Whole organ pancreas and pancreatic islet transplantation

History and early results

On December 20, 1893, P. Watson Williams grafted three pieces of sheep pancreas into the subcutaneous tissues of a child with diabetes; the child died three days later of unrelenting diabetic ketoacidosis. This first attempt to treat diabetes with transplantation, although unsuccessful, was followed by several decades of animal experimentation in which investigators developed the methods necessary to perform a vascularized pancreas transplant and subsequently used it as a model to study diabetes and glucose homeostasis.

The first clinical vascularized pancreas transplant was performed on December 17, 1966, by William Kelly and Richard Lillehei at the University of Minnesota. The patient had temporary insulin independence but eventually required graft removal and ultimately died of postoperative complications. The early experience with pancreas transplantation that followed at Minnesota and at a few other centers was characterized by some technical success, but no graft functioned beyond 1 year, and consequently the enthusiasm for this procedure waned.

During 1975, only six pancreas transplants were performed worldwide. However, the introduction of cyclosporine as an immunosuppressive medication and further technical refinements allowed for improved outcomes after pancreas transplantation, such that throughout the 1980s and early 1990s, the number of pancreas transplants increased dramatically. By 2004, almost 1500 pancreas transplants were performed in the United States. However, since that peak year, the number has declined with fewer than 1000 pancreas transplants in the United States in 2020.

Indications and patient selection

Most patients who undergo pancreatic transplantation have both type 1 DM and renal failure. In these individuals, pancreas transplantation is either performed with a simultaneous kidney transplantation (SPK; 86% of US pancreas transplants in 2020) or are pancreas after kidney transplant (PAK). The precise glucose control achieved by the pancreas transplant protects the transplanted kidney from recurrent diabetic nephropathy and is beneficial from an overall quality of life perspective. In a small proportion of patients with diabetes that is very brittle and difficult to manage, but with preserved renal function, pancreas transplantation alone (PTA) may be indicated. It should be noted that SPK and PAK recipients require immunosuppressive therapy to protect both the kidney and the pancreas from rejection, whereas in the case of PTA recipients, the initiation of immunosuppression is solely for the pancreas. This difference becomes important when weighing the risk versus the benefit for each category of recipient.

One notable change in pancreas transplantation has been the inclusion of some patients with type 2 diabetes and kidney failure as candidates for a simultaneous pancreas and kidney transplant. This group includes individuals that meet a traditional definition of type 2 diabetes and individuals that have maturity-onset diabetes of the young (MODY). Carefully selected patients with type 2 diabetes that have a body mass index (BMI) of 30 or less can undergo a successful simultaneous pancreas and kidney transplant, provided they meet listing criteria and have an insulin requirement that is below 1 to 1.5 units per kilogram per day. In the past, very few patients with type 2 diabetes underwent an SPK; however, in recent years nearly 20% of patients on the pancreas waiting list are individuals with type 2 diabetes.

Potential pancreas recipients are carefully screened for contraindications to transplantation, such as an ongoing infectious process or malignancy. These candidates almost always have medical comorbidities because of secondary complications from diabetes; as a result, a thorough assessment of a candidate’s cardiovascular status is essential. Cardiac contraindications to pancreas transplantation include the presence of uncorrected coronary artery disease, significantly decreased ejection fraction, or myocardial infarction within the preceding 6 months. Recipient age is also important, and in most programs, recipients older than 60 years of age are not considered candidates because of an increased risk of perioperative complications coupled with the uncertainty of long-term benefit in the setting of life expectancy compromised by comorbidities.

Donor operation (see Chapter 126 )

Selection of an appropriate deceased pancreas donor includes standard donor selection criteria. In addition, a bias exists toward using organs from younger, leaner, and more hemodynamically stable deceased donors. Donors with hemodynamic instability or those that require high doses of vasopressors are considered at higher risk for graft failure and graft-related complications. In addition, pancreata with significant steatosis are usually avoided because they are associated with a greater likelihood of postoperative complications, such as pancreatitis, peripancreatic fat necrosis, and infection. Based on these selection criteria, which are relatively stringent compared with those applied to the liver or kidney, only a fraction of deceased donors are deemed suitable for whole-organ pancreas donation. In the United States, there were 12,588 deceased donors during 2020. Of these, only 962 pancreata were transplanted (7.6%), compared with 8415 livers (66.8%) and 17,583 kidneys.

The procurement of the pancreas is often performed concurrent with the liver procurement, requiring careful delineation of the blood supply to the liver to ensure that both organs can be removed and safely transplanted (see Chapter 109 ). In the majority of cases, variation in vascular anatomy should not preclude the transplantation of both organs. Initial dissection involves entering the lesser sac by division of the gastrocolic ligament to expose the anterior surface of the pancreas. Visual inspection is an essential element to the pancreas procurement process to assess the organ for the presence of infiltrating fat or hematoma that might preclude transplantation. The porta hepatis is carefully dissected, with division of the common bile duct and the gastroduodenal artery. In addition, the common hepatic, proximal left gastric, and proximal splenic arteries are all dissected free of surrounding nerve and lymphatic tissues. Further mobilization of the pancreas includes a Kocher maneuver to free the head and division of the lienophrenic and lienocolic ligaments to mobilize the body and tail. Of note, the spleen is left in continuity with the pancreas. The duodenum is decontaminated by flushing the lumen with povidone-iodine solution through a nasoduodenal tube by many but not all centers performing this procedure.

After the patient has been systemically heparinized, the abdominal aorta is ligated at its bifurcation and is cannulated in a retrograde direction for perfusion. The liver team may elect to place a cannula for portal perfusion through the inferior mesenteric vein. The supraceliac aorta is cross-clamped, the vena cava is vented, and the abdominal organs are flushed in situ with preservation solution, typically University of Wisconsin (UW) solution, at 4°C. In addition, topical cooling with saline slush is standard. Some centers prefer that only arterial flush is performed or that the portal flush is limited to avoid increased portal pressure during the flushing period.

Once the organs have been adequately flushed, the liver and pancreas are either separated in situ and removed individually from the donor, or both organs are removed en bloc and divided at the back table. In the in situ separation situation, the liver is removed first by dividing the portal vein approximately 1 cm cephalad to the superior margin of the pancreatic head (at the level of the coronary vein) and dividing the splenic artery 5 mm beyond its origin, thus preserving the entire celiac axis with the liver.

Next, removal of the pancreas proceeds. The proximal duodenum just beyond the pylorus and the distal duodenum are divided with a gastrointestinal (GI) anastomosis (GIA) stapler. The small bowel and colonic mesentery that lies inferior to the pancreas is divided, and the superior mesenteric artery (SMA) is divided at its origin from the aorta. Long segments of donor iliac vessels are removed to use for vascular reconstruction during back-table preparation of the pancreas.

Back-table preparation of the pancreas (see Chapter 126 )

Relative to other solid organs, the pancreas requires more extensive preparation before implantation into the recipient. This back-table preparation is performed in ice-cold preservation solution to minimize any further ischemic injury to the organ. The duodenum is often shortened with a GIA stapler, being careful to exclude any gastric tissue and also being careful not to compromise the opening of the ampulla of Vater. The small bowel mesentery in the donor is shortened by firing a stapler across this mesentery and then reinforcing the staple line with a running vascular suture. The spleen is removed by dividing the vessels in the splenic hilum, being careful not to injure the tail of the gland. Finally, the arterial inflow to the graft must be reconstructed because the organ has two major sources of blood supply that are not in continuity: the splenic artery supplies the body and tail, and branches of the SMA supply the head.

In most instances, arterial reconstruction can be performed using the donor iliac artery as a bifurcated Y graft. The internal iliac artery is joined to the splenic artery, and the external iliac artery is joined to the SMA. The common iliac artery of the donor Y graft can then be anastomosed to the recipient iliac artery, serving as the arterial inflow to the pancreas. In rare instances, it is necessary to create a portal vein extension graft on the back table using donor iliac vein; however, this technique should be avoided if possible because it may increase the risk of venous thrombosis of the pancreas graft.