Category Archives: Gastroenterology

IBD and Pregnancy

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While managing inflammatory bowel disease during pregnancy is not within the scope of my practice as a pediatric gastroenterologist, it is helpful to have some familiarity with the issues.

Here’s a full-text link to AGA Guidelines: The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy

From the abstract, an excerpt:

Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti–tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn’s disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy.

Gastro March2016

European Experience with Biosimilars

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While there are numerous concerns regarding the use of biosimilar products, the preliminary experience with biosimilar infliximab has been favorable.

Full text link: European Experience of Infliximab Biosimilars for IBD (Gastroenterology & Hepatology)

Key points:

  • Biosimilars are leading to cost reductions of 30-40%.  In addition, to lowering the cost of infliximab, this is leading to reductions in costs for adalimumab and vedolizumab which are competing as 1st line therapies.
  • In the authors study of the first 210 patients, they did not find any difference in terms of immunogenicity or side effects.  In addition, efficacy was comparable to the ‘originator’ drug.

My take: Infliximab and adalimumab have been blockbuster medications for pharmaceutical companies, in part because they provide a great clinical benefit.  However, if biosimilars are truly biosimilar, the cost reductions will result in their widespread adoption.

Related blog post: Biosimilars -Position Statement  GutsandGrowth  This position statement: “Treatment of a child with sustained remission on a specific medication should not be switched to a biosimilar until clinical trials in IBD are available to support the safety and efficacy of such a change”

Castillo San Felipe del Morro

Castillo San Felipe del Morro

Microbiome Predicts Constipation plus two

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In brief:

G Parthasarathy et al. Gastroenterol 2016; 150: 367-79.  Mucosal and fecal microbiota samples were collected from 25 healthy women and 25 women with chronic constipation.  Key finding: The mucosal, but not fecal, microbiota profile were 94% predictive of constipation. The associated editorial (pg 300) provides a framework for understanding these findings and show the complexity of trying understand the interations between diet, motility and microbes.

S Fukudo et al. Gastroenterol 2016; 150: 358-66.  This prospective study of Ramosetron for 576 women with IBS-D.  Key finding: 50.7% of treatment patients reported global improvement compared with 32.0% of control patients.  Patients had less abdominal pain, less discomfort, and better stool consistency.  Ramosetron, a 5-HT3 antagonist, has not been reported to cause ischemic colitis (in contrast to alosetron).

In followup to a post earlier in the week, another worrisome study on the Zika virus in pregnancy from NEJM. Here’s an excerpt:

Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses).

Farjado, Puerto Rico

Farjado, Puerto Rico

Guidelines: Microscopic Colitis & Vascular Diseases of the Liver

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In brief:

AGA Microscopic Colitis Guideline: GC Nguyen et al. Gastroenterol 2016; 150: 242-6. Technical review DS Pardi et al. Gastroenterol 2016; 150: 247-74. Patient guide: pg 275.

EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatology 2016; 64: 179-202.  Topics covered include Budd-Chiari, Portal vein obstruction, Heriditary hemorrhagic telangiectasia, veno-occlusive disease of the liver, management of anticoagulation in liver disease

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.

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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