New Approaches for the

Treatment of Acute
Pancreatitis

Raffaele Pezzilli, Lorenzo Fantini, Antonio Maria

Morselli-Labate
Department of Internal Medicine and Gastroenterology,
Alma Mater Studiorum - University of Bologna,
SantOrsola-Malpighi Hospital. Bologna, Italy

Summary

In recent years, a number of articles have been published on the treatment of

acute pancreatitis in experimental models and most of them were published about
animals with mild disease. However, it is difficult to translate these results into
clinical practice. For example, infliximab, a monoclonal TNF antibody, was
experimentally tested in rats and it was able to significantly reduce the pathologic
score and serum amylase activity, and also alleviate alveolar edema and acute
respiratory distress syndrome; no studies are available in clinical human acute
pancreatitis. Another substance, such as interleukin 10, was efficacious in
decreasing the severity and mortality of lethal pancreatitis in rats, but seems to
have no effect on human severe acute pancreatitis. Thus, the main problem in
acute pancreatitis, especially in the severe form of the disease, is the difficulty of
planning clinical studies capable of giving hard statistically significant answers
regarding the benefits of the various proposed therapeutic agents previously
tested in experimental settings.

According to the pathophysiology of acute pancreatitis, we may re-evaluate the

efficacy of the drugs already available, such as gabexate mesilate, lexipafant and
somatostatin which should be probably administered in a different manner. Of
course, also in this case, we need large studies to test this hypothesis.

Another great problem is prevention of the infection of pancreatic necrosis. A

randomized study has been published to test the hypothesis that probiotics and
specific fibres used as supplements in early enteral nutrition may be effective in
reducing pancreatic sepsis and the number of surgical interventions. A study
named PROPATRIA (Probiotic Prophylaxis in Patients with Predicted Severe Acute
Pancreatitis) has been planned to give a more robust confirmation to the previous
study. Furthermore, the open question of the prevention of the fungal infection of
necrosis is still being debated.

Pathophysiology and Clinical

Phases of Acute Pancreatitis
PHASE INITIALEARLY
TIMING

Hours1st week

MIDDLE LATE

2nd week
3rd-4th week

Inappropriate
Altered intra-acinar
activation Microcirculatory
of
protein traffic
proteases
disorders

MAJOR
EVENTSAccumulation of

trypsinogen in the Necrosis

interstitial space

DEATHS
M.O.F.
Causes
Infection

?
?
?

32%
26%
0%

Gut and biliary

bacteria

Progression of
necrosis
Macrophage
activation

12%
0%
5%

Infection
of necrosis

19%
0
12%

37%
0
28%

R. Pezzilli, et al. Ospedali Italiani Chirurgia 2004; 10: 314-23. [1]

The Therapeutic Window

Therapeutic Window

Pain
Cytokine cascade
Organ dysfunction
0

12

24

36

48

60

72

84

90 hrs
96

Norman J. Am J Surg 1998; 175:76-83. (modified) [2]

We Should Thank

Bradley EL 3 rd.
A clinically based classification system for
acute pancreatitis.
Summary of the International Symposium
on Acute Pancreatitis,

Pancreatitis:
from the Pathological to the Clinical
Point of View
Marseille

(pathological
classification) [4]
Edematous

acute
pancreatitis
Necrotizing acute
Atlanta (clinical
classification)
pancreatitis
[3]

Mild

acute pancreatitis
Severe acute pancreatitis
Bradley EL 3rd. Arch Surg 1994; 128: 586-90. [3]
Sarles H, et al. Digestion 1989; 43: 234-36. [4]

Treatment of Acute Pancreatitis

The treatment needs

to be tailored to
each individual
patient, considering
the techniques
available in each
Institution

Practical Guidelines for the

Management of Acute
Pancreatitis

The practical guidelines

represent
a new approach
for the treatment of
acute pancreatitis

Published Papers on Practical

Guidelines
ATLANTA: Bradley EL 3rd. Arch Surg 1994; 128:586
90. [3]
UNITED KINGDOM: Gut 1998; 42(Suppl 2):1S-13S.
[5]
Gut 2005; 54(Suppl 3):iii1-9. [6]
SSAT: J Gastrointest Surg 1998; 2:487-8. [7]
SANTORINI: Dervenis C, et al. Int J Pancreatol 1999;
25:195-210. [8]
AISP: Uomo G, et al. It J Gastroenterol Hepatol 1999;
31:635-42. [9]
WCG: Toouli J, et al. J Gastroenterol Hepatol 2002;
17(Suppl):S15-39. [10]

Congruence of Specific Practical

Guidelines
Atlanta
UK
SSAT Santorini
1994 1998
2
- 005 1998
1999
APACHE IIAPACHE II
Stratification of
CRP
BMI
severity
CECT Chest X-ray
CECT scanning Severe APSevere AP

AISP
1999

WCG
2002

JSAEM
2002

IAP
2003

BMI Chest X-ray +

Chest X-ray
creatinine
II
N/a APACHEserum
APACHE IIAPACHE IIAPACHE II
CRP
APACHE-O CECT
CRP
N/a

Severe AP Severe AP Severe APSevere AP

N/a

Treatment of pain N/a

N/a

Yes

N/a

N/a

Yes

Yes

N/a

Treatment of nausea,
N/a
vomiting, ileum

N/a

N/a

N/a

Yes

N/a

N/a

N/a

Yes
Yes
N/a
Yes
Yes
N/a
N/a
Fluid replacement N/a
Necrotizing
Necrotizing
Necrotizing
NecrotizingNecrotizingNecrotizing
Necrotizing
Necrotizing
Early antibioticspancreatitis
pancreatitis
pancreatitis
pancreatitispancreatitispancreatitis
pancreatitis
pancreatitis
Severe AP
Severe AP Severe AP Severe APSevere AP
CholangitisCholangitis
Cholangitis
CholangitisCholangitisCholangitis
CholangitisCholangitis
ERCP+ES
Jaundice Jaundice
Jaundice Jaundice Jaundice Jaundice Jaundice
Surgery for sterileRarely
N/a
N/a
Rarely
Rarely
Rarely
Rarely
Rarely
necrosis
FNA to identify infected
Yes
Yes
N/a
Yes
Yes
Yes
Yes
Yes
pancreatic necrosis
Enteral nutrition

N/a

N/a
Efficacy of antiproteases
Pancreas Units

Yes

Yes

N/a

Yes

N/a

Yes

Yes

Yes

No

N/a

No

Severe AP

No

Yes

N/a

Yes

Yes

Yes

Yes

Yes

Yes

N/a

cute pancreatitis; N/a: not availableBradley EL 3rd. Pancreatology 2003; 3:139-43. (modified) [13]

Evidence Level in the

Various Practical Guidelines
Atlanta UK SSAT
Santorini
AISPWCGJSAEM IAP
19941998-20051998 1999 19992002 2002 2003
Stratification of severity
B
B
N/a
B
B N/a
A
N/a
CECT scanning
B
B
N/a
A
A N/a
B
N/a
Treatment of pain
N/a
N/a
N/a N/a N/a N/a N/a N/a
Treatment of nausea, N/a
N/a
N/a N/a
C N/a N/a N/a
vomiting, ileus
Fluid replacement
N/a
B
B
C
C
C
N/a N/a
Early antibiotics
N/a
B
B
A
A
B
B
A
ERCP+ES
N/a
A
B
B
A
B
B
N/a
Timing of cholecystectomy
N/a
B
N/a N/a
B
B
N/a
B
Surgery for sterile necrosis
N/a
B
N/a
A
B
B
B
B
FNA to identify infected
B
N/a
B
A N/a
A
B
pancreatic necrosis N/a
Enteral nutrition
N/a
A
N/a
B
N/a A
B
B
Efficacy of antiproteases
N/a
A
N/a
A
A
A
A
N/a
Pancreas Units
B
B
B
C
B N/a
B
N/a

B: non-randomized clinical studies; C: expert opinion; N/a: not available

Bradley EL 3rd. Pancreatology 2003; 3:139-43. (modified) [13]

The Participants of the

Santorini Consensus Meeting

What Do We Ask of Practical

Guidelines?

Guiding the Reluctant [13]

but we need to

Address the Guideline

Writers Efforts
in order to

Unify the Guidelines

Bradley EL 3rd. Pancreatology 2003; 3:139-43. [13]

Revision of the UK Practical Guidelines

ngdom guidelines for the management of acute pan

Gut 1998; 42 (Suppl 2):1S-13S [5]

ngdom guidelines for the management of acute pan

Gut 2005; 54(Suppl 3):iii1-9 [6]

Gurusamy KS, Farouk M, Tweedie JH.

nes for management of acute pancreatitis: is it time
Gut 2005; 54:1344-5. [14]

European Gastroenterologists
Awareness
of Practical Guidelines
German Consensus Conference 2000

Atlanta Symposium 1992

World Congress of Gastroenterology 2002

British Society of Gastroenterology 1998

International Association of Pancreatology 2002

Santorini Consensus Conference 1999

Society for Surgery of the Alimentary Tract 1998

Japanese Society of Abdominal Emergency Medicine 2002

92%

53%

49%

40%

31%

20%

14%

6%

Lankisch PG, et al. Pancreatology 2005; 5:591-3. [15]

Guidelines for the management of gallstone

acute pancreatitis are not being met,
Sargen
K, Kingsnorth
AN. JOP.of
J Pancreas
(Online) 2001; 2:317-22.
[16]
resulting in
high
rates
readmission
with

Basic Management of Acute

Pancreatitis

The
The

Control of Pain

Control of Nausea, Vomiting,

Ileus

Basic Management of Acute

Pancreatitis

The

Control of Pain

The

Control of Nausea, Vomitin

Th
e
Co
ntr
ol
of
the
Pai
n

Pharmacological Control of the Pain

Study

Patients with
acute pancreatitis

Ebbehoj N
Scand J Gastroenterol
1985 [17]
Double-blind, placebocontrolled
Jakobs R
Scand J Gastroenterol
2000 [18]
Double-blind,
controlled
Stevens M
Appl Nurs Res 2002
[19]
Double-blind,
controlled
Kahl S
Digestion 2004 [20]
Open, controlled

Analgesics

Results

30

Indomethacin

Indomethaci
n better
than placebo

40

Buprenorphine

Buprenorphi
ne better
than
procaine

32

10
7

suppositories, 50 mg
twice daily

constant i.v. infusions

Procaine constant i.v.
infusion
Fentanyl TTS
Demerol i.m.
Procaine

continuous
i.v. infusion
Pentazocine every 6 h
(i.v. bolus)

No
statistically
significant
difference
Pentazocine
better than
procaine

Basic Management of Acute

Pancreatitis

The

Control of Pain

The

Control of Nausea, Vomitin

The Control of
the Nausea,
Vomiting, Ileus

The Naso-Gastric Suction

Study

Patients and
Study Design

Patients

Results

Naeije R
Br Med J
1978 [21]
R ando mize
d

58 patients NG = 27
with mild to
moderately no NG =
31
severe AP

Most patients with mild to

moderately severe acute
pancreatitis do not benefit
from nasogastric suction

Navarro S
Digestion
1984 [22]
R andomize
d

88
NG = 44
unselected
patients with no NG =
44
acute
pancreatitis

Nasogastric suction should

be reserved for patients
presenting with intestinal
ileus, a situation which
occurred in 1 out of every 8
cases in the present series

Sarr MG
Surgery
1986 [23]
Randomized

60 patients with NG = 29
acute pancreatitis
of mild to
no NG
moderate severity
=31

NG tended to resume oral

intake later and remain
hospitalized longer

NG: naso-

Gastric Acid Secretion Inhibition

Study

Patients

18 pts with
Maisto OE,
acute alcoholic
S Afr Med J 1983 [24]
pancreatitis
15 pts did not
Open study
receive antacid
therapy

Results

There
was
no
statistical difference in
the course of the
illness between the
two groups as regards
duration of abdominal
pain,
epigastric
tenderness,
hospital
stay
or time taken for
40 controls
Pirenzepine-treated
Moreno-Otero R,
the patient to resume
36 pts: 10 mg of patients showed a
Digestion 1989 [25]
a significant
normal dietdifference
pirenzepine
in the duration of
Double blind studyevery 12 h i.v.
39 pts: 20 mg of hyperamylasemia
and duration of pain
pirenzepine
Complications were
every 12 h i.v.
less frequent and

Experimental Treatment of Acute

Pancreatitis
More than 2,000 papers on the
treatment of acute pancreatitis in
experimental
models
have
been
published in the last 5 years
About a half of these studies were
carried out on edematous pancreatitis
Only a few of the substances tested in
these studies have been applied in
clinical practice
MEDLINE Search, August 2005

Infliximab in Acute Pancreatitis

Infliximab,

a
monoclonal
TNF
antibody, was tested in 100 rats
randomly assigned to 10 groups

In

acute edematous pancreatitis and

in severe necrotizing pancreatitis,
the drug significantly decreased
serum amylase activity and the
histopathologic score

In

severe necrotizing pancreatitis, it

ameliorated both parenchymal and
fatty tissue necrosis of the pancreas

Oruc N, et al. Pancreas 2004; 28:E1-8. [26]

Resveratrol in Acute Pancreatitis

To evaluate the protective and

antioxidative effect of resveratrol,
a stilbene derivative, in acute
pancreatitis induced by tert-butyl
hydroperoxide injection

Changes in pancreata were much

less pronounced in the rats which
received resveratrol for 8 days
prior to tert-butyl hydroperoxide
injection

Lawinski M, et al. Pancreas 2005; 31:43-7. [27]

Limitations of Experimental Models for

the Treatment of Acute Pancreatitis

The utility of such experimental models might have

limitation, and a full extrapolation of experimental data
Pastor CM, must
Frossard JL.
FASEB
J 2001;
15:893-7.
from laboratory animals to humans
be
done
with

Interleukin-10 in Acute Pancreatitis

P<0.05

New organ failure (%)

icacy in experimental study

No effect in humans

P NS

u WG, et al. J Surg Res 2002; 103:121-6. (modified) [29]

Villoria A, et al. Pancreatology 2003; 3:466. [30]

Polyunsaturated Fatty Acids in Acute

Pancreatitis

cacy in experimental study and in humans

P<0.05

P NS

P<0.05

P<0.05

P<0.05

P<0.01

Foitzik T, et al. JPEN 2002; 26:351-6. [31] Lasztity N, et al. Clin Nutr 2005; 24:198-205. [32]

Problems in Performing
Studies on Therapeutic
Agents
In

the last 5 years, only 11 studies

have been published on the treatment
of human severe acute pancreatitis
(most of them on the early antibiotic
treatment)

It

is difficult to plan clinical studies on

acute pancreatitis capable of giving
specific answers regarding the benefits
of the various proposed therapeutic
agents in human clinically severe acute

Designing Future Clinical

Trials in Acute Pancreatitis
Therapeutic

trials need to record the time from

onset of symptoms to intervention

There

is the need of using widely accepted

prognostic indices to categorize the severity of
acute pancreatitis

There

is the need for relevant and interpretable

end-points:
Mortality is important but more work is necessary in
developing patient outcomes
Good alternatives include the measurement of
permanent target organ damage, disability, quality
of life, pain scores, category of intervention,
Siriwardena
AK. Pancreatology
surgery, in-patient Mason
stayJ, and
return
to work2005; 5:113-5. [33]

Immune-Manipulation in Acute
The- study
included 290
patients:
The Pancreatitis
Lexipafant
Example
-

151 in the Lexipafant group and 139 in the placebo

group
4 patients were subsequently excluded (three due to
incorrect diagnosis and one fdue to a major violation
of the protocol)
The analysis of complications regarded 138 patients
of the Placebo group and 148 of the Lexipafant group
The analysis of attributable mortality was carried out
in 147 patients of the Lexipafant group and in 136 of
the Placebo group
The analysis of treatment performed within 48 hours
from the onset of symptoms of acute pancreatitis was
performed in 104 patients of the Lexipafant group
LexipafantgroupPlacebo
Significance
Complications
and in 95 patients of the Placebo
85/148 (57%)
Organ failure
80/138 (58%) NS
4/148 (3%)
Systemic sepsis
13/138 (9%) P=0.023
8/148 (5%)
Pseudocyst
19/138 (14%)P=0.025
Attributable deaths (pts treated 48 hrs
8/104 (8%) 17/95 (18%)
P=0.034

Johnson CD, et al. Gut 2001; 48:62-9.

Lexipafant: Critical Appraisal of the

Clinical Trials
The

trials
with
infliximab
are
an
example of the magic
bullet
approach
which
has
typified
anticytokine trials

The

restoration
of
homeostasis with a
single
intervention
belies the complex and
coordinated nature of
the
inflammatory
response
Abu-Zidan FM, Windsor JA. Eur J Surg 2002; 168:215-9. [35]

Adverse Events of ImmuneManipulation

we must be aware of several autoimmune phenom

treated with
andofanticytokine
therapies
cytokine
Development
anti-DNA antibodies
Development of antinuclear antibodies
Development of anticardiolipin antibodies
Infliximab
Systemic lupus erythematosus
&
Etanercept Neurological signs and symptoms
associated with demyelinating lesions of
the CNS
Development of antithyroid antibodies
Thyroid dysfunction
Interleuki Arthritis
n2
Myositis
Systemic sclerosis
Pemphigus vulgaris
Vitiligo
Carpal tunnel
syndrome
Furthermore
Pezzilli R, et al. JOP. J Pancreas (Online) 2004; 5:15-21. [36]

The Need for Clinical Research

Scientific

method: clinical trials should be

preceded by experimental and pilot studies in
order to confirm the safety and the correct
dosage and to estimate the necessary efficacy
of future trials

Communication

of
the
results:
Communication of the results from the clinical
trials in acute pancreatitis should be improved.
Editors share the responsibility of publishing
well-designed and conducted clinical studies
whether or not the results are negative

Commercial

influence: The risks associated

with dealing with biotechnology companies are
Abu-Zidan FM,can
Windsorbe
JA. Eur under
J Surg 2002; 168:215-9.
[35]
well-known. Companies
severe

Treatment of Acute
Pancreatitis with Protease
Inhibitors

Ten articles of randomized controlled trials

evaluating the effects of protease inhibitors
(Aprotinin
and
Gabexate)
for
acute
pancreatitis
were
retrieved
by
systematically searching Medline, Cochrane
Library and Ovid databases published from
January 1966 through December 2003.
The main outcome of interest was the
overall
mortality
rate
from
acute
pancreatitis
When protease inhibitors were given to
patients with mild pancreatitis, they were
not significant (pooled RD 0.00; 95% CI
from -0.04 to 0.05)
Seta T, et al. Eur J Gastroenterol Hepatol 2004; 16:1287-93. [37]

A Critical Appraisal of the

Clinical Trials in Acute
Pancreatitis
Several

steps may have to be blocked at the

same time and this may be achieved by
using combinations of several drugs at the
same time or by the multiple actions of a
Trypsinogen
Acute Pancreatitis
single drug
Trypsin
PSTI
PSTI + Trypsin
Alfa1-AT
Alfa1-AT + Trypsin

Systemic circulation
Alfa2-M
Alfa2 + Trypsin

RES
Mesotrypsin
Trypsin
Enzyme Y
Liver
Spleen
Procolipase
Prokallycrein
Bone marrow
Proelastase
C3
Nodes
Chymotrypsinogen
C5
Prophospholipase A2
Plasminogen
Clearance
Xanthynedehydrogenase
XII Factor
Kininogens
Colipase
Kallycrein
Elastase
C3a
Kinins
Chymotrypsin
C5a
Phospholipase A2
Plasminogen
Xanthynedehydrogenase
XIIa Factor

IL-1

IL-6
IL-8

N.O.

TNF
PAF

Other leucocyte
products
Oxygen radicals
Elastase
IFN-,
IL-10
IL-2

Complications:
Vascular leakage
Hypovolemia
Shock
ARDS
Acute renal tubular necrosis

Norman J. Am J Surg 1998; 175:76-83. (modified) [2]

The Prevention of Infection of the

Necrosis
September 1st, 2004

September 7th, 2004

October 26th, 2004

Enteral Feeding and Severe Acute

Pancreatitis
34

severe acute pancreatitis patients

SIRS,

sepsis, organ failure, and ICU stay were

globally improved in the enterally-fed patients

The

acute phase response and disease severity

scores (CRP, APACHE II) were significantly
improved following enteral nutrition without any
change in the CT scan scores

Enteral

feeding modulates the inflammatory and

sepsis response in acute pancreatitis and is
clinically beneficial

Windsor AC. Gut 1998; 42:431-5. [38

Early Naso-Gastric vs. Naso-Jejunal

Feeding
in Severe Acute Pancreatitis
A

total of 50 consecutive patients with

objectively graded severe acute pancreatitis
were randomized to receive either NG or NJ
feeding via a fine bore feeding tube
A total of 27 patients were randomized to NG
feeding and 22 to NJ
Clinical differences between the two groups
were not significant
Overall mortality was 24.5% with five deaths in
the NG group(18.5%) and seven in the NJ
group (31.8%)
The simpler, cheaper, and more easily used NG
naso-gastric;
FC, et al.
Am J Gastroenterol
100:432-9. [3
feedingNJ:isnaso-jejunal
as good Eatock
as NJ
feeding
in 2005;
patients

Probiotics and Fibre Supplement

in Patients with Acute
Pancreatitis

To determine whether lactic acid bacteria such as

Lactobacillus
plantarum
299
could
prevent
colonization of the gut by potential pathogens and
thus reduce the endotoxaemia associated
with acute
Controls (n=23) Lactobacillus (n=22)
pancreatitis

Age (yrs) (meanSD)

46.513.6

44.111.1

Sex ratio (M:F)

17:6

16:6

Etiology (Alcohol: Other)

16:7

13:9

Duration of symptoms (hrs) (meanSD)

21.414.1

26.113.3

Necrotizing pancreatitis

11 (47.8%)

9 (40.9%)

Severe pancreatitis

15 (65.2%)

17 (77.3%)

Controls

Lactobacillus

P value

Positive aspiration culture

7/23 (30.4%)

1/22 (4.5%)

<0.05

Septic complications requiring operation

7/23 (30.4%)

1/22 (4.5%)

<0.05

Olah A, et al. Br J Surg 2002; 89:1103-

Probiotic Prophylaxis in
Patients with Severe Acute
Pancreatitis

Double-blind,
placebo-controlled
randomised
multicenter trial in which patients will be randomly
allocated to a multispecies probiotic preparation (Ecologic
641) or placebo; it will be performed in 15 Dutch Hospitals
The study-product is administered twice daily through a
nasojejunal tube for 28 days or until discharge
Inclusion criteria: adult patients with a first onset of
predicted severe acute pancreatitis: Imrie criteria 3 or
more, CRP 150 mg/L or more, APACHE II score 8 or more
Exclusion criteria: post-ERCP pancreatitis, malignancy,
infection/sepsis caused by a second disease, intra-operative
diagnosis of pancreatitis and use of probiotics during the
study
The study-product administration starts within 72 hours
after onset of abdominal pain
Primary
endpoint:
total
number
of
infectious
complications
Secondary endpoints: mortality, necrosectomy, antibiotic
resistance, hospital stay and adverse
events
Besselink
MG, et al. BMC Surg. 2004; 4:12. [41

Antibiotics and Severe Acute

Pancreatitis: Pros
Pancreatic
infection

ARR: 12%

Sepsis

ARR: 21%

Mortality

ARR: 12%

-60

-40

-20

20

40

60

Absolute Risk Reduction (ARR)

95% CI
Sharma VK, Howden CW. Pancreas 2001; 22:28-31. (modified) [42]

Antibiotics and Severe Acute

Antibiotic Pancreatitis:
prophylaxis Pros
significantly
reduced sepsis by 21.1% and mortality
by 12.3% compared with no prophylaxis
There

was also a non-significant trend

toward a decrease in local pancreatic
infections

Antibiotic

prophylaxis decreases sepsis

and mortality in patients with acute
necrotizing pancreatitis

All

patients with acute necrotizing

pancreatitis should receive prophylaxis
VK, Howden CW. efficacy
Pancreas 2001; 22:28-31. [42]
with an antibioticSharma
of proven

Antibiotics and Severe Acute

Pancreatitis: Cons

Ciprofloxacin (Cip: 400mg x 2/day)+Metronidazole (Met: 500mg x

2/day) (AB) vs. Placebo (P)
Switch to Open treatment: infection, sepsis and MOF
114 ptsMicrobiological
with CRP >150mg/L
and/or
necrosis at
CT (58 with AB
Findings
in Infected
Necrosis
and 56 with P)
Placebo (P)
Cip/Met
Staphylococcus
(AB)
3
epidermidis
1
2
Enterococci
1
1
Staphylococcus aureus
3
1
Escherichia coli
0
3
Enterobacter
1
1
Lactobacillus spp.
0
0
Candida albicans
1
1
Candida
0
glabrata/tropicalis
12% of
AB patients developed infected necrosis vs. 9% in P
(P=0.585) (expected: 40% vs. 20%)
5% mortality rate in AB patients vs. 7% in P (P NS)
In 76 patients with necrotizing pancreatitis, no differences (also
in pts with necrosis >30% )
Cross-over rate: 28% of the
AB patients
require a switch
to open[4
Isenmann
R, et al. Gastroenterology
2004;126:997-1004.

Prophylactic Antibiotic Treatment in

Patients with Predicted Severe
Pancreatitis: A Frank Discussion

The pancreatic necrosis was confirmed by CT criteria in only 58 patients

5 patients had Staphylococcus epidermidis coagulase negative strains and
the dectection of this species might be considered more a contamination than
a true infection
Once the presence of infected necrosis was determined, it was not clear if
surgical intervention was immediate or if this was preceded by the open
administration of antibiotics
28% of antibiotic-treated patients and 46% of the patients of the placebo
group had received an open treatment
These data could suggest not only the need, but the inevitability, in everyday
clinical practice, of prescribing early antibiotic treatment in the management
of severe necrotizing pancreatitis, either prophylactically or on demand

Bassi C, Falconi M. Gastroenterology 2004; 127:1015-6. [44]

Why did the authors choose antibiotics such as fluoroquinolones which, in a

previous clinical study , did not demonstrate efficacy similar to imipenem?
How many patients were fed enterally?
Pezzilli R. JOP. J Pancreas (Online) 2004; 5:161-4. [45]

What Are the Criteria for Predicting

the Pain During Refeeding in Acute
Pancreatitis?
Logistic Score to Predict the Risk of Pain
Relapse
=
0.64 a + 1.11 b + 2.18 c - 9.06

a = Balthazars CT score (5 classes)

b = Duration of painful period (5 classes)
c = Serum lipase concentration on the day before
refeeding <3xN (2 classes)
9.06
= Constant

Levy P, et al. Gut 1997; 40:262-6. [46

Suggested Caloric and Fat Content

During the First Five Days of
Refeeding
Day

Caloric content (kcal)Lipids (g)

250

<5

1,000

5-10

1,500

15-20

1,600

25-30

1,700

35-40

Levy P, et al. Gut 1997; 40:262-6. [46

Lanreotide after Oral Refeeding in

Patients with Necrotizing Acute
Pancreatitis (Study Design)
To

assess the frequency of pain relapse in

patients with acute necrotizing pancreatitis
after treatment with one intramuscular
injection of lanreotide 30 mg on the day
before refeeding

The

refeeding procedure was standardized

and progressive

23

patients: 11 alcoholic, 7 biliary, 5 other

causes
12 had 3 or more Ranson's
criteria
23 had a Balthazar score of D or
E

Levy P, et al. Pancreatology 2004; 4:229-32. [47

Patients
with Necrotizing Acute Pancreatitis
(Results)

Because of this is an uncontrolled pilot study, these

results should be taken with caution and should be
further confirmed through a double-blind controlled

Levy P, et al. Pancreatology 2004; 4:229-32. [47

Studies on Exocrine Pancreatic

Function After an Acute Attack of
Pancreatitis

Ibars EP, et al. World J Surg 2002;

26:479-86. [48]
Pareja E, et al. Pancreatology 2002;
2:478-83. [49]
Sabater L, et al. Pancreas 2004;
28:65-8. [50]

Exocrine Pancreatic Function

After Alcoholic or Biliary Acute
Pancreatitis
P=0.0026

P<0.001

P<0.003

Migliori M, et al. Pancreas 2004; 28:359-63. (modified) [5

Enzyme Supplementation After Acute

Pancreatitis