I. INTRODUCTION
The World Health Organization estimates that approximately 347 million people have been diagnosed with diabetes, worldwide.1
In the United States, there are approximately 29 million people, or 9.3% of the population, who have diabetes.2
Diabetes is classified into two main types: type 1 and type 2.
Type 1 diabetes results from cellular-mediated autoimmune destruction of pancreatic islet beta cells causing the loss of insulin production.
Type 1 diabetes (insulin dependent) affects 5% of those with diabetes, and although disease onset can occur at any age, it peaks in mid teenage years.2
Type 2 diabetes (non-insulin dependent) is the more common type, affecting 95% of those with diabetes.2
Type 2 diabetes usually occurs in adulthood and is characterized by insulin resistance. As resistance rises, the beta cells are eventually unable to produce the necessary amount of insulin to lower and maintain normal blood glucose levels.
In recent years, there has been an increase in type 2 diabetes diagnosed in children and adolescents.
Diet and obesity, older age, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity are associated with development of type 2 diabetes.
Pancreas transplantation has been performed since 1966.3
Goals of pancreas transplantation are
To restore normoglycemia in patients with labile diabetes
To halt or prevent secondary complications of diabetes3
The International Pancreas Transplant Registry (IPTR) reports3:
Greater than 35,000 pancreas transplants were performed between 1966 and 2011.
TABLE 15-1 Patient and Graft Survival by Type of Pancreas Transplant
Procedure
1-Year Patient Survival*
1-Year Graft Survival*
5-Year Graft Survival*
Pancreas transplant alone (PTA)
>95%
77.8%
82%
Simultaneous pancreas-kidney (SPK) transplant
>95%
Pancreas: 85.5%
Kidney: 93.4%
Pancreas: 72%
Kidney: 80%
Pancreas after kidney (PAK) transplant
>95%
79.9%
78%
* Per 2011 IPTR data. Data from Gruessner AC. 2011 Update on pancreas transplantation: comprehensive trend analysis of 25,000 cases followed up over the course of twenty-four years at the International Pancreas Transplant Registry (IPTR). Rev Diabet Stud. 2011;8:6-16.
More than 24,000 transplants were performed in the United States during this period.
More than 12,000 pancreas transplants were performed outside the United States during this period.
Table 15-1 depicts patient and graft survival by type of pancreas transplant.
Distribution of pancreas transplant volume by type of transplant is displayed in Figure 15-1.
Patients with severe or “brittle” diabetes are very limited in their ability to pursue normal activities of daily living due to
Frequent problems with high and/or low blood glucose
Hyperglycemia, which causes microvascular, macrovascular, and autonomic complications:
Microvascular complications:
Diabetic nephropathy
Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD), accounting for more than 44% of all new cases annually in the United States.4
Diabetic retinopathy
Macrovascular complications:
Accelerated cardiovascular disease including myocardial infarction (MI), cerebrovascular accidents (CVA), and peripheral arterial disease (PAD).
FIGURE 15-1 Distribution of transplant volume by type of transplant.
Autonomic complications:
Gastroparesis
Peripheral neuropathy
Neurogenic bladder
Sexual dysfunction
Orthostatic hypotension
Hypoglycemia, reoccurring over time, causes a shift in the threshold for symptoms and counterregulatory responses to occur, referred to as hypoglycemic unawareness.
If not corrected, hypoglycemia may progress to diabetic coma and cause brain cell death or injury as the brain is the only organ that requires glucose for function.5
Quality of life may be dramatically enhanced.
Progression of complications of diabetes (neuropathy, nephropathy, and retinopathy) may be arrested.
II. INDICATIONS10
Diagnosis of diabetes:
Most candidates for pancreas transplantation have had type 1 diabetes manifested by poor metabolic control, especially hypoglycemic unawareness, for many years.
Candidates must meet the following criteria10:
On insulin and C-peptide ≤ 2 ng/mL OR
On insulin and C-peptide ≥2 ng/mL AND a body mass index (BMI) less than or equal to the maximum allowable BMI (currently ≤28 kg/m2)
Pancreatic exocrine insufficiency
Patients with type 2 diabetes are seldom evaluated for pancreas transplantation and account for only 7% of all pancreas transplant recipients in 2010.3
Diagnosis of diabetes or pancreatic exocrine insufficiency with renal insufficiency
III. CANDIDATE SELECTION CRITERIA
C-peptide deficiency
Frequent or severe metabolic complications:
Hypo- or hyperglycemia
Ketoacidosis
Hypoglycemic unawareness despite optimized medical management
Evidence of secondary complications such as
Peripheral neuropathy
Retinopathy
Gastroparesis
Coronary artery disease
Numbness, tingling, or loss of perception in extremities
Lethargy
Nausea
Dizziness
Blurred vision, low vision, or blindness
IV. PREOPERATIVE PHASE
Evaluation protocols vary by institution and are individualized according to patient’s medical history and physical examination.
Table 15-2 lists typical evaluation tests.
Principles of patient education
Before providing education, assess the patient for
Readiness to learn
TABLE 15-2 Typical Evaluation Tests
Laboratory
Cardiovascular
Electrolyte panel
Phosphate and magnesium
Uric acid
Liver function tests
Hgb A-1C
C-peptide
Fasting lipid panel
Amylase and lipase
CBC with differential
Coagulation profile
Serologies (CMV; HIV; EBV; HBV surface antigen, antibody, and core antibody; HCV antibody; and HAV IgG)
Urinalysis
24-hour protein/creatinine clearance
Glomerular filtration rate
Thyroid function studies (T3, T4, TSH)
FANA (flourescent) and/or ANA
Blood type (ABO)
Prostate-specific antigen
PAP smear
12-lead EKG
Chest radiograph
Echocardiogram
Ultrasound of carotid arteries
Nuclear stress test/or cardiac catheterization
Doppler ultrasound of peripheral vessels to detect vascular disease
Letter of clearance from cardiologist
Immunogenetics
Radiology
PRA
HLA typing/tissue typing
Bone density scan
Mammogram
Sigmoidoscopy/barium enema or colonoscopy
Dental exam
Psychosocial and financial consultation
CBC, complete blood count; Hgb A-1C, glycosylated hemoglobin; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HCV, hepatitis C; HBV, hepatitis B; HLA, human leukocyte antigen; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; FANA, fluorescent antinuclear antibody; ANA, antinuclear antibody; PRA, preformed reactive antibody; HLA, human lymphocyte antibody; EKG, electrocardiogram.
Level of health literacy
Potential barriers to learning, for example:
Physiological (e.g., visual impairment)
Psychological (e.g., anxiety)
Preferred learning style
Education begins with the initial referral and continues throughout the transplant continuum. Topics discussed at one point in the continuum will often need to be reemphasized at subsequent time points. For the purposes of this chapter, key transplant phase-specific educational topics will be highlighted in the discussion of each particular phase.
Preoperative phase: key education topics include, but are not limited to, the following:
Topics required by the Centers for Medicare and Medicaid:
Evaluation process:
Results of physical exam, labs, and diagnostic testing
Patient selection criteria and suitability for transplant
Relationship of psychosocial issues to transplant success
Financial responsibilities for transplant
Requirement to follow a strict medical regimen
Outcome of the evaluation
Surgical procedure:
Detailed discussion of surgical procedure
Anesthesia risk; other potential risks
Risk related to the use of blood or blood products
Expected postsurgical course
Benefits and risk of transplant surgery relative to other alternatives
Alternative treatment options
Potential medical risks of transplantation:
Wound infection
Pneumonia
Blood clot formation
Organ rejection, failure, or retransplant
Lifetime immunosuppression therapy
Arrhythmias
Cardiovascular collapse
Multiorgan failure
Death
Potential psychosocial risks:
Depression.
Posttraumatic stress disorder.
Generalized anxiety.
Feelings of guilt.
Future health problems may not be covered by insurer.
Alternative financial resources.
Future attempt to obtain medical, life, or disability may be affected.
National and transplant program outcomes from most recent Scientific Registry of Transplant Recipients center report:
1-year patient survival.
1-year graft survival.
Transplant program does or does not meet outcomes.
If center does not meet outcomes, Medicare B will not pay for immunosuppression medications.
Web sites for additional information www.ustransplant.org and www.optn.org.
Organ donor risk factors:
Health risk of donor could affect organ related to donor.
Medical and social history and age of donor.
Condition of the organ.
Risk of disease transmission including
Human immunodeficiency virus, hepatitis B, and hepatitis C
Cancer
Malaria
Disease not detectable at time of donor recovery
Right to refuse transplantation; right to withdraw consent for transplantation
Medicare B coverage for immunosuppressive medications:
Transplant must be performed at a Medicare-approved facility for Medicare to pay for immunosuppressive medications
United Network for Organ Sharing required topics:
Right to be listed at more than one transplant center and the ability to transfer accumulated wait time between transplant centers
Coverage plan for transplant program medical and surgical provider
Increased donor risk: advise patient at time of organ offer
Other potential topics:
Patient’s expectations regarding transplantation
Role of interdisciplinary team members
Waitlist and organ allocation
Preoperative or intraoperative immunosuppression
Posttransplant immunosuppression
The standard immunosuppression for pancreas transplant recipients typically includes
Tacrolimus (Prograf; FK506)
Mycophenolate mofetil (CellCept)
Prednisone (steroid)
See chapter on Patient Education for additional information.
V. SURGICAL APPROACH
Allows the exocrine function of the native pancreas to be preserved.
There are two surgical approaches to handle exocrine secretions produced by the transplanted pancreas.
Exocrine secretions are generally drained into
Enteric drainage (ED): bowel drainage:
When the pancreas is drained enterically, much of the approximate 2 L of exocrine enzymatic fluid and bicarbonate produced by the pancreas is reabsorbed in the bowel.
The donor portal vein is anastomosed to the side of the recipient’s superior mesenteric vein.
FIGURE 15-2 Enteric drainage technique.
The transplanted donor duodenal segment is attached to the recipient’s jejunum to establish exocrine drainage.
The enteric drainage technique is shown in Figure 15-2.
The benefit of ED is that no fluid and electrolyte changes occur posttransplant due to its similarity to natural anatomy.
Bladder drainage (BD)12:
The systemic-bladder drainage technique directs venous outflow and insulin drainage into the iliac vein.
Exocrine drainage is via anastomosis of a donor duodenal segment to the recipient’s urinary bladder.
The bladder drainage technique is shown in Figure 15-3.
FIGURE 15-3 Technique of a combined pancreas-kidney transplantation through a lower midline approach.
The benefit of bladder drainage is that rejection episodes in the pancreas can be detected more readily by measuring the exocrine enzyme (amylase) in the urine.
Bladder drainage may predispose the patient to
Dehydration
Recurrent urinary tract infections (UTIs), especially if patient has a history of neurogenic bladder with poor bladder emptying.
Cystitis
Metabolic acidosis (large amounts of sodium bicarbonate are emptied into the bladder)
Reflux pancreatitis
Hematuria
IPTR data indicate that there is no significant difference in the success rates between ED and BD techniques in SPK recipients.3
Most centers use the ED technique.
Approximately 10% to 25% of BD recipients undergo a surgical procedure called “enteric conversion” in the first 5 years following transplant due to recurrent UTIs, large duodenal leaks, severe or recurrent hematuria, or significant cystitis.7,11
Enteric conversion moves the duodenal segment (and as such, exocrine drainage) from the bladder to the bowel
When the pancreas is transplanted simultaneously with a kidney from the same donor, the kidney can serve as the early rejection detection mechanism.
4 to 8 hours for combined kidney-pancreas transplant
3 to 4 hours for isolated pancreas transplant
VI. POSTTRANSPLANT PHASE
Average length of stay: 7 to 14 days
May require 24- to 48-hour stay in intensive care unit for cardiac monitoring, depending on individual transplant center policy
Nasogastric (NG) tube in place for approximately 1 to 2 days, or until bowel function returns.
Foley catheter in place for generally 2 to 3 days.
Compression stockings or device to prevent deep vein thrombosis.
Incentive spirometer; coughing/deep breathing 10 times an hour while awake.
Central venous catheter for parenteral medications and fluid management until diet is advanced.
Surgical drain, if indicated.
Insulin infusion may be utilized to address hyperglycemia for the first 24 to 48 hours posttransplantation to “rest” the insulin-producing islet cells.7
It is important to continually assess the patient’s level of pain and response to analgesia throughout hospitalization.
Strategies to manage pain are guided by institutional protocols.
TABLE 15-3 Potential Complications and Appropriate Interventions | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Most patients receiving pancreas transplants will receive triple therapy immunosuppression although regimens vary at individual transplant centers, including steroid-sparing protocols.
Triple therapy includes
A calcineurin inhibitor: tacrolimus (Prograf) or cyclosporine (Neoral or Gengraf)
An antiproliferative agent: mycophenolate mofetil (CellCept) or mycophenolic acid (Myfortic)
A corticosteroid: methylprednisolone (Solu-Medrol) IV or oral prednisone
Sirolimus (Rapamycin/Rapamune) is being used for some patients in lieu of a calcineurin inhibitor to minimize the nephrotoxic effects associated with calcineurin inhibitors.
Most patients will remain on tacrolimus and mycophenolate long term but may taper off prednisone within the months following transplant (if they initially received prednisone).
Induction therapy is utilized by some pancreas transplant centers to minimize or avoid steroids due to the impact steroids have on blood glucose levels. These agents include
Basiliximab (Simulect), monocolonal antibody
Alemtuzumab (Campath), monoclonal antibody
Antilymphocyte globulin (Thymoglobulin), polyclonal antibody
See the Chapter on Transplant Pharmacology for additional information regarding immunosuppression medications and their side effects.
See Chapter on Noninfectious Diseases for additional information about posttransplant medications.
TABLE 15-4 Commonly Prescribed Nonimmunosuppressive Drugs | ||||||||||||||||||||||||||
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