The small intestine (jejunum to ileum) makes up the graft in an ITx. But in any particular recipient, the small intestine can be combined with the liver or with any of the abdominal viscera, including the abdominal wall if necessary (according to the “cluster” concept originally proposed by Starzl [2]). Therefore, the small intestine can be transplanted in isolation (an isolated intestinal transplant, or I-ITx), in combination with part or all of the liver (a liver–intestine transplant, or L-ITx), in combination with the stomach, liver, duodenum, and pancreas, all commonly transplanted en bloc, especially in small children (a multivisceral transplant, or MVTx), or in combination with the stomach, duodenum, and pancreas—excluding the liver (a modified MVTx). In addition, in certain recipients, the colon and/or part of the abdominal wall have been added. The use of living donors, though limited to specific centers in the USA, has been shown to be an effective option in ITx recipients.

The fundamental basis for an ITx is failure of the small intestine to maintain life with enteral intake. Short-bowel syndrome (SBS), a term often used synonymously with intestinal failure, refers to a malabsorptive state that results from an anatomical deficiency of the small intestine. SBS may also be functional in nature, where there is adequate length but poor function.

Etiology

In infants, intestinal failure is frequently caused by anatomical SBS. Most infants who undergo extensive resection of the small intestine now survive. The common congenital defects resulting in anatomical SBS are gastroschisis, intestinal atresia, and malrotation [3,4]. The improved survival of premature infants has resulted in a proportional increase in the number of infants whose SBS is due to resection for necrotizing enterocolitis. Other than anatomical SBS, intestinal failure is also caused by diffuse neuromuscular dysfunction, such as the total aganglionic form of Hirschsprung disease. In children and adults, a less frequent cause of intestinal failure is hollow visceral myopathy and neuropathy, resulting clinically in pseudo-obstruction. Diffuse mucosal disease (e.g. microvillus inclusion disease) is fatal without treatment; malabsorption can occur with polyposis [5].

In adults, the most common underlying cause of SBS is small-intestinal Crohn disease [6]. Other causes include a mesenteric vascular event such as arterial or venous thrombosis, arterial embolism, midgut volvulus, or other complications of surgery; extensive resection after trauma or after tumor removal; and radiation injury. Increasingly, complications after bariatric surgery, particularly after Roux-en-Y gastric-bypass procedures, are a cause of SBS [7].

Parenteral nutrition (PN) can be a lifesaving therapy for patients with intestinal failure. However, in PN patients, the liver may develop steatosis or cholestasis. In infants with SBS who are on chronic PN, cholestasis is more likely than steatosis. Liver disease is multifactorial and is associated with repeated sepsis; it may progress to liver failure. In children, clear progress in the management of SBS has occurred, so increasing numbers have been successfully weaned off PN. Surgical procedures to lengthen the small intestine have been developed, most notably the operation popularized by Bianchi [8] and the more recently described serial transverse enteroplasty (STEP) [9]. PN-related liver disease has been reversed by manipulating PN, specifically by lowering the amount of intravenous lipid infused daily and by changing to or adding a fish oil-based lipid preparation rich in omega-3 fatty acids [10].

A short segment of remaining small intestine, an absence of the ileocecal valve and colon, and severe dysmotility all are predictive of a poor outcome in patients with SBS; the level of the amino-acid citrulline has proven to be surrogate marker of small-intestinal function [11].

Prevalence

The exact prevalence of intestinal failure is unknown. Home PN Registry data, widely quoted, from 1992 show that about 40 000 patients required PN each year at that time in the USA [12]. An Italian study estimated that 2.5 in every million children had intestinal failure [13]. Of course, the use of PN does not imply intestinal failure in every case, and most cases of SBS do not result in intestinal failure.

An ITx is considered a rescue therapy with broad indications, as recognized by the US Centers for Medicare and Medicaid Services (CMS); these indications include development of progressive liver disease, loss of central-line access with thrombosis at two or more major line sites, recurrent episodes of dehydration despite intravenous therapy, and systemic fungal infection [7].

Ultimately, the need for an ITx will be determined by the individual patient’s underlying intestinal pathology and size. Another key factor is whether or not a liver transplant is also required. For instance, in the case of pseudo-obstruction, repeated sepsis and loss of line sites are likely, so either an I-ITx or a modified MVTx may be necessary. Alternatively, in a small infant with SBS and progressive liver disease, the appropriate transplant is most likely an MVTx.

Clear contraindications to an ITx include systemic infection, preexisting severe neurological dysfunction, and the presence of malignancy. Severe cardiac dysfunction, whether acute or chronic, may also be a contraindication. Immune deficiency will present challenges. Age is not a usual limitation, but the overall health of the patient and their ability to tolerate an ITx are of importance. Patients with intestinal failure who live at home before being hospitalized for their transplant, as compared with inpatients, have a better outcome [7].

Evaluation of ITx candidates is based on similar protocols developed for other abdominal organ-transplant candidates and overlaps with protocols for liver-transplant candidates. In particular:

• In all ITx candidates, nutritional deficiency must be addressed.
  
• Detailed imaging of the intraabdominal vascular and enteric anatomy with computed tomography (CT) or magnetic resonance imaging (MRI) is a prerequisite, as is assessment for patency of central venous access sites.
  
• A liver biopsy and assessment for portal hypertension should be considered.
  
• ITx candidates with a history of vascular thrombosis should be evaluated for a procoagulant state.

The overriding principle for graft selection is to obtain a match with the recipient, both immunologically and physically. In the prospective donor, a history of gastrointestinal disorders and abdominal operations should be fully evaluated. Before graft procurement, the donor’s cardiovascular integrity, perfusion, and the degree of ischemia should be estimated. The presence of bowel sounds, documentation of a bowel movement, and the absence of blood in the stool are reassuring for intestinal integrity. Because most ITx recipients have a loss of abdominal domain due to prior surgeries, donors are usually selected whose weight is around 50–60% of the recipient’s [14]. In most cases, vascular conduits are necessary; the need for them must be anticipated and agreed to with the other procurement teams preoperatively. The descending thoracic aorta, subclavian artery, and carotid artery may be useful when the iliac vessels are required by the liver and pancreatic procurement teams. Similarly, any pretreatment of the donor with Thymoglobulin, as is the practice in some centers, must be agreed to in advance with the other procurement teams.

The donor operation commences with a midline incision from the xiphisternum to the symphysis pubis. In general, the distal abdominal aorta is cannulated for flushing with University of Wisconsin (UW) solution. In I-ITx procurement, cannulation of the inferior mesenteric vein should be avoided, because it can cause graft edema due to outflow obstruction. The supraceliac aorta is encircled in preparation for crossclamping—taking care, in pediatric donors, to do so as proximally as possible, in order to use the descending thoracic aorta for necessary conduits.

I-ITx procurement

In the warm phase of I-ITx graft procurement, careful dissection is carried out at the base of the mesentery; the portal vein and superior mesenteric artery (SMA) are dissected just below the pancreatic uncinate process. Doing so makes it possible to use separately, from the same donor, both the pancreas and the small intestine. The small intestine is stapled just below the ligament of Treitz; distally, the colon is stapled at the level of the left branch of the middle colic vessel. If the pancreas is not to be procured as a separate graft for another recipient, I-ITx procurement is much easier. The SMA can be circled at its origin after a Catell maneuver and after a Kocher maneuver; then, after a cold flush, the pancreatic neck can be bisected and the intestine removed.

Procurement of other organs

After dissection of the vessels as already described, the tail of the pancreas and the spleen are mobilized from the retroperitoneum, taking care to avoid injury to the superior mesenteric vessels or to the inferior pancreaticoduodenal arcade. The proximal duodenum is then dissected and divided at the level of the pylorus. A Carrel patch containing origins of the celiac trunk and SMA is taken with a wide margin, so that an aortic conduit can be used if required. The entire pancreas, spleen, small intestine, and liver are removed en bloc with an intact inferior vena cava (IVC) and duodenum. For an MVTx, the stomach is taken as well; for a modified MVTx, the liver is left.