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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.

Liver biopsy risk in children

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A recent retrospective study from Oslo looks at risk factors and safety of liver biopsy (JPGN 55: 82-87).

Among 190 patients who underwent 275 ultrasound-guided liver biopsies (interventional radiology), there were four major complications –two were due to post-biopsy bleeding, one was due to variceal bleeding within 12 hours, and one was due to the development of pain/acidosis, and tachycardia.  28 patients had minor bleeding.   There were no mortalities, though one patient dropped hemoglobin in half (11.6 to 5.3).

In their patient population, the following had increased risk for major complications:

  • Focal space-occupying lesion/tumor (n=25) OR 2.84  for all bleeding risk; patients with these lesions typically had more biopsy passes (average 4.9)
  • Acute liver failure (n=12) OR 26.1 for major complication risk
  • Low-molecular weight heparin therapy (n=18)  OR 2.43 for all bleeding risk

Not identified as risk factors for complications in this cohort:

  • Low platelet count (<70 [n=14])or coagulopathy (INR>1.7 [n=18]),  –all received blood products before biopsy
  • Aspirin treatment (often used in transplant population to prevent hepatic artery thrombosis) (n=55)  OR 0.96
  • Liver transplant patients (n=97) -odds ratio was lower than entire cohort (OR 0.52)

Additional references:

  • -JPGN 2011; 53: 202. Good safety results with IR liver biopsy, n=249. 2/249 had drop in Hgb of 2g -no transfusions needed, no mortalities.
  • -Clin Gastro & Hep 2010; 8: 877. 0.5% complication rate, n=2740. No deaths. Bleeding was most common risk –increased with advanced liver disease.
  • -Hepatology 2009; 49: 1017. AASLD Position Paper
  • -Gastroenterol 1978; 74: 101 & 103. Early article discussing safety of LBx and that most pts could be d/c’d w/in 6 hours.
  • -JPGN 2005; 41: 639. Safety of liver biopsy in infants less than 3 months (w/o U/S). complication rate was 18% including sedation-related, 1 bile leak, and 3 needed PRBCs.
  • -JPGN 2003; 36: 364. Ultrasound useful.
  • -Can J Gastroenterol 2000; 14: 543-548.  Mortality rate 3/10,000
  • -Clin Perspectives Gastroenterol 2002; 5: 117. Rec ultrasound, plts >75K, PT c/in 3 secs of normal; observation for 3-6hrs in adults.
  • -NEJM 2001; 344: 495. Liver bx review.
  • -Hepatol 27: 1220-26, 1998. U/S marking reduces complications
  • -Fox VL, Cohen MB, Whitington PF, Colletti RB. Outpatient liver biopsy in children (n=450). J Pediatr Gastroenterol Nutr 1996;23:213-6.  High mortality rate reported, primarily in bone marrow transplant patients
  • -JPGN 2000; 31: 536-39. Safety of liver biopsy in children, n=249.

More on anti-glycan antibodies in Crohn’s disease

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As noted in recent blog entry (Serology in IBD), anti-glycan antibodies have some usefulness in inflammatory bowel disease.  More data on the utility of these antibodies is available in a study which examined the presence of these antibodies in both a pediatric and adult cohort (Inflamm Bowel Dis 2012; 18: 1221-31).

Anti-L, Anti-C, anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside and anti-Saccaromyces cervisiae (ASCA) antibodies were tested in 131 pediatric patients (59 CD, 27 UC, 45 controls) and in 728 adult patients (355 CD, 129 UC, 244 controls).  In this study, 78% of pediatric CD patients had at least one serological marker.  ASCA was most accurate for CD diagnosis; it was present in 63% of the pediatric cohort. 

Combined usage of these antibodies helped differentiate CD from UC.  While sensitivity for detecting CD was 78% with the presence of one serological marker, the presence of three (or more) markers increased the specificity to 93% (for CD compared to UC); however, the presence of this many markers occurred in only 28%. Increasing antibody levels also correlated with complicated CD behavior, CD-related surgery and ileal disease location.

Serology in IBD

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Serological antibodies against a number of antigens have shown some utility in differentiating inflammatory bowel disease (IBD) from non-IBD and in distinguishing Crohn’s disease (CD) from ulcerative colitis (UC).  A recent article evaluated 204 articles in a systematic review of these serological markers (Inflamm Bowel Dis 2012; 18: 1340-55).

The study has several useful tables and a long list of references.  In its Table 1, 10 serologies are listed with a range for prevalence in CD, UC, alternative GI conditions, and in healthy population.  Table 2 summarizes the data in terms of sensitivity, specificity, positive predictive value, negative predictive value for these antibodies in determining IBD from non-IBD.

With regard to specific antibodies, the review highlights 10 antibodies:

1. Anti-neutrophil cytoplasmic antibodies (ANCA).  Autoantibody directed against a constituent of neutrophil granules.  With IBD (especially UC), an atypical perinuclear (pANCA) staining pattern with indirect immunofluorescence and DNase-sensitive make this pattern different from ANCA due to vasculitis.

2-7. Anti-glycan antibodies –directed against cell wall microbes and reflect interaction between the immune system and glycosylated cell wall components of microbiota.

2. Anti-Saccharomyces cerevisiae (ASCA IgA and IgG) –antibodies directed against yeast cell wall.  While ASCA antibodies are commonly found in CD patients, 20-25% (or higher in some studies) of healthy relatives will test positive for these antibodies as well.  Approximately 6% of relatives of UC patients will be ASCA-positive.

3. Anti-laminaribioside carbohydrate IgG antibodies (ALCA) –antibodies directed against laminaribioside

4. Anti-chitobioside carbohydrate IgA antibodies (ACCA) –antibodies directed against chitobioside

5. Anti-mannobioside carbohydrate IgG antibodies (AMCA) –antibodies directed against mannobioside

6. Anti-L –antibodies directed against laminarin (large polysaccharide)

7. Anti-C –antibodies directed against chitin (large polysaccharide)

8. Anti-OmpC.  OmpC is a transport protein of E coli

9. Anti-I2.  I2 is a Pseudomonas-associated antigen

10. Anti-CBir1.  CBir1 is a bacterial flagellin antigen

Conclusions:

  • Serology has only limited value for the initial diagnosis of IBD.
  • Serology has ‘better value’ in differentiating CD from UC, though there is substantial variability in serologic responses in both diseases.  Probably, serology is most useful in unclassified IBD (IBD-U) in preoperative setting; serology may help predict risk of developing complications among patients undergoing pouch surgery.
  • Serology is useful in predicting a complicated disease course. The presence and magnitude of these antibodies are strong predictors of disease progression.

Additional references:

  • Pediatrics. 2010 Jun ;125 (6):1230-6.  Shortcomings of the inflammatory bowel disease Serology 7 panel. 
  • -Clin Gastro & Hep 2008; 6: 1105. Increased immune reactivity/markers associated with aggressive disease.
  • -IBD 2006; 12:1122. Expression of I2 antibodies (against a bacterial antigen of psedomonas fluorescens) was highly associated with clinical response to diversion. 15/16 with I2-pos had clinical response; 2/11 I2-neg had clinical response.
  • -IBD 2008; 14: S4 abstract 0010. Practical experience with IBD serology (n=90) much less accurate than reported by Prometheus: overall accuracy of 63% (vs 92%), 66% sensitivity (vs 93%), 59% specificity (vs 95%), 75% PPV (vs 96%), and 49% NPV (vs 90%). In this population, 34% of known IBD were incorrectly predicted. Of 32 who did not have any evidence of IBD after clinical investigation, 40% (13) were seropositive.
  • -Clin Gastro & Hep 2008; 6: 1105. Increased immune reactivity/markers associated with aggressive disease.
  • -IBD 2008; 14; 129. Serologic markers not very useful clinically.
  • -Pediatrics 2007; 119: e193. IBD serology performed poorly in comparison to combination of Hgb/ESR with regard to sensitivity (60% vs. 83%), specificity (92% vs. 96%), positive predictive value (60% vs. 79%) for IBD in children, n=227. Also one third of all positive serology in patients w/o IBD. The positive predictive value in patients w/o rectal bleeding was 35% vs 60% for routine tests.
  • -Gastroenterol 2006; 131: 366. antibodies against laminaribioside, chitobioside, and mannan have predictive value in detecting Crohn’s disease.
  • -Gastroenterol 2006; 130: 1078. Unaffected relatives positive for either OmpC or ASCA in 20% in large cohor (n=619 unaffected relatives. OmpC present in up to 44% of CD pts, up to 24% of UC pts, and 6% of controls.

α1-antitrypsin review

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For a brief and useful review of α1-antitrypsin (A1AT) deficiency: Clin Gastroenterol Hepatol 2012; 10: 575-80.

One of the pieces of information that is fairly new in the review: “the most promising strategy for treating liver disease in patients with A1AT deficiency is to decrease the accumulation of polymerized A1AT by stimulating its autophagy in hepatocytes.”  Both carbamazepine and rapamycin have been capable of this in transgenic mice; this has been associated with reduced liver fibrosis.

General recommendations from review:

  • In patients with cirrhosis due to A1AT deficiency, screening for HCC is appropriate (Looking for trouble)
  • Limit alcohol consumption and tobacco exposure
  • Assure vaccination for hepatitis A & B
  • Decompensated liver disease managed in standard fashion

Additional references:

  • Tegretol may help treat/prevent fibrosis –study in Pittsburgh (at least 14yrs old, ZZ) –can call 855-428-2281 David Perlmutter
  • -NEJM 2010; 363: 1863-64.  Autophagy in A1AT deficiency
  • -Hepatology 2007; 45: 1313. Review of meeting on A1AT deficiency
  • -JPGN 2006; 44: 99. High prevalence of alpha-1 heterozygosity in chronic liver disease. Multiple other polymorphisms may contribute to liver disease in some (heterozygous HFE gene, 1 mutation for Alagille may worsen EHBA [Hepatology 2002; 36: 904-12.], glutathione-S-transferase P1 polymorphism seen c CF liver disease
  • -JPGN 2006; 43: 136-138. Variable degree of liver involvement in Sibs with PiZZ disease.
  • -Clin Gastro & Hep 2005; 3: 390. factors associated c severe dz in adults include male gender and obesity.
  • -JPGN 2003; 37: 347 (62A) NSAIDs may worsen liver dz.
  • -Clin Perspect in Gastro 2002; 5 (1) : 40. (review)

An unexpected finding with gastroschisis management

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A presumption that paralysis in infants with gastroschisis leads to quicker resolution in silo-assisted closure is not correct (J Pediatr 2012; 161: 125-8).  This presumption had been based on the idea that abdominal muscular relaxation with paralysis would facilitate visceral reduction.

This retrospective Canadian study examined 186 infants with gastroschisis, between 2005-2009.  Standardized data for this study was collected prospectively from 16 perinatal centers in Canada. Findings:

  • 79 had paralysis and 88 did not.  These groups were nearly identical in birth weight, gestational age, and presence of bowel atresia.
  • Paralyzed infants took longer to achieve closure, 8 days versus 5 days.  In addition, the paralyzed group had longer ventilation period, 12 days versus 7 days.
  • These findings persisted after regression analysis/adjusting for other variables.  The analysis included examination of illness severity scores (SNAP-II); it was not simply the sicker infants receiving paralysis.
Besides debunking a false premise with gastroschisis management, this study highlights the necessity of collecting data so that our presumptions can be challenged.

Additional references:

  • -J Pediatr Surg 2011; 46: 801-7.  Outcomes/variation in diaphragmatic hernia and gastroschisis from Canadian Pediatric Surgery network.
  • -J Pediatr Surg 2008; 43: 30-4.  Outcomes in 100 cases of gastroschisis.

Diagnosing hemophagocytic lymphohistiocytosis (HLH)

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HLH is difficult to diagnose –patients without HLH can meet the established criteria (see links below); and, especially early in the disease, patients with HLH may not meet the established criteria.  A study which will help with this difficulty has been published (J Pediatr 2012; 160: 984-90 and summary pg A1).  For pediatric gastroenterologists, HLH is important because some of our IBD patients may develop HLH and because some patients presenting with liver disease have HLH.

This study examined 756 consecutive patients with fever in Hematology/Oncology unit of China’s Children’s Hospital of Zhejiang between 2005-2010.  Three control groups also were studied: hematology-oncology patients without fever (n=202), healthy children (n=100), and previously-healthy children with bacterial sepsis (n=85).

A highly discriminating cytokine pattern was identified in 71 episodes of HLH.

  • Highly elevated IFN-γ : 94% sensitivity, 97% specificity for HLH using a cutoff of 100 pg/mL
  • Highly elevated IL-10
  • Modestly elevated IL -6
  • Combined use of IFN-γ (>75 pg/mL) & IL-10 (>60 pg/mL) had sensitivity of 93% and specificity of 99% for HLH

Using these cytokines may help establish a more rapid diagnosis of HLH and allow institution of critical therapy while avoiding implementation of the wrong treatment in patients who have other conditions.  In other studies (see below), there are other useful markers that have been identified.

Additional references:

  • -J Pediatr 2011; 159: 808.  HLH increased with Crohn’s Rx.  If fever >5days, can screen for HLH with ferritin (>500mcg/L) & lymphopenia.  Need to discontinue immunosuppression.  100-fold increase risk of HLH.  Diagnostic criteria for HLH pg 809. Newer criteria: molecular, low/absent NK activity & soluble CD-25 (ie. soluble IL-2 receptor) >2400 U/mL.
  • Hemophagocytic Syndrome  Link with powerpoint case presentation including diagnostic criteria for primary and secondary HLH.
  • Hemophagocytic lymphohistiocytosis (HLH) and related disorders  Link with review article by leader in field (A Filipovich, 2009).
  • -J Peds 2006; 149: 134-7.  Aftrican-american infants c HLH often have a specific defect in perforin gene -50delT-PRF1
  • -NEJM 2004; 351: 1120. case of twins c FELS. Impaired NK cell activity is key with absence of NK intracytoplasmic perforin in 20-40%.
  • -JPGN 2002; 34: 3A (pg 433.)  Liver failure with HLH.  mortality 84%, n=25.

What’s the best medical therapy for Clostridium difficile?

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More data on the superiority of fidaxomicin versus vancomycin in adult patients has been published (Lancet 2012; 12: 281-9).  While this study was a ‘double-blind, non-inferiority, randomized controlled trial,’ the data tilt in favor of fidaxomicin.  This study enrolled 535 patients from 45 sites in Europe and 41 sites in U.S.

On an intention-to-treat basis, a clinical cure was noted in 88% of fidaxomicin group (200 mg BID x 10 days) and 86% of vancomycin group (125 mg QID x 10 days).  Clinical cure was defined as resolution of diarrhea and no need for further treatment.  The big difference was in recurrence risk:  13% of patients receiving fidaxomicin compared with 27% of patients receiving vancomycin.  Recurrence was defined as development of three unformed bowel movements in 24 h, a positive stool toxin, and need for retreatment within 30 days of treatment completion.  A sustained response (=”global cure”) was noted in 77% with fidaxomicin compared with 63% of vancomycin group.

Both groups of patients had similar variables: severity of illness, frequency of B1/027 strains, geographic distribution, concomitant antibiotics, previous C difficile infection, age, and inpatient status.  In the group with concomitant antibiotics, fidaxomicin outperformed vancomycin with respect to cure rate: 90% versus 73%.  Adverse reactions were similar as well (Table 7).

To underscore the severity of C difficile in this population, there was a significant mortality rate in both groups.  8% of patients receiving at least one dose of fidaxomicin died compared with 7% of vancomycin-treated patients.

Why does fidaxomicin have a lower recurrence rate?  Probably due to a more narrow antibiotic spectrum and minimal effect on commensal gut flora.  Fidaxomicin also has roughly eight times more potency in vitro than vancomycin against clinical isolates of C difficile.

Previous related blog entries/reference:

BRIC, PFIC, and nasobiliary drainage

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Case reports, when effective, help clinicians understand meaningful differences in disease presentation; in addition, they highlight practical treatment approaches.  An excellent example of one such case report is the following:

  • Zellos A et al.  JPGN 2012; 55: 88-90

These authors present a case with unique features that highlight some of the clinical problems with benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis (PFIC).  BRIC1 and PFIC1 are associated with mutations in ATP8B1; BRIC2 and PFIC2 are associated with mutations in ABCB11.  The primary difference between BRIC and PFIC is the phenotypic expression.  In BRIC, individuals have episodes of cholestasis; in PFIC, progressive chronic liver disease develops in the first months of life.  PFIC2/ABCB11 mutations cause defective bile salt export pump (BSEP) at the bile-canniculus membrane.

Both ATP8B1 and ABCB11 intrahepatic cholestasis conditions present in a similar fashion with low GGT values.  In this case report, a 5-year-old presented with jaundice, acholic stools and dark urine.  His laboratory values revealed an ALT of 60 U/L, direct bilirubin of 7.6 mg/dL and gamma-glutamyl transpeptidase (GGT) of 10 U/L.  Initially, after exclusion of other liver conditions (eg. NL MRCP, copper studies, α-1 antitrypsin, autoimmune serology, infectious etiologies), the authors suspected ‘a clinicopathologic intergrade between BRIC and PFIC’ likely due to ATP8B1 as there was BSEP expression on liver biopsy immunostaining.  After sequencing did not demonstrate any ATP8B1 mutations, the authors identified two heterozygote mutations in ABCB11.

From a treatment standpoint, once nasobiliary drainage (NBD) was in place, the patient quickly improved.  This occurred after >6 weeks of failure with urosdeoxycholic acid/conservative measures.  As a precaution, the authors cultured the bile once a week and instituted antibiotic treatment when positive cultures were identified.

One other point alluded to by the authors is that the natural history of BRIC2 is poorly described.  Whether this disorder is truly ‘benign’ as the name suggests is unclear.  In patients with similar mutations who develop PFIC2, there is a high risk of hepatocellular carcinoma (HCC).

Intrahepatic Cholestasis Genes/Disorder (Clin Liver Dis 2006; 10: 27-53.)

Gene: Disorder (protein)
ABCB11: PFIC 2, BRIC 2 (BSEP)
ABCB4: PFIC 3, ICP (MDR3)
CFTR: CF (CFTR)
ATP8B1: PFIC1 -Byler’s (FIC1), BRIC, GFC -Greenland Familial
CLDN1: NISCH (Claudin 1) -neonatal sclerosing cholangitis/icthyosis
VPS33B: ARC syndrome (Vascular protein sorting 33) -arthrogryposis-renal dysfn-cholestasis, low GGT
AKR1D1: BAS: Bile acid synthetic defect: neonatal cholestasis with giant cell hepatitis
(5β-reductase)
HSD3B7: BAS (C27-3β-HSD)
CYP7BI: BAS (CYP7BI)
TJP2: (ZO-2) FHC: Familial hypercholanemia (tight junction protein)
BAAT: FHC (BAAT)
EPHX1: FHC (epoxide hydrolase)
JAG1: Alagille (JAG1) JAG1 is transmembrane cell-surface protein important in regulating cell fate during embryogenesis
PKHD1: ARPKD (fibrocystin -important in ciliary function and tubulogenesis)
PRKCSH: ADPLD (hepatocystin)
ABCC2: Dubin-Johnson syndrome (MRP2)
CIRH1A: NAIC -N Amer Indian childhood cirrhosis (Cirhin)

Additional references for BRIC/low GGT PFIC:

  • -JPGN 2010; 51: 494.  Use of biliary diversion –helpful in 18 PFIC2 cases with long-term f/u.
  • -Liver Transplantation 2010; 16: 856.  6 patients developed recurrent low gamma-glutamyl transpeptidase cholestasis, that mimics BSEP disease, following transplantation. All had documented genetic defects in ABCB11 that were predicted to lead to a congenital absence of BSEP protein.
  • -NEJM 2009; 361: 1359. Recurrence of BSEP deficiency p OLT due to antibodies against BSEP
  • -Hepatology 2010; 51: 1645. n=62 children & clinical course.
  • -Gastroenterol 2008; 134: 1203. Severe BSEP –82 different mutations in 109 families. (n=132 patients)
  • -JPGN 2008; 46: 241. Excellent review. FIC1 caused by mutations in ATP8B1, PFIC 2 caused by mutations in ABCB11 which encodes BSEP – bile salt export pump. Increased risk of HCC in PFIC2 especially.
  • -J Pediatr 2007; 150: 556.  Increase risk of HCC in PFIC2.
  • -Hepatology 2006; 44: 478-486. Cases of pediatric HCC in PFIC-2
  • -Gastroenterol 2006; 130: 908. Review of canalicular transport defects.
  • -Hepatology 2005; 42: 222. summary of cholestasis workshop
  • -Gastroenterol 2004; 126: 322. Review of bile salt transporters.
  • -JPGN 2002; 34: 7A. FTT, diarrhea persist p biliary diversion or transplant.

PFIC3 -High GGT

  • -Gastroenterol 2003; 124: 1037-42. MDR3 mutations causing cholelithiasis, cholestasis, biliary cirrhosis, & pregnancy cholestasis.
  • -Gastroenterol 2001; 120: 1448-1458. n=31 cases. MDR3 mutations. ABCB4 gene
  • -Gastroenterol 2001; 120: 1459-67. Gallbladder stones & chronic cholestasis in 6 MDR3+ pts. Avg age of presentation: 2.9yrs. Avg age of Tx: 7.5yrs.  Sx/S : high ggt cholestasis, pruritus, intrahepatic cholestasis of pregnancy in heterozygotes (& c contraception)
  • -Hepatology 1996; 23: 904-8. MDR3 gene assoc c PFIC

Colonoscopy, Split-dosing bowel preps, and Ottawa scores

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Adequate bowel cleansing improves the results of colonoscopy.  Since colonoscopy is a big part of gastroenterology/pediatric gastroenterology, a lot has been written comparing bowel preparations.  A recent study has examined a split-dose polyethylene glycol (PEG) preparation (Gastrointest Endosc 2012; 75: 583-90).

This prospective study from a single center in South Korea examined the effectiveness of a split-dose regimen in 366 patients (18 -65 years).  An interval of 3 to 5 hours between the completion of the last dose of the preparation and the start of the colonoscopy had the highest scores for bowel cleansing.  The authors used the “Ottawa Bowel Preparation Scale” for assessing a quality score.  Favorable odds ratios were noted with optimal preparation interval (OR 1.85), amount of PEG ingested (OR 4.34), and adherence with diet instructions (OR 2.22).

Instructions for preparation in this study:

  • 1. Low-fiber diet for 3 days prior
  • 2. Regular diet for breakfast & lunch day prior; soft diet for dinner, then only clear liquids
  • 3. Two liters of PEG on day prior and then two liters early in morning (5-7 am) on day of procedure –NPO for at least two hours prior to procedure.  While taking PEG, patients were instructed to consume 250 mL every 10 minutes.

Ottawa Scale –score right, mid, and left colon:

  • 0    no liquid
  • 1    minimal liquid –no suctioning required
  • 2    suctioning required to see mucosa
  • 3    wash and suctioning needed
  • 4    solid stool, not washable
  • Plus 0-2 points for overall quantity of fluid.
  • Max score 14 points

In this study, a prolonged interval (> 7 hours) between prep and colonoscopy had increasingly higher scores.  Score for 3-4 hours was 4.25; score for 7-8 hours was 5.20 and score for > 8 hours was 5.92.

As alluded to above, individuals who consumed adequate volume of preparation, had good bowel cleansing.  99% of patients who took at least 75% of PEG (> 3 liters) had a satisfactory preparation.  And, 95% of patients who took less than 75% of PEG had an unsatisfactory preparation.  Compliance with diet instruction was associated with a satisfactory prep in 89% and poor compliance was associated with a poor prep in 81%.

While this study identified these risk factors, it is telling that even in a research study, 141 patients had an unsatisfactory preparation (Ottawa scale 6-14); 225 had a satisfactory preparation (Ottawa scale 0-5).

Additional references –bowel preparations:

  • -JPGN 2011; 53: 71. 2 day prep: Miralax 2 gm/kg, bisacodyl 5mg. n=111.
  • -JPGN 2010; 51: 254. Review of bowel preparations
  • -Gastroenterol 2006; 130: 2240. Oral phospho fleets associated with alarming risk of nephropathy. 21 additional cases identified
  • -J Am Soc Nephrol 2005; 16: 3389-3396
  • -NEJM 2003; 349: 1006. acute phosphate nephropathy after oral phospho fleets in a 71yo woman
Additional references –colonoscopy screening:
  • -Gastroenterol 2010; 138: 73, 27 (ed). Overutilization of colon screening in low risk situations and underutilization in high risk situations in clinical practice.
  • -Clin Gastro & Hep 2009; 7: 1217.  Fewer polyps detected as day progresses at a VA hospital n=477 pts. 27% decline in polyp detection.
  • -NEJM 2009; 361: 1179. Review of screening for colorectal cancer.
  • -Gastroenterol 2009; 137: 792. Use of CT colonography -current appraisal.
  • -Ann Intern Med 2009; 150: 1-8. Says endoscopists miss most cancers on right side & colonosopy reduces cancer by ~60% primarily due to left-sided cancers.  Most, 73%, of colonoscopies not done by GI/colorectal surgery in this study.
  • -Gastroenterol 2008; 134: 1570. Update recommendations from ACS, ACR, US Multi-society task force.
  • -Gastroenterol 2008; 134: 1311. Screening in 40-49 detects similar # of adenomas as in older groups (>50) but fewer advanced Ca.

Other references/links:

1. “Take it easy, Doc, you’re boldly going where no man has gone before.”
2. “Find Amelia Earhart yet?”
3. “Can you hear me NOW?”
4. “Are we there yet? Are we there yet? Are we there yet?”
5. “You know, in Arkansas, we’re now legally married.”
6. “Any sign of the trapped miners, Chief?”
7. “You put your left hand in, you take your left hand out. You do the
Hokey Pokey….”
8. “Hey! Now I know how a Muppet feels!”
9. “If your hand doesn’t fit, you must acquit!”
10. “Hey, Doc, let me know if you find my dignity.” and
11. “Could you write me a note for my wife, saying that my head is not, in fact, up there?”

Iron and hepcidin –not just for grownups

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As alluded to in a previous post (Help with hepcidin), hepcidin is integral to iron metabolism.  In a recent study (J Pediatr 2012; 160: 949-53), serum and urine hepcidin concentrations in preterm infants were found to correlate well with iron homeostasis markers in preterm infants.

This study examined 31 preterm infants (23-32 weeks gestational age).

Findings:

  • Serum hepcidin was highest in infants with systemic inflammation.
  • Both serum and urine hepcidin correlated strongly with ferritin (Figure 2 in study) and negatively with soluble transferrin receptor/ferritin-ratio.
  • Infants with lower hemoglobin concentrations and higher reticulocyte counts had lower serum hepcidin.
  • There was good correlation between urine and serum hepcidin (Figure 1 in study). As such, urine hepcidin may become useful non-invasive marker for iron status in sick preterm infants