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the portal vein to reach without tension. The common iliac artery component of the donor Y-graft is

then anastomosed in end-to-side fashion to either the recipient external iliac artery or common iliac

artery; the distal aorta can also serve as the site of anastomosis. A pancreas placed on the left side in the

recipient may be placed either medial or lateral to the sigmoid colon. Multiple variations have been

described.

Because of concerns about the systemic hyperinsulinemia that invariably develops with systemically

drained pancreas transplants, portal venous drainage is also utilized (Fig. 40-5). As 50% of insulin is

removed with the first pass through the liver, systemic drainage leads to elevated peripheral insulin

levels, which is not observed following portal venous drainage. Since hyperinsulinemia has been

associated with dyslipidemia and accelerated atherosclerosis, portal venous drainage theoretically ought

to decrease cardiovascular risk compared with systemic drainage.64 Portal drainage is associated with

stimulation of the IGF-I/GH axis, contributing to glucose control despite lower insulin levels.65

However, despite a nearly 10-year experience with the procedure, no effect on cardiac morbidity or

mortality has been shown, and graft and patient survival are essentially equivalent.66–68

Although the type of venous drainage typically depends on the preferences of individual surgeons or

transplant centers, the decision to perform portal or systemic drainage may also depend upon the

anatomy of an individual patient. Patients with multiple previous abdominal operations or who have a

thickened mesentery may be more suited for systemic venous drainage. Alternatively, patients who

have had multiple transplants or other operations on the iliac vessels may be candidates for portal

venous drainage.

For portal venous drainage the superior mesenteric vein is dissected out just below the transverse

mesocolon.69 The right common iliac artery is almost completely dissected. An end-to-side anastomosis

of the donor portal vein to the recipient superior mesenteric vein is performed with the duodenum

oriented superiorly and the tail pointed inferiorly. The iliac artery graft of the donor is then passed

through a hole created in the small bowel mesentery, and anastomosed to the recipient common iliac

artery.

Most centers currently use enteric exocrine drainage for simultaneous kidney/pancreas transplant and

some centers use enteric drainage for all transplants including solitary pancreas transplantation. This

shift to enteric drainage occurred as a result of the significant morbidity associated with bladder-drained

pancreas transplants. Morbidity includes recurrent urinary tract infections, hematuria, chemical

urethritis, severe bicarbonate wasting, and dehydration. Historically, approximately 25% of individuals

who receive a bladder-drained pancreas transplants require enteric conversion because of persistent

complications,70 but an additional percentage endure significant morbidity early after transplant. The

major advantage of bladder drainage is the ability to monitor urinary amylase, a decrease in which can

be associated with rejection. This can be helpful in solitary pancreas transplants, but is not as important

for simultaneous pancreas/kidney transplants where graft function may be monitored by serum

creatinine. Improved immunosuppression and an increased utilization of biopsy to diagnose rejection

have led to a decreased reliance on urinary amylase.71

Enteric drainage is achieved by creating a side-to-side or end-to-side anastomosis of donor duodenum

to recipient jejunum. This may be a loop of jejunum, or a Roux-en-Y configuration may be created. For

bladder drainage a side-to-side anastomosis between the donor duodenum and the bladder is performed.

Enteric drainage is always used for pancreas transplants with portal venous drainage because the

orientation of the pancreas precludes anastomosis of the duodenum to the bladder.

If a simultaneous kidney–pancreas transplant is performed, the kidney transplant is usually placed in

the left iliac fossa. The anastomoses, as with a kidney transplant via a retroperitoneal incision, are

typically to the external iliac artery and external iliac vein. The kidney is typically placed in an

intraperitoneal location, which increases the potential for torsion of the kidney on its vascular pedicle

compared with kidney-alone transplants which are usually placed in a retroperitoneal location. Some

surgeons prefer to raise a retroperitoneal flap to place the kidney retroperitoneally after implantation.

Advantages to this approach include improved percutaneous access should biopsy be required, and a

decreased risk of postbiopsy hemorrhage.

Following revascularization of the pancreas, attention is paid to bleeding from the pancreas which can

be quite brisk. This is controlled with ties or suture ligatures. Since thrombosis is a common

complication of pancreas transplantation, anticoagulation in the perioperative period is frequently

employed, particularly for solitary pancreas transplantation. Thrombosis is less frequent in simultaneous

pancreas–kidney transplantation, where uremic platelet dysfunction is protective. The extent of

anticoagulation may range from the intraoperative administration of heparin prior to clamping of

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vessels, followed up by low-dose heparin infusion and warfarin anticoagulation, to more conservative

approaches such as the use of low-dose heparin for a limited interval postoperatively, or the use of

aspirin or other antiplatelet agents. Hypercoagulability states may predispose to graft thrombosis in a

significant number of individuals, although definitive data are lacking; anticoagulation is individualized

based on risk.72 Whatever the approach, patients should be monitored for bleeding, since as many as

10% of patients experience postoperative hemorrhage requiring reoperation.73

Figure 40-5. Back-table preparation of the pancreas. Before transplantation, the pancreas must be prepared in a slush-filled basin

to maintain cold preservation. Preparation includes unifying the arterial blood supply of the pancreas by anastomosis of the donor

external iliac artery to the superior mesenteric artery and the donor internal iliac artery to the splenic artery. The donor common

iliac artery is used for anastomosis to the recipient iliac artery. During back-table preparation, donor splenectomy is performed.

Following revascularization serum glucose levels are obtained hourly. It is common for the blood

glucose to decline significantly following revascularization, and it is not uncommon for it to fall to

normal levels soon after the patient’s arrival in the recovery room. At some point intravenous fluids

should be converted to dextrose-containing solution in order to prevent hypoglycemia. Pancreas

transplant recipients with enteric drainage require only maintenance fluid with consideration of thirdspace losses. Simultaneous kidney–pancreas transplant recipients may require the additional fluid

replacement that would be administered following kidney transplantation alone. Individuals who

receive bladder-drained pancreas transplants require replacement of pancreatic exocrine losses, which

can be quite profound in the early postoperative period.

Immunosuppression

7 Immunosuppression for pancreas transplantation is similar to that for kidney transplantation. The

immunogenicity of a pancreas transplant is considered to be greater than the majority of solid-organ

transplants because of the extensive lymphoid component of the gland. In addition, the difficulty in

diagnosing rejection compared to other solid-organ transplants makes the choice of immunosuppression

more significant for pancreas transplants. Most centers use some forms of triple maintenance therapy

utilizing a calcineurin inhibitor, an antiproliferative agent, and steroids, although steroid-free regimens

are becoming more common. According to data from the Scientific Registry of Transplant Recipients,

92% of kidney–pancreas recipients in 2012 received tacrolimus as maintenance therapy, compared to

only 3.5% who received cyclosporine.50 Mycophenolate mofetil is the antiproliferative agent of choice

in pancreas transplantation; the use of sirolimus declined from a peak of 19% in 2001 to 7% in 2012.

The use of steroids for pancreas transplantation, while still much lower than prior to 2000, increased

from 61% in 2007 to 68% in 2012.

The use of induction therapy to inhibit lymphocyte function is common. Several large randomized

multicenter trials utilizing either T-cell–depleting antibody induction (OKT3, ATGAM, and

thymoglobulin) or interleukin-2 (IL-2) receptor antibody inhibition (daclizumab and basiliximab)

showed a reduction in the incidence of acute rejection but failed to demonstrate a significant effect on

patient or graft survival.74,75 Despite this modest impact on overall graft outcome, 89% of kidney–

pancreas transplant recipients received induction therapy in 2012, 79% T-cell–depleting agents, and

12% IL-2 receptor antibody.50 The International Pancreas Transplant Registry (IPTR) has demonstrated

a lower risk of pancreas graft loss in all categories of pancreas transplantation with the use of

tacrolimus, and also demonstrated similar associations with the use of mycophenolate mofetil.56

Consistent with the multicenter trials, IPTR analyses also fail to demonstrate a beneficial effect of

induction therapy on patient and graft survival.

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Several groups have reported excellent intermediate-term patient and graft outcomes utilizing steroid

minimization protocols.76–78 These protocols generally employ an induction agent (usually a depleting

T-cell antibody), tacrolimus, and either MMF or sirolimus. Steroids are given for a maximum of 3 days.

These steroid minimization protocols, as in kidney transplantation, aim to avoid the significant shortand long-term side effects associated with corticosteroids. Regimens employing maintenance

monotherapy have also been successfully employed, although based on registry data, these appear to be

falling into disfavor.50,79

Complications

Thrombosis of the pancreas transplant is the most common cause of graft loss in the early postoperative

period, occurring in 5% to 10% of transplants. Why pancreas transplants are more prone to thrombosis

than other solid-organ transplants is uncertain. The most likely mechanism is that ischemia reperfusion

injury in the pancreas, characterized by the release of cytokines and activation of pancreatic enzymes,

leads to accelerated injury and a procoagulant state. Diabetic patients have impaired fibrinolysis and

are, therefore, relatively hypercoagulable. The relatively low venous flow through the portal vein,

which leads to diminished flow velocity, may be contributory. Thrombosis is slightly more common in

solitary pancreas transplantation than in SPK, probably due to the absence of uremic platelet

dysfunction present in SPK recipients. The risk of thrombosis has been associated with donor factors

such as older patient age, renal dysfunction, cold ischemic time, body mass index, DCD status, and

cerebrovascular cause of death.55,80,81

Pancreas transplant thrombosis is usually heralded by a sudden rise in blood glucose in a pancreas

that was previously functioning. Confirmation of the diagnosis is usually obtained with duplex

ultrasound. Although anecdotal reports have described successful surgical and angiographic

thrombectomy or thrombolysis in restoring flow to the pancreas,82,83 the usual treatment is removal of

the infarcted pancreas. While this usually occurs immediately after diagnosis, some centers opt to relist

the patient urgently and wait until another pancreas transplant becomes available. Depending on the

waiting time for another pancreas, the added morbidity of delaying the graft pancreatectomy is usually

not significant. In contrast, asymptomatic thrombosis, whether partial or even complete, has been

successfully managed with anticoagulation, especially if late in onset.84,85 Because of the high risk of

thrombosis, some degree of anticoagulation is frequently employed after pancreas transplantation.86 It

is likely due to these efforts and improvements in immunosuppression that the thrombosis rate for

simultaneous pancreas–kidney transplants has decreased to less than 5% for simultaneous pancreas–

kidney transplant and to less than 10% for isolated pancreas transplants (Fig. 40-6).

Bleeding is another frequent cause for reoperation in the early postoperative period. Because of the

large number of vessels that enter and exit the pancreas, bleeding following reperfusion is not unusual.

While readily controllable, it is not uncommon for bleeding points to emerge later in the procedure, and

postoperatively. This can be minimized by meticulous attention to ligating vascular structures during

pancreas procurement. The use of anticoagulation in the perioperative period, as described above, adds

to the bleeding risk. Pancreas transplant recipients are monitored carefully in the early postoperative

period for signs and symptoms of intra-abdominal hemorrhage.

The other major early complication is leak from the donor duodenum. Duodenal leaks occur in

approximately 5% to 10% of cases, usually 1 to 2 weeks after the transplant.87 A leak may present as

fever, abdominal pain, leukocytosis, lower abdominal tenderness, and persistent ileus. The diagnosis

may be supported by the finding of a focal fluid collection near the head of the pancreas on CT scanning

or ultrasound. Alternatively, diffuse peritonitis may reflect disseminated contamination. For bladderdrained pancreas transplants, the diagnosis may be made by cystograp