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Pancreas Transplant

Pancreas Transplant - Indications

  • Most common indication:
    • Type 1 diabetes with CKD (usually requiring kidney transplant)
    • Benefits:
      • Prevents progression of retinopathy and cardiomyopathy
      • Reduces frequent life-threatening hypoglycemic episodes
  • Type 2 diabetes with CKD:
    • Indication in patients with documented life-threatening hypoglycemic episodes despite insulin therapy.
    • Efficacy in Type 2 diabetes is not clearly established.
  • Exocrine Insufficiency:
    • Post-surgical management after procedures for chronic pancreatitis (based on case reports).

Types of Pancreas Transplant

  • SPK (Simultaneous Pancreas-Kidney Transplant):
    • Most commonly performed type of pancreas transplant.
  • PTA (Pancreas Transplant Alone):
    • Indicated for Type 1 diabetes with recurrent life-threatening hypoglycemia or ketoacidosis.
    • Candidates must have stable renal function with:
      • GFR > 70-80 mL/min.
      • Proteinuria less than 1 g/day.
  • PAK (Pancreas After Kidney Transplant):
    • Indicated in patients with GFR > 50 mL/min.
  • Most common cause of death after pancreas transplant:
    • Cardiovascular complications.

Pancreas Donor Risk Index - Components

  • Age
  • Sex
  • Race
  • BMI (Body Mass Index)
  • Height
  • Cause of death
  • Preservation time
  • DCD (Donation after Circulatory Death)
  • Terminal creatinine
  • Cold ischemia time

Pancreas Transplantation: Key Points

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This diagram illustrates the "Y" graft technique used in pancreas transplantation, where the pancreas is connected to the donor's iliac artery for arterial inflow and to either the portal or systemic circulation for outflow.

  • Arterial Inflow:
    • Common iliac artery
  • Portal Outflow:
    • Superior Mesenteric Vein (SMV)
  • Systemic Outflow:
    • Inferior Vena Cava (IVC)
  • Metabolic Considerations:
    • No significant metabolic advantage of portal versus systemic drainage.
    • Systemic drainage can lead to hyperinsulinemia.

Bladder Drainage vs Enteric Drainage in Pancreas Transplantation

Bladder Drainage Enteric Drainage
20% of patients have bladder drainage. 80% of patients have enteric drainage.
Associated with recurrent UTI, urethritis, urethral disruption, and metabolic acidosis. Avoids urinary tract complications.
Easy monitoring of rejection via urinary amylase. More physiologic drainage method.
Leaks are easier to manage non-operatively via Foley catheter, but there is an increased leak rate. Leaks present with abdominal sepsis, urgent laparotomy, graft loss; decreased leak rate.

Pancreas Transplant Rejection

  • Monitoring: Rejection is closely monitored by assessing renal allograft dysfunction in patients with simultaneous pancreas-kidney (SPK) transplants.
  • Exocrine Pancreas: The exocrine pancreas is typically affected first during rejection.
  • Beta Cells: Beta cells have a functional reserve, so insulin production continues despite early rejection.
  • Hyperglycemia: A late sign of pancreas rejection, indicating advanced damage.
  • Amylase and Lipase: These enzymes are non-specific markers as they can be elevated due to graft pancreatitis or infection.

Graft Thrombosis in Pancreas Transplantation

  • Most Common Cause:
    • Non-immunologic cause of graft failure.
  • Type:
    • Venous thrombosis is more common than arterial thrombosis.
  • Donor Factors:
    • Interposition grafts used for lengthening the portal vein.
  • Recipient Factors:
    • Diabetes increases risk.
    • Coagulopathy due to uremia can have a protective effect.
  • Diagnosis:
    • USG Doppler is used to assess venous or arterial thrombosis.
  • Clinical Signs:
    • Graft tenderness.
    • Elevation in amylase and lipase.
    • Decrease in urinary amylase.
  • Bleeding:
    • The most common indication for relaparotomy.

MCQs for Pancreas Transplantation

  1. Which of the following candidates is ideal for Pancreas Transplant Alone (PTA)?
    • A. Type 1 diabetes with chronic kidney disease
    • B. Type 2 diabetes with recurrent hypoglycemic episodes
    • C. Chronic pancreatitis with exocrine insufficiency post-surgery
    • D. Type 1 diabetes with hypoglycemic episodes and stable renal functionAnswer: D
  2. Graft survival is highest in which of the following cases?
    • A. PTA
    • B. SPK (Simultaneous Pancreas-Kidney Transplant)
    • C. PAK (Pancreas After Kidney Transplant)
    • D. Same in allAnswer: B
  3. Which of the following is not true about exocrine drainage of the transplanted pancreas?
    • A. Bladder drainage can allow early detection of rejection
    • B. Bladder drainage is associated with recurrent UTI and metabolic acidosis
    • C. Bladder drainage leaks require urgent laparotomy and are more difficult to manage than enteric drainage
    • D. Currently, more than 80% of drainage is via the enteric routeAnswer: C (Bladder drainage leaks are easier to manage with non-operative methods like Foley catheter)

MCQs for Pancreas and Islet Cell Transplantation

  1. Highest incidence of rejection is observed in which of the following organs?
    • A. Liver
    • B. Kidney
    • C. Pancreas
    • D. Small bowelAnswer: D
  2. A 50-year-old diabetic underwent SPK transplantation. Which of the following is not true regarding secondary complications of diabetes and pancreatic transplantation?
    • A. Reversal of diabetic retinopathy
    • B. Improvement in motor and sensory functions in autonomic neuropathy
    • C. Stabilization of diabetic gastropathy
    • D. Reversal of histological changes in diabetic nephropathyAnswer: A (Reversal of diabetic retinopathy takes 5-10 years)
  3. Most common site for islet cell transplantation:
    • A. Portal vein
    • B. IVC
    • C. Liver
    • D. SMVAnswer: A

  4. Edmonton protocol involves which of the following drugs?

    • A. Sirolimus, tacrolimus, and daclizumab
    • B. MMF, steroids, and basiliximab
    • C. Cyclosporine, MMF, and steroids

    • D. None of the above

      Answer: A

    • Edmonton Protocol:

      • Most common site: Portal vein.
      • Most common complication: Portal vein thrombosis.
      • Drug regimen: Sirolimus, Tacrolimus, and Daclizumab.
    • Most common complication after pancreas transplant:
    • A. Graft rejection
    • B. Graft thrombosis
    • C. Small bowel obstruction
    • D. Graft pancreatitisAnswer: D
    • Most common cause of graft failure following pancreatic transplant:
    • A. Graft pancreatitis
    • B. Graft thrombosis
    • C. Enteric leak
    • D. BleedingAnswer: B

Types of Solid Organ Pancreas Transplant

1. Simultaneous Pancreas–Kidney Transplant (SPK)

  • Most common type of pancreas transplant.
  • Both pancreas and kidney are from the same deceased donor.
  • Indications:
    • Type 1 diabetes with chronic renal failure (on or nearing dialysis) due to diabetic nephropathy.
    • Includes patients with renal failure from non-diabetic causes.

2. Pancreas Transplant Alone (PTA)

  • Indicated for:
    • Type 1 diabetes patients with repeated hypoglycaemic episodes and hypoglycaemic unawareness.
    • Life-threatening situations affecting independence and employment.
  • Alternative: Islet cell transplant for similar indications.

3. Pancreas-After-Kidney Transplant (PAK)

  • Performed after a prior kidney transplant (from living or deceased donor).
  • Suitable for patients who:
    • Have already received a kidney transplant.
    • Require subsequent pancreas transplantation.

4. Simultaneous Deceased Donor Pancreas and Live Donor Kidney Transplant

  • Combines a deceased donor pancreas with a live donor kidney.
  • Advantages:
    • Shortened waiting times.
  • Challenges:
    • Logistically complex.
    • Rarely performed.

Indications for Pancreas Transplantation

With Renal Failure

  • SPK Transplant:
    • Type 1 diabetes with end-stage renal failure due to diabetic nephropathy.
    • Glomerular filtration rate (GFR) <20 mL/min or dialysis expected within 6 months.

Without Renal Failure

  • PTA:
    • Type 1 diabetes with life-threatening hypoglycaemic unawareness.
    • Annual mortality rate: 3-6%.

Type 2 Diabetes Considerations

  • SPK for selected type 2 diabetics:
    • Non-morbidly obese.
    • Insulin requirements <1 unit/kg/day (to exclude insulin resistance).
    • Outcomes similar to type 1 diabetics when carefully selected.

Patient Selection

Comprehensive Preoperative Assessment

  • Cardiovascular Fitness:
    • Anaesthetic review.
    • Echocardiogram.
    • Assessment for inducible cardiac ischaemia (e.g., myocardial perfusion scan, stress echocardiogram).
    • Angiography and revascularisation if occult ischaemic heart disease is detected.
  • Evaluation of Diabetic Complications:
    • Sensory neuropathy
    • Retinopathy
    • Gastropathy
    • Peripheral vascular disease
    • Foot ulcers
    • Autonomic neuropathy (e.g., postural hypotension)

Special Considerations

  • Retinopathy:
    • Anticoagulation post-transplant may exacerbate retinal hemorrhage leading to vision deterioration or blindness.
  • Gastropathy:
    • May require a feeding jejunostomy during transplant surgery due to potential postoperative exacerbation.
  • Body Mass Index (BMI):
    • BMI cutoff typically <32 kg/m².
    • Severely overweight patients may face increased surgical and immunosuppression risks.

Organ Donation and Preservation

Organ Retrieval

  • Donation Sources:
    • Donation After Brain Death (DBD): 75% of pancreas donors.
    • Donation After Circulatory Death (DCD): 25% of pancreas donors.
  • Retrieval Methods:
    • Pancreas alone or en bloc with the liver.
    • Vascular Y-Graft Construction:
      • Bifurcation of iliac vessels sent with pancreas.
      • Creates a single arterial inflow for easier anastomosis.

Challenges in Pancreas Donation

  • High Discard Rate:
    • Only ~50% of retrieved pancreases are transplanted.
  • Reasons for Discard:
    • Fatty infiltration or fibrosis.
    • Injury during retrieval (pancreas is delicate and easily damaged).
  • Acceptance Criteria:
    • Varies by center; includes donor age, BMI, alcohol intake, lifestyle factors.
    • Adverse factors: prolonged agonal phase in DCD donors, raised transaminases, amylase, lipase, and complex vascular anatomy.

Organ Preservation

  • Static Cold Storage (SCS):
    • Gold standard since 1966.
    • Procedure:
      • Pancreas submerged in preservation solution.
      • Placed in an icebox for transport.
  • University of Wisconsin (UW) Solution:
    • Developed to improve pancreas preservation.
    • Contains hydroxyethyl starch (HES) to reduce pancreatitis and thrombosis.
  • Machine Perfusion:
    • Hypothermic machine perfusion: Promising in experimental studies, not yet standard.
    • Normothermic machine perfusion: Led to organ injury due to high autolytic enzymes.

Surgical Techniques

Preparation for Transplant

  • Inspection and Preparation:
    • Remove spleen and ligate splenic vessels.
    • Shorten duodenum, staple, and bury staple lines with sutures.
    • Remove excess fat and omentum.
    • Ligate inferior mesenteric vein.
  • Arterial Y-Graft Formation:
    • Connect SMA and SA using donor iliac vessels.
    • Creates a single arterial anastomosis point.

Transplantation Procedure

Approaches

  • Intraperitoneal (most common) or extraperitoneal placement.
  • Exocrine Drainage Options:
    • Enteric drainage: Anastomosis to the small intestine.
    • Bladder drainage: Anastomosis to the urinary bladder.

Steps of the Procedure

  1. Midline Laparotomy:
    • Access the abdominal cavity.
  2. Exposure and Control:
    • Dissect and control the inferior vena cava (IVC) and common iliac artery (CIA).
  3. Organ Positioning:
    • Enteric drainage: Pancreas head towards the liver, tail towards the pelvis.
    • Bladder drainage: Pancreas head towards the pelvis, tail towards the liver.
  4. Vascular Anastomoses:
    • Portal Vein (PV): End-to-side anastomosis to the IVC.
    • Arterial Anastomosis: Typically to the right CIA using the Y-graft.
    • Heparin administered before clamping the artery.
  5. Reperfusion:
    • Organ is reperfused and hemostasis ensured.
  6. Duodenal Anastomosis:
    • Enteric Drainage:
      • Jejunum anastomosed to donor duodenum in two layers.
      • Techniques: Roux-en-Y, passing through colonic mesentery, or adjacent placement under the colon.
    • Bladder Drainage:
      • Donor duodenum anastomosed to urinary bladder in two layers.
      • Urinary catheter kept for 7-10 days to prevent leaks.

Enteric Conversion

  • Indication:
    • To eliminate complications from bladder drainage.
  • Timing:
    • Typically 1 year post-transplant, or sooner if needed.
  • Procedure:
    1. Lower midline laparotomy.
    2. Disconnect duodenum from bladder.
    3. Close bladder in two layers.
    4. Anastomose duodenum to small bowel in two layers.
    5. Place surgical drains near anastomoses.
    6. Urinary catheter kept for 14 days post-procedure.

Postoperative Management

Anticoagulation

  • Purpose: Minimize graft thrombosis risk.
  • Protocols:
    • Vary by center; balance anticoagulation to prevent thrombosis vs. bleeding risks.
  • Medications:
    • Intravenous unfractionated heparin
    • Dextran
    • Epoprostenol
  • Monitoring:
    • Prothrombin Time (PT)
    • Thromboelastography (TEG):
      • Real-time coagulation assessment.
      • Immediate results and encompasses entire clotting cascade and platelet function.
  • Care:
    • 24-48 hours in high-dependency care.
    • Close blood glucose monitoring:
      • High systemic insulin levels due to direct drainage into the IVC.
      • Intravenous glucose supplementation may be required; stabilizes within 48 hours.
      • Blood glucose >8 mmol/L: Perform arterial phase contrast imaging to assess for thrombosis.
      • Thrombosis Indicators:
        • Small thrombus in distal SMA is normal.
        • Propagation into SMA or SA thrombus requires full anticoagulation.
        • Complete thrombosis may necessitate graft pancreatectomy.

Complications

  • Intraoperative:
    • Bleeding following reperfusion → blood transfusion, inotropic support.
    • Up to 1 in 3 patients may require further surgery due to reperfusion pancreatitis or bleeding.
  • Postoperative:
    • Reperfusion Pancreatitis:
      • Amylase-rich transudate in abdominal cavity.
      • May require drainage or washout.
    • Thrombosis:
      • Occurs in up to 8% of patients.
      • Can lead to early graft loss or β-cell dysfunction.
    • Anastomotic Leaks:
      • Rare from duodenum.
      • Managed with direct drainage or surgical revision.
    • Bladder-Drained Pancreases:
      • Cystitis from pancreatic enzymes.
      • Electrolyte disturbances, acidosis, dehydration.
      • Up to 50% may require enteric conversion within the first year.
      • Symptoms: Chemical cystitis, urinary tract infections (UTI), need for high-dose oral sodium bicarbonate.
    • Late Complications:
      • Pseudoaneurysm formation due to fungal infection or vascular anastomosis issues.
      • Importance of culturing preservation fluid and treating any microorganisms.

Immunosuppression and Follow-Up

Immunosuppression

Induction Therapy

  • Purpose: Immediate post-transplant immunosuppression.
  • Types:
    • Non-depleting antilymphocyte antibodies:
      • Basiliximab: Blocks interleukin-2 receptor, inhibits T-cell expansion.
    • T-cell-depleting antibodies:
      • Polyclonal ATG
      • Monoclonal antibody alemtuzumab (Sanof):
        • Preferred by some units due to ease of administration and lower viral infection rates.
  • Benefits:
    • Reduced rejection rates.

Maintenance Therapy

  • Current Regimen:
    • Tacrolimus + Mycophenolate Mofetil (MMF).
  • Evolved From:
    • Triple therapy with ciclosporin, azathioprine, and steroids.
  • Steroid-Free Regimens:
    • Aim to minimize insulin resistance and wound infections.
    • Favored by some centers.
  • Evidence:
    • EUROSPK 001 trial:
      • Tacrolimus + MMF + induction with ATG:
        • Reduced severe rejection rates.
        • Lower graft loss at 3 years compared to ciclosporin.

Long-Term Monitoring

  • Blood Glucose Monitoring:
    • HbA1c levels: Predictor of long-term graft function.
    • Oral glucose tolerance testing: Assess organ dysfunction.
    • Fasting C-peptide and insulin levels: Indicate pancreatic function.
  • Rejection Detection:
    • SPK Transplants:
      • Serum creatinine as a surrogate marker (for kidney component).
      • Renal biopsy if needed.
      • Discordant rejection: Pancreas rejects without kidney rejection, requiring imaging and clinical suspicion.
    • PTA:
      • Urinary amylase levels: Biomarker for pancreatic function and rejection.
      • Cystoscopic duodenal biopsy: Difficult to interpret; presence of lymphocytes not definitive.
      • Computed tomography angiography: Detects peripancreatic inflammation indicative of rejection.
  • Follow-Up:
    • Regular monitoring of liver biochemistries and immunosuppressive therapy levels.
    • Liver biopsy before stopping immunosuppressants to assess histologic response.

Summary Points

  • Types of Pancreas Transplants:
    • SPK: Most common, for type 1 diabetics with renal failure.
    • PTA: For type 1 diabetics with hypoglycaemic unawareness.
    • PAK: After a prior kidney transplant.
  • Patient Selection:
    • Comprehensive cardiovascular and surgical fitness assessments.
    • Evaluation of diabetic complications and BMI.
  • Organ Preservation:
    • Static Cold Storage (SCS) with UW solution remains standard.
    • High discard rates due to pancreas fragility and quality issues.
  • Surgical Techniques:
    • Intraperitoneal transplant with enteric drainage is preferred.
    • Vascular Y-graft facilitates arterial anastomosis.
  • Postoperative Management:
    • Anticoagulation to prevent graft thrombosis.
    • Close monitoring for complications like reperfusion pancreatitis and thrombosis.
    • Enteric conversion often required for bladder-drained transplants.
  • Immunosuppression:
    • Induction with T-cell-depleting antibodies.
    • Maintenance with Tacrolimus and MMF.
    • Regular monitoring for graft rejection and function.
  • Outcomes:
    • SPK offers superior patient survival compared to deceased donor kidney transplants.
    • Graft survival rates are higher for SPK compared to PAK and PTA.
    • Immunosuppressive protocols have improved rejection rates without adversely affecting graft or patient survival.

Note: Always evaluate the risks and benefits of pancreas transplantation on an individual basis and collaborate with a multidisciplinary team for optimal patient outcomes.