What are the updates on hormone, enzyme, and peptide replacement therapies for a patient who has undergone a total pancreatectomy?

Post-Total Pancreatectomy Hormone, Enzyme, and Peptide Replacement: Current Updates

Immediate Postoperative Initiation

All patients undergoing total pancreatectomy require immediate initiation of pancreatic enzyme replacement therapy (PERT) at 50,000 units of lipase with meals and 25,000 units with snacks, comprehensive insulin therapy with endocrinology referral, and nutritional support with dietitian consultation. 1

For patients with total pancreatectomy, no further diagnostic testing for exocrine pancreatic insufficiency is needed—PERT should be initiated immediately postoperatively. 2

Pancreatic Enzyme Replacement Therapy (PERT)

Dosing Strategy

• Start PERT at 50,000 units of lipase per main meal and 25,000 units per snack immediately after surgery. 1
• The typical adult starting dose is 500 units of lipase per kg per meal (approximately 40,000 U for an 80 kg patient) and 250 units of lipase per kg per snack (20,000 U for an 80 kg patient). 2
• Maximum dose is 2,500 units of lipase per kg per meal or 10,000 units of lipase per kg per day. 2
• Titrate upward if steatorrhea, gastrointestinal symptoms, weight loss, or micronutrient deficiencies persist. 1

Administration Timing

• PERT must be taken during the meal, not before or after, to maximize mixing with nutrients and optimize digestion. 3

FDA-Approved Formulations

• All FDA-approved PERT formulations are porcine-derived and equally effective at equivalent lipase doses, including Creon, Zenpep, Pancreaze, Pertzye, and Viokace. 3
• In clinical trials of patients with pancreatectomy, CREON increased mean coefficient of fat absorption from 42% to 84% at the end of treatment. 4

Management of PERT Intolerance

• If PERT is not tolerated, treat underlying small intestinal bacterial overgrowth (SIBO) first before continuing enzyme therapy, using Rifaximin 550 mg twice daily for 1-2 weeks as first-line treatment. 1

Insulin and Diabetes Management

Insulin Therapy Approach

• Consider continuous subcutaneous insulin infusion (insulin pump therapy) for optimal glucose control in the post-pancreatectomy state. 1
• CSII therapy achieves better glycemic control (median HbA1c 7.3%) compared to multiple daily injections (median HbA1c 8.1%) and is associated with significantly fewer severe hypoglycemic events (P = 0.02). 5

Diabetes Characteristics Post-Total Pancreatectomy

• The diabetes resulting after total pancreatectomy is characterized by complete loss of endogenous insulin and counterregulatory hormones (including glucagon), leading to "brittle diabetes" with important glycemic variations. 6
• Improvements in postoperative management include advances in insulin formulations and the use of glucagon rescue therapy, which allow much tighter control of blood glucose and markedly lessen the risk of life-threatening hypoglycemia. 7

Hypoglycemia Risk Factors

• Factors increasing hypoglycemia risk include use of insulin, impaired counterregulatory response, hypoglycemia unawareness, frailty and older age, cognitive impairment, alcohol use, and polypharmacy. 2

Nutritional Support and Micronutrient Replacement

Dietitian Referral

• All patients require referral to a registered dietitian nutritionist for medical nutrition therapy to address malabsorption, early satiety, and weight loss. 1

Fat-Soluble Vitamin Supplementation

• Routine supplementation and monitoring of vitamins A, D, E, and K are required, with vitamin K dosing ranging from 0.3-1 mg/day for infants to 1-10 mg/day for older children and adults. 3
• A low-moderate fat diet with frequent smaller meals is recommended, while avoiding very-low-fat diets, which are counterproductive. 3

Monitoring Schedule

• Baseline and serial measurements should include body mass index, fat-soluble vitamin levels, quality-of-life assessment, and dual-energy x-ray absorptiometry (DEXA) scan, which should be repeated every 1-2 years. 3
• Adults should be assessed every 6 months for stable patients, with ongoing monitoring including anthropometric measurements, serum markers, and hemoglobin A1c for diabetes screening. 3

Special Consideration: Islet Autotransplantation

Indications

• For patients undergoing total pancreatectomy for chronic pancreatitis (not cancer), islet autotransplantation should be considered to prevent postsurgical diabetes. 2, 1
• Approximately one-third of patients undergoing total pancreatectomy with islet autotransplantation are insulin-free at 1 year postoperatively, with observational studies demonstrating islet graft function up to a decade after surgery in some patients. 2, 1

Patient Selection

• Both patient and disease factors should be carefully considered when deciding the indications and timing of this surgery, and surgeries should be performed in skilled facilities that have demonstrated expertise in islet autotransplantation. 2

Surveillance and Follow-Up

Monitoring Schedule

• Monitor patients at 3-6 month intervals for recovery of treatment-related toxicities and recurrence, and assess symptom burden, psychological status, and social supports at each visit. 2, 1
• The role of serial cross-sectional imaging, the extent to which surveillance intervals should be prolonged over time, and the duration of recommended surveillance are all undefined. 2

Oncologic Considerations

• For patients with resected pancreatic cancer, initiate adjuvant chemotherapy within 8 weeks of surgical resection, assuming complete recovery, and offer 6 months of adjuvant chemotherapy (gemcitabine and capecitabine doublet preferred). 2, 1

Markers of Treatment Success

• Effective PERT produces reduction in steatorrhea and gastrointestinal symptoms, weight gain, improved muscle mass and function, and normalization of fat-soluble vitamin levels. 3
• Low doses of pancreatic enzymes are associated with unintentional weight loss and gastrointestinal symptoms. 5

Palliative Care and Supportive Services

• Patients should receive a full assessment of symptom burden, psychological status, and social supports as early as possible, preferably at the first visit, which may indicate a need for formal palliative care consult and services. 2
• Mandatory access to palliative care specialists for all post-pancreatectomy patients is recommended. 1