Ivan Pedrosa

Prevalence of Incidental Pancreatic Cysts in the Adult Population on MR Imaging

OBJECTIVES:The reporting of incidental pancreatic cystic lesions on cross-sectional imaging studies has dramatically increased over the last few years. The prevalence of incidental pancreatic cysts in the adult population, however, is unknown. The aim of our study was to determine the prevalence of incidentally detected pancreatic cysts in the adult population undergoing abdominal magnetic resonance (MR) imaging.METHODS:MR imaging examinations of 616 consecutive patients obtained between January 2001 and February 2002 were retrospectively reviewed by two radiologists and the following information was recorded: the total number of pancreatic cysts; the maximum diameter, location, and characteristics of the largest cyst; documentation of the cyst(s) within the radiology report; and characteristics of the cyst(s) at imaging follow-up.RESULTS:Incidental pancreatic cysts were present in 13.5% (83/616) of patients, with 60% of the cysts being solitary, and 88% of the cysts being simple. Largest cyst mean and median diameters were 7.4 mm (2–24 mm) and 6 mm, respectively. Both the prevalence of pancreatic cysts and the mean size of the largest cyst increased with age (P=0.007, r=0.893 and P=0.003, r=0.929, respectively). Only 31% (26/83) of incidental pancreatic cysts were documented in the radiology report. The mean size of reported pancreatic cysts was larger than those cysts that were not reported (P<0.001).CONCLUSIONS:The prevalence of incidentally detected pancreatic cysts on MR imaging is 13.5%, and increases with age. A majority of these cysts are not reported on MR imaging studies.

Renal Cell Carcinoma: Dynamic Contrast-enhanced MR Imaging for Differentiation of Tumor Subtypes—Correlation with Pathologic Findings

PURPOSE To retrospectively evaluate whether the enhancement patterns of pathologically proved clear cell, papillary, and chromophobe renal cell carcinomas (RCCs) measured on clinical dynamic contrast agent-enhanced magnetic resonance (MR) images permit accurate diagnosis of RCC subtype. MATERIALS AND METHODS This study was Institutional Review Board approved and HIPAA compliant; informed consent was waived. One hundred twelve patients (76 men, 36 women; age range, 25-88 years; mean age, 58.1 years) underwent MR imaging of 113 renal masses (mean diameter, 5.4 cm) with pathologic diagnoses of clear cell (n = 75), papillary (n = 28), or chromophobe (n = 10) RCC. A 1.5-T clinical MR protocol was used before and after (corticomedullary and nephrographic phases) intravenous administration of contrast agent. Region-of-interest measurements within tumor and uninvolved renal cortex were used to calculate percentage signal intensity change and tumor-to-cortex enhancement index. Subtype groups were compared by using linear mixed-effects models. Receiver operating characteristic (ROC) curve analysis was performed for the comparison of clear cell and papillary RCCs. RESULTS On both the corticomedullary and nephrographic phase images, clear cell RCCs showed greater signal intensity change (205.6% and 247.1%, respectively) than did papillary RCCs (32.1% and 96.6%, respectively) (P < .001). Chromophobe RCCs showed intermediate change (109.9% and 192.5%, respectively). The tumor-to-cortex enhancement indexes at corticomedullary and nephrographic phases were largest for clear cell RCCs (1.4 and 1.2, respectively), smallest for papillary RCCs (0.2 and 0.4, respectively), and intermediate for chromophobe RCCs (0.6 and 0.8, respectively). Signal intensity changes on corticomedullary phase images were the most effective parameter for distinguishing clear cell and papillary RCC (area under ROC curve, 0.99); a threshold value of 84% permitted distinction with 93% sensitivity and 96% specificity. CONCLUSION Clear cell, papillary, and chromophobe RCCs demonstrate different patterns of enhancement on two-time point clinical dynamic contrast-enhanced MR images, allowing their differentiation with high sensitivity and specificity.

MR Imaging of Renal Masses: Correlation with Findings at Surgery and Pathologic Analysis

Magnetic resonance (MR) imaging is useful in the characterization of renal masses. The MR imaging manifestations and pathologic diagnoses of 82 renal masses were reviewed and correlated. The MR imaging appearance of clear cell type renal cell carcinoma varies depending on the presence of cystic components, hemorrhage, and necrosis. Papillary renal cell carcinomas appear as well-encapsulated masses with homogeneous low signal intensity on T2-weighted images and homogeneous low-level enhancement after the intravenous administration of contrast material, or as cystic hemorrhagic masses with peripheral enhancing papillary projections. Transitional cell carcinoma may be seen as an irregular, enhancing filling defect in the pelvicaliceal system or ureter. Lymphomatous masses are usually hypointense relative to the renal cortex on T2-weighted images and enhance minimally on delayed gadolinium-enhanced images. Bulk fat is a distinguishing feature of angiomyolipoma. Oncocytoma has a variable and nonspecific appearance at MR imaging. MR imaging findings may allow the characterization of various renal masses and can provide valuable information for their clinical management.

Angiomyolipoma with Minimal Fat: Can It Be Differentiated from Clear Cell Renal Cell Carcinoma by Using Standard MR Techniques?

PURPOSE To retrospectively assess whether magnetic resonance (MR) imaging with opposed-phase and in-phase gradient-echo (GRE) sequences and MR feature analysis can differentiate angiomyolipomas (AMLs) that contain minimal fat from clear cell renal cell carcinomas (RCCs), with particular emphasis on small (<3-cm) masses. MATERIALS AND METHODS Institutional review board approval and a waiver of informed consent were obtained for this HIPAA-compliant study. MR images from 108 pathologically proved renal masses (88 clear cell RCCs and 20 minimal fat AMLs from 64 men and 44 women) at two academic institutions were evaluated. The signal intensity (SI) of each renal mass and spleen on opposed-phase and in-phase GRE images was used to calculate an SI index and tumor-to-spleen SI ratio. Two radiologists who were blinded to the pathologic results independently assessed the subjective presence of intravoxel fat (ie, decreased SI on opposed-phase images compared with that on in-phase images), SI on T1-weighted and T2-weighted images, cystic degeneration, necrosis, hemorrhage, retroperitoneal collaterals, and renal vein thrombosis. Results were analyzed by using the Wilcoxon rank sum test, two-tailed Fisher exact test, and multivariate logistic regression analysis for all renal masses and for small masses. A P value of less than .05 was considered to indicate a statistically significant difference. RESULTS There were no differences between minimal fat AMLs and clear cell RCCs for the SI index (8.05%±14.46 vs 14.99%±19.9; P=.146) or tumor-to-spleen ratio (-8.96%±16.6 and -15.8%±22.4; P=.227) when all masses or small masses were analyzed. Diagnostic accuracy (area under receiver operating characteristic curve) for the SI index and tumor-to-spleen ratio was 0.59. Intratumoral necrosis and larger size were predictive of clear cell RCC (P<.001) for all lesions, whereas low SI (relative to renal parenchyma SI) on T2-weighted images, smaller size, and female sex correlated with minimal fat AML (P<.001) for all lesions. CONCLUSION The diagnostic accuracy of opposed-phase and in-phase GRE MR imaging for the differentiation of minimal fat AML and clear cell RCC is poor. In this cohort, low SI on T2-weighted images relative to renal parenchyma and small size suggested minimal fat AML, whereas intratumoral necrosis and large size argued against this diagnosis.

Targeting renal cell carcinoma with a HIF-2 antagonist

Clear cell renal cell carcinoma (ccRCC) is characterized by inactivation of the von Hippel-Lindau tumour suppressor gene (VHL). Because no other gene is mutated as frequently in ccRCC and VHL mutations are truncal, VHL inactivation is regarded as the governing event. VHL loss activates the HIF-2 transcription factor, and constitutive HIF-2 activity restores tumorigenesis in VHL-reconstituted ccRCC cells. HIF-2 has been implicated in angiogenesis and multiple other processes, but angiogenesis is the main target of drugs such as the tyrosine kinase inhibitor sunitinib. HIF-2 has been regarded as undruggable. Here we use a tumourgraft/patient-derived xenograft platform to evaluate PT2399, a selective HIF-2 antagonist that was identified using a structure-based design approach. PT2399 dissociated HIF-2 (an obligatory heterodimer of HIF-2α–HIF-1β) in human ccRCC cells and suppressed tumorigenesis in 56% (10 out of 18) of such lines. PT2399 had greater activity than sunitinib, was active in sunitinib-progressing tumours, and was better tolerated. Unexpectedly, some VHL-mutant ccRCCs were resistant to PT2399. Resistance occurred despite HIF-2 dissociation in tumours and evidence of Hif-2 inhibition in the mouse, as determined by suppression of circulating erythropoietin, a HIF-2 target and possible pharmacodynamic marker. We identified a HIF-2-dependent gene signature in sensitive tumours. Gene expression was largely unaffected by PT2399 in resistant tumours, illustrating the specificity of the drug. Sensitive tumours exhibited a distinguishing gene expression signature and generally higher levels of HIF-2α. Prolonged PT2399 treatment led to resistance. We identified binding site and second site suppressor mutations in HIF-2α and HIF-1β, respectively. Both mutations preserved HIF-2 dimers despite treatment with PT2399. Finally, an extensively pretreated patient whose tumour had given rise to a sensitive tumourgraft showed disease control for more than 11 months when treated with a close analogue of PT2399, PT2385. We validate HIF-2 as a target in ccRCC, show that some ccRCCs are HIF-2 independent, and set the stage for biomarker-driven clinical trials.

Spectrum of diverse genomic alterations define non–clear cell renal carcinoma subtypes

To further understand the molecular distinctions between kidney cancer subtypes, we analyzed exome, transcriptome and copy number alteration data from 167 primary human tumors that included renal oncocytomas and non–clear cell renal cell carcinomas (nccRCCs), consisting of papillary (pRCC), chromophobe (chRCC) and translocation (tRCC) subtypes. We identified ten significantly mutated genes in pRCC, including MET, NF2, SLC5A3, PNKD and CPQ. MET mutations occurred in 15% (10/65) of pRCC samples and included previously unreported recurrent activating mutations. In chRCC, we found TP53, PTEN, FAAH2, PDHB, PDXDC1 and ZNF765 to be significantly mutated. Gene expression analysis identified a five-gene set that enabled the molecular classification of chRCC, renal oncocytoma and pRCC. Using RNA sequencing, we identified previously unreported gene fusions, including ACTG1-MITF fusion. Ectopic expression of the ACTG1-MITF fusion led to cellular transformation and induced the expression of downstream target genes. Finally, we observed upregulation of the anti-apoptotic factor BIRC7 in MiTF-high RCC tumors, suggesting a potential therapeutic role for BIRC7 inhibitors.

MR classification of renal masses with pathologic correlation

To perform a feature analysis of malignant renal tumors evaluated with magnetic resonance (MR) imaging and to investigate the correlation between MR imaging features and histopathological findings. MR examinations in 79 malignant renal masses were retrospectively evaluated, and a feature analysis was performed. Each renal mass was assigned to one of eight categories from a proposed MRI classification system. The sensitivity and specificity of the MRI classification system to predict the histologic subtype and nuclear grade was calculated. Subvoxel fat on chemical shift imaging correlated to clear cell type (p < 0.05); sensitivity = 42%, specificity = 100%. Large size, intratumoral necrosis, retroperitoneal vascular collaterals, and renal vein thrombosis predicted high-grade clear cell type (p < 0.05). Small size, peripheral location, low intratumoral SI on T2-weighted images, and low-level enhancement were associated with low-grade papillary carcinomas (p < 0.05). The sensitivity and specificity of the MRI classification system for diagnosing low grade clear cell, high-grade clear cell, all clear cell, all papillary, and transitional carcinomas were 50% and 94%, 93% and 75%, 92% and 83%, 80% and 94%, and 100% and 99%, respectively. The MRI feature analysis and proposed classification system help predict the histological type and nuclear grade of renal masses.

Magnetic Resonance Imaging–Measured Blood Flow Change after Antiangiogenic Therapy with PTK787/ZK 222584 Correlates with Clinical Outcome in Metastatic Renal Cell Carcinoma

Purpose: To measure changes in tumor blood flow following treatment with PTK787/ZK 222584, a pan–vascular endothelial growth factor receptor tyrosine kinase inhibitor, and their association with clinical response in patients with metastatic renal cell carcinoma. Experimental Design: In 10 patients with metastatic renal cell carcinoma treated with PTK787/ZK 222584, tumor blood flow was evaluated by arterial spin labeling (ASL) magnetic resonance imaging before and 1 month on treatment. Changes in blood flow after 1 month of treatment were compared with bidimensional tumor response at 4 months of treatment using the Mann-Whitney test. Results: Changes in blood flow at 1 month and changes in tumor size measured at 4 months or at time of disease progression were significantly correlated (P = 0.01). Patients with progressive disease within 4 months on treatment (n = 4) had a nonsignificant increase in tumor blood flow at 1 month (+25 ± 33%; P = 0.43), whereas patients with stable disease or partial response at 4 months (n = 6) had a significant decrease in tumor blood flow at 1 month (−42 ± 22%; P = 0.02). Conclusion: These results suggest that decreasing tumor blood flow with PTK787/ZK 222584 therapy, as shown as soon as 1 month on therapy by ASL, may predict for a favorable clinical outcome. These data are consistent with a hypothetical functional role for tumor ischemia in the mechanism of response to anti–vascular endothelial growth factor therapy. ASL blood flow magnetic resonance imaging shows promise as an early predictor of clinical response to antiangiogenic therapies.

Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma.

BACKGROUND Vascular endothelial growth factor (VEGF)-targeted therapy has become standard treatment for patients with metastatic renal cell cancer (mRCC). Since these therapies can induce tumor necrosis and minimal tumor shrinkage, Response Evaluation Criteria in Solid Tumors (RECIST) may not be optimal for predicting clinical outcome. OBJECTIVE To systematically determine the optimal early posttherapy imaging changes (EPTIC) to separate responders and nonresponders at the first posttreatment follow-up computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS Seventy mRCC patients with 155 target lesions treated with first-line sunitinib, sorafenib, or bevacizumab at academic medical centers underwent contrast-enhanced thoracic and abdominal CT at baseline and first follow-up after therapy initiation (median: 78 d after therapy initiation; range: 31-223 d). MEASUREMENTS Evaluations were performed according to (1) RECIST 1.0; (2) Choi criteria; (3) tumor shrinkage (TS) of ≥10% decrease in sum of the longest unidimensional diameter (SLD); and (4) 15% or 20% decrease in mean CT tumor density. Correlation with time to treatment failure (TTF) and overall survival (OS) were compared and stratified by response to each of the radiologic criteria. RESULTS AND LIMITATIONS Eleven patients were considered responders by RECIST 1.0; 49 based on Choi criteria; 31 patients had ≥10% decrease in the SLD; and 36 and 32 patients had ≥15% and ≥20% decrease, respectively, in mean tumor density on CT. Only the threshold of 10% decrease in the SLD was statistically significant in predicting TTF (10.4 vs 5.1 mo; p=0.02) and OS (32.5 vs 15.8 mo; p=0.002). Receiver operating characteristic analysis yielded a 10% decrease in SLD as the optimal size change threshold for responders. The retrospective nature of the study and measurements by a single oncoradiologist are inherent limitations. CONCLUSIONS In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.

Pregnant Patients Suspected of Having Acute Appendicitis: Effect of MR Imaging on Negative Laparotomy Rate and Appendiceal Perforation Rate

PURPOSE To investigate the effect of magnetic resonance (MR) imaging on the negative laparotomy rate (NLR) and the perforation rate (PR) in pregnant patients suspected of having acute appendicitis (AA) and to assess the need for computed tomography (CT) in this setting. MATERIALS AND METHODS The data of 148 consecutive pregnant patients (mean age, 29 years; age range, 15-42 years; mean gestational age, 20 weeks; gestational age range, 4-37 weeks) who were clinically suspected of having AA and examined with MR imaging between March 2002 and August 2007 were retrospectively analyzed in an institutional review board-approved HIPAA-compliant protocol. One hundred forty patients underwent ultrasonography (US) before MR imaging. The clinical and laboratory data and the findings of the initial US and MR image interpretations were recorded and analyzed at Student t and Fisher exact testing. The NLR and PR were calculated. RESULTS Fourteen (10%) patients had AA, and perforation occurred in three (21%) of them. US results were positive for AA in five (36%) patients with proved AA. MR results were positive in all 14 patients with AA. MR results were negative in 125 of the 134 patients without AA; there were nine false-positive cases (two positive, seven inconclusive). Among the patients without AA, the normal appendix could be visualized on US images in less than 2% (two of 126) of cases and on MR images in 87% (116 of 134) of cases (P < .0001). Twenty-seven (18%) patients underwent surgical exploration, and eight of them had negative laparotomy results, yielding an NLR of 30% and a PR of 21% (three of 14 patients). Only four (3%) patients underwent CT. CONCLUSION For pregnant patients clinically suspected of having AA, use of MR imaging yields favorable combinations of NLR and PR compared with previously reported values. The radiation exposure associated with CT examination can be avoided in most cases.