The Centennial Allograft: Cumulative Kidney and Liver Function for More Than 100 Years.

The maximum cumulative life span of kidneys and livers first in donors and then in transplant recipients has not been established. The purpose of this study was to determine if cumulative organ function for more than 90 years is possible for transplanted kidneys and livers. This study included kidney and liver transplants from living or deceased donors ≥55 years. Cumulative organ function (COF) = Organ Age at Donation [Years] + Tx Allograft Function [Years]. Univariate and multivariable methods were used to describe characteristics and outcomes. Between 1987 and 2022, a total of 81,807 kidney and 37,099 liver transplants were included in this study. Of all kidney grafts 2.7% but 16.6% of all liver grafts reached the 90-year COF mark. There were only 2 living donor kidneys that surpassed the 100-year mark versus 29 deceased liver grafts. The longest kidney function was 104 years and longest liver function 108 years. Multivariate analysis showed that optimal donor and recipient selection and management are predictors for allograft longevity. COF in organs exceeding 100 physiologic years is possible. Extended organ longevity was 5 times more common for livers than kidneys. These analyses support that age alone should not exclude older kidney and liver donors from consideration for transplantation.

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.

Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.

Outcome After Intestinal Transplantation From Living Versus Deceased Donors: A Propensity-matched Cohort Analysis of the International Intestinal Transplant Registry.

OBJECTIVE: To describe the worldwide experience with living donation (LD) in intestinal transplantation (ITx) and compare short-term and long-term outcomes to a propensity-matched cohort of deceased donors. BACKGROUND: ITx is a rare life-saving procedure for patients with complicated intestinal failure (IF). Living donation (LD)-ITx has been performed with success, but no direct comparison with deceased donation (DD) has been performed. The Intestinal Transplant Registry (ITR) was created in 1985 by the Intestinal Transplant Association to capture the worldwide activity and promote center's collaborations. METHODS: Based on the ITR, 4156 ITx were performed between January 1987 and April 2019, of which 76 (1.8%) were LD, including 5 combined liver-ITx, 7 ITx-colon, and 64 isolated ITx. They were matched with 186 DD-ITx for recipient age/sex, weight, region, IF-cause, retransplant, pretransplant status, ABO compatibility, immunosuppression, and transplant date. Primary endpoints were acute rejection and 1-/5-year patient/graft survival. RESULTS: Most LDs were performed in North America (61%), followed by Asia (29%). The mean recipient age was: 22 years; body mass index: 19kg/m²; and female/male ratio: 1/1.4. Volvulus (N=17) and ischemia (N=17) were the most frequent IF-causes. Fifty-two percent of patients were at home at the time of transplant. One-/5-year patient survival for LD and DD was 74.2/49.8% versus 80.3/48.1%, respectively ( P =0.826). One-/5-year graft survival was 60.3/40.6% versus 69.2/36.1%, respectively ( P =0.956). Acute rejection was diagnosed in 47% of LD versus 51% of DD ( P =0.723). CONCLUSION: Worldwide, LD-ITx has been rarely performed. This retrospective matched ITR analysis revealed no difference in rejection and in patient/graft survival between LD and DD-ITx.

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.

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.

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.

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.

A new model to determine Optimal Exposure to Tacrolimus and Mycophenolate Mofetil after renal transplantation.

BACKGROUND: Drug dosing for Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) after kidney transplantation remains challenging. Therapeutic drug monitoring (TDM) offers a means to individualize drug dosing and improve outcomes. METHODS: In this observational study, patients having mycophenolic acid (MPA) exposure assessed by limited sampling strategy (LSS) within the first 6 months were included and followed for 1 year. RESULTS: A total of 113 clinical events occurring in 110 patients were classified into 3 groups: Group 1 Stable (n = 34), Group 2 Over drug exposed (n = 64) having infections or drug toxicity and Group 3 Under drug exposed (n = 15) developing rejection or de novo donor-specific alloantibodies. Although TAC levels, MMF dose, MPA, and MPA Glucuronide (MPAG) exposure, expressed as area under curve (AUC), individually failed to predict outcomes, a scoring model incorporating all 3 drug levels TAC TDM × (MPA AUC + MPAG/10 AUC) correctly classified outcomes. A score over 1071 had a sensitivity and specificity of 0.94 (95% CI 0.56-0.83) and 0.84 (95% CI 0.69-0.89) for over exposure. A score below 625 had a sensitivity and specificity of 0.76 (95% CI 0.53-0.93) and 0.80 (95% CI 0.41-0.70) for under exposure. CONCLUSIONS: This integrated model of assessing TAC and MMF exposure may facilitate individualized therapy.

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.

Real-Time, Intraoperative Doppler/Ultrasound Monitoring of Islet Infusion During Total Pancreatectomy With Islet Autotransplant: A First Report.

Chronic pancreatitis (CP), secondary to a wide variety of etiologies, is a progressive and irreversible disease. Initially, CP is managed with endoscopic interventions, long-term analgesia for its associated chronic abdominal pain syndrome and pancreatic enzyme replacement for exocrine dysfunction. As the disease advances, pancreatic drainage procedures and partial resections are considered, but they leave diseased tissue behind and usually result in short-term relief only. Total pancreatectomy alone is widely viewed as a last resort treatment option because it causes brittle diabetes mellitus. However, total pancreatectomy with islet autotransplantation (TPIAT) can prevent the development of diabetes and cure the chronic pain syndrome. One serious, albeit rare, complication of TPIAT is (partial) portal vein thrombosis. Its incidence is probably about 5%. To prevent the occurrence of portal vein thrombosis, we propose herein, and have successfully performed, continuous real-time Doppler ultrasonography during the islet infusion to study portal vein and intrahepatic flow patterns, as well as changes in Doppler signals. Flow and signal changes may allow for timely adjustment of the infusion rate, before a marked increase in portal vein pressure is noted and decrease the risk of portal vein thrombosis.

Kidney After Intestinal Transplantation Using Two Different Living Donors: A First Case Report.

We describe a unique case of a 53-year-old woman who underwent a nonrelated living donor kidney transplant 9 years after a previous small bowel transplant from her sister. The patient had suffered from short bowel syndrome secondary to volvulus after undergoing bariatric surgery for morbid obesity. Her entire small bowel had to be resected emergently, but she also developed acute kidney failure at the time. This initial kidney injury associated with long-term exposure to calcineurin-inhibitor medication eventually led to end-stage renal disease. A successful kidney transplant from a different, nonrelated adult donor was performed. Of note, the unrelated kidney donor matched exactly the 2 HLA-A and HLA-B antigens that the recipient had not matched with her sister. We discuss the unique HLA configuration between the patient and her 2 living donors, the absence of posttransplant rejection and posttransplant immunosuppressive therapy. To our knowledge this is the first published report of a successful kidney after a previous bowel transplant using (2 different) living donors.

Saving the split: the benefits of VATS thymectomy.

BACKGROUND: With the advent of minimally invasive techniques, the standard approaches to many surgeries have changed. We compared the financial costs and health care outcomes between standard thymectomy via sternotomy and video assisted thoracoscopic surgery (VATS). METHODS: A 3-year review [2010-2012] of the National Inpatient Sample (NIS) was performed. All patients undergoing thymectomy were included. Patients undergoing VATS thymectomy were identified. Outcomes measured were hospital length of stay (LOS), hospital charges, and mortality. Univariate and multivariate analyses were performed to control for demographics and comorbidities. RESULTS: The results of 2,065 patients who underwent thymectomy were analyzed, of which 373 (18.1%) had VATS thymectomy and 1,692 (81.9%) had standard thymectomy. Mean age was 52.8±16, 42.5% were male, and 65.5% were Caucasian. There was a significant interval increase in number of patients undergoing VATS thymectomy (10% in 2010 vs. 19.2% in 2012, P<0.001). Patients undergoing standard thymectomy had longer hospital LOS (6.8±6.6 vs. 3.3d±3.4 d, P<0.001), hospital charges $88,838±$120,892 vs. $57,251±$54,929) and hospital mortality (0.9% vs. 0%, P=0.01). In multivariate analysis, thymectomy via sternotomy was independently associated with increased hospital LOS B =1.6 d, P<0.001) and charges (B = $13,041, P=0.041). CONCLUSIONS: Our study demonstrates decreased hospital length of stay and reduced hospital charges in patients undergoing VATS thymectomy compared to standard thymectomy. Our data demonstrates that the prevalence of VATS thymectomies is increasing, likely related to improved healthcare and financial outcomes.

Trends and outcomes in dual kidney transplantation- A narrative review.

Dual kidney transplantation (DKT) is a viable option to increase the donor pool and improve access equity to kidney transplantation. Dual kidneys are procured from carefully selected marginal donors that are not generally acceptable to most transplant centers. This is a narrative review of literature focusing on donor kidney allocation systems and selection of the ideal recipient for DKT. We also discussed surgical approaches for DKTs as well as patient and allograft outcomes. We found that most studies to date showed that DKTs has similar graft survival and delayed graft function rates when compared to single kidney transplants (SKTs). DKT is technically feasible with outcomes that are comparable to expanded criteria donor kidneys (ECD); and has substantial potential in expanding the donor pool. For allograft survival, most studies with strict allocation criteria showed that graft survival was similar in DKT as compared to SKT - ECD transplants.. Our review may encourage transplant centers to review their policies for donor and recipient selection leading to increase in DKT.

Pancreas Transplantation for Patients with Type 1 and Type 2 Diabetes Mellitus in the United States: A Registry Report.

Successful pancreas transplantation is still the only method to restore short-term and long-term insulin independence and good metabolic control for patients with diabetes. Since the first transplant in 1966, tremendous progress in outcome was made; however, transplant numbers have declined since 2004. This article describes the development and risk factors of pancreas transplantation with or without a kidney graft between 2001 and 2016. Patient survival and graft function improved significantly owing to careful recipient and donor selection, which reduced technical failure and immunologic graft loss rates.