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Clinical Perspectives on Pancreatic Disorders

Disclosures

Baillie, MD

New Orleans, Monday, May 17, 2004 -- The first full day of the Digestive Disease

Week (DDW) scientific session offered a rich and diverse group of presentations

on pancreatic disorders, providing an effective forum for the discussion of

original work and expert opinion on topical issues in the field.

This report highlights some of the more key presentations in pancreatic disease,

as held during the core meeting proceedings on Monday, and places the material

in appropriate and relevant context to emphasize its place in clinical practice.

Acute Pancreatitis -- Predictor of Severity

During an American Gastroenterological Association (AGA) topic forum on

pancreatic disorders, Papachristou and colleagues[1] introduced the concept of

using serum proteomic patterns to predict severity in acute pancreatitis. Serum

proteomic pattern analysis is based on the theory that patterns of

low-molecular-mass biomarkers can definitively reveal an underlying,

organ-specific pathology. The clinical and radiologic scoring systems for acute

pancreatitis (eg, the Ranson criteria, Balthazar score) in practice have

significant limitations. Looking at the pattern of changes in an array of serum

proteins may well prove to be the most sensitive and specific way to determine

which patients are likely to develop multisystem failure and thus require

intensive care.

Pancreatic Endoscopic Ultrasound

This bedside application of novel technology is true " translational " research,

as is the use of advanced genetic analysis in the evaluation of pancreatic cyst

aspirates. Khalid and colleagues[2] reported that analysis of free-floating DNA

in cyst aspirates can predict the underlying malignant potential of pancreatic

cystic lesions. Determining which pancreatic cysts are malignant or have

malignant potential is a familiar diagnostic dilemma. Telltale clues in DNA

found in aspirates of pancreatic cysts appear to be a promising way to unlock

their underlying biologic behavior. Thus, this mutational allelotyping of

free-floating DNA in pancreatic cyst aspirates serves as a marker of their

genetic composition, making such a mutational map a potential and supplementary

tool in the standard work-up of pancreatic cysts.

Acute Pancreatitis -- Effect of Gastroenterology Consultation on Outcome

In a retrospective study going back over 12 years, Gardner and colleagues[3]

assessed the impact of gastroenterology consultation on process and outcome in

patients admitted (by primary care physicians) with acute pancreatitis. These

investigators sought to determine whether the input of a gastroenterology

consult team altered the outcome of management in the setting of acute

pancreatitis. It was interesting to note that this " intervention " did not

improve mortality or hospital length of stay. Indeed, the mean length of stay

was actually longer for patients receiving a consultation than for those who did

not. The study authors believed that the lack of influence of consultation on a

population of patients with mainly " mild pancreatitis " reflects the unfortunate

lack of available interventions for this disease. The retrospective nature of

the study and its long duration were thought to be potential confounding factors

in interpretation, but these data are provocative, nonetheless.

Post-ERCP Pancreatitis

The AGA clinical symposium addressing the issue of prevention of post-ERCP

(endoscopic retrograde cholangiopancreatography) pancreatitis attracted a

significant audience during these meeting proceedings. Freeman, MD,[4]

from the University of Minnesota, launched the session with an all-important

question: " Just how risky is ERCP? " Freeman and his collaborators in the Midwest

Pancreatitis Study Group have made a major contribution to our understanding of

post-ERCP pancreatitis in the last decade, particularly in relation to risk

factors. Freeman showed the odds ratios for post-ERCP pancreatitis and how they

are cumulative. As evidenced by a report he quoted indicating 7 deaths from this

complication in Denmark, 6 fit the profile of patients at high risk for this

outcome: women in the 40- to 65-year age group being evaluated for pain without

evidence of biliary ductal dilatation or abnormal liver function tests. Freeman

went on to debunk what he called " myths " of ERCP -- that diagnostic ERCP is safe

(he showed data to support the concept that the complication rate is barely

lower for diagnostic vs therapeutic ERCP); that sphincter of Oddi manometry

(SOM) is the cause of post-ERCP pancreatitis in patients with sphincter of Oddi

dysfunction (it is the manipulation of ERCP, and not the manometry, that causes

the problem); that experience alone can prevent post-ERCP pancreatitis; and that

the risk of post-ERCP pancreatitis is the same after SOM and empiric

sphincterotomy without previous SOM.

Pancreatic stenting in " at-risk " patients has been shown in 5 randomized

controlled trials, and in at least as many case series, to greatly reduce the

risk of post-ERCP pancreatitis. Even more impressive has been the reduction in

cases of severe pancreatitis in this setting. Five- and 7-French (Fr) gauge

pancreatic stents have the tendency to cause ductal changes that are often

irreversible. Three-Fr gauge soft, unflanged, single pigtail pancreatic stents

protect against post-ERCP pancreatitis without damaging the pancreas, and the

majority (90%) spontaneously migrate out of the body, obviating the need for

repeat endoscopy to retrieve them.

Pier-Alberto Testoni, MD,[5] from Milan, Italy, reviewed the challenging history

of chemoprevention for post-ERCP pancreatitis. Many pharmacologic interventions

have been attempted in an effort to reduce the toll of pancreatitis in the

post-ERCP setting. Often, the initial results are favorable (and sometimes

spectacular), but larger clinical trials typically show lack of true therapeutic

effect. Corticosteroids, antibiotics, anticholinergics, interleukin-10, and

lexipafant have all ended up in the post-ERCP pancreatitis chemoprevention

" graveyard, " so to speak. The work of Dr. Testoni and other Italian researchers

on gabexate, a protease inhibitor, has shown benefit, but the need for at least

6 hours of pretreatment with this agent by intravenous infusion makes this a

rather cumbersome intervention.

Jowell, MD,[6] from Duke University, reviewed the impact of a trial of

intravenous secretin given immediately before ERCP as a chemopreventive

strategy. This pancreatic secretagogue was shown to significantly reduce the

risk of post-ERCP pancreatitis in certain high-risk groups of patients,

including those individuals undergoing biliary sphincterotomy. A further

randomized controlled trial looking specifically at patients with a predicted

high risk of post-ERCP pancreatitis is planned for the near future. Also

mentioned was a recently published study from Glasgow, Scotland,[7] using a

nonsteroidal anti-inflammatory drug, diclofenac, given by suppository after

ERCP, which showed benefit. This all raises the intriguing possibility of using

drugs that interfere with the post-ERCP pancreatitis process after the

initiating event.

Carr-Locke, MD,[8] from Brigham and Women's Hospital, concluded the

symposium with his personal thoughts regarding how to avoid post-ERCP

pancreatitis. He reminded the audience that avoiding ERCP altogether is the best

prevention, a strategy increasingly facilitated by a myriad of less invasive or

noninvasive techniques, including endoscopic ultrasound magnetic resonance

cholangiopancreatography.

Concluding Remarks

Thus, as evidenced by key presentations at this year's DDW meeting, issues in

pancreatic disease remain a significant challenge for the practicing

gastroenterologist. It is hoped that the above discussion helps to frame these

issues in the appropriate clinical perspective, perhaps with a view toward

future directions.

References

1.. Papachristou GI, Malehorn DE, Avula H, et al. Serum proteomic pattern as a

predictor of severity in acute pancreatitis. Gastroenterology. 2004;126(suppl

2):A-29. [Abstract 253]

2.. Khalid A, Finkelstein SD, Brody D, et al. Mutational allelotyping of

aspirated free-floating DNA predicts the biological behavior of cystic

pancreatic neoplasms Program and abstracts of Digestive Disease Week 2004; May

15-20, 2004; New Orleans, Louisiana. [Abstract 264]

3.. Gardner TB, Mackenzie TA, Oringer JA, on DJ. The effect of

gastroenterology consultation on practice patterns and outcomes in acute

pancreatitis. Gastroenterology. 2004;126(suppl 2):A-30. [Abstract 257]

4.. Freeman M. Just how risky is ERCP? In: AGA Clinical Symposium: Prevention

of Post-ERCP Pancreatitis (PEP). Program and abstracts of Digestive Disease Week

2004; May 15-20, 2004; New Orleans, Louisiana. [sp318]

5.. Testoni PA. Chemoprevention of post-ERCP pancreatitis. In: AGA Clinical

Symposium: Prevention of Post-ERCP Pancreatitis (PEP). Program and abstracts of

Digestive Disease Week 2004; May 15-20, 2004; New Orleans, Louisiana. [sp319]

6.. Jowell PS. Does secretin prevent post-ERCP pancreatitis? In: AGA Clinical

Symposium: Prevention of Post-ERCP Pancreatitis (PEP). Program and abstracts of

Digestive Disease Week 2004; May 15-20, 2004; New Orleans, Louisiana. [sp320]

7.. Murray B, R, Imrie C, S, O'Suilleabhain C. Diclofenac reduces

the incidence of acute pancreatitis after endoscopic retrograde

cholangiopancreatography. Gastroenterology. 2003;124:1786-1791.

8.. Carr-Locke DL. How I Avoid Post-ERCP Pancreatitis. In: AGA Clinical

Symposium: Prevention of Post-ERCP Pancreatitis (PEP). Program and abstracts of

Digestive Disease Week 2004; May 15-20, 2004; New Orleans, Louisiana. [sp321]

I hope this finds you and yours well

Mark E. Armstrong

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