Pancreas Transplantation

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Pancreas Transplantation

• Jonathan A Fridell, MD, FRCSC
• Director of Pancreas Transplantation
• IU School of Medicine

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Pancreas Transplantation

• Introduction to Pancreas Transplantation
• Definitions
• Indications and contraindications
• Donor and recipient operations
• Complications and outcomes

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Transplantation

• Implanting in one part a tissue or organ taken
  from another part or from another individual.
• Clinically, used to replace the function of a
  failed organ

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Transplantation

• Implanting in one part a tissue or organ taken
  from another part or from another individual.
• Clinically, used to replace the function of a
  failed organ
• Liver Transplant for ESLD and cirrhosis

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Transplantation

• Implanting in one part a tissue or organ taken
  from another part or from another individual.
• Clinically, used to replace the function of a
  failed organ
• Liver Transplant for ESLD and cirrhosis
• Renal Transplant for ESRD /- dialysis

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Transplantation

• Implanting in one part a tissue or organ taken
  from another part or from another individual.
• Clinically, used to replace the function of a
  failed organ
• Liver Transplant for ESLD and cirrhosis
• Renal Transplant for ESRD /- dialysis
• SBTx for short gut

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• What is the End-Stage Organ Dysfunction for
  Pancreas Transplantation?

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Pancreas

• Endocrine Insulin, Glucagon, Somatostatin
• Exocrine Digestive enzymes (ex amylase,
  lipase, trypsin etc) and bicarbonate.

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Discovery of Insulin
Banting Best
1922 Banting and Best (Nobel Prize) isolated an
extract from the dog pancreas which was able to
control or lower the blood glucose level of
diabetic patients
Banting FG, Best CH, Collip JB, Campbell WR,
Fletcher AA. Pancreatic extracts in the
treatment of diabetes mellitus. Preliminary
report. CMAJ 192212141-6
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Discovery of Insulin
Before after pictures of a 1922 diabetic
patient of Dr. H. Rawle Geyelin
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Diabetes in the U.S.

• Pandemic of the new millennium
• 21 million U.S. diabetics (14 million diagnosed),
  1-2 million type 1, 6 overall)
• In Type 1 or 2 diabetes, 30-40 develop ESRD
  incidence of ESDN increasing at twice the rate of
  all other causes of ESRD
• Among dialysis patients, those with diabetes have
  higher annual costs and higher mortality

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Diabetes

• Leading cause of Blindness between 20-70 years
• Leading cause of lower extremity vascular disease
  and amputation
• Disabling neuropathy affects 50 pts

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LIFE EXPECTANCY 1/3 less than that of general
population
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Diabetes

• Quality of life- Needle Sticks
• 4 x 365 1460
• 8 x 365? 3000!

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Diabetes Can be Treated by Transplantation
Kelly, W, Lillehei, R., Merkel, F., Idezuki, Y.,
Goetz, F. Allotransplantation of the pancreas
and duodenum along with the kidney in diabetic
nephropathy. Surgery 61827-837, 1967.
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The First Kidney/Pancreas Transplant

• 1966 Richard C. Lillehei and William D. Kelly
• University of Minnesota
• 28 year old woman, diabetic since age of 9, with
  renal failure.
• She had normal blood sugars and was insulin
  independent following the procedure, but died at
  2 months from rejection and sepsis.

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Pancreas Transplants Worldwide
Total n 23,051 ? Non USA n 5,924 ?
USA n 17,127
8/01
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Purpose of Pancreas Transplantation

• Improve quality of life by establishing
  insulin-independent, normoglycemic state
• Prevent / ameliorate secondary complications of
  diabetes

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Pancreas transplant
Diabetes
Immunosuppression
Insulin
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Diabetes
Pancreas transplant
Immunosuppression
Insulin
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Diabetes
Pancreas transplant
Immunosuppression
Insulin
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Diabetes
Problematic DM
Pancreas transplant
Immunosuppression
Insulin
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Pancreas Transplant Recipient Categories

• SPK Simultaneous Pancreas/Kidney
• PAK Pancreas Transplant After Kidney
• PTA Pancreas Transplant Alone

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Pancreas Transplant Categories
USA SPK, PAK and PTA Transplants
1/07
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SPK characteristics

• More involved technically
• Easier to detect rejection
• Higher risk patients
• ESRD
• longer time on waiting list

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Advantages of PAK

• Benefit of living donor kidney transplant
• Shorter operation
• Operate on non-uremic
• No drain on cadaveric kidney donor pool
• Decreased waiting time
• Difficult to detect rejection
• 2 operations

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RECIPIENT SELECTION CRITERIA SPK or PAK

• Low c-peptide and insulin dependence
• Existing or impending end-stage renal disease.
• Intact or correctable urological system.
• Relative contraindications
• Smoking.
• Age gt 60 years old?
• BMI of gt35?
• Ongoing problems with medical noncompliance.
• Peripheral vascular disease?
• Absolute contraindications
• Untreated drug/ETOH addictions.
• Non-correctable cardiac disease.
• Malignancy
• active infection.

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Pancreas Transplant Alone

• History of frequent, acute and severe metabolic
  complications (hypoglycemia, hyperglycemia,
  ketoacidosis).
• Hypoglycemic unawareness
• Glycogen Hepatopathy
• surgical diabetes following total pancreatectomy

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Pancreas Transplant Alone

• History of frequent, acute and severe metabolic
  complications (hypoglycemia, hyperglycemia,
  ketoacidosis).
• Hypoglycemic unawareness
• Glycogen Hepatopathy
• surgical diabetes following total pancreatectomy
• AND
• Preserved kidney function

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RECIPIENT SELECTION CRITERIA PTA

• Low c-peptide and insulin dependence
• Total Pancreatectomy
• Cystic Fibrosis
• Acceptable CreaCl
• Relative contraindications
• Age gt 60 years old?
• Ongoing problems with medical noncompliance
• BMI gt 35?
• Peripheral vascular disease
• Absolute Contraindications
• Untreated drug/ETOH addictions
• Non-correctable cardiac disease
• active infection
• Malignancy

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Contraindications

• heart disease precluding major surgery
• active or recent malignancy
• relative contraindications
• known or suspected non-compliance
• severe peripheral vascular disease
• Age? BMI?

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Unusual Indications

• Glycogen Hepatopathy
• Cystic Fibrosis
• IPMN

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Pancreas Transplantation in the Recipient with
Cystic Fibrosis

• Simultaneous Liver and Pancreas
• Simultaneous Bilateral Sequential Lung and
  Pancreas

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Cystic Fibrosis

• Cystic fibrosis (CF) is an inherited disorder
  that affects epithelial chloride transport and
  presents as a multisystem disease.
• The most common life-threatening autosomal
  recessive disease of Caucasians in the USA
• 1/3000 live births
• 84 of CF patients die from respiratory disease

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Cystic Fibrosis

• Improvements in pulmonary and nutritional care
• Median life expectancy 36.5 years

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Cystic Fibrosis

• As patients are surviving longer, manifesting
  non-pulmonary complications of CF such as
  cirrhosis intestinal malabsorption and pancreatic
  insufficiency (including CFRD)

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Purpose of Pancreas Transplantation in CF

• Improve quality of life by establishing
  insulin-independent, normoglycemic state
• Prevent / ameliorate secondary complications of
  diabetes
• With enteric drainage, improve nutritional status
  by restoring pancreatic exocrine function

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Transplantation Proceedings. 37(8)3567-9, 2005
Oct.
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SIMULTANEOUS LIVER AND PANCREAS TRANSPLANTATION
IN PATIENTS WITH CYSTIC FIBROSIS
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SIMULTANEOUS LIVER AND PANCREAS TRANSPLANTATION
IN PATIENTS WITH CYSTIC FIBROSIS
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SIMULTANEOUS LIVER AND PANCREAS TRANSPLANTATION
IN PATIENTS WITH CYSTIC FIBROSIS
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Donor Selection
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Pancreas Donor Criteria

• ABO compatibility
• age lt55?
• no history of diabetes
• no history of acute or chronic pancreatitis
• no trauma to pancreas, retroperitoneal hematoma
• BMI

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Pancreas Procurement

• En-bloc procurement with the liver
• preservation of duodenum with head
• spleen left on to assist in handling the gland

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Surgery

• midline incision
• intraabdominal placement
• heterotopic graft
• artery to common iliac artery usually right
  side
• portal vein to common iliac vein or mesenteric
  vein
• graft duodenum to bladder or to small intestine
• SPK Which order? Ipsilateral placement

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Vascular Management

• Systemic vs. Portal

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Methods (technique)
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Methods (technique)
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Portal Venous Drainage Advantages

• technical advantage
• retransplantation
• absence of hyperinsulinemia
• lower rejection rates?

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Systemic Insulin Levels
plt0.01
Gaber et al., Ann Surg, 1995221613.
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Vsc.Mgmt

n Txs
1Yr Surv.

Systemic
1509

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,

Portal
411
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p gt
0.97
'
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Duct Management
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Bladder Drainage

• Advantages
• monitoring of urine amylase
• Disadvantages
• alkalinization of urine -gt infections
• irritation by enzymes -gt infections
• loss of bicarb -gt acidosis and dehydration
• urine in the pancreas -gt pancreatitis

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Enteric Drainage Advantages

• avoid metabolic complications
• avoid infectious complications
• avoid dysfunctional bladder
• lower reoperation rate
• lower leak rate

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Enteric Drainage Disadvantages

• lack of monitoring for rejection
• anastomotic leaks more likely to lead to
  technical failure and graft loss

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Pancreas position

• Bilateral vs. ipsilateral

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Postoperative management
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Postoperative management

• SICU immediately post transplant
• Frequent Accuchecks
• Urine output
• Hemodynamic monitoring
• US on POD 1 or with any changes

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Postoperative management

• NG removed immediately post transplant
• Foley catheter removed POD 3
• JP x 1 usually removed prior to discharge
• IV fluids try to avoid D5
• Continue frequent Accuchecks
• Daily renal profile, Amylase and Lipase
• Liberal use of Reglan for gastroparesis

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Complications

• Bleeding (intraperitoneal, gastrointestinal)
• Vascular thrombosis
• Enteric anastomotic leak
• Pancreatitis, pseudocyst, pancreatic fistula
• SBO

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Immunosuppression
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Paradox of Immunosuppression in Pancreas
Transplantation

• No data to support any specific IS regimen in
  diabetic recipients for improved outcomes
• Steroids induce insulin-resistance CNIs are
  islet toxic insulin sensitivity reduced 25-50
• Patients with gastroparesis may not tolerate MPA
  SRL may induce severe dyslipidemia
• Development of a non-nephrotoxic,
  non-diabetogenic, non GI-toxic regimen desired

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Anti-T-Cell Induction
USA DD Primary Pancreas Transplants 1/1/1988
12/31/2006
4/07
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Antibody Therapy
USA DD Primary Pancreas Transplants 1/1/2000
12/31/2006
? No ABs ? Depl. AB ? NonDepl. AB ? Both ABs
3/07
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Major Immunosuppressive Protocols
USA Primary DD Pancreas Transplants 1/1/2000
12/31/2006
3/07
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Steroid Withdrawal

• Steroids are diabetogenic
• Osteoporosis
• Peptic ulcer disease
• Cushingoid features and weight gain
• Initial success in islet cell transplantation

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Patients off Steroids
USA DD Primary Pancreas Transplants 1/1/2000
12/31/2005
3/06
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ImmunosuppressionRapid Steroid Elimination

• Thymoglobulin 1mg/kg in OR Day 1,2,4,6
• Solumedrol OR 120 mg
• POD1 120 mg
• POD2 D/C
• Prograf Start POD1 2 mg BID
• Rapamycin 2 mg Qd
• or
• Cellcept 1000 mg BID

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Patient and Graft Survival
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Patient Survival
USA DD Primary Pancreas Transplants 1/1/2000
6/6/2004
Cat. n 1Yr Surv. PAK 1,112 95 PTA
429 98 SPK 3,842 95
p 0.05
8/04
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Pancreas Graft Survival
USA CAD Primary Pancreas Transplants 1/1/2000
6/6/2004
Cat. n 1Yr Surv. PAK 1,109 78
PTA 429 76 SPK 3,841 85
p lt 0.0001
8/04
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PTA 1-year survival curves
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5-Year Pancreas Graft Function
USA DD Primary Pancreas Transplants, 1/1/1988
12/31/2003
8/04
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Pancreas Graft Survival
USA CAD Primary Pancreas Transplants 1/1/2000
6/6/2004
Cat. n 1Yr Surv. PAK 1,109 78
PTA 429 76 SPK 3,841 85
p lt 0.0001
8/04
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Pancreas Graft Survival at IU
1 yr survival PAK 93 PTA 90 SPK 90
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In Conclusion

• Pancreatic transplantation offers the potential
  for normalization of blood sugar levels in
  patients with diabetes mellitus.
• Most often done in the context of a patient
  receiving immunosuppression for another allograft
  or for problematic DM

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In Conclusion

• Despite the requirement for an abdominal surgical
  procedure and life-long immunosuppression,
  currently the most reliable way to provide long
  term glucose control in the diabetic patient with
  the appropriate indications.

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