Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.

STUDY QUESTION: Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)? SUMMARY ANSWER: WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA. WHAT IS KNOWN ALREADY: At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE. STUDY DESIGN, SIZE, DURATION: In a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein. MAIN RESULTS AND THE ROLE OF CHANCE: Deleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)]. LARGE SCALE DATA: Data available on request. LIMITATIONS, REASONS FOR CAUTION: More data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings. WIDER IMPLICATIONS OF THE FINDINGS: Our results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene-confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Failure of sterilization after clip placement.

BACKGROUND: Tubal sterilization is a common method of contraception used worldwide. The Filshie clip is a device designed to occlude the fallopian tubes. It is common practice to apply the clips across the isthmus using laparoscopy. It is often suggested that failures occur due to problems with the technique used to occlude the fallopian tubes. CASE: After insertion of an intrauterine device, a patient experienced an unplanned pregnancy and subsequent abortion. The intrauterine device was removed, and bilateral Filshie clips were applied by an experienced surgeon. After this procedure, the patient experienced a second unplanned pregnancy and subsequent abortion. A partial salpingectomy was performed after the fallopian tubes were examined, and it was confirmed that the Filshie clips were applied appropriately. CONCLUSION: It is important to understand why sterilization clips lead to contraceptive failure and to inform patients of this risk. Contraceptive failure after female sterilization remains a medical issue.

[Pravastatin-induced dermatomyositis]. / Dermatomyosite induite par la pravastatine.

INTRODUCTION: The toxic myopathy caused by statins (HMG-CoA reductase inhibitors) is well established. Recent reports add to these effects systemic immune diseases including systemic lupus erythematosus, vasculitis, polymyositis or dermatomyositis. EXEGESIS: We report a case of dermatomyositis in a 69-year-old patient treated with pravastatin [Elisor]. She presented with typical features of dermatomyositis 2 years after she started a treatment with pravastatin. The treatment was discontinued and she slowly improved, with a transient dermocorticosteroid treatment. Eight other patients with dermatomyositis and chronic treatment with HMG-CoA reductase inhibitors are reported in the literature. All of them presented with classical features of dermatomyositis. The discontinuation of the treatment was followed by spontaneous clinical and biological improvement in 3/9 patients. The other patients received high doses of corticosteroids and improved, except one patient who died of respiratory failure (pulmonary fibrosis) despite the adjunction of oral cyclophosphamide [Endoxan]. In these patients, dermatomyositis can be considered as a severe adverse reaction to HMG-CoA reductase inhibitors although a distinct casual link cannot be definitely established. CONCLUSION: The increasing prescription of statins has led to the parallel increment of reported side-effects, where autoimmune diseases are now described. Among them, our case of dermatomyositis in a patient receiving pravastatin adds to the eight reported cases in the literature and highlights the potential role of statins as triggers of immune systemic diseases.

Abdominal wall metastasis of a cervical adenocarcinoma at the laparoscopic trocar insertion site after ovarian transposition: case report and review of the literature.

BACKGROUND: Laparoscopic ovarian transposition is currently used in the preirradiation management of cervical cancer in young women. This surgical technique helps avoid the short- and long-term complications of early menopause. Because there remains a risk of metastasis at the site where the laparoscopic trocar is inserted, more precise indications for this surgery are required. CASE: We report the case of a patient with an abdominal wall metastasis that followed laparoscopic ovarian transposition performed before radiation therapy and surgical treatment for a stage IIb cervical adenocarcinoma. Observations during the laparotomy nonetheless led us to resect the transposed ovary during the laparotomy. The pathology examination of the ovary found a microscopic metastasis. Several months later, a left abdominal parietal nodule, corresponding to a metastasis of the adenocarcinoma, was found on the site through which the trocar had been inserted during the laparoscopy and was probably associated with the ovarian transposition. CONCLUSION: This is the only published case to describe an abdominal wall metastasis due to laparoscopic trocar insertion during ovarian transposition. The decision to perform a laparoscopic ovarian transposition in cervical cancer must take into account the frequency of trocar site metastases, which seems to be higher with advanced-stage cervical cancers, in cases of lymph node involvement and especially in adenocarcinomas.

[Ovarian choriocarcinoma: about one case]. / Choriocarcinome ovarien: à propos d'un cas.

We report the case of a woman, 43 years old, presenting with an ovarian choriocarcinoma. This patient, addressed for a right-side suspicious pelvic mass, had an exploratory laparotomy. Frozen section found an ovarian cancer. The patient had total hysterectomy, left annexectomy and a complete staging surgery. Histology concluded to an ovarian gestational choriocarcinoma. It is a rare germinal tumour, the treatment of which was medical, with radical exeresis and complete staging surgery associated with polychemotherapy.

Severe acute asthma with bowel infarction and pneumatosis intestinalis in a young adult.

A young patient presented with a small bowel infarction with pneumatosis intestinalis in the early course of life-threatening severe acute asthma. Low cardiac output with severe congestive right heart failure combined with the use of high doses of epinephrine to reverse the near-fatal bronchospasm probably contributed to this previously unreported complication. The presence of gas collections in the submucosal space was possibly the consequence of diffuse small bowel mucosal disruption. Early recognition of this unusual complication is of major importance to ensure appropriate therapeutic management.