Do Reflux Medications Increase Risk of Esophageal and Throat Cancer?

Image by Steven Fruitsmakk from Wikipedia

Over the last 30 years, the incidence of esophageal cancer has been steadily rising in spite of increased use of reflux medications. In fact, one can almost say that there is an inverse relationship between risk of esophageal cancer and reflux medication usage.

BUT, it is also a foregone conclusion that reflux increases the risk of esophageal and throat cancer too. So, why would there be an increased incidence of esophageal cancer when reflux is being better "controlled" now more than ever with medical acid suppression?

The answer might be bile... the substance made in the liver and secreted into the small intestine via the gallbladder. Bile is what helps the body digest dietary fat.

But when bile not uncommonly refluxes into the esophagus... bad things may happen, especially when acid production has been suppressed by reflux medications.

Disclaimer... The following is hypothetical and unproven.

Bile, if it happens to be in the esophagus or throat, is more destructive to the mucosal lining when acid is suppressed.

Bile salts/acids have fairly complicated acid-base properties, but an over-simplified explanation for the purpose of this blog is as follows.

Bile in a chemically unconjugated state has a pKa of 7. When such bile is in an acid environment (pH less than 6), it is insoluble and relatively harmless. However, when unconjugated bile enters a relatively alkaline environment (pH greater than 6), it becomes water soluble and "active" in its ability to damage mucosal linings.

As such, when acid suppression is induced by medications like zantac and prilosec, yes... the acid is suppressed but by the very fact that it raises the stomach and distal esophageal pH to a relative alkaline state, any bile that may be present now becomes activated and causes potentially just as much damage as acid.

And that's why over a prolonged period of time repeated bile exposure in a relative alkaline environment may explain why esophageal cancer incidence seems to be increasing as the use of acid reflux medications has increased.

Proof?

Regardless of the "how," does taking reflux medications actually increase risk of cancer???

In one study (2011), patients taking proton pump inhibitors were 61.3% to 81.5% more likely to develop esophageal pre-cancerous lesions or frank cancer (adenocarcinoma).

In another study published in the summer of 2013, it was found that patients with reflux were found to have a 78% increased risk of developing throat cancer. What researchers also found was that taking antacids for reflux (but NOT proton pump inhibitors or H2 blockers) seemed to protect against the development of throat cancer by 41% in patients with frequent heartburn.

To reiterate, antacids reduced risk of throat cancer... but NOT proton pump inhibitors like prilosec and H2 blockers like zantac.

Why? Because antacids work transiently to neutralize acid, but not suppress acid production whereas proton pump inhibitors and H2 blockers actually suppress acid production for a prolonged period of time.

The transient nature of acid neutralizers like TUMS allow for acid to still be produced thereby theoretically preventing bile from becoming soluble and damaging.

Prediction

So which is worse for you? Acid reflux or bile reflux? I'm not sure... but personally, I predict that once additional studies are performed that may ultimately strengthen the relationship between bile reflux and mucosal injury that may lead to cancer formation, reflux medications may go out-of-favor along with a class-action lawsuit. That's a big if... I might end up being completely wrong.

Of course, that may be the reason why drug companies specify that such reflux medications should not be used longer than 2 months and prescribing information stress "short-term" treatment rather than long-term.

More Confusion

We can also throw more mud into this messy predicament... Pepsin, which is a stomach enzyme that breaks down proteins, can also damage esophageal and laryngeal mucosa. However, it is most active in an acidic environment. Once pH levels rise above 6.5, pepsin becomes inactivated. At pH 8.0, it becomes irreversibly inactivated.

As such, acid and pepsin cause damage in an acidic environment. Taking reflux medications to eliminate the acid creates an alkaline environment.

However, an alkaline environment than activates bile which can also cause damage.

Treatment

So what to do?

Ideally, given this no-win situation, the best way to treat reflux would be to keep bile where it is supposed to be (in the small intestine) and acid/pepsin in the stomach where it is supposed to be.

As such, I suspect that even more emphasis will be placed on lifestyle/dietary changes for reflux control. Medication-wise, use of antacids and barrier-type medications like alginate will become the main way of treating reflux long-term while medications that suppress acid will be prescribed only for short-term treatment spans.

Surgical management of reflux will become much more accepted and popular for patients who suffer from bad reflux to try and restore proper anatomical compartmentalization of bile, acid, and pepsin. Surgical management will include LINX, TIF, Nissen, etc. (more info)

At the very least, certainly caution should be present when placing a patient on long-term acid suppression with medications like prilosec and zantac, especially when such medications are already known to cause a whole host of other problems including bone fractures, clostridium difficile infections,  and malabsorption of vitamins and minerals. (more info)

Special thanks to Dr. Kevin Gillian who assisted in writing this blog.


References:
Bile Acid. Wikipedia

Gastroesophageal reflux disease symptom severity, proton pump inhibitor use, and esophageal carcinogenesis. Arch Surg. 2011 Jul;146(7):851-8. doi: 10.1001/archsurg.2011.174.

Gastric Reflux Is an Independent Risk Factor for Laryngopharyngeal Carcinoma. Cancer Epidemiology Biomarkers & Prevention. Published Online First May 23, 2013; doi: 10.1158/1055-9965.EPI-13-0183

The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991 Apr;101(4 Pt 2 Suppl 53):1-78.

Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux? Gut 2001 Sep;49(3):359-63.

Acid and bile reflux in erosive reflux disease, non-erosive reflux disease and Barrett's esophagus. Hepatogastroenterology. 55 (82-83), 442-7.

The role of bile acids in the neoplastic progression of Barrett's esophagus - a short representative overview. Z Gastroenterol. 50 (9), 1028-34.

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Sinus Infection Leads to Skull Removal in Child

The UK reported a 9 years old boy who had an extremely rare sinusitis complication that ultimately resulted in the left skull being removed temporarily.

Briefly, in Feb 2013, the child developed headaches and a droopy eyelid. Surgeons ultimately had to remove his left skull due to brain swelling and concern the bone itself was infected. Over the next few months, the child had to wear a bike helmet to protect his brain which was no longer protected by his skull. A few weeks ago, he underwent another surgery to cover the hole in his left skull with a custom-shaped ceramic plate.

No mention was made in the media about which sinus cavity led to this horrible problem.

But here's a guess without benefit of more information...

Based on the skull defect shown (see pics here), it appears that the parietal and temporal skull bones were removed. There are actually no sinus cavities in these regions. As such, the only thing that makes sense to me is that the left cerebral dural sinus (large blood vessels of the brain) became clotted off and infected secondary to a sinus infection, probably the ethmoid sinus cavities located between the eyes.

The blood supply from the ethmoid sinus cavities communicates with the cavernous sinus found at the bottom of the brain. This anatomic structure is a major source of venous drainage of the brain.

If the cavernous sinus gets inflamed/infected due to a sinus infection, it could lead to multiple facial abnormalities due to injury of the numerous cranial nerves that go through it including:

• Inability to move the eyeballs (CN3, 4, 6)
• Numbness, pain of the skin over the forehead and cheeks (CNV1, V2)
• Loss of pupillary constriction (CN3)
• Visual loss/changes (CN1)

Ultimately, the cavernous sinus could also become thrombosed.

Cavernous Sinus shown by red arrow. Taken from Sonoworld.

From there, the infection can spread to the rest of the brain via the dural sinus cavities and potentially can even lead to death if not treated promptly and aggressively.

How aggressively? In this particular case, the child had half his skull removed!

Thankfully, the vast, vast, vast majority of sinus infections do not lead anywhere close to this type of complication.

Source:

Boy, 9, has half his skull removed after sinus infection spreads to his brain - but he still manages to attend school thanks to a BICYCLE HELMET. MailOnline 8/26/13

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Local Anesthetic Allergy

Rarely, a patient presents with a history of being allergic to lidocaine or another kind of local anesthetic. Often, the "allergic" reaction described (racing heart, light-headed, dizziness, etc) is more attributable to the epinephrine which is often used in conjunction with the anesthetic; therefore not a true allergy, but a not unexpected possible side effect.

Also, if a true allergy is present, it may not be to the anesthetic itself, but the preservative contained within, typically metabisulfite and/or methylparaben. The exception are single-dose vials which are preservative-free, unless they contain epinephrine. Any local anesthetic containing epinephrine, whether a single-dose or multi-dose vial, has metabisulfite in it. The preservative in the multi-dose vial of lidocaine and other anesthetics typically contain methylparaben. As such, the muti-dose vial of lidocaine with epinephrine would contain both metabisulfite and methylparaben.

In any case, if a true allergy to the anesthetic itself is present, there is the possibility that another type of anesthetic can be used. Why?

There are two different classes of local anesthetics divided into amino esters and amino amides. Chemically, amino amides have an amide link between the intermediate chain and the aromatic end, whereas amino esters have an ester link between the intermediate chain and the aromatic end.

Amino Ester

Amino Amide

There are other differences. Pharmacologically, amino esters are metabolized in the plasma whereas amino amides are metabolized in the liver. Amino esters are unstable in solution, but amino amides are very stable in solution.

Amino esters are also much more likely than amino amides to cause allergic hypersensitivity reactions.

Amino Esters (only one "i" in the spelling of the name):

• Cocaine
• Procaine
• Tetracaine (in the form of cetacaine)*
• Chloroprocaine*
• Benzocaine (in the form of cetacaine)*
• Cetacaine (benzocaine and tetracaine)*
• Propoxycaine

Amino Amides (two "i"'s in the spelling of the name):

• Lidocaine*
• Mepivacaine*
• Prilocaine
• Bupivacaine*
• Ropivacaine*
• Levobupivacaine
• Articaine
• Etidocaine
• Trimecaine
• EMLA (lidocaine/prilocaine)

* is next to those commonly carried in hospitals.

Much appreciate the assistance of Margaret Rowe, PharmD who helped write this blog article.

Source:
Local Anesthetics. Emedicine 4/19/13

Local Anesthetic. Wikipedia

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Unhappy with Your Appointment Day/Time with your Doctor?

A common complaint for patients is how long it may take to get in to see a medical specialist. A new patient appointment may be 1-2 weeks away when an earlier appointment may be desired.

What to do?

Of course, one can call around to every single specialist office in the region to see who has the next earliest appointment.

Other options which may work just as well include the following:

• Do NOT limit yourself to a specific day of the week and time. Always use the phrase "the very next available appointment whenever that may be."

• Ask your regular doctor to call and make an appointment for you. Be aware that if you resort to this option, you will have to accept whatever day/time you are given. Do not use this option if you will most likely end up changing the appointment to suit your schedule, otherwise risk being given an appointment far into the future.

• Although in theory, there are appointment wait lists you can put yourself into, it only works if the medical office checks it regularly... which typically does not happen. What works better is to call everyday! On a daily basis, there are ALWAYS cancellations that occur. In my office daily, there are usually 1-2 new patient appointment cancellations and double that in established patient appointment cancellations. Such cancellations usually are called in by 10AM for that afternoon or 4PM for next day cancellations. So call around that time to see if any appointment slots have opened up that you can slip into. This is why medical offices beg patients to always call if you are not going to show up and even charge a fee if you fail to inform in advance. It is to help other patients who desperately want to be seen and who could have been scheduled into your appointment slot that ended up being wasted.

Based on a study by ZocDoc, here are other appointment related trivia:

• Tuesday is the most popular day for doctor appointments; it's also the day with the most last-minute openings.
• For pediatricians, the most popular day for doctor appointments is Monday
• The most popular appointment of the week is Friday at 10AM, followed closely by Friday at 2PM.
• Thursday has the longest wait time.

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What are the Risks for Throat Cancer? (Humor)

Check out this info-advertisement photographed by Twitter user @durf showing the risks of throat cancer.

I truly think the American public is a bit smarter than this... though not perhaps in Ann Arbor, MI where this ad most likely got published (I suspect AATA is the Ann Arbor Transportation Authority). jk...

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Facial Plastic Surgery Leading to Clones? Scandal? Divorce? Lawsuits?

Earlier this year, pictures of the 20 finalists for Miss Korea 2013 went viral due to the clone-like appearance of the women. Such clone-like appearance is due to suspected plastic surgery undergone by many if not all of the contestants towards the idealized "Korean plastic face look." Fueling plastic surgery in Korea is the acceptance and popularization of plastic surgery encouraged by celebrity worship culture. Check it out:

Image Taken from MailOnline

Of course, it could be all the makeup and photoshopping that made these contestants all look alike. The reality is a bit more disappointing as shown in pre-makeup pictures published in KoreaBang.

In any case, a scandal of sorts occurred when before and after pictures of Miss Korea 2012 Kim Yu-Mi  surfaced. Note the complete lack of resemblance between her natural looks and her winning appearance (see pics below):

Image Taken From KoreAm

It is perhaps little wonder that with such high prevalence of plastic surgery, that it was only a matter of time before marital strife and even divorce would occur by men who have been "deceived" by a woman's "natural" beauty which was anything but.

Indeed, a Chinese man divorced and sued his wife in 2012 for being ugly... and won [link]. Apparently his wife's appearance became an issue when his daughter was born and resembled nothing like either parent (and allegedly was "incredibly ugly" to boot). After initially thinking his wife cheated on him, the wife admitted spending $100,000 on plastic surgery to become beautiful, and never disclosed this information before marrying him. The lawsuit was based on his belief that he married her under false pretenses of her being beautiful. See pics below.

Image taken from KDVR

I wonder if potential marriages in Asia are now preceded by full disclosure of any plastic surgery done along with the more usual disclosures of educational, family, and financial background.

Sources:

Chinese man sues wife for being ugly, wins $120,000. KDVR 10/26/12

Has plastic surgery made these beauty queens all look the same? Koreans complain about pageant 'clones'.  MailOnline 4/25/13

Miss Korea’s Plastic Surgery Scandal After Photos Surface. KoreAm 7/20/12

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Does Stridor HAVE to be Present for Diagnosis of Vocal Cord Dysfunction?

Laryngospasm, the most severe form of vocal cord dysfunction, does include stridor as a symptom. However, a patient can still suffer from vocal cord dysfunction and even laryngospasm without an obvious stridor present.

In order to understand stridor's relationship to vocal cord dysfunction (VCD), one must first understand what exactly is happening anatomically... or skip to the bottom of the article if you already understand the basics.

When a person breathes, the vocal cords move apart allowing air to pass easily through and into the windpipe. When a person talks, the vocal cords come together and vibrate allowing for voice production. [watch video]

Vocal cord dysfunction is when the vocal cords come together (instead of apart) when a person is trying to inhale air. Given the physically smaller airway created by the approximated vocal cords, the patient would typically experience shortness of breath and some wheezing.

Laryngospasm is when the vocal cords come completely together when a patient is trying to breath and stridor is typically produced with attempted strong inhalation against closed vocal cords.

Watch a video showing both types here.

As such, in order for stridor to be produced, TWO things must be present:

1) The vocal cords need to be nearly or completely closed together.
2) There must be strong breathing attempts

If any two elements are absent, stridor will not occur.

For example, if a patient is in a full-fledged laryngospasm attack, but is either breath-holding or making weak attempts at breathing, no stridor will occur.

Conversely, if a patient is suffering from a severe case of vocal cord dysfunction and is breathing hard enough, due to venturi effect against vocal cords that are almost closed (but still open), stridor like sounds may occur.

Venturi effect???

What's that?

In essence, it is a physics concept whereby there is a reduction in pressure when a fluid (or air) flows through a constricted section of a pipe (or airway) in this case.

In essence, the venturi effect as it applies to the voicebox, is a highly localized area of negative pressure created between the vocal cords when a person is breathing fast causing the vocal cords to come together even more... leading to more "sound" with breathing even if the vocal cords are not completely together.

It is perhaps one reason why athletes who suffer from vocal cord dysfunction may sound like they are suffering from laryngospasm during a VCD attack while exercising. Technically, it may not be laryngospasm because the vocal cords are still apart, but due to the venturi effect, causes a functional vocal cord closure leading to aggressive vocal cord vibration and a stridor-like sound production.

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