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Proximal Polyps: When YouFind One, Look for Another

Compared with patients who have distal-

only adenomas removed, those with

proximal-only lesions removed have a

higher risk for missed advanced adenomas.

In patients who undergo colonoscopic clear-

ing of adenomas followed by colonoscopic

surveillance, the initial lesions tend to be

found in the distal colon, whereas those

detected in subsequent exams tend to be in

the proximal colon. Now, researchers haveevaluated this effect among individuals who

participated in the Polyp Prevention Trial.

All 1864 study participants had ade-

nomas at baseline: 55% in the distal colon

only, 27% in the proximal colon only, and

18% in both locations. Patients underwent

baseline colonoscopic clearing and then

follow-up colonoscopies at years 1 and 4.

Adenomas detected at year 1 were con-

sidered to have been missed at baseline,

whereas those at year 4 were considered

recurrences.At 1 year, 35% of patients had an ade-

noma: 35% in the distal colon only and

48% in the proximal colon only. Patients

with proximal-only adenomas at baseline

were more likely than those with distal-

only adenomas at baseline to have a missed

adenoma at year 1 (relative risk, 1.3) and,

more specifically, a proximal-only missed

adenoma (RR, 2.0) . They were also more

likely to have a missed advanced adenoma

overall (RR, 1.8) and a missed advanced

proximal adenoma (RR, 3.3).

At 4 years, 39% of patients had an

adenoma recurrence: 50% in the proximal

colon only and 31% in the distal colononly. Proximal-only adenomas at baseline

predicted overall adenoma recurrence (RR,

1.1), proximal-only adenoma recurrence

(RR, 1.5), and proximal-only advanced

adenoma recurrence (RR, 3.6). Proximal-

only adenomas at baseline were inversely

associated with distal-only adenoma

recurrence and with distal-only advanced

adenoma recurrence.

COMMENT

Many experienced endoscopists will likely

recognize the patterns described here that patients with proximal adenomas

have a higher risk for adenoma recurrence

overall and, specifica lly, recurrence in the

proximal colon. Of particular importance

is the evidence that proximal adenomas

are associated with a higher risk for missed

advanced adenomas and subsequent ad-

vanced adenomas, particularly in the

proximal colon. Clearly, these results indi-

cate that colonoscopy is the preferred sur-

veillance strategy for patients with adeno-

mas. In addition, when single or multiple

adenomas are detected in the proximal co-

lon, endoscopists might consider a second

check of the proximal colon during thesame examination to ensure that nothing

has been missed. These results will likely

prompt guideline panels to carefully con-

sider whether the finding of proximal ade-

nomas should inf luence postpolypectomy

surveillance recommendations.

Douglas K. Rex, MD

Laiyemo AO et al. Likelihood of missed and re-

current adenomas in the proximal versus the distal

colon. Gastrointest Endosc 2011 Aug; 74:253.

New Imaging TechniquesEnhance Polyp Detectionand Differentiation

High-definition colonoscopy and digital

chromoendoscopy hold promise.

Researchers continue to explore ways to

improve the detection of polyps during

colonoscopy and to allow for real-time

differentiation between adenomatous and

hyperplastic polyps. Two new studies add

to the evidence base.

In a multicenter, randomized trial,

Rastogi and colleagues compared standard-definition white-light colonoscopy, high-

definition white-light colonoscopy, and

narrow-band imaging (NBI) in 640 adults

who had been referred for screening or

surveillance colonoscopy. No difference

was found across the groups in terms of

the proportion of patients with adenomas.

However, the number of adenomas detected

Proximal Polyps: When You Find One,

Look for Another .......................................................81

New Imaging Techniques EnhancePolyp Detection and Differentiation .....................81

Is Earlier Colonoscopy Betterfor Polyp Detection? ................................................ 82

Monitored Anesthesia Care:Less Safe than You Think ........................................ 83

Thalidomide for Refractory Bleeding from

Vascular Malformations .......................................... 83

Linaclotide Effectivefor Chronic Constipation ......................................... 84

Endoscopic Submucosal Dissection in FranceInferior to That in Japan ..........................................84

Ulcers Heal While Patients

Continue Aspirin Therapy ............................ 85

End-Stage Renal Disease Increases Riskfor Gastrointestinal Rebleeding ............................. 85

A Trefoil Factor Family Protein Might Be Usefulfor Gastric Cancer Screening ................................ 85

Gene Expression Might ExplainPrognostic Differences in Gastric Cancer .......... 86

Predictors of ERCP Complications in Patients

with Primary Sclerosing Cholangitis .................... 86

Child-Pugh Score Predicts Prognosisin Hepatitis C Virus Infection .................................. 87

MELD Score Predicts Outcomes inPregnant Women with Cirrhosis ........................... 87

Interferon-Free Regimen Shows Promisefor Chronic HCV Infection .......................................88

CONTENTS

GASTROENTEROLOGY

November 2011 Vol. 12 No. 11

From the publishers of

The New England Journal of Medicine


2/8

per patient was 60% higher in the high-

definition and NBI groups than in the

standard-definition group. Most of this

difference was attributed to the enhanced

detection of flat and right-sided adenomas

in the high-definition and NBI groups.

With regard to polyp differentiation, NBI

was superior to white light in terms of both

sensitivity (90%) and accuracy (82%) for

predicting adenomas.

In a single-center, observational cohort

study in Korea, Lee and colleagues com-

pared the effectiveness of two types of digi-

tal chromoendoscopy NBI and i-SCAN

(Pentax) in differentiating diminutive

colon polyps that were identified during

high-definition white-l ight colonoscopy.

Seventy patients had a total of 156 diminu-

tive polyps evaluated by NBI; 51.3% of

these polyps were adenomas. Similarly,

72 patients had 140 polyps evaluated by

i-SCAN, and 52.9% were adenomas. Both

NBI and i-SCAN were superior to high-

definition white-light colonoscopy for

differentiating adenomatous from hyper-

plastic polyps. The two electronic methods

had similar sensitivity for real-time identi-

fication of adenomas (88.8% for NBI and

94.6% for i-SCAN). High-confidence

predictions of adenomas had 90.3% accu-

racy with NBI and 90.9% accuracy with

i-SCAN. Similarly, high-confidence pre-

dictions of hyperplastic polyps had 92.1%accuracy with NBI and 94.7% with i-SCAN.

COMMENT

The study by Rastogi and colleagues sup-

ports the concept that high-definition

colonoscopy improves detection. Although

the results are striking, the literature on

this topic remains mixed. In my opinion,

high-definition colonoscopy remains the

most promising technology for improved

detection of endoscopically flat and subtle

lesions. Both studies advance the concept

that digital chromoendoscopy can accu-rately differentiate adenomatous from

hyperplastic polyps. In addition, we now

have an uncontrolled but direct compari-

son of accuracy with two different digital

technologies, and the results suggest that

multiple companies will be able to develop

accurate tools for differentiating the his-

tology of diminutive and small polyps.

Douglas K. Rex, MD

Rastogi A et al. Randomized, controlled trial of

standard-definition white-light, high-definition

white-light, and narrow-band imaging colonoscopy

for the detection of colon polyps and prediction

of polyp histology. Gastrointest Endosc 2011

Sep; 74:593.

Lee CK et al. Narrow-band imaging versus I-Scan

for the real-time histological prediction of diminu-

tive colonic polyps: A prospective comparative study

by using the simple unified endoscopic classification.Gastrointest Endosc 2011 Sep; 74:603.

Is Earlier ColonoscopyBetter for Polyp Detection?

Endoscopists seem to detect fewer adenomas

as the workday progresses, but direct

measures of fatigue and rushing are absent

from studies.

Some previous studies have found that the

adenoma detection rate (ADR) is higher

for morning versus af ternoon colonosco-

pies and that ADRs deteriorate hourly asthe workday progresses (JW Gastroenterol

May 2011, p. 35, andJ Clin Gastroenterol

2011; 45:253) . However, authors who

observed this phenomenon noted that it

might be endoscopist dependent. Now,

two new studies explore this issue.

In a retrospective analysis, Lee and

colleagues assessed 1083 outpatient colonos-

copies performed by 28 endoscopists and

found that each elapsed hour of the day was

associated with a 4.6% reduction in polyp

detection (P=0.005). Also, for each increasein the number of procedures performed

earlier that day by the endoscopist, polyp

detection decreased by 5.4% (P=0.016).

The authors contend that this latter

measure of queue position was a novel

surrogate for endoscopist fatigue.

In another retrospective analysis,

Gurudu and colleagues analyzed 4665

colonoscopies performed by 29 endosco-

pists. For those working a full day, the ADR

was significantly higher in the morning

than in the af ternoon (26.1% vs. 21.0%),whereas for endoscopists working a half

day, the ADR did not change between

morning and afternoon (26.6% vs. 27.6%).

Similarly, ADRs declined on an hourly ba-

sis in the afternoon among endoscopists

working full-day but not half-day sched-

ules. Finally, although the authors noted

that most individual endoscopists had

higher ADRs when working half days

versus full days, the number of these

endoscopists was only 12 (out of 21).

EDITOR-IN-CHIEF

M. Brian Fennerty, MD, Professor of Medicine,

Division of Gastroenterology at Oregon Health &

Science University, Portland

EXECUTIVE EDITOR

Philip J. LoPiccolo, MS

Massachusetts Medical Society

DEPUTY EDITOR

David J. Bjorkman, MD, MSPH (HSA), SM (Epid.),Dean, University of Utah School of Medicine;

Executive Medical Director, University of Utah

Medical Group, Salt Lake City

ASSOCIATE EDITORS

Chris E. Forsmark, MD, Professor of Medicine,

Division of Gastroenterology/Hepatology/Nutrition,

University of Florida College of Medicine,

Gainesville

David A. Johnson, MD, Professor of Medicine,

Chief of Gastroenterology, Eastern Virginia School

of Medicine, Norfolk

Douglas K. Rex, MD, Professor of Medicine,

Director of Endoscopy, Division of

Gastroenterology/Hepatology, Indiana University

Medical Center, Indianapolis

Atif Zaman, MD, MPH, Associate Professor,

Department of Gastroenterology and Hepatology,

Oregon Health & Science University, Portland

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82 GASTROENTEROLOGY Vol. 12 No. 11


3/8

COMMENT

Several patterns emerge from this and prior

studies. First, adenoma detection does

seem to decline throughout the workday.

However, it is clearly endoscopist depen-

dent and possibly unit dependent, which

means that application of restrictive sched-

uling policies might not be necessary for all

endoscopists.

Second, some key variables are miss-

ing. None of the relevant studies has direct-

ly measured endoscopist fatigue, even

though this is the most common explana-

tion given for declining polyp or adenoma

detection with time. Another possible ex-

planation is that endoscopists might rush if

they are behind in their schedules and con-

sequently detect (or at least remove) fewer

lesions. Thus, a comparison of detection

rates with regard to scheduled versus actual

start times would be useful. Also, the study

by Lee and colleagues shows an effect on

polyp detection but is unable to determine

whether adenoma detection is affected. A

drop in the measured polyp resection rate

could be caused by factors other than a re-

duction in detection is affected. For exam-

ple, an endoscopist might be more likely

to perform a biopsy on a rectosigmoid

hyperplastic polyp in the early versus late

morning, indicating a change in behavior

rather than development of fatigue. These

issues warrant additional study before wedevelop policies regarding endoscopy

scheduling. Douglas K. Rex, MD

Lee A et al. Queue position in the endoscopic

schedule impacts effectiveness of colonoscopy.

Am J Gastroenterol 2011 Aug; 106:1457.

Gurudu SR et al. Adenoma detection rate is not

influenced by the timing of colonoscopy when

performed in half-day blocks. Am J Gastroenterol

2011 Aug; 106:1466.

Monitored Anesthesia Care:Less Safe than You Think

Rates of respiratory complications were higher

with MAC than those previously reported

with endoscopist-directed propofol sedation.

Research on safety outcomes of monitored

anesthesia care (MAC) is lacking. Only

one small study of MAC provided by certi-

fied registered nurse anesthetists has been

reported.

To document adverse outcomes of

MAC, researchers retrospectively reviewed

17,999 endoscopic procedures performed

during 8 years in a hospital in Italy. Pa-

tients received MAC in cases of increased

anxiety or therapeutic difficulty of the

procedure.

Complications during MAC occurred

in 792 patients (4.5%). Hypotension,

which necessitated intervention, occurredin 312 patients (1.8%) and involved intra-

venous (IV) fluids or colloid in all pa-

tients; 22% received pharmacologic sup-

port with IV ethylephrine. Aspiration

occurred in 18 patients (0.1%). The sever-

ity of these events was unclear; no patients

died, but all received antibiotics. Among

217 patients (1.2%) experiencing desatura-

tion , all received bag/mask ventilation, and

13 received endotracheal intubation. Four-

teen patients who experienced respiratory

depression were treated with bag/mask

ventilation, and two underwent endo-

tracheal intubation. Seven patients went

into respiratory arrest; al l were bag/

maskventilated, and three required

endotracheal intubation. Seven patients

required cardiopulmonary resuscitation

for cardiac arrest. In all, three patients

died, although the causes were not clearly

related to sedation; two died from massive

variceal bleeding and one from severe

bradyarrhythmia after gallstone extraction

from the common duct.

COMMENT

This first known report of MAC safety

shows very high rates of complications,

particularly with regard to respiratory

depression, desaturation, and the need for

endotracheal intubation. Much lower rates

of respiratory complications have been de-

scribed with endoscopist-directed propofol

(EDP). The differences might lie partly in

patient selection, given that complicated

procedures were selected for MAC in this

study and EDP studies typically involved

low-risk patients. In addition, propofol wasadministered by continuous infusion in

this study versus the small, intermittent

boluses used in EDP studies. Finally, the

authors might have had a low threshold

for initiating endotracheal intubation.

The rate of aspiration requiring anti-

biotic treatment in this study seems high.

I predict that an increase in the rate of

hospitalization for aspiration developing

during endoscopy will be one of the

consequences of the increasing use of MAC

in the U.S. The results of this study do not

suggest that MAC is safer than EDP.

Douglas K. Rex, MD

Agostoni M et al. Adverse events during monitored

anesthesia care for GI endoscopy: An 8-year experi-

ence. Gastrointest Endosc 2011 Aug; 74:266.

Thalidomide forRefractory Bleeding fromVascular Malformations

In a small, randomized, controlled trial,

thalidomide reduced bleeding episodes,

blood transfusions, and hospitalizations.

Every experienced gastroenterologist has

encountered patients who have refractory

bleeding from gastrointestinal vascular

malformations and are dependent on iron

replacement or blood transfusion. Now, in

an open-label, randomized trial, researchersin China investigated the efficacy and safety

of administering thalidomide in 55 patients

with bleeding that was unresponsive or un-

suited to treatment by means such as en-

doscopy, colonoscopy, and double-balloon

enteroscopy. Twenty-eight of the partici-

pants were transfusion dependent before

randomization; 3 with gastric antral vascu-

lar ectasia (GAVE) had failed to respond to

argon plasma coagulation treatment. Ex-

clusion criteria included portal hyperten-

sion, severe comorbidities, peripheral neu-

ropathy, or a history of thromboembolic

disease; treatment with steroids, non-

steroidal anti- inflammatory agents, or

antiplatelet drugs; or current cancer

chemotherapy.

After a 1-year observation period,

participants were randomized to receive

either 25 mg of thalidomide or 100 mg of

iron four times daily for 4 months; they

were followed for 1 year thereafter. Tha-

lidomide recipients did not take iron dur-

ing the treatment period. Bleeding episodes

were determined using a fecal immuno-

chemical test for blood, but clinical ly rele-

vant endpoints such as blood transfusion

and hospitalization were also followed.

During the first year of follow-up,

the proportion of patients with a 50%

decrease in bleeding episodes was signifi-

cantly higher in the thalidomide group

than in the iron group (71.4% vs. 3.7%).

The decreases in the thalidomide group

occurred during the first 8 months of

November 2011 JWatch.org 83


4/8

follow-up and were maintained after-

ward. The thalidomide group also showed

a significantly greater decrease in blood-

transfusion rates (78.6% vs. 7.3%), a

significantly greater increase in mean he-

moglobin level (+3.06 g/dL vs. 0.01 g/dL),

and significantly greater decreases in hos-

pitalization rates both overall and for

bleeding. Vascular lesions resolved in the

two thalidomide recipients with GAVE

but not in the iron recipient with this con-

dition. All the results remained significant

in analyses excluding the patients with

GAVE.

After the 4-month treatment period,

the mean plasma concentration of vascular

endothelial growth factor (VEGF) de-

creased significantly in the thalidomide

group (from 118 to 58 pg/mL) ; the reduc-

tion was greater in responders than in non-

responders (67 vs. 36 pg/mL). Two pa-

tients discontinued thalidomide because

of leukopenia and somnolence, respectively.

Fatigue occurred in more thalidomide

recipients than iron recipients (32.1% vs.

11.1%). Neither serious events nor preg-

nancy occurred in either group during

the study.

COMMENT

Thalidomide is notorious for its teratogenic

effects. It can also induce a dose-dependent,

sensorimotor length-dependent axonal neu-

ropathy and should be used judiciously, with

close neurological monitoring. Nonetheless,

in this randomized, controlled trial, thalido-

mide had an impressive effect on intestinal

bleeding from gastrointestinal vascular

malformations and could represent an im-

portant treatment option for patients with

recurrent or refractory bleeding. The drug

might act by reducing elevated VEGF levels,

which have been associated with abnormal

growth of new blood vessels. Use of tha-

lidomide at the comparatively low dose

employed here (100 mg/day) could helpto limit adverse events. In addition, the

persistent benefits of thalidomide after

cessation of therapy are encouraging.

Douglas K. Rex, MD

Ge Z-Z et al. Efficacy of thalidomide for refractory

gastrointestinal bleeding from vascular malforma-

tion. Gastroenterology 2011 Jul 25; [e-pub ahead

of print]. (http://dx.doi.org/10.1053/j.gastro.2011

.07.018)

Linaclotide Effectivefor Chronic Constipation

This synthetic peptide significantly im-

proved bowel and abdominal symptoms

and reduced constipation severity.

Linaclotide is a synthetic peptide that acti-

vates the guanylate cyclase C receptor on

the surface of intestinal epithelial cells,resulting in secretion of chloride and bi-

carbonate into the intestinal lumen, there-

by accelerating transit. In two similar

manufacturer-supported, multicenter,

double-blind, phase III t rials conducted

in the U.S. and Canada, researchers

evaluated the safety and efficacy of this

agent in adults with chronic constipation.

In all, 1276 patients were randomized

to receive linaclotide (145 g or 290 g)

or placebo, once daily, at least 30 minutes

before breakfast. The primary efficacyendpoint was defined as both a weekly

frequency of3 complete spontaneous

bowel movements (CSBMs) and an increase

of1 CSBMs from baseline per week for

9 weeks of the 12-week treatment period.

In the two trials, the primary endpoint

was met by 21% and 16% of patients re-

ceiving the 145-g dose of l inaclotide and

by 19% and 21% of patients receiving the

290-g dose, compared with 3% and 6% of

patients receiving placebo. The mean num-

ber of CSBMs per week was 2.4 and 2.2

with the 145-g dose and 2.4 and 2.9 with

the 290-g dose, versus 0.9 with placebo

(in both trials ). In addition, compared

with placebo recipients, linaclotide recipi-

ents showed significantly greater improve-

ments in number of SBMs per week, stool

consistency, straining severity, abdominal

discomfort and bloating, and constipation

severity; they also scored significantly

higher in constipation relief and in treat-

ment satisfaction at week 12. Treatment

was discontinued because of adverse events

(most often, diarrhea) in 7% of linaclotiderecipients and 4% of placebo recipients.

COMMENT

No agent for the treatment of constipation

is effective for all patients. Therefore, the

availability of new, safe treatment options

is welcome. Douglas K. Rex, MD

Lembo AJ et al. Two randomized trials of linaclotide

for chronic constipation. N Engl J Med 2011

Aug 11; 365:527.

Endoscopic SubmucosalDissection in FranceInferior to That in Japan

Rates of R0 resection and complications

were not as good.

Endoscopic submucosal dissection ( ESD)

was developed in Japan for the treatment

of patients with early gastric cancers. Manyreports from Asia have now described its

successful use for both gastric and colorec-

tal tumors, but the technique is still seldom

used in the West. Compared with endo-

scopic mucosal resection, ESD provides a

greater chance of R0 resection (resection

with clear deep and lateral margins), a

higher rate of cure at first follow-up, and

superior specimens for histologic assess-

ment. In Japan, the perforation rate of

ESD is about 5%, but most perforations are

closed with endoscopic clips. After under-

going ESD in Japan, patients are typical ly

observed in the hospital for several days

to a week.

Now, 22 gastroenterologists from

16 centers in France have assessed their

early experience with ESD. They analyzed

188 consecutive case reports from 1 to

43 per center (median, 6). The patients

involved had lesions in the stomach (75),

the rectum (72), the esophagus (27), the

colon proximal to the rectum (13), or the

duodenum (1) . The median lesion size was

26 mm (range, 2150 mm), and the medi-

an procedure duration was 105 minutes

(range 20450 minutes).

Results were as follows:

The overall R0 resection rate was

72.9%.

The R0 resection rate was higher for

tumors in the stomach than for those

in the rectum (84.0% vs. 61.1%).

21 patients (11.2%) experienced bleed-

ing; 4 of them required transfusion.

34 patients (18.1%) experienced

perforation, which was recognized

endoscopically during the initial ESD

procedure in all instances; 6 of these

patients required surgery.

The complication rate was lower when

ESD was performed with a single

dissecting knife than when multiple

knives were used (9.6% vs. 40.3%;

P=0.005).



5/8

The median hospital stay was 2 days

for uncomplicated cases and 5 days

for complicated ones.

No deaths occurred.

COMMENT

ESD has been slow to catch on in the West

for a variety of reasons, including the low

incidence of early gastric cancer compared

with that in Asia, the lack of appropriate

reimbursement for prolonged endoscopic

procedures, the relatively poor medical

legal climate with regard to perforation,

and (particularly in the U.S.) the relatively

high cost of hospitalization. This new study

from France suggests two additional deter-

rents: a steep learning curve and, without

extensive endoscopist experience, in-

creased risk for complications. New endo-

scopic tools are certainly needed to make

ESD safer, quicker, and easier to learn. Douglas K. Rex, MD

Farhat S et al. Endoscopic submucosal dissection in

a European setting: A multi-institutional report

of a technique in development. Endoscopy2011

Aug; 43:664.

Ulcers Heal While PatientsContinue Aspirin Therapy

Efficacy of rabeprazole in treating ulcers

was high with either aspirin or clopidogrel.

Aspirin and clopidogrel are antiplatelet

drugs used to prevent thrombotic vascularevents. However, both are associated with

increased risk for bleeding from peptic ul-

cer disease (PUD). Aspirin induces peptic

ulcers, and both drugs prevent their heal-

ing aspirin through inhibiting mucosal

prostaglandin generation and clopidogrel

by decreasing platelet-related growth

factors. Proton-pump inhibitor (PPI)

treatment is effective for healing aspirin-

associated PUD, but for patients requiring

continued antiplatelet therapy, it is unclear

whether the outcomes are different inpatients taking clopidogrel versus aspirin.

To investigate this issue, researchers

randomized 218 patients with aspirin-

related, nonbleeding, symptomatic PUD

to receive rabeprazole (20 mg/day) with

either clopidogrel (75 mg/day) or aspirin

(100 mg/day) for 12 weeks. Endoscopy

was used to both determine PUD diagnosis

and evaluate the primary outcome of

ulcer healing.

The healing rate was similar in both

groups after 12 weeks (90% for clopidogrel

and 86% for aspirin). In multivariate

regression analyses, independent risk fac-

tors for treatment failure were ulcer size

>10 mm (odds ratio, 6.3) and a history of

PUD (OR, 3.7). One patient in each group

had a major adverse cardiovascular event.

No patient developed PUD-related bleeding.

COMMENT

The authors conclude that rabeprazole

plus aspirin is not inferior to rabeprazole

plus clopidogrel for healing of symptomatic

aspirin-related peptic ulcer disease. These

study findings show that PPI therapy

successfully heals aspirin-related PUD

whether patients continue on aspirin or

switch to clopidogrel. Of note, patients who

had Helicobacter pylori infection were not

treated until the end of the study. H. pyloriinfection was not an independent risk

factor for treatment failure, but a history

of PUD (a possible marker ofH. pylori

infection) was. Therefore, eradication of

H. pylori infection should be considered

in addition to PPI therapy in patients with

PUD. The question of potential reduction

in clopidogrel efficacy in the setting of PPI

therapy was not addressed in this small

study.

David J. Bjorkman, MD, MSPH (HSA),

SM (Epid.)

Luo J-C et al. Randomised clinical trial: Rabepra-

zole plus aspirin is not inferior to rabeprazole plus

clopidogrel for the healing of aspirin-related peptic

ulcer. Aliment Pharmacol Ther 2011 Sep; 34:

519.

End-Stage Renal DiseaseIncreases Risk forGastrointestinal Rebleeding

A study of Taiwanese hospitalizations is the

first to evaluate long-term risks for peptic

ulcer rebleeding in patients with ESRD.

Multiple studies have shown that the inci-dence of peptic ulcer disease is decreasing

throughout the world. However, upper

gastrointestinal bleeding (UGIB) remains

a common cause of hospitalization and

morbidity. Potential reasons for this situa-

tion include unstudied long-term effects

of comorbidities.

To assess the long-term effect of end-

stage renal disease (ESRD) on the risk for

repeat peptic ulcer bleeding, investigators

in Taiwan identified 6447 patients with

ESRD and 25,788 age- and sex-matched

controls without ESRD who were hospital-

ized for UGIB during a 10-year period.

Rebleeding was defined as a repeat hospi-

talization for UGIB. Data on demograph-

ics, drug history, and other possible risk

factors for UGIB were also determined

from the records.

Patients with ESRD were more likely

than those with ESRD to experience re-

bleeding (hazard ratio, 1.38; P


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COMMENT

This study identifies several predictors of

post-ERCP complications in patients with

PSC, some of which are modifiable and

might allow biliary endoscopists to target

approaches to minimizing frequency or

severity of such complications. First, as

shown in many previous studies of ERCP,

endoscopist training and experience seem

essential to limiting complications from

these particularly complex procedures.

Second, many endoscopists seek to avoid

sphincterotomy in patients with PSC, and

this study supports that goal. However,

contrary to the findings of this study, many

biliary endoscopists tend to prefer biliary

dilation rather than chronic biliary stent-

ing in this population. This is an area that

needs to be clarified with additional stud-

ies. Finally, the low number of post-ERCP

infections supports the continued routineuse of antibiotics, both intraprocedural and

postprocedural, in PSC patients.

Chris E. Forsmark, MD

Alkhatib AA et al. Comorbidities, sphincterotomy,

and balloon dilation predict post-ERCP adverse

events in PSC patients: Operator experience is

protective. Dig Dis Sci 2011 Jul 26; [e-pub ahead

of print]. (http://dx.doi.org/10.1007/s10620-011-

1830-8)

Child-Pugh Score

Predicts Prognosis inHepatitis C Virus Infection

Disease progression accelerates when

Child-Pugh scores are 7.

The prospective, multicenter Hepatitis C

Antiviral Long- term Treatment against

Cirrhosis (HALT-C) trial showed that

3.5 years of weekly maintenance therapy

with peginterferon alfa-2a did not im-

prove outcomes in hepatitis C virus

(HCV)-infected patients with advanced

fibrosis ( JW GastroenterolJun 2009,

p. 6, and N Engl J Med2008; 359:2429).

In that trial, 1050 patients (60% with

stage 3 or 4 fibrosis; 40% with cirrhosis)

were randomized, af ter a lead-in treat-

ment phase, to receive either 90 g of

peginterferon or no further treatment.

Now, researchers have combined the

treatment and control groups from the

HALT-C trial to determine the rate of

liver-disease progression from advanced

fibrosis to cirrhosis during 4 years of

follow-up. They also tracked clinical

events Child-Pugh score 7, hepatic

decompensation (ascites, encephalopathy,

variceal hemorrhage, bacterial peritoni-

tis), liver transplantation, hepatocellular

carcinoma, and death (liver related or

from any cause) during 8-years of

follow-up.

Among patients with baseline fibrosis,

the incidence of cirrhosis was 9.9% per

year. Clinical events initially occurred in

more patients with cirrhosis than in those

with fibrosis (7.5% vs. 3.3% per year).

Specifically, the rate of death was initially

higher in patients with cirrhosis than with

fibrosis (3.9% vs. 1.7%), as was the rate of

decompensation (variceal hemorrhage,

ascites, bacterial peritonitis, or encephalop-

athy; 3.9% vs. 1.2%). However, once the

Child-Pugh score was 7 in these patients,

the rate of death increased to 10.0%, and

the rate of decompensation rose to 12.9%

per year. In patients with Child-Pugh

scores 7, the most common clinical events

were ascites, encephalopathy, death, and

hepatocellular carcinoma. Death or liver

transplant occurred in more patients with

cirrhosis than fibrosis (31.5% vs. 12.2%).

COMMENT

By providing accurate information on rates

of disease progression in HCV-infected pa-

tients with advanced fibrosis or cirrhosis,

these data should allow clinicians to better

counsel such individuals. A key finding is

that once Child-Pugh scores reach7,

disease progression accelerates.

Atif Zaman, MD, MPH

Dienstag JL et al. A prospective study of the rate of

progression in compensated, histologically advanced

chronic hepatitis C. Hepatology2011 Aug; 54:396.

MELD Score Predicts

Outcomes in Pregnant Womenwith Cirrhosis

A MELD score 10 at conception predicted

maternal liver-related complications,

whereas a score 6 indicated no excess risk.

Maternal mortality as high as 10% has

been reported in pregnant women with

cirrhosis. Now, investigators have assessed

whether the model for end-stage liver

disease (MELD) and similar prognostic

scores are able to predict pregnancy out-

comes for women with cirrhosis.

The researchers collected data on pa-

tients who reported pregnancies at a single

medical center in the U.K. between 1984

and 2009. MELD, MELD-Na, and Child-

Pugh scores were calculated from informa-

tion obtained at the clinic visit immediatelyprior to the report of pregnancy. Outcomes

of interest included maternal complications

(including hepatic decompensation) and

spontaneous abortions.

Sixty-two pregnancies were recorded

among 29 women (median age at concep-

tion, 29), of whom 24 carried their preg-

nancies to full term. The live birth rate was

58%, and the spontaneous abortion rate

was 26%. One pregnancy resulted in ma-

ternal death (1.6%) and six (10%) in ma-

ternal complications, including three epi-sodes of variceal hemorrhage, two episodes

of ascites, and one episode of encephalopa-

thy. The median MELD score was 7 (range,

617); the median MELD-Na score was 9

(range, 617); and the median Child-Pugh

score was 5 (range, 58) . A MELD score

10 was associated with increased risk for

liver-related complications (P=0.01; sensi-

tivity, 83%; specificity 83% ; area under

the curve, 0.8). Also, women with MELD

scores 6 did not develop complications. In

contrast, the MELD-Na and Child-Pugh

Scores were not predictive of outcomes.

COMMENT

These findings confirm past reports of

higher rates of maternal complications and

spontaneous fetal loss among women with

cirrhosis. Moreover, half (3 of 6) of maternal

complications involved variceal hemor-

rhage. Of note, the MELD score predicted

maternal outcomes, with a score 10 indi-

cating the highest risk. Clinicians should

therefore follow the guidelines of the Ameri-

can Association for the Study of Liver Dis-

eases that recommend variceal screening

in the second trimester of pregnancy and,

based on this study, use the MELD scoring

system to advise women regarding their

risks for adverse outcomes.

Atif Zaman, MD, MPH

Westbrook RH et al. Model for end-stage liver

disease score predicts outcome in cirrhotic patients

during pregnancy. Clin Gastroenterol Hepatol

2011 Aug; 9:694.

November 2011 JWatch.org 87


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This is one of four questions in a recent Journal

Watch Online CME exam.

from Ulcers Heal While Patients Continue

Aspirin Therapy (p. 85)

To determine whether proton-pump inhib-

itors (PPIs) are effective while patients take

aspirin or clopidogrel, researchers studiedpatients with aspirin-related, nonbleeding,

symptomatic peptic ulcer disease (PUD)

who received rabeprazole plus aspirin or

clopidogrel. Which of the following best

describes their findings?

A. The healing rate was higher among

aspirin recipients than clopidogrel

recipients.

B. The healing rate was lower in patients

with an ulcer size >10 mm.

C. A history of PUD was not associated

with a lower healing rate.

D. All of the above are true.

Category: Gastroenterology

Exam Title: JW Gastroenterology: PPIs, EoE,UGIB, CRC

Posted Date: Sep 6 2011

View this exam and others at http://cme.jwatch.org

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CME FACULTY: Norton Greenberger, MD

Interferon-Free RegimenShows Promisefor Chronic HCV Infection

In a phase Ib trial, the combination of a

polymerase inhibitor, a protease inhibitor,

and ribavirin demonstrated potent activity.

Although the new triple regimens are effec-

tive for the treatment of patients with chron-

ic hepatitis C virus (HCV) infection, they

have been linked to serious adverse events.

Interferon the backbone of all current

therapies is a major contributor to these

effects. Now, researchers have conducted an

industry-sponsored, phase Ib, international,open-label trial to evaluate the efficacy and

safety of an interferon-free regimen.

Treatment-naive adults with HCV

genotype 1 infection were randomized

to receive 4 weeks of therapy with either

400 mg or 600 mg of BI 207127 (a non-

nucleoside polymerase inhibitor, 3 times

daily) . Patients also received BI 201335

(a protease inhibitor, 120 mg daily) and

ribavirin (1000 mg or 1200 mg daily) . The

primary endpoint was virologic response

(HCV RNA

meld outcome cirrhosis and pregnant

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