Digital breast tomosynthesis versus mammography and breast ultrasound: a multireader performance study

Objectives

To compare the diagnostic performance of single-view breast tomosynthesis (BT) with that of dual-view mammography (MX); to assess the benefit of adding the craniocaudal (CC) mammographic view to BT, and of adding BT to MX plus breast ultrasound, considered to be the reference work-up.

Methods

One hundred and fifty-five consenting patients with unresolved mammographic and/or ultrasound findings or breast symptoms underwent conventional work-up plus mediolateral oblique-view BT of the affected breast. The final study set in 130 patients resulted in 55 malignant and 76 benign and normal cases. Seven breast radiologists rated the cases through five sequential techniques using a BIRADS-based scale: MX, MX + ultrasound, MX + ultrasound + BT, BT, BT + MX(CC). Multireader, multicase receiver operating characteristic (ROC) analysis was performed and performance of the techniques was assessed from the areas under ROC curves. The performance of BT and of BT + MX(CC) was tested versus MX; the performance of MX + ultrasound + BT tested versus MX + ultrasound.

Results

Tomosynthesis was found to be non-inferior to mammography. BT + MX(CC) did not appear to be superior to MX, and MX + ultrasound + BT not superior to MX + ultrasound.

Conclusions

Overall, none of the five techniques tested outperformed the others. Further clinical studies are needed to clarify the role of BT as a substitute for traditional work-up in the diagnostic environment.

Key Points

? Digital breast tomosynthesis is a new adjunct to mammography and breast ultrasound. ? We compared the diagnostic performance of these investigations in an experimental observer study. ? Single-view breast tomosynthesis was confirmed as non-inferior to dual-view mammography. ? None of the investigations (or combinations) tested outperformed the others. ? Further prospective studies are needed to clarify precise role of tomosynthesis for diagnostic application.     

Cancer du rein métastatique : évolution à l’arrêt du traitement antiangiogénique chez des patients en réponse complète, à propos de cinq cas

Antiangiogenic therapies have led to substantial progress in the management of kidney cancer, highly vascular tumor, and chemoresistant. These molecules have improved the prognosis of metastatic renal cancer. However, only a few isolated cases of complete response have been described and the evolution of these patients after treatment discontinuation remains unclear. From a series of patients treated for kidney cancer with antiangiogenic in first line, the purpose of this study was to identify patients in complete response in whom treatment had been interrupted. Complete response was defined according to RECIST criteria and data were collected retrospectively at the Centre François Baclesse - Caen. Five patients were identified in complete response with a treatment discontinuation among sixty-seven patients. These five patients of good or intermediate prognosis received an initial nephrectomy followed by a first-line treatment by Sunitinib (ten cycles on average). After one year of stopping treatment, two patients are still in complete response and three patients relapsed at three, 12 and 15 months. The treatment of relapsing disease was surgical followed by monitoring or resumption of sunitinib resulting in new complete response for the all three patients. The interruption of antiangiogenic treatment seems acceptable after a complete response.     

Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells

Human dendritic cells (DC) generated from CD34⁺ hematopoieticprogenitors cultured in the presence of granulocyte macrophagecolony stimulating factor (GM-CSF) and tumor necrosis factor(TNF)- are related to Langerhans cells (DLC) and have been shownto induce a strong proliferation of allogeneic CD4⁺ T cells.The present study shows that recombinant human IL-10 (h-IL-10)inhibits the primary and secondary proliferative responses ofboth CD4⁺ and CD8⁺ T cells induced by allogenelc CD1a⁺ DLC.The alloreaction induced by DLC generated after 5–18 daysof culture of CD34⁺ HPC was equally inhibited by h-IL-10, thusindicating that DLC were sensitive to h-IL-10 at all stagesof differentiation. This is further indicated by the h-IL-10-inducedinhibition of the T cell alloreaction mediated by interdigitatingDC freshly isolated from tonsils. h-IL-10 specifically actedon DLC as it did not affect the proliferation induced by Epstein-Ban-viruslymphoblastoW cell lines (EBV-LCL) nor that induced by immobilizedanti-CD3. The inhibitory effect of h-IL-10 was not due to theproduction of suppressive factors by the DLC, as the additionof DLC and IL-10 did not inhibit EBV-LCL-induced T cell proliferation.Rather, the inhibition of cytokine production (IL-2, GM-CSF,TNF, IFN-) observed after 24 h of co-culture may explain theinhibition of T cell DNA synthesis detected 3 days later. Theh-IL-10-lnduced inhibition of human DC mediated alloreactionadvocates considering the use of h-IL-10 In the prevention oftransplant refection and graft versus host disease, phenomenainitiated by DC.     

Polymérisation de l'ε-caprolactone par des catalyseurs dérivés du bore

The cationic polymerization of ε-caprolactone catalyzed by boron derivatives, namely acyl fluoroborates, triethyloxonium fluoroborate (Meerwein's salt), boron trifluoride etherate and boron trifluoride was investigated. The acyl fluoroborates, especially the acetyl fluoroborate, produced high molecular weight polymers with fairly poor yields, whereas triethyloxonium fluoroborate gave a high yield of a rather low molecular weight polymer. The results were compared with those obtained with the two non-ionic catalysts. It seems that the acylium or ethylium group of the catalyst initiates the molecular chain and that the fluoroborate anion serves as catalyst and keeps the activity of the reaction site at the end of the growing chain. The mechanism is that of a polymerization without termination reaction (living-polymer type). However, according to the results of the kinetic study, this is true only in the case of acyl fluoroborates. The following relation between the viscosity and the number-average molecular weight of our samples was obtained: [η] = 1,25·10^?4M?_n^0,82.     

Identification of predictive factors of response to the BH3‐mimetic molecule ABT‐737: An ex vivo experiment in human serous ovarian carcinoma

Ovarian cancers are addicted to Bcl‐x_L and Mcl‐1, antiapoptotic members of the Bcl‐2 family. Bcl‐x_L can be inhibited by the BH3‐mimetic ABT‐737. In vitro, ABT‐737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl‐1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes to ABT‐737 when combined with carboplatin, which can indirectly inhibit Mcl‐1. Fresh samples from 25 patients with high‐grade serous ovarian cancer (HGSOC) who were chemo‐naïve and had undergone surgery were prospectively exposed ex vivo to ABT‐737 ± carboplatin. The treatment effect was studied on sliced tumor nodes by assessment of cleaved‐caspase 3 immunostaining. We also studied the association between baseline Bcl‐2 family protein expression (via immunohistochemistry) and the response of nodes to treatment. ABT‐737 induced apoptosis as a single agent but its efficacy was not improved by the addition of carboplatin. Bim was frequently expressed (20/25) and its absence or low expression was associated with the absence of response to ABT‐737, p value = 0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66–100). Moreover, we observed that in tumors in which Bim was expressed, a low expression of phospho‐Erk1/2 or Mcl‐1 improved the proportion of responses. This pilot study showed that ABT‐737 has promise as monotherapy for HGSOC in a specific subgroup of tumors. Bim, Mcl‐1, and phospho‐Erk1/2 appeared to be relevant biomarkers that could be used for the selection of patients in the design of clinical trials using Navitoclax (an orally available compound related to ABT‐737).     

Transient receptor potential vanilloid 1 (TRPV1) channels in cultured rat Sertoli cells regulate an acid sensing chloride channel

Sertoli cells provide a controlled microenvironment for regulation and maintenance of spermatogenesis for which an acidic milieu is crucial for male fertility. Sertoli cells also contribute to protection of spermatogenetic cells. Here, we showed that TRPV1 is expressed in rat Sertoli cells and regulates an acid sensing Cl(-) channel (ASCC). The expression of TRPV1 in rat Sertoli cells was demonstrated by RT-PCR, immunostaining and calcium measurement experiments. ASCC activity was inhibited by capsaicin (IC(50)=214.3+/-1.6 nM), olvanil (IC(50)=400+/-1.7 pM) and resiniferatoxin (IC(50)=9.3+/-1.5 nM) but potentiated by capsazepine (EC(50)=5.3+/-1.3 microM) and ruthenium red (EC(50)=2.3+/-1.5 microM). In the human airway epithelial cell line Calu-3 in which ASCC can be detected but not TRPV1, capsaicin and capsazepine were without any effect. Finally the application of the non-steroidal anti-inflammatory drug ibuprofen prevented the control of ASCC by TRPV1. Our study provides the first evidence for a regulation by TRPV1 of an acid sensing chloride channel in rat Sertoli cells. TRPV1 and ASCC may thus be considered as new potential physiological regulators of spermatogenesis and targets for pharmacological treatments of reproductive disorders as cryptorchidism, Sertoli cell tumors or torsion of the spermatic cord.     

Microenvironnement et angiogenèse des métastases hépatiques d’origine colorectale : implications chirurgicales

Stephen Paget's proposed an original “seed and soil” theory, with organ-preference patterns of tumor metastasis resulting in interaction between metastatic tumor cells and their specific microenvironment. There is many experimental and clinical data showing that this theory is validated. More recently, it has been suggested that early changes in the microenvironment at the distant sites, could be induced by the primary tumor, reported as “pre-metastatic niche” formation. Tumor cells could produce growth factors, cytokines which could facilitate the recruitment and the mobilization of the bone marrow-derived endothelial progenitor cells, and thus necessary for the tumor neovascularization and metastasis growth. Although the clinical value of the concept of the premetastatic niche is not yet elucidated, these data could encourage surgeons to perform the colorectal surgery first and then the liver surgery, in patients with synchronous colorectal liver metastases. The reciprocal interactions between primary tumor and microenvironment at the distant sites are therefore determinant for tumor progression. Taken together, the microenvironment is an important therapeutic target and surgeons and oncologist could discuss the choice of different surgical strategy for patient with synchronous colorectal liver metastases regarding the interaction with the microenvironment affected by primary tumor resection.     

Increase in breast cancer mortality in Southern Brazil from 1980 to 2002

Breast cancer is the most prevalent form of cancer in the world. Breast cancer mortality rates are high in Brazil and show striking variations between geographic regions. A time-trend ecological study was performed in Southern Brazil from 1980 to 2002. Data were collected from the Mortality Information System (Ministry of Health) to assess age-standardized mortality rates. Linear regression for mortality time-trend analysis and multiple regression for mortality differences among three States were calculated. The highest mean mortality rate (14.45) was observed in Rio Grande do Sul, significantly greater (p < 0.001) than in Santa Catarina (8.93) and Paraná (9.95). An annual increase of 0.47 in the mortality rate was observed in the three States of Southern Brazil. According to these results, the South of Brazil and especially the State of Rio Grande do Sul showed a significant upward trend in breast cancer mortality. Continued efforts are needed to help explain these numbers and reverse the present situation.