Pancreas transplantation (SPK/PAK/PTA)

Pancreas transplantation is the surgical placement of a healthy whole or segmental pancreas, almost always from a deceased donor, into a recipient with diabetes mellitus to restore endogenous, glucose-responsive insulin secretion. It is the most established means of achieving durable, insulin-independent normoglycemia in selected patients with type 1 diabetes, and it is increasingly offered to selected patients with insulin-treated type 2 diabetes. [1][2] Because the procedure requires major abdominal surgery and lifelong immunosuppression, it is generally reserved for patients who also need or have a kidney transplant, or for nonuremic patients whose diabetes is otherwise unmanageable, for example those with frequent severe hypoglycemia and hypoglycemia unawareness. [1][3]

Pancreas transplantation is performed in three principal recipient categories: simultaneous pancreas-kidney transplant (SPK), pancreas-after-kidney transplant (PAK), and pancreas transplant alone (PTA). [1][2] The pancreas graft provides exocrine secretions that must be drained surgically and endocrine (insulin) secretions that must reach the systemic circulation, requirements that define the two main technical decisions in the operation. Whole-organ pancreas transplantation is distinct from Islet transplantation, in which isolated insulin-producing islet cells are infused rather than the whole organ implanted. [4]

Categories

The three categories differ chiefly by the recipient's kidney status and by timing relative to a kidney transplant. [1][2] SPK is the most frequently performed category, followed at much lower volumes by PTA and PAK. [5][6]

| Category | Definition | Typical candidate | |---|---|---| | SPK (simultaneous pancreas-kidney) | Pancreas and kidney transplanted from the same donor in one operation | Diabetic with end-stage or near-end-stage renal disease (GFR below roughly 20 mL/min or on dialysis) [1][3] | | PAK (pancreas-after-kidney) | Pancreas transplanted at a later date after a prior (often living-donor) kidney transplant | Diabetic with good function of an existing kidney graft [1][3] | | PTA (pancreas transplant alone) | Pancreas transplanted with no kidney transplant | Nonuremic diabetic with preserved kidney function and disabling glycemic instability, for example severe recurrent hypoglycemia [1][3] |

A fourth, less common configuration combines a deceased-donor pancreas with a living-donor kidney. [1]

Indications

Type 1 diabetes

Type 1 diabetes is the classic indication. SPK is now considered a first-choice treatment for patients with type 1 diabetes and associated end-stage renal disease, because it addresses both the renal failure and the underlying insulin deficiency in a single operation. [1] For nonuremic patients, PTA is considered when diabetes cannot be controlled despite optimal medical therapy, typically in the setting of frequent severe hypoglycemic episodes with hypoglycemia unawareness. Reported PTA selection criteria include a history of more than two severe hypoglycemic episodes within the preceding 24 months together with preserved renal function. [1]

Type 2 diabetes

Pancreas transplantation, principally as SPK, is increasingly performed in selected patients with insulin-treated type 2 diabetes who have end-stage renal disease, and in older candidates. [1][2] According to the OPTN/SRTR Annual Data Report, the share of US pancreas transplants performed in recipients with type 2 diabetes rose to 25.4% in 2023 (from 22.5% in 2022) and was 25.7% in 2024, a trend that had been rising before plateauing in recent years. [5][6] (Figures as of the 2023 and 2024 reports.)

Recipient selection

Candidate selection relies on a multidisciplinary pretransplant evaluation, including cardiac assessment, given the high cardiovascular risk in long-standing diabetes. [1] Reported absolute contraindications include age over 65 years, uncorrectable significant coronary artery disease, myocardial infarction within the prior 6 months, left ventricular ejection fraction below 30%, incurable malignancy (other than localized skin cancer), and active sepsis. Relative contraindications include body mass index above 30 kg/m2, very high insulin requirements (above about 1.5 units/kg/day), active hepatitis B or C, and ongoing substance abuse. [1] These thresholds are guideline-level and vary by program.

Surgical technique

The donor pancreas is usually transplanted whole, together with a segment of donor duodenum, and placed heterotopically in the iliac fossa or lower abdomen while the native pancreas is left in place. [1] Donor iliac artery is commonly reconstructed as a Y-graft to supply the two arteries feeding the pancreas. [1] A pancreas-alone operation typically takes about 3 to 4 hours; a combined SPK operation takes longer. [1] Two technical choices define the operation: how exocrine secretions are drained and how venous (insulin-bearing) outflow is routed.

Exocrine drainage: enteric versus bladder

• Enteric drainage anastomoses the donor duodenal segment to the recipient small bowel (a duodenojejunal or duodenoduodenal anastomosis), routing pancreatic exocrine secretions into the gut. This is the contemporary standard technique. [1][7]
• Bladder drainage anastomoses the donor duodenum to the recipient bladder. It was the dominant technique through the late 1980s and 1990s and allows graft surveillance via urinary amylase measurement, but it is complicated by metabolic acidosis, dehydration, and chemical cystitis from bicarbonate and enzyme loss. A substantial fraction of bladder-drained recipients (reported around 10% to 25%) ultimately require enteric conversion. [1][7]

Venous drainage: systemic versus portal

• Systemic venous drainage anastomoses the graft portal vein to a systemic vein (recipient iliac vein or inferior vena cava). This is technically simpler but bypasses the liver, producing peripheral hyperinsulinemia. [1]
• Portal venous drainage anastomoses the graft to the recipient superior mesenteric vein, delivering insulin first to the liver in a more physiologic pattern. Proposed advantages include avoidance of systemic hyperinsulinemia and possible immunologic benefit from hepatic antigen processing; long-term graft survival is broadly comparable between the two approaches in registry and trial data. [1]

Donor selection and the Pancreas Donor Risk Index

Pancreas grafts are sensitive to donor quality, and many recovered pancreata are not used. The US pancreas nonuse rate was 23.4% in 2023, improved from 28.7% in 2022. [5] Donor-selection considerations reported in the literature include younger donor age (commonly preferred in roughly the 5 to 50 year range, with use up to about 60 years), lower BMI, absence of pancreatic disease or diabetes, and avoidance of grafts showing significant fibrosis or fatty infiltration at procurement, which are associated with severe reperfusion pancreatitis. [1]

Two scoring tools are used to grade donor and graft suitability:

• The Pre-Procurement Pancreas Allocation Suitability Score (P-PASS) combines donor variables to estimate suitability before procurement. [1][8]
• The Pancreas Donor Risk Index (PDRI), introduced by Axelrod and colleagues in 2010, models the relative risk of pancreas graft failure from donor and transplant factors: donor sex, age, Black race, Asian race, BMI, height, cerebrovascular cause of death, the interaction of cerebrovascular death with PAK, donation after circulatory death, serum creatinine, and pancreas cold ischemia (preservation) time. The index is scaled so the median donor has a value of 1.0, with higher values indicating higher predicted risk; the reference donor is a 28-year-old white man, BMI 24, height 173 cm, no cerebrovascular accident, creatinine below 2.5 mg/dL, not donation-after-cardiac-death, and 12 hours cold ischemia. [8][9]

Outcomes and graft survival

Pancreas transplantation generally produces durable insulin independence and normalization of HbA1c, with reported long-term metabolic benefit and improvement in some secondary diabetic complications. [1] Reported patient survival exceeds roughly 96% at 1 year and 83% at 5 years across categories. [1]

Registry graft-survival figures from the OPTN/SRTR Annual Data Report are the standard US benchmark. For pancreas grafts transplanted in 2022, reported 1-year pancreas graft survival was 90.8% for SPK, 87.5% for PTA, and 84.4% for PAK; the SPK kidney graft 1-year survival was 96.2%. [5] (Figures as of the 2023 report.) Early graft loss within the first 90 days posttransplant in 2024 was 5.9% for SPK, 5.1% for PAK, and 17.6% for PTA; the PTA figure rose sharply from 8.3% in 2023, while PAK early loss fell from 16.7% in 2023, illustrating the year-to-year volatility that small annual volumes produce in the PAK and PTA categories. [6] (Figures as of the 2024 report.)

Registry graft failure is defined by removal of the transplanted pancreas, re-registration for a pancreas transplant, registration for an islet transplant after a pancreas transplant, recipient death, or total insulin use of 0.5 units/kg/day or more for 90 consecutive days. [6]

Comparison to islet transplantation

Islet transplantation infuses isolated pancreatic islets, usually into the hepatic portal vein, rather than implanting the whole organ. It is far less invasive than whole-organ pancreas transplantation, typically allowing same-day or next-day discharge, but it generally provides less durable insulin independence and may require islets from more than one donor. [4][10] Both modalities require lifelong immunosuppression. [4][10] In June 2023, the US Food and Drug Administration approved donislecel (Lantidra), the first allogeneic pancreatic islet cellular therapy, for adults with type 1 diabetes who cannot reach target HbA1c because of repeated severe hypoglycemia despite intensive management; it is administered by infusion into the hepatic portal vein. [4][11] (Approval date June 28, 2023.) Whole-organ pancreas transplantation remains the preferred option when a simultaneous kidney transplant is also indicated, since SPK addresses both organs at once. [1][2]

Immunosuppression

Pancreas transplantation is generally considered to require relatively intensive immunosuppression. [1] Contemporary regimens typically pair induction therapy, using agents such as antithymocyte globulin, alemtuzumab (anti-CD52), or basiliximab (an IL-2 receptor antagonist), with maintenance immunosuppression most commonly built on tacrolimus plus mycophenolate mofetil, with or without low-dose corticosteroids. [1] Antithrombotic prophylaxis (for example low-molecular-weight heparin, sometimes followed by an oral agent) is commonly used because of the high early thrombosis risk, and early imaging is used to monitor graft perfusion. [1] General principles of allograft rejection and tolerance are discussed in Transplant immunology.

Complications

Pancreas transplantation carries a relatively high rate of surgical complications, and a reported 10% to 20% of recipients require a relaparotomy for surgical complications. [1] Major categories include:

• Vascular graft thrombosis: the leading cause of early nonimmunologic graft loss; reported incidence in the range of about 10% to 35% without anticoagulation, and complete thrombosis typically necessitates urgent thrombectomy or causes graft loss. [1]
• Graft pancreatitis: often reperfusion-related, and more severe with fatty or fibrotic donor grafts. [1]
• Anastomotic leaks and fistulas: enteric anastomotic leak is reported in roughly 5% to 8% of cases; leaks and duodenal-graft complications are an important source of reoperation and infection. [1]
• Infection: bacterial infection is most common, and cytomegalovirus reactivation is reported in roughly a quarter of recipients in the setting of intensive immunosuppression. [1]
• Rejection: reported acute rejection rates range widely (roughly 5% to 25%) depending on the immunosuppression protocol and category, and acute rejection is a risk factor for chronic rejection. Percutaneous biopsy is the diagnostic gold standard; in SPK, the kidney graft can serve as a surrogate marker, though discordant rejection of the two organs occurs. [1]
• Bladder-drainage-specific complications: metabolic acidosis, dehydration, recurrent urinary tract infection, and chemical cystitis, sometimes requiring enteric conversion. [1]

US volumes and trends

US pancreas transplant volume has been broadly flat to modestly declining in recent years, with year-to-year fluctuation. The OPTN/SRTR Annual Data Report recorded 915 pancreas transplants in 2023 (versus 918 in 2022), of which roughly 810 were SPK, about 46 PTA, and 36 PAK, the last being the lowest PAK figure in a decade. [5] In 2024, the number of adult pancreas transplants fell to 821, an 8.0% decrease from the prior year. [6] As of December 31, 2023, the pancreas transplant waiting list held 2,687 candidates, predominantly SPK candidates (about 79%). [5] (Figures as of the 2023 and 2024 reports; re-confirm against the live OPTN/SRTR pages before relying on any single year.) The long, slow decline in pancreas-alone and pancreas-after-kidney volumes has been attributed in part to improved diabetes technology, including continuous glucose monitoring and automated insulin delivery, and to renewed interest in islet-based therapies. [1][5][6]

History

The first pancreas transplant was performed on December 17, 1966, at the University of Minnesota by Richard Lillehei and William Kelly, who placed a duct-ligated segmental pancreas graft together with a kidney from the same deceased donor into a 28-year-old woman with diabetes. [12][13] Over subsequent decades the field evolved from segmental grafts and varied duct-management strategies toward standardized whole-organ pancreaticoduodenal transplantation. [12] Bladder drainage became the dominant exocrine-drainage technique during the mid-1980s and through the following decade before enteric drainage became standard. [12] The introduction of tacrolimus and mycophenolate mofetil in the mid-1990s markedly improved outcomes and was followed by increased transplant volumes in many countries. [12] The International Pancreas Transplant Registry, established in 1984, has documented tens of thousands of pancreas transplants worldwide. [1]

See also

• Islet transplantation
• Kidney transplantation
• Organ transplantation
• Transplant immunology

References

• Khanmoradi K, et al. Pancreas Transplantation. StatPearls, NCBI Bookshelf, National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK562338/
• Dholalkar et al. Pancreas transplantation: review. PMC, National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC4943828/
• Multi-Centre UK Analysis of Simultaneous Pancreas and Kidney (SPK) Transplant in Recipients With Type 2 Diabetes Mellitus. PMC, National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869449/
• Regulatory approval of islet transplantation for treatment of type 1 diabetes: Implications and what is on the horizon. PMC, National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC10638039/
• Kandaswamy R, et al. OPTN/SRTR 2023 Annual Data Report: Pancreas. American Journal of Transplantation / PMC, National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC12334190/
• OPTN/SRTR 2024 Annual Data Report: Pancreas. American Journal of Transplantation, ScienceDirect. https://www.sciencedirect.com/science/article/pii/S160061352600986X
• OPTN/SRTR 2022 Annual Data Report: Pancreas. American Journal of Transplantation. https://www.amjtransplant.org/article/S1600-6135(24)00078-9/pdf
• The Role of Pre-Procurement Pancreas Suitability Score (P-PASS) and Pancreas Donor Risk Index (PDRI) in the Outcome of Simultaneous Pancreas and Kidney or Pancreas After Kidney Transplantation. PMC, National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC6681688/
• Utilization of the Pancreas From Donors With an Extremely High Pancreas Donor Risk Index: Report of the National Registry of Pancreas Transplantation. Transplant International / PMC, National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229828/
• Transplantation for type 1 diabetes mellitus. Whole organ or islets? PMC, National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC2633258/
• US Food and Drug Administration. Summary Basis for Regulatory Action: Lantidra (donislecel), June 28, 2023. https://www.fda.gov/media/170457/download
• Squifflet JP, et al. Pancreas transplantation: 50 years of experience. Cirugía Española / PubMed, National Library of Medicine. https://pubmed.ncbi.nlm.nih.gov/28595751/
• Richard C. Lillehei (history of first pancreas transplant). Supporting historical account, Pancreas transplantation review. PMC, National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943828/