Fetal aortic valvuloplasty for critical aortic stenosis: single-center retrospective study focusing on postnatal outcome.

OBJECTIVE: We aimed to report our experience on fetal aortic valvuloplasty (FAV) for critical aortic stenosis (AS) focusing on the postnatal evolution of the patients. METHODS: This retrospective study was approved by our local Institutional Review Board (n°2002-0128143827). All fetuses with critical AS who underwent FAV in a single center between 01/2011 and 06/2022 were included. FAV were performed under ultrasound guidance. Technical success was based upon balloon inflation across the aortic valve and improvement of the anterograde aortic flow across the aortic valve. At birth, biventricular circulation (BVC) strategy was decided assuming the left ventricle (LV) systolic and diastolic functions would ensure the systemic circulation. RESULTS: Sixty-three FAV were performed on 58 fetuses at 24.6[21.4-32.4] weeks of gestation. The procedure was successful in 52/58(89.6%) fetuses. There were 11/58(19%) in utero demises and 9/58(15.5%) terminations of pregnancy. There were no liveborn patients after the unsuccessful procedures. 38/58(65.5%) infants were delivered at a median gestational age of 38.1[29-40.6] weeks and 21/38(55.3%) of them required prostaglandin. 28/38(73.7%) [28/58(48.3%)] children entered the BVC path at birth. Among them, 20 required an aortic valvuloplasty at birth (11 percutaneous, 9 surgical) and 8 did not require any treatment at birth but of those, 5/8 underwent a surgical valvuloplasty between day 26 and day 1200 of life. 11/28(39.3%) infants with BVC at birth required a second intervention and four of them required a third intervention. Two infants who entered the BVC at birth underwent a conversion to UVC. None of the surviving children with BVC developed pulmonary hypertension. The global survival rate in case of BVC was 22/28(78.6%) at 23.3[8-112] months of life. 10 patients had UVC at birth. Among them, 6 received comfort care from birth and only 4 underwent surgery. 3/10 patients were still alive at the latest assessment (48[22-102] months). CONCLUSION: FAV for critical aortic stenosis led to anterograde aortic flow in 89.6% of the fetuses, with BVC being achieved in 48.3% (73.7% of the live born). Among patients with BVC at birth, the rate of reintervention is high but long-term survival is satisfactory. This article is protected by copyright. All rights reserved.

Quantitative fetal MRI with diffusion tensor imaging in cases with 'short' corpus callosum.

OBJECTIVES: It has been suggested previously that the presence of Probst bundles (PB) in cases with a short corpus callosum (SCC) on diffusion tensor imaging (DTI) may help to differentiate between corpus callosal (CC) dysplasia and a variant of normal CC development. The objectives of this study were to compare DTI parameters between cases of SCC vs normal CC and between cases of SCC with PB (SCC-PB+) vs SCC without PB (SCC-PB-). METHODS: This was a retrospective study of patients referred to the Necker Hospital in Paris, France, for magnetic resonance imaging (MRI) evaluation of an apparently isolated SCC detected by sonography between November 2016 and December 2022 (IRB: 00011928). MRI was performed using a 1.5-Tesla Signa system. T2-weighted axial and sagittal sequences of the fetal brain were used to measure the length and thickness of the CC. 16-direction DTI axial brain sequences were performed to identify the presence of PB and to generate quantitative imaging parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) of the entire CC, genu, body and splenium. Cases in which other associated brain abnormalities were detected on MRI were excluded. Cases were matched for fetal gender and gestational age with controls in a 1:3 ratio. Control cases were normal fetuses included in the LUMIERE on the FETUS trial (NCT04142606) that underwent the same DTI evaluation of the brain. Comparisons between SCC and normal CC cases, and between SCC-PB+ and SCC-PB- cases were performed using ANOVA and adjusted for potential confounders using ANCOVA. RESULTS: Twenty-two SCC cases were included and compared with 66 fetuses with a normal CC. In 10/22 (45.5%) cases of SCC, PB were identified. As expected, dimensions of the CC were significantly smaller in SCC compared with normal CC cases (all P < 0.01). In SCC-PB+ vs SCC-PB- cases, FA values were significantly lower in the entire CC (median, 0.21 (range, 0.19-0.24) vs 0.24 (range, 0.22-0.28); P < 0.01), genu (median, 0.21 (range, 0.15-0.29) vs 0.24 (range, 0.17-0.29); P = 0.04), body (median, 0.21 (range, 0.18-0.23) vs 0.23 (range, 0.21-0.27); P = 0.04) and splenium (median, 0.22 (range, 0.16-0.30) vs 0.25 (range, 0.20-0.29); P = 0.03). ADC values were significantly higher in the entire CC, genu and body in SCC-PB+ vs SCC-PB- cases (all P < 0.05). In SCC-PB+ cases, all FA values were significantly lower, and ADC values in the CC body were significantly higher compared with normal CC cases (all P < 0.05). In SCC-PB- cases, there was no significant difference in FA and ADC compared with normal CC cases (all P > 0.05). CONCLUSIONS: Fetal DTI evaluation of the CC showed that FA values were significantly lower and ADC values tended to be significantly higher in SCC-PB+ compared with normal CC cases. This may highlight alterations of the white matter microstructure in SCC-PB+. In contrast, isolated SCC-PB- did not demonstrate significant changes in DTI parameters, strengthening the possibility that this is a normal CC variant. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of prenatal estimation of the risk of respiratory distress in neonates with congenital pulmonary malformations on the choice of delivery site.

BACKGROUND: The vast majority of prenatally diagnosed congenital pulmonary malformations (CPM) remain asymptomatic at birth. The maximal value of the CPM volume ratio (CVRmax) predicts the risk of neonatal respiratory distress (NRD), and should allow for better assessment of the level of expertise needed at the delivery site. AIM: This study evaluated the level of maternity units currently chosen for the delivery of CPMs, and determined the impact of the choice of delivery site based on the CVRmax, with a threshold of 0.4 cm2. METHODS: Data were extracted from the French prospective MALFPULM cohort, with inclusion between March 2015 and June 2018. RESULTS: The final study population consisted of 383 women. Deliveries in level 1 or 2 maternity units (n = 98, 25%) involved CPMs with lower CVRmax (p<0.001), causing fewer signs of prenatal compression (p = 0.025). Among the 62 children (16%) who presented with NRD, only seven (11%) were born in level 1 or 2 units (p = 0.0078). Choosing the maternity level according to the CVRmax would have increased the number of births in level 1 or 2 maternity hospitals by 70%. In these maternity units, the percentage of children with NRD would have increased from 8% in the actual distribution to 10% in the new strategy. CONCLUSION: Our results showed an overuse of level 3 maternity hospitals for the delivery of newborns with a prenatal diagnosis of CPM. The use of CVRmax should enable a reduction in the use of expertise centers without an adverse impact on newborns.

[High risk localized and locally advanced prostate cancer: Long-term oncological outcomes after prostatectomy]. / Cancer de la prostate localisé de haut risque et localement avancé : résultats oncologiques à long terme de la prostatectomie.

INTRODUCTION: High risk localized and locally advanced forms are responsible for the vast majority of specific deaths from prostate cancer among non-metastatic diseases at diagnosis. No randomized study has yet been published to establish the best local treatment in terms of survival. AIM: Conduct a large-volume cohort study with long-term follow-up to analyze specific and overall survival outcomes after surgery. METHOD: A single-center retrospective study of all patients operated on for localized high-risk and locally advanced prostate cancer was performed. Actuarial survival analyses and multivariate analyses were performed to discern predictive risk factors. RESULTS: Five hundred patients were included. MRI stage was≥iT3a in 40.7% of cases and 50.2% of patients had a Gleason score≥8 on biopsy. The mean follow-up was 63.1 months. The overall, specific and biological recurrence-free survival were respectively 77.6%, 93.9% and 26.8% at 10 years. A PSA level≥20, a Gleason score on biopsy≥9 and a MRI stage≥iT3a were significantly associated with the 10-years biological recurrence risk. CONCLUSION: This study shows very good long-term oncological results. In the absence of a randomized controlled trial, these results suggest the primary role of surgery in this indication and support the evolution of current practices. We pointed out very pejorative features that might help selection of the best candidates for surgical treatment.

[Assessment of positive surgical margins in the management of patients after radical prostatectomy for pT2 prostate cancer]. / Impact des marges chirurgicales positives après prostatectomie radicale chez les patients atteints d'un cancer de la prostate localisé pT2.

INTRODUCTION: Few data are available regarding positive surgical margins (PSM) in patients who underwent surgery for localized prostate cancer (PC). Our objective was to evaluate the impact of PSM on biochemical recurrence-free survival (BRFS) for patients who underwent PC for pT2 tumor without adjuvant treatment. METHODS: We included each patient who underwent radical prostatectomy for pT2N0 PC between 1988 and 2018. Primary endpoint was biochemical recurrence (BR). BRFS was calculated using Kaplan-Meier method. Univariate and multivariate analyses were used to determine factors associated with BR and PSM. RESULTS: Overall, 2429 patients were included whom 420 patients had PSM (17.3%). Median follow-up was 116 months. BRFS at 10 years was 66.6% in case of PSM, and 84% in the negative margins group (P<0.0001). Parameters associated with BR were preoperative PSA level (P<0.0001), Gleason score (P<0.0001), tumor volume in biopsies, and margins length (P<0.04). CONCLUSION: PSM in pT2N0 CP are associated with poor prognosis in terms of BR. Nevertheless, only a small number of pT2R1 cancer will present biological recurrence. The use of adjuvant radiotherapy in these patients therefore represents a risk of overtreatment, with the risk of adverse effects inherent to irradiation. Clinical and biological monitoring in case of PSM seems acceptable.

Prenatal diagnosis and outcome of fetuses with isolated agenesis of septum pellucidum: cohort study and meta-analysis.

OBJECTIVE: To evaluate the postnatal outcome of children with a prenatal diagnosis of apparently isolated agenesis of the septum pellucidum (ASP). METHODS: A retrospective cohort study of cases of prenatally diagnosed ASP followed in two tertiary centers and a meta-analysis combining data from the cohort study with data from published studies identified in a systematic review were carried out. Only cases with apparently isolated ASP on antenatal ultrasound and/or magnetic resonance imaging and with available postnatal follow-up data were considered eligible for inclusion. The following outcomes were analyzed: incidence of chromosomal anomalies, agreement between antenatal and postnatal findings, overall incidence of septo-optic dysplasia (SOD) and incidence of major neurological disability (motor, language, coordination or behavioral disorder or epilepsy) in non-SOD children. The incidence of SOD in infants with apparently normal optic pathways on antenatal imaging was also evaluated. RESULTS: Fifteen cases of isolated ASP, with median postnatal follow-up of 36 months (range, 12-60 months), were selected from the two centers. Six previously published studies met the inclusion criteria for the systematic review and a total of 78 cases were eligible for the analysis, including the 15 cases from our series. Genetic tests were carried out antenatally in 30 fetuses, of which two had an abnormal result (pooled proportion, 9.0% (95% CI, 1.8-20.7%); I2 = 0%). Additional or discordant imaging findings were noted postnatally in 9/70 (pooled proportion, 13.7% (95% CI, 3.5-29.0%); I2 = 63.9%) cases. Of all 78 neonates with available follow-up, SOD was diagnosed postnatally in 14 (pooled proportion, 19.4% (95% CI, 8.6-33.2%); I2 = 51.2%). In 60 cases, the optic pathways were considered to be normal on antenatal imaging, and six of these (pooled proportion, 9.1% (95% CI, 1.1-24.0%); I2 = 62.0%) were diagnosed postnatally with SOD. Of the 46 infants with available neurological follow-up who were not affected by SOD, a major neurological disability was diagnosed in three (pooled proportion, 6.5% (95% CI, 0.5-18.6%); I2 = 40.1%). CONCLUSIONS: In the vast majority of cases with a prenatal diagnosis of apparently isolated ASP, the prognosis is favorable. However, an additional anomaly is detected after birth in about 14% of cases and has a negative impact on clinical outcome. Detailed antenatal assessment of the brain and optic pathways is strongly recommended in order to identify the presence of associated anomalies. Antenatal visualization of apparently normal optic pathways does not rule out SOD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Feasibility and Added Value of Fetal DTI Tractography in the Evaluation of an Isolated Short Corpus Callosum: Preliminary Results.

BACKGROUND AND PURPOSE: Prognosis of isolated short corpus callosum is challenging. Our aim was to assess whether fetal DTI tractography can distinguish callosal dysplasia from variants of normal callosal development in fetuses with an isolated short corpus callosum. MATERIALS AND METHODS: This was a retrospective study of 37 cases referred for fetal DTI at 30.4 weeks (range, 25-34 weeks) because of an isolated short corpus callosum less than the 5th percentile by sonography at 26 weeks (range, 22-31 weeks). Tractography quality, the presence of Probst bundles, dysmorphic frontal horns, callosal length (internal cranial occipitofrontal dimension/length of the corpus callosum ratio), and callosal thickness were assessed. Cytogenetic data and neurodevelopmental follow-up were systematically reviewed. RESULTS: Thirty-three of 37 fetal DTIs distinguished the 2 groups: those with Probst bundles (Probst bundles+) in 13/33 cases (40%) and without Probst bundles (Probst bundles-) in 20/33 cases (60%). Internal cranial occipitofrontal dimension/length of the corpus callosum was significantly higher in Probst bundles+ than in Probst bundles-, with a threshold value determined at 3.75 for a sensitivity of 92% (95% CI, 77%-100%) and specificity of 85% (95% CI, 63%-100%). Callosal lipomas (4/4) were all in the Probst bundles- group. More genetic anomalies were found in the Probst bundles+ than in Probst bundles- group (23% versus 10%, P = .08). CONCLUSIONS: Fetal DTI, combined with anatomic, cytogenetic, and clinical characteristics could suggest the possibility of classifying an isolated short corpus callosum as callosal dysplasia and a variant of normal callosal development.

[Radical prostatectomy in patients with Gleason 6 (ISUP 1) prostate cancer: 10-year follow-up]. / Recul à 10 ans des patients opérés pour un cancer de prostate Gleason 6 (ISUP1).

OBJECTIVE: To evaluate extraprostatic extension and 10 years cancer specific survival in a population of patients with Gleason 6 (ISUP 1) prostate cancer (PCa) treated by radical prostatectomy (RP) in two French third referral centers. MATERIALS AND METHODS: The data were extracted from 2 university hospital databases according to the following criteria: PCa classified ISUP 1 following both biopsy (PB) and surgery (RP) between 1998 and 2008. Pathology slides of patients having presented an extraprostatic extension and/or a recurrence were reviewed by a uropathologist. RESULTS: Among the 534 patients who met the inclusion criteria, 66 (12.2%) had a pT3 stage. One patient out of 198 who received lymph node dissection had a positive node. Median follow-up was 10.3 years. Only one patient presented with metastatic progression. No cancer specific death was observed. An independent pathologist reviewed the slides of 58 out of the 70 patients who presented pT3 disease and/or a recurrence (in 12 cases, pathological material was not available). After review, all pT3b stages and 12 pT3a (out of 14) were upgraded to ISUP2 or higher. Similarly, the patient with a positive node and the patient who progressed towards a metastatic disease were both upgraded to ISUP 3. CONCLUSION: No pT3b or pN+stage was associated with ISUP 1 PCa in our study. With a median follow-up of more than 10 years, biological progression was the only type of progression observed.

First-trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS.

OBJECTIVE: To evaluate the feasibility of amplification of the viral genome by polymerase chain reaction (PCR) analysis of trophoblast samples obtained by chorionic villus sampling (CVS) in cases of maternal primary infection (MPI) with cytomegalovirus (CMV) in early pregnancy. METHODS: This was a prospective study carried out at the Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M., between October 2019 and October 2020. Following CMV serology screening in early pregnancy, CVS was offered to women at 11-14 weeks' gestation after CMV-MPI ≤ 10 weeks. Array-comparative genomic hybridization and amplification of the viral genome by PCR were performed on the trophoblasts obtained by CVS. All cases also underwent amniocentesis from 17 weeks onwards and PCR was performed on the amniotic fluid. Secondary prevention with valacyclovir was initiated as soon as MPI was diagnosed, to decrease the risk of vertical transmission. We evaluated the diagnostic performance of CMV-PCR of trophoblast obtained by CVS, using as the reference standard PCR of amniotic fluid obtained by amniocentesis. RESULTS: CVS was performed in 37 pregnancies, at a median (range) gestational age of 12.7 (11.3-14.4) weeks. CMV-PCR in chorionic villi was positive in three and negative in 34 cases. CMV-PCR following amniocentesis, performed at a median (range) gestational age of 17.6 (16.7-29.9) weeks, was positive for the three cases which were positive following CVS and, of the 34 patients with a negative finding following CVS, amniocentesis was negative in 31 and positive in three. The sensitivity of CMV-PCR analysis of trophoblast obtained by CVS for the diagnosis of CMV, using as the reference standard PCR analysis of amniotic fluid obtained by amniocentesis, was 50% (95% CI, 19-81%), specificity was 100% (95% CI, 89-100%), positive predictive value was 100% (95% CI, 44-100%) and negative predictive value was 91% (95% CI, 77-97%). CONCLUSIONS: Diagnosis of placental infection following MPI in early pregnancy can be achieved by PCR amplification of the CMV genome in chorionic villi. We propose that negative CMV-PCR in the trophoblast after 12 weeks could be used to exclude CMV-related embryopathy leading to sequelae. However, this needs to be confirmed through long-term follow-up evaluation. These findings could help to establish CVS as the diagnostic test of choice following maternal serology screening in early pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Heterogeneity in defining fetal corpus callosal pathology: systematic review.

OBJECTIVE: Fetal anomalies of the corpus callosum (CC) have been reported in the prenatal imaging literature since 1985, and, especially when isolated, pose challenges for both the patient and fetal medicine specialist. The purpose of this study was to review systematically the literature on prenatally diagnosed abnormalities of the CC, focusing on the terminology used to describe abnormalities other than complete agenesis of the CC, and to assess the heterogeneity of the nomenclature and definitions used. METHODS: This study was conducted in accordance with the PRISMA statement for reporting systematic reviews. A literature search was performed to identify prospective or retrospective case series or cohort studies, published in English, French, Italian, German or Spanish, reporting fetal imaging findings and describing anomalies of the CC. Quality and risk of bias of the studies were evaluated using the Newcastle-Ottawa scale and a modification of the scale developed by Conde-Agudelo et al. for other fetal imaging studies. The data extracted included the number of patients, the number of different anomalies identified, the descriptive names of the anomalies, and, where applicable, the definitions of the anomalies, the number of cases of each type of anomaly and the biometric charts used. Secondary tests used to confirm the diagnosis, as well as the postnatal or post-termination tests used to ascertain the diagnosis, were also recorded. RESULTS: The search identified 998 records, and, after review of titles and abstracts and full review of 45 papers, 27 studies were included initially in the review, of which 24 were included in the final analysis. These 24 studies had a broad range of quality and risk of bias and represented 1135 cases of CC anomalies, of which 49% were complete agenesis and the remainder were described using the term partial agenesis or nine other terms, of which five had more than one definition. CONCLUSIONS: In comparison to the postnatal literature, in the prenatal literature there is much greater heterogeneity in the nomenclature and definition of CC anomalies other than complete agenesis. This heterogeneity and lack of standard definitions in the prenatal literature make it difficult to develop large multicenter pooled cohorts of patients who can be followed in order to develop a better understanding of the genetic associations and neurodevelopmental and psychological outcomes of patients with CC anomalies. As this information is important to improve counseling of these patients, a good first step towards this goal would be to develop a simpler categorization of prenatal CC anomalies that matches better the postnatal literature. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[Prenatal path of care following the diagnosis of a malformation for which a novel prenatal therapy is available]. / Parcours prénatal devant une malformation pour laquelle un traitement in utero émergent est disponible.

OBJECTIVES: Fetal therapy is part of the available care offer for several severe malformations. The place of these emergent prenatal interventions in the prenatal path of care is poorly known. The objective of this study is to describe the decision-making process of patients facing the option of an emergent in utero intervention. METHODS: We have conducted a retrospective monocentric descriptive study in the department of maternal-fetal medicine of Necker Hospital. We collected data regarding eligibility or not for fetal surgery and the pregnancy outcomes of patients referred for myelomeningocele, diaphragmatic hernia, aortic stenosis and low obstructive uropathies. RESULTS: All indications combined, 70% of patients opted for fetal surgery. This rate was lower in the case of myelomeningocele with 21% consent, than in the other pathologies: 69% for diaphragmatic hernias, 90% for aortic stenoses and 76% for uropathy. When fetal intervention was declined, the vast majority of patients opted for termination of pregnancy: 86%. In 14% of the considering fetal surgery, the patient was referred too far. CONCLUSION: The acceptance rate for fetal surgeries depends on condition. It offers an additional option and is an alternative for couples for which termination of pregnancy (TOP) is not an option. Timely referral to an expert center allows to discuss the place of a fetal intervention and not to deprive couples of this possibility.

Biometric and morphological features on magnetic resonance imaging of fetal bladder in lower urinary tract obstruction: new perspectives for fetal cystoscopy.

OBJECTIVES: Incompatibility between currently available fetoscopes and the anatomical constraints of the distended fetal bladder, with the resulting curvature around the bladder neck, account for most technical difficulties during fetal cystoscopy in lower urinary tract obstruction (LUTO). The aim of this anatomical study was to assess by magnetic resonance imaging (MRI) the variation in three bladder angles (bladder-neck angle (BNA), vesicourethral angle (VUA) and angle between bladder dome and posterior urethra (DUA)), according to gestational age (GA), bladder volume and the presence of LUTO. METHODS: From our fetal medicine database, we retrieved for review 46 MRI examinations of male fetuses between 2015 and 2019, including 17 with LUTO, examined at a mean GA of 28.1 (range, 17.3-35.0) weeks and 29 age-matched controls, examined at 29.9 (range, 21.9-35.0) weeks. We measured bladder volume, bladder-wall thickness and the three bladder angles, and used the Mann-Whitney U-test to compare values between groups. Variations according to GA and bladder volume were determined using analysis of variance (ANOVA). A reliability study was performed using the Bland-Altman method and Lin's correlation coefficient was calculated. RESULTS: Both bladder volume and bladder-wall thickness were significantly greater in the LUTO group (P < 0.01). BNA was significantly larger in LUTO compared with control fetuses: the mean (range) was 127.1° (101.6-161.6°) vs 111.2° (88.5-157.3°) (P < 0.01). DUA averaged 117° and showed no difference between the groups (P = 0.92). No statistical comparison was performed on VUA since this was not measurable in most control fetuses. ANOVA showed no variation of any angle with bladder volume in both LUTO fetuses and control fetuses. BNA in LUTO fetuses was the only angle to vary with GA, being larger after, compared with at or before, 25 weeks (P = 0.04). The reliability study showed an acceptable bias for both intra- and interobserver reproducibility for all three angles. CONCLUSION: The findings that BNA is increased by approximately 15° in fetuses with LUTO and DUA averages 117° could aid in development of a customized fetal cystoscope and help to overcome the current technical challenges of fetal cystoscopy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

[When to introduce hormone therapy after total prostatectomy with positive lymph nodes? Study of the factors influencing the time of introduction of hormone therapy]. / Quand introduire une hormonothérapie après prostatectomie totale avec curage ganglionnaire positif ? Étude des facteurs influençant le délai d'introduction de l'hormonothérapie.

INTRODUCTION: Adjuvant hormone therapy is the standard treatment after total prostatectomy with positive lymph node. However, this treatment has side effects and at the time of the PSA era and extensive lymph node dissection, this principle is questioned. The aim of this study is to describe the oncological characteristics of patients that may explain the delay in introducing hormone therapy in patients with positive lymph node. METHODS: Monocentric, retrospective study of 161 patients from November 1988 to February 2018 in a single French University Hospital, having undergone radical prostatectomy with positive lymph nodes on pathology. For each patient, preoperative data (age, clinical stage, biopsy results, d'Amico classification) and postoperative data (pathological results, number of lymph nodes removed, number of positive lympnodes, recurrence free survival, specific survival and overall survival) were collected. The date of introduction of hormone therapy was noted and survival without hormonal therapy was established according to the Kaplan Meier curve. The pre- and post-operative oncological factors that could influence hormone therapy introduction were investigated with Chi2 and Student tests (statistically significant when P<0.05). RESULTS: The mean number of lymph nodes removed was 12 [1-40]. The mean number of positive lymph nodes was 2.5 [1-24], the mean percentage of positive lymph nodes was 25% (2.5-100). After a mean follow-up of 95 months (3-354), 88 patients (54.6%) had no hormonal treatment. The average time to hormonal treatment was 40 months [0-310]. At 3 years, survival without hormone therapy was 52% and 51% at 5 years. Only the percentage of positive lymphnodes appeared to be a significant predictor of the introduction of hormone therapy. (29.32% vs. 21.99%, P=0.047). Hormone-free survival was significantly higher in patients with lymph node involvement less than 25% (P<0.0001) or with less than 2 positive lymph nodes (P=0.0294). CONCLUSION: Lymph node invasion is a factor of poor prognosis after total prostatectomy and leads to introduce hormone therapy. Our study identified the percentage and number of positive lymph nodes as factors that identify patients who may be delayed in introducing this hormone therapy. LEVEL OF PROOF: 3.

Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis.

OBJECTIVE: To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis. METHODS: A search of MEDLINE, EMBASE and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. Eligible for inclusion were large controlled studies reporting data for pregnancy loss prior to 24 weeks' gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had an invasive procedure and controls were inputted into contingency tables and the risk of miscarriage was estimated for each study. Summary statistics based on a random-effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Subgroup analyses were performed according to the similarity in risk levels for chromosomal abnormality between the invasive-testing and control groups. Heterogeneity was assessed using the I2 statistic. Egger's bias was estimated to assess reporting bias in published studies. RESULTS: The electronic search yielded 2943 potential citations, from which 12 controlled studies for amniocentesis and seven for CVS were selected for inclusion in the systematic review. A total of 580 miscarriages occurred following 63 723 amniocentesis procedures, resulting in a weighted risk of pregnancy loss of 0.91% (95% CI, 0.73-1.09%). In the control group, there were 1726 miscarriages in 330 469 pregnancies with a loss rate of 0.58% (95% CI, 0.47-0.70%). The weighted procedure-related risk of miscarriage following amniocentesis was 0.30% (95% CI, 0.11-0.49%; I2 = 70.1%). A total of 163 miscarriages occurred following 13 011 CVS procedures, resulting in a risk of pregnancy loss of 1.39% (95% CI, 0.76-2.02%). In the control group, there were 1946 miscarriages in 232 680 pregnancies with a loss rate of 1.23% (95% CI, 0.86-1.59%). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95% CI, -0.13 to 0.52%; I2 = 52.7%). However, when studies including only women with similar risk profiles for chromosomal abnormality in the intervention and control groups were considered, the procedure-related risk for amniocentesis was 0.12% (95% CI, -0.05 to 0.30%; I2 = 44.1%) and for CVS it was -0.11% (95% CI, -0.29 to 0.08%; I2 = 0%). CONCLUSIONS: The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions were compared to control groups of the same risk profile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Riesgo de aborto después de una amniocentesis o una biopsia de vellosidades coriónicas: revisión sistemática de bibliografía y metaanálisis actualizado OBJETIVO: Estimar el riesgo de aborto relacionado con el procedimiento de la amniocentesis o la biopsia de vellosidades coriónicas (BVC) mediante una revisión sistemática de bibliografía y un metaanálisis actualizado. MÉTODOS: Se realizó una búsqueda en MEDLINE, EMBASE y The Cochrane Library para identificar estudios que reportaron sobre complicaciones después de una BVC o amniocentesis. Se consideraron elegibles para su inclusión los estudios controlados de gran tamaño que reportaron datos sobre la pérdida del embarazo antes de las 24 semanas de gestación. Se estableció contacto con los autores de los estudios cuando fue necesario para identificar datos adicionales necesarios. Se introdujeron en tablas de contingencia los datos de los casos que se sometieron a un procedimiento invasivo y controles y se estimó el riesgo de aborto para cada estudio. Las estadísticas resumen basadas en un modelo de efectos aleatorios se calcularon después de tener en cuenta la ponderación para cada estudio incluido en la revisión sistemática. El riesgo de aborto relacionado con cada procedimiento se estimó como una diferencia de riesgo ponderada de las estadísticas resumen para los casos y controles. Los análisis de subgrupos se realizaron de acuerdo con la similitud en los niveles de riesgo de anomalías cromosómicas entre los grupos de prueba invasiva y de control. La heterogeneidad se evaluó mediante el test estadístico I2 . Se estimó el sesgo de Egger para evaluar el sesgo de información reportada en los estudios publicados. RESULTADOS: La búsqueda electrónica arrojó 2943 citas potenciales, de las cuales se seleccionaron para su inclusión en la revisión sistemática 12 estudios controlados para la amniocentesis y siete para la BVC. Después de los 63723 procedimientos de amniocentesis sucedieron un total de 580 abortos, lo que resultó en un riesgo ponderado de pérdida de embarazo del 0,91% (IC 95%, 0,73-1,09%). En el grupo de control hubo 1726 abortos en 330469 embarazos, con una tasa de pérdida del 0,58% (IC 95%, 0,47-0,70%). El riesgo ponderado de aborto relacionado con el procedimiento de amniocentesis fue del 0,30% (IC 95%, 0,11-0,49%; I2  = 70,1%). Después de 13011 procedimientos de BVC se produjeron un total de 163 abortos, lo que resultó en un riesgo de pérdida de embarazo del 1,39% (IC 95%, 0,76-2,02%). En el grupo de control hubo 1946 abortos en 232680 embarazos, lo que supuso una tasa de pérdida del 1,23% (IC 95%, 0,86-1,59%). El riesgo ponderado de aborto relacionado con el procedimiento de BVC fue de 0,20% (IC 95%, -0,13-0,52%; I2  = 52,7%). Sin embargo, cuando se consideraron los estudios que incluyeron sólo mujeres con perfiles de riesgo similares para la anomalía cromosómica en los grupos de intervención y control, el riesgo relacionado con el procedimiento de la amniocentesis fue de 0,12% (IC 95%, -0,05-0,30%; I2  = 44.1%) y para el MVC fue de -0,11% (IC 95%, -0,29-0,08%; I2  = 0%). CONCLUSIONES: Los riesgos de aborto relacionados con el procedimiento de la amniocentesis y la BVC son menores que los actualmente mencionados a las mujeres. El riesgo parece ser insignificante cuando estas intervenciones se compararon con grupos de control del mismo perfil de riesgo.

Who is dying after nephrectomy for cancer? Study of risk factors and causes of death after analyzing morbidity and mortality reviews (UroCCR-33 study).

BACKGROUND AND METHODS: Nephrectomy is the treatment for renal cell cancer from T1-4 tumors but remains at risk. To determine the thirty-day mortality rate after nephrectomy for cancer and to identify causes and risk factors of death in order to find clinical applications. From 2014 to 2017, we performed a retrospective multicentric analysis of prospectively collected data study involving the French network for research on kidney cancer (UroCCR). All patients who died after nephrectomy for cancer during the first thirty days were identified. Patients' characteristics, causes of death and morbidity and mortality reviews reports were analyzed for each death. RESULTS AND LIMITATIONS: In total, 2578 patients underwent nephrectomy and 35 deaths occurred. The thirty-day mortality rate was 1.4%. In univariate analysis, symptoms at diagnosis (P=0.006, OR=2.56 IC (1.3-5.03)), c stage superior to cT1 (P<0.0001, OR=6.13 IC (2.8-13.2)), cT stage superior to cT2 (P<0.0001, OR=8.8 IC (4.39-17.8)), nodal invasion (P<0.0001, OR=4.6 IC (1.9-10.7)), distant metastasis (P=0.001, OR=4.01 IC (1.7-8.9)), open surgery (P<0.0001, OR=0.272 IC (0.13-0.54)) and radical nephrectomy (P=0.007, OR=2.737 IC (1.3-5.7)) were risk factors of thirty-day mortality. In a multivariable model, only cT stage superior to T2 (P=0.015, OR=3.55 IC (1.27-10.01)) was a risk factor of thirty-day mortality. The main cause of postoperative death was pulmonary (n=15; 43%). The second cause was postoperative digestive sepsis for 7 patients (20%). Only 2 morbidity and mortality reviews had been done for the 35 deaths. Limitations are related to the thirty-day mortality criteria and descriptive study design. CONCLUSIONS: Symptomatic patients, stage cTNM and type and techniques of surgery are determinants of thirty-day mortality after nephrectomy for cancer. The first cause of postoperative death is pulmonary. Morbidity and mortality reviews should be considered to better understand causes of death and to reduce early mortality after nephrectomy for cancer. LEVEL OF EVIDENCE: 4.

Outcome of non-visualization of fetal gallbladder on second-trimester ultrasound: cohort study and systematic review of literature.

OBJECTIVES: To investigate the ultrasound characteristics and outcome of fetuses with non-visualization of the fetal gallbladder (NVFGB) followed in our tertiary university hospital, and to provide a comprehensive review of the literature on prenatal findings and outcome of NVFGB. METHODS: NVFGB was defined as non-visualization of the gallbladder on two targeted ultrasound examinations performed within a 1-week period. First, we reviewed the medical records of NVFGB cases managed in our center over a 9-year period. Then, we performed a systematic review of the literature to identify studies on NVFGB. The incidence of chromosomal anomalies, later visualization of the gallbladder, gallbladder agenesis, cystic fibrosis and biliary atresia was assessed in fetuses with isolated and non-isolated NVFGB. The role of hepatic enzyme measurements in the diagnosis of cystic fibrosis and biliary atresia in fetuses with NVFGB was also reviewed. RESULTS: Sixteen cases of NVFGB were followed in our center, in 10 (62.5%) of which it was an isolated finding. The incidence of biliary atresia was 12.5% and that of gallbladder agenesis was 12.5%, while no case of cystic fibrosis was reported. The gallbladder was visualized later in pregnancy or postnatally in 43.8% and 25.0% of cases, respectively. A total of seven studies, including our cohort, involving a total of 280 NVFGB cases, met the inclusion criteria for the systematic review. Overall, 20.5% of fetuses had an associated ultrasound anomaly, and the incidence of chromosomal anomaly in this group was 20.4%. In cases with isolated NVFGB, the incidence of chromosomal anomaly was 1.9%. In fetuses with normal karyotype and isolated NVFGB, the gallbladder was later visualized in 70.4% of cases, while the incidence of gallbladder agenesis, cystic fibrosis and biliary atresia was 25.2%, 3.1% and 4.8%, respectively. In fetuses with non-isolated NVFGB, the incidence of cystic fibrosis and biliary atresia was 23.1% and 18.2%, respectively. The negative predictive value of amniotic fluid enzyme levels for the prediction of severe disease (including biliary atresia or cystic fibrosis) ranged between 94% and 100% when evaluated before 22 weeks' gestation, and dropped to 88% after 22 weeks. CONCLUSIONS: In cases with persistent NVFGB, the risk of a severe postnatal condition should be considered. A detailed ultrasound scan should be offered and parents tested for cystic fibrosis gene mutation. An invasive procedure for karyotyping and measurement of liver enzyme concentrations before 22 weeks constitutes a reasonable work-up. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

No visualización de la vesícula biliar fetal en la ecografía del segundo trimestre del embarazo: estudio de cohortes y revisión sistemática de la literatura sobre el resultado postnatal OBJETIVOS: Investigar las características ecográficas y los resultados de los fetos con no visualización de la vesícula biliar fetal (NVFGB, por sus siglas en inglés) a los que se ha dado seguimiento en un hospital universitario terciario, y ofrecer una revisión exhaustiva de la literatura sobre los hallazgos prenatales y los resultados de la NVFGB. MÉTODOS: La NVFGB se definió como la no visualización de la vesícula biliar en dos exámenes ecográficos específicos realizados en un período de una semana. Primero, se revisó los registros médicos de los casos de NVFGB tratados en este hospital durante un período de 9 años. Luego, se realizó una revisión sistemática de la literatura para identificar estudios sobre NVFGB. Se evaluó la incidencia de anomalías cromosómicas, la visualización posterior de la vesícula biliar, la agenesia vesicular, la fibrosis quística y la atresia biliar en fetos con NVFGB aislada y no aislada. También se examinó la función de las mediciones de las enzimas hepáticas en el diagnóstico de la fibrosis quística y la atresia biliar en fetos con NVFGB. RESULTADOS: Se siguieron dieciséis casos de NVFGB en este centro hospitalario, lo cual fue un hallazgo aislado en 10 de ellos (62,5%). La incidencia de atresia biliar fue del 12,5% y la de agenesia vesicular del 12,5%, mientras que no se reportó ningún caso de fibrosis quística. La vesícula biliar se visualizó más tarde en el embarazo o después del parto en el 43,8% y 25,0% de los casos, respectivamente. Un total de siete estudios cumplieron los criterios de inclusión para la revisión sistemática, incluidos los de la cohorte del mencionado hospital, con un total de 280 casos de NVFGB. En total, el 20,5% de los fetos presentaban una anomalía ecográfica asociada, y la incidencia de anomalías cromosómicas en este grupo fue del 20,4%. En los casos con NVFGB aislada, la incidencia de anomalías cromosómicas fue del 1,9%. En los fetos con cariotipo normal y NVFGB aislada, la vesícula biliar se visualizó posteriormente en el 70,4% de los casos, mientras que la incidencia de agenesia vesicular, fibrosis quística y atresia biliar fue del 25,2%, 3,1% y 4,8%, respectivamente. En los fetos con NVFGB no aislada, la incidencia de fibrosis quística y atresia biliar fue del 23,1% y 18,2%, respectivamente. El valor predictivo negativo de los niveles de enzimas del líquido amniótico para la predicción de una enfermedad grave (como la atresia biliar o la fibrosis quística) se situó entre el 94% y el 100% cuando se evaluó antes de las 22 semanas de gestación, y bajó al 88% después de las 22 semanas. CONCLUSIONES: En casos con NVFGB persistente, se debe considerar el riesgo de una condición postnatal severa. Se debe ofrecer una ecografía detallada y la madre y el padre deben someterse a pruebas para detectar mutaciones del gen de la fibrosis quística. Un examen diagnóstico razonable incluye un procedimiento invasivo para el cariotipado y la medición de las concentraciones de enzimas hepáticas antes de las 22 semanas.

Migration in last decade to high-risk prostate cancer after radical prostatectomy.

OBJECTIVE: There is controversy around prostate cancer (PCa) screening through the use of PSA, due to the risk of overtreatment. The current trend observed in various European and American studies is a decrease in the number of radical prostatectomy (RP) in low-risk PCa and an increase for intermediate or locally advanced diseases. The objective of this study was to observe the migration of the pathological stages from radical prostatectomy (RP) over 10 years in France through 2 French centers. METHODS: It was a multicentric retrospective study, where all the RP realized in 2 French tertiary centers, in a laparoscopic or retropubic approach for each of the years 2005, 2010 and 2015 were included. Preoperative data (age, PSA, clinical stage, number of positive biopsies, Gleason biopsy score) and postoperative data (pTNM, pathological Gleason score (pGS)) were analyzed and compared. RESULTS: In all, 1282 RP were realized (503 in 2005, 403 in 2010, 376 in 2015). Respectively between 2005, 2010, 2015 the average number of positive biopsy increased significantly from 2.30 vs. 2.88 vs. 5.3 (P=0.0001). The distribution of D'Amico's risk evolves with time: low-risk: 49.9 vs. 44.4 vs. 15.7% (P=0.0001); intermediate risk: 40.95 vs. 43.92 vs. 64.1% (P=0.0001) and high-risk: 9.15 vs. 11.66 vs. 20.2% (P=0.0001) between 2005, 2010 and 2015 respectively. pGS evolved to higher score with SG<7: 22.8 vs. 29.9 vs. 7.1% et SG≥7: 77.2 vs. 70.1 vs. 92.9% (P=0.001). Also, pTNM increased to non-organ-confined disease: pT2: 66.9 vs. 51.9 vs. 48.7%; pT3: 33.1 vs. 48.1 vs. 51.3% (P=0.0001). CONCLUSION: This study showed a change in the management of PCa since new recommendations from medical authorities about PSA screening and evolving of conservative treatment. Number of RP increase for higher risk PCa. This change corresponds to better patient selection for RP: decrease for low-risk and increase for high-risk organ-confined disease. LEVEL OF EVIDENCE: 3.