Texture analysis on MR images helps predicting non-response to NAC in breast cancer.

BACKGROUND: To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI. METHODS: Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC. RESULTS: A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction. CONCLUSION: Pre-NAC texture and kinetic parameters help predicting non-benefit to NAC. Further testing including larger groups of patients with different tumor subtypes is needed to improve the generalization properties and validate the performance of the predictive model.

The place of extensive surgery in locoregional recurrence and limited metastatic disease of breast cancer: preliminary results.

UNLABELLED: The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence. MATERIAL AND METHODS: Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable. RESULTS: The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival. CONCLUSION: Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent.

Fibroadenoma: can fine needle aspiration biopsy avoid short term follow-up?

OBJECTIVE: To confirm whether fine needle aspiration biopsy (FNAB) can avoid close monitoring, a source of worry for women patients with a suspected fibroadenoma found by ultrasound, and requiring their compliance. PATIENTS AND METHODS: Over 39months, 427 nodules with a diagnosis of fibroadenoma were sampled in 372 patients using ultrasound-guided FNAB. The sonographic appearance of all the nodules suggested BI-RADS category 3 fibroadenomas. The mean size of the fibroadenomas was 9mm. The mean duration of follow-up was 29.7months. RESULTS: Seven nodules had atypical cytology: a microbiopsy and/or excision found a simple fibroadenoma (n=3), mastitis (n=1), a fibroadenoma associated with a papilloma (n=1), fibrosis (n=1) and normal tissue (n=1). Seven other nodules were resected during treatment for synchronous cancer, and were diagnosed as fibroadenomas. Two hundred and seventy-six nodules were followed-up (121 patients were lost to follow-up [n=132]) and the appearance of 263 nodules (95.29%) was stable. Seven nodules, which had increased in size, underwent another FNAB or microbiopsy or surgery. Five nodules were not found again. The borders of one nodule showed modifications. CONCLUSION: The use of fine needle aspiration biopsy, interpreted by an experienced cytologist, means that short term follow-up of fibroadenomas can be avoided.

Spontaneous metritis related to the presence of vaginal septum in pregnant Sprague Dawley Crl:CD(SD) rats: impact on reproductive toxicity studies.

Recently, 6% of 1,176 Sprague Dawley rats examined in our reproductive toxicity studies presented with dark-red uterine contents with or without fetuses demonstrating delayed development. Sometimes, a high proportion of the litter was found dead, and dystocia with death or preterminal euthanasia of the dam occurred. Microscopic findings in the uterus consisted of necrohemorrhagic and suppurative periplacentitis associated with the presence of bacterial colonies identified as Escherichia coli. In the vagina, similar findings were observed that were associated with mucus accumulation and the presence of a transverse occlusive or partially occlusive thin membrane identified as a vaginal septum. Microscopically, this septum consisted of a thin band of connective tissue covered on both sides by a mucous epithelium that was continuous with vaginal epithelium. In some cases, there was only mucus accumulation retained by a septum in the vagina without evidence of bacterial infection. Serological and histological examinations did not reveal any specific pathogenic agent. The presence of these septa in the vagina most likely favored mucus accumulation, nonspecific ascending bacterial infection, and dystocia. This colony of rats presented with an unusually high incidence of vaginal septa as it was described in different strains of mice and rats in the past. We hypothesized that the use of an impedance meter by the breeder--to determine the phase of the estrous cycle by introducing a probe in the vagina--likely facilitated gestation by perforating the vaginal septum in some cases.

[Breast liposarcoma]. / Breast liposarcoma.

Liposarcoma of the breast constitutes 1% of all malignant breast tumors. We report the case of a 42-year-old woman presented with a 5 cm-mass in the left breast. Mammography, ultrasonography and MRI showed a non-specific appearance and the histological evaluation was necessary for definitive diagnosis.

Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1).

No therapy is known to improve health-related quality of life (HRQoL) or dyspnoea in patients with idiopathic pulmonary fibrosis. The present study investigated longitudinal changes in HRQoL and dyspnoea and explored the effects of bosentan on these end-points during the Bosentan Use in Interstitial Lung Disease (BUILD)-1 trial. In total, 154 subjects received oral bosentan (n = 71) or placebo (n = 83). Changes in HRQoL and dyspnoea from baseline to month (M) 6 and up to M12 were measured using the St George's Respiratory Questionnaire (SGRQ), 36-item short-form health survey (SF-36), Transition Dyspnoea Index and Borg dyspnoea index. Overall, minimal changes occurred in measures of HRQoL and dyspnoea among placebo-treated subjects during the study. The effects of bosentan treatment on HRQoL and dyspnoea in the all-treated population were minimal. However, in the subset of subjects who had undergone surgical lung biopsy for diagnosis of idiopathic pulmonary fibrosis, treatment effects were observed up to M12 in the impact domain of the SGRQ and the physical functioning, general health and role emotional domains of the SF-36. HRQoL and dyspnoea changed minimally during the course of the present study. Observations from exploratory analyses suggested benefits of bosentan on HRQoL among patients who had undergone surgical lung biopsy for diagnosis, and they merit further investigation.

[Contribution of MRI for monitoring response to neoadjuvant chemotherapy in the management of breast cancer]. / Contribution of MRI for monitoring response to neoadjuvant chemotherapy in the management of breast cancer.

In the management of breast neoplasms, two breast MR examinations are performed, one before initiation of neoadjuvant chemotherapy (NAC) and one at the end. However, a third MR exam may be performed between two courses of chemotherapy in order to assess tumor response to treatment. The assessment criterion currently used is measurement of tumor diameter according to RECIST (Response Evaluation Criteria In Solid Tumors) and WHO. But according to the preliminary results of the American College of Radiology Imaging Network protocol, using measurement of tumor volume as a reference may be valuable. Larger series are therefore necessary to estimate the value of diffusion MR, spectroscopy and diffusion studies.

[Contribution of sonoelastography to the characterization of breast lesions]. / In Process Citation.

We evaluate the performances of sonoelastography in the characterization of breast nodules with histologic correlation. Elastosonography was performed immediately after mode B sonography in 59 patients (65 nodules) by two radiologists, independently. All sequences of elastosonography were recorded. An intra and inter -observers correlation was calculated. Each nodule was classified with BI-RADS lexicon and with Ueno elastography classification. The scores 1-3 were considered as benign and 4-5 as malignant. A cytologic/histologic diagnosis was available for all nodules. At histology, 16 nodules were malignant and 49 nodules were benign. The intra and inter-observer correlations of elastosonography were excellent. The sensitivity, specificity, PPV, NPV of sonoelastography were 87.5%, 98%, 93.3%, 96%, respectively comparing with 100%, 93.9%, 84%, 100% of Mode B sonography. Thus, 95% (36/38 nodules) of BI-RADS 3 nodules were reclassified score 2 or 1 with elastosonography, decreasing the rates of fine needle aspiration and short-term follow-up. Elastosonography is a simple, rapid and complementary method to mode B sonography that can improve the specificity in the characterization of breast nodules and the management of BI-RADS 3 nodules, leading to a decrease of false-positive and short term follow-up rates.

[US and dense breasts: where do we stand?]. / Echographie et seins denses: où en est-on?

The use of ultrasonography in dense breast remains a controversial topic. It is acknowledged that ultrasound as an adjunct to mammography increases the detection rate of breast cancers. However, the main limitation of US, in addition to its operator dependent nature, is its low specificity, leading to a high rate of false positive results. Several techniques can be used to improve the performance of US and cost/effectiveness ratio, such as Doppler imaging, harmonic imaging, spatial and frequency compound imaging, all of which are routinely available, and elastosonography, contrast US and 3D US which are still in development.

Safety and tolerability of bosentan in idiopathic pulmonary fibrosis: an open label study.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease for which no effective treatment exists. In the present study, 12 IPF patients underwent analysis of gas exchange properties using the multiple inert gas elimination technique on day 1 before and after the administration of 125 mg bosentan, a dual endothelin antagonist. Following this, patients received chronic administration for 12 weeks (62.5 mg b.i.d. in week 1, 125 mg b.i.d. thereafter). The primary objective was to determine the effect of bosentan on gas exchange (day 1) and on oxygen saturation and minute ventilation (week 2). With one exception, where redistribution of total pulmonary blood flow from normal ventilation/perfusion (V'/Q') areas (93% before, 72% after bosentan) to low V'/Q' areas (0% before, 22.2% after) was encountered, no patient showed any change in gas exchange (mean+/-SD shunt flow (% of cardiac output) 8.5+/-3.4% before, 6.1+/-2.3% after bosentan; day 1) or oxygen saturation and minute ventilation (week 2). Similarly, none of the secondary parameters was significantly changed either at week 2 or at the end of the study period (week 12). Five patients developed respiratory infections and two died because of pneumonia; this was judged as being unrelated to bosentan intake. In conclusion, bosentan administration does not seem to induce clinically relevant gas exchange abnormalities in idiopathic pulmonary fibrosis patients.

[Juvenille papillomatosis]. / Papillomatose juvénile mammaire.

The authors report a patient with juvenile papillomatosis of the breast presenting with a palpable mass and illustrate the correlation between mammographic, sonographic and pathologic features.

Hepatic perfusion parameters in chronic liver disease: dynamic CT measurements correlated with disease severity.

OBJECTIVE: The aim of our study was to determine if hepatic perfusion parameters measured with CT change in relation to disease severity in patients with chronic liver disease. SUBJECTS AND METHODS: Dynamic contrast-enhanced single-section CT scans of the liver were obtained in 40 individuals who included six control subjects, 16 patients with noncirrhotic chronic liver disease, and 18 patients with cirrhosis. Hepatic, aortic, and portal venous time-density curves were fitted to a dual-input one-compartment model to calculate the liver perfusion, arterial fraction, distribution volume, and mean transit time. RESULTS: Liver perfusion decreased in patients with cirrhosis (67 +/- 23 mL. min(-1). 100 mL(-1) versus 108 +/- 34 mL. min(-1). 100 mL(-1) in control subjects [p = 0.009] and 98 +/- 36 mL. min(-1). 100 mL(-1) in patients with noncirrhotic chronic liver disease [p = 0.003]), and the arterial fraction and the mean transit time increased (41 +/- 27% and 51 +/- 79 sec versus 17 +/- 16% and 16 +/- 5 sec in control subjects, and 19 +/- 6% and 17 +/- 8 sec in patients with noncirrhotic chronic liver disease [p < 0.05]). A significant correlation was seen between these three perfusion parameters and the severity of chronic liver disease based on clinical and biologic data (p < 0.001). No significant change in distribution volume was observed. CONCLUSION: Hepatic perfusion parameters measured with CT were significantly altered in cirrhosis and correlated with the severity of chronic liver disease.

Early changes in liver perfusion caused by occult metastases in rats: detection with quantitative CT.

PURPOSE: To determine whether computed tomography (CT) can depict liver hemodynamic changes caused by occult hepatic micrometastases in rat. MATERIALS AND METHODS: Liver micrometastases (mean diameter, 500 micrometer +/- 300) were produced in seven BD IX rats by injecting 10(7) DHDK12 PROb colorectal carcinoma cells into the spleen. Macrometastases (mean diameter, 7 mm +/- 3) were produced in four other rats. Five normal rats were studied as controls. CT images were obtained every 300 msec for 30 seconds during the injection of 1 mL per kilogram of body weight of contrast medium. The time-attenuation curves of the aorta, portal vein, and liver were used to calculate liver perfusion with a deconvolution model designed for the dual blood supply. RESULTS: Micrometastases in an apparently normal liver caused a 34% decrease in portal blood flow and a 25% increase in the mean transit time for the blood to pass through the liver. These findings suggest increased resistance in the sinusoidal capillaries. Similar but greater changes were found in the macrometastases. CONCLUSION: Occult liver micrometastases in rats generate changes in liver perfusion that can be detected with CT.

Non-invasive quantification of liver perfusion with dynamic computed tomography and a dual-input one-compartmental model.

Various liver diseases lead to significant alterations of the hepatic microcirculation. Therefore, quantification of hepatic perfusion has the potential to improve the assessment and management of liver diseases. Most methods used to quantify liver perfusion are invasive or controversial. This paper describes and validates a non-invasive method for the quantification of liver perfusion using computed tomography (CT). Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass iodinated contrast agent. Hepatic, aortic and portal-venous time-density curves were fitted with a dual-input one-compartmental model to calculate liver perfusion. Validation studies consisted of simultaneous measurements of hepatic perfusion with CT and with radiolabelled microspheres in rabbits at rest and after adenosine infusion. The feasibility and reproducibility of the CT method in humans was assessed by three observers in 10 patients without liver disease. In rabbits, significant correlations were observed between perfusion measurements obtained with CT and with microspheres (r=0.92 for total liver perfusion, r=0.81 for arterial perfusion and r=0.85 for portal perfusion). In patients, total liver plasma perfusion measured with CT was 112+/-28 ml.min(-1).100 ml(-1), arterial plasma perfusion was 18+/-12 ml.min(-1).100 ml(-1) and portal plasma perfusion was 93+/-31 ml.min(-1).100 ml(-1). The measurements obtained by the three observers were not significantly different from each other (P>0.1). Our results indicate that dynamic CT combined with a dual-input one-compartmental model provides a valid and reliable method for the non-invasive quantification of perfusion in the normal liver.

Focal nodular hyperplasia: natural course observed with CT and MRI.

PURPOSE: The purpose of this work was to assess the natural course of biopsy-proven focal nodular hyperplasia (FNH). METHOD: Eighteen biopsy-proven FNHs in 14 patients (12 women and 2 men) who were followed for at least 6 months with CT and/or MRI were included in the study. The volume of the lesions was calculated twice by two observers using the summation of areas method. Intra- and interobserver variability was assessed by intraclass correlation coefficients. Longitudinal data analysis was performed with generalized estimating equations. RESULTS: The volume of FNH was stable in 6 cases, decreased in 10 cases, and increased in 2 cases. Intra- and interobserver variability in size measurements was 5-10%. Intraclass correlation coefficients were >0.992. Longitudinal data analysis showed that there was a general trend of lesion regression. CONCLUSION: Long-term follow-up and objective measurements performed in patients with biopsy-proven lesions show that the natural course of FNH is variable. In particular, lesion regression is not rare.

Adenoviral-mediated expression of antisense RNA to basic fibroblast growth factor reduces tangential stress in arterialized vein grafts.

PURPOSE: The purpose of this study was to test whether basic fibroblast growth factor (bFGF) participates in arterialized vein graft remodeling. METHODS: Rabbits underwent in vivo gene transfer and carotid interposition vein grafting. Segments of external jugular vein were infected with an adenovirus that expressed antisense bFGF RNA (Ad.ASbFGF) at 1 x 10(10) PFU/mL to inhibit new synthesis of bFGF by cells in the vein graft wall. Control rabbits were treated with either adenovirus that encoded beta-galactosidase (Ad.lacZ) at 1 x 10(10) PFU/mL or vehicle (phosphate-buffered saline solution [PBS]). At 3 days, 3 grafts per treatment group were harvested for the determination of gene expression of ASbFGF RNA by reverse transcriptase-polymerase chain reaction. Rabbits were killed, and perfusion was fixed 2 months after the grafting. Total wall thickness and lumen circumference of vein grafts and normal arteries were measured in cross sections. Calculated mean tangential stress (+/-SD) for the ASbFGF-treated group and controls was compared for significance. Grafts were immunohistochemically stained to assess bFGF protein production. RESULTS: Only the grafts infected with the Ad.ASbFGF gene expressed ASbFGF RNA. Grafts that were treated with Ad.ASbFGF displayed lower tangential stress (10.9 +/- 2.3 dynes/cm(2)) than PBS alone (22 +/- 2.8 dynes/cm(2)) or Ad. lacZ-treated controls (20.6 +/- 5.4 dynes/cm(2); P <.001). Tangential stress in the Ad.ASbFGF group was comparable to a normal carotid artery (13.9 +/- 2.1 dynes/cm(2)). The difference in mean total wall thickness was significant among the 3 treatment groups: Ad.ASbFGF, 164 +/- 3.4 microm); Ad.lacZ, 100 +/- 3.3 microm; and PBS, 96 +/- 3.6 microm; P <.01). Luminal circumference was not different among the groups. The Ad.ASbFGF-treated vein graft wall was composed of thick layers of concentric smooth muscle cells and elastin fibers in contrast to the sponge-like appearance observed in control arterialized vein grafts. Reduction in bFGF protein was noted only in the Ad.ASbFGF-treated group. CONCLUSION: Inhibition of bFGF synthesis in vivo with the use of adenoviral gene transfer of antisense RNA to bFGF promotes a vein graft with decreased tangential stress while maintaining the luminal area. The vein graft wall is remodeled and qualitatively resembles an artery so that wall tangential stress in Ad.ASbFGF and normal artery are not significantly different. The lack of significant difference in lumen circumference among groups suggests that wall thickening in the Ad. ASbFGF grafts is not at the expense of luminal narrowing. Our results suggest that ASbFGF RNA expression may represent an effective strategy in limiting the failure of arterialized venous conduits.

Mechanisms of action of liver contrast agents: impact for clinical use.

New contrast agents for magnetic resonance imaging are continually being developed by pharmaceutical companies in order to better image the liver. These agents can be divided into hepatobiliary agents directed to the hepatocytes and nanoparticulate agents directed to the reticulo-endothelial system. After intravenous injection, all these agents concentrate in the liver and induce profound changes in signal intensity. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a brief description of the principal characteristics of the agents, this paper will attempt to summarize the utility of these agents for the detection and characterization of focal liver disease.

A peptide leptin antagonist reduces food intake in rodents.

OBJECTIVE: The purpose of the present study was to investigate the continuing validity of the hypothesis that leptin is a physiologically important regulator of food intake, using the human leptin mutant R128Q leptin. DESIGN: In a cellular proliferation assay, based on BAF-3 cells transfected with the murine ObRb receptor, R128Q leptin was shown to be devoid of agonistic activity and to competitively inhibit the proliferative effects of leptin. To determine whether R128Q leptin was also an antagonist of leptin in vivo, the leptin mutant was injected intracerebroventricularly (i.c.v.) into rats in the absence and presence of leptin. R128Q was also injected intraperitoneally (i.p.) into ob/ob and into db/db mice expressing, respectively, either normal or defective ObRb receptors. RESULTS: R128Q was shown to be a competitive antagonist of leptin induced cellular proliferation in vitro. Surprisingly, in vivo R128Q leptin produced a strong dose-dependent decrease in food intake, and was only slightly less potent than leptin itself. In fasted rats, the inhibitory effects of leptin and R128Q leptin (i.c.v.) on post-fast refeeding were additive. Finally, R128Q leptin produced the same inhibition of food intake as leptin when injected i.p. in ob/ob mice and, like leptin, was inactive after i.p. injection to db/db mice. CONCLUSION: R128Q leptin is a leptin agonist in vivo, but behaves as an antagonist against leptin induced proliferation in vitro. The data demonstrate that the human leptin mutant R128Q leptin is not a suitable tool for investigating the physiological actions of leptin.