Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers.

BACKGROUND: This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy. PATIENTS AND METHODS: Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. RESULTS: Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin, and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD. CONCLUSIONS: Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.

Fourteen-gauge ultrasonographically guided large-core needle biopsy of breast masses.

OBJECTIVE: Large-core needle biopsy of the breast can be performed with stereotactic or ultrasonographic guidance. However, ultrasonographically guided large-core needle biopsy has notable advantages, including the absence of ionizing radiation, increased patient comfort, and greater cost-effectiveness. The purpose of this study was to evaluate the accuracy of ultrasonographically guided large-core needle biopsy for the diagnosis of breast cancer in palpable and nonpalpable breast masses. METHODS: The study was a retrospective review of consecutive ultrasonographically guided large-core needle biopsies for indeterminate breast masses. A total 424 ultrasonographically guided core biopsies were performed in 367 patients with 1 or more breast masses. Ultrasonographically guided core biopsy was performed with a 14-gauge spring-loaded needle and a freehand technique. Correlation of ultrasonographically guided core biopsy pathologic findings with subsequent surgical pathologic findings or long-term imaging follow-up was performed. RESULTS: Of 424 indeterminate breast lesions for which histopathologic findings were obtained by ultrasonographically guided core biopsy, 234 cancers were diagnosed. Twenty-eight additional lesions had either questionable but not definitively malignant pathologic features (n = 11) or radiologic-pathologic discordance (n = 17) and were surgically excised. Of these, 8 additional cancers were diagnosed. Patients or surgeons chose excision of 41 additional lesions that were benign on ultrasonographically guided core biopsy No cancer was found in these surgical specimens. One additional cancer was diagnosed at a 6-month imaging follow-up because of interval growth. On the basis of surgical and long-term imaging follow-up, the sensitivity of ultrasonographically guided core biopsy for the diagnosis of breast carcinoma was 99.2% (95% confidence interval, 95.6%-99.9%) in 173 palpable breast masses and 93.2% (95% confidence interval, 87.1%-97%) in 251 nonpalpable masses. In cancers diagnosed on the basis of immediate surgical excision as a result of ultrasonographically guided core biopsy that showed either questionable pathologic features or radiologic-pathologic discordance, the sensitivity of ultrasonographically guided core biopsy for the diagnosis of breast cancer was 99.2%. CONCLUSIONS: Ultrasonographically guided large-core needle biopsy is a sensitive percutaneous biopsy method for the diagnosis of breast cancer in palpable and nonpalpable breast masses.

Nonpalpable breast cancer: percutaneous diagnosis with 11- and 8-gauge stereotactic vacuum-assisted biopsy devices.

PURPOSE: To compare the accuracy of diagnosis of invasive breast cancer with 11- and 8-gauge stereotactic vacuum-assisted biopsy (SVAB) devices and to correlate lesion diameter and accuracy of breast cancer diagnosis at SVAB. MATERIALS AND METHODS: During a 22-month period, 489 SVAB procedures were performed with an 11-gauge probe and 305 with an 8-gauge probe. SVAB and surgical pathologic results of 104 breast carcinomas were reviewed and correlated with lesion size, number of specimens obtained, and type of SVAB probe used. RESULTS: Four of 38 ductal carcinoma in situ (DCIS) lesions diagnosed with 11-gauge SVAB demonstrated invasion at surgery, whereas one of 23 DCIS lesions diagnosed with 8-gauge SVAB demonstrated invasion at surgery (P =.6). A mean of 12 specimens per lesion were obtained in each group. In lesions 30 mm or larger, the underestimation rate for DCIS was 43% (three of seven) with 11-gauge SVAB and 17% (one of six) with 8-gauge SVAB (P =.6). Overall, the rate of underestimation for DCIS was significantly higher in lesions 30 mm or larger (four of 13) than in smaller lesions (one of 48, P =.006). CONCLUSION: This study demonstrated no difference in breast cancer diagnosis with the 8- and 11-gauge SVAB systems, but the accuracy of breast cancer diagnosis was greater in lesions smaller than 30 mm than in larger lesions.

Reliability of histologic diagnosis of breast cancer with stereotactic vacuum-assisted biopsy.

The purpose of this study was to determine the accuracy of 11-gauge stereotactic vacuum-assisted breast biopsy (SVAB) for the diagnosis of breast cancer. Percutaneous biopsies of 426 suspicious breast lesions in 365 patients using 11-gauge SVAB were performed between September 1996 and June 1998. Of these biopsies 59 (13.8%) resulted in a diagnosis of breast carcinoma and 56 (95%) were surgically excised. These 56 lesions constitute the basis of this study. Pathology of SVAB and surgically excised tissue of the 56 carcinomas as well as imaging findings were correlated. At percutaneous biopsy 34 (61%) lesions demonstrated ductal carcinoma in situ (DCIS) and 22 (39%) invasive carcinomas. Surgical excision demonstrated the presence of an invasive cancer in three lesions percutaneously diagnosed as DCIS (9%; confidence interval 2-24%). No residual carcinoma was surgically demonstrated in seven (12.5%) lesions. Sensitivity of 11-gauge SVAB for the diagnosis of invasion in breast cancer was 88 per cent. Using SVAB the diagnosis of invasive carcinoma is reliable. However, a percutaneous finding of DCIS does not exclude the presence of invasion in 9 per cent of cases as confirmed by subsequent surgery. Using SVAB 12.5% of carcinomas are completely excised.

Radiologist detection of microcalcifications with and without computer-aided detection: a comparative study.

AIM: To compare the sensitivity and specificity of microcalcification detection by radiologists alone and assisted by a computer-aided detection (CAD) system. MATERIALS AND METHODS: Films of 106 patients were masked, randomized, digitized and analysed by the CAD-system. Five readers interpreted the original mammograms and were blinded to demographics, medical history and earlier films. Forty-two mammograms with malignant microcalcifications, 40 with benign microcalcifications and 24 normal mammograms were included. Results were recorded on a standardized image interpretation form. The mammograms with suspicious areas flagged by the CAD-system were displayed on mini-monitors and immediately re-reviewed. The interpretation was again recorded on a new copy of the standard form and classified according to six groups. RESULTS: Forty-one out of 42 (98%) malignant microcalcifications and 32 of 40 (80%) benign microcalcifications were flagged by the CAD-system. There was an average of 1.2 markers per image. The sensitivity for malignant microcalcifications detection by mammographers without and with the CAD-system ranged from 81% to 98% and from 88% to 98%, respectively. The mean difference without and with CAD-system was 2.2% (range 0-7%). CONCLUSION: No statistically significant changes in sensitivity were found when experienced mammographers were assisted by the CAD-system, with no significant compromise in specificity.

Sonographic appearance of ductal carcinoma in situ diagnosed with ultrasonographically guided large core needle biopsy: correlation with mammographic and pathologic findings.

The purpose of this study was to evaluate sonographic features of ductal carcinoma in situ diagnosed percutaneously at ultrasonographically guided large core needle biopsy. Of 619 biopsies, 203 breast carcinomas were diagnosed, of which nine were pure ductal carcinoma in situ. All ductal carcinoma in situ lesions appeared sonographically as hypoechoic masses without a pseudocapsule. Grade 1 lesions (n = 2; mean size, 9.5 mm), grade 2 lesions (n = 4; mean size, 18 mm) and grade 3 lesions (n = 3; mean size, 32 mm) had means of 0, 1, and 5 malignant sonographic features, respectively. Ductal carcinoma in situ appeared mammographically as a mass, with two of four grade 2 lesions and all grade 3 lesions demonstrating suspicious microcalcifications. One grade 3 ductal carcinoma in situ was spiculated. In conclusion, ductal carcinoma in situ lesions tended to show more malignant mammographic and sonographic features as histologic grade and size increased.

[Induced expectoration or endoscopic samples in case of bronchopulmonary infection?]. / Expectorations induites ou prélèvements endoscopiques en cas d'infection bronchopulmonaire?

The aim of this study was to compare induced sputum versus bronchoscopy in a non selected population. An induced sputum and a bronchoscopy with aspiration of secretions and bronchoalveolar lavage (BAL) were proposed to 30 patients with suspected lower respiratory tract infection, including 14 subjects with AIDS. Induced sputum failed in 3 patients, while endoscopy could not be performed (contra-indication, refusal or failure due to lack of cooperation) in 7 patients; a technical failure for BAL was observed in 3/23 cases. Contamination by oral germs was significantly less frequent with BAL (4/20) than with aspiration (15/23) or induced sputum (17/27). A relevant pathogen was cultured from induced sputum in 7/27 cases (3 mycobacteria, 4 usual pathogens) from aspiration in 3/23 cases (one mycobacterium, 2 usual pathogens) and from BAL in 4/20 cases (one mycobacterium, 3 usual pathogens). These results suggest that induced sputum is a promising method when difficulties in performing bronchoscopy are expected (severe respiratory insufficiency, psychiatric disease, lack of cooperation).