A short anogenital distance on MRI is a marker of endometriosis.

STUDY QUESTION: Could the anogenital distance (AGD) as assessed by MRI (MRI-AGD) be a diagnostic tool for endometriosis? SUMMARY ANSWER: A short MRI-AGD is a strong diagnostic marker of endometriosis. WHAT IS KNOWN ALREADY: A short clinically assessed AGD (C-AGD) is associated with the presence of endometriosis. STUDY DESIGN SIZE DURATION: This study is a re-analysis of previously published data from a case-control study. PARTICIPANTS/MATERIALS SETTING METHODS: Women undergoing pelvic surgery from January 2018 to June 2019 and who had a preoperative pelvic MRI were included. C-AGD was measured at the beginning of the surgery by a different operator who was unaware of the endometriosis status. MRI-AGD was measured retrospectively by a senior radiologist who was blinded to the final diagnosis. Two measurements were made: from the posterior wall of the clitoris to the anterior edge of the anal canal (MRI-AGD-AC), and from the posterior wall of the vagina to the anterior edge of the anal canal (MRI-AGD-AF). MAIN RESULTS AND THE ROLE OF CHANCE: The study compared MRI-AGD of 67 women with endometriosis to 31 without endometriosis (controls). Average MRI-AGD-AF measurements were 13.3 mm (±3.9) and 21.2 mm (±5.4) in the endometriosis and non-endometriosis groups, respectively (P < 10-5). Average MRI-AGD-AC measurements were 40.4 mm (±7.3) and 51.1 mm (±8.6) for the endometriosis and non-endometriosis groups, respectively (P < 10-5). There was no difference of MRI-AGD in women with and without endometrioma (P = 0.21), or digestive involvement (P = 0.26). Moreover, MRI-AGD values were independent of the revised score of the American Society of Reproductive Medicine and the Enzian score. The diagnosis of endometriosis was negatively associated with both the MRI-AGD-AF (ß = -7.79, 95% CI (-9.88; -5.71), P < 0.001) and MRI-AGD-AC (ß = -9.51 mm, 95% CI (-12.7; 6.24), P < 0.001) in multivariable analysis. Age (ß = +0.31 mm, 95% CI (0.09; 0.53), P = 0.006) and BMI (ß = +0.44 mm, 95% CI (0.17; 0.72), P = 0.001) were positively associated with the MRI-AGD-AC measurements in multivariable analysis. MRI-AGD-AF had an AUC of 0.869 (95% CI (0.79; 0.95)) and outperformed C-AGD. Using an optimal cut-off of 20 mm for MRI-AGD-AF, a sensitivity of 97.01% and a specificity of 70.97% were noted. LIMITATIONS REASONS FOR CAUTION: This was a retrospective analysis and no adolescents had been included. WIDER IMPLICATIONS OF THE FINDINGS: This study is consistent with previous works associating a short C-AGD with endometriosis and the absence of correlation with the disease phenotype. MRI-AGD is more accurate than C-AGD in this setting and could be evaluated in the MRI examination of patients with suspected endometriosis. STUDY FUNDING/COMPETING INTERESTS: N/A. TRIAL REGISTRATION NUMBER: The protocol was approved by the 'Groupe Nantais d'Ethique dans le Domaine de la Santé' and registered under reference 02651077.

Anogenital distance in adult women is a strong marker of endometriosis: results of a prospective study with laparoscopic and histological findings.

STUDY QUESTION: Could anogenital distance (AGD) be a non-invasive marker of endometriosis and correlated to the American Society for Reproductive Medicine revised score (r-ASRM) and ENZIAN classifications? SUMMARY ANSWER: Surgically and histologically proven endometriosis is associated with a short AGD in women of reproductive age but not correlated either to the severity or to the location of the disease. WHAT IS KNOWN ALREADY: AGD is a marker of intrauterine androgen exposure and exposure to oestrogen-like chemicals such as phthalates. Moreover, exposure to endocrine disruptors, such as organochlorine chemicals, is associated with endometriosis. It has been suggested that a short AGD in women is associated with an increased risk of endometriosis based on clinical and ultrasound exams. STUDY DESIGN SIZE DURATION: A prospective cohort study was conducted from January 2018 to June 2019 in a tertiary-care centre including 168 adult women undergoing pelvic surgery. PARTICIPANTS/MATERIALS SETTING METHODS: Of the 168 women included, 98 patients had endometriosis (endometriosis group) and 70 did not (non-endometriosis group). An operator (not the surgeon) measured the distance from the clitoral surface to the anus (AGD-AC) and from the posterior fourchette to the anus (AGD-AF) before surgery using a millimetre accuracy ruler. Endometriosis was diagnosed on exploration of the abdominopelvic cavity, and the r-ASRM and ENZIAN scores were calculated. All removed tissues underwent pathological examination. MAIN RESULTS AND THE ROLE OF CHANCE: Mean (±SD) AGD-AF measurements were 21.5 mm (±6.4) and 32.3 mm (±8.1), and average AGD-AC measurements were 100.9 mm (±20.6) and 83.8 mm (±12.9) in the endometriosis and non-endometriosis groups (P < 0.001), respectively. Mean AGD-AF and AGD-AC measurements were not related to r-ASRM stage (P = 0.73 and 0.80, respectively) or ENZIAN score (P = 0.62 and 0.21, respectively). AGD-AF had a better predictive value than AGD-AC for discriminating the presence of endometriosis (AUC = 0.840 (95% CI 0.782-0.898) and 0.756 (95% CI 0.684-0.828)), respectively. For AGD-AF, an optimal cut-off of 20 mm had a specificity of 0.986 (95% CI 0.923-0.999), sensitivity of 0.306 (95% CI 26.1-31.6) and positive predictive value of 0.969 (95% CI 0.826-0.998). In multivariable analysis, the diagnosis of endometriosis was the only variable independently associated with the AGD-AF (ß = -9.66 mm 95% CI -12.20--7.12), P < 0.001). LIMITATIONS REASONS FOR CAUTION: The sample size was relatively small with a high proportion of patients with colorectal endometriosis reflecting the activity of an expert centre. Furthermore, we did not include adolescents and the AGD-AF measurement could be particularly relevant in this population. WIDER IMPLICATIONS OF THE FINDINGS: The measurement of AGD could be a useful non-invasive tool to predict endometriosis. This could be especially relevant for adolescents and virgin women to avoid diagnostic laparoscopy and empiric treatment. STUDY FUNDING/COMPETING INTERESTS: None.

Invasive and in situ cervical cancer associated with pregnancy: analysis from the French cancer network (CALG: Cancer Associé à La Grossesse).

PURPOSE: To describe the oncologic and obstetric outcomes of patients diagnosed with invasive cervical cancer (ICC) and in situ adenocarcinoma (ISA) during pregnancy or during the year following delivery. METHODS: This retrospective observational study involved a cohort of 28 patients diagnosed with invasive cervical cancer (20 patients) or in situ adenocarcinoma (eight patients) during pregnancy or during the year following delivery who received expert opinion from physicians of the Cancer Associé à La Grossesse (CALG) network between 2005 and 2018. Descriptive results were expressed in median, range and interquartile range (IQR). RESULTS: Between 2005 and 2018, 20 patients with ICC and eight with ISA received expert opinion from physicians of the CALG network. Both ICC and ISA were mostly diagnosed during pregnancy with a median term at diagnosis of 23.3 weeks of gestation (WG) for ICC and 7.3 WG for ISA. Overall, the median age at diagnosis for both ICC and ISA was 33 years. Most ICCs (n = 9) had FIGO stage ≥ IB2 and five underwent neoadjuvant chemotherapy at a median term of 22.5 WG. Seventeen patients with ICC underwent surgery. Three patients had medical termination of the pregnancy. Two patients experienced recurrence and three died. Median time of follow-up was 59.3 months (IQR 30.5-129.2). CONCLUSION: Management of cervical cancer during pregnancy is challenging especially in terms of maternal outcomes with a relative poor prognosis requiring a multidisciplinary expert advice.

A new animal model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing mice in the treatment of peritoneal carcinomatosis of ovarian origin.

AIM OF THE STUDY: We set out to develop and evaluate the morbidity of a non-invasive hyperthermic intraperitoneal chemotherapy (HIPEC) procedure in mice. HIPEC has been shown to improve overall survival in treating ovarian cancer with peritoneal carcinomatosis. However, related complications, toxicity and the lack of randomized trials limits its widespread use. To improve the surgical technique, there is a need for animal models that allow teams to work on large groups without burdensome logistics. MATERIALS AND METHODS: To develop the model, we first determined optimal HIPEC conditions in 20 Black Six mice without carcinomatosis. To evaluate HIPEC morbidity, peritoneal carcinomatosis cells of ovarian origin were injected into the peritoneum of 10 pathogen-free Nude mice. The mice underwent HIPEC 21 days later under general anesthesia. An inflow catheter was introduced into the left hypochondria and an outflow catheter was introduced into the left iliac fossa. Bath infusion was oxaliplatin (920mg/m2) at 43°C for 12minutes. The mice were monitored and sacrificed two weeks after the procedure. RESULTS: No deaths were observed during the procedure and infusion was well tolerated throughout the HIPEC. One mouse died the day after the procedure. No major dehydration, hemoperitoneum or evisceration was observed. CONCLUSION: This mouse model of closed abdomen HIPEC has limited morbidity and could be a useful model to study HIPEC regimens and its effects on peritoneal carcinomatosis.

First-trimester determination of fetal gender by ultrasound: measurement of the ano-genital distance.

INTRODUCTION: Early ultrasound fetal sex determination is of obvious interest, particularly in the context of X-linked diseases. In the human, the anogenital distance, i.e., the distance between the caudal end and the base of the genital tubercule is sexually dimorphic. This difference is apparent from 11 weeks of gestation. The aim of this prospective study was to evaluate the accuracy of anogenital distance measurement during the first trimester ultrasound in the early determination of fetal gender. MATERIALS AND METHODS: Fetal gender was assessed by ultrasound in 310 singleton pregnancies at 11-14 weeks of gestation. The optimal cut-off was determined by the minimal p-value technic and validated using bootstrap simulation. RESULTS: 310 women were included. A cut-off of 4.8mm was determined to predict male (≥4.8mm) or female (<4.8mm) fetuses. Sex was correctly determined for 87% of the males and 89% of the females. The inter-observer variability was excellent. CONCLUSION: This study presents a new sonographic sign for early fetal sex determination that has not been previously explored. It appears to be an accurate tool but it requires further validation in larger series.

[Operative technique: The clitoral transposition]. / Technique opératoire: la transposition clitoridienne.

Female sexual mutilations result in an important physical and mental suffering. A large number of women have been affected and require a global management, including surgical clitoral transposition. This surgical technique is allowing a rapid improvement of clinical symptoms. In this article, we will describe the indications and operative technique of the clitoral transposition.

High and prolonged sulfamidase secretion by the liver of MPS-IIIA mice following hydrodynamic tail vein delivery of antibiotic-free pFAR4 plasmid vector.

Mucopolysaccharidosis type IIIA (MPS-IIIA) or Sanfilippo A syndrome is a lysosomal storage genetic disease that results from the deficiency of the N-sulfoglucosamine sulfohydrolase (SGSH) protein, a sulfamidase required for the degradation of heparan sulfate glycosaminoglycans (GAGs). The accumulation of these macromolecules leads to somatic organ pathologies, severe neurodegeneration and death. To assess a novel gene therapy approach based on prolonged secretion of the missing enzyme by the liver, mediated by hydrodynamic gene delivery, we first compared a kanamycin and an antibiotic-free expression plasmid vector, called pFAR4. Thanks to the reduced vector size, pFAR4 derivatives containing either a ubiquitous or a liver-specific promoter mediated a higher reporter gene expression level than the control plasmid. Hydrodynamic delivery of SGSH-encoding pFAR4 into MPS-IIIA diseased mice led to high serum levels of sulfamidase protein that was efficiently taken up by neighboring organs, as shown by the correction of GAG accumulation. A similar reduction in GAG content was also observed in the brain, at early stages of the disease. Thus, this study contributes to the effort towards the development of novel biosafe non-viral gene vectors for therapeutic protein expression in the liver, and represents a first step towards an alternative gene therapy approach for the MPS-IIIA disease.

Widespread biochemical correction of murine mucopolysaccharidosis type VII pathology by liver hydrodynamic plasmid delivery.

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a deficiency of the acid hydrolase beta-glucuronidase. MPS VII mice develop progressive lysosomal accumulation of glycosaminoglycans (GAGs) within multiple organs, including the brain. Using this animal model, we compared two plasmid gene administration techniques: muscle electrotransfer and liver-directed transfer using hydrodynamic injection. We have evaluated both the expression kinetics and the biodistribution of beta-glucuronidase activity after gene transfer, as well as the correction of biochemical abnormalities in various organs. This study shows that MPS VII mice treated with a plasmid-bearing mouse beta-glucuronidase cDNA, acquire the ability to produce the beta-glucuronidase enzyme for an extended period of time. The liver seemed to be more appropriate than the muscle as a target organ to enable enzyme secretion into the systemic circulation. A beneficial effect on the MPS VII pathology was also observed, as liver-directed gene transfer led to the correction of secondary enzymatic elevations and to the reduction of GAGs storage in peripheral tissues and brain, as well as to histological correction in many tissues. This work is one of the first examples showing that non-viral plasmid DNA delivery can lead to improvements in both peripheral and brain manifestations of MPS VII disease. It confirms the potential of non-viral systemic gene transfer strategy in neurological lysosomal disorders.

Stent angioplasty: an effective alternative in selected infants with critical native aortic coarctation.

Management of native aortic coarctation during early months of life poses therapeutic challenges, and there is no consensus among medical professionals regarding a management plan. Much can be argued about the benefits, limitations, and/or complications of transcatheter versus surgical intervention in such cases. Occasionally, the complexity of the lesions limits management options. Therefore, each patient requires individual management decisions because there is no one therapeutic plan that satisfies all patients. In this report, four critically ill infants who had complex native coarctation are presented. Surgical repair was not possible because of relative contraindications. The patients underwent transcatheter stent implantation (six procedures and seven stents) as a nondefinitive procedure with acceptable results. Three patients improved. One patient did not survive, mainly due to other major complications. Multiple reexpansions of the stents were carried out when indicated. After a mean follow-up of 45 months (range, 41-49), the three survivors were doing fine and had gained an average weight of 9.7 kg (range, 6.6-13.3). At the time of reporting, the relative contraindications no longer exist and the final surgical repair can be carried out. Our experience suggests that in certain situations and in critically ill infants with complex form of coarctation, stent angioplasty can be used as a life-saving palliative procedure. Further reexpansions can be done when required. This may serve as a bridge to major surgical repair in the future.