Between Pathological Prostate Cancer Lymph Nodes and Sentinel Nodes: Which Information Is the Leader?

PURPOSE: On the basis of the concept of sentinel lymph node biopsy (SLNB), SLNs should contain decisive information for clinical outcomes. In localized prostate cancer patients, this study assessed retrospectively clinical outcome after radical laparoscopic prostatectomy associated with SLNB and extensive pelvic lymph node dissection. METHODS: A total of 231 consecutive patients of intermediate to high risk were analyzed. Recurrence-free survival (RFS) was assessed with Kaplan-Meier curves. Various pathological parameters were analyzed using univariable and multivariable analyses through Cox regression analysis. The study was approved and registered under 2007-R41. RESULTS: The median follow-up was 7.1 years (95% confidence interval, 6.6-7.5). In total, 38/231 (16.5%) patients were pN1. Of these 38 patients, 27 had only SLN involvement (SLNI), 10 patients had both SLN and non-SLNI, and 1 patient had isolated non-SLNI, indicating a false-negative (FN). If the updated Briganti nomogram threshold set at >7% for recommending extensive pelvic lymph node dissection had been applied to these patients, we would have missed 44% (12/27) of patients with SLNI and 50% (5/10) of patients with SLNI and non-SLNI, as well as the FN patient. At the time of final follow-up, 84/231 (36.5%) patients had recurrence. In multivariable analysis, and regarding node status, the most significant prognostic factor was SLN with macrometastases and/or micrometastases, respectively, P = 10-3 and P < 10-3. No more information was obtained with non-SLN status. Probabilities of RFS between negative and positive SLN patients presented a major significant difference (P < 10-15) with a risk of event 8.75 times more frequent if SLN was involved than if it was metastasis-free. CONCLUSIONS: SLNB seems to contain decisive information for the clinical outcome of patients with localized intermediate- and high-risk prostate cancer patients. The question raised is thus whether immediate additional postoperative treatment should be offered to patients with metastatic SLN.

Early prenatal diagnosis of causative homozygous variants in ASCC1 in a fetus with cystic hygroma and additional homozygous variants of unknown significance associated with a neurological phenotype not visible in early gestation: Dual diagnosis or not?

A consanguineous couple was referred at 10 weeks of gestation (WG) for prenatal genetic investigations due to isolated cystic hygroma. Prenatal trio exome sequencing identified causative homozygous truncating variants in ASCC1 previously implicated in spinal muscular atrophy with congenital bone fractures. Prenatal manifestations in ASCC1 can usually include hydramnios, fetal hypo-/akinesia, arthrogryposis, contractures and limb deformities, hydrops fetalis and cystic hygroma. An additional truncating variant was identified in CSPP1 associated with Joubert syndrome. Presentations in CSPP1 include cerebellar and brainstem malformations with vermis hypoplasia and molar tooth sign, difficult to visualize in early gestation. A second pregnancy was marked by the recurrence of isolated increased nuchal translucency at 10 + 2 WG. Sanger prenatal diagnosis targeted on ASCC1 and CSPP1 variants showed the presence of the homozygous familial ASCC1 variant. In this case, prenatal exome sequencing analysis is subject to a partial ASCC1 phenotype and an undetectable CSPP1 phenotype at 10 weeks of gestation. As CSPP1 contribution is unclear or speculative to a potentially later in pregnancy or postnatal phenotype, it is mentioned as a variant of uncertain significance. The detection of pathogenic or likely pathogenic variants involved in severe disorders but without phenotype-genotype correlation because the pregnancy is in the early stages or due to prenatally undetectable phenotypes, will encourage the clinical community to define future practices in molecular prenatal reporting.

Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool.

Introduction: Prenatal ultrasound (US) anomalies are detected in around 5%-10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on the inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following the detection of anomalies on US. Patients and methods: We prospectively performed prenatal trio-ES in 150 fetuses with at least two US anomalies or one US anomaly known to be frequently linked to a genetic disorder. Trio-ES was only performed if the results could influence pregnancy management. Chromosomal microarray (CMA) was performed before or in parallel. Results: A causal diagnosis was identified in 52/150 fetuses (34%) with a median time to diagnosis of 28 days, which rose to 56/150 fetuses (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) fetuses and unfavorable vital and/or neurodevelopmental prognosis was made in 13/56 (24%) fetuses. The overall diagnostic yield was 41% (37/89) with first-line trio-ES versus 31% (19/61) after normal CMA. Trio-ES and CMA were systematically concordant for identification of pathogenic CNV. Conclusion: Trio-ES provided a substantial prenatal diagnostic yield, similar to postnatal diagnosis with a median turnaround of approximately 1 month, supporting its routine implementation during the detection of prenatal US anomalies.

Five-year Results from the Prospective, Multicenter, Observational SOUNDS Study of Patients with Overactive Bladder Treated with the InterStim System for Sacral Neuromodulation.

BACKGROUND: Although sacral neuromodulation (SNM) for overactive bladder (OAB) is an established therapy, there is a lack of high-quality, long-term data on real-life practice. OBJECTIVE: To report on real-life therapeutic effectiveness, quality of life (QoL), disease severity, and safety as well as patient-reported symptom bother after approximately 5 yr of follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 291 OAB patients were enrolled at 25 French sites according to local standard of care. Sacral neuromOdUlation with InterStim therapy for intractable lower uriNary tract DySfunctions (SOUNDS) enrolled both de novo and replacement patients, and a total of 229 patients were permanently implanted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over the course of the study, patients were followed up six times with two follow-ups in the year after implantation and annually thereafter. Of the patients, 154 completed the final follow-up after a mean of 57.7 ± 3.9 mo. RESULTS AND LIMITATIONS: The mean number of daily leaks in urinary urge incontinence (UI) patients was reduced from 4.4 ± 3.3 at baseline to 1.8 ± 2.6 after 5 yr in de novo and from 5.4 ± 4.9 to 2.2 ± 3.0 in replacement patients (both p < 0.001). Likewise, the number of voids in urinary frequency patients was reduced compared with baseline (de novo: reduced from 12.6 ± 4.0 [baseline] to 9.6 ± 4.3 [5 yr]; replacements: reduced from 11.5 ± 4.3 [baseline] to 9.2 ± 3.1 [5 yr]; both p < 0.05). Complete continence rates after 5 yr were 44% (25/57) in de novo and 33% (5/15) in replacement UI patients, and 68% (39/57) and 67% (10/15) of UI patients were categorized as therapy responders by showing a >50% improvement in leaks. Disease severity (Urinary Symptom Profile domain 2), Numeric Rating Scale-based symptom bother, and disease-specific QoL (Ditrovie) improved significantly in both groups at all visits (p < 0.001). Adverse events related to device or procedure occurred in 51% (140/274) of patients, with 66% (152/229) of the events being classified as minor (Clavien-Dindo grade I and II). Surgical revisions were reported in 39% (89/229), which include permanent explants in 15% (34/229) of patients. CONCLUSIONS: SOUNDS demonstrates the sustained effectiveness and QoL improvements of SNM in OAB patients after 5 yr in real-world conditions while maintaining an acceptable safety profile consistent with literature. PATIENT SUMMARY: This study confirmed that French overactive bladder patients had a sustained symptom and bother reduction, and improvements in quality of life up to 5 yr after sacral neuromodulation device implantation.

Radioisotope-guided Lymphadenectomy for Pelvic Lymph Node Staging in Patients With Intermediate- and High-risk Prostate Cancer (The Prospective SENTINELLE Study).

PURPOSE: Our aim was to prospectively evaluate the diagnostic accuracy of sentinel lymph node biopsy-guided lymph node dissection compared to extended pelvic lymph node dissection in patients with intermediate- or high-risk prostate cancer. MATERIALS AND METHODS: We conducted a prospective, single-arm, multicenter study at 3 tertiary centers in France between February 2012 and May 2019. Eligible patients had clinically localized intermediate- or high-risk prostate cancer. After intraprostatic injection of (99m)Tc-nanocolloid, the locations of the sentinel lymph nodes were defined by preoperative lymphoscintigraphy. Surgical excision of the sentinel lymph nodes was performed using intraoperative gamma probe guidance. After resection of the sentinel lymph nodes, extended pelvic lymph node dissection was performed in all patients. We assessed the diagnostic accuracy of the sentinel lymph node biopsy method using extended pelvic lymph node dissection as the reference standard. This trial was registered in ClinicalTrials.gov (NCT02732392). RESULTS: A total of 162 men cN0M0 (CT scan and bone scan) were enrolled: 106 (65.4%) and 56 (34.6%) patients had intermediate- and high-risk prostate cancer, respectively. The median number of nodes retrieved was 14 (mean 16, IQR 10-21) per patient. At final pathological analysis, 22 patients (13.6%) were pN+. Sensitivity, specificity, negative predictive value, and positive predictive value of sentinel lymph node biopsy method in detecting patients with at least 1 lymph node metastasis were 95.4% (95% CI, 75.1-99.7), 100% (95% CI, 96.6-100), 99.2% (95% CI, 95.5-99.9), and 100% (95% CI, 80.7-100), respectively. CONCLUSIONS: Our multicenter prospective study supports that sentinel lymph node biopsy is a very effective and sensitive method for pelvic lymph node staging in patients with intermediate- or high-risk localized prostate cancer.

Same performance of exome sequencing before and after fetal autopsy for congenital abnormalities: toward a paradigm shift in prenatal diagnosis?

Prenatal exome sequencing could be complex because of limited phenotypical data compared to postnatal/portmortem phenotype in fetuses affected by multiple congenital abnormalities (MCA). Here, we investigated limits of prenatal phenotype for ES interpretation thanks to a blindly reanalysis of postmortem ES data using prenatal data only in fetuses affected by MCA and harboring a (likely)pathogenic variant or a variant of unknown significance (VUS). Prenatal ES identified all causative variant previously reported by postmortem ES (22/24 (92%) and 2/24 (8%) using solo-ES and trio-ES respectively). Prenatal ES identified 5 VUS (in four fetuses). Two of them have been previously reported by postmortem ES. Prenatal ES were negative for four fetuses for which a VUS were diagnosed after autopsy. Our study suggests that prenatal phenotype is not a limitation for implementing pES in the prenatal assessment of unsolved MCA to personalize fetal medicine and could influence indication of postmortem examination.

Sacral Neuromodulation with the InterStim System for Overactive Bladder: 3-Year Results from the French Prospective, Multicenter, Observational SOUNDS Study.

BACKGROUND: SOUNDS strengthens the evidence basis of sacral neuromodulation (SNM) for overactive bladder (OAB) through real-world data. OBJECTIVE: To analyze diary-based effectiveness, quality of life (QoL), disease severity, symptom bother, and safety data for SNM with the InterStim system up to 3 yr after implantation. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five representative French sites enrolled 291 patients with OAB followed according to the local standard of care. Overall, 229 patients received a de novo or replacement InterStim implant and had four follow-up visits, two within the first yr and annually thereafter. A total of 190 patients completed the fourth follow-up visit after a mean of 33.7 ± 3.7 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The effectiveness outcomes measured were changes in daily voids and leaks and the therapy responder rates. Other outcomes included validated QoL data (Ditrovie and EuroQol 5-dimension 5-level questionnaires), disease severity (Urinary Symptom Profile [USP]), symptom bother rated using a numeric rating scale (NRS), and safety data. Follow-up data were compared to baseline results using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Average daily voids and leaks were significantly reduced at all time points up to 3 yr after implantation (p < 0.05) except for voids at 21 mo in the group receiving a replacement device. The therapeutic response for urinary urge incontinence at the fourth follow-up was 72% for the de novo group and 86% for the replacement group. Disease-specific QoL (Ditrovie), OAB-specific symptom severity (USP domain 2), and NRS-rated disease bother were significantly improved at all visits (p < 0.001). Device- or procedure-related adverse events occurred in 49% of patients, with 68% of the events classified as minor (Clavien-Dindo grade I or II). Surgical revisions were performed in 33% of patients, including permanent removal in 13%, over a mean exposure time of 44.4 ± 15.3 mo. CONCLUSIONS: This study confirms the safety and effectiveness of SNM for OAB and improvements in QoL and disease bother in real life. PATIENT SUMMARY: Our study in French patients with overactive bladder showed that disease symptoms and bother were significantly reduced and quality of life was significantly improved over a study duration of approximately 3 yr after implantation of a device to stimulate nerves that control the bladder. This trial is registered at ClinicalTrials.gov as NCT02186041.

Should prenatal chromosomal microarray analysis be offered for isolated fetal growth restriction? A French multicenter study.

BACKGROUND: Compared with standard karyotype, chromosomal microarray analysis improves the detection of genetic anomalies and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of chromosomal microarray analysis in cases of isolated fetal growth restriction. OBJECTIVE: This study aimed to estimate the proportion of copy number variants detected by chromosomal microarray analysis and the incremental yield of chromosomal microarray analysis compared with karyotype in the detection of genetic abnormalities in fetuses with isolated fetal growth restriction. STUDY DESIGN: This retrospective study included all singleton fetuses diagnosed with fetal growth restriction and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over 1 year in 2016. Fetal growth restriction was defined as an estimated fetal weight of

Sacral Neuromodulation with the InterStim™ System for Intractable Lower Urinary Tract Dysfunctions (SOUNDS): Results of Clinical Effectiveness, Quality of Life, Patient-Reported Outcomes and Safety in a French Multicenter Observational Study.

BACKGROUND: Real-world data that support the use of sacral neuromodulation (SNM) for lower urinary tract dysfunctions are of continued interest. OBJECTIVE: To evaluate the effectiveness, quality of life (QoL), patient-reported outcomes (PROs), and safety of SNM with the InterStim™ system in real life during 1-yr postimplant. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, multicenter, observational study at 25 representative public and private French sites. Eligible patients received SNM therapy for overactive bladder (OAB) and non-obstructive urinary retention based on local standard of care. Overall, 320 patients were enrolled; 247 received permanent implant or replacement; 204 implanted patients completed second follow-up after mean of 10.0±3.8 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness outcomes were change in voids, leaks, and catheterizations/day. Other outcomes included validated QoL and disease severity scores as well as PROs and adverse event data. Outcomes at follow-ups were compared with baseline using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Voids in urinary frequency (UF) and leaks/day in urinary urge incontinence (UI) patients were significantly reduced after 10 mo in both de novo (mean baseline voids/day UF de novo: 12.7 vs 8.6 after 10 mo; p<0.001; mean baseline leaks/day UI de novo: 4.3 vs 1.1 after 10 mo; p<0.001) and replacement patients (mean baseline voids/day UF replacement: 11.5 vs 7.9 after 10 mo; p<0.001; mean baseline leaks/day UI replacement: 5.4 vs 1.0 after 10 mo; p<0.001). Disease bother, Urinary Symptom Profile score, and Ditrovie questionnaire score were also significantly improved. Revisions postimplant occurred in 20% of patients including in 9% due to permanent explantation during a mean exposure time of 24.3 mo. CONCLUSIONS: Through a real-life study, SOUNDS (Sacral neuromOdUlation with InterStim™ therapy for intractable lower uriNary tract DySfunctions) confirms the clinical effectiveness, safety, and positive effect of SNM on QoL and PROs for the treatment of OAB patients. PATIENT SUMMARY: These analyses on French patients who received sacral neuromodulation (SNM) for retention or OAB during a 10-mo period showed that SNM improved OAB symptoms, quality of life, and reduced disease bother. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186041.

Haute Couture or Ready-to-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection.

Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.

Cardiomyopathy due to PRDM16 mutation: First description of a fetal presentation, with possible modifier genes.

PRDM16 (positive regulatory domain 16) is localized in the critical region for cardiomyopathy in patients with deletions of chromosome 1p36, as defined by Gajecka et al., American Journal of Medical Genetics, 2010, 152A, 3074-3083, and encodes a zinc finger transcription factor. We present the first fetal case of left ventricular non-compaction (LVNC) with a PRDM16 variant. The third-trimester obstetric ultrasound revealed a hydropic fetus with hydramnios and expanded hypokinetic heart. After termination of pregnancy, foetopathology showed a eutrophic fetus with isolated cardiomegaly. Endocardial fibroelastosis was associated with non-compaction of the myocardium of the left ventricle. Exome sequencing (ES) identified a de novo unreported p.(Gln353*) heterozygous nonsense variant in PRDM16. ES also identified two rare variants of unknown significance, according to the American College of Medical Genetics and Genomics guidelines, in the titin gene (TTN): a de novo missense p.(Lys14773Asn) variant and a c.33043+5A>G variant inherited from the mother. Along with the PRDM16 de novo probably pathogenic variant, TTN VOUS variants could possibly contribute to the severity and early onset of the cardiac phenotype. Because of the genetic heterogeneity of cardiomyopathies, large panels or even ES could be considered as the main approaches for the molecular diagnosis, particularly in fetal presentations, where multiple hits seem to be common.

Placental volume and other first-trimester outcomes: are there differences between fresh embryo transfer, frozen-thawed embryo transfer and natural conception?

RESEARCH QUESTION: Does mode of conception influence placental volume and other first-trimester outcomes? DESIGN: This retrospective single-centre case-control study led in Dijon University Hospital included 252 singleton pregnancies (84 IVF with either fresh embryo transfer or frozen-thawed embryo transfer [FET] and 168 natural conceptions). First-trimester placental volume, uterine artery pulsatility index and maternal serum PAPP-A and beta-HCG were measured. Statistical analyses were adjusted for gestational age, the newborn's gender, maternal age, parity, body mass index and smoking status. RESULTS: Placental volume was significantly greater in the FET group than in the control group (P = 0.043) and fresh embryo transfer (P = 0.023) groups. At birth, fresh embryo transfer newborns were significantly smaller than controls (P = 0.01) and FET newborns (P = 0.008). Postpartum haemorrhage was far more frequent in FET than in controls and fresh embryo transfer group (38.1%, 2.6% and 1.9%, respectively; P < 0.0001). Placental volume positively correlated with PAPP-A, beta-HCG and the newborn's birth weight, and negatively correlated with uterine artery pulsatility index. CONCLUSIONS: Placental volume and other first-trimester parameters are modified by IVF with fresh embryo transfer and FET compared with natural conception, but with opposite trends. Given the different protocols used for these techniques, hormonal treatment per se may have a major effect on pregnancy outcomes through the modification of placental invasiveness.

Singleton fetal growth kinetics depend on the mode of conception.

OBJECTIVE: To study the impact of in vitro fertilization, with or without intracytoplasmic sperm injection (IVF/ICSI), frozen-embryo transfer (FET), and intrauterine insemination (IUI) on fetal growth kinetics throughout pregnancy and to compare the different modes of conception. DESIGN: Retrospective cohort study. SETTING: University. PATIENT(S): A total of 560 singleton pregnancies were included (96 IVF, 210 ICSI, 121 FET, and 133 IUI). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We compared crown-rump length (CRL) at the first trimester (T1: 11-13 weeks of gestation [WG] + 6 days), estimated fetal weight (EFW) at the second (T2: 21-23 WG + 6 days) and third (T3: 31-33 WG + 6 days) trimesters, and birth weight (BW) z-scores with those in the reference curves (Papageorghiou for T1, and Ego M2 for T2, T3, and birth). Multivariate analyses were performed. RESULT(S): For T1, the CRL was longer than the reference curve whatever the assisted reproductive technique (ART). For T2, EFW was significantly greater for all groups compared with the reference curve, and for T3 only FET singletons had a greater EFW. ICSI, IVF, and IUI singletons had a significantly lower BW compared with reference curves. For all ART fetuses, growth kinetics differed from T2. Only FET fetuses maintained their significantly above-reference growth values. The proportion of fetuses for which at least one period of growth loss was observed from T2 to birth was higher after IVF, ICSI, and IUI than after FET. CONCLUSION(S): For the first time, we have highlighted that fetal growth kinetics differed from T2 depending on the ART protocols used. They could have an impact on trophoblastic invasiveness and might lead to long-term health effects.

Complete genome sequence of Bacillus velezensis QST713: A biocontrol agent that protects Agaricus bisporus crops against the green mould disease.

Bacillus subtilis QST713 is extensively used as a biological control agent in agricultural fields including in the button mushroom culture, Agaricus bisporus. This last use exploits its inhibitory activity against microbial pathogens such as Trichoderma aggressivum f. europaeum, the main button mushroom green mould competitor. Here, we report the complete genome sequence of this bacterium with a genome size of 4 233 757 bp, 4263 predicted genes and an average GC content of 45.9%. Based on phylogenomic analyses, strain QST713 is finally designated as Bacillus velezensis. Genomic analyses revealed two clusters encoding potential new antimicrobials with NRPS and TransATPKS synthetase. B. velezensis QST713 genome also harbours several genes previously described as being involved in surface colonization and biofilm formation. This strain shows a strong ability to form in vitro spatially organized biofilm and to antagonize T. aggressivum. The availability of this genome sequence could bring new elements to understand the interactions with micro or/and macroorganisms in crops.

Laparoscopic sentinel lymph node dissection in prostate cancer patients: the additional value depends on preoperative data.

AIM: In intermediate- or high-risk prostate cancer (PC) patients, to avoid extended pelvic lymph node dissection (ePLND), the updated Briganti nomogram is recommended with the cost of missing 1.5 % of patients with lymph node invasion (LNI). Is it possible to reduce the percentage of unexpected LNI patients (nomogram false negative)? We used the isotopic sentinel lymph node (SLN) technique systematically associated with laparoscopic ePLND to assess the potential value of isotopic SLN method to adress this point. METHODS: Two hundred and two consecutive patients had procedures with isotopic SLN detection associated with laparoscopic ePLND for high or intermediate risk of PC. The area under the curve (AUC) of the receiver operating characteristics (ROC) analysis was used to quantify the accuracy of different models as: the updated Briganti nomogram, the percentage of positive cores, and an equation of the best predictors of LNI. We tested the model cutoffs associated with an optimal negative predictive value (NPV) and the best cutoff associated with avoiding false negative SLN detection, in order to assist the clinician's decision of when to spare ePLND. RESULTS: LNI was detected in 35 patients (17.2 %). Based on preoperative primary Gleason grade and percentage of positive cores, a bivariate model was built to calculate a combined score reflecting the risk of LNI. For the Briganti nomogram, the 5 % probability cutoff avoided ePLND in 53 % (108/202) of patients, missing three LNI patients (8.6 %), but all were detected by the SLN technique. For our bivariate model, the best cutoff was <10, leaving no patient with LNI due to positive SLN detection (four patients = 11.4 %), and avoiding ePLND in 52 % (105/202) of patients. CONCLUSION: For patients with a low risk of LNI determined using the updated Briganti nomogram or bivariate model, SLN technique could be used alone for lymph node staging in intermediate- or high-risk PC patients.

Severe X-linked chondrodysplasia punctata in nine new female fetuses.

OBJECTIVES: Conradi-Hünermann-Happle [X-linked dominant chondrodysplasia punctata 2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in men while affected women show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only six antenatal presentations. METHODS: To better characterize the phenotype in female fetuses, we included nine antenatally diagnosed cases of women with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism. RESULTS: The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation. CONCLUSION: Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially because the majority of such cases involve de novo mutations.

Fetal presentation of congenital fibrosarcoma of the meninges: case report and literature review.

AIM: Congenital infantile fibrosarcoma (CIFS) exceptionally occurs in the meninges, with no cases reported before or at birth. We report herein a meningeal CIFS diagnosed in a fetus at 40 weeks of gestation (WG). CASE REPORT: A 24-year-old pregnant woman was referred to the obstetrics department for vaginal bleeding. A severe right hydrocephalus due to a large tumor invading the left hemisphere and ventricles was discovered in the fetus, and medical termination of the pregnancy was achieved. RESULTS: Histological examination revealed a highly cellular spindle or ovoid shaped cell proliferation organized in interlacing bundles; it was diffusely positive for vimentin, and scarcely for SMA (smooth muscle actin). NFs (neurofilaments), NeuN, S100 protein, desmin, GFAP (glial fibrillary acidic protein), Olig2, chromogranin, synaptophysin, CD31, CD34, BCL2, and EMA (epithelial membrane antigen) antibodies were negative. Ki67 antibody labeled 20% of the nuclei. A reverse transcription polymerase chain reaction assay was performed to detect the gene fusion ETV6-NTRK3 transcript. Despite negative results, it was concluded to be a CIFS of the meninges. DISCUSSION: CIFS of the meninges during the fetal period has never been reported. Its diagnosis is based on immunohistochemistry, and, whenever possible, on the detection of the reciprocal translocation t (12;15) resulting in the gene fusion ETV6-NTRK3. Its prognosis depends on rapid growth and local invasiveness leading to cerebral structure damage.

Laparoscopic sentinel lymph node versus hyperextensive pelvic dissection for staging clinically localized prostate carcinoma: a prospective study of 200 patients.

UNLABELLED: Lymph node metastasis is an important prognostic factor in prostate cancer (PC). The aim of this prospective study was to validate, through laparoscopic surgery, the accuracy of the isotopic sentinel lymph node (SLN) technique correlated with hyperextensive pelvic resection (extended pelvic lymphadenectomy dissection) in patients with localized PC, candidates for local curative treatment. METHODS: A transrectal ultrasound-guided injection of (99m)Tc-sulfur rhenium colloid (0.3 mL/100 MBq) in each prostatic lobe was performed the day before surgery. Detection was performed intraoperatively with a laparoscopic probe, followed by extensive resection. SLN counts were performed in vivo and confirmed ex vivo. Histologic analysis was performed by hematoxylin-phloxine-safran staining, followed by immunohistochemistry if the SLN was free of metastasis. RESULTS: Two hundred three patients with PC at intermediate or high risk of lymph node metastases were included. The intraoperative detection rate was 96% (195/203). Thirty-five patients had lymph node metastases, 19 only in the SLN. The false-negative rate was 8.5% (3/35). Unilateral surgical SLN detection did not validate bilateral pelvic lymph node status, and extended pelvic lymphadenectomy dissection was necessary on the opposite side of detection to minimize the false-negative rate (2.8% [1/35]). A significant metastatic sentinel invasion in the common iliac region existed (9.3%) but was always associated with other metastatic node areas. The internal iliac region was the primary metastatic site (40.7%). Finally, this series invalidated any justification for a standard or limited dissection, which would have missed 51.9% and 74.1% of lymph node metastases, respectively. CONCLUSION: The radioisotope SLN identification method up to the common iliac region is successful to identify sentinel nodes during laparoscopic surgery per hemipelvis to be acceptably considered as an isolated procedure and should be validated for intermediate- and high-risk patients.

Reference ranges and distribution of placental volume by 3-dimensional virtual organ computer-aided analysis between 11 weeks and 13 weeks 6 days.

OBJECTIVES: The purpose of this study was to determine the feasibility, reproducibility, and distribution of placental volume measurements according to the crown-rump length between 11 weeks and 13 weeks 6 days. METHODS: Images were acquired in 128 pregnancies followed in Burgundy during first-trimester screening sonography using an abdominal 3-dimensional transducer. The placental volume was then calculated by the virtual organ computer-aided analysis method with a rotation angle of 30° by a single operator. RESULTS: Placental volumes ranged from 33.3 to 107.6 cm(3) with a mean ± SD of 62.3 ± 14.8 cm(3); the 5th and 10th percentiles were 38.0 and 44.20 cm(3), respectively, whereas the 90th and 95th percentiles were 80.25 and 86.68 cm(3). An exponential relationship was found between placental volume and crown-rump length: ln placental volume = 0.018 × crown-rump length + 2.93425; ln SD = 0.15; r(2) = 0.58. Finally, the mean placental quotient, defined as the ratio of placental volume to crown-rump length, was 1 ± 0.1 cm(3)/mm; the respective percentile values were 0.74, 0.81, 1.18, and 1.29 cm(3)/mm. No associations were found between parity or smoking and the placental quotient or between obesity and the placental quotient. Intraobserver reproducibility was good, with a mean difference of 0.2 cm(3). CONCLUSIONS: Measurement of placental volume between 11 weeks and 13 weeks 6 days is reliable and reproducible and correlates strongly with crown-rump length.