Category Archives: Pediatric Gastroenterology Intestinal Disorder

NASPGHAN Postgraduate Course 2012

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Postgraduate course syllabus: naspghn.informz.net/

So far I’ve looked at the first few talks from the postgraduate course syllabus (see link above), including CVS slides by B Li.  Several good pointers are given.  For example, for abortive therapy, he recommends use of Zofran 0.3 mg/kg/dose.  Page 17 of course book details preventative measures.  Also, with regard to amitriptyline, he recommends starting at 0.3 mg/kg and titrating as needed up to 1-1.5 mg/kg/day.  Mitochondrial-type support often helpful as well (eg. CoQ10 10 mg/kg/day divided BID).

At the end of this lecture are a couple of questions –see how you do:

  1. Which NASPGHAN Consensus diagnostic criteria for CVS is the most specific?
    1. positive family history of migraine
    2. vomiting at least 4 times/hour at peak
    3. well between episodes of vomiting
    4. each attack resembles the others
    5. associated pallor and listlessness
  2. All of the potential mechanisms below have been implicated in CVS except:
    1. HPA axis activation
    2. migraine vascular changes
    3. autonomic nervous dysfunction
    4. mitochondrial dysfunction
    5. serotonin receptor polymorphisms

page22image7408 page22image7568

3. NASPGHAN recommended evaluation of a child with episodic vomiting:

  1. a. electrolytes, BUN, Cr
  1. electrolytes, BUN, Cr & UGI
  2. electrolytes, BUN, Cr, UGI & ultrasound
  3. electrolytes, BUN, Cr, UGI, ultrasound & endoscopy
  4. electrolytes, BUN, Cr, UGI, ultrasound, endoscopy & MRI
  1. Which is the best initial approach to the 11 year old child with CVS who has failed multiple medications and missed 4 weeks of school?
    1. consult psychology for anxiety and stressors
    2. redo all laboratory and radiographic testing
    3. consider induced sleep in the PICU
    4. hospitalize and observe teenager in episode
    5. add a second prophylactic medication
  2. Which statement best applies to the preventative approach to CVS?
    1. step‐wise increases in medicines are rarely required
    2. life style modifications are not recommended
    3. after anti‐migraine agents, anticonvulsants are used
    4. toddlers should receive propranolol first line
    5. topirimate does not cause cognitive dysfunction

    Answers: 1. d;2.e;3.b;4.a;5.c

Foreign body talk: if object >2cm or longer than 5 cm, may have difficulty passing.

Also a link to the meeting notes and abstracts:
naspghan.org/wmspage.cfm?parm1=723 …

NASPGHAN POSTGRADUATE COURSE Table of Contents

MODULE A: WHAT GOES IN, MUST COME OUT: CLINICAL GASTROINTESTINAL ISSUES

FROM PROPRANOLOL TO INDUCING COMA: CARING FOR A CHILD WITH INTRACTABLE CYCLIC VOMITING SYNDROME (CVS)………………………13 INCONTINENCE WITHOUT FECAL IMPACTION    …………………………….23 ELIMINATION DIETS: RISKS AND BENEFITS……………………………………..37

MODULE B: LIVER BEYOND VIRUS, METABOLIC, STORAGE, TUMORS

METABOLIC LIVER DISEASE: WORKING THROUGH THE MAZE ……………….51 UPDATE ON ALPHA‐1‐ANTITRYPSIN DEFICIENCY         ……………………………61 THERE IS A LIVER MASS ON THE ULTRASOUND: WHERE DO YOU GO FROM HERE? ….75

MODULE C: THE INFLAMED INTESTINE

GI INFLAMMATION, IMMUNE FUNCTION AND IBD          ………………………………87 MY STOMACH IS BUGGING ME!: THE MICROBIOME IN IRRITABLE BOWEL SYNDROME ……………………………………………………………………………………………101                                                                                                THE SORE BOTTOM: PERIANAL INFLAMMATORY BOWEL DISEASE         ……111 RESCUE ME FROM MY IBD: UPDATES ON INFLAMMATORY BOWEL DISEASE THERAPY ………………………………………………………………………………………………125

MODULE D: IMAGING AND ACCESSING THE TUBES

LOOKING DEEPLY INTO THE NOT SO SMALL INTESTINE ……………………………..137 PUTTING TUBES WITHIN TUBES: ENTERAL THERAPEUTIC ACCESS    ………….151 IMAGING THE PANCREATO‐BILIARY TREE                …………………………………….169 UPDATE ON CRITICAL FOREIGN BODY INGESTIONS  ………………………………….189

MODULE E: WHEN ALL ELSE FAILS: LIVER, INTESTINE AND POUCH

THE KID IS ON THE LIST: KEEPING COMPLICATIONS AT BAY FOR THE
NON‐TRANSPLANT HEPATOLOGIST ……………………………………………………201 TRICKS OF THE TRADE FOR INTESTINAL FAILURE ……………………………….213 GASTROINTESTINAL AND LIVER COMPLICATIONS OF BONE MARROW TRANSPLANT                                                                    …………………………225 POUCH DYSFUNCTION AND SURVEILLANCE: WHAT ARE MY OPTIONS? .235

IFfy outcome

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More long-term data on the outcome of intestinal failure (IF) are available (Squire RH et al. J Pediatr 2012; 161: 723-8).

A retrospective analysis of infants <12 months (n=272) who were receiving parenteral nutrition (PN) for more than 60 days was performed by the Pediatric Intestinal Failure Consortium (PIFCon).  This study took place between January 2000-December 2007.

Key findings:

  • Etiologies: necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), aganglionosis (11, 4%), other/multiple causes (94, 35%)
  • Residual small bowel length in 144 patients was 41 cm (25-65.5cm).
  • Catheter-related blood stream infections: 8.9 per 1000 catheter days.  (Newer techniques like antibiotic & ethanol locks were not commonly used during study period.)
  • Enteral autonomy continued into 5th year after study entry & occurred in 47%. Of the 154 patients who were alive without transplant, 27 remained on PN at the completion of the study period.  Of the patients who acheived enteral autonomy, this occurred in 31% of initial cohort  at 12 months, 40% by 24 months, 44% by 36 months, and 47% at 60 months.
  • At 72 months, a high incidence of death, 27%, was noted in this cohort. 58 died without transplantation & 10 deaths occurred in patients after transplant. Sepsis was 2nd leading cause of death (after multisystem organ failure).
  • At 72 months, cumulative percentage of intestinal transplantation was 26%.

Previous related blog entries:

Screening for subclinical PSC in IBD?

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In children with IBD, elevated liver enzymes raise the concern for primary sclerosing cholangitis (PSC).  PSC is thought to develop in up to 5% of patients with IBD.  To look more closely at this issue, a group of investigators examined 73 children (median age 12 years) with IBD with MRCP to look for evidence of PSC (JPGN 2012; 55: 308-13).

The majority of these patients had an MRCP at the time of an MRE; this was ordered independently from specific laboratory or clinical factors.  On average, the date for MRCP was about one year after the date of diagnosis.  In this group, 49 (67%) had Crohn’s disease (CD), 19 (26%) had indeterminate colitis (IC), and 5 (6.8%) had ulcerative colitis (UC) [In the results section, the authors state a discrepancy from previous: 47 with CD, 18 with IC, and 8 with UC.]

11 (15%) children had PSC-type lesions identified by MRCP.  6 of these patients had CD, 3 had IC, and 2 had UC.  Among the PSC group, 5 had abnormal AST & ALT, 4 had abnormal GGT, and 1 had abnormal bilirubin at time of diagnosis & similar numbers were present at the time of MRCP.  A much lower percentage of the non-PSC group (n=62), had abnormal LFTs.  Though, at time of MRCP, 9 (14.5%) had abnormal ALT.

An editorial in the same issue (page 238), concludes that “screening for PSC by MRCP in all of the newly diagnosed patients with IBD seems promising.”  Really?  Given a lack of therapeutic options, I don’t think identifying preclinical PSC makes any sense.  An exception would be in patients with persistent liver test abnormalities to avoid attributing this to medication toxicity.

Previous RELATED BLOG ENTRies

Challenges with primary sclerosing cholangitis | gutsandgrowth

Colonic disease and PSC | gutsandgrowth

Additional reference:

-Hepatology 2009; 50: 808-14.  High-dose ursodeoxycholic acid not effective for PSC (worsened outcomes noted)

INSPPIRE for pancreatitis

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While anyone who follows this blog knows that I like acronyms, I must say that many investigators have taken lessons from Krispy Kreme on spelling.  INSPPIRE is named for the International Study Group of Pediatric Pancreatitis: In Search for a Cure.  A study from this group reports on definitions of pediatric pancreatitis & surveys current practice (JPGN 2012; 55: 261-65).

The literature regarding acute recurrent pancreatitis and chronic pancreatitis in children is limited.  This consortium hopes to change this.  As a start, the authors assigned subcommittees to establish definitions, reviewed the literature, and assessed current practice.

Definitions:

  • Acute pancreatitis (AP): requires at least 2 of 3 criteria:
  1. Abdominal pain consistent with AP
  2. Serum amylase and/or lipase activity at least 3 times ULN
  3. Imaging findings compatible with AP
  • Acute recurrent pancreatitis (ARP): requires at least two episodes of AP along with

Complete resolution of pain (≥ 1-month pain-free interval) OR complete normalization of pancreatic enzyme levels along with resolution of pain (can be shorter interval than 1 month)

  • Chronic pancreatitis (CP): requires one of the following:
  1. Abdominal pain and imaging suggestive of chronic pancreatic damage
  2. Exocrine pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
  3. Endocrine  pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
  4. Surgical/histologic specimen consistent with chronic pancreatitis

Managing pancreatitis:

Typical tests for these three conditions are shown in figure 2 and vary widely.  For AP, most respondents (63%) routinely checked liver enzymes, triglycerides, calcium and abdominal ultrasound.  For ARP and CP, most respondents (69%) obtained additional imaging modalities (eg. MRCP), genetic testing, and sweat chloride. If ERCP was needed, 88% of practices relied on adult gastroenterology colleagues.

Related blog posts:

Recurrent pancreatitis and genetic underpinnings | gutsandgrowth

Does pancreas divisum cause pancreatitis? | gutsandgrowth

How helpful are antioxidants for chronic pancreatitis pain …

Picking the right diet for EoE

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A study from Philadelphia/CHOP offers more insight into food selection diets for eosinophilic esophagitis (EoE) (Spergel JM, et al, J Allergy Clin Immunol 2012; 130: 461-7) –thanks to Seth Marcus for forwarding this article to my attention.

For this study, the authors examined their database of 1187 patients.  While the data was collected prospectively, this was a retrospective study.  Of this 1187, the authors excluded patients with proton pump inhibitor-responsive EoE (n=191) along with patients with more extensive eosinophilic GI diseases (n=55).

Among the remaining 941, the male-to-female ratio was 2.8:1 and the average age was 6.4 years. Concurrent atopic disorders were common: 64% had rhinitis, 50% had asthma, and 24% had atopic dermatitis.  Only 18% had no atopic disorders.

The actual number for the study though was 319.  Among the 941 noted above, 148 were receiving medications (n=130 for topical steroids), and causative foods were not identified in 474.  In some of these patients, families were content to stick with a multiple food elimination without determining with certainty which foods were truly necessary.

In less than 5% of patients, a strict elemental diet was used.  In this group, the population was younger (average 2.8 years).  Biopsy improvement was noted in “upward of 98%.”

Key findings:

  • Elimination of foods based on combined skin prick tests (SPT)/atopy patch tests (APT) had an identical response to the six food group diet –53%.  The allergy testing group had less eliminated foods (average 3.2 foods) compared with 8 food groups in SFED.
  • Elimination of milk with SPT/APT testing resulted in 77% response.  Authors note that there was a “particularly high false-negative rate (34%)” with milk testing (SPT/APT).
  • Elimination of top 8 allergens: milk, soy, egg, wheat, and meats [chicken, turkey, pork, beef] had an identical response of 77%.
  • Elimination of milk, egg, and wheat had a success rate of 48%.  Milk only elimination had a 30% response rate.
  • Most common foods by biopsy: milk (35%), egg (13%), wheat (12%), soy (9%), corn (6%)
  • Most common foods by symptoms: milk (19%), egg (11%), wheat (9%), soy (10%), beef (8%)
  • IgE-mediated foods:  milk (10%), egg (17%), soy (4%), peanut (22%)

Additional useful information in the addendum of methods notes their technique for APT testing (which is not standardized across centers).  The authors use 2 g of dry foods in 2 mL of isotonic saline solution for most foods; for milk, they use 3 g of powdered milk with 1 mL of isotonic saline.  Then these mixtures are placed in aluminum cups (6- or 12-mm Finn chambers on Scanpore).  These cups are placed on patient’s backs and removed at 48 hours and read at 72 hours.

In addition, for each food, their tables list predictive values (positive predictive value, negative predictive value, sensitivity, and specificity) for SPTs, and for APTs.  Overall, the predictive values are quite variable and much different from the general population. For example, in the general population, the negative predictive value is essentially 100% for combination of SPT/APT.

Previous related blog entries:

Choosing topical therapy for EoE | gutsandgrowth

Guidelines for Eosinophilic Esophagitis | gutsandgrowth

Looking better or feeling better in EoE?

Look of improvement on an EoE diet

Eosinophilic Esophagitis -Six Food Group Diet

MicroRNA signature for eosinophilic esophagitis

The undiscovered country

According to the study which you would never qualify for…

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When I give patients advice on treatment, I rely on well-designed studies to help select the medications/treatments that are most likely to be effective.  It is interesting to ponder how applicable these studies are and how closely they reflect the patient population that I’m seeing.  A recent article indicates that in a tertiary referral center for inflammatory bowel disease, the majority of patients would be excluded from participation in these studies (Clin Gastroenterol Hepatol 2012; 10: 1002-07).

These authors performed a retrospective cohort study of patients presenting to the Mount Sinai Medical Center between January 2008 and June 2009.  For Crohn’s disease (CD) patients, the authors selected 7 published randomized control trials of biological therapy for patients with moderate-severe disease (ACCENT 1, CLASSIC 1, CHARM, PRECISE 1, ENCORE, ENACT, and SONIC).  For Ulcerative Colitis (UC), they selected ACT 1 and ACT 2 trials for moderate-severe UC.

Only 31.1% of 206 patients with IBD would have been eligible to participate in any of the selected RCTs.  The average age of their patients was about 35 and did not differ significantly among patients who would qualify compared to those who would not.

Among the CD patients, the inflammatory phenotype was most likely to qualify; 37 patients with inflammatory disease behavior would have been eligible.  While only 54% (37 of 68) of the inflammatory phenotype would have qualified, this accounted for 86% of the total population who would have qualified (only 34% of the entire CD cohort would have been eligible for study participation).

Among the UC patients, there were no disease characteristics or demographics associated with eligibility; that is, there was a similar distribution of disease extents, Mayo scores, disease duration, gender, and age among the patients who qualified and those who did not.

Reasons for exclusion: stricturing or penetrating disease, steroid dosing, comorbities, concomitant therapies, or prior exposure to biologics.

The authors note that the results from this study mirror that from similar studies with other chronic diseases including rheumatoid arthritis, chronic obstructive pulmonary diseases, and congestive heart failure.

When the authors looked at the trial-ineligible patients, 60% had a response to biological therapy. The response rates for ineligible patients (compared to eligible patients) were lower for CD patients but not for UC patients (Figure 2 in study).

While stringent criteria for eligibility limit the external validity of the study results, these criteria are in place for multiple reasons.  Less rigid selection criteria would require larger study populations, longer duration studies, and greater costs.

The issue of study applicability is even a bigger problem in pediatrics.  This is primarily due to fewer high quality studies in children. As such, many clinical judgements require extrapolation from adult studies.

Related blog post:

Interpreting industry-funded studies

GI & Nutrition Problems in Rett Syndrome

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A nationwide survey of 983 patients with Rett syndrome identifies a high prevalence of GI and nutritional problems (Motil KJ et al. JPGN 2012; 55: 292-98).

Parents from 983 female patients with Rett syndrome responded to the study questionnaire; this was a 59% response rate from the 1666 families in the North American Rett Database.  Patients included those who fulfilled clinical criteria for diagnosis or who had MECP2 gene (methyl-CpG-binding-protein).

Prevalence of GI problems were listed in article’s Table 2 and included the following:

  • Gastrointestinal problems 92%
  • Feeding problems 81%
  • Constipation 80%
  • Poor weight gain 38%
  • Gastroesophageal reflux 39%

Z-scores for height-for-age, weight-for-age, and BMI are presented for ages 0-40 (see Table 1) -these are all significantly lower than age-matched healthy children.

Important findings:

  • Surgical interventions were common: 11% had fundoplication, 28% gastrostomy, 3% and cholecystectomy
  • Many gastrointestinal symptoms improved with age.  However, short stature, gastrostomy tube, and bone health issues were more common in older patients.
  • Bone fractures are 3- to 4-fold higher than in healthy children

Addtional references:

  • -J Pediatr 2010; 156: 135.  Longevity in Rett syndrome –about 1/2 survive to age 40.
  • -Ann Neurol 2010; 68: 944-50.  Rett diagnostic criteria
  • -JPGN 2007; 45: 582-90.  Growth/feeding issues in Rett syndrome

What is the risk of colon cancer in IBD?

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Some recent studies have shown that colorectal cancer complicating IBD may not be as common as previously thought or may be decreasing in incidence (Gastroenterology 2012; 143: 375-81 & Gastroenterology 2012; 143: 382-89 ).

The first study used a nationwide cohort of 47,374 Danish patients with IBD over a 30-year period.  During a 178 million person-years of follow-up evaluation, 268 patients with ulcerative colitis (UC) and 70 patients with Crohn’s disease (CD) developed colorectal cancer (CRC).  The risk was comparable to the general population (RR 1.07)!  Furthermore, the relative risk for CRC decreased over sequential time periods: 1.34  (1979-88) to 0.57 (1999-2008).

Increased risk:

  • UC diagnosed in childhood or adolescence
  • longer disease duration
  • patients with primary sclerosing cholangitis

Their conclusion, ‘the overall risk of CRC in patients with UC has decreased markedly over time and no longer exceeds that of the general population, at least in the first decade after diagnosis.”  And, based on their data, patients with Crohn’s disease are not at increased risk for CRC.

The second study from California used a large Kaiser Permanente database from 1998-June 2010.  29 cancers were identified in CD (n=5603) and 53 in UC (n=10,895) patients.  The incidence per 100,000 for CRC was 75 for CD, 76 for UC, and 47 for general population.

These authors conclude that there is an increased risk of CRC in a community-based IBD population between 1998-2010 despite advances in medical treatment.

To understand the discrepancy of these reports, the same issue provides an editorial (page 288).  My take is that the current incidence of CRC is lower than in previous reports but that the risk factors identified in the Danish cohort (see above) likely remain important.

Additional references:

  • -Gastroenterol 2009; 136: 718. 22% of cancers occurred before recommended surveillance in adults (only 9% if exclusion of patients who had IBD and cancers diagnosed at same time).
  • Colon Cancer Survival Calculator http://www.mayoclinic.com/calcs-Gastro 2010; 138: 207-2177 (entire issue)
  • -JAMA 2009; 302: 649. Aspirin use likely increases survival after dx of colon cancer. Commentary-Gastro 2010;138: 2012.
  • -NEJM 2009; 361: 2449. molecular basis of colorectal cancer
  • -Gut 2008; 57: 1246. IBD and colon cancer
  • -IBD 2007; 4: 367. 5ASA Rx did not reduce rate of cancer in large study of UC/CD -review of 18,000 colorectal cancer cases. IBD increased risk of CRC 6-7-fold..
  • -Clin Gastro & Hep 2006; 4: 1346. aminosalicylates reduce CRC.
  • -Gastroenterol 2006; 130: 1030, 1039, 1350. 600 patients followed for 35 yrs: CRC by colitis duration: 2.5% @ 20yrs, 7.6% @ 30yrs, 10.8% @ 40yrs. 5 year survival was 73% among those with cancer. 2nd study showed main CRC risk in UC pts is among those with extensive colitis.
  • -Clin Gastro & Hepatol 2004; 2: 1088. Lower cancer risk in this cohort, n=1460. CRC 0.4 @10yrs, 1.1% @ 20yrs, 2.1% @ 30yrs. Lower CRC may be due to more surgery in Rx failures & use of 5-ASA.
  • -Clinical perspectives in Gastro 1999; 2: 9 & 25. (review) surveillance/ overview take 4 bx q10cm. start p 8yrs in pancolitis & 15yrs for left-sided dz. Cancer risk: ~5% at 20yrs + 1%/yr p 20yrs in pancolitis.
  • -Gastroenterol 2003; 125: 1311. Advancement of dysplasia to cancer in UC.

Gluten avoidance -quite common

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In a pediatric Boston cohort of 579 patients presenting for celiac evaluation but no previous diagnosis, 7.4% had previous gluten avoidance (J Pediatr 2012; 161: 471-5). In this cohort, the mean age at presentation was 8.7 years.

Independent predictors of gluten avoidance and the odds ratio (OR) included the following:

  • Irritability OR 3.2
  • Family history of celiac OR 2.2
  • Diarrhea OR 2.5
  • Pervasive developmental disorder OR 5.3

From my perspective, many families and sometimes referring physicians are convinced that their child has celiac disease before subspecialty evaluation. While a gluten-free diet may reduce some gastrointestinal symptoms even in the absence of celiac disease, it is probably helpful for families to complete diagnostic testing and to obtain dietary counseling prior to implementing a gluten-free diet.

Previous related blog entries:

More intriguing than helpful

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A recent study reports that a pH-impedance (pH-MII) may help identify children with allergen-induced gastroesophageal reflux disease (GERD) after exposure to cow’s milk (J Pediatr 2012; 161: 476-81).  The study population included 17 children (average age 14 months) with a clinical diagnosis of cow’s milk allergy (CMA) who had responded to an elemental diet.

Given the limitations of the study, it is hard to take seriously the conclusions of the authors that in “selected cases of children with CMA in whom GERD is suspected” pH-MII “should be considered as part of diagnostic workup.”

The limitations:

  • CMA diagnosed clinically based on response to dietary therapy
  • GERD diagnosed based on Infant GER Questionnaire, though authors acknowledge that “we are aware that no symptom or cluster of symptoms have been shown to reliably predict the diagnosis of GERD”
  • Statistically-significant findings only for weakly acidic reflux which was induced on second day after switching from elemental formula to cow’s milk
  • No endoscopic correlation of mucosal disease or exclusion of eosinophilic esophagitis
  • Small number of patients

I cannot see how obtaining a pH-MII study would offer a meaningful benefit to these patients; though, it is intriguing that one potential measure of clinical deterioration like increased weakly acid episodes can be detected when these patients are challenged with cow’s milk.

Some related blog entries:

Impedance recommendations from PIG

Gastroesophageal Reflux: I know it when I see it

Guidelines for Eosinophilic Esophagitis