Multifocal Pancreatic Ductal Adenocarcinomas

Yasuhisa Mori, Takao Ohtsuka, Kosuke Tsutsumi, Takaharu Yasui, Yoshihiko Sadakari,
Junji Ueda, Shunichi Takahata, Masafumi Nakamura, Masao Tanaka
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University.
Fukuoka, Japan
ABSTRACT
Context Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been detected with increasing frequency as a result
of the progression of diagnostic modalities. Recently, invasive ductal carcinoma of the pancreas concomitant with IPMNs has been
the focus of attention. Case report We report the case of a 57-year-old man with multifocal ductal carcinomas of the pancreas
concomitant with IPMNs detected by intraoperative cytology. During a follow-up for branch duct IPMNs, a stenotic lesion of the
main duct in the pancreatic body was found by ERCP, and brush cytology of the stenosis revealed an adenocarcinoma. A distal
pancreatectomy was proposed; however, intraoperative pancreatic juice cytology from the pancreatic head also revealed
adenocarcinoma, and a total pancreatectomy was finally carried out. Pathological examination of the resected specimen showed
multifocal ductal carcinomas and IPMNs in the distal pancreas, and invasive ductal carcinoma in the pancreatic head which had not
been detected by preoperative imaging studies. Conclusions Surgeons should be aware of the possibility of multifocal carcinomas in
patients with concomitant IPMNs. Intraoperative pancreatic juice cytology should always be performed in order to confirm the
absence of carcinoma in the pancreas to be left in place after planned resection.
INTRODUCTION
Intraductal papillary mucinous neoplasms (IPMNs) of
the pancreas were first reported in 1982 by Ohashi et
al. [1] and have been detected with increasing
frequency as a result of the progression of diagnostic
modalities. Recently, invasive ductal carcinoma of the
pancreas concomitant with IPMNs has been the focus
of attention [2], and ductal carcinoma of the pancreas
in addition to IPMN has been reported to develop in
9.2% of patients with IPMNs [3]. We herein report the
case of a patient having multifocal ductal carcinomas
concomitant with IPMNs which were detected by
intraoperative pancreatic juice cytology and were
treated by total pancreatectomy.
CASE REPORT
A 57-year-old man was admitted to our hospital in
2003 due to cystic lesions in the pancreas which had
been detected by health screening ultrasonography. He
had had a past history of diabetes mellitus but did not
have a family history of malignancy. Laboratory tests
including blood cell counts, blood chemistry and tumor
markers, carcinogenic embryonic antigen (CEA) and
carbohydrate antigen 19-9 (CA 19-9) were all within
normal limits. Enhanced computed tomography (CT)
showed a low density mass measuring 10 mm in the
tail of the pancreas. Magnetic resonance cholangio-
pancreatography demonstrated two small cystic
lesions, 10 mm in diameter in the pancreatic tail and 5
mm in the pancreatic head. Endoscopic retrograde
cholangiopancreatography revealed a cystic dilatation
of the branch duct measuring 10 mm in the tail of the
pancreas without dilation of the main pancreatic duct.
Cytologic examination of the pancreatic juice collected
by the use of secretin (ChiRhoStimTM, ChiRhoClin,
Inc., Burtonsville, MD, USA) during ERCP
demonstrated no malignant cells (Class II). Based on
these results, a diagnosis of multiple benign branch
duct IPMNs was made, and follow-up observations
were scheduled for every 6 months. In 2006, CT and
MRI revealed that the size of the IPMN in the
Received May 12th, 2010 - Accepted May 18th, 2010
Key words Carcinoma, Pancreatic Ductal; Neoplasms, Cystic,
Mucinous, and Serous; Pancreatectomy; Pancreatic Juice /cytology
Correspondence Masao Tanaka
Department of Surgery and Oncology, Graduate School of
Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka
812-8582, Japan
Phone: +81-92.642.5444; Fax: +81-92.642.5458
E-mail: masaotan@surg1.med.kyushu-u.ac.jp
Document URL http://www.joplink.net/prev/201007/10.html

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 4 - July 2010. [ISSN 1590-8577]
390
pancreatic tail had slightly increased to 15 mm in
diameter; however, cytology of the pancreatic juice
during ERCP showed no atypical cells (Class II) and,
therefore, the patient continued to be followed up.
The findings of CT and MRI in 2009 showed no
remarkable change; however, ERCP demonstrated
dilatation of the orifice of the duodenal papilla with
mucin excretion and a irregular stenotic lesion
measuring 5 mm in the main pancreatic duct of the
pancreatic body (Figure 1). Both brush cytology from
the stenotic lesion and subsequent pancreatic juice
cytology collected by a balloon catheter placed in the
pancreatic head demonstrated adenocarcinoma (Class
V). At this time, the serum CEA level was normal
while the CA 19-9 level was slightly elevated to 38.4
U/mL (reference range: 37.0 U/mL). A distal
pancreatectomy was proposed with a diagnosis of
pancreatic ductal carcinoma concomitant with branch
duct IPMNs. Hypersecretion of mucin was considered
to be from the IPMN in the pancreatic tail, and was
expected to be resected. However, to avoid the
possibility of co-existent pancreatic cancer in the
remnant pancreas, intraoperative pancreatic juice
cytology in the remnant pancreas was also planned.
During surgery, there was neither peritoneal
dissemination nor liver metastasis. The pancreas was
cut above the portal vein, and then a 4 French tube was
inserted into the main pancreatic duct of the remnant
pancreas about 2 cm from the cut margin. Fluid for
cytology was obtained by saline irrigation through the
tube with a syringe. Although the surgical cut margin
was pathologically negative for cancer cells, cytologies
of the pancreatic juice obtained 3 times from the
remnant pancreas proved to be positive. Therefore, a
total pancreatectomy was performed, followed by
hepaticojejunostomy and duodenojejunostomy in the
Billroth-II fashion. Operating time was 10 hours and
blood loss was 1,185 g.
Pathological examination of the resected specimen
revealed that there were two invasive carcinomas in the
head and tail of the pancreas, and two non-invasive
ductal carcinomas as shown in Figure 2. The sizes of
the two invasive carcinomas in the pancreatic head and
tail were 12 mm and 3 mm, respectively. Those lesions
had no definitive communication with each other.
There were two cystic dilations of the branch ducts in
the body and tail of the pancreas, both of which were
intraductal papillary mucinous adenomas. A regional
lymph node on the posterior surface of the pancreatic
head contained carcinoma cells. The postoperative
course was uneventful, and the patient has received
chemotherapy using gemcitabine for 6 months to date
without any sign of recurrence. The patient had also
been treated to control pancreatic diabetes with a
satisfactory nutrient status and quality of life.
DISCUSSION
It is well known that an IPMN is often accompanied by
malignant diseases including gastric, colon and lung
cancers [4]. In addition to such extrapancreatic cancers,
we previously stated that attention should be paid to the
possible presence of ductal carcinoma of the pancreas
because 7 of the 76 (9.2%) patients of our series of
patients with IPMNs had ductal carcinoma of the
pancreas [5]. Using the latest technology, we have
recently reported that concomitant ductal carcinoma
was detected synchronously or metachronously in 22 of
236 patients with IPMN (9.3%) [3]. Of note, all of
these 22 patients had a benign branch duct IPMN, and
our patient also had two branch duct IPMNs. We have
also demonstrated that a worsening of diabetes mellitus
and elevated serum CA 19-9 levels are indicators for
coexisting ductal carcinoma during a follow-up of
IPMNs, although these were not observed in the
current patient. The precise mechanisms of the
coexistence of ductal carcinoma with branch duct
IPMNs of the pancreas remains unknown. In addition,
multifocal ductal carcinomas concomitant with IPMNs
are a very rare condition, and, in our experience, this is
first case to date. Further clinical and molecular-based
investigations are necessary to elucidate the
mechanism of the development of ductal carcinoma
and an IPMN in the same pancreatic organ. However,
an IPMN could be an indicator of coexisting pancreatic
ductal carcinoma, and careful attention should be paid
to the possibility of concomitant malignant diseases
including pancreatic ductal carcinoma, even when the
existing IPMN is diagnosed as benign.
Eguchi et al. and Ishikawa et al. [6, 7] demonstrated
that intraoperative pancreatic juice cytology as well as
frozen-section histology during resection of an IPMN
are necessary to detect continuous or skip lesions. They
collected the pancreatic juice from the pancreatic head,
body and tail by the use of a balloon catheter, in
Figure 1. a. Computed tomogram showing a low density mass in the
tail of the pancreas, the size of which had slightly increased to 15
mm in diameter (arrow). b. Magnetic resonance cholangio-
pancreatogram demonstrating two small cystic lesions; 10mm in
diameter in the pancreatic tail (long arrow) and 5mm in the
pancreatic head (short arrow). c. ERCP showing a cystic lesion
measuring 10 mm in the tail of the pancreas (arrow with broken line),
and stenotic lesions in the main duct of the pancreatic body (arrows).
d. Endoscopic photograph of the dilated orifice of the duodenal
papilla with mucin excretion.

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JOP. J Pancreas (Online) 2010 Jul 5; 11(4):389-392.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 4 - July 2010. [ISSN 1590-8577]
391
addition to frozen-section histology of the surgical
margin, during pancreatectomy for IPMNs, and
showed that 42% of the patients required additional
pancreatic resection for intraductal carcinomas. At our
institution, intraoperative irrigation cytology is
routinely performed three times during a
pancreatectomy for IPMN, when there are IPMN(s) in
the remnant pancreas or preoperative pancreatic juice
cytology is positive for cancer cells. Although the two
IPMNs were included in the initially resected side in
our patient, preoperative pancreatic juice cytology was
positive for cancer cells and, therefore, intraoperative
cytology was also performed. As a result, we could
detect the ductal carcinoma in the pancreatic head,
which had not been detected by any preoperative
imaging studies. We previously reported two patients
having a branch duct IPMN with a concomitant
carcinoma in situ which was likewise not detected by
imaging studies but was diagnosed by pancreatic juice
cytology preoperatively [8]. The reason for carrying
out irrigation cytology three times is to negate the
possibility of migration of the floating cancer cells in
the resected side into the portion to be left unremoved.
During collection of the pancreatic juice, operators
should pay attention to leakage of the pancreatic juice
into the abdominal cavity to prevent later possible
dissemination.
Total pancreatectomy was first introduced in 1943 by
Rockey [9]; however, the indication for such a
procedure has been limited to date because of its high
morbidity and mortality. Recently, several reports have
shown the efficacy and safety of total pancreatectomy
in selected patients [10, 11, 12, 13]. Reddy et al. [14]
demonstrated that operative mortality after total
pancreatectomy decreased over time from 40.0% to
1.9%. Our patient had an uneventful postoperative
course and his postoperative nutrition and quality of
life have been satisfactory due to the control of the
pancreatic diabetes. Total pancreatectomy seems to
have become a feasible procedure in selected patients,
and should be considered when the oncological
situation leaves no choice.
In conclusion, careful attention should be paid to the
possible presence of ductal carcinoma in patients with
IPMNs. During surgery for IPMN(s), intraoperative
irrigation cytology from the remnant pancreas could be
useful in detecting the lesions which were not observed
in the preoperative imaging studies. If this is the case,
Figure 2. Upper panel. Schematic representation of the location of intraductal papillary mucinous neoplasms (IPMNs) and non-invasive and
invasive ductal carcinomas. Lower panel. Microscopic photographs corresponding to the lesions are also shown (H&E; left x40; middle x200; right
x40, insert x100).

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 4 - July 2010. [ISSN 1590-8577]
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then total pancreatectomy should be considered when
the oncological situation leaves no choice.
Conflict of interest The authors have no potential
conflict of interest
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