Category Archives: Gastroenterology

Herbal Medicines for IBD and IBS

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A nice review (Holtmann G, Talley NJ. Clin Gastroenterol Hepatol 2015; 13: 422-32) provides a summary of the experience of herbal medicines for disorders that include irritable bowel syndrome (IBS), functional dyspepsia, and inflammatory bowel disease (IBD).

A recurring theme in the review is that herbal medicines are poorly studied and vary greatly in the quality of their manufacturing.  “Physicians and regulators need to remain very cautious about the use of herbal remedies.” The available trials, with a long list of plant extracts, are summarized in tables in the review.

Specific points:

  • “A meta-analysis also showed that supplementation of peppermint oil, in addition to pharmacologic standard treatments, was of benefit to both constipation-predominant IBS and diarrhea-predominant IBS patients.”
  • “The use os STW5 [iberogast] also has been found to be effective compared with placebo in the treatment of IBS symptoms.”
  • Very small clinical studies have suggested possible efficacy of aloe vera and curcumin in the treatment of IBD.
  • Adverse effects: “there are numerous case reports on adverse events related to herbal medicines.” Some of these have been severe.
  • “The main driver for the use of herbal and complementary medicines is the unmet need of patients.” However, given that these preparations are non patentable, “there is limited investment of producers.”

Bottomline: There is little financial incentive for companies to determine more conclusively whether these agents are effective for functional disorders or for inflammatory bowel disease.

Related blog posts:

NPR: “Craptastic Voyage” and Fart Analysis

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Surely a story for every gastroenterologist: “Before The Gas is Passed, Researchers Aim to Measure it in The Gut.”

An excerpt:

Kalantar-Zadeh and his colleagues propose in a paper in Trends in Biotechnologyonline Thursday two new devices that could keep a vigilant eye, or a nose in this case, on what’s going on deep in the gut….

The jar is pretty straightforward. A spoonful of poop goes in and a technician squeezes on a lid containing a sensor that detects the molecules of gas fuming inside and at what concentration…but he’s most excited about their other invention.

It’s a robotic pill that sniffs its way along a craptastic voyage through the gut. As the pill tumbles through, a membrane on the pill lets gasses pass onto a small molecular sensor inside that serves as its nose. The membrane blocks the other stuff sloshing around in the gut.

The pill notes the gasses that gut microbes produce, including oxygen, methane, hydrogen and hydrogen sulfide, which smells like rotten eggs. The pill’s sensor figures out how much of each gas is present, and beams the information out of the patient’s body through a tiny antenna…

The researchers aim to detect changes in gas content. As people’s health waxes or wanes because of stress or disease their intestinal ecosystems change too. Certain microbes may thrive in the new conditions while others struggle. As the populations shift, so will the concentrations of their distinctive gassy waste products.

My Take: This story reminds me about the joke I heard from a mentor about how can you tell if a person is an optimist.  An optimist is a person who finds a pile of manure under the tree on Christmas morning and declares: ‘Oh boy, I’m getting a pony.’

This story shows us that some researchers are true optimists as well; they see a lot of opportunity in studying stool and intestinal gases. Will this research will be useful or wind up being a pile of stool?

Also on NPR: Why Is Insulin So Expensive in the U.S. -summarizes recent commentary (N Engl J Med 2015; 372:1171-1175). This article is important for anyone concerned about escalating medicine costs.

Related blog post: “There is No ‘Healthy’ Microbiome” | gutsandgrowth

Transoral Fundoplication for Refractory Gastroesophageal Reflux

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A new endoscopic technique’s efficacy has recently been reported (Gastroenterol 2015; 148: 324-33).  Since this technique is not likely to be broadly applicable to the pediatric population for some time, I will not delve into all of the details.

In essence, a carefully selected group (n=129 from a screened group of 696) of adult patients with persistent regurgitation underwent transoral fundoplication; this eliminated troublesome regurgitation in 67% compared to 45% who were randomized to sham/PPI.  Severe complications were rare.

Here is a picture of the technique:

Transoral Fundoplication

Transoral Fundoplication

Link: Description and a video animation of the procedure

Bottomline: This endoscopic procedure along with the Stretta procedure and the LINX device (using magnets) offer alternatives to surgical fundoplication in carefully-selected patients with refractory gastroesophageal reflux symptoms.

New drugs approved by FDA:

Ceftolozane (Zerbaxa) -combines a cephalosporin with a beta-lactamase inhibitor (tazobactam).  Indications: complicated intra-abdominal infections (in combination with metronidazole), and complicated urinary tract infections. From FDA: FDA approves new antibacterial drug Zerbaxa

Viekira Pak -combination of 3 new drugs: ombitasvir, paritaprevir, and dasabuvir along with  older drug: ritonavir.  Indications: Hepatitis C genotype 1. From FDA: FDA approves Viekira Pak to treat hepatitis C

Related blog posts to fundoplication:

Updated Guidelines on Genetic Testing/Management for Hereditary GI Cancer Syndromes

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Here’s a link to abstract: Updated Guidelines on Genetic Testing/Management for Hereditary GI Cancer Syndromes (The American Journal of Gastroenterology 110, 223-262 (February 2015) | doi:10.1038/ajg.2014.435).  This ACG guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz–Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.

I glanced at the guideline –it is about 40 pages in length.  It provides a lot of in-depth information on these infrequent disorders.

Some online resources for similar information:

When A Disease Turns Out to Be Fictitious -The Sad Story on Sphincter of Oddi Dysfxn

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When parents make up diseases in their children, the consequences can be dire.  What happens when doctors find out that a disease that they have been treating probably doesn’t exist?

  • Cotton PD et al. “Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial” JAMA 2014; 311: 2101-2109.

A detailed analysis of this study (Gastroenterol 2015; 148: 440-44) and the author’s reply provides some insight into that questions and helps place this study and its results into context.

Key points from the Gastroenterology Selected Summary:

Background:

  • “Sphincter of Oddi dysfunction (SOD) is the term used to describe an episodic abdominal pain syndrome, typically occurring in young to middle-aged women in the setting of prior cholecystectomy…SOD remains a diagnosis of exclusion.”

Design:

  • “The investigators conducted a double-blind, sham-controlled, randomized trial at 7 US tertiary centers, enrolling 214 adult post-cholecystectomy patients with debilitating abdominal pain due to suspected biliary SOD (predominantly type III).” Sham patients underwent ERCP, manometry, and pancreatic duct stenting.
  • Patients were randomized 2:1 to sphincterotomy or sham; those randomized to sphincterotomy and subsequently shown to have a hypertensive pancreatic sphincter were then re-randomized (1:1) to have biliary or combined biliary/pancreatic sphincterotomies.

Results:

  • “Most patients in both study groups experienced considerable reduction in their pain disability scores…the proportion meeting the trial’s 1-year primary endpoint was higher among those treated with sham compared with sphincter ablation (37% vs. 23%, P=.01)”
  • “The manometry findings did not predict treatment success.”  There were no other useful predictors of success identified (eg. elevated liver enzymes, prior stone at cholecystectomy)
  • Adverse effects from procedures included 26 cases of acute pancreatitis (2 severe) and 2 perforations.

Discussion:

  • “The results of this trial are fascinating…the authors, many of whom had dedicated entire careers to the management of these patients using the very procedure they have now conclusively shown to be futile, may be understandably disheartened by the results.”
  • Numerous limitations of the study are noted.  In particular, “the 1-year time frame of the trial is likely to have been too short to capture the deleterious impact of prophylactic pancreatic duct stenting, which…has been associated with interval induction of pancreatic ductal abnormalities mimicking chronic pancreatitis.”
  • “It is our view that the authors’ data…provide an unambiguous mandate for imposing an immediate moratorium on subjecting this group of patients to ERCP.“

Dr. Cotton’s reply:

  • “It may be premature to discard the whole concept of sphincter dysfunction as a cause of pain.”
  • He indicates that “gallbladder dyskinesia” is another related question and was the reason for surgery in half of EPISOD subjects.
  • The results of the study “clearly show the need for equally stringent studies to answer the many remaining questions.”

For those who read this much of this post:  I wanted to let you know that yesterday’s online post on early peanut introduction was updated with recommendations from the associated editorial.

Related blog posts:

Another headline from Freaknomics Website follows. Of course I probably should think twice about poking fun at typos given the volume of them on this blog.

Screen Shot 2015-02-22 at 9.33.13 AM

Taking One ‘Bite’ At A Time -For Celiac Diagnosis

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A small study (reference from KT Park’s Twitter feed –Gastrointestinal Endoscopy DOI: http://dx.doi.org/10.1016/j.gie.2014.10.024) suggests that taking a single biopsy per pass rather than two biopsies per pass results in better quality specimens:

Link: Endoscopic Biopsy Technique in the Diagnosis of Celiac Disease

Here are the results and conclusion of the abstract:

Results

Patients (N = 86) were enrolled, 47% with known celiac disease, 36% with suspected celiac disease, and 17% with an unknown celiac disease status. Well-oriented biopsy specimens were noted in 66% of patients with the single-biopsy technique and 42% of patients with the double-biopsy technique (P < .01). Analysis of matched pairs showed improved orientation with the single-biopsy technique (odds ratio 3.1; 95% confidence interval, 1.5-7.1; P < .01). This persisted in subgroup analysis of patients with known celiac disease (P = .02), villous atrophy (P = .02), and a final diagnosis of celiac disease (P < .01).

Conclusion

The single-biopsy technique improves the yield of well-oriented duodenal biopsy specimens. Endoscopists should consider taking only 1 biopsy specimen per pass of the forceps in patients undergoing biopsies of the duodenal mucosa.

Related blog posts:

I'm the one on the right

I’m the one on the right

Accelerated Infliximab Dosing in Acute Severe Ulcerative Colitis -plus one link

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A small retrospective study (n=50) suggests that more rapid induction with infliximab may improve response and lower colectomy rate in acute severe ulcerative colitis (UC).

Link: Accelerated Infliximab in Acute UC

Here’s the abstract:

Background & Aims

Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect.

Methods

We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods.

Results

There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03).

Conclusions

In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.

One other link: IBD and College: Do the two play nicely (from Jeremy Adler and UofM) -describes college transition issues for our IBD patients.  Probably the most important piece of advice: “Take your medicine.”  Many really good kids decide to see what happens off therapy, often to their detriment.

Do We Still Need PPI-REE?

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“It is on shaky ground that one defines a disease by a response to therapy rather than by its clinical and mechanistic characteristics.” This is noted in a recent editorial (Clin Gastroenterol Hepatol 2014; 12: 2023-25, study: 2015-22).

The editorial makes this comment because the related study finds that the esophageal tissue from eosinophilic esophagitis (EoE) patients with proton-pump responsive EoE (PPI-REE) was indistinguishable from patients with EoE who do not respond to PPIs.

The study examined 196 consecutive patients and performed immunohistochemistry to examine major basic protein (MP), eotaxin-3, and tryptase.  Key finding: none of these markers were able to distinguish EoE from PPI-REE; however, these 3 assays did identify EoE with 100% accuracy compared with controls.

From the editorial: “We can approach EoE as a disease in which use of PPIs is the first step in treatment, and diet and steroids represent step-up therapy…We may not understand why some patients with EoE respond to PPIs yet others do not.”  It is possible that genetic testing in the future will allow us to distinguish which patients will benefit from PPIs, topical steroids or diets.

Bottomline: Now that it is well-recognized that a substantial portion of EoE patients benefit from PPIs, is it necessary to try to use a separate label for this subset? Probably not.

Related blog posts:

In the News …CRE due to ERCPs

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Carbapenem-Resistant Enterobacteriaceae (CRE) are difficult to treat infections.  A recent story in USA Today noted their association with endoscopic retrograde cholangiopancreatography (ERCP)/duodenoscopes.  According to the article, the FDA is working with the manufacturers to eliminate this risk.  Compared to other endoscopes, the side-viewing scopes are more technically-difficult to clean because of its “elevator” mechanisms.  “The biggest cases involved dozens of patients and multiple deaths.”  It is likely that more frequent and easier-to-treat infections may be transmitted as well; these types of infections generally do not result in full-fledged epidemiological investigations. Here’s the link: “Deadly bacteria on medical scopes trigger infections” This link has particularly good diagrams explaining resistant organisms.  It is important to emphasize that these infections, to my knowledge, have not been reported with the more common endoscopic procedures.  Because of technical differences in the scopes, the standard cleaning procedures are effective for upper endoscopies and colonoscopies. Related posts: