Category Archives: Pediatric Gastroenterology Intestinal Disorder

Endoscopic Experts Needed In Pediatrics

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A recent study (A Schmidt et al. Gastroenterol 2018; 155: 674-86) shows how a new endoscopic technique, over-the-scope clips (OTSC), are more effective than standard endoscopic therapy for patients with recurrent bleeding of peptic ulcers.

Key finding: A multicenter prospective randomized unblinded study with 66 patients (33 in each arm) with found that hemostasis with OTSC had a failure rate (further bleeding) of 15.2% compared with 57.6% in those with standard therapy.

The authors note that standard endoscopic techniques are effective in more than 90% with rebleeding rates of 2-10%.  In those with rebleeding, followup endoscopy has a much lower success rate.

My take:

  • This study highlights a problem in pediatric endoscopy –the lack of expertise in these rare cases.  To learn even ‘standard’ endoscopic therapy, most pediatric GI fellows will need to collaborate with adult gastroenterologists in order to have exposure to a sufficient number of cases.
  • The development of alternatives like hemospray (Hemospray for GI Bleeding) which is technically-easy should be helpful for pediatric endoscopists with less endoscopic training.

Related article: 

P Tran et al. JPGN 2018; 67: 458-63.  This retrospective analysis of 11 pediatric cases (median age 14.7 yrs) reported technical success in all cases, though 2 patients with anastomotic ulcers requred additional medical intervention. The article has some pretty cool pictures.

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#NASPGHAN18 -Our Poster on Antibiotic Stewardship and PEG Placement

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Thanks to Chelly Dykes for presenting poster later today and to co-authors for collaborating on this project: Jeffery Lewis, Bonney Reed-Knight and Cate Crenson.

Full abstract below.

ABSTRACT:

 Background: While there is general agreement that antibiotic prophylaxis for percutaneous gastrostomy (PEG) tube insertion reduces the risk of infection at the site of placement (Lipp A, Cochrane Review 2013), optimal antibiotic selection and regimen remain unclear; as a result, there is widespread practice variation.  In addition, in order to limit the development of bacterial resistance and complications from antibiotic use (eg. Clostridium difficile infection), antibiotic stewardship programs have aimed to limit antibiotic usage, particularly broad-spectrum antibiotics.

Methods: From December 1, 2016 through May 1, 2018, the charts of all patients who underwent PEG tube placement in our children’s hospital were reviewed.  This period coincided with an optional practice change in antibiotic prophylaxis.  Prior to the study period, the typical patient received prophylaxis with a three-dose regimen of cefoxitin.  During the study period, at the discretion of the gastroenterologist, patients received either a three-dose regimen of cefoxitin (n=38) or treatment with cefazolin (n=109); 73 patients received a single dose of cefazolin prior to PEG placement and 36 received multiple doses.  The initial dose of either regimen was given within thirty minutes of placement.  All patients were observed for at least 24 hours.  In patients with PEG tube site infections based on clinical assessment, rescue antibiotic treatment was prescribed.

Results: In total, 144 subjects had PEG placement. The main indications for PEG placement were swallow dysfunction (56.2%), poor growth (17.6%), feeding aversions (18.9%) and malignancy (6%).  In the cefoxitin group, clinical infection occurred in 3 of 35 (8.6%).  In the cefazolin group, clinical infection occurred in 20 of 109 (18.3%). In the subset of patients who received multiple doses of cefazolin, the clinical infection rate was 6 of 36 (16.7%). Patients in the cefazolin group had a 2.39 times higher odds (95% CI  0.667-8.612) of infection compared to the cefoxitin group. Although rates of infection were more than twice as high in the cefazolin group compared to the cefoxitin group, this association did not differ statistically using a chi square test (x^2 = 1.89, p = 0.20).

Conclusion: This study highlights the ongoing uncertainty regarding optimal antibiotic prophylaxis for PEG tube placement.  The difference in the clinical infection rate between cefazolin and cefoxitin was not statistically significant; however, the absolute rate of infection in the cefazolin group was more than twice as high as the cefoxitin group and this may influence selection of antibiotic prophylaxis for PEG tube insertion.

 

Almost Everybody Needs Flu Shot –IBD Patients at Higher Risk

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Link: CDC Recommendations for Influenza Vaccination

  • Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications.
  • Vaccination should be offered by end of October; however, vaccination should continue to be offered as long as influenza viruses are circulating and unexpired vaccine is available.

 

Expert Advice for Diagnosis and Treatment of Rumination Syndrome

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Full text: M Halland et al Clinical Gastroenterol Hepatol 2018; 16: 1549-1555 provide an excellent review and practical recommendations for rumination syndrome.

The article describes the high prevalence which is ~0.8-0.9% of adults and ~5% of children.  Some populations like patients with eating disorders and fibromyalgia have even higher rates.

Other key points:

  • Long delay in diagnosis: patients “visit an average of 5 physicians over 2.7 to 4.9 years before being diagnosed correctly”
  • The diagnosis is a clinical based on Rome IV criteria, though most patients undergo an esophagogastroduodenoscopy or barium study to rule out other disorders
  • Best Practice Advice 1: Clinicians strongly should consider rumination syndrome in patients who report consistent postprandial regurgitation. Such patients often are labeled as having refractory gastroesophageal reflux or vomiting.
  • Best Practice Advice 2: Presence of nocturnal regurgitation, dysphagia, nausea, or symptoms occurring in the absence of meals does not exclude rumination syndrome, but makes the presence of it less likely.
  • Best Practice Advice 3: Clinicians should diagnose rumination syndrome primarily on the basis of Rome IV criteria after an appropriate medical work-up.
  • Best Practice Advice 4: Diaphragmatic breathing with or without biofeedback is the first-line therapy in all cases of rumination syndrome.
  • Best Practice Advice 5: Instructions for effective diaphragmatic breathing can be given by speech therapists, psychologists, gastroenterologists, and other health practitioners familiar with the technique.
  • This article gives instructions on this technique: “Diaphragmatic breathing can be learned easily by putting a hand on the chest and on the abdomen during respiration, and only allowing the hand on the abdomen to move out with inspiration while the chest remains in position (Figure 3). We instruct patients to take breaths by protruding the abdomen while keeping the chest as stationary as possible. Each inhalation or exhalation should be slow and complete, aiming for 6 to 8 respirations per minute. We recommend diaphragmatic breathing for 15 minutes after each meal, or longer if the sensation of impending rumination remains. The technique also should be practiced in the absence of meals to become expert at the technique. Uncontrolled studies and case series have reported resolution or improvement in rumination symptoms after diaphragmatic breathing in 20%–66% of patients. Figure 3: The patient slowly inhales through the nose while protruding the abdomen and keeping the chest stationary. (B) The patient slowly exhales via the mouth and allows the abdomen to retract.”
  • Best Practice Advice 6: Objective testing for rumination syndrome with postprandial high-resolution esophageal impedance manometry can be used to support the diagnosis, but expertise and lack of standardized protocols are current limitations.
  • Best Practice Advice 7: Baclofen, at a dose of 10 mg 3 times daily, is a reasonable next step in refractory [adult] patients.

My take: This is a useful review article.  Rumination needs to be considered particularly in patients with regurgitation, often labelled vomiting by families, that happens quickly after meals.

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In the news…from Washington Post:

Time to Diagnosis in Eosinophilic Esophagitis

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According to a recent retrospective study (CC Reed et al. Clin Gastroenterol Hepatol 2018; 16: 1667-9) the time to diagnosis of eosinophilic esophagitis (EoE) has NOT improved  between 2000 and 2014.  In this single tertiary-care center study with 677 cases, the predicted length of symptoms prior to diagnosis was the following:

  • 2000-2006: 6.1 years
  • 2007-2011: 7.2 years
  • 2011-2014: 7.2 years

While in the pediatric cohort the trend was the same, the length of symptoms preceding diagnosis was shorter: 2.8 years, 3.5 years and 3.7 years respectively for the above-mentioned time periods.

My take: In GI circles, EoE is quickly considered for a variety of clinical presentations.  This study suggests that

  • #1 for families and primary care doctors that many are unaware of this entity
  • #2 the symptoms of EoE are often insidious

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Updated Consensus Guidelines for Eosinophilic Esophagitis

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Full text: ES Dellon, CA Liacouras,  J Molina-Infante, GT Furuta et al. Gastroenterol 2018; 155: 1022-33.

This article provides a thorough review of EoE -including clinical features, differential diagnosis, diagnostic criteria, and treatments.

Key point: “The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.”

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Tofacitinib -Where Does it Fit in Treatment Algorithm for Ulcerative Colitis?

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A few recent articles provide a lot of practical information regarding implementation of tofacitinib into treatment regimens for ulcerative colitis (UC).

  • S Danese et al. Inflamm Bowel Dis 2018; 24: 2106–12. Review article on Tofacitinib.
  • J-F Colombel.  Inflamm Bowel Dis 2018; 24: 2173–80. Review article on Herpes Zoster due to JAK Inhibitors (eg Tofacitinib).
  • KL Winthrop et al.  Inflamm Bowel Dis 2018; 24:  2258-65. Clinical study detailing the risk of Herpes Zoster in patients with UC receiving Tofacitinib.

The first of these articles reviews the mechanism of action of tofacitinib (TFB) and the relevant studies showing efficacy for UC.  A summary of the results are listed in Table 1. Some of the reported results –with TFB dosed at 10 mg BID:

  • In 2012, Sandborn et al: clinical response in 61% at wk 8 and clinical remission of 48% at wk 8.
  • In 2017 (OCTAVE Induction 1): clinical response in 18.5% at wk 8 and clinical remission of 31.3% at wk 8.
  • In 2017 (OCTAVE Induction 2): clinical response in 16.6% at wk 8 and clinical remission of 28.4% at wk 8.
  • In 2017 (OCTAVE Sustain):clinical response in 40.6% at wk 8 and clinical remission of 45.7% at wk 8.
  • In all of these studies, TFB outperformed the placebo arm and has had a good safety profile

Most common adverse effects had similar rates in the placebo arm:

  • Nasopharyngitis
  • Arthralgia
  • Headache

Other adverse effects have included pneumonia, herpes zoster (HZ) infection, and increased lipid levels (more common than with placebo group).  Trials in patients with rheumatoid arthritis have indicated an increased incidence of nonmelanoma skin cancer, lymphoma, breast cancer, lung cancer, and gastric cancers.

Preclinical studies have shown that TFB could cause fetal malformations when given at much higher doses.  Though, clinical experience in humans have not found teratogenic effects; this is based on one study with 9815 RA/psoriasis patients and 47 women who became pregnant.

Role for tofacitinib:

  • “Tofacitinib could be used in patients suffering mild, moderate and severe UC…after aminosalicylates (5-ASA)…and as second-line therapy in patients who have been treated with TNF inhibitors.”

Advantages of tofacitinib:

  • Oral administration with rapid absorption
  • Short serum half-life
  • Good experience in large number of patients with rheumatoid arthritis
  • No immunogenicity.
  • Effective in patients who have had previous anti-TNF agents

More on Herpes Zoster Infection:

  • The other two references detail the risk of Herpes Zoster infections with TFB usage.
  • Winthrop et al identified 65 (5.6%) of patients developed HZ among phase II/III open-label, long-term extension trials.
  • The review by Colombel notes that patients with UC have “an increased risk of HZ compared with the general population, and this risk can be increase by the use of immunosuppressive therapy.  JAK inhibitors, including tofacitinib, have been associated with HZ risk…The majority of HZ casees are noncomplicated.”
  • In this review, Colombel details an algorithm for treatment of HZ cases and indicates that adults receiving TFB should consider vaccination to lower the risk of HZ.

My take: A significant portion of patients with UC either do not respond to anit-TNF agents or lose response.  Tofacitinib provides an alternative treatment with a different mechanism of action.  Given the few other non-surgical treatment options, I expect it will be rapidly incorporated into treatment algorithms.

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Are Probiotics Effective in Changing the Microbiome?

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Two recent papers in Cell provide additional questions about the effectiveness of probiotics.

Full Studies:

The coverage of these studies in the media has created some controversy; enough so that the International Scientific Association of Probiotics and Prebiotics disseminated a very critical review:

CLINICAL EVIDENCE AND NOT MICROBIOTA OUTCOMES DRIVE VALUE OF PROBIOTICS

Here is a small excerpt:

Two recent papers have generated much adverse publicity for the probiotic field. Headlines driven by sensationalism, not data, claim “Probiotics labelled ‘quite useless’” (BBC) and “Probiotics ‘not as beneficial for gut health as previously thought’” (The Guardian). The quotes are from author Eran Elinav, who generalizes the study findings to all ‘probiotics’ as a class – a generalization that ignores that specific probiotic are meant for specific purposes…

The scope of these papers is limited to microbiome data; no clinical endpoints are assessed. Without clinical evidence, it is not possible to conclude about the tested probiotic’s usefulness, and it is certainly not possible to conclude about probiotic usefulness in general…. The authors discount the existing body of evidence for probiotic health benefits, including Level 1 placebo-controlled, randomized trials. Cochrane reviews (the gold standard used by physicians and public health policy makers) of the totality of evidence show that specific probiotics can prevent antibiotic associated diarrhea (AAD) and C. difficile diarrhea. This evidence has been translated into evidence-based recommendations for probiotics issued by medical groups. Regardless of an effect on the microbiota, these are established, evidence-based benefits of probiotics.

My take: This controversy points to the problem that probiotics are often considered more effective than the science merits.  While there are some conditions that may respond to probiotics, it should be understood that each probiotic needs to be looked at for each specific clinical scenario.

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IBD Shorts October 2018

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C Ma et al. Clin Gastroenterol Hepaatol 2018; 16: 1407-19.  This study examined endpoints in randomized controlled trials (RCTs) of Crohn’s disease.  Key finding: Among 116 included RCTs (n=27,263 patients), there were 38 unique definitions of clinical response or remission and 32 definitions of loss of response. The most common endpoint was CD activity index.

RP Hirten et al. Clin Gastroenterol Hepatol 2018; 16: 1374-84. This review examines the topic of combining biologics in inflammatory bowel disease. Currently, there is little data in IBD.  From studies completed in rheumatology and dermatology, there are some safety concerns. One current study, the EXPLORER study, which is a phase 4 open label trial evaluating the use of vedolizumab in combination with adalimumab and methotrexate, will provide some useful information.  With regard to safety, gut-specific anti-integrin therapies are likely to be safer in combination than other biologic therapies.

RJ Colman et al. Inflamm Bowel Dis 2018; 24: 2135-41.  This systematic review and meta-analysis which included 14 eligible studies showed that the pooled clinical remission rate with methotrexate monotherapy for pediatric Crohn’s disease was 57.7% at 3-6 months and 37.1% at 1 year.

AA Wren et al. Inflamm Bowel Dis 2018; 24: 2093-2105. This study with 93,668 patients in a cohort from Truven MarketScan Database (2007-2015) identified a high rate of opioid therapy usage in U.S. adolescents and young adults (15-29 year olds).  Annual prevalence of chronic opioid use was 9.3% in 2007 and peaked at 12.2% in 2011. In 2015, the prevalence dropped to 10.8%.  Overall, 18.2% had received chronic opioid therapy.  Among the 2503 with chronic opioid usage who were followed longitudinally, 30.5% received opioids for 2 years and 5.3% for 4 years. The associated editorial (ME Kuenzig, EI Benchimol, pg 2140-5) note that these prevalence data may underestimate the true rate of opioid use due to the case definition of IBD used when analyzing the administrative data.

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