Measurement of histological clearance margins in basal cell carcinoma.

AIMS: Basal cell carcinoma (BCC) is a common cancer, with a high risk of local recurrence. A quantifiable measurement of the histological margins of BCC in excisions is a recurrent demand of clinicians; however, there are currently no international guidelines indicating its value. METHODS AND RESULTS: A questionnaire validated by four experts in dermatopathology and formatted under a 'Google Forms'-type interface was sent by e-mail to physicians specializing in surgical pathology or dermatopathology and practising in France from 20 March 2018 to 20 May 2018. The results were compared between subgroups according to age and subspecialisation, especially dermatopathology. The questionnaire was completed by 225 practitioners. Microscopic margins were systematically measured in 77.3% of cases, sometimes in 19.6% and never in 3.1%. The main reason was to report factually insufficient margins (66.5%), followed by laboratory routine (45%) or clinician requests (43.1%). For 72% of respondents, the clinical or histopathological criteria did not influence their practice. The most used tool was a graduated ruler placed under a microscope (44.3% of cases). Compared to other groups, dermatopathologists measured BCC margins less systematically [only in certain situations (33.3 versus 14.9%) or never (10.5 versus 0.6%) (P < 0.001)] and used an eyepiece reticle more extensively (53.1 versus 29.8%; P = 0.0029). CONCLUSION: The measurement of histological margins in BCC is common practice in France, although there are no recommendations. Our survey suggests that it represents a way for pathologists to specify an insufficient margin and therefore the need for scar revision.

Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance.

The influence of the gut microbiome on metabolic and behavioral traits is widely accepted, though the microbiome-derived metabolites involved remain unclear. We carried out untargeted urine 1H-NMR spectroscopy-based metabolic phenotyping in an isogenic C57BL/6J mouse population (n = 50) and show that microbial-host co-metabolites are prodromal (i.e., early) markers predicting future divergence in metabolic (obesity and glucose homeostasis) and behavioral (anxiety and activity) outcomes with 94%-100% accuracy. Some of these metabolites also modulate disease phenotypes, best illustrated by trimethylamine-N-oxide (TMAO), a product of microbial-host co-metabolism predicting future obesity, impaired glucose tolerance (IGT), and behavior while reducing endoplasmic reticulum stress and lipogenesis in 3T3-L1 adipocytes. Chronic in vivo TMAO treatment limits IGT in HFD-fed mice and isolated pancreatic islets by increasing insulin secretion. We highlight the prodromal potential of microbial metabolites to predict disease outcomes and their potential in shaping mammalian phenotypic heterogeneity.