Procurement Biopsy Research Articles

Arterial Intimal Fibrosis in Reperfusion Biopsy Correlates with Graft Function after Kidney Transplant

Introduction: Alterations to the procurement biopsy are one of the main reasons that kidneys are not suitable for transplant and are discarded. The literature on procurement and reperfusion biopsy is inconsistent and heterogeneous. The objective of this study is to describe the correlation of the different histological characteristics detected by the procurement and reperfusion biopsies in relation to graft function. Methods: This is a retrospective cohort study of deceased donor kidney transplants performed from 2013 to 2017. All of the different histological components of procurement and reperfusion biopsies were analyzed with nonparametric tests and multivariate regressions. Graft function was expressed as glomerular filtration rate (GFR) at 1, 3, 6, and 12 months after transplant. All tests were based on a level of significance of α = 0.05. Results: A comparison of procurement and reperfusion biopsies revealed that 60.4% of the grafts exhibited more arterial intimal fibrosis and 55.6% more arteriolar hyalinosis in the reperfusion biopsy than in the procurement biopsy. Arterial intimal fibrosis in reperfusion biopsy correlated with GFR at all time points, and it was the only histological characteristic of the reperfusion biopsy that remained significant in multivariate analysis. Glomerulosclerosis in the procurement biopsy correlated with graft function and remained significant in multivariate analysis, but only at 6 months. Arterial intimal fibrosis in the reperfusion biopsy is significantly associated with graft function independently of clinical characteristics. Conclusion: Our study highlights the importance of arterial intimal fibrosis in predicting kidney function after transplant. Because arterial intimal fibrosis is a chronic change not related to ischemia-reperfusion injury, the differences between the 2 biopsies may be due to the biopsy technique. In order to increase the prognostic accuracy of the procurement biopsy, the technique should be improved to better evaluate the vasculature.

Procurement Biopsies Can Predict Unfavorable Outcomes in Kidneys With Low MAPI Score Values

BackgroundThere are few reports about the usefulness of Maryland Aggregate Pathology Index (MAPI) score in procurement biopsies. This study aimed to evaluate the association between histopathological analysis according to MAPI and unfavorable outcomes in the first year after kidney transplantation (KT). MethodsThis retrospective study included deceased-donor KT patients whose grafts were biopsied before transplantation and had low MAPI scores (<8) in frozen sections (FSs). Paraffin sections (PSs) were analyzed after KT. MAPI parameters were global glomerulosclerosis in more than 15% (2 patients), periglomerular fibrosis (4 patients), wall-lumen ratio of arteries >0.5 (2 patients), arteriolar hyalinosis (4 patients), and interstitial scar (3 patients). Multivariable models were used to analyze risk factors for delayed graft function (DGF), prolonged DGF, inferior renal function, and graft loss (P < .05). ResultsOne hundred fifty-nine KTs were included. Donors (n = 120) were predominantly men (70%) and young adults (37.68 ± 12.50 years old) who suffered a traumatic death (55.8%). Recipients were predominantly men (62.26%) and adults (45.70 ± 15.80 years old) with kidney disease of unknown etiology (39.6%). Low rates of agreement between FS and PS were observed for all MAPI criteria, with kappa values ranging from 0.28 to 0.51. Using FS, no histologic parameter was independently associated with outcomes. After adjustment, glomerulosclerosis was an independent risk factor for prolonged DGF (odds ratio = 6.18: 95% confidence interval, 1.27-30.18) and wall-lumen ratio >0.5 for inferior renal function at 1 year (odds ratio = 4.08; 95% confidence interval, 1.21-13.76). ConclusionProcurement biopsies can be useful to predict inferior outcomes even in kidneys with low MAPI scores.

Impact of Deceased Donor Kidney Procurement Biopsy Technique on Histologic Accuracy

IntroductionThe factors that influence deceased donor kidney procurement biopsy reliability are not well established. We examined the impact of biopsy technique and pathologist training on procurement biopsy accuracy.MethodsWe retrospectively identified all deceased donor kidney-only transplants at our center from 2006 to 2016 with both procurement and reperfusion biopsies performed and information available on procurement biopsy technique and pathologist (n = 392). Biopsies were scored using a previously validated system, classifying “suboptimal” histology as the presence of at least 1 of the following: glomerulosclerosis ≥11%, moderate/severe interstitial fibrosis/tubular atrophy, or moderate/severe vascular disease. We calculated relative risk ratios (RRR) to determine the influence of technique (core vs. wedge) and pathologist (renal vs. nonrenal) on concordance between procurement and reperfusion biopsy histologic classification.ResultsA total of 171 (44%) procurement biopsies used wedge technique, and 221 (56%) used core technique. Results of only 36 biopsies (9%) were interpreted by renal pathologists. Correlation between procurement and reperfusion glomerulosclerosis was poor for both wedge (r2 = 0.11) and core (r2 = 0.14) biopsies. Overall, 34% of kidneys had discordant classification on procurement versus reperfusion biopsy. Neither biopsy technique nor pathologist training was associated with concordance between procurement and reperfusion histology, but a larger number of sampled glomeruli was associated with a higher likelihood of concordance (adjusted RRR = 1.12 per 10 glomeruli, 95% confidence interval = 1.04−1.22).ConclusionsBiopsy technique and pathologist training were not associated with procurement biopsy histologic accuracy in this retrospective study. Prospective trials are needed to determine how to optimize procurement biopsy practices.

A call to action: Feasible strategies to reduce the discard of transplantable kidneys in the United States

Changes to the United States kidney allocation system targeted at reducing organ discard have failed to improve organ utilization. High Kidney Donor Profile Index kidneys continue to be discarded at high rates as a result of the regulatory and financial barriers to widespread utilization of these organs. However, there are potential changes to clinical practice that could improve organ utilization. Expediting the time from initial offer to final organ acceptance would reduce cold ischemic time and should improve utilization. Implementation of procurement biopsy standards to avoid biopsy of low risk organs may prevent organ discards due to inaccurate data or excessive cold ischemia time. Further, standardization of procurement biopsy pathological interpretation coupled with electronic accessibility would enable early acceptance of difficult to transplant organs. These changes to allocation practice patterns are vital given proposals to expand the geographic sharing of deceased donor kidneys. Implementation of new allocation policies must be evaluated to ensure they result in higher transplant rates and acceptable post-transplant outcomes.

Reproducibility of Deceased Donor Kidney Procurement Biopsies.

Unfavorable histology on procurement biopsies is the most common reason for deceased donor kidney discard. We sought to assess the reproducibility of procurement biopsy findings. We compiled a continuous cohort of deceased donor kidneys transplanted at our institution from 1/1/2006 to 12/31/2016 that had at least one procurement biopsy performed, and excluded cases with missing biopsy reports and those used in multiorgan transplants. Suboptimal histology was defined as the presence of advanced sclerosis in greater than or equal to one biopsy compartment (glomeruli, tubules/interstitium, vessels). We calculated κ coefficients to assess agreement in optimal versus suboptimal classification between sequential biopsy reports for kidneys that underwent multiple procurement biopsies and used time-to-event analysis to evaluate the association between first versus second biopsies and patient and allograft survival. Of the 1011 kidneys included in our cohort, 606 (60%) had multiple procurement biopsies; 98% had first biopsy performed at another organ procurement organization and their second biopsy performed locally. Categorical agreement was highest for vascular disease (κ=0.17) followed by interstitial fibrosis and tubular atrophy (κ=0.12) and glomerulosclerosis (κ=0.12). Overall histologic agreement (optimal versus suboptimal) was κ=0.15. First biopsy histology had no association with allograft survival in unadjusted or adjusted analyses. However, second biopsy optimal histology was associated with a higher probability of death-censored allograft survival, even after adjusting for donor and recipient factors (adjusted hazard ratio, 0.50; 95% confidence interval, 0.34 to 0.75; P=0.001). Deceased donor kidneys that underwent multiple procurement biopsies often displayed substantial differences in histologic categorization in sequential biopsies, and there was no association between first biopsy findings and post-transplant outcomes.

Can Behavioral Research Improve Transplant Decision-Making? A Mock Offer Study on the Role of Kidney Procurement Biopsies.

The use of procurement biopsies for assessing kidney quality has been implicated as a driver of the nearly 20% kidney discard rate in the United States. Yet in some contexts, biopsies may boost clinical confidence, enabling acceptance of kidneys that would otherwise be discarded. We leveraged a novel organ offer simulation platform to conduct a controlled experiment isolating biopsy effects on offer acceptance decisions. Between November 26 and December 14, 2018, 41 kidney transplant surgeons and 27 transplant nephrologists each received the same 20 hypothetical kidney offers using a crossover design with weekend "washout" periods. Mini-study 1 included four, low serum creatinine (<1.5 mg/dl) donor offers with arguably "poor" biopsy findings that were based on real offers that were accepted with successful 3-year recipient outcome. For each of the four offers, two experimental variants-no biopsy and "good" biopsy-were also sent. Mini-study 2 included four AKI offers with no biopsy, each having an offer variant with "good" biopsy findings. Among low serum creatinine donor offers, we found approximately threefold higher odds of acceptance when arguably poor biopsy findings were hidden or replaced with good biopsy findings. Among AKI donor offers, we found nearly fourfold higher odds of acceptance with good biopsy findings compared with no biopsy. Biopsy information had profound but variable effects on decision making: more participants appeared to have been influenced by biopsies to rule out, versus rule in, transplantable kidneys. The current use of biopsies in the United States appears skewed toward inducing kidney discard. Several areas for improvement, including reducing variation in offer acceptance decisions and more accurate interpretation of findings, have the potential to make better use of scarce, donated organs. Offer simulation studies are a viable research tool for understanding decision making and identifying ways to improve the transplant system.

No Time to Wait: Optimizing Use of Deceased Donor Kidneys.

The critical shortage of organs available for transplantation is now well recognized, with individual transplant centers responsible for managing ever-growing lists of patients awaiting an offer for a kidney that will improve their quality of life and survival. What is less known, particularly to

Variation in use of procurement biopsies and its implications for discard of deceased donor kidneys recovered for transplantation.

The use of procurement biopsies in deceased donor kidney acceptance is controversial. We analyzed Scientific Registry of Transplant Recipients data (n=59328 allografts, 2014-2018) to describe biopsy practices across US organ procurement organizations (OPOs) and examine relationships with discards, using hierarchical modeling to account for OPO and donor factors. Median odds ratios (MORs) provide the median of the odds that allografts with identical reported traits would be biopsied or discarded from 2 randomly drawn OPOs. Biopsies were obtained for 52.7% of kidneys. Biopsy use rose in a graded manner with kidney donor profile index (KDPI). Biopsy rates differed significantly among OPOs (22.8% to 77.5%), even after adjustment for KDPI and other donor factors. Discard rates also varied from 6.6% to 32.1% across OPOs. After adjustment for donor factors and OPO, biopsy was associated with more than 3 times the likelihood of discard (adjusted odds ratio [95%LCL aOR95%UCL ], 3.29 3.513.76 ). This association was most pronounced for low-risk (KDPI<20) kidneys (aOR, 5.45 6.477.69 ), with minimal impact at KDPI>85 (aOR, 0.88 1.151.51 ). Adjusted MORs for kidney discard and biopsy were greatest for low-risk kidneys. Reducing the rate of unnecessary biopsy and improving the accuracy of histologic assessments in higher KDPI organs may help reduce graft discard rates.

Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation.

BackgroundDespite careful clinical examination, procurement biopsy and assessment on hypothermic machine perfusion, a significant number of potentially useable deceased donor kidneys will be discarded because they are deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may be useful as a means to further assess high-risk kidneys to determine suitability for transplantation.MethodsFrom June 2014 to October 2015, 7 kidneys (mean donor age, 54.3 years and Kidney Donor Profile Index, 79%) that were initially procured with the intention to transplant were discarded based on a combination of clinical findings, suboptimal biopsies, long cold ischemia time (CIT) and/or poor hypothermic perfusion parameters. They were subsequently placed on EVNP using oxygenated packed red blood cells and supplemental nutrition for a period of 3 hours. Continuous hemodynamic and functional parameters were assessed.ResultsAfter a mean CIT of 43.7 hours, all 7 kidneys appeared viable on EVNP with progressively increasing renal blood flow over the 3-hour period of perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid increase in blood flow to 200 to 250 mL/min, urine output of 40 to 260 mL/h and increasing creatinine clearance.ConclusionsFavorable perfusion characteristics and immediate function after a 3-hour course of EVNP suggests that high-risk kidneys subjected to long CIT may have been considered for transplantation. The combined use of ex vivo hypothermic and normothermic perfusion may be a useful strategy to more adequately assess and preserve high-risk kidneys deemed unsuitable for transplantation. A clinical trial will be necessary to validate the usefulness of this approach.

Is preimplantation renal biopsy essential prior to deceased donor renal transplant?

The striking discrepancy in the number of end-stage renal disease patients added to the transplant wait list and the shortage of standard criteria donors has stimulated the development of strategies aimed to expand acceptance criteria from marginal deceased donors. Renal biopsy done before transplant will be useful to predict short- and long-term outcomes of kidney transplantation. It also serves as a reference in interpretation of subsequent biopsies. It also helps in deciding whether it should be discarded. However, systemic reviews concluded that there was no consistent association between donor biopsy findings and posttransplant outcomes. A well-designed randomized control trial could ascertain the extent of procurement biopsy leading to discards, whether outcomes are indeed better when preimplantation biopsies are used to justify declining kidneys for transplantation.

Procurement Biopsies in the Evaluation of Deceased Donor Kidneys.

Biopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial. We compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (n=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (n=116 kidneys). For kidneys on which more than one procurement biopsy was performed (n=116), category agreement was found in only 64% of cases (κ=0.14). For all kidneys (n=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (κ=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (κ=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (κ=0.13) and 80% (κ=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure. We found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes.

Procurement Biopsy Findings Versus Kidney Donor Risk Index for Predicting Renal Allograft Survival.

Efforts to maximize transplantation by matching organ quality to recipient longevity require reliable tools. The US kidney allocation system uses the Kidney Donor Risk Index (KDRI) for this purpose, and many centers additionally rely on donor biopsies. The Leuven score combines donor age with procurement histology (glomerulosclerosis and interstitial fibrosis/tubular atrophy) to predict allograft survival. We compared KDRI with Leuven scores for associations with kidney discard, delayed graft function, and allograft function and survival. We used Cox, modified Poisson, and linear regression to calculate risks based on KDRI and (separately) Leuven scores, adjusting for important transplant and recipient variables. From 890 donors, 1729 kidneys were procured and biopsied. Five hundred eighty-five (34%) kidneys were discarded. Median donor age was 53 years (interquartile range [IQR], 44-61 years). Median KDRI and Leuven scores were 1.56 (IQR, 1.28-1.90) and 59 (IQR, 49-69). Relative risk for discard was 1.21 (95% confidence interval [CI], 1.17-1.24) per 0.2-unit increase in KDRI and 1.38 (1.31-1.46) per 10-unit increase in Leuven score. Adjusted relative risks for delayed graft function were 0.98 (95% CI, 0.94-1.02) and 0.94 (95% CI, 0.90-0.99), adjusted hazard ratios for graft failure were 1.10 (95% CI, 1.04-1.16) and 1.11 (95% CI, 1.02-1.21), and adjusted linear regression coefficients for 3-year estimated glomerular filtration rate were -3.88 (-4.63 to -3.13) and -5.18 (-6.19 to -4.18). In kidneys clinically selected for procurement biopsy, the Leuven score was more strongly associated with discard but performed similarly to KDRI for predicting transplant outcomes, suggesting the need to reevaluate current procurement biopsy practices. Given modest associations for both tools; however, neither KDRI nor the Leuven score should be used in isolation for individual organ acceptance decisions.

Limitation of Terminal Serum Creatinine as a Kidney Donor Profile Index Variable in Predicting Long-Term Kidney Transplant Outcomes

BackgroundDonor final serum creatinine (SCr) is a dynamic variable and is 1 of 10 factors used in calculating kidney donor profile index (KDPI). We hypothesize that deceased-donor kidneys (DDKs) with higher SCr were likely accepted for transplantation if procurement biopsy findings were favorable and with long-term outcomes no worse than kidneys with lower final SCr within a KDPI group. MethodsUsing the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified DDK transplant recipients from 2000 to 2015 who received induction and calcineurin inhibitor/mycophenolate mofetil maintenance. Patients were divided into 4 KDPI groups: 0–20%, 21%–50%, 51%–85%, and >85%. In each KDPI category, long-term outcomes were compared, with the use of Cox models, between patients who received kidneys with final SCr >2 versus ≤2 mg/dL. ResultsA total of 59,644 patients were divided into KDPI groups 0–20% (SCr >2 mg/dL, n = 478; SCr ≤2 mg/dL, n = 14,769), 21%–50% (SCr >2 mg/dL, n = 1,592; SCr ≤2 mg/dL, n = 17,762), 51%-85% (SCr >2 mg/dL; n = 1,388, SCr ≤2 mg/dL, n = 18,024), and >85% (SCr >2 mg/dL, n = 349; SCr ≤2 mg/dL, n = 5,282). Adjusted overall graft failure risks (hazard ratio [HR] 0.88, P = .04; HR, 0.86, P = .007) and patient death risks (HR, 0.86, P = .04; HR, 0.84, P = .01) for final SCr >2 versus ≤2 mg/dL groups were lower in KDPI categories 21%-50% and 51%-85%, respectively, with similar death-censored graft failure risks. DiscussionOutcomes of transplanting DDKs with elevated final SCr are no worse than transplanting kidneys with lower final SCr, highlighting the limitation of the single value of final SCr as a variable for calculating KDPI.

YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation

Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m2) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant.

The Role of Procurement Biopsies in Acceptance Decisions for Kidneys Retrieved for Transplant

There is a shortage of kidneys for transplant, and many patients on the deceased donor kidney transplant waiting list would likely benefit from kidneys that are currently being discarded. In the United States, the most common reason given for discarding kidneys retrieved for transplant is procurement biopsy results. This study aimed to compare biopsy results from discarded kidneys with discard attributed to biopsy findings, with biopsy results from comparable kidneys that were successfully transplanted. In this retrospective, observational, case-control study, biopsy reports were examined from 83 kidneys discarded in 2010 due to biopsy findings (cases), 83 contralateral transplanted kidneys from the same donor (contralateral controls), and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls). A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). The quality of biopsy reports was low, with amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis often not indicated; 69% were wedge biopsies and 94% used frozen tissue. The correlation between first and second procurement biopsies was poor; only 25% of the variability (R(2)) in glomerulosclerosis was explained by biopsies being from the same kidney. The percentages of glomerulosclerosis overlapped substantially between cases, contralateral controls, and randomly matched controls: 17.1%±15.3%, 9.0%±6.6%, and 5.0%±5.9%, respectively. Of all biopsy findings, only glomerulosclerosis>20% was independently correlated with discard (cases versus contralateral controls; odds ratio, 15.09; 95% confidence interval, 2.47 to 92.41; P=0.003), suggesting that only this biopsy result was used in acceptance decisions. One-year graft survival was 79.5% and 90.7% in contralateral and randomly matched controls, respectively, versus 91.6% among all deceased donor transplants in the Scientific Registry of Transplant Recipients. Routine use of biopsies could lead to unnecessary kidney discards.

Abstract 4499: Loss of ATM (distal chromosome 11q) as a prognostic marker in HPV-negative head and neck squamous cell carcinomas

Abstract Introduction: HPV-negative head and neck squamous cell carcinomas (HNSCC) represent a subset of head and neck cancers with poor response to treatment and worse prognosis compared to HPV-positive HNSCC. In our prior pre-clinical experiments with HNSCC cell lines, we demonstrated that copy number loss of ATM as a marker for loss of distal chromosome 11q loss leads to defectiveγ-H2AX focus formation, increased chromosomal instability, and reduced sensitivity to ionizing radiation. We hypothesize that in HPV-negative HNSCC, ATM loss is a biomarker for poor outcome. Methods: We performed a single center, retrospective analysis of 42 HNSCC patients to determine if ATM loss is associated with poor overall survival in HPV-negative HNSCC. We performed fluorescence in situ hybridization using probes to cyclin D1 (CCND1) and ATM to assess copy number changes in paraffin sections from HNSCC tumors. Disease-specific survival was defined as time from the date of tissue procurement (surgery or biopsy) until death from disease (HNSCC). Patients who were alive at last follow-up or had died from causes unrelated to their disease were censored. Disease-specific survival by ATM loss status was estimated by the Kaplan-Meier method and tested for a difference by a two-tailed log rank test. Three covariates, age, T stage and N stage were investigated and the effect of ATM loss upon disease-specific survival was assessed with proportional hazards regression by adjusting for these covariates as needed to determine if ATM loss could be considered independently associated with cancer mortality. Results and Conclusions: HPV-negative HNSCC patients with ATM copy number loss have a median disease-specific survival of only 19 months compared to 65 months for patients without ATM loss (log rank p = .0401). We investigated whether the association between ATM loss and disease-specific survival was due to the confounding influence of other clinical variables. Age and T stage were modestly associated with survival, but neither covariate was correlated with ATM loss. We estimated the hazard ratio for ATM loss alone and conditional upon age and T stage was unchanged (.040 alone vs .047 adjusting for age and T stage). Therefore, distal 11q loss, marked by copy number loss of ATM appears to increase the risk of disease-specific mortality independently of age, N stage and T stage. Our results demonstrate that ATM loss in HPV-negative HNSCC may be prognostic of poor outcome and novel therapeutic strategies may be required in this subset of patients. Further studies to elucidate the mechanisms of distal 11q loss and study potential treatment options are underway in our laboratory. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4499. doi:1538-7445.AM2012-4499

Utility of liver allograft biopsy obtained at procurement

Extended-donor criteria (EDC) liver allografts potentiate the role of procurement biopsy in organ utilization. To expedite allocation, histologic evaluation is routinely performed upon frozen-section (FS) specimens by local pathologists. This descriptive study compares FS reports by local pathologists with permanent-section (PS) evaluation by dedicated hepatopathologists, identifies histologic characteristics underrepresented by FS evaluation, and evaluates the efficacy of a biopsy decision analysis based on organ visualization. Fifty-two liver transplants using EDC allografts evaluated by FS with PS were studied. Pathologic worksheets created by an organ procurement organization were applied in 34 FS. PS analysis included 7 staining procedures for 8 histologic criteria. PS from 56 additional allografts determined not to require donor biopsy were also analyzed. A high correlation was observed between FS and PS. Underestimation of steatosis by FS was associated with allograft dysfunction. Surgical assessment of cholestasis, congestion, and steatosis was accurate whereas inflammation, necrosis, and fibrosis were underestimated in allografts suffering parenchymal injury. In conclusion, the correlation between FS and PS is high, and significant discrepancies are rare. Biopsy is not a prerequisite for EDC utilization but is suggested in hepatitis C, hypernatremia, donation after cardiac death, or multiple EDC indications. Implementation of a universal FS worksheet could standardize histologic reporting and facilitate data collection, allocation, and research.

Cytokine Gene Expression in Kidney Allograft Biopsies After Donor Brain Death and Ischemia-Reperfusion Injury Using In Situ Reverse-Transcription Polymerase Chain Reaction Analysis

This study focuses on the cytokine genes expression after brain-death, ischemia-reperfusion injury, and during allograft rejection. A total of 49 needle core biopsies from kidney transplant recipients, performed before and during transplantation procedures were studied. The first biopsy was taken during procurement of the organ, the second after cold ischemia, and the third after approximately 30 min of reperfusion. We also assessed 34 allograft biopsies obtained during acute rejection. Tubular and glomerular expression of interferon (IFN)-gamma, transforming growth factor (TGF)-beta1, platelet-desired growth factor-B (PDGF-B), interleukin (IL)-2, IL-6, IL-10 mRNA was analyzed with reverse-transcription polymerase chain reaction (RT-PCR) in situ technique, which allows to detect a few copies of the target gene without destruction of the tissue architecture. Compared with normal kidney tissue from living donor, high gene expression of IFN-gamma, TGF-beta1, PDGF-B, IL-2, IL-6, and IL-10 was detected in all procurement specimens. After reperfusion gene expressions of IL-2, IL-6, and IL-10 were significantly upregulated in renal tubules compared to biopsies taken after cold ischemia. The gene expression of IFN-gamma, TGF-beta1, and PDGF-B remained stable after organ procurement, during cold ischemia, and after reperfusion. Gene expression of IFN-gamma, IL-2, IL-6, IL-10, and PDGF-B in procurement biopsies, as well as in those taken after cold ischemia and reperfusion, were significantly higher than during the period of acute rejection. The data presented herein strongly point out the importance of the immunological and morphological injury that occurs before and during transplantation. The increase of inflammatory response after brain death is important for further stimulation of the immune response and long-term kidney survival.

Dual-kidney transplants: long-term results.

Dual-kidney transplantation, where two usually aged adult kidneys are placed into an adult recipient, is one way to help alleviate the continuing disparity between the number of patients on the kidney transplant waiting list and those who receive kidney transplants each year. The Dual Kidney Registry was developed to analyze donor and recipient data and outcomes at several centers. Two hundred eighty-seven patients who have undergone transplantation since 1994 have been entered into the relational database. The patients were followed yearly after initial entry into the database. The mean donor age was 58+/-13 years and the mean terminal creatinine clearance was 77+/-40 mL/min. The mean glomerular sclerosis on procurement biopsy was 16+/-13%. Delayed graft function (DGF), defined as dialysis in the first 7 days after transplantation, was a predictor of poor outcome, and increased cold storage time was a predictor of DGF. The overall incidence of DGF was 27%. In recipients with prompt graft function (PGF), the mean cold storage time was 22+/-9 hr versus 29+/-10 hr in recipients with DGF (P<0.001). The overall 1- and 5-year graft survival was 86% and 69%, respectively. The 1- and 5-year graft survival rates were significantly better in recipients with PGF (90% and 74%) versus DGF (79% and 54%) (P<0.002). Cold storage time and DGF have a significant impact on the 1- and 5-year graft survival in recipients of dual-kidney transplants. The 5-year graft survival in recipients of dual-kidney transplants is excellent.

Morphologic changes in renal procurement biopsy and onset of graft function

Morphologic changes in renal procurement biopsy and onset of graft function