Category Archives: Gastroenterology

How Many Biopsies Are Sufficient for Diagnosis of Microscopic Colitis?

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Briefly noted: Microscopic colitis is much more frequent in adults than in children; nevertheless, it is often important to exclude. A recent study (B Virine et al. Clin Gastroenterol Hepatol 2020; 18: 2003-2009. Full text: Biopsies From Ascending and Descending Colon Are Sufficient for Diagnosis of Microscopic Colitis) indicates that biopsies can be limited to the ascending and descending colon.

Methods: This was a retrospective study using biopsies from 101 consecutive patients with MC (52 cases of collagenous colitis, 42 cases of lymphocytic colitis, 7 combined cases),

Key finding:

  • In this study, microscopic colitis was detected with 100% sensitivity by analyzing biopsy specimens from the ascending and descending colon

My take: The authors note that previous guidelines have suggested taking 8 biopsy specimens.  Their findings support taking much fewer biopsies.

Related blog post/related article:

 

Intestinal Barrier Function and Risk of Crohn’s Disease

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Several recent studies have examined biomarkers to predict Crohn’s disease.  A recent prospective study (W Turpin et al. Gastroenterol 2020; DOI: https://doi.org/10.1053/j.gastro.2020.08.005. Increased Intestinal Permeability is Associated with Later Development of Crohn’s Disease) sought to determine whether increased intestinal permeability, as measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), is associated with future development of CD.

Methods: 1420 asymptomatic first-degree relatives (6–35 years old) of patients with CD (collected from 2008 through 2015) had LMR measured and were then followed for a diagnosis of CD from 2008 to 2017, with a median follow up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017

Key findings:

  • An abnormal LMR (> 0.03) was associated with diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64–5.63; P=3.97×10 -4).
  • This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62, 95% CI, 1.051–2.50; P=.029).

My take:  It remains unclear whether abnormal barrier function primarily precedes or follows CD development.  The authors state that these findings support a model in which altered intestinal barrier function contributes to pathogenesis.

Yellow or Blue for Cautery of Non-pedunculated Polyps

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Almost all polyps that pediatric gastroenterologist manage are pedunculated polyps.  Nevertheless, a recent study (H Pohl et al. Gastroenterol 2020; 159: 119-28. Full text: Effects of Blended (Yellow) vs Forced Coagulation (Blue) Currents on Adverse Events, Complete Resection, or Polyp Recurrence After Polypectomy in a Large Randomized Trial) on cautery for non-pedunculated polyps was intriguing.

Methods: This multicenter, randomized, controlled, single-blinded study enrolled patients with a large colorectal polyp across 18 medical centers between April 2013 and October 2017. N=928.  ERBE device.

Key finding:

  • Equivalent results were noted with both blended current (Yellow) or forced coagulation (Blue)
    • “Serious adverse events occurred in 7.2% of patients in the Endocut (blended) group and 7.9% of patients in the forced coagulation group, with no significant differences in the occurrence of types of events.”
    • Proportions of polyps that were completely removed: 96% in the Endocut group vs 95% in the forced coagulation group
    • Proportion of polyps found to have recurred at surveillance colonoscopy: 17% for both groups
    • “Endocut more frequently caused intraprocedural bleeding that required treatment than forced coagulation (17% vs 11%). In contrast, small residual tissue islands were more frequently described in the forced coagulation group than in the Endocut group.”

Discussion: 

  • “We also did not include pedunculated polyps. Because these polyps have a greater risk of immediate bleeding, we may infer from our study that it may be safer to apply a coagulation current with a lower risk of immediate bleeding to these polyps.”

My take: Both of these settings yielded similar results.  For now, with pedunculated polyps, probably best to rely on the coagulation setting (Blue).

Related blog posts:

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Does a Low Vitamin D Level Increase the Risk of Crohn’s Disease? And Other Biomarkers

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A recent study (BN Limketkai et al. Clin Gastroenterol Hepatol 2020; 18: 1769-76. Levels of Vitamin D Are Low After Crohn’s Disease Is Established But Not Before) takes advantage of stored serum from U.S. military personnel.

Key finding: By examining 240 with Crohn’s disease (CD) along with 240 control patients, the authors show that vitamin D levels prior to CD diagnosis are not associated with the development of CD up to 8 years preceding the diagnosis.

Two other articles on predictive biomarkers for CD and an associated editorial:

  • N Nair et al. Gastroenterol 2020; 159: 383-5. Association Between Early-life Exposures and Inflammatory Bowel Diseases, Based on Analyses of Deciduous Teeth
  • J Torres, F Petralia et al. Gastroenterol 2020; 159: 96-104. Serum Biomarkers Identify Patients Who Will Develop Inflammatory Bowel Diseases Up to 5 Years Before Diagnosis
  • New Biomarkers for Crohn’s Disease (editorial) C Bernstein. Gastroenterol 2020; 159: 30-32. Key points from editorial:
    • “In the article by Nair et al, the authors relate the presence of heavy metals in baby teeth to the later development of Crohn’s disease…The finding of metals that can be tracked to the in utero state suggests that the offspring who will ultimately present with IBD and have high values of these metals are likely acquiring these metals from their mothers.”
    • “In the study by Torres et al, a serum bank of Department of Defense recruits was accessed to study for microbial antibodies and immune-inflammatory markers for ≤5 years antedating diagnoses of either Crohn’s disease or ulcerative colitis. Anti-Flagellin X and ASCA-IgA were predictive of Crohn’s disease…The authors have convincingly showed that these microbial antibodies and immune-inflammatory mediators are present years before the first clinical manifestation of Crohn’s disease. These phenomena very likely are early biological manifestations of Crohn’s disease. They may not be risk factors that Crohn’s disease is coming, but rather that it is already present.”

My take: Stored tissue/blood eventually may help predict who will develop CD.  Given a lack of current treatment options in those at risk, the importance of these predictive markers is unclear.

Drug Therapy for Celiac Disease: Case Report

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Briefly noted: L Waters et al. Annals Int Med 2020; doi:10.7326/L20-0497. Celiac Disease Remission With Tofacitinib

The authors describe a male with a well-documented case of celiac disease and alopecia areata.  He was placed on tofacitinib off-label for his alopecia areata and it was discovered that his celiac disease had developed “complete histologic and serologic remission…while he was still on a gluten-containing diet.”  Prior to medication, he had confirmation of both severe histologic changes and high tTG IgA titers.

The authors note that tofacitinib inhibits CD8+ T-cell mediated enteropathy in a transgenic mouse model.

My take (borrowed from authors): Tofacitinib has many potential adverse effects but may considered for further study, especially in refractory celiac disease.

Table –From Annals of Internal Medicine Twitter Feed

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How Effective Are PPIs for Eosinophilic Esophagitis?

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Emilio J. Laserna‐Mendieta et al. AP&T 2020; https://doi.org/10.1111/apt.15957.  Full article link: Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry

“This cross‐sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database.” Overall, 630 patients (76 children) received PPI as initial therapy (n = 600) or after failure to respond to other therapies (n = 30)

Key findings:

  • PPI therapy achieved eosinophil density below 15 eosinophils per high‐power field in 48.8% and a decreased symptom score ≥50% from baseline in 71.0% of patients.
  • More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico‐histological remission after PPI therapy (OR 3.7; 95% CI, 1.4‐9.5)
  • PPI treatment is more effective in achieving clinico‐histological remission of the disease when used in higher instead of standard or lower doses (50.8% vs 35.8%), and when the duration of therapy is prolonged from 8 to 12 weeks (50.4% vs. 65.2%)

My take: This study confirms previous studies which have generally found that PPIs are effective in 40-50% of patients with eosinophilic esophagitis.  Higher doses of PPIs are needed to achieve the highest response rates.

“Bar chart for histological (A) and symptomatic (B) responses for proton pump inhibitor (PPI) mono‐therapy to induce and maintain remission in patients with eosinophilic oesophagitis. For induction of remission, patients were classified according to the PPI dosage prescribed: high dose was double dosage or higher, and low dose was standard dosage or lower. For maintenance therapy, only patients with dosage reduction from that used for induction were included. eos/hpf: eosinophils per high power field”

Related blog posts:

Current Thinking with Laryngopharyngeal Reflux Symptoms

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A recent study (H-C Lien et al. Clin Gastroenterol Hepatol 2020; 18: 14-66-74) adds a bit more insight into the topic of larygnpharyngeal symptoms (related blog post:  Gastroestophageal Reflux Phenotypes and Where ‘Rome, Lyon, and Montreal Meet’ provides more information on treatment outcomes).

Methods: In this prospective multi-center observational study with adults aged 20-70 years, n=142 completed study), enrollment required chronic laryngitis symptoms >3 months and “laryngoscopic” signs suggestive of reflux.  Subsequently, patients were examined with multiple modalities, including 24-pH testing, manometry, and Bernstein test followed by treatment with omeprazole 40 mg twice a day.

Key Findings:

  • Pathologic reflux was identified in 146/252 (58%) of those meeting inclusion criteria.  Thus, approximately 40% did NOT have objective findings of reflux despite suspicion of laryngopharyngeal reflux (LPR); this is similar to other studies.
  • In those with documented reflux, those with and without typical reflux symptoms had improvement in LPR with omeprazole therapy: 57% and 63% respectively; whereas, omeprazole therapy was effective in 32% in those without objective (pH probe) findings of reflux. In previous studies, reflux laryngitis response to PPIs has been similar to placebo.

My take: Typical reflux symptoms are not needed for patients with LPR to respond to PPIs.  However, more than 40% of individuals with LPR do NOT have objective evidence of reflux; in this subset, response to PPI therapy is low.

Related blog posts:

New Agent for Refractory Reflux

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In the June issue of Gastroenterology (158: 2015-16), a tribute to George Sachs (1935-2019) recognizes his work in the field of gastroenterology and his development of proton pump inhibitors (PPIs).

Much more work remains as ~30% of patients with gastroesophageal reflux remain symptomatic despite PPI therapy.   In the same issue, IW-3718, a bile acid sequestrant colsevelam with a gastric-retentive formulation was studied in 280 patients (MF Vaez et al. Gastroenterol 2020; 158: 2017-19).

Methods: The authors performed a multicenter, double-blind, placebo-controlled 8-weel treatment trial (2016-17); patients received the study drug (500, 1000, 1500 mg) or placebo twice daily.  The authors enrolled symptomatic patients (≥4 times per week) with erosive esophagitis or pathologic reflux based on Bravo study (pH<4 for ≥4.2% during at least one 24-hour period). They continued PPI therapy which they had been receiving for a minimum of 8 weeks prior to starting study medication.

Key findings:

  • Improvement in heartburn severity scores for placebo, 500, 1000, and 1500 mg groups: 46%, 49%, 55%, and 58%.  The 11.9% difference between 1500 mg group compared to placebo reached statistical significance (P=.04)
  • There was an improvement in weekly regurgitation frequency score as well from baseline to week 8 in 1500 mg group of 17.5% compared to placebo.
  • No serious drug related serious adverse events were identified.  Constipation was noted in 8% of study drug recipients compared 7% for placebo recipients.

Limitations: lack of a centralized review for endoscopy images, high placebo response rate, once daily use of PPI in study, and problems with overlap of functional symptoms

My take: This study shows why a placebo control is needed in reflux studies.  While IW-3718 at higher doses was effective, its response appears much less notable when compared with placebo-recipients.

Study May Indicate Biologic Basis for Brain Fog in Persons with Celiac Disease

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From The Onion: Dumbass Dog Wearing Face Mask All Wrong

From The Onion

A recent study (ID Croall, et al. Gastroenterol 2020; 158: 2112-22), using a UK Biobank with 500,000 adults, compared 104 participants with celiac disease to 198 healthy age-matched controls (mean age 63 years).

The authors examined cognitive outcomes, mental health outcomes and imaging data (MRI, diffusion tensor imaging).

Key findings: 

  • The celiac cohort had significant deficits in reaction time (P=.004), anxiety (P=.025), depression (P=.015), thoughts of self-harm (P=.025), and health-related unhappiness (P=.01)
  • Imaging studies showed white matter changes “which match up well anatomically with the regions affected in the celiac-related neurologic syndrome gluten ataxia.”

Limitations: study lacked data on celiac treatment status –whether better control or earlier diagnosis/treatment would reduce CNS complications is uncertain.  Also, whether these findings are more or less prevalent in individuals with undiagnosed celiac disease is unclear.

My take: This study provides further evidence that celiac disease results in significant neurologic problems and further reasons for those with celiac disease to adhere to a strict gluten-free diet (as other studies of neurologic outcomes indicate that a GFD can improve/reverse neurologic morbidities).

Related blog posts:

 

 

PPIs Associated with Increased Risk of COVID-19 Infection

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Here is link to original study: Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors 

Almario CV, Chey WD, Spiegel BMR. Increased risk of COVID-19 among users of proton pump inhibitors. Am J Gastroenterol 2020 (pre-print posted online July 7, 2020)

From ACG:  Information Sheet and FAQs About Proton Pump Inhibitors (PPIs) and Risk of COVID-19

This study shows an association but does not prove that PPIs increase risk of COVD-19.  Patients taking PPIs may have other attributes that increase their risk compared to those who are not taking PPIs.

Here is some more information on twitter thread of this topic: