Tag Archives: pediatric gastroenterology

Training for Tomorrow

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To those in the Pediatric GI community who follow this blog, particularly fellowship directors, I would urge you to have a forthright discussion about training in our field with your fellows.

After reading a recent NASPGHAN newsletter, I was concerned to find more than 110 first-year trainees (a significant increase over the last few years).  While some of these trainees have international origins and will return to their home countries, many others will be looking for job positions across the USA.  I personally think that the type of available job openings will be disappointing for many, though I recognize that “manpower” (is there a more politically correct word?) predictions have a poor track record.

My belief is that it is the ethical responsibility of each program to inform their applicants and their trainees of their potential job prospects. Ultimately, the number of pediatric gastroenterologists will adjust based on job openings and satisfaction along with other “market forces.”  Unfortunately, some in training may not be aware that their job prospects may be quite limited due to an overabundance of trainees.  Perhaps, trainees with specific niche area training such as neurogastroenterology or hepatology will have less difficulty.

The upside of the increase in trainees will be the availability of pediatric gastroenterologists to fill the spots repeatedly vacated by more senior physicians due to dissatisfaction.

My two cents…

GIKids Resource

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For those of you who have not visited GIKids.org website:

GIKids – A Resource for Pediatric Digestive Disorders

It has literally A-Z handouts on pediatric GI problems for families, including four new handouts:

One year later

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It has been one year and 300 posts since I’ve started this blog.  I’ve enjoyed putting together my thoughts about recent articles.  In addition, I like being able to search for previous blogs for information that I find helpful.

Currently there are close to ~35 hits per day in addition to the email/wordpress followers (about 30).  This number has been increasing and it is fascinating to see that people from all over the world will sometimes stumble across this blog.

If you have suggestions for topics, articles or other ways to improve this pediatric GI blog, please send me an email at jjhochman@gmail.com.

Delays in diagnosing Crohn’s disease

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Delayed diagnosis remains a problem in Crohn’s disease (Inflamm Bowel Dis 2012; 18: 496-505).  This study included a total of 1591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS).

  • Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 versus 4 months, P < 0.001).
  • 75% of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients.
  •  Independent risk factors for long diagnostic delay in CD (>24 months)  included age <40 years at diagnosis (odds ratio [OR] 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025)
  • In UC patients, nonsteroidal antiinflammatory drug (NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) were associated with long diagnostic delay (>12 months)

Diagnostic delay has been a problem for quite a long time; in children, delays can worsen growth failure.  In 1988, Kanof et al reported that decreased height velocity preceded the diagnosis of CD in 88% of their patients (pediatric cohort). In addition, 42% of their population had a reduction in height velocity before intestinal symptoms were noted.

Especially when there is not a lot of colonic disease, a high degree of suspicion needs to be maintained.  This is not difficult for pediatric gastroenterologists.  For pediatricians and family physicians, the increased availability of biomarkers (Biomarkers identify patients who benefit and how) should be helpful in reducing diagnostic delays.

Additional blog entries and references:

  • Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and adolescents before the diagnosis of Crohn’s disease. Gastroenterology.1988; 95 :1523– 1527.
  • Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America.  North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Colitis Foundation of America, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, et al.J Pediatr Gastroenterol Nutr. 2007 May; 44(5):653-74.

Pediatric HCV Guidelines

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A useful recent article, ‘NASPGHAN Practice Guidelines for pediatric HCV’ (JPGN 2012; 54: 838-55) needs to be a handy reference.  However, given the rapid changes in the HCV field, it is likely that this reference will need to be updated soon to incorporate new information (eg. IL28b) as well as emerging therapies.

Highlights:

Epidemiology: 0.2% of children & 0.4% of adolescents are HCV-infected; primary mode is mother to child (vertical) transmission which occurs in 5-7% if mother not coinfected with HIV

Testing: For infants of HCV-infected mothers, check HCV antibody after 18 months or HCV RNA at younger ages.  Need two negative HCV RNAs to exclude infection (guidelines suggest checking 6 months apart).  Most individuals should be screened with antibody testing and confirmed with RNA test.

Screening for HCC (U/S, AFP): suggested only “for those with significant liver disease (ie. cirrhosis)” due to rarity of HCC in pediatric HCC.

Treatment:

  • Not if patient younger than 3 years
  • Probably Pegylated-interferon with ribavirin –references for pediatric studies indicate response rates of about 50% for genotype 1 and about 80% for types 2 & 3.
  • Who should be treated? Not always clear.  Probably those with elevated aminotransferases or progressive disease based on liver biopsy.  Possibly those with mild disease to eradicate virus.
  • Dosing: ribavirin  15/kg/day divided twice daily; weekly PEG-IFN-α-2a 180 microgram/1.73 m2 or weekly PEG-IFN-α-2b 60 microgram*m2

Treatment monitoring (Table 8):

  • CBC/diff, Hepatic panel, glucose 0, 1, 2, 4, 8, 12 weeks, then every  4-8 weeks
  • T4/TSH 0, 12, 24, 36, 48 weeks
  • Urine HCG 0, 24 weeks (if female >12 years)
  • Prothrombin, Urinalysis at week 0
  • HCV RNA 0, 24, 48, 72 weeks

Anticipatory Guidance: “no legal requirement” to disclose HCV infection in U.S.; however, CDC suggests revealing this information to sexual partners (http://www.cdc.gov/hepatitis/hcv/)

  • Avoid sharing toothbrush, shaving equipment with household contacts, unprotected sexual activity with multiple partners, tattooing/piercing
  • Do not need to screen household or casual contacts

Special issues:

  • Vaccines: HCV patients should receive all standard vaccines
  • Obesity and alcohol both can worsen the outcome
  • Fetal scalp probes and prolonged rupture of membranes but not route of delivery may increase risk of HCV transmission
  • Breastfeeding is not contraindicated but should be avoided during mastitis/bleeding

Additional related blog links:

HCV now more deadly than HIV

The cost of progress in treating Hepatitis C

Increased ferritin predicts poor response in Hepatitis C

Curing Hepatitis C without interferon

Looking for trouble

Additional references:

  • –Hepatology 2011; 54: 1433. AASLD guidelines.  See teleprevir & boceprevir as well.-http://www.aasld.org/eweb/docs/hepatitisc
  • -Hepatology 2011; 53: 1468. PEG/RBV have minimal effect on QOL/cognitive/emotional outcomes, n=114.
  • -Gastroenterology 2011; 140: 389, 450-58. HEP-C STUDY. Comb RBV (15mg/kg div BID) & PEG-2a (180mcg/1.73m2 body surface q week) is better than PEG monotherapy. 53% SVR in combo group. Neutropenia in 40% –needed to reduce dose see below). “The Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents With Chronic Hepatitis C.”
  • -Hepatology 2009; 49: 1335. Comprehensive review and guidelines
  • -J Hepatology 2010; 52: 501-07. n=107. Pediatric study. Wirth et al. Efficacy of PEG alfa-2b (1.5/g/d) & RBV (15/kg/day): Genotypes 2/3 96% SVR, genotype 1 55%.
  • -JPGN 2006; 43: 499.  Study of PEG-IFN-α-2a in children.  dose BSA m2/1.73 x 180microgm weekly x 48 weeks.  6/14 (43%) had sustained response.  all genotype 1.  Article states that IFN (3/week) + RBV has now been approved by FDA for those over 3 years

PEG-Interferon Dosing:

Dosing adjustment from hep C study in children –needed in ~40%

PEG -2a
original: 180mcg/1.73m2
1. level 1: 135 mcg, level 2: 90mcg, level 3: 45 mcg

If ANC 750-999 week 1-2: level 1 adjustment, weeks >3: no adjustment
If ANC 500-749: week 1-2: hold dose ’til >750, then level 1; weeks >3, level 1 adjustment
If ANC 250-499: week 1-2, hold until >750, then level 2 adjustment, weeks >3, then hold ’til 750, then level 1 adjustment
If ANC <250, stop drug

If PLTs 35-49K, hold til >50, then level 1
If PLTs 25-34, hold til >50, then level 2
If PLTs <25, stop drug

If Hgb <10, reduce RIBA dose by 1/2 & increase dose when hgb>10
If hgb <8.5, stop RIBA

If indirect bili >5, stop drug.  If <2.5, restart dose at one-half and if remains less than 2.5, can resume full dose after 4 weeks.

IF ALT 5-10 ULN, recheck in 1 week.  If stays high, level 1 adjustment.
IF ALT10 ULN for more than 1 week, then if drops to 5-10, level 1 but if remains >10 ULN, then stop drug.

Side effect frequency:
flu symptoms: 91%, h/a, 62%, GI symptoms 56%, injection pain 45%, muscle aches 36%, irritable 31%, fatigue 27%, rash 20%, itching 15%, anorexia 13%, trouble sleeping 11%, depression 4-12%

Outcomes of Biliary Atresia

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A retrospective study from the Netherlands showed that timely surgery and postoperative antibiotics were associated with better outcomes in Biliary Atresia (BA) (J Pediatr 2012; 160: 638-44).  While these results are not surprising, due to the length of the study period (1987-2008) and the number of patients (n=214), the study offers insight into a number of unresolved issues with regard to BA.

The type of BA in this series:

  • type I      14  (6.5%)
  • type II      27 (12.6%)
  • type III   172 (80.4%)
  • undetermined  1 (0.9%)

Other notable findings:

  • 10% of their patients had splenic malformations; no significant change in outcome was noted in this subgroup.
  • 18% received high-dose corticosteroids –no benefit was identified in this subgroup.  The authors state that previous studies are inconclusive; a large US trial of prednisolone (4 mg/kg/day initially) is pending.
  • 31% received ursodeoxycholic acid –no benefit was identified in this subgroup.
  • Overall survival improved a little during the study period, mostly due to increased availability of liver transplantation. 4-year transplant-free survival was 46% and 4-year overall survival was 73%.   Table II (pg 641) in their study lists six other international studies.  Recent studies in some countries have reported 4-year survivals of 82-91%.
  • Antibiotic usage (most commonly co-trimoxazole) was associated with improved outcomes, presumably due to less frequent bouts of cholangitis.  Yet, in this study the reported incidence of cholangitis was not lower.  The authors do not have an explanation for this finding.

Age at time of Kasai:

  • ≤45 days 19%
  • 46-60 days 37%
  • 61-89 days 36%
  • ≥90 days 8%
  • Median was 59 days.  Authors note that Netherland guidelines call for all infants with jaundice at 3 weeks to have a fractionated bilirubin.

Related blog entries:

Minimizing malnutrition in Biliary Atresia

The heart connection

MicroRNAs and biliary atresia

Additional references:

  • -JPGN 2010; 51: 631.  n=91.  Operation w/in 100 days.  Data suggesting that 60 day cutoff is not valid. (Hong Kong)
  • -J Pediatr Surg 2003; 38: 997-1000. n=735.  90 day cutoff was key with 5-yr & 10-yr survival. (Japan)
  • -JPGN 2010; 51:61.  Canadian experience. n=230.  Center size did not affect outcome.  Overall 39% at 4yrs had survival with native liver.
  • -Liver transplantation 2009; 15: 829, 876.  With combo of Kasai & Tx, >95% exteneded survival (previously 100% fatal).  >80% will need a liver Tx at some point –~50% before age 2.  Increased fibrosis & genes for fibrosis may increase risk for poor outcome.
  • -JPGN 2009; 48: 72.  Review of 13 year experience. n=91.
  • -Pediatrics 2008; 121: e1438.  Single center (Australia?) noted longer delay in dx of BA over 15-year period from 48.5 days (1990-94) to 59.5 (95-99) to 69 days (2000-2004).
  • -JPGN 2008; 46: 238, 299.  More data on age of dx of BA and outcomes from Sweden.
  • -J Pediatr 2006; 149: 393.  Long term outcome of BA -28yrs in England.  7/56 survived long term with native liver; 5-yr native liver survival was 46%, 10-yr was 32%.
  • -J Pediatr 2006; 148: 467, 432..  Outcome of BA in US.  Avg age of referral was 53 days and HPE avg at 61 days.  one-third will survive to age 10 with native liver; overall 90% survival with kasai/hpe & Tx; 50-60% clear jaundice p Kasai.  yellow alert campaign: www.childliverdisease.org/jaundice
  • -Clin Gastro & Hep 2006; 1411.  BA with choledochal cyst. Nice pics of types of BA. Japanese pathologic classification:  Type 1 with atresia after gallbladder (CBD), type II atresia of common hepatic duct/CBD/GB  c normal intrahepatic ducts, Type III atresia of entire ductal system.
  • -Pediartics 2006; 117: 1147.  Usefulness of stool color cards for screening program.
  • -J Pediatr 2005; 147: 142 & 180-5.  23% c BA survive c native liver for more than 20 yrs; 88% survival for 3 yrs p-OLT; risk factors for poor outcome discussed including poor nutrition & age <5 months.
  • -J Pediatr 2004; 144: 123-5.  severity of fibrosis at time of Kasai inversely correlated with survival
  • -JPGN 2003; 37: 430-33.  Residual fibrosis/cirrhosis noted in 54%/40% respectively of pts with normal labs, median age 13 yrs.
  • -JPGN 2003; 37: 4-21. Review of BA

Magnetic resonance enterography for Crohn’s disease

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Magnetic resonance enterography (MRE) has increasingly been recognized as an effective way to characterize small bowel disease in Crohn’s disease (Inflamm Bowel Dis 2012; 18: 520-28).

In this retrospective pediatric study, 95 patients with Crohn’s disease underwent MRE from 2006-2009.  As expected, terminal ileal disease was the most common site of involvement with 54%; this was followed by ileum with 19%, and jejunum with 17%.  Other findings included solitary jejunal inflammation (3.7%), small bowel stenosis (1.9%) fistula (1%), and abscess (1%).  Specific evidence of inflammation included contrast enhancement, bowel wall thickening or derangement of bowel wall shape.  The images in the article are excellent.

The main advantage of MRE over CT enterography (CTE) is the lack of ionizing radiation.  In addition, MRE can better detect soft tissue contrast suggestive of bowel wall edema.  This helps distinguish acute from chronic inflammation.  Obtaining an MRE is technically more challenging and more costly.  The youngest patient in the study was seven; though the authors note that the youngest patient they have performed MRE was six.

Additional references:

  • More imaging needed?
  • -JPGN 2010; 51: 603.  MRE for suspected IBD.  Useful in pediatric Crohn’s disease.
  • -IBD 2009; 15: 1635. U/S compared favorably with endoscopy in correlating postoperative recurrence with Crohn’s.
  • -Clin Gastro Hepatol 2006; 3: 1221. MRI as accurate in evaluating ileocolonic disease with flareups as endoscopy.
  • -IBD 2004; 10: 452-61. U/S was very helpful in identifying disease and complications.

Vitamin D, IBD, and Causality

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The importance of vitamin D has been noted in this blog previously (Common to be “D-ficient” ).  Now a study implicates vitamin D as a risk factor for developing inflammatory bowel disease, especially for Crohn’s disease (Gastroenterology 2012: 142: 482-89).  It is known that vitamin D influences innate immunity.  As such, it may play a role in the susceptibility to Crohn’s disease (CD) and Ulcerative colitis (UC).

This prospective study included 72,719 women (age 40-73) enrolled in the Nurses’ Health Study.  Research subjects completed an assessment of diet and lifestyle along with 25-hydroxy vitamin D [25(OH)D] levels.  The 25(OH)D levels were predicted; this prediction was based on a validated model which included vitamin D intake, sun exposure, race, and body mass index (J Natl Cancer Inst 2006; 98: 451-9).  This model was validated against directly measured 25(OH)D levels.

During nearly 1.5 million person-years of followup, 122 incident cases of CD and 123 cases of UC occurred.  The adjusted hazard ratio (HR) for the highest quartile of 25(OH)D was 0.54 for CD and 0.65 for UC compared to the lowest quartile.  Compared with a level less than 20, the highest quartile HR was 0.38 for CD and 0.57 for UC.

In addition, the authors identified a significant inverse association between dietary supplemental vitamin D and UC; an insignificant reduction in CD risk was noted with dietary intake.  Although it is difficult to determine causality, these data convincingly show that ‘healthy’ levels of vitamin D are associated with a lower risk of IBD.

Ivacaftor for Cystic Fibrosis

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Recent FDA approval of Ivacaftor (Kalydeco) is a promising step for a subset of patients with cystic fibrosis who have the G551D mutation.  This drug enhances the cystic fibrosis transmembrane regulator (CFTR) gene in these patients; only ~4% of CF patients or about 1200 patients in the US have this genetic defect.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm289633.htm

Additional references:

-NEJM 2011; 365: 1663. Effect of VX-770 -a CFTR potentiator -mild improvement in study of 167 pts. (Ivacaftor).
-NEJM 2010; 363: 1991. Effect of VX-770 -a CFTR potentiator -mild improvement in study of 39 adults.

All bleeding stops

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Although the title is technically true, there are preferred ways to stop GI bleeding (Clinical Gastroenterol & Hepatol 2012; 10: 234-39).  This article summarizes the approach for nonvariceal upper GI bleeding.

Recommendations:

  • Endoscopy within 24 hours following ABCs/adequate resuscitation.  Use of a promotility agent prior to endoscopy may be helpful (in pediatric patients: erythromycin ~3 mg/kg)
  • Correct coagulopathy but do not delay endoscopy.
  • Consider nasogastric tube placement.
  • Do not use somatostatin or octreotide.
  • High-risk endoscopic stigmata should receive endoscopic hemostasis.  These lesions include actively spurting, oozing blood, nonbleeding visible vessel, and an adherent clot.
  • Pigmented dots or clean base ulcers do not require endoscopic hemostasis.
  • Endoscopic management includes clips, thermocoagulation, or sclerosant injection alone or in combination with epinephrine injection.  Epinephrine alone is not recommended for high risk lesions.
  • If a clot is found, attempts to remove it should be made to visualize underlying lesion.  If clot is adherent, intensive IV PPI therapy may be sufficient.  A typical dose would be esomeprazole 80mg bolus (for an adult) followed by 8 mg/hour for 72 hours.
  • Stable patients can be fed within 24 hours.
• IV PPI dose: 1mg/kg bolus followed by 0.1mg/kg/hr infusion.

Additional references:

  • -Ann Intern Med 2010; 152: 101-113. Consensus recommendations on UGI bleeding. Early endoscopy (<24hrs), data support attempts to dislodge clots, consider clips or thermocoagulation for Rx. Preendosocpy PPI can be helpful.
  • -Clin Gastro & Hep 2010; 8: 651. Article suggests second look only if difficult visualization on initial endoscopy (eg unable to remove clot).
  • -Ann Intern Med 2010; 152: 101-13. Systematic review of on UGI bleeding. Use IV PPI bolus, then continuous PPI if high risk stigmata after endoscopic Rx. Hospitalize for at least 72hrs.
  • -Gastroenterology 2010; 138: 1252. Review of upper GI bleeding.
  • -Clin Gastro & Hep 2009; 7: 828. Review of recurrent GI bleeding with negative initial evaluation.
  • -Gastroenterology 2008; 134: 1836. Frequent high dose oral PPI also effective with bleeding ulcers: prevacid 120mg x1, then 30mg q3hrs compared favorably with 90mg IV followed by 9mg/hr. n=66. intragastric pH >6 for 68% of study in IV PPI vs. 65% in oral PPI. 1st hour -more rapid onset with IV PPI.
  • -Gastroenterology 2007; 133: 1694. Position statement & review on obscure bleeding.
  • -Ann Intern Med 2003; 139: 843-857. Consensus on nonvariceal bleeding. Rec: lansoprazole 90mg bolus, then 6mg/hr x 72hrs or pantoprazole 80mg then 8mg/hr in high risk lesions
  • -Clin Gastro & Hep 2006; 4: 1459. Trends in non-variceal bleeding between 1993-2003 do NOT show improved outcomes with PPI. Overall mortality fairly steady @3.5%
  • -Clin Gastro & Hep 2005; 3: 959. WCE should be 2nd step in obscure bleed, p egd/col.
  • -NEJM 2004; 351: 488. case review.
  • -Gastroenterology 2002; 123: 17-23. IV erythromycin, 20 minutes before endoscopy, helped clear stomach (82% clear vs. 33% c placebo). Adults in this study received 250 mg. (thus, children probably need 3-4 mg/kg)
  • -Gastro Endosc 2002; 56: 174. erythromycin helpful-3mg/kg IV over 30 min
  • -Gastroenterology 2002; 123: 407-13. Endoscopic Rx of adherent clots c PUDz helpful (epinephrine injection, cold guillotining of clot, then coagulation cautery); Editorial on 632-635 emphasizes vigourous washing BUT NOT to remove adherent clot unless in centers with low rebleeding rates. Additionally, PPIs very helpful in preventing rebleeding in this situation (NEJM 1997; 336: 1054-8).
  • -NEJM 1999; 341: 38. Occult bleeding
  • -Gastroenterology 2000; 118: 197. AGA position statement.
  • -Gastro Endosc 2001; 53: 853 & 859. ASGE guidelines/algorithm for upper & lower GI bleeding