Evolution of Pancreas Transplantation At A Single Institution-50+ Years and 2,500 Transplants.

OBJECTIVE: To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past five decades. BACKGROUND: The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. METHODS: A single-center retrospective review of 2,500 pancreas transplants performed over >50 years in bivariate and multivariable models. Transplants were divided into six eras; outcomes are presented for the entire cohort and by era. RESULTS: All measures of patient and graft survival improved progressively through the six transplant eras. The overall death censored (DC) pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year DC pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. CONCLUSIONS: Pancreas outcomes have significantly improved over time via sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

Dual living donor organ transplants.

INTRODUCTION: Dual organ donation and transplantation from living donors (LDs) is a rare practice. Dual organ transplants can be done from the same LD or from different LDs and either simultaneously or sequentially. Simultaneous dual organ transplants from the same LD are of considerable concern due to the magnitude of the donor procedure. METHODS AND RESULTS: According to the UNOS/OPTN and IPTR databases, the US experience of LD dual organ transplants from 1981 to 2021 comprised 101 simultaneous or sequential dual organ transplants from the same LD and 111 transplants from different LDs for a total of 212 LD dual transplants. The first simultaneous or sequential dual organ transplants from either the same LD or different LDs were pancreas-kidney transplants (n = 92). Four additional LD organ transplant combinations have been performed in the United States: liver-kidney (n = 93), lung-kidney (n = 16), liver-intestine (n = 9), and intestine-kidney (n = 2). Only for dual pancreas-kidney (n = 49) and liver-intestinal transplants (n = 4), organs from the same LD have been procured simultaneously. Importantly, no donor deaths have been reported after any simultaneous or sequential procurement. LD dual organ outcomes in all recipient categories have been excellent. CONCLUSIONS: LD dual organ donation and transplantation is safe and successful. Any potential dual organ LD candidate must be subject to the highest level of evaluation scrutiny. A (dual) organ donor registry is warranted for long-term follow-up.

New Insurance Product Needed for Physicians: Coverage for Sham Peer Review and Hospital Immunity.

This commentary article highlights the need for an insurance product for hospital-employed physicians that provides coverage against sham peer review and a complete defense against wrongful hospital allegations of incompetent, whistleblowing, or disruptive behavior.

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Simultaneous Pancreas and Kidney Transplantation-Is It a Treatment Option for Patients With Type 2 Diabetes Mellitus? An Analysis of the International Pancreas Transplant Registry.

PURPOSE OF REVIEW: Pancreas transplantation remains the best long-term treatment option to achieve euglycemia and freedom from insulin in patients with labile diabetes mellitus. It is an approved procedure for type 1 (T1DM), but it is still considered controversial for type 2 diabetes mellitus (T2DM). RECENT FINDINGS: This study analyzed all primary deceased donor pancreas transplants in patients with T2DM reported to IPTR/UNOS between 1995 and 2015. Characteristics, outcomes, and risk factors over time were determined using univariate and multivariate methods. The focus was on simultaneous pancreas/kidney (SPK) transplants, the most common pancreas transplant category. Patient, pancreas, and kidney graft survival rates increased significantly over time and reached 95.8, 83.3, and 91.1%, respectively, at 3 years posttransplant for transplants performed between 2009 and 2015. SPK is a safe procedure with excellent pancreas and kidney graft outcome in patients with T2DM. The procedure restores euglycemia and freedom from insulin and dialysis. Based on our results, SPK should be offered to more uremic patients with labile T2DM.

Long-term outcome after pancreas transplantation: a registry analysis.

PURPOSE OF REVIEW: Pancreas transplantation provides the only proven method to restore long-term normoglycemia in patients with insulin-dependent diabetes mellitus. Although many studies describe the most important risk factors for short-term survival of a pancreas transplant, more information about factors that distinguish short-term from long-term graft function is needed. RECENT FINDINGS: Analysis of 21 328 pancreas transplants from the International Pancreas Transplant Registry, performed from 1984 to 2009 (minimum 5-year follow-up), shows a significant improvement in long-term patient survival and pancreas graft function. Total 5-and 10-year pancreas graft function rates are 73 and 56%, respectively, for simultaneous pancreas-kidney transplants; 64 and 38%, respectively, for pancreas after kidney; and 53 and 36%, respectively, for pancreas transplants alone. The most influential period is the first year posttransplant. Recipients who reach this time point with a functioning graft have a much higher probability for excellent long-term graft function. Important factors influencing long-term function were features that described the quality of the deceased donor. Pancreas transplants in younger, high panel reactive antibody, or African-American recipients also showed an increased risk of early graft failure. Anti-T-cell induction therapy had a significant impact on long-term survival in solitary transplants. SUMMARY: With careful recipient and donor selection and close follow-up in the first year posttransplant, not only good short-term but also long-term pancreas graft function and, therefore, durable metabolic control can be achieved for the diabetic patient.

Pancreas transplantation: a decade of decline.

PURPOSE OF REVIEW: In the past decade, the annual number of pancreas transplants performed in the United States has steadily declined. The purpose of this review is to discuss the multifactorial nature of this decline. RECENT FINDINGS: In 2014, only 954 pancreas transplants were performed in the United States. From 2004 to 2011, the annual number of simultaneous pancreas-kidney transplants in the United States declined by 10%, whereas the corresponding annual decreases in pancreas after kidney and pancreas transplants alone were 55 and 34%, respectively. Paradoxically, this drop-off has occurred in the setting of improvements in graft and patient survival and transplanting higher risk patients. This national trend in decreasing numbers of pancreas transplants is related to a number of factors, including lack of a primary referral source, lack of acceptance by the diabetes care community, improvements in diabetes care and management, changing donor and recipient considerations, inadequate training opportunities, and increasing risk aversion because of regulatory scrutiny. SUMMARY: Given that the incidence of end-stage renal disease secondary to diabetes remains high, a national initiative is needed to 're-invigorate' either simultaneous pancreas kidney or pancreas after kidney as preferred transplant options for appropriately selected uremic patients taking insulin irrespective of C-peptide levels or 'type' of diabetes. Moreover, many patients may benefit from pancreas transplants alone as well because all categories of pancreas transplantation are not only life-enhancing but life-extending procedures.

Early liver retransplantation in adults.

Up to 23% of liver allografts fail post-transplant. Retransplantation is only the recourse but remains controversial due to inferior outcomes. The objective of our study was to identify high-risk periods for retransplantation and then compare survival outcomes and risk factors. We performed an analysis of United Network for Organ Sharing (UNOS) data for all adult liver recipients from 2002 through 2011. We analyzed the records of 49,288 recipients; of those, 2714 (5.5%) recipients were retransplanted. Our analysis included multivariate regression with the outcome of retransplantation. The highest retransplantation rates were within the first week (19% of all retransplantation, day 0-7), month (20%, day 8-30), and year (33%, day 31-365). Only retransplantation within the first year (day 0-365) had below standard outcomes. The most significant risk factors were as follows: within the first week, cold ischemia time >16 h [odds ratio (OR) 3.6]; within the first month, use of split allografts (OR 2.9); and within the first year, use of a liver donated after cardiac death (OR 4.9). Each of the three high-risk periods within the first year had distinct causes of graft failure, risk factors for retransplantation, and survival rates after retransplantation.

A critical analysis of early death after adult liver transplants.

INTRODUCTION: The 15% mortality rate of liver transplant recipients at one yr may be viewed as a feat in comparison with the waiting list mortality, yet it nonetheless leaves room for much improvement. Our aim was to critically examine the mortality rates to identify high-risk periods and to incorporate cause of death into the analysis of post-transplant survival. METHODS: We performed a retrospective analysis on United Network for Organ Sharing data for all adult recipients of liver transplants from January 1, 2002 to October 31, 2011. Our analysis included multivariate logistic regression where the primary outcome measure was patient death of 49,288 recipients. RESULTS: The highest mortality rate by day post-transplant was on day 0 (0.9%). The most significant risk factors were as follows: for one-d mortality from technical failure, intensive care unit admission odds ratio (OR 3.2); for one-d mortality from graft failure, warm ischemia >75 min (OR 5.6); for one-month mortality from infection, a previous transplant (OR 3.3); and for one-month mortality from graft failure, a previous transplant (OR 3.7). CONCLUSION: We found that the highest mortality rate after liver transplantation is within the first day and the first month post-transplant. Those two high-risk periods have common, as well as different, risk factors for mortality.

MRI prediction of islet yield for autologous transplantation after total pancreatectomy for chronic pancreatitis.

OBJECTIVE: The relationship between magnetic resonance imaging (MRI), histopathology, and islet yield was examined for chronic pancreatitis patients undergoing total pancreatectomy and autologous islet cell transplant (TP-AIT) to determine if the yield can be predicted by pre-operative MRI. METHODS: MRI sequences and histopathology were scored and compared for patients from whom ≤2,500 islet equivalents/kg were obtained with those from whom >2,500 islet equivalents/kg were obtained. RESULTS: Twenty patients, 14 female, mean age 40.20 ± 12.5 years, (range 19-63) underwent MRI before TP-AIT; mean 3,724 ± 891 islet equivalents/kg body weight, median 2,970, (range 76-17,770) were procured. There was no correlation between islet cell numbers and pancreas weight, HgbA1c, or c-peptide. The most common MRI sequence abnormality was the delayed interstitial phase, 14/18 (78 %). The other common MRI sequence abnormalities were, precontrast T1W 3D GRE sequence, 13/19 (68 %), and the arterial perfusion phase, 11/18 (61 %). The pancreatic duct was dilated in 10/20 (50 %). Parenchymal atrophy was noted in 10/20 (50 %). Median scores for individual MRI sequences were greater in patients with an islet cell yield of ≤2,500 islet equivalents/kg; for the delayed interstitial phase the difference was significant (median 2.5, range 1-3 versus median 0.5, range 0-3, P = 0.034). Histologically the most common feature was fibrosis, (17/17, 100 %); the score for fibrosis was greater for patients with an islet cell yield of ≤2,500 islet equivalents/kg (median 6.0, range 5-7 versus median 4.0, range 3-7, P = 0.024). CONCLUSION: A diminished islet yield may be predicted on the basis of the delayed interstitial phase MRI sequence.

Recognition of complications after pancreaticoduodenectomy for cancer determines inpatient mortality.

CONTEXT: While perioperative mortality after pancreaticoduodenectomy is decreasing, key factors remain to be elucidated. OBJECTIVE: The purpose of this study was to investigate inpatient mortality after pancreaticoduodenectomy in the Nationwide Inpatient Sample (NIS), a representative inpatient database in the USA. METHODS: Patient discharge data (diagnostic and procedure codes) and hospital characteristics were investigated for years 2009 and 2010. The inclusion criteria were a procedure code for pancreaticoduodenectomy, elective procedure, and a pancreatic or peripancreatic cancer diagnosis. Chi-square test determined statistical significance. A logistic regression model for mortality was created from significant variables. RESULTS: Two-thousand and 958 patients were identified with an average age of 65±12 years; 53% were male. The mean length of stay was 15±12 days with a mortality of 4% and a complication rate of 57%. Eighty-six percent of pancreaticoduodenectomy occurred in teaching hospitals. Pancreaticoduodenectomy performed in teaching hospitals in the first half of the academic year were associated with higher mortality than in the latter half (5.5% vs. 3.4%, P=0.005). On logistic regression analysis, non-surgical complications are the largest predictor of death (P<0.001) while operations in the latter half of the academic year are associated with decreased mortality (P<0.01). CONCLUSIONS: The timing of pancreaticoduodenectomy for cancer remained more predictive of mortality than age or length of stay; only complications were more predictive of death than time of year. This suggests that there remains a clinically and statistically significant learning curve for trainees in identifying complications; further study is needed to prove that identification of complications leads to a decrease in mortality rate by taking corrective actions.

Isolated intestinal transplants vs. liver-intestinal transplants in adult patients in the United States: 22 yr of OPTN data.

We examined the outcomes of adult intestinal transplants (ITx); isolated ITx vs. liver-intestinal transplants (L-ITx) were compared using the UNOS database (1987-2009). Of 759 ITx transplants in 687 patients, 463 (61%) were isolated and 296 (39%) were L-ITx. Patient survival for primary isolated ITx at one, three, and five yr was 84%, 66.7%, and 54.2%; and primary L-ITx was, 67%, 53.3%, and 46% (p = 0.0005). Primary isolated ITx graft survival at one, three, and five yr was 80.7%, 57.6%, 42.8%; primary L-ITx was 64.1%, 51%, 44.1% (p = 0.0003 at one, three yr, Wilcoxon test). For retransplants (n = 72), patient and graft survival for isolated ITx (n = 41) at five yr was 40% in era 1 (1987-2000) and 16% in era 2 (p = 0.47); for retransplanted L-ITx (n = 31), it improved from 14% to 64% in era 2 (p = 0.01). Cox regression: creatinine >1.3 mg/dL and pre-transplant hospitalization were negative predictors for outcome of both; bilirubin >1.3 mg/dL was a negative predictor for isolated ITx and donor age >40 yr for L-ITx. Isolated ITx should be considered prior to liver disease for adults with intestinal failure; L-ITx is preferable for retransplantation.

Single-incision robotic-assisted living donor nephrectomy: case report and description of surgical technique.

The introduction of laparoscopic surgery, and more recently of robotics, has increased the number of living donor kidney transplants. This approach has already improved living donor acceptance rates. Even newer developments in the field have now been introduced with the purpose of further reducing postoperative pain and length of hospital stay, while offering better cosmetic results. In particular, single-incision surgery has gained popularity by improving the well-known benefits of minimally invasive surgery. In this case report, we present the first single-incision robotic-assisted living donor nephrectomy.

Long-term outcome after pancreas transplantation.

PURPOSE OF REVIEW: Pancreas transplantation provides the only proven method to restore long-term normoglycemia in patients with insulin-dependent diabetes mellitus. Although many studies describe the very important risk factors for short-term survival of a pancreas transplant, there is not a lot of information available about factors that distinguish short-term from long-term graft function. RECENT FINDINGS: The analysis of 18,159 pancreas transplants from the International Pancreas Transplant Registry, performed from 25 July 1978 to 31 December 2005, showed an improvement not only in short-term but also in long-term graft function. Most recent 5-year, 10-year and 20-year graft function for transplants with the appropriate follow-up time showed 80, 68 and 45%, respectively, for simultaneous pancreas/kidney transplants; 62, 46 and 16%, respectively, for pancreas after kidney; and 59, 39 and 12%, respectively, for pancreas transplants alone. Important factors influencing long-term function were factors that described the quality of the deceased donor. Pancreas transplants in younger or African-American recipients showed a higher risk of graft failure. Anti-T-cell induction therapy had a significant impact on long-term survival in solitary transplants. SUMMARY: With a careful donor selection, not only short-term but also long-term pancreas graft function and, therefore, good metabolic control can be achieved for the diabetic patient.

25 Years of a Standardized Technique for Living Donor Intestinal Transplantation: A Systematic Review.

A safe, reproducible and standardized surgical technique for intestinal procurement and transplantation from a living donor (LD) was introduced in 1997 and has been used in the majority of cases since. The key principles are: 1. procurement of 180-200 cm of distal ileum in adults (about 60-150 cm in pediatric recipients depending on age and weight) on a vascular pedicle comprising the LD ileocolic vessels or terminal branches of the superior mesenteric vessels, 2. the terminal ileum (30-40 cm of the most distal ileum), the ileocecal valve and the cecum remain with the donor to not interfere with B12-absorption and bowel transit time, 3. systemic venous drainage with anastomoses between the LD ileocolic vessels and the recipient's infrarenal aorta and vena cava, and 4. restoration of recipient bowel continuity through proximal anastomosis and distal graft ileostomy for biopsy access and graft monitoring. Recipients of a successful LD intestinal transplant become total parenteral nutrition (TPN)-independent within a few weeks posttransplant. LD vs deceased donor (DD) intestinal transplants can be performed in a more timely fashion. Hence, LD (in contrast to DD) intestinal transplants are also pre-emptive procedures in patients with advanced, but still reversible, TPN-induced liver disease and help reduce the wait-list mortality for combined DD intestinal and liver transplants. Life-saving combined LD intestinal and liver transplants, albeit rare, have also been successfully performed either simultaneously or subsequently. There have been no reported deaths or major complications of living intestinal donors. A better metabolic profile has been reported in some donors post-donation. In total, 85 documented LD intestinal transplants have been performed worldwide at over 20 different transplant centers in 12 different countries. In about 70 transplants, the standardized technique was used. There has been no difference in outcome between LD vs DD intestinal transplants. Long-term studies have shown that > 10 year of graft function is not uncommon. Since the introduction of the standardized surgical technique, LD intestinal transplantation has evolved from an experimental to an established and standardized procedure.

The 2022 International Pancreas Transplant Registry Report-A Review.

Over the last decades, the number of pancreas transplants has increased all over the world. Since the first pancreas transplant in 1966, patient and graft survival after simultaneous pancreas and kidney as well as after solitary pancreas transplantation have improved significantly. Patient survival at 1 year is >96% in all 3 recipient categories and pancreas graft survival is >90% for simultaneous pancreas and kidney and >86% for solitary transplants. For transplants performed between 2001 and 2010, with >10 years' follow-up time, the half-life (50% graft function) was 13 years for simultaneous pancreas and kidney, almost 10 years for a pancreas after kidney transplant, and >6 years for a pancreas transplant alone. These excellent results are even more astonishing because more high-risk patients were transplanted. The main reasons for improvement in outcome were reductions in technical failures and immunologic graft losses. These decreases were due to better patient and donor selection, standardization of surgical techniques, and superior immunosuppressive protocols.

Long-term outcome in 42 pediatric liver transplant patients with alpha 1-antitrypsin deficiency: a single-center experience.

INTRODUCTION: We examined the long-term outcome of transplantation for alpha 1-antitrypsin deficiency (A1ATD). METHOD: Data were reviewed on 42 transplants in 35 children with A1ATD over 42 yr and compared with 129 transplants in 116 children with biliary atresia (BA). RESULTS: Over 50% of patients were followed up for >10 yr. A1ATD were older than BA at transplantation, median age, 6.0 vs. 1.0 yr (p < 0.0001), and transplanted earlier in the course of liver failure (total bilirubin, 2.7 mg/dL [1.4-6.9] vs. 9.7 mg/dL [2.9-15.4], p = 0.005). Patient survival was greater in A1ATD than BA: one-yr post-transplant, 82.7% vs. 67.9%; five yr, 76.5% vs. 60.2%; and 10 yr, 76.5% vs. 55.9% (p = 0.03). Death-censored graft survival was similar: one-yr post-transplant, 68.4% vs. 66.2%; five yr, 68.4% vs. 55.8%; and 10 yr, 68.4% vs. 52.5% (p = 0.2). Deaths were from infection, hemorrhage, and graft failure <6 months post-transplant. Patient survival improved at five yr from 33.3% pre-cyclosporine (CSA) (1969-1984) (n = 6) to 76.5% in the CSA era (1985-1994) (n = 17) and 100% with tacrolimus (1995-2006) (n = 12) (p = 0.007). CONCLUSIONS: The age at transplantation and the degree of liver dysfunction were related to the differences in graft and patient survival between A1AT and BA.

Pancreas transplantation in the United States: a review.

PURPOSE OF REVIEW: The goal of pancreas transplantation is to restore normoglycemia in patients with labile diabetes. The results of this procedure improved over the years, but, although pancreas transplantation is not considered experimental anymore, there is often reluctance to recommend this procedure because of the complexity, especially for solitary pancreas transplants. This article reviews the current status of pancreas transplantation. RECENT FINDINGS: Many improvements have been made in the surgical techniques and immunosuppressive regimens. The overall rate of technical problems decreased, yet immunologic graft loss is still a problem in solitary pancreas transplants. Careful donor selection significantly decreased the risk of graft failure and therefore improved patient survival. SUMMARY: With modern immunosuppressive protocols and careful donor selection, patient survival rates and pancreas transplant graft function can be further improved in all three pancreas transplant categories.

Hospital-Acquired Conditions after Liver Transplantation.

Hospital-acquired conditions (HACs) are used to define hospital performance measures. Patient comorbidity may influence HAC development. The National Inpatient Sample database was used to investigate HACs for the patients who underwent liver transplantation. Multivariate analysis was used to identify HAC risk factors. We found a total of 13,816 patients who underwent liver transplantation during 2002-2014. Of these, 330 (2.4%) had a report of HACs. Most frequent HACs were vascular catheter-associated infection [220 (1.6%)], falls and trauma [66 (0.5%), catheter-associated UTI [24 (0.2%)], and pressure ulcer stage III/IV [22 (0.2%)]. Factors correlating with HACs included extreme loss function (AOR: 52.13, P < 0.01) and major loss function (AOR: 8.11, P = 0.04), hepatopulmonary syndrome (AOR: 3.39, P = 0.02), portal hypertension (AOR: 1.49, P = 0.02), and hospitalization length of stay before transplant (AOR: 1.01, P < 0.01). The rate of HACs for liver transplantation is three times higher than the reported overall rate of HACs for GI procedures. Multiple patient factors are associated with HACs, and HACs may not be a reliable measure to evaluate hospital performance. Vascular catheter-associated infection is the most common HAC after liver transplantation.