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Transplantation of organs exposed to hepatitis C virus (HCV) into uninfected patients has yielded excellent outcomes and more widespread adoption may lead to fewer discarded organs and more transplants. Patient perceptions may shed light on acceptability and likely the uptake of HCV+/HCV- transplantation, gaps in understanding, and perceived benefits/risks.We surveyed 435 uninfected kidney and liver transplant candidates at four centers about their attitude towards HCV-infected organs.The percentage of patients willing to accept HCV-infected organs increased from 58% at baseline, to 86% following education about HCV, direct-acting antiviral agents (DAAs), and HCV+/HCV- transplantation benefits/risks. More willingness to accept an organ from an intravenous drug user (P 0.001), age50 y old (P = 0.02), longer waiting time (P = 0.02), more trust in the transplant system (P = 0.03), and previous awareness of DAAs (P = 0.04) were associated with higher willingness to accept an HCV-infected organ. The most important reasons for accepting an HCV-infected organ were a decrease in waiting time (65%), lower mortality and morbidity risk while on the waiting list (63%), effectiveness of DAAs (54%), and a quicker return to higher functional status (51%).Presenting patients with information about HCV+/HCV- transplantation in small doses that are calibrated to account for varying levels of health and numerical literacy is recommended.

Transplant referral and evaluation are critical steps to waitlisting yet remain an elusive part of the transplant process. Despite calls for more data collection on pre-waitlisting steps, there are currently no national surveillance data to aid in understanding the causes and potential solutions for the extreme variation in access to transplantation. As population health scientists, epidemiologists, clinicians, and ethicists we submit that the transplant community has an obligation to better understand disparities in transplant access as a first necessary step to effectively mitigating these inequities. Our position is grounded in a population health approach, consistent with several new overarching national policy and quality initiatives. The purpose of this Perspective is to (1) provide an overview of how a population health approach should inform current multisystem policies impacting kidney transplantation and demonstrate how these efforts could be enhanced with national data collection on pre-waitlisting steps; (2) demonstrate the feasibility and concrete next steps for pre-waitlisting data collection; and (3) identify potential opportunities to use these data to implement effective population-level interventions, policies, and quality measures to improve equity in access to kidney transplantation.

Management of patients on the kidney transplant waitlist lacks oversight, and transplant centers can delist candidates without consequence. To better understand between-center differences in waitlist management, we examined delisting rates and mortality after delisting within 3 years of removal from the kidney transplant waitlist.This is a retrospective cohort study using data from the Scientific Registry of Transplant Recipients of adults listed for deceased donor kidney transplant in 2015 and followed until the end of 2018. Patients of interest were those delisted for reasons other than transplant, death, or transfer. Centers were excluded if they had fewer than 20 waitlisted patients per year. We calculated probability of delisting and death after delisting using multivariable competing risk models.During follow-up, 14.2% of patients were delisted. The median probability of delisting within 3 years, adjusted for center-level variability, was 7.0% (interquartile range [IQR]: 3.9% to 10.6%). Median probability of death was 58.2% (IQR: 40% to 73.4%). There was no meaningful correlation between probability of delisting and death (τ = -0.05, p = 0.34).There is significant variability in the rate of death after delisting across kidney transplant centers. Likelihood of transplant is extremely important to candidates, and improved data collection efforts are needed to inform whether current delisting practices are successfully removing patients who could not meaningfully benefit from transplant, or whether certain populations may benefit from remaining on the list and maintaining eligibility.

BACKGROUND: The 240,000 rural patients with end stage kidney disease in the United States have less access to nephrology care and higher mortality than those in urban settings. The Advancing American Kidney Health initiative aims to increase the use of home renal replacement therapy. Little is known about how rural patients access home dialysis and the availability and quality of rural dialysis facilities. METHODS: Incident dialysis patients in 2017 and their facilities were identified in the United States Renal Data System. Facility quality and service availability were analyzed with descriptive statistics. We assessed the availability of home dialysis methods, depending on rural versus urban counties, and then we used multivariate logistic regression to identify the likelihood of rural patients with home dialysis as their initial modality and the likelihood of rural patients changing to home dialysis within 90 days. Finally, we assessed mortality after dialysis initiation on the basis of patient home location. RESULTS: Of the 97,930 dialysis initiates, 15,310 (16%) were rural. Rural dialysis facilities were less likely to offer home dialysis (51% versus 54%, P

The goal of deceased donor kidney allocation policy is to provide objective prioritization for donated kidneys, and policy has undergone a series of revisions in the past decade in attempt to achieve equity and utility in access to kidney transplantation. Most recently, to address geographic disparities in access to kidney transplantation, the Kidney Allocation System changed to a distance-based allocation system-colloquially termed "KAS 250"-moving away from donor service areas as the geographic basis of allocation. We review the early impact of this policy change on access to transplant for patients, and on complexity of organ allocation and transplantation for transplant centers and organ procurement organizations.Broader sharing of kidneys has increased complexity of the allocation system, as transplant centers and OPOs now interact in larger networks. The increased competition resulting from this system, and the increased operational burden on centers and OPOs resulting from greater numbers of organ offers, may adversely affect organ utilization. Preliminary results suggest an increase in transplant rate overall but a trend toward higher kidney discard and increased cold ischemia time.The KAS 250 allocation policy changed the geographic basis of deceased donor kidney distribution in a manner that is intended to reduce geographic disparities in access to kidney transplantation. Close monitoring of this policy's impact on patients, transplant center behavior, and process measures is critical to the aim of maximizing access to transplant while achieving transplant equity.

Deceased donor kidney procurement biopsies findings are the most common reason for kidney discard. Retrospective studies have found inconsistent associations with post-transplant outcomes but may have been limited by selection bias because kidneys with advanced nephrosclerosis from high-risk donors are typically discarded. We conducted a retrospective cohort study of kidneys transplanted in the United States from 2015 to 2019 with complete biopsy data available, defining "suboptimal histology" as glomerulosclerosis ≥11%, IFTA ≥mild, and/or vascular disease ≥mild. We used time-to-event analyses to determine the association between suboptimal histology and death-censored graft failure after stratification by kidney donor profile index (KDPI) (≤35%, 36%-84%, ≥85%) and final creatinine (1 mg/dl, 1-2 mg/dl,2 mg/dl). Among 30 469 kidneys included, 36% had suboptimal histology. In adjusted analyses, suboptimal histology was associated with death-censored graft failure among kidneys with KDPI 36-84% (HR 1.22, 95% CI 1.09-1.36), but not KDPI≤35% (HR 1.24, 0.94-1.64) or ≥ 85% (HR 0.99, 0.81-1.22). Similarly, suboptimal histology was associated with death-censored graft failure among kidneys from donors with creatinine 1-2 mg/dl (HR 1.39, 95% CI 1.20-1.60) but not1 mg/dl (HR 1.07, 0.93-1.23) or2 mg/dl (HR 0.95, 0.75-1.20). The association of procurement histology with graft longevity among intermediate-quality kidneys that were likely to be both biopsied and transplanted suggests biopsies provide independent organ quality assessments.

At every stage in the transplantation process for a deceased-donor kidney, time means ischemia. Donation after circulatory death (DCD) kidneys are already subject to warm ischemia in the donor, but another underappreciated component of warm ischemia time is the time required for anastomosis prior to reperfusion. We studied the effect of anastomosis time (AT) on outcomes after DCD kidney transplantation.This is a retrospective study of the Scientific Registry of Transplant Recipients, including all US adult DCD kidney transplantation recipients from 2009 to 2015 (N = 6,397). Our exposure was AT (time out of cold storage until reperfusion, quartiles). Outcomes included delayed graft function (DGF), death-censored graft survival, and overall patient survival. Multivariable logistic and Cox regression quantified the association of AT with outcomes, adjusting for donor and recipient factors (including donor warm ischemia time).AT accounted for 67% of total warm ischemia time on average, with a median AT of 38 minutes (median total warm ischemia 56 minutes). Longer AT (fourth [≥48min] vs first quartile [≤30min]) was associated with increased DGF (odds ratio = 1.19, p = 0.024) and increased graft failure (hazard ratio = 1.21, p = 0.043) but was not associated with patient survival. Comparing patients with the longest vs shortest AT, adjusted DGF incidence was 44.0% vs 36.7% (p = 0.024), and 5-year graft survival was 84.8% vs 88.2% (p = 0.004).Prolonged AT is associated with worse graft outcomes in DCD kidney transplant recipients. Efforts to minimize rewarming during implantation and optimize AT may improve graft outcomes.

ImportanceLarge-scale motorcycle rallies attract thousands of attendees and are associated with increased trauma-related morbidity and mortality.ObjectiveTo examine the association of major US motorcycle rallies with the incidence of organ donation and transplants.Design, Setting, and ParticipantsThis population-based, retrospective cross-sectional study used data from the Scientific Registry of Transplant Recipients for deceased organ donors aged 16 years or older involved in a motor vehicle crash and recipients of organs from these donors from March 2005 to September 2021.ExposureDates of 7 large US motorcycle rallies and regions near these events.Main Outcomes and MeasuresThe main outcomes were incidence of motor vehicle crash–related organ donation and number of patients receiving a solid organ transplant from these donors. An event study design was used to estimate adjusted rates of organ donation during the dates of 7 major US motorcycle rallies compared with the 4 weeks before and after the rallies in rally-affected and rally-unaffected (control) regions. Donor and recipient characteristics and metrics of organ quality were compared between rally and nonrally dates.ResultsThe study included 10 798 organ donors (70.9% male; mean [SD] age, 32.5 [13.7] years) and 35 329 recipients of these organs (64.0% male; 49.3 [15.5] years). During the rally dates, there were 406 organ donors and 1400 transplant recipients. During the 4 weeks before and after the rallies, there were 2332 organ donors and 7714 transplant recipients. Donors and recipients during rally and nonrally dates were similar in demographic and clinical characteristics, measures of organ quality, measures of recipient disease severity, and recipient waiting time. During rallies, there were 21% more organ donors per day (incidence rate ratio [IRR], 1.21; 95% CI, 1.09-1.35; P = .001) and 26% more transplant recipients per day (IRR, 1.26; 95% CI, 1.12-1.42; P Conclusions and RelevanceIn this cross-sectional study, major motorcycle rallies in the US were associated with increased incidence of organ donation and transplants. While safety measures to minimize morbidity and mortality during motorcycle rallies should be prioritized, this study showed the downstream association of these events with organ donation and transplants.

Disparities are well-documented across the continuum of surgical care. Counteracting such disparities requires new multidisciplinary approaches that utilize the expertise of affected individuals, such as community-based participatory research (CBPR). CBPR is an approach to research that is anchored in equitable, sustainable community-academic partnerships, and has been shown to improve intervention implementation and outcomes. In this article, community stakeholders and researchers outline the principles and benefits of CBPR, examples of CBPR in trauma and transplant, and future directions for CBPR within surgery.

Living donor kidney transplant (LDKT) is the best treatment for endstage kidney disease, but there are racial disparities in LDKT rates. To study putative mechanisms of these disparities, we identified 58,752 adult kidney transplant candidates first activated on the United States kidney transplant waitlist 2015-2016 and defined 4 exposure groups by race/primary payer: African American/Medicaid, African American/NonMedicaid, Non-African American/Medicaid, Non-African American/NonMedicaid. We performed competing risk regression to compare risk of LDKT between groups. Among included candidates, 30% had African American race and 9% had Medicaid primary payer. By the end of follow up, 16% underwent LDKT. The cumulative incidence of LDKT was lowest for African American candidates regardless of payer. Compared to African American/Non-Medicaid candidates, the adjusted likelihood of LDKT was higher for Non-African American/Medicaid (HR 1.60, 95%CI 1.43- 1.78) and Non-African American/Non-Medicaid payers (HR 2.66, 95%CI 2.50-2.83). Results were similar when analyzing only candidates still waitlisted >2 years after initial activation or candidates with type O blood. Among 9639 candidates who received LDKT, only 13% were African American. Donor-recipient relationships were similar for African American and Non-African American recipients. These findings indicate African American candidates have a lower incidence of LDKT than candidates of other races, regardless of primary payer. This article is protected by copyright. All rights reserved.

Key Points Question Are patient, facility, and/or kidney transplant waitlisting characteristics associated with variations in dialysis center quality? Findings In this cohort study of US Renal Data System and Medicare Dialysis Facility Compare data, higher-quality dialysis facilities were associated with approximately 47% higher odds of transplant waitlisting. Meaning These findings suggest that waitlisting rates for kidney transplantation should be considered for integration into the current Centers for Medicare & Medicaid Services Dialysis Facility Compare star ratings to improve care quality and access., This cohort study examines whether patient, facility, and kidney transplant waitlisting characteristics are associated with variations in dialysis center quality., Importance Improving the quality of dialysis care and access to kidney transplantation for patients with end-stage kidney disease is a national clinical and policy priority. The role of dialysis facility quality in increasing access to kidney transplantation is not known. Objective To determine whether patient, facility, and kidney transplant waitlisting characteristics are associated with variations in dialysis center quality. Design, Setting, and Participants This population-based cohort study is an analysis of US Renal Data System data and Medicare Dialysis Facility Compare (DFC) data from 2013 to 2018. Participants included all adult (aged ≥18 years) patients in the US Renal Data System beginning long-term dialysis in the US from 2013 to 2017 with follow-up through the end of 2018. Patients with a prior kidney transplant and matched Medicare DFC star ratings to each annual cohort of recipients were excluded. Patients at facilities without a star rating in that year were also excluded. Data analysis was performed from January to April 2021. Exposures Dialysis center quality, as defined by Medicare DFC star ratings. Main Outcomes and Measures The primary outcome was the proportion of patients undergoing incident dialysis who were waitlisted within 1 year of dialysis initiation. Secondary outcomes were patient and facility characteristics. Results Of 507 581 patients beginning long-term dialysis in the US from 2013 to 2017, 291 802 (57.4%) were male, 266 517 (52.5%) were White, and the median (interquartile range) age was 65 (55-75) years. Of 5869 dialysis facilities in 2017, 132 (2.2%) were 1-star, 436 (7.4%) were 2-star, 2047 (34.9%) were 3-star, 1660 (28.3%) were 4-star, and 1594 (27.2%) were 5-star. Higher-quality dialysis facilities were associated with 47% higher odds of transplant waitlisting (odds ratio [OR], 1.47; 95% CI, 1.39-1.57 for 5-star facilities vs 1-star facilities; P

BACKGROUND: Anatomic abnormalities increase the risk of deceased donor kidney discard, but their effect on transplant outcomes is understudied. We sought to determine the effect of multiple donor renal arteries on early outcomes after deceased donor kidney transplantation. METHODS: For this retrospective cohort study, we identified 1443 kidneys from 832 deceased donors with ≥1 kidney transplanted at our center (2006–2016). We compared the odds of delayed graft function and 90-day graft failure using logistic regression. To reduce potential selection bias, we then repeated the analysis using a paired-kidney cohort, including kidney pairs from 162 donors with one single-artery kidney and one multiartery kidney. RESULTS: Of 1443 kidneys included, 319 (22%) had multiple arteries. Multiartery kidneys experienced longer cold ischemia time, but other characteristics were similar between groups. Delayed graft function (50% multiartery versus 45% one artery, P=0.07) and 90-day graft failure (3% versus 3%, P=0.83) were similar between groups before and after adjusting for donor and recipient characteristics. In the paired kidney analysis, cold ischemia time was significantly longer for multiartery kidneys compared with single-artery kidneys from the same donor (33.5 versus 26.1 hours, P

BACKGROUND While kidney transplantation is optimal for the treatment of end-stage kidney disease, available organs do not meet demand. Little is known about the outcomes of patients who are delisted (removed from the waitlist) and unable to benefit from transplant. We describe patients who are delisted and their life expectancy after delisting. METHODS Patients ≥ 18 years listed for deceased donor kidney transplant between 01/2003 and 12/2013 were identified in the Scientific Registry of Transplant Recipients and followed through 12/2018. A competing risk model was used to measure the association of demographic and clinical factors with waitlist outcomes of delisting, transplant, and death. Multivariate Cox modeling was used to evaluate factors associated with death after delisting. RESULTS Of 324,582 patients listed, 18.0% were delisted, most common reasons were "too sick" or "other." After delisting, half (49.7%) had died by end of follow-up; time to death after removal was 5 years. Increasing age and public insurance were associated with increased risk of death. CONCLUSIONS Nearly one in five patients will be delisted from the kidney transplant waitlist. These patients live a surprisingly long time after removal. Much remains unknown about these patients, which could be improved through data collection. Delisting is an important patient outcome that warrants further exploration.

Background Efforts to ameliorate the organ shortage have predominantly focused on improving processes and interventions at multiple levels in the organ donation process, but no comprehensive review of hospital-level features contributing to organ donation exists. We undertook a systematic review of the literature to better understand current knowledge and knowledge gaps about hospital-level metrics and interventions associated with successful organ donation. Methods We searched six electronic databases (PubMed, Embase, CINAHL, Web of Science, Health Business Elite, and Google scholar) and conference abstracts for articles on hospital-level features associated with the final outcome of organ donation (PROSPERO CRD42020187080). Editorials, letters to the editor, and reviews without original data were excluded. Our main outcomes were conversion rate, donation rate, number of organs recovered, number of donors, and authorization rate. Results Our search yielded 2177 studies, and after a thorough assessment, 72 articles were included in this systematic review. Studies were thematically categorized into 1) Hospital-level interventions associated with metrics of organ donation; these included patient- and family-centric measures (i.e. standardized interviews, collaborative requesting and decoupling, and dedicated in-house coordinators), and donor management goals that significantly increased conversion rates by up to 64%; 2) Hospital-level multi-stage programs/policies; which increased authorization rates between 30 and 50%; and 3) Hospital characteristics and qualities; being an academic center, trauma center and larger hospital correlated with higher authorization and conversion rates. Most studies had considerable risk of bias and were of low quality. Conclusions There is a lack of well-designed studies on hospital-level metrics and interventions associated with organ donation. The use of thoughtful, patient- and family-centric approaches to authorization generally is associated with more organ donors. Future work can build on what is known about the hospital role in organ donation to improve the entire organ donation process.

The deceased donor kidney allocation system in the United States has undergone several rounds of iterative changes, but these changes were not explicitly designed to address the geographic variation in access to transplantation. The new allocation system, expected to start in December 2020, changes the definition of "local allocation" from the Donation Service Area to 250 nautical mile circles originating from the donor hospital. While other solid organs have adopted a similar approach, the larger number of both kidney transplant centers and transplant candidates is likely to have different consequences. Here, we discuss the incredible increase in complexity in allocation, discuss some of the likely intended and unintended consequences, and propose metrics to monitor the new system.

For patients with kidney failure due to diabetes, pancreas transplantation is often considered in addition to kidney transplantation to provide optimal glycemic control. Most commonly, this is accomplished via simultaneous pancreas-kidney (SPK) transplantation. Sequential pancreas after kidney (PAK) transplantation, following either a living or deceased donor kidney transplant, is another viable option and may be the preferred approach for certain patients. With improved graft survival, PAK is a viable option for patients with a living donor for kidney transplantation. Here, we discuss the benefits and decision-making surrounding SPK versus PAK.

There is no consensus regarding the optimal surgical treatment for transplantable hepatocellular carcinoma (HCC) patients with well-compensated cirrhosis. Our aim was to compare outcomes between Child-Pugh A (CPA) cirrhotics who underwent liver resection or transplantation for HCC. Clinicopathologic data were retrospectively collected for all surgically treated HCC patients between 7/1992 and 12/2015. Disease-free survival (DFS) and overall survival (OS) were calculated from the time of operation or diagnosis (intention-to-treat analysis including patients removed from the transplant list). The average overall cost including pre-operative and post-operative procedures was calculated for each group. Of the 513 surgically treated HCC patients, 184 had CPA cirrhosis and fulfilled the Milan criteria (MC). Of those, 95 (52%) were resected and 89 (48%) were transplanted. Twenty-two patients were removed from the transplant list. Transplanted patients were younger (p

Background Although residential segregation has been implicated in various negative health outcomes, its association with kidney transplantation has not been examined. Methods Age- and sex-standardized kidney transplantation rates were calculated from the Scientific Registry of Transplant Recipients, 2000–2013. Population characteristics including segregation indices were derived from the 2010 U.S. Census data and the U.S. Renal Data System. Separate multivariable Poisson regression models were constructed to identify factors independently associated with kidney transplantation among Blacks and Whites. Results Median age- and sex-standardized kidney transplantation rates were 114 per 100,000 for Blacks and 38 per 100,000 for Whites. 16.1% of the U.S. population lived in counties with high segregation. There was no difference in the kidney transplantation rates across the levels of segregation among Blacks and Whites. Conclusion Factors other than residential segregation may play roles in kidney transplantation disparities. Continued efforts to identify these factors may be beneficial in reducing transplantation disparities across the U.S. Summary Using the Scientific Registry of Transplant Recipients and U.S. census data, we aimed to determine whether residential segregation was associated with kidney transplantation rates. We found that there was no association between residential segregation and kidney transplantation rates.

Transplant centers may decline an import pancreas offer based on demographics and laboratory test results, without information on actual gland quality. The relationship between position on the match run, indicative of the number of centers that chose not to use a pancreas, and patient and death-censored graft survival, is not known. We studied all 199 isolated pancreas grafts transplanted at the University of Wisconsin since July 2000 and compared overall patient and death-censored graft survival based on import vs local status. Of the 199 isolated pancreas transplants, 184 (92.5%) were imported from another donor service area with a median match rank of 49 (interquartile range 14-129). Median cold ischemia time was longer for imported pancreata (16.6 vs 13.4 hours, P = .02). In multivariate Cox modeling, there was no association with position on the rank list and patient (P = .44) or death-censored graft survival (P = .99). There was an overall rate of 6.5% of graft failure within 30 days; however, there was no association with position on the rank list and graft failure at 30 days (P = .33). Although the logistics may be challenging, sound judgment to accept offers independent of prior centers' decisions can result in quality utilization of imported pancreata.

Diverticulitis is a common and morbid disease with incompletely understood risk factors and pathophysiology. Geographic and, recently, seasonal trends in diverticulitis have been described in the United States.The purpose of this study was to investigate and compare seasonal trends in urgent hospital admission for diverticulitis in geographically distinct populations in the northern and southern hemispheres.Inpatient, urgent admissions for diverticulitis were identified within the Dr Foster Intelligence Global Comparators Dataset, a global benchmarking collaborative.Admissions to participating hospitals in the United Kingdom, Australia, and the United States were identified between 2008 and 2013.A total of 18,672 urgent admissions for diverticulitis were identified among 5.5-million admissions.Four separate hypothesis testing methods were used to identify seasonal trends in diverticulitis admissions among international patient populations.Seasonal trends were present in all 3 countries. A summer peak was observed in both hemispheres using multiple statistical testing methods. Logistic regression analyses identified summer months as significantly associated with diverticulitis admission in all 3 countries.This study is limited by restriction to inpatient admissions, reliance on administrative data, and participation of select hospitals within the database.These data suggest a shared seasonal risk factor among geographically distinct populations for diverticulitis.

BACKGROUND Organ procurement organizations (OPOs) are currently evaluated on donation rates and number of organs per donor. However, there is significant variability in market characteristics which affect transplant programs' donor organ acceptance practices and OPOs' ability to successfully place higher risk organs. The impact of transplant market characteristics on OPO performance metrics has not been evaluated. METHODS The OPO performance measures were correlated annually with the Herfindahl Hirschman Index, a standard measure of market competition for centers within the OPO donor service areas from 2003 to 2011. RESULTS More competitive donor service areas were associated with increased number of donors (P = 0.01) and eligible deaths (P < 0.001). Market competition was associated with increased use of high Donor Risk Index for kidney (P = 0.03) and liver (P = 0.01) allografts. The OPOs with increased competition in liver transplant also were noted to have a higher donor conversion rate (P < 0.001), more donors per million population (P < 0.001), and a higher utilization rate for liver allografts (P = 0.007). CONCLUSIONS These data suggest that proposals to increase district size to increase competition among transplant programs could result in improved organ utilization over time by incentivizing the use of marginal donor organs and increasing access to transplantation.

In the early experience of pancreas transplantation, bladder drainage was favored, but it often caused urologic, metabolic, and infectious complications that necessitated conversion to enteric drainage. Long-term graft survival after enteric conversion and the impact of time interval from transplantation to enteric conversion on graft survival is poorly understood. We studied all bladder-drained first-time pancreas transplantations performed at the University of Wisconsin from 1985 to 2000. Time to conversion was estimated with the Kaplan-Meier technique, whereas risk factors associated with conversion were estimated via a time-varying Cox proportional hazards model. Of 386 bladder-drained pancreata, 162 (41.9%) eventually required enteric conversion, 29 (17.9%) within the first year. Median time to conversion varied by indication: 0.68 years for surgical, 3.1 years for urologic, and 2.7 years for metabolic disorders. In a time-varying Cox model adjusting for donor and recipient factors, enteric conversion did not affect the risk of pancreas graft loss (hazard ratio [HR] 0.86, P = .26). Kidney survival was not associated with enteric conversion. When necessary due to symptoms or complications, enteric conversion of bladder-drained pancreata is safe and does not affect overall graft survival. This relationship appears to be true no matter when the conversion is performed.

Public perception and misperceptions of socioeconomic disparities affect the willingness to donate organs. To improve our understanding of the flow of deceased donor kidneys, we analyzed socioeconomic status (SES) and racial/ethnic gradients between donors and recipients. In a retrospective cohort study, traditional demographic and socioeconomic factors, as well as an SES index, were compared in 56,697 deceased kidney donor and recipient pairs transplanted between 2007 and 2012. Kidneys were more likely to be transplanted in recipients of the same racial/ethnic group as the donor (p

OBJECTIVE To evaluate the impact of market competition on patient mortality and graft failure after kidney transplantation. BACKGROUND Kidneys are initially allocated within 58 donation service areas (DSAs), which have varying numbers of transplant centers. Market competition is generally considered beneficial. METHODS The Scientific Registry of Transplant Recipients database was queried and the Herfindahl-Hirschman index (HHI), a measure of market competition, was calculated for each DSA from 2003 to 2012. Receipt of low-quality kidneys (Kidney Donor Profile Index ≥ 85) was modeled with multivariable logistic regression, and Cox proportional hazards models were created for graft failure and patient mortality. RESULTS A total of 127,355 adult renal transplants were performed. DSAs were categorized as 7 no (HHI = 1), 17 low (HHI = 0.52-0.97), 17 medium (HHI = 0.33-0.51), or 17 high (HHI = 0.09-0.32) competition. For deceased donor kidney transplantation, increasing market competition was significantly associated with mortality [hazard ratio (HR): 1.11, P = 0.01], graft failure (HR: 1.18, P = 0.0001), and greater use of low-quality kidneys (odds ratio = 1.39, P < 0.0001). This was not true for living donor kidney transplantation (mortality HR: 0.94, P = 0.48; graft failure HR: 0.99, P = 0.89). Competition was associated with longer waitlists (P = 0.04) but not with the number of transplants per capita in a DSA (P = 0.21). CONCLUSIONS Increasing market competition is associated with increased patient mortality and graft failure and the use of riskier kidneys. These results may represent more aggressive transplantation and tolerance of greater risk for patients who otherwise have poor alternatives. Market competition should be better studied to ensure optimal outcomes.

Publicly reported hospital ratings aim to encourage transparency, spur quality improvement, and empower patient choice. Travel burdens may limit patient choice, particularly for older adults (aged 65 years and more) who receive most medical care. For 3 major hospital ratings systems, we estimated travel burden as the additional 1-way travel distance to receive care at a better-rated hospital.Distances were estimated from publicly available data from the US Census, US News Top Hospitals, Society of Thoracic Surgeons composite rating for coronary artery bypass grafting (STS-CABG), and Centers for Medicare and Medicaid Services Hospital Consumer Assessment of Healthcare Providers and Services (HCAHPS).Hospitals were rated for HCAHPS (n = 4656), STS-CABG (n = 470), and US News Top Hospitals (n = 15). Older adults were commonly located within 25 miles of their closest HCAHPS hospital (89.6%), but less commonly for STS-CABG (62.9%). To receive care at a better-rated hospital, travel distances commonly exceeded 25 miles: HCAHPS (39.2%), STS-CABG (62.7%), and US News Top Hospital (85.2%). Additional 1-way travel distances exceeded 25 miles commonly: HCAHPS (23.7%), STS-CABG (36.7%), US News Top Hospitals (81.8%).Significant travel burden is common for older adults seeking "better" care and is an important limitation of current hospital ratings for empowering patient choice.

To determine travel patterns for patients undergoing gastrectomy for cancer and to identify factors associated with patient decision.Support for regionalization of complex surgery grows; however, little is known about the willingness of patients to travel for care. Furthermore, utilization of outcomes data in patients' hospital selection processes is not well understood.Analysis of the California Office of Statewide Health Planning and Development database from 1996 to 2009. Outcome measures included total distance traveled and rate of bypassing the nearest gastrectomy-performing hospitals. Multivariate analyses to identify predictors of bypassing local hospitals were performed.Total study population was 10,022. Majority (67.1%) of patients underwent gastrectomy at the nearest providing hospitals. Distance traveled to destination hospitals in California averaged 17.04 miles. Bypassing patients traveled approximately 16 miles beyond the nearest hospitals to receive care, selecting lower volume destination hospitals in 27.9% of cases. Annual gastrectomy volumes for nearest and for destination hospitals averaged 4.4 and 6.8 cases, respectively, and inhospital mortality rates were 5.9% and 4.8%, respectively. A few patients (19.2%) sought care at teaching hospitals. Rural county residence significantly reduced the likelihood of bypass (P0.001). High volume (7 cases) and teaching status of destination hospitals (both P0.001) were predictive of hospital bypass, though no significant association between mortality rate and bypass was identified.The majority of gastric cancer patients underwent gastrectomy at providing hospitals nearest to home, reflecting little regionalization of gastrectomy in California. Patients' hospital selection appears not to be driven by outcomes data.

INTRODUCTION Early allograft thrombosis is a devastating complication that often leads to graft loss after living donor kidney transplantation. In addition to the psychological effects on donor and recipient, it could make future kidney matches challenging due to sensitization. PATIENTS AND METHODS The Scientific Registry of Transplant Recipients (SRTR) was queried for adult patients undergoing living donor renal transplantation from 2001 to 2010. Sensitization was defined as a panel reactive antibody of ≥50%. Early allograft thrombosis included events within 30 d of transplantation. RESULTS In multivariable logistic regression, recipient female gender (odds ratio [OR] 2.24, p < 0.001) and right kidneys (OR 1.46, p < 0.001) were associated with increased risk of thrombosis, while increasing recipient age per 10 yr (OR 0.62, p < 0.001) and recipient Asian race/ethnicity (OR 0.34, p = 0.02) were protective. In a time-varying Cox model examining factors affecting the likelihood of retransplantation, the chance of retransplantation was 37% lower (p = 0.01) once patients became sensitized. The median time to sensitization after transplantation was 288 d. CONCLUSIONS Even with relatively brief exposure to foreign antigen, sensitization occurs and delays retransplantation for recipients of living donor kidneys with early allograft thrombosis.

Standards for posttransplant graft/survival rates do not reward transplant centers for performing riskier transplants to increase population benefit.

BACKGROUND Kidney transplant centers are distributed unevenly throughout 58 donor service areas (DSAs) in the United States. Market competition and transplant center density may affect transplantation access and outcomes. We evaluated the role of spatial organization of transplant centers in conjunction with market competition in the conduct of kidney transplantation. METHODS The Scientific Registry of Transplant Recipients was queried for market characteristics associated with kidney transplantation between 2003 and 2012. Market competition was calculated using the Herfindahl Hirschman Index. Kidney transplant centers were geocoded to measure spatial organization by the average nearest neighbor (ANN) method. Kidney quality was assessed by kidney donor risk index. A hierarchical negative binomial mixed effects model tested the relationship between market characteristics and annual kidney transplants by DSA. RESULTS About 152,071 kidney transplants were performed at 229 adult kidney transplant centers in 58 DSAs. Greater market competition was associated with kidney transplant center spatial clustering (P < 0.001). In multivariable analysis, more kidney transplant centers (incidence rate ratio [IRR], 1.04; P = 0.005), 100 more new listings (IRR, 1.02; P = 0.003), 100 more deceased donors (IRR, 1.23; P < 0.001), 100 more new dialysis registrants (IRR, 1.01; P < 0.001), and higher kidney donor risk index (IRR, 1.98; P < 0.001) were associated with increased kidney transplants. CONCLUSIONS After controlling for market characteristics, larger numbers of kidney transplant centers were associated with more kidney transplants and increased utilization of deceased donor kidneys. This underlines the importance of understanding geography as well as competition in improving access to kidney transplantation.

Minimally invasive parathyroidectomy for primary hyperparathyroidism depends on accurate preoperative imaging, which is traditionally accomplished by 99mTc-sestamibi scanning. Cervical ultrasound is gaining in use, but it is unclear how much information it adds to the routine use of 99mTc-sestamibi scans. A prospectively maintained database of patients undergoing parathyroidectomy for primary hyperparathyroidism was queried, and the utility of cervical ultrasound in preoperative planning was analyzed. Between July 2002 and November 2009, 310 patients with primary hyperparathyroidism underwent both 99mTc-sestamibi and ultrasound imaging. Ultrasound added new information to 99mTc-sestamibi in 43 patients (14%) by finding either the correct enlarged gland (n = 40, 88%) or additional enlarged glands (n = 5, 12%). Ultrasound correctly localized glands in 38 of 85 (45%) patients with a negative 99mTc-sestamibi, allowing for a minimally invasive parathyroidectomy in those patients. However, in the 206 patients (66%) who had a 1-gland positive 99mTc-sestamibi, ultrasound only added information for 8 patients (4%). When compared with radiology-performed ultrasound, surgeon-performed ultrasound was successful in localizing additional glands in 27 (15%) versus 17 patients (10%) (P

Background Minimally invasive parathyroidectomy for primary hyperparathyroidism depends on accurate preoperative imaging. Cervical ultrasound is commonly used to localize parathyroid adenomas, but can lead to discovery of concomitant thyroid gland pathology requiring modification of the operative approach. How the identification of incidental thyroid lesions affects patient management is unclear. Study Design A prospective database of patients undergoing parathyroidectomy was analyzed for thyroid pathology discovered by ultrasound. Lesions were biopsied if indicated, and operative management was adjusted accordingly. Clinical data were correlated with operative decision-making. Results Between July 2002 and November 2009, 310 patients with primary hyperparathyroidism underwent ultrasound. Concomitant thyroid pathology was noted in 89 (29%) patients. Thirty-seven patients (42% of pathology) underwent fine-needle aspiration of a thyroid nodule. Thirteen patients (4% of all patients) underwent a thyroid operation not related to parathyroid disease: 9 thyroid lobectomies for presumably benign nodules and 4 total thyroidectomies for malignancy. Two were for confirmed papillary thyroid cancer, and the other 2 were for an indeterminate biopsy that later proved to be papillary thyroid cancer. One lobectomy discovered microscopic papillary thyroid cancer independent of the biopsied nodule. In total, 5 (2% of all patients) malignancies were discovered. Conclusions Twenty-nine percent of patients with primary hyperparathyroidism had concomitant thyroid pathology on ultrasound. Forty-two percent of these patients underwent biopsy, and 2% had malignant pathology. Routine use of ultrasound in patients with primary hyperparathyroidism leads to discovery of unrecognized thyroid pathology and cancer.

Background—While representing only 3% of thyroid malignancies, medullary thyroid cancer (MTC) accounts for 14% of thyroid cancer deaths. MTC has a high rate of recurrence and lacks effective treatments. The histone deacetylase (HDAC) inhibitors valproic acid (VPA) and suberoyl bis-hydroxamic acid (SBHA) activate the Notch1 signaling pathway, while lithium chloride inhibits the glycogen synthase kinase-3s (GSK-3s) pathway. These compounds have been shown to limit growth and suppress hormonal secretion; thus, targeting different signaling pathways may be an effective treatment. Methods—MTC cells were treated with varying combinations of up to 20 mM lithium chloride with either 3 mM VPA or 20 μM SBHA for 48 hours. Western analysis was used to measure the effects on Notch1, GSK-3s, and neuroendocrine (NE) markers. Growth was assessed by a methylthiazolyldiphenyl-tetrazolium (MTT) bromide cellular proliferation assay. Western analysis was used to determine the mechanism of growth regulation Results—Combination therapy increased active Notch1, inhibited the GSK-3s pathway, and decreased NE markers,. Additive inhibition of growth was observed with combination therapy. Lower-dose combination therapy achieved greater decreases on NE markers and growth than treatment with any of the drugs alone. Moreover, an increase in the cleavage of the apoptotic markers caspase-3 and PARP was observed. Conclusions—Combination therapy with lithium chloride and HDAC inhibitors suppresses NE markers and decreases growth via apoptosis of MTC cells in vitro. With the possibility of increased efficacy and decreased toxicity, combination therapy may represent a new strategy to treat MTC.

Distance from pediatric kidney transplant centers may be a significant barrier in accessing care for patients and families, particularly due to the lower number of pediatric kidney transplant centers compared with the number of adult centers. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients to determine the effect of distance on pediatric kidney transplant waitlist outcomes. We found that distance did not play a role in the likelihood of transplantations for patients who were placed on the waitlist. However, living a greater distance from the transplant center was associated with a greater risk of death while on the waitlist. Larger volume centers attracted patients from greater distances, many of whom had other centers closer to their home. Further investigation on the role of distance to transplant center and the likelihood of being evaluated and listed for a kidney transplant would elucidate whether there are additional barriers these patients face.

Operative resection is the only curative treatment for pheochromocytomas. Inhibition of the phosphatidylinositol-3 kinase (PI3K)-Akt pathway has been shown to be an effective treatment of neuroendocrine (NE) tumors in vitro. We hypothesized that inhibition of the PI3K-Akt pathway would be a viable strategy to inhibit growth and hormonal secretion in pheochromocytoma cells.Sixteen pheochromocytomas were analyzed for expression of phosphorylated Akt and the NE marker achaete scute complex-like 1 (ASCL1). Pheochromocytoma PC-12 cells were treated with up to 100 microM of the PI3K-specific inhibitor LY294002 for 48 h. Western blot analysis was used to measure phosphorylated Akt, total Akt, ASCL1, chromogranin A (CgA), and markers of apoptosis. Growth was assessed by a methylthiazolyldiphenyl-tetrazolium (MTT) bromide cellular proliferation assay for six days.Human pheochromocytomas expressed significant amounts of phosphorylated Akt, and there was a significant correlation between malignant pheochromocytomas and the amount of expressed ASCL1. LY294002 significantly inhibited the PI3K-Akt pathway. Treatment led to a dose-dependent decrease in both ASCL1 and CgA, indicating an alteration in the NE phenotype and hormonal suppression. Treatment decreased cellular proliferation, and cleavage of the apoptotic markers caspase-3 and PARP was observed.Human pheochromocytoma tumor samples express high levels of phosphorylated Akt. LY294002 effectively inhibits the PI3K-Akt pathway, suppresses NE tumor markers, and decreases cellular proliferation via apoptosis in vitro. Inhibition of the PI3K pathway may represent a new strategy in the treatment of pheochromocytomas.

Medullary thyroid cancer (MTC) is a relatively uncommon neuroendocrine tumor that arises from the calcitonin-secreting parafollicular cells of the thyroid gland. Unfortunately, MTC frequently metastasizes, precluding curative surgical resection and causing significant morbidity. Thus, there is an urgent need for new treatment modalities. Tautomycin and tautomycetin are antifungal antibiotics isolated from Streptomyces spiroverticillatus and Streptomyces griseochromogens, respectively. Glycogen synthase kinase-3β is a serine/threonine protein kinase that regulates multiple cellular processes and is important in various cancers, including MTC. Treatment with tautomycin and tautomycetin decreased neuroendocrine markers, suppressed hormonal secretion, and inhibited growth through apoptosis in MTC cells. Importantly, we describe a novel action of these compounds: inhibition of glycogen synthase kinase-3β.[Mol Cancer Ther 2009;8(4):914–20]

Background The histone deacetylase (HDAC) inhibitors valproic acid (VPA) and suberoyl bis-hydroxamic acid (SBHA) have been demonstrated recently to be strong Notch-1 activators. Upregulation of the Notch-1 pathway has been shown to limit growth and suppress hormonal secretion in neuroendocrine (NE) neoplasms. We hypothesized that HDAC inhibition would be an effective strategy to activate the Notch-1 pathway and inhibit growth and hormonal secretion in pheochromocytoma cells. Methods Pheochromocytoma PC-12 cells were treated with up to 8 mmol/L VPA or 40 μmol/L SBHA for 2 days. NE tumor markers achaete-scute complex-like 1 (ASCL1) and chromogranin A (CgA) were measured by Western analysis after treatment. Growth was assessed by a cellular proliferation assay; Western analysis was used to determine the mechanism of growth regulation. Results HDAC inhibitor treatment caused a dose-dependent decrease in ASCL1 and CgA while increasing the amount of active Notch-1 protein; with a 6-day treatment, dose-dependent growth inhibition and cleavage of the apoptotic markers caspase-3 and poly-ADP ribose phosphate was observed. Conclusion VPA and SBHA upregulate Notch-1 effectively, suppress NE tumor markers, and decrease growth via apoptosis of pheochromocytoma cells in vitro. Activation of the Notch-1 signaling pathway with HDAC inhibitors may represent a new strategy for treating pheochromocytomas.

Hürthle cell neoplasms (HCNs) are rare tumors of the thyroid gland. The definitive treatment for Hürthle cell carcinoma (HCC) is total thyroidectomy, while thyroid lobectomy is adequate for Hürthle cell adenoma (HCA). However, differentiating HCC from HCA either before or during surgery is a challenge. The purpose of this study was to identify factors that predict malignancy in patients with HCN.Between May 1994 and January 2007, 1,199 patients underwent thyroid surgery at an academic medical center. Medical records of 55 consecutive patients who underwent thyroid resections for the preoperative diagnosis of HCN were reviewed.Of the 55 patients with HCN, 46 (84%) had adenomas and 9 (16%) had carcinomas. Patients with HCC were significantly older than those with HCA (66 +/- 6 years versus 53 +/- 2 years, P = 0.01). Patients with carcinoma also had significantly larger thyroid nodules (4.5 +/- 0.7 cm versus 2.5 +/- 0.2 cm, P0.001). All HCNs less than 2 cm in diameter were benign. The malignancy rate increased with nodule size: 18% of nodules measuring 2-4 cm, and 44% of those larger than 4 cm were HCC. One patient with HCC had recurrence of the disease, but there were no disease-related deaths.Advanced patient age and larger nodule size are two important factors that predict malignancy in patients with HCN. In patients with these and other known risk factors for HCC, total thyroidectomy should be considered.

To examine the effects of valproic acid (VPA) on Notch1 expression and cancer cell proliferation in medullary thyroid cancer (MTC) cells.Other than surgery, there are no effective treatments for MTC, a neuroendocrine malignancy that frequently metastasizes. We have previously shown that over-expression of Notch1 in MTC cells inhibits cell growth and hormone production. VPA, a drug long used for the treatment of epilepsy, has recently been identified as a potential Notch1 activator. We hypothesized that VPA might activate Notch1 signaling in MTC cells, with antiproliferative effects.Human MTC cells were treated with VPA (0-5 mM) and Western blotting was performed to measure levels of Notch1 pathway proteins and neuroendocrine tumor markers. After confirming that VPA is a Notch1 activator in MTC cells, we performed cell proliferation assay. Finally, to determine the mechanism of growth inhibition, we measured protein levels of various markers of apoptosis.Notch1 was absent in MTC cells at baseline. VPA treatment resulted in an increase in both full-length and active Notch1 protein. Notch1 activation with VPA suppressed 2 neuroendocrine tumor markers, ASCL1 and chromogranin A. Importantly, VPA inhibited the growth of MTC cells in a dose-dependent manner. Immunoblot analysis demonstrated caspase activation and poly(ADP-ribose) polymerase cleavage, indicating the induction of apoptosis.VPA activates Notch1 signaling in MTC cells and inhibits their growth by inducing apoptosis. As the safety of VPA in human beings is well established, a clinical trial using this drug to treat patients with advanced MTC could be initiated in the near future.

It is well established that quality of life improves after parathyroidectomy. Less well understood is the impact of surgical approach on quality of life during recovery. This study was undertaken to determine whether surgical approach influences quality of life after surgery for hyperparathyroidism.A total of 146 consecutive patients who underwent surgery for hyperparathyroidism were administered the SF-36 Health Survey 1 week before, 1 week after, and 1 year after surgery.Ninety-eight patients had minimally invasive parathyroidectomies, while 48 patients had bilateral explorations. All patients were normocalcemic6 months after surgery. Hospital length of stay was significantly shorter in those undergoing a minimally invasive operation (mean +/- SE, .2 +/- .0 vs. .9 +/- .0 days, P.001). The rate of complications was not statistically different (3.1% vs. 6.3%, P = .40). Quality of life improved after surgery for hyperparathyroidism, irrespective of surgical approach. The minimally invasive group greatly improved in four scales 1 week after operation, while those with a bilateral exploration improved in two. After 1 year, the minimally invasive group had statistically improved in eight categories, while the bilateral exploration group did so in only four (P.05 for all).With improvements in surgical outcomes and quality of life, these data provide additional evidence that minimally invasive parathyroidectomy is the operation of choice for patients with hyperparathyroidism.

Background While open adrenalectomy is often performed for malignant adrenal tumors, increasing numbers of surgeons have adopted the laparoscopic approach. The postoperative benefits of laparoscopic adrenalectomy are well established, but questions persist about long-term oncologic outcomes when used for malignant lesions. The current study was undertaken to compare laparoscopic with open adrenalectomy for isolated adrenal metastases. Methods From March 1993 to April 2006, 20 adults underwent adrenalectomy for isolated metastases to the adrenal gland. Three patients were excluded because of a concomitant nephrectomy (2) and an unresectable tumor (1). Patient demographics, tumor characteristics, and oncologic outcomes of the remaining patients were reviewed and analyzed. Results Of the 17 patients who received adrenalectomy for an isolated metastasis, there were 11 men and 6 women with a mean age of 58 ± 3 y. Nine patients underwent laparoscopic adrenalectomy, and 8 patients had open adrenalectomy. Laparoscopic adrenalectomy was associated with less blood loss (63 ± 8 mL versus 2207 ± 1067 mL, P = 0.05), a lower complication rate (0% versus 63%, P = 0.009), and a shorter length of stay (2.4 ± 0.6 d versus 5.4 ± 0.7 d, P = 0.02). With a follow-up of up to 97 mo, there were no port site metastases, no tumor recurrences, and no difference in survival between laparoscopic and open adrenalectomy (median 19 months versus 17 months, 5-year survival 34% versus 54%, P = 0.96). Conclusions When not limited by tumor size or invasion of surrounding tissue, laparoscopic adrenalectomy is a safe alternative to open adrenalectomy with equivalent oncologic outcomes and clear postoperative benefit for patients with isolated metastases to the adrenal gland.