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jeanL
07-21-2015, 02:06 AM
A recent Danish nationwide study of ~10,000 with Barrett oesophagus found no evidence for the usage of PPI's to prevent high-grade dysplasia and oesophageal adenocarcinoma(EAC). Interestingly enough they actually found an increased incidence of both high-grade dysplasia and EAC amongst those taking PPIs in higher doses and for a longer time, but couldn't explain why the correlation was happening.

Proton pump inhibitor use may not prevent high-grade dysplasia and oesophageal adenocarcinoma in Barrett's oesophagus: a nationwide study of 9883 patients. (http://www.ncbi.nlm.nih.gov/pubmed/24617286/)




Abstract
BACKGROUND:

Proton pump inhibitors (PPI) may potentially modify and decrease the risk for development of oesophageal adenocarcinoma in Barrett's oesophagus (BO).

AIM:

To investigate if the intensity and adherence of PPI use among all patients with BO in Denmark affected the risk of oesophageal adenocarcinoma.

METHODS:

We performed a nationwide case-control study in Denmark among 9883 patients with a new diagnosis of BO. All incident oesophageal adenocarcinomas and high-grade dysplasias were identified, and risk ratios were estimated on the basis of prior use of PPIs. Sex- and age-matched BO patients without dysplasia or malignancies in a 10:1 ratio were used for comparison. Conditional logistic regression was used for analysis, adjusting for low-grade dysplasia, gender and medication.

RESULTS:

We identified 140 cases with incident oesophageal adenocarcinomas and/or high-grade dysplasia, with a median follow-up time of 10.2 years. The relative risk of oesophageal adenocarcinoma or high-grade dysplasia was 2.2 (0.7-6.7) and 3.4 (95% CI: 1.1-10.5) in long-term low- and high-adherence PPI users respectively.

CONCLUSIONS:

No cancer-protective effects from PPI's were seen. In fact, high-adherence and long-term use of PPI were associated with a significantly increased risk of adenocarcinoma or high-grade dysplasia. This could partly be due to confounding by indication or a true negative effect from PPIs. Until the results from future studies hopefully can elucidate the association further, continuous PPI therapy should be directed at symptom control and additional modalities considered as aid or replacement.

Now a newer study has released a putative mechanism as to how PPI's might in fact contribute to the development of Barrett's Oesophagus and subsequently EAC.

Proton Pump Inhibitors: The Culprit for Barrett’s Esophagus? (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288325)




Barrett’s esophagus (BE) is a condition in which the stratified squamous epithelium (SSE) of the distal esophagus undergoes intestinal metaplasia (transformation to columnar epithelium), which predisposes the epithelium to esophageal adenocarcinoma (EAC) (1). The etiologic consensus for BE, remains a matter of debate; however, strong association with chronic gastroesophageal reflux disease (GERD) has been documented (2). An accurate representation of the prevalence for BE is still not clear, most likely due to a lack of protocol for screening (3). The alarming increase of EAC by 600% for the past 25 years suggests that BE has increased as well, as the latter represents the main risk factor for EAC (4–6). This emphasizes the importance of better understanding the causal process leading to intestinal metaplasia (BE) and suggests that a possible re-evaluation of the current protocol for the management and treatment of GERD and BE may be beneficial.

Etiologic Hypothesis: PPIs Transiently Increase Intra-Gastric pH Leading to Bile Salt Toxicity

Originally, it was believed that chronic acid reflux was responsible for BE, as most patients who develop intestinal metaplasia have GERD. However, this may not be the case, as the increased use of proton pump inhibitors (PPIs) – introduced in the late 1980s (7) – appears to be associated with the increased incidence of EAC (8, 9). For example, a recent nationwide case–control study in Denmark showed that chronic long-term use of PPIs was associated with a significant increase in the risk of developing EAC in patients with BE (10). Thus, it is possible that chronic PPI use might promote the metaplasia (BE)-dysplasia-carcinoma (EAC) sequence (8, 11); however, a mechanistic explanation of the proposed scenario is currently missing. We hypothesize that (i) a temporally sustained albeit transient increase in the gastric pH, may cause bile salts to become soluble in the proximity of the lower esophageal sphincter (LES) where they may mobilize to the esophageal tract during reflux episodes, and (ii) during a short event of failed acid suppression in the esophagus, protonated bile salts may diffuse into the epithelial cells causing the mucosal metaplasia that could lead to BE.

As someone who suffers from heartburn which ranges from a weekly to a daily basis during flare-ups, this is important information! I actually took omeprazole for about 3 weeks but it made me feel like sh!t, so I haven't taken any PPI's or H2-blockers since. Instead now I just take anti-acid(Magnesium Hydroxide) every once in a while when I have really bad heartburn.

Thoughts??

Arbogan
07-21-2015, 03:31 AM
Id not touch them unless I'd absolutely have to. I have airway reflux caused by a loose lower esophageal sphincter and a small hiatal hernia acquired during my weight lifting days. When I first trialled PPIs ( nexium and pantoprazole) they gave me disasterous side effects like intense brain-fog. Turned me from a functional individual to a demented case. I experienced some of the more debilitating side effects. While they somewhat help control reflux. Atleast in my experience the side effects outweigh any benefits. Some lifestyle changes like lowering fat intake and eating smaller meals and sleeping on the left side is all i needed to control it. Besides not entirely hindering stomach acid entirely going up the esophagus (which is what causes the metaplasia signifying barret esophagus), they also cause nutritional deficiencies over the time via malabsorption and degrade tissue in the stomuch lining.

jeanL
07-21-2015, 04:07 AM
Id not touch them unless I'd absolutely have to. I have airway reflux caused by a loose lower esophageal sphincter and a small hiatal hernia acquired during my weight lifting days. When I first trialled PPIs ( nexium and pantoprazole) they gave me disasterous side effects like intense brain-fog. Turned me from a functional individual to a demented case. I experienced some of the more debilitating side effects. While they somewhat help control reflux. Atleast in my experience the side effects outweigh any benefits.

I too have a hiatal hernia, a small one though, but my reflux did not start until after I had my gallbladder removed at age 23, I guess the liver constantly dumping bile into the intestines, or not having enough bile at once to allow the food to pass rapidly through the stomach could be the main cause. I had the same reaction with omeprazole, basically I had some anxiety issues, started taking omeprazole and 3 weeks in I felt like the life had been sucked out of me, started having panic attacks, couldn't sleep, had shortness of breath, crazy shit!

I should also mention that the study above shows that it is not the stomach acid that causes the metaplasia, but instead they are postulating that bile acids are creeping up the oesophagus due to the high stomach PH level, that is, if you had enough acid the bile couldn't make it to the oesophagus.

Gray Fox
07-21-2015, 12:56 PM
I've went two rounds with Prilosec in the past four or so years. Both associated with binge drinking in my case. Anyways, the first time out the ppi's seemed to help, but it didn't completely resolve the episode. Simply not eating excessively greasy or spicy foods helped during that bout. As well as not drinking excessively, which I don't typically do. I had family in that I hadn't seen for years, so the occasion warranted less than responsible behavior. The next time out, the prilosec didn't do diddly squat for me. So instead of using it for the full course, which I had only intended to do so sparingly anyways, I tried a more natural approach. I began taking apple cider vinegar in order to even out my pH levels and drinking a glass of water with a small amount of baking soda for the occasional flare ups. Within a week of doing so, my severe symptoms had completely resolved. I won't touch ppi's anymore. As was mentioned earlier, sleeping on ones left side is paramount to reducing reflux. I've done so for the past four or so years and my symptoms have greatly been diminished.

DMXX
10-13-2015, 06:53 PM
PPIs were assumed to be completely safe up until recently, where they're now linked to clostridium difficile infection, which is a major infectious cause of diarrhoea in hospital wards across the West.

So, it looks like overzealous PPI prescription by family physicians/GPs over the past decade or so has made a modest contribution to C. Diff infection rates.

PPIs have their place (I used them at several points), but they're clearly not the completely benign drug they were assumed to be.

rock hunter
06-06-2016, 03:32 PM
My two cents is this ,along with changing the side you sleep on as Gray Fox pointed out and thereby keeping your plumbing angled the best for keeping things down you also must avoid sugars for at least a few hours before going to sleep and if you cannot then pop a tum or two.

As far as believing the phrase "completely safe" this was also said of Smoking ,Ford Pintos and large cruise ships named after Greek deities

Many feel that if they go to a doctor and are not prescribed something , they are cheated . This is why super germs are winning and hospitals are dangerous places to stay now, a problem predicted in the1970s and mostly ignored by the medical profession.

Some Doctors today, the bad ones who should not even be in the profession also practice a form of “legally defensive medicine” which is not always in the best interest of the patient, running every test in the book needed or not but not to look for a problem but in case you (or your next of kin) try to sue them. I am going to get hate mail for this one ,,,bring it on .