Category Archives: Gastroenterology

Breath Test Reliability for Bacterial Overgrowth

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While breath test reliability for bacterial overgrowth has been a concern for a long time, another study (EC Lin, BT Massey. Clin Gastroenterol Hepatol 2016; 14: 203-08) takes a new approach to show that the glucose breath tests are subject to a high false-positive rate.  This is often related to rapid transit time.

Here’s what they did:

In a retrospective study, they examined data from 139 patients with suspected small bowel bacterial overgrowth (SBBO) (2003-2013).  Abnormal glucose breath tests were indicated by either hydrogen or methane >15 parts per million within 90 minutes after glucose ingestion.  In addition, they used concurrent scintigraphy (by labeling glucose with a Tc99m compound) to determine whether this increase occurred before or after glucose bolus arrived in the cecum.

Findings:

  • 46 (33%) had abnormal breath tests.  Of these 22 (48%) had false-positive results due to colonic fermentation.
  • False-positives were higher (65%) in the subset of patients with prior upper gastrointestinal surgery.  The nonsurgical group had a 13% false-positive rate.
  • This study shows that with rapid transit, significant glucose malabsorption is possible.

Because direct culture of small bowel contents is expensive, invasive and subject to contamination, physicians have relied on breath tests for diagnosis of SBBO or have empirically treated for SBBO.  The discussion and related editorial (pg 209) explain that lactulose breath testing is not more reliable than glucose breath testing.

My take: For patients with prior GI surgery (who are at the highest risk for SBBO), breath testing may not be more reliable than flipping a coin.  True positive results are more likely if hydrogen peak occurs within 60 minutes of glucose administration.

Related blog post: 

Flamenco Beach, Culebra

Flamenco Beach, Culebra

Common Sense: Lifestyle Intervention in Gastroesophageal Reflux Disease

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“Common sense is not so common” –Voltaire

A recent study (E Ness-Jensen et al. Clin Gastroenterol Hepatol 2016; 14: 175-82) reviewed the literature and identified 15 original studies which met inclusion criteria regarding lifestyle interventions in gastroesophageal reflux disease (GERD).

Key findings:

  • Weight loss lowered esophageal acid exposure in 2 RCTs: 5.6% –>3.7% and 8.0%–>5.5% and reduced reflux symptoms in prospective observational studies
  • Tobacco cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study OR 5.67
  • Head-of-the-bed elevation decreased supine acid exposure from 21% to 15%.
  • Early evening meals decreased supine acid exposure by 5.2% point change.

My take: With the increasing incidence of obesity, these type of lifestyle modifications need to be implemented in our teenagers with GERD.  For those who want to decrease use of medications, these interventions, if emphasized with conviction, are a good first step.

GERD cover

Clinically Useful Biomarkers for Irritable Bowel Syndrome?

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A selected summary (Gastroenterol 2016; 150: 277-79) provides good insight into the subject of irritable bowel syndrome (IBS) biomarkers.  This summary focuses on a study by Pimental M et al (PLoS One 2015; 10: e0126438).

“In this study, the authors validated 2 serum biomarkers, antibodies (Abs) to cytolethal distending toxin (CdtB) and vinculin, primarily focused on differentiating diarrhea-predominant IBS (IBS-D) from IBD. CdtB is a bacterial toxin commonly produced by Campylobacter jejuni, as well as Escherichia coli, Salmonella, and Shigella…presence of Cdtb seems to be positively associated with the likelihood of developing a postinfectious IBS phenotype…Vinculin is a host cell adhesion protein, with which anti-CdtB Abs are known to cross-react.”

The study recruited 2681 participants (18-65 years) from 180 centers; most (n=2375) had Rome III IBS-D.

Key findings:

  • Anti-CdtB levels were higher in IBS-D 2.53 (± 0.69) compared with Crohn’s disease 1.72 (± 0.81), ulcerative colitis 1.54 (± 0.68), celiac disease 2.23 (± 0.70), and healthy subjects 1.81 (± 0.73)
  • Anti-vinculin Abs were higher in IBS-D as well: 1.34 (± 0.85) compared with Crohn’s disease 1.05 (± 0.91),ulcerative colitis 0.96 (± 0.77), celiac disease 1.07 (± 0.98), and healthy subjects 0.81 (± 0.59)

“Using a cutoff point of >2.80 for anti-CdtB Abs, the sensitivity was 43.7%, specificity was 91.6%.”  The positive likelihood ratio (LR) was 5.2 with this cutoff.  For vinculin, a cutoff of >1.68, resulted in a sensitivity of 32.6%, specificity of 83.8%, and a positive LR of 2.0.

For comparison, the commentary notes that the Rome III criteria in one study had a sensitivity of 68.8%, specificity of 79.5%, and positive LR of 3.35.

“The current study is important for 2 reasons.  First, that these 2 Abs were able to differentiate IBS-D from IBD and healthy controls, with a reasonable degree of accuracy, suggests that a substantial proportion of individuals with IBS may have an overt or subclinical postinfectious trigger, resulting in intestinal microbial disturbances…Second, the ability of these tests, if positive, to rule in IBS-D and rule out IBD is encouraging.”

But…

  • This study may not be representative of a typical primary care population with IBS
  • And,”as a rule of thumb, positive LRs of >10 are very useful in ruling in a disease…the complex, and likely multifactorial etiology of IBS may mean that a single biomarker that can diagnose IBS with the accuracy required for a test to be clinically useful is not possible.”

My take: I would like to see pediatric studies, perhaps this would help determine if a postinfectious mechanism is more common in children and adolescents.

Related blog posts:

Plantains

Plantains

Turning Conventional Colonoscopy Positioning Upside Down

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A recent article (The American Journal of Gastroenterology 110, 1576-1581 (November 2015) | doi:10.1038/ajg.2015.298) indicates that right-sided positioning rather than left-side down results in quicker and more comfortable colonoscopy.  While it is disconcerting to realize that I had been trained exactly opposite, if this technique works for me, it will be particularly helpful when patients undergo combination procedures since this means that the bed would not need to be rotated.  Thanks to Mike Hart for this reference.

Right Or Left in COLonoscopy (ROLCOL)? A Randomized Controlled Trial of Right- versus Left-Sided Starting Position in Colonoscopy

N Vergis, A K McGrath, C H Stoddart and Jonathan M Hoare

OBJECTIVES:

Colonoscopy is technically challenging and can cause discomfort for patients. We aimed to test whether right-sided starting position for colonoscopy would result in shorter procedure time and greater patient comfort when compared with conventional left-sided starting position.

METHODS:

We conducted a randomized controlled trial in which patients were randomized to begin in either the right- (RL) or conventional left-lateral (LL) position. One hundred and sixty-three adult patients undergoing scheduled colonoscopy were stratified by age, gender, body mass index, and experience of the endoscopist. Patients were then randomized 1:1 in permuted blocks. The primary outcome measure was time to cecal intubation and secondary outcome measures included patient comfort that was evaluated by visual analog comfort scale.

RESULTS:

Median time to reach the cecum was quicker when colonoscopy began with patients positioned RL rather than LL (P=0.0078). Moreover, patients found RL more comfortable than LL (P=0.02). Multiple linear regression confirmed starting position in colonoscopy as an independent determinant of time to reach the cecum (P=0.007). Women and those who had previously undergone abdominal surgery gained the greatest benefit from right-sided positioning (RL vs. LL: 498 vs. 824 s; P=0.03 and 498 vs. 797 s; P=0.006, respectively).

CONCLUSIONS:

Our study reveals that right-sided positioning at the start of colonoscopy results in more comfortable and quicker procedures. Of the factors identified by multiple linear regression to independently have an impact on time to reach the cecum, only starting position is modifiable. Right-sided starting position may therefore be of benefit in colonoscopy, in particular for women and patients who have previously undergone abdominal surgery.

PPIs Alter the Microbiome

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A couple of comments –today’s blog (below) and yesterday’s blog both point out potential concerns with proton pump inhibitors (PPIs).  There is a danger that when publications emphasize the potential consequences of PPI use (including NPR’s recent piece on kidney disease and PPIs) that physicians and families will overlook the value of these medications.

With regard to the benefits of PPIs, there are a large number of studies supporting the effectiveness of PPIs for various GI conditions.  As a result, there is little being published on drug effectiveness at this time.  On a daily basis, these medications prevent a great deal of suffering, heal esophagitis, heal ulcers and contribute to improved health.  If one looks only at the negative side of the ledger, this could create harm.

My personal belief is that when PPIs are used, that it is important to consider both the advantages and the disadvantages.  If the benefits are unclear, this increases the necessity of evaluating the risks, especially in vulnerable populations.  In addition, when the benefits are unclear, determining the length of therapy and/or performing appropriate diagnostic workup becomes essential.

Also, for pediatric gastroenterologists reading this blog, it is important to realize that my blog’s following is tiny in comparison to the circulation of the Journal of Pediatrics and news organizations like NPR.  Therefore, we need to engage our pediatrician/family medicine colleagues to help make sure that PPIs are used effectively.  I am looking forward to the January 26 NASPGHAN webinar on this topic.

——–

The degree to which proton pump inhibitors (PPIs) affect the gut microbiome is unclear.  A recent study of 12 healthy volunteers (DE Freedberg et al. Gastroenterol 2015; 149: 883-85, Clearing Out My Desk | gutsandgrowth) indicated that this was not much; however, an even more recent study (F Imhann et al. Gut 2015 December 9 (Gut doi:10.1136/gutjnl-2015-310376))  suggests otherwise (abstract below) -their conclusion: “On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.”  

Link: Proton pump inhibitors affect the gut microbiome

Abstract

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome.

METHODS: The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis.

RESULTS: 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon’s diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10(-38)). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli.

CONCLUSIONS: The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.

My take: It is likely that the effects on the microbiome are even more notable in infants/younger children; in neonates, the changes in the microbiome could increase the risk of serious diseases like necrotizing enterocolitis.

Related blog posts:

Yosemite

Yosemite

Burden of GI Diseases in U.S.

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A useful article (AF Peery et al. Gastroenterol 2015; 149: 1731-41) provides data on the huge impact that GI & Liver diseases have.

Here are some key findings:

Leading GI symptoms (Ambulatory visits) in 2010 (Table 1):

  • Abdominal pain 27.1 million
  • Diarrhea 5.6 million
  • Vomiting 5.5 million
  • Nausea 4.7 million
  • Bleeding 3.6 million

Most Common Diagnosis from Hospital Admissions in 2012 (Table 5):

  • GI hemorrhage 507,440 admissions
  • Cholelithiasis with cholecystitis 389,180 admissions
  • Acute pancreatitis 275,170 admissions
  • Intestinal obstruction 256,775 admissions
  • Appendicitis 248,080 admissions
  • Chronic liver disease/viral hepatitis 243,170 admissions

Causes of Death in U.S. in 2012 (Table 7):

  • Colorectal cancer 51,139
  • Pancreatic cancer 38,797
  • Liver/bile duct cancer 22,973
  • Cirrhosis 17,495
  • Alcoholic liver disease 17,419
Gastroenterology Cover

Gastroenterology Cover

Trying to Understand Gastroparesis

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…all I know is that I know nothing. –Socrates

Perhaps Socrates was a gastroenterologist.  So much of what we think we know, we are finding out is poorly understood.  This applies to gallbladder dyskinesia, sphincter of Oddi dysfunction and now gastroparesis.

A recent study (PJ Pasricha et al. Gastroenterol 2015; 149: 1762-74, commentary 1666-68) and commentary show how little we understand about gastroparesis.

The study was a large prospective surgery of 262 adult patients with gastroparesis (either diabetic or idiopathic).

Key findings:

  • 28% had improvement in the gastroparesis cardinal symptom index (GCSI) at 48 weeks.  Beyond 48 weeks, there were no significant reductions through week 192.
  • Favorable characteristics: male gender, age 50 and older, initial infectious prodrome (18% of cohort), antidepressant usage, and 4-hour gastric retention greater than 20%.
  • Unfavorable characteristics: obesity, smoking, use of pain modulators, moderate to severe abdominal pain, severe reflux, and moderate to severe depression.

The commentary suggests that those with the higher GCSI improved, in part, because of a regression toward the mean bias.  Other important commentary:

  • “More severely delayed gastric emptying was associated with a greater likelihood of improvement”
  • “There was no differences in outcome between diabetic or idiopathic gastroparesis.”
  • Gastric emptying tests are not reliable:  “Pathophysiologic tests are useful in clinical practice if they are reproducible, explain the symptoms, guide therapeutic choices, and determine response to therapy and long-term prognosis.  Despite its popularity, the gastric emptying test scores low on most of these criteria.”
  • “A metaanalysis found no correlation between the change in gastric emptying rate and the symptom response during prokinetic therapy…A 5-year prospective follow-up study of …functional dyspepsia…found that more than 50% improved…with no relation to the presence of delayed gastric emptying.”
  • “Using the term gastroparesis also can lead to premature closure in our efforts to understand the pathophysiology of symptoms…can lead to botulinum injections into the pylorus or placement of gastric stimulators (formerly called gastric pacemakers) for gastroparesis, both of which have been shown to be nonefficacious in controlled trials.”

My take: It is unclear “when to consider gastric emptying testing and how to use it in patient management.”  For the pediatric population, gastroparesis is more likely to be associated with a prodromal infection which increases the likelihood of recovery.

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Banning Mills

Banning Mills

NEJM: Functional Dyspepsia

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A recent NEJM had a concise review of functional dyspepsia (Talley NJ, Ford AC. NEJM 2015; 373: 1853-63).

With regard to functional dyspepsia in adults, the authors note that using the Rome III criteria, the global prevalence is between 5% and 11%.

While symptoms do not reliably distinguish organic and functional dyspepsia, they note that “with a relatively low rate of identification of organic disease, it is neither desirable nor realistic to perform this test [upper gastrointestinal endoscopy] in all patients with dyspepsia.”

Their review suggests several criteria to consider to help determine who needs endoscopy including age >55 yrs, GI bleeding, dysphagia, persistent vomiting, unintentional weight loss, family history of gastric or esophageal cancer, and iron-deficiency anemia.

With regard to workup, they suggest testing for H pylori non invasively with either breath testing or stool antigen testing.  The review covers treatment approaches including acid suppression (“effect is modest”), antidepressants (“tricyclic antidepressants…should be preferred over selective serotonin-reuptake inhibitors”), prokinetic agents, psychological treatments, and complementary approaches.  Figure 3 provides a helpful algorithm.

With regard to prognosis, “approximately 15 to 20% of people with functional dyspepsia have persistent symptoms and 50% have resolution of symptoms; in the remaining 30 to 35% of patients symptoms will fluctuate and meet the criteria for another functional gastrointestinal disorder.”

Briefly noted: “Acute Anxiety and Anxiety Disorders are Associated with Impaired Gastric Accommodation in Patients with Functional Dyspepsia” HG Ly et al. Clin Gastroenterol Hepatol 2015; 13: 1584-91.

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Sunrise in Sandy Springs

Sunrise in Sandy Springs

Which Diet is Best for Irritable Bowel Syndrome?

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As noted in this blog previously, there has been increasing evidence that a low FODMAPs (fermentable oligo-, di-, monosaccharides and polyols) diet is an effective option for irritable bowel syndrome (IBS) in adults and children. Now, a study (L Bohn et al. Gastroenterol 2015; 149: 1399-1407) directly compares a low FODMAPs diet with an IBS diet in a multicenter, parallel, single-blind study of 75 patients (adults) with Rome III criteria for IBS.

The comparison IBS diet recommended regular meal patterns, avoidance of large meals, reduced intake of fat and reduced insoluble fibers, caffeine, and gas-producing foods, such as beans, cabbage and onions.  In addition, this diet recommended avoidance of spicy foods, coffee, alcohol, soft drinks, and sweeteners that end with “-ol.” This diet has been recommended by the British Dietetic Association and by the National Institute for Health and Care Excellence (NICE).  NICE Guidelines for IBS

Key findings:

  • 67 patients completed the study.  The severity of IBS symptoms improved in both groups (P<.0001) without a difference between the two groups
  • 19 (50%) of low FODMAPs had reductions in IBS severity scores of >50 compared with baseline and 17 patients (46%) in the ‘traditional’ IBS diet group had this degree of improvement.

My take: Diet changes often result in symptom improvement in IBS.  Both of these diets can be recommended in patients with IBS.

Atlanta Sky

Atlanta Sky