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Depletion of Core Needle Biopsy Cellularity and DNA Content as a Result of Vigorous Touch Preparations

Rekhtman, Natasha; Kazi, Sofia; Yao, JinJuan; Dogan, Snjezana; Yannes, Angela; Lin, Oscar; Silk, Mikhail; Silk, Tarik; Durack, Jeremy C
CONTEXT/BACKGROUND:Touch preparations (TP) of core needle biopsies (CNBs) are used at some institutions for on-site assessment of CNB adequacy. In our clinical practice, we have encountered instances in which TPs resulted in substantial depletion of CNB cellularity. OBJECTIVE:To examine the effect of increasingly vigorous TPs on cellularity and DNA content of CNBs. DESIGN/METHODS:Ex vivo CNBs (n = 56) were performed on resected lung and kidney tumor specimens. For each specimen, CNBs were performed in quadruplicate on tumor and nontumor tissue and subjected to 1 of 4 TP methods: imprint, 1-cm drag, 2-cm drag, or full-slide drag. Overall cellularity in TPs relative to corresponding CNBs was estimated semiquantitatively. DNA was extracted and quantified from 12 TPs and corresponding CNBs. Two cytopathologists performed a blinded diagnostic assessment of Diff-Quik-stained TPs. RESULTS:Cellularity of imprint, 1-cm, 2-cm, and full-slide TPs represented, on average, 19%, 33%, 41%, and 46% of total CNB cellularity, respectively (p = .003). Average DNA content in imprint, 1-cm, and 2-cm TPs was 0.3 μg (range, 0.1-0.8 μg), 0.4 μg (range, 0.1-1 μg), and 0.6 μg (range, 0.2-1.3 μg), respectively, which represented on average 15%, 36%, and 50%, respectively, of total CNB DNA content. Diagnostic accuracy was not inferior for less-extensive TPs, compared with more-extensive TPs. CONCLUSIONS:Vigorous TPs may contain a substantial fraction of CNB cellularity and DNA content, whereas more-limited TPs are less disruptive to CNBs but remain suitable for cytologic assessment. We suggest avoiding excessively forceful TPs and, whenever clinically feasible, obtaining additional samples to ensure sufficient cellularity for potential ancillary studies.
PMID: 25521802
ISSN: 1543-2165
CID: 5333372

Performance of intra-procedural 18-fluorodeoxyglucose PET/CT-guided biopsies for lesions suspected of malignancy but poorly visualized with other modalities

Cornelis, F; Silk, M; Schoder, H; Takaki, H; Durack, J C; Erinjeri, J P; Sofocleous, C T; Siegelbaum, R H; Maybody, M; Solomon, S B
PURPOSE: We sought to evaluate the safety and the diagnostic success rate of percutaneous biopsies performed under intra-procedural (18)F-deoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) guidance for lesions difficult to see with conventional cross-sectional imaging. METHODS: From 2011 to 2013, consecutive clinically indicated percutaneous PET/CT-guided biopsies of 106 masses (mean size, 3.3 cm; range, 0.7-15.9 cm; SD, 2.9 cm) in bones (n = 33), liver (n = 26), soft tissues (n = 18), lung (n = 15) and abdomen (n = 14) were reviewed. The biopsy procedures were performed following injection of a mean of 255 MBq (SD, 74) FDG. Mean maximal standardized uptake value (SUV) of lesions was 8.8 (SD, 6.3). A systematic review of the histopathological results and outcomes was performed. RESULTS: Biopsies were positive for malignancy in 76 cases (71.7%, 76/106) and for benign tissue in 30 cases (28.3%, 30/106). Immediate results were considered adequate for 100 PET/CT biopsies (94.3%, 100/106) requiring no further exploration, and for the six others (5.7%, 6/106) benign diagnoses were confirmed after surgery (n = 4) or follow-up (n = 2). The consequent overall sensitivity and the diagnostic success of biopsy were therefore 100%. No significant differences in terms of detection of malignancy were observed between the different locations. Lesions > 2 cm or with SUV > 4 were not significantly more likely to be malignant. Complications occurred after four biopsies (3.7%, 4/106). CONCLUSION: Intra-procedural PET/CT guidance appears as a safe and effective method and allows high diagnostic success of percutaneous biopsies for metabolically active lesions.
PMID: 25106463
ISSN: 1619-7089
CID: 2406092

The impact of genetic heterogeneity on biomarker development in kidney cancer assessed by multiregional sampling

Sankin, Alexander; Hakimi, Abraham A; Mikkilineni, Nina; Ostrovnaya, Irina; Silk, Mikhail T; Liang, Yupu; Mano, Roy; Chevinsky, Michael; Motzer, Robert J; Solomon, Stephen B; Cheng, Emily H; Durack, Jeremy C; Coleman, Jonathan A; Russo, Paul; Hsieh, James J
Primary clear cell renal cell carcinoma (ccRCC) genetic heterogeneity may lead to an underestimation of the mutational burden detected from a single site evaluation. We sought to characterize the extent of clonal branching involving key tumor suppressor mutations in primary ccRCC and determine if genetic heterogeneity could limit the mutation profiling from a single region assessment. Ex vivo core needle biopsies were obtained from three to five different regions of resected renal tumors at a single institution from 2012 to 2013. DNA was extracted and targeted sequencing was performed on five genes associated with ccRCC (von-Hippel Lindau [VHL], PBRM1, SETD2, BAP1, and KDM5C). We constructed phylogenetic trees by inferring clonal evolution based on the mutations present within each core and estimated the predictive power of detecting a mutation for each successive tumor region sampled. We obtained 47 ex vivo biopsy cores from 14 primary ccRCC's (median tumor size 4.5 cm, IQR 4.0-5.9 cm). Branching patterns of various complexities were observed in tumors with three or more mutations. A VHL mutation was detected in nine tumors (64%), each time being present ubiquitously throughout the tumor. Other genes had various degrees of regional mutational variation. Based on the mutations' prevalence we estimated that three different tumor regions should be sampled to detect mutations in PBRM1, SETD2, BAP1, and/or KDM5C with 90% certainty. The mutational burden of renal tumors varies by region sampled. Single site assessment of key tumor suppressor mutations in primary ccRCC may not adequately capture the genetic predictors of tumor behavior.
PMID: 25124064
ISSN: 2045-7634
CID: 5333362

Radiofrequency Ablation of T1 Lung Carcinoma: Comparison of Outcomes for First Primary, Metachronous, and Synchronous Lung Tumors

Ridge, Carole A; Silk, Mikhail; Petre, Elena N; Erinjeri, Joseph P; Alago, William; Downey, Robert J; Sofocleous, Constantinos T; Thornton, Raymond H; Solomon, Stephen B
PURPOSE: To report and compare outcomes after radiofrequency ablation for treatment-naive first primary, metachronous, and synchronous T1 lung tumors. MATERIALS AND METHODS: This institutional review board-approved retrospective study reviewed 29 patients (12 men and 17 women; median age, 73 y; age range, 55-86 y) with treatment-naive T1 lung tumors treated with radiofrequency ablation. Tumors in the 29 patients included 21 T1a and 8 T1b first primary (n = 11), metachronous (n = 14), or synchronous (n = 4) tumors (adenocarcinoma, n = 25; squamous cell carcinoma, n = 3; unspecified, n = 1). Median tumor diameter was 14 mm (range, 10-26 mm). Surveillance computed tomography or positron emission tomography-computed tomography was performed over a median period of 28 months (range, 12-83 mo). Technical success and effectiveness rates and overall and progression-free 1-year, 3-year, and 5-year survivals were calculated according to stage, first primary, metachronous, and synchronous tumor status. RESULTS: Technical success and effectiveness was 97%. Local control occurred in 17 of 21 T1a tumors (81%) and 5 of 8 T1b tumors (62.5%). The local progression rate of first primary tumors (5 of 11; 45%) was higher than that of metachronous (2 of 14; 14%; P = .07) and synchronous (0 of 4; P = .01) tumors. Estimated 1-year, 3-year, and 5-year local tumor progression-free survival was 79%, 75%, and 75%. Estimated 1-year, 3-year, and 5-year overall survival was 100%, 60%, and 14%. Survival outcomes were similar for patients with first primary, metachronous, or synchronous tumors. CONCLUSIONS: Radiofrequency ablation results in good local control and progression-free survival in patients with treatment-naive T1 lung tumors, including patients with metachronous and synchronous tumors.
PMID: 24703321
ISSN: 1051-0443
CID: 919862

The state of irreversible electroporation in interventional oncology

Silk, Mikhail; Tahour, David; Srimathveeravalli, Govindarajan; Solomon, Stephen B; Thornton, Raymond H
A new ablation modality, irreversible electroporation (IRE), has been of increasing interest in interventional radiology. Its nonthermal mechanism of action of killing tumor cells allows physicians the ability to ablate tumors in areas previously contraindicated for thermal ablation. This article reviews the current published clinical outcomes, imaging follow-up, and the current knowledge gaps in the procedure for patients treated with IRE.
PMID: 25053862
ISSN: 0739-9529
CID: 5333352

Percutaneous ablation of peribiliary tumors with irreversible electroporation

Silk, Mikhail T; Wimmer, Thomas; Lee, Kyungmouk S; Srimathveeravalli, Govindarajan; Brown, Karren T; Kingham, Peter T; Fong, Yuman; Durack, Jeremy C; Sofocleous, Constantinos T; Solomon, Stephen B
PURPOSE/OBJECTIVE:To assess biliary complications after irreversible electroporation (IRE) ablation of hepatic tumors located < 1 cm from major bile ducts. MATERIALS AND METHODS/METHODS:A retrospective review was conducted of all percutaneous IRE ablations of hepatic tumors within 1 cm of the common, left, or right hepatic ducts at a single institution from January 2011 to September 2012. Computed tomography imaging performed before and after treatment was examined for evidence of bile duct dilatation, stricture, or leakage. Serum bilirubin and alkaline phosphatase levels were analyzed for evidence of biliary injury. RESULTS:There were 22 hepatic metastases in 11 patients with at least one tumor within 1 cm of the common, left, or right hepatic duct that were treated with IRE ablations in 15 sessions. Median tumor size treated was 3.0 cm (mean, 2.8 cm ± 1.2, range, 1.0-4.7 cm). Laboratory values obtained after IRE were considered abnormal after four treatment sessions in three patients (bilirubin, 2.6-17.6 mg/dL; alkaline phosphatase, 130-1,035 U/L); these abnormal values were transient in two sessions. Two patients had prolonged elevation of values, and one required stent placement; both of these conditions appeared to be secondary to tumor progression rather than bile duct injury. CONCLUSIONS:This clinical experience suggests that IRE may be a treatment option for centrally located liver tumors with margins adjacent to major bile ducts where thermal ablation techniques are contraindicated. Further studies with extended follow-up periods are necessary to establish the safety profile of IRE in this setting.
PMID: 24262034
ISSN: 1535-7732
CID: 5333342


Sankin, Alexander; Mikkilineni, Nina; Hakimi, A. Ari; Silk, Mikhail; Liang, Yupu; Mano, Roy; Durack, Jeremy C.; Coleman, Jonathan; Russo, Paul; Hsieh, James
ISSN: 0022-5347
CID: 5333432

ORGN 777-Progress toward novel polycyclic aromatic hydrocarbons by corannulene oligomerization [Meeting Abstract]

Rose, Jonathan A.; Silk, Mikhail T.; Scott, Lawrence T.
ISSN: 0065-7727
CID: 5333422