Mitchell C. Posner

Management of the clinically inapparent adrenal mass ("incidentaloma").

The adrenals are triangular glands that sit atop each kidney. They influence or regulate the bodys metabolism, salt and water balance, and response to stress by secreting various hormones. Based on autopsy studies, adrenal masses are among the most common tumors in humans. At autopsy, an adrenal mass is found in at least 3% of persons older than age 50 years. Most adrenal masses cause no health problems. A small proportion, however, can lead to many serious hormonal diseases; approximately 1 of every 4000 adrenal tumors is malignant. Clinically inapparent adrenal masses are discovered inadvertently during diagnostic testing or treatment for other clinical conditions that are not related to suspicion of adrenal disease; thus, they are commonly known as incidentalomas. The definition of incidentaloma excludes patients undergoing imaging procedures as part of staging and work-up for cancer. Improvements in abdominal imaging techniques and technologies have increased detection of adrenal incidentalomas. Increasing clinical and scientific interest is reflected in a 20-fold increase in publications about this condition over the past three decades. When detected, clinically inapparent adrenal masses raise challenging questions for physicians and their patients. Diagnostic evaluation determines whether the lesion is hormonally active or nonfunctioning and whether it is malignant or benign. The test results will influence whether the mass is removed surgically or treated nonsurgically. Because the prevalence of these masses increases with age, appropriate management of adrenal tumors will be a growing challenge in our aging society. Over the past three decades, new information has become available regarding the epidemiology, biology, screening, treatment, and follow-up of adrenal tumors. For example, recent refinements in the field of minimally invasive surgery have made laparoscopic adrenalectomy a more frequently used method for removing adrenal masses. Recent reports suggest that up to 20% of patients with adrenal incidentaloma have some form of subclinical hormonal dysfunction and may represent a population at higher risk for metabolic disorders and cardiovascular disease. It is important to determine whether groups of patients with subclinical disease benefit from treatment. The psychological effect of the patients knowing that he or she harbors an adrenal incidentaloma, an incompletely understood clinical problem, merits investigation. A 2.5-day National Institutes of Health (NIH) state-of-the-science conference, Management of the Clinically Inapparent Adrenal Mass (Incidentaloma), was convened on 46 February 2002 to explore and assess the current knowledge regarding adrenal incidentalomas, so that health care providers and the general public can make informed decisions about this important public health issue. After 1.5 days of expert presentations and questions and public discussion by members of the panel and the audience of interested attendees on incidental adrenal masses, an independent, nonfederal panel weighed the evidence and drafted a statement that was presented on the third day of the conference. Expert presentations and the panels statement addressed the following questions: 1) What are the causes, prevalence, and natural history of clinically inapparent adrenal masses? 2) Based on available scientific evidence, what is the appropriate evaluation of a clinically inapparent adrenal mass? 3) What criteria should guide the decision on surgical versus nonsurgical management of these masses? 4) If surgery is indicated, what is the appropriate procedure? 5) What is the appropriate follow-up for patients for each management approach? and 6) What additional research is needed to guide practice? The panels draft statement was posted on the NIH Consensus Program Web site (consensus.nih.gov) on 6 February 2002. The primary sponsors of this meeting were the National Institute of Child Health and Human Development and the NIH Office of Medical Applications of Research. Cosponsors included the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. 1. What are the Causes, Prevalence, and Natural History of Clinically Inapparent Adrenal Masses? Clinically inapparent adrenal masses are detected incidentally with imaging studies conducted for other reasons. They may be clinically important because some are caused by adrenal cortical carcinomas (estimated prevalence, 4 to 12 per million), which have a high mortality rate. The other clinical concern is hormone overproduction from pheochromocytomas, aldosteronomas, and subclinical hypercortisolism, which may be associated with morbidity if untreated. Prevalence of Clinically Inapparent Adrenal Masses In autopsy series, the prevalence of clinically inapparent adrenal masses is about 2.1%. Because of increased use of noninvasive high-resolution imaging technology, clinically inapparent adrenal masses are being recognized more often. Estimates range from 0.1% for general health screening with ultrasonography to 0.42% among patients evaluated for nonendocrinologic symptoms to 4.3% among patients who have a previous diagnosis of cancer. In addition to source of data (autopsy versus clinical series) and reasons for imaging (cancer work-up, nonendocrinologic symptoms, and general health screening), the prevalence of clinically inapparent adrenal masses varies with age. The prevalence of clinically inapparent adrenal masses detected at autopsy is less than 1% for patients younger than 30 years of age and increases to 7% in patients 70 years of age or older. Many of these lesions detected at autopsy are very small. More patients with clinically inapparent adrenal masses are women. This probably reflects the sex distribution of the population undergoing imaging procedures. Autopsy studies or general health examinations show no evidence of difference in prevalence between men and women. There is insufficient information to determine whether the prevalence of clinically inapparent adrenal masses differs by the initial diagnostic test. Causes of Clinically Inapparent Adrenal Masses Clinically inapparent adrenal masses can be benign or malignant. These include adenomas, pheochromocytomas, myelolipomas, ganglioneuromas, adrenal cysts, hematomas, adrenal cortical carcinomas, metastases from other cancers, and other rare entities. The distributions of the pathologic origins of clinically inapparent adrenal masses vary with several clinically important factors, including cancer history and mass size. Three fourths of clinically inapparent adrenal masses among patients with cancer are metastatic lesions. In contrast, two thirds of clinically inapparent adrenal masses in populations with no history of cancer are benign tumors. Prevalence of primary adrenal cortical carcinoma is clearly related to the size of the tumor. Adrenal cortical carcinoma accounts for 2% of tumors that are 4 cm or less, 6% of tumors that are 4.1 to 6 cm, and 25% of tumors that are greater than 6 cm. Among unselected patients and those with nonendocrinologic symptoms, clinically inapparent adrenal masses are most often nonfunctioning tumors (approximately 70%). Approximately 5% to 10% of patients being evaluated for nonendocrinologic symptoms have subclinical hypercortisolism (sometimes called subclinical Cushing syndrome). The percentage of patients with subclinical hypercortisolism depends on the testing methods and cortisol levels achieved after dexamethasone suppression. The distribution of clinically inapparent adrenal masses derived from surgical series will overestimate the prevalence of adrenal cortical carcinoma, since suspicion of adrenal cortical carcinoma is an indication for surgery. Moreover, the reported frequency of adrenal cortical carcinomas is derived from highly selected patient populations and does not reflect the prevalence rates seen in population-based studies. The age and sex of the patient do not seem to help predict the presence of adrenal cortical carcinoma. Distribution estimates from autopsy studies are not biased by surgical indications but may not reflect the risk for adrenal cortical carcinoma among the subset of people undergoing abdominal imaging studies. A precise estimate of the risk for adrenal cortical carcinoma that could guide clinical decision making may not be possible. Almost all the reported large studies used imaging equipment that is now considered obsolete. The use of contemporary equipment may increase the prevalence of detected clinically inapparent adrenal masses and enhance our ability to differentiate adrenal cortical carcinomas from adenomas. In addition, the literature comprises mainly small, retrospective studies with variable definitions of clinically inapparent adrenal masses, which cause variation in the relative proportions of adrenal pathologic classifications. Natural History of Clinically Inapparent Adrenal Masses The observed natural history of clinically inapparent adrenal masses varies, depending on the composition of the study sample and the size and pathologic classification of the adrenal mass. Patients with or without a previous cancer diagnosis found to have adrenal gland metastatic lesions will have a clinical course defined by the stage, grade, and site of the primary tumor. Usually, large clinically inapparent adrenal masses (>6 cm) are treated surgically. Approximately 25% of masses greater than 6 cm in diameter are adrenal cortical carcinomas, and these patients have poor clinical outcomes. Most studies report less than 50% 5-year overall survival for adrenal cortical carcinoma, and several report less than 50% 2-year overall survival. Inconclusive evidence suggests that adrenalectomy at stage 1 or 2 may improve the survival rate. Follow-up of patients with nonfunctioning adrenal masses suggests that 5% to 25% of masses increase in size by at least 1 cm. The threshold for clinically significant

Phase II Trial of Intratumoral Administration of ONYX-015, a Replication-Selective Adenovirus, in Patients With Refractory Head and Neck Cancer

PURPOSE To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 x 10(11) particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation. RESULTS Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication > or = 22 days after injection. CONCLUSION ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested.

Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial

IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation. RESULTS Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7% of laparoscopic resection cases (95% CI, 76.8%-86.6%) and 86.9% of open resection cases (95% CI, 82.5%-91.4%) and did not support noninferiority (difference, -5.3%; 1-sided 95% CI, -10.8% to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3% of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95% CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95% CI, -0.6 to 1.1), readmission within 30 days (3.3% vs 4.1%; difference, -0.7%; 95% CI, -4.2% to 2.7%), and severe complications (22.5% vs 22.1%; difference, 0.4%; 95% CI, -4.2% to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5% of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3% open resection; P = .11). Distal margin result was negative in more than 98% of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00726622.

A prospective randomized trial of total parenteral nutrition after major pancreatic resection for malignancy.

ObjectivesThe authors examined the impact of adjuvant total parenteral nutrition after major pancreatic resection for malignancy. Summary Background DataPrevious studies have suggested a benefit to perioperative nutritional support for patients undergoing major gastrointestinal surgery. MethodsA prospective, randomized study was conducted using patients who had undergone a major pancreatic resection with randomization on postoperative day one to either receive or not receive adjuvant total parenteral nutrition. ResultsNo benefit could be demonstrated by the use of adjuvant parenteral nutrition in this setting. Complications were significantly greater in the group receiving total parenteral nutrition. These complications tended to be those associated with infection. ConclusionsRoutine applications of postoperative parenteral nutrition to patients undergoing major pancreatic resection for malignancy cannot be recommended. Further studies are required to determine the reason that infectious complications in these patients are increased.

Complete Barrett's Eradication Endoscopic Mucosal Resection: An Effective Treatment Modality for High-Grade Dysplasia and Intramucosal Carcinoma—An American Single-Center Experience

OBJECTIVES:Complete Barretts eradication endoscopic mucosal resection (CBE-EMR) is the endoscopic removal of all Barretts epithelium with the curative intent of eliminating high-grade dysplasia (HGD)/intramucosal carcinoma (IMC) and reducing the risk of metachronous lesion development. We report our single tertiary referral centers long-term clinical experience using this modality in HGD/IMC management.METHODS:In this study, we retrospectively reviewed all patients who had CBE-EMR for Barretts esophagus (BE) with HGD/IMC who had been entered into our centers prospectively collected database. High-definition white-light and narrow-band imaging examinations were used according to the protocol. Staging endoscopic ultrasound was done before CBE-EMR to exclude invasive disease or suspicious lymphadenopathy. High-dose proton pump inhibition was instituted after initial treatment, and Seattle-type surveillance biopsies were performed on follow-up every 6 months once the CBE-EMR procedure was completed.RESULTS:A total of 49 patients (mean age 67 years, median 65, s.d. 11; 75% men) with histologically confirmed BE and HGD (33), IMC (16), underwent CBE-EMR from August 2003 to August 2008. The mean BE segment length was 3.2 cm (median 2, s.d. 2.2); 26 patients had short-segment BE, and 30 had visible lesions. A total of 106 EMR procedures were performed. On initial EMR, two patients had superficial submucosal carcinoma invasion (sm1) and two had IMC with lymphatic channel invasion. All four patients were referred for esophagectomy, but one opted for continued endoscopic management, without evidence of residual or recurrent carcinoma. A total of 14 patients await completion of EMR (9) or first follow-up endoscopy (5). CBE-EMR therapy was completed in 32 patients by an average of 2.1 sessions (median 2, s.d. 0.9). Surveillance biopsies showed normal squamous epithelium in 31 of 32 (96.9%) patients (mean remission time 22.9 months, median 17, s.d. 16.7, interquartile range 11–38). In all, 10 of 46 patients who continued in the endoscopic protocol had subsquamous Barretts epithelium on EMR specimens and/or treatment endoscopy biopsies. Overall, 1 of these 10 patients had Barretts underneath squamous mucosa on most recent surveillance biopsies. CBE-EMR upstaged pre-EMR pathology results in 7 of 49 (14%) of patients and downstaged pathology in 15 of 49 (31%) patients. In all, 18 of 49 (37%) patients developed symptomatic esophageal stenosis after a mean of 24.4 days (median 13.5, s.d. 27.8); all were successfully managed by endoscopic treatment. No perforations or uncontrollable bleeding occurred.CONCLUSIONS:To our knowledge, this is the largest American single-center experience demonstrating that CBE-EMR with close endoscopic surveillance is an effective treatment modality for BE with HGD/IMC. Although the rate of stenosis development is significant, it is easily treated by endoscopic dilation. Patients considering endoscopic ablation should be counseled appropriately. The role of CBE-EMR in patients with lymphatic invasion or superficial submucosal invasion remains to be defined.

Future Directions in the Treatment of Neuroendocrine Tumors: Consensus Report of the National Cancer Institute Neuroendocrine Tumor Clinical Trials Planning Meeting

Neuroendocrine tumors (NETs) arise from a variety of anatomic sites and share the capacity for production of hormones and vasoactive peptides. Because of their perceived rarity, NETs have not historically been a focus of rigorous clinical research. However, the diagnosed incidence of NETs has been increasing, and the estimated prevalence in the United States exceeds 100,000 individuals. The recent completion of several phase III studies, including those evaluating octreotide, sunitinib, and everolimus, has demonstrated that rigorous evaluation of novel agents in this disease is both feasible and can lead to practice-changing outcomes. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trials planning meeting to identify key unmet needs, develop appropriate study end points, standardize clinical trial inclusion criteria, and formulate priorities for future NET studies for the US cooperative group program. Emphasis was placed on the development of well-designed clinical trials with clearly defined efficacy criteria. Key recommendations include the evaluation of pancreatic NET separately from NETs of other sites and the exclusion of patients with poorly differentiated histologies from trials focused on low-grade histologies. Studies evaluating novel agents for the control of hormonal syndromes should avoid somatostatin analog washout periods when possible and should include quality-of-life end points. Because of the observed long survival after progression of many patients, progression-free survival is recommended as a feasible and relevant primary end point for both phase III studies and phase II studies where a delay in progression is expected in the absence of radiologic responses.

Vascular endothelial growth factor enhances endothelial cell survival and tumor radioresistance.

PURPOSEVascular endothelial growth factor (VEGF) is an important mediator of endothelial cell proliferation and survival. The purpose of the present studies was to investigate the role of VEGF in the tumor response to ionizing radiation. METHODSTwo ras-transformed murinefibrosarcoma cell lines, VEGF+/+ and VEGF−/− were exposed to ionizing radiation (0, 1, 3, 5, 7 or 9 Gy) in vitro, and clonogenic survival was determined. VEGF+/+ and VEGF-\- xenografts were generated in athymic nude mice and then treated with ionizing radiation (ten 5-Gy fractions = 50 Gy). Mean fractional tumor volume was used to evaluate treatment efficacy. To determine whether VEGF enhances tumor radioresistance by targeting endothelial cells, we performed clonogenic survival assays with human umbilical vein endothelial cells. Surviving fractions were calculated after treatment with ionizing radiation (5 Gy) and recombinant hVEGF165 (0, 1, 10, and 100 ng/mL). To determine whether VEGF neutralization enhances tumor radio-sensitivity, we employed anti-VEGF165 monoclonal antibody to treat human tumor xenografts. Tumors were exposed to ionizing radiation (four 5-Gy fractions = 20 Gy) and treated with anti-VEGF antibody (0, 5, and 25 μg/kg in four intraperitoneal doses). Mean fractional tumor volume was used to evaluate treatment efficacy. To elucidate the molecular mechanism contributing to the observed anti-VEGF/ionizing radiation interaction, we exposed human umbilical vein endothelial cells to ionizing radiation (5 Gy) in the presence of anti-VEGF antibody (1 μg/mL). Sodium dodecyl sulfate polyacrylamide gel electrophoresis of cell lysates was probed for mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK1/MEK2). RESULTSThe in vitro radiosensitivities of the VEGF+/+ and VEGF−/− clones were equivalent (Do = 146 vs 149). However, the VEGF+/+ xenografts were more resistant to the cytotoxic effects of ionizing radiation than the VEGF−/− xenografts. VEGF+/+ xenografts demonstrated a faster doubling time (4.5 vs 6.0 days) and a shorter growth delay (15 vs 23 days) than VEGF−/− xenografts. The surviving fraction of human umbilical vein endothelial cells after exposure to ionizing radiation was significantly enhanced in the presence of VEGF (6.4% vs 12.5%). Western blot analysis demonstrated that stimulation of MAPK and MEK1/MEK2 was abrogated after exposure to anti-VEGF antibody. DISCUSSIONThese findings represent the first genetic evidence that factors other than inherent tumor cell radiosensitivity are important determinants of radiocurability. Antitumor strategies targeting VEGF and other endothelial cell survival mechanisms may be used to enhance the cytotoxic effects of radiotherapy.

Should internal mammary nodes be sampled in the sentinel lymph node era

BackgroundControversy exists regarding internal mammary lymph nodes (IMNs) in the staging and treatment of breast cancer. Sentinel lymph node identification with radiocolloid can map drainage to IMNs and directed biopsy can be performed with minimal morbidity. Furthermore, recent studies suggest that IMN drainage of breast tumors may be underestimated. To gain further insight into the prognostic value of IMNs, we reviewed the outcome of patients in whom the IMN status was routinely assessed.MethodsA retrospective review of 286 patients with breast cancer who underwent IMN dissection between 1956 and 1987 was conducted.ResultsMedian follow-up is 186 months, age was 52 years (range, 21–85 years), tumor size was 2.5 cm, and number of IMNs removed was 5 (range, 1–22); 44% received chemotherapy, 16% endocrine therapy, and 5% radiotherapy. Presence of IMN metastases correlated with primary tumor size (P<.0001) and number of positive axillary nodes (P<.0001) but did not correlate with primary tumor location or age. Overall, the 20-year disease-free survival is significantly worse for the 25% of patients with IMN metastases (P<.0001). In patients with positive axillary nodes and tumors smaller than 2 cm, there was a significantly worse survival (P<.0001) in the patients with IMN metastases. This difference in survival was not seen in women with tumors larger than 2 cm.ConclusionsPatients with IMN metastases, regardless of axillary node status, have a highly significant decrease in 20-year disease-free survival. Treatment strategies based on knowledge of sentinel IMN status may lead to improvement in survival, especially for patients with small tumors. At present, sentinel IMN biopsies should be performed in a clinical trial setting.

Progression of Barrett's Metaplasia to Adenocarcinoma Is Associated with the Suppression of the Transcriptional Programs of Epidermal Differentiation

We did expressional profiling on 24 paired samples of normal esophageal epithelium, Barretts metaplasia, and esophageal adenocarcinomas. Matching tissue samples representing the three different histologic types were obtained from each patient undergoing esophagectomy for adenocarcinoma. Our analysis compared the molecular changes accompanying the transformation of normal squamous epithelium with Barretts esophagus and adenocarcinoma in individual patients rather than in a random cohort. We tested the hypothesis that expressional profiling may reveal gene sets that can be used as molecular markers of progression from normal esophageal epithelium to Barretts esophagus and adenocarcinoma. Expressional profiling was done using U133A GeneChip (Affymetrix), which represent approximately two thirds of the human genome. The final selection of 214 genes permitted the discrimination of differential gene expression of normal esophageal squamous epithelium, Barretts esophagus, and adenocarcinoma using two-dimensional hierarchical clustering of selected genes. These data indicate that transformation of Barretts esophagus to adenocarcinoma is associated with suppression of the genes involved in epidermal differentiation, including genes in 1q21 loci and corresponding to the epidermal differentiation complex. Correlation analysis of genes concordantly expressed in Barretts esophagus and adenocarcinoma revealed 21 genes that represent potential genetic markers of disease progression and pharmacologic targets for treatment intervention. PCR analysis of genes selected based on DNA array experiments revealed that estimation of the ratios of GATA6 to SPRR3 allows discrimination among normal esophageal epithelium, Barretts dysplasia, and adenocarcinoma.

MicroRNA profiles in allograft tissues and paired urines associate with chronic allograft dysfunction with IF/TA

Despite the advances in immunosuppression, renal allograft attrition over time remains unabated due to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA). We aimed to evaluate microRNA (miRNA) signatures in CAD with IF/TA and appraise correlation with paired urine samples and potential utility in prospective evaluation of graft function. MiRNA signatures were established between CAD with IF/TA versus normal allografts by microarray. Validation of the microarray results and prospective evaluation of urine samples was performed using real‐time quantitative‐PCR (RT‐qPCR). Fifty‐six miRNAs were identified in samples with CAD‐IF/TA. Five miRNAs were selected for further validation based on array fold change, p‐value and in silico predicted mRNA targets. We confirmed the differential expression of these five miRNAs by RT‐qPCR using an independent set of samples. Differential expression was detected for miR‐142‐3p, miR‐204, miR‐107 and miR‐211 (p < 0.001) and miR‐32 (p < 0.05). Furthermore, differential expression of miR‐142‐3p (p < 0.01), miR‐204 (p < 0.01) and miR‐211 (p < 0.05) was also observed between patient groups in urine samples. A characteristic miRNA signature for IF/TA that correlates with paired urine samples was identified. These results support the potential use of miRNAs as noninvasive markers of IF/TA and for monitoring graft function.