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Intestine transplantation, intestinal transplantation, or small bowel transplantation is the immunosuppressive regiments, surgical technique, PN, and the clinical management of pre and post-transplant patients.
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 cyclosporine 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 cyclosporine. In the two decades since, intestine transplant efforts have improved tremendously in both volume and outcomes.[1][2]
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.[3] 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.[4] 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.[5][6] 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.[7] Natural SBS is mercifully rare, estimated to be 3 per 100,000 births.[8] 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.[9]
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.[3] 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.[5][10] Over long periods of time, PN can lead to numerous health conditions, including severe dehydration, catheter-related infections, and liver disease.[2][11] PN-associated liver disease strikes up to 50% of patients within 5–7 years, correlated with a mortality rate of 2-50%.[11]
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.[12] Nevertheless, a positive reception to either procedure may reduce the level of PN required, if not negate its required use altogether.[8][13]
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.[14][15] 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.[11][16]
Other
Receiving an organ transplant of any kind is a highly significant investment financially, but a successful, well-functioning transplant can be very cost-efficient relative to alternate therapies. Total charges to maintain PN at home can reach upwards of $150,000 a year, even though the actual cost of nutrition is typically only $18 to $22 a day.[5][14] This excludes the cost for additional home support, equipment, and the care of PN-related complications. The cost involved in undergoing intestinal transplantation, including the initial hospitalization for the transplant, can range from $150,000 to $400,000, and reoccurring hospitalizations are common up through the second year. Two to three years post-transplant, the financial cost of transplantation reaches parity with PN and is more cost-effective thereafter.[11][14]
The improvement to quality of life following an intestinal transplantation is significant. Of living patients 6 months after transplant, 70% are considered to have regained full intestinal function, 15% are at partial function, and 15% have had their grafts removed.[9][14] For those with full function, enteral nutritional autonomy is high.[7] The ability to resume regular activities such as the ability to consume food and exert control over digestive function is certainly a welcome return for patients. The low quality of life induced by intestinal failure is oftentimes further supplemented by significant psychosocial disability and narcotic dependence. Following transplantation, these have been found to generally decrease.[15] According to surveys comparing patients who have undergone transplants and those that have not, there seems to be a remarkable improvement for transplant recipients in such areas as anxiety, depression, appearance, stress, parenting, impulsiveness, optimism, medical compliance, and the quality of relationships.[14][15][31]
Several factors relating to superior patient and graft prognosis have proven to be statistically significant. Patients who have been admitted for transplant directly from home rather than the hospital, younger patients over one year of age, those receiving their first transplant, those receiving transplants at experienced transplant centers, and who receive antibody or sirolimus-based induction therapies have increased rates of survival.[9][15] Furthermore, underlying etiology,[29] the presence of comorbidity, the frequency of previous surgery, nutritional status, and the level of liver function have been found to affect patient-graft survival .[30] Patients with a pre-transplant diagnosis of volvulus were found to possess a lower risk of mortality.[29] As of 2008, the longest recorded surviving transplant survived for 18 years.[14] Between 1999 and 2008, 131 retransplant procedures were performed in the United States.[7]
[14] After 4 years, pediatric survival significantly worsens compared to adults.[15][14]. Very young (<1 year) and very old (>60 years) patients receiving a transplant have pronounced rates of mortality.morbidity 60%), depending on underlying disease and presurgical mean The five-year survival rate for patients and transplants ranges from 50 to 80% (overall [14] Intestinal transplant outcomes have improved significantly in recent years. Despite mild incongruities in survival rate percentages between centers in
Intestinal transplants are highly susceptible to infection even morso than the standard immunocompromised recipient of other organs due to the great composition and variety of the gut flora.[11] A complex assortment of microorganisms inhabits the human digestive tract, with concentrations of up to 104-107 CFU/mL in the jejunoileum and 1011-1012 CFU/mL in the colon.[28] While suppression of the immune system may prevent immune attack on the new allograft, it may also prevent the immune system’s ability to keep certain gut microbial populations in line. Despite pre and post-decontamination of the transplant, recipients are at risk of local and systemic infection by both natural and external flora. The common symptom of graft dysfunction, whether due to infection, rejection, or some other condition, is diarrhea.[15]
Intestinal transplantation is the least performed type of transplant due to a number of unique obstacles. The most major of these is the profound immunosuppression required due to the ability of the intestine to elicit strong immune responses. Because of exposure to a wide range of gut flora and material consumed by the body, the intestinal epithelium possesses a highly developed innate immune system and antigen-presenting abilities. Immunosuppression is the primary determinant of outcome in small bowel transplantation; the risk for graft rejection is increased by under-immunosuppression and for local and systemic infection with over-immunosuppression.[11] Ensuring an appropriate dose of immunosuppressant can therefore be difficult, especially as both cyclosporine (14-36%) and tacrolimus (8.5-22%) have generally low bioavailabilities.[27] A major problem due to immunosuppression in intestinal transplant patients is post-transplant lymphoproliferative disorder, in which B-lymphocytes excessively proliferate due to infection by EBV and result in infectious mononucleosis-like lesions.[7] Intestinal transplant recipients are also at risk for chronic renal failure because calcineurin inhibitors are toxic to the kidneys. A transplant recipient must remain on immunosuppressants for the rest of his or her life.[14]
It is ideal to commence enteral nutrition as early as possible following transplantation. Therefore, a feeding tube connecting to the stomach or jejunum is quickly placed to facilitate rehabilitation.[11] If gastrointestinal function is restored, a diet can be reestablished and cautiously advanced as tolerated. Most patients are weaned from PN within 4 weeks of transplantation, and nearly all are free from additional enteral supplementation by one year.[14] Evidence for the restoration of function includes decreasing gastrostomy tube returns and increasing gas and enteric contents in the ileostomy.[2] Routine surveillance endoscopy and biopsies via the ileostomy should be performed with decreasing frequency over several months to observe signs of rejection, ideally before clinical symptoms present themselves. Should the patient continue to perform well through the first post-transplant year, the ileostomy would generally be closed. Should rejection be suspected in the future, endoscopies would be performed and an appropriate antirejection therapy will be tailored. The median time for hospital discharge varies between procedures. The median times for isolated intestine, intestine-liver, and multivisceral transplants are 30, 60, and 40 days post-operation respectively.[14] Within the first several months, carbohydrate and amino acid absorptive capacity should normalize, followed by the absorptive capacity for fats. Once enteral nutrition is capable of providing all nutritional needs, PN can be discontinued.[2] Nearly all patients with a successful transplant are free of PN within one year.[14]
Following the procedure, the patient is actively monitored in an intensive care unit (ICU). Broad-spectrum antibiotics are administered, bleeding monitored, and serum pH and lactate levels measured for evidence of intestinal ischemia. The patient’s immune system is strongly modulated immediately post-operation. The initial phase of treatment consists of the administration of tacrolimus with corticosteroids to suppress T-lymphocyte activation. Next, various assortments of interleukin-2 (IL-2) receptor antagonists (daclizumab, basiliximab), anti-proliferation agents (azathioprine, mycophenolate mofetil), and the drugs cyclophosphamide and sirolimus are administered on an individual patient basis to further suppress the immune system.[11] The bioavailability of these drugs is dependent on intestinal surface area and transit time, and therefore the length of the allograft determines the immunosuppression regiment.[2] Intravenous administration of prostaglandin E1 is occasionally performed for the first 5 to 10 days following transplant to improve intestinal circulation and a potential dispensing of immunosuppressive effects.[2][11] The gut is selectively decontaminated against high-risk flora and preventative care is taken against CMV and fungal infections.[11]
[11], pancreas, and duodenum during a multivisceral transplant can reduce the risk of additional complications related to these structures.spleen Preservation of the native [18] When a liver is being transplanted in conjunction with the intestine, the recipient must first have their own
First, any abdominal infrarenal vena cava.,[15] but may also be drained portally into the hepatic portal or superior mesenteric vein.[17] The graft is then reperfused with blood and any bleeding is stopped before the proximal and distal ends of the transplant bowel are connected to the original digestive tract. A loop ileostomy is then created as to provide easy access for future endoscopic observation and biopsies. A gastronomy or jejunostomy feeding tube may be placed before the abdominal wall is closed.[2]
Once donor preparation is accomplished, procurement can begin by utilizing the same standard techniques for all abdominal organ procurements. The team exposes the abdominal cavity and inserts two drained of blood, flushed with cool preservation solution, and removed from the body.[2][18] In an isolated intestinal transplant, the colon will be detached from the small intestine. The cecum and ascending colon are devascularized, while care is taken to preserve major vasculature in the ileum. The jejunum will be separated from the duodenum while preserving the vasculature of the jejunum, ileum, mesentery, and the pancreas. If healthy, the pancreas can oftentimes be retrieved as an additional isolated procurement. The intestinal allograft, when ready to be extracted, is attached by the mesenteric pedicle, where the vessels converge out of the intestinal system. This pedicle will be stapled closed, and can be separated from the body via a transverse cut to create a vascular cuff. The complete intestinal allograft can then be removed and wrapped in a surgical towel.[18] The protocols for combined liver and multivisceral procurements are far more complicated and meticulous than isolated intestine alone.
Following matching of the organ, the complicated procurement of the small bowel can be performed by a team of abdominal transplant surgeons. Once a donor has been selected and approved for donation, several pretreatments may be initiated to destroy immune cells. The donor intestine must be decontaminated with several antibiotics, including neomycin, erythromycin, amphotericin B, and cephalosporin.[18] They may also be treated with anti-lymphocyte antibodies (anti-thymocyte globulin, alemtuzumab), irradiation directed against excessive mesenteric lymphatic tissue, and have their bowel irrigated.[17]
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 waitlist, 94% of whom were U.S. citizens.[7] Regardless of transplant type, over half of new registrants are 5 years of age or younger. Adults compromise the next largest cohort, followed by pediatric patients aged 6 and older. In 2008, the ethnic composition of the intestinal transplant waitlist was 65% White, 18% Black, 16% Hispanic, 1% Asian, and 0.5% other or mixed race, resembling the demographics of the American general population at the time aside from a below-average Asian cohort. ABO blood types also matched the general population, with 31% A, 14% B, 5% AB, and 50% O.[7] In 2004, the average waiting period to receive a transplant was 220 days,[21] with a median of 142 days in 2008.[7] The rate of waitlist additions has shifted from year to year; gains increased until 2006 (with 317 added), but then decreased in 2012 (to 124 added).[26] In 2007, only 9% of patients on the U.S. waitlist died while waiting for a transplant.[7] Waitlist mortality peaked around 2002 and was highest for liver-intestine (pediatric) patients. Deaths among all pediatric groups awaiting intestine-liver transplants have decreased in the years leading up to 2014 whereas adult intestine-liver deaths have dropped less dramatically. The decrease in recent years is likely due to improved care of infants with intestinal failure and subsequently a decrease in referrals for transplant.[26] Although many improvements have been made in the States, outcomes everywhere still demonstrate much room for improvement. Worldwide, 25% of pediatric patients on the waitlist for an intestinal transplant die before they can receive one.[8]
[8], cannot find a transplant due to the lack of size-matched donors.kg, particularly those weighing less than 5 children Furthermore, many young, small [9] 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.[11] 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 [9] 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.
[2] To ensure proper histocompatibility, tissue quality, and safety from infection,
[25] Organ rejection is the unfortunate circumstance of the host
organ rejection by the body is all but certain.
There are three major types of intestine transplants: an isolated intestinal jejunum and ileum are transplanted.[18] 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 intraabdominal tumors that have not yet metastasized, extensive venous thrombosis or arterial ischemia of the mesentery, and motility syndromes.[11][17]
[14] for intestine transplantation; desperate terminal patients may accept a transplant from a HIV-positive donor if they are willing to expose themselves to HIV.relative contraindication HIV infection is a [17]
Magnetic resonance imaging, Positron emission tomography, Projectional radiography, Tomography, Neuroimaging
Image, YouTube, Esophagogastroduodenoscopy, Respiratory tract, Bronchoscopy
World wide web, Dermatology, Urology, Vascular surgery, Radiology
Stomach, Latin, Duodenum, Greek language, Liver
Medical imaging, Liver, Endoscopy, University of Pittsburgh, Stomach
Medicine, University of Illinois Medical Center, Immunology, Fish, Psychiatry
Medical imaging, Rectum, Endoscopy, Abdomen, Perineum
Medical imaging, Surgery, Endoscopy, Emergency medicine, Stomach
New York City, Bone grafting, Skin grafting, Hiv, Hepatitis B