CT scan for early diagnosis of anastomotic leak after colorectal surgery: is rectal contrast useful?

BACKGROUND: Computed tomography (CT) scan with rectal contrast enema (RCE-CT) could increase the detection rate of anastomotic leaks (AL) in the early postoperative period following colorectal surgery, compared to CT scan without RCE. The aim of this study was to assess the benefit of RCE-CT for the early diagnosis of AL following colorectal surgery. METHODS: Patients who had a RCE-CT for suspected AL in the early postoperative period following colorectal surgery with anastomosis between January 2012 and July 2019 at the Dijon University Hospital were retrospectively included. All images were reviewed by two independent observers who were blinded to the original report. The reviewers reported for each patient whether an AL was present or not in each imaging modality (CT scan, then RCE-CT). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were then calculated to determine the diagnostic performance of each modality. RESULTS: One hundred and thirty-nine patients were included. RCE-CT had an increased NPV compared to CT scan (82% vs 77% (p = 0.02) and 84% vs 68% (p < 0.0001) for observers 1 and 2, respectively). RCE-CT had an increased sensitivity compared to CT scan (79% vs 48% (p < 0.0001) for observer 2). RCE-CT had a significant lower false-negative rate for both observers: 18% vs 23% (p = 0.02) and 16% vs 32% (p < 0.0001). CONCLUSIONS: RCE-CT improved the detection rates of AL in the early period following colorectal surgery. RCE-CT should be recommended when a CT scan is negative and AL is still suspected.

Do assisted reproductive technologies and in vitro embryo culture influence the epigenetic control of imprinted genes and transposable elements in children?

STUDY QUESTION: Do assisted reproductive technologies (ART) and in vitro embryo culture influence the epigenetic control of imprinted genes (IGs) and transposable elements (TEs) in children? SUMMARY ANSWER: Significant differences in the DNA methylation of IGs or transposon families were reported between ART and naturally conceived children, but there was no difference between culture media. WHAT IS KNOWN ALREADY: There is concern that ART may play a role in increasing the incidence of adverse health outcomes in children, probably through epigenetic mechanisms. It is crucial to assess epigenetic control, especially following non-optimal in vitro culture conditions and to compare epigenetic analyses from ART-conceived and naturally conceived children. STUDY DESIGN, SIZE, DURATION: This follow-up study was based on an earlier randomized study comparing in vitro fertilization outcomes following the use of two distinct culture media. We compared the epigenetic profiles of children from the initial randomized study according to the mode of conception [i.e. ART singletons compared with those of a cohort of naturally conceived singleton children (CTL)], the type of embryo culture medium used [global medium (LifeGlobal) and single step medium (Irvine Scientific)] and the mode of in vitro fertilization (i.e. IVF versus ICSI). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 57 buccal smears were collected from 7- to 8-year-old children. The DNA methylation profiles of four differentially methylated regions (DMRs) of IGs (H19/IGF2: IG-DMR, KCNQ1OT1: TSS-DMR, SNURF: TSS-DMR, and PEG3: TSS-DMR) and two TEs (AluYa5 and LINE-1) were first assessed by pyrosequencing. We further explored IGs and TEs' methylation changes through methylation array (Human MethylationEPIC BeadChip referred as EPIC array, Illumina). MAIN RESULTS AND THE ROLE OF CHANCE: Changes in the IGs' DNA methylation levels were found in ART children compared to controls. DNA methylation levels of H19/IGF2 DMR were significantly lower in ART children than in CTL children [52% versus 58%, P = 0.003, false discovery rate (FDR) P = 0.018] while a significantly higher methylation rate was observed for the PEG3 DMR (51% versus 48%, P = 0.007, FDR P = 0.021). However, no differences were found between the culture media. After observing these targeted modifications, analyses were performed at wider scale. Again, no differences were detected according to the culture media, but imprinted-related DMRs overlapping promoter region near the genes major for the development (MEG3, BLCAP, and DLX5) were detected between the ART and CTL children. LIMITATIONS, REASONS FOR CAUTION: The sample size could seem relatively small, but the high consistency of our results was ensured by the homogeneity of the cohort from the initial randomized study, the standardized laboratory techniques and the robust statistical analyses accounting for multiple testing. WIDER IMPLICATIONS OF THE FINDINGS: Although this study did not report DNA methylation differences depending on the culture medium, it sheds light on epigenetic changes that could be observed in some children conceived by ART as compared to CTL children. The clinical relevance of such differences remains largely unknown, and it is still unclear whether such changes are due to some specific ART procedures and/or to parental infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by funding from the Agence Nationale pour la Recherche ('CARE'-ANR JCJC 2017). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Not concerned.

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study.

BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: results from the multicenter, randomised trial Fédération Francophone de Cancérologie Digestive 9601.

OBJECTIVE: To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC). DESIGN: Among the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test. RESULTS: Among the 216 patients with stage IV CRC (median follow-up, 33 months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p=0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval [CI], 0.4-0.8; p=0.0002) and OS (HR, 0.4; CI, 0.3-0.6; p<0.0001). Both median PFS (5.1 [4.6-5.6] versus 2.9 [2.2-4.1] months; p=0.001) and OS (16.3 [13.7-19.2] versus 9.6 [7.4-12.5]; p<0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary (n=43). CONCLUSION: Resection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.