Early Onset Idiopathic Chronic Pancreatitis

Armando Gabbrielli
Department of Digestive Diseases, Università Campus Bio Medico. Rome, Italy
Layer et al. were the first to describe a
different clinical course in patients with
idiopathic chronic pancreatitis (ICP) as
compared to those having alcoholic
pancreatitis (AP) [1]. They found that patients
with early onset ICP (onset before 35 years of
age) have, initially and thereafter, a long
course of severe pain but develop
morphological and functional pancreatic
damage slowly, whereas patients with late-
onset ICP (onset after 35 years of age) have a
mild and often painless course (pain absent in
nearly 50% of patients) confirming the earlier
observations of Ammann et al. [2]. Both
forms differ from AP in their equal gender
distribution and much slower rate of
calcification. In contrast, Lankisch et al. [3]
found that the clinical course is the same in
alcohol- and non-alcohol- induced chronic
pancreatitis. Even when they divided the non-
alcoholic group into teetotallers and patients
with little alcohol consumption, and
compared their course of pain with alcoholics
separately, there were no differences
concerning pain among the three groups [4].
Probably, one of the reasons for the
differences between the data of Layer et al.
[1] and Lankisch et al. [3] is patient selection.
To determine the specific and distinguishing
features of each type of chronic pancreatitis
and avoid any overlap between the groups,
Layer et al. [1] included patients in the
idiopathic group only if they absolutely
abstained from alcohol and had no recognized
causes of chronic pancreatitis and included
patients in the alcoholic group only if they
abused alcohol. Consequently, they excluded
from the study all patients with an uncertain
etiology of chronic pancreatitis, including
patients who consumed a moderate or
unknown amount of alcohol. Using these
strict criteria, they obtained very
homogeneous and selected groups of patients
within the idiopathic groups which permitted
the identification of early and late onset
idiopathic pancreatitis. The clinical findings
in the early onset group (slow destruction of
the parenchyma and late development of
pancreatic insufficiency and calcification) are
very important because it may be difficult to
make an early diagnosis due to the lack of
diagnostic criteria such as structural
abnormalities on ERCP or calcification. This
has been confirmed in a recent paper [5] in
which the time lapse between the onset of the
symptoms and the diagnosis averaged 5 years.
The recent introduction of magnetic
resonance cholangiopancreatography (MRCP)
allows a non-invasive visualization of the
pancreatic ducts [6]. In the initial phases of
early onset ICP, the main pancreatic duct
(MPD) has a normal size; one limitation of
MRCP is the difficulty of visualizing the side
branches of the pancreas, whose alterations
are indicative of early chronic pancreatitis.
Improved visualization of the side branches at
MRCP with secretin stimulation (s-MRCP)
allows an earlier diagnosis of chronic
pancreatitis and reduces the false negative
rate of MRCP to make it a valid non-invasive
alternative to diagnostic ERCP in patients
suspected of having pancreatic disease [7, 8].

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JOP. Journal of the Pancreas – http://www.joplink.net – Vol. 4, No. 4 – July 2003
Furthermore, functional studies can be
performed to quantitate duodenal filling
before and after secretin stimulation [9].
In the experience of Layer et al. [1],
significantly more patients having early onset
ICP undergo surgery as compared to those
having late onset ICP (60% vs. 32%),
intractable pain being the indication for
operation in all cases. The origin of pancreatic
pain in patients with chronic pancreatitis is
not completely understood and is probably
multifactorial, including inflammation, duct
obstruction with increased pressure within the
duct [10], high pancreatic tissue pressure
(compartment syndrome) [11], fibrotic
encasement of sensory nerves, and
neuropathy characterized by both increased
numbers and the size of intrapancreatic
sensory nerves, and by inflammatory injury to
the nerve sheaths allowing exposure of the
neural elements to toxic substances [12, 13].
Surgical options for the treatment of pain
include drainage procedures and pancreatic
resection. Drainage procedures are based
upon the presence of a widely dilated main
pancreatic duct (greater than 6-7 mm) and
resection procedures should be considered in
patients whose ducts are not dilated. It has
been suggested that resectional surgery should
be avoided to preserve, as far as possible, the
remaining function especially in young
patients. In the derivative series, short pain
relief is achieved in about 80% of patients
with very low morbidity and mortality (0-
5%). The series with a long term follow-up
show that pain not uncommonly recurs; pain
relief persists for more than 2 years in only
60% of patients [14]. Therapeutic endoscopy
offers several modalities for pancreatic duct
sphincterotomy (EPS), stone removal,
(ESWL) in case of pancreatic duct stones
unextractable by endoscopic techniques alone
and the insertion of a pancreatic stent for
strictures of the distal main pancreatic duct
[15]. The effectiveness of endotherapy must
be correlated with the ability to achieve
decompression and complete clearance of
stones from the main pancreatic duct.
Endoscopic treatment should be reserved for
patients with a dilated MPD. MRCP allows
the selection of patients who might benefit
from endoscopic treatment. No data are
available on surgical treatment in patients
with early onset ICP. Recently, a paper on
endoscopic treatment in this highly selected
subgroup of patients has been published [5].
This is the only paper which has been
published on endoscopic treatment in patients
with early onset ICP. Results of the study
indicate that endoscopic treatment is highly
effective in short, medium and long term
follow up. Unfortunately, it is a retrospective,
non randomized versus surgery study. As
noted by Cotton [16], it is extremely difficult
to randomize patients to two treatments that
have such different levels of invasiveness.
Furthermore, Cotton [16] believes that most
of our knowledge of effectiveness does and
will come from non-randomized studies, in
which precise definitions for each element are
used, as suggested by the American Gastro-
enterological Association (AGA), for the
treatment of patients with pain caused by
chronic pancreatitis [14]. In the Italian study
[5], the efficacy of endoscopic treatment was
confirmed by the statistically significant
difference between rates of hospitalization
during the year before and at 1, 3 and 6 years
after endoscopic treatment. The number of
hospitalizations appears to be an objective
method of analyzing the effectiveness of
endotherapy for the relief of pain. A mean
follow up of 6 years must be considered
necessary to confirm treatment efficacy even
in patients with relapsing pain. Moreover
recurrences of pain were successfully
managed endoscopically in all cases. This is
very important for two main reasons: the
possibility of repeated treatment is an
advantage compared with surgery in patients
with a chronic disease like chronic
pancreatitis and furthermore, endotherapy
does not preclude subsequent surgery if it
should become necessary. Unfortunately, in
the study, there are no data about the exocrine
function of the pancreas. More long term
studies are needed to assess the effect of
endoscopic treatment on endocrine and

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JOP. Journal of the Pancreas – http://www.joplink.net – Vol. 4, No. 4 – July 2003
exocrine functions (with the aid of s-MRCP)
especially in young patients. Another very
important point that should be stressed is that
endoscopists interested in chronic pancreatitis
treatment must be familiar with all the
procedures needed to obtain clearance and
detension of MPD such as ESWL. Also in
patients with early onset ICP, ESWL was
required in 5 of 6 patients with pancreatic
stones. As previously outlined [17], ESWL
should be considered complementary and not
alternative to the endoscopic drainage of the
MPD and increase the success rate of non-
surgical treatment of patients with chronic
pancreatitis. All patients treated in the Italian
study [5] had a dilated MPD as demonstrated
by pancreatography. With the advent of non-
invasive imaging modality for the pancreas
(s-MRCP), it will be very interesting to
analyze the efficacy of endotherapy in
modifying the natural history in patients in the
initial stages of chronic pancreatitis. We are
waiting for the preliminary results of
endotherapy in patients with clinical
symptoms (pain and elevation of amylase and
lipase) and small alterations of side branches
with a normal MPD or only the alteration of
the pancreatic juice outflow as demonstrated
by prolonged modification of the main
pancreatic duct diameter after secretin
stimulation. Endotherapy is characterized by
low morbidity and no mortality. This is true
for patients with severe chronic pancreatitis
having a fibrotic pancreas but what will the
results be of the endoscopic treatment - in
term of morbidity and mortality - in a "normal
pancreas" at the initial stage of the disease?
Moreover, will the recent discovery of genetic
mutations in patients with chronic pancreatitis
[18, 19] help us to recognize patients with
“different patterns" of chronic pancreatitis?
In conclusion, endoscopic treatment of
patients with early onset chronic pancreatitis
could be considered an effective treatment
and could be regarded as the initial
management of choice in this very selective
group of patients.
Magnetic Resonance Imaging; Pancreatic
Disease; Pancreatitis; Pancreatitis, Alcoholic;
Sphincterotomy, Endoscopic
alcoholic pancreatitis; EPS: endoscopic
extracorporeal shock-wave lithotripsy; ICP:
idiopathic chronic pancreatitis; MPD: main
pancreatic duct; MRCP: magnetic resonance
cholangiopancreatography; s-MRCP: MRCP
with secretin stimulation
Armando Gabbrielli
Department of Digestive Diseases
Università Campus Bio Medico
Via Longoni 83
00155 Rome
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