Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry.

Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole-organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10-year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1- and 5-year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft-function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.

Pancreas Transplantation: An Alarming Crisis in Confidence.

In the past decade, the annual number of pancreas transplantations performed in the United States has steadily declined. From 2004 to 2011, the overall number of simultaneous pancreas-kidney (SPK) transplantations in the United States declined by 10%, whereas the decreases in pancreas after kidney (PAK) and pancreas transplant alone (PTA) procedures were 55% and 34%, respectively. Paradoxically, this has occurred in the setting of improvements in graft and patient survival outcomes and transplanting higher-risk patients. Only 11 centers in the United States currently perform ≥20 pancreas transplantations per year, and most centers perform <5 pancreas transplantations annually; many do not perform PAKs or PTAs. This national trend in decreasing numbers of pancreas transplantations is related to a number of factors including lack of a primary referral source, improvements in diabetes care and management, changing donor and recipient considerations, inadequate training opportunities, and increasing risk aversion because of regulatory scrutiny. A national initiative is needed to "reinvigorate" SPK and PAK procedures as preferred transplantation options for appropriately selected uremic patients taking insulin regardless of C-peptide levels or "type" of diabetes. Moreover, many patients may benefit from PTAs because all categories of pancreas transplantation are not only life enhancing but also life extending procedures.

Age-based disparity in outcomes of intestinal transplants in pediatric patients.

Outcomes of intestinal transplants (ITx; n = 977) for pediatric patients are examined using the United Network for Organ Sharing data from 1987 to 2009. Recipients were divided into four age groups: (1) <2 years of age (n = 569), (2) 2-6 years (n = 219), (3) 6-12 years (n = 121) and (4) 12-18 years (n = 68). Of 977 ITx, 287 (29.4%) were isolated ITx and 690 (70.6%) were liver and ITx (L-ITx). Patient survival for isolated ITx at 1, 3 and 5 years, 85.3%, 71.3% and 65.0%, respectively, was significantly better than L-ITx, 68.4%, 57.0% and 51.4%, respectively, (p = 0.0001); this was true for all age groups, except for patients <2 years of age. The difference in graft survival between isolated ITx and L-ITx was significant at 1 and 3 years (Wilcoxon test, p = 0.0012). After attrition analysis of graft survival of patients who survived past first year, 3 and 5 years, graft survival for L-ITx patient was significantly better than those for isolated ITx. Isolated ITx should be considered early before the onset of liver disease in children >2 with intestinal failure but is not advantageous in patients <2 years.

The history of pancreas transplantation: past, present and future.

The first attempt to cure type 1 diabetes by pancreas transplantation was done at the University of Minnesota, in Minneapolis, on December 17, 1966, followed by a series of whole pancreas transplantation. Due to the lack of potent immunosuppressive drugs, rejections and infections, it was concluded that pancreas was less antigenic than the kidney which was less antigenic than the duodenum. It opened the door to a period, between the mid 70's to mid 80's where only segmental pancreatic grafts were used in the recipient. Numerous techniques for diverting or dealing with the pancreas juice secretion were described, none of them being satisfactory. In the late 70's - early 80's, three major events happened and boosted the development of pancreas transplantation: firstly the introduction of Cyclosporine A in the clinical field, secondly the organization on March 1980, of the first international meeting on Pancreas Transplantation with the first report of the International Pancreas Transplantation Registry (IPTR) and finally in 1982, the organization of the first informal so-called Spitzingsee meetings where pancreas transplantation successes but mainly failures were discussed which precluded the onset of IPITA (International Pancreas and Islet Transplantation Association), EuroSPK (European Study Group for simultaneous Pancreas and Kidney Transplantation) and EPITA (European Pancreas and Islet Transplantation Association). During one of the Spitzingsee meetings, participants had the idea to renew the urinary drainage technique of the exocrine secretion of the pancreatic graft with segmental graft and eventually with whole pancreaticoduodenal transplant. That was clinically achieved during the mid 80's and remained the mainstay technique during the next decade. In parallel, the Swedish group developed the whole pancreas transplantation technique with enteric diversion. It was the onset of the whole pancreas reign. The enthusiasm for the technique was rather moderated in its early phase due to the rapid development of liver transplantation and the need for sharing vascular structures between both organs, liver and pancreas. During the modern era of immunosuppression, the whole pancreas transplantation technique with enteric diversion became the gold standard for simultaneous pancreas and kidney transplantation (SPK), with portal drainage of the venous effluent of the pancreas, even for pancreas after kidney (PAK) or pancreas transplantation alone (PTA). Today, there remains room for improvement: safety of using the duodeno-duodenal anastomosis technique must be confirmed by prospective analysis while preventing ischemic reperfusion injuries, using specific drugs; that must be assessed in new trials.

Solid-organ Transplants From Living Donors: Cumulative United States Experience on 140,156 Living Donor Transplants Over 28 Years.

BACKGROUND: Transplantation of organs from living donors helps to decrease the organ shortage and shortens waiting times. Living donor (LD) transplantation is also generally associated with better outcomes. Unfortunately, there has been no comprehensive analysis and comparison of all types of solid-organ transplantation from living donors since the inception of the United Network for Organ Sharing (UNOS). METHODS: Using the UNOS/Organ Procurement and Transplantation Network (OPTN) database, all LD transplants from October 1, 1987, to December 31, 2015, were studied with univariate and multivariate analyses. RESULTS: A total of 140,090 organs were transplanted from LDs, accounting for 21% of all transplants in the United States. Over 95% were kidney; 4% were liver; and <1% intestine, lung, and pancreas LDs. Only LD kidney transplant patient and graft survival rates were significantly higher compared deceased donor transplants over the period of analysis. The best long-term LD transplant results were achieved in pediatric liver recipients. Significantly more women than men donated organs and significantly more men than women received solid-organ transplants. A regional disparity was observed for LD kidney as well as for LD liver transplants. Despite improvements in outcomes and increased use of nonbiologic donors, the number of LD transplants in the United States has declined. This decline was greater in children than adults and was noted for all types of organ transplants. CONCLUSION: Further efforts are needed to educate the public, health professionals, and transplant candidates on the advantages of living vs deceased donor organ transplantation. Compared with other countries, LD transplantation has yet to reach its full potential in the United States.

Pancreas transplantation: indications, clinical management, and outcomes.

Although many advances have been made, pancreas transplantation still poses several challenges to the surgeon, internist and patient. With success rates now above 80% and improving yearly, diabetic patients must make a major life-style decision when considering a pancreas transplant. The main concerns are will the benefits of insulin-independence off-set the risks of surgery and immunosuppression. For diabetics near dialysis and considering a kidney transplant, the decision may not be as difficult. However, for those patients who are failing insulin therapy (brittle control) and remain with good renal function, the options are limited. As the success of pancreas transplantation improves, the procedure may become routine at more centers and become accepted by more third-party carriers. However, as with other solid organs, the availability of pancreases is limited and the supply soon to be exhausted. Thus, further advances are required for the prevention and treatment of Type 1 diabetes. Hopefully, the new frontiers of the next century will allow physicians to identify and preventively treat those at risk for the development of diabetes. Thus, the population of patients suffering from the consequences of this dreadful disease will be greatly reduced. With new developments in immunosuppression and islet transplantation, diabetic patients of the future may be offered the option of a procedure with reduced risks, less morbidity, and improved long-term cure rates.

Pancreas transplant pathology. A morphologic, immunohistochemical, and electron microscopic comparison of allogeneic grafts with rejection, syngeneic grafts, and chronic pancreatitis.

In an effort to establish diagnostic criteria for rejection and recurrent disease in transplanted pancreas, a comparative study was performed based on clinical diagnosis. Clinical rejection was diagnosed in patients who had decreased urinary amylase or increased blood glucose; they were treated for rejection and improved. A clinical diagnosis of recurrent diabetes was made in syngeneic transplant recipients with islet dysfunction. In addition, two control groups were used--nontransplant, nondiabetic pancreatitis patients and pretransplant normal biopsies from patients in the study. Morphologically, tissues were assessed for acinar inflammation, ductal changes, islet and nerve inflammation, and vascular changes. Immunohistochemical staining for insulin and glucagon was also performed to quantitate differences between the groups. Vascular changes (endothelialitis, vasculitis, obliterative endarteritis) were specific for rejection. Also, rejection was characterized by a lymphocytic or mixed infiltrate that involved the ducts. Recurrent diabetes was characterized by selective loss of beta cells with isletitis. Leukocyte common antigen and UCHL1 staining was helpful in identifying islet inflammation. An insulin/glucagon ratio of less than 1.0 appears to be specific for recurrent disease and in the absence of isletitis is a reasonable method for detecting recurrent disease at an early stage.

Laparoscopic biopsy after pancreaticoduodenal transplantation. A first report.

Over the past 5 years, graft biopsy has become the gold standard for diagnosing rejection or graft dysfunction after pancreas transplantation. Until now, only three types of pancreas graft biopsies have been described: percutaneous, transcystoscopic, and open laparotomy. Percutaneous biopsy (whether computerized tomography scan or ultrasound guided) is unsuccessful 20% of the time. In recipients of enterically drained pancreas grafts, a transcystoscopic biopsy cannot be done. The only other alternative has been an open laparotomy. We report one case of laparoscopic biopsy of an enterically drained pancreas graft, after a percutaneous biopsy was unsuccessful. We conclude that laparoscopic pancreas graft biopsy is a safe and effective method for diagnosing graft dysfunction. It also avoids the complications and prolonged hospitalization of an open laparotomy. Laparoscopic biopsy should become another valuable tool for diagnosing pancreas graft dysfunction.

Living-related intestinal transplantation: first report of a standardized surgical technique.

BACKGROUND: Intestinal transplants using cadaver donors have become an alternative to total parenteral nutrition (TPN) for the treatment of irreversible intestinal failure. Intestinal transplants using living-related donors have rarely been attempted, and the surgical technique has not been standardized. METHODS: We performed a living-related intestinal transplant for a paraplegic, 16-year-old boy with life-threatening TPN complications, including lack of vascular access, recurrent line infections, and intermittent liver dysfunction. RESULTS: A four antigen-matched donor (father) underwent resection of 200 cm of the ileum on a vascular pedicle comprising the ileocolic artery and vein. This resection left the donor with 300 cm of proximal small bowel, 20 cm of the most distal terminal ileum, the ileocecal valve, and all of the large intestine. The donor's ileocolic artery and vein were anastomosed to the recipient's infrarenal aorta and cava; bowel continuity was restored with an end-to-end anastomosis between the recipient's jejunum and the donor's ileum. Both donor and recipient had uneventful postoperative courses. Recipient maintenance immunosuppression has been with tacrolimus, mycophenolate mofetil, and prednisone. One year after transplant, urine methylmalonic acid indicates good vitamin B12 absorption in both the donor and recipient. The recipient has been completely off TPN since discharge (posttransplant day 21), has gained 20 kg, and has had no evidence of rejection, infection, or graft-versus-host disease. CONCLUSIONS: Intestinal transplants from living-related donors can be lifesaving for selected patients with chronic intestinal failure and can be done with minimal risk to the donor.

Simultaneous kidney and segmental pancreas transplants from living related donors - the first two successful cases.

Simultaneous pancreas and kidney transplants (SPKs) from cadaver donors have become a widely accepted treatment option for insulin-dependent (Type I diabetic) patients with end-stage nephropathy. However, for technically successful transplants, long-term success is better with living donors (LDs). Sequential kidney and pancreas transplants from LDs have been done, but until now SPKs from LDs have not been attempted. We report here 2 successful SPKs from LDs. Both recipients received a right kidney and distal pancreas: the first (a 28-year-old woman, diabetic since age 7) from her 54-year-old mother; the second (a 46-year-old man, diabetic since age 31) from his 44-year-old sister. Six months posttransplant both recipients have function of both grafts (serum creatinine < or = to 1.5 mg/dl; serum C-peptide normal range, fasting and stimulated). Thus, SPKs from LDs are technically feasible and could be an alternative to segmental transplants or cadaver SPKs for selected type I diabetic patients with end-stage nephropathy.

Donor iliac vein interposition during liver transplantation in a patient with a migrated transjugular intrahepatic portosystemic shunt.

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) are sometimes used to reduce the risk of variceal bleeding or treat intractable ascites before orthotopic liver transplantation (OLT). TIPS usually do not make OLT more difficult, but rarely, malposition of TIPS can significantly complicate OLT. METHOD AND RESULTS: The following report describes a patient in whom an initially well-placed Wallstent migrated to the confluence of the splenic and superior mesenteric veins. During liver transplantation, the portal vein containing the Wallstent was completely resected, and the portal vein was reconstructed with donor iliac vein. After sewing the iliac vein onto the portal remnant, the liver transplant was completed under portosystemic bypass. The patient had an uneventful recovery. CONCLUSIONS: Wallstents can migrate within the portal vein. An interposition graft of donor vein allows full resection of the portal vein containing a migrated stent and facilitates portosystemic bypass and portal anastomosis.

Correlation of rejection of the duodenum with rejection of the pancreas in a pig model of pancreaticoduodenal transplantation.

To assess the correlation of rejection in the duodenum and the pancreas, we examined pancreatic and duodenal tissue from pancreaticoduodenal transplants in 32 outbred Yorkshire Landrace pigs. After streptozotocin-induced hyperglycemia, they were transplanted and treated with prednisone, AZA, and CsA. Immunosuppression was reduced by 50% weekly and discontinued at 3 weeks. The tissues were harvested at necropsy at various time points. Each organ was graded for interstitial rejection and vascular rejection separately as no, mild, moderate, and severe. All but 1 animal rejected their organs. Complete concordance of rejection between duodenum and pancreas considering both interstitial and vascular findings was found in 15/32 (47%) animals. In 11/17 (65%) of the remaining allografts, the pancreas had a higher rejection grade (3 interstitial, 5 vascular, 3 both) and in 6/17 (35%) the duodenum had higher rejection grades (2 interstitial, 4 vascular). Considering interstitial and vascular rejection separately, 23/32 (72%) and 20/32 (63%) showed concordance, respectively. Most cases (7/9, 78%) of discordant interstitial rejection showed higher interstitial rejection grades in the pancreas. Five cases (4 pancreas, 1 duodenum) showed interstitial discordance of 2 grades or more. Discordant cases with higher vascular rejection were 7 pancreas (58%) and 5 duodenum. Five cases (3 pancreas, 2 duodenum) showed vascular discordance of 2 grades or more. Interstitial rejection was seen alone (11 cases) and with vascular rejection (20 cases), but vascular rejection was never seen alone. We made the following conclusions. (1) Concordance of duodenal and pancreas rejection occurs in 47% of cases. (2) Discordant cases usually show higher grades of rejection in the pancreas (65%), but the opposite can also occur. (3) Therefore, if duodenal biopsies are positive, they are likely to be representative of pancreatic pathology, but when negative, they do not rule out rejection of the pancreas. (4) Interstitial rejection appears to precede vascular rejection, suggesting that factors released during interstitial rejection play a role in endothelial cell activation and vascular rejection.

Optimal timing for a pancreas transplant after a successful kidney transplant.

BACKGROUND: For certain uremic, diabetic patients, a sequential transplant of a kidney (usually from a living donor) followed by a cadaver pancreas has become an attractive option. But how long to wait after the kidney transplant before proceeding with a pancreas transplant is unclear. We studied outcomes in recipients of a pancreas at varying times after a kidney to determine the optimal timing for the second transplant. METHODS: We compared pancreas after kidney (PAK) transplants performed early (< or =4 months) and late (>4 months) after the kidney transplant to determine any significant differences in surgical complications or outcomes between the two groups. RESULTS: Between January 1, 1994, and September 30, 1998, we performed 123 cadaver PAK transplants. Of these, 25 (20%) were early and 98 (80%) were late. Characteristics of the two recipient groups were similar. We found no significant differences in outcome between the two groups. The incidence of surgical complications (bleeding, leaks, thrombosis, infections) and of opportunistic infections (such as cytomegalovirus) did not significantly differ between the two groups. Graft and patient survival rates were also equivalent (P=NS). The incidence of acute rejection by 3 months posttransplant was 20% in both groups. CONCLUSION: The timing of the pancreas transplant for PAK recipients does not seem to influence outcome. As long as an acceptable organ is available and the recipient is clinically stable, a PAK transplant can be performed relatively soon after the kidney transplant.

Solitary pancreas transplantation for nonuremic patients with labile insulin-dependent diabetes mellitus.

BACKGROUND: Simultaneous pancreas-kidney transplantation has become a widely accepted treatment option for selected uremic patients with insulin-dependent diabetes mellitus (IDDM). Patient survival rates at 1 year exceed 90%, and rates of pancreas graft survival, 70%. However, solitary pancreas transplantation for nonuremic patients with IDDM has been controversial because of the less favorable outcome and the need for long-term immunosuppression with its associated morbidity and mortality. METHODS: We studied the outcome of 225 solitary pancreas transplants during three immunosuppressive eras: the precyclosporine (CsA) era (n=83), the CsA era (n=118), and the tacrolimus era (n=24). Only patients with labile IDDM (e.g., hypoglycemic unawareness, insulin reactions, > or = 2 failed attempts at intensified insulin therapy for metabolic control) underwent solitary pancreas transplantation. Using univariate and multivariate analyses, we looked at patient and graft survival, the risk of surgical complications, and native kidney function during these three eras. RESULTS: Pancreas graft survival improved significantly over time: 34% at 1 year after transplantation in the pre-CsA era, 52% in the CsA era, and 80% in the tacrolimus era (P=0.002). Pancreas graft loss due to rejection decreased from 50% at 1 year in the pre-CsA era, to 34% in the CsA era, to 9% in the tacrolimus era (P=0.008). The rate of technical failures (i.e., the risk of surgical complications) decreased from 30% in the pre-CsA era, to 14% in the CsA era, to 0% in the tacrolimus era (P=0.001). Patient survival rates at 1 year have ranged between 88% and 95% in the three eras (P=NS). Matching for at least one antigen on each HLA locus and avoiding HLA-B mismatches significantly decreased the incidence of rejection. The incidence of native kidney failure due to drug-induced toxicity decreased significantly over time, in part because only recipients with pretransplant creatinine clearance > or = 80 ml/min received transplants. CONCLUSIONS: Solitary pancreas transplantation has become a viable alternative for nonuremic patients with labile IDDM. The risks of surgical complications and drug-induced nephrotoxicity have significantly decreased over time. Using tacrolimus as the mainstay immunosuppressant, patient and graft survival rates now no longer trail those of simultaneous pancreas-kidney transplantation.

Donor-specific portal blood transfusion in intestinal transplantation: a prospective, preclinical large animal study.

BACKGROUND: Unlike in kidney and heart transplantation, the role of pretransplant donor-specific blood transfusion (DST) has not been studied prospectively in a large animal model of bowel transplantation. We investigated the impact of portal versus systemic DST on overall survival, rejection, graft-versus-host disease (GVHD), and infection after total (small and large) bowel transplantation in pigs. METHODS: Mixed lymphocyte culture-reactive, outbred pigs underwent total enterectomy and orthotopic total bowel transplantation with portal vein graft drainage. One unit of donor blood was transfused via the portal or systemic circulation (according to a randomization protocol) before graft implantation was begun. We studied six groups, all of which underwent at least a total bowel transplant: group 1 (n=5) comprised nonimmunosuppressed control pigs with portal DST; group 2 (n=6), nonimmunosuppressed control pigs with systemic DST; group 3 (n=5), cyclosporine (CsA)-treated pigs with portal DST; group 4 (n=5), CsA-treated pigs with systemic DST; group 5 (n=5), tacrolimus-treated pigs with portal DST; and group 6 (n=5), tacrolimus-treated pigs with systemic DST. All immunosuppressed pigs received prednisone (2 mg/kg/day) and either CsA (to maintain levels between 250 and 350 ng/ml) or tacrolimus (to maintain levels between 10 and 30 ng/ml). Stomal biopsies and autopsies were obtained to study the incidence of rejection, GVHD, and infection. RESULTS: Portal DST and tacrolimus-based immunosuppression resulted in the highest survival rates. At 7, 14, and 28 days after transplantation, survival rates in group 5 were 100%, 100%, and 80%; in group 6, 100%, 60%, and 40%; and in group 3, 100%, 0%, and 0%, respectively. Only the combination of portal DST and tacrolimus prevented the occurrence of, and death from, rejection. Death from rejection at 7, 14, and 28 days in group 5 was 0%, 0%, and 0%; in group 6, 0%, 33%, and 67%; and in group 3, 0%, 100%, and 100%, respectively. Of note, if immunosuppression was used, the groups with portal (versus systemic) DST had a higher risk of death from infection but a lower risk of death from GVHD. Simultaneous immunologic events were noted more frequently in groups with systemic (versus portal) DST. Long-term survival was noted only in groups with tacrolimus-based immunosuppression and was more common for those with portal (versus systemic) DST. CONCLUSIONS: Portal DST at the time of total bowel transplantation and posttransplant immunosuppression with tacrolimus prevent rejection and significantly increase graft survival. The combination of portal antigen presentation and tacrolimus needs to be studied in clinical bowel transplantation.

Successful living related simultaneous pancreas-kidney transplant between identical twins.

Simultaneous pancreas-kidney transplant from living donors has been recently proposed as an effective therapeutic option in selected uremic patients with type I diabetes. We report the first simultaneous pancreas-kidney transplant performed between identical twins. Posttransplant, the recipient has been maintained on low dose cyclosporine to avoid recurrent auto-immune insulitis. At the 1-year follow-up, both donor and recipient are well with normal renal function and excellent glucose control. Simultaneous pancreas-kidney transplant between identical twins can be performed successfully using cyclosporine to prevent recurrent auto-immune insulitis.

Mycophenolate mofetil in pancreas transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has been shown to decrease the incidence of acute rejection episodes after kidney transplantation. The use of MMF along with tacrolimus for > or =1 year after pancreas transplantation has not been studied in a large single-center analysis. METHODS: Between July 1, 1995 and June 30, 1997, both MMF and tacrolimus were given to 120 pancreas transplant recipients. By category, 61 underwent simultaneous pancreas-kidney transplantation (SPK); 44 underwent pancreas transplantation after previous kidney transplantation (PAK); and 15 underwent pancreas transplantation alone (PTA). By donor source, 86% of the grafts were from a cadaver, and 14% were from a living-related donor. Induction therapy was with MMF, tacrolimus, prednisone, and antithymocyte globulin (n=109) or OKT3 (n=2). Until oral intake was resumed, recipients initially received intravenous azathioprine. Side effects were as follows: gastrointestinal (GI) toxicity in 53% of recipients receiving combined MMF and tacrolimus therapy; bone marrow toxicity in 24% of recipients receiving MMF alone; nephrotoxicity in 18% and neurotoxicity in 11% of recipients receiving tacrolimus alone. We did a matched-pair analysis to compare outcome in MMF versus azathioprine recipients, using the database of the International Pancreas Transplant Registry. Matching criteria included transplantation category, transplantation number, recipient and donor age, duct management, HLA typing, and transplantation year. RESULTS: One-year patient survival rates were 98% for SPK, 98% for PAK, and 100% for PTA (P=NS). For SPK recipients, 1-year pancreas graft survival rates were 86% with MMF versus 79% with azathioprine (P=NS); kidney graft survival rates were 96% with MMF versus 86% with azathioprine (P=NS). The incidence of first rejection episodes at 1 year was significantly lower for MMF recipients (15% with MMF versus 43% with azathioprine) (P = 0.0003). For recipients of solitary pancreas transplants (PTA and PAK), we found no difference in graft survival rates between MMF and azathioprine. The conversion rate from MMF to azathioprine at 1 year was 14% for SPK recipients, 26% for PAK, and 39% for PTA (P < 0.007). The most common reason for conversion was GI toxicity, in particular for nonuremic (PTA) or posturemic (PAK) recipients. The rates of posttransplant infection and lymphoproliferative disease were low for recipients on MMF and tacrolimus. CONCLUSIONS: The combination of MMF and tacrolimus after pancreas transplantation is highly effective and safe. For SPK recipients, the incidence of acute reversible rejection episodes was significantly lower with MMF than with azathioprine. The conversion rate from MMF to azathioprine because of GI toxicity was lowest for SPK and highest for PTA recipients.

Pregnancy after pancreas transplantation in the cyclosporine era: report from the International Pancreas Transplant Registry.

BACKGROUND: As of December 31, 1996, a total of 9012 pancreas transplants have been reported to the International Pancreas Transplant Registry (IPTR). Over 75% of these recipients were < or = 40 years of age at the time of their transplant. With continued improvement in short- and long-term outcome after transplant, an increasing number of female recipients have become pregnant. However, outcome after pregnancy in pancreas transplant recipients has not been studied in detail. METHODS: To evaluate the risks of pregnancy after pancreas transplantation in the cyclosporine era, we surveyed the institutions reporting to the IPTR. RESULTS: Nineteen cases of pregnancy in 17 female recipients of simultaneous pancreas-kidney transplants resulted in 19 live births. Metabolic control during pregnancy was good in all cases. Mean duration of gestation was 35.2-2.2 weeks. Mean birth weight was 2150+/-680 g. Two congenital malformations were reported (one bilateral cataract and one double aortic arch). One child developed type I diabetes at age 3 years. Only one pancreas graft and one kidney graft were lost (in two different recipients). The pancreas graft was lost after delivery (because of acute rejection). The kidney graft was lost 3 months after delivery (impaired function due to previous amphotericin B treatment). One case of a worsened secondary complication (retinopathy) was reported. One recipient died of myocardial infarction 7 years after transplant and 5 years after delivery, in spite of a normal pretransplant coronary angiogram and good pancreas function. CONCLUSION: This study shows that simultaneous pancreas-kidney transplantation can restore fertility in uremic type I diabetic female recipients. Thus, both posttransplant contraception and fertility counseling are options for female recipients. However, our analysis demonstrates that, when discussing the possibility of pregnancy with female pancreas recipients, these potential risks must be considered: (1) graft loss, (2) progressive maternal morbidity and mortality even with good glycemic control, and (3) diabetes transmission to offspring.

Cytomegalovirus disease recurrence after ganciclovir treatment in kidney and kidney-pancreas transplant recipients.

BACKGROUND: With the introduction of ganciclovir, the clinical pattern of cytomegalovirus (CMV) disease has changed; CMV disease recurrence after successful treatment of the initial episode has emerged as a more common problem. We studied CMV disease recurrence in kidney transplant (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients, and identified risk factors for recurrence. METHODS: Between January 1987 and December 1995, of 1272 KTx and 287 SPK recipients, 332 developed CMV disease and were treated with a 14-day course of i.v. ganciclovir, followed by a 10-week course of oral acyclovir. Among these 332 recipients, 103 (31%) developed CMV disease recurrence more than 30 days after treatment for the initial episode; this group was compared with those recipients who did not develop recurrence (n=229). Risk factors examined were age, presence of diabetes, type of transplant (KTx vs. SPK), donor source (cadaver vs. living donor), treatment for acute rejection, pretransplant CMV serologic status, evidence of tissue-invasive CMV, and treatment of the initial episode with human immune globulin in addition to ganciclovir. RESULTS: Univariate analysis found that patients with recurrence were more likely to be diabetic (70.9% vs. 53.7%; P=0.04), to have undergone an SPK (39.8% vs. 20.5%; P=0.004), to have received a cadaver organ (78.6% vs. 61.6%; P=0.002), and to have received treatment for acute rejection (78.6% vs. 59.8%; P=0.001). Using multivariate analysis, two statistically significant risk factors were found: receiving a cadaver organ (relative risk [RR]=1.90; P=0.03) and treatment for acute rejection (RR=2.02; P=0.008). Diabetes (RR=1.44; P=0.18) and a cadaver SPK transplant (RR=1.55; P=0.12) tended toward increased risk for recurrence, but the difference did not reach statistical significance. The remaining variables were not significant. Interestingly, CMV recurrence did not significantly diminish 5-year graft survival (52.0% vs. 54.4%; P not significant) or patient survival (67.0% vs. 68.3%; P not significant) rates. CONCLUSIONS: CMV disease recurs in roughly one-third of KTx and SPK recipients after treatment of the initial episode with ganciclovir. A cadaver organ source and treatment for acute rejection were the most significant clinical risk factors for recurrence. Clinical predictors of recurrence such as these may help to identify those recipients who need more intensive therapeutic and prophylactic regimens.