Sleeve GastrectomyProton Pump Inhibitors &GastrinGastric Cancer & Other Froms of Cancer

1. Sleeve Gastrectomy
Proton Pump Inhibitors &
Gastrin
Gastric Cancer &
Other Froms of Cancer

2. “Long-term PPI Use Tied to
Doubled Risk for Gastric Cancer”
• Long term Proton-pump inhibitors (PPI)
• More than doubles the Risk of Gastric Cancer,
• in a population-based study
• “Long-term use of PPIs associated with an increased
Gastric Cancer Risk
Even in subjects after H.Pylori Rx”
• http://gut.bmj.com/content/early/2017/09/18/gutjnl-2017-314605
• https://www.medscape.com/viewarticle/887863

3. Hypergastrinemia and Gastric Cancer
• Sleeve gastrectomy induces hypergastrinemia
• Gastrin has been identified as the principal effector of gastric
secretion,
• Several studies have demonstrated its role as a biomarker of
cancer risk & Growth factor for colorectal, stomach, liver, and
pancreatic cancer.
• Gastrin: from pathophysiology to cancer prevention and treatment.
• https://www.ncbi.nlm.nih.gov/pubmed/24469263
• Surg Endosc. 2015 Mar;29(3):723-33. The effect of duodenojejunostomy and sleeve gastrectomy on type 2 diabetes
mellitus and gastrin secretion in Goto-Kakizaki rats. Grong E

4. Gastrin and Gastric Cancer - NCBI - NIH
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239792/
• by HL Waldum - 2017 - Cited by 8 - Related articles
• Jan 17, 2017 - The role of gastrin in gastric
carcinogenesis implies caution in the long-term treatment
with inhibitors of gastric acid secretion inducing secondary
hypergastrinemia, in a common disease like
gastroesophageal reflux disease.

5. Sleeve => Increased Gastrin
=> Gastric Cancer
• SG may be associated with increased gastrin levels in both
human and rodents [13, 14]
• Gastrin levels of the SG group increased significantly compared
with those of the control group.
• Food Nutr Res. 2016 Apr 15; Metabolic and histopathological effects of sleeve gastrectomy
and gastric plication: an experimental rodent model. Gulcicek OB

6. 1. Sleeve Gastrectomy
2. => Lifetime GERD
3. => PPIs
4. => Hypergastrinemia
5. => Gastric Cancer

7. Sleeve gastrectomy & proton pump
inhibitors after surgery
• "Proton pump inhibitors and gastric cancer: a
long expected side effect"
• "For 30 years, we have worked with the role of
gastrin and the risk of PPI treatment with
respect to gastric cancer and published more
than 200 papers and letters in this field. "

8. Sleeve gastrectomy & proton pump
inhibitors after surgery
• (Ed Note: Sleeve => Increased Gastrin Levels =>
Increased Risk of GI cancers)
• "we always have concluded that PPI treatment in
the long term would cause gastric cancer, "
• "Around 1980, it became clear that
hypergastrinemia, ... resulted in ... tumours.

9. Sleeve gastrectomy & proton pump
inhibitors after surgery
• "PPIs ... caused tumours in the rat.Ref 3 "
• " Omeprazole was accepted for use in patients with
severe diseases due to gastric acid hypersecretion.
However, PPIs were soon used in less severe
cases and are now prescribed to patients with
minor complaints from the upper abdomen (10% of
the population in the Western world)."

10. Sleeve gastrectomy & proton pump
inhibitors after surgery
• "We recall Kenneth Wormsley’s words
about the acceptance of omeprazole for
clinical use: “The first compound accepted
for use in humans after having induced
cancer in its target organ”; a taboo was
broken. "

11. Sleeve gastrectomy & proton pump
inhibitors after surgery
• "Early, it was recognised that PPIs induced
hypergastrinemia and ECL cell hyperplasia.9"
• "Recently, a study from Finland found that patients with
high gastrin values in samples from the eighties had
increased risk of gastric cancer,10"
• (Ed Note: Sleeve => Increased Gastrin Levels =>
Increased Risk of GI cancers)
• "the carcinogenic effect of H. pylori infection is best
explained by the hypergastrinemia"

12. Sleeve gastrectomy & proton pump
inhibitors after surgery
• "We conclude that the carcinogenic effect
by PPI treatment is due to
hypergastrinemia, which should have
been realised decades ago before
exposing so many patients to a risk of a
serious disease."

13. Sleeve gastrectomy & proton pump
inhibitors after surgery
• "We conclude that the carcinogenic effect by PPI
treatment "(and the Sleeve?)
• "is due to hypergastrinemia, "
• which
• "should have been realised decades ago"
• "before exposing so many patients to a risk of a
serious disease."

14. Gastroesophageal Reflux Disease After
Laparoscopic Sleeve Gastrectomy
New-onset GERD in 47%
• Obes Surg. 2018 Apr;28(4)
• Prevalence and Predictors of Gastroesophageal Reflux Disease After
Laparoscopic Sleeve Gastrectomy.
• Althuwaini S

15. Sleeve Long Term Failure
• Meta-analysis on published data with at least 7
years of follow-up
• Nine cohort studies met the inclusion criteria, with a
total of 2280 patients
• At ≥7 years, the long-term weight failure rate was
estimated to be 28%; Revision 20%
• Surg Obes Relat Dis. 2018 Mar 6, Long term (7 or more years)
outcomes of the sleeve gastrectomy: a meta-analysis. Clapp B

16. Gastroesophageal reflux disease (GERD)
after sleeve gastrectomy
• “CONCLUSIONS: One year after SG,
esophageal acid exposure globally
worsened, mostly because of de novo
GERD”
• Obes Surg. 2018 Mar;28(3):838-845. Gastroesophageal
Reflux After Sleeve Gastrectomy: a Prospective
Mechanistic Study. Coupaye M

17. Surg Obes Relat Dis. 2018 Gastroesophageal reflux disease symptoms and
esophageal lesions after sleeve gastrectomy. Soricelli E
• After a mean follow-up of 66 months,
GERD symptoms and PPI intake were
recorded in 70% & 64% of patients
• Erosive esophagitis 60%, Barrett's
esophagus 13%.
• Esophageal biliary reflux was 68%.

18. Swiss Multicenter Bypass or Sleeve Study
(SM-BOSS)
• Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group
randomized trial, was conducted from January 2007 until November 2011
(last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for
bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled
• Gastric reflux worsened (more symptoms or increase in therapy) more often
after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass
(6.3%). The number of patients with reoperations or interventions was 16/101
(15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y
gastric bypass.
• JAMA. 2018 Jan 16;319(3):255-265. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on
Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial. Peterli R

19. Prevalence of GERD symptoms, EE, and
HH was increased after LSG
• Prospective observational study. 18-month follow-up
• GERD symptoms increased from 33% to 44%
• EE from 20.1% to 33.9%
• HH from 22% to 34.8%
• Postoperative findings on symptomatic patients were as follows:
• EE was found in 64.5%,
• HH in 23%,
• Only 12.5% had normal EGD.
• Symptoms de novo were observed in 36.9% of patients, EE in 28.7%, and HH in 16.4%.
•
• J Laparoendosc Adv Surg Tech A. 2018 Jan;28(1):71-77 Laparoscopic Sleeve Gastrectomy: Endoscopic Findings and
Gastroesophageal Reflux Symptoms at 18-Month Follow-Up. Viscido G

20. Sleeve Causes GERD. And Need for PPI Rx.
• After LSG, 60% (n = 60) of patients reported
recurring GERD symptoms and
• 44% were treated with proton pomp inhibitors
(PPI).
• In 93% of these cases, GERD has developed de
novo.
• Obes Surg. 2018 Jan;28(1):130-134. doi: 10.1007/s11695-017-2795-2.
• Long-Term Outcomes of Laparoscopic Sleeve Gastrectomy-a Single-Center, Retrospective Study.
• Kowalewski PK1

21. GERD & PPIs following sleeve gastrectomy
• At 12 months postoperatively,
• sleeve gastrectomy patients had a high rate of
• overall PPI use (48%),
• new PPI use (35%), and
• persistent PPI use (79%)
• and Significantly higher when compared to gastric bypass
patients.
• Surg Endosc. 2017 Jan;31(1), GERD and acid reduction medication use
following gastric bypass and sleeve gastrectomy. Barr AC

22. HelicoBacter, Gastric & Gastric Cancer
• Helicobacter pylori infection is associated with atrophic
• gastritis, which can progress to gastric cancer in some
patients.
• Proton pump inhibitor (PPI) use has also been reported
• as a risk factor for atrophic gastritis. The risk is particularly
• high among individuals infected with H. pylori who
• are susceptible to the development of corpus atrophy

23. Sleeve, PPIs, Hyper-gastrin & Cancer
• Sleeve & PPIs => INCREASED Gastrin
• “causal effect of gastrin on neoplastic
progression in Barrett’s esophagus (BE)”