Impact of molecular genotyping on the diagnosis and treatment of human chorionic gonadotropin-producing tumors.

OBJECTIVES: To assess the use of molecular genotyping to accurately diagnose and treat human chorionic gonadotropin (hCG)-producing tumors and to evaluate the discriminating capacity of molecular testing on prognosis and overall survival. METHODS: We conducted a retrospective descriptive study of patients registered with the French Reference Center for Trophoblastic Disease between 1999 and 2021. We included all patients with hCG-producing tumors for whom results of molecular genotyping were available. RESULTS: Fifty-five patients with molecular genotyping were included: 81.2 % (n = 45) had tumors of gestational origin, 12.7 % (n = 7) of non-gestational origin and 5.5 % (n = 3) of undetermined origin. The results of molecular genotyping influenced the treatment decisions for 17 % of patients in this cohort. Overall survival was 93.3 % for patients with gestational tumors (after a median follow-up of 74 months) compared to 71.4 % for patients with non-gestational tumors (after a median follow-up of 23 months). CONCLUSION: In atypical presentations of hCG-producing tumors, molecular genotyping is a valuable tool to guide diagnosis and tailor treatment recommendations.

Clinical profiles of placenta accreta spectrum: the PACCRETA population-based study.

OBJECTIVE: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section. DESIGN: Prospective population-based study. SETTING: All 176 maternity hospitals of eight French regions. POPULATION: Two hundred and forty-nine women with PAS, from a source population of 520 114 deliveries. METHODS: Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared. MAIN OUTCOME MEASURES: Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes. RESULTS: The PAS population-based incidence was 4.8/10 000 (95% CI 4.2-5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally. CONCLUSION: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean. TWEETABLE ABSTRACT: Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes.

[Conservative placenta percreta management using uterine arterial embolization procedure: A series of 12 cases]. / Prise en charge conservatrice du placenta percreta vésical avec embolisation des artères utérines : à partir d'une série continue de 12 cas.

We report a retrospective series of 12 placentas percreta with bladder invasion and for which an expected initially multidisciplinary conservative surgical treatment associated with uterine artery embolization was programmed. Conservative surgical treatment was only performed in 7 women. Radical surgical treatment was necessary during the caesarean section and complicated by massive hemorrhage in three women and secondary in two other women for infectious diseases. Radical surgical treatment was associated with partial cystectomy complicated with urinary disorder sequelae in three women. Maternal morbidity of the placenta percreta bladder remains high despite the establishment of a multidisciplinary care protocol.

Oral probiotic treatment of Lactobacillus rhamnosus Lcr35® prevents visceral hypersensitivity to a colonic inflammation and an acute psychological stress.

AIMS: This study evaluated the efficacy of a repeated oral treatment with two active pharmaceutical ingredients (Lcr Lenio® and Lcr Restituo® ) derivated from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35® in two animal models mimicking different features of irritable bowel syndrome (IBS). IBS is characterized by visceral pain associated with alteration of bowel transit. IBS patients present visceral hypersensitivity with peripheral and central origins. METHODS AND RESULTS: The injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the proximal colon as well as an acute partial restraint stress (PRS) produces colonic hypersensitivity measured in conscious rats by a decrease in pain threshold in response to distal colonic distension. Visceral hypersensitivity was produced by injection of TNBS 7 days before colonic distension or by acute PRS on testing day. Treatments were performed once a day during eight consecutive days. CONCLUSIONS: This study indicates that an 8-day probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity activity in both TNBS and PRS visceral pain models. As this probiotic strain attenuates peripherally and centrally induced visceral hypersensitivity in rats, it may be active in treatment of IBS symptoms. An immunomodulatory effect of the probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a mechanism of action involving a regulation of the local IL-23/Th17 immune activation. SIGNIFICANCE AND IMPACT OF THE STUDY: Two formulas of Lcr35® probiotic strain show very encouraging results for the treatment of IBS patients. Further studies are needed to better understand the role and mechanisms of probiotics on the pathogenesis of IBS.

Fetal phenotypes in otopalatodigital spectrum disorders.

Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra-skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.

Very early twin-to-twin transfusion syndrome and discordant activation of the renin-angiotensin system.

We present evidence of a first-trimester discordant renin-angiotensin system (RAS) response and structural abnormalities of the kidneys in twins with twin-to-twin transfusion syndrome (TTTS). A dark red fetus and a pale fetus were spontaneously delivered at 13.5 weeks of gestation following a double intra-uterine death. Pathological examination confirmed the placentation as monochorionic, with arteriovenous anastomoses on the chorionic plate. The donor twin had a normal heart and mildly hypoplastic kidneys, and the recipient twin had cardiomegaly and hypertrophic kidneys. Immunohistochemical analysis of the kidneys showed secretion of renin occurring in the donor but not in the recipient twin, more intense expression of angiotensin II receptor type 1 in the donor, and modifications of renal architectures in both twins. Renin protein appeared qualitatively higher in the placental territory of the recipient compared to that of donor. These findings indicate that hemodynamic discordance caused by vascular anastomoses may lead to serious physiologic and organic consequences as early as the first trimester. To our knowledge, this case presents the earliest first-trimester TTTS confirmed by a complete anatomopathological examination and is the first TTTS case to show a first-trimester discordant RAS response confirmed by immunohistochemistry.

Molecular heterogeneity in fetal forms of type II lissencephaly.

Type II lissencephaly (type II LIS) is a group of autosomal recessive congenital muscular dystrophies (CMD) associated with defects in alpha-DG O-glycosylation, which comprises Walker-Warburg syndrome, Fukuyama cerebral and muscular dystrophy, or muscle-eye-brain disease. The most severe forms of these diseases often have a fetal presentation and lead to a pregnancy termination. We report here the first molecular study on fetal type II LIS in a series of 47 fetuses from 41 unrelated families. Sequencing of the different genes known to be involved in alpha-DG O-glycosylation allowed the molecular diagnosis in 22 families: involvement of POMT1 was demonstrated in 32% of cases, whereas POMGNT1 and POMT2 were incriminated in 15% and in 7% of cases, respectively. We found 30 different mutations in these three genes, 25 were described herein for the first time, 15 in POMT1, and five in POMT2 and POMGNT1. Despite sequencing of FKRP, FCMD, and LARGE, no definitive molecular diagnosis could be made for the other half of our cases. Preliminary results concerning genotype-phenotype correlations show that the choice of the first gene sequenced should depend on the clinical severity of the type II LIS; POMT1 and POMT2 for severest clinical picture and POMGNT1 for milder disease. The other genes, FKRP, FCMD, and LARGE, seem not to be implicated in the fetal form of CMD.

Favourable outcome of a tight constriction band secondary to amniotic band syndrome.

Amniotic band syndrome or amniotic disruption complex is a well-known congenital limb abnormality, which occurs in 1 in 1200 to 1 in 15,000 live births. In cases of an isolated band constriction, it has been speculated that the bands lead to decreased blood flow in the constricted limb and subsequent natural amputation. Fetal surgery could be considered in these situations in order to release the constriction band in threatened limb amputation. We present a case of a tight constriction ring secondary to amniotic band syndrome with a favourable outcome, despite the failure of an attempted surgical procedure.

[Amniotic band syndrome: pathogenesis, prenatal diagnosis and neonatal management]. / Maladie des brides amniotiques: étiopathogénie, diagnostic anténatal et prise en charge néonatale.

Amniotic band syndrome is a collection of fetal congenital malformations, affecting mainly the limbs, but also the craniofacial area and internal organs. Two mains pathogenic mechanisms are proposed: early amnion rupture (exogenous theory) leading to fibrous bands, which entrap the fetal body; the endogenous theory privileges vascular compromise, mesoblastic strings not being a causal agent. The outcome of the disease depends on the gravity of the malformation. Termination of the pregnancy is usually proposed at the time of the diagnostic of severe craniofacial and visceral abnormalities, whereas minor limb defects can be repaired with postnatal surgery. In case of an isolated amniotic band with a constricted limb, in utero lysis of the band can be considered to avoid a natural amputation. However, as the exact etiology of amniotic band syndrome remains unknown and its natural course unpredictable, prenatal surgery continues to be controversial. Doppler studies of the constricted limb could be of useful predictive value of in utero amputation, and therefore could be helpful to determine when in utero treatment should be considered.