G-POEM: non-invasive pyloroplasty

by Jim Sliney Jr

For patients whose primary symptoms of gastroparesis are nausea and vomiting, and in whom other gastric procedures have failed, there is a hopeful procedure and a related study going on.

G-POEM stands for Gastric per-oral Endoscopic Myotomy, which is a procedure using endoscopy (a camera attached to a tube that, in this case, goes down your throat and into your stomach) to perform myotomy, which is the cutting of muscle tissue. In this procedure the pyloric sphincter, which is the muscle between the stomach and the small intestine which is meant to open and close to let food out or keep it in as needed, is cut allowing a wider vent for food to leave the stomach. The desired result of a G-POEM procedure is to improve the gastric emptying rate which in turn should reduce the nausea and vomiting which are associated with slow gastric emptying.

I spoke with Dr. Mouen Khashab, the Director of Therapeutic Endoscopy at Johns Hopkins Medical Center, and the principal investigator of a study that looks at the safety of the G-POEM procedure and its effectiveness over the course of two-years. Dr. Khashab explained that not everyone is a good candidate for G-POEM, noting that only those who present with nausea and vomiting as their primary symptoms would be right for his study. However, the procedure is showing itself to be effective to relieve nausea, vomiting, and to a lesser degree, abdominal pain, while improving the rate of gastric emptying.

Pyloroplasty is a similar procedure, the goal of which is also to cut the pyloric sphincter allowing for food to leave the stomach faster. There are also stent placing procedures designed to do this. The primary difference between pyloroplasty, stent placement and G-POEM is that pyloroplasty is performed laparoscopically (a small incision is made in the wall of the abdomen and an instrument is inserted through it) while G-POEM is non-invasive. Also, stents run a risk of moving over time, losing their effectiveness and requiring follow up procedures.

diagram_showing_the_parts_of_the_stomach_cruk_336-svg

Dr. Kenneth Koch, Director of the Digestive Health Center of Wake Forest School of Medicine (and member of the medical advisory board of G-PACT) added that patients with pyloric dysfunction, a subgroup of GP patients, might benefit from procedures like G-POEM and pyloroplasty since pyloric dysfunction is associated with delayed gastric emptying, which in turn is associated with nausea and vomiting.

Dr. Khashab recently presented the results of his study at an international meeting of gastroenterologists and has an article in the Gastrointestinal Endoscopy journal. His findings include the following:

During the first six months of observation after the G-POEM procedure,

  • 47% of the patients reported that their nausea was completely resolved and 50% reported that it was improved, while one patient reported that nausea was worsened.
  • 57% of patients reported their vomiting was resolved, while 10% reported improvement. 33% reported no change to vomiting while 1 patient reported worsening of vomiting symptom.
  • 53% of patients reported that abdominal pain was resolved, 20% said it improved, 23% reported no change, and 1 patient reported worsening of abdominal pain.

Of note, the patients in this study had gastroparesis either from diabetes, post-surgery, or of unknown origin. The 1 patient who reported worsening of nausea, vomiting and abdominal pain had diabetic gastroparesis.

Studies investigating the safety and effectiveness of G-POEM as a treatment for GP related nausea and vomiting are ongoing, including Dr. Khashab’s study.

If your primary GP symptoms are nausea and vomiting and you have tried different therapies and they have not worked, and you wish to consider Dr. Khashab’s study. You can learn more about it and how to contact Dr. Khashab by following this link .

 

Jim Sliney Jr is the Editor for ThePactBlog, G-PACT’s newsletter. He is a part time student at Columbia University and a freelance writer, working in both fiction and medical writing. He lives in New York City with his wife, an ophthalmic researcher.

*graphics from creative commons

FDA Meeting on Compounding Domperidone

On October 28, 2015 there was an FDA meeting to discuss the request from the Pharmacy Compounding Advisory Committee (PCAC) to allow compounding pharmacies in the United States to compound domperidone.    Below are notes from that meeting.

The FDA presented information that, in the past 6 years in the United States, 7500-11600 prescriptions were written for domperidone annually.  77% of the prescriptions were written for women and most commonly for gastroparesis.

There have been three trials that proved the efficacy of domperidone for gastroparesis and nausea and vomiting trial showed clinical relevance for improvement of nausea and vomiting.

The FDA brought up the following safety concerns:

  1. QT Prolongation
  2. Proarrythmia Risk

If there is a heart event, it usually happens in the first week.  It most commonly happens in doses greater than 30 mg a day for individuals over age 65, or those taking other drugs that can cause OT prolongation.

From prior studies, it shows a 1.5 to 2.0 fold risk of sudden cardiac death.  And they indicated that there may be an under-reporting of adverse events because it is not an approved drug.

The final recommendation was that there are enough safety concerns to say that there could be significant harms to the public if domperidone is used without important safeguards.  It was NOT recommended to be added.

They did explain that domperidone is available through the IND program, but there was considerable discussion about the difficulty involved in this process and problems that physicians in individual practices might have in completing the requirements of the process.

A presenter for the other side of the argument dug deeper into the statistical studies to show that most studies were not statistically significant and that the mean age of 72.5 years shows that they started with a population that was historically a higher risk group.   In addition, not all the studies showed doses so you cannot make a determination based on the results of that study.

In addition, there are many approved drugs that increase the long QT interval.  Also, the countries that have increased restrictions for domperidone have also restricted reglan even more due to safety concerns.   He showed information that indicated that there were more adverse events with reglan that were life-threatening than there were with domperidone.  He admits that there is a risk but says that we need to evaluate better the scope of the risk.

He also brought up the May FDA meeting and the number of patients who expressed the amount of relief they get from domperidone and how difficult it is to obtain.   He also said that many doctors are not willing to deal with the IND process.

Dr. Moon said that prescribers and patients approach compounding pharmacists many times monthly asking for domperidone to be dispensed.  He said that there are plenty of nausea and vomiting drugs but they do not have the prokinetic effects.   He said that patients should not have to go outside of the country to get their medications.   He said that if a patient and physician choose an option that is available worldwide, then they should be able to obtain it.

In the public comments, Dr. Mark Burns (gastroenterologist) said that domperidone serves a vital need for those with gastroparesis.  He currently has 46 patients, ages 17 to 89, who are getting regular prescriptions for domperidone.  He appealed to the FDA to allow this drug to be compounded because of its efficacy for numerous gastrointestinal diseases.   For side effects, he saw higher prolactin in 3 and some cases of lactation. Even his older population shows no change in their regular EKG’s.  He said it is ideal for long-term use for upper and lower gastrointestinal diseases.

Baxter Phillips, from Neurogastrics, spoke of his company’s support of the FDA’s denial of the addition of domperidone.  His company is currently developing a new formulation that will work for gastroparesis.

The final speaker, Dr. Alan Diamond (gastroenterologist), spoke of the difficulty of prescribing reglan since he considers it to be a dangerous drug.  Many of his patients will refuse reglan when he explains the side effects.  People are also frightened by the lack of FDA approval for domperidone, so they take nothing.    The IND Process is cumbersome and time consuming and no one is willing to do it.

After considerable discussion by the committee, both pro and con, the committee voted 8-3 NOT to approve domperidone to be added to the bulk compounding list.  The majority seem to think that the IND process should be sufficient but that it might need to be streamlined so that more doctors are able to use that process to prescribe for their patients.

Communicating with your Doctor

A beginner’s guide to understanding medical terminology, Jim Sliney Jr, November 2015

I have spent almost 25 years working in medicine as a Medical Assistant. I’ve worked in several different departments, doing both clinical and research work. Thousands of patients and hundreds of healthcare workers later, I have learned some important lessons. Take those lessons and add what I’ve learned as a patient and I come away with what I hope is a bit of wisdom.

The most important element of healthcare is COMMUNICATION.

STEVE: “Doctor Jones I have pain in my stomach, help me”.

DR BOB: “Where is it precisely?”

STEVE: “It’s kind of just below my belly button, but in the back, like over here <waive your hand over your back>”

DR BOB: “What kind of pain is it?”

STEVE: “uh…I don’t know…it hurts!”

DR BOB: “Hurts like what?”

STEVE: “uh…I don’t know…kind of like a bruise. And I have high blood pressure and I think when my pressure is really high its worse”.

DR BOB: “And how long has it been going on?”

STEVE: “Well it first started when I was twelve but by the time I was thirty five it was gone and then when I was thirty eight it came back and now that I’m fifty seven it’s really bad”.

DR BOB: “So, this isn’t a new problem?”

STEVE: “No, it is, because I have blood in my pee now and the way it feels now is worse than….”

DR BOB: “LET’S just get you on the table.”

This is inefficient communication to say the least. Let’s break this down and see what could have been done better.

ONE: Why are you going to the doctor? The CHIEF COMPLAINT

When you go to the doctor the doctor is expecting you to PRESENT with a CHIEF COMPLAINT. You can have ten complaints but your doctor is always going to focus on your chief one.

Some Chief Complaints:

  • I think I have a fever
  • I have a nail stick in my head and it hurts
  • I am nearly out of my prescription, I need a refill please
  • I haven’t been sleeping well

What do these have in common? They are medical problems that require solutions. But problems aren’t always easily understood, so, kind of like a medical detective a doctor must INVESTIGATE the nature of the problem. Dr. Bob asks Steve some questions to try to get more information but Steve’s answers aren’t very precise.

TWO: What do you have to say about your Chief Complaint?

Doctors need specifics. A pain on the right side of your abdomen that is sharp points at a whole different problem than a pain on your left side that is dull.

When asked where it was, Steve could have:

  • Put his hand where the pain was concentrated
  • Used terms of orientation
TERMS OF ORIENTATION (see neighboring graphic)

Article graphic

 

Term Definition
Distal situated farthest from the body part
Lateral towards the sides, away from the middle (or midline)
Medial towards the middle (or midline)
proximal situated nearest to the body part
Anterior the front
posterior the back
superior above a thing
Inferior below a thing
Prone face down on a horizontal plane
Supine face up on a horizontal plane
Deep away from the exterior surface, further into the body
superficial on the surface, or shallow
Vertical up and down
horizontal like the horizon, side to side

So it seemed like when Steve said “in my stomach” and “just below my belly button, but in the back” was confusing things. If he said, “In the posterior hypogastric region and deep” and not make reference to his “stomach” which isn’t where Steve’s pain is.

Article 2

When Dr. Bob asked about Steve’s pain, Steve could have chosen from some better terms:

Aching Heaviness Piercing Sore Throbbing
Burning Icy coldness Pounding Stabbing Tightness
Crawling Intermittent Pressure Tearing Tingling
Crushing Numbing Sharp Tenderness

An intermittent aching in the posterior hypogastric region. We’ve got some good information there. With it Dr. Bob can rule out all kinds of issues and narrow down the source of the problem significantly.

THREE: Duration – “how long has this been going on?”

It has either been

  • CHRONIC – persisting for a long time
  • ACUTE – having severe symptoms and a short course, or
  • INTERMITTENT – marked by alternating periods of activity and inactivity

Steve could say “this is a chronic pain, I’ve had it intermittently since I was twelve years old, but now the pain is acutely different than it has been in the past”. This tells Dr. Bob a lot. It’s not new, it’s been around, but it has changed.

This could be a very good time to share other characteristics like

  • It only bothers me when laying down or
  • It’s worse after dinner or
  • It wakes me up in the middle of the night

Those are also important clues for your detective-doctor!

If you can communicate with your doctor in the language he/she has been trained to think in, you may have more successful communication. Successful communication can save time, frustration, money, and misery. It may require some preparation on your part, but it pays off.  Good luck and be well. – Jim

I intend to write further installments of “Communicating with your doctor” so if you have specific terms you would like to have explained please feel free to email me at slineyj@g-pact.org

References:

Definitions were pulled from the following sources:

https://www.nlm.nih.gov/medlineplus/mplusdictionary.html (uses http://www.merriam-webster.com/)

http://medical-dictionary.thefreedictionary.com/ (make sure you are on the Medical Dictionary tab)

http://apma.gostart.com.au/descriptors

Fecal Transplants

Writer: Sam Hyde, M.S. PhD, MPH

One of our members recently saw a TV show PBS series called ‘Second Opinion’ where fecal transplants were discussed as having a 91% success rate for curing C-Diff. Since people with digestive tract issues many times have problems with C-Diff, we asked our Science Advisor, Dr. Sam Hyde, to research this procedure. Below are her findings:

Fecal Transplantation Therapy

Clostridium difficile (C. difficile) is a bacterium related to those that cause tetanus and botulism. It causes gastrointestinal infections that can be potentially life-threatening. Patients most at risk for C. difficile infections include those who have recently been on antibiotics, those who have been treated in an inpatient hospital setting, and those with feeding tubes1. C. difficile is therefore of particular interest to patients with gastroparesis and other chronic digestive disorders. Traditional antibiotic therapies are often ineffective in curing C. difficile infections; thus, new techniques are being developed to treat patients suffering from this disease. One such therapy is known as fecal transplantation, and has been used with considerable success in a number of cases1-3.

Nearly 90% of C. difficile infections are caught in a hospital setting1. Patients who have been on antibiotics are at a particularly high risk for infection, as antibiotics kill the “good” bacteria that normally lives in the gut, leaving the intestine vulnerable to disease-causing bacteria like C. difficile1. These disease-causing bacteria are resistant to antibiotics, and so can quickly spread throughout the intestines. In the case of C. difficile, this results in severe diarrhea, and can cause dehydration.

Because C. difficile infections often occur when the good bacteria in the gut have been killed, one approach to fighting C. difficile is to put new good bacteria in the gut. This, essentially, is the goal of fecal transplantation. Feces (poop) contain a very high level of bacteria that come from the gut, so feces from healthy people contain a lot of good bacteria. The approach is thus simple, if a little “aesthetically unpleasing.” Feces from a healthy patient are introduced into the gut of someone with a C. difficile infection. The bacteria from the feces can then grow and get rid of the C. difficile. In non-scientific terms: poop from a healthy person is put into a sick person to restore the good bacteria that have been killed.

Fecal transplantation can be remarkably effective, with over 80% of patients showing immediate improvement1, 2. However, barriers exist to such treatments. For one thing, the FDA has had trouble deciding how to regulate the procedure4; fecal transplantation is currently considered an experimental procedure5. Also, physicians may be unaware or uncomfortable with performing fecal transplantation, and there is always the “ick factor” to consider. Finally, diseases can be transferred with the fecal transplant if the feces are not screened for diseases. Still, when considering the dangers of C. difficile infections and the high success rate of fecal transplantations in treating such infections, it is likely that fecal transplantation will play an increasingly important role in clinical practice.

Sam Hyde, M.S. PhD, MPH


Useful Websites:

  1. http://www.mayoclinic.org/medical-professionals/clinical-updates/digestive-diseases/quick-inexpensive-90-percent-cure-rate
  2.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365524/
  3. http://www.foxnews.com/health/2014/06/27/fda-grapples-with-oversight-fecal-transplants/

Sources:

  1. Iv EC, Iii EC, Johnson DA. Clinical update for the diagnosis and treatment of Clostridium difficile infection. World J Gastrointest Pharmacol Ther 2014;5(1):1-26. 
  2.  Petrof EO, Gloor GB, Vanner SJ, et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome 2013;1(1):3. 
  3.  Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S. Bacteriotherapy using fecal flora: toying with human motions. J Clin Gastroenterol 2004;38(6):475-83. 
  4.  PERRONE M. FDA GRAPPLES WITH OVERSIGHT OF FECAL TRANSPLANTS. In: Associated Press. http://hosted.ap.org/dynamic/stories/U/US_FECAL_TRANSPLANTS_FDA?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT&CTIME=2014-06-26-12-06-42; 2014. 
  5. FDA. Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies. In: Services USDoHaH, Administration FaD, Research CfBEa, eds. Biologics Guidances; 2013.