Journal of Cancer Therapy, 2013, 4, 1-6
Published Online November 2013 (
Open Access JCT
Endoscopic Methods in the Diagnosis and Treatment of
Pancreatic Cancer
Zoltán Berger*, Maria Ester Bufadel Godoy, Alex Navarro Reveco
University of Chile Clinical Hospital, Department of Medicine, Gastroenterology Section, Santiago, Chile.
Email: *
Received July 15th, 2013; revised August 16th, 2013; accepted August 24th, 2013
Copyright © 2013 Zoltán Berger et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Endoscopic methods are widely used in the diagnosis and palliative treatment of pancreatic cancer. The most sensitive
method in early diagnosis is endosonography (EUS) which can also provide histological diagnosis. Diagnostic ERCP
became a rather rare procedure as a consequence of wide availability of Magnetic Resonance Cholangiopancreatogra-
phy (MRCP) but ERCP assisted intraductal methods have gained importance (brush-cytology, intraductal ultrasound,
optical coherence tomography) and finally, peroral pancreatoscopy has become technically feasible but available only in
some specialized centers. Minimally invasive endoscopic methods play an important role in the palliative treatment of
unresectable pancreatic cancer which represents the majority of cases. EUS-guided histological confirmation of adeno-
carcinoma is crucial in the election of chemotherapy. Celiac plexus blockade and endoscopic biliary and pancreatic
stent placement contribute to pain reduction, drainage of obstructed bile duct and assure a better quality of life.
Keywords: Endoscopist; Early Diagnosis; Palliative Treatment
1. Introduction
Pancreatic cancer continues to be one of the most lethal
malignancies: surgical resection is possible in only about
20% of detected cases and even in this group, the 5 year
survival is low [1]. The diagnosis of cancer is established
with conventional imaging procedures in the majority of
these cases: CT-scan demonstrates the presence of the
pathological mass and, at the same time, estimates the
eventual vascular invasion, hepatic or peritoneal metas-
tases, i.e. evident criteria of unresectability. If the tumor
is considered resectable, surgery is the next step, without
previous histological diagnosis except in those patients
with clinical or radiological suspicion of another benign
disease mimicking pancreatic cancer. Thus endoscopists
face principally two extreme stages of pancreatic cancer:
efforts in early diagnosis of small lesions and, on the
other hand, palliative treatment of patients with advanced
2. Endoscopy in the Early Diagnosis
Thanks to systematic studies of surgical specimens, can-
cer precursor PanIN lesions have been identified. Unfor-
tunately, direct endoscopic access to visualize and resect
these lesions—as in the case of adenomatous colon pol-
yps—is not possible in everyday practice. A different
emerging entity, pancreatic cystic lesions permit curative
pancreatic surgery in initial phases of malignant trans-
formation or even before, which consequently prevents
cancer. However, early diagnosis of the most typical and
most frequent adenocarcinoma of the pancreas continues
to be unresolved. Five-year survival is far better in the
subgroup of patients operated on with small malignant
lesions, without metastasis. Early diagnosis is particu-
larly important in genetically high -risk individu als. How-
ever, detection of small tumors—although not impossi-
ble—is extremely difficult.
There are some benign diseases of the pancreas which
can produce tumor-like lesions or masses [2]. The dif-
ferentiation of these diseases from pancreatic cancer is
seldom easy. Our knowledge ab out the autoimmune pan-
creatitis has increased and differential diagnosis has be-
come possible in the vast majority of these cases even
without pancreatic biopsy [3,4]. Endoscopic methods,
biopsy from the Vater papilla or even from gastric mu-
cosa can be useful: IgG4 positive lymphoplasmocytic
infiltration was found in every biopsy of Vater’s papilla
*Corresponding a uthor.
Endoscopic Methods in the Diagnosis and Treatment of Pancreatic Cancer
[5-7] and 12 of 13 cases of autoimmune pancreatitis in
gastric mucosa [7]. These findings can be considered as
histological proof of the IgG4 related benign disease with
systemic involvement. Underdiagnosis of autoimmune
pancreatitis can lead to unnecessary operations. On the
other hand, “treatment” of pancreatic cancer with ster-
oids could be the result of an opposite diagnostic error.
Other benign disease, groove-pan creatitis [8] has no spe-
cific medical treatment and surgery is sometimes neces-
2.1. ERCP
Pancreatography used to be the most sensitive method in
detecting ductal changes [9] such as stenosis and con-
secutive dilatation of the pancreatic duct. Nevertheless,
ERCP is an invasive method with potential complications,
pancreatitis being the most frequent among them [10],
which could make impossible to continue with the diag-
nostic work-up and delay the eventual surgery. MR
cholangiography also provides excellent images of the
pancreatic duct and its sensitivity seems comparable to
that of ERCP [11]. However, cannulation of the pancre-
atic duct offers some advantages: we can obtain pancre-
atic juice or samples from the stenotic segments for brush
cytology [12]. Pancreatic sphincterotomy and guide-wire
placement also allow the introduction of special endo-
scopes (“babyscope”) or accessories (spy-glass or intra-
ductal ultrasound) in order to further investigate the le-
sions [11,13,14].
ERCP does not add more information to a pancreatic
focal lesion that was clearly demonstrated and character-
ized by other non-invasive images. In contrast, it can be
useful to differentiate pancreatic cancer from benign in-
flammatory diseases which can produce ductal changes.
Focal stenosis can be a part of inflammatory pancreatic
diseases. However, in cancer patien ts upstream dilatation
is almost always present with atrophy of surrounding
parenchyma, but these changes are almost always lacking
in autoimmune [3,4] or groove-pancreatitis [8]. Brush
cytology can help to confirm the presence of cancer. Al-
though specificity was high, the sensitivity of brush cy-
tology has never been over 70% (only about 40% - 50%
in most publications) and its negative predictive value
was about 30%—reaching almost 50% in combination
with intraductal biopsy [15]. In a recent publication, sen-
sitivity of cytology was 65.8%, specificity 100% and
overall diagnostic accuracy 76.4% [12], with only 2 mild
pancreatitis in 58 ERCPs. These values are quite similar
to those obtained 10 years ago [16], in spite of progress
in technology. Some additional advanced techniques can
improve the results of cytology [17], but the negative
predictive value remains low. Both brush cytology and
intraductal forceps biopsy under fluoroscopic control are
technically demanding and invasive methods, having a
relatively high probability of sampling error. However,
both are reasonably safe and represent a real possibility
of early detection of some small malignant lesions. As
expected, pancreatoscopy-guided tissue sampling has
dramatically improved diagnostic accuracy and sensitiv-
ity [13] but this method is only exceptionally available.
2.2. Endosonography (EUS)
EUS provides an excellent high resolution image of the
pancreas. Pancreatic cancer is seen as a hypoechoic in-
homogeneous solid mass with irregular borders. The sen-
sitivity of EUS in detection of pancreatic masses is
somewhat superior to CT scan and MRI, particularly in
the case of small lesions [18,19]. EUS alone is highly
sensitive to demonstrate focal lesions and eventual vas-
cular involvement. Using contrast-enhancement [20]
with the Doppler method or digital image procession [21]
can further improve its sensitivity. Diagnostic accuracy
of EUS is over 80%. It seems to be the method of choice
to establish diagnosis and define unresectability, being
cost-effective avoiding unnecessary and hopeless surgery.
However, EUS is a more expensive, minimally invasive
method with some complications; it is not widely avail-
able and is operator-dependent. In addition, its 60% -
65% negative predictive value is relatively low, particu-
larly in the presence of chronic pancreatitis and/or a pre-
viously implanted biliary stent [22]. As a consequence,
CT scan continues to be the first method in the diagnostic
work-up for pancreatic cancer, followed by EUS only in
case of doubts in diagnosis or when biopsy is required.
Linear EUS allows us to obtain biopsy specimens from
virtually any pancreatic region, whatever its origin: not
only from lesions related to the ductal system as is the
case of brush cytology. On the other hand, although tu-
mor seeding does exist [23] it is rather exceptional in
spite of several passes as compared to US or CT-guided
percutaneous biopsies. However, an acute inflammatory
reaction provoked by EUS-FNA, can transform a small
tumor into a nonresectable lesion [24]. EUS was also
used to tattoo a small, otherwise undetectable lesion
preoperatively and the small tumor was surgically re-
solved [25]. Marking the small tumor with silver pins
provided the same result in another case reported [26].
Diagnostic sensitivity of FNA cytology improves with
increasing tumor size, i.e. it is less useful in early diag-
nosis. The negative predictive value is also lower in the
case of small lesions. This means that a negative cytol-
ogy result does not exclude malignant nature of a small
lesion and surgery is the next step even despite of nega-
tive cytology if the clinical suspicion is strong enough.
Like any other endoscopic technique, direct visualize-
tion of the pancreatic ductal system could be of great
Open Access JCT
Endoscopic Methods in the Diagnosis and Treatment of Pancreatic Cancer 3
value. Thanks to pancreatoscopy, visualization is already
a real possibility, although its availability is limited to
rather few specialized centers. Apart from its cost and
restricted availability, the small caliber of normal pan-
creatic duct represents a technical difficulty and limita-
tion. Furthermore, tortuosity and strictures may prevent
the scope from reaching the lesion in question. Intraduc-
tal US sondes [27] and intraductal optical coherence to-
mography [28] also offer greater precision to investigate
ductal lesions and distinguish benign from malignant
strictures, as compared to pancreatography. Utility of
these methods is also limited to lesions originating in the
main duct.
3. Advanced Cancer
Unfortunately, pancreatic cancer is advanced in the vast
majority of cases at the time of diagnos is. Even relatively
small <2 cm lesions are not really early cancers; although
resectable, lymph node metastasis, portal vein invasion
and survival did not differ significantly as compared to
major lesions [29]. The diagnosis is sometimes estab-
lished during an ERCP performed for an obstructive
jaundice of unknown cause. In such cases, if the ob-
structed bile duct is contrasted and probably contami-
nated, plastic stent placement is recommended. Self-ex-
panding metal stents cou ld probably interfere with poste-
rior surgery [30]. In contrast, if the diagnosis of a re-
sectable pancreatic cancer is established via other non-
invasive methods, preoperative stent placement has no
clinical utility, although it decreases the bilirubin-level
Nowadays, the principal role of endoscopic methods is
the palliative treatment of unresectable tu mors.
1) Obstructive jaundice: This is one of the first clinical
manifestations of tumors located in the head of the pan-
creas. Resolution of the obstruction and consecutive de-
crease in the jaundice reduces or completely controls
pruritus. Technical success rate of endoscopic palliation
is high. The placement of self-expanding metal endo-
prosthesis is the method of choice: they remain patent
significantly longer than plastic stents. Obstruction and
cholangitis are more frequent with plastic stents, needing
emergency hospitalizations and repeated endoscopic in-
terventions, thus deteriorating the quality of life. How-
ever, no difference was found in the survival in compar-
ing polyethylene and metal stents [32]
2) Pain: The mechanism of pain in pancreatic cancer is
complex and only partially understood. However, one of
the components is probably the obstruction of the pan-
creatic duct. If pancreatography reveals a stricture with
upstream dilatation it seems reasonable to place a plastic
stent through the stricture and drain the obstructed pan-
creatic segment. Insufficient literature data prevent mak-
ing definitive conclusion s, but several results support the
usefulness of pancreatic stents in the treatment of the
pain [33]. There are also some initial results with radio-
active stents placed either in the common bile duct or in
the pancreatic duct which could stabilize the disease and
delay progression [34]. Metal stents covered by a pacli-
taxel-incorporated polyurethane membrane gave similar
results in 9 patients with bile duct strictures caused by
unresectable pancreatic cancer [35].
3) Gastric outlet obstruction, duodenal stenosis: Si-
multaneous or consecutive obstruction of the bile duct
and duodenum has been the cause of relatively complex
surgical interventions in advanced pancreatic cancer
(gastro-jejunal anastomosis and hepatico-jejunostomy).
In addition, these are frequently a high surgical risk pa-
tients or even unfit for operations. Self-expanding metal
stent placement by endoscopy [36] reestablishes almost
normal caliber duodenal lumen, avoids vomiting and
allows although somewhat limited but oral feeding. It
also makes posterior endoscopic access to the papilla
possible for the treatment of obstructive jaundice.
3.1. Endosonography (EUS)
1) EUS is the most sensitive method in the diagnosis of
focal pancreatic lesions. However, in the case of ad-
vanced cancer the pancreatic mass has already been de-
tected and declared unresectable by other methods. There
are two questions to answer: a) Is the mass a ductal ade-
nocarcinoma or of different histological nature? b) Is the
patient fit for chemotherapy or another minimally inva-
sive palliative treatment? If the patient’s general condi-
tion does not allow even minimally invasive interven-
tions and chemotherapy is considered unsuitable, the
only possibility is conservative symptomatic treatment.
Histological diagnosis is useless in these cases. On the
other hand, except in th e terminal stage, histological con-
firmation of the lesion is recommended to exclude be-
nign diseases mimicking pancreatic cancer or malignant
lesions different from adenocarcinoma, which may re-
quire different treatment and have better prognosis. The
best way to obtain histological samples at present is the
EUS-guided fine-needle biopsy [37-39], with high diag-
nostic accuracy and low risk of complications, including
tumor seeding. The only argument against EUS is the
cost and lack of wide availability in several countries.
2) EUS guided interventions:
a) Celiac plexus blockade (CPB) and neurolysis (CNL)
are safely performed when guided by EUS. Results in
pain control are similar to the radiologically-guided per-
cutaneous or surgical interventions: CPB and/or CNL
permit a reduction in the dose of analgesic drugs and re-
sult in better pain control. Published complications have
been mild and transient [40].
Open Access JCT
Endoscopic Methods in the Diagnosis and Treatment of Pancreatic Cancer
b) EUS-guided drainage can facilitate pancreatic or
biliary stent placement via “rendez-vous” techniques.
Bilio-digestive drain age, choledocho-duodenostomy with
stent placement can also be performed in cases of duo-
denal ste nosis.
c) There are also some rather experimental interven-
tions guided by EUS. Jin et al. [41] implanted iodine-125
seeds inside of unresectable pancreatic tumors of 22 pa-
tients. Combined with traditional chemotherapy, partial
remission was achieved in 3 and stabilized the disease in
another 10 patients, while pain diminished in 18 of the 22
patients with a statistically significant decrease in pain
intensity as measured by visual analogue scale. Half of
the patients presented fever which was treated with anti-
biotics, but no other serious complication was observed.
EUS was used to guide intratumoral injection of a virus:
ONYX-015, which selectively replicates in and destroys
tumor cells, that are deficient in p53 function but not in
cells with functional p53 [42,43]. This treatment was also
associated with gemcitabine and the cancer did not pro-
gress in 8 of 21 patiens who participated in the study.
4. Conclusion
Algorithm of diagnosis and treatment of pancreatic can-
cer is depicted in Figure 1. Early diagnosis has some-
what improved but has not been resolved. The best, most
sensitive and more and more widely available method for
early detection is the EUS, with or without FNA, but it is
not good enough. Its negative predictive value has im-
proved in recent years, but surgery must be performed in
spite of negative EUS and cytology results if the clini-
cal suspicion is strong. More direct methods to visualize
ductal lesions are in progress. On the other hand, endo-
scopic methods play an increasingly important role in
Other images,
, biopsy
of papilla
± 2 weeks steroid
and palliative
Unfit for
chemot he ra py, only
Focal pancreati c mas s or
upstream duct dilatation
nature, AIP
Small lesion,
no vascular inva sio n,
no metastasis
Advance d cancer wit h
vascular invasion
and/or metast a si s
Figure 1. Endoscopic methods in the algorithm of diagnosis
and treatment of pancreatic cancer. Pancreatic lesion ini-
tially detected with generally non-invasive imaging (CT,
RM), rarely with ERCP. EUS is the best method in the dif-
ferential diagnosis, with or without FNA. Other endoscopic
methods have their dominant role in the palliative treat-
ment of advanced lesions.
the palliative treatment of pancreatic cancer patients.
Self-expanding metal duodenal and biliary stents repre-
sent a good alternative treatment to replace relatively
complex surgery in patients with less than 1 year life
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EUS: Endosonography;
FNA: Fine Needle Aspiration;
AIP: Autoimmune pancreatitis.