Organ Transplantation

Genetic relationship between the donor and the recipient. Physicians should remember that allografts and xenografts require immunosuppression; otherwise, they will fail because of rejection.

Autograft describes tissue transfer within the same individual (e.g., skin graft).

Isograft describes tissue transfer between genetically identical individuals (e.g., identical twins).

Allograft describes tissue transfer between genetically nonidentical members of the same species (includes living related donor and cadaver donor human transplants). Immunosuppression is required.

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Xenograft describes tissue transfer between different species. Immunosuppression is required.

Surgical position

Orthotopic. The old organ is removed, and the new one is placed in the same position.

Heterotopic. The new organ is placed in a different position.

C Donors

Cadaver donors are individuals with severe brain injury resulting in brain death, which is defined as complete irreversible cessation of all brain function, including the brain stem.

Diagnosis. The mainstay of diagnosis is the neurologic examination, which must demonstrate unresponsiveness, absence of spontaneous movement, and absence of reflexes from the brain stem and higher. Also:

The patient must be normothermic.

Depressant drugs (especially barbiturates) must not be present.

An apnea test result must be negative (i.e., no respiratory effort despite a high arterial carbon dioxide level).

Electroencephalogram (EEG) and cerebral blood flow studies are optional.

Causes. Cerebrovascular disease is most common, followed by trauma.

Exclusions. Disseminated or uncured extracranial cancers, sepsis, or poor organ function.

Living donors are individuals motivated by altruism.

Types of living donors

Living unrelated donors on average share no more genes with a recipient than a cadaver donor. An example is the patient's spouse.

Living related donors share a substantial portion of their genomes with the recipient.

Requirements. Living donors must be in almost perfect health, have normal function of the organ under consideration, and be good candidates for anesthesia and the operative procedure. The workup

includes:

ABO typing, tissue typing, and cross matching (see I F)

Complete history and physical examination; chest radiography; ECG; complete blood count; sequential multiple analysis (SMA) for 6 and 12 serum tests (SMA-6, SMA -12); 24 -hour creatinine clearance and protein; RPR test; serology for hepatitis B and C, CMV, and HIV; urinalysis; PPD

For renal donors, arteriography and intravenous pyelogram (now combined as a helical computed tomography [CT] scan).

Risks. Perioperative mortality for living kidney donors is 0.03% (3 per 10,000). A living donor provides one kidney, and the remaining kidney hypertrophies and achieves 80% of creatinine clearance before donation. Newer procedures include donation of the left lateral segment or a lobe of the liver and segment(s) or lobe(s) of the lung. In these procedures, the safety of the donor is not assured. Although, traditionally, most living kidney donations are performed as an open surgical procedure, there is increasing experience with laparoscopically performed nephrectomy. This method potentially offers the advantage of minimally invasive surgery while still producing an excellent kidney.

D Removal of the donor organ

The donor organ is removed in a formal surgical procedure, wherein the blood supply of the organ is controlled and then the organ is rapidly flushed with a cold (4 °C) solution to render it cold and ischemic. All organs are more tolerant of cold ischemia than warm (normothermic) ischemia.

E

The practical limit of cold ischemia with current preservation methods is 4 hours for the heart, 6 hours for a lung, 12 hours for the liver, 36 hours for the pancreas, and 40–48 hours for a kidney. As the limit is approached or passed, the risk increases for delayed function, damage, or nonfunction of the organ.

F

The immunologic compatibility of the donor and recipient influences the outcome for any type of organ transplant (Table 24 -1).

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TABLE 24-1 Effects of Immunologic Compatibility on Transplant Outcome

HLA, human leukocyte antigen; PRA, panel-reactive antibody.

ABO blood group compatibility. The same rules apply as for red blood cell transfusions.

Cross -match compatibility must be present for kidney, pancreas, and some heart transplants. The recipient's serum is tested for the presence of cytotoxic antibodies directed against surface antigens (usually antihuman leukocyte antigen [HLA]) on the T lymphocytes of the donor. If antidonor cytotoxic antibodies are present, the donor is unacceptable because the recipient's antibodies will immediately attack the new kidney and rapidly destroy it (hyperacute rejection; see I G 1).

A positive cross match is positive for the presence of preformed antidonor antibodies in the serum of the prospective recipient and precludes transplantation between that donor and the recipient.

A negative cross match (i.e., absence of antidonor antibodies) is mandatory before the transplant.

A few patients have antibodies against most other humans (so-called high panel -reactive antibody [PRA] patients). High-PRA patients have formed antibodies against a high proportion of a panel of human cells, which is used to screen for reactivity; therefore, acceptable donors are difficult to find. Also, high-PRA patients are at higher risk for early graft failure.

Human leukocyte antigen (HLA). These are the histocompatibility antigens and are defined by tissue typing.

Six human HLA genes (HLA -A, -B, -C, -DR, -DP, and -DQ) are located on chromosome 6.

HLA -C, -DP, and -DQ are not believed to be important in clinical transplantation.

The contents of each chromosome 6 is a haplotype, and all humans have two of these chromosomes —one from the mother and one from the father. Therefore, six HLA antigens are defined by tissue typing (i.e., two each for HLA -A, -B, and -DR).

HLA -A and -B have more than 40 defined types, which are designated numerically. HLA -DR has more than 10 defined types. An example of an HLA type is HLA -A2, 27; B1, 44; DR 3, 7. An example of a haplotype is HLA -A2; B1; DR7.

G Rejection

The three types of rejection are hyperacute, acute, and chronic.

Hyperacute rejection occurs when the serum of the recipient has preformed antidonor antibodies. These antibodies adhere to and kill endothelium, which results in rapid graft infarction (within 24 hours). Because hyperacute rejection can be predicted by a positive cross match (see I F 2 a), it is avoidable. However, once hyperacute rejection begins, it cannot be treated.

Acute rejection is a cell -mediated immune response initiated by helper T cells. The pace of proliferation of alloreactive T cell clones dictates that acute rejection usually occurs after the sixth

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post-transplant day. In some cases, a memory immune response can trigger cellular rejection sooner.

The diagnosis is usually made via the detection and workup of graft dysfunction, culminating in a biopsy.

Acute rejection is treatable and reversible by a short course of high-dose immunosuppressive drugs.

When acute rejection is refractory to treatment or recurs, graft failure can result.

Acute rejection usually takes place within 3 months of transplant and rarely occurs after 1 year, unless triggered by an event such as infection or lack of adequate immunosuppression.

Chronic rejection usually occurs late. It has an insidious onset and is multifactorial, with both the cell - mediated and humoral arms of the immune system involved. Chronic rejection is poorly understood and therefore not treatable or reversible.

H Immunosuppression (Table 24-2)

Almost all allografts require indefinite suppression of the recipient's immune system to prevent rejection. This is in contrast to tolerance, in which the recipient's immune system responds normally to all antigens except those of the donor (i.e., the donor antigens are “tolerated”).

Immunosuppression attempts to disable or destroy components of the immune response (typically lymphocytes).

Conventional immunosuppression is created by drug therapy; administration of biologic reagents (sera); and, rarely, radiation therapy.

Multiple drug therapy is standard and aims for synergistic immunosuppression while minimizing the side effects.

Immunosuppression can be loosely classified into three types: induction regimens, antirejection regimens, and maintenance therapy.

Induction regimens aim to avoid rejection and establish good graft function within the first two posttransplant weeks. Induction regimens use an antilymphocyte serum plus part of the maintenance regimen (see I H 2 c), withholding one drug to avoid unwanted side effects.

The nephrotoxicity of cyclosporine and tacrolimus is of particular concern after any transplant.

Impaired healing of the bronchial anastomosis from high-dose steroids is disadvantageous after lung transplantation.

Antirejection regimens are high-dose, short-term (<3 weeks) treatments aimed at reversing acute rejection episodes. These regimens include high-dose (pulse) corticosteroids, typically methylprednisolone, antilymphocyte sera, or monoclonal antibodies.

Maintenance therapy provides long-term immunosuppression to prevent rejection. These regimens usually include two or three drugs. The principal drugs are cyclosporine or tacrolimus. One of these is combined with a corticosteroid (e.g., prednisone), and a third drug may be added. More recently, coritcosteroids have been eliminated from maintenance regimens.

Corticosteroids have broad anti -inflammatory and immunosuppressive effects. Generally, they inhibit all types of leukocytes, in contrast to the other immunosuppressive drugs, which are more lymphocyte selective.

Methylprednisolone is used intravenously for induction or antirejection therapy.

Prednisone or prednisolone is given orally as maintenance therapy. With good bioavailability, drug levels are not needed.

Side effects are common and include obesity, cushingoid facies, poor wound healing, atrophic skin, striae, and acne.

In contrast to the prevalent side effects, complications include diabetes, hypertension, osteoporosis, aseptic necrosis (usually of the hips), cataracts, peptic ulcer disease, and psychiatric disturbances. These broad complications have led many centers to successfully eliminate steroids from maintenance protocols.

Calcineurin inhibitors have become the mainstays of most immunosuppressive regimens owing to their superior effectiveness. These drugs block the calcineurin -dependent pathway

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of helper T -cell activation, thus blocking transcription of cytokine genes that initiate and amplify the immune response. This mechanism is more specific for the alloimmune response to an organ allograft than the older drugs (e.g., corticosteroids, azathioprine). Therefore, lower doses of other immunosuppressive drugs can be used, the incidence and severity of rejection are decreased, and outcomes are improved. They are typically used for maintenance therapy.

TABLE 24-2 Immunosuppressive Drugs

Cyclosporine dosing is adjusted to achieve a desired trough blood level because bioavailability is low and varies greatly.

Toxicity includes nephrotoxicity, hypertension, neurotoxicity, hirsutism, gingival hyperplasia, and hyperlipidemia.

At appropriate levels, cyclosporine does not cause progressive deterioration in renal function.

Tacrolimus (FK-506) is more potent than cyclosporine. Dosing is done by trough levels. Toxicity is similar to cyclosporine without hirsutism, hyperlipidemia, and gingival hyperplasia but with headache, diarrhea, and an increased risk of diabetes.

Antimetabolites are drugs that inhibit purine or pyrimidine metabolism, thereby inhibiting rapidly dividing cells, including clonally proliferating alloreactive T cells. They are usually used as third maintenance immunosuppressants with corticosteroids and a calcineurin inhibitor.

Azathioprine is a purine metabolism inhibitor. Toxicity causes leukopenia.

Mycophenolate mofetil is a purine metabolism inhibitor that appears to be more lymphocyte specific than azathioprine. When used as a third drug, the incidence of acute rejection is significantly decreased. Toxicity includes reversible bone marrow suppression and gastrointestinal side effects.

Antilymphocyte sera are biologic agents derived from animals immunized against human determinants. Two agents that are used for either induction or antirejection therapy are muromonab CD3 (OKT3) and antithymocyte globulin (ATG). Muromonab CD3 is a murine monoclonal immunoglobulin (IgG) to an antibody that binds to the CD3 antigen on human T cells. Antithymocyte globulin is a polyclonal antilymphocyte serum harvested from horses or rabbits, which depletes T cells.

Interleukin-2 (IL-2) receptor blockers. Two IL -2 receptor blockers have been developed. Studies have suggested that when used as part of an immunosuppressive regimen including steroids and cyclosporine, these agents can reduce the frequency of acute rejection in kidney transplant recipients. IL -2 receptor blockers bind to the IL -2 receptor alpha chain on the surface of activated T lymphocytes. One agent is a humanized monoclonal antibody, dacliximab (Zenapax) and the other a mouse -human chimeric monoclonal antibody, basiliximab (Simulect). Simulect is given at transplant and is repeated 4 days later, whereas Zenapax is given within 24 hours of transplant and then at 14 -day intervals for four doses. No significant adverse reactions or drug interactions have been reported with these agents. The long-term effects of these agents are not yet known.

Sirolimus (Rapamycin) is the newest drug. It binds to the same intracellular carrier site as does tacrolimus and may partially antagonize its effects. It is synergistic with cyclosporine. It acts at a separate, later site of T -cell activation than the calcineurin inhibitors. Side effects include hypercholesterolemia, hypertriglyceridemia, and mild bone marrow suppression.

I General complications of immunosuppression

Infections. The nonspecificity of current immunosuppression also impairs host defenses against a diverse group of pathogens (e.g., opportunistic infections).

A broad range of bacterial, fungal, and protozoal organisms are an uncommon cause of infections, but they require prompt diagnosis and treatment, as they can be lethal.

CMV is a frequent infectious problem in the early months after a transplant. The risk is related to prior exposure (serostatus), and seronegative recipients of organs from seropositive donors are at highest risk. The agent for prophylaxis and treatment of CMV infection is ganciclovir.

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Neoplasia. The three major areas of increased risk are skin cancer, post-transplant lymphoproliferative disorders (PTLDs), and oral squamous cell cancers or female genital tract cancers.

Skin cancer. Squamous cell cancers of sun -exposed skin are very common in post-transplant patients.

PTLD is a form of lymphoma, commonly arising from B cells and usually associated with EBV. Early stages may respond to acyclovir and profound reduction in immunosuppression. Later stages are treatable with chemotherapy, but the prognosis is poor.

Oral squamous cell cancers and female genital tract cancers (e.g., cervical, vaginal, labial) occur with greater frequency in post-transplant patients.

Parenthood after transplantation

Acute rejection is common. Severity is determined histologically.

Chronic rejection is manifest as graft coronary artery disease. This process has a different distribution from atherosclerotic coronary disease because it favors smaller arteries. Accordingly, it is difficult to treat with angioplasty or bypass surgery and may require retransplantation.

Hypertension and renal insufficiency from cyclosporine or tacrolimus can be difficult to manage.

Mortality. Almost 10% of recipients die in the first month after transplantation. These deaths are often related to multiple organ failure or initial graft failure. Another 5% die during the next 11 months. Patient survival at 1 year is 85%.

Long -term patient survival is 70% at 5 years. Patient survival for heart and liver recipients is very similar.

III Lung Transplantation

Lung transplantation can involve one or two lungs.

A

Candidates have end -stage pulmonary parenchymal or vascular disease. They are New York Heart Association class III or IV, and they have an anticipated survival of less than 2 years without transplantation. Abstinence from tobacco for a minimum of 6 months is mandatory. Three common indications account for 70% of candidates: emphysema or chronic obstructive pulmonary disease, including α 1 -antitrypsin deficiency (45%), primary

pulmonary hypertension (12%), and cystic fibrosis (10%).

B

Specific assessment of the following is critical.

Cardiac function. If left ventricular function is too poor, or if surgically uncorrectable congenital heart defects are present (usually Eisenmenger's syndrome), the patient is not a candidate for lung transplantation but may be considered for a heart -lung transplant.

If patients have bilateral pulmonary infections (e.g., from cystic fibrosis), they require double -lung transplants, because retention of an infected lung allows spread to the transplanted lung. Otherwise, single - lung transplants are used.

Renal and hepatic function must be adequate. Contraindications include current or recent tobacco or alcohol use and advanced pulmonary disease (e.g., ventilator-dependent conditions, intractable pulmonary infections, or excessive steroid requirements [for bronchospasm]).

C Operative strategy

Lung transplants are orthotopic, with excision of the diseased lung(s).

Lung transplantation has gained acceptance only recently. Many obstacles have appeared en route to success.

The question of whether a single transplanted lung is adequate to treat patients has been resolved affirmatively, at least for restrictive lung diseases.

Substantial difficulties with healing of the bronchial anastomosis have been improved.

The lung represents a large immunologic target, requiring more immunosuppression than most other transplants.

Single -lung transplants are performed via lateral thoracotomy. Cardiopulmonary bypass is not usually required, unless pulmonary artery pressures rise excessively or blood gases deteriorate excessively when the pulmonary artery is clamped.

An adult cadaver liver is split, and the left lobe or lateral segment is transplanted to the child.

Adult living donors donate their left lateral segment to the child.

E Operative strategy

The procedure generally requires 6–10 hours to perform.

Removal of the diseased liver requires dissection of the porta hepatitis, the inferior vena cava, and the diaphragmatic and retroperitoneal attachments of the liver. The blood flow to the diseased liver is interrupted, and the liver is removed. The patient is then anhepatic and requires intensive monitoring to maintain homeostasis. A segment of the retrohepatic vena cava may be removed with the liver, interrupting venous return.

Implantation of the new liver

External venovenous bypass from the femoral and portal veins to the axillary vein may be used to bypass the inferior vena cava.

Venous anastomoses are created for the suprahepatic vena cava, infrahepatic vena cava, and portal vein. These veins can then be opened, supplying the liver with warm, oxygenated blood and reestablishing caval flow. Alternatively, a piggyback method is used. The donor suprahepatic cava is anastomosed to the preserved recipient vena cava, and the donor infrahepatic cava is closed.

Hemostasis is obtained, the hepatic artery is reconstructed, and the biliary tract is reconstituted to complete the procedure. The donor bile duct is anastomosed either to the recipient's bile duct or a Roux -en -Y segment of jejunum (see Chapter 11).

F

Postoperatively the function of the new liver can be ascertained by production of bile, uptake of potassium by hepatocytes (hypokalemia), correction of coagulopathy, and metabolism of the citrate anticoagulant of blood products (alkalosis).

Nonfunction of the liver graft is manifest by the absence of bile, persistent coagulopathy, and the inability to fully awaken. This uncommon complication (<10%) requires urgent retransplantation.

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Immunosuppression is achieved by either cyclosporine or tacrolimus with steroids and often an antimetabolite.

G Complications and results

Surgical complications requiring reoperation are common, and they relate to any of the five anastomoses between the donor and the recipient. Hepatic artery thrombosis is especially common in children (5%– 10%) and often requires retransplantation. Biliary complications are also fairly common. Anastomotic strictures are more common than leaks, and these usually happen early. Late strictures can be related to rejection.

Acute rejection usually manifests as increased liver function tests and occurs in about 40% of recipients. Fever or jaundice can occur with rejection. Diagnosis is made by liver biopsy. Rejection is almost always reversible.

Chronic rejection , also called vanishing bile duct syndrome, represents immunologic attack on the bile ducts and the small arteries that nourish them. This is uncommon but may require retransplantation because it is generally untreatable.

Post -transplant death is usually related to multiple organ failure. It is usually brought on by a combination of infection or rejection plus nephrotoxicity from cyclosporine or tacrolimus.

Recurrence of hepatitis. Hepatitis B recurrence can be treated with lamivudine. Recurrence of hepatitis C is universal and usually takes an insidious course. The long-term outcome of recurrent hepatitis C is mild or no hepatitis in 40%, moderate hepatitis in 45%, and recurrent cirrhosis in 15% (at 5 years).

Survival of pediatric patients after liver transplantation is slightly better than that of adults.

Survival of adult patients is more variable than survival of children (Table 24 -3). Again, two factors have strong statistical influence.

Diagnosis. The diagnoses of cancer and fulminant hepatic failure are associated with poorer outcomes.

Patients who are more ill at the time of transplantation do not fare as well as those who are less ill.

TABLE 24-3 Patient Survival after Liver Transplantation

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V Renal Transplantation

When renal transplantation is successful, patients return to normal lives unencumbered by dialysis.

A Candidates

Patients from newborn to 70 years of age with end -stage renal disease and on maintenance dialysis are typical candidates. Patients with declining renal function who are almost at the stage of requiring dialysis are also candidates.

Renal transplantation is elective in the sense that dialysis is always an option. Therefore, candidates should be stable before transplantation.

Common indications for renal transplant in adults include glomerulonephritis (41%), diabetes mellitus (16%), polycystic disease (13%), hypertension (12%), and pyelonephritis or interstitial nephritis (6%). In children, approximately 50% of candidates have congenital or hereditary renal disease, and the remaining 50% have acquired renal disease.

B Donors

Living related donors represent 30% of kidney transplants. A related donor and recipient share more genes than do unrelated pairs. Three types of histocompatibility match occur between related individuals.

A perfect match (two haplotypes). Two siblings share the same HLA haplotype from both their mother and father. Siblings have a 25% chance of being a perfect match.

A half match (one haplotype). The donor and recipient share one of two HLA haplotypes. Siblings have a 50% chance of being a half match; all parent–child pairs are a half match.

A zero match (no haplotypes). Two siblings share neither haplotype. This situation occurs in 25% of sibling pairs.

Cadaver donors represent 70% of kidney transplant donors. The donor and the recipient can match from zero to six of their HLA antigens (see I F 3 c).

Living unrelated donors represent 3%–4% of kidney transplants and have the same types of matches as

Acute rejection occurs in approximately 40% of recipients who receive prednisone, cyclosporine, ± azathioprine. The incidence of acute rejection is lowered with the addition of either an anti–IL -2 receptor antibody (see I H 7) or replacing azathioprine with mycophenolate mofetil. Only 20% of perfect-match living related recipients will experience acute rejection.

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Treatment is pulse corticosteroids or antilymphocyte sera. Approximately 80% of episodes of acute rejection are reversible. If the episode is irreversible, the graft fails and the patient returns to dialysis.

Chronic rejection is reflected in the half -life (Table 24 -4). A prior episode of acute rejection is the strongest predictor of increased risk of chronic rejection. Chronic rejection results in graft failure and return to dialysis.

Surgical complications are not uncommon, and they can usually be treated if they are recognized at an early stage.

Vascular complications include renal artery stenosis or thrombosis and renal vein thrombosis and occur in 3%–5% of recipients. Patients may present with sudden anuria or hypertension.

Lymphatic complications occur in less than 5% of recipients and appear as a perinephric lymph collection (lymphocele). The diagnosis is made by decreased urine output or an elevated creatinine level, which prompts a diagnostic ultrasound. The lymphocele is drained by percutaneous aspiration or, optimally, by (laparoscopic) drainage into the peritoneal cavity.

Urologic complications occur in less than 10% of renal transplant patients and include urine leakage at the ureter -bladder anastomosis and ureter obstruction or infarction caused by compromise of the ureteral blood supply, which may occur during donor nephrectomy. Arteries leading to the lower pole of the kidney usually vascularize the upper ureter and must be preserved. The diagnosis of urologic complications can be confirmed by means of radioisotope scanning, ultrasound examination, or cystography.

VI Pancreas Transplantation

Pancreas transplantation provides an entire cadaver donor pancreas as an endogenous source of insulin to replace exogenous insulin for patients with type I insulin -dependent diabetes mellitus. With long-term euglycemia, improvement or stabilization of diabetic complications of the eyes, kidneys, and diabetic neuropathy can be demonstrated. Transplantation of the islets of Langerhans without the exocrine pancreatic tissue (islet transplants) is now performed under experimental protocols with excellent short-term results. As of yet, the longevity of islet transplants has not equalled that of whole pancreas transplants.

A

Candidates are usually 25–55 years of age, as it takes 10–20 years of diabetes to develop diabetic complications, particularly nephropathy.

Candidates can be considered in three groups.

Diabetic patients with end -stage renal disease are candidates for a simultaneous pancreas -kidney (SPK) transplant.

Diabetic patients with renal failure may opt for a kidney transplant first (particularly if they have a good living donor) and later undergo pancreas after kidney (PAK) transplantation.

Recipients without nephropathy but with other severe complications (e.g., retinopathy, severe neuropathy, hypoglycemic unawareness) are candidates for pancreas transplantation alone (PTA).

The high prevalence of coexistent coronary artery disease mandates cardiac evaluation , including stress testing.

Contraindications to pancreas transplantation include age higher than 60 years, severe peripheral vascular or coronary artery disease, obesity, and type II diabetes.

B

Donors are younger than 60 years. Contraindications to donation include current or prior pancreatitis, pancreatic damage from trauma, diabetes (any type), and alcoholism.

Operatively, the blood supply of the liver and pancreas of the donor must be identified and shared when both organs will be used.

Pancreas donors also donate the iliac artery bifurcation for arterial reconstruction.

The spleen is removed with the pancreas and is separated after revascularization.

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C Types of operations

SPK transplantation. Rejection is the most common cause of pancreas graft loss. Unfortunately, it is difficult to diagnose and often is irreversible. An important advantage to SPK transplantation is that the kidney serves as a marker for rejection of the pancreas.

Advantages. Other advantages to SPK transplantation include the following:

Only one surgery is needed.

High doses of induction immunosuppression drugs are needed only once.

Disadvantages to SPK transplantation are the extended procedure for some patients and, until recently, the inability to use potential living kidney donors. A newer procedure, the simultaneous cadaver pancreas and living donor kidney transplantation (the SPLK), is currently used in select centers. This procedure avoids the necessity of two separate operations.

PAK transplantation

Advantage. The advantage to the PAK approach is that this group is selected by their good response to a kidney transplant. It is hoped that these patients have a relatively low risk of rejection.

Disadvantages include two separate procedures: a repeat course of induction immunosuppression drugs, and the kidney not serving as a marker for rejection because the pancreas is from a different donor.

D Operative strategy

Anatomy. Embryologically, the pancreas is derived at the foregut -midgut junction and therefore receives blood supply from the celiac axis and the superior mesenteric artery. The splenic artery from the celiac axis supplies the tail, whereas the inferior pancreaticoduodenal arteries from the superior mesenteric artery supply the head.

Recipients receive the whole pancreas along with a segment of duodenum.

The exocrine secretions pass via the ampulla of Vater into the duodenum, which is anastomosed either to the bladder or to the small bowel.

In children, causes include congenital atresias, volvulus, necrotizing enterocolitis, and gastroschisis.

In adults , causes include Crohn's disease, volvulus, trauma, and vascular accidents, such as superior mesenteric artery occlusion.

C Operative strategy

Venous outflow can be to the portal or systemic veins. Options for gastrointestinal continuity include no bowel anastomoses and two stomas, two bowel anastomoses and no stomas, or one bowel anastomosis and one stoma. The last option is preferred because it provides proximal bowel continuity plus a distal stoma for easy biopsy access.

D

Postoperative immunosuppression is usually with tacrolimus plus other drugs.

E

Complications include sepsis, stomal complications (including retraction and ischemia), and graft failure resulting from vascular thrombosis or hemorrhage. Lymphatic drainage problems are usually short term but may affect longchain fatty acid absorption.

Because the small bowel is rich in lymphoid tissue, graft-versus-host disease has been a problem more prevalent in small bowel transplantation than in other organ transplants. This cascade of events is caused by the proliferation of donor-derived immunocompetent cells manifested as skin rash, diarrhea, altered liver functions, and anemia and can appear in the intestine as sloughing, shortening, and blunting of the villi.

Graft function is monitored by looking at various absorption studies (including ethylenediaminetetraacetic acid [EDTA] and maltose) and direct biopsy techniques.

The histologic appearance of the gut during rejection includes blunting of microvilli, mononuclear infiltration of the intestinal wall, and epithelial cell attenuation.

F

Graft survival rates have been reported to be approximately 70% at 1 year for small bowel only and approximately 60% for liver and small bowel. Experience is still limited, and surgical and immunologic challenges lie ahead.