• Department of Cardiothoracic Surgery

Department of
Cardiothoracic Surgery
Outline and Research Objectives
Our department specializes in all areas of cardiothoracic surgery including congenital and
acquired cardiac diseases, thoracic and abdominal aortic diseases, and benign and malignant
diseases of respiratory and mediastinal organs, except for diseases of the esophagus and
mammary glands. The Department of Cardiothoracic Surgery, University of Tokyo, was
established in December 15, 1964 as the first department of this field in the Japanese
national universities. Since then it has played an internationally leading role and con-
tributed to development of the field. Professors and Chairs in the history of the department
are as follows; Seiji Kimoto (1964.12.15 ~ 1968.3.31), Masahiro Saigusa (1968.4.1 ~
1981.3.31), Ken-ichi Asano (1981.4.1 ~ 1986.3.31), Akira Furuse (1986.4.1 ~ 1997.3.31) and
Shinichi Takamoto (1997.6.1 ~). The cardiothoracic department of the University of Tokyo
has created highly active research programs in the every field of cardiothoracic surgery.
Recently, most of the basic research activities are focused in the fields of brain and spinal
cord protection during aortic surgery, homo- and xeno-transplantation of the heart, lung,
heart valves and trachea, and surgical oncology of the pulmonary and thymic neoplasms.
Although, there are many other active research projects such as stent-graft repair for tho-
racic aortic aneurysm, minimally invasive cardiac surgery, and intraoperative real-time 3-D
echocardiography.
Faculties and Students
Professor and Chair Shinichi Takamoto,M.D. (1997-)
Associate Professors Yutaka Kotsuka, M.D
Jun Nakajima, M.D.
Lecturer Arata Murakami, M.D. and
Toshiya Ohtsuka, M.D.
Associate .................................8
Graduate Students ................10
Research Students...................1
Past Research and Major Accomplishments Fig 1
Dr. Takamoto invented a new method of brain
protection during surgery of a distal arch aneurysm
under deep hypothermia (Fig 1). The new method is a
kind of retrograde cerebral perfusion, which simplify
the retrograde perfusion system for patients of distal
aortic arch aneurysmon. This new method has been
accepted as a standard procedure of a distal arch
replacement in all over the world. The method has
been applied to many patients, and it was clarified
that the method provides a prolongation of safety lim-
its of circulatory arrest and a beneficial effect in pre-
vention of brain embolism.
Fig 2
Allograft tissue has sevral advantages in that anti-
infection, softness, and less compliance mismatching. tissue transplantation including the cardiac valve,
Cell viability of the tissue can be maintained for more aorta and trachea 8 years ago. We founded the
than hundred years if properly preserved under the Universty of Tokyo Tissue Bank (UTTB) in 1999,
liquid nitrogen. We started basic study on homografts where human cardiac valves, vessels and tracheas
223
obtained from non-brain dead donors are cryopre- tion was performed in primates, which have a closer
served. Cardiac valves are used for the patients of anatomical and immunological relation with humans
infective endocarditis, congenital heart disease. than other animals, to confirm the possible clinical
Vessels are used for artificial graft infection, liver feasibility of cryopreserved tracheal allotransplanta-
transplant recipients. The number of donor and usage tion. Immunogenicity was attenuated by cryopreser-
of these allogaft tissus are increasing every year, and vation, and cryopreserved tracheal allografts were
more and more patients are being saved with these incorporated in all animals (Fig 4).
allograft tissues (Fig 2). Stent-graft repair: We developed ultrathin-wall
As for clinical activities, surgical cases are remark- vascular grafts with a wall thickness of 42 to 137μm
ably increasing as shown in the table below. for endovascular surgery. We studied the physical
properties of the ultrathin-wall grafts in in vitro
Table 1: Patients who underwent surgery in the department
experiments. We conclude that the newly developed
ultrathin-wall grafts are suitable for endovascular sur-
1997 1998 1999 2000 2001 gery (Table 2).
Cardiovascular 152 157 179 225 272
After animal experiments, we applied the grafts to
General Thoracic 178 202 170 197 185
clinical patients with good results. We also developed
Total 330 359 349 422 457
auto-swelling vascular grafts, using ultrathin-wall
Dacron vascular grafts and superabsorbent polymer.
These grafts were designed to prevent endoleak fol-
Current Research
lowing stent-graft repair of aortic aneurysm. Stent-
Thirteen staff members including professors and grafts covered with auto-swelling grafts are expected
lecturers all participate not only in surgeries but also to have beneficial effects in preventing endoleak.
patient care on both in-patient and out-patient bases. Minimally invasive cardiac surgery: We have been
They are all engaged in research activities for clinical using minimally invasive techniques in various proce-
and experimental subjects. As the subjects of cardio- dures of thoracic and cardiac surgery. We have
thoracic surgical fields are so close one another, we do employed video-assisted thoracoscopic surgery (VATS)
not have sectioned research groups within our depart- for pulmonary or mediastinal surgery since 1992. We
ment. Instead, we make a project team for each have made retrospective studies on feasibility and sur-
research subject with most appropriate staff members gical outcome of VATS for diagnosis and treatment of
and residents. Every associate takes part in at least lung neoplasms. We have concluded that VATS for
one to several project teams. Main subjects of current diagnosing pulmonary indeterminate nodules and
research includes brain and spine protection during
aortic surgery, homo- and xeno-transplantation of the
heart, lung, heart valves and and trachea, surgical
fig3
oncology of the pulmonary and thymic neoplasms,
stent-graft repair for thoracic aortic aneurysm, mini-
mally invasive cardiac surgery, and intraoperative 3-D
echocardiography.
Spinal cord protection: Paraplegia remains one of
the most serious complications after thoracoabdomi-
nal aortic aneurysm repair. In order to prevent para-
plegia, it is important to identify and preserve critical
segmental arteries. We developed new method to
identify critical segmental artery. The ultrasonograph-
ic evaluation of the hemodynamics of intercostal
arteries was the key to identify critical segmental fig4
artery (Fig 3).
Cryopreserved allotransplantation: Cryopreserved
allogeneic heart valves and vessels have come to be
widely utilized in cardiothoracic surgery because of
their excellent durability. We have studied the allo-
genicity of the cryopreserved tissues using cell cul-
tures of the airway epithelium, vascular endothelium,
and fibroblasts. We have investigated whether cryop-
reserved tracheal allotransplantation is applicable.
Experimental cryopreserved tracheal allotransplanta-
224
Table 2
Wall thickness (µm) 137 117 95 85 75 64 50 42
Transverse Microscopic 0 0 0 0 0 11.3±13.6 57.4±25.0 75.9±18.8
Porosity (µm)
Longitudinal Microscopic 0 0 0 0 0 36.9±7.8 39.0±7.9 132.3± 7.8
Porosity (µm)
Planimetric Porosity 0 0 0 0 0 416±494 2,238±1193 >10,000
(µm2)
Longitudinal Tensile 22.5±2.0 19.4±1.2 15.3±0.8 14.1±1.8 13.1±0.9 9.5±0.9 7.4±0.5 –
Strength (Kg)
Water Permeability 330±17 220±20 250±36 180±17 380±53 1,700±361 2,960±443 3,840±668
(ml/min/cm2)
fig6
fig5
VATS for pulmonary metastasectomy are justified as a
standard therapeutics. Off-pump coronary artery
bypass is achieved without hemodynamic assistance
by cardiopulmonary bypass, and it has been applied
to increasing number of patients with multi-vessel
ischemic heart disease. A single bypass from the
internal mammary artery (IMA) to the left anterior
descending coronary artery has been accomplished via cytometry to associate it with the degree of tumor
a mini-thoracotomy approach. Valvular disease or atri- malignancy. CD4+CD8+ or CD10+ T-lineage cells were
al septal defect have been repaired via a limited ster- the most reliable markers of the benignancy of thymic
notomy using a special retractor and port-accessible epithelial tumors. CD4 / CD8 single positive cells or
heart-lung machine. Video-endoscopy has been posi- CD20-positive cells were characteristic in thymic carci-
tively used for minimally invasive approach. noma. Flow-cytometry on the maturity of lymphoid
Thoracoscopy has been used for mobilization of ITA cells infiltrating thymic epithelial tumors was feasible
graft (Fig 5), and cardioscopy has been used in valvu- for determining their degree of malignancy. Recently
lar repair, correction of intra-cardiac anomaly, and we have investigated T-cell receptor (TCR) gene rear-
left-atrial cryo-ablation. rnagement of the TIL. We have observed the appear-
Real-time 3-D echocardiography: We have devel- ance of clonal bands in TCR-beta and gamma, suggest-
oped real-time three-dimensional echocardiography ing that partial gene rearrangement occurred in the
(RT3DE) and applied it to monitoring heart opera- TIL.
tions, especially ASD closure, as a means of assisting
treatment (Fig 6). In the animal experiment, ASD was
successfully closed by RT3DE monitoring, and exami- Future Prospects
nation of the excised heart showed that all sutures Cardiac Transplantation is established treatment in
were located, and the reliability of the images the world. However, this treatment has not been well
obtained by RT3DE was confirmed. developed in Japan due to domestic reasons. We are
Surgical oncology of the thymic neoplasms: To now preparing clinical cardiac transplantation. We are
classify the thymic epithelial neoplasms, the matura- going to develop basic and clinical research on cardiac
tion stage of T-lineage lymphoid cells infiltrating transplantation as well as clinical application.
thymic neoplasms (TIL) was examined by flow-
225
 10. Kotsuka Y, Tanaka O, Takamoto S, Furuse A.
Research Grants Intravalvular implantation technique for aortic valve
1. Grant-in Aid for Scientific Research from the replacement in aortitis syndrome. Ann Thorac Surg
Japanese Ministry of Education, Science, Sports and 67, 89-92, 1999.
Culture (A)(1): Studies on management of heart 11. Imanaka K, Takamoto S, Murakami A, Kaneko Y.
transplant recipients and maintenance of donor Minimally invasive extracardiac conduit replacement
organs. 1998-2000 via a left anterior small thoracotomy. J Thorac
2. Grant-in-Aid for Publication of Scientific Research Cardiovasc Surg 118, 1124-5, 1999.
Results: Japan Adult Cardiovascular Surgery 12. Imanaka, K, Takamoto S, Kaneko Y, Murakami A,
Database. 2002 Shibuya K. Extracardiac conduit replacement with
3. Grant-in-Aid for University and Society autologous tissue only, via a left anterior small thora-
Collaboration: Establishment of Tissue Banking cotomy. Thorac Cardiovasc. Surg 47, 251-2, 1999.
System on the basis of regional linkage. 2000-2002 13. Imanaka, K, Takamoto S, Murakami A, Kaneko Y.
4. Grant-in Aid for Scientific Research from the Right ventricular thrombosis early after bidirectional
Japanese Ministry of Education, Science, Sports and Glenn shunt. Ann Thorac Surg 68, 563-5, 1999.
Culture (B)(2): Basic and clinical study on percuta- 14. Ohtsuka T, Imanaka K, Endoh M, Kohno T,
neous endovascular surgery with ultrathin-wall vas- Nakajima J, Kotsuka Y, Takamoto S. Hemodynamic
cular grafts. 1997-1998 effects of carbon dioxide insufflation under single-
5. Grant-in Aid for Scientific Research from the lung ventilation during thoracoscopy. Ann Thorac
Japanese Ministry of Education, Science, Sports and Surg 68, 29-33, 1999.
Culture (B)(2): Development of auto-swelling vascular 15. Nakajima J, Poindexter NJ, Hillemeyer PB, Trulock
grafts using super-absorbent polymer. 1999-2001 EP, Cooper JD, Patterson GA, Mohanakumar T,
Sundaresan RS. Cytotoxic T lymphocytes directed
against donor HLA class I antigens on airway epithe-
Select Publications lial cells are present in bronchoalveolar lavage fluid
from lung transplant recipients during acute rejec-
1. Imanaka, K., Takamoto S. Furuse A. Mitral regurgi-
tion. J Thorac Cardiovasc Surg 117, 565-71, 1999.
tation late after Manouguian’s anulus enlargement
16. Nakajima J., Furuse A, Kohno T, Ohtsuka T,
and aortic valve replacement. J Thorac Cardiovasc
Matsumoto J, Oka T. Transthoracoscopic needle
Surg 115, 727-9, 1998.
biopsy for indeterminate lung nodules. Surgical
2. Ono, M, Takamoto S, Ohtsuka T. Right ventricular
Endoscopy 13, 386-9, 1999.
rupture in a minimally invasive direct coronary
17. Tanaka K, Takamoto S, Ohtsuka T, Kotsuka Y.
artery bypass grafting. Eur Journal Cardiothorac Surg
Advaseal for acute aortic dissection: experimental
14, 536-537, 1998.
study. Eur J Cardio-thorac Surg 15, 114-115, 1999.
3. Imanaka K. Shimizu S. Matsumoto J. Hashizume K.
18. Tanaka K, Takamoto S, Ohtsuka T, Kotsuka Y,
Tsuchiya K. Takemura T. Unilateral absence of pul-
Kawauchi M. Application of Advaseal for acute aortic
monary artery and ventricular defect in an infant.
dissection: experimental study. Ann Thorac Surg 68,
Ann Thorac Surg 66, 251-2, 1998.
1308-1313, 1999.
4. Kawauchi M, Nakajima J, Takeda M, Oka T,
19. Murakawa T, Nakajima J, Ono M, Murakami A,
Takamoto S. Aortic valves are antigenic but less so
Suematsu Y, Takamoto S.: Allogenicity of cryopre-
than myocardium. J Thorac Cardiovasc Surg 116,
served human fibroblasts: cryopreservation does not
532, 1998.
downregulate the allogenicity of fibroblasts making
5. Miyaji K, Sugiura S, Omata S, Kaneko Y, Ohtsuka T,
up the matrices of allografts. J Thorac Cardiovasc
Takamoto S. Myocardial tactile stiffness: A variable
Surg 120, 712-9, 2000.
of regional myocardial function. J Am Coll Cardiol
20. Murakawa T, Nakajima J, Kohno T, Tanaka M,
31, 1165-1173, 1998.
Matsumoto J, Takeuchi E, Takamoto S. Results from
6. Kubota H, Takamoto S. Takeshita M. Miyaji K.
surgical treatment for thymoma: 43 years of experi-
Kotsuka Y. Furuse A. Atrial ablation with an IRK-151
ence. Jpn J Thorac Cardiovasc Surg 48, 89-95, 2000.
infrared coagulator. Ann Thorac Surg 66, 95-100,
21. Kubota H, Furuse A, Kotsuka Y, Ninomiya M, Miyaji
1998.
K, Endo M, & Takamoto S: Cardiac function evaluat-
7. Ohtsuka T, Takamoto S, Endoh M, Ono M, Minami
ed by transesophageal echocardiography during car-
M. Ultrafast computed tomography for minimally
diopulmonary bypass. Jpn J Thorac Cardiovasc Surg
invasive coronary artery bypass grafting. J Thorac
48, 261-266, 2000.
Cardiovasc Surg 116, 173-4, 1998.
22. Kubota H, Takamoto S, Kotsuka Y, & Furuse A:
8. Ohtsuka T, Endoh M, Takamoto S. Minimally inva-
Successful treatment of massive pulmonary tumor
sive left anterior descending coronary artery bypass
embolism from renal cell carcinoma. Ann Thorac
with right gastroepiploic artery graft. J Thorac
Surg 69, 972-3, 2000.
Cardiovasc Surg 116, 528-9, 1998.
23. Kubota H, Takamoto S, Takeshita M, Miyaji K,
9. Ohtsuka T. How high should mammary artery be
Kotsuka Y, & Furuse A: Atrial ablation using an lRK-
harvested for the minimally invasive approach? Ann
Thorac Surg 66, 985-6, 1998.
226
 151 infrared coagulator in canine model. J Cardiovasc liver chirrhosis: Our experience with 3 patients. Jpn J
Surg 4, 835-47, 2000. Thorac Cardiovasc Surg 49, 391-394, 2001.
24. Nakajima J, Takamoto S, Oka T, Tanaka M, 39. Mikio Ninomiya, Haruo Makuuchi, Toshiya
Takeuchi E, Murakawa T : Flow cytometric analysis Ohtsuka, Shinichi Takamoto: Ischemic heart disease
of lymphoid cells in thymic epithelial neoplasms. Eur associated with protein C deficiency. Eur J
J Cardiothorac Surg 18, 287-92, 2000. Cardiothorac Surg 20, 883-885, 2001.
25. Nakajima J, Takamoto S, Tanaka M, Takeuchi E, 40. Mikio Ninomiya, Shinichi Takamoto, Yutaka
Murakawa T : Thoracoscopic resection of the pul- Kotsuka, Takeshi Miyairi, Tetsuro Morota, Hiroshi
monary aspergilloma - Report of two cases. Chest Kubota: Midterm results after aortic valve-sparing
118, 1490-2, 2000. operation. Jpn J Thorac Cardiovasc Surgery 49, 706-
26. Nakajima J, Takamato S, Kohno T, Ohtsuka T: Costs 710, 2001.
of videothoracoscopic surgery versus open resection 41. Ono M., Takamoto S., Miyairi T., Kubota H.: An
for patients with of lung carcinoma. Cancer 89, 2497- extended repair of thoracic aorta through left thora-
2501, 2000. cotomy after aortic root replacement. Ann Vasc Surg
27. Kotsuka Y, Ezure M, Kawauchi M, Takamoto S: 15, 488-90, 2001.
Swinging motion of intimal flap through the aortic 42. Ono M., Wolf R.K.: Heart injury and endocarditis
valve in acute aortic dissection. J Cardiovasc Surg 41, caused by a needle migrated from the left arm. Eur J
395-397, 2000. Cardiothorac Surg 20, 1073-4, 2001.
28. Ono M., Takamoto S., Kawauchi M., Egami M., 43. Ueno K, Takamoto S, Miyairi T, Morota T, Shibata
Kotsuka Y.: Aortobronchial fistula late after trans- K, Murakami A, Kotsuka Y: Arterial blood gas man-
verse arch replacement. Ann Thorac Surg 70, 964-6, agement in retrograde cerebral perfusion: the impor-
2000. tance of carbon dioxide. Eur J Cardiothorac Surg. 20,
29. Suematsu Y. Ohtsuka T. Miyaji K. Murakami A. 979-85, 2001.
Miyairi T. Eyileten Z. Kotsuka Y. Takamoto S. Right 44. Takeshi Miyairi, Yutaka Kotsuka, Tetsuro Morota,
heart mini-pump bypass for coronary artery bypass Hiroshi Kubota, Ko Shibata, Yorinobu Ikeda, Tadashi
grafting: experimental study. Eur J Cardio-Thoracic Kitamura, Takeshi Kashima, Shinichi Takamoto:
Surg 18, 276-81, 2000. Paraplegia after open surgery using endovascular
30. Murakawa T, Nakajima J, Tanaka M, Karita M, stent grafting for aortic arch. J Thorac Cardiovasc
Takamoto S.: Primary low-grade B-cell lymphoma in Surg 122: 1240-3, 2001.
mucosa-associated lymphoid tissue of the lung. Jpn J 45. Takeshi Miyairi, Shinichi Takamoto, Yutaka
Thorac Cardiovasc Surg 49, 621-4, 2001. Kotsuka, Arata Murakami, Hiroshi Kubota, Toshiya
31. Ohtsuka T, Suematsu Y, Kubota H, Takamoto S, Ohtsuka: Strategy for redo surgery on the thoracic
Makuuchi M. Salvage of right gastroepiploic artery aorta. Keio University International Symposia for
graft before pancreatoduodenectomy. J Thorac Life Science and Medicine, Ed by S. Kawada, Vol. 7:
Cardiothorac Surg 121, 1013-4, 2001. 90-98, 2001. Tokyo.
32. Ohtsuka T, Kubota H, Motomura N, Takamoto S. 46. Suematsu Y. Takamoto S. Ohtsuka T. Intraoperative
Thoracoscopy for minimally invasive axillo-coronary echocardiographic imaging of coronary arteries and
artery bypass. Eur J Cardiothorac Surg 20, 856-7, graft anastomoses during coronary artery bypass
2001. grafting without cardiopulmonary bypass. J Thorac
33. Ohtsuka T, Nakajima J, Kotsuka Y, Takamoto S. Cardiovasc Surg 122, 1147-54, 2001.
Hemodynamic responses to intra-pleural insufflation 47. Murakawa T, Nakajima J, Motomura N, Murakami
with hemipulmonary collapse. Surg Endosc 15, 1327- A, Takamoto S.: Successful allotransplantation of
30, 2001. cryopreserved tracheal grafts with preservation of
34. Ohtsuka T, Takamoto S, Ono M, Motomura N. the pars membranacea in nonhuman primates. J
Aortic root replacement and coronary Interposition Thorac Cardiovasc Surg 123, 153-60, 2002.
using a cryopreserved allograft and its branch. Eur J 48. Kubota H, Takamoto S, Murakami A, Kotsuka Y, &
Cardiothorac Surg 20, 631-2, 2001. Furuse A: Biologic glue-molded “bio-mini-paddle”
35. Mikio Ninomiya, Jun Nakajima, Makoto Tanaka, electrode used for atrial and ventricular pacing and
Eriho Takeuchi, Tomohiro Murakawa, Takeshi defibrillation. Ann Thorac Surg 322-4, 2002.
Fukami, Shinichi Takamoto: Effects of lung metasta- 49. Kotsuka Y, Ezure M, Tanaka K, Takamoto S,
sectomy on respiratory function. Jpn J Thorac Kuwahara K, Ikeda H. Ultrathin-wall vascular grafts
Cardiovasc Surg 49, 17-20, 2001. for endovascular surgery. J Art Org 5: 108-112, 2002．
36. Mikio Ninomiya, Shinichi Takamoto, Yutaka 50. Suematsu Y. Ohtsuka T. Miyairi T. Motomura N.
Kotsuka, Takeshi Miyairi, Munemoto Endo: Stent- Takamoto S. Ultrasonic evaluation of graft anasto-
graft implantation through partial sternotomy. J moses during coronary artery bypass grafting with-
Thorac Cardiovasc Surg 121: 992-993, 2001. out cardiopulmonary bypass. Ann Thorac Surg 74,
37. Mikio Ninomiya, Shinichi Takamoto, Yutaka 273-5, 2002.
Kotsuka, Toshiya Ohtsuka: Indication and periopera-
tive management for cardiac surgery in patients with
227
 Department of
Gastrointestinal Surgery /
Department of Surgical
Metabolism and Nutrition and
Endocrine Surgery
Outline and Research Objectives
Since 2001, the former Third Department of Surgery, which was located in a branch hos-
pital of the University of Tokyo, has been divided into two departments, the Department of
Gastrointestinal Surgery and the Department of Surgical Metabolism and Nutrition and
Endocrine Surgery, in line with the integration of the main and branch hospitals the eleva-
tion to a department in the graduate school of medicine at our university. Our research
activities in both departments have been well organized and ultimately successful by main-
taining a close connection.
The main research activities of the department of Gastrointestinal Surgery are focused
on diagnosis and therapy for gastrointestinal diseases and clinical and basic research for
gastrointestinal carcinogenesis. A historical and outstanding achievement of the department
of Gastrointestinal Surgery is the successful innovation of the “Gastrocamera” a half century
ago. Thereafter, we have been active in the diagnosis and treatment of gastric cancer and
established the feasibility of extended gastrectomy with intraoperative chemotherapy for
advanced cancer, and limited lymph node dissection for early gastric cancer. With a view to
further development of research for gastrointestinal carcinogenesis, we established the
Japanese Society for Gastroenterological Carcinogenesis in 1989, and have been studying
the underlying mechanisms of development, progression and prevention of digestive can-
cer.
The department of Surgical Metabolism and Nutrition and Endocrine Surgery has been
studying one of the most fundamental issues in surgery, i.e., “surgical stress,” which indi-
cates postoperative physiological and endocrinological internal reaction, and nutritional sup-
port for the postoperative patients. Our department is a pioneer in this area in Japan, and
we established the Japanese Society for Surgical Metabolism and Nutrition in 1965. In addi-
tion, we have been studying endocrine issues, i.e., surgical therapy for breast, thyroid and
parathyroid diseases.
Faculties and Students Past Research and Major Accomplishments
Professor and Chairman Michio Kaminishi, MD., Ph.D. In research on gastrointestinal carcinogenesis, we
(since 1997) have established experimental models of gastric car-
Associate Professor Ken-ichi Mafune, MD., Ph.D. cinogenesis and looked closely at the important roles
(Yoshikazu Mimura, M.D., Ph.D. of repetition of injury and regeneration of gastric
from Division of Surgical mucosa. In particular, we demonstrated that infection
Operation Center) of Helicobacter pylori acts not only in promotion but
Lecturer Shouji Shimoyama, MD., Ph.D. also in co-initiation of gastric carcinogeneis. This was
Toshihisa Ogawa, MD., Ph.D., the first report in the world to show the direct rela-
Mitsue Saito MD., Ph.D., tionship between H.p. infection and gastric carcino-
Associate ...............................12 genesis using experimental models. Furthermore, we
Postdoctor Fellow ...................8 verified that duodenogastric reflux and denervation of
Graduate Student....................9 the gastric mucosa enhance gastric mucosal injury,
Secretary .................................4 resulting in development of gastric remnant cancer.
228
Based on these results, we have adopted new opera- 3) Minimally invasive treatment of upper GI can-
tions for gastric cancer and obtained better results in cers
terms of postoperative QOL and outcome. Our ･ Indication and results of laparoscopic surgery
detailed histopathological analysis of colon carcino- ･ Sentinel node navigation surgery for early gastric
genesis revealed de novo carcinogenesis other than cancer
adenoma-carcinoma sequence, leading to the current ･ Evaluation of results of PPG and jejunal interposi-
hypothesis of the dysplasia-carcinoma sequence. tion after gastrectomy in terms of postoperative
In research on surgical metabolism and nutrition, QOL
we clearly showed the importance of nutritional sup-
port under condition of postoperative hypoxia and 4) Multimodal treatment for esophageal and gas-
endotoxemia. Fatty acids reduced the morbidity and tric cancers
mortality due to panperitonitis, and glutamine attenu- ･ Neoadjuvant or definitive chemoradiation therapy
ated acute lung injury after the organism was chal- for esophageal cancer
lenges with endotoxin. Research on the metabolism ･ Apoptosis induced by TRAIL
of phosphate, calcium and sodium is one of the most ･ Prediction of gastric cancer recurrence by molecu-
important means to clarify the mechanism of the lar analysis of samples of peritoneal washes
postoperative physiological reaction. We demonstrat- ･ Mechanisms of adverse effects of chemotherapy
ed the close relationship between these metabolites for gastrointestinal cancer on the intestinal
and catecholamine after surgical stresses such as mucosa and its preventive therapy
hypoxia, endotoxiemia and ischemic reperfusion
injury. These studies aim to reduce the intra- and 5) Gastrointestinal motility
post-operative stresses that would be risky for ･ Mechanism of peppermint oil solution on relax-
patients. ation of digestive tract
･ Role of cytokine and COX-2 in gastrointestinal
motility
Current Research
･ Effects of intra- and extra-abdominal environ-
The main focus of our current research in the field ments on gastrointestinal motility
of Gastrointestinal Surgery is the tailor-made treat- ･ Gastric motility after gastrectomy
ment of cancer based on its stage and characteristics.
We try to establish the optimal limited surgery for The main focus of our current research in the field
early cancer by application of sentinel node naviga- of Surgical Metabolism and Nutrition is “adaptive
tion system and molecular analysis of lymph node response to surgical stresses”. In particular, “cross tol-
micrometastasis. For advanced cancer, multimodal erance among different stresses” is a very challenging
therapy combined with extended surgery and periop- and important phenomenon to be elucidated, and the
erative chemotherapy is required. In regard to clinical application of findings will lead to reduction
chemotherapy, a new strategy using apoptosis-related of morbidity and mortality due to severe surgical
and/or cell differentiation-related agents is likely to stresses and endotoxin shock. On the other hand,
achieve better prognosis in advanced cases. there is a definite difference in adaptive response to
Current research topics in the department of surgical stress between genders. We have clearly
Gastrointestinal Surgery are the followings. demonstrated the gender difference in cytokine secre-
tion after endotoxin challenge.
1) Carcinogenesis of gastrointestinal cancer In the field of Endocrine Surgery, we have intro-
･ Roles of Helicobacter pylori infection in gastric duced minimally invasive surgery for breast cancer
carcinogenesis and thyroid tumors through the application of laparo-
･ Roles of Trefoil Peptides in gastric metaplasia scopic procedures. In terms of differential diagnosis of
･ Clinical and experimental studies on Barrett thyroid tumors, we established a method for the
esophagus immunohistochemical detection of telomerase
reverese ranscriptase (hTERT) by in situ hybridiza-
2) Molecular mechanisms of gastrointestinal cancer tion, providing a good marker for distinction between
･ Effects of hypoxia and nutritional deprivation on follicular adenoma and follicular cancer.
cancer development and progression Current research topics in the department of
･ Roles of PPARr in gastric carcinogenesis and treat- Surgical Metabolism and Nutrition and Endocrine
ment of gastric cancer by PPARr ligands Surgery are the followings
･ Angiogenic factors in gastrointestinal cancer
･ Telomerase activity in gastrointestinal tumors
･ Lymph node micrometastasis of gastric cancer
229
1) Surgical metabolism and nutrition inflammation, acute and chronic. Under acute inflam-
･ Mechanisms of cross tolerance among different mation or acute stress, injured tissue recovers to nor-
stresses (endotoxin-hypoxia/ hypoxia-endotoxin) mal promptly after subsidence of the acute causes. In
after surgery that case, the organ represses apoptosis and main-
･ Role of catecholamines in adaptation to surgical tains or restores the normal tissue. Many factors such
stress such as endotoxemia as cytokines, NO, NF-κB, and HSP play important
･ Bacterial translocation after major surgery and roles in development and progression of the inflam-
anti-cancer chemotherapy matory process. Conversely, these molecular factors
･ Gender difference is a modulation factor for post- play a key role in the attenuation of morbidity
operative morbidity through across tolerance mechanism. Clinical applica-
･ Parathyroid function after surgical stress tion of therapy based on cross tolerance leads to a bet-
･ Ischemic preconditioning and its underlying ter prognosis for morbid patients after severe surgical
mechanism (NO, HSP, metalothionein) stress.
Under chronic inflammation, for, example, In
2) Endocrine surgery cases of chronic gastritis, however repetition of injury
･ Cytology of breast and thyroid tumors by in situ and subsequent regeneration is observed regardless of
hybridization of telomerase reverse transcriptase the causes. The accelerated regeneration of the gastric
(hTERT) mucosa induces a newly developed tissue that is
･ Effects of preoperative endocrine therapy of breast adapted for chronic injury by balancing cell prolifera-
cancer tion and apoptosis. This phenomenon is widely recog-
･ Detection of breast cancer cell in the drainage vein nized as metaplasia and all metaplastic change in the
from the breast by using RT-PCR human organ is considered to be a result of adaptive
･ Molecular analysis of heterogeneity in breast and reaction. Furthermore, the metaplastic cells and/or the
thyroid cancers