PEG Decisions

In pediatric gastroenterology, percutaneous endoscopic gastrostomy (PEG) tube placement is not typically a palliative measure and there is a very low mortality rate.  In adult medicine, PEG tube placements are often part of palliative care and used to allow easier management in nursing homes.

A few studies this past month highlight the mortality and potential ethical dilemmas focused around PEG tube placement.

Clin Gastroenterol Hepatol 2013; 11: 1437-44.  “In-hospital mortality was 10.8% among 181,196 patients who underwent PEG in 2006.”

Clin Gastroenterol Hepatol 2013; 11: 1445-50.  Between 2004-2010, among 1327 patients with prospectively collected data from 2 UK hospitals, 344 (23%) did not undergo gastrostomy placement after multidisciplinary team discussion. This group had 35.5% mortality at 30 days compared with 11.2% of the 1027 who proceeded with PEG.  Age >60 and low albumin were predictors of 30-day mortality.

Clin Gastroenterol Hepatol 2013; 11: 1451-52.  The editorial on these two studies tries to redirect the focus from futility to quality of life in terms of PEG decision-making.  “An objective scoring system to predict survival, minimize futility, and promote justice in the allocation of resources toward PEG placement is not the direction endoscopists should be taking.” If, for example, PEG tube provides palliative decompression for outlet obstruction or allows transfer to nursing home, this may align with the principle of patient autonomy.  The editorial argues that if the potential goals of PEG placement can be met, this is the key factor.

Bottomline: Information on outcomes and potential futility should be discussed as part of the informed consent process.  But, I bet this will not make those decisions any easier.

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PPIs -another reference for EoE

“The outcome of patients with oesophageal eosinophilic infiltration after an eight-week trial of a proton pump inhibitor”

  1. G. Vazquez-Elizondo1,
  2. S. Ngamruengphong1,
  3. M. Khrisna2,
  4. K. R. DeVault1,
  5. N. J. Talley1,
  6. S. R. Achem1,*

Article first published online: 5 OCT 2013

DOI: 10.1111/apt.12513

Link to article: bit.ly/18bA3SS (from John Pohl’s twitter feed)

Methods: Sixty consecutive symptomatic patients with documented oesophageal eosinophilia received open-label omeprazole 20 mg orally twice daily before meals for 8 weeks.  Mean age 48.7 years (18-79).

Results: Clinical improvement occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%) obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete clinical and histological remission

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Top Cited 100

In a recent commentary, the authors provide a list of the most commonly cited digestive disease articles from 1967-2007.  (Gastroenterol 2013; 144: 673-76)

The top three:

  1. Manns, M, et al. Lancet 2001; 358: 958-65. This study compared peginterferon alfa-2b with ribavirin against interferon with ribavirin for hepatitis C
  2. Fried M, et al. NEJM 2002; 347: 975-82. This study examined the use of peginterferon alfa-2a with ribavirin for hepatitis C
  3. Marshall B, Warren J. Lancet 1984; 1: 1311-15.  This study identified a bacteria (now called Helicobacter pylori) as a cause of ulcers and gastritis.

http://dx.doi.org/10.1053/j.gastro.2013.02.013

EPT for Achalasia

EPT or esophageal pressure topography (using high-resolution manometry) can help predict outcomes for achalasia (Gastroenterol 2013; 144: 718-25, editorial 681-83).

Background:  Patients with achalasia often present with dysphagia, chest pain, and regurgitation.  These symptoms result from impaired lower esophageal sphincter relaxation and aperistalsis.  While the main treatment has focused on disruption of the sphincter, esophageal body pressures may be important in long-term outcomes.

Three patterns of esophageal body pressures with achalasia:

  • type 1 absence of peristalsis and minimal pressurization
  • type 2 absence of peristalsis with panesophageal pressurization (≥30 mm Hg)
  • type 3 evidence of spasm

According to the cited study which reviewed data from 176 patients in the European achalasia trial (time period: 2003-2008, 18-75 year old), success rates were better with type 2 achalasia (96%, n=114) compared with type 1 (81%, n=44) or type 3 (66%, n=18).

In addition, the EPT findings may influence treatment selection.  Pneumatic dilation (PD) was more successful than Heller myotomy (HM) for type 2 patients (100% vs. 93%, p < 0.05).  However, HM was considered successful more frequently for patients with type 3 achalasia (86% vs. 40% –though not statistically significant due to small numbers).  For type 1, no significant difference was noted between HM and PD at 2 year followup, 81% vs. 85% respectively.

The commentary discusses some of the pertinent issues.   For example, HM may be better than PD among type 1 patients; the exclusion of patients with severe dilatation of esophagus.

Take-home message (from editorial) “The task at hand is to determine whether these distinct categories truly matter in clinical practice…it seems that the subtypes of achalasia do have prognostic value…we …need to determine…whether subtypes can inform treatment options.”

Hemorrhoids and asstronauts

A recent review on hemorrhoids (Clin Gastroenterol Hepatol 2013; 11: 593-603) had a few useful quotes:

“Why are hemorrhoids called hemorrhoids and asteroids called asteroids? Wouldn’t it make more sense if it was the other way around? But if that were true, then a proctologist would be an astronaut.”  Robert Schimmel

“My troubles are all behind me” George Brett (on returning to World Series after treatment for a thrombosed external hemorrhoid)

Besides the quotes, the review article provides a concise approach to the epidemiology, anatomy, pathophysiology, diagnosis, and management of hemorrhoids.

Specific points:

  • The word ‘Hemorrhoid’ is derived from the Greek words “haima” meaning blood and “rhoos” meaning flow.  The word “pile” is derived from the Latin word “pila” meaning a ball.
  • Conservative treatment: increasing fiber, avoidance of straining/minimizing time on toilet, and sitz baths several times per day.
  • “Well-designed studies have found no evidence to support the use of any of the myriad of over-the-counter topical preparations that contain low-dose local anesthetics, corticosteroids, keratolytics, protectants, or antiseptics.”  “Long-term use of these products, particularly steroid preparations, …should be discouraged.”
  • Rubber band ligation: “highly effective…in a meta-analysis of 18 prospective, randomized trials, RBL was overall superior to injection sclerotherapy or infrared coagulation in the treatment of grades I, II, and III (internal) hemorrhoids.”  “Risk of complications is low <1-3%, including pain, bleeding, and vasovagal symptoms.” Higher rates of pain are reported in some studies and may be dependent on location of RBL.
  • Cryosurgery and Lord’s procedure ..”have lost favor in the United States.”
  • Surgical treatment: “Nonsurgical approaches are successful in 80-99% of patients.” “Surgical hemorrhoidectomy is more effective than RBL in the treatment of grade III hemorrhoids but incurs additional complications, pain, and disability.”  Complications have included urinary retention, bleeding, infection, anal stenosis, and incontinence (2-12%)–Ouch!

Barrett’s Esophagus –refer to cardiology?

According to a study which examined cause-specific mortality, patients with Barrett’s esophagus may be better off following up with a cardiologist than a gastroenterologist (Gastroenterol 2013; 144: 1375-83).

This study derived data from UK’s Clinical Practice Research Datalink.  8448 patients with Barrett’s esophagus were matched with 155,212 controls based on age, sex and general practice.

Key findings:

  • Patients with BE had increased risk of death from esophageal cancer leading to a 10-year risk of 1.9%.  The absolute mortality rate due to esophageal cancer was 1.44 per 1000 person-years.  Compared to the general population, this was a 4.5 fold relative increase.
  • Ischemic heart disease resulted in 168 patient deaths, nearly 4-fold the number that died of esophageal cancer.
  • Overall, individuals with Barrett’s esophagus had a 21% relative increased risk of all causes of death; the majority were not due to esophageal cancer.  32% were related to circulatory disorders, 24% were due to nonesophageal cancer, and 15% were due to respiratory disease.

While this was a large study, there remain several limitations; most of these are due to reliance on electronic records for the diagnosis of Barrett’s.  Also, some individuals with Barrett’s may have been identified due to other high risk conditions such as cirrhosis (endoscopy for varicose) which could contribute to excess mortality.  In addition, many controls likely had undiagnosed Barrett’s.  Even the attribution of the cause of death can be quite difficult, especially with a database study.

Nevertheless, the population-based setting likely means that the results are likely meaningful to a broad population.

Take-home message: While Barrett’s esophagus increases the risk of death from esophageal cancer, it is possible that strategies which focus on nonesophageal causes of death may be more effective than esophageal surveillance for increasing longevity.

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What to Feed Your Baby

“What to Feed Your Baby” — is the title of a recent, easy-to-read, practical book written by one of my colleagues, Stan Cohen.  I had the opportunity to read it and recommend it as an excellent resource for parents.  This book is not just for selecting formula and introducing foods, but it also reviews gastroesophageal reflux, colic, stooling problems, poor weight gain, overweight issues, prematurity, and allergies.  In addition, the subtitle, “Cost-Conscious Nutrition for Your Infant,” is an important element throughout the book.

The first few chapters highlight the advantages of breastfeeding but acknowledge that formula-feeding is an acceptable alternative.  Specific advantages that are outlined in Table 2.2 include decreased infections, decreased risk for several illnesses like sudden infant death syndrome (along with many others like diabetes and obesity), protection from allergies, and improved intelligence.  Advantages for the mother, like weight loss and better emotional health, are discussed as well.

Almost any question that a new mother would ask about the logistics of breastfeeding are answered in the 3rd chapter: “How long should each feeding be?” “Should I wake the baby?” “Do I need to stop if I have a cold?” “How long can the breastmilk be stored?”  The latter question has its own table 3.1 and the answer depends on the storage temperature.  At room temperature, covered breastmilk should be durable for 6-8 hours.  In addition, Dr. Cohen explains the need for vitamin D supplementation.

Chapters 4 and 5 help parents understand the highly marketed formulas and to understand a rationale for choosing one formula over another, including cost as a factor.  Dr. Cohen provides data on mean docosahexaenoic acid (DHA) content in breastmilk throughout the world.  In the U.S., the level is relatively low at 0.29 (as a percentage of fatty acids).  The breastmilk DHA level is nearly three times higher in Japan and Artic Canada.  These discrepancies account in part why formula companies may choose different target concentrations for some of their components when trying to mimic breastmilk.

While Dr. Cohen explains that some of the differences between formulas are akin to differences between Coke and Pepsi, he expresses a preference for the current Mead Johnson formula Enfamil Premium due to its higher DHA content –“though the research is not thoroughly established.”  However, he states that the differences probably do not justify a much higher cost.  For a generic brand, the Costco brand, “Kirkland Signature…are reasonable and less expensive, FDA-approved options.”

In addition, these chapters question whether infant organic formulas are truly organic (page 55), explain the issue of burping, and discuss the pragmatic advise regarding cleaning nipples/bottles; “kitchen clean” with soap and a washing with hot water should suffice and sterilization is not needed.

The most inciteful comments, in my opinion, are in chapter 5:

  • Lactose-free formulas: “Mead Johnson pulled its product from the market because lactose sensitivity is rare, rare, rare in infants…Abbott, in a shrewd marketing move, renamed its formula, originally called Lactofree, to Similac Sensitive, and that labeling has convinced an enormous number of mothers that this formula makes a difference.”  Similac Sensitive accounts for >10% of formula market.  A similar product is Gerber (previously Nestle) Good Start Soothe.
  • Elemental formulas: “cost as much as a monthly Porsche payment.”  Monthly costs of each type of formula are detailed in Table 5.3.  Routine cow’s milk based formula $149.88, soy-based $153.56, cow’s milk with rice starch $159.39, hydrolyzed (broken down protein) formula (e.g.. Alimentum, Nutramagen) $223.56, and elemental amino acid based $511.83.
  • Among extensively hydrolyzed formulas, Dr. Cohen indicates a preference for Alimentum (from Abbott) over its competitors due to better acceptance by infants.
  • The rationale for not switching from contracted WIC products is explained.  When changing from a contracted product to a non-contract product, the costs are much greater and among the same type of formula there is not a scientific rationale.
  • Reasons why goat’s milk are not a good choice and “dangerous” for infants are detailed.  “The protein content is over three times higher than cow’s milk…additionally, goat’s milk is deficient in folate and vitamin B6.”

As noted above, the book covers a variety of pediatric gastroenterology problems in the newborn.  As part of the chapter on undernutrition, additives to increase calories are detailed (pg 136).  For example, a tablespoon of polycose adds 23 cal, a tablespoon of rice cereal 15 cal, and  a tablespoon of vegetable oil 124 cal.

The last few chapters provide ample advice on transitioning to solid foods, reviews nutrients and mineral oils.  In addition, he provides growth charts (for full term, premature infants, and infants with Down syndrome) as well as tables on infant formula contents.

Take-home message: this is a terrific resource for parents to help understand the what, why and when of feeding their infant.  At the same time, the book provides advice on the most common pediatric gastroenterology problems of infancy like reflux, colic, stooling difficulties, allergies, and poor weight gain.

Book’s website and how to purchase:

http://www.what2feedyourbaby.com

To purchase the book:

Here is the link:

Reviews:

Other favorable reviews (http://what2feedyourbaby.com/reviews/) have come from influential pediatricians like Jay Berkelhammer and pediatric gastroenterologists like Jeff Hyams and Allan Walker.

In this book, Dr. Stanley Cohen, a pediatric gastroenterologist and nutritionist with longstanding interest in infant nutrition, provides a practical and pragmatic approach to a major concern for new mothers, namely What to Feed Your Baby.

— Allan Walker, M.D., director, Division of Nutrition, Conrad Taff professor of pediatrics and nutrition, Harvard Medical School

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Early Surgery for Acute Uncomplicated Cholecystitis

Data in adults suggests that early surgery is the best approach for acute uncomplicated cholecystitis:

From the following link: Early cholecystectomy beats delayed in acute cholecystitis : Internal : Acute cholecystitis patients fared significantly better with early rather than delayed laparoscopic cholecystectomy in the largest-ever randomized trial addressing surgical timing for this common condition.

Patients assigned to early cholecystectomy – that is, surgery within 24 hours of presentation to the hospital – had one-third the morbidity, markedly shorter hospital lengths of stay, and correspondingly lower hospital costs compared with patients who underwent surgery on day 7-45, according to Dr. Markus W. Buchler of Heidelberg (Ger.) University….

The optimal timing of surgical intervention in acute cholecystitis is a subject of long-standing controversy. The ACDC trial was conducted because in a Cochrane review of five smaller randomized trials totaling 451 acute cholecystitis patients, researchers concluded there was insufficient evidence to say which surgical strategy was best (Cochrane Database Syst. Rev. 2006 Oct 18;4:CD005440).

Dr. Buchler noted that surveys indicate many American surgeons prefer to delay laparoscopic cholecystectomy, while in Germany the surgical preference is for immediate surgery in patients with uncomplicated acute cholecystitis.

The ACDC trial involved 618 patients with uncomplicated acute cholecystitis who were placed on the same antibiotic – moxifloxacin – and randomized to early laparoscopic cholecystectomy or to delayed surgery on day 7-45. Pregnant patients were excluded from the trial, which was conducted at 35 European hospitals, including seven German university medical centers. All participating hospitals were staffed by surgical teams experienced in performing difficult laparoscopic cholecystectomies.

The primary endpoint was total morbidity within 75 days. This included cholangitis, pancreatitis, biliary leak, stroke, myocardial infarction, abscess, bleeding, peritonitis, infection, and renal failure. The rate was 11.6% in the early cholecystectomy group compared with 31.3% with delayed surgery. Among less challenging patients with an ASA score of 2 or less, the rates were 9.7% and 28.6%, respectively. Patients with an ASA score above 2 had an overall morbidity rate of 20% with early surgery compared with 47% with delayed laparoscopic cholecystectomy.

The rate of conversion to open surgery was 9.9% in the early laparoscopic cholecystectomy group and similar at 11.9% in the delayed surgery group…Total hospital stays averaged 5.4 days in the early surgery group compared with 10.0 days with delayed surgery. Mean total hospital costs calculated via the German DRG system were 2,919 euro in the early cholecystectomy group and 4,261 euro with delayed surgery.

Discussant Dr. Andrew L. Warshaw…“There’s no doubt in my mind that immediate cholecystectomy is superior in this patient population,” said Dr. Warshaw, professor and chairman of the department of surgery at Harvard Medical School, Boston.

Why Eliminating Gluten May Help Irritable Bowel Syndrome

As noted in previous posts, gluten-free diets (GFDs) have become commonplace for individuals without celiac disease.  Clinically, subgroups of patients with irritable bowel syndrome (IBS) were noted to have gluten sensitivity.  But, these subgroups were difficult to define and the mechanisms of improvement with a GFD were purely speculative.  A new study identifies changes in the frequency of bowel habits and mucosal permeability associated with a GFD among diarrhea-predominant IBS patients (Gastroenterol 2013; 144: 903-11).

While the investigators conducted a trial of short duration (4 weeks) and only enrolled 45 patients, they completed a number of sophisticated studies.

Design: 45 patients were randomized into either a gluten-containing diet (GCD, n=22) or GFD (n=23).  In each group, there were 11 patients who were HLA-DQ2/8 positive.

Measurements:

  • Daily bowel frequency
  • Small bowel and colonic transit
  • Mucosal permeability using lactulose/mannitol excretion.  Lactulose is normally not absorbed except with increased permeability. Mannitol is passively absorbed throughout intestine.  Higher lactulose:mannitol ratio in urine reflects intestinal permeability.
  • Cytokine production
  • Rectosigmoid biopsies (from 28 patients) to analyze messenger RNA for tight junction proteins and immunohistochemical staining

Key Results:

  • Fewer bowel habits were noted in patients receiving GFD.  In this group, bowel habits decreased from ~2.6/day to 2/day.  This was significant compared with GCD group.  Furthermore, this effect was more pronounced among patients positive for HLA-DQ2 or HLA-DQ8.
  • There was no significant change in stool form or ease of passage between GFD and GCD groups.
  • GCD had increased small bowel permeability as shown by mannitol excretion and lactulose-to-mannitol ratio (specific #s Table 1). Again, this effect was more pronounced among patients positive for HLA-DQ2 or HLA-DQ8.
  • GCD group had a reduced mRNA expression of mucosal tight junction proteins.
  • GCD was not associated with significant effects on colonic transit, immunocyte activation, or altered histology (eg. increased intraepithelial lymphocytes, change in crypt:villus ratio).

The increased changes in HLA-DQ2/HLA-DQ8 suggest a role for adaptive immune response in mediating GCD effects on barrier function.

Conclusion: “our data provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS.”

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