Value of high-resolution full-field optical coherence tomography and dynamic cell imaging for one-stop rapid diagnosis breast clinic.

BACKGROUND: Full-field optical coherence tomography combined with dynamic cell imaging (D-FFOCT) is a new, simple-to-use, nondestructive, quick technique that can provide sufficient spatial resolution to mimic histopathological analysis. The objective of this study was to evaluate diagnostic performance of D-FFOCT for one-stop rapid diagnosis breast clinic. METHODS: Dynamic full-field optical coherence tomography was applied to fresh, untreated breast and nodes biopsies. Four different readers (senior and junior radiologist, surgeon, and pathologist) analyzed the samples without knowing final histological diagnosis or American College of Radiology classification. The results were compared to conventional processing and staining (hematoxylin-eosin). RESULTS: A total of 217 biopsies were performed on 152 patients. There were 144 breast biopsies and 61 lymph nodes with 101 infiltrative cancers (49.27%), 99 benign lesions (48.29%), 3 ductal in situ carcinoma (1.46%), and 2 atypias (0.98%). The diagnostic performance results were as follow: sensitivity: 77% [0.7;0.82], specificity: 64% [0.58;0.71], PPV: 74% [0.68;0.78], and NPV: 75% [0.72;0.78]. A large image atlas was created as well as a diagnosis algorithm from the readers' experience. CONCLUSION: With 74% PPV and 75% NPV, D-FFOCT is not yet ready to be used in clinical practice to identify breast cancer. This is mainly explained by the lack of experience and knowledge of this new technic by the four lectors. By training with the diagnosis algorithm and the image atlas, radiologists could have better outcomes allowing quick detection of breast cancer and lymph node involvement. Deep learning could also be used, and further investigation will follow.

Positive association between progestins and the evolution of multiple fibroadenomas in 72 women.

OBJECTIVE: Multiple fibroadenomas (MFA) of the breast is a rare benign disease, thus its natural history is poorly understood. The aim of our study was to describe the radiological evolution of MFA and to evaluate the influence of different factors on this evolution. METHODS: This was a longitudinal cohort study. All patients included had two clinical and radiological assessments (breast ultrasound (US) and/or MRI) at least 5 years apart. RESULTS: Seventy-two women were followed for 7.6 ± 2.1 years. The radiological evolution showed a decrease or stability in the number of fibroadenomas (FA) in 26/44 cases on the MRI and in 38/64 cases on the US. There was a decrease of size in 35/44 cases on the MRI and in 53/64 cases on the US. An increase in the number of FAs was found in 18/44 cases in the MRI and 26/64 cases in the US with, for the majority, a decrease of size (19/26 by MRI and 16/18 by MRI). Older age at the first FA (P < 0.0001) and at the diagnosis of MFA (P < 0.0001), pregnancy (P = 0.003) and progestin use (P < 0.001), particularly lynestrenol (P < 0.0001), had a beneficial effect on the evolution of MFA. CONCLUSION: This is the first longitudinal study describing women with MFA. The radiological evolution of MFA seamed favorable and similar to that expected for a single FA. We identified factors influencing the evolution of the disease, including progestin treatments such as lynestrenol, which could have a beneficial effect. Our cohort should be followed further in order to expand our knowledge of MFA, especially concerning the risk of breast cancer.

Inter-reader agreement in HRCT detection of pleural plaques and asbestosis in participants with previous occupational exposure to asbestos.

OBJECTIVES: To investigate inter-reader agreement for the detection of pleural and parenchymal abnormalities using CT in a large cross-sectional study comprising information on individual cumulative exposure to asbestos. METHODS: The project was approved by the hospital ethics committee, and all patients received information on the study and gave their written informed consent. In 5511 CT scans performed in a cohort of retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey programme (Asbestos Related Diseases Cohort, ARDCO), double randomised standardised readings, triple in case of disagreement, were performed by seven trained expert radiologists specialised in thoracic imaging and blind to the initial interpretation. Inter-reader agreement was evaluated by calculating the κ-weighted coefficient between pairs of expert readers and results of routine practice and final diagnosis after expert reading. RESULTS: κ-Weighted coefficients between trained experts ranged from 0.28 to 0.52 (fair to good), 0.59 to 0.86 (good to excellent) and 0.11 to 0.66 (poor to good) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. κ-Weighted coefficients between results of routine practice and final diagnosis after expert reading were 0.13 (poor), 0.53 (moderate) and 0.11 (poor) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. CONCLUSIONS: Interpretation of benign asbestos-related thoracic abnormalities requires standardisation of the reading and trained readers, particularly for participants asking for compensation, and with a view to the longitudinal survey of asbestos-exposed workers.

Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia.

OBJECTIVE: Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility. DESIGN: Case/control study. METHODS: Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28 ± 3 days), were included. LH pulse patterns over 6 h were determined in patients and controls. RESULTS: No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels. CONCLUSIONS: LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

Resumption of ovarian function and pregnancies in 358 patients with premature ovarian failure.

CONTEXT: Resumption of ovarian activity and spontaneous pregnancies are described in patients with premature ovarian failure (POF), but there is a lack of data concerning the prevalence of and predictive factors for these phenomena. OBJECTIVE: The aim of the study was to determine both the prevalence of and predictive factors for spontaneous resumption of ovarian function in POF patients. DESIGN AND SETTING: A mixed retrospective and prospective study was performed at a referral center for reproductive endocrinology. PATIENTS: A total of 358 consecutive POF patients were followed from 1997 to 2010 in our center. MAIN OUTCOMES MEASURES: The cumulative incidence of resumption of ovarian function was determined, and predictive factors were identified by univariate and multivariate analysis. RESULTS: Of 358 patients with idiopathic POF, 86 (24%) patients presented features indicating resumption of ovarian function, and in 77 cases (88%) within 1 yr of diagnosis. Twenty-one spontaneous pregnancies (16 births, five miscarriages) occurred in 15 (4.4%) patients. Multivariate analysis (Cox model) showed that a familial history of POF, secondary amenorrhea, presence of follicles at ultrasound, and inhibin B and estradiol levels were significantly predictive of resumption of ovarian function (P < 0.01), whereas association with an autoimmune disease, anti-mullerian hormone level, the presence of follicles on biopsy, and/or genetic abnormalities did not appear predictive. We created a predictive score for resumption of ovarian function comprising age at diagnosis, presence of follicles at ultrasound, and inhibin B level. CONCLUSION: Intermittent ovarian activity in patients with POF is not a rare phenomenon. The predictive score described in this study may help us to identify POF patients most likely to recover intermittent ovarian function.

Noninvasive contrast-enhanced US quantitative assessment of tumor microcirculation in a murine model: effect of discontinuing anti-VEGF therapy.

PURPOSE: To determine, by using contrast material-enhanced ultrasonography (US), how quickly renal tumors grafted in mice begin to revascularize after stopping bevacizumab treatment. MATERIALS AND METHODS: All experiments were approved by the regional ethics committee. A human tumor cell line SK-NEP-1 was grafted at day 0 in the left kidney of 50 nude mice. Forty-two mice developed tumors and longitudinal follow-up was performed on 32 surviving mice. From day 13, 14 controls received biweekly saline; 11 mice received biweekly bevacizumab until day 35 (continuous); and seven received biweekly bevacizumab until day 22, then biweekly placebo until day 35 (discontinued). Contrast-enhanced US was performed on days 13, 14, 22, 27, and 35. Once the injected contrast material distribution reached an equilibrium phase, high-acoustic pressure pulses were applied to destroy microbubbles in the capillary bed in the imaged plane. Reperfusion was monitored, and time-signal intensity (SI) curves were obtained from the linear average of SIs in intratumoral and matched-depth renal cortex regions of interest. A kinetic parameter calculated from reperfusion curves reflects local perfusion, normalized with respect to adjacent renal cortex perfusion. Normalized perfusion obtained from each group was compared with that from the other groups and with necrosis percentages and microvascular density assessed histologically at day 35. Comparisons were made by using analyses of variance and Tukey-Kramer tests. RESULTS: The lowest excised mean tumor weights (+/- standard deviation) corresponded to the longest bevacizumab-treatment duration: 1.4 g +/- 1.1 (continuous-treatment) compared with 2.3 g +/- 2.1 (discontinued) and 3.7 g +/- 1.9 (control) (P = .01). On day 35, the respective control and continuously treated groups had comparable and significantly larger necrotic areas: 37% +/- 14 and 32% +/- 17 larger than the discontinued-treatment group (15% +/- 9; P < .05). Normalized perfusion increased significantly with time (P = .02) in the discontinued-treatment group after therapy ceased (day 22). CONCLUSION: Noninvasively measured contrast-enhanced US parameters demonstrated tumor revascularization after stopping antiangiogenic therapy in this murine tumor model.

Characterization of two constitutively active prolactin receptor variants in a cohort of 95 women with multiple breast fibroadenomas.

BACKGROUND: The role of prolactin (PRL) and its receptor (hPRLR) in promoting breast tumors is debated. We recently identified a gain-of-function hPRLR variant (I146L) in four women with multiple breast fibroadenomas (MFA) and no control subject. OBJECTIVES: The specific aims were to describe this cohort of women presenting with MFA to identify and functionally characterize germline variants of hPRL/hPRLR genes and compare phenotypes of all patients. DESIGN: Ninety-five patients prospectively underwent clinical examination, breast ultrasonography, magnetic resonance imaging, and hormonal evaluation of gonadal and lactotrope functions. We analyzed hPRL/hPRLR coding sequences and made comparisons with a control population of 194 women. Functional characterization of hPRLR variants was performed. Pathology and immunochemistry were systematically carried out after surgical removal of tumors. RESULTS: One third of patients had a family history of breast disease. No hormonal imbalance was observed, except 30.7% of explosive stimulated PRL. Prolactin receptor variants were identified in exon 5 (I76V: 10 patients, eight controls) and exon 10 (one patient, no control). Both I146L and I76V variants exhibited constitutive activity. Pathology showed common fibroadenomas and identified six benign phyllodes tumors. Estrogen and progesterone receptors were detected in 85 and 98% of samples, respectively. Ki-67 median staining was less than 5%. No phenotypic difference was observed between carriers and noncarriers of either hPRLR variant. CONCLUSION: We present the largest population with MFA ever described, 15% of which had a hPRLR exhibiting basal activity in vitro. This questions the involvement of the hPRLR in MFA etiology and the potential relevance of therapeutic inhibition of PRLR signaling in patients.

Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure.

OBJECTIVE: Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis. DESIGN AND METHODS: We performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center. RESULTS: Seventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turner's syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1. CONCLUSION: A genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.

Incidence of chest tube malposition in the critically ill: a prospective computed tomography study.

BACKGROUND: Malposition of percutaneously inserted chest tubes is considered as a rare complication in critically ill patients. Its incidence, however, remains uncertain. The aims of the study were to assess the true incidence of chest tube malposition in critically ill patients and to identify predicting factors. METHODS: The authors prospectively studied 122 chest tubes percutaneously inserted in 75 consecutive critically ill patients. For clinical reasons independent of the study, thoracic computed tomography scanning was performed in 63 patients, allowing direct visualization of 106 chest tubes. Based on these findings, chest tube position was classified as intrapleural, intrafissural, or intraparenchymal. Factors predicting chest tube malposition were analyzed by univariate and multivariate analysis. RESULTS: The mean delay between chest tube placement and thoracic scan was 3.5+/-2.9 days. Twenty-two chest tubes were diagnosed as being intrafissural (21%), and 10 were diagnosed as being intraparenchymal (9%). The only predicting factor associated with the risk of malposition was the use of a trocar for the percutaneous insertion of the chest tube (P=0.032). CONCLUSIONS: Malposition was detected in 30% of percutaneously inserted chest tubes, a higher incidence than previously reported. Avoiding the use of a trocar may reduce significantly the incidence of chest tube malposition.