Category Archives: Pediatric Gastroenterology Intestinal Disorder

Trends in Adolescent Bariatric Surgery

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Despite increased numbers of obese adolescents, the number of inpatient bariatric surgery cases has plateaued (JAMA Pediatr 2013; 167: 126-32).  Thanks to Ben Gold for sharing this reference.

In this retrospective cross-sectional study using an administrative dataset (Healthcare Cost and Utilization Project Kids’ Inpatient Database), the authors documented the following bariatric surgery rates:

  • In 2000: 0.8 per 100,000 (328 procedures)
  • In 2003: 2.3 per 100,000 (987 procedures)
  • In 2006: 2.2 per 100,000 (925 procedures)
  • In 2009: 2.4 per 100,000 (1009 procedures)

The other observations in this study were that procedures were predominantly performed on females (75%), the prevalence of comorbidites increased (49% in 2003 vs. 59% in 2009), and complications rates were low.  68.3% had private insurance.

Take-home points:

The number of adolescents who would qualify for bariatric surgery has increased but the rates have not changed.  Why?

  1. Societal barriers.  Obesity is more common in lower socioeconomic groups with lower educational levels.  Yet, the rates of bariatric procedures is the same in low-income and high-income populations.
  2. Insurance coverage.  In many states, medicaid does not cover bariatric surgery.
  3. Physicians limiting access.  After initial enthusiasm (2000-2003), published guidelines to identify appropriate patients and to highlight recommendations prior to surgery may have led to more cautious referral patterns.

Over the past decade, there are increased numbers of qualified surgeons and there has been more use of laparascopic techniques.  The Roux-en-Y gastric bypass (RYGB) was the most common bariatric procedure in this population, accounting for 67.6% of cases in 2009 (60.6% were laparascopic, 7% were open).  Laparascopic adjustable gastric banding (LAGB) accounted for the remaining 32.1% of cases.

Since this study relied on administrative data, there are several limitations.  Billing codes may not reflect the procedures accurately.  For example, ICD-9 codes for laparascopic sleeve gastrectomy were not available until 2011.  Nevertheless, this study provides some insight into the trends with bariatric procedures in adolescents.

Related blog link:

Six year outcomes with bariatric surgery | gutsandgrowth

Closer to Star Trek Medicine

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In Star Trek, Dr. Leonard McCoy used a medical tricorder to effortlessly diagnose a lot of conditions (Tricorder – Wikipedia, the free encyclopedia, Medical tricorder – Wikipedia, the free encyclopedia).  While many of the newest diagnostic tests are not as portable, they share a feature of being able to diagnose a wide range of conditions quickly.  These tests include imaging studies like MRI and CT, genetic microarrays, and now PCR panels to diagnose a broad array of respiratory and gastrointestinal ailments.

One of the newest is the “xTAG GPP.”  With one stool sample, this Gastrointestinal Pathogen Panel (GPP) can detect at least 11 common bacteria, viral, and parasitic pathogens in about five hours.  Thus, all patients with identifiable gastroenteritis illnesses can be diagnosed more quickly.  The test relies on a “multiplex nucleic acid test.”

FDA News Release Jan 15, 2013  (Press Announcements > FDA permits marketing of first test that can …):

“Infectious gastroenteritis is an inflammation of the stomach and intestines caused by certain viruses, bacteria, or parasites. Common symptoms include vomiting and diarrhea, which can be more severe in infants, the elderly, and people with suppressed immune systems. Gastroenteritis can be spread easily through person-to-person contact and contaminated food, water, and surfaces. 
 
The Centers for Disease Control and Prevention reports that between 1999 and 2007 gastroenteritis-associated deaths in the United States increased from nearly 7,000 to more than 17,000 per year. Norovirus and Clostridium difficile accounted for two-thirds of the deaths. 
 
The xTAG Gastrointestinal Pathogen Panel (GPP), a multiplexed nucleic acid test, detects the following causes of gastroenteritis:
 
Bacteria
  • Campylobacter
  • Clostridium difficile (C. difficile) toxin A/B
  • Escherichia coli (E. coli) O157
  • Enterotoxigenic Escherichia coli (ETEC) LT/ST
  • Salmonella
  • Shigella
  • Shiga‐like Toxin producing E. coli (STEC) stx 1/stx 2
 
Virus
  • Norovirus
  • Rotavirus A
 
Parasite
  • Cryptosporidium
  • Giardia
 
“Tests such as the XTag GPP that can detect viruses, bacteria, and parasites from one sample at the same time can help clinicians more quickly identify and treat what’s causing gastroenteritis,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiology at the FDA’s Center for Devices and Radiological Health. “The test could also allow clinicians and public health professionals to more quickly identify and investigate the source of potential gastroenteritis outbreaks.”
The manufacturer demonstrated the performance of the xTAG GPP by collecting samples from 1,407 patients with suspected infectious gastroenteritis and comparing the xTAG GPP results to individual tests that are known to separately and reliably detect the 11 viruses, bacteria, or parasites associated with the xTAG GPP. The manufacturer also ran the test on 203 samples from patients with previously confirmed infectious gastroenteritis, and 313 additional specimens from pediatric patients with suspected infectious gastroenteritis. Results were comparable to the individual tests. Due to the risk of false positives, all positive results from the xTAG GPP need to be confirmed by additional testing (blog entry underlined for emphasis, not in original FDA release).
 
Luminex, Inc., of Austin, Texas, manufactures the xTAG.”
According to manufacter’s website, the test also detects Yersinia, Entamoeba histolytica, and adenovirus.  It reports sensitivity of of >94% for almost all pathogens (except Salmonella which was 84%) and specificity of >94% for all of the pathogens.

Is functional pain more common in children with Celiac disease?

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A recent study adds information to the title question but does not resolve it (J Pediatr 2013; 162: 505-09).

The authors note that they expected to find a higher prevalence of abdominal pain and abdominal pain/functional gastrointestinal disorders among children with diagnosis of celiac disease.  They note that functional disorders have been more common after acute gastroenteritis and cow’s milk hypersensitivity of infancy presumably due to preceding inflammation.  Persistent low-grade intestinal inflammation and immune activation have been proposed as precipitating susceptibility to functional abdominal pain.

In this small retrospective study, a statistically significant difference in functional GI disorders was not observed.  Enrolled families were contacted by telephone at least 6 months after the diagnosis of Celiac disease.  They completed a telephone questionnaire and a separate Rome III questionnaire.

Celiac cases (n=49):  abdominal pain (24.5%), functional abdominal pain (4.8%), IBS (6.1%), dyspepsia (4.8%), abdominal migraine (4.8%), nonspecific abdominal pain (6.1%)

Control cases (n=48): abdominal pain (14.6%), functional abdominal pain (6.3%), IBS (2.1%), nonspecific abdominal pain (6.1%)

Given the question that the authors were trying to answer, this study was unlikely to be helpful.  Problems with the study:

  • The biggest problem is the small number of patients.
  • Cross-sectional design
  • Reliance of recall symptoms
  • Lack of information on dietary adherence
  • Collection of information from only parents contributed

Bottomline: While screening for celiac disease is common in patients with possible functional abdominal pain, treatment with a gluten-free diet may not resolve these symptoms. Functional abdominal pain is at least as common in children with celiac disease as in the general population.

Related blog post:

Early antibiotic use and the development of inflammatory bowel disease

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Another study adds weight to the idea that early antibiotic use may increase the risk of developing inflammatory bowel disease (IBD) (J Pediatr 2013; 162: 510-4).

Using a nested case-control design, the authors matched 2377 controls to 294 children with IBD in a population-based database from Manitoba, Canada.  Specifically, the authors looked at the frequency of otitis media diagnosis and the likelihood of subsequent IBD.  By age 5 years, 89% of IBD cases had at least one diagnosis of otitis media, compared with 82% of the controls.  Despite the high frequency in both groups, the authors determined that individuals with a diagnosis of otitis media before age 5 years were 2.8-fold more likely to be an IBD case.

Some of the strengths of this study included the fact that it was a population-based analysis dating back to 1984 and likely captured almost all pediatric IBD cases (<19 years).  Nearly all physicians in Manitoba submit billing claims to a single publicly funded source.  Due to the nature of administrative data, this eliminates recall bias.

However, administrative data have several limitations as well.  Other confounding conditions may have been present and not identified; this could include family history and autoimmune diseases.

The authors “suspect” that the linkage between otitis media and IBD relates to the usage of antibiotics and subsequent alterations of the intestinal microflora.  Otitis media may serve as a “sensitive proxy measure” of antibiotic use.  Also, as boys are more frequently treated for otitis media, this may relate to the generally higher incidence of pediatric IBD in males.

For anyone interested in the association between antibiotic exposure and IBD, this study is useful and provides a number of references as well.

Related blog entries:

Does negative testing reassure patients?

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Probably not according to a recent study (JAMA Intern Med, published online Feb 25, 2013, d0i:10.1001/jamainternmed.2013.2762).

Citation: A Rolfe, C Burton. JAMA Intern Med. 2013;173(6):407-416. Open access! Reassurance After Diagnostic Testing With a Low Pretest Probability of Serious Disease

In this study, the authors systematically reviewed the literature and, after screening 9742 studies, identified 14 randomized controlled trials (n=3828 patients) which met inclusion criteria, including the following:

  • Randomized control trial
  • Adult participants with symptoms indicating a low probability of serious disease

Studies were excluded if they were not published in a peer-reviewed journal or if they were undertaken in a tertiary care setting.  Eight trials involved diagnostic testing for dyspepsia (mainly endoscopy), three involved radiography for back pain, and the other three included testing for chest pain, headache and palpitations.  Long-term follow-up varied from 4 to 18 months.

Key Findings:

  • Patients’ illness concern (odds ratio 0.87 in three trials) and anxiety (standardized mean difference 0.06 [-0.16 to 0.28] in two trials) were not reduced in the short or long term.
  • No overall long-term effect on symptom persistence was noted (odds ratio 0.99)

Limitations:

  • The authors examined only reassurance for patients, not for physicians.
  • Participants were not blinded
  • Overall, small number of study participants

In the discussion, the authors note that observational studies “suggest that illness concerns reappear within hours of receiving a normal (negative) test  result.”

For pediatric gastroenterologists, the conclusions from this article add another wrinkle when deciding how much workup is indicated for conditions like recurrent abdominal pain.  Previous data indicate that maternal anxiety is the most consistent predictor of outcome for recurrent abdominal pain (Acta Paediatr 2007; 96: 697-701); this study does not address whether patient proxies are reassured by negative testing.  And, other studies have shown that patients rate their care higher after diagnostic testing (Don’t miss the gorilla! | gutsandgrowth).

As a fellow, I was told: “Don’t just do something, stand there” from Bill Balistreri; he also recommended avoiding the mentality of “Scope first, think second.” While this current study suggests that there is a lack of long-term benefit when testing is done primarily for reassurance, convincing families that their child does not need testing is often difficult.

Update for Peutz-Jegher Syndrome

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A recent case series provides some useful insight into this rare condition (JPGN 2013; 56: 191-95).  Peutz-Jegher syndrome (JPS) has an incidence between 1 in 8500 to 1 in 120,000.  It is caused by a germline mutation in the STK11 gene.  It is associated with a serine threonine kinase that functions as a tumor suppressor.

14 children were identified through a medical records review at the Children’s Hospital Colorado between 2000-2011.  Inclusion required 2 or more of the following criteria:

  • 2 or more characteristic hamartomatous polyps of the small intestine
  • typical mucocutaneous pigmentation
  • positive family history (absent in about 25% of cases historically)

Results: Median age at first clinical evaluation was 4.5 years.  Intussusception was noted 7 times in 5 children (ages 5 to 16 years). Surgical reduction was required in 5 of the events. Polyps were found in the stomach/duodenum in 5 (36%), small bowel in 7 (50%), and colon in 3 (21%). Sertoli cell tumors was identified in 2 of the 10 boys at ages 8 years and 11 years.

Based on their experience, the authors suggest the following:

  • Initial screening start at age 4-5 years of age.  They recommend capsule endoscopy, upper endoscopy, and colonoscopy (CE/EGD/colon) as initial screen.  Then, they suggest repeating every 1-2 years until no polyps and then every 2-3 years.
  • In boys, they recommend breast exams for gynecomastia and testicular exams annually to screen for Sertoli cell tumor.  In girls, monitoring for precocious puberty and if present, then further evaluation for Sertoli cell tumor.

Given the small size of their cohort and the likelihood that asymptomatic children may not have been seen, it is too early to know if the approach recommended by the authors is justified.  Will earlier screening result in any long-term benefit &/or reduce complications related to JPS?

Mortality from IBD

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A large Danish cohort provides useful information on the mortality effects of having inflammatory bowel disease (IBD) and how this has changed over the last three decades (Clin Gastroenterol Hepatol 2013; 11: 43-48).

Using a national cohort of all individuals living in Denmark between 1982-2010 (on average 5.3 million), the authors studied 36,080 patients with ulcerative colitis (UC) and 15,361 with Crohn’s disease (CD) in comparison to data from 2,858,096 matched controls (50 controls from each IBD patient) from the general population.  For UC, the median age was 45.2 years and for CD 36.3 years.

Findings:

  • With UC, the first year of diagnosis carried a higher risk of dying (HR 2.43) then rapidly declined to around HR 1.1 after 2 years.  Overall, long-term mortality was increased 10% among UC patients.  Mortality from UC decreased from 1982 to 2010 due to decreased mortalities from gastrointestinal disorders, including colorectal cancer.
  • Mortality was higher among patients diagnosed at younger ages.  Patients diagnosed with UC in childhood or adolescence had a 2.15-fold higher relative mortality than patients diagnosed with UC at 60-79 years.
  • Cause-Specific Mortality: during the first year after UC diagnosis, the HR ratio was increased markedly for gastrointestinal disease (HR 13.3) and infection (HR 9.17).  These areas were most prominent at 10+ years, but the HR ratios had decreased to 1.95 and 1.64 respectively at that time.
  • For CD, mortality was markedly increased in the first year with HR 3.69 and declined to HR 1.53 during years 2-4; HR was 1.49 at 10+ years following diagnosis.  Overall, long-term mortality was increased 50% among CD patients.  Unlike UC, no improvement in mortality rate occurred during the study.
  • Cause-Specific Mortality: during the first year after CD diagnosis, the HR ratio was increased markedly for gastrointestinal disease (HR 23.02) and infection (HR 10.19). These areas were most prominent at 10+ years, but the HR ratios had decreased to 3.67 and 2.70 respectively at that time.  Infections were not increased in the most recent decade, indicating that thiopurines and biologics have not increased the overall risk of fatal infections.
  • While the relative risk of cardiovascular disease was only slightly increased (HR 1.11 for both CD and UC), this is important given the overall frequency of cardiovascular disease in the population.  Presumably, systemic inflammation contributes to the formation of atherosclerosis.
  • Suicide was also increased, especially in the first year after diagnosis (HR 2.05 for UC and HR 1.37 for CD)

Strengths of study: since Denmark has free access to health care and all citizens have a unique 10-digit personal identification, this enables capture of virtually all patients with IBD.  Previous studies have validated the database to be accurate and that the IBD diagnoses have been validated.

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Gut microbiome and endogenous alcohol

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At first glance, it sounds like an ambitious project -develop a gut microbiome that produces alcohol.  It could obviate the need for “Duff” beer (Duff Beer – Wikipedia, the free encyclopedia).  Yet, a recent article has found that an altered microbiome with increased endogenous alcohol already exists and it is associated with nonalcoholic steatohepatitis (NASH) (Hepatology 2013; 57: 601-609).

In this study, the authors examined three pediatric populations: a healthy control group (n=16), obese group (n=25), and NASH group (n=22).  All NASH patients had undergone liver biopsy and met Kleiner’s criteria; in contrast, the obese group had normal LFTs.

Key study findings:

1. The microbiome from the obese and NASH patients were similar but had some striking differences compared with the control group patients (pie chart –Figure 2):

  • Bacteroidetes (including Bacteroides): 28.65% in healthy controls, 50.28% in obese, and 49.11% in NASH
  • Firmicutes (including Blautia and Faecalibacterium): 66.78% in healthy controls, 42.62% in obese, and 42.39% in NASH
  • Proteobacteria (including Escherichia): 0.87% in healthy controls, 3.13% in obese, and 6.03% in NASH

2. Elevated serum ethanol concentrations only in NASH population: ~26 μM in both control and obese groups compared with ~35 μM in NASH patients.

Under normal conditions, endogenous alcohol is produced in the human body and the intestinal microflora are the major source.  This gut-produced alcohol is quickly metabolized by the liver.  Due to similar histology between NASH patients and patients with alcoholic liver disease, it has been hypothesized that NASH patients may have elevated blood alcohol.  This study adds further evidence to this hypothesis and provides a potential mechanism; namely, increased bacteria like Escherichia and Bacteroides can increase endogenously-produced alcohol.

Will efforts to revert the microbiome to normal have therapeutic effects on NASH?  This important question will need to be addressed given the growing problem of fatty liver disease.

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Cognitive Behavioral Therapy for Childhood Abdominal Pain

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Cognitive behavioral therapy (CBT) can be effective for children with functional abdominal pain (JAMA Pediatr 2013; 167: 178-84).  Thanks to Ben Gold for this reference.

This prospective, randomized study recruited 200 children and their parents.  One group of child-parent dyads received ‘social learning and cognitive behavioral therapy’ (SLCBT) and the other group ‘education and support’ (ES).  Over the course of a year, children in the SLCBT group reported greater baseline decreases in gastrointestinal symptom severity and better pain-coping responses.  Parents in the SLCBT group reported greater decreases in ‘solicitous responses’ to their child’s symptoms along with decrease in maladaptive beliefs regarding their child’s pain.

The intervention in the SLCBT group was three 1-hour sessions approximately 1 week apart in which parents were taught social learning strategies 1) to reduce ‘solicitous responses’ to illness behavior, and 2) to model /reinforce healthier ways to respond to gastrointestinal discomfort.  Then, assessments were made at 1 week, 3 months, 6 months, and 12 months.

This study shows that CBT can be effective for functional abdominal pain, if you can find skilled therapist and families willing to participate.

Related blog entries:

Stopping reflux with magnets

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Gastroesophageal reflux disease (GERD) can be treated by bolstering the lower esophageal sphincter with a surgically-implanted bracelet of powerful magnets (NEJM 2013; 368: 719-27).

In a prospective study, 100 patients with GERD were enrolled in this study.  The study was conducted in 13 centers in the U.S. and 1 in the Netherlands.  It was designed by Torax Medical.  There was no control group. The primary outcome was normalization of esophageal acid exposure or a 50% greater reduction in exposure at 1 year.

Patient selection:

  • Inclusion criteria: 18-75 years with at least 6-month history of GERD and partial response to proton pump inhibitor treatment.  All patients had to have abnormal pH probe studies at baseline.
  • Exclusion criteria: large hiatal hernia, grade C or D esophagitis (Los Angeles classification), BMI >35, Barrett’s esophagus, motility disorder, dysphagia more than three times a week, or allergy to implant components.

Results:

  • Primary outcome was achieved in 64% of patients.
  • Secondary outcomes: a reduction of proton-pump inhibitor (PPI) use of 50% or more was achieved in 93%.  In fact, at 3 years, 87% had completely eliminated the use of PPIs. Quality of life scores improved in 92%.
  • Adverse effects: most common was dysphagia (68% postop, 11% at 1 year, 4% at 3 years).  This often resolved after esophageal dilatation.
  • Six patients had the device removed.

The bracelet of beads contained sealed magnetic neodymium iron boride.  Each bead is connected by a small wire to the next.  The small wires allow for expansion of the bracelet. It is also designed to avoid compression of the esophagus as the beads can rest against each other.  In addition, the beads separate with the transport of food or if increased intragastric pressure (eg. belch or vomit).

The median time for the procedure of laparascopic placement was 36 minutes. This study brings the worldwide clinical experience to 497 magnetic implants.  To date, there have been no reported erosions or migrations.

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