Shetal N. Shah

Morphology, Attenuation, Size, and Structure (MASS) Criteria: Assessing Response and Predicting Clinical Outcome in Metastatic Renal Cell Carcinoma on Antiangiogenic Targeted Therapy

OBJECTIVE The objective of our study was to evaluate response assessment and predict clinical outcome in patients with metastatic renal cell carcinoma (RCC) receiving antiangiogenic targeted therapy. Target lesions were assessed on routine contrast-enhanced CT (CECT) images obtained during the portal venous phase using new response criteria. MATERIALS AND METHODS Standard CECT examinations of patients with metastatic clear cell RCC on first-line sunitinib or sorafenib therapy (n = 84) were retrospectively evaluated using Mass, Attenuation, Size, and Structure (MASS) Criteria; Response Evaluation Criteria in Solid Tumors (RECIST); Size and Attenuation CT (SACT) Criteria; and modified Choi Criteria. The objective response to therapy was compared with clinical outcomes including time to progression (TTP) and disease-specific survival. The Kaplan-Meier method was used to estimate survival functions. RESULTS A favorable response according to MASS Criteria had a sensitivity of 86% and specificity of 100% in identifying patients with a good clinical outcome (i.e., progression-free survival of > 250 days) versus 17% and 100%, respectively, for RECIST partial response. The objective categories of response used by MASS Criteria-favorable response, indeterminate response, and unfavorable response-differed significantly from one another with respect to TTP (p < 0.0001, log-rank test) and disease-specific survival (p < 0.0001, log-rank test). CONCLUSION Assessment of metastatic RCC target lesions on CECT for changes in morphology, attenuation, size, and structure by MASS Criteria is more accurate than response assessment by SACT Criteria, RECIST, or modified Choi Criteria. Furthermore, the use of MASS Criteria for imaging response assessment showed high interobserver agreement and may predict disease outcome in patients with metastatic RCC on targeted therapy.

Assessing Tumor Response and Detecting Recurrence in Metastatic Renal Cell Carcinoma on Targeted Therapy: Importance of Size and Attenuation on Contrast-Enhanced CT

OBJECTIVE The aim of this study was to improve response assessment in patients with metastatic renal cell carcinoma (RCC) on antiangiogenic targeted therapy by evaluating changes in both tumor size and attenuation and by detecting unique patterns of contrast enhancement on contrast-enhanced CT (CECT). MATERIALS AND METHODS Tumor long-axis measurements and volumetric mean tumor attenuation of target lesions on CECT images were correlated with time to progression in 53 patients with metastatic clear cell RCC treated with first-line sorafenib or sunitinib. The frequencies of specific patterns of tumor progression were assessed. The data were used to develop new imaging criteria, the size and attenuation CT (SACT) criteria. CECT findings were evaluated using the SACT criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and modified Choi criteria, and the Kaplan-Meier method was used to estimate survival functions. RESULTS One or more target metastatic lesions had decreased attenuation of >or=40 HU in 59% of patients with progression-free survival of >250 days (n=44) after initiating targeted therapy; 0% of patients with earlier disease progression (n=9) had this finding. A favorable response based on SACT criteria had a sensitivity of 75% and specificity of 100% for identifying patients with progression-free survival of >250 days, versus 16% and 100%, respectively, for RECIST and 93% and 44% for the modified Choi criteria. CONCLUSION Objectively measuring changes in both tumor size and attenuation on the first CECT study after initiating targeted therapy for metastatic RCC markedly improves response assessment. Distinct patterns of disease recurrence are seen in patients with metastatic RCC on targeted therapy.

Bosniak Category IIF and III Cystic Renal Lesions: Outcomes and Associations

PURPOSE To evaluate clinical outcomes, pathologic subtypes, metastatic disease rate, and clinical features associated with malignancy in Bosniak category IIF and III cystic renal lesions. MATERIALS AND METHODS This retrospective study was institutional review board approved and HIPAA compliant. Informed consent was waived. Radiology and hospital information systems were searched for Bosniak IIF and Bosniak III lesions in computed tomographic (CT) reports from January 1, 1994 to August 31, 2009. Patients 18 years and older with unenhanced and contrast material-enhanced CT results and with lesions either surgically resected or with 1 year or more of surveillance were included. Data recorded were history of renal cell carcinoma, number of renal lesions, presence of a coexistent solid renal mass, surgical pathologic findings, and presence of metastatic disease from a renal malignancy. Sixty-two patients with 69 Bosniak IIF lesions and 131 patients with 144 Bosniak III lesions were identified. Proportions from independent groups were compared by using the Fisher exact test; continuous variables were compared by using a two-tailed two-sample t test or a Wilcoxon two-sample test. RESULTS The malignancy rate of resected Bosniak IIF lesions was 25% (four of 16) and that for Bosniak III lesions was 54% (58 of 107) (P = .03). Thirteen percent (nine of 69) of Bosniak IIF lesions progressed at follow-up, and 50% (four of eight) of these resected cysts were malignant. History of primary renal malignancy, coexisting Bosniak category IV lesion and/or solid renal mass, and multiplicity of Bosniak III lesions were each associated with an increased malignancy rate in Bosniak III lesions. No patients developed locally advanced or metastatic disease from a Bosniak IIF or III lesion. CONCLUSION Although the malignancy rate in surgically excised Bosniak IIF and Bosniak III cystic renal lesions was 25% and 54%, respectively, in our study, the malignancy rate was higher in patients with a history of primary renal malignancy or coexisting Bosniak IV lesion and/or solid renal neoplasm.

The Effect of Sunitinib on Primary Renal Cell Carcinoma and Facilitation of Subsequent Surgery

PURPOSE We investigated the effect of sunitinib on locally advanced primary renal carcinoma tumors and the ability to facilitate subsequent surgery. MATERIALS AND METHODS Patients with an unresectable primary renal tumor, with or without distant metastases, received 50 mg sunitinib with continuous daily dosing in a phase II trial. Computerized tomography was performed every 12 weeks to determine surgical resectability. The primary end point of the trial was the percentage of patients with renal cell carcinoma and initially unresectable primary tumors who could undergo nephrectomy after sunitinib therapy. RESULTS Of 30 patients enrolled in the study (19 with distant metastases) 28 (35 total renal tumors) were evaluable for response. The median change in primary renal cell carcinoma tumors was a 22% decrease, corresponding to a median absolute reduction of 1.2 cm. The median reduction in primary renal cell carcinoma tumors of clear cell histology was -28% (absolute reduction 1.7 cm) compared to a 1.4% increase (0.1 cm absolute increase) in nonclear cell tumors. Of these patients 13 (45%) met the primary end point of being able to undergo nephrectomy after preoperative sunitinib. All patients had viable renal cell carcinoma in the surgical specimen and surgical morbidity was consistent with prior experience of nephrectomy in patients without preoperative therapy. CONCLUSIONS Sunitinib as initial therapy in patients with locally advanced features of the primary tumor was feasible and resulted in an antitumor effect that enabled subsequent surgery in a subset of patients. Further prospective study is required to refine the most suitable application of this approach.

Reversal of sarcopenia predicts survival after a transjugular intrahepatic portosystemic stent.

Background Sarcopenia is the most frequent complication of cirrhosis. A transjugular intrahepatic portosystemic stent (TIPS) lowers portal pressure in cirrhosis and alters the body composition. Changes in the skeletal muscle area and adipose tissue volume were quantified by computed tomography (CT) before and after TIPS. Materials and methods Fifty-seven consecutive cirrhotics who had a CT scan before and after TIPS were studied. Simultaneous age-matched, sex-matched, Child’s score-matched, and Model for End-Stage Liver Disease score-matched cirrhotics (n=32) who did not undergo TIPS comprised the disease control and 57 healthy individuals who had undergone CT abdomen comprised the healthy control population. Muscle area and fat volume were obtained at the mid-L4 vertebra level on the CT scans. Results Patients (mean age 55.5±8.1 years) were followed up for a mean of 13.5±11.9 months following TIPS. Total psoas and paraspinal muscle area increased significantly (P<0.0001) after TIPS (from 22.8±0.9 to 25.1±0.9 cm2 and 54.5±1.3 to 57.9±1.5 cm2, respectively). After TIPS, muscle area increased in 41 patients but remained unchanged or decreased in 16 patients. Post-TIPS visceral fat volume decreased significantly (47.7±4.1 to 40.5±3.4 cm3; P<0.001). Failure to reverse sarcopenia after TIPS was accompanied by higher (P=0.007) mortality (43.5%) compared with patients in whom the total muscle area increased (9.8%). On multivariate analysis, predictors of reversal of sarcopenia after TIPS included male sex and lower pre-TIPS muscle area. Cirrhotic patients who did not undergo TIPS showed no change in the mean muscle area over 13.1±1.3 months. Conclusion TIPS reverses sarcopenia in cirrhotic patients. Failure to improve muscle area after TIPS was accompanied by a higher mortality.

Post‐liver transplantation sarcopenia in cirrhosis: A prospective evaluation

Pre‐transplant sarcopenia (reduced skeletal muscle mass) predicts poor outcome in cirrhosis. In contrast, whether muscle mass increases post‐orthotopic liver transplantation (OLT) is not known and was studied prospectively.

Hepatocellular adenomas: Current update on genetics, taxonomy, and management

Hepatocellular adenomas (HCAs) are uncommon, benign hepatocellular neoplasms that commonly occur in young women. Recent advances in pathology and cytogenetics have thrown fresh light on the pathogenesis of HCAs leading to classification of HCAs into 3 distinct subtypes, each with a characteristic epidemiology, histopathology, oncogenesis, and imaging findings. The aim of the article was to provide a comprehensive review of contemporary taxonomy of HCAs, with an emphasis on cross-sectional imaging findings and management.

Sarcopenia and a physiologically low respiratory quotient in patients with cirrhosis: a prospective controlled study

Patients with cirrhosis have increased gluconeogenesis and fatty acid oxidation that may contribute to a low respiratory quotient (RQ), and this may be linked to sarcopenia and metabolic decompensation when these patients are hospitalized. Therefore, we conducted a prospective study to measure RQ and its impact on skeletal muscle mass, survival, and related complications in hospitalized cirrhotic patients. Fasting RQ and resting energy expenditure (REE) were determined by indirect calorimetry in cirrhotic patients (n = 25), and age, sex, and weight-matched healthy controls (n = 25). Abdominal muscle area was quantified by computed tomography scanning. In cirrhotic patients we also examined the impact of RQ on mortality, repeat hospitalizations, and liver transplantation. Mean RQ in patients with cirrhosis (0.63 ± 0.05) was significantly lower (P < 0.0001) than healthy matched controls (0.84 ± 0.06). Psoas muscle area in cirrhosis (24.0 ± 6.6 cm(2)) was significantly (P < 0.001) lower than in controls (35.9 ± 9.5 cm(2)). RQ correlated with the reduction in psoas muscle area (r(2) = 0.41; P = 0.01). However, in patients with cirrhosis a reduced RQ did not predict short-term survival or risk of developing complications. When REE was normalized to psoas area, energy expenditure was significantly higher (P < 0.001) in patients with cirrhosis (66.7 ± 17.8 kcal/cm(2)) compared with controls (47.7 ± 7.9 kcal/cm(2)). We conclude that hospitalized patients with cirrhosis have RQs well below the traditional lowest physiological value of 0.69, and this metabolic state is accompanied by reduced skeletal muscle area. Although low RQ does not predict short-term mortality in these patients, it may reflect a decompensated metabolic state that requires careful nutritional management with appropriate consideration for preservation of skeletal muscle mass.

Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post-Radioembolization 90Y PET

Background: Radioembolization with Yttrium-90 (90 Y) microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC). Using post-treatment 90 Y positron emission tomography/computerized tomography (PET/CT) scans, the distribution of microspheres within the liver can be determined and quantitatively assessed. We studied the radiation dose of 90 Y delivered to liver and treated tumors. Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres®) to the frequency of complications with modified response evaluation criteria in solid tumors (mRECIST). 90 Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL) to an absorbed dose (Gy). Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90–120 Gy; range 0–570 Gy). Tumor response by mRECIST criteria was performed for 48 tumors that had follow-up scans. There were 21 responders (mean dose 215 Gy) and 27 non-responders (mean dose 167 Gy). The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p = 0.099). Normal liver tissue received a mean dose of 67 Gy (mode 60–70 Gy; range 10–120 Gy). There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p = 0.036). Conclusion: Our cohort of patients showed a possible dose–response trend for the tumors. Collateral dose to normal liver is non-trivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose that the tumor or normal liver received.

Detection of Urolithiasis: Comparison of 100% Tube Exposure Images Reconstructed with Filtered Back Projection and 50% Tube Exposure Images Reconstructed with Sinogram-affirmed Iterative Reconstruction

PURPOSE To compare images acquired with 50% tube exposure with a dual-source computed tomographic (CT) scanner and reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE) with 100% exposure images reconstructed with filtered back projection (FBP) for reader ability to detect stones, reader confidence, and findings outside the urinary tract. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board-approved study, imaging examinations in 99 patients with urolithiasis were assessed. Data from both tubes were reconstructed with FBP; data from the primary tube only were reconstructed with SAFIRE. Seven readers evaluated randomized studies for calculi in nine regions. Reader confidence was scored by using a five-point scale. Ancillary findings were noted. Nonparametric methods for clustered data were used to estimate the area under the receiver operating characteristic curves with 95% confidence intervals to test for noninferiority of 50% exposure with SAFIRE. RESULTS Calculi were found in 113 locations (pyelocalyceal ureter, 86; proximal ureter, seven; midureter, four; distal ureter, 15; bladder, one) and not found in 752 locations. Mean area under the receiver operating characteristic curve for FBP was 0.879 (range, 0.607-0.967) and for SAFIRE, 0.883 (range, 0.646-0.971; 95% confidence interval: -0.025, 0.031). The SAFIRE images were not significantly inferior to FBP images (P = .001). Reader confidence levels for images with stones were similar with FBP and SAFIRE (P = .963). For the 52 patients who had extraurinary findings, readers reported them correctly in 74.4% (271 of 364) and 72.0% (262 of 364) of cases (P = .215) for FBP and SAFIRE, respectively. For the nine patients with potentially important findings per the reference standard, the detection rates were 44% (28 of 63) and 33% (21 of 63, P = .024), respectively. For the 43 patients with unimportant or likely unimportant findings, the false detection rates were 15% (44 of 301) and 14% (43 of 301, P = .756), respectively. CONCLUSION The 50% tube exposure CT images reconstructed with SAFIRE were not inferior to 100% exposure images reconstructed with FBP for diagnosis of urolithiasis, without decreases in reader confidence.