Figure 40-6. Technical graft failure rates for U.S. pancreas transplant recipients by year. (Data from Scientific Registry of Transplant

Recipients. 2013 Annual Report. Rockville, MD: Health Resources and Services Administration, Department of Health and Human

Services; 2015).

The management of a suspected duodenal leak is operative. Peripancreatic sepsis or abscess can occur

in the absence of a frank duodenal leak. This is caused by the growth of organisms transmitted into the

peritoneal cavity during performance of the duodenal anastomosis. The peritoneum should be lavaged

and all necrotic debris removed. If a leak is present it is usually at the stapled end of the duodenum

rather than at the anastomosis. The likelihood of success for repair of a duodenal leak depends on the

viability of the duodenum at the point of the leak, the patient’s overall hemodynamic stability, and the

degree of surrounding inflammation. Usually one attempt at repair is made, but failure may necessitate

removal of the pancreas in order to control life-threatening sepsis. Some surgeons have adopted a

practice of managing leaks from duodenal enteric anastomoses by conversion to bladder drainage. This

minimizes the risk of recurrent contamination of the peritoneal cavity with enteric contents and allows

for Foley catheter decompression of the duodenum, but has the morbidity associated with bladder

drainage. Occasionally a fluid collection or leak which presents late and without systemic sepsis can be

treated with percutaneous CT-guided drainage.88 In addition, drainage of infection without primary

repair of the duodenal leak has been successfully employed in situations where inflammation is so

profound that the leak could not be primarily repaired. However, the morbidity associated with these

duodenal fistulas dictates that these options be employed only when definitive repair is not possible.

In contrast to renal transplantation, the complications of pancreas transplantation can be severe and

life threatening if not properly managed. Even in the most experienced centers, occasional patients who

suffer extended intensive care unit stays and even death are not unusual. This is a consequence of both

the tenuous medical status of longstanding diabetics and the substantial morbidity of pancreas

transplant complications. Therefore, given the limited survival benefit of pancreas transplantation,

particularly compared with kidney transplantation, patients should be counseled frankly about the

potential magnitude of these complications so that they have a realistic expectation of outcomes. Even

with honest discussion and informed consent, most individuals will elect pancreas transplantation, and

many will pursue multiple pancreas transplants even with a history of significant complications from

previous pancreas transplants.

Diagnosis and Treatment of Rejection

The timely and accurate diagnosis of pancreas transplant rejection is one of the most important and

challenging aspects of posttransplant management. As with kidney transplant rejection, pancreas

rejection, whether acute cellular rejection or antibody-mediated rejection, is associated with inferior

graft survival.89 Furthermore, both pre- and posttransplant donor-specific antibody (DSA) are associated

with antibody-mediated rejection and reduced pancreas and kidney graft survival.89,90 The incidence of

pancreas rejection is about 20% to 25% in the first 2 years.50 Therefore, the implications of delayed or

missed antirejection treatment can be profound.

There is no single laboratory abnormality capable of diagnosing rejection. Amylase and lipase serum

levels are commonly elevated, and can arouse suspicion, but are not specific. Hyperglycemia is also

nonspecific, and if due to rejection occurs late, signifies significant pancreatic endocrine injury and has a

dismal prognosis. While imaging modalities including ultrasound may identify abnormalities in

parenchyma or perfusion, they are neither sensitive nor specific.91 Hence, the diagnosis of rejection is

best made with histologic examination of a pancreatic biopsy specimen.92 The pancreas graft in SPK

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transplants may be monitored by following the serum creatinine, as the concordance rate for rejection

between kidney and pancreas grafts is believed to be high, although isolated pancreas rejection clearly

occurs.93,94 Improvements in the outcome of solitary pancreas transplants are attributable to

improvements in overall quality of immunosuppression, and to more accurate diagnosis and treatment

of pancreas rejection.

The technique of pancreas transplant biopsy has evolved over the years. In the era of bladder-drained

pancreas transplants, cystoscopic biopsy of both the pancreas and transplant duodenum was common.95

As more enteric-drained pancreas transplants have been performed, a greater reliance on percutaneous

biopsy has developed, using either ultrasound or CT-guided techniques.96 Laparoscopic-assisted or open

pancreas biopsy may be utilized for patients whose pancreas transplant is not accessible to percutaneous

approaches, although the need for operative biopsy is decreasing as the percutaneous procedure has

become more routine.97 Enteroscopic biopsy has been described, and a high jejunal anastomosis can

facilitate utilization of this method.98 The indications for pancreatic biopsy include hyperamylasemia,

hyperlipasemia, hyperglycemia, or unexplained pain in the vicinity of the pancreas transplant. The

differential diagnosis includes pancreatitis, cytomegalovirus (CMV) infection, and toxicity from

calcineurin inhibitors and, in the early postoperative period, peripancreatic infection. The histologic

grading system developed at the University of Maryland for determining rejection grade in pancreas

biopsies is generally used (Table 40-3).99 Indeterminate rejection may be treated with increases in

calcineurin inhibitor dose or pulse corticosteroids. More substantial rejection is generally treated with

depleting antilymphocyte antibody therapy, either OKT3 or Thymoglobulin.

As long-term survival of pancreas transplants becomes more commonplace, chronic rejection is

emerging as an important problem.100 Unfortunately, as with kidney transplantation, while newer

agents have improved short-term survival by preventing acute rejection, improvement of short-term

survival has not translated into improved long-term graft survival.101 Chronic rejection is histologically

characterized as expansion of fibrous septa within the pancreatic parenchyma. This may progress to

lobular atrophy or loss of both acini and β-cells. Although there are parallels to chronic allograft

nephropathy, whether chronic calcineurin inhibitor toxicity contributes to chronic pancreas rejection is

unknown.

Table 40-3 Diagnosis: Revised Banff Classification for Diagnosis and Grading

Pancreas Allograft Rejection86

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Recurrent Autoimmunity

Selective β-cell destruction in pancreas transplants may occur in a pattern similar to the insulitis seen in

type 1 diabetes. This pattern is histologically distinct from cellular rejection. Although recurrent

autoimmunity has been documented in both immunosuppressed pancreas transplant recipients and

nonimmunosuppressed living donor recipients from identical twin siblings, well-documented case series

have been infrequent. A variety of associations have been suggested with autoantibodies to glutamic

acid decarboxylase (GAD-65) and islet cells (IA-2), but patterns of autoantibody expression have not

proven reliable enough to establish their etiologic relevance or prognostic value.102,103

Posttransplant Viral Infections

The higher level of immunosuppression given to pancreas transplant recipients compared with kidney

transplant recipients, particularly with respect to lymphocyte-depleting induction therapy, places

pancreas transplant recipients at risk for conditions known to be influenced by overall

immunosuppressive exposure. While rates of CMV infection are generally higher than for kidney

recipients, especially when the donor is known to carry the virus, the use of intravenous and oral

ganciclovir has reduced the incidence of significant CMV-associated disease.104,105 The incidence of CMV

disease may also be lower in those recipients receiving steroid-free immunosuppression.105 Data are

mixed with respect to the incidence of polyoma-associated, or BK, nephropathy, with some analyses

suggesting a higher rate and other an equivalent incidence in SPK recipients compared with kidneyalone recipients.106,107 As with kidney-alone recipients, those SPK recipients with BK nephropathy have

inferior kidney graft survival. Posttransplant lymphoproliferative disorder (PTLD), often associated

with Epstein–Barr virus (EBV) infection, has a 5-year incidence of approximately 2%, which is similar to

or higher than kidney recipients.108,109 Pancreas recipients with PTLD have a worse prognosis than

other abdominal organ transplants recipients with PTLD.

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Figure 40-7. Pancreas graft survival among adult pancreas transplant recipients, 2008. (Data from Scientific Registry of Transplant

Recipients. 2013 Annual Report. Rockville, MD: Health Resources and Services Administration, Department of Health and Human

Services; 2015).

Results of Kidney–Pancreas Transplantation

Current kidney graft survival at 1 and 5 years following SPK transplantation is 96% and 80%,

respectively.50 African Americans have historically had somewhat poorer 5-year graft survival than

whites. Kidneys from older donors have the poorest graft survival; 5-year graft survival from donors

older than 50 is 68% compared with approximately 80% from donors aged 11 to 34. As opposed to

previous decades, 5-year kidney graft survival is not associated with HLA matching.

Pancreas graft survival at 1 and 5 years following SPK transplantation is 86% and 73%, respectively

(Fig. 40-7). Worse 5-year graft survival is seen in African-American recipients compared with whites.

Recipients with a previous transplant (kidney, pancreas, or both) have worse pancreas graft survival. As

with kidney survival, there is no difference in 5-year pancreas graft survival with increasing levels of

HLA mismatch.

Registry analyses demonstrate a mortality benefit of SPK transplantation compared with dialysis

110 or

deceased donor kidney transplantation alone.111 These benefits diminish with higher-risk donors,

particularly older donors.112 Patient survival at 1 year and 5 years following SPK transplantation is 98%

and 92%, respectively. Race, ethnicity, gender, and transplant center volume are not associated with

decreased patient survival at 5 years, and patient survival has improved since 1995 but not appreciably

in the past 10 years.50

Results of Solitary Pancreas Transplantation

The 1-year pancreas graft survival for recipients of a PAK transplant has improved in the last 5 years,

from 78% for PAK transplants performed in 2005 to 88% for transplants performed in 2011.50 Graft

survival for PAK at 5 years is currently 53%. One-year pancreas graft survival for PTA has improved in

the last 5 years to 80%. The unadjusted graft survival for PTA at 5 years is 53%. Graft survival rates for

PTA are better than PAK early, but the rate of graft failure in the long term is greater for PTA than for

PAK. Patient survival for both SPK and PAK recipients is excellent, >90% at 1 year and >80% at 5

years.

8 Whether pancreas transplantation positively impacts patient mortality is controversial. One study

reported that registrants on the waiting lists for PAK and PTA had better survival rates than recipients

who underwent these procedures.110 Subsequently, another group, using a similar cohort but different

analytical methods, reported better survival rates for recipients of solitary pancreas transplantation than

registrants on the waiting list.113 These discrepancies are in part related to the differing methodologies

used in the two studies with respect to deaths among those removed from the waitlist and also to

variability in the year-to-year death rates on the waiting list. In contrast, both studies demonstrated a

conclusive benefit for SPK recipients compared with remaining on the waiting list, which illustrates the

importance of restoration of kidney function in this population, as with kidney-alone transplant. While

opinions on the specific benefit of the pancreas transplant differ in light of the differing conclusions of

these two studies, together the studies indicate any survival benefit conferred by the pancreas transplant

is likely to be modest. In fact, most studies do not demonstrate a graft or patient survival advantage of

SPK over living donor kidney transplant.111,114 The survival benefit of SPK over deceased donor kidney

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