Inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by diffusion-weighted imaging (DWI) in small renal masses.

BACKGROUND: Diffusion-weighted imaging (DWI) is increasingly used to diagnose renal lesion subtypes. Especially in small renal masses, identification of less aggressive tumor types is of clinical interest, as active surveillance strategies can be applied. PURPOSE: To evaluate the inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by DWI in small renal masses ≤4 cm (SRM). MATERIAL AND METHODS: This retrospective IRB-approved study included 39 patients (46 SRM: 12 benign, 34 malignant). All underwent a 3 T DWI of SRM prior to surgery. Two radiologists independently analyzed all imaging data by three measurements. Limits of agreement, intraclass correlation coefficients (ICC), group comparisons by t-tests, and ROC analysis were performed. RESULTS: Reliability of ADC measurements was very high with an ICC of >0.9 for both observers. Inter-rater reliability was high with an ICC of 0.82. Limits of agreement for average ADC values between both observers were -23.5% to 38.3% with a mean difference of 7.5% between both observers. No significant differences were found between benign and malignant lesions (P value Observer 1: 0.362, Observer 2: 0.622). Papillary carcinoma showed lower ADC values compared to non-papillary carcinoma (P value Observer 1: 0.008, Observer 2: 0.012). Consequently, ROC analysis revealed a significant (P < 0.001, respectively) area under the ROC curve of 0.853 (Observer 1) and 0.837 (Observer 2) without significant differences between both readers (P = 0.772). CONCLUSION: ADC measurements of SRM at 3 T show a high reproducibility and differentiate papillary from non-papillary carcinoma subtypes. However, measurement variability may limit the application of fixed ADC thresholds for lesion diagnosis.

Diagnosis of renal tumors by in vivo proton magnetic resonance spectroscopy.

PURPOSE: To evaluate the diagnostic potential of choline measurements by in vivo magnetic resonance spectroscopy (MR spectroscopy) for diagnosis of renal masses. METHODS: Twenty-eight patients with 29 renal lesions underwent prospectively preoperative 3 T MR spectroscopy of renal masses before diagnostic tissue confirmation. A respiratory-triggered single-voxel MR spectroscopy was performed in these masses using the point-resolved spectroscopy (TR, 2,000 ms, TE, 135 ms) sequence. The spectra were analyzed for choline resonances at 3.23 ppm, which were normalized by the noise outside the diagnostic range of the spectra. Image and spectra analyses were conducted blinded to all patient-related data. Histological results of the surgical resection or image-guided biopsy specimen were defined as the standard of reference. Appropriate statistical tests were used. RESULTS: Seventeen lesions were histopathologically malignant, and 12 lesions were benign. Mean choline SNR in malignant lesions was 2.9 and 1.33 in benign lesions (P = 0.019). ROC analysis revealed an area under the curve of 0.721 and SE 0.0763 with a P value of 0.0038. A Cho SNR ≥2 as cutoff for malignancy resulted in a sensitivity and specificity of 52.9 % (95 % CI 27.8-77.0 %) and 91.7 % (61.5-99.8 %), respectively. Although not significant, choline was observed more regularly in G3 (4 out of 5) compared with G2 (5 out of 12) RCC (P > 0.05). CONCLUSIONS: We could demonstrate the potential role of in vivo MR spectroscopy as a tool for differentiating benign from malignant masses with a high positive predictive value of 90 %. Furthermore, choline may be a biomarker of RCC aggressiveness.

Quantitative apparent diffusion coefficient measurements obtained by 3-Tesla MRI are correlated with biomarkers of bladder cancer proliferative activity.

PURPOSE: To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer. MATERIALS AND METHODS: Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied. RESULTS: Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018). CONCLUSION: ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.

Prospective evaluation of diffusion-weighted MRI of the bladder as a biomarker for prediction of bladder cancer aggressiveness.

OBJECTIVES: To prospectively test the utility of diffusion-weighted magnetic resonance imaging (DW-MRI) for bladder cancer (BCA) staging and grading. METHODS AND MATERIALS: We prospectively enrolled 51 consecutive patients (median age = 64 y, range: 30-90y) with suspected BCA with or without gross hematuria who received 3-T DW-MRI before transurethral resection of the bladder. Parametric apparent diffusion coefficient (ADC) maps were automatically calculated from DW-MRI. ADC values (given in × 10(-3)mm(2)/s) of bladder lesions were independently measured by 2 radiologists blinded to histopathology. Comparisons of ADC values with histopathologic features were performed using unpaired t tests. Diagnostic performance was calculated by means of receiver operating characteristics (ROC) statistics. RESULTS: We excluded 8 patients: 1 presenting with metastatic melanoma to the bladder, 1 who had an incomplete examination, and 6 without BCA. In the 43 remaining patients (median age = 68 y, range: 41-85 y), the ADC values were lower in high-grade (n = 19, ADC = 0.787) compared with low-grade (n = 24, ADC = 1.233) tumors (P<0.0001) and in muscle-invasive tumors (n = 10, ADC = 0.759) compared with non-muscle-invasive tumors (n = 33, ADC = 1.120, P = 0.0004). The area under the ROC curve was 0.884 for prediction of muscle invasion and 0.906 for prediction of high grade by using ADC values. Rule-in ADC criteria for high-grade lesions and rule-out ADC criteria for muscle invasion were identified by ROC analysis. CONCLUSIONS: ADC measurements obtained by DW-MRI are a promising imaging biomarker for prediction of BCA stage and grade providing high sensitivity and specificity. Further studies are necessary to establish the value of this test in guiding decision making in clinical practice.

Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: the gender-specific differences.

The aim of this study was to compare the side effects of the pentagastrin test and the calcium stimulation test in patients with increased basal calcitonin concentration, especially the gender-specific differences of side effects. A total of 256 patients (123 females and 133 males, mean age of 56 ± 27 years, range 21-83 years) had both pentagastrin and calcium stimulation tests. All patients filled in a questionnaire regarding the side effects within 30 min after completion of the stimulation tests. The differences of side effects between female and male patients as well as between the pentagastrin stimulation test and the calcium stimulation test were evaluated. Warmth feeling was the most frequent occurring side effect in all patients who had both pentagastrin and calcium stimulation tests, followed by nausea, altered gustatory sensation, and dizziness. The incidences of urgency to micturate (p < 0.05) and dizziness (p < 0.05) were significantly increased in the female patients as compared to male patients by calcium stimulation test. Significant higher incidences of urgency to micturate (p < 0.05) and warmth feeling (p < 0.05) were found by calcium stimulation test as compared with those by pentagastrin test in female patients. The incidences of nausea (p < 0.05) and abdominal cramping (p < 0.05) in male patients were significantly higher by pentagastrin stimulation test than by calcium stimulation test. There is a significant gender-specific difference in side effects induced by calcium stimulation test. Female patients have fewer side effects by pentagastrin test than by calcium stimulation test. Male patients may tolerate the calcium stimulation test better than the pentagastrin test.

CD19(+)CD21(low) B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS), pathognomonic for chronic graft-versus-host disease (cGVHD) of the lung, is a progressive and often fatal complication after allogeneic hematopoietic cell transplantation (HCT). Biomarkers for the prediction and diagnosis of BOS are urgently needed to improve patients' prognosis. We prospectively evaluated B-cell subpopulations and B-cell activating factor (BAFF) in 136 patients (46 BOS, 41 no cGVHD, 49 cutaneous cGVHD) to define novel biomarkers for early diagnosis of National Institutes of Health-defined BOS diagnosed a median of 11 mo after HCT. Patients with newly diagnosed BOS had significantly higher percentages of CD19(+)CD21(low) B cells (25.5 versus 6.6%, P < .0001), BAFF (7.3 versus 3.5 ng/mL, P = .02), and BAFF/CD19(+) ratio (0.18 versus 0.02 ng/10(3) CD19(+) B cells, P 5 .007) compared with patients without cGVHD. The area under the receiver operating curve for CD19(+)CD21(low) B cells was 0.97 (95% confidence interval, 0.94-0.99) and a cutoff point >9% was optimal for diagnosing BOS in patients with first drop of pulmonary function tests with a sensitivity of 96% and a negative predictive value of 94%. Thus, elevated levels of CD19(+)CD21(low) B cells are a potential novel biomarker for HCT patients at risk for developing BOS at an early stage and could allow improvement of patient outcome.

Can galactography-guided stereotactic, 11-gauge, vacuum-assisted breast biopsy of intraductal lesions serve as an alternative to surgical biopsy?

The purpose of this study was to determine the value of galactography-guided, stereotactic, vacuum-assisted breast biopsy (VABB) for the assessment of intraductal breast lesions and its potential as a therapeutic tool that could eliminate the need for surgical excision. Eighteen patients (median age 64 years, range 37-80) with nipple discharge and galactography-verified intraductal lesions underwent galactography-guided, stereotactic, 11-gauge VABB followed by surgery. Histopathology findings from VABB and subsequent surgery were compared. Underestimation and false-negative rates were assessed. After VABB, histopathology revealed invasive ductal carcinoma (IDC) in three (17%), ductal carcinoma in situ (DCIS) in six (33%), high-risk lesions in six (33%) and benign lesions in three (17%) cases. After surgical biopsy, histopathology confirmed the previously established diagnosis in 11 lesions (61%). The underestimation rate for high-risk lesions and DCIS was 50% (6/12). The false-negative rate was 7% (1/14). Histopathology examination after surgery showed that not a single lesion had been completely removed at VABB. Galactography-guided VABB is a feasible diagnostic tool. However, its value as a therapeutic procedure is limited because of the high number of underestimated and missed lesions and because of the histopathological detection of lesions' remnants in every case. Surgical excision should be the therapeutic gold standard in cases of pathological nipple discharge and galactography abnormalities.

US-guided 14-gauge core-needle breast biopsy: results of a validation study in 1352 cases.

PURPOSE: To retrospectively determine the false-negative rate and the underestimation rate of ultrasonography (US)-guided 14-gauge core-needle breast biopsy (CNB) in nonpalpable lesions, with validation at surgical excision histologic examination and with stability during clinical and imaging follow-up. MATERIALS AND METHODS: Informed consent was waived by the institutional review board for this retrospective review of 1352 cases. In 1061 cases, patients underwent surgical excision of lesions visible at US subsequent to US-guided 14-gauge CNB. Follow-up of another 291 benign lesions at US-guided 14-gauge CNB histologic examination showed stability during clinical and imaging follow-up for at least 2 years. US and histologic findings were reviewed and compared for agreement. A false-negative finding was defined as pathologically proved cancer for which biopsy results were benign. The false-negative rate was defined as the proportion of all breast cancers with a diagnosis of benign disease at US-guided 14-gauge CNB. The underestimation rate was defined as an upgrade of a high-risk lesion at US-guided 14-gauge CNB to malignancy at surgery. RESULTS: US 14-gauge CNB yielded 671 (63.2%) malignant, 86 (8.1%) high-risk, and 304 (28.7%) benign lesions. Each of the 291 benign lesions without surgery remained stable during follow-up. The agreement of US-guided 14-gauge CNB results, surgical excision findings, and follow-up results was 95.8% (kappa = 0.93). False-negative findings were encountered in 11 (0.8%) of 1352 cases, and the false-negative rate was 1.6% (11 of 671 malignancies). All false-negative findings were prospectively identified owing to discordance between imaging results and US-guided 14-gauge CNB histologic findings. The underestimation rate was 31.4%. CONCLUSION: US-guided 14-gauge CNB is an alternative to surgical excision for assessing nonpalpable breast lesions.

Magnetic resonance imaging of the breast improves detection of invasive cancer, preinvasive cancer, and premalignant lesions during surveillance of women at high risk for breast cancer.

PURPOSE: To assess the diagnostic accuracy of mammography, ultrasound, and magnetic resonance imaging (MRI) of the breast in the surveillance of women at high risk for breast cancer. EXPERIMENTAL DESIGN: In this prospective comparison study, women at high risk for breast cancer were offered annual surveillance examinations, consisting of mammography, ultrasound, and MRI, at a single tertiary care breast center. The sensitivity and specificity of each modality was based on the histopathologic evaluation of suspicious findings from all modalities plus the detected interval cancers. RESULTS: Three hundred and twenty-seven women underwent 672 complete imaging rounds. Of a total of 28 detected cancers, 14 were detected by mammography, 12 by ultrasound, and 24 by MRI, which resulted in sensitivities of 50%, 42.9%, and 85.7%, respectively (P < 0.01). MRI detected not only significantly more invasive but also significantly more preinvasive cancers (ductal carcinoma in situ). Mammography, ultrasound, and MRI led to 25, 26, and 101 false-positive findings, which resulted in specificities of 98%, 98%, and 92%, respectively (P < 0.05). Thirty-five (35%) of these false-positive findings were atypical ductal hyperplasias, lesions considered to be of premalignant character. Nine (26%) of those were detected by mammography, 2 (6%) with ultrasound, and 32 (91%) with MRI (P < 0.01). CONCLUSION: Our results show that MRI of the breast improves the detection of invasive cancers, preinvasive cancers, and premalignant lesions in a high-risk population and should therefore become an integral part of breast cancer surveillance in these patients.