intestine transplantation intestine transplantation intestine transplantation (intestinal transplantation, or small bowel transplantation) is the surgical replacement of the small intestine for chronic and acute cases of intestinal failure. while intestinal failure can oftentimes be treated with alternative therapies such as parenteral nutrition (pn), complications such as pn-associated liver disease and short bowel syndrome may make transplantation the only viable option. one of the rarest type of organ transplantation performed, intestine transplantation is becoming increasingly prevalent as a therapeutic option due to improvements in immunosuppressive regimens, surgical technique, pn, and the clinical management of pre and post-transplant patients. intestine transplantationresected diseased ileum. the prior removal of sections of small intestine for treatment of precursor conditions is the primary cause of short bowel syndrome (sbs), the leading cause of intestinal transplantation.other namessmall bowel transplantationicd-9-cm46.97 history intestine transplantation dates back to 1959, when a team of surgeons at the university of minnesota led by richard c. lillehei reported successful transplantation of the small intestine in dogs. five years later in 1964, ralph deterling in boston attempted the first human intestinal transplant, albeit unsuccessfully. for the next two decades, attempts at transplanting the small intestine in humans were met with universal failure, and patients died of technical complications, sepsis, or graft rejection. however, the discovery of the immunosuppressant ciclosporin in 1972 triggered a revolution in the field of transplant medicine. due to this discovery, in 1988, the first successful intestinal transplant was performed in germany by e. deltz, followed shortly by teams in france and canada. intestinal transplantation was no longer an experimental procedure, but rather a life-saving therapy. in 1990, a newer immunosuppressant drug, tacrolimus, appeared on the market as a superior alternative to ciclosporin. in the two decades since, intestine transplant efforts have improved tremendously in both number and outcomes. pre-transplant diagnoses and short bowel syndrome failure of the small intestine would be life-threatening due to the inability to absorb nutrients, fluids, and electrolytes from food. without these essential substances and the ability to maintain energy balances, homeostasis cannot be maintained and one's prognosis will be dismal. causes of intestinal failure may be clinically complex, and may result from a combination of nutritional, infectious, traumatic, and metabolic complications that affect ordinary anatomy and physiology. many underlying conditions that serve as precursors to failure are genetic or congenital in nature. for example, severe inflammation, ulceration, bowel obstruction, fistulation, perforation, or other pathologies of crohn's disease may severely compromise intestinal function. despite the danger these conditions may pose in themselves, they may lead to even further, more serious complications that necessitate replacement of the diseased intestine. the single leading cause for an intestinal transplant is affliction with short bowel syndrome, oftentimes a secondary condition of some other form of intestinal disease. short-bowel syndrome was the cause for 73% of american intestinal transplantations in 2008, followed by functional bowel problems for 15% and other causes representing 12% of cases. natural sbs is mercifully rare, estimated to be 3 per 100,000 births. surgical removal is the most common cause, performed as a treatment for various gastroenterological and congenital conditions such as crohn's disease, necrotizing enterocolitis, mesenteric ischemia, motility disorder, omphalocele/gastroschisis, tumors, and volvulus. alternative treatments prescription parenteral nutrition formulation. regardless of the underlying condition, the loss of intestinal function does not necessarily necessitate a transplant. several conditions, such as necrotizing enterocolitis or volvulus, may be adequately resolved by other surgical and nonsurgical treatments, especially if sbs never develops. an individual can obtain nutrients intravenously through pn, bypassing food consumption entirely and its subsequent digestion. long-term survival with sbs and without pn is possible with enteral nutrition, but this is inadequate for many patients as it depends on the remaining intestine's ability to adapt and increase its absorptive capacity. although more complicated and expensive to perform, any person may receive pn. although pn can meet all energy, fluid, and nutrient needs and can be performed at home, quality of life can be significantly decreased. on average, pn takes 10 to 16 hours to administer but can take up to 24. over this time frame, daily life can be significantly hindered as a consequence of attachment to the iv pump. over long periods of time, pn can lead to numerous health conditions, including severe dehydration, catheter-related infections, and liver disease. pn-associated liver disease strikes up to 50% of patients within 5–7 years, correlated with a mortality rate of 2–50%. another alternative treatment to transplant for patients with sbs is surgical bowel lengthening via either serial transverse enteroplasty (step) or the older longitudinal intestinal lengthening and tailoring (lilt) technique. although both procedures contribute to an approximate 70% increase in length, step appears somewhat more favorable in terms of lower mortality and progression to transplant. nevertheless, a positive reception to either procedure may reduce the level of pn required, if not negate its required use altogether. indications there are four medicare and medicaid-approved indications for intestine transplantation: a loss of two of the six major routes of venous access, multiple episodes of catheter-associated life-threatening sepsis, fluid and electrolyte abnormalities in the face of maximal medical therapy, and pn-associated liver disease. transplants may also be performed if the growth and development of a pediatric patient fails to ensue, or in extreme circumstances for patients with an exceptionally low quality of life on pn. a multidisciplinary team consisting of transplant surgeons, gastroenterologists, dieticians, anesthesiologists, psychiatrists, financial representatives, and other specialists should be consulted to evaluate the treatment plan and ensure transplantation is the patient's best option. psychological preparations should be made for the transplant team and patient as well. early referral requires trust between all parties involved in the operation to ensure that a rush to judgment does not lead to a premature transplant. other absolute contraindications to receiving an intestinal transplant include the presence of systemic and untreated local infections, malignant cancer, severe neurological impairment, and severe cardiac and/or pulmonary disease. these criteria are similar to established guidelines for transplants of other organ types. hiv infection is a relative contraindication for intestine transplantation; desperate terminal patients may accept a transplant from a hiv-positive donor if they are willing to expose themselves to hiv. transplant types there are three major types of intestine transplants: an isolated intestinal graft, a combined intestinal-liver graft, and a multivisceral graft in which other abdominal organs may be transplanted as well. in the most basic and common graft, an isolated intestinal graft, only sections of the jejunum and ileum are transplanted. these are performed in the absence of liver failure. in the event of severe liver dysfunction due to pn, enzyme deficiencies, or other underlying factors, the liver may be transplanted along with the intestine. in a multivisceral graft, the stomach, duodenum, pancreas, and/or colon may be included in the graft. multivisceral grafts are considered when the underlying condition significantly compromises other sections of the digestive system, such as intra-abdominal tumors that have not yet metastasized, extensive venous thrombosis or arterial ischemia of the mesentery, and motility syndromes. pre-operative period donated intestines, like all organs, should be matched to a recipient prior to recovery, as to prepare him or her and minimize the time the organ spends outside the body. potential recipients are placed on the international intestinal transplant registry (itr), where they contribute to the world's growing understanding of intestine transplantation. before a transplant may be performed, an organ must first be located. in the united states, the matching of all organs is coordinated by the united network for organ sharing (unos). the standard intestinal donor is deceased with a diagnosis of brain death. in terms of transplant outcomes, brain-dead donors are highly preferable to donors who have suffered cardiopulmonary death. if respiration can be assisted by a ventilator, brain-dead donors may exhibit maintainable cardiac, endocrine, and excretory function. if appropriately managed, the continuation of blood flow and bodily metabolism allows for healthier organs for procurement and additional time to prepare recipients for transplant. furthermore, terminal ileum recovery from living donors is possible., and a laparoscopic technique is being developed to harvest limited sections of small bowel from living donors. when determining potential donor-recipient matches, important characteristics include donor size, age, tissue quality, and abo and histo-compatibility. if the intestine is too large, it may be not transplantable into young or small patients. ideally, intestines should be selected from donors of lighter weight than the proposed recipients to ensure simple closure of the abdominal wound. if a patient is too young or too old, they may not be hardy enough to survive the operation and recovery period. if the donor and recipient organs do not meet compatibility requirements, the threat of organ rejection by the body is all but certain. organ rejection is the unfortunate circumstance of the host immune system recognizing the transplanted organ as foreign. this is the most notable complication facing transplant recipients. through t-cell receptors, t-lymphocytes are able to distinguish between self and non-self by recognizing human leukocyte antigens (hla) bound to the major histocompatibility complex (mhc) protein located on the surface of organ cells. once identified as foreign, the immune system proceeds to destroy the transplanted tissue. the panel-reactive antibody (pra) test measures the proportion of the population to which a recipient will react via pre-existing antibodies to various hla antigens; in other words, how likely a patient is to acutely reject their new transplant. therefore, it is essential that hla and pra statuses are tested for and demonstrate low immunoreactivity of the patient to the graft. in some cases, a recipient may suffer from graft-versus-host disease, in which cells of the transplanted organ attack the recipient's cells. to ensure proper histocompatibility, tissue quality, and safety from infection, blood work should be collected and tested in the laboratory. in addition to hla and pra typing, the complete blood count (cbc), coagulation profile, complete metabolic panel, and abo blood group determination tests should be performed for both the donor and recipient. abo-incompatible grafts can sometimes be performed on very young pediatric patients, as their immune systems have not fully developed and for whom waiting list mortality remains high. additionally, blood serum should be tested for the presence of viruses, including hiv, hepatitis b and c, cytomegalovirus (cmv), and epstein–barr virus (ebv) antibodies to prevent infection. particularly in the immunocompromised system necessitated by the transplant, these viruses can wreak havoc on the body and become extremely dangerous, even fatal. even with healthy physiological levels, abo and hla compatibilities, and no signs of bacterial, viral, and fungal infections, organ transplantation is not without extrasurgical risk. waitlist and donation outcomes a major challenge facing the intestinal transplant enterprise is meeting the need for transplantable intestines, particularly in the united states where the majority of intestinal transplants take place. there exists a narrow timeslot between procurement and transplantation that any organ remains viable, and logistical challenges are faced regarding bringing organ and recipient together. during procurement, organs that are being recovered are cooled and perfused with preservation solution. this slows organ activity and increases the time they remain viable for transplant. although chilling and perfusion may extend intestinal lifespans by several hours, failure is still imminent unless transplanted. this duration between the cooling of the organ during procurement and the restoration of physiological temperature during implantation is the cold ischemic time. due to the sensitivity of the intestine to ischemic injury, many potential donor intestines are lost to the events following brain death and trauma. furthermore, irreversible intestinal damage is seen after approximately only 5 hours of cold ischemia in the form of mucosal damage and bacterial translocation outside the gastrointestinal tract. therefore, ensuring cardiac survival and nearby donor-recipient proximity before procurement are essential so organs do not wait too long outside the body and without blood flow. not only is there a lack of transplantable intestines, but a deficiency in the number of centers possessing the capability to carry out the complicated transplant procedure as well. as of 2005, there were only 61 medical centers in the world capable of executing an intestinal transplant. furthermore, many young, small children, particularly those weighing less than 5 kg, cannot find a transplant due to the lack of size-matched donors. despite these challenges, obtaining an intestine for transplant is rather probable in the united states. in 2008, there were 212 people on the u.s. intestinal transplant