NYSGE 2017 Finishes With A Bang!

The December, 2017 NYSGE Annual Course had the most registrants ever, totaling 735!!

In fact, registration was 60 people more than last year!! We also had over 200 Workshop and Symposia registrants, at last count. This remains the largest regional GI meeting in the USA each year, and trails behind only DDW and the ACG meeting in terms of attendance.

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There were about 87 faculty, 41 presentations in the main session, 24 presentations in the Nurses and Associates program, and countless others in the satellite seminars.

Additionally, there were 5 separate satellite and hands-on sessions during the Course, and several other special Programs. These sessions are each unique, innovative and in a word, outstanding.

We had attendees from all over the US and around the world, a testimony to the far reaching word of mouth “buzz” there is about this Course each year.

On top of all that, there were five innovative lunchtime symposia, and 11 special lectures, including the Florence Lefcourt Lecture given by Dr. Larry Brandt, the David Falkenstein Lecture, given by Dr. David Carr-Locke, the Ed Bini Lecture, given by Dr. Jon Cohen, the ASGE President’s Lecture by Karen Woods, the NYSGE President’s Address by Dr. Chris DiMaio, the Richard Mc Cray Lecture, given by Dr. Sid Winawer, and the Peter Steven’s lecture, given by Dr. Phil Katz. We also were pleased to welcome the current ACG President, Dr. Irving Pike, to our Faculty.

We had an incredible scientific poster session, again led by Drs. Satish Nagula and Susana Gonzalez. This year we had over 80 different authors who submitted nearly 50 posters, with several entries from outside the NYC area!!  The poster session review was done along with a cocktail reception on Thursday evening. The room was packed; this is indeed a popular event!  The always popular Peter Steven’s Video Forum, led by Drs. Anthony Starpoli, Tamas Ganda and Nikhil Kumta, again was a huge success, with 4 outstanding videos.  The Fellow’s Forum on Thursday evening was superb, coordinated by Drs. Michelle Kim and Brian Bosworth; the feedback was all good.

The Doris C. Barnie Nurses and Associates Program, skillfully arranged as always by Barbara Zuccala and Nancy Schlossberg, again was a huge success, with outstanding lectures and interactive sessions. The Nurses and Associates program this year attracted well over 200 participants, all of whom were raving about the quality of the program. A huge thank you to Barbara and Nancy; we appreciate their efforts immensely.

The Live from New York Course was packed with a range of incredible cases again this year…our most sincere gratitude to Dr. Gregory Haber for the unbelievable amount of energy and effort he puts into directing this truly outstanding piece of the Course each and every year.  Big time thanks to Dr. Frank Gress as well for his co-leadership again this year.   The NYU-Langone location was excellent.  The quality of the HD transmission is spectacular; even more impressive is the quality of the material being presented and the quality of the Faculty doing the procedures and commenting on the care…fascinating procedures at the cutting edge of gastroenterology explained by masters in their field!!

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Thanks to our out of town guests at NYU, Drs. Juergen Hochberger, Laurent Palazzo, Chris Thompson and Shyam Varadarajulu, who were simply amazing, as well as to our NYC Faculty, who were equally awesome!

Thanks as well to all the panelists at the Marriott, who really were very lively and provocative this year, many of whom spent parts of both days with us…the panel discussions really brought out critical decision making points in each case…many thanks!! Special thanks on the panels to Drs. Doug Howell and Mouen Khashab, and Nancy Schlossberg, who traveled from far away to join our educational panels.  We had special “Mentored by the Masters” programs, enhancing Fellows’ education during the live cases on Thursday afternoon and Friday morning; many thanks to the ten Faculty members who led the way there.

Also, we can’t thank Dr. David Robbins enough.  David is now the master of the hugely important role of being behind the scenes at the live course…really making it all happen, but rarely seen!!  We couldn’t have done it without him!!

Phil Joseph and his team at Advance Concepts get big time kudos as well.  Their audiovisual and technical expertise is beyond amazing and we appreciate their help greatly!!

Also thanks to the NYU staff (there are many, many people involved there)!!

The Satellite Courses, both hand-on and didactic, continue to be a huge draw. Small groups, great teaching…what more could you ask for??  Nearly every session was filled to capacity, a fairly amazing thing when you consider all that is going on and the proximity of the meeting to the Holidays.  A huge thank you to Drs. Brian Bosworth and Jon Cohen, who really innovated years ago to get these Programs going and who continue to help them thrive.  The directors of each satellite session are truly responsible for the success of each individual program, and so we want to thank those individuals specifically:  Drs. Felice Schnoll-Sussman, Reem Sharaiha, Ira Jacobson, Frank Kasmin and David Hass; all did an amazing job!!

The Hands-on and Demonstration areas, a unique and very popular feature of the Course, again conceived years ago and designed expertly by Dr. Jon Cohen, was superb once more, and seems to always be popular. Many thanks to Brian Bosworth, who continued this year to greatly help with the organization of this piece of the course. Thanks once again to Dr. Kai Matthes and his “team”, who are invaluable in getting this together and who provide many of the ex-vivo models and tissue specimens that we use. Finally, many thanks to the many faculty who helped out in the hands-on areas.

A special huge thank you to Karen Cervenka, the Society’s Managing Director, for being who she is.  Karen works seemingly endlessly to put every aspect of this very complicated Course together, and she once again, incredibly, did a simply phenomenal job.  Her enthusiasm, energy and dedication are very much appreciated!!!!  Many others at Digestive Health Works also worked very hard on our behalf…thanks to Bina Mesheimer, Robin Weidy, Barbara Connell and everyone else who contributed behind the scenes.

Thanks also to Montefiore CME, and in particular Nada Piacentino, Marilyn Sasso and Vic Hatcher for their help.

We still miss Florence Lefcourt, the “heart and the soul of the Society”, but she “continues to be there” as well. Regular tributes to her remind us all of the wonderful woman who led us for so many years!!

The NYSGE Council helped whip the Program into shape many months ago, and we appreciate their efforts as well.  Today’s version of the Course is really built on the Courses of 20, 30 and now over 40 years ago…we thank the many NYSGE council members over all the years, as well as the original founders of the Society, and appreciate all they did to shape the Society and to shape this Course. Also, congratulations to the Society’s current President, Dr. Chris DiMaio, who has had a most successful year as President!!

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Most of all, we want to thank you, the Faculty of this year’s Course. You took time away from your busy schedules to join us, traveling from far and wide (France, Germany and every corner of the US), worked really hard on syllabus contributions and high quality presentations packed with videos, photos and cutting edge information.  We know how difficult that can be, and just want to express our sincere gratitude for all that each of you did. The spirit of collegiality is so readily apparent; we all work together really well, and that is terrific.  One more truly important thing…we all seemed to have loads of fun, and that’s maybe the best marker that things continue to go so well!!

Yes, the 41st Annual NYSGE Course was indeed a special one, and so thanks one more time for being part of it.   Best wishes for a Happy and Healthy New Year from all of the course directors and organizers to the faculty and attendees!!

David A. Greenwald, MD
Director of Clinical Gastroenterology and Endoscopy
Mount Sinai Hospital

RECURRENT ACUTE PANCREATITIS

 

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Acute pancreatitis (AP) and chronic pancreatitis (CP) were originally described as two well defined entities on the opposite end of a disease spectrum. We now think that recurrent acute pancreatitis (RAP) is a transition stage between acute and chronic pancreatitis.

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Acute pancreatitis is defined as an acute inflammatory condition characterized by epigastric pain, elevated amylase and lipase and imaging consistent with pancreatitis. There is currently no consensus definition of chronic pancreatitis. One consistent requirement is that there is documentation of irreversible changes either histologically (i.e., fibrosis, atrophy) or morphologically (i.e., calcifications, ductal abnormalities with or without other accompanying features (e.g., pain, AP, or RAP), organ dysfunction (diabetes, exocrine deficiency), and impaired quality of life.  

Recurrent acute pancreatitis is defined as two or more distinct episodes of acute pancreatitis with near complete resolution of symptoms between episodes with no evidence of chronic pancreatitis. The difference between RAP and CP is based on morphology and histology of the pancreas. The difference is based on whether or not there are definitive changes of CP in cross sectional studies, like a CT scan or a MRI.  

In the United States, acute pancreatitis is one of the most common gastrointestinal causes of hospitalization. Although most cases of acute pancreatitis are self-limited, studies have shown that up to one quarter of patients can have a reoccurrence of acute pancreatitis and up to ten percent of patients go on to develop chronic pancreatitis.

Recurrent acute pancreatitis by definition occurs when a patient has two or more episodes of acute pancreatitis. A challenge in the diagnosis acute recurrent pancreatitis is that there is often symptom overlap with chronic pancreatitis. Patients may present with an acute attack, a recurrence or may have an acute on chronic flare with minimal imaging findings consistent with chronic pancreatitis. In addition, sometimes determining the etiology of RAP remains challenging. Alcohol and gallstones are by far the most common causes of RAP and together they account for 70% of the cases. Other common etiologies include toxins, metabolic, idiopathic, genetic, autoimmune and obstructive causes. Patients with RAP also are younger with a higher incidence in patients (<40 years old).  

The risk of developing acute recurrent pancreatitis can be reduced by encouraging alcohol abstinence and by performing a cholecystectomy after the first episode of acute pancreatitis in patients diagnosed with biliary disease. It is also important to note that because up to thirty percent of patients have no defined etiology of recurrent acute pancreatitis on routine lab work and imaging treatment options are limited. Etiologies such as pancreas divisum, occult stone disease and sphincter of Oddi dysfunction and genetic causes are overrepresented in idiopathic RAP patients.

A patient’s history and standard tests such as blood chemistry, trans-abdominal ultrasound, MRCP, and CT scan generally detect the causes of recurrent episodes in about 70% of cases. When no cause is found at the initial diagnostic work-up, these patients should have a more advanced diagnostic work-up, that includes specific pancreatic tests, genetic testing, MRCP with secretin stimulation, sphincter of Oddi motility evaluation, EUS, and in selected cases ERCP. Genetic and autoimmune pancreatitis can be diagnosed by testing respectively for CFTR or SPINK1/PRSS1 gene mutations and IgG 4.

In patients with idiopathic RAP, endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy with or without pancreatic duct stent placement have been suggested to offer some benefit however the long term benefit and outcomes have not been adequately defined in the literature.  Laparoscopic cholecystectomy is curative when gallbladder stones or sludge are detected; however, the clinical benefit for sludge is less evident. In documented SOD endoscopic sphincterotomy is currently the standard therapy.
Amit H. Sachdev

Clinical Instructor of Medicine, Interventional Gastroenterology, Columbia University College of Physicians and Surgeons

John M. Poneros M.D.

Associate Professor of Medicine, Associate Director of Endoscopy, Columbia University College of Physicians and Surgeons

 

REFERENCES:

Amann, S.T., Yadav, D., Barmada, M.M., O’Connell, M., Kennard, E.D., Anderson, M., Baillie, J., Sherman, S., Romagnuolo, J., Hawes, R.H., et al. (2013). Physical and mental quality of life in chronic pancreatitis: a case-control study from the North American Pancreatitis Study 2 cohort. Pancreas 42, 293–300.

Attwell, A., Borak, G., Hawes, R., Cotton, P., and Romagnuolo, J. (2006). Endoscopic pancreatic sphincterotomy for pancreas divisum by using a needle-knife or standard pull-type technique: safety and reintervention rates. Gastrointest. Endosc. 64, 705–711.

Bertin, C., Pelletier, A.-L., Vullierme, M.P., Bienvenu, T., Rebours, V., Hentic, O., Maire, F., Hammel, P., Vilgrain, V., Ruszniewski, P., et al. (2012). Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations. Am. J. Gastroenterol. 107, 311–317.

Chacko, L.N., Chen, Y.K., and Shah, R.J. (2008). Clinical outcomes and nonendoscopic interventions after minor papilla endotherapy in patients with symptomatic pancreas divisum. Gastrointest. Endosc. 68, 667–673.

Das, R., Clarke, B., Tang, G., Papachristou, G.I., Whitcomb, D.C., Slivka, A., and Yadav, D. (2016). Endoscopic sphincterotomy (ES) may not alter the natural history of idiopathic recurrent acute pancreatitis (IRAP). Pancreatol. Off. J. Int. Assoc. Pancreatol. IAP Al 16, 770–777.

Etemad, B., and Whitcomb, D.C. (2001). Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology 120, 682–707.

Gardner, T.B., Kennedy, A.T., Gelrud, A., Banks, P.A., Vege, S.S., Gordon, S.R., and Lacy, B.E. (2010). Chronic pancreatitis and its effect on employment and health care experience: results of a prospective American multicenter study. Pancreas 39, 498–501.

Garg, P.K., Tandon, R.K., and Madan, K. (2007). Is Biliary Microlithiasis a Significant Cause of Idiopathic Recurrent Acute Pancreatitis? A Long-term Follow-up Study. Clin. Gastroenterol. Hepatol. 5, 75–79.

van Geenen, E.J.M., van der Peet, D.L., Mulder, C.J.J., Cuesta, M.A., and Bruno, M.J. (2009). Recurrent acute biliary pancreatitis: the protective role of cholecystectomy and endoscopic sphincterotomy. Surg. Endosc. 23, 950–956.

Hall, T.C., Dennison, A.R., and Garcea, G. (2012). The diagnosis and management of Sphincter of Oddi dysfunction: a systematic review. Langenbecks Arch. Surg. 397, 889–898.

Heetun, Z.S., Zeb, F., Cullen, G., Courtney, G., and Aftab, A.R. (2011). Biliary sphincter of Oddi dysfunction: response rates after ERCP and sphincterotomy in a 5-year ERCP series and proposal for new practical guidelines. Eur. J. Gastroenterol. Hepatol. 23, 327–333.

Jacob, L., Geenen, J.E., Catalano, M.F., and Geenen, D.J. (2001). Prevention of pancreatitis in patients with idiopathic recurrent pancreatitis: a prospective nonblinded randomized study using endoscopic stents. Endoscopy 33, 559–562.

Lans, J.I., Geenen, J.E., Johanson, J.F., and Hogan, W.J. (1992). Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial. Gastrointest. Endosc. 38, 430–434.

Machicado, J.D., and Yadav, D. (2017). Epidemiology of Recurrent Acute and Chronic Pancreatitis: Similarities and Differences. Dig. Dis. Sci. 62, 1683–1691.

Mariani, A. (2014). Outcome of endotherapy for pancreas divisum in patients with acute recurrent pancreatitis. World J. Gastroenterol. 20, 17468.

Michailidis, L. (2017). The efficacy of endoscopic therapy for pancreas divisum: a meta-analysis. Ann. Gastroenterol.

Nøjgaard, C., Becker, U., Matzen, P., Andersen, J.R., Holst, C., and Bendtsen, F. (2011). Progression from acute to chronic pancreatitis: prognostic factors, mortality, and natural course. Pancreas 40, 1195–1200.

Nordback, I., Pelli, H., Lappalainen-Lehto, R., Järvinen, S., Räty, S., and Sand, J. (2009). The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial. Gastroenterology 136, 848–855.

Park, S.-H., Watkins, J.L., Fogel, E.L., Sherman, S., Lazzell, L., Bucksot, L., and Lehman, G.A. (2003). Long-term outcome of endoscopic dual pancreatobiliary sphincterotomy in patients with manometry-documented sphincter of Oddi dysfunction and normal pancreatogram. Gastrointest. Endosc. 57, 483–491.

Rebours, V., Boutron-Ruault, M.-C., Schnee, M., Férec, C., Le Maréchal, C., Hentic, O., Maire, F., Hammel, P., Ruszniewski, P., and Lévy, P. (2009). The natural history of hereditary pancreatitis: a national series. Gut 58, 97–103.

Roberts, J.R., and Romagnuolo, J. (2013). Endoscopic Therapy for Acute Recurrent Pancreatitis. Gastrointest. Endosc. Clin. N. Am. 23, 803–819.

Romagnuolo, J., Durkalski, V., Fogel, E.L., Freeman, M.L., Tarnasky, P.R., Wilcox, C.M., Cotton, P.B., Warth, S., Orrell, K., and Williams, A.W. (2013). Mo1427 Outcomes After Minor Papilla Endoscopic Sphincterotomy (MPES) for Unexplained Acute Pancreatitis and Pancreas Divisum: Final Results of the Multicenter Prospective FRAMES (Frequency of Recurrent Acute Pancreatitis After Minor Papilla Endoscopic Sphincterotomy) Study. Gastrointest. Endosc. 77, AB379.

Whitcomb, D.C. (2004). Mechanisms of disease: Advances in understanding the mechanisms leading to chronic pancreatitis. Nat. Clin. Pract. Gastroenterol. Hepatol. 1, 46–52.

Yadav, D., and Lowenfels, A.B. (2013). The Epidemiology of Pancreatitis and Pancreatic Cancer. Gastroenterology 144, 1252–1261.

Yaghoobi, M., and Romagnuolo, J. (2015). Sphincter of Oddi Dysfunction: Updates from the Recent Literature. Curr. Gastroenterol. Rep. 17, 31.

Genes Behind Pancreatic Cancer

Pancreatic cancer is the third most common cause of cancer-related deaths in the United States, with over 43,000 deaths expected in 2017.1 While most pancreatic cancers are sporadic, approximately 10% of pancreatic cancers appear to have a familial component.2

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Familial Pancreatic Cancer (FPC) is defined as families that have > 2 affected individuals who are first-degree relatives of each other. FPC can also include families with > 3 affected individuals on the same side of the family, even if they are not first-degree relatives of each other.

Germline mutations in BRCA1, BRCA2, PALB2, ATM, p16, PRSS1, STK11, and the mismatch repair genes (Lynch syndrome) are associated with a significantly increased risk of pancreatic cancer; however, these genes have a low penetrance for pancreatic cancer, and often the family history is more notable for other cancers.

Despite what appears to be an autosomal dominant mechanism for inheritance, a genetic mutation leading to pancreatic cancer is found only 10% of seemingly hereditary cases.

Several large-volume centers have begun to study screening for pancreatic cancer in high-risk patients, and consensus-based guidelines have been published.3  Candidates for screening may include:

1) First-degree relative of an affected individual in a FPC family

2) First-degree relative of an affected individual in a family with > 2 pancreatic cancers

3) BRCA2, PALB2, p16, ATM, and mismatch repair gene mutation carriers with affected first-degree relatives

4)  BRCA2 mutation carriers with 2 affected relatives, even if no first-degree relative is affected

5) All Peutz-Jegher’s syndrome (STK11 mutation) patients regardless of their family history

6) All PRSS1 mutation carriers

Consensus guidelines recommend pancreatic cancer screening in high-risk individuals at age 50, with the exception being PRSS1 mutation carriers who start screening at age 40.

The goals of pancreatic cancer screening include:

1)  Detection and treatment of precancerous lesions (i.e., high grade multifocal pancreatic intraepithelial neoplasms, or high-grade dysplasia within an intraductal papillary mucinous neoplasm).

2) The detection and treatment of a T1N0M0 cancer.

3) Detection of any resectable pancreatic carcinoma.

Detection of these early pancreatic cancers or pre-malignant lesions is dependent on our ability to identify and screen high-risk individuals before the onset of symptoms.  Current tools for pancreatic cancer screening include Magnetic Resonance Imaging (MRI) with MR Cholangiography (MRCP) and endoscopic ultrasound (EUS.)

MRI has the benefit of being a non-invasive test, but is sometimes limited by the patient’s ability to lie still for the duration of the study. 

EUS is a more invasive examination which requires anesthesia, but offers an opportunity to sample any abnormalities that may be detected on examination.

Emerging data suggest that MRCP may be more effective in detecting cystic lesions of the pancreas, while EUS may be more sensitive to detect small solid lesions.4 Computer tomography (CT scan), abdominal ultrasound, and endoscopic retrograde cholangiopancreatography are not generally used in pancreatic cancer screening.

For further information on pancreatic cancer screening studies, or to arrange a consultation please visit  http://www.mountsinai.org/profiles/aimee-lucas or  http://labs.icahn.mssm.edu/lucas

Amiee Lucas, MD  Professor of Medicine – Gastroenterology  Mt. Sinai Hospital

References

1. Society AC. Cancer Facts & Figures 2017. Atlanta: American Cancer Society 2017.

2. Klein AP, Hruban RH, Brune KA, et al. Familial pancreatic cancer. Cancer J 2001;7:266-73.

3. Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 2012.

4. Harinck F, Konings IC, Kluijt I, et al. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut 2015.

Controversies in GERD Management

Gastroesophageal reflux disease, or GERD, is defined by the Montreal Classification as “a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications.” This characterization has always been intentionally broad, as symptoms of GERD can vary widely in patients, and the frequency of symptoms does not necessarily correlate with the quantity of reflux in an individual patient. To further complicate matters, only certain patients have long-term esophageal injury from GERD. Progression of GERD to Barrett’s esophagus and even esophageal adenocarcinoma can occur, but the majority of patients with GERD do not develop these long-term sequelae. In patients without concerning esophageal injury, and accumulating data on the potential risks of long-term proton pump inhibitor (PPI) therapy, how are we to think long-term about their reflux disease? If the symptoms are not able to be managed with dietary and lifestyle changes alone, should we now be considering alternative medical and procedural therapies in more of our patients?

To have a chance to answer these questions, I believe it is vital to step back and ask: why does my patient have GERD? Sometimes, the answer is obvious: it could be a recent dietary change or weight gain, or a clear anatomic process at the esophagogastric junction (EGJ) such as a hiatal hernia. However, if the cause is not obvious, further evaluation of the mechanisms of GERD in a patient can be important. The attention and interest in the pathophysiology of GERD has been increasing in recent years. For example:

-Without a hiatal hernia, traditionally it has been unclear whether a low pressure lower esophageal sphincter (LES) may have a role in contributing to worsening GERD. In addition, with the advent of high-resolution esophageal manometry studies, other LES metrics, one being the “EGJ contractility integral,” are being deciphered to study the EGJ comprehensively. Still other technology, with impedance planimetry, is being studied to assess the compliance of the LES in patients with GERD.  

-There is a body of literature suggesting that the LES may shorten over time, and this decreasing LES length may be a surrogate for progression of GERD. Here too, esophageal manometry may be beneficial in determining the primary underlying cause of GERD.

-Transient LES relaxations have been a known mechanism of GERD for many years. However, the majority of evidence suggests that the quantity of these relaxations may not be the most significant factor, and GERD patients instead will likely reflux more when the relaxations occur. Thus, the physiology of the proximal stomach may have a function in GERD, and indeed an “acid pocket” has been described at the EGJ from which reflux can originate after a meal. The location of this reservoir may vary amongst patients.

There are many potential mechanisms for GERD, and these are but a few that have received recent attention. Work to decipher the major etiologies of GERD in patients is encouraging, and eventually we can hope for different “phenotypes” of GERD patients based on mechanisms.

Importantly, we know that an overall balance of symptom triggers (causticity of gastric contents, volume of reflux) and symptom modulators (ability to clear reflux, tissue sensitivity) exist to create the condition of GERD. There are a variety of technologies now that attempt to quantify reflux in patients and correlate that reflux to particular symptoms (wireless pH as well as catheter-based pH and impedance-pH testing), and even focus on the chronicity of reflux in an individual patient (mucosal impedance testing). Further study of these technologies is expected to improve our categorization of GERD patients. Lastly, our options for treating GERD continue to widen, at the same time there is increasing physician and patient concern over long-term potential adverse consequences of PPIs. There are several modern procedural options for treating GERD, with both endoscopic and laparoscopic approaches emerging in recent years.

So how should I treat my patient with GERD on long-term PPI? My approach has always been: if there is no clear indication for indefinite PPI, the goal should be to decipher if there is a therapeutic option that will allow the patient to stop it. This may be a dietary, medical, endoscopic, or surgical approach. Thinking long-term about GERD coincides with considering its mechanisms. In the current landscape, a meticulous individualized approach to care, with a concise discussion on the risks and benefits of both medical and procedural therapies for GERD, is warranted.

As we improve our ability to categorize and “phenotype” patients with GERD, as well as use our motility, pH, and impedance technologies to assess GERD in individual patients, carefully done studies should allow us to develop appropriate diagnostic and treatment algorithms. Certainly, not every patient with GERD will be expected to improve with an LES augmentation procedure, but the goal will be to answer: which patients should get which procedure? As of now, we know that the patients that do best with LES surgery are also the patients who respond best to PPI. We have to do better than that. In the coming years, I expect that we will.

 

Abraham Khan, M.D.

Director, Center for Esophageal Disease

NYU Langone Medical Center

 

Fecal Microbiota Transplantation: Beyond the treatment of Recurrent Clostridium Difficile

Do your patients ask you a lot of strange questions? Since I’ve begun doing fecal transplants (FMT), here are some of the typical questions I’ve been getting:

• “Is the FMT donor fat?”
• “Was the FMT donor breastfed?”
• “I have two great FMT donors and don’t want to hurt anybody’s feelings. Could you mix their stools?”
• “How do you extract the stool from the FMT donor?”
• “What if it doesn’t agree with my own poop?”

Image result for free fecal transplant image

Today, FMT has one approved use: the treatment of recurrent Clostridium Difficile colitis. For that use, the success rates are extremely high. Of all the things we prescribe as doctors, this is one we can feel unambiguously proud of. It’s fast, effective, and inexpensive. This is no small matter: about 30,000 Americans die every year of Clostridium Difficile . Millions of dollars are spent treating this infection, which can be devastating. One can administer FMT though the upper GI tract or directly into the colon. Since Clostridium Difficile colitis affects the colon, today most gastroenterologists administer it via colonoscopy.

As a result of this success, now some patients will try anything to convince you that they need a fecal transplant to cure a whole host of maladies. Others will refuse one even when they have been debilitated by years of infectious colitis and multiple hospital admissions.

But will there be other clinical uses for fecal transplant?

To do justice to this question, it is important first to consider the topic of the microbiome. Recently, FMT has inspired the medical community to look at this “newly discovered organ” we had been ignoring for so long. The “organ” is our microbiota: an enormous number of cells living in an organized dynamic ecosystem and playing so many roles in virtually every aspect of our health and disease. Our gut microbes interact with each other and with us, the host. We have coevolved and developed a mutually beneficial relationship: we provide them with food and shelter and they help with our nutrition, our ability to fight infections, our metabolism, and even our neurologic development. Their study is particularly fascinating because it brings together medicine, ecology, and evolution.

To better understand the microbiota, we have used several tools that have allowed us to gather an enormous amount of information: more information than we can actually interpret. In a sense one could say that technology is ahead of science. Today, for example, we have the ability to sequence the genetic material of the organisms that live in the gut instead of culturing them.

We have observed that the microbiota of patients with IBS, IBD, metabolic syndrome, obesity, autoimmune diseases, and even autism is different from the “normal” microbiome, but association and causation are of course two different things.

Moreover, it has become clear that in order to understand the effects of the microbiota, we need to not only identify these microorganisms, but also measure the products of their metabolism. The mere presence of a particular microbe or a group of microbes may not be as important as what they are doing.

FMT has also helped to advance our understanding of the microbiome and its role: If for example a disease or a trait can be transmitted though FMT, that could support at least some role of the microbiota in causing that disease or trait.

But studying the effects of stool transplant is a lot more complicated than studying the effects of a regular drug. Even though stool (when used for FMT) is now considered a drug, there are many unknowns: dose, ideal route of administration, mechanism of action, etc. Also, each individual person’s stool is different, like a fingerprint. And it may therefore interact in a unique way with the recipient’s microbiota.

A few months ago we started to enroll patients in a multicenter study with doctors at Montefiore, Yale, and Concorde Medical Group to investigate the possible use of FMT in IBS-D (diarrhea predominant IBS).

IBS-D, especially when it is moderate to severe, can be a debilitating disease and very frustrating to treat. Most patients have typically tried conventional therapies like special diets, probiotics, antidiarrheals, antispasmodics, and sometimes antibiotics like rifaximin, which was recently approved for this use.

Why are there currently so many different conventional therapies prescribed for IBS? Likely this is because the pathogenesis of IBS is so little understood. Visceral hypersensitivity, low-grade inflammation, and dysbiosis have been thought to play a role.  Regarding dysbiosis, we know that there is an abnormal microbiota: the numbers of lactobacilli and bifidobacteria, for example, are lower in patients who suffer from IBS than in those who don’t. Also their microbiota seems to be less diverse. Replacing “good bacteria” is the idea behind the use of probiotics, which seem to help some patients. But why are they not sufficient to cure IBS in most patients? The answer is not clear today. Perhaps the numbers of bacteria that survive the passage through the GI tract are not sufficient. Or maybe in order to change that whole ecosystem that is our microbiota in a permanent way, one has to modify it more radically instead of just adding a few specific strains of bacteria.

Despite the unanswered questions about IBS-D, we hypothesize that IBS-D is a condition that occurs secondary to an altered microbiota in the small bowel. Therefore, instead of administering the FMT via colonoscopy as we would do for recurrent Clostridium Difficile colitis, we are using “poop capsules.” It’s a 6-month, randomized, placebo-controlled trial and at 3 months there is a crossover so by the end of the study 100% of the patients will have received the active drug.

Image result for free fecal transplant image

As doctors and investigators, we are eager to help our patients with this very debilitating disease. In the process, we also hope to learn more about the microbiota, its effects on our health, and how this new knowledge will lead to exciting new therapies.

To learn more about this trial, go to clinicaltrials.gov

Caterina Oneto, M.D. (@caterina_oneto) | Twitter