Pancreas transplantation is now performed as a routine treatment for uremic diabetic recipients of kidney transplants either simultaneously with or after the kidney. Such patients are obligated to immunosuppression and with a successful pancreas transplant can achieve insulin independence as well as a dialysis-free state. Pancreas transplants alone are less commonly applied because of the need for immunosuppression, but the trade off to achieve an insulin-independent state may be worthwhile for individual patients, particularly those who are labile with hypoglycemic unawareness. This option should certainly be a part of the treatment armentation of the modern diabetologist. A positive effect on secondary complications will certainly occur with an early transplant, and even late can have an impact as has been shown for neuropathy. Whether the simpler procedure of islet transplantation will replace pancreas transplants remains to be seen. Of more than 200 islet allografts performed in the 1990s, less than 10% of the recipients have achieved insulin independence at 1 year. Clinical islet trials are ongoing but limited to patients who accept a low individual probability of success to assist in development, or to those in whom the surgical risks of a pancreas transplant is high. Islet transplantation has held promise for over 25 years, but candidates for endocrine replacement therapy must honestly be told the difference in success rates, which are currently much higher with the pancreas.

Diabetes Mellitus, Type 1↗

PubMed1998

Living versus cadaver donor pancreas transplants.

Explore the source record for details and available documents.

Adolescent↗

PubMed1998

Preservation of dog pancreas before islet isolation with the two-layer method.

Explore the source record for details and available documents.

Adenosine↗

PubMed1998

Renal pedicle torsion after simultaneous kidney-pancreas transplantation.

BACKGROUND: Simultaneous kidney-pancreas transplantation has become a recognized therapy for type I diabetes mellitus patients with diabetic nephropathy, neuropathy, and retinopathy. In the vast majority of these procedures, both grafts are placed intraperitoneally, which reduces posttransplant morbidity. Recently, in some of our recipients, we noted renal dysfunction related to complications of the renal pedicle. Our objectives in this study were to identify the cause of this renal dysfunction and to prevent its occurrence in future recipients. STUDY DESIGN: We undertook a retrospective chart review of simultaneous kidney-pancreas recipients who experienced renal dysfunction related to renal pedicle complications. RESULTS: We found four recipients with renal dysfunction related to renal pedicle torsion, diagnosed by serial ultrasound scans and kidney graft biopsies. Early diagnosis allowed salvage of three kidney grafts, but one was lost after late diagnosis. CONCLUSIONS: A high level of suspicion is needed to diagnose renal pedicle torsion. If simultaneous kidney-pancreas recipients have recurrent renal dysfunction, and rejection has been excluded, serial ultrasound scans with color flow Doppler examinations are needed. Once the diagnosis is made, a nephropexy to the anterior abdominal wall is indicated to prevent further torsion and save the kidney graft. We recommend prophylactic nephropexy of left renal grafts if the renal pedicle is > or = 5 cm long and if there is a 2 cm or more discrepancy between the length of the artery and the vein.

Adult↗

PubMed1998

Surgical complications requiring early relaparotomy after pancreas transplantation: a multivariate risk factor and economic impact analysis of the cyclosporine era.

OBJECTIVES: To study significant surgical complications requiring early (< or = 3 months posttransplant) relaparotomy (relap) after pancreas transplants, and to develop clinically relevant surgical and peritransplant decision-making guidelines for preventing and managing such complications. SUMMARY BACKGROUND DATA: Pancreas grafts are still associated with the highest surgical complication rate of all routinely transplanted solid organs. However, the impact of surgical complications on morbidity, hospital costs, and graft and patient survival rates has not been analyzed in detail to date. METHODS: We retrospectively studied surgical complications requiring relap in 441 consecutive cadaver, bladder-drained pancreas transplants (54% simultaneous pancreas and kidney [SPK]; 22% pancreas after kidney [PAK]; 24% pancreas transplant alone [PTA]; 37% retransplant). Outcome and hospital charges were analyzed separately for recipients with versus without reoperation. RESULTS: The overall relap rate was 32% (SPK, 36%; PAK, 25%; PTA, 16%; p = 0.04). The most common causes were intraabdominal infection and graft pancreatitis (38%), pancreas graft thrombosis (27%), and anastomotic leak (15%). Perioperative relap mortality was 9%; transplant pancreatectomy was necessary in 57% of all recipients with one or more relaps. The pancreas graft was lost in 80% of recipients with versus 41% without relap (p < 0.0001). Patient survival rates were significantly lower (p < 0.05) for recipients with versus without relap. By multivariate analysis, significant risk factors for graft loss included older donor age (SPK, PAK), retransplant (PAK), relap for infection (SPK, PAK), and relap for leak or bleeding (PAK). For death, risk factors included older recipient age (SPK, PAK),retransplant (SPK, PAK), relap for thrombosis (PAK), relap for infection or leak (SPK), and relap for bleeding (PTA). CONCLUSIONS: Posttransplant surgical complications requiring relap were frequent, resulted in a high rate of pancreas (SPK, PAK, PTA) and kidney (SPK, PAK) graft loss, and had a major economic impact (p = 0.0001). Complications were associated with substantial perioperative mortality and decreased patient survival rates. The focus must therefore shift from graft salvage to preservation of the recipient's life once a pancreas graft-related complication requiring relap occurs. Thus, the threshold for pancreatectomy should be low. In this context, acceptance of older donors and recipients must be reconsidered.

Adolescent↗

PubMed1998

Pancreas and pancreas-kidney transplantation.

Pancreas transplantation consistently results in an insulin-independent normoglycemic state in insulin-dependent diabetic recipients. Registry data show insulin independence is achieved in 80% of simultaneous kidney and pancreas recipients, more than 70% of pancreas after kidney recipients, and more than 60% of nonuremic pancreas transplant alone recipients. Advances in immunosuppression and careful monitoring for rejection in conjunction with biopsies are largely responsible for improved results. However, complications do occur, and improvements in surgical technique and patient care continue to evolve.

Costs and Cost Analysis↗

PubMed1998

Successful islet autotransplantation in humans: functional insulin secretory reserve as an estimate of surviving islet cell mass.

Islet autotransplantation for treatment of chronic painful pancreatitis in nondiabetic patients reliably establishes normoglycemia and phasic insulin secretion and can achieve prolonged insulin independence. Whether functional transplanted beta-cell reserve is normal after intrahepatic islet transplantation is not known, nor is it known whether conventional measures of insulin secretion accurately reflect the functional beta-cell mass. To determine insulin secretory reserve after islet transplant, we performed studies of glucose potentiation of arginine-induced insulin secretion (GPAIS) in eight recipients of intrahepatic islet autotransplants. All eight subjects (and matched, healthy controls) were studied cross-sectionally 49 +/- 12 months posttransplant, and four subjects were studied pre- and posttransplant. Subjects had received a mean +/- SE of 479,000 +/- 79,000 islets, and all were insulin independent and normoglycemic at the time of study. Acute insulin responses to arginine, glucose, and GPAIS were significantly reduced after islet transplantation in both study groups. Importantly, the magnitudes of these three responses were highly correlated to the mass of islets transplanted (response to glucose: r = 0.84, P < 0.01; response to arginine: r = 0.69, P < 0.05; response to GPAIS = 0.81, P < 0.01). Data from hemipancreatectomized and normal control subjects generally agreed with the regression lines. These findings demonstrate that despite normoglycemia and insulin independence, recipients of intrahepatic islet transplantation have significantly reduced functional beta-secretory reserve and that after islet transplantation, functional beta-cell mass can be estimated by measurements of glucose and arginine-induced insulin responses. Thus, these measurements can be used to estimate the mass and functional capacity of islets surviving intrahepatic transplantation in humans.

Adult↗

PubMed1998

Analysis of United States (US) and non-US pancreas transplants as reported to the International Pancreas Transplant Registry (IPTR) and to the United Network for Organ Sharing (UNOS).

As of November 1998, more than 11,000 pancreas transplants had been reported to the IPTR, including more than 8,800 US and more than 2,600 non-US cases. The 1994-98 cases (> 4,500) were analyzed, including more than 4,000 US and more than 500 non-US transplants. For all US 1994-98 SPK transplants (n = 3,409), one-year patient, pancreas and kidney graft survival rates were 94%, 90% and 83%, respectively; for all PAK cases (n = 375), one-year patient and graft survival rates were 95% and 71%; and for all PTA cases (n = 181), one-year patient and graft survival rates were 95% and 64%, respectively. Recipient age had only a small impact on outcome, with one-year patient survival rates for all recipients < 45 years of 95% (n = 3,215) versus 91% for those > or = 45 years old (n = 758) (p = 0.005). Pancreas graft survival rates at one year for those < 45 versus > or = 45 years old were 84% versus 78% in the SPK (p < 0.02), 70% versus 78% in the PAK (p = 0.13), and 62% versus 79% in the PTA (p = 0.23) categories, respectively). Nearly one-third of US pancreas transplants for 1994-98 were done by the ED drainage technique. For SPK transplants, the one-year pancreas graft survival rate was 83% for BD (n = 2,369) and 82% for ED (n = 912) (p < or = 0.09). For PAK and PTA transplants, pancreas graft survival rates were significantly higher with BD, 74% (n = 261) and 68% (n = 115), respectively, at one year. The drawback for BD was the need for conversion to ED in 7% of the cases at one year and 11% at 2 years. For TS transplants, the pancreas graft loss due to rejection was very low for SPK transplants, 2% at one year versus 9% for PAK and 15% for PTA cases. The various initial maintenance immunosuppressive regimens (Tac + MMF, Tac + Aza, CsA + MMF, CsA + Aza) resulted in only minor differences in pancreas graft survival rates in the SPK cases (80-86% at 1 year), but in PAK and PTA cases the Tac + MMF combination was associated with significantly higher pancreas graft survival rates. For BD PAK transplant recipients given Tac + MMF, the one-year pancreas graft survival rate was 83% (n = 100). For the corresponding BD PTA group it was 75% (n = 44). For non-US cases the outcomes were similar. For non-US SPK transplants (n = 586), one-year patient, kidney and pancreas graft survival rates were 93%, 85% and 81%, respectively. Cox multivariate analyses and logistical regression were done in each recipient category to assess the factors that influence pancreas graft loss. BD was associated with a significantly lower risk than ED in all categories. Increasing donor age was a risk factor in most categories. MMF was associated with a decreased risk for graft loss in the SPK category, and Tac in the PAK and PTA categories.

Adult↗

PubMed1998

Long-term quality of life after kidney and simultaneous pancreas-kidney transplantation.

We are using a validated questionnaire (SF-36) to annually assess health-related quality of life (QOL) in kidney and pancreas-kidney transplant recipients. The SF-36 consists of eight scales to assess physical functioning, general health, and mental functioning. Norms and 95% confidence intervals (C.I.) have been developed for the US population. At present, 1138 recipients with functioning grafts (520 Type I diabetic; 618 nondiabetic) 1-10 yr post-transplant have completed the questionnaire. Of the recipients, 446 completed the questionnaire once; 632 twice; and 53 three times (305 after 1 yr; 266 after 2 yr; 256 after 3 yr; 206 after 4 yr; 192 after 5 yr; 150 after 6 yr; 130 after 7 yr; 138 after 8 yr; 125 after 9 yr; 92 after 10 yr). For both diabetic and nondiabetic recipients, there was little change in average scores for each scale between years (p = NS). In relation to the US population, average scores for nondiabetics were below the 50th percentile on all 8 scales; for diabetics < 25th percentile on the physical functioning and vitality scales, < 50th percentile on all others. For both diabetic and nondiabetic recipients, average scores were higher than reported norms for patients with CHF, COPD, or depression but were similar to those with Htn or recent MI. Individual scores were then compared with age-matched means (+/- 2 SEMs) (95% C.I.) for the US population. At each year post-transplant, up to 40% of nondiabetic and up to 65% of diabetic recipients had scores below the 95% C.I. on individual scales (particularly the physical functioning and general health scales)--e.g. over 30% nondiabetic and up to 60% diabetic recipients had scores on the physical functioning scales below the 95% C.I. More diabetic recipients (vs. nondiabetics) reported poor QOL on the physical functioning, general health and social functioning scales. There was little difference in the mental health scales. For those with Type I diabetes, a similar percentage of kidney and K/P recipients reported QOL below the 95% C.I. for the age-matched population, except on the GH scale (better QOL for K/P recipients). We conclude that successful transplant recipients report health-related QOL below that of the age-matched general population but similar to those with other chronic diseases. Diabetic and nondiabetic recipients have similar scores on the mental health scales; nondiabetic recipients score better on the general health and physical functioning scales.

Adult↗

PubMed1998

Conversion from bladder to enteric drainage after pancreaticoduodenal transplantations.

BACKGROUND: Bladder drainage is the most common technique for managing the exocrine secretions of pancreaticoduodenal grafts. However, bladder drainage can cause urinary, pancreatic, and metabolic complications that may require conversion to enteric drainage. With enteric drainage, urinary amylase levels cannot be monitored as a marker for rejection. After enteric conversion, rejection is the major cause of graft loss. Timing the conversion to reduce immunologic graft loss would greatly improve patient and graft survival rates. Our study was designed to assess the incidence of, indications for, and complications of converting from bladder to enteric drainage after pancreaticoduodenal transplantations. METHODS: We retrospectively reviewed our experience with 80 recipients who underwent enteric conversion. We studied the recipient category, the interval from transplantation to conversion, the interval from the last rejection episode to conversion, the indications for conversion, the type of enteric drainage at conversion (loop versus Roux-en-Y), the results of the conversion, and postconversion complications. RESULTS: The major indications for conversion were metabolic acidosis (n = 26, 33%), recurrent urinary tract infections (UTIs) (n = 16, 20%), reflux pancreatitis (n = 15, 19%), and hematuria (n = 12, 15%). For most recipients, their symptoms resolved after conversion (n = 76, 95%). The cumulative probability of undergoing conversion was 13% at 12 months, 21% at 36 months, and 25% at 60 months. Of the recipients with surgical complications after conversion (n = 12, 15%), one lost his graft as a result of pancreatitis. Overall, of the 80 recipients who underwent conversion, 12 (15%) lost their graft, most due to rejection (n = 8, 75%). Immunologic graft loss was highest for recipients of pancreas transplants alone who underwent conversion < or = 6 months after transplantation or < or = 1 year after their last rejection episode. CONCLUSIONS: Enteric conversion is safe and therapeutic in recipients with complications related to the exocrine secretions of bladder-drained pancreas grafts. After conversion, rejection accounted for 75% of the grafts lost. However, waiting at least 1 year after the last rejection episode significantly reduced immunologic graft loss.

Acidosis↗

PubMed1997

Effect of pancreatic warm ischemia on islet yield and viability in dogs.

BACKGROUND: Defining tolerable warm ischemia (WI) is mandatory before nonheartbeating cadavers can be used to enlarge the donor pool. No studies to date have precisely evaluated the effect of pancreatic WI on islet yield and viability in a large animal model. METHODS: We used mongrel dogs in our study at the University of Minnesota. Excised pancreases were left in situ for a designated period (0, 30, 45, and 60 min in groups 1 to 4, respectively) of WI. Then, they were digested by the automated collagenase digestion method of Ricordi, purified on Euro-Ficoll discontinuous gradients with the COBE cell processor, and autotransplanted into the liver via a mesenteric vein. We compared the four groups in terms of islet yield, expressed as islet equivalents (IE; diameter standardizing to 150 microm) per pancreas weight (IE/g pancreas), and viability, assessed by functional success (maintenance of normoglycemia for 2 weeks) after transplant. RESULTS: Mean islet yield (+/- SD) and the functional success rate after transplant were as follows: 6200+/-1800 IE/g pancreas and 4 of 4 (100%) in group 1; 6300+/-4400 and 4 of 4 (100%) in group 2; 3800+/-2600 and 2 of 4 (50%) in group 3; and 1400+/-1300 and 0 of 4 (0%) in group 4 (P=0.01 vs. group 1). CONCLUSIONS: With 30 min or less of WI, there are no deleterious effects on islet yield and viability. However, with periods of WI longer than 30 min, the loss in islet yield is severe, resulting in functional failure after autotransplantation. The limit of WI that is tolerable for islets is shorter than for a whole pancreas.

Animals↗