Phase 1/2 clinical trial of interferon alpha2b and weekly liposome-encapsulated all-trans retinoic acid in patients with advanced renal cell carcinoma.

To evaluate the feasibility, efficacy, and biologic effects of weekly liposome-encapsulated all-trans retinoic acid (ATRA-IV) plus interferon alpha2b (IFN) in patients with advanced renal cell carcinoma (RCC). Twenty-six patients with metastatic RCC were treated on a phase 1/2 trial with weekly ATRA-IV and IFN SQ daily 5 d/wk. Twelve patients received ATRA-IV at three dose levels (60, 75, and 90 mg/m2) according to phase 1 methodology, and 14 additional patients received 90 mg/m2. Response was assessed according to an intention-to-treat analysis. Serum retinoic acid (RA) concentrations were assayed and peripheral blood mononuclear cell mRNA expression of RA and IFN-inducible genes (RARalpha, RARbeta2, IRF1, CRABP2, and TRAIL) were examined. No dose limiting toxicities occurred at 60 mg/m2; grade 3 leukopenia affected 1/6 patients at 75 mg/m2, whereas 3 patients received 90 mg/m2 without a dose limiting toxicities. Fourteen additional patients received 90 mg/m2 ATRA-IV without grade 3/4 toxicity. Five of 26 (19%) patients achieved a major response, with a median duration of 14 months (range 9 to 23); 9 additional patients (41%) demonstrated stable disease or minor response lasting > or =4 months. No significant differences in serum (RA) after ATRA infusion were detected between weeks 1 and 8 of treatment. Peripheral blood mononuclear cell mRNA expression did not correlate with clinical response. The addition of weekly ATRA-IV to IFN therapy is feasible and well tolerated, resulting in sustainable increased serum (RA). This regimen demonstrates antitumor activity in metastatic RCC, and suggests ATRA-IV augments IFN therapy.

Update on radiological imaging of renal cell carcinoma.

US is frequently used as the initial imaging in patients with suspected renal disease. US contrast agents offer the potential to increase the sensitivity in patients who cannot undergo CT or MTI. Harmonic imaging has helped with the evaluation of renal cystic lesions. CT remains the reference standard for staging and lesion characterization. The rapid technological advances mean that ultra-thin slices and 3D imaging have now become more widely available. MRI has also greatly advanced in speed and image quality, but at present, imaging time and scanner availability mean that MRI is generally used as a problem-solving tool. It is particularly helpful for smaller lesions and complex cystic lesions, where subtraction can be used to accurately identify the presence of enhancement. MRI is used as the primary diagnostic tool for patients with radiation concerns and those with renal failure. Caution must now also be taken in these patients, given the recent studies raising the association of gadolinium-based compounds and NSF. There have been dramatic improvements in renal imaging over the last decade, offering better resolution, shorter imaging times and better patient acceptance. The progress in minimally invasive techniques has driven the need to provide better preoperative information to the surgeon. The future of renal imaging is an exciting field; perhaps with fluorodeoxyglucose-based positron emission tomography we will be able to predict the biological behaviour of a tumour, and molecular imaging agents will become available to identify and hopefully treat specific tumour types.

Analysis of changes in attenuation of proven renal cysts on different scanning phases of triphasic MDCT.

OBJECTIVE: The purpose of this study is to document changes in attenuation values on triphasic MDCT of histologically or surgically proven cystic renal lesions. MATERIALS AND METHODS: A retrospective study of all renal lesions greater than 1 cm that underwent triphasic MDCT was performed in 90 patients before partial nephrectomy. Three reviewers independently measured the mean attenuation of all lesions in three phases (unenhanced, corticomedullary, and parenchymal) in a blinded retrospective fashion. Forty-three lesions identified at CT in 27 patients had pathologic or surgical confirmation as cysts (fluid-filled lesions). Mean change in attenuation between phases was calculated and correlated with size, unenhanced density, and percentage of the lesion exophytic from renal parenchyma. All scans were obtained after 150 mL of nonionic contrast material was injected at 3 mL/sec. Scanning delays were 30-40 sec (corticomedullary phase) and 120 sec (parenchymal phase). RESULTS: The mean change in attenuation coefficient of the cysts from the unenhanced to the parenchymal phase was -1.8 H (SD, +/- 4.4 H); from the unenhanced to the corticomedullary phase was -2.3 H (+/- 3.9 H); and from the corticomedullary to the parenchymal phase was 0.6 H (+/- 4.2 H). No cyst increased more than 10 H between the unenhanced and the parenchymal phases; more than 95% of cysts increased less than 8 H between any scanning phases. No significant difference was seen in enhancement related to lesion size (p > 0.054), unenhanced attenuation (p > 0.255), or percentage of the lesion that was exophytic (p > 0.124). CONCLUSION: The attenuation coefficient of a cystic renal lesion increased by no more than 10 H among the unenhanced, corticomedullary, and parenchymal phase scans.

Enhancement characteristics of papillary renal neoplasms revealed on triphasic helical CT of the kidneys.

OBJECTIVE: The purpose of this study was to determine whether renal tumor enhancement or heterogeneity on triphasic helical CT scans is predictive of the papillary cell subtype or nuclear grade of renal cell carcinoma. MATERIALS AND METHODS: We reviewed the CT scans of 90 consecutive patients with renal masses who had undergone triphasic renal helical CT before a complete or partial nephrectomy (12 with papillary renal cell carcinomas, 66 with nonpapillary renal cell carcinomas, and 12 with benign lesions). Three radiologists who were unaware of the patients' diagnoses retrospectively and independently measured the attenuation of each patient's tumor, abdominal aorta, and normal renal parenchyma on the scans obtained during all three phases. Ratios of tumor-to-aorta enhancement and tumor-to-normal renal parenchyma enhancement were calculated for both of the phases performed after contrast material had been administered. Tumor heterogeneity was calculated as the difference between the highest and lowest attenuation values divided by the value of the enhancement of the aorta. Values were correlated with cell type and nuclear grade found at surgical pathology. RESULTS: Low tumor-to-aorta enhancement and low tumor-to-normal renal parenchyma enhancement ratios on the vascular phase scans significantly correlated (p < 0.001) with papillary renal cell type carcinoma. Homogeneity and tumor-to-parenchyma enhancement ratios on the parenchymal phase scans also significantly correlated (p < 0.001) with papillary renal cell type carcinoma. Heterogeneity and tumor enhancement ratios did not correlate with the nuclear grade of the carcinoma. CONCLUSION: Papillary renal cell carcinomas are typically hypovascular and homogeneous. A high tumor-to-parenchyma enhancement ratio (> or = 25%) essentially excludes the possibility of a tumor being papillary renal cell carcinoma. A low tumor-to-aorta enhancement ratio or tumor-to-normal renal parenchyma enhancement ratio is more likely to indicate papillary renal cell carcinoma.

Relationship of spontaneous passage of ureteral calculi to stone size and location as revealed by unenhanced helical CT.

OBJECTIVE: Prior studies using radiography have examined the relationship of ureteral stone size and location to the probability of spontaneous passage. Given the improved accuracy and new role of unenhanced CT in the diagnosis of acute ureterolithiasis, we studied the relationship of stone size and location as determined by unenhanced CT to the rate of spontaneous passage. MATERIALS AND METHODS: Over a 29-month period, 850 patients with acute flank pain were evaluated with unenhanced CT. Confirmation of the CT diagnosis was obtained retrospectively for 172 patients with ureteral stones: 115 stones passed spontaneously and 57 required intervention. Stone size was defined as the maximum diameter within the plane of the axial CT section. Stone location was classified as proximal ureter (above the sacroiliac joints), mid ureter (overlying the sacroiliac joints), distal ureter (below the sacroiliac joints), and ureterovesical junction. RESULTS: The spontaneous passage rate for stones 1 mm in diameter was 87%; for stones 2-4 mm, 76%; for stones 5-7 mm, 60%; for stones 7-9 mm, 48%; and for stones larger than 9 mm, 25%. Spontaneous passage rate as a function of stone location was 48% for stones in the proximal ureter, 60% for mid ureteral stones, 75% for distal stones, and 79% for ureterovesical junction stones. CONCLUSION: The rate of spontaneous passage of ureteral stones does vary with stone size and location as determined by CT. These rates are similar to those previously published based on radiography.