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NASPGHAN Postgraduate Course 2017 (Part 1): Strictures, GI Bleeding, Pancreatic Fluid Collections

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Over the next 2 weeks or so, I am posting my notes/pictures from this year’s annual meeting.  The first few days will review the postgraduate course.  For the most part, I find the postgraduate course reassuring that I have kept up with current approaches; there is usually not a lot of new information but a solid review of the topics.

Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Strictures beyond the esophagus

Petar Mamula, Children’s Hospital of Philadelphia

Some useful points:

  • Fluoroscopy very useful with most strictures –may improve safety and effectiveness. Helps define anatomy
  • Reviewed strictures in stomach –rare. May be due to caustic ingestion, Crohn’s disease or chronic granulomatous disease
  • Intestinal/colonic strictures (or narrowing): duodenal webs -can be treated with needle knife, Crohn’s disease strictures -can be balloon dilated, Short gut syndrome, Graft versus host disease

GI Bleeding Update

Diana Lerner  Medical College of Wisconsin

Useful points

Upper GI Bleeding:

  • IV PPIs reduce risk of transfusion and reduce risk of re-bleeding
  • IV PPI BID treatment has been shown to be noninferior to continuous drip
  • Conservative transfusion therapy
  • Erythromycin can be helpful
  • Lecture had good videos with review of techniques: clipping, heater probe, epinephrine injection (not recommended as monotherapy), argon plasma coagulation, and bipolar electrocautery

Cleveland et al. World J Pediatr 2012

Lower GI Bleeding:

  • Etiologies include the followiing: Post-polypectomy, Solitary Rectal Ulcer syndrome, Blue Rubber Bleb syndrome, anastomotic ulcer bleeding, Meckel’s diverticulum
  • Lower GI evaluation is best after prep –much higher yield

Management of Pancreatic Fluid Collections

Matt Giefer Seattle Children’s Hospital

Key points:

  • Imaging in first 7 days of diagnosis may miss the development of fluid collections
  • With necrotizing pancreatitis, fluid collections are either ANC: acute necrotic collection (<4 weeks) or WON: walled off necrosis (>4 weeks); Bryan et al. Radiographics 2016; 36: 675
  • With interstitial edematous pancreatitis, fluid collections are either acute peripancreatic fluid collection (<4 weeks) or Pseudocyst: >4 weeks,
  • Fluid collections do not preclude feeding patients
  • Drainage often needed if fluid collection becomes infected or if fluid collection causes obstruction
  • Endoscopic drainage is first-line approach: equally effective as surgery, fewer complications, equal efficacy, and lower cost

 

 

Three Studies Show the Benefit of Concomitant Therapy for Inflammatory Bowel Disease (Part 2)

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Continued from yesterday…

The third study (HM Kansen et al. JPGN 2017; 65: 425-29) retrospectively (2009-2014) examined 162 children (with available data) with Crohn’s disease (CD) for the development of anti-infliximab antibody (ATI) while receiving either monotherapy or concomitant therapy. This was a collaborative study from the Kids with Crohn’s Colitis (KiCC) working group (Netherlands).  In the majority of their patients (222 of 229), IFX was initiated as step-up therapy. Key findings:

  • 15% developed ATIs
  • 6 of 62 (10%) developed ATIs while receiving ongoing concomitant immunosuppression
  • 11 of 81 (14%) developed ATIs after receiving early concomitant immunosuppression (median of 6.2 months of concomitant immunosuppression followed by IFX monotherapy) 10 of 11 who developed ATIs  within the first 12 months, compared to 1 of 26 (4%) after 12 months.
  • 8 of 19 (42%) developed ATIs on IFX monotherapy

In their discussion, the authors note concerns regarding the safety of thiopurines. However, they point out that “the benefit of combination therapy (reduction of ATI formation) relative to IFX monotherapy should outweigh the risk of serious infections and malignancies to achieve an optimal treatment strategy for paediatric CD.” The authors: “combination therapy for approximately 12 months from initiation of IFX, followed by IFX monotherapy, may be equally effective alternative to continuous combination therapy.”

Overall, the totality of the evidence favors combination therapy for most patients with CD.  Yet, there is wide variation in clinical practice. As I was thinking about this, I came across a recent commentary: “The Power of Regret” (J Groopman, P Hartzband. NEJM 2017; 377: 1507-9).  The authors note that “disappointment is an unavoidable aspect of making difficult choices…but disappointment is not associated with self-recrimination and thus differs notably from regret.”  They indicate that “process regret” occurs when patients do not consider information about all available choices before making a decision.  I wonder if many patients/families fear using concomitant therapy because they worry they will regret the decision if a complication occurs.  Perhaps, working with all available information, some reluctant patients/families will feel better about their decision if the process for their decision was thorough, considering the risks/benefits of the treatment but also the risks/benefits of not choosing the treatment. .

My take: Overall, for most pediatric patients with CD, to date, concomitant therapy has been the most effective treatment.  More prospective studies are needed to determine more conclusively the benefit and optimal duration/timing of combined therapy, particularly with the more frequent use of therapeutic drug monitoring. Also, as will be noted in future posts from annual meeting, thiopurine use is declining.

Related blog posts:

Three Studies Show Benefit of Concomitant Therapy for Inflammatory Bowel Disease (Part 1)

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In the first study (J Cheng et al. Inflamm Bowel Dis 2017; 23: 1762-73), the authors retrospectively reviewed 148 children (113 with Crohn’s disease, 35 with ulcerative colitis). 90 patients received concomitant therapy (infliximab with either a thiopurine [n=67], methotrexate [n=23]) and 58 received infliximab monotherapy. Key findings:

  • Concomitant therapy >6 months  significantly lowered the risk of secondary loss of response in Crohn’s disease (CD) (HR =0.39) compared to monotherapy.   A similar trend was noted with ulcerative colitis (UC) but did not reach statistical significance.
  • Steroid-free remission rates at 1 year were 78% for CD patients with concomitant therapy compared with 54% on monotherapy
  • Among primary nonresponders, 67% of CD patients and 75% of UC patients were receiving IFX monotherapy.
  • No differences in adverse events were evident between patients receiving monotherapy compared with concomitant therapy. One patient (receiving azathioprine) developed a follicular lymphoma; this patient was well 10 years later.

The second study (Y Qui et al. Clin Gastroenterol Hepatol 2017; 15: 1359-72) was a systemic review of 35 studies that met the authors’ inclusion criteria. In total, 6790 patients with inflammatory bowel disease were enrolled in these studies. This study looked at multiple anit-TNF agents including infliximab, adalimumab, certolizumab, and golimumab. Key finding:

  • Antidrug antibodies were reduced by 51% in patients receiving concomitant therapy
  • Conclusion from authors: “concomitant use of immunomodulators should be considered in patients treated with anti-TNF treatment.”

My take: Overall, for most pediatric patients with CD, to date, concomitant therapy has been the most effective treatment.  More prospective studies are needed to determine more conclusively the benefit and optimal duration/timing of combined therapy, particularly with the more frequent use of therapeutic drug monitoring.  Also, as will be noted in future posts from annual meeting, thiopurine use is declining.

More on this topic tomorrow.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Infliximab Infusions Without Premedication

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Briefly noted:

A recent study (SQ Hutsell, M Wu, KT Park. JPGN 2017; 65: 430-31) examined two practice changes with regard to infliximab (IFX) infusions:

  1. 1-hour infusions
  2. Omission of premedications

The authors reviewed ~900 IFX infusions; though, only 111 infusions were administered without premedications.  These two changes resulted in a 51% decrease in infusion hours, despite a 9% increase in total number infusions. No increase in adverse reactions was identified.

The authors state that these changes improve patient experience, shorten monitoring time, and reduce costs.

 

>99% Accuracy in Non-Biopsy Diagnosis of Celiac Disease

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Another large study (KJ Werkstetter et al. Gastroenterol 2017; 153: 924-35) shows a high accuracy of diagnosing celiac disease (CD) without a biopsy when very high celiac titers are identified in symptomatic patients. A previous study (n=898) this year also showed similar findings: The Non-Biopsy Diagnosis of Pediatric Celiac Disease

The current study (2001-2014) identified 743 consecutive pediatric patients with positive celiac serology (TTG-IgA). Key findings:

  • If TTG-IgA was higher than 10-fold the upper limit of normal and a separate sample tested positive for endomysial antibodies, then non-biopsy approach had a positive predictive value >99.6%.  The authors utilized a variety of TTG-IgA assays.
  • The authors noted that HLA-DQ2/DQ8 typing did not improve the accuracy of CD diagnosis.  “Negative results for HLA-DQ2/DQ8 in patients with TGA or EMA positivity are most likely false negative …or due to very rare risk-allele combinations not recognized by the test systems.”
  • “At least 50% of affected children in clinical practice will benefit from this nonbiopsy approach, which reduces burden and risks of endoscopy and anesthesia” and is more cost-effective.

The authors’ conclusion: “allowing omission of biopsies enables a correct diagnosis of CD in symptomatic children if TTG-IgA exceed 10xULN and positive EMA-IgA confirms celiac disease autoimmunity in a second blood sample. If one of these criteria is not fulfilled, biopsy should be performed to confirm the diagnosis.”

My take: This study provides convincing data that CD diagnosis does NOT require an intestinal biopsy under specific conditions.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Breastfeeding: Protection from Inflammatory Bowel Disease

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Xu L, et al. Systematic review with meta-analysis: breastfeeding and the risk of Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2017;46:780-789.

https://doi.org/10.1111/apt.14291Thanks to Mike Hart for this reference.

From abstract:

Results

A total of 35 studies were included in the final analysis, comprising 7536 individuals with CD, 7353 with UC and 330 222 controls. Ever being breastfed was associated with a lower risk of CD (OR 0.71, 95% CI 0.59-0.85) and UC (OR 0.78, 95% CI 0.67-0.91). While this inverse association was observed in all ethnicity groups, the magnitude of protection was significantly greater among Asians (OR 0.31, 95% CI 0.20-0.48) compared to Caucasians (OR 0.78, 95% CI 0.66-0.93; P = .0001) in CD. Breastfeeding duration showed a dose-dependent association, with strongest decrease in risk when breastfed for at least 12 months for CD (OR 0.20, 95% CI 0.08-0.50) and UC (OR 0.21, 95% CI 0.10-0.43) as compared to 3 or 6 months.

From associated editorial by David Rakel:

This meta-analysis of 35 studies shows that there is a dose–response protective effect of the duration of breastfeeding on inflammatory bowel disease. The association shows as much as an 80% reduction in risk for both Crohn’s disease and ulcerative colitis for breastfeeding more than 12 months.

Breast Feeding Graph

Inflammatory bowel disease arises from a complex set of interactions related to genetic susceptibility, environmental exposures, and a dysregulated immune response to dysbiotic intestinal microbiota, according to the study authors. These data will give us one more reason to encourage breastfeeding, ideally for a year or more.

Related blog post: Nutrition Week (Day 7) Connecting Diet and Epidemiology in IBD

 

 

Prospective Outcome Data for Infants with Gastroschisis

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A recent study (BS Fullerton et al. J Pediatr 2017; 188: 192-7) reports outcome data from 4420 neonates with gastroschisis from 175 North Amercan centers.

This study, using prospectively-collected data from the Vermont Oxford Network, was restricted to infants with birth weights >1500 g and gestational age >28 weeks.

Key findings from this cohort:

  • Survival was 97.8%
  • Length of stay (LOS) 37 day median
  • Sepsis, confirmed with either positive blood culture or CSF culture, “was the only independent predictor of mortality.”
  • In addition to gastroschisis repair, abdominal surgery was needed in 22.3%
  • At discharge, 57.0% were <10% weight for age; whereas, only 37.2% were born small for gestational age.
  • There were no outcome differences based on mode of delivery (eg. vaginal vs. cesarean)
  • Other congenital anomalies were noted in many infants, with 5.8% had an intestinal atresia: 4.6% jejunal/ileal, 1.9% colonic, 0.4% duodenal atresia.

My take: This contemporary study shows excellent survival of neonates with gastroschisis.  Sepsis, need for additional surgery, and poor growth remain important challenges.

Related blog posts:

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