The clinical and phenotypical assessment of seronegative villous atrophy; a prospective UK centre experience evaluating 200 adult cases over a 15-year period (2000-2015).

BACKGROUND: Seronegative villous atrophy (SNVA) is commonly attributed to coeliac disease (CD). However, there are other causes of SNVA. More recently angiotensin-2-receptor-blockers (A2RBs) have been reported as an association but data on SNVA have been limited to centres evaluating complex case referrals and not SNVA in general. OBJECTIVES: To provide clinical outcomes and associations in a large prospective study overseeing all newcomers with SNVA. DESIGN: Over a 15-year period (2000-2015) we evaluated 200 adult patients with SNVA at a UK centre. A diagnosis of either seronegative CD (SNCD) or seronegative non-CD (SN-non-CD) was reached. Baseline comparisons were made between the groups, with 343 seropositive CD subjects serving as controls. RESULTS: Of the 200 SNVA cases, SNCD represented 31% (n=62) and SN-non-CD 69% (n=138). The human leucocyte antigen (HLA)-DQ2 and/or DQ8 genotype was present in 61%, with a 51% positive predictive value for SNCD. The breakdown of identifiable causes in the SN-non-CD group comprised infections (27%, n=54), inflammatory/immune-mediated disorders (17.5%, n=35) and drugs (6.5%, n=13; two cases related to A2RBs). However, no cause was found in 18% (n=36) and of these 72% (n=26/36) spontaneously normalised duodenal histology while consuming a gluten-enriched diet. Following multivariable logistic regression analysis an independent factor associated with SN-non-CD was non-white ethnicity (OR 10.8, 95% CI 2.2 to 52.8); in fact, 66% of non-whites had GI infections. On immunohistochemistry all groups stained positive for CD8-T-cytotoxic intraepithelial lymphocytes. However, additional CD4-T helper intraepithelial lymphocytes were occasionally seen in SN-non-CD mimicking the changes associated with refractory CD. CONCLUSIONS: Most patients with SNVA do not have CD, in particular those who are not white. Furthermore, a subgroup with no obvious aetiology will show spontaneous histological resolution while consuming gluten. These findings suggest caution in empirically prescribing a gluten-free diet without investigation.

Radioprotective potential of Lagenaria siceraria extract against radiation-induced gastrointestinal injury.

The cucurbits (prebiotics) were investigated as novel agents for radio-modification against gastrointestinal injury. The cell-cycle fractions and DNA damage were monitored in HCT-15 cells. A cucurbit extract was added to culture medium 2 h before irradiation (6 Gy) and was substituted by fresh medium at 4 h post-irradiation. The whole extract of the fruits of Lagenaria siceraria, Luffa cylindrica, or Cucurbita pepo extract enhanced G2 fractions (42%, 34%, and 37%, respectively) as compared with control (20%) and irradiated control (31%). With cucurbits, the comet tail length remained shorter (L. siceraria, 28 µm; L. cylindrica, 34.2 µm; C. pepo, 36.75 µm) than irradiated control (41.75 µm). For in vivo studies, L. siceraria extract (2 mg/kg body weight) was administered orally to mice at 2 h before and 4 and 24 h after whole-body irradiation (10 Gy). L. siceraria treatment restored the glutathione contents to 48.8 µmol/gm as compared with control (27.6 µmol/gm) and irradiated control (19.6 µmol/gm). Irradiation reduced the villi height from 379 to 350 µm and width from 54 to 27 µm. L. siceraria administration countered the radiation effects (length, 366 µm; width, 30 µm, respectively) and improved the villi morphology and tight junction integrity. This study reveals the therapeutic potential of cucurbits against radiation-induced gastrointestinal injury.

Assessment of conjunctival microvilli abnormality by micro-Raman analysis - by G. Rusciano et al.

Conjunctival microvilli are microscopic cellular membrane protrusions on apical epithelial cells, which increase the surface area available for tear adherence. Pathological alterations of microvilli structure affect the tear film stability and, conversely, dysfunctions of tear film composition can lead to a suffering epithelium (dry-eye syndrome). In this work we propose the use of micro-Raman analysis to reveal conjunctival microvilli abnormalities. Samples were obtained by impression cytology from patients by different stage of dry-eye syndrome. Our experimental outcomes demonstrate that Raman analysis, combined with the use of Principal Component Analysis, is able to detect different stages of microvilli reduction. Globally, these results hold promise for the use of Raman analysis for an objective, effective, non-invasive and potentially also in-vivo analysis of the conjunctiva in all the cases of microvilli-related ocular pathologies.

Quantitative assessment of endoscopic images for degree of villous atrophy in celiac disease.

BACKGROUND: The degree of villous atrophy in celiac disease is difficult to assess at endoscopy. We sought to develop a quantitative technique for the evaluation of villous atrophy in endoscopic images. METHOD: In ten celiac patients as identified by standard endoscopy with biopsy, and ten control patients, standard and videocapsule endoscopic images of the duodenum were digitized. Subimages 7.5 × 7.5 mm(2) in area from random locations within each image were assessed by measuring the length of mucosal fissures per unit area (L), and correlating L with the histologic grade of villous atrophy as determined by modified Marsh criteria. RESULTS: Mean L values for standard endoscopic images were 37.8, 43.3, 64.1, and 83.5 mm for Marsh grades II, IIIa, IIIb, and IIIc, respectively. Mean L values for videocapsule images were 49.1, 50.0, 64.7, and 72.4 mm for Marsh grades II, IIIa, IIIb, and IIIc, respectively. Significant differences in the means existed between celiac images (Marsh scores II-IIIc) versus controls (p < 0.001) for both endoscopic and videocapsule images. There were no significant differences between measurements obtained from endoscopic versus videocapsule images. CONCLUSIONS: Quantified image analysis correlates with the histologic grade of villous atrophy, is automated, and lacks observer bias, thus lending itself to standardization.

Quantitative assessment of the degree of villous atrophy in patients with coeliac disease.

BACKGROUND: Endoscopy and biopsy are used to diagnose coeliac disease. There are, however, observer-dependent interpretations of the degree of villous atrophy in biopsies. A pilot study using quantitative image-processing procedures was performed to quantify the degree of villous atrophy in patients with coeliac disease. METHOD: The degree of villous atrophy in duodenal biopsy images was quantified by calculating the ratio of villous edge-to-piecewise arc length (E/P ratio), and this value was compared with the blinded assessment of Marsh score for degree of villous atrophy. RESULTS: Mean E/P ratios for n = 31 biopsy images, 2.76 (SD 0.44) (Marsh IIIa), 1.91 (0.50) (Marsh IIIb) and 1.18 (0.22) (Marsh IIIc), were significantly different (p = 0.006). Based on non-parametric testing, the E/P ratios were inversely correlated with Marsh scores (Spearman coefficient rho = -0.798, Kendall tau = -0.681; p<0.0001). CONCLUSIONS: Biopsy images quantified by image analysis correlated exceedingly well with the histopathological grade of villous atrophy. Since quantified measurements are real-numbered values and lack observer bias, measurement of villous atrophy based on image analysis lends itself to standardisation of histological grading.