The world’s first clinical pancreas transplant was performed, simultaneously with a kidney graft, on December 16, 1966, to treat a uremic diabetic patient at the University of Minnesota Hospital. 1 Since then, more than 12,000 pancreases have been transplanted worldwide;2 of these, nearly 10% have been done at the University of Minnesota, as reported here (Fig. 1). 



Figure 1. Number of pancreas transplants according to recipient category (SPK, simultaneous pancreas–kidney; PTA, pancreas transplant alone; PAK, pancreas after kidney; SPL, simultaneous pancreas–liver) from living related donors (LRD) ...



The cumulative experience with pancreas transplantation at the University of Minnesota has been periodically presented at the American Surgical Association, 3–6 and the historical evolution of transplantation for diabetes (kidney, pancreas, islets) at this institution has been described. 7

For diabetic patients dependent on exogenous insulin for survival, the objectives of pancreas transplantation are to make them insulin-independent and normoglycemic, improve day-to-day quality of life, and ameliorate secondary complications. That the first objective could be achieved was obvious from the first case;1 the others had to be proven, and that is part of the multidecade story told here.

The evolution of pancreas transplantation at the University of Minnesota is closely intertwined with the advances in surgical techniques, 8–13 organ preservation technology, 14 and immunosuppressive modalities 15–19 that have occurred in other pioneering programs, but some aspects of the Minnesota program have been decidedly different. 7 An analysis of outcome over such a long time span in a constantly changing field can be done only by eras. Although each era has distinctive features, there is much overlap between eras as well as heterogeneity within eras. The similarities and differences with other programs are indicated in the following description of the Minnesota pancreas transplant program by eras.

Lessons learned from more than 1,000 pancreas transplants at a single institution.

Many complications after renal transplantation can be prevented if they are detected early. Guidelines have been developed for the prevention of diseases in the general popu- lation, but there are no comprehensive guidelines for the pre- vention of diseases and complications after renal transplanta- tion. Therefore, the Clinical Practice Guidelines Committee of the American Society of Transplantation developed these guidelines to help physicians and other health care workers provide optimal care for renal transplant recipients. The guide- lines are also intended to indirectly help patients receive the access to care that they need to ensure long-term allograft survival, by attempting to systematically define what that care encompasses. The guidelines are applicable to all adult and pediatric renal transplant recipients, and they cover the outpa- tient screening for and prevention of diseases and complica- tions that commonly occur after renal transplantation. They do not cover the diagnosis and treatment of diseases and compli- cations after they become manifest, and they do not cover the pretransplant evaluation of renal transplant candidates. The guidelines are comprehensive, but they do not pretend to cover every aspect of care. As much as possible, the guidelines are evidence-based, and each recommendation has been given a subjective grade to indicate the strength of evidence that sup- ports the recommendation. It is hoped that these guidelines will provide a framework for additional discussion and research that will improve the care of renal transplant recipients.

Recommendations for the Outpatient Surveillance of Renal Transplant Recipients

Reestablishment of the euglycemic state by successful transplantation of the pancreas might halt or reverse diabetic neuropathy. To test this possibility we evaluated neurologic function by clinical examination, nerve conduction studies, and autonomic-function tests in patients with insulin-dependent (Type I) diabetes mellitus before and after successful pancreatic transplantation. Sixty-one patients were studied before and 12 months after transplantation, 27 again after 24 months, and 11 again after 42 months. A control group of patients with Type I diabetes treated with insulin underwent the same studies at similar intervals — 48 patients before and after 12 months had elapsed, 21 again after 24 months, and 12 again after 42 months. In the control group, neuropathy tended to worsen during the follow-up period. The scores on the clinical examination indicated increased impairment after 12 months. Composite indexes of the degree of abnormality found on neurophysiologic testing of the function of ...

Effects of Pancreatic Transplantation on Diabetic Neuropathy

A working knowledge of contraception will assist the pediatrician in both sexual health promotion as well as treatment of common adolescent gynecologic problems. Best practices in adolescent anticipatory guidance and screening include a sexual health history, screening for pregnancy and sexually transmitted infections, counseling, and if indicated, providing access to contraceptives. Pediatricians' long-term relationships with adolescents and families allow them to help promote healthy sexual decision-making, including abstinence and contraceptive use. Additionally, medical indications for contraception, such as acne, dysmenorrhea, and heavy menstrual bleeding, are frequently uncovered during adolescent visits. This technical report provides an evidence base for the accompanying policy statement and addresses key aspects of adolescent contraceptive use, including the following: (1) sexual history taking, confidentiality, and counseling; (2) adolescent data on the use and side effects of newer contraceptive methods; (3) new data on older contraceptive methods; and (4) evidence supporting the use of contraceptives in adolescent patients with complex medical conditions.

/pdf/contraception-for-adolescents-6a8non6djk.pdf

Contraception for adolescents.

Restoration of a long-lasting euglycemic state by a functioning pancreatic transplantation (PTx) is the most logical treatment for insulin-dependent diabetes mellitus and for amelioration of secondary complications, including neuropathy We evaluated neurological function by clinical examination, nerve conduction studies, and autonomic function tests in 115 patients with a functioning PTx and in 92 control patients treated with insulin, at baseline and 1, 2, 35, 5, 7, and 10 years later In control patients, neuropathy progressively worsened during follow-up The clinical examination score and composite indices of abnormality of motor and sensory nerve conduction decreased significantly at all intervals tested Autonomic function indices also decreased, but significantly only after 1 year In patients who received a successful PTx the neuropathy improved The motor and sensory nerve conduction indices increased significantly at all intervals after transplantation, whereas the clinical examination and autonomic tests improved only slightly Patients who received either a PTx alone, a PTx after a kidney graft, or simultaneous pancreatic and kidney transplantations improved similarly over the follow-up These results indicate that a functioning PTx halts the progression and improves the signs of diabetic polyneuropathy by restoration of a normoglycemic state

Long‐term effects of pancreatic transplantation on diabetic neuropathy

Since our report at the 1984 American Surgical Association meeting of 100 pancreas transplants from 1966 through 1983, another 190 have been performed. The current series, begun in 1978, now numbers 276 cases, and includes 133 nonuremic recipients of pancreas transplants alone (PTA), 46 simultaneous pancreas/kidney transplants (SPK), and 97 pancreas tranplants after a kidney transplant (PAK). Duct management techniques used were free intraperitoneal drainage in 44 cases, duct occlusion in 44, enteric drainage in 89, and bladder drainage in 128. The 1-year patient and graft survival rates in the entire cohort of 276 were 91% and 42%. One-year patient survival rates were 88% in the first 100, 91% in the second 100, and 92% in the last 76 cases; corresponding 1-year graft survival rates were 28%, 47%, and 56% (p less than 0.05). A prospective comparison of bladder drainage (n = 82) versus enteric drainage (n = 46) in PAK/PTA cases since November 1, 1984 favored bladder drainage (1-year graft survival rates of 52% vs. 41%) because of urinary amylase monitoring. The best results were in recipients of primary SPK bladder-drained transplants (n = 39), with a 1-year pancreas graft survival rate of 75%, kidney graft survival rate of 80%, and patient survival rate of 95%. Logistic regression analysis, with 1-year graft function as the independent variable, showed significant (p less than 0.05) predictors of success (odds ratio) to be technique: bladder drainage (5.8) versus enteric drainage (2.5) versus duct injection (1.0); category: SPK (6.0) versus PAK from same donor (3.2) versus PAK from different donor (1.2) versus PTA (1.0); and donor HLA DR mismatch: 0 (5.0) versus 1 (2.5) versus 2 (1.0) antigens. On April 1, 1989, 90 patients had functioning grafts (60 euglycemic and insulin-free for more than 1 year, 10 for 5 to 10 years); these, along with 24 others whose grafts functioned for 1 to 6 years before failing, are part of an expanding cohort in whom the influence of inducing a euglycemic state on pre-existing secondary complications of diabetes is being studied. Only preliminary data is available. In regard to neuropathy, at more than 1 year after transplant in patients with functioning grafts, conduction velocities in some nerves were increased over baseline. In regard to retinopathy, deterioration in grade occurred in approximately 30% of the recipients by 3 years, whether the graft functioned continuously or failed early, but thereafter retinopathy in the patients with functioning grafts remained stable.(ABSTRACT TRUNCATED AT 400 WORDS)

A 10-year experience with 290 pancreas transplants at a single institution.

Transplantation is the treatment of choice for children with end-stage renal disease However, the long-term quality of life and socioprofessional outcome for those with successful transplants have not previously been reported We studied these factors in patients transplanted when less than 18 years old who currently have greater than or equal to 10 years of graft function A total of 57 questionnaires were sent out; 57 (100%) responded [24 female and 33 male patients; average (+/- SD) age at tx = 10 +/- 5 years (09-177); average f/u = 156 +/- 3 years (10-26); current age = 26 +/- 5 years (12-38); 26 had greater than 1 transplant] Of the 57 respondents, 9 are less than 18 (all are in school); 48 are greater than or equal to 18 (7 in school, 37 employed, 4 unemployed); 12 are married, 1 engaged, and 2 divorced; and 9 have children While in school, 43 (75%) had participated in sports, 37 (65%) in other extracurricular activities; 7 (12%) were A and 33 (58%) B students; 15 (26%) received awards or scholarships For those working, the range of occupations is broad (average work week = 41 +/- 5 hr) Health-related absence from work has been nonexistent for 93% Health is rated as good to excellent by 91% and fair by 9% The future is regarded as hopeful or promising by 80% Similarly, 89% are satisfied with life in general; 95% said health never or seldom interferes with family life; 95% feel health and drug side effects are of no or minor concern in sexual relationships Only 3% feel health is a problem in maintaining a sexual relationship (41% are not sexually active) Only 4% stated that health often interferes with social life; 98% meet with friends on a regular basis; 76% are satisfied with personal relationships and 8% dissatisfied; 91% are satisfied with their ability to perform at work or school and 5% dissatisfied Of note, 32% are dissatisfied with body appearance Major concerns are short stature and brittle bones Major suggestions include education/support groups to deal with teasing at school and peer problems We conclude that transplanted children with long-term graft function have a favorable social and professional outcome Overall, quality of life seems excellent

Long-term quality of life after kidney transplantation in childhood.

The long-term kidney function (KF) in the three categories of diabetic type 1 pancreas (P) transplant recipients (simultaneous P and kidney [SPK]; P after K [PAK]; PTx alone [PTA] was studied sequentially over a 2-year period in 62 patients who received a bladder-drained allograft that functioned for at least 1 year. Fifty-three (85%) patients were analyzed at 1 month, 42 (68%) at 1 year, and 16 (26%) at 2 years posttransplant. Comparison of KF was made within each recipient category and between categories. In addition, the KF in the SPK and PAK patients was compared to a matched group of diabetic type 1 recipients of KTx alone (functioning at least 1 year). In the SPK group, KF was stable over time: the mean +/- SD serum creatinine (mg/dl) was 1.5 +/- 0.5 at 1 month, 1.8 +/- 1.0 at 1 year, and 1.7 +/- 0.5 at 2 years. In the PAK category, the pre-PTx serum creatinine value was 1.4 +/- 0.5, and then remained stable after the PTx (1.3 +/- 0.2 at 1 month, 1.3 +/- 0.4 at 1 year, and 1.2 +/- 0.4 at 2 years). In the recipients of a PTA, the values at 1 month (1.1 +/- 0.4), 1 year (1.4 +/- 0.5), and 2 years (1.3 +/- 0.5) were significantly higher (P less than or equal to 0.03) than the pre-PTx value (0.9 +/- 0.2); and results at 1 month and 2 years were lower than those at 1 year, a significant difference compared to the 1-month value (P = 0.01). Comparisons between the categories of PTx recipients demonstrated that the pre-PTx value in the PTA group (0.9 +/- 0.2) was significantly lower (P = 0.01) than in the PAK group (1.4 +/- 0.5). At 1 month the serum creatinine value in the PTA category (1.1 +/- 0.4) was significantly lower (P = 0.02) than in the SPK category (1.5 +/- 0.5), but thereafter (1 and 2 years) the difference was not significant (P greater than 0.1). KF in recipients of KTx alone was similar at each post-Tx time point when compared to the SPK and PAK categories. We concluded that a PTx can be performed in diabetics without a detrimental effect on a simultaneously or a previously transplanted kidney and that a statistically significant, albeit minimal to moderate, initial but not progressive deterioration in native KF occurs in recipients of a PTx alone.

P. Morel

Papers

A 10-year experience with 290 pancreas transplants at a single institution.

Long-term quality of life after kidney transplantation in childhood.

Assessment of renal function in type I diabetic patients after kidney, pancreas, or combined kidney-pancreas transplantation.

Detrimental effect of prednisone on canine islet autograft function.

Donor age and cause of death affect cadaver renal allograft outcome.