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Introduction Type II AEG is now considered as oesophageal cancer in the seventh and eighth edition of TNM classification but optimal surgical approach for these tumors remains debated. The objective of the study is to assess and compare surgical and oncological outcomes of two surgical approaches: superior polar oesogastrectomy (SPO) or total gastrectomy (TG) in patients with type II adenocarcinoma of the oesophagogastric junction (AEG). Material and methods 183 patients with type II AEG treated from 1997 to 2010 in 21 French centers by SPO or TG were included in a multicenter retrospective study. The surgical and oncological outcomes were compared between these two surgical approaches. Results A TG was performed in 64 (35%) patients whereas 119 (65%) patients were treated by SPO with transthoracic approach in 100 of them (83.2%) and transhiatal approach with cervicotomy in 19 (16.8%). Surgical outcomes were comparable between the two approaches with a postoperative mortality rate of 4.9% and a severe operative morbidity rate within 30 days of 15.3%. Median survival in patients operated on by TG was of 46 months compared to 27 months in patients treated by SPO (p = 0.118). At multivariate analysis, TG appears to be an independent good prognostic factor compared to SPO (HR = 1.847; p = 0.008). However, TG was also associated with a higher rate of incomplete resection, (12.5% vs 5.9%; p = 0.120). Conclusion When TG allows obtaining tumor-free resection margins, this approach should be preferred to SPO.

Anorexia nervosa (AN) is a severe psychological and potentially life-threatening eating disorder. The activity-based anorexia (ABA) mouse model is commonly used to investigate physiological abnormalities associated with this disorder. Characterizing the holistic biochemical alterations induced by anorexia is essential to understanding AN pathophysiology as well as to define biomarkers for prognosis.To unravel the adaptive biochemical mechanisms occurring in this model in response to self-starvation, the urinary, plasma and fecal metabolic phenotypes of mice under different experimental conditions were compared. This included control mice with and without physical activity (CT and CTPA mice), a group with limited food access (LFA), and a group with both limited food access and physical activity (ABA). UsingPhysical activity altered the abundance of 14 fecal metabolites, including those involved in gut microbial metabolism and proteolysis. Food restriction disrupted a wide range of metabolic pathways including gut microbial metabolism, proteolysis and fatty acid breakdown (24 urinary and 6 plasma metabolites). The combined impact of food restriction and physical activity resulted in the same pattern of metabolic disruption (24 urine, 6 plasma).This work defined the metabolic signatures of ABA mice and provides novel insights into biological adaptations of mice in response to both food restriction and physical activity. These results should be further confirmed in AN patients.

Objective A retrospective case–control study was conducted to evaluate whether frequent binge drinking between the age of 18 and 25 years was a risk factor for alcohol dependence in adulthood. Setting The Department of Addictive Medicine and the Clinical Investigation Center of a university hospital in France. Participants Cases were alcohol-dependent patients between 25 and 45 years and diagnosed by a psychiatrist. Consecutive patients referred to the Department of Addictive Medicine of a university hospital between 1 January 2017 and 31 December 2017 for alcohol dependence were included in the study. Controls were non-alcohol-dependent adults, defined according to an Alcohol Use Disorders Identification Test score of less than 8, and were matched on age and sex with cases. Data on sociodemographics, behaviour and alcohol consumption were retrospectively collected for three life periods: before the age of 18 years; between the age of 18 and 25 years; and between the age of 25 and 45 years. Frequency of binge drinking between 18 and 25 years was categorised as frequent if more than twice a month, occasional if once a month and never if no binge drinking. Results 166 adults between 25 and 45 years were included: 83 were alcohol-dependent and 83 were non-alcohol-dependent. The mean age was 34.6 years (SD: 5.1). Frequent binge drinking between 18 and 25 years occurred in 75.9% of cases and 41.0% of controls (p

Background Impulsivity is a psychological trait linked to health issues such as obesity. However, few studies have explored the relation between impulsivity, dietary intake, and eating disorders (EDs) in a general population. Objective The aim of this cross-sectional study was to assess whether impulsivity was associated with energy intake, food-group consumption, snacking, and risk of EDs. Design In 2014, 51,368 adult participants from the NutriNet-Sante Study completed the 11th version of the Barratt Impulsiveness Scale (BIS-11), which assesses impulsivity. Food-group consumption and diet quality were evaluated by using ≥3 self-reported 24-h dietary records (n = 35,830), whereas snacking behavior was evaluated by an ad hoc question (n = 48,562). Risk of EDs was assessed with the Sick-Control-One-Fat-Food Questionnaire (SCOFF), and categories of ED (restrictive, bulimic, hyperphagic, and other types of EDs) were determined with the Expali algorithm (n = 48,824). Logistic and linear regressions were used to analyze the associations between impulsivity and energy intake, food-group consumption, diet quality, snacking, and risk of EDs, taking into account sociodemographic and lifestyle factors. Results Positive associations were found between impulsivity and consumption of alcoholic beverages and appetizers, whereas negative associations were found for fruit and vegetables, meat and poultry, processed meat, dairy products, milk-based desserts, and starchy foods. Impulsivity was positively associated with energy intake and negatively associated with diet quality. Impulsivity was also positively associated with snacking (OR: 3.32; 95% CI: 2.99, 3.68) and risk of EDs (OR: 3.02; 95% CI: 2.74, 3.33). The strongest associations were found for bulimic disorders (OR: 4.38; 95% CI: 3.66, 5.23) and hyperphagic disorders (OR: 2.91; 95% CI: 2.56, 3.31). Conclusion Impulsivity was associated with food intakes, snacking, and risk of EDs and could be taken into account in the promotion of healthy eating behavior. This study was registered at clinicaltrials.gov as NCT03335644.

The oncogenic role of TCL1 in chronic lymphocytic leukemia is well established in transgenic mice. TCL1 expression in other B-cell malignancies has been also described: post-germinal center-derived malignancies, such as multiple myeloma, classically do not express TCL1. Waldenström macroglobulinemia is a post-germinal center malignancy that is known to be similar to chronic lymphocytic leukemia in terms of its gene expression profile. TCL1 expression has not been so far assessed in Waldenström macroglobulinemia. Transcriptomic explorations show that TCL1A expression is linked to signaling pathways and biological functions that are known to be involved in Waldenström macroglobulinemia as well as to gene signatures of interest in B-cell malignancies. We investigated TCL1 expression at the protein level in the bone marrow of a series of 59 patients with Waldenström macroglobulinemia: 76% of patients expressed TCL1, which appeared to be associated with a pejorative prognostic impact. TCL1 could have an oncogenic role in Waldenström macroglobulinemia, and deserves further exploration.

Summary Background BRAF was identified as an oncogene in skin melanoma in 2002, and since 2011 has been a therapeutic target in the treatment of metastatic melanoma. The role of BRAF mutation in tumour initiation and the disease course remains to be elucidated. Objectives The main objective of our study was to determine whether there is a relationship between BRAF status and overall survival in patients with a melanoma and a positive sentinel lymph node. We also sought an association between BRAF status and the clinicopathological features of the melanoma. Finally, we looked for a potential heterogeneity of BRAF status in primary and metastatic tumours. Methods All patients (n = 72) treated for melanoma and with a positive sentinel lymph node at the University Hospital of Clermont-Ferrand, France, between January 2000 and January 2010 were enrolled in the study. We investigated BRAF status in primary melanoma and lymph node metastatic tissue in our molecular pathology laboratory and collected the clinical and survival data. Results Of the 72 patients, 32 had at least one BRAF mutation. There was a statistically significant difference in overall survival between the BRAF-mutated and wild-type populations. The only clinical feature related to BRAF status was metastatic burden. Of the 25 patients in whom we obtained the status in both locations, five had a discordant result. Conclusions BRAF mutation is an indicator of poor prognosis in patients with stage III melanoma with a positive sentinel lymph node. BRAF status could be used in the staging of this population. BRAF has a role not only in cellular immortalization but also in metastatic spread.

We report a case of a 15-year-old girl who is a known case for proximal focal femoral deficiency. She underwent several surgical lengthening procedures. Her course was complicated by femur nonunion, knee joint dislocation, stiff knee, and final lower limb discrepancy of over 15 cm. Rotationplasty was performed to salvage her previous surgical failures and restore her function. Surgery was uneventful and the patient was able to walk with the prosthesis in a few months after index surgery. Although the outcome of rotationplasty is visually unusual, for some children restored function and physical capabilities outweigh cosmetic concerns. The aim of the present study was to report a case of rotationplasty in salvaging a failed primary limb reconstruction in a patient with proximal femur focal deficiency.

Blastic plasmacytoid dendritic cell neoplasm is a rare clinicopathologic entity, characterized by strong skin tropism and a poor prognosis. The diagnosis is generally made by skin biopsy with appropriate immunohistochemical studies. To identify potential biological prognostic factors for blastic plasmacytoid dendritic cell neoplasm, we performed an extended clinico-immunohistochemical study on a series of 91 well-documented cases collected since 1995 by the French Study Group on Cutaneous Lymphomas. Skin biopsies were analyzed using a panel of 12 immunohistochemical markers (CD4, CD56, CD123, CD303, TCL1, CD68, CD2, CD7, TdT, Ki-67, S100, and MX-1). The results were correlated with survival. The 5 most characteristic markers of this entity (CD4, CD56, CD123, CD303, and TCL1) were expressed simultaneously in only 46% of patients. However, when 4 markers were expressed the diagnosis could still be reliably made without resorting to any additional stains. Expression of TdT and/or S100 correlated with varying degrees of maturation. Statistical survival analyses showed that CD303 expression and high proliferative index (Ki-67) were significantly associated with longer survival.

Summary Background and objectives Congenital anomalies of the kidney and urinary tract (CAKUT) are a frequent cause of renal failure in children, and their detection in utero is now common with fetal screening ultrasonography. The clinical course of CAKUT detected before birth is very heterogeneous and depends on the level of nephron reduction. The most severe forms cause life-threatening renal failure, leading to perinatal death or the need for very early renal replacement therapy. Design, setting, participants, & measurements This study reports the screening of two genes (HNF1B and PAX2) involved in monogenic syndromic CAKUT in a cohort of 103 fetuses from 91 families with very severe CAKUT that appeared isolated by fetal ultrasound examination and led to termination of pregnancy. Results This study identified a disease-causing mutation in HNF1B in 12 cases from 11 families and a mutation in PAX2 in 4 unrelated cases. Various renal phenotypes were observed, but no case of bilateral agenesis was associated with HNF1B or PAX2 mutations. Autopsy identified extrarenal abnormalities not detected by ultrasonography in eight cases but confirmed the absence of extrarenal defects in eight other cases. A positive family history of renal disease was not significantly more frequent in cases with an identified mutation. Moreover, in cases with an inherited mutation, there was a great phenotypic variability regarding the severity of the renal disease within a single family. Conclusions Our results suggest that mutations in genes involved in syndromic CAKUT with Mendelian inheritance are not rare in fetal cases with severe CAKUT appearing isolated at prenatal ultrasound, a finding of clinical importance because of genetic counseling.

Fetal brain tumors are rare and have different histologies. Although the definitive diagnosis relies on the histopathology of the tumor, it is useful to distinguish the tumors potentially curable from the tumors rapidly fatal after birth. Nevertheless, some intracranial masses are not tumors. We report four cases of intracerebral masses diagnosed prenatally corresponding to different histological lesions: teratoma, fetus-in-fetu, chraniopharyngioma, hemangioma. We discuss the elements of the differential diagnosis, which can be identified prenatally.

Purpose: The aims were to compare peak oxygen uptake (VO2peak) predicted from four standard equations to actual V O2peak measured from a cardiopulmonary exercise test (CPET) in obese patients with metabolic syndrome (MetS), and develop a new equation to estimate V O2peak in obese women with MetS. Methods: Seventy-five obese patients with MetS performed a CPET. Anthropometric data were also collected for each participant. V O2peak was predicted from four prediction equations (from Riddle, Hansen, Wasserman or Glaser) and then compared with the actual VO2peak measured during the CPET. The accuracy of the predictions was determined with the Bland–Altman method. When accuracy was low, a new prediction equation including anthropometric variables was proposed. Results: VO2peak predicted from the equation of Wasserman was not significantly different from actual VO2 peak in women. Moreover, a significant correlation was found between the predicted and actual values (p r = 0.69). In men, no significant difference was noted between actual VO2peak and VO2peak predicted from the prediction equation of Glaser, and these two values were also correlated (p = 0.03, r = 0.44). However, the LoA95% was wide, whatever the prediction equation or gender. Regression analysis suggested a new prediction equation derived from age and height for obese women with MetS. Conclusions: The methods of Wasserman and Glaser are valid to predict VO2peak in obese patient with MetS, respectively. However, the accuracy of the predictions was low for both methods. Consequently, a new prediction equation including age and height was developed for obese women with MetS. However, new prediction equation remains to develop in obese men with MetS.

Fraser syndrome (FS) is a rare malformation recessive disorder. Major criteria are cryptophtalmos, syndactyly, respiratory, genital and urinary tract anomalies. Few prenatal presentations have been reported.We analyzed the prenatal and postnatal fetal phenotype in 38 cases of FS, including 25 pregnancy termination cases, 8 intra-uterine death cases and 4 cases that died after birth.Including both prenatal and postnatal fetal phenotypic evaluation, all cases presented dysmorphic features with nose and ear dysplasia. Renal anomalies and syndactyly were present in 37/38 cases, cryptophtalmos in 36/38, airways anomalies in 30/37 and genital anomalies in 30/35 cases. Anomalies of the abdominal wall such as low set umbilicus and omphalocele were found in 31 cases. Among the 26 cases for which ultrasound data were available, detectable anomalies included oligohydramnios (22), ascites/hydrops (9), renal anomalies (20), evidence for high airways obstruction (11), ophthalmologic anomalies (4), ear dysplasia (2) and syndactyly (2).This study shows that the postnatal phenotype of FS is very specific, whereas oligohydramnios hampers the prenatal recognition of the cardinal FS diagnosis criteria. Association of oligohydramnios, kidney agenesis and CHAOS should lead to consider this diagnosis. © 2016 John WileySons, Ltd.

International audience; Background Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. Methods This retrospective study was conducted at a single center (University Hospital of ClermontFerrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb-IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. Results Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p

Biopsy remains the gold standard for the diagnosis of chronic liver diseases. However, the variability in the diagnostic between readers leads to define a method to objectively describe histologic tissue. A complete framework has been implemented to analyze images of any tissue. Based on subset selection and feature ranking approaches, a feature selection computes the most relevant subset of descriptors in terms of classification from a wide initial list of descriptors. In comparison with equivalent methods, this implementation can find lists of descriptors which are significantly shorter for an equivalent accuracy. Furthermore, it enables the classification of slides using combinations of global and local measurements. The results have pointed that it could reach an accuracy of 90.5% (ROC-AUC=81.1%) in a human liver fibrosis grading approach by selecting 3 of the 457 global and local descriptors. The feature ranking approach gave less accurate subsets than the subset selection.

The aim of this retrospective study was to evaluate the survival impact of perioperative chemotherapy (PCT) in patients with gastric signet ring cell (SRC) adenocarcinoma.PCT is a standard treatment for advanced resectable gastric adenocarcinoma (GA). SRC has a worse prognosis compared to non-SRC and the chemosensitivity of SRC is uncertain.Among 3010 patients registered in 19 French centers between January 1997 and January 2010, 1050 (34.9%) were diagnosed with SRC. Of those treated with curative intent (n = 924), 171 (18.5%) received PCT with surgery (PCT group), whereas 753 (81.5%) were treated with primary surgery (S group). PCT was based mainly on a fluorouracil-platinum doublet or triplet regimen.The groups were comparable regarding age, gender, American Society of Anesthesiologists (ASA) score, malnutrition, tumor location and cTNM stage. 60 patients did not undergo resection because of tumor progression (10) or metastases (50) found at operation. The R0 resection rates were 65.9% and 62.3% in the S and PCT groups, respectively (P = 0.308). Fewer patients received adjuvant chemotherapy in the S group than in the PCT group (35.2% vs. 66.5%, P0.001). At a median follow-up of 31.5 months, the median survival was shorter in the PCT group (12.8 vs. 14.0 months, P = 0.043). On multivariate analysis, PCT was found to be an independent predictor of poor survival (HR = 1.4, 95% CI 1.1-1.9, P = 0.042).PCT provides no survival benefit in patients with gastric SRC. Clinical Trial.gov record: ADCI001, Clinical Trial.gov identifier NCT01249859.

A retrospective analysis of 173 skin biopsy specimens of myeloid leukemia cutis (MLC) was performed to determine histologic and immunophenotypic criteria that could distinguish the varied myeloid disorders from one another. For the study, 11 relevant histologic items were scored and 12 antigens were studied (CD68 [KP1], CD163, CD14, CD4, myeloperoxidase [MPO], CD33, CD117, CD34, CD56, MIB-1, CD303, and CD123). Underlying myeloid disorders were essentially acute myeloid leukemias (65.3%), chronic myelomonocytic leukemias (11.0%), and refractory anemia (10.4%). Skin lesions were de novo in 7.5%, concurrent in 26.6%, and subsequent in 60.7%. Several morphologic characteristics (density, size of tumor cells, inflammatory background) were statistically useful in distinguishing between varied myeloid disorders. De novo MLCs displayed a specific morphologic profile. Association of CD68, CD33, and MPO could diagnose 100% of the cases of MLC. However, the immunohistochemical panel could not distinguish between the varied underlying myeloid disorders, with the exception that CD123 was particularly powerful in recognizing chronic myelomonocytic leukemia and also permitted reclassification of 4 cases as blastic plasmacytoid dendritic cell neoplasm.

Uterine lipomas are uncommon. Several histology hypotheses are described. Ultrasound is firstly performed but diagnosis is sometimes difficult. Magnetic resonance imaging is more specific and helpful to make a differential diagnosis with a dermoid ovarian cyst. Despite those imaging exams we detail a case of a patient where a laparoscopic hysterectomy with bilateral salpingo-oophorectomy and preliminary adhesiolysis has been necessary to establish diagnosis. Among her medical history some previous abdominal surgeries could be the cause of this lesion.

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome, is an autosomal-recessively inherited prenatal lethal disorder characterized by hydranencephaly; brain stem, basal ganglia, and spinal cord diffuse clastic ischemic lesions with calcifications; glomeruloid vasculopathy of the central nervous system and retinal vessels; and a fetal akinesia deformation sequence (FADS) with muscular neurogenic atrophy. To identify the molecular basis for Fowler syndrome, we performed autozygosity mapping studies in three consanguineous families. The results of SNP microarrays and microsatellite marker genotyping demonstrated linkage to chromosome 14q24.3. Direct sequencing of candidate genes within the target interval revealed five different germline mutations in FLVCR2 in five families with Fowler syndrome. FLVCR2 encodes a transmembrane transporter of the major facilitator superfamily (MFS) hypothesized to be involved in regulation of growth, calcium exchange, and homeostasis. This is the first gene to be associated with Fowler syndrome, and this finding provides a basis for further studies to elucidate the pathogenetic mechanisms and phenotypic spectrum of associated disorders.

The mechanisms promoting postoperative peritoneal tumor dissemination are unclear. This study aimed to investigate postoperative tumor dissemination over time on both tissue and molecular levels.For this study, C57BL6 mice were randomized into four groups: anesthesia alone (control), carbon dioxide (CO(2)) pneumoperitoneum at low (2 mmHg) or high (8 mmHg) intraperitoneal pressure (IPP), and laparotomy. A mouse ovarian cancer cell line (ID8) was injected intraperitoneally just before surgery. The groups were further subdivided into three groups, and a laparotomy was performed to evaluate tumor dissemination on postoperative day (POD) 7, 14, or 42.The incidence of cancer cell invasion into the muscle layers of the abdominal wall was significantly higher in the laparotomy and high-IPP groups than in the low-IPP and control groups on PODs 7 and 42. Expression levels of beta 1 integrin, cMet, urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), and type-1 plasminogen activator inhibitor (PAI-1) mRNA in the disseminated nodules were not significantly different among the four groups on POD 7. However, the expression levels of all these genes in the disseminated nodules in the laparotomy group were significantly higher on POD 14 than on POD 7. They then returned to control levels on POD 42. There were no significant differences in the expression levels of any of these genes among the groups on POD 42.The current study suggests that the molecular mechanisms underlying postoperative peritoneal tumor dissemination may differ between a laparotomy and CO(2) pneumoperitoneum. Therefore, strategies targeting postoperative tumor dissemination likely will need to account for the surgical environment.

Ovarian epithelial dysplasia has been described in the ovarian surface epithelium by histologic, morphometric and nuclear profile studies. It could represent a potential precursor of ovarian malignancy in patients with genetic risk of ovarian cancer, although its natural history and progression to carcinoma are unpredictable. Diagnosis and identification of ovarian dysplasia would certainly be useful to understand the early steps of ovarian carcinogenesis. However, dysplasia in relation with ovulation induction seems to have a different pattern. We report dysplasia definitions and the current clinical management.

We report one case of unilateral ovarian Sertoli-Leydig tumor with intermediate grade and heterologous element, in a young woman with clinical and biological typical presentation. We discuss 2D and 3D ultrasonographic and doppler features.

Objective To evaluate the effect of protein kinase C inhibition on surgically induced endometriosis in mice. Design Prospective, randomized study. Setting Academic facility. Animals Sixty adult female C57BJ6 mice. Intervention(s) On day −7, oral gavage of a vehicle alone or of a protein kinase C inhibitor (100 mg/kg/day, once a day) was started and continued for 1 week in donor groups A and B, respectively. On day 0, uterine fragments from donor group A were implanted into recipient mice. Recipient mice were divided randomly into two groups: group 1 (vehicle) and group 2 (protein kinase C inhibitor). Uterine fragments from donor group B were implanted into recipient mice, and they were divided randomly into two groups: group 3 (vehicle) and group 4 (protein kinase C inhibitor). Oral gavage of a protein kinase C inhibitor (100 mg/kg/day, once a day) or vehicle was continued for 1 week. Main Outcome Measure(s) Presence and number of ectopic implants. Result(s) The number of mice that developed ectopic implants was significantly lower in groups 3 (40%) and 4 (30%) than in group 1 (100%). The number of ectopic implants was significantly lower in groups 2, 3, and 4 than in group 1. Conclusion(s) Protein kinase C inhibitor use partially prevented the development of ectopic implants in a mouse model of endometriosis.

Resume Introduction La valeur pronostique de la presence de signes histologiques de regression dans la tumeur primitive de melanome est discutee. Objectif Determiner s’il existe une association entre la presence de signes de regression dans la tumeur primitive de melanome et la presence de micrometastases ganglionnaires. Malades et methode Il s’agissait d’une etude monocentrique, retrospective, portant sur 84 tumeurs primitives de melanome d’epaisseur superieure a 1 mm et le ganglion sentinelle correspondant. L’analyse des signes de regression a ete effectuee par deux examinateurs independants. L’indice de Breslow, l’âge, le sexe, la localisation du melanome ont ete notes pour chaque tumeur. Resultats Parmi les 84 melanomes etudies, 40 avaient des signes de regression et 24 etaient associes a des micrometastases ganglionnaires. Parmi ces derniers, seules 10 avaient des signes de regression. Il n’y avait pas d’association entre signes de regression et micrometastases (RR = 0,5 ; p = 0,5). Seuls un indice de Breslow superieur a 2 mm (RR = 4,6, p = 0,03) et le sexe masculin (RR = 7,6, p = 0,006) apparaissaient comme predictifs de l’atteinte du ganglion sentinelle. En analyse multivariee, ces deux derniers facteurs etaient independants avec, pour RR respectifs 3,2 (IC95 p. 100 : 1,1-9,1.) et 4,6 (IC95 p. 100 : 1,5-13,8.). Discussion Ces resultats suggerent qu’il n’y a pas une forte association entre la regression au sein de la tumeur primitive et la presence d’une micrometastase dans le ganglion sentinelle. Ils confirment que l’indice de Breslow est significativement predictif de la presence de micrometastases.

Endometrial ablation has emerged as a viable alternative to hysterectomy in the treatment of medically intractable dysfunctional uterine bleeding. However, this procedure cannot guarantee complete removal of the entire endometrium. Cases of endometrial cancer after endometrial ablation have been reported in the literature. We reviewed the cases of patients who underwent hysteroscopic endometrial ablation by endometrial resection for abnormal uterine bleeding from 1994 to 2005 at the Department of Obstetrics and Gynecology, Polyclinique, Clermont-Ferrand University. Of the 3769 patients having had hysteroresections, four developed endometrial cancer after complete endometrial ablation (1.06 out of 1000). All four of these patients showed histological evidence of endometrial polyps at endometrial resection, and all of them presented risk factors for endometrial carcinoma, such as obesity and/or arterial hypertension. Endometrial cancer after hysteroscopic endometrial ablation is a rare but possible occurrence, even a long time after the operation. Close monitoring of patients who have undergone endometrial ablation for endometrial polyps and who present risk factors, such as obesity or hypertension, even after apparent total ablation of the endometrium is strongly recommended, independently of the presence of abnormal bleeding that can represent a late symptom of advanced endometrial cancer.

International audience; Le lycopène, le principal caroténoïde présent dans les tomates, est un puissant antioxydant associé à la prévention de maladies dégénératives telles que le cancer du sein. Cet effet pourrait être dû à l'interaction entre les récepteurs du lycopène et de l'acide rétinoïque ainsi qu'à la stimulation de la communication par jonction lacunaire et de la synthèse de la connexine 43. L'expression des protéines RARalpha, RARbeta et Cx43 a été analysée par immunohistochimie dans deux lignées cellulaires de cancer du sein. , MCF-7 et MDA-MB-231, et dans une lignée cellulaire de dystrophie fibrokystique, MCF-10a, après une exposition de 48 heures à 10 μM de lycopène. Une analyse PCR quantitative en temps réel a ensuite été effectuée pour mesurer l'expression de l'ARNm. L'expression de RARalpha et de Cx43 a été augmentée aux niveaux d'ARNm et de protéines dans deux lignées de cellules mammaires.

Although malignant degeneration of cutaneous endometriosis is rare at only 0.3-1% in endometriosis surgical scars, diagnosis and management need to be defined. A case of malignant degeneration of perineal endometriosis is reported, with a review of literature. Physiopathology, epidemiological data, diagnostic and therapeutic methods are discussed for malignant degeneration of cutaneous endometriosis. Any scar lesion that evolves in response to the menstrual cycle should be considered endometriosis until proven otherwise, and thus could require surgical resection, with histological analysis. A history of cutaneous endometriosis with frequent recurrences can indicate malignant degeneration. All cases require long-term clinical follow-up because, despite the rarity of this diagnosis, the delay between benign endometriosis and malignant transformation can vary from a few months to over 40 years.

AIMS: Aggressive epidermotropic cutaneous CD8+ lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8+ lymphomas.METHODS & RESULTS: Sixty-one CD8+ cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed & recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8+ lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and have striking pagetoid epidermotropism histologically. A CD8+ CD45RA+ CD45RO- CD2- CD5- CD56- phenotype, with 1 or more cytotoxic markers was found in 7/18 with a very similar phenotype in the remainder.. The tumours seldom involve lymph nodes but mucosae and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8+ mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp presented the typical features well documented in the CD4+ forms of those diseases.CONCLUSIONS: Aggressive Epidermotropic Cutaneous CD8+ Lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications. This article is protected by copyright. All rights reserved.

Background Deep infiltrating endometriosis (DIE) is commonly associated with severe pain. The pain can be managed successfully with GnRH agonists or continuous progestins. The precise molecular mechanism by which DIE causes pain or why hormonal treatment is effective, however, remains unclear. We recently identified three potential candidate genes that might be involved in DIE pain pathways: tyrosine kinase receptor B (TrKB), mu-opioid receptor (MOR) and serotonin transporter (5HTT). We hypothesized that if these three genes were involved in DIE-associated pain, their expression levels would probably be modulated by GnRH agonist or progestin. In this study, we compared mRNA expression levels of TrKB, MOR and 5HTT in DIE among patients pre-operatively treated with GnRH agonist, progestin or without pre-operative medical treatments. Methods The expression levels of TrKB, MOR and 5HTT mRNA in DIE were determined using laser capture microdissection and real-time RT-PCR techniques. Results The expression levels of TrKB in epithelial cells and MOR in stromal cells from DIE were significantly decreased in patients with pre-operative GnRH agonist or progestin. There was no significant difference in 5HTT expression levels among untreated, GnRH agonist- and progestin-treated patients. Conclusion The expression levels of TrKB and MOR genes in DIE appeared to be modulated by GnRH agonist or progestin. However, the functional roles of TrKB and MOR in DIE remain to be clarified.

Objective To investigate whether WT1 protein expression is altered in eutopic endometrium of endometriosis patients. Design Prospective study. Setting University hospital. Patient(s) Patients with endometriosis and fertile women with macroscopically normal pelvic cavities. Intervention(s) During surgery, endometrial tissues were obtained from 59 patients with deep infiltrating endometriosis, ovarian endometriosis, or only superficial peritoneal endometriosis. Control endometrial tissue samples were obtained from 40 fertile women who underwent laparoscopic tubal ligation or reversal of tubal sterilization. Main Outcome Measure(s) The percentage of nuclear surface positively immunostained for WT1 (PI) and WT1-positive microvessel density. Result(s) The PI was significantly lower in endometrial stromal cells from patients with deep infiltrating endometriosis than in stroma from control subjects during the midsecretory phase, whereas there was no significant difference between the two populations during the proliferative, early secretory, and late secretory phases. The PI was also significantly lower during the midsecretory phase in endometrial stromal cells from patients with ovarian endometriosis and superficial peritoneal endometriosis compared with control subjects. Conclusion(s) During the midsecretory phase, PI in endometrial stromal cells is down-regulated in patients with deep infiltrating endometriosis, ovarian endometriosis, and superficial peritoneal endometriosis compared with endometrium from healthy control subjects.

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression ( P = .0003), multiple skin lesions ( P = .004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2–positive and bcl-2–negative patients were 41% and 89%, respectively ( P < .0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.

Summary There is a growing body of evidence to support the efficacy of topical imiquimod in the treatment of primary skin carcinomas. Conflicting data exist concerning the use of imiquimod for the treatment of skin melanoma metastases. To date, only the impact of imiquimod on cytokines involved in immunological processes has been studied extensively. We report a woman successfully treated with imiquimod (once daily for 8 weeks) for skin melanoma metastases in whom we investigated the expression of molecules involved in metastasis and angiogenesis. Before and after treatment, a skin lesion was biopsied and the expression of the following molecules was investigated using real-time reverse transcription–polymerase chain reaction: matrix metalloproteinase (MMP)-1, 2 and 9 and their inhibitors KiSS-1 and tissue inhibitor of metalloproteinase (TIMP)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor-2, and angiogenesis inhibitors (thrombospondin-1 and 2). Interferon (IFN)-α was also investigated as an in vivo marker of imiquimod activity. IFN-α was upregulated by the treatment. Under imiquimod, the following molecules were upregulated: TIMP-1, KiSS-1 and MMP-1. MMP-2 expression was not modified. MMP-9 expression was dramatically decreased. The expression of angiogenesis inhibitors was slightly increased but VEGF expression remained at a basal level. These results suggest that imiquimod could downregulate metastasis invasion and angiogenesis. However, these data were obtained at a transcriptional level and from a single case, and further investigations should include migration assays and additional cases in order to confirm that imiquimod may be safely used for treatment of melanoma metastases.