Pancreatic Islet Cell Transplant

Pancreatic Islet Cell Transplant

Anesthesia type
Airway
Lines and access
Monitors
Primary anesthetic considerations
Preoperative
Intraoperative
Postoperative
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Pancreatic islet cell transplantation involves removing the entire pancreas (total pancreatectomy) and then reinfusing the extracted islet cells into the patient’s portal vein. After the pancreas is removed, islet cells are isolated and suspended in a solution for infusion. This autotransplantation procedure helps patients achieve better glycemic control, reducing complications and enhancing quality of life for those with type 1 diabetes.

Overview

Indications

Pancreatic islet cell transplantation is indicated primarily for patients with type 1 diabetes who experience severe hypoglycemia despite intensive diabetes management and education. According to the American Diabetes Association, allogeneic islet transplantation is specifically indicated for adults with type 1 diabetes who are unable to achieve their A1C goals due to recurrent severe hypoglycemia.

Additionally, autologous islet cell transplantation is indicated for patients undergoing total pancreatectomy for medically refractory chronic pancreatitis to prevent postsurgical diabetes. This procedure is also considered for patients with benign or borderline pancreatic tumors, hereditary/genetic pancreatitis, and high-risk pancreatic stump.

Surgical procedure

1. Total Pancreatectomy

• Patient Preparation: The patient is positioned and prepped for surgery under general anesthesia.
• Pancreas Removal: The surgeon performs a total pancreatectomy, carefully removing the pancreas while preserving other vital structures, such as the spleen (if possible) and adjacent blood vessels.
• Pancreas Transport: The excised pancreas is quickly transported to an islet processing lab, ideally within the same facility, to minimize ischemia time.

2. Islet Cell Isolation and Purification

• Enzymatic Digestion: The excised pancreas is treated with digestive enzymes to break down the tissue and isolate the islet cells, which are clusters of insulin-producing beta cells.
• Islet Cell Purification: Using density gradient centrifugation, islet cells are separated from the surrounding pancreatic tissue. This step requires precision to yield a high concentration of viable islet cells.
• Suspension Preparation: The purified islet cells are suspended in a sterile solution, creating an infusion-ready preparation to be delivered to the patient.

3. Portal Vein Infusion of Islet Cells

• Portal Vein Access: During or immediately after surgery, the patient is brought to an interventional radiology suite (or similar setting) where a catheter is inserted into the portal vein, typically via percutaneous access to the liver or through a small surgical incision.
• Islet Cell Infusion: The islet cell suspension is slowly infused into the portal vein, allowing the cells to travel into the liver. Within the liver, these cells ideally lodge in the small blood vessels and start producing insulin.
• Monitoring for Complications: The infusion process is carefully monitored to prevent portal vein thrombosis (blood clots), a known risk of islet cell infusion.

Preoperative management

Patient evaluation

Preoperative evaluation for patients undergoing pancreatic islet cell autotransplantation after total pancreatectomy is critical to optimize surgical outcomes and assess eligibility, especially since these patients often have chronic pancreatitis and complex metabolic needs. The evaluation typically involves a multidisciplinary approach, including thorough assessment of metabolic, endocrine, and psychological health.

1. Medical and Surgical History

• Chronic Pancreatitis Severity: Evaluating the history and severity of chronic pancreatitis, including frequency of pain episodes, previous surgeries, and use of pain medications. This assessment helps to predict the potential benefits of surgery.
• Diabetes and Glycemic Control: Since many patients with chronic pancreatitis have altered insulin production, a detailed assessment of blood glucose levels, insulin use, and any history of hypoglycemia or hyperglycemia is essential. Patients with longstanding diabetes may have fewer islet cells available for autotransplantation.

2. Endocrine and Metabolic Assessment

• Islet Cell Function Testing: Tests like fasting blood glucose, HbA1c, and C-peptide levels provide information about residual pancreatic islet function, which can indicate how much islet cell mass might be available for autotransplantation.
• Insulin Sensitivity and Resistance: Assessing insulin sensitivity is essential, as patients with higher insulin resistance may have different postoperative glycemic control needs.

3. Imaging Studies

• Pancreatic Imaging: MRI or CT scans of the pancreas are crucial to assess pancreatic anatomy, ductal structures, and identify any areas of fibrosis or calcifications, which may impact the islet cell yield.
• Portal Vein and Liver Imaging: Since the portal vein will be the route for islet infusion, it is examined through ultrasound or Doppler imaging to ensure there is no thrombosis or obstruction.

4. Liver Function Tests

• Liver Function Panel: Evaluating liver enzymes, bilirubin, albumin, and coagulation status provides an understanding of liver function, which is vital since the transplanted islets will engraft in the liver and produce insulin there.
• Portal Hypertension Screening: For patients with long-standing pancreatic disease, it is important to evaluate for signs of portal hypertension, as this could complicate the infusion procedure.

5. Nutritional and Gastrointestinal Evaluation

• Nutritional Status: Many patients with chronic pancreatitis have malnutrition or deficiencies due to malabsorption. Nutritional evaluation with serum vitamin levels, albumin, and prealbumin, as well as consultation with a nutritionist, helps to optimize nutrition pre-surgery.
• Gastrointestinal Function: Assessment of exocrine pancreatic insufficiency and history of steatorrhea can indicate the need for enzyme replacement therapy postoperatively.

6. Psychological Evaluation

• Mental Health Screening: Chronic pain and long-term management of diabetes or pancreatitis can impact mental health. Psychological evaluation helps identify any existing mental health issues, such as depression or anxiety, and ensures the patient is prepared for the postoperative recovery process.
• Assessment of Expectations: Counseling patients regarding the limitations and potential outcomes of islet cell autotransplantation is important for setting realistic expectations.

7. Anesthesia and Surgical Risk Assessment

• Cardiovascular and Pulmonary Evaluation: Patients are assessed for cardiovascular and pulmonary health, especially if they have a history of smoking or other risk factors. Standard evaluations may include ECG, chest X-ray, and, if necessary, stress tests.
• Pain Management Planning: Preoperative consultation with an anesthesiologist and pain management specialist helps develop a strategy to manage perioperative and postoperative pain, which is often significant in patients with chronic pancreatitis.

8. Laboratory Testing

• Complete Blood Count and Coagulation Panel: Baseline blood work is needed to identify any anemia, thrombocytopenia, or coagulopathy that may impact the surgery.
• Kidney Function Tests: Renal function assessment is important, as kidney impairment can impact drug dosing and postoperative management.

In summary, preoperative evaluation for pancreatic islet cell autotransplantation includes comprehensive assessment of pancreatic function, metabolic and nutritional status, liver health, imaging studies, psychological readiness, and surgical risk. This multidisciplinary approach helps identify candidates likely to benefit most from the procedure and reduces the risk of postoperative complications

System	Considerations
Airway	Assess for potential difficulties in airway management due to history of smoking or chronic pancreatitis-related malnutrition, which can affect respiratory function. - Evaluate the risk of aspiration, especially if the patient has delayed gastric emptying (common in chronic pancreatitis).
Neurologic	- Evaluate for any history of diabetic neuropathy or chronic pain, as these may affect perioperative pain management and postoperative recovery. - Perform a mental health screening to assess for chronic pain-related depression or anxiety, which can influence postoperative outcomes and adherence to medical guidance. - Assess for hepatic encephalopathy if any liver dysfunction is present, as the liver will host the transplanted islets.
Cardiovascular	Conduct cardiovascular assessment, especially if there is a history of diabetes, which increases risk for coronary artery disease. - Evaluate for hypertension and possible portal hypertension. - Perform ECG and other cardiac tests as needed, given the risk of intraoperative hypotension due to anesthetic agents and chronic malnutrition.
Pulmonary	Assess lung function and smoking history; chronic pancreatitis patients may have compromised respiratory function due to malnutrition or chronic illness. - Screen for restrictive lung disease if patients have undergone previous abdominal surgeries. - Consider perioperative pulmonary function tests, especially in patients with reduced exercise tolerance or respiratory issues.
Gastrointestinal	- Assess for delayed gastric emptying, which is common in chronic pancreatitis and can increase the risk of aspiration. - Evaluate nutritional status and existing deficiencies, as many patients have malabsorption and may require nutritional support. - Discuss the need for pancreatic enzyme replacement therapy postoperatively, as the pancreas is being removed.
Hematologic	Assess for anemia and coagulopathy, which may be due to chronic disease or liver dysfunction. - Perform a complete blood count (CBC) and coagulation studies to identify any risk of bleeding or thrombosis. - Evaluate platelet count, especially important in patients with portal hypertension, as splenomegaly can cause thrombocytopenia.
Renal	- Evaluate kidney function, especially important in patients with diabetes or those requiring frequent use of NSAIDs for chronic pain. - Check electrolyte levels, as chronic malnutrition or gastrointestinal issues may lead to imbalances. - Assess for any history of renal dysfunction, which could impact postoperative medication metabolism and dosing.
Endocrine	- Assess insulin production, sensitivity, and glycemic control with HbA1c and fasting blood glucose levels; many patients may already have insulin-dependent diabetes. - Evaluate for hypoglycemic unawareness, which is crucial for managing postoperative blood glucose fluctuations. - Screen for other endocrine disorders related to chronic pancreatitis, such as adrenal insufficiency.
Other	- Pain Management: Plan for perioperative pain management, as these patients often have a high opioid requirement due to chronic pain. - Psychological: Assess for psychological readiness and support needs, given the impact of chronic illness on mental health. - Infectious Disease: Screen for infections due to immunocompromised states from malnutrition and chronic illness. - Immunology: Prepare for immune modulation in case of any complications, although immunosuppression is not typically required for autotransplantation.

Operating room setup

Fluid warmers and patient warming devices

Patient preparation and premedication

Standard premedications

Regional and neuraxial techniques

Possible Thoracolumbar Epidural or TAP block

Intraoperative management

Monitoring and access

2 large bore PIV (16 g or larger) or central line (8 Fr or 9 Fr double lumen)

Arterial line

Foley catheter

NG tube (remains in place post-op)

Induction and airway management

Standard induction and airway management

Positioning

Supine

Maintenance and surgical considerations

Type and cross for 4 units PRBC's

Cell saver

Cefoxitin antibiotic of choice

Plasmalyte crystalloid of choice

Blood glucose monitoring q30 min after pancreatectomy for goal of 110-130 using insulin infusion.

Heparin drip may be started after islet cell infusion is complete

During the islet cell infusion, portal venous pressures will be monitored off the arterial line transducer (need male-to-male connection). If pressures exceed 25 cmH20, the infusion will be held until pressures returns below at least 12 cmH20.

Emergence

Remain intubated (if surgeon's preference) and go to ICU.

Postoperative management

Disposition

ICU for glucose management

Pain management

• Epidural Analgesia: An epidural catheter is often placed before surgery to provide continuous local anesthetic infusion, typically a combination of a local anesthetic (e.g., bupivacaine) with a small dose of opioid (e.g., fentanyl or hydromorphone). This can significantly reduce the need for systemic opioids postoperatively.
• Regional Nerve Blocks: Transversus abdominis plane (TAP) blocks or quadratus lumborum blocks may be used to target the abdominal wall nerves, reducing incisional pain. These are typically administered by the anesthesia team.
• IV Lidocaine and Ketamine: Intravenous lidocaine and low-dose ketamine may be used intraoperatively to provide additional analgesia and reduce the risk of chronic pain postoperatively. Ketamine has both analgesic and opioid-sparing effects, particularly helpful in patients with a history of opioid tolerance.
• Patient-Controlled Analgesia (PCA): If an epidural is not used or after it is removed, a PCA pump with opioids (e.g., morphine or hydromorphone) is often provided, allowing patients to control their pain relief within safe dosing limits.
• Scheduled Non-Opioid Analgesics: Non-opioid medications, such as acetaminophen and NSAIDs (if not contraindicated), are scheduled regularly to provide a baseline level of pain control.
• Gabapentinoids: Gabapentin or pregabalin may be included as part of the regimen to control neuropathic pain, especially in patients with a history of chronic pain.
• Adjuvant Medications: Adjuvant medications, including tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors (SNRIs), can be considered for patients with neuropathic pain or mood-related pain components.
• Psychological Support: Pain management also includes psychological support, as chronic pain patients often benefit from coping strategies, relaxation techniques, or cognitive behavioral therapy (CBT) to help manage both pain and the psychological impact of long-term illness.

Potential complications

1. Surgical Complications

• Bleeding: The pancreas is highly vascular, and total pancreatectomy can lead to significant blood loss. Intraoperative or postoperative bleeding is a risk, especially if patients have underlying coagulopathy or portal hypertension.
• Infection: Surgical site infections, abscesses, and sepsis are potential complications due to the extensive nature of the surgery. Pancreatitis patients are often at higher risk for infections.
• Anastomotic Leak: If any gastrointestinal reconnections are made (e.g., bile duct anastomosis), there’s a risk of leakage at the surgical site, leading to peritonitis and other complications.
• Pancreatic Fistula: Though less common in total pancreatectomy than in partial resections, pancreatic duct leaks can sometimes occur and require drainage or further surgery.

2. Metabolic and Glycemic Complications

• Diabetes Mellitus: With the pancreas removed, most patients develop diabetes due to the loss of insulin-producing islet cells. Although autotransplanted islet cells aim to provide some insulin production, not all patients achieve full insulin independence.
• Hypoglycemia: Especially early postoperatively, transplanted islets may produce unpredictable insulin levels, leading to hypoglycemia. Patients may also develop hypoglycemia unawareness due to reduced insulin stability.
• Hyperglycemia: Ineffective islet cell function or insufficient cell mass can result in hyperglycemia, requiring insulin therapy or medication adjustments.
• Electrolyte Imbalances: Removal of the pancreas can lead to changes in blood electrolytes, such as calcium and magnesium, which require monitoring and correction.

3. Portal Vein Complications from Islet Infusion

• Portal Vein Thrombosis: The infusion of islet cells into the portal vein can increase the risk of thrombosis (clot formation) in the portal venous system. This may lead to complications such as portal hypertension, liver dysfunction, or infarction in severe cases.
• Hepatic Steatosis: The liver can accumulate fat as a response to insulin production by islet cells engrafted within it. Over time, this may progress to hepatic steatosis (fatty liver), which can impair liver function.
• Hepatic Enzyme Elevation: Transient elevations in liver enzymes (e.g., AST, ALT) are common after islet infusion and generally resolve with time, though persistent elevation may indicate a problem.

4. Endocrine Complications

• Exocrine Pancreatic Insufficiency: Removal of the pancreas results in loss of digestive enzymes, leading to exocrine insufficiency and symptoms like malabsorption, diarrhea, and weight loss. Patients typically require lifelong pancreatic enzyme replacement therapy.
• Nutritional Deficiencies: Due to malabsorption, patients may develop deficiencies in fat-soluble vitamins (A, D, E, K) and other nutrients, leading to complications such as osteoporosis, anemia, or delayed wound healing if not managed with supplements.

5. Pain and Chronic Pain Recurrence

• Chronic Abdominal Pain: Despite the removal of the pancreas, some patients continue to experience chronic pain due to nerve sensitization or post-surgical nerve damage, requiring ongoing pain management.
• Opioid Dependence: Many patients with chronic pancreatitis have a history of high-dose opioid use. After surgery, managing and weaning off opioids can be challenging, and patients may experience withdrawal or require long-term pain management plans.

6. General Surgical and Postoperative Complications

• Delayed Gastric Emptying: Surgery involving the pancreas often affects gastric motility, resulting in delayed gastric emptying or "gastroparesis." This can lead to nausea, vomiting, bloating, and prolonged hospital stays.
• Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE): Long surgical times and limited postoperative mobility increase the risk of thromboembolic events like DVT or PE.
• Psychological Impact: Patients often experience significant emotional distress, including anxiety and depression, due to chronic pain, diabetes management, and the physical challenges of recovery. Mental health support is essential for a positive long-term outcome.

7. Long-term Complications

• Insufficient Islet Cell Function: Over time, the autotransplanted islet cells may lose function, potentially leading to increased dependence on insulin therapy.
• Fatty Liver Disease: As transplanted islets produce insulin within the liver, fatty liver disease can develop over the long term, impacting liver health and function.

Procedure variants

	Variant 1	Variant 2
Unique considerations
Indications
Position
Surgical time
EBL
Postoperative disposition
Pain management
Potential complications