Overview
Definition:
Total pancreatectomy with islet autotransplant is a complex surgical procedure involving the complete removal of the pancreas, followed by the isolation and transplantation of insulin-producing islet cells from the resected pancreas into the patient's liver or portal vein
This procedure is primarily indicated for debilitating, unresectable pancreatic diseases where preserving endocrine function is a critical goal.
Epidemiology:
Total pancreatectomy is a rare procedure, performed in a small percentage of patients undergoing pancreatectomy, often for specific indications like diffuse intraductal papillary mucinous neoplasm (IPMN) or certain types of neuroendocrine tumors
Islet autotransplantation is performed in a subset of these patients to mitigate the profound metabolic consequences of pancreatectomy, namely diabetes mellitus.
Clinical Significance:
This procedure is crucial for managing patients with severe pancreatic pain and metabolic dysfunction caused by conditions such as chronic pancreatitis, unresectable pancreatic cancer, or diffuse pancreatic neoplasms
It offers a potential solution for pain relief while aiming to preserve some degree of endogenous insulin production, thereby avoiding or mitigating the severity of surgically induced diabetes
It represents a last resort for select patients facing significant morbidity.
Indications
Primary Indications:
Severe, intractable pain from chronic pancreatitis unresponsive to medical or less extensive surgical management
Diffuse pancreatic neoplasms (e.g., IPMN) that involve the entire pancreas and cannot be managed with organ-sparing resections
Certain unresectable pancreatic neuroendocrine tumors where pancreatectomy is deemed necessary for oncologic control and palliative benefit.
Relative Indications:
Certain genetic syndromes predisposing to diffuse pancreatic disease
Significant pancreatic ductal dilation and mucin production throughout the gland
Cases where pancreas-preserving resections carry unacceptable oncologic risk or have failed.
Contraindications:
Active infection
Severe comorbid conditions precluding major surgery
Widespread metastatic disease making the procedure futile
Inadequate islet yield expected due to pancreatic fibrosis or disease extent
Patients unwilling or unable to adhere to lifelong immunosuppression or metabolic monitoring.
Preoperative Preparation
Patient Evaluation:
Comprehensive assessment of pancreatic exocrine and endocrine function
Evaluation of nutritional status and comorbid conditions
Detailed imaging (CT, MRI, EUS) to assess the extent of pancreatic disease and rule out distant metastases
Assessment of liver function for potential islet engraftment.
Nutritional Optimization:
Management of malabsorption and malnutrition
Pancreatic enzyme replacement therapy (PERT) optimization
Vitamin and micronutrient supplementation
Preoperative counseling regarding the metabolic consequences and lifelong management.
Surgical Planning:
Multidisciplinary team discussion involving surgeons, endocrinologists, anesthesiologists, and gastroenterologists
Preoperative antibiotics and DVT prophylaxis
Planning for potential blood loss and fluid management
Donor islet isolation facility and plan for immediate transplantation.
Procedure Steps
Pancreatectomy:
Laparotomy or laparoscopic approach
Mobilization of the pancreas, duodenum, spleen, and surrounding structures
Ligation of vascular supply (splenic artery/vein, superior/inferior mesenteric vessels)
Transection of the pancreas at the appropriate level, typically near the superior mesenteric vein
Complete removal of the pancreatic parenchyma, islets, ducts, and often the spleen and duodenum.
Islet Isolation:
The resected pancreas is immediately transported to an islet isolation laboratory
The pancreatic tissue is digested with enzymes (e.g., collagenase) to break down the tissue and release islets
Islets are then purified and concentrated using density gradient centrifugation or fluorescence-activated cell sorting (FACS) to remove exocrine tissue and debris.
Islet Transplantation:
The isolated islets are infused, usually via percutaneous transhepatic catheterization, into the portal vein of the liver
Alternatively, they can be infused directly into the portal venous system during laparotomy
Engraftment and function are monitored post-transplant
Post-operative care focuses on immunosuppression and metabolic monitoring.
Postoperative Care
Pain Management:
Aggressive multimodal pain control including patient-controlled analgesia (PCA), epidural analgesia, and judicious use of opioids and adjuvants
Monitoring for surgical pain versus visceral pain related to pancreatitis.
Metabolic Monitoring:
Frequent blood glucose monitoring (SMBG, continuous glucose monitoring - CGM)
Insulin therapy initiation and titration based on blood glucose levels and islet graft function
Monitoring for hypoglycemia, which can be severe due to immature islet graft function and exogenous insulin
Electrolyte monitoring.
Nutritional Support:
Continued PERT
Nasogastric or jejunal feeding may be required
Nutritional assessment and supplementation as needed
Monitoring for signs of exocrine insufficiency and malabsorption
Hydration and fluid management.
Complications
Early Complications:
Hemorrhage from the pancreatic resection site or portal vein catheterization
Infection (intra-abdominal abscess, wound infection)
Postoperative pancreatitis (rare but significant)
Portal vein thrombosis
Biliary complications (leakage or stricture)
Acute kidney injury
Respiratory complications
Severe hypoglycemia or hyperglycemia.
Late Complications:
Chronic pain recurrence
Exocrine insufficiency requiring lifelong PERT
Endocrine insufficiency (Type 3c diabetes mellitus) requiring lifelong insulin therapy and careful glycemic control
Islet graft failure or dysfunction
Liver dysfunction or complications related to transhepatic access
Nutritional deficiencies
Adhesives bowel obstruction.
Prevention Strategies:
Meticulous surgical technique to minimize bleeding and pancreatic stump leak
Judicious use of prophylactic antibiotics and DVT prophylaxis
Aggressive glycemic monitoring and management
Early mobilization and pulmonary physiotherapy
Close metabolic and nutritional monitoring post-discharge
Optimizing islet isolation and transplantation techniques.
Prognosis
Factors Affecting Prognosis:
The underlying pathology (benign vs
malignant), success of islet engraftment and function, development of diabetes, management of pain, presence of complications, patient's nutritional status, and adherence to follow-up and treatment regimens
Oncologic outcomes are paramount for malignant disease.
Outcomes:
For patients with chronic pancreatitis, the goal is significant pain relief and avoidance or reduction of severe diabetes
For malignant disease, the prognosis is largely dictated by the cancer stage
Successful islet autotransplantation can significantly improve quality of life by mitigating the severity of diabetes
However, many patients still require insulin therapy and PERT.
Follow Up:
Lifelong follow-up is essential
This includes regular monitoring of blood glucose, HbA1c, and need for insulin adjustments
Pancreatic enzyme replacement therapy assessment
Nutritional status evaluation
Imaging surveillance for recurrent or metastatic disease (if malignant)
Monitoring for complications of immunosuppression if employed (though less common in autotransplantation)
Pain assessment and management.
Key Points
Exam Focus:
Indications for total pancreatectomy with islet autotransplant
The technical steps involved in islet isolation and transplantation
Management of surgically induced diabetes (Type 3c)
Complications of the procedure, both early and late
Differentiating indications from contraindications for this complex surgery.
Clinical Pearls:
Islet autotransplantation aims to preserve endocrine function and improve quality of life, not cure the underlying disease
Pain relief is a major goal for chronic pancreatitis
Meticulous surgical technique and post-operative metabolic management are critical for success
Understand the challenges of managing labile blood glucose post-transplant
Islet yield is a critical determinant of graft success.
Common Mistakes:
Performing total pancreatectomy without adequate consideration for islet autotransplant when endocrine preservation is feasible
Inadequate preoperative assessment of pancreatic function or comorbidities
Poor management of post-operative glycemic lability
Underestimating the lifelong metabolic and nutritional demands on the patient
Failure to adhere to strict follow-up protocols.