Outcomes of pancreas transplantation in patients with underlying inflammatory bowel disease: a retrospective case series.

Despite having emerged as a definitive treatment for diabetes mellitus (DM), pancreas transplantation remains a formidable surgical task owing to complications like graft pancreatitis, enteric leaks, and rejection. This becomes more challenging in the setting of underlying bowel pathology, such as inflammatory bowel disease (IBD), which has a strong immune-genomic association of co-existence with DM. Risk of anastomotic leaks, dose adjustments of immunosuppressants and biologicals, and management of IBD flares constitute some of the major perioperative challenges calling for a protocol-based, systematic, multidisciplinary approach. Patients and methods: This was a retrospective case series of patients between January 1996 and July 2021, with all patients being followed up until December 2021. All consecutive patients with end-stage DM who underwent pancreas transplantation (alone, simultaneous with kidney transplantation or after kidney transplantation) and had pre-existing IBD were included in the study. A Comparison of 1-, 5-, 10-year survival was done with pancreas transplant recipients without underlying IBD using Kaplan-Meir curves. Results: Of the total 630 pancreas transplants performed between 1996 and 2021, eight patients had IBD, mostly Crohn's disease. Following pancreas transplantation, two of the eight patients had duodenal leaks, with one a requiring graft pancreatectomy. The 5-year graft survival rate for the cohort was 75% compared to 81.6% for the overall cohort of patients undergoing pancreas transplantation (P=0.48) with a median graft survival of 48.4 months compared to 68.1 months in the latter (P=0.56). Conclusion: The findings of the series provide a snapshot of the outcome of pancreas transplantation in the background of IBD, suggesting a graft and overall patient survival rates comparable with pancreas transplantation in patients without underlying IBD, with further validation of the findings required in a larger cohort of patients in the future.

Engaging high school students about organ donation and transplantation: an evaluation of the High School Outreach Initiative (HSOI) program.

Adolescents can be influential in changing societal perceptions of organ donation and transplantation (ODT) but current studies on youth are limited. We sought to (1) assess the baseline knowledge in ODT among students in Toronto, Canada, and (2) evaluate the effectiveness of the High School Outreach Initiative (HSOI) program presentations in changing awareness and interest about ODT. Pre- and post-presentation surveys were administered to high school students about their knowledge of ODT, awareness of donor registration, importance of donation, intent to register, and willingness to talk to their families about donation. Descriptive statistics were used to characterize the students' baseline knowledge and interest. Wilcoxon and McNemar tests were used to analyze changes in perceptions before and after the presentation. A total of 449 HSOI presentations were delivered to 33,090 students at 102 high schools in the Greater Toronto Area between 2012 and 2019. Data from 3327 surveys completed by students before a presentation showed 46.5% were not knowledgeable about ODT. For the 2-year period between 2017 and 2019, 1224 matched pre- and post-presentation surveys were collected. The 49.8% of students who stated they were not knowledgeable about ODT prior to the presentation decreased to 3.8% after (p < 0.001). Those who were not willing to register decreased by half after the presentation (p < 0.001). The HSOI is an effective educational program in improving youth's attitudes and perceptions toward ODT. Further directions of the program include the expansion to other cities and the collection of demographic information of students.

Randomized open-label crossover assessment of Prograf vs Advagraf on immunosuppressant pharmacokinetics and pharmacodynamics in simultaneous pancreas-kidney patients.

INTRODUCTION: We assessed the pharmacokinetic and pharmacodynamic impact of converting stable simultaneous pancreas-kidney (SPK) recipients from standard tacrolimus (Prograf) to long-acting tacrolimus (Advagraf). METHODS: In a randomized prospective crossover study, stable SPK recipients on Prograf were assigned to Prograf with 1:1 conversion to Advagraf or vice versa. Demographics, tacrolimus, mycophenolic acid levels, and Cylex CD4 + ATP levels were taken at specified intervals in addition to standard blood work. RESULTS: Twenty-one patients, who were a minimum of 1 year post-transplant, were entered into the study. No difference in tacrolimus or mycophenolic acid levels was noted between patients who were first assigned to Prograf or Advagraf. Additionally, Cylex levels as well as serum creatinine, lipase, and blood sugar levels were unchanged. There were no episodes of rejection during the 6-month study. CONCLUSIONS: It is safe to convert between Prograf and Advagraf 1:1, without major impact on pharmacokinetics or pharmacodynamics in SPK recipients.

Preserving the Pancreas Graft: Outcomes of Surgical Repair of Duodenal Leaks in Enterically Drained Pancreas Allografts.

BACKGROUND: Duodenal leak remains a major cause of morbidity and graft loss in pancreas transplant recipients. The role and efficacy of surgical and image-guided interventions to salvage enterically drained grafts with a duodenal leak has yet to be defined. METHODS: We investigated the incidence, treatment, and outcome of duodenal leak in 426 pancreas transplantation recipients from 2000 to 2015. RESULTS: Duodenal leak developed in 33 (7.8%) recipients after a median follow-up of 5.3 (range, 0.5-15.2) years. Most leaks occurred during the first year (n = 22; 67%), and most were located near the proximal and distal duodenal staple line. Graft pancreatectomy was performed in 8 patients as primary therapy because of unfavorable local and/or systemic conditions. Salvage was attempted in 25 patients using percutaneous drainage (n = 4), surgical drainage (n = 4), or surgical repair (n = 17). Percutaneous or surgical drainage failed to control the leak in 7 of these 8 patients, and all 7 ultimately required graft pancreatectomy for persistent leak and sepsis. Surgical repair salvaged 14 grafts, and 13 grafts continue to function after a median follow-up of 2.9 (range, 1.1-6.3) years after repair. CONCLUSIONS: Our study shows that in selected patients a duodenal leak can be repaired successfully and safely in enterically drained grafts.

Conservative Pancreas Graft Preservation at the Extreme.

Because of the value some patients place in remaining insulin-independent after pancreas transplantation, they may be reluctant to undergo graft pancreatectomy, even in the face of extreme complications, such as graft thrombosis and duodenal segment leak. Partly, for this reason, a variety of complex salvage techniques have been described to save the graft in such circumstances. We report a case of a series of extreme complications related to a leak from the duodenal segment after a simultaneous pancreas and kidney transplant. These included infected thrombosis of the inferior vena cava associated with a graft venous thrombosis and a retroperitoneal fistula. The patient retained graft function with insulin independence and repeatedly declined graft pancreatectomy against the advice of the transplant team. Conservative treatment with percutaneous drainage, antibiotics, and anticoagulation was eventually successful. This outcome is unique in our experience and may be instructive to teams caring for pancreas transplant recipients.

The significance of pre-operative coronary interventions on outcome after pancreas transplantation.

Pancreas transplant candidates are at very high risk of coronary vascular disease. We hypothesized that the requirement for pre-operative coronary intervention (PCI) may be associated with an adverse impact on short- and long-term outcomes. Retrospective analysis of 366 consecutive primary pancreas transplants was undertaken. Outcomes were compared between recipients who had undergone PCI (n = 48) and those who had not (n = 318). In 48% (23/48) of instances, the PCI was initiated by the transplant cardiology evaluation. The recipients undergoing PCI were older than those not undergoing PCI (47.6 yr vs. 41.9 yr, respectively, p < 0.0001). Although not statistically significant, there was a higher rate of post-operative major cardiovascular events (MCVE) in the PCI group (10.4%) compared with those not undergoing PCI (4.7%) (RR [95% CI]: 2.0 [0.90-4.5]; p = 0.17). In the long term, there were no differences in the rate of death with graft function (p = 0.77) or rejection (p = 0.17). There were no statistically significant differences between the groups with respect to patient (p = 0.54), kidney (p = 0.76), or pancreas (p = 0.63) graft survival. PCI is not a risk factor for short-term perioperative events, and long-term transplant outcomes are equivalent to patients not requiring PCI. PCI, by itself, should not be considered a contraindication for pancreas transplantation, but should raise awareness of perioperative risk.

Duodenal leaks after pancreas transplantation with enteric drainage - characteristics and risk factors.

Pancreas-kidney transplantation with enteric drainage has become a standard treatment in diabetic patients with renal failure. Leaks of the graft duodenum (DL) remain a significant complication after transplantation. We studied incidence and predisposing factors of DLs in both simultaneous pancreas-kidney (SPK) and pancreas after kidney (PAK) transplantation. Between January 2002 and April 2013, 284 pancreas transplantations were performed including 191 SPK (67.3%) and 93 PAK (32.7%). Patient data were analyzed for occurrence of DLs, risk factors, leak etiology, and graft survival. Of 18 DLs (incidence 6.3%), 12 (67%) occurred within the first 100 days after transplantation. Six grafts (33%) were rescued by duodenal segment resection. Risk factors for a DL were PAK transplantation sequence (odds ratio 3.526, P = 0.008) and preoperative immunosuppression (odds ratio 3.328, P = 0.012). In the SPK subgroup, postoperative peak amylase as marker of preservation/reperfusion injury and recipient pretransplantation cardiovascular interventions as marker of atherosclerosis severity were associated with an increased incidence of DLs. CMV-mismatch constellations showed an increased incidence in the SPK subgroup, however without significance probability. Long-term immunosuppression in PAK transplantation is a major risk factor for DLs. Early surgical revision offers the chance of graft rescue.

Outcomes of pancreas retransplantation after simultaneous kidney-pancreas transplantation are comparable to pancreas after kidney transplantation alone.

BACKGROUND: There is a paucity of contemporary data describing the results of pancreas retransplantation (PRT). As a measure of utility, we wished to determine whether PRT could produce equivalent short-term and long-term recipient outcomes to primary pancreas after kidney (PAK) transplantation. METHODS: Retrospective analysis of 96 consecutive pancreas only transplants performed from 2003 to May 2012. Primary PAK transplants (n = 78) were compared to PRT (n=18). RESULTS: Donor and recipient demographics were similar. Pancreas graft survival was similar for PAK and PRT at 1 year (88.2% vs. 100%) and 3 years (85.1% vs. 85.1%). Pancreas graft failure occurred in 14 PAK and two PRT patients with a mean follow-up of 61.6 ± 38.7 and 37.8 ± 26.1 months, respectively. There were no differences in postoperative length of stay (9.9 days vs. 8.7 days; P = 0.9) or postoperative complications in the first 3 months (47.4% vs. 38.9%, P = 0.6). At 3-year follow-up, both groups had comparable HBA1c (0.06 vs. 0.05; P = 0.8), serum creatinine (116.6 µmol/L v 131.7 µmol/L; P = 0.09), and oral glucose tolerance tests. CONCLUSION: Pancreas retransplantation is a safe and effective therapy for select recipients after graft loss. Pancreas retransplantation is associated with the same risk of postoperative complications and has similar intermediate-term graft survival compared to primary PAK transplantation.

Optimizing pancreas transplantation outcomes in obese recipients.

BACKGROUND: Pancreas transplant recipient obesity has been associated with increased risk of perioperative complications, graft failure, and death. The imperative to maximize organ utility must be balanced against the need to maintain equity of access, including for the increasing number of obese diabetic patients. METHODS: We compared the outcomes of pancreas transplant recipients with body mass index (BMI) greater than 30 kg/m(2) (n=60, mean ± SD BMI 32.1 ± 1.7 kg/m(2)) to those with BMI less than 30 kg/m(2) (n=308, mean ± SD BMI 24.5 ± 2.7 kg/m(2)) between 1996 and 2013. RESULTS: There were no differences in the pretransplant recipient or donor characteristics apart from BMI. The BMI greater than 30 group were more likely to suffer a rejection episode (43% vs. 29%; P = 0.03). The median time to first rejection was shorter (1 vs. 6 months; P = 0.04), and wound infection was more common in the BMI greater than 30 group (P = 0.03). There was no difference in the rate of patient, pancreas, or kidney graft survival or difference in graft function between the two groups. CONCLUSION: The obese recipients in this study were in the lower range of the obese category. Although there was an increased risk of rejection and wound infection in the obese group, there was no difference in patient or graft survival. This finding, when compared with previous reports, may be related to stringent recipient selection and posttransplant care particularly with respect to cardiovascular disease.

Cytomegalovirus infection post-pancreas-kidney transplantation--results of antiviral prophylaxis in high-risk patients.

BACKGROUND: Cytomegalovirus (CMV) is a major pathogen affecting solid organ transplant (SOT) recipients. Prophylactic strategies have decreased the rate of CMV infection/disease among SOT. However, data on the effect of current prophylactic strategies for simultaneous pancreas-kidney (SPK) or pancreas after kidney (PAK) transplant remain limited. We report our experience of CMV prophylaxis in SPK/PAK recipients. METHODS: A total of 130 post-SPK/PAK patients were analyzed retrospectively for the rate of CMV and the risk factors associated with the acquisition of CMV. All patients received antiviral prophylaxis. The follow-up period was one yr post-transplant or until death. RESULTS: The rate of CMV post-SPK/PAK transplant was 24%, 44%, and 8.2% among the whole cohort, the D+/R- and the R+ groups, respectively. Median time of prophylaxis was 49 (0-254) d. In the whole cohort, risk factors for CMV infection/diseases were D+/R- CMV status (odds ratio [OR] = 16.075), preceding non-CMV (infection caused by bacteria or fungi and other viruses) infection (OR = 6.362) and the duration of prophylaxis (OR = 0.984). Among the CMV D+/R- group, non-CMV infection was the only risk factor for CMV disease (OR = 10.7). CONCLUSIONS: Forty-four per cent (25/57) of the D+/R- recipients developed CMV infection/disease despite CMV prophylaxis. Current CMV prophylaxis failed to prevent CMV infection/disease in this group of patients.

Pancreas-after-kidney versus synchronous pancreas-kidney transplantation: comparison of intermediate-term results.

BACKGROUND: Controversy persists over the safety and efficacy of pancreas transplantation in patients with insulin-dependent diabetes mellitus who have received a prior kidney transplant. METHODS: We compared the outcomes of recipients who received either Synchronous-Pancreas Kidney-Transplantation (SPK, n=123) or Pancreas-After-Kidney-Transplants(n=49)at our institution between August 2002 to January 2010. RESULTS: Donor and recipient demographics were similar. Time interval between kidney and pancreas transplantation was 5.9 ± 3.8 (4.8 [1.6-12.2]) years. The majority of kidney-recipients in PAK group were transplanted at outside institutions and referred to us for PAK. Most patients received thymoglobulin induction and were maintained on tacrolimus, MMF, and prednisone. For SPK versus PAK recipients, there was no difference in median of length of hospital stay or incidence of overall complications. All PAK recipients are alive with functioning kidney grafts, whereas the 1-, 3-, and 5-year SPK patient survival rates were 98%,96%,and 94%, P=0.09. The 1-,3-, and 5-yr uncensored pancreas survival rates for SPK versus PAK were 93% vs. 90%, 90% vs. 90%, and 82% versus 85%, respectively (P=0.4). CONCLUSION: Glycemic control and intermediate survival outcomes were similar in both groups. Pancreas-graft outcomes in SPK and PAK were equivalent in our study, but our specific population entailed among other factors a long K to PAK time interval; PAK could be a comparable option to SPK for patients with access to kidney grafts.

Thymoglobulin versus basiliximab induction therapy for simultaneous kidney-pancreas transplantation: impact on rejection, graft function, and long-term outcome.

BACKGROUND: Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation. METHODS: We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed. RESULTS: ATG versus basiliximab therapy was associated with decreased 3-month (6% vs. 21%; P=0.01) and 1-year (14% vs. 27%; P=0.049) rejection rate. Steroid-resistant rejections were decreased with ATG (3%) vs. basiliximab (14%) (P=0.01). In a univariate regression analysis, basiliximab induction was a risk factor for rejection (HR, 7.1; CI, 3.8-13). No differences were observed regarding complications and graft function up to 5 years. ATG versus basiliximab therapy resulted in identical 1-year (90% vs. 93%), 3-year (87% vs. 89%), and 5-year (78% vs. 83%) pancreas survival (P=0.7). No difference was observed in kidney survival after 1 year (99% vs. 98%), 3 years (97% vs. 98%), and 5 years (95% vs. 95%) (P=0.4). CONCLUSIONS: ATG versus basiliximab induction therapy results in decreased acute cellular rejection in the first year after SPK with similar side effects. Long-term graft function and survival are not affected by induction regimen.