Michael Douek

Intra-Lymph Node Prime-Boost Vaccination Against Melan A and Tyrosinase for the Treatment of Metastatic Melanoma: Results of a Phase 1 Clinical Trial

Purpose: The goal of this study was to test the safety and activity of a therapeutic vaccine, MKC1106-MT, in patients with metastatic melanoma. Experimental Design: MKC1106-MT comprises a plasmid (pMEL-TYR) and two peptides (E-MEL and E-TYR), corresponding to Melan A and tyrosinase, administered by intra–lymph node injection in a prime-boost sequence. All 18 patients were HLA-A*0201 positive and received a fixed priming dose of plasmid and a low or a high peptide dose. Enumeration of antigen-specific T cells was done prior to and throughout the treatment. Patients who did not exhibit disease progression remained on study and could receive up to eight cycles of treatment. Results: The MKC1106-MT regimen was well tolerated and resulted in an overall immune response rate of 50%. The treatment showed disease control, defined as stable disease that lasted for 8 weeks or more in 6 of 18 (33%) of the patients: 14% and 46% in the low and high peptide dose, respectively. Interestingly, four patients, all with tumor burden largely confined to lymph nodes and Melan A–specific T cells at baseline, showed durable disease control associated with radiologic evidence of tumor regression. There was no noticeable correlation between the expansion of antigen-specific T cells in blood and the clinical outcome; yet, there was evidence of active tumor-infiltrating lymphocytes (TIL) in two regressing lesions. Conclusions: MKC1106-MT showed immunogenicity and evidence of disease control in a defined patient population. These findings support further development of this investigational agent and the concept of therapeutic vaccination in metastatic melanoma. Clin Cancer Res; 17(9); 2987–96. ©2011 AACR.

MR Imaging and US of Female Urethral and Periurethral Disease

The spectrum of female urethral and periurethral disorders includes both benign and malignant entities. Establishing an accurate clinical diagnosis may be challenging because symptoms and physical findings frequently overlap among the various entities. Recent technologic advances in magnetic resonance (MR) imaging and ultrasonography (US) allow more detailed evaluation of urethral and periurethral abnormalities. Advances in MR imaging hardware and pulse sequences allow high-resolution, high-contrast static and dynamic imaging of the female urethral and periurethral region in the context of the entire pelvic floor. Similarly, the introduction of high-resolution surface and intracavitary transducers in conjunction with three-dimensional acquisition have enhanced the role of US in this clinical setting. High-resolution MR imaging and real-time US have exciting potential as tools for more comprehensive analysis of the pathophysiologic features of the complex disorders that affect the female urethra and periurethral tissues.

Performance of relative enhancement on multiphasic MRI for the Differentiation of Clear Cell Renal Cell Carcinoma (RCC) from Papillary and Chromophobe RCC subtypes and oncocytoma

OBJECTIVEnThe objective of our study was to investigate the performance of relative enhancement on multiphasic MRI to differentiate clear cell renal cell carcinoma (RCC) from other RCC subtypes (papillary and chromophobe) and oncocytoma.nnnMATERIALS AND METHODSnFor this study, we derived a cohort of 34 clear cell RCCs, nine oncocytomas, 12 papillary RCCs, and 10 chromophobe RCCs with a preoperative multiphasic dynamic contrast-enhanced MRI study with up to four phases (i.e., unenhanced, corticomedullary, nephrographic, excretory) from 2005 to 2016. These groups were evaluated for multiphasic enhancement and were compared using Kruskal-Wallis and Mann-Whitney tests. ROC curves were constructed and logistic regression analyses were performed to evaluate the performance of multiphasic enhancement in differentiating clear cell RCCs from the other three groups.nnnRESULTSnClear cell RCCs exhibited significantly greater relative signal intensity compared with uninvolved renal cortex in the corticomedullary phase (mean, 2.9) than oncocytomas (-21.7, p = 0.001), papillary RCCs (-53.0, p < 0.001), and chromophobe RCCs (-21.0, p < 0.001). Relative signal intensity in the corticomedullary phase differentiated clear cell RCCs from oncocytomas with an AUC of 0.90 and with an accuracy of 84% (32/38), sensitivity of 90% (27/30), and specificity of 63% (5/8) after controlling for lesion size, patient age, and patient sex. Relative corticomedullary signal intensity differentiated clear cell RCCs from oncocytomas and other RCC subtypes with an AUC of 0.93 and with an accuracy of 90% (53/59), sensitivity of 90% (27/30), and specificity of 90% (26/29) after controlling for lesion size, patient age, and patient sex.nnnCONCLUSIONnMultiphasic MRI enhancement may assist in differentiating clear cell RCC from oncocytomas and other RCC subtypes, if validated in prospective studies.

Preliminary Outcome of Microwave Ablation of Hepatocellular Carcinoma: Breaking the 3-cm Barrier?

PURPOSEnTo evaluate preliminary outcomes after microwave ablation (MWA) of hepatocellular carcinoma (HCC) up to 5 cm and to determine the influence of tumor size.nnnMATERIALS AND METHODSnElectronic records were searched for HCC and MWA. Between January 2011 and September 2014, 173 HCCs up to 5 cm were treated by MWA in 129 consecutive patients (89 men, 40 women; mean age, 66.9 y ± 9.5). Tumor characteristics related to local tumor progression and primary and secondary treatment efficacy were evaluated by univariate analysis. Outcomes were compared between tumors ≤ 3 cm and tumors > 3 cm.nnnRESULTSnTechnical success, primary efficacy, and secondary efficacy were 96.5%, 99.4%, and 94.2% at a mean follow-up period of 11.8 months ± 9.8 (range, 0.8-40.6 mo). Analysis of tumor characteristics showed no significant risk factor for local tumor progression, including subcapsular location (P = .176), tumor size (P = .402), and perivascular tumor location (P = .323). The 1-year and 2-year secondary or overall treatment efficacy rates for tumors measuring ≤ 3 cm were 91.2% and 82.1% and for tumors 3.1-5 cm were 92.3% and 83.9% (P = .773). The number of sessions to achieve secondary efficacy was higher in the larger tumor group (1.13 vs 1.06, P = .005). There were three major complications in 134 procedures (2.2%).nnnCONCLUSIONSnWith use of current-generation MWA devices, percutaneous ablation of HCCs up to 5 cm can be achieved with high efficacy.

Clear cell renal cell carcinoma: identifying the gain of chromosome 12 on multiphasic MDCT

PurposeTo determine whether multiphasic MDCT enhancement can help identify the gain of chromosome 12 in clear cell renal cell carcinomas (RCCs).MethodsWith IRB approval for this HIPAA-compliant case control study, we derived a cohort of 65 clear cell RCCs with preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images in all phases. A computer-assisted detection (CAD) algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. Attenuation in each phase between clear cell RCCs with and without the gain of 12 was compared using t-tests.ResultsWhile the entire cohort of clear cell RCCs exhibited peak enhancement in the corticomedullary phase, the subcohort of lesions with the gain of 12 exhibited significantly greater enhancement in the nephrographic (179 vs. 145xa0HU, pxa0=xa00.004) and excretory phases (147 vs. 118xa0HU, pxa0=xa00.004) than the subcohort of lesions without the gain of 12. A nephrographic threshold of 186xa0HU identified the gain of 12 with an accuracy of 86% (56/65), specificity of 93% (51/55), and negative predictive value of 91% (51/56).ConclusionMultiphasic MDCT enhancement, specifically enhancement in the nephrographic and excretory phases, may potentially assist in identifying the gain of 12 in clear cell RCCs.

Safety of Hydroinfusion in Percutaneous Thermal Ablation of Hepatic Malignancies

PURPOSEnHydroinfusion is a commonly used ancillary procedure during percutaneous thermal ablation of the liver that is used to separate and protect sensitive structures from the ablation zone. However, risks of hydroinfusion have not been systematically studied. The purpose of the present study was to systematically examine the frequency and severity of local and systemic complications related to hydroinfusion.nnnMATERIALS AND METHODSnFrom January 2009 to April 2012, 410 consecutive patients underwent percutaneous thermal hepatic tumor ablation. One hundred fifty patients in the study group underwent hydroinfusion and 260 in the control group did not. Patient charts and imaging studies of both groups were reviewed to compare incidences of complications that could potentially be caused by hydroinfusion, including pleural effusion, bowel injury, infection, electrolyte imbalance, and hyperglycemia.nnnRESULTSnPleural effusions were found to occur more commonly in the hydroinfusion group (45.3%) than in the control group (16.5%). Pleural effusions were significantly larger (P < .001) and more likely to be symptomatic (six of 150 patients; P = .006) in the hydroinfusion group than in the control group (one of 260 patients). Multiple patient and tumor characteristics were analyzed for association with development of major hydroinfusion-type complications (requiring therapy or extended/repeat hospitalization). Subcapsular location of tumor was the only variable to reach statistical significance (P = .009), with all major hydroinfusion-type complications (n = 10) occurring in patients with subcapsular tumors.nnnCONCLUSIONSnHydroinfusion is a safe procedure overall. However, pleural effusions occur commonly after hydroinfusion, tend to be moderate or large in size, and are occasionally symptomatic.

Type 1 papillary renal cell carcinoma: differentiation from Type 2 papillary RCC on multiphasic MDCT

PurposeTo investigate whether multiphasic MDCT enhancement can help differentiate type 1 papillary renal cell carcinoma (RCC) from type 2 papillary RCC.MethodsWith IRB approval for this HIPAA-compliant retrospective study, we derived a cohort of 36 type 1 papillary RCCs and 33 type 2 papillary RCCs with preoperative multiphasic MDCT with up to four phases (unenhanced, corticomedullary, nephrographic, and excretory) from 2000 to 2013. Following segmentation, a computer-assisted detection (CAD) algorithm selected a 0.5xa0cm-diameter region of maximal attenuation within each lesion in each phase; a 0.5xa0cm-diameter region of interest was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as [(Lesion attenuation−cortex attenuation)/cortex attenuation]xa0×xa0100. Absolute and relative attenuation values were compared using Mann–Whitney tests with Bonferroni correction for multiple comparisons.ResultsRelative excretory phase attenuation of type 2 papillary RCCs was significantly greater than that of type 1 papillary RCCs (2.0 vs. −18.3, pxa0=xa00.005). Relative excretory phase attenuation differentiated type 1 papillary RCCs from type 2 papillary RCCs with an accuracy of 73% (36/49), sensitivity of 87% (26/30), positive predictive value of 74% (26/35), and negative predictive value of 71% (10/14).ConclusionMultiphasic MDCT enhancement may assist in differentiating type 1 papillary RCCs from type 2 papillary RCCs, if prospectively validated.

Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography

ObjectiveTo evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML).Materials and methodsWe queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]. A whole lesion 3D contour was obtained in all four phases. The CAD algorithm determined a region of interest (ROI) of peak lesion attenuation within the 3D lesion contour. For comparison, a manual ROI was separately placed in the most enhancing portion of the lesion by visual inspection for a reference standard, and in uninvolved renal cortex. Relative lesion attenuation for both CAD and manual methods was obtained by normalizing the CAD peak lesion attenuation ROI (and the reference standard manually placed ROI) to uninvolved renal cortex with the formula [(peak lesion attenuation ROIxa0−xa0cortex ROI)/cortex ROI]xa0×xa0100%. ROC analysis and area under the curve (AUC) were used to assess diagnostic performance. Bland–Altman analysis was used to compare peak ROI between CAD and manual method.ResultsThe study cohort comprised 200 patients with 200 unique renal masses: 106 (53%) ccRCC, 32 (16%) oncocytomas, 18 (9%) chRCCs, 34 (17%) pRCCs, and 10 (5%) fp-AMLs. In the CM phase, CAD-derived ROI enabled characterization of ccRCC from chRCC, pRCC, oncocytoma, and fp-AML with AUCs of 0.850 (95% CI 0.732–0.968), 0.959 (95% CI 0.930–0.989), 0.792 (95% CI 0.716–0.869), and 0.825 (95% CI 0.703–0.948), respectively. On Bland–Altman analysis, there was excellent agreement of CAD and manual methods with mean differences between 14 and 26xa0HU in each phase.ConclusionA novel, quantitative CAD algorithm enabled robust peak HU lesion detection and discrimination of ccRCC from other renal lesions with similar performance compared to the manual method.

The cost of screening esophageal varices: traditional endoscopy versus computed tomography.

Objective Under current guidelines, patients diagnosed with cirrhosis are to undergo initial and continued screening endoscopy for esophageal varices throughout the course of disease. Recent literature suggests that computed tomography (CT) of the abdomen is adequately sensitive for detecting grade 3 varices, those in need of immediate intervention. This study presents a cost comparison of traditional endoscopy versus CT of the abdomen. Methods Using TreeAge Pro software, a budget impact cost model was created for a hypothetical managed care organization covering 1 million lives over a 10-year period. Incidence figures for cirrhosis and the progression of esophageal varices were applied to the patient population. National Medicare reimbursement costs were used to compare screening with traditional endoscopy versus CT. Costs utilizing screening with combined endoscopy and CT were also examined. Results The results of comparing screening paradigms under a budget impact cost model results in an outcome measure termed “per-member, per-month” (PMPM) cost of implementing a new strategy. Computed tomography was the least expensive modality with an average 10-year cost per screened patient of

Reproducibility of Laplacian Wall Thickness Measurements of the Gallbladder with Varying CT Slice Thickness

1097.30 and PMPM of