Direct sac puncture versus transarterial embolization of type II endoleaks after endovascular abdominal aortic aneurysm repair: Comparison of outcomes.

PURPOSE: Type 2 endoleak (T2EL) is the most common type of endoleak after endovascular abdominal aortic aneurysm repair (EVAR), and increases the risk of aneurysm sac rupture if it persists beyond 6 months. The purpose of this study is to compare the efficacy and safety of direct sac puncture versus transarterial embolization of T2ELs. METHODS: Retrospective review of 42 consecutive T2EL embolization procedures, 19 by DSP and 23 by transarterial technique, between January 2015 and December 2020. Primary outcome was aneurysm sac stability and resolution of endoleak at follow-up imaging. Adverse events (AE) were classified based on the Society of Interventional Radiology (SIR) practice guidelines. RESULTS: Technical success was 94.7% (18/19) in the DSP group and 86.9% (20/23) in the transarterial group (p = 0.32 (-0.77-0.25)). Treatment efficacy was evaluated in 16 patients in the DSP group and 18 patients in the transarterial group who had follow-up imaging ≥6 months after embolization. Mean imaging follow-up was 17.1 ± 11.2 (range, 6-41) months in the DSP group and 26.5 ± 15.4 (range, 6-48) months in the transarterial group (p = 0.06, -19.24-0.37). Treatment efficacy was 75% (12/16) in the DSP group and 33.3% (6/18) in the transarterial group (p = 0.02, 95% CI, 0.09-0.97). There was no procedure-related mortality. Moderate-severe AE occurred in 15.7% (3/19) in the DSP group and 8.7% (2/23) in the transarterial group (p = 0.44, -0.12-0.26). CONCLUSION: In this study, DSP embolization of T2EL was equally safe and more effective than transarterial embolization in achieving aneurysm sac stability and resolution of endoleak.

Next-generation biobanking of metastases to enable multidimensional molecular profiling in personalized medicine.

Great advances in analytical technology coupled with accelerated new drug development and growing understanding of biological challenges, such as tumor heterogeneity, have required a change in the focus for biobanking. Most current banks contain samples of primary tumors, but linking molecular signatures to therapeutic questions requires serial biopsies in the setting of metastatic disease, next-generation of biobanking. Furthermore, an integration of multidimensional analysis of various molecular components, that is, RNA, DNA, methylome, microRNAome and post-translational modifications of the proteome, is necessary for a comprehensive view of a tumor's biology. While data using such biopsies are now regularly presented, the preanalytical variables in tissue procurement and processing in multicenter studies are seldom detailed and therefore are difficult to duplicate or standardize across sites and across studies. In the context of a biopsy-driven clinical trial, we generated a detailed protocol that includes morphological evaluation and isolation of high-quality nucleic acids from small needle core biopsies obtained from liver metastases. The protocol supports stable shipping of samples to a central laboratory, where biopsies are subsequently embedded in support media. Designated pathologists must evaluate all biopsies for tumor content and macrodissection can be performed if necessary to meet our criteria of >60% neoplastic cells and <20% necrosis for genomic isolation. We validated our protocol in 40 patients who participated in a biopsy-driven study of therapeutic resistance in metastatic colorectal cancer. To ensure that our protocol was compatible with multiplex discovery platforms and that no component of the processing interfered with downstream enzymatic reactions, we performed array comparative genomic hybridization, methylation profiling, microRNA profiling, splicing variant analysis and gene expression profiling using genomic material isolated from liver biopsy cores. Our standard operating procedures for next-generation biobanking can be applied widely in multiple settings, including multicentered and international biopsy-driven trials.

Performance of clear cell likelihood scores in characterizing solid renal masses at multiparametric MRI: an external validation study.

PURPOSE: The purpose of this study is to evaluate the accuracy and interobserver agreement of ccLS in diagnosing clear cell renal cell carcinoma (ccRCC). METHODS: This retrospective single-center study evaluated consecutive patients with solid renal masses who underwent mpMRI followed by percutaneous biopsy and/or surgical excision between January 2010 and December 2020. Predominantly (> 75%) cystic masses, masses with macroscopic fat and infiltrative masses were excluded. Two abdominal radiologists independently scored each renal mass according to the proposed ccLS algorithm. The diagnostic performance of ccLS categories for ccRCC was calculated using logistic regression modeling. Diagnostic accuracy for predicting ccRCC was calculated using 2 × 2 contingency tables. Interobserver agreement for ccLS was evaluated with Cohen's k statistic. RESULTS: A total of 79 patients (mean age, 63 years ± 12 [SD], 50 men) with 81 renal masses were evaluated. The mean size was 36 mm ± 28 (range 10-160). Of the renal masses included, 44% (36/81) were ccRCC. The area under the receiver operating characteristic curve was 0.87 (95% CI 0.79-0.95). Using ccLS ≥ 4 to diagnose ccRCC, the sensitivity, specificity, and positive predictive value were 93% (95% CI 79, 99), 63% (95% CI 48, 77), and 67% (95% CI 58, 75), respectively. The negative predictive value of ccLS ≤ 2 was 93% (95% CI 64, 99). The proportion of ccRCC by ccLS category 1 to 5 were 10%, 0%, 10%, 57%, and 84%, respectively. Interobserver agreement was moderate (k = 0.47). CONCLUSION: In this study, clear cell likelihood score had moderate interobserver agreement and resulted in 96% negative predictive value in excluding ccRCC.

Copy number and transcriptome alterations associated with metastatic lesion response to treatment in colorectal cancer.

BACKGROUND: Therapeutic resistance is the main cause of death in metastatic colorectal cancer. To investigate genomic plasticity, most specifically of metastatic lesions, associated with response to first-line systemic therapy, we collected longitudinal liver metastatic samples and characterized the copy number aberration (CNA) landscape and its effect on the transcriptome. METHODS: Liver metastatic biopsies were collected prior to treatment (pre, n = 97) and when clinical imaging demonstrated therapeutic resistance (post, n = 43). CNAs were inferred from whole exome sequencing and were correlated with both the status of the lesion and overall patient progression-free survival (PFS). We used RNA sequencing data from the same sample set to validate aberrations as well as independent datasets to prioritize candidate genes. RESULTS: We identified a significantly increased frequency gain of a unique CN, in liver metastatic lesions after first-line treatment, on chr18p11.32 harboring 10 genes, including TYMS, which has not been reported in primary tumors (GISTIC method and test of equal proportions, FDR-adjusted p = 0.0023). CNA lesion profiles exhibiting different treatment responses were compared and we detected focal genomic divergences in post-treatment resistant lesions but not in responder lesions (two-tailed Fisher's Exact test, unadjusted p ≤ 0.005). The importance of examining metastatic lesions is highlighted by the fact that 15 out of 18 independently validated CNA regions found to be associated with PFS in this study were only identified in the metastatic lesions and not in the primary tumors. CONCLUSION: This investigation of genomic-phenotype associations in a large colorectal cancer liver metastases cohort identified novel molecular features associated with treatment response, supporting the clinical importance of collecting metastatic samples in a defined clinical setting.

Preoperative Embolization and Complete Tumoral Resection of a Cervical Aggressive Epithelioid Osteoblastoma.

BACKGROUND: Epithelioid "aggressive" osteoblastoma (EOB) is a rare and more aggressive subtype of osteoblastoma (OB) with a higher recurrence rate, greater risk of malignant transformation, larger size, and greater intraoperative blood loss. The present case report illustrates that preoperative angioembolization of an EOB can be safely performed with low intraoperative blood loss. CASE DESCRIPTION: A 21-year-old male patient presented to our institution with a 4-month history of neck discomfort, radicular pain in the proximal right arm, and mild weakness of the right biceps and triceps muscles. Imaging was suggestive of EOB, and computed tomography-guided biopsy confirmed the diagnosis. The patient underwent same-day preoperative angioembolization of the major feeding vessels and subsequent complete tumor resection. During the procedure, he experienced minimal blood loss and did not require blood transfusion. CONCLUSIONS: EOB is a highly vascular primary bony lesion. To minimize intraoperative blood loss, preoperative angioembolization should be considered in the treatment of cervical spine EOB.

Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas.

PURPOSE: Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) is fatal in 90% of patients, and yet little is known about its biology. EXPERIMENTAL DESIGN: Using exome sequencing, we characterized the mutation profiles of 38 rrDLBCL biopsies obtained at the time of progression after immunochemotherapy. To identify genes that may be associated with relapse, we compared the mutation frequency in samples obtained at relapse to an unrelated cohort of 138 diagnostic DLBCLs and separately amplified specific mutations in their matched diagnostic samples to identify clonal expansions. RESULTS: On the basis of a higher frequency at relapse and evidence for clonal selection, TP53, FOXO1, MLL3 (KMT2C), CCND3, NFKBIZ, and STAT6 emerged as top candidate genes implicated in therapeutic resistance. We observed individual examples of clonal expansions affecting genes whose mutations had not been previously associated with DLBCL including two regulators of NF-κB: NFKBIE and NFKBIZ We detected mutations that may be affect sensitivity to novel therapeutics, such as MYD88 and CD79B mutations, in 31% and 23% of patients with activated B-cell-type of rrDLBCL, respectively. We also identified recurrent STAT6 mutations affecting D419 in 36% of patients with the germinal center B (GCB) cell rrDLBCL. These were associated with activated JAK/STAT signaling, increased phospho-STAT6 protein expression and increased expression of STAT6 target genes. CONCLUSIONS: This work improves our understanding of therapeutic resistance in rrDLBCL and has identified novel therapeutic opportunities especially for the high-risk patients with GCB-type rrDLBCL. Clin Cancer Res; 22(9); 2290-300. ©2015 AACR.

Iatrogenic exacerbation of pulmonary arteriovenous malformation in a patient with benign metastasizing leiomyoma.

We present a case of a middle-aged woman with known benign metastasizing leiomyoma presenting with pleural effusion. After ultrasound-guided drainage of the largest cyst was performed, the patient became hypoxemic. Chest computerized tomography (CT) showed a large tortuous vessel adjacent to the biggest cyst that had been drained. A 10-fold increase in the diameter of this vessel was noted when compared to CT scan performed 24 h before the procedure. A 20% right-to-left shunt was observed on nuclear medicine shunt study. To our knowledge, this is the first reported case of metastasizing leiomyoma with coexistent pulmonary arteriovenous malformation.

Methods for sample acquisition and processing of serial blood and tumor biopsies for multicenter diffuse large B-cell lymphoma clinical trials.

Increasingly, targeted therapies are being developed to treat malignancies. To define targets, determine mechanisms of response and resistance, and develop biomarkers for the successful investigation of novel therapeutics, high-quality tumor biospecimens are critical. We have developed standard operating procedures (SOPs) to acquire and process serial blood and tumor biopsies from patients with diffuse large B-cell lymphoma enrolled in multicenter clinical trials. These SOPs allow for collection and processing of materials suitable for multiple downstream applications, including immunohistochemistry, cDNA microarrays, exome sequencing, and metabolomics. By standardizing these methods, we control preanalytic variables that ensure high reproducibility of results and facilitate the integration of datasets from such trials. This will facilitate translational research, better treatment selection, and more rapid and efficient development of new drugs. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology."