Jean Gondry

Place du caryotype féminin en assistance médicale à la procréation (AMP)

It has been known for some 25 years that there is a causal relation between chromosomal aberrations and male infertility and that the major indication for karyotyping an infertile man is still usually an abnormal sperm analysis. The value of karyotyping women in the routine work-up of couples referred for sterility has long been debated. A French recent cytogenetic study found an overall increased frequency of chromosomal aberrations in the female and confirmed that in some cases of poor reproductive outcome there may be a contribution of maternal chromosome aberrations. Indeed, the existence of a chromosome abnormality in the female partner was associated with the group of infertile men in which there was no apparent cause of infertility. These results emphasise the need for thorough genetic work-up in couples referred for sterility. This work-up should include karyotyping of the female for some indications explained in this work.

Comparaison des facteurs épidémiologiques des tumeurs frontières séreuses et mucineuses de l’ovaire : implications thérapeutiques

The goals of this multicenter French retrospective study were to compare epidemiological factors within borderline ovarian tumors (BOT) according to their serous (SBOT) or mucinous (MBOT) type and according to the presence of pejorative histological criteria. We analysed 224 SBOT and 164 MBOT diagnosed between 1990 and 2009. The patients mean age was not different according to serous or mucinous type (46.9 ± 16.7 years and 44.6 ± 17.6 years). Women with SBOT, had more frequently history of infertility (17.2% versus 3.9%, P < 0.0001) than women with MBOT. SBOT were more often asymptomatic (52.3% versus 33.5%, P < 0.001), bilateral (26.4% versus 4.3%, P = 0.0001), smaller (9.1 cm versus 14.5 cm, P = 0.0001) and diagnosed at advanced stage (81.2% of stage I versus 95.1%, P < 0.0001) than MBOT. The micropapillary pattern found in 10.3% of SBOT was observed at younger age (38 ± 15.4 years versus 47.9 ± 16.6 years, P = 0.007) and was more often associated with peritoneal implants (26.1% versus 6.5%, P = 0.02). The intraepithelial carcinoma found in 6.7% of MBOT, was more often associated with micro-invasion (36.4% versus 4.6%, P = 0.003). The existence of epidemiologic differences between SBOT and MBOT underlines that the BOT series analysis can not be considered without taking into account this parameter.

Cancer de l’endomètre. Enquête sur les pratiques chirurgicales en France en 2008

OBJECTIVES Endometrial cancer is the most common gynecologic malignancy. We aimed to assess the management of this disease among French surgeons as regards to the French guidelines. MATERIALS AND METHODS Six hundred questionnaires were given to surgeons during two national French Meetings in 2008. They focused on the surgeon (age, gender, center of work, number of treated cancers individually and in the center) and on the disease (initial work-up, surgical management). Three case reports related to endometrial cancer were proposed to assess the conformity of the French guidelines (two case reports about endometrioid carcinomas stages IB and II and one about serous papillary adenocarcinoma). RESULTS Nineteen percent of surgeons (n=114) answered the questionnaire. The French Guidelines were respected in less than 60 % in the answers of the three case reports (only 13.3 % of the answers were conformed in all the three cases). The surgeons who respected the recommendations took care of more than five treated patients per year (92.9 % versus 57.8 %, P=0.01), they were younger (41 year versus 49 years, P=0.01), and the post-graduation delay was shorter (9.1 versus 20.5 years, P=0.002). The center where the surgeon worked was not a determinant factor for treatment. The surgical procedures were mostly transverse laparotomy in 35.4 %. Peritoneal cytology and lymphadenectomy were provided in 69.9 % and 74.7 % of cases, respectively. CONCLUSION Despite the limits of our study based on volunteer answers of surgeons to a questionnaire, our results highlight the efforts of learned societies and medical authorities should be used to standardize the treatment of cancer. A reflection should be conducted on the basis of initial training and throughout a professional career to provide patients optimal care of their pathology.

Defining the Most Appropriate Delivery Mode in Women with Inflammatory Bowel Disease: A Systematic Review

Introduction: High cesarean section (CS) rates are observed in patients with inflammatory bowel disease (IBD), but limited data are available to support this decision. We conducted a comprehensive review to evaluate the most appropriate mode of delivery in women with IBD according to disease phenotype and activity, as well as surgical history. Materials and Methods: We searched MEDLINE (source PubMed) and international conference abstracts, and included all studies that evaluated digestive outcome after delivery in patients with IBD. Results: A total of 41 articles or abstracts were screened, and 18 studies were considered in this review, with sample sizes ranging from 4 to 229 patients and follow-up ranging from 2 months to 7.7 years. Pooled CS rates in patients without Perianal Crohns disease (PCD), healed PCD or active PCD, were 27%, 43%, and 46%, respectively. Regarding the median rate of new PCD (3.0% [IQR, 1.5–11.5] versus 6.5% [0–19.7]) or PCD recurrence (13.5% [3.2–32.7] versus 45% [0–58]), no increase was observed in patients with vaginal delivery compared to CS, but for patients with an active disease, worsening of symptoms was noted in two-thirds of cases. Episiotomy, perianal tears, and instrumental delivery did not influence the incidence of PCD. In patients with ileal pouch anal anastomosis, uncomplicated vaginal delivery seemed to moderately influence pouch function, with no significant difference in terms of overall continence, daytime, or night-time stool frequency, or incontinence. However, these parameters seemed negatively impacted by a complicated vaginal delivery. Conclusions: New long-term data from well-designed studies are needed, but our review suggests that systematic CS in patients suffering from IBD should probably be limited to women at risk of perineal tears and obstetric injuries, with an active PCD, or with ileal pouch anal anastomosis.

Involvement of Interstitial Telomeric Sequences in Two New Cases of Mosaicism for Autosomal Structural Rearrangements

Mosaicism for an autosomal structural rearrangement that does not involve ring or marker chromosomes is rare. The mechanisms responsible for genome instability have not always been explained. Several studies have shown that interstitial telomeric sequences (ITSs), involved in some mosaic constitutional anomalies, are potent sources of genomic instability. Here we describe two cases of mosaicism for uncommon constitutional autosomal rearrangements, involving ITSs, identified by karyotyping and characterized by FISH and SNP‐array analysis. The first patient, a boy with global developmental delay, had a rare type of pure distal 1q inverted duplication (1q32‐qter), attached to the end of the short arm of the same chromosome 1, in approximately 35% of his cells. The second patient, a phenotypically normal man, was diagnosed as having mosaic for a balanced non‐reciprocal translocation of the distal segment of 7q (7q33qter), onto the terminal region of the short arm of a whole chromosome 12, in approximately 80% of his cells. The remaining 20% of the cells showed an unbalanced state of the translocation, with only the der(7) chromosome. He was ascertained through his malformed fetus carrying a non‐mosaic partial monosomy 7q, identified at prenatal diagnosis. We show that pan‐telomeric and subtelomeric sequences were observed at the interstitial junction point of the inv dup(1q) and of the der(12)t(7;12), respectively. The present cases and review of the literature suggest that the presence of ITSs at internal sites of the chromosomes may explain mechanisms of the patientss mosaic structural rearrangements.

A Patient With Simpson-Golabi-Behmel Syndrome, Biliary Cirrhosis and Successful Liver Transplantation

Simpson–Golabi–Behmel syndrome type 1 (SGBS1) ‐OMIM 312870‐ is a rare X‐linked inherited overgrowth syndrome caused by a loss of function mutation in the GPC3 gene. Affected patients present a variable phenotype with pre‐ and post‐natal macrosomia, distinctive facial dysmophism, organomegaly, and multiple congenital anomalies. Intellectual disability is not constant. About 10% of patients have an increased risk of developing embryonic tumors in early childhood. Only one case of biliary disease has been described so far. GPC3 is localized on Xq26. It encodes for glypican 3, a heparan sulfate proteoglycan, which among its different known roles, negatively regulates liver regeneration and hepatocyte proliferation. This report concerns a male with a SGBS1, carrier of a GPC3 pathogenic mutation, and neonatal liver disease, who developed an early biliary cirrhosis. Together with the associated risk of cancer and developmental delay, liver transplantation was discussed and then successfully performed at the age of 19 months. A hypothesis on the role of GPC3 in the patients liver disease is also proposed.

Should isolated fetal ventriculomegaly measured below 12 mm be viewed as a variant of the norm? Results of a 5-year experience in a prenatal referral center

Abstract Background: Fetal ventriculomegaly (VM) is defined as lateral ventricles measured above 10 mm. Some authors believe VM <12 mm are variants of the norm and need not be addressed for referral ultrasound. Methods: A retrospective continuous cohort study of 127 confirmed fetal VM was divided into three groups after initial referral sonographic assessment: isolated VM <12 mm (group A), isolated VM ≥12 mm (group B), and VM associated with other malformations (group C). We reviewed obstetric outcome and neonate evolution after 1 month with the aim of defining a pertinent prenatal workup. Results: We reported fetal infections in all groups (p = .24) and chromosomal abnormalities only in group C (p = .41). Fetal magnetic resonance imaging (MRI) found initially undiagnosed brain abnormalities in groups B and C (12.5 and 14.1%, p < .05). Ratios of healthy children after 1 month stemming, respectively, from groups A, B, and C were 66.7, 62.5, and 20.2% (p < .05). Conclusions: Our results are in favor of a systematic referral ultrasound for every fetal VM, regardless of size, as soon as definition criterion is met. Additional paraclinical assessment (maternal serologic status for toxoplasmosis and cytomegalovirus, amniocentesis, fetal cerebral MRI) should be discussed depending on the situation.

Impact of Age at Conization on Obstetrical Outcome: A Case-control Study

Objective The aim of the study was to assess whether an age younger than 25 years at conization affected future pregnancy outcome as an independent factor. Materials and Methods A retrospective study of 115 women who underwent both loop electrosurgical excision procedure (LEEP) and subsequent pregnancy follow-up in a referral center was conducted. Two groups were considered: patients younger than 25 years at the time of LEEP (n = 42) and 25 years or older (n = 73). Analyzed data were occurrence of preterm adverse obstetrical event and, specifically, preterm labor (PL) and preterm rupture of membranes; stratification based on term of occurrence was performed: less than 37 weeks of amenorrhea (WA), less than 34 WA, and less than 26 WA. Results Patients characteristics were comparable in terms of excised specimen thickness and pathological analysis, as well as for tobacco intoxication during pregnancy. Although there was no difference of term at delivery or total number of preterm adverse obstetrical events, we found a significant increase of events (19% vs 4.1%) and PL (19% vs 0%) before 26 WA in the group of patients younger than 25 years. After adjusting for excised specimen thickness, the same results were found for thickness of 15 mm or less (respectively, 16.7% vs 3.3% and 16.7% vs 0%). For thickness of greater than 15 mm, only ratio of PL before 26 WA was higher in the group of patients younger than 25 years (33.3% vs 0%). Conclusions Age younger than 25 years at the time of LEEP seems to be is associated with a more frequent occurrence of extremely early preterm adverse obstetrical events, particularly PL.

Benefits of Direct Colposcopic Vision for Optimal LLETZ Procedure: A Prospective Multicenter Study

Objective The aim of the study was to assess whether direct colposcopic vision (DCV) of the cervix during large loop excision of the transformation zone (LLETZ) is associated with a decrease in the volume and dimensions of specimens or affects margin status at histology. Materials and Methods A prospective multicenter observational study of 216 women who underwent LLETZ for grades 2 and 3 cervical intraepithelial neoplasia was conducted. The volume and dimensions (circumference, length, and thickness) of the surgical specimens were measured before fixation. Data were compared according to the use of colposcopy during LLETZ. The following 3 groups were considered: LLETZ performed without colposcopy (n = 91), LLETZ performed immediately after colposcopy (n = 51), and LLETZ performed under DCV (n = 74). Results Patient characteristics were comparable with regard to age, parity, history of excision, indication of the procedure, and the size of the cervix. We found a significant decrease in all dimensions of the specimens obtained under DCV (p < .001). Margin status was not affected. After adjusting for confounders, the mean volumes were significantly lower in the DCV group (adjusted mean difference = −0.66 mL; 95% CI = −1.17 to −0.14). The probability that negative margins would be achieved together with the attainment of a volume less than 5 mL and a thickness less than 10 mm was the highest in the DCV group (adjusted OR = 2.80; 95% CI = 1.13 to 6.90). Conclusions Direct colposcopic vision is associated with a significant decrease in the volume and in all dimensions of LLETZ specimens with no compromise in the margin status.

Carcinomes épidermoïdes primitifs du sein : étude clinique et revue de la littérature

From the analysis of our series and a review of the literature, we have done a summary of the clinicopathologic patterns and treatment of squamous cell carcinoma of the breast. It usually presents as a large palpable mass in a woman over 50 years old. There are no specific iconographic features, but a relative frequency of presentation as abscess or cyst. The overall and disease-free survivals are worse than other histological types of breast cancer. These neoplasms have a basal-like and triple negative profile and they respond poorly to standard treatment of breast carcinomas. They are usually treated by radical surgery. Optimal chemotherapy regimens is not yet determined and platin based chemotherapy could offer an effective alternative as the developpement of specific targeted therapies (anti Her1) could do.