New Japanese Classification of Pancreatic

Cancer

Shuji Isaji, Yasuhiro Murata, and Masashi Kishiwada

Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1022
Definition of Parts of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1023
Category of Tumor Extension (T) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1023
Reappraisal of Anatomy of Extrapancreatic Nerve Plexus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1024
Description of Regional Lymph Nodes of the Pancreas and Lymph Node Metastasis . . . . . . . 1028
Stage Grouping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1031
Classification of Resectability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1032
Criteria of Histological Response to Drug Therapy and/or Radiotherapy . . . . . . . . . . . . . . . . . . . . 1035
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1036
Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1036
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1036

Abstract
Background: The Japanese classification of pancreatic cancer, seventh edition,
has been released by Japan Pancreas Society (JPS) in July 2016.
Methods: Revision concepts and major revision points of the seventh edition
of Japanese classification of the pancreatic cancers were reviewed.
Results: The principal points of revision are as follows:

Conflicts of Interest: Shuji Isaji, Yasuhiro Murata, and Masashi Kishiwada declare that they have
no competing interests.
S. Isaji (*) · Y. Murata · M. Kishiwada
Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu,
Mie, Japan
e-mail: shujiisaji1@mac.com; yasumura@clin.medic.mie-u.ac.jp; yasumura7300@gmail.com;
kishiwad@clin.medic.mie-u.ac.jp

# Springer Science+Business Media, LLC, part of Springer Nature 2018 1021

J. P. Neoptolemos et al. (eds.), Pancreatic Cancer,
https://doi.org/10.1007/978-1-4939-7193-0_84
1022 S. Isaji et al.

1. Definition of the parts of the pancreas.

2. T category and stage grouping: consistency with those of the UICC seventh
edition was obtained.
3. Reappraisal of anatomy of extrapancreatic nerve plexuses.
4. N category: classification based on numbers of lymph nodal metastasis among
the regional lymph nodes; N1a, metastasis in one to three regional lymph
nodes; and N1b, metastasis in four or more regional lymph nodes.
5. Histopathological classification which is consistent with the WHO classification.

The following new items have been added: (1) diagnostic guideline of tumor
extension and lymph node metastasis based on multidetector CT (MD-CT),
(2) objective criteria defining resectability status only based on the findings of
MD-CT, (3) cytopathology guideline, and (4) criteria of histological response to
drug therapy and/or radiotherapy.
Conclusion: The revised seventh edition of JPS pancreatic cancer classifica-
tion focuses on establishing consistency to UICC seventh edition, while original-
ity of JPS classification is maintained.

Keywords
Pancreatic cancer · Japanese classification · Staging system · UICC/AJCC
staging system

Introduction

The purpose for establishment of pancreatic cancer classification is to make rules and
guidelines so that clinicians and pathologists can compare and discuss collected
cancer status and clinical outcomes based on a common criteria. As for the classi-
fication of pancreatic cancer, the first edition of the Japanese edition of the General
Rules for the Study of Pancreatic Cancer was released in 1980 by the Japan Pancreas
Society (JPS). The sixth edition by JPS was published in 2009 [1], and at the same
year, the Union Internationale Contre le Cancer (UICC) [2] published its seventh
edition. Two classifications adopted TNM classification, but they had been quite
different in T category, N category, and Staging system, constituting obstacles to
compare status and clinical outcomes of pancreatic cancer patients between Japan
and western countries. Therefore, the revision committee of JPS (Isaji S. is the
chairperson), which consists of 12 pancreatic surgeons, 4 gastroenterologists,
7 pathologists, 1 radiologist, 1 anatomist, and 1 doctor from Pancreatic Cancer
Registry Committee in JPS, started its work in April 2013, and the seventh edition
has been published in July 2016. The current revision by JPS focuses on establishing
consistency between the Japanese and UICC classifications; however, originality of
JPS classification, which is more precise and contains more information, is
maintained.
New Japanese Classification of Pancreatic Cancer 1023

In the seventh edition, major revisions have been carried out by comparing the
sixth edition in the following points:

1. Definition of the portions of the pancreas: the border between the pancreatic body
and tail is defined as the left side line of the abdominal aorta.
2. T category: consistency with that of the UICC seventh edition.
3. Reappraisal of anatomy of extrapancreatic nerve plexuses.
4. N category: new classification based on numbers of lymph nodal metastasis
among the regional lymph nodes.
5. (5)Stage grouping: consistency with UICC staging system.
6. Histopathological classification: consistency with the WHO classification.

In the current revision, the following new items have been added: (1) criteria of
diagnosis for T category based on MD-CT, (2) criteria of diagnosis for lymph nodal
metastasis based on MD-CT, (3) criteria defining resectability, (4) cytopathology
guideline, and (5) criteria of histological response to drug therapy and/or
radiotherapy.

Definition of Parts of the Pancreas

The definition of portion of the pancreas is shown in Fig. 1. The border between
pancreatic head and body is defined as the left side of the superior mesenteric vein
(SMV) and portal vein (PV). The neck of the pancreas (a part anterior to the SMV
and PV) and uncinate process are included in the pancreatic head. In the sixth edition
by JPS, the boundary between the body and tail of the pancreas was the line dividing
the distal pancreas into two equal halves. In the seventh edition, its boundary is
revised as the left border of the aorta, which is the same as UICC classification. This
is attributed to the fact that pancreatic cancer arising from the site between the left
side of SMV/PV and left border of the aorta tends to be frequently unresectable due
to the involvement of celiac axis (CA) and/or superior mesenteric artery (SMA).

Category of Tumor Extension (T)

Comparison of T categories between JPS sixth and seventh, UICC seventh edition, and
the American Joint Committee on Cancer (AJCC) eighth edition is summarized in
Table 1. T1 and T2 are almost the same in the three (JPS sixth and seventh and UICC
seventh) classifications. T3 and T4 are quite different between JPS sixth edition and
UICC seventh edition. In JPS seventh edition, however, T3 and T4 are the same as
those of UICC seventh edition. Clinically, the involvement of CA and SMA is clearly
defined as tumor with contact or invasion of arterial wall based on dynamic CT
findings. Among T1, T1 is divided into subclassifications: T1a, 5 mm or less; T1b,
more than 5 mm but 10 mm or less; and T1c, more than 10 mm but 20 mm or less.
1024 S. Isaji et al.

PV

Pb Pt

Ph

UP
SMV SMA

Fig. 1 Portion of pancreas in Japanese classification of pancreatic cancer, seventh edition

(Kanehara & Co., Ltd., Tokyo, Japan). The border between pancreatic head and body is defined
as the left side of SMV and PV. The neck of the pancreas (a part above SMV and PV) and the
uncinate process are included in the pancreatic head. The border between pancreatic body and tail
was defined as left side line of abdominal aorta. Ph pancreatic head, Pb pancreatic body, Pt
pancreatic tail, PV portal vein, SMA superior mesenteric artery, SMV superior mesenteric vein,
UP uncinate process

The AJCC proposed changes for T staging in its eighth edition [3]. These changes
have focused on improving the reproducibility of T stage, decreasing the percentage
of tumors designated as T3, because the term “extension beyond the pancreas” for
description of T3 in AJCC seventh edition has been thought to be potentially
inconsistent between pathologists and the T stage defined as such was not found to
have any correlations with survival [4]. A revised T stage protocol was devised that
defined pT1 as 2 cm or smaller, pT2 as >2–4 cm, and pT3 as larger than 4 cm. The
multi-institutional comparative study proved that the proposed cutoff points for T
stage were statically valid, and its utilization was more reproducible between
institutions and pathologists [5].

Reappraisal of Anatomy of Extrapancreatic Nerve Plexus

From the third to sixth edition by JPS, the extrapancreatic nerve plexuses, which
were originally defined in Japan according to the literature reported by Yoshioka
et al. [6], were divided into seven parts of the plexus: PLphI, pancreatic head plexus
I; PLphII, pancreatic head plexus II; PLsma, SMA plexus; PLcha, CHA plexus;
PLhdl, plexus within the hepatoduodenal ligament; PLspa, SPA plexus; and PLce,
celiac plexus. Several problems were pointed out for the scheme which had been
used until the sixth edition (Fig. 2). First, PLphI and PLphII were drawn on the same
New Japanese Classification of Pancreatic Cancer 1025

Table 1 Comparison of T categories between JPS sixth and seventh, UICC seventh edition, and
AJCC eighth
JPS sixth edition JPS seventh edition UICC seventh AJCC eighth
(2009) (2016) edition (2009) edition (2016)
T1 Tumor limited to Tumor limited to Tumor limited to Maximum tumor
pancreas, 2 cm or pancreas, 20 mm or pancreas, 2 cm or diameter <=2 cm
less in greatest less in greatest less in greatest
dimension dimension dimension
T1a: 5 mm or
less
T1b: more than
5 mm but 10 mm or
less
T1c: more than
10 mm but 20 mm
or less
T2 Tumor limited to Tumor limited to Tumor limited to Maximum tumor
pancreas, more than pancreas, more than pancreas, more than diameter >2 cm
2 cm in greatest 20 mm in greatest 2 cm in greatest < =4 cm
dimension dimension dimension
T3 Tumor that has Tumor extends Tumor extends Maximum tumor
extended into any of beyond pancreas, beyond pancreas, diameter > 4 cm
the following: bile but without but without
duct (CH), involvement of involvement of
duodenum (DU), celiac axis or celiac axis or
peripancreatic superior mesenteric superior mesenteric
tissue (S, RP) artery artery
T4 Tumor that has Tumor involves Tumor involves Tumor involves the
extended into any of celiac axis or celiac axis or celiac axis or the
the following: superior mesenteric superior mesenteric superior mesenteric
adjacent large artery (Tumor artery artery (unresectable
vessels (PV, A), contant or primary tumor)
extrapancreatic involvement on the
nerve plexus (PL), dynamic CT
other organs (OO) findings)
CH distal bile duct invasion, DU duodenal invasion, S serosal invasion, RP retropancreatic tissue
invasion, PV portal venous system invasion, A arterial system invasion, PL extrapancreatic nerve
plexus invasion, OO invasion of other organs

cross section as shown in Fig. 2a. However, it is not correct to draw these plexuses
on the same cross section, because PLphI is located at the cranial side and PLphII is
located at the caudal side. Second, PLphI and PLph2 were drawn just like thick nerve
bundles as shown in the yellow colored site in Fig. 2b. Third, the third and fourth
portion of the duodenum is located at the right side of the SMA, which is not correct
anatomy (Fig. 2b).
In JPS seventh edition, anatomy of the extrapancreatic nerve plexuses had been
reappraised based on cadaveric anatomical findings reported by Yi et al. [7] and
several discussions between anatomists and surgeons, and finally the revision
committee of JPS decided to make a new scheme as shown in Fig. 3. The current
1026 S. Isaji et al.

Fig. 2 Anatomical scheme of a

the extrapancreatic nerve Duodenum PL ph II
plexuses including pancreatic
head nerve plexuses (PLph) in SMA
Japanese classification of PV Pancreas
pancreatic cancer, sixth
edition (Kanehara & Co., Ltd.,
Tokyo, Japan). (a) Pancreatic PL ph I
nerve plexuses (cross-
sectional diagram). (b)
Aorta
Extrapancreatic nerve
plexuses. PV portal vein, SMA
Right kidney Celiac ganglion
superior mesenteric artery,
PLphI pancreatic head Inferior vena cava Left kidney
plexus I, PLphII pancreatic
head plexus II, PLCe celiac b Right celiac ganglion
plexus, Plsma superior
PL ce
mesenteric arterial plexus
Left celiac ganglion

PL ph I
PL ph II
Uncinate process

PL sma
Duodenum

SMA

reappraisal of anatomy of extrapancreatic nerve plexuses has clarified that nerves

within PLphI and PLphII are much less and thinner than those previously consid-
ered. Although they can be actually defined as nerve plexus from the perspective that
sympathetic nerve and parasympathetic nerve cross and make a network of nerve,
the membranous structures which are drawn as PLphI and PLphII have been proven
to include not only nerve tissue but also fibrous tissue, capillaries, and fat tissue.
Taken together with operative finding and cadaveric anatomical finding, PLphI is a
region which mainly includes nerve tissue distributed to the dorsal surface of
pancreatic head from the celiac plexus, while PLphII includes nerve tissue distrib-
uted to the uncinate process from the SMA plexus. Because PLphI and PLphII are
frequently involved by pancreatic head carcinoma and invasion of these areas is the
main cause of incomplete resection [8–10], it is very important to understand the
anatomy of extrapancreatic nerve plexus for making proper diagnosis of plexus
nerve invasion based on MD-CT and for determining the level of plexus nerve
dissection during pancreatectomy.
In the seventh edition, the term “mesopancreas” is not adopted, because its
concept and anatomical definition remain uncertain. Gockel et al. [11] has
defined a membranous structure between SMA and pancreatic head as meso-
pancreas, which contains nerve tissue, capillaries, fibrous tissue, and fat tissue.
New Japanese Classification of Pancreatic Cancer 1027

CHA

GDA

SMA

PLphI

PLphII

IPDA

J1A

MCA

CHA plexus (PLcha)

Pancreatic head plexus I (PLphI) Celiac plexus (PLce)

Plexus within the
hepatoduodenal ligament
(PLhdl)

SPA plexus (PLspa)

SMA plexus (PLsma)

Pancreatic head plexus II (PLphII)

＊PV and SMV are omitted.

Fig. 3 Anatomical scheme of the extrapancreatic nerve plexuses including pancreatic head nerve
plexuses (PLph) in Japanese classification of pancreatic cancer, seventh edition (Kanehara & Co.,
Ltd., Tokyo, Japan)
1028 S. Isaji et al.

Mesopancreas seems to be consistent with PLphII, but they did not mention
PLPhI. The term “meso” is not a proper word, because the mesentery and
mesocolon contain all blood vessels and lymphatics with peritoneal attachment.

Description of Regional Lymph Nodes of the Pancreas and Lymph

Node Metastasis

In the sixth edition by JPS, the lymph nodes related to the pancreas were classified
into three groups: Groups 1, 2, and 3. Lymph node metastasis was described
according to existence of metastasis in each group lymph nodes: N0 (no lymph
node metastasis), N1 (lymph node metastasis in Group 1), N2 (lymph node metas-
tasis in Group 2), and N3 (lymph node metastasis in Group 3). In the seventh edition,
regardless of tumor location, the regional lymph nodes of the pancreas are defined as
the following lymph node station numbers (Fig. 4) [12]: 5, 6, 7, 8a, 8p, 9, 10, 11p,
11d, 12a, 12b, 12p,13a, 13b,14p,14d, 17a, 17b, and 18 (Table 2). In case of
metastasis in the other lymph node number (1, 2, 3, 4, 15, 16a1, 16a2, 16b1, 16b2,
etc.), it is defined as M1.
The committee of JPS classification for seventh edition reevaluated the patient
survival according to metastasis in the lymph node groups and the total numbers
of lymph node metastasis using pancreatic cancer registry data by Japan Pancreas
Society from 2001 to 2007 [13]. As a result, overall survivals between the
patients with N2 and those with N3 were comparable and very poor, while
there was significant difference between the patients with N0 and those with
N1. According to the total numbers of lymph node metastasis, overall survival
was significantly better in the patients with no lymph node metastasis followed
by the patients with one to three lymph node metastases and those with four or
more lymph node metastases in decreasing order (MST: 34.7, 21.9, 15.7 months,
respectively) (Fig. 5). Given these results, the recording of lymph node metasta-
sis in the seventh edition by JPS is shown as follows:

NX: Regional lymph nodes cannot be assessed.

N0: No regional lymph node metastasis.
N1: Regional lymph node metastasis.
N1a: Metastasis in one to three regional lymph nodes.
N1b: Metastasis in four or more regional lymph nodes.

Similarly, the AJCC proposed the change for N definitions in the eighth edition as
follows: N0 = node negative, N1 = one to three nodes positive for metastatic
disease, and N2 = four or more nodes positive for metastatic disease. The multi-
institutional collected data analysis for all patients (n = 1,551) who underwent a R0
resection found that these two separate cutoffs were useful for stratification of
prognosis [5].
New Japanese Classification of Pancreatic Cancer 1029

12a
12b 9 10

8a
11p
11d
8p
16
13a 17a 14p

14d
18
17b
13b 15

b
#3
#4
#1

SPA SPV

#2
#10
#11d

LHA PHA
RHA #8a CHA
#12a
LGV LGA CHD

CA
#7 SPV

#8p
RHA #12p
#16a1 #9

#5
GDA
#17a
CBD
SPV CBD

#14d
#14p
SMA

#12b SMA #13a

PV
#16a2

SMV SMV #15 SMA

MCA
#17b SMA

Du

Du
JV

#13b
#16b1

Fig. 4 Lymph node station numbers related to the pancreas in Japanese classification of pancreatic
cancer, seventh edition (Kanehara & Co., Ltd., Tokyo, Japan). (a) Scheme of lymph node station
numbers related to the pancreas. (b). MD-CT finding (cross section) showing peripancreatic lymph
1030 S. Isaji et al.

Table 2 Numbers and names of lymph nodes related to the pancreas

Number Name
1 Right cardial lymph nodes
2 Left cardial lymph nodes
3 Lymph nodes along the lesser curvature of the stomach
4 Lymph nodes along the greater curvature of the stomach
5a Suprapyloric lymph nodes
6a Infrapyloric lymph nodes
7a Lymph nodes along the left gastric artery
8aa Lymph nodes in the anterosuperior group along the common hepatic artery
8pa Lymph nodes in the posterior group along the common hepatic artery
9a Lymph nodes around the celiac axis
10a Lymph nodes at the splenic hilum
11pa Lymph nodes along the proximal splenic artery
11da Lymph nodes along the distal splenic artery
12aa Lymph nodes along the hepatic artery
12pa Lymph nodes along the portal vein
13aa Lymph nodes on the posterior aspect of the superior portion of the head of the
pancreas
13ba Lymph nodes on the inferior aspect of the superior portion of the head of the pancreas
14pa Lymph nodes along the proximal superior mesenteric artery
14da Lymph nodes along the distal superior mesenteric artery
15 Lymph nodes along the middle colic artery
16 Lymph nodes around the abdominal aorta
16a1 Lymph nodes around the aortic hiatus of the diaphragm
16a2 Lymph nodes around the abdominal aorta (from the superior margin of the celiac trunk
to the inferior margin of the left renal vein
16b1 Lymph nodes around the abdominal aorta (from the inferior margin of the left renal
vein to the superior margin of the inferior mesenteric artery)
16b2 Lymph nodes around the abdominal aorta (from the superior margin of the inferior
mesenteric artery to the aortic bifurcation)
17aa Lymph nodes on the anterior surface of the superior portion of the head of the pancreas
17ba Lymph nodes on the anterior surface of the inferior portion of the head of the pancreas
18a Lymph nodes along the inferior margin of the pancreas
a
The regional lymph nodes of the pancreas

Fig. 4 (continued) node station numbers. SPA splenic artery, SPV splenic vein, RHA right hepatic
artery, LHA left hepatic artery, LGV left gastric vein, LGA left gastric artery, CHD common hepatic
duct, CHA common hepatic artery, CA celiac axis, GDA gastroduodenal artery, CBD common bile
duct, SMA superior mesenteric artery, MCA middle colic artery
New Japanese Classification of Pancreatic Cancer 1031

number of lymph nodal metastasis

100
0
1-3
80
>=4
survival rate(%)

60

40

20

0
0 1 2 3 4 5
years
MST (mo) 1-yr 2-yr 3-yr 5-yr

0 (n=1003) 34.7 81.7% 61.3% 48.8% 33.8%

p<0.0001
1-3 (n=892) 21.9 72.8% 45.1% 26.8% 15.8%
p =0.0001
>=4 (n=409) 15.7 60.7% 25.0% 14.8% 4.9%

Fig. 5 Survival curves in the PDAC patients with resection according to the number of lymph node
metastasis among regional lymph nodes of the pancreas (Kanehara & Co., Ltd., Tokyo, Japan).
Pancreatic cancer registry data by Japan Pancreas Society 2001–2007 (n = 2304). PDAC pancreatic
ductal adenocarcinoma

Table 3 Stage grouping in Japanese classification of pancreatic cancer seventh edition

Stage 0 Tis N0 M0
Stage IA T1 (T1a, T1b, T1c) N0 M0
Stage IB T2 N0 M0
Stage IIA T3 N0 M0
Stage IIB T1 (T1a, T1b, T1c), T2, T3 N1 (N1a, N1b) M0
Stage III T4 Any N M0
Stage IV Any T Any N M1

Stage Grouping

Stage grouping in the seventh edition by JPS is shown in Table 3. In the sixth
edition, staging system was made based on data for resected cases of pancreatic
cancer registry by JPS, focusing on stratification of prognosis according to each
stage. In contrast, the JPS seventh edition basically adopted staging system of
UICC seventh edition, focusing on enabling clinicians to decide treatment option
for each stage. Roughly, stages I and II are initially resectable pancreatic cancer.
Stage III is borderline resectable or locally advanced pancreatic cancer for which
1032 S. Isaji et al.

Fig. 6 Survival curves in the PDAC patients who underwent resection according to stage
(Kanehara & Co., Ltd., Tokyo, Japan). Pancreatic cancer registry data by Japan Pancreas Society
2001–2007 (n = 3315). PDAC pancreatic ductal adenocarcinoma

neoadjuvant therapy may be recommended on the setting of clinical trial. Stage

IV has distant metastasis for which systemic chemotherapy is recommended.
When survival rates were retrospectively evaluated using pancreatic cancer
registry data by JPS according to the current stage grouping, 5-year survival
rates of stages IA, IB, IIA, IIB, III, and IV were 54.1, 36.2%, 29.9%, 11.8%,
10.7%, and 6.5% (Fig. 6). The significant difference of overall survival rates was
found between IA and IB, IIA and IIB, and III and IV. In contrast, the survival
rates were comparable between stages IIB and III: 11.8% versus 10.7%
( p = 0.4195).

Classification of Resectability

Surgical resection is the only potentially curative therapy for long-term survival for
pancreatic cancer. At the time of diagnosis of pancreatic cancer, however, only
approximately 10–20% of patients are considered candidates for curative resection
[14]. Therefore, it is important to define the resectability using common criteria from
the perspective of determining treatment option and comparing outcomes. In the
sixth edition of JPS and UICC seventh edition, there are no classification and criteria
defining resectability.
New Japanese Classification of Pancreatic Cancer 1033

The National Comprehensive Cancer Network (NCCN) has developed guidelines

to define tumor resectability in pancreatic cancer based on MD-CT finding since
2006, in order to improve patient selection for surgery and to identify the likelihood
of an R0 resection [15]. Using their criteria, pancreatic cancer is classified as
resectable (R), borderline resectable (BR), locally unresectable (LUR), or metastatic.
BR pancreatic cancer can be defined as one that increases the likelihood of an
incomplete resection. On the contrary, LUR pancreatic cancer is locally advanced
pancreatic cancer including tumors with SMA or CA encasement greater than 180
and unreconstructable portal vein (PV)/SMV occlusion. However, this guideline has
been revised periodically and detailed, and this criteria focus on the final decision of
resectability by only pancreatic surgeons. In the seventh edition by JPS, therefore,
criteria defining resectability status based on the findings of dynamic CT have been
established by thorough discussion among pancreatic surgeons, gastroenterologist,
radiologist, and pathologist, taking NCCN guideline 2015 into consideration as
follows:

Resectable: R
No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) or
less than 180 contact or invasion without occlusion. Clear fat planes around the
superior mesenteric artery (SMA), celiac axis (CA), and common hepatic artery
(CHA), showing no contact or invasion
Borderline Resectable: BR
Subclassified according to SMV/PV invasion alone or arterial invasion
BR-PV (SMV/PV Invasion Alone)
No findings of contact and invasion of the SMA, CA, and CHA. Tumor
contact or invasion of the SMV/PV of 180 or more degrees or occlusion of
the SMV/PV, not exceeding the inferior border of the duodenum
BR-A (Arterial Invasion)
Tumor contact or invasion of the SMA and/or CA of less than 180 without
showing stenosis or deformity. Tumor contact or invasion of the CHA without
showing tumor contact or invasion of the proper hepatic artery (PHA) and/or
CA
Unresectable: UR
Subclassified according to the status of distant metastasis
UR-LA (Locally Advanced)
Tumor contact or invasion of the SMV/PV of 180 or more degree or occlusion
of the SMV/PV, exceeding the inferior border of the duodenum. Tumor contact
or invasion of the SMA and/or CA of 180 or more degree. Tumor contact or
invasion of the CHA showing tumor contact or invasion of the PHA and/or
CA. Tumor contact or invasion of the aorta
UR-M (Tumor with Distant Metastasis)
Distant metastasis including non-regional lymph node metastasis.

BR pancreatic cancer is classified into the following two types according to the
vascular invasion: BR-PV means the tumor whose vascular invasion is limited
1034 S. Isaji et al.

within PV (portal vein) alone, and BR-A means the tumor with involvement of
peripancreatic arteries such as SMA, CA, and hepatic artery (HA). This subclassi-
fication is based on the multicenter data collection by the Japanese Society of
Pancreatic Surgery that BR-A increases the likelihood of an incomplete resection
in comparison with BR-PV, showing significantly poor prognosis in the patients with
BR-A [16, 17].
Resectability criteria of the seventh edition by JPS are considered to be utilizable
for not only pancreatic surgeons but also gastroenterologist and radiologist, because
they are objective criteria only based on dynamic CT findings by avoiding the
subjective definitions such as “SMV/PV involvement allowing for safe and complete
resection and vein reconstruction” in BR pancreatic cancer and “unreconstructible
SMV/PV due to tumor involvement or occlusion” in UR pancreatic cancer
[15]. Instead of these subjective definitions for SMV/PV involvement, the authors
have adopted the objective definition: SMV/PV involvement exceeding or not
exceeding the inferior border of the duodenum, as shown in Fig. 7. In the case of
BR-PV in Fig. 7a, the tumor of pancreatic head has 180 or more degree contact/

Fig. 7 Resectability criteria according to the degree of tumor invasion of the SMV/PV. (a) A
case of BR-PV: the tumor of pancreatic head (black arrows) has 180 or more degrees of contact/
invasion of the SMV/PV (black arrow heads), but not exceeding the inferior border of the
duodenum (right break line). In this case, pancreaticoduodenectomy with combined resection of
portal vein followed by reconstruction using the external iliac vein graft was performed after
preoperative chemoradiotherapy in the Mie University School of Medicine, and negative surgical
margin was confirmed (operative finding in middle pictures). (b) A case of UR-LA: the tumor of
pancreatic head (black arrows) invades and occludes the PV/SMV, exceeding the inferior border of
the duodenum (right break line). SMV/PV is completely occluded and collateral venous formation
is found (blue arrows). This case was evaluated as unresectable even after chemoradiotherapy, and
systemic chemotherapy was performed in the Mie University School of Medicine
New Japanese Classification of Pancreatic Cancer 1035

invasion of the SMV/PV, but not exceeding the inferior border of the duodenum. In
this case, pancreaticoduodenectomy with combined resection of portal vein followed
by reconstruction using the external iliac vein graft was performed after preoperative
chemoradiotherapy in the Mie University Hospital, and negative surgical margin
was confirmed. In the case of UR-LA in Fig. 7b, the tumor of pancreatic head
invades and occludes the PV/SMV, exceeding the inferior border of the duodenum.
SMV/PV is completely occluded and collateral venous formation is found. This case
was evaluated as unresectable even after chemoradiotherapy, and systemic chemo-
therapy was performed in the Mie University Hospital.

Criteria of Histological Response to Drug Therapy and/or

Radiotherapy

Chemoradiotherapy and chemotherapy before surgery may provide for the early
treatment of micrometastatic disease and allow for the identification of patients with
metastatic disease and increase the R0 resection rate, resulting in a reduced risk for
local recurrence and improvement in outcome. Especially for BR and UR-LA cases,
systemic chemotherapy and chemoradiotherapy followed by curative-intent surgery
have been widely adopted in recent years [14]. Given these background, it is
required to establish uniformed criteria of histological response of drug therapy
and/or radiotherapy for pancreatic cancer. The Evans grading system and the clas-
sification by the American Pathologists (CAP) grading protocol are the best studied
scores [18, 19], and the relationship between histologic response and prognosis has
been reported in recent years [20, 21]. The grading system of histological response in
the seventh edition by JPS is shown as follows:

Grade 1: Poor or no response

Response to therapy is poor (estimated rate of residual tumor is 50% or more).
Grade 1a: estimated rate of residual tumor is 90% or more.
Grade 1b: estimated rate of residual tumor is 50% or more and less than 90%.
Grade 2: Moderate response
Cancer cells which are considered viable are moderately present (estimated rate
of residual tumor is 10% or more and less than 50%).
Grade 3: Marked response
Cancer cells which are considered viable are few (estimated rate of residual tumor
is less than 10%).
Grade 4: Complete response
No viable cancer cells are present.
*The estimated rate (%) of residual tumor is defined as the volume of cancer cells
considered viable/the estimated tumor volume before treatment. As of host
reaction to tumor destruction by preoperative therapy, xanthoglanulomatous
change containing foamy histiocytes, pooling of mucin without cancer cells,
infiltration of inflammatory cells, and fibrosis are important pathological features
which enable us to estimate the tumor volume before treatment.
1036 S. Isaji et al.

These criteria basically adopted the principle of both Evans grading system and
CAP grading protocol, but they clearly describe how to estimate the rate of residual
tumor cells. The estimated rate (%) of residual tumor is defined as the volume of
cancer cells considered viable/the estimated tumor volume before treatment. As of
host reaction to tumor destruction by preoperative therapy, xanthoglanulomatous
change containing foamy histiocytes, pooling of mucin without cancer cells, infil-
tration of inflammatory cells, and fibrosis are important pathological features which
enable us to estimate the tumor volume before treatment.

Conclusions

The revised seventh edition of JPS pancreatic cancer classification focuses on

establishing consistency to UICC seventh edition, while originality of JPS classifi-
cation is maintained as follows: anatomical definition of extrapancreatic nerve
plexuses, N category based on numbers of lymph nodal metastasis among the
regional lymph nodes, objective criteria of resectability only based on dynamic CT
findings by avoiding the subjective definitions, and criteria of histological response
to drug therapy and/or radiotherapy.

Cross-References

▶ Borderline Resectable Pancreatic Cancer

▶ Pancreatic Adenocarcinoma: CT and PET/CT

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