Perspectives Template - American Gastroenterological Association

Transcription

AGAPerspectives
Vol. 6 No. 3 | June/July 2010
Where
should we
focus our
training?
Endoscopy changed
the field of
gastroenterology,
but should the focus on
training be technology
or cognitive based?
LAWRENCE S. FRIEDMAN, MD, AGAF,
and PANKAJ JAY PASRICHA, MD,
explore both aspects.
Also inside…
Best Test for CRC Screening?.....................................8
Screening Strategies for Minorities........................10
Interacting with Industry ..............................................16
Solo Practice — Dying, or Alive and Well? ...........22
International Lab and Clinical Interests .................23
AGA Institute
4930 Del Ray Ave.
Bethesda, MD 20814
AGAPerspectives
Vol. 6, No. 3 | June/July 2010
AGA Perspectives Editor
Michael Camilleri, MD, AGAF
AGA Institute Executive Committee
Ian L. Taylor, MD, PhD, AGAF
President
C. Richard Boland, MD, AGAF
President-Elect
Loren Laine, MD, AGAF
Vice President
J. Sumner Bell III, MD, AGAF
Secretary/Treasurer-Elect
Gail Hecht, MD, MS, AGAF
Past President
Committee Chairs
John M. Inadomi, MD, AGAF
Clinical Practice & Quality Management Committee
Suzanne Rose, MD, MSEd, AGAF
Education & Training Committee
Kim E. Barrett, PhD, AGAF
Ethics Committee, Audit Committee
Peter R. Holt, MD, AGAF
International Committee
Mark H. DeLegge, MD, AGAF
Practice Management & Economics Committee
Robert Burakoff, MD, MPH, AGAF
Public Affairs & Advocacy Committee
Sheila E. Crowe, MD, AGAF
Publications Committee
Don C. Rockey, MD, AGAF
Research Policy Committee
Maria T. Abreu, MD
Deborah D. Proctor, MD, AGAF
Underrepresented Minorities Committee
In this issue
Cognitive GI Must Be Resurrected....................................................................................4
Lawrence S. Friedman, MD, AGAF
Procedural Training Should Be Emphasized..................................................................5
Pankaj Jay Pasricha, MD
Colorectal Cancer Screening: Which is the Best Test?...........................................8
Sidney J. Winawer, MD, AGAF, MACG, FASGE
Preventing CRC in Underrepresented Minorities:
Do Minority Populations Need Alternative Screening Strategies?............10
John M. Carethers, MD, AGAF
The Impact of Decreased Industry Funding on AGA:
Interacting with Industry in an Era of Ethical Concerns ...............16
Do the Colonic Microbial Flora Serve to Trigger Colon Cancer?.......................18
Cynthia L. Sears, MD; Hassan Ashktorab, PhD; and Hassan Brim, PhD
Should We Screen for Hepatocellular Carcinoma in Patients with Cirrhosis?
If So, in Whom and How? ...........................................................................................20
Hashem B. El-Serag, MD, MPH
Solo Practice — Dying, or Alive and Well?...................................................................22
Kimberly M. Persley, MD
Lab and Clinical Interests: An International Perspective.......................................23
Tarik Asselah, MD, PhD
Women’s Committee
Editorial Staff
Alissa J. Cruz
Managing Editor
Aaron R. White
Editorial Director
Jennifer P. Halbert
Designer/Production Manager
Jessica W. Duncan
VP of Communications
Funding for AGA Perspectives is
provided by Takeda Pharmaceuticals
North America, Inc.
Cover illustration by Charles Waller, Images.com
AGA Perspectives Departments
AGA Online Education .....................................................................................................................................................6
AGA Meeting Preview.....................................................................................................................................................7
Author Disclosures ..........................................................................................................................................................9
AGA on Social Media....................................................................................................................................................11
Journal Editors’ Picks...................................................................................................................................................19
AGA Member News .....................................................................................................................................................21
The ideas and opinions expressed in AGA Perspectives are those of the authors, and do not necessarily reflect those
of the American Gastroenterological Association, or the editorial staff.
Publication of an advertisement or other product mention in AGA Perspectives should not be construed as an endorsement of the product or
the manufacturer’s claims. Readers are encouraged to contact the manufacturer with any questions about the features or limitations of the
product mentioned. The AGA assumes no responsibility for any injury and/or damage to persons or property arising out of or related to any use
of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the methods and duration of administration, or contraindications. It is the responsibility of the treating physician or other health-care professional, relying on independent experience and knowledge
of the patient, to determine drug dosages and the best treatment for the patient.
AGA Perspectives, ISSN 1554-3366 (print) and ISSN 1555-7502 (online), is published bi-monthly by the AGA Institute,
4930 Del Ray Ave., Bethesda, MD 20814.
2 | AGA PERSPECTIVES
Copyright © 2010 by the AGA Institute. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any
means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from
the publisher. Printed in the U.S. Correspondence regarding permission to reprint all or part of any article published in this newsletter should include
a copy of the author’s written permission and should be addressed to: AGA Perspectives, 4930 Del Ray Ave., Bethesda, MD 20814.
www.gastro.org
AGA LEADERSHIP N O TES
➨ AGA’s New President Aims to Ensure Society
Is a Constant Advocate for its Members
We welcome member
feedback on all of the
Ian L. Taylor, MD, PhD, AGAF, AGA’s new president, is ready to
lead the AGA Institute through the challenges it may face in the year
ahead. Dr. Taylor’s term began at the conclusion of DDW® 2010.
Dr. Taylor is focused on several issues, including the development of
an organization-wide clinical data registry, as well as making certain
gastroenterology clinicians and scientists are represented in the
government’s reform of the health-care system.
He sees his upcoming tenure as AGA president as an extension of
the leaders who have gone before him. “It is my job to keep the
AGA strong and ensure that we are a constant and clear advocate
Ian L.Taylor, MD, PhD, AGAF
for both our clinical and scientific members,” he said. “My goal is
to keep up the good work that has gone before.”
Armed with a road-tested and refined strategic plan, the wisdom of a talented team of volunteers and
staff, and a wealth of experience, the senior vice president for biomedical education and research and
dean of the College of Medicine at the State University of New York Downstate Medical Center,
Brooklyn, said he’s excited to continue strengthening an already superior organization.
“I’ve had an interesting life, and I think one of the most important things I’ve learned is that if
you have good people around you, you will succeed,” he said. “The AGA Governing Board is such
an amazing collection of talent that this can never be just a one-man or one-woman entity. There is
so much experience here — on the board, the committees, and on what I believe has to be the most
talented office staff of any national organization — that nothing falls on the shoulders of the
president alone.”
A longtime advocate of GI education, Dr. Taylor started working on the AGA Subcommittee on
Training and Education in GI in 1987. “I think this organization is a terrific advocate for all of GI —
both clinical and academic — and has done a lot of innovative things with regard to education of its
members,” Dr. Taylor said. “The curriculum now used by most GI programs in the U.S. was initiated
by the AGA when I was chair of the Subcommittee on Training and Education, and it became a project
that all four GI societies completed as a joint venture.”
“I think it really laid out the go-to training program for producing competent, well-trained GIs, and I
think it has benefited both GI fellows and their patients. The educational programs the AGA puts on
are absolutely first-rate,” he said.
perspectives presented in
this issue.
Send your letters and
comments to
communications@gastro.org
and include “AGA
Perspectives” in the
subject line.
➨ AGA Perspectives Welcomes New Editor
The role of Michael Camilleri, MD, AGAF, as editor of AGA Perspectives
concluded at DDW® 2010. We thank him for his insight and guidance during his
term, and welcome Sheila E. Crowe, MD, AGAF, as our new editor. Should you
have any comments or suggestions for Dr. Crowe, please e-mail them to
communications@gastro.org.
Sheila E. Crowe,
MD, AGAF
For more information on any of the topics in AGA Perspectives, visit www.gastro.org. If you do not receive AGA eDigest, the AGA’s weekly e-mail newsletter with the latest news affecting the science and practice of GI,
make sure the AGA has your e-mail address. Log onto www.gastro.org or call AGA Member Services at 301-941-2651 to update your information.
w w w.gastro.org
A G A P ERSPECTIVES | 3
WHERE SHOULD WE
FOCUS
OUR
TRAINING?
Endoscopy changed GI, but should the focus
Cognitive GI
Must Be Resurrected
Lawrence S. Friedman, MD, AGAF
Professor of Medicine, Harvard Medical School; Professor of Medicine, Tufts University School of Medicine;
Chair, Department of Medicine, Newton-Wellesley
Hospital, Newton, MA; Assistant Chief of Medicine,
Massachusetts General Hospital, Boston, MA
or me, gastroenterology has always been a cognitive discipline. I was drawn to the field by the breadth of clinical
problems; multitude of laboratory, imaging and endoscopic
tools available to address clinical challenges; expanding application
of technological and basic innovations to patient care; and potential to study a broad array of research questions that were — and
in many cases remain — unanswered.
Surely, the introduction of endoscopy to the study and practice
of gastroenterology has been transformational. It is hard to
imagine practicing gastroenterology today without endoscopy.1
Now, we take for granted the capability to remove polyps and
thereby prevent colon cancer by colonoscopy, apply a variety of
methods to stem ulcer or variceal bleeding and reduce the risk of
rebleeding by upper endoscopy, relieve bile duct obstruction and
remove stones by ERCP, detect the smallest pancreatic neoplasms
by endoscopic ultrasonography, and examine every inch of the
gastrointestinal lumen, now that capsule endoscopy and deep
enteroscopy are available.
F
Cognitive GI is central to practice
Clearly, none of these techniques is, or should be, done by technicians, but by fully trained gastroenterologists (or surgeons) who
understand the implications of endoscopic findings, pitfalls of interpretation, treatment alternatives and potential complications (and
their management) of therapeutic interventions.2 On the other hand,
we also recognize that endoscopy alone does not necessarily solve a
patient’s problem. My consultative practice derives in large part from
patients referred after endoscopy has failed to address their concerns
adequately. Challenging cases are familiar to all gastroenterologists
and span a gamut that includes unexplained abdominal pain, diarrhea and liver biochemical test abnormalities. When the final diagnoses are familial Mediterranean fever, bile salt malabsorption and
celiac disease, respectively, it is easy to appreciate that endoscopy
may be non-diagnostic or not considered in the evaluation. We all
have memorable cases that were not solved by endoscopy, like my
patient with rectal burning that proved to be a manifestation of
pancreatic insufficiency or the one with throat spasms who turned
out to have reflex headache syndrome that responded to NSAIDs.
The component of functional gastrointestinal disease (FGID) that
makes up a large part of gastroenterology practice further increases
the challenges of diagnosis and management considerably, and
demonstrates the failure of endoscopy to significantly impact the
diagnosis or management of the patient with FGID.
But the premise that cognitive gastroenterology and endoscopic
skill represent a dichotomy is false; both are central to the practice
of gastroenterology.3 As our armamentarium of interventions avail-
Clinicians are most likely to be successful
when they utilize both cognitive and
technical skills to treat the patient’s illness,
rather than merely technical approaches
to address a disease or lesion.
able to help patients expands, so does the cognitive base required
for rational decision making. The endoscopist must have answers
to many “cognitive” questions. How should we manage Barrett’s
esophagus with low-grade dysplasia? What is the significance of a
serrated polyp in the cecum? Is genetic testing indicated in a
patient with multiple hyperplastic polyps throughout the colon?
When is endoscopic therapy appropriate in a patient with pancreatic necrosis? Endoscopy plays a role in each of these disorders,
but the application of endoscopy requires an understanding of the
significance of the findings, natural history of the disease and
consideration of alternative or additional approaches. There is no
substitute for expertise — both technical and cognitive.
continued on page 6
www.gastro.org
Are our fellows receiving enough or too much endoscopy training?
Is gastroenterology losing its role in solving complex diseases that
present with a limited symptom repertoire?
Where are our priorities at a time when technology such as
CT colonography may take over colon cancer screening?
on training be technology or cognitive based?
Procedural Training
Should Be Emphasized
Pankaj Jay Pasricha, MD
Professor of Medicine; Chief, Division of
Gastroenterology and Hepatology,
Stanford University School of Medicine, CA
he modern specialty of gastroenterology owes much of its clinical, academic and scientific success to endoscopic procedures:
endoscopic extraction of gallstones, control of gastrointestinal
bleeding, biopsy demonstrating the link between Helicobacter pylori
and peptic ulceration, monitoring of patients with propensity to
develop colorectal cancer (CRC), etc. Our patients have benefited
tremendously from these procedures and so have we as gastroenterologists. Private practitioners have seen astounding increases in their
income with the adoption of endoscopy, while academic gastroenterologists have enjoyed the prestige and political clout that comes
with being a major contributor to departmental and institutional
finances. All of these considerations, along with the instant gratification that comes from performing a successful procedure with diagnostic or curative intent, has attracted the best and brightest in the
medical profession to our field.
So why is there so much angst about endoscopy? Since more
than half of the workday of a practicing gastroenterologist is spent
doing mundane and undemanding procedures like screening
colonoscopy, it can be argued that our emphasis on procedural
training has turned out a generation of technicians who have lost
touch with the cognitive aspects of their specialty. Further, the
dependence predominantly on a single procedure (screening
colonoscopy) has left us financially and intellectually vulnerable to
any major shifts in the current paradigm of CRC screening techniques or their reimbursement. However, as I will discuss, pointing
the finger at the procedure itself misplaces the blame for the current
state of affairs. Indeed, attempts to “de-emphasize” procedures and
procedural training across the board will have unintended and
significantly adverse consequences for our specialty.
T
w w w.gastro.org
Linkage between gastroenterology and procedures is
necessary, and will only become stronger with time
The GI tract is inherently amenable to procedures because of its
unique accessibility via the endoscope. I have often compared the GI
tract to the skin in this regard: the vast majority of skin diseases are
diagnosed by direct visualization and biopsy and treated topically;
similarly, many digestive disorders can potentially be managed endoscopically. However, we are a long way from realizing that goal, and
it is only by continuing to emphasize endoscopic approaches that we
will attain the goal. In the future, there should be no need to treat
conditions such as IBD, ulcers or pancreatic disorders with systemic
drugs when local approaches might prove just as effective, with fewer
side effects and costs.
Procedures are also likely to grow in importance as the GI tract is
increasingly recognized as the portal to other organs, as in Natural
Orifice Translumenal Endoscopic Surgery®, which can provide access
Medicine in general, and gastroenterology
in particular, have become so technology
dependent that reverting to a pure “cognitive”
era is no longer possible or desirable.
to the peritoneal cavity and, at least experimentally, to the heart,
pelvic organs, etc. Most importantly, physio-anatomical modifications of the GI tract have immense therapeutic potential for important systemic diseases such as obesity, diabetes and their health consequences. Such procedures are increasingly being attempted
endoscopically and it is quite likely that, in the foreseeable future,
they will replace traditional surgery for such procedures as gastric
bypass for obesity. Who will blaze this trail and lead us forward into
this brave new world?
An artist and his tool are inseparable
The endoscope is a very important and unique tool that provides
easy access to the GI tract, is generally safe and, unlike surgery, lends
itself to iterative, re-doable and reversible procedures. The true potential has not yet been fully exploited in gastroenterology. Indeed, the
vast majority of digestive diseases (dysmotility syndromes, painful
continued on page 7
Friedman: continued from page 4________________________________________________
It has been argued that the combination of open-access
endoscopy and market forces that limit access to expert consultative services may ultimately be detrimental to patient care.4
Moreover, an endoscopic intervention may remove a lesion, but
may not fully address a patient’s concerns and anxieties. Fully
effective therapy often requires dialogue, compassion, understanding and, above all, time. Clinicians are most likely to be
successful when they utilize both cognitive and technical skills to
treat the patient’s illness, rather than merely technical approaches
to address a disease or lesion.5, 6
The future of cognitive GI
The frontiers of gastroenterology are expanding at a rapid pace,
and the knowledge required of a gastroenterologist is growing
proportionately. Essential now to gastroenterologic practice is an
understanding of the role of genetic testing in colon cancer, meta-
Technology evolves,
procedures come and go, and
methods just emerging or
not yet imagined may render endoscopy
a fading option, but the field of
gastroenterology will remain vibrant
because of its rich cognitive base.
hypertension and end-stage liver disease, as well as hepatocellular
carcinoma; to name a few. Even the most motivated primary care
physician will not have the expertise needed to manage this array
of problems.
These advances are occurring as endoscopic progress is accelerating. Intriguingly, as we press the boundaries of endoscopic intervention with Natural Orifice Translumenal Endoscopy®, we are
learning that exploration of the final frontiers is not for the fainthearted. Most endoscopists continue to perform non-complex
endoscopic procedures, particularly screening colonoscopy. Few, I
suspect, will master the high-end or complex techniques. Clearly,
endoscopic specialization mirrors specialization within the field of
gastroenterology. Many gastroenterologists who “do endoscopy”
will want to be stimulated and challenged by the expanding
knowledge base of the field.
Conclusion
We risk making ourselves irrelevant if we focus solely on our
role as technicians or proceduralists. Technology evolves, procedures come and go, and methods just emerging or not yet imagined may render endoscopy a fading option, but the field of
gastroenterology will remain vibrant because of its rich cognitive
base. We all became gastroenterologists to take care of patients,
not merely to do procedures. We need to embrace the entire field
for our patients’ sakes and for our own. References _____________________________________________________
1. DiSario JA, Waring JP, Sanowski, RA, Wadas DD. The gastroenterologist: physician or
technician? Gastrointest Endosc 1991; 37:315-8.
2. Standards of Training Committee, American Society for Gastrointestinal Endoscopy.
Principles of training in gastrointestinal endoscopy. Gastrointest Endosc 1999; 49:485-52.
3. Spiro HM. Parsnips and pomegranates—training in gastroenterology then and now. Am J
Gastroenterol 1983; 78:57-62.
bolic liver diseases, pancreatic disorders and drug prescribing;
second- and third-line therapeutic regimens for eradication of
Helicobacter pylori; serologic testing in IBD; an expanding repertoire of antiviral agents for hepatitis B and C, and biologic agents
for IBD; and various approaches to the management of portal
4. Shaheen NJ, Bozymski EM. Open access endoscopy: cognition, technician, or some of
both? Gastrointest Endosc 1997; 46:85-7.
5. Brandt LJ. Thank you for taking time to listen to me: a reflection on clinical practice in
the era of patient consumerism. Am J Gastroenterol 2005; 100:1224-5.
6. Rogers AI. The cornerstone of medicine: the physician-patient relationship. Am J
Gastroenterol 2007; 102:1594-5.
AGA ONLINE EDUCATION
GI SAM® — AGA Institute’s
Online Self-Assessment Modules
Just Released! “Disorders of the Pancreas & GI Motility”
Assess and enhance your command of the treatment, diagnosis, symptoms and risk factors
associated with gastroenterology- and hepatology-related topics. Earn maintenance of
certification points and CME credits with this interactive, intuitive product. All modules
include 25 questions with instant feedback as well as additional references for further study.
Also available: “IBD & GI Bleeding.”
Visit www.gilearn.org/gisam for more information.
www.gastro.org
Pasricha: continued from page 5_________________________________________________
should not only involve traditional aspects of gastroenterology,
and so-called functional conditions, and inflammatory disorders)
but also encompass the art and science of technological tools and
have not been considered to be amenable to endoscopic approaches
their development. At Stanford, we have introduced such training
for diagnosis or therapy. This reflects a failure of our imagination,
by initiating within our fellowship a GI bio-design track, which is
not the tools. Failure to make significant headway in this group of
offered in partnership with the Stanford bio-design program. The
disorders is a reflection of the lack of emphasis on procedures, rather
objective is to teach the trainee how to identify unmet medical
than the opposite. We have not done a good job inspiring our
needs, harness resources to come up with creative solutions, take
trainees to harness the full power of the endoscope by acquiring the
these concepts to proof-of-principle and put together a team that
procedural skills and knowledge base to test physiological
could bring forth a successful clinical product. The fruits of this
hypotheses, obtain original information that identifies the biological
program will take many years to be apparent, but it is a reflection
insight, identify novel targets for treatment, and develop novel proceof our philosophy that separation of the cognitive and procedural
dures to address the unmet needs of their patients.
aspects of gastroenterology is artificial and should increasingly
become irrelevant.
Elevate, not eliminate procedural emphasis
in training programs
Conclusion
Technology holds the key to advances in medicine, and this is
Medicine in general, and gastroenterology in particular, have
especially true for specialties like ours. However, technology
become so technology dependent that reverting to a pure “cognitive”
development should not be a tinkerer’s weekend effort in the
era is no longer possible or desirable. We must take advantage of all
garage or, at the other extreme, left to the capability of corporate
that technology offers and use it for improving the lives of our
research and development teams. The development of new
patients. In the future, the intellectualization of technology developprocedures and devices to address unmet needs is an intensely
ment should become the basis of a major cognitive discipline that we
cognitive exercise that needs to be formally incorporated into the
must teach our trainees. training program of future gastroenterologists. Cognitive training
AGA MEETING PREV I EW
AGA Clinical Congress of Gastroenterology and
Hepatology: Best Practices in 2011
Jan. 14 & 15, 2011
Loews Miami Beach Hotel, FL
Don’t miss this two-day, multi-topic course that will present an evidence-based
approach to GI clinical care based on the most recent and best available research.
Special Add-On Programs
Jan. 13 & 14
– AGA Practice Managers Course
Jan. 16
– AGA Hands-On Video Endoscopy Course
– AGA Practice Skills Workshop
New for interns, residents and fellows — submit an abstract
Selected abstracts will be published in Clinical Gastroenterology and Hepatology.
Register now for all events at www.gilearn.org/clinicalcongress.
w w w.gastro.org
SCREEN I N G
Colorectal Cancer Screening: Which is the Best Test?
Sidney J. Winawer, MD, AGAF, MACG, FASGE
Paul Sherlock Chair in Medicine, Memorial Sloan-Kettering Cancer Center;
Professor of Medicine, Weill Cornell Medical College, New York
Is CRC screening effective?
The effectiveness of CRC screening was
challenged from the start. Early results of
screening programs were glowing, with a
predominance of early-stage cancers
reported. This can be misleading. Many
early-stage cancers may not surface and
death may be from another cause (overdiagnosis bias). Cancers may be detected
before symptoms appear, identifying the
disease longer, but not improving outcome
(lead-time bias). Screening may uncover
less aggressive cancers more often (length
bias). Long-term randomized controlled
trials (RCTs) that have a mortality
endpoint of the entire cohort eliminate
these biases. For CRC screening, three
RCTs of quiaiac fecal occult blood test
(FOBT) showed significant mortality
reductions.1
The NYT articles cited the increase in
annual incidence and lack of a mortality
reduction nationally for breast and
prostate cancer. The articles did not cite
the decrease in annual incidence and
mortality of CRC during the same time
frame, decreased cancer incidence from
Figure 1: Death Rates from CRC per 100,000 Population
35
30
1990
2005
(-) 31.8%
25
20
(-) 28.0%
15
10
5
0
Male
Female
Figure 2: CRC Incidence Rates per 100,000 Age >50 Years
90
Rate per 100,000
Anyone reading the eye-catching headlines or the full New York Times (NYT)
cancer screening articles this past year
would most likely conclude that screening
has little value. Only by reading carefully
and completely, would it be apparent that
breast and prostate cancer were being
specifically addressed. The reporters state
later and briefly that colorectal cancer
(CRC) screening is recommended and is
effective. Not stated is that CRC screening
is unique, having the potential to prevent
cancer altogether, unlike breast and
prostate cancer screening.1
80
70
60
50
40
30
20
Males
Females
10
0
1975
1980
1985
1990
1995
2000
2005
www.gastro.org
U.S. multi-society guidelines. Issues are:
whole stool requirement and intervals
(DNA), radiation, extra-colonic findings,
flat adenoma miss rate (CTC) and costeffectiveness (both).3 The future first-stage
screening test may be a highly sensitive and
specific molecular blood test.
No test is perfect.
All have issues.
All provide some level of protection.
The best test is the one that gets done, and done well.
removing adenomatous polyps, the
predominant neoplastic screening outcome,
and the decreased mortality from earlier
stage of cancers detected (figures 1 and 2).2
“One-stop shopping”
Colonoscopy provides screening, diagnosis and treatment, and is the most
commonly selected option in the U.S. and
many other countries. We have learned
much about its performance: 5 percent of
a mixed gender cohort ages greater than or
equal to 50 have advanced adenomas; less
than 1 percent have cancer, and complications are rare.3, 4 Removal of all visible
adenomatous polyps during colonoscopy
results in about a 90 percent CRC incidence and mortality reduction.5
Retrospective studies have suggested a 50
percent to 75 percent mortality reduction
in the general population, but the impact
appears to be greater for distal as
compared to proximal disease either due to
a difference in biology or a less effective
examination of the right colon.6, 7
Outcome is better when performed by a
gastroenterologist. Precise data will be
forthcoming in 10 to 15 years from several
RCTs in Europe and the U.S.
Although screening colonoscopy has
prevention potential, this screening
modality results in a large resource expenditure. Polyps of all histological types are
found in 30 percent of men and women,
requiring polypectomy with its attendant
risks. Of the 5 percent of a mixed gender
cohort with advanced adenomas, 10
percent may progress to cancer over 10
years: an estimated 200 colonoscopies and
60 polypectomies to prevent one cancer. It
is possible that high-definition/advanced
imaging endoscopes may obviate the need
to remove adenomatous polyps or alternatively, to resect and discard small polyps.
Two-stage approach
It would be desirable to have an effective two-stage screening approach, with the
first stage identifying high-risk patients for
targeted colonoscopy. Compliers who are
q-FOBT positive and have colonoscopy
have a 40 percent CRC mortality reduction, but only a 20 percent reduction in
incidence, and therefore prevention is
largely lost. Fecal immunochemical tests
have a higher sensitivity and specificity. It
is becoming the preferred FOBT since it
can be done in one day and requires no
dietary restrictions. The FOBT effect is
limited since less than 50 percent of
patients adhere to annual testing. Flexible
sigmoidoscopy followed by colonoscopy, if
positive, significantly reduced the incidence
and mortality of distal colorectal cancer
over an 11-year period of observation in
an RCT in the U.K.8 Stool DNA testing
and CT colonography (CTC) are promising and are included as options in the
Best test
CRC screening is a package. In addition
to high-quality screening, it needs timely
diagnosis, timely effective treatment and
appropriate surveillance. It is effective.
Deaths can be avoided, and many cancers
prevented.6 The NYT articles raise the
issue of which is the best test. No test is
perfect. All have issues. All provide some
level of protection. The best test is the one
that gets done, and done well. References ______________________________
1. Winawer SJ, Fletcher RH, Miller L, et al. Colorectal
Cancer Screening: Clinical Guidelines and Rationale.
Gastroenterology 1997;112:594-642.
2. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2009.
CA Cancer J Clin 2009;59:225-249.
3. Levin B, Lieberman DA, McFarland B, et al. Screening and
surveillance for early detection of colorectal cancer and
adenomatous polyps, 2008: a joint guideline from the
American Cancer Society, the US Multi-Society Task Force
on Colorectal Cancer, and the American College of
Radiology. Gastroenterology 2008;134:1570-1595.
4. Regula J, Rupinski M, Kraszewska E, et al. Colonoscopy
in Colorectal-Cancer Screening for Detection of Advanced
Neoplasia. N Engl J Med 2006;355:1863-1872.
5. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of
colorectal cancer by colonoscopic polypectomy. N Engl J
Med 1993;329:1977-1981.
6. Brenner H, Haug U, Arndt V, et al. Low Risk of Colorectal
Cancer and Advanced Adenomas More Than 10 Years
After Negative Colonoscopy. Gastroenterology
2010;138:870-876.
7. Baxter NN, Goldwasser MA, Paszat LF, et al. Association
of Colonoscopy and Death from Colorectal Cancer. Ann
Intern Med 2009;150:1-8.
8. Atkin W, Cuzik J, Duffy S, et al. 283 UK Flexible
Sigmoidoscopy Screening Trial: Colorectal Cancer
Incidence and Mortality Rates at 11 Years After a Single
Screening Examination. Gastroenterology 2010;138:S-53.
AUTHOR D I S C LO S U RES
Dr. Camilleri is a former member of the AGA Governing Board.
Dr. El-Serag is a consultant for Vertex Pharmaceuticals Incorporated. He
has received significant research support via a grant from Bayer, and he
is a member of AASLD’s Research Policy Committee.
Dr. Friedman is the editor of ASGE News.
Dr. Persley is a speaker’s bureau participant for Abbott, UCB and Salix
Pharmaceuticals, Inc.
Dr. Sears is treasurer of the Infectious Diseases Society of Americas
(2010–2013) and vice president of the Anaerobe Society of the Americas
(2008–2010).
Dr. Pasricha is a consultant for GI Supply, PENTAX, Apollo
Endosurgery and Tranzyme Pharma.
w w w.gastro.org
CRC IN M I N O RI TI ES
Preventing CRC in Underrepresented Minorities:
Do Minority Populations Need Alternative Screening Strategies?
John M. Carethers, MD, AGAF
Professor of Internal Medicine, University of Michigan, Ann Arbor
Colorectal cancer (CRC) is one of the
most prevalent cancers in the U.S.,
affecting 146,970 persons in 2009, and is
the second most common cause of cancer
deaths (behind lung cancer) with 49,920
deaths in 2009.1 Key risk factors for CRC
development are:
• Age, with dramatic increases in CRC
incidence after age 50 (this age is used
to initiate screening due to the asymptomatic nature of CRC development
in average-risk individuals).
• Family or personal history, which puts
the patient or relatives at risk for
developing cancer at a younger age.
• Environmental influences, such as
consumption of meat and fat, which
are epidemiologically linked to cancer
development.
• Inflammation, particularly in the
colon from IBD.
• Ethnicity and race.2
CRC screening can detect cancers at
earlier stages or as precursor adenomas,
and removal of these lesions as a result of
screening improves the prognosis of
patients who otherwise may have
progressed to advanced disease. Current
screening paradigms for CRC are based on
age, with patients at higher risk (i.e., those
with IBD and personal or family history of
CRC) put into surveillance programs.3
There are no guideline considerations for
environmental factors, which are difficult
to measure, or ethnicity or race.
Principles for modification of current
screening guidelines must include consideration for higher risk individuals. Screening
should begin before the age of significant
increases in cancer incidence for a group,
and screening should be adjusted by the
observed biology or epidemiology of risk
1 0 | AGA PERSPECTIVES
Incidence and Death Rates for Colon and Rectal Cancers
(Combined) by Race and Ethnicity, 2001–2005
All
White
Black
Asian
American
Indian
Hispanic
Incidence: Male
61.2
58.9
71.2
48.0
46.0
47.3
Incidence: Female
44.8
43.2
54.5
35.4
41.2
32.8
Deaths: Male
21.0
22.1
31.8
14.4
20.5
16.5
Deaths: Female
14.6
15.3
22.4
10.2
14.2
10.8
Rates are per 100,000 and age adjusted to the 2000 U.S. standard population
(adapted from Jemal et al., CA Cancer J Clin 2009;59:225-249).
group. This approach is followed for
patients with familial adenomatous polyposis, Lynch syndrome and IBD, once they
are recognized. Practitioners in general are
less aware of the higher risk for CRC
among ethnic or racial groups, but the
same principles should be applied to these
groups based on knowledge of the natural
history and biology for those groups.4 For
instance, in Ashkenazim, a specific
missense mutation in the adenomatous
polyposis coli gene (I1307K) doubles the
risk for adenoma development and confers
an increased prevalence of CRC.2
Blacks have the highest incidence and
death rates for CRC among all major races
or ethnicities in the U.S. (table), and have a
higher proportion of CRCs under the age
of 50 compared with whites (10.6 percent
versus 5.5 percent).5 There is a higher
preponderance of right-sided colon cancers
in blacks,5, 6 perhaps predicted by a higher
prevalence of right-sided adenomas greater
than 9 mm in older blacks compared to
whites,7 and blacks are more likely to
present at later stages of disease.8 It is not
clear to what extent genetic, dietary,
lifestyle, socio-economic, genetic or preven-
tative issues account for the differences
detected in blacks. However, screening has
been suggested to begin at age 45 years6
due to the higher prevalence of CRC
below the age of 50 years, matching the
prevalence of whites with CRC at the age
of 50 years. This proposal has not been
put into widespread practice, as this
recommendation was omitted from the
multi-society guidelines.3
Because of the prevalence of relevant
right-sided polyps and cancer among
blacks, colonoscopy is the recommended
test of choice for this population6 over all
other screening approaches outlined by the
multi-society group.3 There is increasing
indirect evidence that screening is reducing
the incidence of CRC in the U.S.,1 but
there are questions regarding colonoscopy
on its effectiveness in reducing mortality in
patients with right-sided cancers when
used as a screening tool.9 Notwithstanding
further evaluation on that point,
colonoscopy is the same test recommended
for other high-risk groups due to involvement of portions of the entire colon, and is
the test that should be employed for blacks
at the age of 45 years as a high-risk group
www.gastro.org
Practitioners in general are less aware of the higher risk for
CRC among ethnic or racial groups, but the same principles
should be applied to these groups…
with a higher prevalence of right-sided
lesions. Any screening is better than no
screening, and patients who either do not
want colonoscopy or don’t have access to
colonoscopy should be screened by the
other recommended modalities3 that may
reduce mortality from CRC as a backup
measure to colonoscopy. Individuals,
regardless of race or ethnicity, who reside
in poorer communities with lower access
to health care do not experience a reduction in CRC incidence compared to more
affluent communities; this remains a key
barrier to colonoscopy screening.10 This
may hold true despite non-colonoscopic
forms of screening because if any of these
tests are positive, a colonoscopy is required
for follow-up. However, practitioners
should advocate the use of screening
colonoscopy in blacks beginning at the age
of 45 years. cancer and adenomatous polyps, 2008: a joint guideline from
the American Cancer Society, the US Multi-Society Task
Force on Colorectal Cancer, and the American College of
Radiology. Gastroenterology 2008;134:1570-1595.
4. Carethers JM. Should African Americans be screened for
colorectal cancer earlier? Nat Clin Pract Gastroenterol
Hepatol 2005;2:352-353.
5. Carethers JM. Racial and ethnic factors in the genetic
pathogenesis of colorectal cancer. J Assoc Acad Minority
Physicians 1999;10:59-67.
6. Agrawal S, Bhupinderjit A, Bhutani MS, Boardman L,
Nguyen C, Romero Y, Srinvasan R, Figueroa-Moseley C.
Colorectal Cancer in African Americans. Am J
Gastroenterol 2005;100:515-523.
1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer
statistics, 2009. CA Cancer J Clin 2009;59:225-249.
7. Lieberman DA, Holub JL, Moravec MD, Eisen GM, Peters
D, Morris CD. Prevalence of colon polyps detected by
colonoscopy screening in asymptomatic black and white
patients. JAMA 2008;300:1417-1422.
2. Grady WM and Carethers JM. Genomic and epigenetic
instability in colorectal cancer pathogenesis.
8. Ghafoor A, Jemal A, Cokkinides V, Cardinez C, Murray T,
Samuels A, Thun MJ. Cancer Statistics for African
Americans. CA Cancer J Clin 2002;52:326-341.
3. Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks
D, Bond J, Dash C, Giardiello FM, Glick S, Johnson D,
Johnson CD, Levin TR, Pickhardt PJ, Rex DK, Smith RA,
Thorson A, Winawer SJ; American Cancer Society Colorectal
Cancer Advisory Group; US Multi-Society Task Force;
American College of Radiology Colon Cancer Committee.
Screening and surveillance for the early detection of colorectal
9. Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach
DR, Rabeneck L. Association of colonoscopy and death
from colorectal cancer. Ann Intern Med 2009;150:1-8.
References _______________________________
10. Hao Y, Jemal A, Zhang X, Ward EM. Trends in
colorectal cancer incidence rates by age, race/ethnicity,
and indices of access to medical care, 1995-2004 (United
States). Cancer Causes Control 2010 (in press).
AGA ON SOCIAL M ED I A
Follow AGA to stay current
• News
• Public policy
• Research
• Resources
Follow AGA at
www.twitter.com/
AmerGastroAssn.
w w w.gastro.org
• Find AGA and its journals,
Gastroenterology and
Clinical Gastroenterology
and Hepatology
Visit
www.facebook.com/
AmerGastroAssn,
www.facebook.com/
gastrojournal and
www.facebook.com/
cghjournal.
• Video abstracts from
Gastroenterology and
Clinical Gastroenterology
and Hepatology
• Patient education videos
• Policy updates
• Highlights from
DDW® 2009 and 2010
www.youtube.com/
AmerGastroAssn.
Visit
• Policy blog for GIs
provides regular updates
on the activities occuring
in Washington and on
Capitol Hill
Visit
AmerGastroAssn.
wordpress.com.
A G A P E RSPECTIVES | 11
BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION
DEXILANT (dexlansoprazole) delayed release capsules
INDICATIONS AND USAGE
DEXILANT is indicated for:
• the healing of all grades of erosive esophagitis (EE) for up to 8 weeks,
• maintaining healing of EE for up to 6 months, and
• the treatment of heartburn associated with non-erosive gastroesophageal
reflux disease (GERD) for 4 weeks.
CONTRAINDICATIONS
DEXILANT is contraindicated in patients with known hypersensitivity to any
component of the formulation. Hypersensitivity and anaphylaxis have been
reported with DEXILANT use [see Adverse Reactions].
WARNINGS AND PRECAUTIONS
Gastric Malignancy
Symptomatic response with DEXILANT does not preclude the presence of
gastric malignancy.
ADVERSE REACTIONS
Clinical Trials Experience
The safety of DEXILANT was evaluated in 4548 patients in controlled and
uncontrolled clinical studies, including 863 patients treated for at least
6 months and 203 patients treated for one year. Patients ranged in age from
18 to 90 years (median age 48 years), with 54% female, 85% Caucasian,
8% Black, 4% Asian, and 3% other races. Six randomized controlled clinical
trials were conducted for the treatment of EE, maintenance of healed EE, and
symptomatic GERD, which included 896 patients on placebo, 455 patients
on DEXILANT 30 mg, 2218 patients on DEXILANT 60 mg, and 1363 patients
on lansoprazole 30 mg once daily.
As clinical trials are conducted under widely varying conditions, adverse
reaction rates observed in the clinical trials of a drug cannot be directly
compared to rates in the clinical trials of another drug and may not reflect
the rates observed in practice.
Most Commonly Reported Adverse Reactions
The most common adverse reactions (≥2%) that occurred at a higher
incidence for DEXILANT than placebo in the controlled studies are presented
in Table 2.
Table 2: Incidence of Treatment-Emergent Adverse Reactions
in Controlled Studies
(N=896)
%
2.9
3.5
2.6
DEXILANT
30 mg
(N=455)
%
5.1
3.5
3.3
DEXILANT
60 mg
(N=2218)
%
4.7
4.0
2.8
DEXILANT
Total
(N=2621)
%
4.8
4.0
2.9
Lansoprazole
30 mg
(N=1363)
%
3.2
2.6
1.8
Upper Respiratory
Tract Infection
0.8
2.9
1.7
1.9
0.8
Vomiting
Flatulence
0.8
0.6
2.2
2.6
1.4
1.4
1.6
1.6
1.1
1.2
Placebo
Adverse Reaction
Diarrhea
Abdominal Pain
Nausea
Adverse Reactions Resulting in Discontinuation
In controlled clinical studies, the most common adverse reaction leading to
discontinuation from DEXILANT therapy was diarrhea (0.7%).
Other Adverse Reactions
Other adverse reactions that were reported in controlled studies at an incidence
of less than 2% are listed below by body system: Blood and Lymphatic
System Disorders: anemia, lymphadenopathy; Cardiac Disorders: angina,
arrhythmia, bradycardia, chest pain, edema, myocardial infarction, palpitation,
tachycardia; Ear and Labyrinth Disorders: ear pain, tinnitus, vertigo; Endocrine
Disorders: goiter; Eye Disorders: eye irritation, eye swelling; Gastrointestinal
Disorders: abdominal discomfort, abdominal tenderness, abnormal feces,
anal discomfort, Barrett’s esophagus, bezoar, bowel sounds abnormal,
breath odor, colitis microscopic, colonic polyp, constipation, dry mouth,
duodenitis, dyspepsia, dysphagia, enteritis, eructation, esophagitis, gastric
polyp, gastritis, gastroenteritis, gastrointestinal disorders, gastrointestinal
hypermotility disorders, GERD, GI ulcers and perforation, hematemesis,
hematochezia, hemorrhoids, impaired gastric emptying, irritable bowel
syndrome, mucus stools, nausea and vomiting, oral mucosal blistering,
painful defecation, proctitis, paresthesia oral, rectal hemorrhage; General
Disorders and Administration Site Conditions: adverse drug reaction, asthenia,
chest pain, chills, feeling abnormal, inflammation, mucosal inflammation,
nodule, pain, pyrexia; Hepatobiliary Disorders: biliary colic, cholelithiasis,
hepatomegaly; Immune System Disorders: hypersensitivity; Infections and
Infestations: candida infections, influenza, nasopharyngitis, oral herpes,
pharyngitis, sinusitis, viral infection, vulvo-vaginal infection; Injury, Poisoning
and Procedural Complications: falls, fractures, joint sprains, overdose,
procedural pain, sunburn; Laboratory Investigations: ALP increased, ALT
increased, AST increased, bilirubin decreased/increased, blood creatinine
increased, blood gastrin increased, blood glucose increased, blood potassium
increased, liver function test abnormal, platelet count decreased, total protein
increased, weight increase; Metabolism and Nutrition Disorders: appetite
changes, hypercalcemia, hypokalemia, Musculoskeletal and Connective
Tissue Disorders: arthralgia, arthritis, muscle cramps, musculoskeletal pain,
myalgia; Nervous System Disorders: altered taste, convulsion, dizziness,
headaches, migraine, memory impairment, paresthesia, psychomotor
hyperactivity, tremor, trigeminal neuralgia; Psychiatric Disorders: abnormal
dreams, anxiety, depression, insomnia, libido changes; Renal and Urinary
Disorders: dysuria, micturition urgency; Reproductive System and Breast
Disorders: dysmenorrhea, dyspareunia, menorrhagia, menstrual disorder;
Respiratory, Thoracic and Mediastinal Disorders: aspiration, asthma,
bronchitis, cough, dyspnoea, hiccups, hyperventilation, respiratory tract
congestion, sore throat; Skin and Subcutaneous Tissue Disorders: acne,
dermatitis, erythema, pruritis, rash, skin lesion, urticaria; Vascular Disorders:
deep vein thrombosis, hot flush, hypertension.
Additional adverse reactions that were reported in a long-term uncontrolled study
and were considered related to DEXILANT by the treating physician included:
anaphylaxis, auditory hallucination, B-cell lymphoma, bursitis, central obesity,
cholecystitis acute, decreased hemoglobin, dehydration, diabetes mellitus,
dysphonia, epistaxis, folliculitis, gastrointestinal pain, gout, herpes zoster,
hyperglycemia, hyperlipidemia, hypothyroidism, increased neutrophils, MCHC
decrease, neutropenia, oral soft tissue disorder, polydipsia, polyuria, rectal
tenesmus, restless legs syndrome, somnolence, thrombocythemia, tonsillitis.
Other adverse reactions not observed with DEXILANT, but occurring with
the racemate lansoprazole can be found in the lansoprazole package insert,
ADVERSE REACTIONS section.
Postmarketing Experience
Adverse reactions have been identified during post-approval of DEXILANT.
As these reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or establish
a causal relationship to drug exposure.
Eye Disorders: blurred vision
Gastrointestinal Disorders: oral edema
General Disorders and Administration Site Conditions: facial edema
Immune System Disorders: anaphylactic shock (requiring emergency
intervention), Stevens-Johnsons syndrome, toxic epidermal necrolysis
(some fatal)
Respiratory, Thoracic and Mediastinal Disorders: pharyngeal edema, throat
tightness
Skin and Subcutaneous Tissue Disorders: generalized rash, leucocytoclastic
vasculitis
DRUG INTERACTIONS
Drugs with pH-Dependent Absorption Pharmacokinetics
DEXILANT causes inhibition of gastric acid secretion. DEXILANT is likely
to substantially decrease the systemic concentrations of the HIV protease
inhibitor atazanavir, which is dependent upon the presence of gastric acid
for absorption, and may result in a loss of therapeutic effect of atazanavir
and the development of HIV resistance. Therefore, DEXILANT should not be
co-administered with atazanavir.
It is theoretically possible that DEXILANT may interfere with the absorption
of other drugs where gastric pH is an important determinant of oral
bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole).
Warfarin
Co-administration of DEXILANT 90 mg and warfarin 25 mg did not affect
the pharmacokinetics of warfarin or INR. However, there have been reports
of increased INR and prothrombin time in patients receiving PPIs and
warfarin concomitantly. Increases in INR and prothrombin time may lead
to abnormal bleeding and even death. Patients treated with DEXILANT and
warfarin concomitantly may need to be monitored for increases in INR and
prothrombin time.
Tacrolimus
Concomitant administration of dexlansoprazole and tacrolimus may increase
whole blood levels of tacrolimus, especially in transplant patients who are
intermediate or poor metabolizers of CYP2C19.
USE IN SPECIFIC POPULATIONS
Pregnancy
Teratogenic Effects
Pregnancy Category B. There are no adequate and well-controlled studies
with dexlansoprazole in pregnant women. There were no adverse fetal effects
in animal reproduction studies of dexlansoprazole in rabbits. Because animal
reproduction studies are not always predictive of human response, DEXILANT
should be used during pregnancy only if clearly needed.
A reproduction study conducted in rabbits at oral dexlansoprazole doses up
to 30 mg per kg per day (approximately 9-fold the maximum recommended
human dexlansoprazole dose (60 mg) revealed no evidence of harm to the
fetus due to dexlansoprazole. In addition, reproduction studies performed in
pregnant rats with oral lansoprazole at doses up to 40 times the recommended
human dose and in pregnant rabbits at oral lansoprazole doses up to 16 times
the recommended human dose revealed no evidence of impaired fertility or
harm to the fetus due to lansoprazole.
Nursing Mothers
It is not known whether dexlansoprazole is excreted in human milk. However,
lansoprazole and its metabolites are present in rat milk following the
administration of lansoprazole. As many drugs are excreted in human milk,
and because of the potential for tumorigenicity shown for lansoprazole in rat
carcinogenicity studies [see Carcinogenesis, Mutagenesis, Impairment of Fertility],
a decision should be made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness of DEXILANT in pediatric patients (less than 18 years
of age) have not been established.
Geriatric Use
In clinical studies of DEXILANT, 11% of patients were aged 65 years and over.
No overall differences in safety or effectiveness were observed between these
patients and younger patients, and other reported clinical experience has not
identified significant differences in responses between geriatric and younger
patients, but greater sensitivity of some older individuals cannot be ruled out.
Renal Impairment
No dosage adjustment of DEXILANT is necessary in patients with renal
impairment. The pharmacokinetics of dexlansoprazole in patients with
renal impairment are not expected to be altered since dexlansoprazole is
extensively metabolized in the liver to inactive metabolites, and no parent
drug is recovered in the urine following an oral dose of dexlansoprazole.
Hepatic Impairment
No dosage adjustment for DEXILANT is necessary for patients with mild
hepatic impairment (Child-Pugh Class A). DEXILANT 30 mg should be
considered for patients with moderate hepatic impairment (Child-Pugh
Class B). No studies have been conducted in patients with severe hepatic
impairment (Child-Pugh Class C).
OVERDOSAGE
There have been no reports of significant overdose of DEXILANT. Multiple
doses of DEXILANT 120 mg and a single dose of DEXILANT 300 mg did
not result in death or other severe adverse events. Dexlansoprazole is not
expected to be removed from the circulation by hemodialysis. If an overdose
occurs, treatment should be symptomatic and supportive.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Antisecretory Activity
The effects of DEXILANT 60 mg (n=20) or lansoprazole 30 mg (n=23) once
daily for five days on 24-hour intragastric pH were assessed in healthy
subjects in a multiple-dose crossover study.
Serum Gastrin Effects
The effect of DEXILANT on serum gastrin concentrations was evaluated in
approximately 3460 patients in clinical trials up to 8 weeks and in 1023 patients
for up to 6 to 12 months. The mean fasting gastrin concentrations increased
from baseline during treatment with DEXILANT 30 mg and 60 mg doses. In
patients treated for more than 6 months, mean serum gastrin levels increased
during approximately the first 3 months of treatment and were stable for the
remainder of treatment. Mean serum gastrin levels returned to pre-treatment
levels within one month of discontinuation of treatment.
Enterochromaffin-Like Cell (ECL) Effects
There were no reports of ECL cell hyperplasia in gastric biopsy specimens
obtained from 653 patients treated with DEXILANT 30 mg, 60 mg or 90 mg
for up to 12 months.
During lifetime exposure of rats dosed daily with up to 150 mg per kg per
day of lansoprazole, marked hypergastrinemia was observed followed by ECL
cell proliferation and formation of carcinoid tumors, especially in female rats
[see Nonclinical Toxicology].
Effect on Cardiac Repolarization
A study was conducted to assess the potential of DEXILANT to prolong the
QT/QTc interval in healthy adult subjects. DEXILANT doses of 90 mg or 300 mg
did not delay cardiac repolarization compared to placebo. The positive control
(moxifloxacin) produced statistically significantly greater mean maximum
and time-averaged QT/QTc intervals compared to placebo.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of dexlansoprazole was assessed using
lansoprazole studies. In two 24-month carcinogenicity studies, Sprague-Dawley
rats were treated orally with lansoprazole at doses of 5 to 150 mg per kg per
day, about 1 to 40 times the exposure on a body surface (mg/m2) basis of a
50 kg person of average height [1.46 m2 body surface area (BSA)] given the
recommended human dose of lansoprazole 30 mg per day.
Lansoprazole produced dose-related gastric ECL cell hyperplasia and ECL
cell carcinoids in both male and female rats [see Clinical Pharmacology].
In rats, lansoprazole also increased the incidence of intestinal metaplasia of
the gastric epithelium in both sexes. In male rats, lansoprazole produced a
dose-related increase of testicular interstitial cell adenomas. The incidence
of these adenomas in rats receiving doses of 15 to 150 mg per kg per day
(4 to 40 times the recommended lansoprazole human dose based on BSA)
exceeded the low background incidence (range = 1.4 to 10%) for this strain
of rat.
In a 24-month carcinogenicity study, CD-1 mice were treated orally with
lansoprazole doses of 15 mg to 600 mg per kg per day, 2 to 80 times
the recommended human dose based on BSA. Lansoprazole produced a
dose-related increased incidence of gastric ECL cell hyperplasia. It also
produced an increased incidence of liver tumors (hepatocellular adenoma
plus carcinoma). The tumor incidences in male mice treated with 300 mg
and 600 mg lansoprazole per kg per day (40 to 80 times the recommended
lansoprazole human dose based on BSA) and female mice treated with 150 mg
to 600 mg lansoprazole per kg per day (20 to 80 times the recommended
human dose based on BSA) exceeded the ranges of background incidences
in historical controls for this strain of mice. Lansoprazole treatment produced
adenoma of rete testis in male mice receiving 75 to 600 mg per kg per day
(10 to 80 times the recommended lansoprazole human dose based on BSA).
The potential effects of dexlansoprazole on fertility and reproductive
performance were assessed using lansoprazole studies. Lansoprazole at oral
doses up to 150 mg per kg per day (40 times the recommended lansoprazole
human dose based on BSA) was found to have no effect on fertility and
reproductive performance of male and female rats.
PATIENT COUNSELING INFORMATION
[see FDA-Approved Patient Labeling in the full prescribing information]
Information for Patients
Tell your patients to watch for signs of an allergic reaction as these could be
serious and may require that DEXILANT be discontinued.
To ensure the safe and effective use of DEXILANT, this information and
instructions provided in the FDA-approved patient labeling should be
discussed with the patient. Inform patients of the following:
DEXILANT is available as a delayed release capsule.
DEXILANT may be taken without regard to food.
DEXILANT should be swallowed whole.
• Alternatively, DEXILANT capsules can be opened and administered as
follows:
- Open capsule;
- Sprinkle intact granules on one tablespoon of applesauce;
- Swallow immediately.
Distributed by
Takeda Pharmaceuticals America, Inc.
Deerfield, IL 60015
U.S. Patent Nos. - 5,045,321; 5,093,132; 5,433,959; 6,462,058; 6,664,276;
6,939,971; and 7,285,668.
DEXILANT is a trademark of Takeda Pharmaceuticals North America, Inc.
and used under license by Takeda Pharmaceuticals America, Inc.
All other trademark names are the property of their respective owners.
©2009, 2010 Takeda Pharmaceuticals America, Inc.
For more detailed information, see the full prescribing information for DEXILANT
or contact Takeda Pharmaceuticals America, Inc. at 1-877-825-3327.
KAP0110 R6-Brf; March 2010
L-LPD-0310-2
Reference: 1. DEXILANT (dexlansoprazole) package insert, Takeda Pharmaceuticals America, Inc.
DEXILANT™ and Dual Delayed Release™ are trademarks of Takeda Pharmaceuticals North America, Inc.,
and are used under license by Takeda Pharmaceuticals America, Inc.
©2010 Takeda Pharmaceuticals North America, Inc.
LPD-01426 6/10 Printed in U.S.A.
FUNDIN G
The Impact of Decreased Industry Funding on AGA
Interacting with Industry in an Era of Ethical Concerns
Professor of Medicine and Physiology, College of Medicine, Mayo Clinic, Rochester, MN
It has been a great honor to serve as a
councillor-at-large on the Governing Board
of the AGA, and editor of AGA
Perspectives. This is my swan song as editor.
Threats to the AGA as the trusted
voice of the GI community
The AGA is the trusted and most
influential voice of the GI community. Its
core values are knowledge, integrity,
inclusiveness and service. The AGA’s core
activities relate to practice, education,
advocacy and research. AGA provides
CME for members and conference
attendees, high-quality education, and a
forum for research presentations, governed
by conflict of interest (COI) disclosure and
management. AGA is the source of trusted
information and education of the public. It
publishes peer-reviewed journals, provides
professional and public advocacy, and
clinical guidelines. AGA balances the needs
of its members in service to the public with
the perceived needs of society at large.
AGA also serves as a role model for
professional members. Finally, AGA
awards research grants and organizes
meetings where interests of industry are
juxtaposed with those of professional
members. In the past, these activities were
supported in part through operational and
CME grants from industry.
There are definite downward trends in
industry funding of national professional
organizations like the AGA. These are
reflected in publication print
advertisements (figure 1).
Reasons for this include PhRMA
guidelines on COI management, a
perceived “hostile” regulatory
Figure 1: Downward Trends in Industry Funding Are Reflected in
Publication Print Advertising Dollars: Three-Year Trend
Oncology
Cardiology
Internal Medicine
Psychiatry
Dermatology
Ob/Gyn
Orthopedic Surgery
Pediatrics
2009
Gastroenterology
($000)
0
5,000
10,000
15,000
Source: Professional Health Communication Measurement
20,000
25,000
30,000
2008
35,000
2007
40,000
45,000
environment leading to industry fleeing
from gastroenterology, anticipation of
reduced revenues for drugs/devices and a
changing landscape of the industries with
interest in GI.
AGA has significant expenses to sustain
its core activities. Given the core AGA
activity of advocacy, the organization has
made contributions to a political action
committee and significant administrative
expenditures on coding and reimbursement
to champion the interests of AGA members.
As members, we have little tradition of
philanthropy towards the AGA.
The last few years have introduced new
challenges: decreased endowment to
support the Foundation for Digestive
Health and Nutrition, decreased research
grant funding, reduced CME symposia
funded by industry during DDW® and
introduction of a DDW registration fee.
As with other professional organizations,
we pay for high-quality programs. A sane,
well-managed relationship with industry
is essential to avoid further financial
constraints on the AGA’s mission.
PMAs and their relationships
with industry
In 2009, there was a proposal1 for
controlling COI in the relationships
between professional medical associations
(PMAs) and industry (table 1). It was
recommended that these measures/sacrifices
were necessary to maintain integrity in the
best interest of the PMAs, the profession,
their members and society at large.
There is a need for balance in managing
potential COI. Any “commercial taint” or
COI of the professional organization or its
leaders might imperil membership,
credibility as a source of continuing
www.gastro.org
education, certification by the
Accreditation Council for Continuing
Medical Education (ACCME), and
credibility and effectiveness as a
“professional voice” to the public and
profession. On the other hand, AGA has
limited revenue streams.
Over the past few years, the AGA has
committed to fulfilling PhRMA guidelines
on the ethical relations with pharma and
device companies. In fact, AGA has
focused on its main missions and
established policies governing corporate
support of its programs (table 2). These
strategies go a long way to rebut the
presumption that relationships with
industry are significantly conflicting, as
reommended elsewhere.2
AGA has designed and implemented
policies for managing COI in research
funded or presented at meetings and in
journals, managing industry relations of
members of its leadership that are issuetriggered, and adhering to federal
regulations in sponsorship of programs
and industry activities at meetings.
Does financial disclosure work?
Financial disclosure is as good as the
mode in which it is communicated;
disclosures may not allow the audience to
determine whether the financial interest is
meaningful or not. Such disclosure may
taint the talk and influence the perception
of the entire educational event so that bias
may be perceived where it is not present,
or missed when it is relevant.
How can AGA establish “best
practice” COI management?
Currently, presidential officers are not
permitted to make public appearances that
are directly paid for (in whole or in part) by
companies in the pharmaceutical, medical
device or biotech industries. All members in
leadership positions, including the
Governing Board, committees, editorial
boards, council and task forces, must
disclose financial relationships with industry.
AGA conforms with ACCME standards for
disclosure. AGA also has an established COI
policy (available to members at
www.gastro.org/corporate-relations).
Table 1: Considerations Regarding the Potential
COI in Relationships between
PMAs and Industry
• Conferences, CME courses, practice guidelines, definitions of ethical norms and public
advocacy carry great weight with MDs and the public.
• PMAs receive extensive funding from pharmaceutical and device companies. Need to
manage both real and perceived COIs.
• Current PMA policies are not uniform and often lack stringency.
• Need guidelines to prevent appearance of undue industry influence.
• Recommendations would require many PMAs to transform mode of operation and
perhaps forgo valuable activities.
Table 2: AGA Policy on Relationships with Industry
• AGA will accept funding from pharmaceutical and device companies for educational,
professional and scientific activities and publications:
— AGA cannot endorse any product, brand or company, or advance its interest.
— AGA has final authority over medical/scientific content and selection of
project/program speakers, editors and authors.
— AGA prefers multiple sources of commercial support for programs.
— Only AGA representatives solicit funding for AGA programs or projects.
— No promises or guarantees as to the content of project reports or opinions.
— Medical writers contracted to AGA have no financial relationship with
sponsor.
• All project participants complete a financial disclosure form.
• AGA will acknowledge commercial support.
• AGA accepts travel funds for trainees; selection on objective criteria.
• AGA adheres to requirements of AGA, ACCME, AMA and FDA.
• All publicity regarding industry/AGA relations are reviewed/approved by AGA.
w w w.gastro.org
It is my opinion that the AGA needs to
implement additional management
strategies:
1. Product samples for professionals,
Internet access kiosks, coffee, snacks
and meals from industry should be
banned at AGA meetings.
2. A graded approach should be
introduced to manage any potential
COI associated with industry
sponsorships to the AGA. This can
be handled by AGA administrative
staff, with oversight by the Ethics
Committee.
• Greater than $10,000:
acknowledge COI by public
disclosure on the Web site.
• Greater than $50,000:
administrative staff manages
the COI and reports to the
Ethics Committee.
• Greater than $100,000: the
Ethics Committee specifically
imposes strategies to manage
the COI, including review of
content and speakers selected.
In principle, I believe that a code of
ethics, appropriate and relevant
disclosure, an honor system, and general
principles can be developed to manage
relationships between AGA and industry.
This code should apply to both direct and
indirect conflicts.
Conclusions
The reduced external fiscal support to
the AGA in the next five years will lead to
reduced subsidy of a registration fee for
DDW, and members shall have to pay
more for high-quality programs, CME
and maintenance of certification. The
AGA needs to establish a group to write
education grants for industry-sponsored
symposia, manage COI in its relationships
with industry, develop philanthropy that
is not pharma-based, engage its members
and grateful patients, streamline the
organization, and manage costs.
References _______________________________
1. Rothman DJ, McDonald WJ, Berkowitz CD, Chimonas SC,
DeAngelis CD, Hale RW, Nissen SE, Osborn JE, Scully JH
Jr, Thomson GE, Wofsy D. Professional medical
associations and their relationships with industry: a
proposal for controlling conflict of interest. JAMA 2009;
301(13):1367-72.
2. Camilleri M, Parke DW. Conflict of interest and
professional organizations: considerations and
recommendations. Acad Med 2010; 85(1):85-91.
COLONI C F LO RA
Do the Colonic Microbial Flora Serve to Trigger
Colon Cancer?
Cynthia L. Sears, MD
Hassan Ashktorab, PhD
Professor, Divisions of Infectious Diseases and
Gastroenterology, Department of Medicine,
Johns Hopkins University School of Medicine,
Baltimore, MD
Professor, Department of Medicine and
Cancer Center, College of Medicine,
Howard University, Washington, DC
Hassan Brim, PhD
Assistant Professor, Pathology Department,
Howard University, Washington, DC
There are several cancers that are now
considered to be triggered by microbes and
are of concern to gastroenterologists. Such is
the case for human papilloma virus (HPV),
which is the main cause of cervical cancer,
anal cancer, as well as some oropharnygeal
tumors, and hepatitis B and C viruses that
are strongly associated with hepatocellular
cancer. Helicobacter pylori (H. pylori) was
designated as a carcinogen by the World
Health Organization in 1995, and Marshall
and Warren were awarded the Nobel Prize
in medicine in 2005 for their seminal
discovery linking H. pylori to gastritis and
peptic ulcer disease. This discovery led to the
linkage between H. pylori and gastric cancer.
Given that the colon mucosa is continuously
in contact with ~1012 bacteria/gm feces
representing at least 500 different bacterial
species, the concept that this bacterial mass
may contribute to colon oncogenesis has
long been of interest. Through elegant
murine investigations, we now believe that
the colonic microbiota is essential to health,
contributing to epithelial, mucosal and
possibly systemic immune development, and
to nutrition. But, is there a potential downside to some of us as a result of the colonic
flora we carry?
The colonic flora adapts to a changing
environment. Both laboratory and epidemiologic data support the concept that diet
alters the composition and likely function of
the colonic microbiota. Changes in diet and
hence, colonic flora, are associated with
changing risk in developing colon cancer,
best illustrated by studies in which individuals move from low to high colon cancer
prevalence regions and then begin to
develop colon cancer at rates associated with
their new locale. A key example is African
Americans who are well known to have a
high incidence of colorectal cancer (CRC).1
African Americans share the same genetic
background with people of African descent
that have a very low rate of colon cancer.
Studies of genetic and/or epigenetic changes
have not yet led to an explanation of the
higher incidence of CRC in African
We will learn a great deal
over the next few years …
and, hopefully, we will
harness this new knowledge
towards improved
approaches to
disease prevention and
population health.
Americans. Such observations point to a
major role of diet, colonic flora and their
interactions on colon homeostasis, and
potentially oncogenesis in this population.
However, the mechanisms by which the
colonic flora may contribute to colon oncogenesis remain largely unknown. Over time,
extensive effort has been devoted to identifying what ingested carcinogens and/or
carcinogenic metabolites generated by the
colonic flora may precipitate oncogenic
epithelial changes in the colon.2 No clear
detectable “biomarkers” for clinical use to
identify those at increased risk for colon
cancer have yet emerged from these
studies. The suggestion that inflammation
is pivotal to oncogenesis dates to initial
observations by Virchow in 1863 and the
increased incidence of bowel tumors in
IBD — both Crohn’s disease and ulcerative
colitis — serve as clear examples
supporting the role of chronic inflammation in bowel oncogenesis. Many, if not
most, common colonic enteric infections
induce inflammation that, in some, persists
for an ill-defined time post-infection with,
in some cases, ongoing colonization by the
microbe. Whether ongoing colonization
and low-level colonic inflammation
induced by specific microbes, usually
bacteria, contribute to colon oncogenesis is
unknown. Certain members of bacterial
species typically classified as commensals
www.gastro.org
(i.e., doing no harm to the host) have been
proposed to possess the ability to trigger
oncogenic events in the colon. Candidate
oncogenic colonic bacteria include
Streptococcus gallolyticus (also known as
S. bovis), Escherichia coli, superoxideproducing Enterococcus fecalis and, most
recently, enterotoxigenic Bacteroides fragilis.3-7 What could be critical is not only
the specific virulence properties of strains
of these bacterial species, but the makeup
of the rest of the colonic microbiome
combined with the character of induced,
low-level mucosal inflammation over time.
High-throughput technologies are
emerging to analyze not only the composition of the bacterial communities (i.e.,
which microbes are present) within populations at high risk for developing colon
cancer, but their expressed genes (transcriptome) and metabolic function (metabolome).
Whether these tools will enable us to discern
an easily detected, affordable “fecal signature” aligned with colon malignancies or
other clinical problems central to the practice of gastroenterology, such as IBD, IBS
and malnutrition, remains the challenge.
Conversely, perhaps we will identify what
constitutes the core members of a microbiota associated with health. We will learn a
great deal over the next few years through
the Human Microbiome Project and associated projects and, hopefully, we will harness
this new knowledge towards improved
approaches to disease prevention and population health. JOURNAL EDITORS’ PICKS
The editors of Gastroenterology and Clinical Gastroenterology and
Hepatology would like to bring to your attention the following
highlighted articles from the June and July issues of the journals:
Gastro for June
Gastro for July
Medications (Nonsteroidal Anti-Inflammatory
Drugs, Statins, Proton Pump Inhibitors) and the
Risk of Esophageal Adenocarcinoma in
Patients With Barrett’s Esophagus
Association of Helicobacter pylori Infection
With Reduced Risk for Esophageal Cancer Is
Independent of Environmental and Genetic
Modifiers
By Dang M. Nguyen, et al.
By David C. Whiteman, et al.
Laparoscopy Improves Short-term Outcomes
After Surgery for Diverticular Disease
By Andrew J. Russ, et al.
Surveillance Colonoscopy is Cost-Effective for
Patients With Adenomas who Are at High
Risk of Colorectal Cancer
By Sameer D. Saini, et al.
Replicated Association between an Interleukin28B Gene Variant and a Sustained Response to
Pegylated Interferon and Ribavirin
By Jeanette J. McCarthy, et al.
Oncogenic K-Ras Turns Death Receptors Into
Metastasis-Promoting Receptors in Human
and Mouse Colorectal Cancer Cells
By Frederik J.H. Hoogwater, et al.
CGH for June
Proton Pump Inhibitors, Irritable Bowel
Syndrome, and Small Intestinal Bacterial
Overgrowth: Coincidence or Newton’s Third
Law Revisited?
By William D. Chey, et al.
References _______________________________
1. Nouraie M, Hosseinkhah F, Brim H, Zamanifekri B,
Smoot DT, Ashktorab H. Clinicopathological Features of
Colon Polyps from African-Americans. Dig Dis Sci 2010.
2. Rowland IR. The role of the gastrointestinal microbiota in
colorectal cancer. Curr Pharm Des 2009;15:1524-1527.
3. Herrera P, Kwon YM, Ricke SC. Ecology and pathogenicity of gastrointestinal Streptococcus bovis. Anaerobe
2009;15:44-54.
4. Swidsinski A, Khilkin M, Kerjaschki D, Schreiber S, Ortner
M, Weber J, Lochs H. Association between intraepithelial
Escherichia coli and colorectal cancer. Gastroenterology
1998;115:281-286.
5. Martin HM, Campbell BJ, Hart CA, Mpofu C, Nayar M,
Singh R, Englyst H, Williams HF, Rhodes JM. Enhanced
Escherichia coli adherence and invasion in Crohn's disease
and colon cancer. Gastroenterology 2004;127:80-93.
6. Huycke MM, Abrams V, Moore DR. Enterococcus faecalis
produces extracellular superoxide and hydrogen peroxide
that damages colonic epithelial cell DNA. Carcinogenesis
2002;23:529-536.
7. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen
HR, Huso DL, Brancati FL, Wick E, McAllister F,
Housseau F, Pardoll DM, Sears CL. A human colonic
commensal promotes colon tumorigenesis via activation of
T helper type 17 T cell responses. Nat Med 2009;15:10161022.
w w w.gastro.org
Proton Pump Inhibitors and Histamine-2
Receptor Antagonists Are Associated With
Hip Fractures Among At-Risk Patients
By Douglas A. Corley, et al.
Interleukin-28B Polymorphism Improves
Viral Kinetics and Is the Strongest
Pretreatment Predictor of Sustained Virologic
Response in Hepatitis C Virus-1 Patients
By Alexander J. Thompson, et al.
Differences in Clinical Profile and Relapse
Rate of Type 1 Versus Type 2 Autoimmune
Pancreatitis
By Raghuwansh P. Sah, et al.
Dissociation Between Intrahepatic
Triglyceride Content and Insulin Resistance in
Familial Hypobetalipoproteinemia
By Anastassia Amaro, et al.
CGH for July
A 52-Year-Old Man With Heartburn: Should
He Undergo Screening for Barrett’s Esophagus?
By Seth D. Crockett, et al.
Increased Incidence of Small Intestinal
Bacterial Overgrowth During Proton Pump
Inhibitor Therapy
By Lucio Lombardo, et al.
Low-Dose Maintenance Therapy With
Infliximab Prevents Postsurgical Recurrence
of Crohn’s Disease
By Dario Sorrentino, et al.
Functional Dyspepsia Impacts Absenteeism
and Direct and Indirect Costs
By Richard A. Brook, et al.
Hepatitis B Virus DNA Level Predicts
Hepatic Decompensation in Patients With
Acute Exacerbation of Chronic Hepatitis B
By Wen-Juei Jeng, et al.
Paris Criteria Are Effective in Diagnosis of
Primary Biliary Cirrhosis and Autoimmune
Hepatitis Overlap Syndrome
By Edith M.M. Kuiper, et al.
Continuous Therapy With Certolizumab
Pegol Maintains Remission of Patients With
Crohn’s Disease for up to 18 Months
By Gary R. Lichtenstein, et al.
Incidence and Prognosis of Different Types of
Functional Renal Failure in Cirrhotic Patients
With Ascites
By Silvia Montoliu, et al.
Spontaneous Bacterial Peritonitis Prior to
Liver Transplantation Does Not Affect
Patient Survivals
By Rawad Mounzer, et al.
LIVER C A N C ER
Should We Screen for Hepatocellular Carcinoma in Patients
with Cirrhosis? If So, in Whom and How?
Hashem B. El-Serag, MD, MPH
Professor of Medicine, Michael E. DeBakey VA Medical Center,
Baylor College of Medicine, Houston, TX
The HCC epidemic
There is an epidemic of hepatocellular
carcinoma (HCC) in the U.S., where HCC is
currently the fastest growing cause of
cancer-related death. As the incidence rates
for HCC have tripled in the past two
decades,1 the distribution of HCC has
shifted towards white Hispanic and nonHispanic individuals of younger ages (45
and 60 years). This increase is at least
partially attributable to a rise in hepatitis C
virus-related HCC.
Most patients with HCC are diagnosed at
an advanced stage of disease when survival
is poor (five-year survival less than 5
percent), except in patients who receive
potentially curative therapy (liver transplant,
surgical resection or ablation) where a
considerable improvement in survival has
been observed (five years range between 40
percent and 70 percent). However, population-based studies in the U.S. indicate that
only approximately 10 percent of patients
with HCC receive these treatments.2
Therefore, HCC surveillance has been advocated to detect HCC at an early stage, when
critical treatment can be applied.
Does HCC surveillance work?
Practice guidelines from AASLD have
recommended HCC surveillance for highrisk patients.3 In a randomized controlled
trial (RCT) of nearly 19,000 hepatitis B
virus (HBV)-infected patients in China, it
was shown that HCC surveillance with
serum alpha fetoprotein (AFP) and abdominal ultrasound at repeated six-monthly
intervals improves survival — a 37 percent
reduction in HCC-related mortality was
reported.4 However, RCT (also in China)
reported that surveillance for HCC is not
beneficial. Several non-randomized trials, as
well as observational studies, have found a
survival benefit in those identified with
small and early tumors, but these have their
unavoidable biases.5 Collectively, the
evidence to support the efficacy of HCC
surveillance in high-risk groups is reasonable, but not very strong. Given the very
with HCC have AFP levels higher than
100 ng/mL. Given the very low rates of
HCC surveillance in community practice, I
have not abandoned the use or the recommendation of using AFP (in combination
with ultrasound), as it is easily used and
interpreted and is widely available. Other
The repetitive nature over relatively short periods of HCC
surveillance, coupled with the need for prompt recall strategies,
somewhat complicated diagnostic evaluation and the limited
availability of potentially curative therapy are likely obstacles in
the face of an effective HCC surveillance program.
low likelihood of new evidence from RCTs,
I generally advocate as well as practice
HCC surveillance in high-risk groups who
have no severe or uncontrolled medical or
psychiatric comorbidities.
Who and how?
I recommend HCC surveillance to
patients with cirrhosis or advanced hepatic
fibrosis irrespective of etiology, and in
adult patients (older than 40 to 50 years)
with HBV, irrespective of cirrhosis. I use a
combination of AFP and liver ultrasound
for HCC surveillance every six months,
although a one-year interval may be
equally effective. Ultrasound has approximately 60 percent to 65 percent sensitivity
and greater than 90 percent specificity.6 At
a serum cutoff level of 20 ng/mL, AFP has
low sensitivity (25 percent to 65 percent)
for detecting HCC and is therefore considered inadequate as the sole screening test;
this is because only one third of patients
tests, such as des-gamma carboxy
prothrombin (DCP) and lectin-bound AFP
(AFP-L3), are available but I have not
started using them. In recent U.S. studies,
AFP was more sensitive than DCP and
AFP-L3 for the diagnosis of early-stage
HCC, especially at cutoff of 10.9 ng/mL.7
A combination of these markers only
marginally improves surveillance for early
HCC (may increase sensitivity, but the
specificity drops). CT and MRI — while
excellent diagnostic tests — have not been
tested for surveillance, and their high cost
as well as possible harms (e.g., radiation
with CT) are likely prohibitive in most
practice settings.
Once a screening test is abnormal, the
most reliable diagnostic tests are triplephase helical CT and triple-phase, dynamic
contrast-enhanced MRI; the latter is
slightly better in the characterization and
diagnosis of HCC. The hallmark of HCC
during CT or MRI is the presence of artewww.gastro.org
rial enhancement followed by delayed
hypointensity of the tumor in the portal
venous and delayed phases. Guidelines state
that the diagnosis of HCC in a patient with
cirrhosis can be confidently established if a
focal hepatic mass greater than 2 cm is
identified with a CT or MRI imaging technique that shows typical features for HCC.
However, I generally require both tests to
be suggestive of HCC if I am to avoid a
biopsy. For focal hepatic mass with atypical
or discrepant (between CT and MRI)
imaging findings, a mass size of 1 to 2 cm
or a focal hepatic mass detected in a noncirrhotic liver should undergo a biopsy. A
negative biopsy result does not completely
rule out malignant disease, and the nodule
should be further studied at three- to sixmonth intervals until it is seen to disappear,
enlarge or display diagnostic characteristics
of HCC. Nodules smaller than 1 cm should
be followed with ultrasound at three- to
six-month intervals. If over a period of two
years growth has not been observed,
routine surveillance at six-month intervals
is suggested.
The extent of utilizing HCC surveillance
in clinical practice is low. At least three
studies found very low rates of screening
among patients diagnosed with HCC. In
the largest of these studies, Davila et al.
(Hepatology 2010, in press) reported that
among 541 patients diagnosed with HCC
during 1994 to 2002 and with a prior
diagnosis of cirrhosis, only 29 percent
received annual surveillance in the three
years before HCC diagnosis. The repetitive
nature over relatively short periods of
HCC surveillance, coupled with the need
for prompt recall strategies, somewhat
complicated diagnostic evaluation and the
limited availability of potentially curative
therapy, are likely obstacles in the face of
an effective HCC surveillance program. References _______________________________
1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma:
epidemiology and molecular carcinogenesis.
2. El-Serag HB, Siegel AB, Davila JA, Shaib YH, CaytonWoody M, McBride R, McGlynn KA. Treatment and
outcomes of treating of hepatocellular carcinoma among
Medicare recipients in the United States: a populationbased study. J Hepatol 2006;44:158-66.
3. Bruix J, Sherman M; Practice Guidelines Committee,
American Association for the Study of Liver Diseases.
Management of hepatocellular carcinoma. Hepatology
2005;42:1208-36.
4. Zhang BH, Yang BH, Tang ZY. Randomized controlled
trial of screening for hepatocellular carcinoma. J Cancer
Res Clin Oncol 2004;130:417-22.
5. El-Serag HB, Marrero JA, Rudolph L, Reddy KR.
Diagnosis and treatment of hepatocellular carcinoma.
6. Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers
MA, Marrero JA. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients
with cirrhosis. Aliment Pharmacol Ther 2009;30:37-47.
7. Marrero JA, Feng Z, Wang Y, Nguyen MH, Befeler AS,
Roberts LR, Reddy KR, Harnois D, Llovet JM, Normolle
D, Dalhgren J, Chia D, Lok AS, Wagner PD, Srivastava S,
Schwartz M. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009;137:110-8.
MEMBER N EW S
Bruce E. Sands, MD, MS, AGAF,
to Lead GI Division of The Mount Sinai
Medical Center
Bruce E. Sands, MD, MS, AGAF, will join Mount Sinai School of
Medicine as chief of the Henry D. Janowitz Division of
Gastroenterology. Dr. Sands’ world-renowned experience in
research, patient care and advocacy in Crohn’s disease and ulcerative colitis makes him a welcome leader at Mount Sinai School of
Medicine’s nationally-ranked gastroenterology program. “Dr.
Sands’ combination of skill and experience as a researcher, clinician, educator and administrator provide the necessary foundation for him to follow in the footsteps of the giants of the field
who built Mount Sinai’s reputation as one of the world’s top
gastroenterology programs,” said Paul E. Klotman, MD,
chairman of the Samuel Bronfman department of medicine and
Murray M. Rosenberg professor of medicine, Mount Sinai School
of Medicine.
Showing his passion for improving patient care, Dr. Sands is
chair of the Clinical Research Alliance of the Crohn’s and
Colitis Foundation of America. He is committed to participating
in ongoing research and has been published in several journals,
including the New England Journal of Medicine,
Gastroenterology and Gut. Dr. Sands is also a reviewer for
many prominent journals, including
Gastroenterology and the New England
Journal of Medicine, and an associate editor
for the journal, Inflammatory Bowel
Diseases. Recognized by his colleagues at
Massachusetts General Hospital for his
extensive work in gastrointestinal diseases,
Dr. Sands is the medical co-director of the
Bruce E. Sands,
Crohn’s & Colitis Center. He is an associate
MD, MS, AGAF
professor of medicine at Harvard Medical
School, and recently served as acting chief
of the gastrointestinal unit at Massachusetts General Hospital.
Several organizations have acclaimed Dr. Sands for his commitment to research and patient care. He is vice chair of the
Immunology, Microbiology and Inflammatory Bowel Disease
Section of the AGA, and a fellow of the AGA and the American
College of Gastroenterology.
In 2006, he was named Humanitarian of the Year by the New
England Chapter of the Crohn’s and Colitis Foundation of
America, and the Massachusetts General Physician Organization
honored him for “Excellence in Action” in recognition of his
distinguished patient care. Dr. Sands has consistently been
chosen as one of the “Best Doctors in America” by Castle
Connolly Medical Ltd.
Source: The Mount Sinai Medical Center
New Job? Promotion? Share Your News. AGA members are invited to send news of promotions,
appointments and awards to communications@gastro.org. Please include “AGA Perspectives” in your subject line.
w w w.gastro.org
SOLO/GRO U P P RA C TI C E
Solo Practice — Dying, or Alive and Well?
Kimberly M. Persley, MD
Gastroenterologist, Texas Digestive Disease Consultants, Dallas
I am a gastroenterologist in a mega group
in northern Texas. I am one of more than
38 gastroenterologists in my group, and one
of 14 gastroenterologists on the medical
staff at a large community hospital. There is
one gastroenterologist on the medical staff
who is in a solo practice. Why are there so
few gastroenterologists going solo these
days? Is this type of practice dying?
When I finished my gastroenterology
fellowship in June 2000, I toyed with the idea
of staying in academic medicine. After much
soul searching, I decided to go into private
practice. I interviewed with mega GI groups,
single-specialty group practices and multispecialty group practices. I finally decided to
join a single-specialty group of four other
physicians. I never thought about a solo practice and did not know anyone in a solo practice. It seemed so “old fashioned.” I felt that a
solo practice would soon become extinct.
I had a list of reasons why a solo practice
was not a good idea. First, I thought starting
a solo practice required a lot of money. I
had a lot of medical school debt and would
need to start repayment of my student loans.
I did not have wealthy family members to
borrow money from in order to start up a
practice, and I was certain that no bank
would loan money to someone just out of
fellowship and unproven as a clinician. In
addition, I did not have good financial
management skills. Therefore, it really
seemed like financial suicide. Second, I did
not want to work in isolation from my
peers. I like to talk about challenging cases
and get another perspective from my
colleagues. I could imagine the hours of
loneliness — without a single patient —
going deeper into debt in my solo practice.
Third, I did not want to be on-call all the
time. I love gastroenterology; however, I
value time out of the hospital and office. I
wanted to take vacations and feel comfortable that my patients would be well cared
for while I was away. In a solo practice, I
would likely spend more time in the office
and less time pursuing the other desires of
the heart. Why would anyone want to take
the financial risk, work in relative isolation
or spend a large amount of time in the
office? This was the life I did not want.
My perspective changed slightly after
joining a group practice. I shared a call
schedule with a gastroenterologist who was
in a solo practice. To my surprise, he seemed
very happy in his practice. Over the years,
we have talked about the pros and cons.
As I see it, the advantage is being your own
boss; there is complete autonomy and
control. Only the physician will make the
without partners or an affiliation with a
group of partners. This can be a lonely experience, e.g., a patient with an unusual clinical
problem comes to the office and there is no
one around to provide an in-office consultation. Second, financial costs are higher. The
fixed cost of running a practice includes rent,
nurse salary, receptionist salary, billing, electronic medical records, computers, bookkeeper, etc.; this cost is borne by one physician. Reimbursements may be lower due to
decreased leverage to negotiate payments.
However, in tough economic times, patients
may cancel office visits and procedures due to
high deductibles. Overhead does not change
and must be paid. Finally, the work days tend
to be longer. Clinical staff is small and the
physician will spend after-office hours going
through charts and results.
Good organizational skills, financial management skills
and a willingness to accept risks are the attributes
needed to consider a solo practice.
decisions on how the practice will function.
No consensus is required to make changes
in office operations, scheduling of patients
or hiring of employees. Let’s be honest: not
everyone plays well in the sandbox.
Sometimes personal quirks make it difficult
to work with others. The other advantage is
the one-on-one patient relationship. Patients
will see the same physician every office visit.
The gastroenterologist may become a friend,
counselor or confidant over time.
Over the years, many of our conversations
were centered on the problems with a solo
practice. First, the physician practices alone
In 2010, is solo practice dying, or alive
and well? It depends on what part of the
country one lives. It also depends on
personal wants and desires of the gastroenterologist. Good organizational skills, financial management skills and a willingness to
accept risks are the attributes needed to
consider a solo practice. Do your homework
and know what is happening in the GI
market. The beauty of medicine is the
freedom to create the practice of your
dreams. This dream for some may be in the
form of a solo practice. Has solo practice
gone the way of the dinosaur? Not yet. www.gastro.org
INTERNATIONA L CORNER
Lab and Clinical Interests:
An International Perspective
Tarik Asselah, MD, PhD
Hepatologist/Scientist, Service d’Hépatologie, Hôpital Beaujon, Clichy, France
An exchange program for the Association
of National European and Mediterranean
Societies of Gastroenterology (ASNEMGE)
rising stars and AGA research scholars was
organized to foster exchange of scientific and
practical experience and ideas between young
U.S. and European researchers; a program of
visits by rising stars and others was initiated
at DDW® 2009.
I grew up in Algiers, Algeria. Then I came
to Paris, where I graduated from medical
school and hold a PhD in virology. I am
currently a hepatologist/scientist at Hôpital
Beaujon (University Paris VII Diderot,
INSERM U773), where I am mainly
involved in viral hepatitis B and C studies.
My research focuses on mechanisms of
non-response to standard care in hepatitis
C. The treatment of chronic hepatitis C
with pegylated interferons (PEG-IFNs) and
ribavirin currently gives a sustained virological response rate of about 55 percent.
Several new molecules are in development
to increase the chance of a response to
treatment. Since a significant number of
patients will fail to respond to treatment or
will experience significant side effects, it is
of major interest to predict response to
treatment as early as possible. This represents the starting point of my group’s
research. The failure to respond to exogenous PEG-IFN in non-responders could
indicate a blunted response to IFN. Most
of the deregulated genes found associated
with response code molecules are secreted
into the serum and can constitute a logical
approach to the development of serum
markers as predictors of the response.
Furthermore, it is an important challenge
to understand mechanisms of non-response
in order to try to overcome this.
w w w.gastro.org
In 2009, I was selected as a rising star
by ASNEMGE and members of the
GASTRO 2009 UEGW/WCOG program
committee for my studies on the mechanisms of failure to treatment in chronic
hepatitis C. When I came to Chicago for
the 2009 DDW meeting, the AGA Institute
International Committee arranged a visit
with Donald M. Jensen, MD, professor of
medicine, director, Center for Liver
Diseases, and his team at the University of
Chicago Medical Center. The day before
my visit, I thought about the importance
of science innovation, medicine and technology in the U.S. I also wondered about
national research budgets, the strength of
the country’s scientific workforce, the
attraction all over the world and the fact
that most medical and scientific reviews
are American. Even if it was a short visit, I
knew I would learn a lot from it.
Early in the morning, I met with
Professor Jensen to discuss the health system
in the U.S. and how different it is from that
of the French. He explained all of the activities of his group: clinical, teaching and
managing clinical trials; he scheduled my
day so that I could learn more about the
department’s clinical work, clinical trials and
research. My visit reinforced my beliefs that
we have to work hard, be self confident and
trust in our ideas.
I met the clinical research team to
discuss hepatitis C virus (HCV) clinical
trials and learned about the organization
of trials, from informed consent to the end
of follow-up. I also received an overview
of the physician practice in U.S. hospitals.
Previously, I thought that I knew others
from scientific meetings, but it is very
different to follow someone in his everyday
job. Afterwards, I visited Glenn Randall,
Evgeniy Baryshnikov, MD, PhD
Evgeniy Baryshnikov, MD, PhD, a
young staff scientist in the bowel disease
division of the Central Research Institute
of Gastroenterology in Moscow, Russia,
visited the IBD center of the University of
Chicago shortly before DDW 2009. He
comments how useful his visit was,
which included learning about how U.S.
physicians treat IBD patients, watching
procedures and visiting the research laboratories. He was particularly amazed
when he viewed the use of a mouse
colonoscope to visualize the progress of
experimental ulcerative colitis in vivo. He
thanked Peter Holt, MD, AGAF, and the
AGA Institute International Committee
as well as Gene Chang, MD, and Eliko
Matagrano, MD.
PhD, and toured his lab, which mainly
focuses on HCV. I learned about the roles
of HCV-host interactions in viral replication and pathogenesis.
In the afternoon, I discussed clinical
processes and met with nurses to hear about
their important role in the follow-up of
patients, the explanations they provide and
the importance of adherence to treatment.
Then I spoke with Rohit S. Satoskar, MD,
and we visited the hospital together. Later, K.
Gautham Reddy, MD, explained to me the
training and organization of the hospital.
Throughout the day, I really appreciated the
hospitality, friendship and high professionalism of the entire group; everyone was very
welcoming. It was really informative for me
to see how a U.S. clinical service is organized. I learned a lot from this visit and I’m
very grateful to all the people who took time
to meet with me.
AGA Digestive Health
Outcomes Registry™
OUTCOME S-DRIVEN QUALI TY
FOR GI C ARE
Find out how the
AGA Registry can
benefit your practice.
Watch an
on-demand
Webinar at
www.AGARegistry.org.
Helping you to:
Improve patient outcomes.
Enhance practice efficiencies and profitability.
Demonstrate value to payors, purchasers and
patients.
Evaluate care of patient populations.
Submit 2010 Physician Quality Reporting
Initiative data for hepatitis C measures group.
Easy-to-use, fully integrated system — the registry is designed to fit seamlessly into your existing
practice workflow. Data can be entered into the registry via a Web interface or directly submitted using
an Eelectronic medical record (EMR) system from an AGA Registry preferred EMR provider. gMed is
the first provider to be designated as a registry preferred EMR provider. Check the registry Web site at
www.AGARegistry.org for an updated list of preferred providers.
Initial clinical areas: IBD and colorectal cancer prevention — additional
clinical areas are in development.
For more information or to enroll,
visit www.AGARegistry.org.
A PROGRAM OF
THE AGA INSTITUTE

Perspectives Template - American Gastroenterological Association

Transcription

Similar documents

March 2016 - AGA Washington, DC Chapter

AGA KHAN PAYS TRIBUTE TO GENOCIDE VICTIMS IN KIGALI

manipede - Jillie Reil

Check Up From The Neck Up

May 2006 - AGA Washington, DC Chapter

Thursday, April 24 @ 7:30pm AMC BarryWoods 24

mti photoscreener - Ruidoso Valley Noon Lions Club

May- June 2014 - Mid-Missouri AGA chapter

- Aga Khan Development Network

HIGHLIGHTS OF PRESCRIBING INFORMATION Clostridium difficile