Total Pancreatectomy with Islet Autotransplantation: Pancreatic Disease

TPIAT is indicated for chronic pain unresponsive to optimal medical and endoscopic approaches or surgical approaches and significantly impaired quality of life with repeated acute pancreatitis episodes, repeated admissions, missed school or work.

Type 3C diabetes describes a pancreatic form of diabetes that is insulin deficient (unlike type 1 autoimmune or type 2 insulin resistant), must meet ADA criteria for diabetes, has negative islet antibodies, and requires insulin therapy not oral hypoglycemic agents.

A normal peak insulin response to oral glucose tolerance load is typically at 30 minutes; a delayed peak at 60 minutes with blood sugar rising to 150 indicates subtle abnormalities in insulin secretion.

Tramadol is useful for mild to moderate pain because it does not generally slow gut motility as much as conventional opioids.

Sensitization in both the enteric and central nervous system from repeated inflammatory insults can lead to pain when all enzymes are normal, which is treated with neuropathic medications like tricyclic antidepressants and gabapentin, not opioids.

The main indication for TPIAT is chronic pain, not the transplant outcome; the primary goal is pain relief and full function, with insulin independence being secondary.

Brittle diabetes, describing unpredictable extreme highs and lows, is reported in less than 1% of type 1 diabetes patients, and recent studies comparing total pancreatectomy patients with type 1 patients show no difference in complications.

TPIAT criteria include diagnosis of acute recurrent pancreatitis or chronic pancreatitis, chronic pain of greater than 6 months duration with either daily opioid use or severely impaired quality of life, absence of reversible cause, failure of medical or endoscopic intervention, and adequate beta cell function.

Contraindications to islet autotransplantation include pre-existing insulin dependent diabetes mellitus, liver disease with portal hypertension or portal vein thrombosis.

Patients with central sensitization of pain, functional pain disorders, drug seeking behavior, or severe psychosocial maladaptation do not do as well after TPIAT.

Splenectomy is performed routinely for TPIAT; attempts to preserve the spleen risk warm ischemia to islets during dissection and potential splenic infarction if relying only on short gastric vessels.

Insulin independence is dependent on the number of islet equivalents transplanted, and there is a relationship between islet yield and severity of chronic pancreatitic changes by imaging or histopathology.

Prior ductal drainage procedures and distal pancreatectomy compromise islet yield.

Surgical drainage procedures are avoided in patients anticipated to require future TPIAT, particularly those with genetic etiologies.

All TPIAT patients have delayed gastric emptying that resolves in several weeks, typically by 3-5 weeks.

Heparin anticoagulation is maintained intraoperatively and for one week postoperatively to prevent portal vein thrombosis from islet infusion.

Portal vein pressures exceeding 25 centimeters of water pressure are associated with higher risk of portal vein thrombosis post TPIAT.

Tight glucose control between 80 and 120 is critical postoperatively to protect from toxic hyperglycemia, as islets do not resume function immediately and rely on diffusion of nutrients and oxygen until neovascularization occurs over weeks to months.

Dexamethasone infusion is used for the first 2 days postoperatively to decrease the instant blood mediated inflammatory response which has a potentially detrimental effect on islets.

Acetaminophen is not used postoperatively because some continuous glucose monitoring systems will read falsely with it.

Significant thrombocytosis occurs after TPIAT, likely not just related to splenectomy but possibly due to increased thrombopoietin levels produced by hepatocytes.

Complications occur in 15-20% of TPIAT cases, including bleeding (5-7%), abscesses, wound infections, bowel obstructions, portal vein thrombosis, and anastomotic leaks.

Up to 85-90% of TPIAT patients can achieve opioid independence, with most improvement occurring over the first several months.

In children, 40% of TPIAT patients achieve insulin independence (typically over the first 12 months), 30% have partial graft function requiring basal insulin only, and 30% require basal-bolus insulin.

Data from Minnesota shows the best outcomes in patients under 12 years old, with up to 55% insulin independence rate.

Higher replicatory capacity of islets in younger children and possible islet neogenesis of ductal origin may explain better outcomes in younger patients.

Islet function has been shown to be durable in children for as long as 10 years post TPIAT and is especially good for patients under 21 or with a short history of pancreatic disease.

The expectation is to wean patients off opioids postoperatively because there is no pancreas to have acute inflammatory disorders, and visceral hyperalgesia from sensitization should not be treated with opioids.