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BACKGROUND: Endometriosis and possible rectal involvement are difficult to assess by physical examination. Previous studies have shown the diagnostic value of magnetic resonance imaging and rectal endoscopic sonography (RES) in this setting, but not that of transvaginal sonography (TVS). The aims of this study were to compare the accuracy of TVS and RES for the diagnosis of pelvic endometriosis, and to compare the results with histological findings. PATIENTS AND METHODS: In a prospective study, 30 consecutive patients referred with clinical signs of endometriosis underwent TVS and RES; the images were interpreted blindly with regard to physical findings. RESULTS: Endometriosis was confirmed histologically in 28 (93%) of the 30 patients. Endometriomas were also present in 67% of cases. For the diagnosis of uterosacral endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 75 and 75%, 83 and 67, 95 and 90%, and 45 and 40% respectively. For the diagnosis of rectosigmoid endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 95 and 82%, 100 and 88%, 100 and 95%, and 89 and 64% respectively. CONCLUSION: Despite the large proportion of our patients who had intestinal endometriosis, representing a possible source of bias, our results suggest that TVS is as efficient as RES for detecting posterior pelvic endometriosis and should therefore be used as the first-line examination. [ABSTRACT FROM AUTHOR]

Background: The sentinel node (SN) is defined as the first node in the lymphatic system that drains a tumor site. If the SN is not metastatic, then all other nodes should also be disease-free. We used serial sections and immunohistochemical (IHC) staining to examine both SN and non-sentinel nodes (non-SNs). Patients and methods: Twenty-three patients (median age 69 years) with early endometrial cancer underwent a laparoscopic SN procedure based on a combined detection method, followed by complete laparoscopic pelvic lymphadenectomy. If the SN was free of metastasis by both hematoxylin and eosin (H&E) and IHC staining, all non-SNs were also examined by the combined staining method. Results: SNs were identified in 19 patients (82.6%). A total of 47 SNs were removed (mean 2.5). Ten SNs (21.3%) from five patients (26.3%) were found to be metastatic at the final histologic assessment. In 14 patients, no metastatic SN involvement was detected by H&E and IHC staining. In these 14 patients, 120 non-SNs were examined by serial sectioning and IHC, and none were found to be metastatic. Conclusion: The SN procedure appears to reliably predict the metastatic status of the regional lymphatic basin in patients with early endometrial cancer. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that histologically undetectable or ‘occult’ metastases in the lymphatic system could explain some recurrences. HPV DNA screening by means of the polymerase chain reaction (PCR) has been proposed as a method to detect occult metastases. This study was designed to determine the frequency of HPV DNA detection by PCR in sentinel lymph node (SN), and its relation to the clinical characteristics and outcome of women with cervical cancer. Patients and methods: The primary cervical tumor and SN were tested for HPV DNA by means of PCR in 59 patients. Results: Fifteen (25.4%) of the 59 women undergoing the SN procedure had an involved SN. HPV DNA was more frequent in positive SN than in negative SN (P Conclusion: In women with cervical cancer, HPV DNA screening of sentinel nodes might help to identify patients at risk of lymph node metastases and recurrence. [ABSTRACT FROM AUTHOR]

The intercalation of pyrazolone-based oxalamide metal complexes into Na-montmorillonite (Na-MMT) for catalytic liquid-phase oxidation of phenol using H 2 O 2 was undertaken by a flexible ligand method using metal ions including Mn(II), Zn(II), and Sn(II). First, the metal ions were exchanged with the sodium ions of Na-MMT, and then these metal ions were complexed with a new pyrazolone-based oxalamide ligand. The intercalated metal complexes were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, elemental analysis, and thermogravimetric analysis. Phenol was successfully oxidized by heterogeneous catalysts based on Mn(II), Zn(II), and Sn(II) pyrazolone-based oxalamide complexes intercalated into Na-MMT. These heterogeneous catalysts catalyze the liquid-phase oxidation of phenol using H 2 O 2 to catechol as the major product and hydroquinone and benzoquinone as the minor products. The Mn(II) and Zn(II) complexes intercalated into Na-MMT showed better activity than the Sn(II) complex intercalated into Na-MMT and the reaction without the catalyst. It has been shown that some metal ion complexes intercalated into Na-MMT are active catalysts for liquid-phase oxidation of phenol with hydrogen peroxide., (© TÜBİTAK.)

The existing reducing agents used in the literature to decolorization of methylene blue are soluble in water and the reduction process is carried out in a homogeneous redox reaction medium. After the decolorization process, the reducing agents and its by-products remain in a homogeneous redox reaction medium. Many of these reducing agents are toxic and cause chemical pollution of textile wastewater. Therefore, there is a need for reducing agents that can be mixed heterogeneously with water from which the reducing agent can be easily removed from a redox reaction medium. For this purpose, water-insoluble redox active azo polymer was synthesized from redox active 1,4-dihydroxybenzene and p-phenylenediamine. The synthesized redox active azo polymer was used for decolorization of methylene blue by heterogeneous reduction and various kinetic parameters were investigated for this redox reaction. At the same time, the investigated results of azo polymer and monomer (1,4-dihydroxybenzene) were compared., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To define the prognostic value of isolated tumor cells (ITC), micrometastases (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a retrospective multicenter cohort study at 13 French sites. All the eligible patients who underwent SLNB from January 1999 to December 2008 were identified, and appropriate data were extracted from medical records and analyzed. Among 8001 patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months, overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were not statistically different in ITC or pN1mi compared to tumor-free nodes. Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single macrometastases were not different from those of ITC or pN1mi. In case of 2 macrometastases or more, survival rates decreased and recurrence rates increased significantly. Micrometastases and ITC do not have a negative prognostic value. Single macrometastases might have an intermediate prognostic value while 2 macrometastases or more are associated with poorer prognosis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST)., Patients and Methods: Retrospective analysis of all patients with T1 BC, who underwent surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized., Results: Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11-15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors., Conclusion: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.

Background: Despite multidisciplinary tumour boards (MTBs), non-compliance with clinical practice guidelines is still observed for breast cancer patients. Computerised clinical decision support systems (CDSSs) may improve the implementation of guidelines, but cases of non-compliance persist., Methods: OncoDoc2, a guideline-based decision support system, has been routinely used to remind MTB physicians of patient-specific recommended care plans. Non-compliant MTB decisions were analysed using a multivariate adjusted logistic regression model., Results: Between 2007 and 2009, 1624 decisions for invasive breast cancers with a global non-compliance rate of 8.3% were analysed. Patient factors associated with non-compliance were age>80 years (odds ratio (OR): 7.7; 95% confidence interval (CI): 3.7-15.7) in pre-surgical decisions; microinvasive tumour (OR: 5.2; 95% CI: 1.5-17.5), surgical discovery of microinvasion in addition to a unique invasive tumour (OR: 4.2; 95% CI: 1.4-12.5), and prior neoadjuvant treatment (OR: 4.2; 95% CI: 1.1-15.1) in decisions with recommendation of re-excision; age<35 years (OR: 4.7; 95% CI: 1.9-11.4), positive hormonal receptors with human epidermal growth factor receptor 2 overexpression (OR: 15.7; 95% CI: 3.1-78.7), and the absence of prior axillary surgery (OR: 17.2; 95% CI: 5.1-58.1) in adjuvant decisions., Conclusion: Residual non-compliance despite the use of OncoDoc2 illustrates the need to question the clinical profiles where evidence is missing. These findings challenge the weaknesses of guideline content rather than the use of CDSSs.

Several genes might explain BRCA1/2 negative breast and ovarian family cases. Deleterious mutations in few genes involved in the Fanconi complex are responsible for Fanconi anemia at the homozygous state and breast cancer (BC) susceptibility at the heterozygous state (BRCA2, PALB2, BRIP1). RAD51C plays an important role in the double-strand break repair pathway and a biallelic missense mutation in the RAD51C gene was found in a Fanconi anemia-like disorder. Subsequently, six monoallelic pathogenic mutations were identified after screening 480 BRCA1/2 negative breast and ovarian cancer (BC/OC) pedigrees. Several reports were unsuccessful to replicate these results. To investigate whether germline mutations in RAD51C are associated with an increased risk of developing BC/OC, we screened, by Sanger sequencing of the coding sequence, 117 index cases of breast and ovarian families from French or European origin, and negative for BRCA1/2 mutations. In our study, we found 3 pathogenic mutations among 117 families screened which corresponds to a 2.6% frequency. Our results confirm that RAD51C is a susceptibility gene for ovarian and BC and that this gene should be screened for mutations in families with multiple BC/OC., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background: Little evidence of the impact of immunohistochemical analysis (IHC) on the indications for adjuvant therapies is available. This study determined the modification rate of adjuvant chemotherapy and lymph node area radiotherapy using IHC and its impact on survival., Patients and Methods: Between 2001 and 2005, 416 patients underwent surgery for invasive breast cancer with sentinel lymph node (SLN) biopsy., Results: A total of 112 patients had positive SLNs: 12.5% isolated tumor cells, 35.7% micrometastasis and 51.8% macrometastasis. Only 4% of patients (14 out of 342 patients) had modified indications for chemotherapy and 7% of patients (25 out of 342) for lymph node area radiotherapy due to IHC findings., Conclusion: IHC analysis led to modifications in adjuvant chemotherapy and lymph node area radiotherapy in 4% and 7% of patients, respectively. The prognosis of patients with nodal metastasis discovered by ultrastaging was similar to that for conventional Haematoxylin-Eosin-Safran (HES) staining. Our data support the use of SLN ultrastaging.

Background: For ductal intraepithelial neoplasia, grade 1B, studies that predict breast cancer risk after an 11-gauge vacuum-assisted breast biopsy have yielded contradictory results. In order to identify a predictive model of breast cancer risk, we assessed the underestimation rate according to radiological and clinical findings., Patients and Methods: Our study involved 212 patients. We compared the area under the receiver operating characteristic curves and the clinical utility of a logistic regression and partitioning model., Results: Overall upgrade to malignancy occurred in 42 (19.8%) out of the 212 cases. The area under the curve for the logistic regression and partitioning model were 0.65 (95% confidence interval=0.61-0.70) and 0.58 (95% confidence interval=0.54-0.62), respectively. The lowest predicted underestimation rate obtained with the logistic regression model was 9.5%., Conclusion: From this large series, we were unable to define any accurate safety model for breast cancer. Surgery should be thus recommended.

Background: The role of DNA ploidy in genomic instability of cancer cells and prognosis has been described in a number of studies. The role of the centrosome in cell cycle has also been reported., Aim: In this study, we aimed to investigate the correlation between the centrosome and DNA ploidy in breast cancer in a search for a cytologic predictive and prognostic marker., Materials and Methods: Cell prints were prepared from cell culture of mesothelial cells, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Indirect immunofluorescence was used with anti-γ-tubulin and centrosomes were quantified using a fluorescence microscope. DNA ploidy was scored with the DNA index analyzed by flow cytometry., Results: The normal mesothelial cells (94% of the cells with one detected centrosome) and MRC5 diploid cells (68% with two centrosomes) were used as quality controls. A correlation between the number of centrosomes and DNA ploidy was found in MCF7 cell lines (64% of the cells with a number of centrosomes ≥ 3). It was not observed in invasive breast cancer samples; however, the frequency of cells with centrosomes ≥ 3 was found to be slightly higher in DNA aneuploid samples than in DNA diploid samples (15% vs 13.3%)., Conclusion: Quantification of centrosome appears to be correlated to DNA ploidy in breast cancer cell lines and slightly associated to DNA aneuploidy in invasive breast cancer. Studies analyzing a larger number of samples as well as morphological abnormalities of the centrosome are needed.

Background. To reduce the incidence of microbial colonization of suture material, Triclosan- (TC-)coated suture materials have been developed. The aim of this study was to assess the incidence of suture-related complications (SRC) in breast surgery with and without the use of TC-coated sutures. Methods. We performed a study on two consecutive periods: 92 patients underwent breast surgery with conventional sutures (Group 1) and 98 with TC-coated sutures (Group 2). We performed subgroups analyses and developed a model to predict SRC in Group 1 and tested its clinical efficacy in Group 2 using a nomogram-based approach. Results. The SRC rates were 13% in Group 1 and 8% in Group 2. We found that some subgroups may benefit from TC-coated sutures. The discrimination obtained from a logistic regression model developed in Group 1 and based on multifocality, age and axillary lymphadenectomy was 0.88 (95% CI 0.77-0.95) (P < 10(-4)). There was a significant difference in Group 2 between predicted probabilities and observed percentages (P < 10(-5)). The predicted and observed proportions of complications in the high-risk group were 38% and 13%, respectively. Conclusion. This study used individual predictions of SRC and showed that using TC-coated suture may prevent SRC. This was particularly significant in high-risk patients.

Unlabelled: The aim of this study was to compare the effectiveness of a hand-held preoperative compact imager (POCI) camera with conventional lymphoscintigraphy using a γ-camera for sentinel lymph node (SLN) detection in breast cancer., Methods: The main objective was to demonstrate the noninferiority of the POCI relative to conventional lymphoscintigraphy and to compare the number of SLNs detected by the 2 imaging devices. Our study, a clinical prospective, double-blind, noninferiority study, planned to include 200 patients with early breast cancer and started in January 2006. A standard SLN protocol (4 periareolar injections of 37 MBq of (99m)Tc-nanocolloids, 2 h before lymphoscintigraphy) was performed preoperatively using a conventional γ-camera and then the POCI camera. Scans were obtained by 2 different nuclear medicine physicians unaware of each other's results. The day after, in the operating room, the surgeon, after receiving the previous results, used the counting probe for surgical SLN biopsy. The number and localization of axillary SLNs obtained by lymphoscintigraphy and the POCI and the duration of the whole procedure were determined., Results: Among the 162 patients included, 138 were evaluable. The POCI detected more SLNs than did lymphoscintigraphy in 50 patients (36%), the same number of in 54 patients (39%), and fewer SLNs in 34 patients (25%), representing 84 (61%) discordant pairs. The noninferiority of preoperative compact imaging of axillary SLNs numbers was found to be statistically significant (95% confidence interval, 30%-52%, P = 0.025) using the McNemar test. The duration of acquisition was shorter using the POCI (<10 min in 84% [n = 117] of patients; mean, 7.5 ± 3.3 min) than lymphoscintigraphy (13% [n = 18] of patients; mean, 15.7 ± 3.4 min), with P < 0.001 using the McNemar test for paired proportions., Conclusion: Preoperative compact imaging using a hand-held camera was able to predict the number and localization of breast cancer SLNs and was not inferior to conventional lymphoscintigraphy in this study. Further studies will determine whether preoperative compact imaging could replace lymphoscintigraphy, especially in surgical centers without an on-site nuclear medicine department.

In breast conserving surgery (BCS), the usefulness to perform systematic cavity shaving is actively debated. Some investigators argued that systematic cavity shaving could avoid surgical re-excision and make diagnosis of unexpected multifocality. Others argued that usefulness of cavity shaving depends on volumes of resection. In this study one hundred patients undergoing BCS with systematic cavity shaving were included. Margins less than 3 mm were considered to be insufficient. We tested clinico-pathological characteristics in order to identify predictive model of cavity margin shaving utility and we sought to determine if cavity margin shaving usefulness depends on volumes of resection. We showed that cavity shaving avoids the need for re-excision in 24% of cases as well as diagnosis of multifocality in 6% of cases. However, the clinical usefulness of cavity shaving was not related to the volumes of resection., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to determine the chemosensitivity of pregnancy-associated breast cancer (PABC) in the neoadjuvant setting by comparing the observed pathological complete response (pCR) rate with the rate predicted by a validated nomogram., Methods: Data from 48 PABC patients who received neoadjuvant chemotherapy (NACT) were collected. To predict the response rate to chemotherapy, we used well-calibrated logistic regression-based nomograms to calculate individual probability of pCR., Results: Observed rates of pCR were concordant with predictions in the whole sample and in the analyzed subgroups. For the whole sample, the area under the receiver-operated curve (AUC) was 0.77 (95% CI 0.66-0.87). The calibration of predicted and observed probabilities was excellent. In the subgroup analyses (NACT initiated during pregnancy or postpartum, NACT with only anthracycline or both anthracycline and taxanes), discriminations assessed by AUC were significantly above 0.5, except for patients treated with anthracycline only. The interpretation was limited by a lack of power., Conclusion: Through the use of nomograms, our study demonstrates that PABC is as chemosensitive as non-PABC and suggests that taxanes should be part of the NACT regimen for PABC. Further studies are warranted to increase the power of the presented data.

Purpose: Estrogen receptor-positive (ER+) and -negative (ER) breast cancers are molecularly distinct diseases. We hypothesized that p53 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of cancers., Experimental Design: We developed a 39-gene p53 signature derived from 213 ER+ and a separate 30-gene signature from 38 ER- cancers with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and ER- cancers, respectively., Results: External validation to predict p53 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant metastasis free survival in ER+ cancers in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant tamoxifen therapy (n = 277, HR = 2.43, P < 0.0001) but it was not prognostic in ER- cancers. It was also associated with higher chemotherapy sensitivity in ER+ but not in ER- cancers. The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER-, p53 signature showed no prognostic or predictive values in ER+ cancers but it was associated with better prognosis in ER- cancers. It also had no chemotherapy response predictive value in ER- or ER+ cancers., Conclusions: P53 dysfunction is prognostically most relevant in ER+ cancers and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of breast cancer., (©2011 AACR.)

Introduction: Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy., Materials and Methods: Our dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype., Results: The interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031) of positive sentinel node biopsy than the ER status by itself (p = 0.016). A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72) and calibration (HL p = 0.28/0.05/0.11) in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated., Discussion: We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.

Background: Lymph node status is an important prognostic factor and a criterion for adjuvant therapy in uterine cancers. While detection of micrometastases by ultrastaging techniques is correlated to prognosis in several other cancers, this remains a matter of debate for uterine cancers. The objective of this review on sentinel nodes (SN) in uterine cancers was to determine the contribution of ultrastaging to detect micrometastases., Methods: Review of the English literature on SN procedure in cervical and endometrial cancers and histological techniques including hematoxylin and eosin (H&E) staining, serial sectioning, immunohistochemistry (IHC) and molecular techniques to detect micrometastases., Results: In both cervical and endometrial cancers, H&E and IHC appeared insufficient to detect micrometastases. In cervical cancer, using H&E, serial sectioning and IHC, the rate of macrometastases varied between 7.1% and 36.3% with a mean value of 25.8%. The percentage of women with micrometastases ranged from 0% and 47.4% with a mean value of 28.3%. In endometrial cancer, the rate of macrometastases varied from 0% to 22%. Using H&E, serial sectioning and IHC, the rate of micrometastases varied from 0% to 15% with a mean value of 5.8%. In both cervical and endometrial cancers, data on the contribution of molecular techniques to detect micrometastases are insufficient to clarify their role in SN ultrastaging., Conclusion: In uterine cancers, H&E, serial sectioning and IHC appears the best histological combined technique to detect micrometastases. Although accumulating data have proved the relation between the risk of recurrence and the presence of micrometastases, their clinical implications on indications for adjuvant therapy has to be clarified.

Objective. To study incidence of abnormal hysteroscopic findings according to age. Methods. We retrospectively studied 557 consecutive office hysteroscopies in patients referred for incapacity to conceive lasting at least 1 year or prior to in vitro fertilization. Rates of abnormal findings were reviewed according to age. Results. In 219 cases, hysteroscopy showed an abnormality and more than a third of our population had abnormal findings that could be related to infertility. Rates of abnormal findings ranged from 30% at 30 years to more than 60% after 42 years. Risk of abnormal finding was multiplied by a factor of 1.5 every 5 years. Conclusion. Our data are an additional argument to propose office hysteroscopy as part of first-line exams in infertile woman, regardless of age.

Specialized cell types exploit endosomal trafficking to deliver protein cargoes to cell type-specific lysosome-related organelles (LROs), but how endosomes are specified for this function is not known. In this study, we show that the clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral recycling endosomal subdomains in melanocytes required for cargo delivery to maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of recycling endosomes redistributes to pericentriolar clusters, resulting in sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and consequent inhibition of melanin synthesis and melanosome maturation. Immunocytochemistry, live cell imaging, and electron tomography reveal AP-1- and KIF13A-dependent dynamic close appositions and continuities between peripheral endosomal tubules and melanosomes. Our results reveal that LRO protein sorting is coupled to cell type-specific positioning of endosomes that facilitate endosome-LRO contacts and are required for organelle maturation.

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.

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

Objective: The aim of this study is to evaluate the accuracy and the safety of stereotactic vacuum-assisted breast biopsy with a 10-gauge hand-held portable system., Materials and Methods: Retrospective data review of 288 consecutive breast lesions that underwent stereotactic 10-gauge hand-held portable vacuum-assisted biopsy from October 2004 through March 2006, was performed. The mean number of core specimens and the percentage of complete radiological removal of the target lesion were analysed. ADH and DCIS under-estimation were evaluated, as were the immediate and delayed complications due to the procedure., Results: The mean number of core specimens obtained per procedure was 9 (range 4-24). Complete radiological excision of the target lesion was achieved in 31.6% (91 of 288) with 91% of these lesions smaller than 10mm (mean size 7 mm; range 4-20mm). Under-estimation of ADH and DCIS was 18.2% (2 of 11) and 19.2% (9 of 47), respectively. There was no false negative result within a 3-year follow-up (from 2005 till date). Complications were mild and consisted of immediate bleeding and delayed haematomas., Conclusion: Breast biopsy using 10-gauge vacuum system is an accurate and safe technique for sampling non-palpable breast lesions.

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.

Background: The sentinel node (SN) is defined as the first node in the lymphatic system that drains a tumor site. If the SN is not metastatic, then all other nodes should also be disease-free. We used serial sections and immunohistochemical (IHC) staining to examine both SN and non-sentinel nodes (non-SNs)., Patients and Methods: Twenty-three patients (median age 69 years) with early endometrial cancer underwent a laparoscopic SN procedure based on a combined detection method, followed by complete laparoscopic pelvic lymphadenectomy. If the SN was free of metastasis by both hematoxylin and eosin (H&E) and IHC staining, all non-SNs were also examined by the combined staining method., Results: SNs were identified in 19 patients (82.6%). A total of 47 SNs were removed (mean 2.5). Ten SNs (21.3%) from five patients (26.3%) were found to be metastatic at the final histologic assessment. In 14 patients, no metastatic SN involvement was detected by H&E and IHC staining. In these 14 patients, 120 non-SNs were examined by serial sectioning and IHC, and none were found to be metastatic., Conclusion: The SN procedure appears to reliably predict the metastatic status of the regional lymphatic basin in patients with early endometrial cancer.

In order to reduce practice variations and offer cancer patients the best treatments according to reference guidelines, therapeutic decisions have to be taken, in France, by "multidisciplinary staff meetings'' (MSMs) as patient-specific care plans which are then implemented by cancer specialists. OncoDoc2 is a CDSS implementing CancerEst guidelines, a "local reference guideline'', on breast cancer management. The system has been assessed in a pragmatic before/after study. The intervention consisted in the routine use of OncoDoc2 during MSMs of Tenon hospital. The MSM decision compliance rate with the reference guideline was significantly higher in the after period, increasing from 79% to 93%. MSM decision analysis showed that missing steps in treatment plans were the main cause of noncompliance during the before period. This cause was drastically reduced in the after period.

Background: It has been suggested that histologically undetectable or 'occult' metastases in the lymphatic system could explain some recurrences. HPV DNA screening by means of the polymerase chain reaction (PCR) has been proposed as a method to detect occult metastases. This study was designed to determine the frequency of HPV DNA detection by PCR in sentinel lymph node (SN), and its relation to the clinical characteristics and outcome of women with cervical cancer., Patients and Methods: The primary cervical tumor and SN were tested for HPV DNA by means of PCR in 59 patients., Results: Fifteen (25.4%) of the 59 women undergoing the SN procedure had an involved SN. HPV DNA was more frequent in positive SN than in negative SN (P < 0.0001). Seven patients had a recurrence, after a mean delay of 17 months (range: 10-26). One of seven patients with a recurrence had an involved SN. HPV DNA was detected in an SN of one of seven patients with recurrence and nine (19.5%) of 46 patients without recurrence (not significant)., Conclusion: In women with cervical cancer, HPV DNA screening of sentinel nodes might help to identify patients at risk of lymph node metastases and recurrence.

The extent to which Rab GTPases, Rab-interacting proteins, and cargo molecules cooperate in the dynamic organization of membrane architecture remains to be clarified. Langerin, a recycling protein accumulating in the Rab11-positive compartments of Langerhans cells, induces the formation of Birbeck granules (BGs), which are membrane subdomains of the endosomal recycling network. We investigated the role of Rab11A and two members of the Rab11 family of interacting proteins, Rip11 and RCP, in Langerin traffic and the biogenesis of BGs. The overexpression of a dominant-negative Rab11A mutant or Rab11A depletion strongly influenced Langerin traffic and stability and the formation of BGs, whereas modulation of other Rab proteins involved in dynamic regulation of the endocytic-recycling pathway had no effect. Impairment of Rab11A function led to a missorting of Langerin to lysosomal compartments, but inhibition of Langerin degradation by chloroquine did not restore the formation of BGs. Loss of RCP, but not of Rip11, also had a modest, but reproducible effect on Langerin stability and BG biogenesis, pointing to a role for Rab11A-RCP complexes in these events. Our results show that Rab11A and Langerin are required for BG biogenesis, and they illustrate the role played by a Rab GTPase in the formation of a specialized subcompartment within the endocytic-recycling system.

Fetal progenitor cells enter the maternal circulation during pregnancy and can persist for decades. We aimed to determine the role of these cells in tissue inflammation during pregnancy. WT female mice were mated to males transgenic for the EGFP (ubiquitous) or the luciferase gene controlled by the VEGF receptor 2 (VEGFR2; V-Luc) promoter. A contact hypersensitivity reaction was triggered during such pregnancies. Fetal cells were tracked by using real-time quantitative amplification of the transgene (real-time PCR), Y chromosome in situ hybridization (FISH), immunofluorescence or in vivo bioluminescence imaging. Real-time PCR disclosed fetal cells in the inflamed areas in all tested mice (17/17) with higher frequency and numbers in the inflamed compared with the control areas (P = 0.01). Double labeling demonstrated CD31+ EGFP+ fetal cells organized as blood vessels. In WT pregnant mice bearing V-Luc fetuses, a specific luciferase activity signal could be detected at the hypersensitivity site only, demonstrating the elective presence of VEGFR2-expressing fetal cells. In conclusion, using various techniques, we found the presence of fetal endothelial cells lining blood vessels in maternal sites of inflammation. These results imply that fetal endothelial progenitor cells are acquired by the mother and participate in maternal angiogenesis during pregnancy.

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/-hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt-PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff-Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or = 5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.

Background: Sentinel lymph node (SN) biopsy based on dual labeling with blue dye and radiocolloid can reliably determine lymph node status in early-stage cervical cancer, but few data are available on its accuracy in more advanced disease. We examined the influence of tumor stage on the accuracy of SN biopsy in patients with cervical cancer., Methods: Between July 2001 and June 2004, 33 patients (mean age 52 years) with early-stage or locally advanced cervical cancer underwent laparoscopic SN biopsy based on dual labeling with patent blue and radiocolloid. Patients with early-stage cervical cancer (stages IA and IB1, 23 patients) underwent complete laparoscopic pelvic lymphadenectomy after the SN procedure. Patients with locally advanced cervical cancer (stage IB2, IIA or IIB, 10 patients) underwent laparoscopic pelvic and para-aortic lymphadenectomy after SN biopsy and prior neoadjuvant concomitant chemoradiotherapy. The SN identification rates and false-negative rates of patients with early-stage and locally advanced disease were compared., Results: The mean numbers of SNs identified per patient with early-stage and locally advanced cervical cancer were 2.3 (range 0-4) and 1.9 (range 0-4), respectively. SNs were identified in 86.9% (20/23) of patients with early-stage disease and in 80% (8/10) of patients with locally advanced disease. When analyzed according to the side of dissection, the identification rate was lower, especially in the patients with locally advanced disease (55% compared with 67.4%). The false-negative rate per patient was zero in early-stage disease and 20% (1/5) in locally advanced disease (no significant difference). When the side of dissection was taken into account, the false-negative rate improved to 42.9% (3/7) in patients with locally advanced disease and remained at zero in early-stage disease (P=0.038). Isolated blue dye was taken up in 53.3% of SNs in patients with locally advanced disease, compared with only 6.4% in patients with early-stage disease., Conclusions: This study suggests that the SN biopsy technique with dual labeling is less accurate in locally advanced cervical cancer than in early-stage cervical cancer.