to the donor. 

  • Midline or cruciate incision for abdomen

  • Aortic control obtained

  • Exposure of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) at the root of the mesentery is the key step in intestine procurement. In multi-organ procurement, the surgeons procuring the liver, pancreas, and intestine usually need to operate together to agree on where to divide these vessels, or which branches of the vein to take. Variations in anatomy may be present. This dissection must be performed meticulously and with strict hemostasis in order to prevent hematomas in the pancreas head or other organs. 

  • Small bowel mesentery and mesocolon are protected during mobilization (Cattell-Braasch).  

  • Division points of GI tract are identified (usually proximal jejunum and distal colon). 

  • After cross clamping, the SMA and SMV are divided at the level of the mesentery root. Intestine, liver, and pancreas are removed sequentially. 

  • Iliac arteries, veins, carotid arteries, and jugular and/or innominate veins are procured for vascular conduits, since donor vessels are shared between liver, pancreas, and intestine teams.

  • Note: for living donors, a technique has been described for laparoscopic removal of the allograft.[22]

Intraoperative Details

The recipient operation proceeds as follows:

  • Once the graft is harvested, the SMA may be lengthened with a vascular conduit from the same donor (eg, carotid artery to SMA) in the recipient operation.

  • Colon graft can be stapled off at terminal ileum if recipient has sufficient functional colon.  

  • Recipient operation starts with exploratory laparotomy and lysis of adhesions, which is usually challenging due to multiple previous surgeries.

  • Remaining intestine is stapled off and removed.  

  • The SMA, infrarenal aorta, and infrarenal vena cava are exposed.

  • If vascular conduit is used, these are sewn first: venous graft to recipient cava and arterial conduit to infrarenal aorta. SMA-to-SMA and SMV-to-SMV approach can be used as well. 

  • After reperfusion, hemostasis is obtained.

  • The proximal and distal ends of the intestinal graft are anastomosed to the proximal and distal ends of the remnant digestive track. Gastrostomy tube is placed for tube feeding. 

  • A loop ileostomy is created for postoperative endoscopic surveillance. 

  • The completed procedure is illustrated in the image below.

  • Isolated intestinal transplant. A gastrostomy tube Isolated intestinal transplant. A gastrostomy tube, jejunostomy tube, and loop ileostomy are in place.
  • Tension-free closure is necessary to prevent graft malperfusion. Mesh closure or staged closure approach are commonly utilized. 

  • Transplantation of the abdominal wall is also described.[30, 31]

Postoperative Care and Immunosupression

Induction therapy is initiated intraoperatively. The most commonly used agents are T-cell–depleting agents (thymoglobulin), interleukin 2 (IL-2) receptor antagonists (basiliximab), anti-CD52 (alemtuzumab).[32, 33] High-dose intravenous corticosteroid is also given in the operating room. Maintenance immunosuppressive regimens are combinations of tacrolimus, steroids, and mycophenolate.

Patients require intensive care unit (ICU) monitoring and frequent lab studies for close postoperative monitoring. 

Endoscopic surveillance and surveillance biopsies start in the first postoperative week and can be done as often as twice weekly. Tube feeding with low-fat formula is initiated if there is no immediate graft concern (usually after first endoscopy). Oral intake usually follows succesful initiation of tube feeds and is advanced gradually. 

The transplanted intestine initiates peristalsis immediately after reperfusion but in a less orderly fashion, because the graft does not have extrinsic innervation. Therefore, ultimate motility and functionality of the graft can be variable. 

The carbohydrate- and amino acid–absorptive capacity of the transplanted intestine normalize within the first several months. Fat absorption is impaired for several months following intestinal transplantation. Absorption of dietary lipids, which are primarily composed of long-chain triglycerides, depends on lymphatic drainage. Medium-chain triglycerides can be directly absorbed into the portal circulation. Consequently, supplemention of enteral feeds with medium-chain triglycerides is necessary for several months following transplantation. Intermittently supplementing the diet with intravenous fats and fat-soluble vitamins (vitamin D, E, A, and K) may be necessary until the intestinal lymphatics are reestablished.

Once patient reaches goal caloric intake via enteral route, total parenteral nutrition (TPN) is discontinued.

Follow-up

Once patients are discharged from hospital, the primary issues are as follows:

  • Nutritional status
  • Oral intake
  • Tolerance of tube feeds
  • Weaning from TPN
  • Keeping up with ileostomy losses
  • Hydration
  • Drain care
  • Surveillance endoscopies

Complications

Infectious Complications 

Patients undergoing intestinal transplant have higher incidence of infectious complications compared with other solid organ recipients due greater immunosuppression levels.[34, 35] Infectious complications and sepsis are the leading cause of death in intestinal transplantation patients, account for 48% of all deaths within 5 years of transplant [36] . An autopsy series found that even in cases in which sepsis was not the immediate cause of death, 94% of patients had a coexisting infection.

Posttransplant lymphoproliferative disease (PTLD) and graft rejection can lead to breakdown of the mucosal barrier, resulting in bacteremia or fungemia.[37]

The most common infectious organisms include Escherichia coli, Klebsiella, Enterobacter, staphylococci, and Enterococcus. A single-center study found the most common pathogens isolated were Pseudomonas (19%), Enterococcus (15%), and E coli (13%).[18]

Primeggia et al reported a 30-day postoperative infection rate of 57.5% and mean time to first infection of 10.78 ± 8.99 days.[18] The most common sites of infection were the abdomen, followed by the lungs, surgical site, and urinary tract.

Cytomegalovirus (CMV) infection reportedly occurs in 15-30% of patients receiving intestinal grafts and often involves the intestine allograft.[38] CMV disease is one of the most serious infections that can occur after a transplant because it can lead to graft loss and even death. The incidence of CMV disease is highest in CMV-negative recipients who receive CMV-positive grafts. For that reason, transplantation of isolated intestines from CMV-positive donors to CMV-negative recipients is often avoided.

Patients can be only viremic or may have tissue/organ disease. Patients with CMV enteritis usually present with fever, increased stoma output, and GI symptoms. Besides routine blood CMV tests, CMV inclusions are investigated in tissue samples (ie, surveillance biopsies from intestine). Endoscopy usually reveals ulcers and friable mucosa and histopathology confirms CMV inclusion bodies.

If CMV is diagnosed, the patient should be treated with therapeutic doses of ganciclovir. Foscarnet or CMV immunoglobulin (CytoGam) should be considered in case of ganciclovir resistance. Immunosuppression should be reduced until the CMV infection is controlled.

Epstein-Barr virus (EBV) is also a concern. The risk is higher in EBV-negative recipients who receive an EBV-positive graft. An acute EBV virus infection is typically associated with severe malaise and fever, flulike symptoms, increase of liver enzyme levels, splenomegaly, and lymphadenopathy. Relapse rates have been measured as high as 20%.[39]

Vascular Complications

Many patients with intestinal failure have prothrombotic state and prior episodes of thromboembolic events, and so are at high risk of having these complications. Early recognition is the key to save the graft. 

Post-transplant Lymphoproliferative Disorder

The incidence of PTLD is higher in intestinal transplant recipients than other solid organ transplant recipients. It occurs 2-4 times more often in children than in adults,[40] and the incidence is higher after multivisceral transplantation than isolated intestinal transplantation. Although PTLD tends to manifest in the first year after transplantation, it can occur any time.

Surveillance for PTLD should begin immediately following the transplant using in situ hybridization staining for EBV, and early RNA and EBV polymerase chain reaction (PCR) surveillance.

Two basic approaches exist to prevent PTLD: One is long-term prophylaxis with ganciclovir, valganciclovir, or intravenous immunoglobulin for 3-12 months. The other involves shorter period of prophylaxis (2–6 wk) followed by monthly surveillance and pre-emptive therapy should surveillance identify increased EBV replication.

In a study examining PTLD in pediatric intestinal transplants, Ramos et al found the highest incidence at 4 months post-transplant.[41] These authors found no correlation between immunosuppressant regimen used and PTLD rates, but did find an increased association between EBV- negative recipients receiving an EBV-positive graft.[41] In their cohort, fever was the most common manifestation of PTLD.[41]

Positron emission tomography (PET) scan can be helpful to identify the active lymph nodes, but confirmatory diagnosis and subtyping of lymphoma require biopsy. If the suspected organ is the intestine graft itself, differentiating PTLD from rejection or CMV infection can be difficult. Evaluating the serum for a typical monoclonal or polyclonal immunoglobulin band, which can sometimes be present, is also useful.

Gene studies are often helpful to identify abnormal karyotypes (eg, C-myc, N-ras, p53), which can aid in diagnosis and prognosis as well as to determine whether the abnormal lymphocytes sites are primarily B cells or T cells. Real-time PCR can also be used to detect changes in viral DNA levels. T-cell lymphomas are less common than B-cell lymphomas in PTLDs.

If the diagnosis of PTLD is made, immunosuppression should be reduced. Some cases may require additional therapies, including chemotherapy using R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or immunotherapy, depending on the subtype of the lymphoma. Radiotherapy may also be considered.[40]

Rejection

Rejection can occur at any time but is most common in the first year, particularly the first 6 months. Early diagnosis of allograft rejection, a major contributor to both the high morbidity and the high mortality associated with small-intestine transplantation, is essential. Intestinal graft rejection can manifest clinically as fever, abdominal pain, increased output from the ostomy, abdominal distention, acidosis, and malabsorption. It can also be asymptomatic.

To detect rejection, surveillance via endoscopy and intestinal biopsy through the ileostomy are used. A rise in the plasma citrulline level may also be indicative of rejection, although this is not commonly used at present.[42] Diagnosis can be difficult because of the patchy nature of rejection and the presence of bleeding.

In order to identify rejection in a timely manner, surveillance endoscopy of the entire graft is perfomed and random multiple biopsies are obtained.

Histologic evidence of allograft rejection includes mucosal necrosis and loss of villous architecture with transmural cellular infiltrate. Histopathology reveals crypt cell apoptosis, cryptitis or crypt loss, necrosis, and endotheliitis.

Treatment of rejection ranges from pulse corticosteroid administration to more aggressive immunosuppressive regimens, including repeat doses of antithymocyte globulin. 

If the rejection is refractory to treatment and donor-specific anti-HLA antibodies are detected, plasmapharesis and IVIG followed by rituximab and/or bortezomib can be used.[43]

Due to the immunologic properties of the liver itself, combined liver-intestine transplantation provides a greater protective benefit against rejection (ie, lower incidence and severity of acute rejection) than isolated intestinal transplantation does. 

Graft versus host disease

Graft versus host disease (GVHD) is a progressive, potentially fatal complication of intestine transplantation. It occurs in 7-9% of intestinal transplants,[44] more commonly in multivisceral transplants and pediatric patients. GVHD may be difficult to diagnose. Patients with acute GVHD usually present 1-8 weeks after transplantation with fever, leukopenia, diarrhea, or rash; therefore, full skin exam is extremely important. Maculopapular rash in the palms and soles is highly suspicious. Other symptoms may include malaise, anorexia, arthralgia, abdominal pain, or organ-specific issues (eg, liver enzyme elevation if the liver is involved).

Diagnosis should be confirmed by biopsy of the skin or suspected native tissue involved. A study by Crowell et al supported the practice of performing a sigmoidoscopy to examine and biopsy the native sigmoid to rule out GVHD.43

Once the diagnosis is confirmed, or if suspicion is high, treatment is promptly initiated with high-dose steroids and/or antithrombocyte globulin.

Outcome and Prognosis

Intestinal transplantation has much more complex immunologic alterations and requires higher immunosuppressive levels compared with other solid organ transplants. As a result, life-threatening opportunistic infections and other rare immunologic complications (eg, graft versus host disease [GVHD]) are more commonly seen in this population. With broader understanding of immonology, advances in immunosuppression, and advances in the management of all complications, patient and graft survival rates are much improved. 

Graft failure has declined since the late 1990s, but plateaued over the past decade, and early graft loss has increased in the past 2 years, notably in recipients of a combined liver and intestine allograft. In 2012‐2014, the 1‐ and 5‐year graft survival for intestine transplants with or without a liver was 81.1% and 60.8%, respectively, for recipients aged younger than 18 years and 68.9% and 44.7% for recipients aged 18 years or older. In 2012--2014, 1- and 5-year graft survival was 75.6% and 45.6%, respectively, for intestine recipients, and 72.4% and 57.5%, respectively, for intestine‐liver recipients.[1]

The incidence of first acute rejection in the first posttransplant year varies by age group and transplant procedure. Among recipients in 2017‐2018, the incidence of acute rejection was highest in pediatric intestine recipients (62.5%) and lowest in adult intestine‐liver recipients (25.9%) Among recipients in 2007‐2017, posttransplant lymphoproliferative disorder developed within 5 years posttransplant in 9.1% of intestine recipients and 7.7% of intestine‐liver recipients.  Patient survival for transplants in 2012‐2014 was similar by transplant type: 1‐ and 5‐year survival was 82.0% and 57.3% for intestine recipients and 77.6% and 63.2% for intestine‐liver recipients.[1]

Chronic rejection can occur up to 40% of cases. Refractory cases may require graft enterectomy. 

Rehospitalization is common. 

Although children may report improved quality of life after intestinal transplantation, such improvement is not guaranteed. In addition, intestinal transplantation does not necessarily lead to a quality of life comparable to that of other transplant recipients (eg, liver) or the general population.[45, 46, 47]

Future and Controversies

Major issues regarding intestinal transplant are:

  • High mortality in patients on the waiting list
  • Organ shortage
  • Very difficult balance between immunosuppression and immunosuppression-related complications (very high infection rates)
  • Other immune alteration–related complications (ie, GVHD, PTLD)

Cutting-edge research is being performed on topics such as regulatory T-cells, mesenchymal stem cells,[48] glucagon-like peptide 2 analogue for the treatment of short bowel syndrome,[49] intestinal adaptation after massive small bowel resection,[50] post-transplantation microchimerism, and tolerance. These studies offer the promise of changing the future of transplantation of the small bowel and other solid organs, minimizing complications and further improving outcomes.