RACCE Study: Impact of an enhanced recovery after surgery program (ERAS) in the management of endometrial cancer: A single-center retrospective study.

OBJECTIVE: This study evaluates the implementation of an ERAS program in the gynecological surgery department of Caen University Hospital and its impact on the management of endometrial cancer. The objective was to show its impact on the length of hospitalization of patients before and after its implementation. PATIENTS AND METHOD: We conducted a retrospective study including all women treated surgically for endometrial cancer at Caen University Hospital between January 1, 2015 and December 31, 2021. The ERAS program started in September 2017. We compared the pre-, intra- and postoperative characteristics of two groups: the first one concerning the period before the implementation of ERAS called « prior ERAS group ¼ and the second one after implementation called « post ERAS group ¼. RESULTS: A total of 198 patients were included in our study. 139 patients were included after ERAS implementation. Our study shows that there is a significant reduction in median length of stay between the post ERAS and prior ERAS groups respectively 3 and 4 days (p = 0.004). There was also a reduction of time to resume ambulation (p < 0.001) and re-feeding (p < 0.001) for the post ERAS group compared to the prior ERAS group. Complication rates (p = 0.87) and readmission rates (p = 0.28) were not significant. Overall survival was not significant (p = 0.28). CONCLUSION: ERAS is a safe and effective method in the overall management of patients allowing an improvement in the quality of patient care and accelerating recovery to a previous physiological state. Finally, this results in a reduction in the patient's length of stay, without impacting morbidity and readmission rate.

Utility of 2D-ultrasound in pelvic floor muscle contraction and bladder neck mobility assessment in women with urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Assessment of pelvic floor muscle (PFM) contraction and bladder neck (BN) mobility in women with stress urinary incontinence (SUI) is essentially clinical. Ultrasound is increasingly used as a method for evaluating BN mobility and PFM contraction, but has not been standardized. The aim of this study was to review ultrasound technics and parameters that might be relevant for PFM contraction and BN mobility assessment in women with urinary incontinence (UI). METHODS: We reviewed articles indexed in the MEDLINE database between 1988 and 2018 and selected articles which had a cohort of women with UI who had undergone functional 2D-ultrasound evaluation of PFM or BN mobility. RESULTS: Transperineal ultrasound provides a panoramic view of the pelvic organs without modifying the anatomical relationship between the urethra and surrounding structural landmarks. One of the measurements used to assess urethral mobility is bladder neck descent (BND), which has been shown to be extremely reliable. Measuring the anteroposterior diameter (APD) of the urogenital levator hiatus can also reliably quantify PFM contraction in women. The more recently developed technique of elastography could be an additional useful non-invasive method for measuring periurethral striated muscle stiffness. CONCLUSIONS: Several ultrasound parameters such as BND, anorectal angle displacement and periurethral stiffness as measured by elastography are relevant for investigating UI in women undertaking pelvic floor muscle training. Our hypothesis is that these ultrasound parameters can be correlated with urinary symptoms and clinical contraction assessment. They need to be validated for clinical use.

BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer.

Germline allele specific expression (ASE), resulting in a lowered expression of one of the BRCA1 alleles, has been described as a possible predisposition marker in Hereditary Breast or Ovarian Cancer (HBOC), usable for molecular diagnosis in HBOC. The main objective of this prospective case-control study was to compare the proportion of ASE between controls without familial history of breast or ovarian cancer, and HBOC cases without BRCA1 or BRCA2 deleterious mutation. BRCA1 ASE evaluated on three SNPs among controls and HBOC patients without deleterious mutation were assessed by pyrosequencing. The allelic ratios and the proportion of ASE were compared between controls and cases using a Student's t test and a Fisher exact test, respectively. The linearity and reproducibility of the ASE dosage was demonstrated with R2 > 0.99 and a coefficient of variation below 10 %, and ASE was detected in two positive controls harbouring BRCA1 truncated mutations. In the heterozygote population, composed of 99/264 controls (37.5 %) and 96/227 patients (42.3 %), we detected a 5 % ASE without truncated mutations, in each population. We failed to detect any significant difference of ASE between controls and patients. So far, BRCA1 Allelic specific expression is not usable in routine diagnosis as a possible predisposition marker in HBOC patients except for the detection of truncated mutations.

Multiple sequence variants of BRCA2 exon 7 alter splicing regulation.

BACKGROUND: Exonic variants of unknown biological significance (VUS) identified in patients can affect mRNA splicing, either by changing 5' or 3' splice sites or by modifying splicing regulatory elements. Bioinformatic predictions of these elements are still inaccurate and only few such elements have been functionally mapped in BRCA2. We studied the effect on splicing of eight exon 7 VUS, selected from the French UMD-BRCA2 mutation database. METHODS: We performed splicing minigene assays and analyses of patient RNA. We also developed a pyrosequencing-based quantitative assay, to measure, in patient RNA, the relative contribution of each allele to the production of exon 7-containing transcripts. Moreover, an exonic splicing enhancer (ESE)-dependent minigene assay was used to evaluate the splicing regulatory properties of wild-type and mutant segments. RESULTS: Six out of the eight variants induced splicing defects. In the minigene assay, c.517G>T and c.631G>A altered the natural splice sites, c.572A>G created a new 5' splice site, and c.520C>T, c.587G>A and c.617C>G induced exon 7 skipping (66%, 25% and 46%, respectively). Pyrosequencing of patient RNA confirmed these levels of exon skipping for c.520C>T and c.617C>G. Results from the ESE-dependent minigene assay indicated that c.520C>T and c.587G>A disturb splicing regulatory elements. CONCLUSIONS: BRCA2 exon 7 splicing is regulated by multiple exonic elements and is sensitive to disease-associated sequence variations. Measurements of allelic imbalance in patient-derived RNA and/or quantitative analyses using minigene assays provide valuable estimates of the extent of partial splicing defects. Assessment of pathogenicity of variants with partial splicing effect awaits additional evidence and especially the completion of segregation analyses.