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100% and the specificity to 64% when compared with ERCP as
the diagnostic gold standard. Although no standardized histo-
logic or cytologic criteria exist for the diagnosis of chronic pan-
creatitis by FNA, a scoring system was used which graded each
specimen with regard to the presence of an inflammatory cellular
infiltrate. The results of this study suggest that FNA is most help-
ful for excluding chronic pancreatitis when mild or patchy
parenchymal abnormalities with unclear significance are identi-
fied on EUS. FNA was generally well tolerated; mild acute pan-
creatitis occurred in 2 of 27 patients studied.
Given the ability to visualize both the pancreatic parenchyma
and duct, in addition to its excellent sensitivity and low associ-
ated procedural risk, the use of EUS for the diagnosis of chronic
pancreatitis has increased over the past decade. As such, the use
of minimal standard terminology to describe endosonographic
findings and the appropriate number of endosonographic
abnormalities required to make the diagnosis of chronic pancre-
atitis are of critical importance. The accuracy of any diagnostic
test is related to the reproducibility of its results [7]. When 11
experienced endosonographers who were blinded to the clinical
history independently evaluated previously taped examinations
for the presence of EUS criteria of chronic pancreatitis, diagnos-
tic agreement was reached at a rate comparable with other
endoscopic or radiographic tests [42]. Agreement was highest
for ductal dilatation and lobularity. As with any diagnostic test,
the clinical history is key to interpreting the results of EUS in the
diagnosis of chronic pancreatitis.
Magnetic resonance cholangio-
pancreatography
While ERCP has been associated with an incidence of acute
pancreatitis in up to 10% of individuals who undergo this
procedure [32], MRCP is able to provide high-quality imaging
of the pancreatic and biliary ducts in a noninvasive manner
[43]. Wallner et al. [44] first described MRCP in 1991. At that
time, the study was time-consuming with questionable image
quality. Over the past 15 years, however, the acquisition time
for single images has gone from 5 min to 2 s, allowing more
widespread use of this technology. In most centers, the imple-
mentation of high-quality MRCP into clinical practice has
replaced diagnostic ERCP [24].
Takehara et al. [45] first compared MRCP, specifically mag-
netic resonance pancreatography, with ERCP for the diagnosis
of chronic pancreatitis. High-quality images of the pancreatic
duct in the head, body, and tail of the gland were obtained in
70%, 64%, and 53%, respectively, of patients, all of whom
had been previously diagnosed with chronic pancreatitis based
on ERCP. Agreement between the two tests was observed in
83–92% of cases of ductal dilatation, 70–92% of cases of
ductal narrowing, and 92–100% of cases with ductal filling
defects. This study also found low interobserver variation for
most findings, although MRCP did tend to overestimate the
extent of pancreatic ductal stenosis [43,45]. Other studies
have yielded similar findings [46].
Secretin is a hormone secreted by the gastrointestinal tract
that leads to rapid secretion of a bicarbonate-rich fluid from
the exocrine pancreas [43,47]. As a result, the volume of fluid
in the pancreatic duct increases. The administration of intra-
venous secretin to improve imaging of the pancreatic duct was
first described in combination with transabdominal ultra-
sonography for the diagnosis of chronic pancreatitis [48,49].
Because of the tendency of MRCP to overestimate pancreatic
ductal stenosis, Takehara et al. [50] studied the use of secretin
stimulation during the acquisition of images in order to
improve signal intensity and imaging of the pancreatic duct in
patients suspected of having pancreatic disease. The investiga-
tors found that the use of secretin improved evaluation of the
main pancreatic duct and its side branches compared with
imaging not using secretin stimulation (Fig. 49.4). These
results have been replicated by other groups [47,51].
Since this initial study, several investigations have focussed
specifically on secretin-enhanced MRCP for the diagnosis of
chronic pancreatitis [52,53]. Manfredi et al. [52] studied this
modality in 31 patients with chronic pancreatitis. The use of
secretin increased the percentage of visible pancreatic duct
segments from 91 to 100% and side branches from 71 to
100%. Although the improved ductal visualization with
secretin was not statistically significant, the authors noted that
improved visualization of the ductal side branches may allow
earlier diagnosis of chronic pancreatitis, thus reducing the
ERCP, MRCP AND EUS IN CHRONIC PANCREATITIS
481
Figure 49.4 Secretin-stimulated magnetic resonance
cholangiopancreatography revealing a markedly dilated main
pancreatic duct with multiple visible side branches. These findings
are consistent with severe chronic pancreatitis.
9781405146647_4_049.qxd 1/30/08 11:46 AM Page 481
false-negative rate and improving the specificity of MRCP for
this diagnosis. Standardized criteria for the diagnosis of
chronic pancreatitis by MRCP have yet to be developed.
Aside from improving delineation of the pancreatic ductal
morphology, secretin-enhanced MRCP may have value in the
measurement of pancreatic exocrine function. Matos et al. [47]
performed MRCP in 10 volunteers and 13 patients with sus-
pected pancreatic disease. Pancreatograms were obtained prior
to and then at 30-s intervals following the administration of
secretin. The volume of filling within the duodenum was used
as a quantitative measure of pancreatic function. The results
were compared with ERCP and secretin stimulation testing.
The study found that the mean duodenal filling score was sig-
nificantly lower in patients with known reduced exocrine func-
tion compared with that in volunteers, thus providing the first
evidence that secretin-stimulated MRCP has the potential to
detect impaired pancreatic exocrine function. These results
have been confirmed by other investigators [52,54–56].
Direct comparisons of MRCP with EUS for the diagnosis of
chronic pancreatitis have yet to be performed. In comparison
with EUS and ERCP, MRCP is certainly the least invasive.
Secretin-stimulated MRCP has the additional advantage of
evaluating pancreatic function, an attribute not shared by EUS
or ERCP. Although not yet studied, this feature may enhance
the specificity of MRCP for the diagnosis of chronic pancreati-
tis. ERCP does not provide detailed images of the pancreatic
parenchyma; this is a potential disadvantage compared with
EUS, which has the ability to detect both ductal and parenchy-
mal abnormalities. Magnetic resonance imaging (MRI) of the
pancreas is possible at the same time as MRCP, although this
adds cost and time to the examination. The MRI findings asso-
ciated with chronic pancreatitis [57] are beyond the scope of
this chapter. Due to its minimally invasive nature and high cor-
relation with ERCP findings, MRCP is often ordered as the
first test for the diagnosis of chronic pancreatitis in cases where
advanced imaging modalities are required [52].
Diagnostic approach
The use of advanced imaging modalities such as ERCP, MRCP,
and EUS for the diagnosis of chronic pancreatitis is not
required in the majority of cases. Indeed, in many cases of
chronic alcoholic pancreatitis, the clinical history alone can be
sufficient to make the diagnosis [11]. However, in some cases,
especially early chronic pancreatitis, advanced imaging is
required. Of these three modalities, EUS likely has the greatest
ability to diagnose early disease. Although it is an invasive
diagnostic test, the complication rate associated with EUS is
less than that of ERCP and it has the ability to detect both mor-
phologic and ductal abnormalities. While MRCP is clearly the
least invasive, it is an expensive test with results that may be
center-dependent. In addition, the ability to visualize the pan-
creatic duct alone may decrease its diagnostic sensitivity for
early disease. Finally, it is the least studied of the three modali-
ties discussed in this chapter. While it is often considered the
gold standard, the high rate of procedure-related complications
associated with ERCP has limited its use in chronic pancreatitis
to the performance of therapeutic interventions.
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Introduction
In the minority of patients (i.e., 5.8–20%), chronic pancreatitis
takes a primarily painless course [1–7]. Exocrine and endocrine
insufficiency are the dominating symptoms. For the majority of
patients, however, pain is the decisive symptom, causing much
discomfort in their daily lives. Some studies have correlated the
course of pain in chronic pancreatitis with the duration of the
disease, progressing exocrine and endocrine pancreatic insuffi-
ciency, and morphologic changes such as pancreatic calcifica-
tion and duct abnormalities. Furthermore, the course of pain
has been studied following alcohol abstinence and after surgery
in some groups.
Pain decrease and duration of chronic
pancreatitis
Whether progressive parenchymal destruction of the pancreas
leads to pain decrease has been repeatedly debated [8,9].
Ammann’s group has claimed that pain decreases with increas-
ing duration of the disease [3,10,11]. In one long-term study,
85% of 145 patients with chronic pancreatitis felt no more pain
after 4.5 years (median) from onset of the disease [3]. In another
series, in which the interval between the onset of alcohol-
induced chronic pancreatitis and pain relief was compared in
surgically and nonsurgically treated patient groups, the curves
were virtually parallel: pain relief was obtained in about 50%
within 6 years and in more than 80% within 10 years from the
onset of illness [12].
The reports from Zürich are at variance with the studies from
Japan and Germany. Miyake et al. [6] found that only 48.2% of
patients with chronic pancreatitis became free of pain within 5
years, but 66–73% became free of pain after more than 5 years.
This showed that every third or fourth patient still suffered
from relapsing pain attacks even after a long observation
period. Our group reported that the incidence of relapsing pain
attacks decreased during the observation period, but more than
half of the patients (53%) still suffered from relapsing pain
attacks after more than 10 years of observation [7].
At present, the course of pain in alcoholic and idiopathic
chronic pancreatitis remains unclarified. Layer et al. [13]
investigated a group of patients with idiopathic chronic
pancreatitis who had never consumed alcoholic beverages dur-
ing their lifetime. They found that patients with early-onset
pancreatitis (under 35 years of age) have a long course of severe
pain from the start of their illness, whereas patients with late-
onset pancreatitis (over 35 years) have a mild and often painless
course. Both forms differ from alcoholic pancreatitis in having
an equal gender distribution and a much slower rate of calcifi-
cation. In contrast, our group has found that the course of pain
is the same in alcohol- and nonalcohol-induced chronic pancre-
atitis [14]. Even when we divided the nonalcoholic group into
teetotallers and patients with little alcohol consumption, and
separately compared their course of pain with alcoholics, there
were no differences concerning pain relief among the three
groups [15]. Further studies are required.
Pain decrease and progressing exocrine
and endocrine pancreatic insufficiency
The Swiss group have repeatedly observed pain decrease when
exocrine and endocrine pancreatic function declines [8–11].
Similarly, Girdwood et al. [16] have reported from South
Africa that pain decreases when exocrine pancreatic function
deteriorates.
Conversely, groups from Denmark and Germany have
reported the opposite. Thorsgaard Pedersen et al. [17] from
Copenhagen found no correlation between pain and exocrine
pancreatic function. Our group in Göttingen [7] have used the
secretin–pancreozymin test and fecal fat analysis to evaluate
exocrine pancreatic insufficiency, whereas the Swiss group had
used only indirect pancreatic function tests, i.e., chymotrypsin
measurements, to evaluate exocrine pancreatic insufficiency
[3]. We used a clear-cut grading of the severity of exocrine pan-
creatic insufficiency: mild impairment was defined as reduced
enzyme output, moderate impairment as a decreased bicarbon-
ate concentration along with reduced enzyme output but nor-
mal fecal fat excretion, and severe impairment was equated
with an abnormal secretin–pancreozymin test plus steatorrhea.
At the end of the observation period, 141 (45%) of 311 patients
with painful chronic pancreatitis had severe exocrine pancreatic
insufficiency. The majority of them (81/144, 57%) still suffered
from pain attacks.
Additionally, we studied the course of pain in correlation with
endocrine pancreatic insufficiency. Endocrine pancreatic insuffi-
ciency was classified as absent, moderate (diabetes mellitus
Natural course of chronic pancreatitis
Paul Georg Lankisch
50
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The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Second Edition
Edited by H. G. Beger, A. L. Warshaw, M. W. Büchler, R. A. Kozarek, M. M. Lerch, J. P. Neoptolemos,
K. Shiratori, D. C. Whitcomb, and B. M. Rau © 2008 Blackwell Publishing Limited, ISBN: 978-1-405-14664-7
treated only by diet with or without oral medication), and severe
(requiring insulin). At the end of the observation period, 117
(38%) patients were classified as having severe endocrine pan-
creatic insufficiency. The majority of them (69/117, 59%) still
suffered from pain attacks [7,18].
Thus, according to our results, the progression of exocrine
and endocrine pancreatic insufficiency has limited, if any,
influence on the course of pain in chronic pancreatitis.
Pain decrease and development of
morphologic changes in the pancreas
(pancreatic calcifications and/or duct
abnormalities)
The Swiss group [3,10] showed an increased incidence of pan-
creatic calcifications, which in turn was associated with pain
decrease. However, in a later survey the same group reported
regression of pancreatic calcifications in a long-term study of
patients with chronic pancreatitis [19]. Thus, the prognostic
role of pancreatic calcifications in determining the course of
pain is unclear.
Furthermore, the Swiss results are at variance with two
other studies. Malfertheiner et al. [20] found that 89% of
patients had pain despite pancreatic calcifications observed on
computed tomography, of whom 39% had very intense pain.
In our study, freedom from pain was significantly higher in the
calcification group compared with the noncalcification group.
However, the majority of patients with pancreatic calcifica-
tions (56%) still had relapsing pain attacks [7].
The correlation between pain and pancreatic duct changes or
pressure in the duct system is also not clear. Ebbehøj et al.
[21,22] measured pancreatic tissue fluid pressure percuta-
neously or intraoperatively and found a significant correlation
with pain in patients with chronic pancreatitis but not with the
results of endoscopic retrograde cholangiopancreatography
(ERCP), i.e., regional pressure tended to be highest in the region
of the pancreas with the largest but not the smallest duct diam-
eter. Jensen et al. [23] found no correlation between pancreatic
duct changes and pain. Warshaw et al. [24] found that 2 of 10
patients, 1 year after lateral pancreaticojejunostomy, had no
pain relief despite a patent anastomosis detected by ERCP.
Two investigations have confirmed the nonparallelism between
pancreatic duct changes and pain relief. Malfertheiner et al. [20]
found severe pain in only 62% of patients who had advanced
pancreatic duct changes demonstrated by ERCP. We found no
significant correlation between pancreatic duct abnormalities
detected by ERCP and pain in 88 patients with chronic pancre-
atitis [7]. Severe pancreatic duct abnormalities, as defined by the
Cambridge classification [25], were present in 42 patients, but
only 16 (31%) of these became free of pain. Despite a normal
pancreatic duct in 14 patients, 10 (71%) suffered from persisting
pain [7].
Thus, morphologic changes such as pancreatic calcifications
or pancreatic duct abnormalities are not necessarily helpful in
determining the prognosis of chronic pancreatitis or predict-
ing the course of pain. Recently it has been shown that smok-
ing has an effect on the natural course of the disease since it
increases the risk of pancreatic calcification in late-onset but
not early-onset idiopathic chronic pancreatitis [26].
Pain decrease and alcohol abuse
Since alcoholism is the leading etiologic factor in chronic pan-
creatitis, several studies have investigated whether alcohol
abstinence influences pain or progression of the disease. Sarles
and Sahel [27] reported that 50% of their patients with
chronic pancreatitis experienced pain relief when alcohol
abuse was discontinued, whereas Trapnell [28] reported a fig-
ure of 75%.
Two other investigations have confirmed that abstinence can
be helpful. Miyake et al. [6] demonstrated pain relief in 60% of
their patients who discontinued or reduced alcohol intake,
whereas spontaneous pain relief was seen in only 26% of the
group who continued drinking. In another study, 66 (31%) of
214 patients with alcoholic chronic pancreatitis were motivated
to stop drinking [7]. Pain relief was obtained in only 52% of
these patients, whereas spontaneous relief in alcoholics was
seen in 37%. Thus, alcohol abstinence in every second patient
with chronic pancreatitis will probably lead to some improve-
ment of pain, but why exactly abstinence helps in some cases
but not others remains to be investigated.
Pain decrease and interventional
procedures
Interventional procedures for pain treatment in chronic pancre-
atitis include fragmentation of stones by extracorporeal shock-
wave lithotripsy (ESWL), endoscopic stone extraction, and
bridging of pancreatic strictures by stent applications. Reports of
the effect of these procedures on pain are controversial and con-
trolled studies are lacking. A large Japanese study of 555 patients
who underwent ESWL for pancreatic stones reported a success
rate of 92.4% (fragmentation of stones) and a complete stone
clearance rate after ESWL alone or in combination with inter-
ventional endoscopy of 72.6%. Symptom relief was achieved in
91.1% of the patients. Complications developed in 6.3% of the
patients, including acute pancreatitis in 5.4%. A total of 504
patients were followed up for a mean of 44.3 months, during
which 122 (22%) suffered stone recurrence (mean time to recur-
rence, 25.1 months); 22 (4.1%) required surgery [29]. In another
series from Japan, a total of 117 patients with pancreatic stones
underwent ESWL and endoscopic treatment. Immediate pain
relief was achieved in 97% and complete removal of stones in
56%. During long-term follow-up over 3 years, 70% of the
patients continued to be asymptomatic [30]. These results are at
variance with a smaller German study in 80 patients with chronic
pancreatitis, in whom ESWL was always followed by a further
NATURAL COURSE OF CHRONIC PANCREATITIS
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endoscopic procedure. Treatment success was defined as com-
plete clearance of the main pancreatic duct or partial clearance
that allowed implantation of a pancreatic stent. Successful treat-
ment was more frequent in patients with solitary stones. The
mean duration of follow-up was 40 (range 24–92) months. Pain
relief and necessity for further analgesia was independent of
ESWL results [31] (Table 50.1). Thus, in this study pancreatic
drainage by ESWL and endoscopy had almost no effect on pain
in chronic pancreatitis in the long term [32].
The effect of pancreatic stents on pain in chronic pancreatitis
is even more controversial. Patients undergoing pancreatic duct
stent placement for disrupted ducts, isolated strictures, pancreas
divisum, and hypertensive pancreatic sphincters showed subse-
quent ductal changes consistent with chronic pancreatitis in
36%, even though 72% of these patients had a normal initial
pancreatogram [33]. Furthermore, patients with preoperative
endoscopic pancreatic stenting had frequent postoperative com-
plications, mostly septic, and a prolonged hospital stay [34].
A surgical review of the pitfalls and liminations of stenting in
chronic pancreatitis reported that the indications for surgery
in patients with a pancreatic stent were severe abdominal pain
in 100%, relapsing pain attacks in 77%, and necrotizing pan-
creatitis in 14%. Before being selected for surgery, 4.5 ERCPs
and 3.7 stent exchanges were performed per patient. Thus, from
the surgical point of view, endoscopic pancreatic duct stenting
in chronic pancreatitis seems not to be indicated because of a
low success rate and a substantial risk of complications [35].
The latter results are in sharp contrast to a long-term out-
come study of pancreatic stenting in severe chronic pancreati-
tis in 100 patients from Belgium. The majority (70%) of
patients who responded to pancreatic stenting remained pain-
free after definitive stent removal. However, a significantly
higher restenting rate was observed in patients with chronic
pancreatitis and pancreas divisum [36]. Obviously, the results
are also different in special subgroups. Endoscopic stenting of
biliary strictures in chronic pancreatitis provided an excellent
short-term but only moderate long-term result in another
study from Germany. Patients without calcifications of the
pancreatic head benefit from biliary stenting. However,
patients with calcifications had a 17-fold increased risk of fail-
ure during the course of a 12-month follow-up [37].
Of special interest is a recent prospective randomized trial
that compared endoscopic with surgical treatment of chronic
pancreatitis. Endoscopic treatment included pancreatic sphinc-
terotomy in all and additional stenting of the pancreatic duct in
33 (52%) patients. Mean duration of stent treatment was 16
(range 12–27) months, and stents were exchanged six times
(range 4–9). Surgical treatment included pancreatic resection in
61 (80%) and drainage procedures in 15 (20%) patients.
Although the short-term effects were similar, the results after
5 years of follow-up showed a comparatively low rate of patients
with complete absence of abdominal pain. However, the results
for surgery were significantly better than for endotherapy
(Table 50.2) [38]. The study has been criticized for the random-
ization, which was agreed to by only 51.4% of the patients.
For the time being, reports of treatment of chronic pancre-
atitis using ERCP by removal or destruction of stones, place-
ment of stents, and dilation of strictures suggest that both
immediate and long-term pain relief are possible. No con-
trolled studies support the generalizability of this finding or
the merit of this approach compared with other management
strategies. Studies of this area would be of value [39].
Pain decrease and surgery
During the course of the disease, every second to fourth patient
needs surgical treatment because of pain and/or organ compli-
cations, such as pancreatic pseudocysts [3,7]. The choice of
surgical procedure depends on the special circumstances of
each patient. However, it is unclear to what extent surgical
treatment influences the course of pain since the different stud-
ies cannot be compared for the following reasons.
• The definition of freedom from pain was often vague, and
pain symptoms were usually not measured. Measurement on
an analog scale is recommended [18].
• Not all patients received the same surgical treatment for the
same indication. Several authors do not recommend perform-
ing an indicated resection in alcoholics because of the difficult
postoperative treatment of diabetes mellitus in these patients
[40,41].
• Although continued alcohol abuse distinctly worsens the
effect of surgical treatment [42–44], it is still difficult to deter-
mine whether postoperative deterioration results from chronic
pancreatitis or continued alcohol abuse, or from the surgical
treatment.
Table 50.1 Long-term effect on pain in 80 patients with chronic
pancreatitis treated with extracorporeal shock wave lithotripsy.
(From ref. 31 with permission.)
Successful Unsuccessful
treatment treatment
(N ϭ 43) (N ϭ 37) P value
Considerable or
complete pain relief 34 (79%) 27 (73%) 0.75
No further analgesia
necessary 27 (63%) 16 (43%) 0.23
Table 50.2 Five years follow-up of abdominal pain in a prospective
randomized trial comparing endoscopic with surgical treatment for
chronic pancreatitis. (From ref. 38 with permission.)
Abdominal Endotherapy Surgery
pain (N ϭ 64) (N ϭ 76) P value
Complete absence 14.3% 36.9% 0.002
Partial relief 50.8% 49.3% NS
No success 34.9% 13.8% NS
NS, not significant.
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NATURAL COURSE OF CHRONIC PANCREATITIS
487
Evaluation of pain differs very much during the course of the
observation period. Independent of the surgical procedure,
postoperative results show that freedom from pain will be
obtained in up to 90% of patients over several years of follow-
up (Table 50.3) [7,45–78]. However, persistence of freedom
from pain has been reported differently. Taylor et al. [79]
(Table 50.4) clearly showed that pain increases during the
course of a longer follow-up. In contrast, Martin et al. [72]
showed that freedom from pain may persist over 5 years of fol-
low-up after pylorus-preserving pancreaticoduodenectomy for
chronic pancreatitis (Fig. 50.1). Whether this difference is due
to the different mode of operation remains to be clarified.
Table 50.3 Freedom from pain after different surgical procedures on the pancreas for chronic pancreatitis.*
Median Pain relief
Reference Surgical procedure observation time N (%)
Way et al. [45] Drainage/resection ~5 years 37 64
Lankisch et al. [46] Drainage/resection 2.5 years 40 60
Mangold et al. [47] Partial duodenopancreatectomy 1 year 8 months 44 73
Total duodenopancreatectomy 2 years 10 months 18 91
Partial left-sided resection 3 years 5 months 37 60
Subtotal left-sided resection 2 years 10 months 17 83
Proctor et al. [48] Pancreaticojejunostomy 11 months 22 50
Rosenberger et al. [49] Resection 6 years 67 69
Nonresective procedures 6 years 40 50
Lankisch et al. [50] Pancreaticojejunostomy 3 years 1 month 17 76
Resection 3 years 1 month 22 64
Prinz and Greenlee [51] Pancreaticojejunostomy 6 years 1 month to 91 35
7 years 11 months
Sato et al. [52] Pancreaticojejunostomy 6.5 years 38 68
Left-sided resection 6.5 years 14 79
Whipple’s operation 6.5 years 9 67
Gall et al. [53] Whipple’s operation, pancreatic duct occlusion Ͼ 1 year 67 93
Morrow et al. [54] Pancreatic duct drainage 4–13 years 46 46
40–80% left-sided resection 4–13 years 21 33
80–95% left-sided resection 4–13 years 8 100
Drainage 6 years 46 80
Subtotal pancreatectomy 7 years 21 24
Sato et al. [55] Left-sided resection Ͼ 6 months 21 91
Whipple’s operation Ͼ 6 months 11 55
Pancreaticojejunostomy Ͼ 6 months 43 91
Bradley [56] Lateral pancreaticojejunostomy 5 years 9 months 46 28
Caudal pancreaticojejunostomy 5 years 9 months 18 17
Cooper et al. [57] Total pancreatectomy 1.5 years 83 72
Frick et al. [58,59] Left-sided resection 6.5 years 74 50
Partial duodenopancreatectomy 6.5 years 62 45
Total duodenopancreatectomy 6.5 years 22 55
Drainage 4 years 7 months 156 48
Lambert et al. [60] Duodenum-preserving total pancreatectomy 9 years 5 months 14 64
Rossi et al. [61] Whipple’s operation 6 months 61 72
2 years 44 61
5 years 33 61
10 years 18 61
15 years 6 83
Mannell et al. [62] Drainage/resection 8.5 years 100 77
Stone et al. [63] Whipple’s operation 6 years 2 months 15 53
Total duodenopancreatectomy 9 years 1 month 15 27
Beger et al. [64] Duodenum-preserving pancreatic head resection 3 years 8 months 128 77
Peiper and Köhler [65] Resection 10 51 79
Drainage 10 24 65
Beger and Büchler [66] Duodenum-preserving pancreatic head resection 3.5 years 141 77
Lankisch et al. [7] Drainage/resection 6 years 70 57
Adams et al. [67] Lateral pancreaticojejunostomy 6 years 4 months 62 42
Frey and Amikura [68] Local pancreatic head resection with 6 months 50 34
longitudinal pancreaticojejunostomy
(Continued)
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In a study of 207 patients with alcoholic chronic pancreatitis
(91 without and 116 with surgical treatment for pain relief),
Ammann et al. [12] discussed the pain pattern of chronic
pancreatitis and its surgical implications. In this study, chronic
pain was typically associated with local complications (mainly
pseudocysts), which were positively relieved by a single drainage
procedure in approximately two-thirds of patients. Additional
surgery was required for late pain recurrence in 39 patients, pri-
marily symptomatic cholestasis. All patients achieved complete
pain relief in advanced chronic pancreatitis. The authors con-
clude that, in their experience, relief of chronic pain regularly fol-
lows selective surgery tailored to the presumptive pain cause or
occurs spontaneously in uncomplicated advanced chronic pan-
creatitis.
Course of exocrine pancreatic
insufficiency
Exocrine pancreatic insufficiency does not play a major prognos-
tic role. Occasionally, massive steatorrhea leading to cachexia
and susceptibility to infection has prognostic significance.
Median Pain relief
Reference Surgical procedure observation time N (%)
Hakaim et al. [103] Different operations: 5 years 2 months 50 30
pancreatic duct drainage (56%)
left-sided resection (20%)
cyst drainage (24%)
Büchler et al. [69] Duodenum-preserving pancreatic head resection 6 months 15 40
Pylorus-preserving Whipple’s operation 6 months 16 75
Fleming and Williamson [70] Total pancreatectomy 3.5 years 40 79
Izbicki et al. [71] Duodenum-preserving pancreatic head resection:
Beger’s procedure 1.5 years 20 95
Frey’s procedure 1.5 years 22 94
Martin et al. [72] Pylorus-preserving pancreaticoduodenectomy 5 years 3 months 45 92
Stapleton and Williamson [73] Proximal pancreaticoduodenectomy: 4.5 years 52 80
pylorus-preserving (N ϭ 45)
Whipple’s operation (N ϭ 7)
Amikura et al. [104] Pancreaticojejunostomy Ն 6 months 69 75
Pancreaticojejunostomy plus pancreatic head Ն 6 months 11 90
resection
Left-sided resection Ն 6 months 37 80
Whipple’s operation Ն 6 months 13 65
Rumstadt et al. [74] Whipple’s operation 8 years 4 months
†
134 66
Traverso and Kozarek [75] Whipple’s operation 3.5 years 47 76
Total pancreatectomy 3.5 years 10 76
Beger et al. [105] Duodenum-preserving pancreatic head resection 5 years 8 months
†
303 88
Berney et al. [76] Different procedures of pancreas resection 6 years 4 months 68 62
Jimenez et al. [106] Whipple’s operation 3 years 5 months 33 53
Pylorus-preserving pancreatic head resection 3 years 5 months 39 40
Sakorafas et al. [77] Whipple’s operation 6 years 7 months 66 67
White et al. [78] Total pancreatectomy 6 months 24 82
Nealon and Matin [107] Pancreaticojejunostomy 6 years 9 months 124 86
Left-sided resection 6 years 9 months 29 67
Pancreatic head resection (duodenum-preserving 6 years 9 months 46 91
or pylorus-preserving)
Sakorafas et al. [108] Left-sided resection 6 years 8 months 31 49
Hutchins et al. [109] Left-sided resection 2 years 10 months 84 48
* Only reports of “total freedom from pain” were included. Further stages of postoperative improvement (e.g., partial freedom from pain) were not
considered. Closure of literature search, December 2005.
†
Median values.
Table 50.4 Percentage of patients who became free from pain
6 months, 2 years, and 5 years after different surgical procedures
for chronic pancreatitis. (From ref. 79 with permission.)
Whipple’s Left-sided
Follow-up operation Pancreaticojejunostomy resection
Alcohol-induced
pancreatitis
6 months 82 87 60
2 years 74 53 39
5 years 71 54 26
Idiopathic
pancreatitis
6 months 50 80 77
2 years 50 60 46
5 years 33 60 20
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Whether exocrine pancreatic function deteriorates during the
course of the disease is disputed. Ammann et al. [3] found that
severe exocrine pancreatic insufficiency developed within 5.65
years (median) in 122 (86.6%) of 145 patients, whereas
Thorsgaard Pedersen et al. [17] observed no significant changes
in exocrine pancreatic insufficiency in their patients during an
observation period of 4 years. We found no change in the
degree of severity of exocrine pancreatic insufficiency in 66
(46.2%) patients, but a deterioration in 61 (42.6%) patients.
Functional improvement was even seen in 16 (11.2%) of our
patients, several of whom no longer required pancreatic enzyme
substitution. Several other studies have furnished evidence of
functional improvement in cases of exocrine pancreatic insuffi-
ciency in chronic pancreatitis [6,80–82]. Improvement was
observed in patients who stopped drinking and/or where
exocrine pancreatic insufficiency was moderate and not severe
prior to conservative and/or surgical treatment [7].
Course of endocrine pancreatic
insufficiency
Whereas almost all patients with chronic pancreatitis have
exocrine pancreatic insufficiency to some degree at the time of
diagnosis, this is not the case for endocrine pancreatic insuffi-
ciency. We found moderate to severe endocrine pancreatic
insufficiency in 335 patients with chronic pancreatitis, includ-
ing 24 patients with painless chronic pancreatitis; 260 (78%)
suffered from diabetes and 133 (40%) needed insulin treat-
ment. After almost 10 years of observation, the incidence of
diabetes had increased 10-fold in only 28 (8%) patients.
However, even after this long observation period, 75 (22%)
patients (i.e., every fifth patient) still had no diabetes [7].
In a large prospective cohort study, Malka et al. [83] com-
pared patients who underwent elective pancreatic surgery with
those who never underwent surgical treatment. The prevalence
of diabetes mellitus did not increase in the surgical group overall,
but was higher 5 years after distal pancreatectomy compared
with pancreaticoduodenectomy, pancreatic drainage, or cystic,
biliary, or digestive drainage. There were no differences between
the other surgical procedures. Pancreatic drainage did not pre-
vent the onset of diabetes mellitus. The risk seemed to be largely
caused by progression of the disease, because it increased by
more than threefold after the onset of pancreatic calcifications.
Endocrine complications may play a major prognostic role, espe-
cially after surgical treatment of chronic pancreatitis, because of
possible hypoglycemia [84]. Hypoglycemia frequently occurs
after subtotal left-sided pancreatic resection [41] and may con-
tribute to an unfavorable prognosis.
The frequency of some complications of diabetes mellitus sec-
ondary to chronic pancreatitis has been studied. Earlier investi-
gations showed that diabetic retinopathy is a rare complication
of pancreatogenic diabetes, with an occurrence rate of 7.4–18%
[85–87]. Gullo et al. [88] have shown that the risk of retinopa-
thy and the characteristics of this complication in patients with
chronic pancreatitis and secondary diabetes are the same as for
patients with type 1 diabetes. About half of the patients studied
in both groups had retinopathy; this was background, minimal,
or mild to moderate without impairment of visual function. The
only significant difference was the longer duration of diabetes in
patients with retinopathy compared with those without this
complication. A longer observation time may explain the higher
frequency of diabetic retinopathy in this study [88] compared
with the earlier investigations [85–87]. Similarly, Tiengo et al.
[89] and Couet et al. [90] found retinopathy in 31% and 41%,
respectively, of patients with chronic pancreatitis. Furthermore,
in 1995, Levitt et al. [91] showed that microvascular complica-
tions (retinopathy, nephropathy) in pancreatic diabetes and
insulin-dependent diabetes mellitus are equally common and
severe.
Nondiabetic retinal lesions and retinal function abnormalities
(increased threshold of dark adaptation, difficulty with night
vision) are also common in patients with chronic pancreatitis,
even in the absence of steatorrhea compared with healthy con-
trols [92]. Electrocardiographic evidence of ischemic heart disease
was found twice as frequently in genetic diabetics compared with
pancreatic diabetes (37% vs. 18%) [93]. Diabetic neuropathy
was reported in about 30% of patients with chronic pancreatitis
(no control group) [94].
Finally, lower extremity arterial disease occurred in 25.3% of
patients with chronic pancreatitis and had the same prevalence
and distribution as in idiopathic pancreatitis [95]. Whether
these complications have major prognostic significance has not
yet been investigated.
Course of complications of chronic
pancreatitis
The list of complications in chronic pancreatitis includes pan-
creatic pseudocysts and abscesses; stenosis of the common bile
NATURAL COURSE OF CHRONIC PANCREATITIS
489
10
0
2
3
4
5
6
8
9
7
1
Pain score
Preoperative 6 months 2 years 5 years1 year
Time
Figure 50.1 Long-term improvement in pain in patients undergoing
pylorus-preserving pancreaticoduodenectomy for chronic
pancreatitis. (From ref. 72 with permission.)
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CHAPTER 50
490
duct, duodenum, and colon; development of pleural ascites;
and gastrointestinal bleeding. All these complications surely
have severe implications for the prognosis of the disease.
However, since these have not been investigated in larger stud-
ies, their exact influence on the outcome of the disease is
uncertain and they are therefore not discussed here.
Course of pancreatic and extrapancreatic
carcinomas in chronic pancreatitis
In clinical studies, the incidence of pancreatic carcinoma in
patients with chronic pancreatitis has been reported as varying
from 1.4 to 2.7% [3,7,17,96,97]. A multicenter historical cohort
study of 2015 subjects with chronic pancreatitis involved clinical
centers in six countries [98]. The cumulative risk of pancreatic
carcinoma in these patients, who were followed for at least
2 years, increased noticeably, and 10 and 20 years after the diag-
nosis of chronic pancreatitis was 1.8 and 4%, respectively (Fig.
50.2) [98]. Thus, the risk of pancreatic carcinoma was signifi-
cantly elevated in patients with chronic pancreatitis, and thus
chronic pancreatitis has to be included in the precanceroses [98].
Unfortunately, it is very difficult to diagnose pancreatic car-
cinoma in chronic pancreatitis. Carcinoma of the pancreas should
certainly be suspected in a patient with chronic pancreatitis if
there is increasing abdominal discomfort, progressive weight
loss, jaundice, and radiologic evidence including nodularity of
the duodenal sweep.
Extrapancreatic carcinomas in chronic pancreatitis are not
rare events and have been reported with varying incidence,
from 3.9 to 12.5% [6,7,17,97,99]. In some of these and other
studies [6,7,97,100], a considerable number of extrapancre-
atic carcinomas involving the upper respiratory tract (oral
cavity, larynx, bronchial tree) have been observed. Since alco-
hol abuse is the dominating etiology of chronic pancreatitis,
and because many alcoholics probably smoke, extrapancreatic
carcinomas involving the upper respiratory tract may reflect
the consequences of another habit abuse.
Socioeconomic situation in chronic
pancreatitis
Some attention has been paid to the socioeconomic situation of
patients with chronic pancreatitis. Gastard et al. [101] found that
one out of two male patients continued to work normally, despite
pain or diabetes, while one out of three was regarded as unfit for
regular work, being totally incapacitated or absent from work
for more than 3 months a year. The figures improved after 15
years due to the death of patients with severe forms of the dis-
ease; at this stage, 68% of the patients were working regularly,
while 6% were totally incapacitated. Thorsgaard Pedersen et al.
[17] found a decline during an observation period of 5 years
(median). Only 15 (40%) of their 38 surviving patients still
worked, whereas the remaining were either on prolonged sick-
leave or retired. Miyake et al. [6] reported that while 63 (71%) of
their 89 patients continued to work, almost all the other patients,
who were either retired or who suffered socioeconomically, con-
tinued their alcohol abuse. In our study [7], the incidence of
unemployed patients increased from 3 to 15% and that of the
retired from 3 to 25% during an observation period of about
11 years. Almost half of the retirements were due to chronic
pancreatitis.
Mortality in chronic pancreatitis
Data on the mortality rate in chronic pancreatitis are difficult to
interpret since etiology and mean observation times vary from
study to study. Three studies with a comparatively similar obser-
vation time (median 6.3–9.8 years) revealed a general death rate
of 28.8–35%, but the death rate related to chronic pancreatitis
was only 12.8–19.8% [3,6,7]. Continued alcohol abuse after
conservative treatment and/or surgery has been associated with
significantly lower survival rates (Fig. 50.3) [3,6,7,40,41,70].
Prognosis of chronic pancreatitis
The prognosis of chronic pancreatitis is independent of con-
servative or surgical treatment. A multicenter investigation in
6
5
3
2
1
4
Cumulative incidence of pancreatic cancer (%)
5101520
Years after diagnosis of pancreatitis
(1160)
(599)
(244)
(64)
Figure 50.2 Cumulative incidence of pancreatic cancer in 1552
subjects with chronic pancreatitis with a minimum of 2 years’
follow-up. The vertical lines represent 95% confidence intervals;
numbers in parentheses are the subjects at risk. One additional case
of cancer developed after 25 years of follow-up. (From ref. 98 with
permission.)
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