Liver transplantation for Alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a major cause of morbidity and mortality worldwide, and a leading indication for liver transplantation (LT) in many countries, including the US. However, LT for ALD is a complex and evolving field with ethical, social, and medical challenges. Thus, it requires a multidisciplinary approach and individualized decision-making. Short and long-term patient and graft survival of patients undergoing LT for ALD are comparable to other indications, but there is continued need to develop better tools to identify patients who may benefit from LT, improving the pre- and post-transplant management of ALD, and evaluating the impact of LT for ALD on the organ donation and transplantation system. In this review, we summarize the current evidence on LT for ALD, from alcohol-associated hepatitis (AAH) to decompensated alcohol-associated cirrhosis. We discuss the indications, criteria, outcomes, and controversies of LT for these conditions, and highlight the knowledge gaps and research priorities in this field.

Utilization of Immunotherapy as a Neoadjuvant Therapy for Liver Transplant Recipients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.

Update on the Screening, Diagnosis, and Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a neoplasm of the biliary tract that has become increasingly prevalent throughout the world. Common risk factors for developing CCA include cirrhosis, primary sclerosing cholangitis, and trematode fluke infestation, although there are no set screening guidelines in high-risk groups. Lesions are typically identified via cross-sectional imaging and/or elevated serum carbohydrate antigen 19-9 levels, often followed by cytology or brushings with fluorescence in situ hybridization for confirmation. Treatments can vary among CCA subtypes but frequently involve systemic therapies such as gemcitabine and cisplatin with durvalumab or pembrolizumab. Targeted therapies may also be effective (eg, ivosidenib, pemigatinib, infigratinib, futibatinib) depending on the molecular alterations present. Resection is the most common surgical treatment for CCA, although liver transplantation is also an option in highly selected patients with liver-limited unresectable disease. Radiotherapy may also be a treatment option, as well as transarterial radioembolization (eg, yttrium-90), which is often utilized in combination with systemic therapy. Although patients with CCA have traditionally had a poor prognosis, recent advances in treatment, including new systemic therapies and increased utilization of liver transplantation, have improved expected survival. This article reviews screening modalities, pros and cons of diagnostic techniques, and therapies that are currently available to treat patients with CCA.

Single-center Outcomes After Liver Transplantation With SARS-CoV-2-Positive Donors: An Argument for Increased Utilization.

Background: The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here. Methods: A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (n = 29 total; 25 index, 4 redo) and COVID-19-negative (n = 472 total; 454 index, 18 redo) deceased donor liver grafts were compared. Results: COVID-19-positive donors were significantly younger (P = 0.04) and had lower kidney donor profile indices (P = 0.04) than COVID-19-negative donors. Recipients of COVID-19-positive donor grafts were older (P = 0.04) but otherwise similar to recipients of negative donors. Donor SARS-CoV-2 infection status was not associated with a overall survival of recipients (hazard ratio, 1.11; 95% confidence interval, 0.24-5.04; P = 0.89). There were 3 deaths among recipients of liver grafts from COVID-19-positive donors. No death seemed virally mediated because there was no qualitative association with peri-LT antispike antibody titers, post-LT prophylaxis, or SARS-CoV-2 variants. Conclusions: The utilization of liver grafts from COVID-19-positive donors was not associated with a decreased overall survival of recipients. There was no suggestion of viral transmission from donor to recipient. The results from this large single-center study suggest that COVID-19-positive donors may be used safely to expand the deceased donor pool.

Bloodstream infections after solid organ transplantation: clinical epidemiology and antimicrobial resistance (2016-21).

Background: Solid organ transplant (SOT) recipients are at risk of bloodstream infections (BSIs) with MDR organisms (MDROs). Objectives: To describe the epidemiology of BSI in the year after several types of SOT, as well as the prevalence of MDRO infections in this population. Methods: We conducted a single-centre, retrospective study of kidney, liver, heart, and multi-organ transplantation patients. We examined BSIs ≤1 year from SOT and classified MDRO phenotypes for Staphylococcus aureus, enterococci, Enterobacterales, Pseudomonas aeruginosa and Candida spp. We compared BSI characteristics between SOT types and determined risk factors for 90 day mortality. Results: We included 2293 patients [1251 (54.6%) kidney, 663 (28.9%) liver, 219 (9.6%) heart and 160 (7.0%) multi-organ transplant]. Overall, 8.5% of patients developed a BSI. BSIs were most common after multi-organ (23.1%) and liver (11.3%) transplantation (P < 0.001). Among 196 patients with BSI, 323 unique isolates were recovered, 147 (45.5%) of which were MDROs. MDROs were most common after liver transplant (53.4%). The most frequent MDROs were VRE (69.8% of enterococci) and ESBL-producing and carbapenem-resistant Enterobacterales (29.2% and 27.2% of Enterobacterales, respectively). Mortality after BSI was 9.7%; VRE was independently associated with mortality (adjusted OR 6.0, 95% CI 1.7-21.3). Conclusions: BSI incidence after SOT was 8.5%, with a high proportion of MDROs (45.5%), especially after liver transplantation. These data, in conjunction with local antimicrobial resistance patterns and prescribing practices, may help guide empirical antimicrobial selection and stewardship practices after SOT.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions.

Intrahepatic cholangiocarcinoma (iCCA) is a rare biliary tract cancer with high mortality rate. Complete resection of the iCCA lesion is the first choice of treatment, with good prognosis after margin-negative resection. Unfortunately, only 12%-40% of patients are eligible for resection at presentation due to cirrhosis, portal hypertension, or large tumor size. Liver transplantation (LT) offers margin-negative iCCA extirpation for patients with unresectable tumors. Initially, iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes. Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA. Another selection criterion is the tumor response to neoadjuvant therapy. Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy. Another index that helps predict the treatment outcome is the biomarker. Improved survival outcomes have also opened the door for living donor LT for iCCA. Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection. The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Molecular profiling in the management of hepatocellular carcinoma.

PURPOSE OF REVIEW: The purpose of this review is to both summarize the current knowledge of hepatocellular carcinoma molecular biology and to suggest a framework in which to prospectively translate this knowledge into patient care. This is timely as recent guidelines recommend increased use of these technologies to advance personalized liver cancer care. RECENT FINDINGS: The main themes covered here address germline and somatic genetic alterations recently discovered in hepatocellular carcinoma, largely owing to next generation sequencing technologies, and nascent efforts to translate these into contemporary practice. SUMMARY: Early efforts of translating molecular profiling to hepatocellular carcinoma care demonstrate a growing number of potentially actionable alterations. Still lacking are a consensus on what biomarkers and technologies to adopt, at what scale and cost, and how to integrate them most effectively into care.

Transplant Oncology: An Emerging Discipline of Cancer Treatment.

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.

Progress in Combined Liver-lung Transplantation at a Single Center.

Combined liver-lung transplantation is an uncommon, although vital, procedure for patients with simultaneous end-stage lung and liver disease. The utility of lung-liver transplant has been questioned because of initial poor survival outcomes, particularly when compared with liver-alone transplant recipients. Methods: A single-center, retrospective review of the medical records of 19 adult lung-liver transplant recipients was conducted, comparing early recipients (2009-2014) with a recent cohort (2015-2021). Patients were also compared with the center's single lung or liver transplant recipients. Results: Recent lung-liver recipients were older (P = 0.004), had a higher body mass index (P = 0.03), and were less likely to have ascites (P = 0.02), reflecting changes in the etiologies of lung and liver disease. Liver cold ischemia time was longer in the modern cohort (P = 0.004), and patients had a longer posttransplant length of hospitalization (P = 0.048). Overall survival was not statistically different between the 2 eras studied (P = 0.61), although 1-y survival was higher in the more recent group (90.9% versus 62.5%). Overall survival after lung-liver transplant was equivalent to lung-alone recipients and was significantly lower than liver-alone recipients (5-y survival: 52%, 51%, and 75%, respectively). Lung-liver recipient mortality was primarily driven by deaths within 6 mo of transplant due to infection and sepsis. Graft failure was not significantly different (liver: P = 0.06; lung: P = 0.74). Conclusions: The severity of illness in lung-liver recipients combined with the infrequency of the procedure supports its continued use. However, particular attention should be paid to patient selection, immunosuppression, and prophylaxis against infection to ensure proper utilization of scarce donor organs.

Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology.

The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk-benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.

Modern Outcomes After Liver Retransplantation: A Single-center Experience.

BACKGROUND: The need for liver retransplantation (reLT) has increased proportionally with greater numbers of liver transplants (LTs) performed, use of marginal donors, degree of recipient preoperative liver dysfunction, and longer survival after LT. However, outcomes following reLT have been historically regarded as poor. METHODS: To evaluate reLT in modern recipients, we retrospectively examined our single-center experience. Analysis included 1268 patients undergoing single LT and 68 patients undergoing reLT from January 2008 to December 2021. RESULTS: Pre-LT mechanical ventilation, body mass index at LT, donor-recipient ABO incompatibility, early acute rejection, and length of hospitalization were associated with increased risk of needing reLT following index transplant. Overall and graft survival outcomes in the reLT cohort were equivalent to those after single LT. Mortality after reLT was associated with Kidney Donor Profile Index, national organ sharing at reLT, and LT donor death by anoxia and blood urea nitrogen levels. Survival after reLT was independent of the interval between initial LT and reLT, intraoperative packed red blood cell use, cold ischemia time, and preoperative mechanical ventilation, all previously linked to worse outcomes. CONCLUSIONS: These data suggest that reLT is currently a safer option for patients with liver graft failure, with comparable outcomes to primary LT.

Intrahepatic cholangiocarcinoma: The role of liver transplantation, adjunctive treatments, and prognostic biomarkers.

Intrahepatic cholangiocarcinoma (iCCA) is a primary epithelial cell malignancy of the liver with rising incidence rate globally. Its insidious presentation, heterogeneous and aggressive biology, and recalcitrance to current therapies results in unacceptably high morbidity and mortality. This has spurred research efforts in the last decade to better characterize it molecularly with translation to improved diagnostic tools and treatments. Much of this has been driven by patient advocacy. This has renewed interest in orthotopic liver transplantation (LT) with adjunctive therapies for iCCA, which was historically disparaged due to poor recipient outcomes and donor organ scarcity. However, the optimal use of LT as a treatment for iCCA care remains unclear. Here, we review the epidemiology of iCCA, the history of LT as a treatment modality, alternative approaches to iCCA local control, the evidence for peri-operative systemic therapies, and the potential roles of biomarkers and targeted agents. In doing so, we hope to prioritize areas for continued research and identify areas where multidisciplinary care can improve outcomes.

A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.

OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes. METHODS: Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury. RESULTS: The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints. CONCLUSIONS: This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.

Pancreatic cancer evolution and heterogeneity: integrating omics and clinical data.

Pancreatic ductal adenocarcinoma (PDAC), already among the deadliest epithelial malignancies, is rising in both incidence and contribution to overall cancer deaths. Decades of research have improved our understanding of PDAC carcinogenesis, including characterizing germline predisposition, the cell of origin, precursor lesions, the sequence of genetic alterations, including simple and structural alterations, transcriptional changes and subtypes, tumour heterogeneity, metastatic progression and the tumour microenvironment. These fundamental advances inform contemporary translational efforts in primary prevention, screening and early detection, multidisciplinary management and survivorship, as prospective clinical trials begin to adopt molecular-based selection criteria to guide targeted therapies. Genomic and transcriptomic data on PDAC were also included in the international pan-cancer analysis of approximately 2,600 cancers, a milestone in cancer research that allows further insight through comparison with other tumour types. Thus, this is an ideal time to review our current knowledge of PDAC evolution and heterogeneity, gained from the study of preclinical models and patient biospecimens, and to propose a model of PDAC evolution that takes into consideration findings from varied sources, with a particular focus on the genomics of human PDAC.

Impact of Research Training on Performance in General Surgery Residency.

INTRODUCTION: It is common for North American surgical trainees to interrupt clinical training to complete 2 or more years of research training. The impact of this practice on surgical aptitudes is unknown. The University of Toronto has large general surgery and surgeon scientist training programs. We compared the examination scores of general surgery residents in continuous clinical training with those of residents whose training was interrupted by research. METHODS: We collected anonymized scores obtained at written and oral annual in-training examinations by general surgery residents at the University of Toronto from 2011 to 2016, inclusive. The written exam assessed knowledge, while the oral exam assessed judgment. Residents were dichotomized into continuous versus non-continuous clinical training streams. We compared performance prior to, during, and following divergence for research training both within and between the 2 groups. RESULTS: At the junior resident level, future enrollment in research training was associated with higher examination performance (Pwritten = .003). Annual scores plateaued during research training, while scores of residents who continued in continuous clinical training improved year over year (Pwritten = .009). Non-continuous stream resident exam scores remained stagnant after 1 year then improved in the second year after return to clinical training (Pwritten = .00007). Scores obtained in the final year of residency training did not significantly differ between residents who underwent continuous versus non-continuous clinical training. Results from written and oral exams trended concordantly. CONCLUSIONS: We demonstrate that interruption of clinical training for 2 or more years of research is associated with a stagnation of performance on annual in-training examinations assessing both knowledge and judgment. This phenomenon is followed by an eventual catching-up after at least 2 years return to full-time clinical training. This may inform residency program curriculum design.

Spontaneous Ureterocolic Fistula between Nonfunctioning Kidney Transplant Ureter and Colon in Setting of Diverticulitis.

Ureterocolic fistula is a rare condition that most commonly occurs in the setting of diverticular disease. The development of a ureterocolic fistula following kidney transplantation is even rarer, with no prior cases in the literature to our knowledge. We describe the case of a patient with three prior failed kidney transplants who developed a fistula between the sigmoid colon and nonfunctioning renal transplant ureter in the setting of diverticulitis.

A simple scoring system to estimate perioperative mortality following liver resection for primary liver malignancy-the Hepatectomy Risk Score (HeRS).

BACKGROUND: Selection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections. METHODS: The 2005-2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7-10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1-4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values. RESULTS: A total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16-8.99), P=0.025; HeRS =3: OR =6.54 (2.39-17.90), P<0.001; HeRS =4: OR =13.69 (4.90-38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model. CONCLUSIONS: The HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.

Decreased graft loss following implementation of the kidney allocation score (KAS).

BACKGROUND: The Kidney Allocation System (KAS) was developed to improve equity and utility in organ allocation. We examine the effect of this change on kidney graft distribution and survival. METHODS: UNOS data was used to identify first-time adult recipients of a deceased donor kidney-alone transplant pre-KAS (Jan 2012-Dec 2014, n = 26,612) and post-KAS (Jan 2015-Dec 2017, n = 30,701), as well as grafts recovered Jan 2012-Jun 2019. RESULTS: Post-KAS, kidneys were more likely to experience cold ischemia time >24 h (20.0% vs. 18.8%, p < 0.001) and experienced more delayed graft function, though competing risks modeling demonstrated a lower hazard of graft loss post-KAS, HR 0.90 (95% CI 0.84-0.97, p = 0.007). Post-policy, KDPI >85% kidneys were more likely to be shared regionally (37% vs. 14%), and more likely to be discarded (60.6% vs. 54.9%) after the policy change. KDPI >85% graft and patient survival did not change. CONCLUSIONS: Implementation of the KAS has increased sharing of high-KDPI kidneys and has decreased the hazard of graft loss without an impact on patient survival.

Outcomes in Kidney Transplantation Between Veterans Affairs and Civilian Hospitals: Considerations in the Context of the MISSION Act.

OBJECTIVE: We sought to compare kidney transplantation outcomes between Veterans Affairs (VA) and non-VA transplant centers. SUMMARY BACKGROUND DATA: Transplant care at the VA has previously been scrutinized due to geographic and systematic barriers. The recently instituted MISSION Act entered effect June 6th, 2019, which enables veteran access to surgical care at civilian hospitals if certain eligibility criteria are met. METHODS: We evaluated observed-to-expected outcome ratios (O:E) for graft loss and mortality using the Scientific Registry of Transplant Recipients database for all kidney transplants during a 15-year period (July 1, 2001-June 30, 2016). Of 229,188 kidney transplants performed during the study period, 1508 were performed at VA centers (N = 7), 7750 at the respective academic institutions affiliated with these VA centers, and 227,680 at non-VA centers nationwide (N = 286). RESULTS: Aggregate O:E ratios for mortality were lower in VA centers compared with non-VA centers at 1 month and 1 year (O:E = 0.27 vs 1.00, P = 0.03 and O:E = 0.62 vs 1.00, P = 0.03, respectively). Graft loss at 1 month and 1 year was similar between groups (O:E = 0.65 vs 1.00, P = 0.11 and O:E = 0.79 vs 1.00, P = 0.15, respectively). Ratios for mortality and graft loss were similar between VA centers and their respective academic affiliates. Additionally, a subgroup analysis for graft loss and mortality at 3 years (study period January 1, 2009-December 31, 2013) demonstrated no significant differences between VA centers, VA-affiliates, and all non-VA centers. CONCLUSIONS: Despite low clinical volume, VA centers offer excellent outcomes in kidney transplantation. Veteran referral to civilian hospitals should weigh the benefit of geographic convenience and patient preference with center outcomes.

Author Correction: Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.