B-type natriuretic peptide measurement for early diagnosis of acute pulmonary edema during pregnancy.

Calcium-channel blockers administered to pregnant women as tocolytic agents can cause acute pulmonary edema. The first signs of this severe complication can be atypical and so delay introduction of appropriate therapy. We describe three cases in whom B-type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema. B-type natriuretic peptide measurement in this setting could contribute to timely diagnosis and improve follow-up.

A plea for the biopsy marker: how, why and why not clipping after breast biopsy?

In the last decade, percutaneous breast biopsies have become a standard for the management of breast diseases. Biopsy clips allow for precise lesion localization, thus minimizing the volume of breast to be resected at the time of surgery. With the development of many imaging techniques (including mammography, sonography, and breast magnetic resonance imaging), one of the challenges of the multidisciplinary became to synthesize all informations obtained from the various imaging procedures. The use of biopsy markers after percutaneous biopsy is one of the keys for optimal patient management, helping the radiologist to deal with multiple lesions, to insure correlation across different imaging modalities and to follow-up benign lesions, helping the oncologist by marking a tumor prior to neoadjuvant chemotherapy, helping the surgeon by facilitating preoperative needle localization, to precisely mark the margins of extensive disease and to guide intraoperative tumor resection, and helping the pathologist to insure the lesion of interest has been removed and to identify the region of interest in a mastectomy specimen. We believe biopsy clip markers should be deployed after all percutaneous interventions and present in this review the arguments to support this statement. Minimal indications for clip deployment will also be detailed.

Comparison of two nomograms to predict pathologic complete responses to neoadjuvant chemotherapy for breast cancer: evidence that HER2-positive tumors need specific predictors.

The aim of this study is to compare two published nomograms, the "Institut Gustave Roussy/M.D. Anderson Cancer Center" (IGR/MDACC) and the Colleoni nomograms, in predicting pathologic complete responses (pCR) to preoperative chemotherapy in an independent cohort and to assess the impact of HER2 status. Data from 200 patients with breast carcinoma treated with preoperative chemotherapy were collected. We calculated pCR rate predictions with the two nomograms and compared the predictions with the outcomes. Sixty percent of the patients with HER2-positive tumors received trastuzumab concomitantly with taxanes. Model performances were quantified with respect to discrimination and calibration. In the whole population, the area under the ROC curve (AUC) for the IGR/MDACC nomogram and the Colleoni nomogram were 0.74 and 0.75, respectively. Both of them underestimated the pCR rate (P = 0.026 and 0.0005). When patients treated with trastuzumab were excluded, the AUC were excellent: 0.78 for both nomograms with no significant difference between the predicted and the observed pCR (P = 0.14 and 0.15). When the specific population treated with trastuzumab preoperatively was analyzed, the AUC for the IGR/MDACC nomogram and the Colleoni nomogram were poor, 0.52 and 0.53, respectively. The IGR/MDACC and the Colleoni nomograms were accurate in predicting the probability of pCR after preoperative chemotherapy in the HER2-negative population but did not correctly predict pCR in the HER2-positive patients who received trastuzumab. This suggests that responses to preoperative chemotherapy, including trastuzumab, are biologically driven and that a specific nomogram or predictor for HER2-positive patients has to be developed.

Nonmasslike enhancement at breast MR imaging: the added value of mammography and US for lesion categorization.

PURPOSE: To determine the value of adding conventional imaging (mammography and ultrasonography [US]) to nonmasslike enhancement (NMLE) analysis with breast magnetic resonance (MR) imaging for predicting malignancy and for building an interpretation model incorporating all imaging modalities. MATERIALS AND METHODS: The institutional ethics committees approved the study and granted a waiver of informed consent. In 115 women (mean age, 48.3 years; range, 21-76 years; 56 malignant, 12 high-risk, and 63 benign lesions), 131 NMLE lesions were analyzed. Two independent readers first classified MR images by using descriptive Breast Imaging Reporting and Data System (BI-RADS) criteria (BI-RADS classification with MR images alone [BI-RADS(MR)]) and later repeated this classification, adding information from conventional imaging (BI-RADS classification with combination of MR images and conventional images [BI-RADS(MR+Con)]). Lesion diagnosis was established with surgical histopathologic findings (n = 68), percutaneous biopsy results (n = 25), or 2 years of stability at MR imaging (n = 38). Receiver operating characteristic curves were built to compare BI-RADS(MR) with BI-RADS(MR+Con). A multivariate interpretation model was constructed and validated in a distinct cohort of 44 women. RESULTS: Values for inter- and intraobserver agreement, respectively, were better for BI-RADS(MR+Con) (κ = 0.847 and 0.937) than for BI-RADS(MR) (κ = 0.748 and 0.861). For both readers, the areas under the receiver operating characteristic curve (AUCs) for diagnosis of malignancy were also superior when BI-RADS(MR+Con) (AUC = 0.91 [reader 1] and 0.93 [reader 2]) was compared with BI-RADS(MR) (AUC = 0.84 [reader 1] and 0.87 [reader 2]) (P < .05). An interpretation model combining conventional imaging with MR imaging criteria showed very good discrimination (AUC = 0.89 [training set] and 0.90 [validating set]). CONCLUSION: Adding conventional imaging to NMLE lesion characterization at breast MR imaging improved the diagnostic performance of radiologists, and the interpretation model used offers good accuracy with the potential to optimize the reproducibility of NMLE analysis at MR imaging.

[Are centrosomal abnormalities correlated to DNA ploidy in breast cancer?]. / Corrélation entre les anomalies centrosomiques et l'ADN-ploïdie dans le cancer du sein.

ADN ploidy was shown to play a role in genomic instability of cancer cells and prognosis. The implication of the centrosome in the cell cycle was also described. Therefore, new prognostic factors could be suggested for a better-tailored therapy. The purpose of this study is to search for correlation between centrosomal abnormality and ADN ploidy in breast cancer. Cell prints were prepared from cell culture of mesothelial ascitis, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Fresh cell prints were also obtained from cases with invasive carcinoma. The centrosome was labelled by an indirect immunofluorescence assay using anti-γ-tubulin antibody and F(ab')(2) FITC before quantification with fluorescence microscopy. ADN ploidy was scored with DNA index obtained by means of flux cytometry. The normal mesothelial cells (94% of cells with only one centrosome) and the diploid cell line MRC5 (68% of cells with two centrosomes) were used as controls. DNA ploidy was found to be correlated with centrosomal abnormality in MCF7 cell line (64% of cells had more than three centrosomes) but not in the 10 cases of invasive ductal carcinoma analysed in this study. The absence of correlation between DNA ploidy and centrosomal abnormality in breast cancer samples may be due to the small numbers of cases, the cell prints or tumorigenesis. Correlation analysis of a larger number of cases and types of breast lesions to numerical and morphological abnormalities of the centrosome are ongoing.

Steroid profiling in preeclamptic women: evidence for aromatase deficiency.

OBJECTIVE: Experimental data have revealed the critical role played by 2-methoxy-estradiol, a metabolite of 17ß-estradiol, in the pathophysiology of preeclampsia. We used gas chromatography/mass spectrometry to measure a whole panel of hormonal steroids in the plasma from women during the third trimester of their pregnancy. STUDY DESIGN: The population study consists of 24 pregnant patients with different outcomes: normal, or complicated by isolated preeclampsia or by severe preeclampsia with Hemolysis Enzyme Liver Low Platelets (HELLP) syndrome. RESULTS: 17ß-estradiol was reduced by 50% in isolated preeclampsia, and by 70% in severe preeclampsia with HELLP syndrome (normal: 8.54 ± 0.9 ng/mL; isolated preeclampsia: 4.65 ± 1.0 ng/mL; severe preeclampsia with HELLP syndrome: 2.64 ± 0.4 ng/mL), as is estrone. Downstream, 2-methoxy-estradiol was decreased only in severe preeclampsia with HELLP syndrome. The concentrations of estrone and 17ß-estradiol precursors were comparable between groups, suggesting that placental aromatase is deficient in preeclampsia. CONCLUSION: The gradual decrease of estrogen levels with increasing severity of preeclampsia suggests an impairment of placental steroidogenesis.

[First results of a breast cancer risk assessment and management consultation]. / Consultation personnalisée d'évaluation du risque de cancer du sein : premiers résultats.

INTRODUCTION: In France, participation in the organized breast cancer screening program remains insufficient. A personalized approach adapted to the risk factors for breast cancer (RBC) should make screening more efficient. A RBC evaluation consultation would therefore make it possible to personalize this screening. Here we report our initial experience. MATERIAL AND METHOD: This is a prospective study on women who were seen at the RBC evaluation consultation and analyzing: their profile, their risk assessed according to Tyrer Cuzick model (TC)±Mammorisk© (MMR), the existence of an indication of oncogenetic consultation (Eisinger and Manchester score), their satisfaction and the recommended monitoring. RESULTS: Among the women who had had a TCS and/or MMR evaluation of SCR (n=153), 76 (50%) had a high risk (n=67) or a very high risk (n=9). Almost half (47%) had a possible (15%) or certain (32%) indication to an oncogenetic consultation. Regarding this consultation, 98% of women were satisfied or very satisfied. In total, 60% of women had a change in screening methods. CONCLUSION: This RBC evaluation consultation satisfies women and for a majority of them, modifies their methods of breast cancer screening.

CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers.

Fetal CD34+ cells enter the maternal circulation during pregnancy and may persist for decades. These cells are usually depicted as hematopoietic stem/progenitor cells. Our objective was to further determine the phenotype of fetal chimeric CD34+ cells in placental maternal blood from the intervillous space (IVS). Human healthy term placentas were analyzed (n=9). All fetuses were male. CD34+ cells were identified in the IVS and further characterized as fetal or maternal using X and Y chromosome fluorescence in situ hybridization. The phenotype of fetal cells was further analyzed using anti-CD117 (c-kit), anti-CD133, anti-CD31, anti-von Willebrand factor (vWF), anti-vimentin, anti-CD45 and anti-cytokeratin (CK) antibodies. We used preeclamptic placentas of male (n=3) and healthy placentas of female fetuses (n=3) as controls. As expected fetal cells were easily identified in the IVS and significantly increased in cases of preeclampsia. Most CD34+ cells in the IVS were of fetal origin (90%) and were not surrounded by CK staining further showing that they were not in fetal trophoblastic villi. Similarly, about 40% of CD31+ and 6% of vimentin+ cells in the IVS were fetal in origin. No CD117+ or CD133+ fetal cells were found in the IVS of examined placentas. Besides, all the CD34+ cells identified in the IVS were co-labeled with vWF or CD31, suggesting their endothelial origin. These results suggest that most CD34+ cells in maternal placental blood at term are fetal in origin from endothelial and not hematopoietic lineages.

Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy.

Pregnancy results in the transfer of stem cells from the fetus to the maternal circulation. These cells are able to migrate and differentiate within various damaged maternal tissues. We recently showed the presence of fetal-derived cells in human breast carcinomas during pregnancy. In this study, we aimed to reproduce these results in a murine model of "pregnancy-associated" breast carcinoma. We bred virgin MMTV-H-Ras transgenic female mice with male mice transgenic for luciferase under the control of the VEGFR2 promoter. Tumors that developed during or following gestation were analyzed and their nuclear grade classified. Fetal cells were detected by Y chromosome Fluorescence in situ hybridization FISH in 9/9 of breast carcinomas but only in 2 liver controls from the same animals. The number of fetal cells was 20 and 4.9 per million maternal cells in these tissues, respectively (p < 0.05). High grade tumors had significantly more fetal cells (p < 0.05). In vivo imaging of the luciferase signal under control of the VEGFR2 promoter as well as von Willebrand staining did not reveal an endothelial phenotype of fetal cells. Sixty two percent of the fetal cells expressed cytokeratins but were not tumoral. In conclusion, fetal cells-expressing cytokeratin-are always present in murine breast carcinomas associated with gestation. Interestingly, high-grade tumors contain more fetal cells.

Validation of the Tenon breast cancer score for predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastasis: a prospective multicenter study.

BACKGROUND: Axillary lymph node dissection (ALND) is the standard treatment for patients with sentinel node (SN) metastasis, but most of these patients have negative non-sentinel nodes (non-SN). We have developed a scoring system (the Tenon score) to help identify a subgroup of patients who have a low risk of having non-SN metastases and who may thus forgo ALND. Here we validated the Tenon score in an independent cohort of SN-positive patients. PATIENTS AND METHODS: We tested the accuracy of the Tenon score for predicting non-SN status in a prospective multicenter study of 226 SN-positive breast cancer patients. We calculated the false-negative rate, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). Receiver operating characteristics (ROC) curves were constructed and the areas under the curve (AUC) were calculated as a measure of discriminatory capacity. RESULTS: At least one non-SN was positive in 63 patients (27.9%). One hundred and twenty (53.1%) of the 226 patients had a Tenon score of 3.5 or less. Among these 120 patients, five had at least one positive non-SN. With a score cut-off of 3.5, the negative predictive value was 95.8% and the false-negative rate was 4.2%. Overall, the Tenon score accurately predicted non-SN status, with an AUC of 0.82 (95% confidence interval, 0.77-0.88). CONCLUSION: In this multicenter study of an independent patient population, the Tenon score was accurate and reproducible for predicting non-SN status in breast cancer patients. The simplicity and reliability of the variables on which the Tenon score is based may be an advantage over other scoring systems.

Neoadjuvant chemotherapy or primary surgery for stage III/IV ovarian cancer: contribution of diagnostic laparoscopy.

BACKGROUND: The aims of this retrospective study were to evaluate laparoscopic triage of patients with advanced ovarian cancer towards primary surgery or neoadjuvant chemotherapy, and to analyze outcome according to the treatment. METHODS: Between January 2001 and December 2006, 55 patients with stage III - IV ovarian cancer underwent diagnostic laparoscopy. Primary surgery was performed when complete cytoreduction was considered feasible, while the other patients received neoadjuvant chemotherapy (platinum-based combination with taxanes) and interval surgery. All the patients received adjuvant chemotherapy. RESULTS: Patients treated with neoadjuvant chemotherapy (n = 29) had a higher mean body mass index (P = 0.048), higher serum CA 125 levels (P = 0.026), and more metastases (P = 0.045) than patients treated with primary surgery (n = 26). In patients treated with primary surgery, complete cytoreduction and a residual tumour size

Anaphylactic shock during the sentinel lymph node procedure for cervical cancer.

BACKGROUND: Patent blue is a commonly used agent in the detection of sentinel nodes (SN) in solid cancer. Similar to any drug, it is possible to have an allergic reaction during surgery. Anaphylactic reactions to patent blue have been rarely reported especially in cervical cancer. CASE: We reported here a rare case of anaphylactic shock due to patent blue in response to injection of patent blue for SN mapping in a woman with cervical cancer. We presented our management of the shock, our diagnostic process of the allergen and the treatment of the cervix cancer after the anaphylactic reaction. CONCLUSION: Surgeons and anesthetists must be aware of the potential allergic of patent blue during the SN procedure.

Impact of pelvic arterial embolization for intractable postpartum hemorrhage on fertility.

OBJECTIVE: This study was to determine the long-term outcomes of arterial pelvic embolization for intractable postpartum hemorrhage and particularly its effect on menses, fertility, and outcomes of subsequent pregnancies. STUDY DESIGN: Fifty-six consecutive patients who underwent emergency pelvic arterial embolization for severe postpartum hemorrhage between April 1995 and July 2005 were included in the study. Patients were contacted to obtain information about menses and fertility after pelvic arterial embolization. RESULTS: Thirty-four women (61.8%) were successfully contacted. One patient had a hysterectomy. Thirty women (91%) reported regular menses. Thirteen women (38.3%) had a total of 20 spontaneous pregnancies. Eight pregnancies ended during the first trimester. The 12 other pregnancies (60%) were all normal and all patients delivered vaginally healthy babies with normal weight for gestational age. CONCLUSION: The current study suggests that fertility is not adversely affected by arterial pelvic embolization for intractable postpartum hemorrhage and that women can conceive after the procedure with normal pregnancy outcomes.

[Breast cancer: nomograms to predict pathologic response after preoperative chemotherapy]. / Cancer du sein: prédictivité de la réponse a la chimiothérapie néoadjuvante.

If the benefit of adjuvant chemotherapy may be determined at the level of a population, to determine the real chemosensitivity of a tumor at the individual level is impossible. The concept of neoadjuvant chemotherapy in patients with localized breast cancer is interesting because it helps to know the chemosensitivity of a tumor "in vivo". It is possible to use a single criterion to predict the effectiveness of targeted therapies. The chemotherapy is not a targeted therapy, and to determine a biological predictive marker of the response has been impossible so far. The development of mathematical models and use of molecular biology may help to predict chemosensitivity. Initial results are promising. The validation of published works is necessary, but applications are numerous.

[Sentinel lymph node biopsy in invasive breast cancer in 2009]. / Mise au point sur le prélèvement du ganglion sentinelle dans le cancer invasif du sein en 2009.

Sentinel lymph node biopsy (SLNB) has become an alternative to axillary lymph node dissection (ALND) despite the limited recidive long-term results. SLNB can not only reduce ALND morbidity but also provide ultrastadification with serial sectionning and immunohistochemistry analysis which increase the sensitivity of detection of sentinel node (SN) metastasis. Micrometastasis or isolated tumor cells are frequently discovered. However, their diagnostic and pronostic values are still subject to controversy. Most of large randomized trials have determined that double detection (colorimetric and isotopic) improved SN identification rate and decreased false negative rate; and that periareolar injection was equally effective, even superior than peritumoral injection with the major advantage of its simplicity in non palpable tumors. One of the unsolved problems of SLNB is to determine if its indications may be extended to larger tumors, to node sampling before or after neoadjuvant chemotherapy, or after previous lumpectomy or breast surgery, in case of palpable axillary node, and in case of multifocal tumor. Another challenge is to determine if complementary ALND in case of SLND metastasis is necessary, because 40 to 70% of non sentinel nodes (NSN) are tumor-free. Several predictive models (nomograms, scores, partitioning recursive models) have been developed to predict non-SN status in SN-positive patients. These models must be validated in independent cohorts to enable their use in routine.

Breast cancer stroma frequently recruits fetal derived cells during pregnancy.

INTRODUCTION: Breast carcinomas associated with pregnancy display a high frequency of inflammatory types, multifocal lesions and lymph node metastasis. Because pregnancy results in transfer to mothers of foetal stem cells that can migrate and differentiate into various tissues, we addressed the issue of whether such cells are present in breast carcinoma associated with pregnancy. METHODS: We analyzed women presenting with such tumours who were pregnant with male foetuses using fluorescence in situ hybridization (FISH), targeting X and Y chromosomes. The foetal cell phenotype was then determined by combining FISH and immunohistochemistry with various antibodies. Statistical analysis was performed using t-test or nonparametric Wilcoxon's test. RESULTS: We found that foetal cells were present in nine out of 10 carcinomas, in contrast with none of four benign mammary lesions (P < 0.05). Counting foetal and maternal cells showed that the mean number of foetal cells per million maternal cells was 36 in breast cancers and 0 in control samples (P < 0.01). By combining FISH and immunolabelling, we found that foetal cells expressed mainly mesenchymal or, to a lesser degree, epithelial or endothelial markers, but never leucocytes. CONCLUSION: These findings demonstrate the frequent presence of foetal derived cells essentially in tumour stroma. Given the role played by stroma in tumour proliferation, these findings raise the issue of whether foetal cell can be targeted to influence tumour behaviour.

Serous and mucinous ovarian tumors express different profiles of MMP-2, -7, -9, MT1-MMP, and TIMP-1 and -2.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in tumorigenesis, but little is known of their expression according to mucinous or serous type. This study aimed to evaluate the immunohistochemical expression of MMP-2, -7, -9, MT1-MMP, TIMP-1 and -2 in these tumors. A tissue microarray was set up including 99 serous (25 benign, 27 borderline, 47 malignant) and 79 mucinous (25 benign, 44 borderline, 10 malignant) ovarian tumors. Immunostaining results were scored by using the HSCORE and assessed by univariate, unsupervised hierarchical clustering and multidimensional scaling analyses. Epithelial expression of MMP-2, -7, -9, MT1-MMP, TIMP-2, but not TIMP-1, was higher in serous than mucinous tumors. Stromal expression of MMP-7 was higher in serous tumors. Alterations in MT1-MMP, MMP-7 and -9 were found in malignant serous tumors, while benign and borderline tumors shared similar expressions. By unsupervised hierarchical clustering analysis, mucinous and serous tumors were better differentiated by epithelial than stromal MMP and TIMP immunolabelling. By multidimensional scaling analysis, the expressions of MMPs and TIMPs were scattered in serous tumors and homogeneous for mucinous tumors. In conclusion, our results support the differential expression in MMPs and TIMPs of ovarian tumors according to serous or mucinous histology.

External validation of a laparoscopic-based score to evaluate resectability of advanced ovarian cancers: clues for a simplified score.

BACKGROUND: The relevance of laparoscopy-based score in identifying patients with advanced ovarian cancer for optimal cytoreductive surgery has been evaluated. METHODS: 55 patients with stage III-IV ovarian cancer, having undergone both laparoscopy and laparotomy for cytoreductive surgery, were retrospectively analyzed. Seven parameters were assessed: omental cake, peritoneal carcinosis, diaphragmatic carcinosis, mesenteric retraction, bowel infiltration, stomach infiltration, liver metastases. Each parameter was assigned 2 points if present and 0 if not (Fagotti score). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were calculated for each parameter. Receiver Operating Characteristic (ROC) curve analysis was used to predict the surgical outcome. RESULTS: A laparoscopy-based score of >or=8 was associated with suboptimal cytoreduction with sensitivity, specificity, PPV, NPV, and accuracy of 46%, 89%, 89%, 44%, and 60% respectively. ROC curve analysis gave an Area Under the Curve (AUC) of 0.74. A modified score was set up by selecting 4 of the 7 parameters which satisfied the inclusion criteria in our population: diaphragmatic carcinosis, mesenteric retraction, stomach infiltration, liver metastases. Thirteen patients (12%) had a modified score of >or=4 and 42 patients (88%) had a score of <4 with an optimal cytoreduction rate of 0% and 43% respectively (P=0.002). A modified score of >or=4 was associated with suboptimal cytoreduction with sensitivity, specificity, PPV, NPV, and accuracy of 35%, 100%, 100%, 43%, and 56% respectively. ROC curve analysis gave an AUC of 0.68. CONCLUSION: This simplified laparoscopy-based score was at least as accurate as the Fagotti score to predict resectability.