Stage I–II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I–II colon cancer patients. A total of 1940 LN from 149 pathologically assessed pN0 colon cancer patients were analysed for the amount of tumour cytokeratin 19 (CK19) messenger RNA (mRNA) with the quantitative reverse transcription loop-mediated isothermal amplification molecular assay One-Step Nucleic Acid Amplification. Patient’s total tumour load (TTL) resulted from the sum of all CK19 mRNA tumour copies/μL of each positive LN from the colectomy specimen. A median of 15 LN were procured per case (IQR 12;20). Molecular positivity correlated with high-grade (p < 0.01), mucinous/signet ring type (p = 0.017), male gender (p = 0.02), number of collected LN (p = 0.012) and total LN weight per case (p < 0.01). The TTL was related to pT stage (p = 0.01) and tumour size (p < 0.01) in low-grade tumours. Multivariate logistic regression showed independent correlation of molecular positivity with gender, tumour grade and number of fresh LN [AUC = 0.71 (95 % CI = 0.62–0.79)]. Our results show that lymph node CK19 mRNA detection correlates with classical high-risk factors in stage I–II colon cancer patients. Total tumour load is a quantitative and objective measure that may help to better stage early colon cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00428-016-1990-1) contains supplementary material, which is available to authorized users.

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

Summary Background Conflicting results have been recently reported for the accuracy of the Endoscopic Reference Score (EREFS), an standardised endoscopic classification, to predict the histological activity of eosinophilic oesophagitis (EoE). Aim To evaluate the accuracy of the EREFS to predict either histological or clinical activity of EoE. Methods Prospective multicentre study conducted in eight Spanish centres evaluating adult EoE patients, either naïve or after treatment. Symptoms were evaluated before upper endoscopy through the Dysphagia Symptom Score, whereas researchers scored the EREFS immediately after the endoscopic procedure, unaware of the histological outcome. Results One hundred and forty‐five EoE patients undergoing 240 consecutive endoscopic procedures were included. Exudates (P = 0.03), furrows (P = 0.03) and a composite score of inflammatory signs (exudates, furrows and oedema) (P < 0.001) accurately predicted histological activity. Exudates were the only endoscopic sign showing a good correlation with histological outcome after therapy. Furrows and oedema persisted in 50% and 70% of patients despite histological remission. No endoscopic feature exceeded 70% accuracy to predict histological activity. Likewise, no endoscopic finding could adequately predict dysphagia severity. Crepe paper mucosa, diffuse exudates and severe rings correlated with higher symptom scores. Conclusions Endoscopic findings assessed by the Endoscopic Reference Score did not correlate with histological or clinical disease activity in adult EoE patients. Only exudates correlated with peak eosinophil count and histological outcome, whereas furrows and oedema persisted in over half of patients despite histological remission.

When de Castro entered the carotid body (CB) field, the organ was considered to be a small autonomic ganglion, a gland, a glomus or glomerulus, or a paraganglion. In his 1928 paper, de Castro concluded: “In sum, the Glomus caroticum is innervated by centripetal fibers, whose trophic centers are located in the sensory ganglia of the glossopharyngeal, and not by centrifugal [efferent] or secretomotor fibers as is the case for glands; these are precisely the facts which lead to suppose that the Glomus caroticum is a sensory organ.” A few pages down, de Castro wrote: “The Glomus represents an organ with multiple receptors furnished with specialized receptor cells like those of other sensory organs [taste buds?]…As a plausible hypothesis we propose that the Glomus caroticum represents a sensory organ, at present the only one in its kind, dedicated to capture certain qualitative variations in the composition of blood, a function that, possibly by a reflex mechanism would have an effect on the functional activity of other organs… Therefore, the sensory fiber would not be directly stimulated by blood, but via the intermediation of the epithelial cells of the organ, which, as their structure suggests, possess a secretory function which would participate in the stimulation of the centripetal fibers.” In our article we will recreate the experiments that allowed Fernando de Castro to reach this first conclusion. Also, we will scrutinize the natural endowments and the scientific knowledge that drove de Castro to make the triple hypotheses: the CB as chemoreceptor (variations in blood composition), as a secondary sensory receptor which functioning involves a chemical synapse, and as a center, origin of systemic reflexes. After a brief account of the systemic reflex effects resulting from the CB stimulation, we will complete our article with a general view of the cellular-molecular mechanisms currently thought to be involved in the functioning of this arterial chemoreceptor.