Category Archives: Pediatric Gastroenterology Intestinal Disorder

Guidelines on Functional Heartburn

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How to diagnose and manage adults with functional heartburn: C Hachem, NJ Shaheen Am J Gastroenterol 2016; 111-53-61 (thanks to Ben Gold for reference).

Functional heartburn is defined as chronic symptoms of heartburn without objective evidence of reflux.  The authors algorithm (Figure 2) recommends endoscopy for patients who have had heartburn that is unresponsive to a 2 month trial of PPI.  If endoscopy is normal, pH-impedance study is recommended.  If abnormal, impedance indicates nonerosive reflux disease.  If normal and there is symptom correlation, this suggests esophageal hypersensitivity.  If normal and there is no symptom correlation, this suggests functional heartburn (though authors note a role for motility testing in this circumstance in their algorithm).

Their conclusions:

  • Functional heartburn (FH) responds poorly to PPI therapy
  • The pathophysiology of FH is unknown but it is often associated with visceral hypersensitivity
  • Modulation of pain perception and alternative therapies (melatonin, TCA, SSRI, biofeedback, acupuncture, or hypnotherapy) may be helpful

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Flamenco Beach -Not the Best Day for the Beach

Flamenco Beach -Not the Best Day for the Beach

Which kids who aspirate need a gastrostomy tube?

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While some may think all children who aspirate should have a gastrostomy tube, a recent study (ME McSweeney et al. J Pediatr 2016; 170: 79-84) indicates a more selective approach is appropriate.

This retrospective review of 114 patients (2006-2013) compared patients fed by gastrostomy tube (g-tube) and those who were fed orally.  In their introduction, the authors note, “there has been a practice shift at many institutions away from g-tube placement and more toward continuing to feed children with aspiration orally.”  All patients in the study had aspiration and/or penetration with thin liquids and/or nectar thick liquids on a videofluoroscopic swallow study (VFSS).

There were 61 who aspirated only thin liquids and 53 who aspirated thin and nectar thick liquids.  All patients were divided into two groups: a g-tube group which did not have a preoperative trial of thickened feeds and an orally-fed group.  Patients who had a fundoplication or post-pyloric feeds were excluded from this study.

Key findings:

  • There were no significant differences in admissions among those who aspirated thins compared with those that aspirated thin & nectar thick liquids.
  • Patients fed by gastrostomy were hospitalized more frequently (median 2 times compared to once with orally-fed) and for longer duration (median 24 days compared with median 2 days for orally-fed)
  • No differences in total pulmonary admissions were noted between gastrostomy-fed and orally-fed group

The authors advocate a trial of oral feeding in all children cleared to take nectar or honey thick liquids prior to g-tube placement.

 

While the authors note that g-tube placement did not result in fewer pulmonary admissions, in their discussion, they also reviewed studies which showed that fundoplication (with g-tube) was not associated with a reduced risk of respiratory complications and in fact, had higher rehospitalizations.

This current study, and previous studies, are limited by their design.  Patients were not randomized and g-tube-fed patients may have had more comorbidities, biasing the results.  The authors note that there were 11 children who failed oral thickening trials and needed g-tube placement.  At the same time, there are substantial numbers of children whose swallow function improve.  Also, the authors note that thickening agents have not been shown to lead to dehydration risk.

My take: the widespread availability of swallow studies has likely led to some children undergoing g-tube placement who may have been fine with ongoing orally-thickened feeds.  Avoiding g-tube placement for children who can tolerate and thrive on thickened feeds is worthwhile.

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Walnut Street Bridge & Tennessee River

Walnut Street Bridge & Tennessee River

Super cool and its effects on the microbiome

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A terrific review (ED Rosen. NEJM 2016; 374: 885-7) explains how cool temperature can alter the microbiome and the implications of this finding.

Background: mammals have at least two types of adipose tissue: “the familiar (and all too abundant) white fat that stores calories, and brown adipose tissue that dissipates energy…studies of mice have identified several drivers of the appearance of beige fat cells in white fat pads, a process known as ‘browning.'”

Reviewed study: Chevalier et al. Cell 2015; 163: 1360-74.

“This new work shows that cold exposure, like dietary change, provokes alterations in the gut microbiota of mice.  Moreover, when cold-adapted flora are transferred to a germ-free animal, the recipient mouse loses fat mass and has improved insulin sensitivity…[they] are better able to defend their body temperature on being placed in the cold.”

  • “This new work shows that prolonged cold exposure induces a massive increase in the absorptive surface of the gut…cold causes a profound increase in the ratio of Firmicutes to Bacteroidetes”
  • “A companion article from the same group suggests that antibiotic therapy, which depletes gut microbiota, also induces browning and weight loss.”

My take: In totality, these studies demonstrate how multiple organs (in this case: adipose tissue and the gut) work together to face an environmental challenge.  Furthermore, changes in the gut microbiome may be important for therapeutic advantage in many disease states including obesity, type 2 diabetes, short bowel syndrome, irritable bowel syndrome and many others.  Now, that is cool.

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View from Walnut Street Bridge, Chattanooga

View from Walnut Street Bridge, Chattanooga

LEAP-ON Study: Early Peanuts Prevent Allergies

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A followup study to the LEAP study (The Peanut Story -From NEJM Blog | gutsandgrowth) shows that early peanut exposure produces a durable protection from peanut allergies. NPR summary: Peanut Mush in Infancy Cuts Allergy Risk

Here’s an excerpt:

Researchers followed the kids for one additional year. The kids were between 5 and 6 years old during this follow-up period. It turned out, these high-risk kids’ tolerance to peanuts held up even if they stopped eating peanuts.

“A 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy,” the authors write in the paper.

This is an important finding, because it wasn’t known whether the kids would need to maintain regular weekly consumption of peanuts in order to stave off developing an allergy…

But that doesn’t mean all parents should just rush in with the peanut mush. The guidance recommends that “infants with eczema or egg allergy in the first 4 to 6 months of life might benefit from evaluation by an allergist” — before they’re introduced to peanut-based foods.

Fajardo, Puerto Rico

Fajardo, Puerto Rico

Is Intestinal Function in Children with Autism Different?

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There has been a lot of concern that abnormal GI function contributes to both behavioral and gastrointestinal symptoms in children with autism.  To categorize some of these problems, the term ‘leaky gut’ has been used.

An upcoming study (RI Kushak et al. JPGN DOI: 10.1097/MPG.0000000000001174) (thanks to Ben Gold for forwarding this reference) examines this issue. Using a case-control design, pediatric patients with autism spectrum disorder (ASD) (n=61) were compared with 50 children with normal development.

Workup:

  • Endoscopy (EGD and colonoscopy) with histologic analysis
  • Disaccharidase analysis
  • Intestinal permeability studies with lactulose and rhamnose
  • Fecal biomarkers: calprotectin and lactoferrin

According to the authors, all of the study subjects underwent endoscopy and “all had clinical indications for diagnostic endoscopy.”  Most common indications were parental reports of abdominal pain and diarrhea.

Key findings:

  • Disaccharidase activity levels were not significantly different between the groups. In agreement with prior studies, there was frequent lactase deficiency, with 66% of ASD children in this study with deficient enzyme activity (<15 μmol/min/g).  However, lactase activity in the children with ASD was not lower than the non-ASD children.
  • There were no significant differences in measures of intestinal permeability.  Normative values for lactulose and rhamnose ratio are not definitively established.  However, when using similar cutoff ratios, there were similar results in both groups.

Calprotectin:

  • Intestinal inflammatory markers (calprotectin/lactoferrin) were not significantly different, after the authors excluded the five “neurotypical” children who were diagnosed with inflammatory bowel disease.
  • For calprotectin, the authors considered a level <50 mcg/g to be normal.  In the ASD group, 31of 49 (63%) had abnormal calprotectin compared with 19 of 31 (61%) in the non-ASD group.
  • For calprotectin levels >150 mcg/g, 9 of 49 (18%) reached this level in the ASD group and 8 of 31 (26%) in the non-ASD group.

Histology:

  • Similar levels of GI tract inflammation were noted in both groups –generally mild.
  • In the ASD group, 32 (52%) had inflammation somewhere in their GI tract, “but it was generally mild and non-diagnostic.”  In the ASD group, five had features consistent with GERD, two had eosinophilic esophagitis (EoE).  There were 12 (19%) who had colonic inflammation and 3 (5%) with ileal inflammation.  None had celiac disease or H pylori.
  • In the non-ASD group, four had EoE, four (8%) had ileal inflammation, and nine (18%) had colonic inflammation.  The authors noted Crohn’s disease in three and a total of five children with IBD.

My take:

  1. This study suggests that symptomatic children with autism have similar (and probably not worse) GI problems as neurotypical children.  The idea that children with autism have a more leaky gut than children without autism is quite dubious based on these results.
  2. The biggest problem for GI physicians is not addressed in this study and involves children with and without autism: appropriate selection for evaluation.  While the authors chose children with “clinical indications,” these, in fact, are often subjective and with permissive interpretation could be used to justify endoscopy in 40% of children.
  3. Another huge problem is interpretation of abnormal results.  While the authors report large numbers with intestinal inflammation in both groups, most of this was considered to be insignificant clinically.  How should trivial inflammation be reported in studies?  This problem is not unique to this study and makes it difficult to assess the value of endoscopy more broadly.

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Law Quad, Univ Michigan

Law Quad, Univ Michigan

 

Torsion of Accessory Spleen

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A case report (PM Guglietta et al. NEJM 2016; 374; 373-82) presents a 9 year-old girl who had repeated episodes of abdominal pain with associated nonbilious vomiting.  These pains started 5 years prior and were often sudden episodes of sharp pain on the left side or epigastric region and were associated with tachycardia.

AXR in Case Report

AXR in Case Report

Ultimately the diagnosis was established with a CT scan.  “Most persons with accessory spleens are asymptomatic, but abdominal pain can occur with torsion.”

While the case report is interesting, one aspect I did not like was the discussants justification of the delay of the diagnosis based on the presumption of constipation.  The radiologist even commented: “a moderate-to-abundant amount of stool distributed in the colon, particularly the ascending colon; these findings are consistent with the clinical history of constipation.”  This and other comments in the case study go against previous expert recommendations to avoid routine radiographs in the diagnosis of constipation and the finding of reviews which have not found a correlation between clinical symptoms and so-called fecal loading on abdominal radiographs.

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Flamenco Beach

Flamenco Beach

 

Adrenal Insufficiency due to Fluticasone in Eosinophilic Esophagitis

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A recent study (MC Golekoh et al. J Pediatr 2016; 170: 240-5) shows that adrenal insufficiency developed in 10% of patients on chronic (>6 months) swallowed corticosteroid therapy for Eosinophilic Esophagitis (EoE).

Background: 58 patients with 67% receiving fluticasone and 33% receiving budesonide.  Median age: 13.7, median fluticasone dose 1320 mcg/day, median treatment duration: 4 yrs.  For budesonide, median dose was 1000 mcg/day and median age 10.7 yrs.

Key findings with low-dose ACTH stimulation:

  • Abnormal peak cortisol (≤ 20 mcg/dL) present in 15% and adrenal insufficiency (< 18 mcg/dL)  (n=6) noted in 10%
  • Only patients receiving >440 mcg/day of fluticasone had adrenal insufficiency
  • No patients taking budesonide had an abnormal cortisol level

Commentary:

  • Higher doses of fluticasone, particularly early in treatment, has been shown to have an improved inflammatory response.  However, as with asthma therapy, higher doses increase the risk of adrenal insufficiency.
  • Adrenal insufficiency can be asymptomatic but pose a risk for life-threatening adrenal crisis.
  • Strengths of study: Fairly large cohort, endoscopic/pathologic reports available, and ACTH stimulation testing which has better sensitivity than random cortisol.
  • Limitations: Lower number of patients receiving budesonide, particularly at a higher dose.  No indication of adherence.

My take: If higher doses of fluticasone are needed for prolonged period, consider screening (endocrinology consultation) for adrenal insufficiency.

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Farjado, Puerto Rico

Farjado, Puerto Rico

CDC Guideline for Prescribing Opioids for Chronic Pain

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Full Text: CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016

D Dowell et al. JAMA. Published online March 15, 2016. doi:10.1001/jama.2016.1464 .

Excerpts:

  • No evidence shows a long-term benefit of opioids in pain and function vs no opioids for chronic pain with outcomes examined at least 1 year later (with most placebo-controlled randomized clinical trials ≤6 weeks in duration).

  • Extensive evidence shows the possible harms of opioids (including opioid use disorder, overdose, and motor vehicle injury).

  • Extensive evidence suggests some benefits of nonpharmacologic and nonopioid pharmacologic therapy, with less harm.

CDC: “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently,”

1st Six Recommendations (12 total)

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate. (Recommendation category: A; evidence type: 3)

2. Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and consider how opioid therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. (Recommendation category: A; evidence type: 4)

3. Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy. (Recommendation category: A; evidence type: 3)

4. When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids. (Recommendation category: A; evidence type: 4)

5. When opioids are started, clinicians should prescribe the lowest effective dosage.  (Recommendation category: A; evidence type: 3)

6. Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than 7 days will rarely be needed. (Recommendation category: A; evidence type: 4)

Other points:

  • Avoid concurrent benzodiazepines
  • Review state prescription drug monitoring program to look for dangerous combination therapies and prior opiod dosing
  • Consider risk mitigation strategies (eg. naloxone)
  • Suggests urine screening at start to screen for illicit substance abuse which increases risk

USAToday’s review of these guidelines: CDC issues new guideline on opiods

Bottomline: This report is very important for those who prescribe opiods for chronic pain.

Law Library, Univ of Michigan

Law Library, Univ of Michigan

More on Hidradenitis Suppurativa and Inflammatory Bowel Disease

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In a population-based inception cohort study (S Yada et al. Clin Gastroenterol Hepatol 2016; 14: 65-70) of 679 patients with inflammatory bowel disease (IBD) followed for a median of more than 19.8 years, it was determined that patients with IBD were ~9 times more likely to develop hidradenitis suppurativa (HS) compared with general population. 8 of 679 patients developed HS; only one had HS prior to IBD.

Other findings:

  • Most Crohn’s disease patients with HS had perianal disease.  Most ulcerative colitis patients developed HS after colectomy.
  • Female sex and obesity were risk factors for HS.

In a second retrospective study (N Kamal et al. Clin Gastroenterol Hepatol 2016; 14: 71-9), the authors identified 15 patients with CD and HS.  10 patients had perianal disease.  In this population, “both diseases were characterized by their severity, requirement of systemic medical therapies including anti-TNF and high operative rate.” this article contained some very helpful pictures.

Unrelated article: F Wang, JL Kaplan, BD Gold et al. Cell Reports; 2016: 14: 945-55.  This highly technical study used two independent cohorts of patients with Crohn’s disease and non-IBD controls.  One cohort, RISK, had over 700 patients and ~30,000 mean number of reads per sample; the other cohort, PIBD-CC, and 87 patients and ~3000 mean number of reads per sample.  Overall, the study showed associations between Crohn’s disease and bacteria in the lumen and the study helps provide an information-based method to depict dysbiosis.

Related blog post: Add it to the list

San Juan

San Juan

“Cat in the Hat” Effect with Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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IL Holster et al (Hepatology 2016; 63: 581-89) provide useful data on the use of transjugular portosystemic shunt (TIPS) compared with endoscopic therapy/Beta-blocker for prevention of variceal rebleeding.

In this multicenter randomized trial, TIPS was compared with either endoscopic variceal ligation or glue injection along with beta-blocker treatment in 72 patients with either a first or 2nd episode of variceal bleeding.  The median followup was 23 months.

Key findings:

  • 0 of 37 (0%) of TIPS patients had rebleeding compared with 10 of 35 (29%) in the endoscopic group.
  • TIPS mortality 32% compared with endoscopic group mortality of 26% (P=0.418)
  • Hepatic encephalopathy was 35% (TIPS) vs 14% (endoscopic group) (P=0.035)

This study shows that rebleeding is common in the endoscopic therapy group but that TIPS, while fixing bleeding, often resulted in other problems.  In “The Cat in the Hat” analogy, this would equate to moving the bathtub stain to the dress or curtains but not really improving the situation.

My take: It is helpful to see how these treatment strategies compare.  The data from this study does not clearly point to one strategy over another for dealing with this serious consequence of cirrhosis.

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Statue at Ferry Dock, Culebra

Statue at Ferry Dock, Culebra