This review summarizes dietary carbohydrate intolerance conditions and recent advances on the possible role of carbohydrate maldigestion and dietary outcomes in patients with functional bowel ...disease. When malabsorbed carbohydrates reach the colon, they are fermented by colonic bacteria, with the production of short-chain fatty acids and gas lowering colonic pH. The appearance of diarrhoea or symptoms of flatulence depends in part on the balance between the production and elimination of these fermentation products. Different studies have shown that there are no differences in the frequency of sugar malabsorption between patients with irritable bowel disease (IBS) and healthy controls; however, the severity of symptoms after a sugar challenge is higher in patients than in controls. A diet low in 'Fermentable, Oligo-Di- and Monosaccharides and Polyols' (FODMAPs) is an effective treatment for global symptoms and abdominal pain in IBS, but its implementation should be supervised by a trained dietitian. A 'bottom-up' approach to the low-FODMAP diet has been suggested to avoid an alteration of gut microbiota and nutritional status. Two approaches have been suggested in this regard: starting with only certain subgroups of the low-FODMAP diet based on dietary history or with a gluten-free diet.
Summary
Background
The causes of seronegative villous atrophy can be grouped as coeliac or noncoeliac related. There is no consensus on how to approach subjects with seronegative coeliac disease.
Aim
...To evaluate the accuracy of both an increase in CD3+ T‐cell receptor gamma delta+ (TCRγδ+) intraepithelial lymphocytes and coeliac lymphogram for the diagnosis of coeliac disease in patients with seronegative villous atrophy.
Methods
Sixty‐seven consecutive patients with seronegative villous atrophy were included. Duodenal biopsies to assess TCRγδ+ and CD3− by flow cytometry were performed at the index endoscopy. Coeliac lymphogram was defined as an increase in TCRγδ+ plus a decrease in CD3− intraepithelial lymphocytes. Sensitivity, specificity and Fagan's nomogram were calculated.
Results
Coeliac disease was diagnosed in 37 patients and noncoeliac villous atrophy in 30. Coeliac patients were younger (39 ± 3 vs 55 ± 3 years; P = 0.001), more often showed HLA‐DQ2/8 (97.6% vs 61%; P = 0.002) and had a more severe histology (61% vs 32% Marsh 3b‐c; P = 0.055), as compared to noncoeliac ones. Coeliac lymphogram was associated with a sensitivity of 87% (CI, 73.7‐95) and specificity of 96.7% (82.7‐99.9), whereas evaluating only TCRγδ+ yielded a sensitivity of 91.3% (79.2‐97.6) and specificity of 83.3% (65.3‐94.3). Among patients with a pre‐test coeliac disease probability of 30%, post‐test probabilities were 92% and 5% for positive and negative coeliac lymphogram, and 70% and 4% for positive and negative TCRγδ+.
Conclusions
Coeliac lymphogram was associated with a high level of diagnostic evidence either against or in favour of coeliac disease in patients with seronegative villous atrophy.
Summary
Background
A limited number of small‐sized studies suggest that bile acid diarrhoea is frequent in patients with chronic watery diarrhoea and previous cholecystectomy.
Aim
To perform a ...systematic review and meta‐analysis to assess the prevalence of bile acid diarrhoea in patients with chronic watery diarrhoea and previous cholecystectomy, and their response to colestyramine, including a new consecutive series of patients.
Methods
MEDLINE and EMBASE were searched up to January 2018. Selected studies included patients with previous cholecystectomy and chronic watery diarrhoea assessed by the 23‐seleno‐25‐homotaurocholic acid (SeHCAT) test. We calculated the pooled rate of bile acid diarrhoea using the inverse double arcsine square root method. Additionally, the medical records of 291 consecutive patients with chronic watery diarrhoea in whom a SeHCAT test was performed were retrospectively reviewed and 74 with previous cholecystectomy were included in the meta‐analysis.
Results
The search strategy identified eight relevant studies, which, together with the data of the present series, comprise 361 individuals. The pooled bile acid diarrhoea rate was 70% (95% CI 56%‐82%), and was similar when using cut‐offs of 10% or 15%. There was substantial heterogeneity (I2 = 84%). Five studies comprising 166 patients evaluated the effect of colestyramine in patients with bile acid diarrhoea. The pooled colestyramine response rate was 79% (95% CI 63%‐91%) with substantial heterogeneity (I2 = 73%).
Conclusions
Two‐thirds of patients with chronic watery diarrhoea and previous cholecystectomy have bile acid diarrhoea. Response to colestyramine in these patients is good.
Summary
Background
Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Biopsies with characteristic histological features are crucial for establishing the diagnosis. The two main ...subtypes are collagenous colitis (CC) and lymphocytic colitis (LC) but incomplete forms exist. The disease course remains unpredictable varying from spontaneous remission to a relapsing course.
Aim
To identify possible histological predictors of course of disease.
Methods
Sixty patients from the European prospective MC registry (PRO‐MC Collaboration) were included. Digitised histological slides stained with CD3 and Van Gieson were available for all patients. Total cell density and proportion of CD3 positive lymphocytes in lamina propria and surface epithelium were estimated by automated image analysis, and measurement of the subepithelial collagenous band was performed. Histopathological features were correlated to the number of daily stools and daily watery stools at time of endoscopy and at baseline as well as the clinical disease course (quiescent, achieved remission after treatment, relapsing or chronic active) at 1‐year follow‐up.
Results
Neither total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria or surface epithelium, or thickness of collagenous band showed significant correlation to the number of daily stools or daily watery stools at any point of time. None of the assessed histological parameters at initial diagnosis were able to predict clinical disease course at 1‐year follow‐up.
Conclusions
Our data indicate that the evaluated histological parameters were neither markers of disease activity at the time of diagnosis nor predictors of disease course.
The histopathological parameters total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria and surface epithelium, and thickness of collagenous band did not correlate to the number of daily stools or daily watery stools at time of diagnosis nor predict clinical disease course at 1‐year follow‐up.
LINKED CONTENT
This article is linked to Olsen et al and Lucendo papers. To view these articles, visit https://doi.org/10.1111/apt.16381 and https://doi.org/10.1111/apt.16403
Summary
Background
Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce.
Aims
...To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD
Methods
Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded.
Results
Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 2.2‐3.3, P < 0.0001), strictures OR 1.8 (1.5‐2.2), P < 0.0001, chronic iron deficiency anaemia OR 2.2 (1.3‐3.2), P < 0.001 and use of second‐line biologics OR 1.7 (1.1‐2.6), P = 0.021. The median stricture‐free time was 14 years (95% CI, 12‐16) for cases vs 21 years (95% CI, 19‐23) for controls (P < 0.0001). Cases with isolated UGI compared to UGI plus ileal/ileocolonic more frequently had localised disease OR 0.5(0.3‐0.8), P = 0.003 and underwent more endoscopic stricture dilations OR 2.7(1.3‐5.4), P = 0.006.
Conclusions
The largest cohort of patients with CD and UGI provides information on the natural history of this particular phenotype. Increased awareness of the clinical picture and therapeutic requirements of these patients could lead to earlier diagnosis and treatment of upper gastrointestinal lesions, preventing the structural damage frequently seen in these patients at diagnosis and during follow‐up.
Clinical features, therapeutic requirements and evolution of patients with Crohn's disease and upper gastrointestinal involvement (CROHNEX study)Study population: Cases: patients with Crohn'sdisease and upper gastrointestinal involvement (n = 854).Controls: patients with Crohn's disease and ileal/ilecocolonic involvement (n = 1708). Patients were identified from the ENEIDA registry (Spanish cohort of patients with inflammatory bowel disease). Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location and those with complex perianal fistula were excluded. Results:
Cases were more likely to have:
Extensive involvement (OR 2.7 2.2‐3.3, P < 0.0001).
Strictures (OR 1.8 1.5‐2.2, P < 0.0001).
Chronic iron deficiency anaemia (OR 2.2 1.3‐3.2, P < 0.001).
Use of second‐line biologics (OR 1.7 1.12.6, P = 0.021).
The median stricture‐free time was 14 years (95% CI, 12‐16) for cases vs 21 years (95% CI, 19‐23) for controls (P < 0.0001).
The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned.
To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the ...diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology.
Double-blind randomized clinical trial of gluten vs placebo rechallenge.
>18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated.
91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01). The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable 'coeliac lite' disease.
This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet.
ClinicalTrials.gov NCT02472704.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prediction models for colorectal cancer (CRC) detection in symptomatic patients, based on easily obtainable variables such as fecal haemoglobin concentration (f‐Hb), age and sex, may simplify CRC ...diagnosis. We developed, and then externally validated, a multivariable prediction model, the FAST Score, with data from five diagnostic test accuracy studies that evaluated quantitative fecal immunochemical tests in symptomatic patients referred for colonoscopy. The diagnostic accuracy of the Score in derivation and validation cohorts was compared statistically with the area under the curve (AUC) and the Chi‐square test. 1,572 and 3,976 patients were examined in these cohorts, respectively. For CRC, the odds ratio (OR) of the variables included in the Score were: age (years): 1.03 (95% confidence intervals (CI): 1.02–1.05), male sex: 1.6 (95% CI: 1.1–2.3) and f‐Hb (0–<20 µg Hb/g feces): 2.0 (95% CI: 0.7–5.5), (20‐<200 µg Hb/g): 16.8 (95% CI: 6.6–42.0), ≥200 µg Hb/g: 65.7 (95% CI: 26.3–164.1). The AUC for CRC detection was 0.88 (95% CI: 0.85–0.90) in the derivation and 0.91 (95% CI: 0.90–093; p = 0.005) in the validation cohort. At the two Score thresholds with 90% (4.50) and 99% (2.12) sensitivity for CRC, the Score had equivalent sensitivity, although the specificity was higher in the validation cohort (p < 0.001). Accordingly, the validation cohort was divided into three groups: high (21.4% of the cohort, positive predictive value—PPV: 21.7%), intermediate (59.8%, PPV: 0.9%) and low (18.8%, PPV: 0.0%) risk for CRC. The FAST Score is an easy to calculate prediction tool, highly accurate for CRC detection in symptomatic patients.
What's new?
Lower gastrointestinal symptoms potentially indicative of colorectal cancer (CRC) are a common reason for physician visits. While the probability that any one of those symptoms is associated with CRC is low, identifying patients for further screening remains a challenge. Here, the possibility of improving CRC diagnostic accuracy and risk stratification was explored using a three‐variable FAST Score based on fecal hemoglobin concentration, age, and sex. Among symptomatic patients referred to colonoscopy, the FAST Score prediction model identified three risk groups, the lowest of which ruled out CRC. Threshold scores were sensitive across variables, including country, age, and sex.
1.
The long-term effect of a gluten-free diet (GFD) on functional bowel disorders (FBDs) has been scarcely studied. The aim was to assess the effect of a GFD on FBD patients, and to assess the role ...of both the low-grade coeliac score and coeliac lymphogram in the probability of response to a GFD. 2.
116 adult patients with either predominant diarrhoea or abdominal bloating, fulfilling Rome IV criteria of FBD, were treated with a GFD. Duodenum biopsies were performed for both pathology studies and intraepithelial lymphocyte subpopulation patterns. Coeliac lymphogram was defined as an increase in TCRγδ
cells plus a decrease in CD3
cells. A low-grade coeliac score >10 was considered positive. 3.
Sustained response to GFD was observed in 72 patients (62%) after a median of 21 months of follow-up, who presented more often with coeliac lymphogram (37.5 vs. 11.4%;
= 0.02) and a score >10 (32 vs. 11.4%;
= 0.027) compared to non-responders. The frequency of low-grade coeliac enteropathy was 19.8%. 4.
A GFD is effective in the long-term treatment of patients with previously unexplained chronic watery diarrhoea- or bloating-predominant symptoms fulfilling the criteria of FBD. The response rate was much higher in the subgroup of patients defined by the presence of both a positive low-grade coeliac score and coeliac lymphogram.
Accurate celiac disease (CD) diagnosis is still challenging for some specific patients or circumstances. Thus, much effort has been expended last decades focused on seronegative or low grade ...enteropathy CD and, especially, on enable early diagnosis of individuals on a gluten-free diet (GFD). We discuss here two diagnostic approaches based on immunophenotyping by flow cytometry that we expect to reduce the persistent low diagnostic rates and the common diagnostic delay. The intraepithelial lymphogram is based on determining the percentage of TCRγδ
and surface CD3
lymphocytes in the intestinal epithelium. The concomitant increase in TCRγδ
and decrease in surface CD3
intraepithelial lymphocytes has been termed the celiac lymphogram and has been proved to be discriminative in seronegative, low grade enteropathy and potential CD, as well as in most CD patients on a GFD. A blood lymphogram based on the analysis of activated gut-homing CD8
T cells combined with a 3-day gluten challenge is also considered, which has shown high sensitivity and specificity to diagnose seropositive Marsh 1 and Marsh 3 CD in individuals following a GFD. In addition, flow cytometry can be extremely useful in cases of refractory CD type II to identify aberrant cells. Those approaches represent highly accurate methods for CD diagnosis, being simple, fast, highly reproducible and of easy implementation in clinical practice.
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