Title: Pancreas Transplantation
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2Pancreas Transplantation
- Jonathan A Fridell, MD, FRCSC
- Director of Pancreas Transplantation
- IU School of Medicine
3Pancreas Transplantation
- Introduction to Pancreas Transplantation
- Definitions
- Indications and contraindications
- Donor and recipient operations
- Complications and outcomes
4Transplantation
- 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
5Transplantation
- 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
6Transplantation
- 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
7Transplantation
- 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
8- What is the End-Stage Organ Dysfunction for
Pancreas Transplantation?
9Pancreas
- Endocrine Insulin, Glucagon, Somatostatin
- Exocrine Digestive enzymes (ex amylase,
lipase, trypsin etc) and bicarbonate.
10Discovery 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
11Discovery of Insulin
Before after pictures of a 1922 diabetic
patient of Dr. H. Rawle Geyelin
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14Diabetes 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
15Diabetes
- Leading cause of Blindness between 20-70 years
- Leading cause of lower extremity vascular disease
and amputation - Disabling neuropathy affects 50 pts
16LIFE EXPECTANCY 1/3 less than that of general
population
17Diabetes
- Quality of life- Needle Sticks
- 4 x 365 1460
- 8 x 365? 3000!
18Diabetes 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.
19The 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. -
20Pancreas Transplants Worldwide
Total n 23,051 ? Non USA n 5,924 ?
USA n 17,127
8/01
21Purpose of Pancreas Transplantation
- Improve quality of life by establishing
insulin-independent, normoglycemic state - Prevent / ameliorate secondary complications of
diabetes
22Pancreas transplant
Diabetes
Immunosuppression
Insulin
23Diabetes
Pancreas transplant
Immunosuppression
Insulin
24Diabetes
Pancreas transplant
Immunosuppression
Insulin
25Diabetes
Problematic DM
Pancreas transplant
Immunosuppression
Insulin
26Pancreas Transplant Recipient Categories
- SPK Simultaneous Pancreas/Kidney
- PAK Pancreas Transplant After Kidney
- PTA Pancreas Transplant Alone
27Pancreas Transplant Categories
USA SPK, PAK and PTA Transplants
1/07
28SPK characteristics
- More involved technically
- Easier to detect rejection
- Higher risk patients
- ESRD
- longer time on waiting list
29Advantages 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
30RECIPIENT 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.
31Pancreas Transplant Alone
- History of frequent, acute and severe metabolic
complications (hypoglycemia, hyperglycemia,
ketoacidosis). - Hypoglycemic unawareness
- Glycogen Hepatopathy
- surgical diabetes following total pancreatectomy
32Pancreas 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
33RECIPIENT 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
34Contraindications
- heart disease precluding major surgery
- active or recent malignancy
- relative contraindications
- known or suspected non-compliance
- severe peripheral vascular disease
- Age? BMI?
35Unusual Indications
- Glycogen Hepatopathy
- Cystic Fibrosis
- IPMN
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43Pancreas Transplantation in the Recipient with
Cystic Fibrosis
- Simultaneous Liver and Pancreas
- Simultaneous Bilateral Sequential Lung and
Pancreas
44Cystic 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
45Cystic Fibrosis
- Improvements in pulmonary and nutritional care
- Median life expectancy 36.5 years
46Cystic Fibrosis
- As patients are surviving longer, manifesting
non-pulmonary complications of CF such as
cirrhosis intestinal malabsorption and pancreatic
insufficiency (including CFRD)
47Purpose 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
48Transplantation Proceedings. 37(8)3567-9, 2005
Oct.
49SIMULTANEOUS LIVER AND PANCREAS TRANSPLANTATION
IN PATIENTS WITH CYSTIC FIBROSIS
50SIMULTANEOUS LIVER AND PANCREAS TRANSPLANTATION
IN PATIENTS WITH CYSTIC FIBROSIS
51SIMULTANEOUS LIVER AND PANCREAS TRANSPLANTATION
IN PATIENTS WITH CYSTIC FIBROSIS
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53Donor Selection
54Pancreas 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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56Pancreas 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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60Surgery
- 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
61Vascular Management
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66Methods (technique)
67Methods (technique)
68Portal Venous Drainage Advantages
- technical advantage
- retransplantation
- absence of hyperinsulinemia
- lower rejection rates?
69Systemic Insulin Levels
plt0.01
Gaber et al., Ann Surg, 1995221613.
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71Vsc.Mgmt
n Txs
1Yr Surv.
Systemic
1509
83
,
Portal
411
83
p gt
0.97
'
72Duct Management
73Bladder 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
74Enteric Drainage Advantages
- avoid metabolic complications
- avoid infectious complications
- avoid dysfunctional bladder
- lower reoperation rate
- lower leak rate
75Enteric Drainage Disadvantages
- lack of monitoring for rejection
- anastomotic leaks more likely to lead to
technical failure and graft loss
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78Pancreas position
- Bilateral vs. ipsilateral
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81Postoperative management
82Postoperative management
- SICU immediately post transplant
- Frequent Accuchecks
- Urine output
- Hemodynamic monitoring
- US on POD 1 or with any changes
83Postoperative 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
84Complications
- Bleeding (intraperitoneal, gastrointestinal)
- Vascular thrombosis
- Enteric anastomotic leak
- Pancreatitis, pseudocyst, pancreatic fistula
- SBO
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90Immunosuppression
91Paradox 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
92Anti-T-Cell Induction
USA DD Primary Pancreas Transplants 1/1/1988
12/31/2006
4/07
93Antibody Therapy
USA DD Primary Pancreas Transplants 1/1/2000
12/31/2006
? No ABs ? Depl. AB ? NonDepl. AB ? Both ABs
3/07
94Major Immunosuppressive Protocols
USA Primary DD Pancreas Transplants 1/1/2000
12/31/2006
3/07
95Steroid Withdrawal
- Steroids are diabetogenic
- Osteoporosis
- Peptic ulcer disease
- Cushingoid features and weight gain
- Initial success in islet cell transplantation
96Patients off Steroids
USA DD Primary Pancreas Transplants 1/1/2000
12/31/2005
3/06
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98ImmunosuppressionRapid 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
99Patient and Graft Survival
100Patient 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
101Pancreas 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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103PTA 1-year survival curves
1045-Year Pancreas Graft Function
USA DD Primary Pancreas Transplants, 1/1/1988
12/31/2003
8/04
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106Pancreas 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
107Pancreas Graft Survival at IU
1 yr survival PAK 93 PTA 90 SPK 90
108In 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
109In 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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