{InsIde thIs Issue}

STAMPEDE Study: A Surgical Perspective p.3

Service Spotlight: Swallowing Center p.4

Pancreatic Cyst Registry Helps Avoid Unneeded Surgery p.6

Digestive Disease institute | Fall | 2012

Digestthis

Fecal Incontinence Therapy: Raising the Bar p.1

in their genes – p.8

DIgESTIvE DISEASE InSTITUTE CHAIR John Fung, MD, PhD

MAnAgIng EDIToR glenn Campbell

ART DIRECToR Mike viars

MARkETIng MAnAgERS Priya Barra Matthew Chaney

ConTRIBUTIng PHoTogRAPHERS Russell Lee Cleveland Clinic Center for Medical Art & Photography

dear Colleagues,genetics-related research is the focus of our cover story in this issue of Digest This.

For clinician researchers, success in unraveling the genetic underpinnings of disease

has at least two key ingredients: a large volume of patients with (or at risk of) a given

disease, and a supportive scientific infrastructure.

As our cover story profiles the recent genetic research achievements of three clini-

cian investigators from across Cleveland Clinic’s Digestive Disease Institute, a pattern

emerges. Each investigator has drawn on specimens and experience from a formidable

base of patients with complex and challenging diseases, and each has deployed clini-

cal insight and scientific know-how to make more sense of these diseases at the popu-

lation level — and, in some cases, even at the patient level. They have been assisted

in their efforts by the size and multidisciplinary expertise of Cleveland Clinic as well as

through collaborations with partners beyond Cleveland Clinic.

The result has been significant steps along the path toward more personalized medicine,

whether in more tailored and effective methods of detecting cancer, enhanced ability to

predict disease recurrence, or insights that may lead to more targeted therapies.

other articles in this issue continue the theme of personalized medicine outside the

context of genetic research. For instance, Dr. R. Matthew Walsh (p. 6) explains how

we have used our extensive pancreatic cyst registry to develop a protocol for pancreatic

cyst management that recognizes that some patients with these cysts do not require

resection and can be safely observed. And Drs. Steven D. Wexner and Brooke gurland

(p. 1) draw on our substantial experience in sacral nerve stimulation for fecal inconti-

nence to give advice on which patients are the best candidates for this highly effective

new intervention.

The personalized medicine promised by genetic research and other investigations is

one more form — albeit an especially potent one — of valuing the individual patient

experience. Putting a premium on patient experience has been a guiding principle

for Cleveland Clinic, as reflected by our reorganization under the patient-oriented

institute model several years ago. Under this model, the Digestive Disease Institute

comprises a breadth of services related to digestive health. I’m delighted that this

issue spotlights clinical and research insights from a wide sampling of those services.

Take a moment to review our diverse activities within these pages, and let me know

if you see opportunities to partner in improving the experience of all our patients.

Respectfully,

John Fung, Md, Phd Chairman, Cleveland Clinic Digestive Disease Institute

Director, Cleveland Clinic Transplant Center Professor of Surgery, Lerner College of Medicine fungj@ccf.org

Cleveland Clinic #2 in the U.S. – Gastroenterology

clevelandclinic.org/digestive 855.REFER.123 {1}

Digestive Disease Institute

95 – 100%of Cleveland Clinic patients

have been able to move

on to implantation of a

permanent stimulator.

sacral nerve stimulation: Raising the Bar in Fecal Incontinence Therapy

special Feature

sacral nerve stimulation (sns) offers patients with chronic fecal incontinence an

opportunity to achieve improved or even complete control of their symptoms. the procedure,

used to treat urinary incontinence in the united states since 1997, received FDa approval for

use in fecal incontinence in 2011. clinical trials of sns for fecal incontinence were completed

at cleveland clinic’s main campus and cleveland clinic Florida, and colorectal surgeons at

both locations now offer the procedure for fecal incontinence.

‘PACEMAkER FoR THE AnAL SPHInCTER’

SnS is like a cardiac pacemaker for the anal sphinc-

ter. Surgeons first implant temporary subcutaneous

stimulators into the sacral nerve. For patients who

experience improvement of more than 50 percent in

the number of fecal incontinence episodes during a

two-week trial, surgeons go on to implant a perma-

nent stimulator in a second procedure.

The procedure requires only local anesthesia and

intravenous sedation and does not have a long

recovery period.

CoMPARES WELL WITH ALTERnATIvES

Steven D. Wexner, MD, Chairman of Colorectal Sur-

gery and Chief Academic Officer at Cleveland Clinic

Florida, was lead international investigator on the SnS

fecal incontinence trials that led to FDA approval. He

presented results at the 2010 meeting of the Ameri-

can Society of Colon and Rectal Surgeons, of which he

is now president, and was lead author of the full study

report published in Annals of Surgery in 2010. He

also was lead author of another key study, examining

infection rates in SnS, published in Journal of Gastro-

intestinal Surgery (see Suggested Reading, p. 2).

Dr. Wexner’s experience with SnS is among the broad-

est in the country. He has performed more than 50 of

the procedures and reports having achieved excellent

outcomes in most patients.

“I have a lot I can compare with SnS, as I have been

lead investigator in numerous trials for several other

predicate devices,” he says. “SnS achieves vastly bet-

ter outcomes with far less frequent and significantly

less severe complications.”

About 95 percent of Dr. Wexner’s patients move on

to the second-stage procedure. Advancement to the

second-stage procedure has been possible for all seven

of the patients treated by Brooke gurland, MD, and as-

sociates in the Colorectal Center for Functional Bowel

Disorders at Cleveland Clinic’s main campus.

BEST CAnDIDATES

Drs. Wexner and gurland both say there is no “ideal

candidate” for this procedure. For example, age (young

vs. old) does not seem to affect outcomes.

“More patients are turning out to be very good

candidates than we expected,” Dr. Wexner says.

Dr. gurland says the best candidates are often those

with the worst control. These are patients who have

tried other treatments, such as bulking agents and

antidiarrheal medications, and perhaps even unsuc-

cessful prior surgical procedures. “We are finding that

patients with loose stools who are poor candidates for

sphincteroplasty may have improvements with SnS,”

she notes.

oTHER InDICATIonS LIkELy

Dr. Wexner expects that, with time, approved indica-

tions for SnS will include chronic constipation and ir-

ritable bowel syndrome. Additionally, success with the

procedure has been reported anecdotally from outside

the United States in patients with rectal pain, sphincter

injuries and anal fissures.

“SnS is not replacing or augmenting the anal sphincter,

but rather creating a neuromodulation that enhances

sensation, alerting patients earlier when they need to

go to the bathroom, which is an entirely different

approach to treating these problems,” he says.

steven d. Wexner, Md

Brooke Gurland, Md

{2} digest this Fall | 2012

Cleveland Clinic

PATIEnTS ARE PLEASED

Patients are delighted with the outcomes, both surgeons report. “I get more positive

comments about SnS than about any other treatment we offer for fecal incontinence,”

Dr. Wexner says. “Patients are very happy, not just mildly happy.”

Many other treatments achieve therapeutic success — a 50 percent or greater reduction in

symptoms — in about 35 to 65 percent of patients, he says. In the Annals of Surgery study, at

12 months, 83 percent of subjects achieved therapeutic success and 41 percent achieved 100

percent continence. Therapeutic success was 85 percent at 24 months. Incontinent episodes

decreased from a mean of 9.4 per week at baseline to 1.9 at 12 months (Figure).

Efficacy appears to endure through at least five years after SNS placement, according to

five-year data (Figure) presented in June at the American Society of Colon and Rectal Surgeons

annual meeting by study co-investigator Tracy Hull, MD, Section Head of Pelvic Floor Disor-

ders at Cleveland Clinic’s main campus.

“Patients can still have a bad day — for instance, if they get diarrhea — but many patients

report improved bowel control,” says Dr. gurland.

“SnS gives patients their lives back,” Dr. Wexner says. “They no longer need to stay home near

a bathroom or carry a change of clothes at all times. SnS is easier and safer and achieves

better results than any of our other options to treat fecal incontinence.”

ADDRESSIng MULTIPLE SyMPToMS

Because urologists and urogynecologists have been able to use SnS for a number of years,

Dr. Gurland often works with colleagues in these fields to identify patients who have multiple

symptoms that could benefit from SNS, particularly those with pelvic floor disorders.

“Previously, with patients who had prolapse or sphincter defects, we had to correct their ana-

tomical problems first, then work on their function,” she explains. “Now we can go directly to

SnS in appropriate patients. It’s great to have options beyond sphincteroplasty, injectables or

medical management and to be able to involve patients in deciding which is best for them.”

Dr. Wexner can be reached at 954.659.5251 or wexners@ccf.org. Dr. Gurland can be

reached at 216.445.3604 or gurlanb@ccf.org. ■

Feca

l inc

ontine

nce

epis

odes

per

wee

k (m

ean)

Years since implant

109.4

1.9 1.7 1.6

9

8

7

6

5

4

3

2

1

0Baseline (n=120)

1 (n=106)

3 (n=78)

5 (n=72)

suggested Reading

Wexner SD, Coller JA, Devroede g, et al. Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study. Ann Surg. 2010;251(3):441-449.

Wexner SD, Hull T, Edden y, et al. Infection rates in a large investiga-tional trial of sacral nerve stimulation for fecal incontinence. J Gastrointest Surg. 2010;14(7):1081-1089.

Another new nAFC Center of ExcellenceIn May 2012, Cleveland Clinic’s Section

of Female Pelvic Medicine and Recon-

structive Surgery at our main campus

location was designated a “Center of

Excellence (CoE): Continence Care for

Women” by the national Association for

Continence (nAFC).

With this designation, our Cleveland

location joins Cleveland Clinic Florida’s

Pelvic Floor Center as one of the few

medical centers in the nation to be

named a CoE by the nAFC, which

takes into account training, clinical

experience, interdisciplinary resources

and patient satisfaction statistics.

The Section of Female Pelvic Medicine

and Reconstructive Surgery is part of

Cleveland Clinic’s ob/gyn & Women’s

Health Institute and the Department

of Colorectal Surgery in the Digestive

Disease Institute.

“This joint recognition reflecting the

collaborative expertise of two separate

institutes underscores our commitment

to interdisciplinary care for women

with urinary and fecal incontinence,”

says Tracy Hull, MD, Section Head

of Pelvic Floor Disorders. “We believe

that each patient deserves to be cared

for by a team of clinicians who work

collaboratively to help the patient

participate fully in the best treatment

pathway for her.”

clevelandclinic.org/digestive 855.REFER.123 {3}

Digestive Disease Institute

the staMpeDe study – a surgical perspective

cleveland clinic’s staMpeDe trial has been making headlines since March (see sidebar

for study details), but much of the buzz has been in diabetes circles. We asked Matthew

D. Kroh, MD, a minimally invasive surgeon in our Digestive Disease institute who performs

many bariatric procedures (but who was not involved in staMpeDe), for his take on the

study’s likely implications for bariatric surgery.

Q: In light of stAMPede, will bariatric surgery

be considered earlier in the management of obese

patients with uncontrolled type 2 diabetes?

dr. Kroh: I believe it will. For years retrospective studies

have shown that bariatric surgery is effective for treat-

ment of type 2 diabetes. now STAMPEDE has demon-

strated that prospectively, using a randomized design

with excellent follow-up and with a control arm of best

medical management. I think this will lead to greater

consideration of bariatric surgery as an earlier interven-

tion as opposed to an end-stage intervention for these

patients, and I certainly believe that is appropriate.

Q: how important were surgical skill and surgical

volume to the results achieved in stAMPede?

dr. Kroh: Cleveland Clinic has been designated a

Center of Excellence by the American Society for Meta-

bolic and Bariatric Surgery (ASMBS), so it would be

inappropriate for these findings to be broadly applied

to every general or bariatric surgeon performing bar-

iatric surgery. But the findings are probably applicable

to the more than 400 ASMBS-designated Centers of

Excellence, which all meet certain criteria for volume,

outcomes and ancillary services.

Q: Which factors should guide patient selection

to optimize the risk-benefit calculation?

dr. Kroh: Historically there has been a misperception

that bariatric surgery has a very high complication

rate. With the advent of ASMBS Centers of Excellence,

complications have been significantly reduced and bar-

iatric surgery is now on par with many other commonly

performed operations. The STAMPEDE results further

confirm this. So the calculation now is whether to in-

tervene earlier to prevent the end-stage manifestations

of diabetes, and I think we should. So any patient with

type 2 diabetes who meets the nIH criteria for bariatric

surgery — BMI of 35 or greater with weight-related

medical conditions, or BMI of 40 or greater — should

be considered, to prevent the progression of what is a

severely disabling chronic disease.

Q: As longer-term results emerge from stAMPede,

what should surgeons pay particular attention to?

dr. Kroh: We know that weight loss after gastric

bypass and sleeve gastrectomy continues beyond 12

months — up to 24 months in some patients. I’ll be

looking to see if the STAMPEDE patients’ glycemic

control improves beyond the initial 12 months as well,

and by how much. The corollary is that at around five

or 10 years, some proportion of patients regain some

weight, although it’s usually insignificant compared

with their initial weight loss. We’ll need to see what ef-

fect that may have on long-term resolution or remission

of diabetes. So looking at the durability of the effects of

surgery on glycemic control over two years, five years

and beyond is going to be very important.

Q: Any last thoughts?

dr. Kroh: I hope this high-quality data will start to

change practice patterns in diabetes management.

In view of these findings, morbidly obese patients

should be given an option to consider bariatric

surgery for potential remission of diabetes earlier

in their treatment course as opposed to prolonged

therapy with antihyperglycemic regimens.

Dr. Kroh has appointments in the Digestive Disease

Institute’s Department of General Surgery and in

the Bariatric & Metabolic Institute. Contact him

at 216.445.9966 or krohm@ccf.org. ■

Matthew d. Kroh, Md

STAMPEDE at a glancedesign: Randomized,

nonblinded, single-center

(Cleveland Clinic) comparison

of intensive medical therapy

alone with medical therapy

plus either Roux-en-y gastric

bypass or sleeve gastrectomy

Population: 150 obese

patients with uncontrolled

type 2 diabetes being

followed for five years

Primary endpoint:

Percentage of patients with

an HbA1c ≤ 6.0 percent

Results: At 12 months

(first planned analysis),

significantly more patients

in the gastric bypass group

(42 percent) and the sleeve

gastrectomy group (37

percent) achieved the primary

endpoint compared with the

medical therapy group (12

percent). Weight loss was

also significantly greater in

both bariatric surgery groups

vs. the medical therapy arm.

Schauer PR, kashyap SR, Wolski D, et al. N Engl J Med. 2012;366(17):1567-1576.

{4} digest this Fall | 2012

Cleveland Clinic

service spotlight: Center for Swallowing and Esophageal Disorders

One of the nation’s few dedicated swallowing centers has a new leader. sigurbjorn

Birgisson, MD, Ma, joined cleveland clinic’s Digestive Disease institute in February 2012

as Director of the center for swallowing and esophageal Disorders (swallowing center).

The appointment marks a homecoming of sorts

for Dr. Birgisson, who trained at Cleveland Clinic in

the mid-1990s and 2000. “Some of the best esoph-

agologists in the nation have practiced and taught

at Cleveland Clinic over the years,” he says. “I am

honored to lead a program with such a rich history

of excellence in swallowing disorder practice

and research.”

Dr. Birgisson, who previously directed the endoscopy

and motility unit at the national University Hospital of

Iceland, rounds out a team of four specialist physicians

in the Swallowing Center. The others are Steven Shay,

MD; Prashanthi Thota, MD; and Monica Ray, MD. Two

full-time nurses perform all the center’s motility, pH

and breath-test studies.

A FoCUS on CoMPLEx CASES

The Swallowing Center team collaborates with mul-

tidisciplinary specialists from across Cleveland Clinic

— radiologists, otolaryngologists, thoracic and general

surgeons, pathologists, speech pathologists and oth-

ers — to manage some 2,500 patients a year. Their

patients fall into two main groups: those with dyspha-

gia from a variety of causes, and those with difficult-

to-manage gERD with typical and atypical symptoms.

The program’s particular strengths lie in dealing with

several complex conditions:

Achalasia. “We see more than 150 new achalasia

patients a year,” says Dr. Birgisson. “Many are referred

from out of state.” Most often they are treated surgically,

mainly by Cleveland Clinic thoracic surgeons such as

Thomas Rice, MD, with whom the Swallowing Center’s

esophagologists closely consult. “Dr. Rice probably has

more experience treating achalasia patients surgically

than anyone in the country,” Dr. Birgisson notes.

Reflux management in lung transplant patients. Reflux

is common in lung transplant recipients and can lead

to organ rejection. Because Cleveland Clinic has one

of the nation’s largest lung transplant programs, there

is great demand for the Swallowing Center’s expertise.

“These patients often have troublesome reflux before

or after surgery, as well as problems with swallowing

or gastroparesis,” explains Dr. Birgisson. “We evaluate

many of them before or after transplant and consult on

reflux management strategies.”

Extraesophageal reflux syndromes, such as chronic

laryngitis, chronic cough and asthma. “It can be very

difficult to establish or exclude the association between

reflux and these symptoms and disorders,” Dr. Birgis-

son says. “A multidisciplinary approach with consider-

able testing is typically needed.” Similarly, the Swal-

lowing Center sees many patients referred to Cleveland

Clinic following failed reflux surgery — another group

that can pose big management challenges.

sigurbjorn Birgisson, Md

“It can be difficult to establish or exclude the association between

reflux and symptoms of extraesophageal reflux syndromes such as

chronic laryngitis, chronic cough and asthma. A multidisciplinary

approach is typically needed.” – Sigurbjorn Birgisson, MD

clevelandclinic.org/digestive 855.REFER.123 {5}

Digestive Disease Institute

RESEARCH PRIoRITIES

Dr. Birgisson sees many of the above conditions as the

Swallowing Center’s priority research areas, largely by

virtue of the volume of patients seen. “We have a great

opportunity to study a variety of motility and reflux prob-

lems in lung transplant recipients,” he says. Likewise,

the center is exploring research initiatives to leverage its

nearly matchless volume of achalasia cases.

Further research opportunities stem from the center’s

registry of approximately 2,000 Barrett’s esophagus

patients — one of the largest such registries in the

nation. About one-third of the registry’s patients have

dysplasia, which drives the center’s use of the registry

to ensure regular follow-up and to monitor patient

progress following ablation therapy, endoscopic muco-

sal resection or other treatments.

CUSToMIzED EMR-InTEgRATED QUESTIonnAIRE

An early priority for Dr. Birgisson has been developing

an electronic patient questionnaire specific to esopha-

geal disease. The questionnaire is being created within

the framework of Cleveland Clinic’s knowledge Pro-

gram, an interactive database that helps quantitatively

measure the effectiveness of medical decisions for

patients with specific diseases. The aim is for patients

to complete the questionnaires on touch-screen tablets

before each clinical visit to allow good longitudinal

tracking and to automatically update the electronic

medical record (EMR) in real time, prior to the visit.

“our questionnaire will cover patients with symptoms

of dysphagia and gERD, and the aim is to correlate

symptoms with findings on tests such as endoscopy,

manometry and pH studies,” explains Dr. Birgisson.

He expects it will enhance treatment monitoring and

promote better-targeted testing. Implementation is

planned for later this year.

RETURn oF ‘SWALLoW THIS’

One smaller but personally significant initiative

Dr. Birgisson has championed is the reintroduction

of the Swallowing Center’s monthly multidisciplinary

“Swallow This” meetings he remembers fondly from his

motility fellowship at Cleveland Clinic in the mid-1990s.

These monthly meetings gather the center’s staff with

colleagues from other relevant specialties to discuss the

management of complex cases. “The sessions are stimu-

lating,” he says, “and underscore the broad expertise

and resources we can bring to bear for patients with the

most challenging swallowing and esophageal disorders.”

Contact Dr. Birgisson at 216.444.0780

or birgiss@ccf.org. ■

2,500 Patients seen annually

>150 new achalasia patients seen annually

>600 pH studies annually

>1,100 Esophageal manometries annually

>500 Breath tests annually

the Center for swallowing and esophageal disorders

By the numbers

“Some of the best esophagologists in the nation have practiced and taught at Cleveland

Clinic over the years. I am honored to lead a program with such a rich history of excellence

in swallowing disorder practice and research.” – Sigurbjorn Birgisson, MD

{6} digest this Fall | 2012

Cleveland Clinic

pancreatic cyst registry Helps patients avoid surgeryRegistry-based protocol guides cyst management when there is no initial indication of cancer.

r. Matthew Walsh, MD, Department chair of general surgery, began compiling a registry

of pancreatic cysts 12 years ago to help differentiate patients with cancer risk from those

with no indications of risk. today, the registry contains more than 1,500 cases, making it

one of the largest such registries in the world.

“Pancreatic cysts have become a major clinical issue,”

says Dr. Walsh, who has a special interest in biliary,

pancreatic and gastrointestinal surgery. “There has

been a huge explosion in their detection, largely due

to improved imaging. About 15 to 20 percent of the

population could develop these cysts at some point,

often later in life.”

A MoRE SELECTIvE APPRoACH To RESECTIon

Cleveland Clinic was the first institution to study these

patients in detail, and its findings have helped change

the way pancreatic cysts are managed worldwide.

“Previously, the perception was that all cysts had to be

removed due to the presumed high likelihood that they

would eventually lead to pancreatic cancer,” Dr. Walsh says.

However, because surgery has about a 2 percent

mortality rate and a 40 percent morbidity rate, iden-

tifying patients who don’t need surgery is important,

especially because patients with cysts often have no

symptoms and should not be subjected to the risks

of surgery, he says.

“By accurately identifying the type of cyst at an early

stage, we can determine which patients require resec-

tion and which can be safely observed,” he explains.

PRoToCoL FoR CyST MAnAgEMEnT

To that end, Cleveland Clinic has used the registry

to develop a protocol for pancreatic cyst management

(Figure 1). “It was important to translate our retro-

spective data into a prospective patient management

scheme that led to the first natural history results

showing that patients could be safely selected not

to undergo surgery,” Dr. Walsh notes.

Patients who have solitary cysts with a normal main

duct, no atypical cytology in fluid aspirated from the

cyst and no appearance of a nodule, among other

factors, are now generally followed without surgery.

Patients with intraductal papillary mucinous neo-

plasms (IPMns) involving the main duct are advised

to have resection, as are those with mucinous cystic

neoplasms. Dr. Walsh says the optimal management

of IPMns arising from side branches of the main

pancreatic duct is less clear, as their natural history

and malignant potential are less well-defined. He notes,

however, that a recent small study indicating a 20

percent incidence of malignancy at 10 years suggests

that at least careful observation is warranted.

“We feel we need to show there is a real risk of cancer

to justify the risk of undertaking surgery; the registry

and systematic protocol have helped us do that,”

R. Matthew Walsh, Md

symptoms

Resection eus aspiration

MRI with secretin

Asymptomatic

≥1.5 cm <1.5 cm

eus cyst aspiration; CeA, amylase, cyto/mucin

symptomatic with suspicious imaging

(nodule/main duct IPMn)

Atypia All neg (serous)

Mucin/CeA Pos amyl

(sB-IPMn)

Mucin/CeA neg amyl

(MCn)

Interval scanning 6 mo, then yearly

size increase

suspicious imaging

Figure 1. Cleveland Clinic protocol for pancreatic cyst management. (IPMn = intraductal papillary mucinous neoplasm; EUS = endoscopic ultrasound-guided; CEA = carcinoembryonic antigen; MCn = mucinous cystic neoplasm; SB-IPMn = side-branch IPMn)

clevelandclinic.org/digestive 855.REFER.123 {7}

Digestive Disease Institute

he explains. “Too many patients had surgery in the

past because they erroneously thought they were at

high risk for cancer.”

Dr. Walsh acknowledges that the protocol is subject

to constant revision, but he notes it has held up well

over time. of the patients

identified for observation,

only about 10 percent

have eventually gone on

to need surgery.

Prior to the registry-based

protocol, almost all pa-

tients with pancreatic cysts

would have been advised

to undergo surgery. Today,

using cyst size as one vari-

able, only 16 percent of

cysts smaller than 3 cm are recommended for

resection. That proportion rises to 50 percent

for cysts larger than 3 cm.

PATIEnTS CRAvE gUIDAnCE

The protocol has been developed in conjunction with

Cleveland Clinic gastroenterologists, who obtain the

fluid samples in these patients (Figure 2). Patients

travel from all over the country to be seen in the

pancreatic clinic held weekly by Dr. Walsh and

gastroenterologist Tyler Stevens, MD.

“Patients often don’t know what to do when they learn

they have a pancreatic cyst, and clearly many are

concerned that they harbor

a diagnosis of pancreatic

cancer,” Dr. Walsh says. “It

is a high-referral diagnosis.”

Some will still want sur-

gery, even if their risk signs

indicate otherwise. Family

history of pancreatic cancer

is often a motivating factor.

“We talk with them about

all the risks, and sometimes

we agree with them,” Dr. Walsh says. “Education is

very important with these patients.”

Moving forward, Dr. Walsh hopes to preserve more

cystic fluid obtained from patients for evaluation

as more sophisticated testing technology emerges,

including proteomics-based assessment.

Dr. Walsh can be contacted at 216.445.7576

or walshm@ccf.org. ■

Figure 2. Ultrasound image of a pancreatic cyst being aspirated.

“We need to show there is a

real risk of cancer to justify the

risk of undertaking surgery; the

registry and systematic protocol

have helped us do that.”

– R. Matthew Walsh, MD

16% The proportion of pancre-

atic cysts smaller than 3 cm

recommended for resection

under the Cleveland Clinic

registry-based protocol

{8} digest this Fall | 2012

Genetics-related investigations increasingly figure at the center of the research

enterprise in cleveland clinic’s Digestive Disease institute. these studies are using

genetic information for everything from understanding causes of disease risk to earlier

disease detection to predicting recurrence and individual response to therapies.

We checked in with three clinician researchers from

across the Institute with significant genetic research

initiatives under way or recently published. Their

stories illustrate how our genetics-related studies

are contributing to the understanding of a range of

digestive diseases — and how they are starting to

change clinical practice.

In PURSUIT oF PERSonALIzED MEDICInE

In CoLoRECTAL CAnCER

A hotbed of genetics research within the Institute is

the Colorectal Cancer Translational Science Research

Laboratory, directed by colorectal surgeon Matthew

kalady, MD.

Colon and rectal cancers are a natural for genetic re-

search, says Dr. kalady, in view of their clinical hetero-

geneity and the fact that their prognosis and outcomes

are determined by underlying molecular and genetic

changes. “our lab uses advanced high-throughput tech-

nology and analysis to develop gene signature profiles

to predict colorectal cancer recurrence and response to

therapies,” he notes. “These types of studies are steps

on the path toward personalized medicine.”

one recent contribution along that path came in a

national Cancer Institute-supported multicenter study

published in Science (2012;336[6082]:736-739) in

May. Dr. kalady collaborated with colleagues from other

institutions for this study that identified variant enhancer

loci (vELs), or “master switches” that control key genes

whose altered expression is defining for colon cancer.

“vELs seem to distinguish colon cancer from normal

colon,” Dr. kalady explains. “They are unique, previ-

ously unidentified factors.” The study’s broad findings

suggest that individual differences within vELs may

exert important influences on individuals’ differing

susceptibilities to colon cancer.

cOver Feature

clevelandclinic.org/digestive 855.REFER.123 {9}

This recent vELs work dovetails with other gene signa-

ture profiling projects from Dr. Kalady’s lab, some with

more near-term clinical implications:

Prediction of recurrent rectal cancer. Dr. kalady’s

lab recently identified a particular gene signature as-

sociated with recurrence of early-stage rectal cancer

(J Am Coll Surg. 2010;211[2]:187-195). now his

team is working to validate its finding in a larger

set of patients so that the signature can be applied

to practice and tested in clinical trials. “About 20

percent of patients with stage I or II rectal cancer are

at risk for recurrent disease,” he says. “We hope to

use this tumor gene expression profile to identify and

target these patients with additional therapy after

surgery to reduce their risk of recurrence.”

Linking mutations with outcomes. Earlier this year the

kalady lab showed that mutations in the BRAF onco-

gene are associated with distinct clinical characteris-

tics and with significantly worse survival in colorectal

cancer (Dis Colon Rectum. 2012;55[2]:128-133).

“This gene has been known to be mutated in colorectal

cancer,” Dr. kalady says. “We examined the impact of

the mutation in a large series of patients and demon-

strated a difference in clinical outcome.”

enhanced cancer staging accuracy. In June the lab

published results showing that distinct gene expres-

sion signatures from primary rectal cancers can help

determine the presence or absence of lymph node

metastasis (Dis Colon Rectum. 2012;55[6]:628-

639). “We’ve identified a signature that seems to

have fairly high accuracy in predicting lymph node

involvement by analyzing tissue from the primary

tumor,” Dr. kalady says. “Lymph node involvement

is one of the most important determinants that guide

preoperative therapy, a decision that must be made

before we have definitive pathologic staging. Tradi-

tional means of preoperative staging are only about

70 to 80 percent accurate in predicting node positivity.

This more objective staging tool can help inform the

management approach to the tumor.”

Predicting response to chemoradiation. Drawing on

the Department of Colorectal Surgery’s large tumor

bank, the lab is using total genome sequencing to

evaluate factors associated with complete response

to preoperative chemoradiation for rectal cancer. “By

isolating RnA from tumor samples collected before

chemoradiation treatment, we are working to identify

key pathways that promote tumor killing or tumor

resistance,” Dr. kalady explains. Statistical evaluation

of these results may help identify which patients will

benefit most from chemoradiation, as 15 to 20 per-

cent of patients have complete tumor regression after

chemoradiation. This work may also ultimately guide

Clinician Investigators Share How Their Genetic Studies Are Already Shaping Digestive Disease Practice

in their genes:

“Using our genetic studies, we have uncovered unique interactions between colorectal

cancer cells and surrounding cells, and we’ve identified novel targets for intervention

that may inhibit cancer cell growth.” — Matthew Kalady, MD

Figure. Endoscopic findings in a patient with IBD-associated flat dysplasia that went undetected on white-light endos-copy (left) and narrow-band imaging endoscopy (right) showing no visible lesions. Adenocarcinoma was detected on random and blind biopsy and histology. genetic markers for cancer were present in the stool specimens obtained at the time of the current endoscopy and stool specimens obtained at the time of endoscopies two years earlier.

development of new therapies that target the key tumor-related

pathways identified.

This potential for new therapies is what Dr. kalady sees as the biggest

potential implication of his lab’s genetics work beyond its opportuni-

ties for greater individualization of patient management. “Using our

genetic studies, we have uncovered unique interactions between

colorectal cancer cells and surrounding cells, and we’ve identified

novel targets for intervention that may inhibit cancer cell growth,” he

says. “We are working on novel therapies and therapy combinations

that may increase treatment effectiveness.”

gEnETIC STooL SCREEnIng —

A FUTURE STAnDARD FoR CAnCER DETECTIon?

Bo Shen, MD, is another Digestive Disease Institute clinician doing

genetics-related research in colorectal cancer — specifically in

patients with underlying inflammatory bowel disease (IBD) and

pouchitis. Although his genetics work focuses solely on diagnosis,

its implications are no less far-reaching. That’s because Dr. Shen,

a prolific researcher in the Department of Gastroenterology and

Hepatology, is working to refine a technology with the potential to

substantially complement screening and surveillance colonoscopy.

“Although colonoscopy with biopsy is the gold standard for colorectal

cancer screening and surveillance,” says Dr. Shen, “it misses about 5

percent of adenomas, particularly those that are flat or serrated” (Figure).

So he and a small group of collaborators from Cleveland Clinic and

Cleveland State University are working to improve detection of these

elusive adenomas and precancerous lesions by refining a battery of

tests to screen stool samples for genetic tumor markers.

Their battery applies customized quantitative PCR techniques to

detect the presence of methylated DnA markers in fecal samples.

Dr. Shen hopes they can do so with enough sensitivity and at a

low-enough cost to make it a competitive method of colorectal

cancer surveillance and screening.

In its current state of development covering a limited number of tumor

markers, the battery has a sensitivity for colon cancer of about 85

percent, Dr. Shen says. The challenge is to screen for as many of the

dozens of identified colon cancer markers as possible — to maximize

sensitivity — without it costing too much. If his team succeeds, the

payoff will be in terms of earlier and more sensitive detection of

adenomas and tumors.

Their work is building on a case report they recently published (Int J

Colorectal Dis. 2011;26:951-953) supporting their hypothesis that

fecal methylated DnA markers may precede endoscopic and histo-

logic detection of colorectal adenocarcinoma by at least 12 months.

That case was one of about 350 for which Dr. Shen has drawn on

his extensive collection of frozen stool samples — more than 4,000

dating back to 2002 — to check for the presence of tumor markers

in earlier samples from IBD patients later found to have adenomas or

colon cancer. In some cases the samples show tumor markers several

years before adenoma or carcinoma was detectable otherwise.

Dr. Shen’s ongoing work to refine the screening battery takes advan-

tage of a proprietary stool preservative, developed by his Cleveland

State University collaborator, that allows samples to be stored at

room temperature for long periods without degradation.

Dr. Shen notes that while a couple of other centers are conducting

similar genetic analyses of stool samples using their own proprietary

{10} digest this Fall | 2012

preservatives, his team’s quantitative PCR technique has achieved

the greatest sensitivity for cancer detection to date. He also believes

his team’s technique has cost advantages. “We are at the forefront in

sensitivity, and our technique is considered to be cost-effective, which

is key to being competitive with colonoscopy,” he says.

Indeed, he sees this screening of stool samples for genetic markers as

a serious competitor to colonoscopy within the next five to 10 years,

especially in populations at risk for inflammation-induced colorectal

cancer, like the IBD patients he often manages. He says that while some

gastroenterologists may not initially welcome the threat to colonoscopy

fees, patient benefits (earlier detection and avoiding the discomforts of

colonoscopy) will ultimately prevail, especially because they align with

the imperative for healthcare cost control.

Meanwhile, Dr. Shen’s team continues to perfect its stool-screening

battery while it applies for nIH grant funding as well as venture capi-

tal investment to conduct a large clinical trial of the battery.

LoCATIng A kEy PIECE oF THE ULCERATIvE CoLITIS PUzzLE

While Dr. Shen pursues his work to genetically detect a potential

complication of IBD — colon cancer — one of his Department of

gastroenterology and Hepatology colleagues, Jean-Paul Achkar, MD,

who holds the kenneth Rainin Endowed Chair in IBD Research, is

working to unravel key genetic risks that predispose patients to the

development of IBD.

“When genetic studies in IBD began over 20 years ago, it was pre-

dicted that there would be only a small number of genes implicated

in causing IBD,” says Dr. Achkar. “However, to date, 163 genes have

been associated with IBD — some only with ulcerative colitis, some

only with Crohn’s disease and some common to both diseases. So

what’s been found has far exceeded what was expected. That un-

derscores the complexity of the genetics of IBD and has led to some

uncertainty about where to go from here with all these genes.”

one point that was clear amid the uncertainty was that the HLA

locus on chromosome 6 was likely to be important in the genetics

of IBD and other inflammatory conditions, as it contains multiple

immune-related genes. “But it has been extremely difficult to pinpoint

a specific gene, let alone a specific abnormality within it, to explain

some of the association with that locus, due to the multiple, closely

positioned genes in that region,” Dr. Achkar says.

So he and the head of the IBD group in Cleveland Clinic’s Lerner Re-

search Institute, Claudio Fiocchi, MD, recently teamed with researchers

from the University of Pittsburgh, led by Richard Duerr, MD, to better

define where the signal for association with IBD was coming from.

They performed genotyping of DnA samples collected at Cleveland

Clinic and the University of Pittsburgh from more than 500 patients

with ulcerative colitis, 600 patients with Crohn’s disease and 1,400

controls and analyzed over 10,000 single nucleotide polymorphisms

across the HLA region. Then, in collaboration with researchers from

Brigham and Women’s Hospital, Carnegie Mellon University and the

University of Pittsburgh, they applied sophisticated imputation and

association techniques to test further genetic and amino acid variants

across the HLA locus. In a paper published online in December 2011

(Genes Immun. 2012;13[3]:245-252), they confirmed the suspicion

that variation in the HLA-DRβ1 gene was strongly related to ulcer-

ative colitis. More notably, they identified a very specific defect in this

gene — a variation at amino acid position 11 — as being strongly

associated with the risk of developing ulcerative colitis. This position

is in a crucial binding pocket likely to have significant influence on

immune response to antigens.

“There are certainly other genes and defects involved in ulcerative

colitis, but this one appears to be one of the big players in driving risk

for the disease,” says Dr. Duerr.

Dr. Achkar adds that the finding is significant for two reasons: “First,

it ties in nicely with theories of abnormal immune response being

triggered by responses to certain antigens. Second, since it opens the

potential to better understand how the body responds to antigens, it

could certainly help lead to different approaches to treatment or to

altering the immune system.”

After this paper was published, another study implicated the exact

same amino acid position as an important cause of rheumatoid ar-

thritis (Nat Genet. 2012;44[3]:291-298). “This independent finding

in another immune-mediated disease is a nice validation of our study,”

Dr. Achkar says. “It confirms that something important is going on at

this position.”

Dr. Kalady can be contacted at 216.445.2655 or kaladym@ccf.org;

Dr. Shen at 216.444.9252 or shenb@ccf.org; and Dr. Achkar at

216.444.6513 or achkarj@ccf.org. ■

Matthew Kalady, Md: Profiling gene signatures to personalize colorectal cancer management.

Bo shen, Md: Refining a screening battery for cancer markers in stool samples.

Jean-Paul Achkar, Md (front), with colleague Claudio Fiocchi, Md: Working to unravel the genetics of IBD.

clevelandclinic.org/digestive 855.REFER.123 {11}

{12} digest this Fall | 2012

Cleveland Clinic

laparoscopic right Hepatectomy eases patient recoveryMultidisciplinary surgical oncology approach offers best chance for cure with smooth recovery.

case stuDy

DECEMBER 2011

A 51-year-old man is referred to Eren Berber, MD, at

Cleveland Clinic for management of liver metastases

from colorectal cancer. He had been diagnosed with co-

lon cancer with synchronous liver and pulmonary metas-

tases and had resection of his colonic primary in october

2010. He was started on the FoLFox chemotherapy

regimen and bevacizumab until September 2011, with

resolution of pulmonary metastases. This was followed

by the FoLFIRI chemotherapy regimen and cetuximab.

Upon presentation to Dr. Berber, CT and PET scans

show four lesions in the right lobe of the liver, with

no evidence of extrahepatic disease (Figure 1). Right

liver resection via a laparoscopic approach is recom-

mended, and the patient gives consent.

FEBRUARy 2012

The patient undergoes laparoscopic resection of the

right liver lobe containing the four tumors. This opera-

tion employs many highly advanced technologies,

including ultrasonic energy devices to divide the liver

parenchyma as well as laparoscopic ultrasound and an

intraoperative navigation device that enables precise re-

moval of the right lobe of the liver with all four tumors

while leaving a remnant liver with adequate inflow and

outflow (Figure 2). The surgical team, which includes

Dr. Berber and Cristiano Quintini, MD, performs the

procedure with incisions smaller than 1 cm and an

8-cm incision used to extract the specimen (Figure 3).

The patient’s recovery is smooth, and he is discharged

home on postoperative day 4 without complications.

eren Berber, Md

Figure 1. CT scan at presentation showing four lesions in the right lobe of the liver.

Laparoscopic liver

procedures require

expertise in advanced

surgical instrumenta-

tion, including energy

devices, ablation tech-

niques, laparoscopic

ultrasound and novel

navigational devices.

– Eren Berber, MD

clevelandclinic.org/digestive 855.REFER.123 {13}

Digestive Disease institute

Figure 3. The small incisions made possible by the laparoscopic approach.

MARCH 2012

At the patient’s two-week follow-up visit, his examina-

tion and laboratory tests are normal. He is back to his

baseline activity at home. The pathology report shows

that his tumors were removed with a clear surgical

margin. He is now under a cancer follow-up protocol

with Dr. Berber that includes office visits, serum CEA

(tumor marker) levels and CT scans every three months

for the first two years.

DISCUSSIon

Management of colorectal cancer metastases to the

liver is challenging. Liver resection gives patients the

best chance for cure, and a laparoscopic approach

provides significant benefits in terms of recovery, such

as decreased pain, earlier return of gastrointestinal

function and a shorter hospital stay. However, there

are not many centers that can do major liver resections

laparoscopically, as this requires advanced skills in

laparoscopic and open liver surgery.

Cleveland Clinic’s Liver Tumor Clinic, which started its

laparoscopic liver resection program in 2006, is able

to offer laparoscopic major liver surgery to patients by

drawing on its ability to form surgical teams skilled

in both advanced laparoscopic and conventional liver

surgery. As demonstrated in this case, laparoscopic

liver procedures require expertise in advanced surgical

instrumentation, including energy devices, ablation tech-

nologies, laparoscopic ultrasound and novel navigational

devices. The Liver Tumor Clinic also brings to bear the

multidisciplinary surgical oncology approach that cases

like this require, in which surgeons collaborate closely

with the oncologist to prepare the patient for surgery

using the latest neoadjuvant chemotherapy options.

Dr. Berber has appointments in the Digestive Disease

Institute’s Department of General Surgery and the

Endocrinology & Metabolism Institute’s Center for

Endocrine Surgery. He specializes in the minimally

invasive treatment of liver tumors with laparoscopic

resection and radiofrequency ablation. He can be

reached at berbere@ccf.org or 216-445-0555. ■

Figure 2. Intraoperative photo of the navigation system showing position of the laparoscopic instruments on the patient’s three-dimensional liver anatomy to enable precise surgical planning.

{14} digest this Fall | 2012

Cleveland Clinic

cirrhosis-related sarcopenia:Cleveland Clinic Researcher Advances Management of a Major but Neglected Complication

A hepatologist in Cleveland Clinic’s Digestive Disease Institute is the recipient of the first

u.s. research grant for studying the molecular mechanisms of malnutrition and muscle

loss in cirrhosis, but he’s not preoccupied with that distinction. in fact, he wishes he

had more fellow grant awardees in this field. “Allocation of more resources to examine

malnutrition in cirrhosis is critically needed,” explains Srinivasan Dasarathy, MD.

That’s because malnutrition in cirrhosis results in

sarcopenia, or loss of skeletal muscle mass, the most

common complication of cirrhosis. Because cirrhosis

is widespread, affecting an estimated 2.5 million U.S.

residents, cirrhosis-related sarcopenia confers a large

clinical burden. Sarcopenia reduces both survival and

quality of life in cirrhotic patients, and it is a major

contributor to other complications of cirrhosis, such

as encephalopathy, ascites and portal hypertension.

It also worsens outcomes after liver transplantation.

“Sarcopenia affects every phase of liver disease,” says

Dr. Dasarathy, a clinician-researcher in the Depart-

ment of gastroenterology and Hepatology with joint

appointments in the Transplant Center and the De-

partment of Pathobiology.

Despite these impacts, there are no effective thera-

pies for sarcopenia of cirrhosis, largely because its

mechanisms are not yet known. This is the result of

a lack of recognition of the condition, scarce research

funding and the dominance of research interest in

aging-related sarcopenia, which is likely to have dif-

ferent mechanisms.

Dr. Dasarathy has been working for more than a

decade to increase understanding of cirrhosis-related

sarcopenia, and his lab has made important advances

in the last few years in both animal and human studies.

THE RoLE oF MyoSTATIn

Dr. Dasarathy’s grant referred to above is a five-year

nIH award to examine the mechanisms of sarcopenia

of cirrhosis using a combination of tracer methodol-

ogy and molecular biology tools both in vivo and with

in vitro cell systems. This work will build on his lab’s

considerable animal research in this field to date,

which includes the first demonstration of the causal

role of the protein myostatin in the reduced skeletal

muscle mass that accompanies cirrhosis (J Hepatol.

2011;54[5]:915-921).

Those animal studies prompted Dr. Dasarathy’s team

to generate a compound called follistatin that blocks

myostatin and its effects on muscle. They used an ani-

mal model to show that follistatin was able to reverse

cirrhosis-related muscle loss without affecting the liver.

Enthusiasm for follistatin is tempered, however, by the

compound’s proliferative effect on cells, which raises

the specter of carcinogenicity.

But Dr. Dasarathy remains undaunted. “There are

certainly ways to generate small-molecule products

that can block myostatin quite specifically, without

follistatin’s effect on other tissues,” he says.

TRAnSLATIon To HUMAnS WELL UnDER WAy

Meanwhile, Dr. Dasarathy’s research team at Cleveland

Clinic is forging ahead with the first human studies

to explore whether large doses of amino acids will

improve muscle mass in cirrhotics.

“We have an ongoing protocol in which we are giving

cirrhotics as well as healthy controls a large dose of

leucine along with other amino acids that cirrhotics

are deficient in,” he says. “We view these amino acids

not as nutrients but rather as signaling molecules, like

drugs that have very specific effects on the down-

stream consequences of myostatin.” Participants un-

dergo muscle biopsy, blood studies, and measurements

of strength and muscle mass before and after the treat-

ment. “The aim is to see if the molecular defects we’ve

identified in human cirrhotic muscle are reversible or

not,” he explains.

srinivasan dasarathy, Md

clevelandclinic.org/digestive 855.REFER.123 {15}

Digestive Disease institute

cirrhosis-related sarcopenia:Cleveland Clinic Researcher Advances Management of a Major but Neglected Complication

So far six cirrhotics and six controls have been evalu-

ated, and preliminary results are “very encouraging,”

says Dr. Dasarathy. His goal is to study 20 cirrhotics

and 20 controls for more definitive results.

Based on its preliminary findings, his lab has been

awarded a grant from the Japanese government to

study precisely how the combination of leucine and

other amino acids is able to prevent and potentially

reverse muscle loss in cirrhosis.

QUESTIonIng ASSUMPTIonS In LIvER TRAnSPLAnT

In a separate human study, Dr. Dasarathy’s team is

doing muscle biopsies in cirrhotic patients before and

after liver transplantation to determine why muscle

mass does not improve — and even declines — follow-

ing transplant. “Transplantation used to be considered

a cure for all cirrhotic complications, but that’s been

found not to be the case for the nutritional complica-

tions,” he notes. “We think sarcopenia may contribute

to impaired quality of life after transplant, and we’d

like to see if we can fix that.”

Fixing or avoiding the effects of sarcopenia — whether

through amino acids or compounds that block the

effects of myostatin overexpression — is the ultimate

goal of Dr. Dasarathy’s research in all cirrhotic patients,

regardless of whether they undergo liver transplant.

“Because loss of muscle mass is nearly universal in

cirrhotics and affects survival, quality of life, other

complications and post-transplant outcomes,” he says,

“reversing sarcopenia has the potential to improve the

life of patients at any stage of liver disease.”

Dr. Dasarathy can be reached at 216.444.2980 or

dasaras@ccf.org. ■

“We think sarcopenia may contribute to impaired quality of life after liver transplant,

and we’d like to see if we can fix that.” – Srinivasan Dasarathy, MD

Biochemical, endocrine, cytokine, metabolic responses

Increased myostatin expression; decreased protein synthesis

decreased survival

Reduced quality of life

Risk of other complications

decreased post- transplant survival

hepotocellular dysfunction

Portacaval shunting

Cirrhosis

sarcopenia

Figure. Schematic showing contributors to, and effects of, sarcopenia of cirrhosis.

40%Proportion of cirrhotics

in whom sarcopenia is

reported.

{16} digest this Fall | 2012

Cleveland Clinic

newstaff}CoLoRECTAL SURgERy

John P. Cullen, Md

Specialty interests: Minimally invasive colorectal surgery, robotic-assisted colorectal surgery, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, colonoscopy, colon and rectal cancer, anal cancer, diverticular disease

Locations: Hillcrest Hospital, Twinsburg Family Health and Surgery Center, Willoughby Hills Family Health Center Office: 440.312.7111

Giovanna da silva, Md

Specialty interests: Laparoscopic surgery, colorectal cancer, ulcerative colitis, Crohn’s disease, diverticulitis, fecal incontinence, benign anorectal diseases

Location: Weston, Fla. Office: 954.659.5278

gASTRoEnTERoLogy AnD HEPAToLogy

Brian Baggott, Md

Specialty interests: Inflammatory bowel disease, gastroenteritis, Barrett’s epithelium, endoscopic mucosal resection

Location: Wooster Milltown Specialty and Surgery Center Office: 330.287.4500

sigurbjorn Birgisson, Md

Specialty interests: Achalasia, Barrett’s esophagus, caustic ingestion, eosinophilic esophagitis, esophageal cancer, esophageal disorders, esophageal varices, esophagitis

Location: Main campus Office: 216.444.0780

Jessica Philpott, Md, Phd

Specialty interest: general gastroenterology

Locations: Main campus, Richard E. Jacobs Health Center (Avon) Office: 216.445.7692

Abdullah shatnawei, Md

Specialty interests: Celiac disease, constipation and fecal incontinence, eosinophilic esophagitis, esophageal motility disorders, GI endoscopy, gastroesophageal reflux disease, gI motility disorders, H. pylori infection, inflammatory bow-el disease, intestinal transplantation, insulin resistance, malabsorption, enteral and parenteral nutrition, medical education and education of fellows/residents, metabolic syndrome, motility disorders, nutritional problems, obesity, peptic ulcer disease, short bowel syndrome, therapeutic endoscopy including difficult colonoscopy and polypectomy

Location: Main campus Office: 216.445.2301

gEnERAL SURgERy

Kareem Abu-elmagd, Md, Phd

Specialty interests: gut rehabilitation and autologous bowel reconstruction, intestinal and multivisceral trans-plantation, surgery for portomesenteric venous thrombosis, portal hypertensive surgery, complex abdominal surgery, solitary pancreas transplant, islet cell transplant, pediatric abdominal organ transplantation

Location: Main campus Office: 216.444.8292

Kalman Bencsath, Md

Specialty interests: Advanced laparoscopic surgery, hiatal hernia repair, nissen fundoplication, gastric surgery, splenectomy, pancreatic surgery, biliary surgery, hernia repair, general surgery

Locations: Hillcrest Hospital, Twinsburg Family Health and Surgery Center Office: 440.449.1101

Jeffrey s. ustin, Md

Specialty interests: Acute care surgery, trauma, surgical critical care

Locations: Main campus, Hillcrest Hospital Office: 216.445.1977

Jane Wey, Md

Specialty interests: Surgical oncology, hepatobiliary and pancreatic surgery, laparoscopic surgery, metastasectomy, gastrointestinal surgery, gastric cancer, retroperitoneal sar-comas, neuroendocrine tumors, HIPEC (tumor debulking/intraperitoneal chemoperfusion), melanoma, breast cancer

Location: Main campus Office: 216.445.6469

WE WELCoME THE FoLLoWIng SPECIALISTS To THE DIgESTIvE DISEASE InSTITUTE

For a complete listing of Digestive Disease Institute staff, visit clevelandclinic.org /digestive.

CMe Calendar: Medical professionals are invited to attend the following continuing education programs

7th Annual Obesity summit oct. 4-5, 2012 Cleveland Clinic, Cleveland, ohio

Multidisciplinary Breast Cancer summit (including sessions on breast surgery) oct. 11-13, 2012 Cleveland, ohio

16th Annual Meeting of the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC) (in joint sponsorship with Cleveland Clinic) oct. 27-29, 2012 Boston, Mass.

47th Annual Gastroenterology update: the next Generation in diagnosis and treatment nov. 8-9, 2012 Cleveland Clinic, Cleveland, ohio

Visit ccfcme.org for more information about the above events and more Cleveland Clinic CMe offerings in digestive disease and other clinical areas.

digestive disease Institute’s International Interdisciplinary education Week

24th Annual Jagelman International Colorectal disease symposium and 34th Annual turnbull symposium Feb. 12-17, 2013 Fort Lauderdale, Fla.

2nd Annual Gastroenterology and hepatology symposium Feb. 14-16, 2013 Fort Lauderdale, Fla.

12th Annual surgery of the Foregut symposium Feb. 17-20, 2013 (with live surgery Feb. 20) Coral gables, Fla.

Visit ClevelandClinicFloridaCMe.org for more information about the above events and more CMe offerings from Cleveland Clinic Florida.

855.REFER.123 for 24/7 referrals and

service assistance from cleveland clinic

The Power of Today: Referring Your Patient to Cleveland Clinic

Cleveland Clinic’s Referring Physician Center has established

a 24/7 hotline for referring physicians and their office staff to

streamline access to our array of medical services. our goal is to

make it as easy as possible for you and your patients when you

entrust us with their care.

you can contact the Referring Physi-

cian Hotline — 855.REFER.123

(855.733.3712) — for informa-

tion on our clinical specialties and

services, to schedule and confirm

patient appointments, for assistance

in resolving service-related issues

and to connect with Cleveland

Clinic specialists.

“We have made physician referrals

a priority,” says James Merlino, MD, Chief Experience Officer.

“We looked at what worked and what didn’t. We collaborated

with referring physicians to develop a one-stop shop for all

their needs. The result is the Referring Physician Center and its

hotline. Today, we’re here 24/7 to give quick service and rapid

resolution of any issues.”

Cleveland Clinic will work with your patient to complete our

registration process and to schedule

an appointment at his or her conve-

nience. You will be notified once the

appointment is scheduled.

“Patients honor and respect their per-

sonal physician,” says Dr. Merlino,

who is also a surgeon in the Diges-

tive Disease Institute’s Department

of Colorectal Surgery. “We realized

that if our referring physicians are

not happy, their patients won’t be

happy. our Referring Physician Center will do whatever it takes

to give all referring physicians and their patients the best out-

come and experience.”

The Referring Physician Hotline can be reached 24 hours a day, 7 days a week, at 855.REFER.123 (855.733.3712).

Digestive Disease InstituteThe Cleveland Clinic Foundation9500 Euclid Avenue/AC311Cleveland, oH 44195

24/7 referralsreferring physician Hotline 855.REFER.123 (855.733.3712)

Hospital transfers 800.553.5056

On the Web at: clevelandclinic.org/refer123

stay connected with us on…

Referring Physician Center and hotlineCleveland Clinic’s Referring Physician Center has established a 24/7 hotline — 855.REFER.123 (855.733.3712) — to streamline access to our array of medical services. Contact the Referring Physician Hotline for information on our clini-cal specialties and services, to schedule and confirm patient appointments, for assistance in resolving service-related issues, and to connect with Cleveland Clinic specialists.

Physician directoryview all Cleveland Clinic staff online at clevelandclinic.org/staff.

track Your Patient’s Care OnlineDrConnect is a secure online service providing real-time information about the treatment your patient receives at Cleveland Clinic. Establish a DrConnect account at clevelandclinic.org/drconnect.

Critical Care transport WorldwideCleveland Clinic’s critical care transport teams and fleet of vehicles are available to serve patients across the globe.

• To arrange for a critical care transfer, call 216.448.7000 or 866.547.1467 (see clevelandclinic.org/criticalcaretransport).

• For STEMI (ST elevated myocardial infarction), acute stroke, ICH (intracerebral hemorrhage), SAH (subarachnoid hemorrhage) or aortic syndrome transfers, call 877.379.COde (2633).

Outcomes dataview clinical outcomes Books from all Cleveland Clinic institutes at clevelandclinic.org/outcomes.

Clinical trialsWe offer thousands of clinical trials for qualifying patients. visit clevelandclinic.org/clinicaltrials.

CMe Opportunities: Live and OnlineThe Cleveland Clinic Center for Continuing Education’s website offers convenient, complimentary learning oppor-tunities. visit ccfcme.org to learn more, and use Cleveland Clinic’s myCME portal (available on the site) to manage your CME credits.

executive educationCleveland Clinic has two education programs for healthcare executive leaders — the Executive visitors’ Program and the two-week Samson global Leadership Academy immer-sion program. visit clevelandclinic.org/executiveeducation.

about cleveland clinicCleveland Clinic is an integrated healthcare delivery system with local, national and international reach. At Cleveland Clinic, 2,800 physicians represent 120 medical special-ties and subspecialties. We are a main campus, 18 family health centers, eight community hospitals, Cleveland Clinic Florida, the Cleveland Clinic Lou Ruvo Center for Brain Health in Las vegas, Cleveland Clinic Canada, Sheikh khalifa Medical City, and Cleveland Clinic Abu Dhabi.

In 2012, Cleveland Clinic was ranked one of America’s top 4 hospitals in U.S. News & World Report’s annual “Amer-ica’s Best Hospitals” survey. The survey ranks Cleveland Clinic among the nation’s top 10 hospitals in 14 specialty areas, and the top hospital in three of those areas.

RESoURCES FoR PHyS IC IAnS

CLEvELAnD CLInIC #2 In THE U.S. – GAstROenteROLOGY