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.

Median Arcuate Ligament Syndrome

Posted on October 14, 2012 by gutsandgrowth

PEDIATRIC SURGERY UPDATE: VOL 39 NO 03 SEPTEMBER 2012 has a concise review of Median Arcuate Ligament Syndrome (MALS) along with some references -listed with other references below (thanks to Ben Gold for this reference). MALS occurs when a fibrous portion of the diaphragmatic crura crosses the celiac artery and compression occurs. This disorder is described as a diagnosis of exclusion. Symptoms may include weight loss, nausea, abdominal pain, vomiting, and diarrhea. Imaging modalities including CT angiography, MR angiography or arteriography can increase the suspicion for this disorder.

While not alluded to in this reference, one of the problems is knowing whether MALS is a spurious finding. That is, in young individuals there is typically a robust blood supply to the intestine and it is not clear whether compression of the celiac trunk is responsible for specific symptoms as there is a compensatory blood supply.

Fortunately this disorder is very rare (or at the very least rarely recognized). One of the most experienced vascular surgeons relayed his experience over more than three decades. He stated that he had operated on four cases of suspected MALS –two improved with surgery. A better batting average than Chipper Jones! –but a lot fewer at bats.

References:

–Median arcuate ligament syndrome – Wikipedia, the free encyclopedia “It is estimated that in 10-24% of normal, asymptomatic individuals the median arcuate ligament crosses in front of (anterior to) the celiac artery, causing some degree of compression.”
– Median Arcuate Ligament Syndrome – YouTube
-Alehan D, Dogan OF: Pediatric surgical image. A rare case: celiac
artery compression syndrome in an asymptomatic child. J Pediatr Surg.
39(4):645-7, 2004
– Gander S, Mulder DJ, Jones S, Ricketts JD, Soboleski DA, Justinich CJ:
Recurrent abdominal pain and weight loss in an adolescent: celiac artery
compression syndrome. Can J Gastroenterol. 24(2):91-3, 2010
– Said SM, Zarroug AE, Gloviczki P, Shields RC: Pediatric median arcuate
ligament syndrome: first report of familial pattern and transperitoneal
laparoscopic release. J Pediatr Surg. 45(12):e17-20, 2010
– Aschenbach R, Basche S, Vogl TJ: Compression of the celiac trunk caused
by median arcuate ligament in children and adolescent subjects: evaluation
with contrast-enhanced MR angiography and comparison with Doppler US
evaluation. J Vasc Interv Radiol. 22(4):556-61, 2011
– Ozel A, Toksoy G, Ozdogan O, et al: Ultrasonographic diagnosis of
median arcuate ligament syndrome: a report of two cases. Medical
Ultrasonography 14(2): 154-157, 2012
– Wani S, Wakde V, Patel R, et al: Laparoscopic release of median arcuate
ligament. J Minim Access Surg 8(1): 16-18, 2012
– “Median arcuate ligament syndrome”.Curr Treat Options Cardiovasc Med 2008 10 (2):
-“Median arcuate ligament syndrome: evaluation with CT angiography”. Radiographics 2005; 25 (5): 1177–82.

NASPGHAN Postgraduate Course 2012

Posted on October 14, 2012 by gutsandgrowth

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:

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
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:

a. electrolytes, BUN, Cr

electrolytes, BUN, Cr & UGI
electrolytes, BUN, Cr, UGI & ultrasound
electrolytes, BUN, Cr, UGI, ultrasound & endoscopy
electrolytes, BUN, Cr, UGI, ultrasound, endoscopy & MRI

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
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

How strong is the case for HCC screening?

Posted on October 13, 2012 by gutsandgrowth

Not that strong. The AASLD guidelines for hepatocellular carcinoma (HCC) have faced additional scrutiny and an editorial reviews the basis for HCC screening recommendations (Hepatology 2012; 56: 793-96).

According to the authors, there have been two randomized controlled trials of HCC screening in China. One that did not demonstrate benefits of HCC screening relied on resection as the treatment for early-stage HCC. However, a large proportion of those with screen-detected HCC did not undergo resection.

The second trial demonstrated benefit but had several issues. First, the statistical analysis has been criticized as faulty due to the cluster randomization method while analyzing with an individual patient basis method. In addition, most North American cases of HCC are related to HCV rather than HBV; thus, the results may not be applicable.

The editorial counters that there are additional lines of evidence that HCC screening is effective for HCV and that an adequate RCT in this country will never be feasible. Specifically, they suggest that an adequate study would need 10,000 subjects. This would be further complicated by informed consent; an Australian study has shown that 90% of patients would refuse randomization and prefer to undergo screening.

The editorial points out that advancement in treatments have lowered the likelihood of morbidity in patients identified through screening as well.

As part of their conclusion, the authors quote Sir Austen Bradford Hill who conducted the first RCT in humans: All scientific work is incomplete…liable to be upset by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action it appears to demand at a given time.”

Related blog entry:

Looking for trouble | gutsandgrowth

Additional references:

-Ann Intern Med 2012; 156: 387-89. HCC screening -‘a rush to judgement’
-Hepatology 2011; 53: 1020-22. AASLD HCC guideline update. Management of Hepatocellular Carcinoma – AASLD

IFfy outcome

Posted on October 12, 2012 by gutsandgrowth

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:

“It is never boring to be a physician”

Posted on October 11, 2012 by gutsandgrowth

…”because patients are so different. Each has a story to tell.” This is the beginning of an excellent editorial (NEJM 2012; 367: 1350-52). The editorial helps translate a study about “Phenotypic Heterogeneity” due to copy-number variants (NEJM 2012; 367: 1321-31). The study itself involved analyzing 32,587 samples from children with developmental delay. Ultimately, the study focused on 2312 children with 72 copy-number variants.

Both the study and the editorial try to explain why individuals with the same genetic defect have variability in the severity/expression. Some of the factors include environment, chance, and modifier genes. Due to the availability of relatively cheap and quick technology, one can sequence all of the 22,000 human genes. The techonology for this study used microarray-based comparative genomic hybridization to interogate the entire genome.

Copy-number variation refers to changes in the number of genes compared to normal. Typically, two gene copies are present. Thus, a deletion or duplications will result in copy-number variants.

In the aforementioned study, investigators found that large copy-number variants contributed to differences in outcomes. That is, persons with “the same chromosomal abnormality may have very different clinical outcomes” because they a have a second genetic event (copy-number variant elsewhere) that “makes matters worse for them.”

These copy-number variants contribute to learning disabilities. Large copy-number variants occur in less than 1% of the unaffected population but in 8.6% of children with learning disabilities. Males are m much more susceptible to have developmental delay due to these copy-number variants and unaffected women are more likely to transmit these copy-number variants. These gender differences are thought to be due to the fact that males have only a single X chromosome and are more vulnerable to genetic insults as a consequence.

Besides learning disabilities, copy-number variants have been implicated in well-known diseases such as schizophrenia, autism, cardiac disease, and epilepsy. In addition, well-defined syndromes, like Smith-Magenis syndrome, Williams-Beuren syndrome, Sotos syndrome, and MAPT (17q21.31) deletion syndrome, are also well-recognized as being associated with de novo copy-number variants.

It really is an exciting time to be a physician. Widely available genetic tests can finally explain a lot of previously unanswered questions.

Screening for subclinical PSC in IBD?

Posted on October 10, 2012 by gutsandgrowth

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)

“Immune-tolerant” — a misnomer for HBV infection

Posted on October 9, 2012 by gutsandgrowth

When hepatitis B virus (HBV) infection occurs in the perinatal period, often the result is high levels of HBV DNA yet immune-mediated damage of the infected liver is generally not observed and serum aminotransferases are normal. This phase of infection has been considered “immune-tolerant.” This phase can last for years or even decades. New data indicate that the during this phase, there is preserved T-cell function and there are indications of good immune function (Gastroenterol 2012; 143: 637-45, & editorial 529-32).

The authors of the study isolated T cells from different age groups of patients with chronic HBV infection. Then, they used flow cytometry methods to measure production of numerous cytokines. In addition, markers of T-cell exhaustion or inhibition were examined.

Key Finding: young patients had more specific HBV-specific T cells with the ability to proliferate and produce cytokines than adult patients.

The study itself is highly technical with graphs of cytokine profiles, quantitation of T-cell expressing exhaustion markers, dot plots, etc. Some of the figures are easy to understand like Figure 5 which plots the multifunctionality of HBV-specific response with three separate charts lined up; these correspond to “Immune tolerant,” “Chronic active,” and “Inactive carriers.”

The editorial is essential to understanding this study & restates the other findings:

“the authors found that T cells from CHB patients were more likely to produce TH1 cytokines …compared with those from healthy subjects”
they “found no global differences in this profile between tolerant and active states”
HBV-specific T-cell response: “a PD-1 high/CD127 low ‘exhausted’ phenotype were actually found to increase with age”
“T-cell responses to HBV core, envelope, and X proteins were readily observable in all patients”

The editorial speculates that so-called ‘tolerance’ may occur at a local/hepatic level, largely a ‘matter of sequestration.’ And, concludes that this study has “view-changing” observations. Ultimately, this may lead to therapeutic treatments aimed at the liver microenvironment & may change our opinion of the suitability of treating younger patients.

INSPPIRE for pancreatitis

Posted on October 8, 2012 by gutsandgrowth

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:

Abdominal pain consistent with AP
Serum amylase and/or lipase activity at least 3 times ULN
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:

Abdominal pain and imaging suggestive of chronic pancreatic damage
Exocrine pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
Endocrine pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
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 …

Coming soon –Fibroscan?

Posted on October 7, 2012 by gutsandgrowth

Transient elastography as measured by the Fibroscan device is used throughout the world, except notably in the U.S. That may change soon as an application is under review by the FDA (Gastroenterology & Hepatology 2012; 8: 605-7).

Fibroscan works by measuring shear wave velocity with a 50-MHz wave that is “passed into the liver from a small transducer on the end of an ultrasound probe.”
“The technology measures the velocity of the sound wave passing through the liver and then converts that measurement into a liver stiffness measurement.”
Takes 5-7 minutes to perform
Fibroscan is particularly reliable when showing either no fibrosis or advanced fibrosis. Less accuracy is noted with moderate fibrosis.
Technology can be augmented with noninvasive biomarkers of fibrosis
Not reliable in several groups: morbidly obese & patients with ascites

Additional references:

Am J Gastroenterol 2011; 106: 2121-22. Staging liver fibrosis for HCV
Gastroenterol 2005; 128: 343-50. Comparison of elastography, biomarkers, and liver biopsy for staging fibrosis

Preventing Type 2 Diabetes

Posted on October 6, 2012 by gutsandgrowth

A ‘perspective’ article reviews data from several studies that show the efficacy of medical treatments aimed at preventing type 2 diabetes (NEJM 2012; 367: 1177-79).

The Diabetes Prevention Program (DPP) was a comparative effectiveness trial of 3234 overweight or obese adults with impaired glucose tolerance (prediabetes). Findings from this study (published in 2002) showed that lifestyle intervention (attempts at weight loss through diet and exercise) reduced conversion to diabetes by 58% over 3 years, whereas metformin reduced this conversion by 31% over 2 years. Lifestyle intervention worked best in patients ≥ 60 years.

Subsequently, 88% of these subjects were enrolled in the 10-year outcome study (DPPOS). The lifestyle intervention group had a 31% 10-year reduction in diabetes compared with 18% for metformin.

The editorial points out that there have been efforts to expand these results across the country through CDC-sponsored programs in cooperation with the YMCA and UnitedHealth.

Potential roadblocks remain:

Most payers do not cover these preventive services.
US Preventive Services Task Force (USPSTF) has not issued a recommendation on these services. this affects both public and private insurance coverage.
Metformin which may be useful in younger populations does not have a specific indication for diabetes prevention from the FDA (off-label use only).

Whether prevention is ‘worth a pound of cure’ may be hard to discern with prediabetes. Since the peak incidence of diabetes is between 50 and 60 years and complications often emerge more than a decade later, the benefits of preventing diabetes may not be fully apparent for quite a long time.

Related blog entries:

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Pediatric Gastroenterology

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