Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

PEG vs. Fiber for constipation

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Which is better for childhood constipation, polyethylene glycol 3350 (PEG) or fiber? A recent study weighs in (J Pediatr 2012; 161: 710-15).

This randomized, prospective, open-label study compared PEG (with electrolytes) to a fiber supplement (acacia fiber, psyllium fiber, and fructose [AFPFF]) in 100 children with chronic functional constipation (Rome III criteria).  Mean age was 6.5 years.  Study design allowed for dosage adjustment.  Initial PEG dosing was 0.5 g/kg but could be increased to 1 g/kg. AFPFF was dosed at 16.8 g daily but could be increased to 22.4 g.  Primary outcome was ≥3 bowel movements per week and improved stool consistency (≥2 on Bristol stool scale).

Key findings:

  • Compliance was better with PEG than AFPFF: 96% for 72%.
  • After 8 weeks, improvement noted in 83% of PEG patients compared to 78% of AFPFF (P=0.788).  At this time point, PEG were having ~5.8 stools/week vs. 5.6 for AFPFF.  Mean Bristol scores were 3.7 and 3.5 respectively.
  • Conclusion: similar efficacy but PEG had better acceptance.  No mention of relative costs of these agents is noted.

Additional references:

Diagnosis and management of idiopathic childhood constipation – BMJ  NICE (Nat’L institute for Health and Clinical Excellence) recommendations 2010

Also, a recent previous post (ACE report -10 year effectiveness | gutsandgrowth) has links to multiple related blog entries.

Microbiome in pediatric ulcerative colitis

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Alterations in the gastrointestinal tract microbiome may play an important role in many digestive conditions.  A recent article examines microbiome alterations in children with severe ulcerative colitis (UC) (Inflamm Bowel Dis 2012; 18: 1799-1808).

Stool samples from 26 healthy children and 27 children with severe UC were prospectively studied.  After DNA extraction, PCR amplification and microarray hybirdization were performed and analyzed.   None of the patients in the study had received antibiotics or probiotics in the preceding month.

Key findings:

  • There were substantial reductions in “richness,” diversity, and evenness of the gut microbiome in UC patients.  (Richness is a term used to reflect the number of detected phylospecies.)
  • There was a decrease in signal in almost all  phylospecies.
  • The number of phylospecies was reduced in UC (266 ± 69) vs controls (758 ± 3)
  • Steroid responders had even fewer phylospecies compared with responders (142 ± 49  vs. 338 ± 62)

It is not surprising that the stools from these children are much different.  The issues of causation and whether a snapshot of the microbiome diversity will have clinical relevance is not clear.  It is possible that antimicrobials may make an individual more susceptible to inflammatory bowel disease by altering the individual’s microbiome.

Related blog entries:

Eat your veggies…if you don’t want to get sick | gutsandgrowth

Why are we seeing so many more cases | gutsandgrowth

ACE report -10 year effectiveness

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More data is now available on the use of antegrade continence enema (ACE) for difficult-to-treat defecation disorders (J Pediatr 2012; 161: 700-4).

This study reports the 10-year (retrospective) experience of a single center.  In total there were 99 patients, median age 8 years.  Mean time for followup was 46 months.  Most procedures were undertaken by interventional radiology with temporary  8.5 Fr Dawson-Mueller catheter which was changed to a Chait Trapdoor catheter after six weeks.  All patients received triple antibiotics for 48 hours and then oral metronidazole for 7 days.  While ACE were not started for 10-14 days, the tube was irrigated with 10 mL of normal saline BID after placement.

Key findings:

  • 71% became symptom-free, and an additional 20% improved significantly
  • Patient population: 35 with functional constipation, 29 with spinal abnormalities, 8 with cerebral palsy, 8 with Hirschsprung’s, 7 with imperforate anus, 7 with combined imperforate anus/tethered cord, and 5 with other causes
  • Irrigations with a stimulant seemed to be more effective.  Specific stimulants included bisacodyl (5 mg if patient <10 years and 7.5 mg if >10 years) and glycerine (median dose 37.5 mL).
  • In the 7 patients without improvement, the stoma was closed after a median time of 7 months & 5 ultimately underwent colostomy.
  • Risk factors for poor outcome: younger age, shorter duration of symptoms, Hirschsprung’s disease, cerebral palsy, previous abdominal surgery, and abnormal colonic manometry (Previous studies have not shown that preop manometry helpful in predicting outcome of ACE).
  • 13% of patients were able to discontinue ACE without recurrence of symptoms
  • Major complications occurred in 12 patients.  12 patients had infections, 4 had abscess, and 3 had peritonitis.  Minor complications were commonplace including leakage in 21 and granulation tissue in 41 patients.

I think this report does provide a balanced view of cecostomy/appendicostomy placement; this will be helpful in counseling families.  While the majority of children will be able to irrigate their colon and thus minimize their intractable constipation, many will have issues with the tube site and particularly early on there is a risk of serious infections.

Related blog entries:

Clues about constipation and more than 2.5 million views …

Stimulants for constipation | gutsandgrowth

It’s worth the cost | gutsandgrowth

thyroid | gutsandgrowth

Additional references:

  • Percutaneous Endoscopic Colostomy (PEC) – YouTube (LEFT-SIDED PROCEDURE)

  • -J Pediatr Surg 2010; 45: 213-9.  ACE highly effective for intractable constipation
  • -JPGN 2011;52: 574.  n=117. 69% success with antegrade enemas.
  • -JPS 2002; 37: 348-51.  sigmoid irrigation.
  • -Lancet 1990; 336: 1217. Malone’s initial description.

Brain and body benefits of chocolate?

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Chocolate has been receiving a lot of good press, including purported benefits in weight loss (Arch Intern Med 2012;172:519-521.) and now for cognitive function (NEJM 2012; 367: 1562-64).

The first article looked at the chocolate consumption of 975 subjects who completed food frequency questionnaires.  The mean age of these participants was 57 years.  “After controlling for multiple potential confounders including sex, physical activity, fruit and vegetable intake, depression, and total caloric intake, frequency of chocolate consumption continued to be associated with lower BMI.”

The second study shows a correlation with a countries’ annual per capita chocolate consumption and the number of Nobel laureates per 10 million population.  The highest per capita rate of Nobel prizes is in Switzerland!  The author notes that cocoa and other flavonols seem to be effective in slowing or reversing reductions in cognitive performance that occurs with aging and have other potential benefits.  One of the limitations in the author’s analysis included reverse causation —that is enhanced cognitive performance could stimulate more countrywide chocolate consumption.  This seems more plausible to me.  Fortunately for readers of this intriguing study, the author did provide a relevant disclosure: “Dr. Meserli reports regular daily chocolate consumption, mostly…Lindt’s dark varieties.”

Vision and persistence in developing liver transplantation

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A concise perspective article examines the history and challenges of developing liver transplantation into an accepted treatment for end-stage liver disease (NEJM 2012; 367: 1483-86).

Key points:

  • Thomas Starzl 1st attempted liver transplant in 1963.  The 3-year-old boy with biliary atresia did not survive the operation; the next 5 attempts were failures as well with the longest survivor lasting only 23 days.  A moratorium of nearly 4 years was placed after these initial failures.
  • Improvements in immunosuppression were a key advance, including antilymphocyte serum in 1966.  During the 1970s, 70% of liver-allograft recipients died shortly after surgery.
  • Brain death concept, accepted in 1968, allowed for better donor organs (less ischemia)
  • Key immunosuppression advance was in 1979 when Roy Calne (Cambridge) reported the use of cyclosporin for organ transplantation.  Between 1980-81, 70% (n=40) of Starzl’s patients survived more than one year.
  • In 1983, National Institutes of Health at a consensus conference concluded that liver transplantation should be considered a ‘clinically applicable, lifesaving procedure.’
  • Other improvements, such as better organ procurement protocols and preservation along with further improvements in immunosuppression have helped improve 1-year and 5-year survival rates to climb, >85% and >70% respectively in 2010.
  • In 2010, 6291 patients underwent liver transplantation.
  • Remaining challenges include inadequate organ supply, recurrent primary hepatic disease (eg. hepatitis C), adverse drug effects, and post-transplantation complications.

The persistence and vision of Starzl and Calne has been recognized with the Lasker-Debakey Award (Lasker-DeBakey Clinical Medical Research Award – Wikipedia, the …).

Once daily Mesalamine

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Based on the literature, it is not clear that there is any need to give melamine more than once a day; this is often in contrast to labeling for many of these products:

  1. Inflamm Bowel Dis 2012; 18: 1785-94 
  2. Inflamm Bowel Dis 2012; 18: 1885-93

The 1st study identified 11 relevant randomized studies, after excluding 6870 that were considered irrelevant. Five of these studies were single blind and one was open-label; the remainder were double-blind randomized trials. In total, these studies examined 4070 patients.

Mesalamine products studied: Mesalazine (Salofalk), MMX mesalamine, Asacol, and Pentasa

Summary of findings:

  • Failure to induce clinical remission: relative risk (RR) with once daily 0.95; absolute risk 421 per 1000 in once daily group
  • Failure to induce clinical improvement: RR 0.87; absolute risk 398 per 1000
  • Failure to maintain clinical remission at 12 months: RR 0.92; absolute risk 286 per 1000
  • Failure to adhere to study medication regimen: RR 1.21; absolute risk 128 per 1000

Thus, this meta-analysis indicates that once daily dosing is as effective as conventional dosing for both induction and maintenance, at least with the formulations that were tested. Also, in this meta-analysis, adherence was not improved with once daily therapy, though some previous studies have indicated that once daily therapy may be helpful particularly in the first few months of treatment.

The 2nd study examined 213 patients for maintenance of UC remission; patients were randomized to receive either Asacol 2.4 g once a day (QD) or 800 mg three times a day (TID). Patients were treated at 32 UK centers and had an average age of 50 years. Relapse rates were 31% for QD therapy and 45% for TID over 1 year.  This study showed that QD was noninferior to TID and possibly superior, perhaps due to improved adherence.

Perhaps it is time to give all mesalamine products once a day.

Six years later-Mediterranean diet comes out on top

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This month a followup letter provides long-term data on the outcomes of individuals assigned to either a low-carb, low-fat, or Mediterranean diet (NEJM 2012; 1373-74).

An initial study posted two-year results.  Now after an additional four years, the following results were noted:

  • Among the 259 participants (80% of original groups and 95% who completed the initial two years), 67% had continued their original assigned diet.
  • For the entire 6-year period, the total weight loss was 3.1 kg in the Mediterranean group, 1.7 kg in the low-carb group and 0.6 kg in the low-fat group.
  • At 6 years the change in the ratio of LDL to HDL were similar in all three groups though the low-carb group had the most favorable results with a reduction of 0.16.
  • At 6 years, the reduction in triglyceride levels from baseline were significant for the Mediterranean group (21.4 mg/dL) and the low-carb group (11.3 mg/dL).
  • All of the groups had regained some of their weight loss from the initial 2-year period.  The most favorable outcomes were noted in the Mediterranean diet and then the low-carb diet in this workplace intervention trial.

Related blog entries:

“Beyond the bombs: cancer risks of low-dose medical radiation”

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The catchy title comes from a Lancet editorial (Lancet 2012; 380: 455-57); the related article (Lancet 2012; 380: 499-505) details the radiation risk posed by CT scans.

While concerns about imaging radiation exposure have become commonplace, the evidence for the risk has been more in the theoretical realm rather than proven.  That is, the risk projection models were based on studies of survivors of the atomic bombs in Japan.

The retrospective study in Lancet examines 178,604 children who underwent CT between 1985-2002.  Typical followup was 10 years (maximum followup of 23 years).  None of these children had cancer at the time of CT.  The study determined the number of leukemias that developed more than 2 years following CT and brain tumors which occurred more than 5 years after CT.  This lag time was done to avoid any confounding of cancer that may have been present and not detected at time of CT.

Key results:

  • 74 patients developed leukemia and 135 developed brain tumors.  There was a dose-related risk: 0.036/mGy for leukemia and 0.023/mGy for brain tumors.  Thus, the relative risk of leukemia in patients who had at least 30 mGy was 3.18; whereas, brain cancer risk for a cumulative dose of > 50 mGy was 2.82. [1 mGy=1 mSv]
  • If typical doses of CT administered, 2-3 head CTs could triple the risk of a brain tumor and 5-10 head CTs could triple the risk of leukemia.
  • The absolute risk remains low.  In patients less than 10 years, one excess case of leukemia and one brain tumor would be expected for 10,000 head CT scans.

Goal with CT scans:

  1. ALARA: as low as reasonably achievable –for every study.  Newer protocols allow lower radiation doses while preserving good image quality.
  2. Think carefully about each CT.  It is estimated that 20-50% of CTs could be replaced with another type of imaging or not done at all.

For the skeptics about the risk of CT scans, the editorialist concludes that this study confirms “that CT scans almost certainly produce a small cancer risk…we must redouble our efforts to justify and optimize every CT scan.”

Related blog entries:

How much radiation from your CT scanner? | gutsandgrowth

More imaging needed? | gutsandgrowth

Magnetic resonance enterography for Crohn’s disease …

Additional references:

  • -AJR 2001; 176: 289-96. Estimated risks of radiation-induced fatal cancer from pediatric CT
  • -Br J Radiol 2012; 85: 523-28.  Justification of CTs -some not needed
  • -AJR 2010; 194: 868-73.  Lower CT radiation doses in pediatric patients.  ‘Image gently’
  • -Arch Intern Med 2009; 169: 2078-86.

Outcomes with STEP procedure

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While the serial transverse enteroplasty (STEP) procedure has been considered a major advance in the management of short bowel syndrome (SBS), long-term data are in short supply.  5-year outcomes from Toronto with regard to 12 patients offers some insight into the effectiveness of this operation (J Pediatr Surg 2012; 47: 931-37).

The 12 patients selected for this study received STEP prior to January 2005.  The other 19 STEP patients at this institution were not included due to lack of long-term followup. Among the 12 patients, 6 had intestinal atresia, 3 had NEC, 1 had gastroschisis, 1 had volvulus, and 1 had Hirschsprung disease.

Key results:

  • 7 patients weaned off parenteral nutrition successfully –one took 4 years; one patient continued on parenteral nutrition.
  • 2 patients died of liver failure, 2 patients received liver-intestinal transplant.
  • STEP increased small bowel length from a median of 110 cm to 128 cm.  The dilated portion that received STEP changed from a median length of 31 cm to a median of 57 cm; this resulted in a median bowel caliber change from 6 cm to 2 cm.  The overall effect was an overall increase in small bowel length of 40%.
  • Biochemical markers improved.  For example, citrulline increased from 18 μmol/L pre-STEP to 33 μmol/L at 12 months, and 48 μmol/L at 5 years post-STEP.  Fecal fat malabsorption (based on 72 hr collections) improved from >40% to ~20% 6 months after STEP.
  • Indications for STEP: bacterial overgrowth (n=7), intestinal failure associated liver disease (IFALD) (n=5).
  • Complications: suture line bleeding due to ulcerations in one patient, 2 patients had leakage at suture line in immediate post-op period.  The latter 2 cases were ascribed to limited experience with technique; the surgeons now use a 2.5 mm staple instead of a 3.5 mm.

Take home points:

  1. Authors comment: “our approach is to only consider patients who plateau in their parenteral nutrition weaning or develop complications such as PN cholestasis…patients who continue to show intestinal adaptation are not offered surgery despite the presence of bowel dilatation”
  2. “It takes up to an average of 1 to 2 years to see the improvement in intestinal function after a STEP.”  While the authors may be correct about this timeframe, in their figure 3, two came off PN at one month post-STEP, four achieved this goal 6 months after STEP and another 12 months following STEP.
  3. Why does STEP work? Either improved intestinal function due to increased absorptive surface or due to healing of existing mucosa; the latter may occur with resolution of dilated,  inflamed bowel associated with bacterial overgrowth.

Related blog entries:

Four advances for intestinal failure | gutsandgrowth

IFfy outcome | gutsandgrowth

Additional STEP references:

  • -JPGN 2007; 45: 174, 257.
  • -J Pediatr Surg 2003; 38: 425-429. Initial description of STEP procedure from Kim HB et al.
  • -Clin Gastro & Hep 2006; 4: 1237. STEP in 4 patients helped to decrease or eliminate TPN requirements.
  • Images for step procedure

Cholestatic Kawasaki Disease

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Periodically, Kawasaki disease (KD) will present with fever and cholestasis (JPGN 2012; 55: 380-83).

The authors of this study which took place between 2003-2010 reviewed the presentation of children less than 16 years of age who presented with fever on admission (>38.5), total bilirubin >3 mg/dL and elevated ALT values.  In all 24 patients who met criteria for review; 5 (21%) had KD.  Patients with KD ranged in age between 1-10 years.

The other causes included viral hepatitis in 13 (EBV, HAV, CMV, Adenovirus, HSV), 4 had drug-induced cholestasis, 1 with cholelithiasis, and 1 with a choledochal cyst.

In almost 20% of KD patients, the presentation does not meet all of the diagnostic criteria: at least 5 days of fever and 4 of 5 following conditions: bilateral nonpurulent conjunctival injection, oral mucosal changes, peripheral extremity changes (edema/erythema of palms/soles, desquamation of fingers/toes), rash, cervical lymphadenopathy (unilateral, >1.5 cm).

Also, for those who did not receive yesterday’s blog on NASPGHAN postgraduate course, check out the following link:

NASPGHAN Postgraduate Course 2012 | gutsandgrowth

Additional references:

  • Kawasaki disease – Wikipedia, the free encyclopedia

  • -J Pediatr 2011; 158: 644.  Infliximab may work better than IVIG for Kawasaki.
  • -J Pediatr 2009; 155: 695.  Reviews recent experience & criteria for Kawasaki.
  • -Pediatrics 2004; 114: 1708. guidelines from AAP for Kawasaki.