Tag Archives: cancer

Staggering cost of obesity

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For a single individual, the burden of obesity can be enormous; for a society, the projected costs for health and economics are hard to fathom (Lancet 2011; 378: 815-25).

By 2030, this report projects that there will be 65 million more obese adults in the US and 11 million more in the UK.  This is expected to cause an additional  6-8.5 million cases of diabetes, 5.7-7.3 million cases of heart disease/stroke, about 500,000 cases of cancer, and loss of 26-55 milion life years.  The medical costs are estimated to increase $48-66 billion/year in the US.

These projections are based on expected increases in the percentage of individuals who are obese.  In 2008, approximately 32% of US adult men were obese based on BMI; in 2030, the projected number is 50-51% for men.  Among US women: 35% in 2008 –> 45-52% in 2030.

To flatten the curve on spending, we will need to look at flattening other curves.

Additional references:

  • A liver disease tsunami
  • -NEJM 2011; 365: 1597. Persistence of hormonal adaptations with weight loss. Due to persistent changes in hormones like leptin & peptide YY, hard to keep wt off -result is increased appetite.
  • -NEJM 2009; 360: 859. Composition of diet does not seem to be important. Total calories important.
  • -Pediatrics 2007; 120: suppl 4: S164-S287.
  • -NEJM 2007; 357: 370. obestiy spreads in social network.  Your friends may be more influential than your genetics.
  • -Gastroenterology 2007; 132: 2085-2276. Special issue on obesity issues.
  • -NEJM 2006; 355: 1593. Case review on obesity c DDx and mgt.
  • -Pediatrics 2003; 112: 424. Position paper on prevention in childhood.
  • -Gastroenterology 2001; 120: 669-681. (review)
  • -J Pediatr 2005; 147: 429. TV viewing predicts adult BMI.
  • -Lancet 2001; 357: 505-8. One extra soda/day incr risk of obesity by 60%
  • -NEJM 1999; 341: 1097. BMI & mortality.

More bad news for smokers

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Add two more cancer risks for tobacco smoke (Gastroenterology 2012: 142: 233-40, 242-47).  There is now evidence linking tobacco smoke to 18 different cancers and tobacco smoke is probably the most preventable cause of death in the world.

In the first study, the investigators examined 3167 patients with Barrett’s esophagus.  This retrospective study followed patients for 7.5 years.  Patients who were current smokers (any form of tobacco) had double the risk of developing high-grade dysplasia or cancer compared to those who had never smoked.  Former cigarette smokers had a hazard ratio of 1.53.

In the second study, 386 patients with Lynch syndrome were analyzed during a 10 month period.  The hazard ratio for developing colorectal adenomas was 6.13 for current smokers and 3.03 for former smokers compared with patients who never smoked.  In addition, the authors identified a trend for developing adenomas based on pack-years.

Two more reasons to quit smoking.  On a side note, my grandmother said quitting smoking was the easiest thing that she ever did.  So easy, she did it a thousand times.

Additional references:

  • -Gastroenterolgy 2005; 129: 1825-31.  1.6% incidence of BE in adult Swedish population. Alcohol & smoking increase risk.
  • -NEJM 2011; 365: 1222. Treating smokers -useful review.
  • -NEJM 2011; 365: 1193. Cytisine -inexpensive- helps with smoking cessation (8.4% success vs 2.4%in placebo)
  • -NEJM 2008 358; 2249. Smoking and role of social networks.
  • -Gastroenterology 2011; 141: 2000. Lower risk of Barrett’s in pts taking NSAIDs & statins. n=570.
  • -Gastroenterology 2011; 141: 1179. Lower risk of Barrett’s in pts with low-grade dysplasia than previously noted -similar to non-dysplastic Barrett’s.
  • -NEJM 2011; 365: 1375. Large Danish study, n=11028. Lower incidence of Barrett’s than previous estimates. Relative risk of 11.3 compared to general population for adenoca of Esophagus with absolute annual risk of 0.12%. Barrett’s patients have the same life expectancy as general population (ed. pg 1437). Detecting cancer only ~1 in 1460 scopes with screening whereas Barrett’s detected in 10% of pts.
  • -Gastroenterology 2011; 140: 1084. AGA statement on Barrett’s . Recs screening only in those with multiple risk factors (age 50, male, chronic GERD, white, incr BMI)
  • -NEJM 2005; 352: 1851. Cases of Lynch can be missed when following screening guidelines.
  • -Gastroenterology 2010; 138: 207-2177 (entire issue) Colon cancer, Lynch syndrome
  • -Gastroenterology 2008; 135: 380.  Review of colon cancer screening and prevention -2008 up-to-date- literature review
  • -Gastroenterology 1967; 53: 517-27.  Seminal article.  Lynch HT showed gene-related cancer in family cancer syndrome -different than polyposis syndromes.

A cure for satiety

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A safe cure for excessive appetite is a holy grail in pharmacology.  Although gluttony is a much more pervasive problem that poor appetite, an effective cure for satiety is also needed.  In the clinical setting, poor appetite remains a common problem with and without underlying problems.  Treatments to this point, such as cyproheptadine or megestrol, may be useful in some patients.  Better treatments are needed.  One drug of interest is ghrelin (Cancer 2012; DOI: 10.1002/cncr.27430).

The introduction summarizes ghrelin’s biologic activity: “Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor and is secreted predominantly by gastric endocrine cells.  It induces dose-dependent, GH-releasing activity; stimulates appetite and food intake; and triggers a positive energy balance through a central mechanism involving hypothalamic neuropeptides.”

Plasma ghrelin levels decrease after gastric resection, helping to maintain weight loss. Therefore, the stomach may act as endocrine organ to maintain appropriate weight. Exogenous administration may increase appetite.

This cited article reports a prospective randomized placebo-controlled phase 2 study in which ghrelin was administered to 21 patients with esophageal cancer, receiving cisplatin-based chemotherapy; the dosage was 3 μcg/kg twice daily for 1 week.  A placebo group  (n=20) received saline.  The ghrelin group consumed 18.2 kcal/kg/day compared with 12.7 kcal/kg/day.  A measure of appetite, an appetite visual analog score, was also higher in the ghrelin-treated patients, 6.2 vs 4.1.  Patients in the ghrelin group had fewer adverse effects of chemotherapy related to anorexia and nausea than patients in the control group.  One patient receiving ghrelin stopped therapy because of excessive diaphoresis.

Although this medication is being studied in adult chemotherapy patients, down the road ghrelin and potential analogs may have a role in pediatric patients with a variety of disorders which inhibit their appetite.

Additional references:

  • -Adachi S, Takiguchi S, Okada K, et al. Effects of ghrelin administration after total gastrectomy: a prospective, randomized, placebo- controlled phase II study. Gastroenterology. 2010;138:1312-1320.
  • -NEJM 2002; 346: 1623-30, 1662. Plasma ghrelin levels decrease after gastric resection.   Therefore, stomach may act as endocrine organ to maintain appropriate weight. However, ghrelin levels are reduced in obesity; so it is not clear that further reduction of these levels is clinically important.
  • -Gastroenterology 2003; 125: 1492. Review of ghrelin.
  • -Yamamoto K, Takiguchi S, Miyata H, et al. Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction. Surgery. 2010;141:31-38.
  • -Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194-198.
  • -Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone- releasing acylated peptide from stomach. Nature. 1999; 402:656- 660.
  • http://www.surgjournal.com/article/S0039-6060(09)00784-3/abstract
  • http://pennmedicine.adam.com/content.aspx?productId=16&pid=16&gid=50495 Review of cited article.

Good News for Celiac Disease

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With the discovery of precise serologies to identify celiac disease, the likelihood of complications of celiac disease has been changing.  In addition, the presentation of celiac disease is different now.  Instead of seeing children with malabsorption and abdominal distention, many children and adults are identified with mild or no symptoms.  Also, the risk of severe complications including malignancy and autoimmune disease has been reevaluated based on larger cohorts.  Twenty years ago, the risk of these complications did serve as a motivator for continuation of a gluten free diet (GFD).   While a GFD remains important, these risks are much lower than previously reported.  The most recent article to support this contention is the following:

Clinical Gastroenterology and Hepatology 2012; 10: 30-36.  This study examined ~45,000 patients with either celiac disease (villous atrophy, Marsh score of 3), duodenal inflammation (Marsh 1 or 2), or latent celiac disease (normal mucosa & positive serology).  After the first year, there was no significant increase risk for GI cancers.  During the first year, cancers that were identified may not have been causally-related to celiac disease but due to coincident detection.

This article due to its large cohort is very useful, but other articles have come to different conclusions.  Irregardless, there are still compelling reasons to continue a GFD.  Many individuals feel better on a GFD & did not recognize prior symptoms.  Maintaining this diet probably lowers the risk of developing certain autoimmune conditions and definitely improves bone health.

Other recent &/or related articles:

–Gastroenterology 2010; 139: 763. Mortality NOT worsened in undiagnosed celiac disease (identified by review of serology) in Olmstead County, though bone density decreased. n=129 of 16,847. (?milder cases undiagnosed)
–J Pediatrics 2010; 157: 373, 353. Even patients without villous atrophy & positive serology, benefited from GFD with regard to GI symptoms and serological markers.
–JAMA 2009; 302: 1171-78. n=29,096. Mortalitiy increased in celiac disease: 35% for latent, 72% for inflammation, 39% for celiac dz.

–Clin Gastro & Hep 2008; 6: 753.  Incidence of autoimmune diseases less in those celiac patients who were compliant with GFD. n=178.

–Gastroenterology 2002; 123; 1428-1435. n=12,000.  Risk for cancer 1.3 odds ratio (lower than in previous studies).