United Network For Organ Sharing Regions Research Articles

Downstaging hepatocellular carcinoma before liver transplantation: A multicenter analysis of the “all-comers” protocol in the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) consortium

Patients with hepatocellular carcinoma meeting united network for organ sharing (UNOS)-downstaging (DS) criteria have excellent liver transplantation (LT) outcomes after DS. However, outcomes for “all-comers” (AC) patients with tumors initially exceeding UNOS-DS are poorly understood. Patients meeting AC (n = 82) or UNOS-DS (n = 229) at 7 LT centers in 4 UNOS regions were prospectively followed from 2015-2020. AC patients had a lower probability of successful DS (67% vs 83% within 12 months; P < .001). The 3-year survival was 69% for UNOS-DS vs 58% for AC (P = .05) and reduced to 30% in patients with Child-Pugh B/C cirrhosis or alpha-fetoprotein (AFP) ≥ 500. Five-year LT probability was 42% for AC vs 74% in UNOS-DS (P = .10). Thirty-eight percent were understaged on explant, with the increasing sum of the largest tumor diameter plus the number of lesions before LT (odds ratio 1.3; P = .01) and AFP ≥ 20 (odds ratio 5.9; P = .005) associated with understaging. Post-LT 3-year survival was 91% for AC vs 81% for UNOS-DS (P = .67). In this first prospective multiregional study of AC patients from the multicenter evaluation of reduction in tumor size before liver transplantation (MERITS-LT) consortium, we observed a 65% probability of successful DS. Three-year survival in AC was nearly 60%, though AC with Child-Pugh B/C or AFP ≥ 500 had poor survival. Explant pathology and 3-year post-LT outcomes were similar between cohorts, suggesting that LT is a reasonable goal in selected AC patients.

Heterogeneity in transplant center responses to the minimum acceptance criteria across UNOS regions.

Transplantation of organs from increased risk donors for infection transmission (IRDs) is increasing. These organs confer survival benefit to recipients. This study examined transplant center acceptance policies for IRD kidneys across United Network for Organ Sharing (UNOS) regions, based on transplant centers' annual responses to the Minimum Acceptance Criteria (MAC) for acceptance of IRD kidneys, and the association with national and regional IRD kidney utilization. De-identified MAC responses from all transplant centers in the United States from 2007 to 2019 were obtained. Implementation of MAC responses into practice was evaluated based on annual rates of recovery and transplantation of IRD kidneys, by MAC and UNOS region. Nationally, the number of transplant centers willing to accept IRD kidneys across all criteria increased from 22% in 2007 to 64% in 2019. Acceptance rates increased markedly from donors with intravenous drug use and other potential HIV exposures. However, significant heterogeneity exists in transplant center willingness to accept IRD kidneys, both regionally and between criteria. Trends towards increasing acceptance are strongly associated with higher rates of recovery and transplantation of IRD kidneys. Further research on provider- and center-based refusal to consider IRD kidneys for waitlisted patients is needed to improve utilization of this organ pool.

Impact of the Coronavirus Disease 2019 Pandemic on Utilization of Mechanical Circulatory Support As Bridge to Heart Transplantation.

Impact of the Coronavirus Disease 2019 Pandemic on Utilization of Mechanical Circulatory Support As Bridge to Heart Transplantation.

Trends in the use of hepatitis C viremic donor hearts

ObjectiveTo examine trends in utilization of hearts from hepatitis C virus (HCV) viremic donors for transplantation, a strategy to expand organ availability. MethodsThe United Network for Organ Sharing (UNOS) registry was queried for adult patients undergoing heart transplantation between 2015 and 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) defined HCV status. ResultsBetween 2015 and 2019, a total of 11,393 adults underwent heart transplantation: 326 from HCV NAT+ donors and 11,067 from NAT− donors. The use of NAT+ hearts increased from 1 in 2015 to 137 in 2018 against a static number of NAT− organs. The use of NAT+ hearts varied significantly across regions and individual centers. More than 75% of NAT+ hearts were transplanted in the Northeast region, leading to further travel (mean, 299 miles vs 173 miles for NAT− transplantations; P < .001), with longer ischemic times (mean: 3.52 hours vs 3.10 hours; P < .001). More than one-half of NAT+ transplantations were performed by 5 individual centers, and a single institution accounted for >20% of all transplantations from viremic donors. Survival in the 2 groups did not differ by Kaplan-Meier analysis (P = .240), and multivariable regression showed no differences in acute rejection (P = .455) or 30-day mortality (P = .490). Of the 326 recipients of NAT+ hearts, 38 seroconverted and 14 became viremic within 1 year. Survival was 100% in the viremic patients and 97.4% in seroconverted patients at 1 year. ConclusionsHeart transplantation from HCV viremic donors continues to increase but varies significantly across UNOS regions and individual centers. Short-term outcomes are comparable, but effects of seroconversion and long-term outcomes remain unclear.

Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.

Medical-refractory severe alcoholic hepatitis (AH) has a high mortality. The national frequency, longer term outcomes and regional practices of AH liver transplantation (LT) in the United States are not well described, despite the increasing mortality from alcohol-associated liver disease. We analyzed the trends in frequency and outcomes of UNOS data on 39455 adult patients who underwent LT from 2014 to 2019, including AH LT recipients. LTs for AH increased 5-fold, from 28 in 2014 to 138 in 2019, varying 8-fold between UNOS regions. Three transplant centers accounted for 50%-90% of AH LTs within each region. The number of transplant centers performing AH LTs increased from 14 in 2014 to 47 in 2019. AH patients were younger (mean=39.4years), had higher MELD scores (mean=36.8), and were more often on dialysis (46.0%) and in ICU (38.4%), compared to other indications (all P<.05). One- and 5-year graft survivals for AH LT recipients were 91.7% and 81.9%, respectively. The frequency of AH LT is increasing rapidly, with excellent medium-term outcomes. An impact of AH recurrence on patient or graft survival is not apparent in this national analysis. There are marked geographic variations in practices, highlighting the lack of selection criteria standardization.

Risk Factors and Center-Level Variation in Hepatocellular Carcinoma Under-Staging for Liver Transplantation.

Liver transplantation (LT) is curative for most patients with hepatocellular carcinoma (HCC). However, 10%-15% of patients experience HCC recurrence. Patients who are reported as within Milan criteria by imaging are frequently found to be outside the criteria on explant. This under-staging of HCC worsens post-LT outcomes. However, risk factors for under-staging have not been elucidated. Furthermore, it is not known if there is regional or center-level variation in under-staging. We conducted a retrospective analysis of adult patients transplanted for HCC in the United Network for Organ Sharing (UNOS) database between 2012 and 2016. Under-staging was determined on the basis of comparing pre-LT imaging to explant findings. Kaplan-Meier methods and Cox regression were used to evaluate the impact of under-staging on HCC recurrence and post-LT survival. Mixed effects logistic regression was used to identify risk factors for under-staging and to study regional and center-level variation in adjusted analyses. A total of 5424 patients were included in the cohort, of whom 24.9% (n=1353) were under-staged. Post-LT HCC recurrence and death were significantly associated with under-staging (each P<0.001). In adjusted analyses, independent predictors of under-staging included age (odds ratio [OR], 1.13 per 10 years; 95% confidence interval [CI], 1.03-1.25), male sex (OR, 1.61; 95% CI, 1.36-1.89), down-staging (OR, 4.03; 95% CI, 2.65-6.11), and pre-LT alpha-fetoprotein (P<0.001). There was also significant variation in under-staging between UNOS regions and among transplant centers, ranging from 14.8% to 38.1%. We report novel risk factors for HCC under-staging, which worsens post-LT outcomes. Significant center-level and regional variation in under-staging highlights the need for standards that achieve greater uniformity in staging.

More Money and More Miles: The Hidden Costs of Donor Procurement with the New Heart Allocation System

In October 2018, the United Network for Organ Sharing (UNOS) implemented extensive changes to the adult heart allocation policy. These changes were developed to better stratify medically urgent patients and provide more equitable geographic distribution of donor hearts. Instead of preferential distribution within a local donor service area, hearts are first considered by centers within 500 nautical miles of a donor hospital. We evaluated the impact of the new system on the mode and associated expense of procurement travel. We retrospectively analyzed data from 5 centers across 5 states and 4 UNOS regions (regions 2, 5, 10, 11). Pre-allocation change (pre-change) was considered 10/1/2016-10/17/2018 and post-allocation change (post-change) was considered 10/18/18-8/31/2019. The share of procurements requiring a flight vs local transportation from all centers was compared. Cost of transportation for procurement and distance from donor hospital to transplant center was available from 4 centers. Total of 693 transplants were performed during the study period: 477 pre-change and 216 post-change. Pre-change, there were 274 flights for procurement compared to 182 flights post-change (57 vs 84%, p <0.0001). There were notable differences in these increases by UNOS region (Figure). Average travel increased from 193 miles pre-change to 269 miles post-change (p<0.0001), corresponding with an increase in average transportation costs from $6,812.07 to $12,383.64 (p<0.0001), respectively. Following the 2018 UNOS change to the heart allocation system, the proportion of flights and distance traveled for organ procurements significantly increased across 5 moderate-high volume centers, nearly doubling the average travel cost for procurement. These findings may guide transplant centers, payers, and policy makers regarding necessary procurement resources. Further study is needed to determine how these changes may affect lower volume centers with fewer resources.

Durable mechanical circulatory support device use in the United States by geographic region and minority status

BackgroundDurable mechanical circulatory support device (MCSD) therapy has experienced rapid dissemination in the United States. Few studies have evaluated geographic patterns of its dissemination based upon patient characteristics that could identify potential variation in its application. MethodsA combined Interagency Registry for Mechanically Assisted Circulatory Support and Medicare dataset identified durable MCSD implants from 2008 through 2014. MCSD implant rates were estimated using yearly US Census population data, estimated from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database and stratified by age, race, and United Network for Organ Sharing (UNOS) region. ResultsOverall, 16,331 patients received an MCSD implant from 232 unique centers. Annual MCSD implant rate (per 1 million population) significantly increased in each UNOS region (absolute range of increase, 5.3-16.4) with UNOS Region 7 demonstrating the highest overall absolute rate (20.9) in 2014 and UNOS Region 11 demonstrating the greatest relative increase in rate (430.5%). Geographical differences in the rate of MCSD implants were observed among whites and minorities with higher rates of MCSD implants observed for minorities for nearly all UNOS regions across all years. Significantly greater relative increases in MCSD implants for minorities compared with whites were observed within UNOS Regions 2, 3, 6, 7, 8, 9, and 11 (P < .001). ConclusionsGeographical differences exist in rates of MCSD implantation among whites and minorities. The reasons for these differences are unknown, but may reflect underlying differences in disease burden or disparities in access to heart transplantation and warrant further study.

National Survey of Pre-Lung Transplant Colon Cancer Screening Practices in High-Volume Centers Across the United States

Introduction: The burden of end-stage lung disease is increasing worldwide with a commensurate rise in lung transplantation (LTx). Colorectal cancer (CRC) screening is necessary prior to LTx listing; however, current nationwide screening practices in this population are unknown. While gastroenterology and cancer society guidelines include colonoscopy (CY) and non-invasive methods for CRC screening, the latter is attractive given the increased risk of sedation during CY for patients with advanced lung disease. Our aim was to understand the approach to CRC screening at high-volume LTx centers to identify whether practice variations existed among programs. Methods: We queried the United Network for Organ Sharing (UNOS) database to identify high-volume LTx centers (greater than 40 transplants) in 2016 or 2017. A ten-question survey was distributed to each center’s medical director or head nurse coordinator for completion using Research Electronic Data Capture (REDcap). Data was analyzed using SPSS v24.0. Results: Twenty-three of 25 (92.0%) centers responded, representing 3083/3290 (93.7%) patients at high volume LTx centers and 3083/4694 (65.7%) of all patients nationwide who received LTx between 2016-2017. 22/23 (95.7%) programs recommended CY as the primary modality for screening and one program allowed either CY or fecal immunochemistry testing (FIT). 3/23 (13.0%) programs accepted only CY for CRC screening. 16/23 (69.6%) programs, on the other hand, accepted CT colonography (CTC), and 8/23 (34.8%) programs accepted at least one form of stool-based testing as alternatives to CY. There were no differences in accepted screening modalities between UNOS regions. To achieve sedation during CY, 5/23 preferred conscious sedation, 10/23 preferred monitored anesthesia care, and 8/23 decided on a case by case basis. Only 8/23 programs started screening African American patients at age 45 compared to age 50. Conclusion: CY is the preferred choice for CRC screening prior to lung transplant listing. Still, discrepancies exist regarding second-line CRC screening with CTC being the most commonly accepted non-invasive method. Stool-based studies are not accepted by most transplant programs. It is important to further investigate the barriers to using non-invasive methods in this patient cohort with high procedural risk and adhering to accepted screening guidelines. In the future, we hope to develop a consensus algorithm for pre-lung transplant CRC screening to reduce variation among transplant centers.296 Figure 1. Distribution of acceptable non-invasive methods use for colorectal cancer screening prior to lung transplant listing

Prediction Model for Wait Times in Cardiac Transplantation

Wait times have increased for patients approved for heart transplants. We reviewed United Network for Organ Sharing (UNOS) data for 14,242 patients listed for isolated heart transplant (2009-2013) to develop a risk score model for timing left ventricular assist device (LVAD) implantation in bridge-to-transplant patients. We used a multivariable Cox proportional hazards regression model with subsequent bootstrap resampling for internal validation to develop a scoring system that combined risk factors, weighted by the corresponding regression coefficients, to define an individual's risk score. Four risk factors were identified (body mass index, blood type, region, and urgency status) to be significantly and independently associated with wait time (p < 0.001), showing adequate model discrimination (C = 0.704) and calibration. Higher risk scores correlated with shorter wait times. Our model corresponded closely with observed transplant rates, predicting longer wait times for lower status, larger size, certain blood groups, and some UNOS regions. This tool has the potential to more accurately describe the wait-time duration for an individual patient, which may influence care decisions. The wait-time discrepancies (blood types/regions) reinforce the need to reevaluate the geographic-allocation policy. The proposed review of the UNOS heart allocation policy may make this model especially relevant.

Variation in practice patterns and outcomes across United Network for Organ Sharing allocation regions.

The number of heart transplants performed is limited by organ availability and is managed by the United Network for Organ Sharing (UNOS). Efforts are underway to make organ disbursement more equitable as demand increases. Significant variation exists in contemporary patterns of care, wait times, and outcomes among patients undergoing heart transplantation across UNOS regions. We identified adult patients undergoing first, single-organ heart transplantation between January 2006 and December 2014 in the UNOS dataset and compared sociodemographic and clinical profiles, wait times, use of mechanical circulatory support (MCS), status at time of transplantation, and 1-year survival across UNOS regions. We analyzed 17 096 patients undergoing heart transplantation. There were no differences in age, sex, renal function, and peripheral vascular resistance across regions; however, there was 3-fold variation in median wait time (range, 48-166 days) across UNOS regions. Proportion of patients undergoing transplantation with status 1A ranged from 36% to 79% across regions (P < 0.01), and percentage of patients hospitalized at time of transplantation varied from 41% to 98%. There was also marked variation in MCS and inotrope utilization (28%-57% and 25%-58%, respectively; P < 0.001). Durable ventricular assist device implantation varied from 20% to 44% (P < 0.001), and intra-aortic balloon pump utilization ranged from 4% to 18%. Marked differences exist in patterns of care across UNOS regions that generally trend with differences in waitlist time. Novel policy initiatives are required to address disparities in access to allografts and ensure equitable and efficient allocation of organs.

Recent trends in liver transplantation for alcoholic liver disease in the United States.

AIMTo examine temporal changes in the indications for liver transplantation (LT) and characteristics of patients transplanted for alcoholic liver disease (ALD).METHODSWe performed a retrospective cohort analysis of trends in the indication for LT using the United Network for Organ Sharing (UNOS) database between 2002 and 2015. Patients were grouped by etiology of the liver disease and characteristics were compared using χ2 and t-tests. Time series analysis was used identifying any year with a significant change in the number of transplants per year for ALD, and before and after eras were modeled using a general linear model. Subgroup analysis of recipients with ALD was performed by age group, gender, UNOS region and etiology (alcoholic cirrhosis, alcoholic hepatitis and hepatitis C - alcoholic cirrhosis dual listing).RESULTSOf 74216 liver transplant recipients, ALD (n = 9400, 12.7%) was the third leading indication for transplant after hepatitis C and hepatocellular carcinoma. Transplants for ALD, increased from 12.8% (553) in 2002 to 16.5% (1020) in 2015. Time series analysis indicated a significant increase in the number of transplants per year for ALD in 2013 (P = 0.03). There were a stable number of transplants per year between 2002 and 2012 (linear coefficient 3, 95%CI: -4.6, 11.2) an increase of 177 per year between 2013 and 2015 (95%CI: 119, 234). This increase was significant for all age groups except those 71-83 years old, was observed for both genders, and was incompletely explained by a decrease in transplants for hepatitis C and ALD dual listing. All UNOS regions except region 9 saw an increase in the mean number of transplants per year when comparing eras, and this increase was significant in regions 2, 3, 4, 5, 6, 8, 10 and 11.CONCLUSIONThere has been a dramatic increase in the number of transplants for ALD starting in 2013.

New organ allocation policy in liver transplantation in the United States.

New organ allocation policy in liver transplantation in the United States.

Urgent listing exceptions and outcomes in pediatric heart transplantation: Comparison to standard criteria patients

United Network for Organ Sharing (UNOS) policy enables listing exceptions to avoid penalizing patients with waitlist mortality not captured by standard criteria. Outcomes among patients listed by exception have not been analyzed. We performed a retrospective analysis of pediatric (≤17 years of age, n = 4,706) listings (2006 to 2015) for primary, isolated heart transplantation within the UNOS data set, assessing Status 1A exception (n = 211, 4.5%) use across regions and patient characteristics and evaluating waitlist outcomes compared with candidates listed using standard criteria. Death or removal for reason other than transplant did not differ between exception and standard criteria patients at 1 month (11.7% vs 16.2%, p = not statistically significant [NS]), 2 months (18.2% vs 29.0%, p = 0.11) or overall (16.1% vs 22.0%, p = NS) on the waitlist. Rates were higher than among Status 1B patients (1 month: 2.8%; 2 months: 5.6%; overall: 14.9%; p < 0.0001). The cumulative incidence of competing risks (transplantation, death/removal for reasons other than transplant and removal) did not differ when comparing Status 1A exception patients with Status 1A standard criteria patients. Use of 1A exceptions varied across UNOS regions (1.9% to 22.3%, p < 0.0001). Risk-adjusted modeling identified patients more (hypertrophic cardiomyopathy: odds ratio [OR] = 2.8, 95% confidence interval [CI] 1.5 to 5.0; restrictive cardiomyopathy: OR = 2.7, 95% CI 1.7 to 4.3) and less (low socioeconomic status: OR = 0.7, 95% CI 0.5 to 1.0) likely to use an exception. Use of exceptions was uncorrelated with regional outcomes. Waitlist mortality among Status 1A exception patients is similar to that among those listed by standard criteria. However, variation in exception use across geography and demography may contribute to inequities in access to transplantation, particularly for those with low socioeconomic status. Standardization of practices may decrease regional variation and minimize inequities.

The Effect of Bridging Locoregional Therapy and Sociodemographics on Survival in Hepatocellular Carcinoma Patients Undergoing Orthotopic Liver Transplantation: A United Network for Organ Sharing Population Study

PurposeTo investigate socioeconomic and demographic factors associated with transplantation outcomes in patients with hepatocellular carcinoma (HCC) treated with bridging locoregional therapy (LRT) before orthotopic liver transplantation (OLT). Materials and MethodsThe United Network for Organ Sharing (UNOS) database was used to identify all patients in the United States with HCC who were listed for OLT between 2002 and 2013. Mean overall survival (OS) after OLT was stratified based on age, sex, ethnicity, transplant year, region, and insurance status. Kaplan-Meier estimation was used for survival analysis with log-rank test and Cox proportional hazards model to assess independent prognostic factors for OS. ResultsOf the 17,291 listed patients with HCC, 14,511 underwent OLT. Mean age was 57.4 years (76.8% male). Favorable sociodemographic factors were associated with increased rates of bridging LRT before OLT and longer wait time on the transplant list and were shown to be independent prognostic factors for prolonged OS after OLT using multivariate analysis. Favorable demographic factors included patient age < 60 years, donor age < 45 years, year of diagnosis between 2008 and 2013, UNOS regions 4 and 5, Asian ethnicity, high functional status, postgraduate education, private payer insurance, and employment at the time of OLT. ConclusionsPatients with favorable sociodemographics had higher rates of LRT before OLT performed for HCC cure. These patients had longer transplant wait times and longer OS after OLT.

Insurance status by region at the time of heart transplantation: Implications for survival

Heart transplantation outcomes differ by health insurance status and geographic region of the United States. We hypothesized that heart transplantation survival would be affected by health insurance status within certain United Network for Organ Sharing (UNOS) regions. We used data from the UNOS thoracic database to classify health insurance status into private or public (private/self-pay or Medicare/Medicaid) for all first-time heart transplant recipients between July 2006 and September 2013. We applied Cox proportional hazards regression to estimate hazard ratio (HR) and 95% confidence interval (CI) for the influences of health insurance status on 1-year and long-term survival in heart transplant recipients by UNOS region. Mean survival time among 10,474 patients was 942 days ± 704. All key demographic and clinical variables varied significantly across UNOS regions. With respect to 1-year survival, patients in Region 2 had a higher hazard of mortality (HR, 1.49; 95% CI, 1.03, 2.15) if they had public vs private insurance. When we restricted the analysis to be conditional on 1-year survival, 2 contiguous regions, Region 10, including Indiana, Ohio, Michigan (HR, 2.30; 95% CI, 1.23, 4.28), and Region 11 (HR, 1.85; 95% CI, 1.15, 2.97), including the upper South, had poor survival associated with public vs private insurance. The data we present invite targeted efforts by certain UNOS regions to improve the standard of care and/or eligibility thresholds for heart transplant recipients.

Racial disparities in reaching the renal transplant waitlist: is geography as important as race?

In the United States, African Americans and whites differ in access to the deceased donor renal transplant waitlist. The extent to which racial disparities in waitlisting differ between United Network for Organ Sharing (UNOS) regions is understudied. The US Renal Data System (USRDS) was linked with US census data to examine time from dialysis initiation to waitlisting for whites (n = 188,410) and African Americans (n = 144,335) using Cox proportional hazards across 11 UNOS regions, adjusting for potentially confounding individual, neighborhood, and state characteristics. Likelihood of waitlisting varies significantly by UNOS region, overall and by race. Additionally, African Americans face significantly lower likelihood of waitlisting compared to whites in all but two regions (1 and 6). Overall, 39% of African Americans with ESRD reside in Regions 3 and 4--regions with a large racial disparity and where African Americans comprise a large proportion of the ESRD population. In these regions, the African American-white disparity is an important contributor to their overall regional disparity. Race remains an important factor in time to transplant waitlist in the United States. Race contributes to overall regional disparities; however, the importance of race varies by UNOS region.

Long-Term Outcomes of Pancreas After Kidney Transplantation in Small Centers: Is It Justified?

BackgroundCurrently, the long-term advantages of having a pancreas transplantation (PT) are debated, particularly in patients receiving pancreas after kidney (PAK) allografts. The United Network for Organ Sharing (UNOS) requires that a transplant center perform a minimum number of PT per year to remain an active PT center. The long-term outcomes and challenges of PAK in small pancreas transplant centers are not well studied. MethodsIn this retrospective analysis, we report short- and long-term outcomes in a small center performing 2–9 PT annually. ResultsForty-eight PT (25 simultaneous pancreas and kidney transplantation [SPK], 23 PAK) were performed in our center. Donor and recipient demographics were similar in both groups. All suitable local donors were used for SPK. All organs for PAK transplantation were imported from other UNOS regions. Mean follow-up was 61 ± 46 and 74 ± 46 months for SPK and PAK, respectively. Patient and graft survival rates were similar in SPK and PAK groups and better than the reported national average. Four patients (11%) died (1 due to trauma, 1 brain lymphoma, 1 ruptured aneurysm; and 1 unknown cause). Two patients (4%; 1 SPK, 1 PAK) lost their grafts because of thrombosis on postoperative days 3 and 5 in 2002. No graft thrombosis occurred since 2002. Seven patients (15%) required reoperation (4 for bleeding, 2 anastomotic leaks, 1 small bowel perforation). Two patients (4%) developed post-transplantation lymphoproliferative disease. Five patients (11%) experienced cytomegalovirus antigenemia which responded well to antiviral therapy. ConclusionsCompared with outcomes for diabetic patients on dialysis, current SPK and PAK short- and long-term results are favorable even in a small PT center. Therefore, unless there is a contraindication, PT should be offered to all type 1 diabetic patients with end-stage renal disease at the time of kidney transplantation or afterward.

Hilar Cholangiocarcinoma: No Longer Hopeless

Cholangiocarcinoma affecting the bifurcation of the common hepatic duct is a devastating disease. Surgical resection is standard therapy, but tumor involvement of vascular and biliary structures in the hilus of the liver often preclude a margin-free resection with preservation of viable liver. During the 1980s, it was thought that liver transplantation would overcome the aforementioned barriers to resection and achieve success in the treatment of unresectable hilar cholangiocarcinoma. The entire tumor can be removed with the liver, including involved vascular and biliary structures, which are simply replaced by implantation of a donor liver. Unfortunately, liver transplantation did not achieve results good enough to justify use of scarce donor livers [1], and hilar cholangiocarcinoma became recognized as a contraindication for liver transplantation. The University of Nebraska attempted to overcome the limitations of transplantation by treating patients with high dose brachytherapy prior to transplantation [2]. Complications from the brachytherapy were prohibitive, but there was an excellent tumor response. Our team at Mayo Clinic Rochester refined this approach and cautiously moved forward with a neoadjuvant therapy protocol that included high-dose external beam therapy, lower dose brachytherapy, and chemosensitization with 5-FU. We proposed that liver transplantation—after careful selection of patients with early stage disease, neoadjuvant therapy, and operative staging—could achieve reasonable survival. We reported our initial results with treatment of 19 patients between 1993 and 2000 [3]. Twelve underwent transplantation with 100 % survival at a median follow-up of 44 months. Since that time, other centers have implemented identical or similar protocols and achieved comparable success. The United Network for Organ Sharing (UNOS) adopted the Mayo Clinic approach, including diagnostic and selection criteria, for MELD (Model for End-stage Liver Disease) exception guidelines [4] and policies. Most commercial insurance plans will cover this treatment, and the CMS (Center for Medicare Services) recently agreed to provide reimbursement as well. In this issue of Digestive Diseases and Sciences, Salgia et al. [5] from the University of Michigan report their findings from a study of the US experience with liver transplantation for cholangiocarcinoma using the US Scientific Registry of Transplant Recipients (SRTR) database. They associate an improvement in patient survival after transplantation with publication of the initial results from Mayo Clinic Rochester in 2000. Their key findings are: (1) national results with liver transplantation for cholangiocarcinoma showed significant improvement after 2000; (2) there were no differences in survival between UNOS regions; (3) the number of transplants for cholangiocarcinoma increased after 2000. They also report that survival was favorably associated with acute cellular rejection. These findings validate the Mayo Clinic protocol, highlight the value of a national registry study, and also demonstrate the limitations of a registry study. Does this report validate the Mayo Clinic protocol? The authors report a significant improvement in survival after 2000 (Figure 4), the time of publication of our initial results. Their study included 595 patients registered for transplantation and 359 transplanted with a diagnosis of cholangiocarcinoma between October 1987 and May 2008. During that time, Mayo Clinic Rochester registered 163 C. B. Rosen (&) Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA e-mail: Rosen.Charles@mayo.edu