ShearWave™ Elastography BE1 multinational breast study: additional SWE™ features support potential to downgrade BI-RADS®-3 lesions.

PURPOSE: To determine the benefit of ShearWave™ Elastography (SWE™) in the ultrasound characterization of BI-RADS® 3 breast lesions in a diagnostic population. MATERIALS AND METHODS: 303 BI-RADS® 3 lesions (mean size: 13.2 mm, SD: 7.5 mm) from the multicenter BE1 prospective study population were analyzed: 201 (66%) had cytology or core biopsy, and the remaining 102 had a minimum follow-up of one year; 8 (2.6%) were malignant. 7 SWE features were evaluated with regard to their ability to downgrade benign BI-RADS® 3 masses. The performance of each SWE feature was assessed by evaluating the number of lesions correctly reclassified and the impact on cancer rates within the new BI-RADS® 3' lesion group. RESULTS: No malignancies were found with an E-color "black to dark blue", which allowed the downgrading of 110/303 benign masses (p < 0.0001), with a non-significant increase in BI-RADS® 3' malignancy rate from 2.6% to 4.1%. E-max ≤ 20 kPa (2.6 m/s) was able to downgrade 48/303 (p < 0.0001) lesions with a lower increase in BI-RADS® 3' malignancy rate (3.1%). No other SWE features were useful for reclassifying benign BI-RADS® 3 lesions. CONCLUSION: Applying simple reclassification rules, SWE assessment of the maximum stiffness of lesions allowed the downgrading of a sub-group of benign BI-RADS® 3 lesions. This was accompanied by a non-significant increase in the malignancy rate in the new BI-RADS® 3 class.

The Atlantic-Mediterranean watershed, river basins and glacial history shape the genetic structure of Iberian poplars.

Recent phylogeographic studies have elucidated the effects of Pleistocene glaciations and of Pre-Pleistocene events on populations from glacial refuge areas. This study investigates those effects in riparian trees (Populus spp.), whose particular features may convey enhanced resistance to climate fluctuations. We analysed the phylogeographic structure of 44 white (Populus alba), 13 black (Populus nigra) and two grey (Populus x canescens) poplar populations in the Iberian Peninsula using plastid DNA microsatellites and sequences. We also assessed fine-scale spatial genetic structure and the extent of clonality in four white and one grey poplar populations using nuclear microsatellites and we determined quantitative genetic differentiation (Q(ST) ) for growth traits in white poplar. Black poplar displayed higher regional diversity and lower differentiation than white poplar, reflecting its higher cold-tolerance. The dependence of white poplar on phreatic water was evidenced by strong differentiation between the Atlantic and Mediterranean drainage basins and among river basins, and by weaker isolation by distance within than among river basins. Our results suggest confinement to the lower river courses during glacial periods and moderate interglacial gene exchange along coastlines. In northern Iberian river basins, white poplar had lower diversity, fewer private haplotypes and larger clonal assemblies than in southern basins, indicating a stronger effect of glaciations in the north. Despite strong genetic structure and frequent asexual propagation in white poplar, some growth traits displayed adaptive divergence between drainage and river basins (Q(ST) >F(ST)), highlighting the remarkable capacity of riparian tree populations to adapt to regional environmental conditions.

[Screening digital mammography: one year result for the Alpes-Maritimes region]. / Numérique en dépistage organisé: bilan à 1 an dans les Alpes-Maritimes.

PURPOSE: After one year of experience with screening digital mammography, the results of this technique (n=9640) are compared to screen-film mammography (n=240 376) with double reading. METHODS: Evaluation for each technique of the rate of call-back, positive results before and after work-up by the first reader and distribution based on the BI-RADS classification by the ACR, rate of complementary US, detected abnormalities (microcalcifications) and detected cancers. RESULTS: The rate of positive mammograms was significantly higher for the digital technique (17.3% versus 15.1%) because of the first reader (16.3% versus 13.9%) whereas it was significantly lower after complementary work-up (3% versus 3.7%). The rate of BI-RADS 0 was significantly higher with digital imaging irrespective of patient age. The rate of US was higher for type 1 and 2 breasts at digital imaging (46% versus 36%, p<0.0001) while the reverse was true for denser breasts (49% versus 54%; p:0.0005). More microcalcifications were detected on digital imaging (24.4% versus 21.8%) without impact on the rate of DCIS and invasive carcinomas. The rate of cancers detected with both technique were identical. CONCLUSION: The increased number of positive results at first reading and increased number of US for digital mammography may relate to a learning curve and difficulties in comparing with prior examinations. These results should continuously be monitored and compared to national averages.

Prognostic factors in 1,038 women with metastatic breast cancer.

BACKGROUND: Treatment of metastatic breast cancer (MBC) remains palliative. Patients with MBC represent a heterogeneous group whose prognosis and outcome may be dependent on host factors. The purpose of the present study was dual: first, to draw up a list of factors easily available in everyday clinical practice requiring no sophisticated or costly methods and second, to provide results from a large cohort of women who underwent diagnostic and treatment at a single institution. PATIENTS AND METHODS: From 1975 to 2005, a total of 1,038 women with MBC during their follow-up were included in this retrospective analysis. Patients were subsequently assigned to five groups according to the period of metastatic diagnosis. RESULTS: It is shown that age at initial diagnosis, hormonal receptor status and site of metastasis are the most relevant prognostic factors for predicting survival from the time of metastastic occurrence. It is also shown that a metastasis-free interval is an easily and immediately available multifactorial prognostic index reflecting the multiparametric variability of the disease. CONCLUSION: These fundamental observations may assist physicians in evaluating the survival potential of patients and in directing them toward the appropriate therapeutic decision.

Effect of butyl benzyl phthalate on early postnatal mortality in rats.

ABSTRACT The present study was undertaken to examine early postnatal mortality in rat pups following exposure to butyl benzyl phthalate (BBP) during pregnancy. Seventeen pregnant rats were given 750 mg/kg bw/day of BBP by oral gavage on gestation days 13, 14, and 15, and the volume of each dose was adjusted to 5 ml/kg body weight. Four rats were given olive oil only and served as control. Natural birth was allowed to take place. One hundred and eighty-three pups were born to the experimental rats and 46 pups to the control group. Close observation of the newborn pups during the first 3 h of life revealed that all the pups in both the control and experimental groups were born alive. Only six pups from the experimental group (3.2%) died within this time period. These and four control pups were fixed and decalcified. Histological examination of the thoracic cavity of the newborn rats in both groups revealed no differences in the position or size of any of the heart chambers, ductus arteriosus, or great vessels. However, the lungs of the six experimental pups that died showed athelectasia and bronchi dilatation. The results therefore suggest that exposure to BBP of rats during pregnancy does not produce significant postnatal mortality in their offspring.

Early versus late local recurrences after conservative treatment of breast carcinoma: differences in primary tumor characteristics and patient outcome.

OBJECTIVES: To investigate whether some aspects of patient or tumor characteristics influence the timing of local recurrence (LR) in breast cancer treated conservatively, and to assess the impact of the timing of LR on patient outcome. METHODS: A retrospective analysis was conducted on patients treated with conservative breast surgery followed by radiotherapy for breast carcinoma who developed LR. Out of 2,008 cases treated in our Institute between 1977 and 2002, 180 ipsilateral LR were observed. Of these, 46 LR were observed within 36 months after treatment, called early local recurrence (ELR), 44 developed between 37 and 60 months, called medium local recurrence (MLR), and 90 occurred after 60 months, called late local recurrence (LLR). Patient and tumor characteristics were analyzed in the 2 groups and compared. RESULTS: Primary tumors >20 mm were more frequently found in patients with ELR (31%) than in patients with LLR (17%, p = 0.047). Grade 3 tumors were more often encountered in patients with ELR than in patients with LLR (27 versus 7%, p = 0.0002). Patients with ELR more frequently had tumors with negative estrogen receptors than patients with LLR (37% versus 6%, p < 0.0001). There was no statistically significant difference in the axillary lymph node (LN) status between patients with ELR and those with LLR (35 and 23% of positive LN, respectively, p = 0.24). Tumor size, grade, LN status, hormone receptors and the timing of LR affected the specific survival (SS) from initial surgery. On multivariate analysis, only LN status and the timing of LR retained an independent prognostic value, with an odds ratio of 6.7 for ELR. After LR, the SS was also influenced by all of the above factors, and on multivariate analysis, LN status, hormone receptors and the timing of LR were independent predictors with an odds ratio of SS of 2.50 in case of ELR (p = 0.006). The 5-year SS after LR for ELR, MLR and LLR were 55.8, 74.8 and 79.5%, respectively. CONCLUSIONS: Unfavorable tumor characteristics such as big size, high grade, lack of hormone receptors, but not LN status, were associated with ELR. These findings suggest that patients with such aggressive tumor characteristics who do not recur early will have a lower risk of LLR than patients with more favorable factors.

[Ultrasound examination of breast microcalcifications: luxury or necessity?]. / Voir les microcalcifications mammaires en échographie: luxe ou nécessite?

PURPOSE: Determine the value of ultrasound for the diagnosis of isolated breast microcalcifications. MATERIAL AND METHODS: Fifty clusters of microcalcifications, including 25 smaller than 10 mm, were examined by ultrasound (5-13 MHz) prior to stereotactic aspiration macrobiopsy (30 benign lesions, three borderline lesions, and 17 malignant lesions, including ten in situ lesions and seven invasive lesions). Mammography had placed 13 of these cases in BI-RADS 3, 24 in BI-RADS 4, and 13 in BI-RADS 5. The BI-RADS classification was also used for ultrasound assessment. RESULTS: Six of the 18 microcalcifications that were not seen by ultrasound were malignant (two invasive ductal cancers [IDC] and four ductal carcinomas in situ [DCIS]). Two of the four cases with no sonographically visible tissue mass proved to be malignant (one IDC, one DCIS); these two lesions had been classified BI-RADS 4 and 5 by mammography and were larger than 10 mm. Ultrasound visualized 16 masses classed BI-RADS 3, ten masses classed BI-RADS 4, and two masses classed BI-RADS 5. One of the lesions classified as BI-RADS 3 by mammography was an IDC that was classed BI-RADS3 by ultrasound. Four of the lesions classed BI-RADS 4 by mammography were malignant (three were classified BI-RADS3 by ultrasound while one was classed BI-RADS4). One benign lesion was classified BI-RADS 5 by ultrasound. Four cancers were mammographically classed BI-RADS 5; ultrasound was in agreement in one case but classed three of the cases as BI-RADS 4. In one case, ultrasound gave a diagnosis of benignity (BI-RADS 3 classification). CONCLUSION: Ultrasound is unsuited for the diagnosis of microcalcifications because it fails to visualize a mass in one-third of cancers and the existence of a mass is correlated with malignancy in one-third of cases. Furthermore, US does not correct the false-negative errors of mammography, and it underestimates the rate of malignancy by ascribing a benign appearance to 50% of cancers, which mammography correctly classifies BI-RADS 4 or 5.

[When should caution be used with regards to histopathologic findings of imaging-guided breast micro- and macro-biopsies?]. / Quand se méfier des résultats des micro et macrobiopsies guidées mammaires?

The development of imaging-guided biopsy techniques has considerably improved the early diagnosis of breast cancers following initial detection by screening. Nevertheless, in a small percentage of cases, histopathologic findings are unsatisfactory owing to false negative errors attributable to operator inexperience or inadequate sample material (this is especially true for microcalcifications with 20% underestimation rates for atypical hyperplasia); repeat biopsy is warranted in such situations. When a discrepancy exists with imaging findings and for cases of atypical epithelial hyperplasia, surgical excision is imperative so as not to overlook or underestimate a malignant lesion. Controversy continues concerning the best approach for radial scars (sclerosing ductal lesions), papillary lesions, atypical lobular hyperplasia and lobular carcinoma in situ: determination of which benign anomalies can merely be followed-up remains a problem. Better awareness of the limitations of percutaneous tissue sampling procedures should lead to refinement of the indications for these techniques and improvement of patient selection and thereby reduce delays in accurate diagnosis.

[Role of imaging in the evaluation of axillary nodes and metastatic disease from breast carcinoma]. / Imagerie dans le bilan d'extension ganglionnaire et métastatique du cancer du sein.

Disease staging of patients with breast cancer is based on the probability of metastatic disease, the reliability of complementary examinations, and therapeutic possibilities, evaluated on a cost/benefit basis. For regional disease staging, nodal status can be assessed by ultrasound, and the value of this approach can be optimized by imaging-guided biopsies. Ultrasound examination of nodes upstream of the sentinel node allows determination of the utility of this node and the indications for axillary resection. Work-up of metastatic spread is performed only after evaluation of risk factors for metastasis. Prior to therapy, and in the absence of any clinical warning signs for resectable tumors, there are no indications for imaging, which is reserved solely for locally advanced tumors.

[Can breast elastography change our strategies? Technology, impact and limitations]. / L'élastographie du sein peut-elle modifier nos stratégies ? Technologie, impact et limites.

Compression or static elastography is based on images deformation (induced by slight manual compression/decompression to the breast) and tissue movement is color-encoded in color map and classified into five scores of increasing malignancy (score of 1 to 3: benign and 4 to 5: malignant). The elasticity shear wave is measured from the propagation velocity of shear waves in the lesions and is expressed in kPa or m/s and in color map. Reproducibility is satisfactory for the two technologies even if the static elastography is only semi-quantitative. Elastography is helpful for lesions classified BI-RADS 3 and 4 and especially when the PPV of these lesions in B mode is low<10% (BI-RADS 3 and 4a). For these two technologies, cancer and biopsy rates are reduced by at least 30% (with threshold values for the shear wave technology of 30kPa and 3m/s depending on the manufacturer). False positives are found with the fibrotic lesions and false negatives by colloid tumors and DCIS. Correlation with prognostic factors is discussed.

Perfluoroctylbromide and hepatosplenic computed tomography. Preliminary clinical study.

The preliminary results of perfluorocytlbromide (PFOB) emulsion when used as an intravenous contrast agent for hepatosplenic CT imaging in humans are reported. Ten patients were examined using dosages ranging from 1 to 2 g/kg. There was good clinical and biochemical tolerance. Diagnostic dose for liver enhancement seems to be at least 2 g/kg, whereas 1 g/kg was sufficient for splenic enhancement.

Systematic ultrasonography in asymptomatic dense breasts.

The purpose of this study was to evaluate the role of ultrasonography in breast cancer screening. 350 Bilateral ultrasound (US) were performed in 350 asymptomatic patients with dense breasts. 7.5, 10 And 13 MHz transducers were used (Esaote Biomedica, Italy). In 185/350 patients, sonograms were normal, abnormalities were seen in 165/350: cysts (117), solid nodules (44) and mixed echogenicity nodules (4). All but two solid lesions were benign. Both malignant lesions were invasive carcinomas, 18 and 11 mm in diameter. In retrospect, they were palpable, but not visible on mammograms. Retroprospective review revealed that 24.7 of cysts and 31% solid nodules could be seen on mammograms. In 4 patients with fibroadenomas, US made a false positive diagnosis of breast cancer. Follow-up was obtained for 6 to 18 months in 45% of patients. Routine supplemental US evaluation for patients with mammographically dense breasts does not appear to significantly contribute to the accuracy of the work-up.

Etiologic diagnosis of hepatic lesions in cancer patients. Value of ultrasound and liver function tests.

The purpose of this study was to evaluate the value of a combination of ultrasound (US) and liver function tests (LFT) for determination of the benign or malignant nature of one or more hepatic lesions in cancer patients. A total of 1235 patients with hepatic metastases and 832 patients with benign liver lesions investigated by US-LFT over a 12-year period were analyzed retrospectively. Ultrasound patterns considered indicative of a benign process (cyst, calcification without mass, irregular hyperechoic area without mass effect, small hyperechoic focal lesion as less than 3 cm) or malignancy (peritumoral halo, hypoechoic focal lesion, multiple solid nodules) were associated with LFT results. A US pattern of a benign process associated with normal LFT led to a diagnosis of benign disease with a false negative rate for malignancy of 11.6%. The highest figure corresponded to small hyperechoic nodules, for which the positive predictive value of malignancy (PPVM) depended on the type of primary cancer: 2.1% for breast cancer versus 62.5% for colorectal cancer. A US criterion of malignancy associated with abnormal LFT led to a diagnosis of malignancy (PPV 96.2% to 100%). Overall, the combination of US and LFT had a sensitivity of 80.6% and a specificity of 99.4%. The US-LFT combination correctly determined the benign or malignant nature of 74.5% of all hepatic lesions; the PPV was never less than 96.2% (small and solitary hyperechoic focal lesions were excluded because their PPV for malignancy is too high).

Ultrasonography of invasive lobular carcinoma of the breast: sonographic patterns and diagnostic value: report of 102 cases.

The aim of this study was to define the ultrasonographic (US) features of the invasive lobular carcinoma (ILC). For this purpose, the clinical histories and the mammographic and sonographic findings observed in 102 patients affected by documented ILC were retrospectively reviewed, and the role and value of US in the diagnosis of palpable and nonpalpable breast tumors were evaluated. At US, five proven tumors were not visualized (sensitivity: 95%), while the remaining 97 showed sonographic images that are considered typically malignant: irregular heterogenic, hypoechoic irregular masses in 94 cases, which were associated with posterior shadowing in 87. The presence of only a posterior shadowing was observed in three cases. There were 16 subclinical tumors, and in two of the four in which a mammography showed an indeterminate lesion, US demonstrated a malignant pattern. All the palpable tumors that were not detected mammographically were demonstrated by US. In 13 of the 102 patients (12.7%), the correct diagnosis of malignancy was established by US. On the basis of the data obtained, it is felt that because of its sensitivity and high specificity for malignancy, US plays a very important role in the diagnosis of ILC, whenever in a patient with positive clinical findings, the mammography is negative or the mammographic features are equivocal.

[Comparison of echography and x-ray computed tomography in cancer of the ovary]. / Comparaison de l'échographie et de la scanographie dans les cancers de l'ovaire.

A retrospective study with an 18 month follow-up period was conducted on 184 patients (with 172 epithelial ovarian tumors) to compare the value of ultrasonography and CT for detection of pelvic masses, adenopathies, urinary stasis, hepatic metastasis and peritoneal or intestinal involvement. Ultrasound and CT findings were compared with histology data for 47 patients; ultrasound and CT data were compared with the clinical course for 53 patients. Ultrasonography was better than CT for the detection of pelvic masses, and was also slightly better for liver metastases and urinary stasis. CT was more effective for the diagnosis of lumbo-aortic and pelvic adenopathies, and peritoneal and intestinal involvement, but the sensitivity of imaging techniques remains insufficient for both of these lesion types. Combined examination by ultrasonography and CT every 6 months suffices for follow-up of patients who have undergone surgery and can evaluate tumoral response in patients treated by first-line chemotherapy.

[Tomodensitometric aspects of brain lymphomas: apropos of 19 cases. Brain lymphoma]. / Aspects tomodensitométriques des lymphomes cérébraux: à propos de 19 cas. Lymphomes cérébraux.

The authors present the results of CT studies for 19 patients with cerebral lymphoma (including 12 primary tumors). CT appearances varied considerably, because 5 of the 12 primary lymphomas presented as multifocal lesions, and lesion sites included the corpus callosum (3 cases), the central caudate nucleus (4 cases), the posterior fossa (3 cases), and the cerebral hemispheres (6 cases). These findings are in agreement with literature data. Although a solitary, hyperdense and homogeneous lesion in the corpus callosum or the central caudate nucleus is indicative of cerebral lymphoma, numerous other aspects are possible and owing to the increasing frequency of this pathology should suggest this diagnosis. There is no specific appearance for secondary lymphomas, but diagnosis is often facilitated by concomitant systemic involvement.

[Echography and computed tomography in the evaluation and follow-up of uterine cancers]. / Echographie et scanographie dans le bilan et la surveillance des cancers de l'utérus.

In this review of 139 cancers of the cervix uteri and 43 cancers of the corpus uteri, the authors compare clinical, sonographic and CT data. For the 58 patients with cervical cancer who presented infiltration of the parametrium at physical examination under general anesthesia, sonography gave 11 false negative errors while CT gave 8 false positives. By contrast, for the 47 tumors staged IIb after examination under general anesthesia, sonography disclosed additional abnormalities in 20 cases and CT in 22 cases. A series of 52 disease recurrences in patients who had received curative treatment for uterine cancer was also reviewed; overall, an association of physical examination and ultrasonography had the same value as CT. In light of these results, the authors propose an algorithm for the exploration of uterine cancers in which the results of physical examination condition examination by ultrasonography or CT.

["Standards, Options and Recommendations 2001" for radiotherapy in patients with non-metastatic infiltrating breast cancer. Update. National Federation of Cancer Campaign Centers (FNCLCC)]. / Standards, Options et Recommandations 2001 pour la radiothérapie des patientes atteintes d'un cancer du sein infiltrant non métastatique, mise à jour. Fédération nationale des centres de lutte contre le cancer (FNCLCC).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of french cancer centers (FNCLCC), the 20 french cancer centers, and specialists from french public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non metastatic breast cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline, web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 148 independent reviewers. RESULTS: This article presents the chapter radiotherapy resulting from the 2001 update of the version first published in 1996. The modified 2001 version of the standards, options and recommendations takes into account new information published. The main recommendations are: (1) Breast irradiation after conservative surgery significantly decrease the risk of local recurrence (level of evidence A) and the decrease in the risk of local recidive after chest wall irradiation is greater as the number of risk factors for local recurrence increases (level of evidence A). (2) After conservative surgery, a whole breast irradiation should be performed at a minimum dose of 50 Gy in 25 fractions (standard, level of evidence A). (3) A boost in the tumour bed should be performed in women under 50 years, even if the surgical margins are free (standard, level of evidence B). (4) Internal mammary chain irradiation is indicated for internal or central tumours in the absence of axillary lymph node involvement (expert agreement) and in the presence of lymph node involvement (standard, level of evidence B1). (5) Sub- and supra-claviculr lymph node irradiation is indicated in patients with axillary node involvement (standard, level of evidence B1).

[Usefulness of the determination of lipids parameters in pleural effusions]. / Utilidad de la determinación de parámetros grasos en los derrames pleurales.

In 160 patients with pleural effusion, consecutively studied in our section, cholesterol and triglyceride concentrations and lipidogram were prospectively measured in the pleural fluid and the blood to rule out the possible occurrence of chylothorax. For the diagnosis of chylothorax the presence of chylomicrons in the pleural fluid was required. The macroscopic appearance of the fluid was a poor indicator of the presence of chylothorax, as in three of the seven patients in which the latter was discovered the characteristically reported milky appearance of the pleural fluid was not found. The mean value of triglycerides in the chylous effusions (162.3 +/- 34.8 mg/dl) was significantly higher (p less than 0.001) than in nonchylous effusions (45.8 +/- 26.3 mg/dl). All patients with chylothorax had triglyceride values higher than 110 mg/dl; using this figure as the cut-off value, 7.5% of the patients with pleural effusion were selected as those in whom, irrespectively of the macroscopic appearance of their effusions, the performance of lipidogram would be indicated to rule out chylothorax.

Prognostic significance of the p185 protein in colorectal cancer.

The amplification and/or overexpression of the c-erbB-2/neu oncogene may play a role in tumor development and progression. The aim of this prospective study was to evaluate the prognostic value of p185 protein in colorectal cancer using immunohistochemical techniques. We analyzed 106 colorectal tumor tissue specimens from patients who had been operated on by the same surgeon and subjected to a median follow-up of 3 years. Thirty-three per cent of patients showed p185 overexpression related to an advanced stage of the disease. In patients with adenocarcinoma tumors of the colon without distant metastases, p185 detection was found to be of clinical prognostic relevance (p = 0.06).