Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers.

Selective inhibition of BCL-2 is expected to enhance therapeutic vulnerability in luminal estrogen receptor-positive breast cancers. We show here that the BCL-2 dependency of luminal tumor cells is nevertheless mitigated by breast cancer-associated fibroblasts (bCAFs) in a manner that defines MCL-1 as another critical therapeutic target. bCAFs favor MCL-1 expression and apoptotic resistance in luminal cancer cells in a IL-6 dependent manner while their own, robust, survival also relies on MCL-1. Studies based on ex vivo cultures of human luminal breast cancer tissues further argue that the contribution of stroma-derived signals to MCL-1 expression shapes BCL-2 dependency. Thus, MCL-1 inhibitors are beneficial for targeted apoptosis of breast tumor ecosystems, even in a subtype where MCL-1 dependency is not intrinsically driven by oncogenic pathways.

Model predicting the ypN0 status after good response to chemoradiotherapy in rectal cancer.

BACKGROUND: The purpose of this study was to identify the predictive factors for ypN0 status in tumors with good pathologic response to chemoradiotherapy (CRT). METHODS: A retrospective chart review was conducted on patients at two tertiary cancer center who underwent rectal resection after good response to CRT between 2000 and 2013. RESULTS: No preoperative treatment (oxaliplatin use, radiotherapy boost of 5,4 Gy, delay CRT-surgery) impacted on the ypN status. In the multivariate analysis, only a ypT<3 (HR 7.5 [2,9-19.5]) was significant and no lymphovascular invasion (HR 8,9 [1.6-49.8]) was limited to significance.The best model predicting the ypN0 status used only the ypT status<3. The major part (92.2%) of patients with ypT0-2 tumors had no LN invasion. CONCLUSION: The risk of lymph node involvement metastases was only 7.8% for the patients with an ypT0-2 status. A fullthickness transanal resection coud be the futur treatment of these patients.

[Inflammatory and infectious breast mastitis outside of pregnancy and lactation: Guidelines]. / Mastites inflammatoires et infectieuses du sein en dehors de la grossesse et de la période d'allaitement : recommandations.

OBJECTIVES: This work's objective was to define the various non-cancerous inflammatory and infectious mastitis, which may occur outside of pregnancy and lactation, and to identify recommendations for their care based on an exhaustive literature review. MATERIALS AND METHODS: A literature review was conducted by consulting Medline, Cochrane Library, Google scholar and international recommendations in French and English until 31st August 2014. RESULTS AND CONCLUSION: Infectious mastitis (periareolar abscess) is the most common form of non-puerperal abscesses and it is recommended that a suction/drainage needle for abscesses under 5 cm, involving antibiotic therapy (grade C). For abscesses over 5 cm, there is no evidence to recommend a first surgery or suction/drainage. Inflammatory mastitis can be primary or secondary to a systemic disease (diabetes, collagen…; LE4). In case of idiopathic granulomatous mastitis, a steroid therapy or surgery may be indicated, without one or the other of these methods can be recommended. In case of plasma cell mastitis or ductal ectasia, no treatment is recommended.

[Benign breast tumors: Recommendations of Collège National des Gynécologues Obstétriciens Français (CNGOF)--Short text]. / Tumeurs bénignes du sein: recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF)--Texte court.

Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4-5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4-5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C).

How to improve the preoperative staging of presumed early-stage endometrioid endometrial cancer?

PURPOSE OF INVESTIGATION: Accurate preoperative staging of early-stage endometrioid endometrial cancer (EEC) is necessary to avoid under or over surgical treatment. The objective is to determine the rate of understaging and to evaluate the accuracy of different methods: hysteroscopy-curettage versus endometrial biopsy in predicting the final stage. MATERIALS AND METHODS: This retrospective single-centre study led from 2000 to 2010, included women with EEC preoperatively assessed at low- or intermediate-risk. Understaging was defined as a postoperative FIGO Stage > 1 or a determination of high risk after the final histopathologic diagnosis. RESULTS: The study included 101 women (75 low-risk and 26 intermediate-risk). Final diagnosis was upstaged for 26 of them, more frequently in the presumed intermediate-risk group (57.7% vs 14.7%, p < 0.001). The rate of preoperative understaging was higher in the women with endometrial biopsies than those with curettage (34.5% vs 15.2%, p = 0.04). CONCLUSIONS: Hysteroscopy-curettage combined with magnetic resonance imaging (MRI) may improve preoperative staging of early-stage EEC, especially for presumed intermediate-risk disease.

Pelvic endometriosis in women under 25: a specific management?

AIM: The aim of this study was to describe the characteristics of women under 25 years with pelvic endometriosis and assess their potential for recurrence and fertility after surgery. METHODS: In a comparative retrospective study, 108 patients aged less than 25 years who underwent surgery for pelvic endometriosis were included: 49 in the DIE group (deep infiltrating endometriosis) and 59 in the SE group (superficial endometriosis). The main outcome measures were complications, recurrence and fertility. This study received the favorable opinion of the CEROG No 2012-GYN-04-02. RESULTS: The diagnosis was made at 21.6 ± 2.8 years, mainly considering clinical signs (78.4%), and on average 4.3 ± 3.7 years after the onset of symptoms; 16.1% of patients had to be reoperated (N.=5/31) due to a recurrence of their endometriosis. There were more recurrent pain (50% vs. 21.7%, P=0.005) and endometriosis (35.7 vs. 19.6%, P=0.08) in the DIE group. 75% (N.=33/44) patients desired pregnancy after surgery and 50% of them became pregnant, with one third thanks to assisted reproductive technology. CONCLUSION: In young women, endometriosis is often more severe. The early treatment does not improve the rate of recurrence and fertility, but can reduce pain and thus improve the quality of life.

[Atypical polypoid adenomyoma: retrospective study about 8 cases from Jeanne-de-Flandre Hospital between 1996 and 2008]. / Adénomyome polypoïde atypique: série rétrospective de 8 cas survenus à l'hôpital Jeanne-de-Flandre entre 1996 et 2008.

OBJECTIVES: To propose a therapeutic approach and follow-up of patients with atypical polypoid adenomyoma (APA) wishing to remain fertile. PATIENTS AND METHOD: We are presenting a retrospective study of eight APA cases. RESULTS: Two patients immediately received radical treatment, and one patient had an endometrial thermocoagulation. The remaining five patients received a conservative treatment with ultrasound and hysteroscopic monitoring. Among them, two had full-term pregnancies, one is being treated for infertility, in one case, the APA disappeared after three hysteroscopy-curettages and macroprogestative treatment. Lastly, one of our patients died from an aggressive endometrioid ovarian bilateral tumour associated with an endometrial adenocarcinoma. DISCUSSION AND CONCLUSION: Radical treatment is necessary for cases of APA in women no longer wishing to remain fertile. For those wishing to remain fertile, we can offer a conservative treatment once they have been informed regarding the associated risk of relapse, degeneration, and ovarian lesions which necessitate stricter follow-up.

[Is radical hysterectomy necessary in surgical procedure for early stage cervical cancer?]. / La colpohystérectomie élargie a-t-elle encore une place dans le traitement des cancers du col débutants?

OBJECTIVE: Radical hysterectomy is one of the treatment options for early stage cervical cancer. This surgery results in significant morbidity, especially urinary complications. The objective of the study is to determine the rate and predictive factors of parametrial involvement in early stage cervical cancer and to define a subset of patient at low risk for parametrial disease and potential applicant to less morbid surgery. METHODS: This review reports recent retrospective and prospective studies and we show randomized trial concerning feasibility of no radical surgery. RESULTS: Parametrial involvement rate in tumors <2 cm, without lymphovascular space invasion, with negative lymph nodes and depth of invasion <10mm is between 0 and 1.96%. CONCLUSION: This result, which suggests simple hysterectomy, is maybe adequate in this case. At present, no randomized trial allows to validate this hypothesis and to change present practices. Radical hysterectomy stays standard of surgical treatment of early stage cervical cancer.

[Indications for prophylactic hysterectomy]. / Hystérectomie prophylactique : quelle indication ?

Endometrial cancer is the most common gynecologic cancer in France with an incidence in France in 2010, of 6560 new cases and 1900 deaths secondary to endometrial cancer. The main risk factors are age, hyperoestrogenic factors and hereditary syndroms. Prophylactic hysterectomy could prevent endometrial cancer in case of risk factors such as genetic syndroms. Actually, only Lynch syndrome is a validate indication and should be discussed in patients older than 40-45 years. Prophylactic hysterectomy does not seem a reasonable option to patients carrying BRCA 1 or 2 mutation.

Value of dynamic contrast-enhanced MRI for tissue characterization of ovarian teratomas: correlation with histopathology.

AIM: To analyse the value of double contrast-enhanced (DCE) magnetic resonance imaging (MRI) in addition to conventional MRI to characterize ovarian teratomas subtypes with histological correlation. MATERIALS AND METHODS: From January 2005 to December 2008, 38 women undergoing MRI and subsequent resection of ovarian teratomas were identified [40 mature cystic teratomas (MCT), two struma ovarii, three immature teratomas]. MRI images were analysed blindly by two radiologists according to morphological and vascular abnormalities. An experienced histopathologist reviewed all slides to determine the presence and histological composition of Rokitansky protuberances. RESULTS: Thirty-one MCT (77%) had at least one small, regular Rokitansky protuberance presenting at an acute angle with the cyst wall. Ten out of 31 MCT did not display any enhancement on contrast-enhanced MRI related to sebaceous glands, adipose lobules, keratin, and pilosebaceous adnexa at histology. Three different time-intensity curve (TIC), types 1, 2, and 3, were related to presence of smooth muscular cells and fibrous, neuroglial, or thyroid tissue, respectively, found at histology of MCT. Type 3 TIC was also present in one struma ovarii and two immature teratomas. CONCLUSION: TIC types are related to the specific content of the solid tissue of ovarian teratomas but cannot be used to differentiate benign and malignant ovarian teratomas.

[Reexcision for positive margins in the surgery of ductal carcinoma in situ: are there any risk factors?]. / Reprise chirurgicale des carcinomes canalaires in situ pour exérèse non in sano : existe-t-il des facteurs de risque ?

OBJECTIVES: Ductal carcinoma in situ (DCIS) is a common breast lesion (10% of breast cancers). In most of the cases the standard treatment is a partial mastectomy combined with adjuvant irradiation. However, when positive margins (<2mm) occur, surgical re-excision is necessary. The purpose of our study was to determine the rate of reoperation for positive margins in DCIS and identify potential preoperative risk factors of unhealthy margins. PATIENTS AND METHODS: This is a retrospective study of 63 patients. We collected cases of DCIS at the Lille and Valenciennes' hospitals from the 1st of January 2007 till the 1st of January 2012. RESULTS: Fifty patients have had a partial mastectomy and 28 patients (56%) have had one or two complementary interventions to get healthy resection margins. The pathologic tumor size (>10mm) appears to be a risk factor for positive margins. DISCUSSION AND CONCLUSION: Few studies were aimed at identifying risk factors for unhealthy margins for DCIS. The main risk factors found in the literature are: the presence of comedonecrosis, tumor greater than 10mm, a palpable tumor, the absence of a preoperative biopsy, the low-grade lesions. Our study confirmed the influence of tumor size greater than 10mm as a risk factor for positive margins.

[Mature and immature ovarian teratomas: US, CT and MR imaging features]. / Tératomes ovariens matures et immatures: caractéristiques en échographie, TDM et IRM.

Mature cystic ovarian teratomas, also called dermoid cysts, are one of the most frequent ovarian tumors of younger female patients and are suggested when a fat-containing cystic tumor is identified on imaging. However, the presence of fat is not pathognomonic for dermoid cyst, and it may also be identified in immature teratomas, whose prognosis and treatment are different. Some imaging features are helpful to differentiate between both tumors, including th epresence of enhancement on CT and MRI. Knowledge of the imaging features of these tumors allows for a confident diagnosis to be made in most cases. A few rare and less typical imaging features should also be recognized.

Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease.

The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n=945). Seventeen genes exhibited at least one polymorphism associated with AD risk, and following correction for multiple testing, we retained the interleukin (IL)-33 gene. We first confirmed that the IL-33 expression was decreased in the brain of AD cases compared with that of controls. Further genetic analysis led us to select three polymorphisms within this gene, which we analyzed in three independent case-control studies. These polymorphisms and a resulting protective haplotype were systematically associated with AD risk in non-APOE epsilon 4 carriers. Using a large prospective study, these associations were also detected when analyzing the prevalent and incident AD cases together or the incident AD cases alone. These polymorphisms were also associated with less cerebral amyloid angiopathy (CAA) in the brain of non-APOE epsilon 4 AD cases. Immunohistochemistry experiments finally indicated that the IL-33 expression was consistently restricted to vascular capillaries in the brain. Moreover, IL-33 overexpression in cellular models led to a specific decrease in secretion of the A beta(40) peptides, the main CAA component. In conclusion, our data suggest that genetic variants in IL-33 gene may be associated with a decrease in AD risk potentially in modulating CAA formation.

Post-traumatic fibro-osseous lesion of the ribs: a relatively under-recognised entity.

AIM: To report the description of a rare benign osseous lesion affecting the ribs entitled post-traumatic fibro-osseous lesion (PTFOL). METHODS: Seven cases of PTFOLs were retrieved from the archives of the University Hospital of Lille. Histological slides were reviewed and lesions were classified according to the histological patterns described by McDermott et al. Clinical and follow-up data were obtained from the patients' charts. RESULTS: PTFOLs occurred principally in men (mean age 31.8 years) with a known or suspected previous chest injury for four of them. No previous cancer was noted. Radiologically, PTFOLs readily presented as an isolated expansive lucency with a sclerotic rim located on the last five ribs. A constant increased uptake of radionucleotide was noted on bone scan. Microscopically, two fibro-osseous, four xanthomatous and one mixed pattern were individualised. Lesions were characterised by a network of anastomosing bone trabeculae without osteoblast lining within a fibrous stroma. A zonal maturation from woven to peripheral lamellar bone was characterised. Central sheets of lipid-laden histiocytes were conspicuous in the xanthomatous type. For each patient, clinical follow-up was excellent, without any recurrence. CONCLUSIONS: This is the second largest series of PTFOLs, which is considered to be a dysplastic healing process after trauma. It may be symptomatic or shown by imaging studies realised for unrelated reason. PTFOL is regularly misdiagnosed with other more common lesions of the ribs, such as fibro-osseous dysplasia, osteoma osteoid and benign fibrous histiocytoma. Its recognition is of importance because no follow-up is needed after resection.