Lymph Node Metastasis in Gastrointestinal Cancer

354 Pages·2019·18.846 MB·English

by  Shoji Natsugoe

Lymph Node
Metastasis in
Gastrointestinal Cancer
Shoji Natsugoe
Editor
123
Lymph Node Metastasis in
Gastrointestinal Cancer
Shoji Natsugoe
Editor
Lymph Node Metastasis in
Gastrointestinal Cancer
Editor
Shoji Natsugoe
Department of Digestive Surgery, Breast and Thyroid Surgery
Kagoshima
Japan
ISBN 978-981-10-4698-8 ISBN 978-981-10-4699-5 (eBook)
https://doi.org/10.1007/978-981-10-4699-5
Library of Congress Control Number: 2018965728
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Preface
There is a famous sentence: “The doctor who controls metastasis controls cancer”.
One of the characteristics of a malignant tumor is the ability to metastasize. If a
tumor has high malignant potential, metastasis is often seen in wide areas. Thus,
lymph node metastasis is one of the most important prognostic factors in various
carcinomas, including gastrointestinal (GI) cancer. There are several biological and
morphological pathways by which lymph node metastasis can arise: invasion into a
deeper layer, detachment of tumor cells from the primary tumor, infiltration into
intramural lymphatics, flow to extramural lymphatics, arrival to afferent lymphatics
of a marginal sinus, movement to the lymph node cortex, and implantation of tumor
cells into the node and formation of metastasis.
When surgeons and oncologists treat cancer patients, it is necessary to have suf-
ficient understanding of both the basic and clinical aspects of nodal metastasis. In
the basic aspect, knowledge of the anatomy and physiology of lymphatics and
lymph nodes is essential when performing surgical treatment. The molecular mech-
anism in lymph node metastasis and immunology for lymph nodes is also important
when doing chemo and/or chemo radiotherapy, molecular target treatment, and
immunotherapy. The theory of basic imaging diagnosis and in vivo imaging is use-
ful in the planning of cancer treatment.
In the clinical aspect, lymph node metastasis and metastatic sites should be ana-
lyzed in detail, because such data are important to plan the treatment strategy, espe-
cially in surgical lymph node dissection and radiation therapy. Usually, histological
examination for lymph node metastasis is performed using representative sections
from the removed nodes. Even if complete lymph node dissection is performed in
patients with early cancer, recurrent disease is sometimes encountered. The devel-
opment of sensitive immunohistochemical techniques and reverse transcription–
polymerase chain reaction (RT-PCR) and other methods has led to the detection of
lymph node micrometastasis (LNM) that could not be found in routine histological
examination. Although overt lymph node metastasis is thought to be related to prog-
nosis, what is the relationship between LNM and prognosis? Clinical evaluation of
LNM is somewhat difficult, but in this book we review the clinical significance of
LNM in each type of GI cancer.
Currently, minimally invasive treatments such as endoscopic submucosal dissec-
tion and laparoscopic surgery with individualized lymphadenectomy are increas-
ingly being performed. Accurate diagnosis of LNM can clarify issues of curability
v
vi Preface
and safety when performing such treatments. Sentinel node navigation surgery
(SNNS), especially, has recently been introduced in treatment of GI cancer. When
SNNS with individualized lymphadenectomy in early cancer is performed, it is
important to consider the balance between postsurgical quality of life and curability.
Increasingly, SNNS will become firmly established as a beneficial procedure for
patients with early cancer.
This book summarizes the current knowledge of lymph node metastasis in GI
cancer from the perspectives of both molecular and biological characteristics, and
from clinical aspects. The book will be helpful as an overview of the current under-
standing of lymph node metastasis and areas requiring further investigation.
Kagoshima, Japan Shoji Natsugoe
Contents
1 Physiology of the Gastrointestinal Lymphatics . . . . . . . . . . . . . . . . . . . 1
Toshio Ohhashi and Yoshiko Kawai
2 Anatomy of Lymphatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Tatsuo Sato
3 Molecular Mechanisms of Lymph Node Metastasis . . . . . . . . . . . . . . . 69
Naohide Oue, Yasuhiko Kitadai, and Wataru Yasui
Part I B asic Science of the Lymphatic System
4 Immunology of a Lymph Node . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Ryota Hokari and Soichiro Miura
5 Lymphoid Tissues Associated with Gastrointestinal (GI) Mucosa . . . . 111
Takahiro Nagatake, Jun Kunisawa, and Hiroshi Kiyono
6 Nonclinical Imaging Studies for the Diagnosis
of Lymph Node Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Kazunobu Ohnuki and Hirofumi Fujii
7 In Vivo Imaging of Lymphatic Vessels and Lymph Nodes . . . . . . . . . . . 159
Takeshi Imamura, Takashi Saitou, Sota Takanezawa,
and Ryosuke Kawakami
Part II L ymph Node Micrometastasis
8 Basic Aspect: Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Shuhei Ito, Takaaki Masuda, Yosuke Kuroda, Hidetoshi Eguchi,
and Koshi Mimori
9 Clinical Aspect: Esophageal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Itaru Omoto, Yasuto Uchikado, Ken Sasaki, Takaaki Arigami,
and Shoji Natsugoe
vii
viii Contents
10 Clinical Aspect: Gastric Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Takaaki Arigami, Yoshikazu Uenosono, Shigehiro Yanagita,
Sumiya Ishigami, and Shoji Natsugoe
11 Clinical Aspects: Colorectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Hirofumi Yamamoto and Masaki Mori
12 Clinical Aspect: Chemo- and/or Radiation Therapy
and Micrometastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Ken Sasaki and Shoji Natsugoe
13 Esophageal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Yoshiaki Kajiyama, Natsumi Tomita, and Takashi Hashimoto
Part III Lymph Node Metastasis: Clinical Significance
14 Gastric Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Koshi Kumagai and Takeshi Sano
15 Colorectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
Kazushige Kawai, Kensuke Otani, Manabu Kaneko, Koji Murono,
Kazuhito Sasaki, and Toshiaki Watanabe
Part IV S entinel Node Navigation Surgery
16 Methodology: Dye and Isotope Method . . . . . . . . . . . . . . . . . . . . . . . . . 305
Shinichi Kinami and Takeo Kosaka
17 Methodology: CT Lymphography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Akira Tangoku, Takahiro Yoshida, Hiroaki Toba, Hirokazu Takechi,
Masakazu Okumua, Takeshi Nishino, Seiya Inoue,
Misako Nakagawa, Masami Morimoto, Toru Sawada,
Mariko Aoyama, Naoki Miyamoto, Kohei Nishioka,
Keisuke Fujimoto, and Hiromitsu Takizawa
18 Clinical Aspect: Esophageal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
Yoshikazu Uenosono, Takaaki Arigami, Shigehiro Yanagita,
Itaru Omoto, Ken Sasaki, Yasuto Uchikado, and Shoji Natsugoe
19 Clinical Aspect: Gastric Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
Hiroya Takeuchi and Yuko Kitagawa
Physiology of the Gastrointestinal 1
Lymphatics
Toshio Ohhashi and Yoshiko Kawai
Abstract
In this chapter, we focus on the physiology of gastrointestinal lymphatic system
and then demonstrate with current inspired studies that (1) functional properties
of the intestinal microcirculation are summarized as higher permeability of
plasma protein, especially albumin through the venule walls, which contribute to
the oncotic pressure-mediated much absorption of interstitial fluid into lym-
phatic capillaries, (2) the larger amount of lymph formation in the intestinal villi
may be related to the presence of lacteal vessels in the tissues, (3) the mesenteric
collecting lymphatics demonstrate marked heart-like spontaneous contractions
working as transport of the larger amount of lymph to chylous cyst, (4) the sen-
tinel lymph node (SLN) may be defined as the node subjected to higher lymph
flow from physiological point of view, and (5) the higher lymph flow may be, in
part, related to develop the suitable microenvironment of the SLN for metastasis
of carcinoma cells, which is produced by the cell surface F/F ATP synthase-
1 0
dependent overexpression of intercellular adhesion molecule-1 on the marginal
endothelial-like cells of SLN.
T. Ohhashi (*)
Department of Innovation of Medical and Health Sciences Research, School of Medicine,
Shinshu University, Matsumoto, Japan
e-mail: [email protected]
Y. Kawai
Faculty of Medicine, Division of Physiology, Tohoku Medical and Pharmaceutical University,
Sendai, Japan
© Springer Nature Singapore Pte Ltd. 2019 1
S. Natsugoe (ed.), Lymph Node Metastasis in Gastrointestinal Cancer,
https://doi.org/10.1007/978-981-10-4699-5_1
2 T. Ohhashi and Y. Kawai
Keywords
Albumin · Starling’s law · Spontaneous contraction · Lipid absorption · Lacteal
vessel
1.1 Introduction
As one of the lymphatic functions, it is well known that transport and drainage of
hydrophilic substances including plasma protein through the lymphatic system play
pivotal roles in maintaining the homeostasis of the internal environment between
the cells in collaboration with the exchange of substances through blood capillaries
and venules [1–3].
Another important function of the lymphatic system is concerned with the
immune system. The lymphatic system provides the anatomical structures which
contain the cellular elements involved in this system and provides the circulatory
pathways for interaction between these cells and other tissues [4]. Thus, there is a
large population of resident lymphocytes within the lymph node. These lympho-
cytes moved from the node into efferent lymph travel to other lymph nodes or to the
blood via the thoracic duct. Similarly, lymphocytes leave the vascular compartment
at high endothelium venules within the node to enter the lymphatic compartment
[5]. These processes are physiologically balanced since lymph nodes do not change
in size with time. Under normal circumstances there is only a low rate of division of
lymphocytes within the node [6].
The two main roles of the lymphatic system should not be considered in isolation
since it is likely that the system has evolved to optimally suite for both functions.
Therefore, we have proposed a new lymphology combined with current knowledge
of lymphatic physiology included with microcirculation, innate immunology, and
oncology from a defense mechanisms point of view [7].
In addition, the functional and anatomical properties of lymphatic system
have also a marked heterogeneity between gut and limbs. Thus, the intestinal
lymphatic system works as the transport of absorbed lipids with long-chain, and
macromolecules such as plasma protein, especially albumin [8]. Figure 1.1
demonstrates a representative photomicrograph showing murine mesenteric
lymphatics contained with white-colored lymph after lipid absorption. In this
chapter, in collaboration with the title of this book, we would like to demon-
strate the gastrointestinal lymphatic physiology included with the specialized
property of higher permeability of albumin through the venular walls in the
intestinal microcirculation, the modified concept of Starling’s law applicable for
the microcirculation, physiological roles of heart-like spontaneous contraction
of the lymphatic smooth muscles and the effects of shear stress stimulation pro-
duced by lymph flow on the lymphatic endothelial cells and sentinel lymph node
(SLN).