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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3721_Библиотеки_им_академика_М_И_Перельмана
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Y. Tamura et al.
Fig. 34.8 Case 1: improvement of maxillary osteolysis
examination. Blood tests revealed severe anemia and elevated liver enzymes. Ultrasonography showed a right atrial
mass, pericardial effusion, bloody ascites, mass in the
abdominal wall, and splenomegaly. In addition, a chest X-ray
showed cardiomegaly caused by cardiac tamponade, and the
patient was tentatively diagnosed with a ruptured hemangiosarcoma of splenic origin and cardiac metastasis (Fig.34.9).
At the time of informed consent, we explained to the
owner that the prognosis of cardiac metastasis of hemangiosarcoma of splenic origin is very poor and that there is no
effective treatment at this time and decided to treat the patient
with ICG-Lipo. At that time, no adjuvant therapy was given.
[Treatment]
Considering the fact that the patient came from a distant
place, ICG-Lipo was administered intravascularly at our hospital, followed by home treatment (daily irradiation). The
owner was instructed to irradiate the heart from the right and
left chest walls for 20minutes each and the upper abdomen
for 20minutes, for a total of 60minutes (output 5W), using
a near-infrared light source (Hyper5000, Tokyo Medical
Research Institute, Inc.) loaned to the owner.
[Outcomes]
From the rst week of treatment, the patient’s appetite
recovered and her energy increased. In the third week, the
patient’s general condition became very good, and blood test
results showed improvement in anemia and normalization of
liver enzymes. In addition, ultrasonography showed the disappearance of ascites, abdominal mass, and cardiac tamponade. Furthermore, although there was no signicant change
in the size of the right atrial mass, an echo-free area was
observed, suggesting degeneration and necrosis inside the
tumor (Fig.34.9).
Case 3: Dog (Miniature Dachshund), Male, 13Years old,
8.2kg
Adrenal Medullary Tumor with Intravascular Invasion
[Present Illness]
On arrival at the hospital (day 0), the patient was in a state
of shock with a body temperature of 37°C, vomiting, rapid
respiratory rate, open mouth breathing, visible mucosal pallor, collapse, and lying down. Blood tests, blood pressure
measurement, radiography, ultrasonography, and unanesthetized CT scan were performed, and an adrenal medullary
tumor with intravascular invasion was suspected (Fig.34.10).
At the first consultation 16th day of illness
At the first consultation Treatment: 69th day of illness Treatment: 121st day of illness
34 Application toTherapy (2): Photoimmunotherapy Using aNear-Infrared Fluorescent Probe
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Fig. 34.9 Case 2: cardiac tamponade and intracardiac metastases of angiosarcoma
261
Fig. 34.10 Case 3: adrenal medullary tumor with intravascular invasion
After informed consent for the owner of the dog, it was
decided to start treatment with ICG-Lipo from the 18th day
of the disease.
[Treatment]
For photoimmunotherapy using ICG-Lipo, light irradiation was performed three times a week using a near-infrared
light source device (Hyper5000, Tokyo Medical Research
Institute), and Answer 20 (alternating between Solution A
and B) was administered subcutaneously.
A total of four courses were conducted with periodic CT
examinations.
[Outcomes]
The size of the tumor before treatment was 20mm×40mm
extravascularly, and a thrombotic tumor plug was identied
in the posterior vena cava, with associated reduced hepatic
venous blood ow. On the 69th day, the extravascular mass
had disappeared and a linearly reduced thrombotic tumor
plug measuring 2.5mm×57mm was identied in the poste-
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Y. Tamura et al.
rior vena cava. An increase in hepatic venous blood ow was
also observed with the reduction of the tumor (Fig.34.10).
On the 121st day, ultrasonography, which also revealed the
disappearance of the linear thrombotic tumor plug, revealed
no abnormalities in the blood ow in the hepatic veins
(Fig.34.10).
3.2.4 Photoimmunotherapy Using ICG-Lipo:
Potential Application toHuman
ClinicalCare
Through the “Consortium for Industry-Academia
Collaboration” described above, research and development
is being conducted to establish the foundation for translating
this safe and secure medical technology based on ICG-Lipo
and near-infrared light irradiation into human medicine. In
the future, the combined use of the ICG-Lipo drug delivery
system and near-infrared diagnostic and therapeutic devices
is expected to create a “noninvasive identication method”
for early cancer detection, a “noninvasive treatment method”
for cases where surgery is not possible, and a “high-quality
palliative medicine” for terminal cancer patients.
Point
• The near-infrared uorescence probe enables a noninva-
sive medical treatment called photoimmunotherapy using
the optical window of the body.
• The IR-700 conjugated antibody (ASP-1929, conjugate
of IR-700, a phthalocyanine derivative, and anti-EGFR
antibody) is now in phase III clinical trials in patients with
squamous cell carcinoma of the head and neck and is also
indicated for the treatment of breast cancer and prostate
cancer by converting anti-EGFR antibody to anti-HER2
antibody and anti-PSMA antibody, respectively.
• ICG derivative-modied liposomes (ICG-Lipo) were
shown to be effective in clinical trials in companion animals with various cancer types.
4 Future Perspectives
Photoimmunotherapy using the IR-700 conjugated antibody,
ICG-Lipo, described in this paper is a therapeutic method
that utilizes the subcutaneous penetration (10–20mm) in the
“optical window of the living body (650–900 nm).” Recently,
in over 1000nm in the near-infrared range (OTN-NIR: 900–
2500nm) where autouorescence and tissue absorption/scattering decrease, the use of the second optical window
(OTN-NIR-II: 1100–1350nm) and the third optical window
(OTN-NIR-III: 1550–1800 nm) have been reported to
improve the subcutaneous penetration up to 20–30mm [8,
9]. In fact, imaging systems and OTN uorescent probes
have already been developed for invivo imaging [10]. In the
near future, novel uorescence probes using OTN-NIR-II
and OTN-NIR-III will also be used for enhancing the efcacy of photoimmunotherapy.
References
1. Chinnathambi S, Shirahata N.Recent advances on uorescent biomarkers of near-infrared quantum dots for invitro and invivo imaging. Sci Technol Adv Mater. 2019;20:337–55.
2. Sato K, Ando K, Okuyama S, etal. Photoinduced ligand release
from a silicon phthalocyanine dye conjugated with monoclonal
antibodies: a mechanism of cancer cell cytotoxicity after nearinfrared photoimmunotherapy. ACS Cent Sci. 2018;4:1559–69.
3. Suganami A, Toyota T, Okazaki S, etal. Preparation and characterization of phospholipid-conjugated indocyanine green. Bioorg Med
Chem Lett. 2012;22:7481–5. [3] Suganami A, Toyota T, Okazaki S
etal Preparation and characterization of phospholipid-conjugated
indocyanine green as a near-infrared probe
4. Toyota T, Fujito H, Suganami A, etal. Near-infrared-uorescence
imaging of lymph nodes by using liposomally. Bioorg Med Chem.
2014;22:721–7. [4] Toyota T, Fujito H, Suganami A et al: Nearinfrared- uorescence imaging of lymph nodes by using liposomally formulated indocyanine green derivatives
5. Matsumura Y, Maeda H. A new concept for macromolecular
therapeutics in cancer chemotherapy: mechanism of tumoritropic.
Cancer Res. 1986;46:6387–92. [5] Matsumura Y, Maeda H.A new
concept for macromolecular therapeutics in cancer chemotherapy:
mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs
6. Suganami A, Iwadate Y, Shibata S, et al. Liposomally formulated
phospholipid- conjugated indocyanine green for intra-operative. Int
J Pharm. 2015;496:401–6.
7. Castano AP, Mroz P, Hamblin MR.Photodynamic therapy and antitumour immunity. Nat Rev Cancer. 2006;6:535–45.
8. Starosolski Z, Bhavane R, Ghaghada KB, etal. Indocyanine green
uorescence in the second near-infrared (NIR-II) window. PLoS
One. 2017;12:e0187563.
9. Ding F, Zhan Y, Lu X, et al. Recent advances in near-infrared II
uorophores for multifunctional biomedical imaging. Chem Sci.
2018;9:4370–80.
10. Uemura M, Soga K.Development of an invivo imaging method
using a near-infrared uorescent probe. Bunseki. 2019;3:114–7.
Afterword
https://t.me/medicina_free
MitsuoKusano
This book describes the introduction, practice, and future
prospects of uorescence-guided surgery in various surgical
elds. The book is very easy to understand not only for doctors who have already introduced this method in their clinical practices but also for those who are about to do so.
The in vivo uorescence imaging has been used in ophthalmology and sentinel node identication of breast cancer
since around 2000 and has been vigorously applied to cardiovascular surgery, neurosurgery, and digestive systems
such as liver, gallbladder, and GI tracts. As you know, rapid
development has been seen in less than 20years since then.
During this period, various uorescent agents have been
used for uorescence imaging, and ICG has been one of the
triggers for the widespread use of this method because of its
high safety and low cost. Now that it has been 20years since
the clinical application of uorescence imaging has become
widespread, the publication of this book, which covers all
surgical elds, is very timely.
In the last few years, this method has been applied to
almost all organs, including pulmonary, gynecological, urological, and other new elds, as well as robot-assisted surgery and photodynamic therapy.
All of the authors, including the editor, Dr. Ishizawa, are
active in the frontline medical eld in Japan and abroad and
are practitioners of this method, and this book contains practical know-hows of this method that can be applied immediately from tomorrow. It should be obvious to readers who
read this book that there are many things to learn from different elds of expertise through the common approach of uorescence imaging. In addition, this book contains a wealth of
essentials that can be applied to various elds, and we
encourage readers to read through the descriptions of elds
other than their own.
Although some applications of intraoperative uorescence imaging, such as evaluation of blood perfusion, sentinel lymph nodes mapping during breast cancer surgery, and
brain tumor identication, have been covered by the Japanese
insurance system, there remains a lot of unapproved imaging
methods. It is necessary to promote further practice and
development to feedback to clinical practice. On the other
hand, it is also expected that the investigation of uorescence
mechanics in cancer cells and specic organs leads to the
development of new diagnostic and therapeutic approaches.
I would thank all contributors who have worked on the
medical application of uorescent imaging and those who
have been involved in the development of imaging equipment such as uorescent endoscopes. I would also like to
take this opportunity to thank Mr. Shingo Nagasawa and his
staff at Medical View and Springer for their efforts in producing this English edition. I hope that this book will be a
stepping stone for the further development of this eld and
that more patients will benet from the spread of this method.
July 2022
M. Kusano
Chief Clinical Director, Yoichi Hospital, Hokkaido
Social Work Association, Yoichi, Japan
Honorary Director, Kushiro Rosai Hospital, Kushiro, Japan
Honorary Member, Japanese Society for Fluorescence
Guided Surgery, Tokyo, Japan
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
T. Ishizawa (ed.), Fluorescence-Guided Surgery, https://doi.org/10.1007/978-981-19-7372-7
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