Fecal calprotectin levels in patients with non-celiac wheat sensitivity: a proof of concept.

Some data suggest the existence of intestinal inflammation in patients with non-celiac wheat sensitivity (NCWS). We aimed to verify whether fecal calprotectin (FCP), a marker of intestinal inflammation, could be used to confirm this inflammatory status and to test its diagnostic performance in differentiating NCWS from irritable bowel syndrome/functional dyspepsia (IBS/FD). We conducted a multicenter study, comparing NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge, with IBS/FD subjects. In the retrospective phase, FCP values were analyzed to define the prevalence of its positivity and its role as a NCWS diagnostic biomarker. In the prospective phase we tested the effects of a strict 6-month wheat-free diet (WFD) on FCP values. 31.3% (n = 63/201) of NCWS patients had above normal FCP values (NCWS FCP +), whereas all IBS/FD patients proved negative (P = 0.0001). FCP using a cut-off value > 41 µg/g showed a 58.6% sensitivity and a 98.0% specificity (AUC 0.755, 95% C.I. 0.702-0.837) in distinguishing NCWS from IBS/FD patients. Of the 63 NCWS FCP+, 65.1% had negative FCP values after ≥ 6 months of WFD, with a significant reduction in FCP values (P < 0.0001). All NCWS FCP- subjects still preserved negative FCP values after ≥ 6 months of WFD. Our study showed that FCP can be a useful but supplementary diagnostic marker for differentiating between NCWS and IBS/FD. Strict WFD adherence reduced FCP values, normalizing them in 65.1% of NCWS FCP + subjects. These data suggest the existence of two NCWS subgroups: NCWS FCP + characterized by a probable predominantly inflammatory/immunologic pattern and NCWS FCP- featuring non-immuno-mediated etiopathogenetic mechanisms. (Registration number NCT01762579).

Duodenal and Rectal Mucosa Inflammation in Patients With Non-celiac Wheat Sensitivity.

BACKGROUND & AIMS: Studies of non-celiac gluten or wheat sensitivity (NCGWS) have increased but there are no biomarkers of this disorder. We aimed to evaluate histologic features of colon and rectal tissues from patients with NCGWS. METHODS: We performed a prospective study of 78 patients (66 female; mean age, 36.4 years) diagnosed with NCGWS by double-blind wheat challenge at 2 tertiary care centers in Italy, from January 2015 through September 2016. Data were also collected from 55 patients wither either celiac disease or self-reported NCGWS but negative results from the wheat-challenge test (non-NCGWS controls). Duodenal and rectal biopsies were collected and analyzed by immunohistochemistry to quantify intra-epithelial CD3+ T cells, lamina propria CD45+ cells, CD4+ and CD8+ T cells, mast cells, and eosinophils and to determine the presence and size of lymphoid nodules in patients with NCGWS vs patients with celiac disease or non-NCGWS controls. RESULTS: Duodenal tissues from patients with NCGWS had significantly higher numbers of intra-epithelial CD3+ T cells, lamina propria CD45+ cells, and eosinophils than duodenal tissues from non-NCGWS controls. Duodenal tissues from patients with NCGWS and dyspepsia had a higher number of lamina propria eosinophils than patients with NCGWS without upper digestive tract symptoms. Rectal mucosa from patients with NCGWS had a larger number of enlarged lymphoid follicles, intra-epithelial CD3+ T cells, lamina propria CD45+ cells, and eosinophils than rectal mucosa from non-NCGWS controls. Duodenal and rectal mucosal tissues from patients with celiac disease had more immunocytes (CD45+ cells, CD3+ cells, and eosinophils) than tissues from patients with NCGWS or non-NCGWS controls. CONCLUSIONS: We identified markers of inflammation, including increased numbers of eosinophils, in duodenal and rectal mucosa from patients with NCGWS. NCGWS might therefore involve inflammation of the entire intestinal tract. Eosinophils could serve as a biomarker for NCGWS and be involved in its pathogenesis. Clinicaltrials.gov: NCT01762579.

ß-amyloid wall deposit of temporal artery in subjects with spontaneous intracerebral haemorrhage.

BACKGROUND: Cerebral Amyloid Angiopathy has been indicated as an important cause of spontaneous non-hypertensive intracerebral haemorrhage (ICH). AIMS: to analyze the presence of ß-amyloid deposit in the temporal artery of consecutive patients with ICH in comparison to control subjects and its relation to APO-E haplotype frequency. METHODS: We enrolled consecutive patients admitted to Neurosurgery Ward of University Hospital "P. Giaccone" of Palermo with a diagnosis of spontaneous non hypertensive ICH and as control 12 subjects without brain haemorrhage. Biopsy of superficial temporal artery has been performed and ß-amyloid deposit was quantified. RESULTS: Among 25 subjects with ICH, 10 (40%) had APOE epsilon 2 allele and among these subjects 7 (70%) showed amyloid accumulation on temporal artery specimens, 8 (32%) subjects had APOE epsilon 3 allele and among these subjects only 2 (25%) showed amyloid accumulation on temporal artery specimens, whereas 7 (28%) had APOE epsilon 4 allele and of these, 7 (100%) showed amyloid accumulation on temporal artery specimens. At multivariable logistic regression analysis for the presence of amyloid, predictive factors for the presence of amyloid in temporal artery biopsies were: age, hypertension, intralobar site of haemorrhage, APOE epsilon 2 and APOE epsilon 4 alleles. DISCUSSION: Our findings of a higher frequency of amyloid deposition in temporal artery specimens in subjects with spontaneous intracerebral haemorrhage indicate a possible role of temporal artery as a possible diagnostic site of biopsy in subjects at high risk to develop intracranial haemorrhage related to Cerebral Amyloid Angiopathy.

Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic Tumor (PHAT).

Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion characterized by slow growth, infiltrative behavior and high rate of local recurrences. Only one case has been described in retroperitoneum, at renal hilum, but not involving pelvis or parenchyma. Here we present the first case of PHAT arising in the renal parenchyma. A nodular lesion in right kidney lower pole was diagnosed to a 61 year old woman. The patient underwent right nephrectomy. Microscopically, the lesion showed solid and pseudo-cystic components with hemorrhagic areas characterized by aggregates of ectatic blood vessels. Pleomorphic cells were characterized by large eosinophilic cytoplasm with irregular and hyperchromatic nuclei. Immunohistochemistry was performed and the lesion was classified as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT). Due to the clinical behavior of this tumor, in spite of its benign nature, review of the surgical margins and close follow up after partial nephrectomy are mandatory.