Yoshitsugu Tajima

Shimane University, Matsu, Shimane, Japan

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Publications (194)370.02 Total impact

  • Journal of the American College of Surgeons 01/2015; DOI:10.1016/j.jamcollsurg.2014.12.054 · 4.45 Impact Factor
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    ABSTRACT: Milk fat globule-epidermal growth factor 8 (MFG-E8) promotes phagocytic clearance of apoptotic cells to maintain normal tissue homeostasis. However, its functions in intestinal inflammation and carcinogenesis are unknown. Experimental colitis was induced in MFG-E8 knockout (KO) and wild-type (WT) mice by dextran sodium sulfate (DSS) administration. Colon tissues were used for assessments of colitis activity and epithelial proliferation. A mouse colitis-associated cancer (CAC) model was induced by intraperitoneal injection of azoxymethane (AOM) and then the animals were given a single administration of DSS. A sporadic colon cancer model was established by repeated intraperitoneal injections of AOM. The role of MFG-E8 in epithelial proliferation with or without treatment of siRNA targeting αv-integrin was examined in vitro using a WST-1 assay. The severity of colitis in KO mice was greater than that in WT mice, while the proliferative potential of colonic epithelial cells in KO mice was lower during the regenerative phase. In both CAC and sporadic models, tumor size in KO was lower as compared to WT mice, while decreased tumor incidence was only found in the CAC model. In vitro findings showed that MFG-E8 promotes epithelial cell proliferation, and treatment with a siRNA targeting αv-integrin reduced the proliferation of Colon-26 cells stimulated with recombinant MFG-E8. MFG-E8 promotes tumor growth regardless of the presence or absence of colonic inflammation, whereas colon tumor development is initiated by MFG-E8 under inflammatory conditions. These MFG-E8 functions may be dependent on integrin-mediated cellular signaling.
    Journal of Gastroenterology 01/2015; DOI:10.1007/s00535-014-1036-x · 4.02 Impact Factor
  • Journal of Cancer Therapy 01/2015; 06(02):153-162. DOI:10.4236/jct.2015.62017
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    ABSTRACT: Abstract Background: Previously it has reported that the incidence of internal hernia can be decreased by closing Petersen's defect, but the perfect closure method, in fact, has not been discovered yet. In this study we have developed an easy and reliable method for closing Petersen's defect in the Roux-en-Y reconstruction after a laparoscopic distal gastrectomy. Materials and Methods: We performed intracorporeal Roux-en-Y reconstruction after laparoscopic distal gastrectomy with antiperistaltic gastrojejunostomy. The greater omentum is placed on the cranial side of the transverse colon through the defect between the elevated jejunum and the transverse mesocolon. Anastomosis is performed of the transverse mesocolon attached to the transverse colon, the greater omentum is passed through the Petersen's defect, and the stump of the mesojejunum is attached to the elevated jejunum by an interrupted suture. Petersen's defect is spread and straightened to stabilize the visual field. The thread is inserted first at the base of the stump of the elevated mesojejunum, next to the greater omentum, which has passed through Petersen's defect, and then to the transverse mesocolon to set the starting point of continuous suture. The stitches of continuous suture are sewn toward the transverse colon. Petersen's defect is closed completely. Results: We performed this technique in 37 patients. All procedures were completed without intraoperative complication or conversion to laparotomy. During the follow-up period, none of the patients developed complications related to the internal hernia, such as Petersen's hernia. Conclusions: We have indicated a novel, easy, and secure closure procedure of Petersen's defect following laparoscopic distal gastrectomy with Roux-en-Y reconstruction.
    Journal of Laparoendoscopic & Advanced Surgical Techniques 12/2014; 25(1). DOI:10.1089/lap.2014.0402 · 1.19 Impact Factor
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    ABSTRACT: Background: Ezrin is a linker protein between actin filaments and cell adhesion molecules, which plays an important role in cancer progression. There are only a few studies available that have investigated ezrin expression in different types of tumors. However, the prognostic importance of ezrin and its correlation with clinicopathological characteristics are yet to be delineated in gastric carcinoma. Methods: Specimens from 124 gastric carcinoma patients of T2 and T3 diseases treated in a defined period with curative operation were evaluated for ezrin, CD8 and cleaved caspase-3 expression by immunohistochemical methods. Results: Ezrin expression was detected in both can-cer cells and interstitial cells (ISCs) infiltrated into the tumor. According to our criterion, 37 pa-tients (29.8%) were positive for ezrin expression and 87 (70.2%) were negative. A significant correlation between ezrin expression and any of the clinicopathological characteristics could not be found. In Spearman-rank correlation test, a significant correlation was found between the num-ber of ezrin-stained ISCs and apoptotic index (AI) of cancer cells. Also the AI of cancer cells was significantly higher in ezrin-positive group when compared with ezrin-negative group. Patients with ezrin-expressing tumors had a significantly better disease-free survival, and in multivariable analysis ezrin expression status remained significant as an independent prognostic factor. Con-clusion: Taken together, our results suggest that ezrin expression may play a vital role in tumor apoptosis and that it can be a useful tool for therapeutic intervention.
    Open Journal of Gastroenterology 09/2014; 4(9):310-320. DOI:10.4236/ojgas.2014.49045
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    ABSTRACT: Abstract Background: The laparoscopic approach would be difficult to perform without causing deformation of the stomach in managing gastrointestinal stromal tumors (GISTs) of the intraluminal type, especially in those that are located in the posterior gastric wall or around the gastroesophageal junction and the pylorus, because intraluminal GISTs usually require an excessive resection of the gastric wall for cure. We present a novel surgical technique for successful management of intraluminal gastric GISTs that minimizes deformation of the stomach regardless of tumor location. Materials and Methods: The operating surgeon handles the tumor by holding tissue surrounding the tumor and performs seromyotomy using an ultrasonically activated device along the outer edge of the tumor. The tumor gradually protrudes like an extraluminal tumor as the seromyotomy proceeds. When seromyotomy along the tumor comes up to the point where the tumor sufficiently turns over the gastric serosa, the tumor looks like a pedunculated extraluminal GIST. Two seromuscular sutures are applied to close the exfoliated seromuscular layer. The tips of two seromuscular sutures are held and then pulled up toward the ventral side so that the staple line is aligned in line with the minor axis of the stomach. Finally, complete tumor removal with minimal seromuscular resection is accomplished by applying a linear stapler. Results: All patients resumed oral ingestion on the day after surgery and showed no signs of anastomotic constriction or obstruction. Conclusions: Our laparoscopic procedure for gastric GISTs is simple and allows us easy and precise removal of the tumor and closure of the gastric wall with minimum necessary resection, regardless of the location and growth form of the tumors.
    Journal of Laparoendoscopic & Advanced Surgical Techniques 09/2014; 24(10). DOI:10.1089/lap.2014.0184 · 1.19 Impact Factor
  • Pancreatology 06/2014; 14(3):S113. DOI:10.1016/j.pan.2014.05.761 · 2.50 Impact Factor
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    ABSTRACT: Zinc (Zn) is related to insulin synthesis, storage, and secretion. This study demonstrates the effects of Zn supplementation in donor rats on the outcomes of islet transplantation. Donor rats received 3 different regimens of dietary Zn supplementation for 2 weeks before undergoing pancreas donation: a standard diet containing Zn at 50 ppm (control), 1 ppm (low-Zn group) or 1000 ppm (high-Zn group), respectively. Diabetic recipient rats underwent islet transplantation, and the blood glucose levels and insulin secretion were monitored for 7 days after transplantation. The serum and pancreatic Zn levels at the time of donation were significantly lower in the low-Zn group (48.8 ± 25.5 µg/dL and 11.3 ± 1.9 µg/g) and higher in the high-Zn group (147.3 ± 17.6 µg/dL and 18.7 ± 2.2 µg/g) when compared with those observed in the controls (118.7 ± 7.9 µg/dL and 14.6 ± 2.0 µg/g) (P < 0.05). The blood glucose levels became re-elevated 2 days after transplantation in rats receiving islet grafts from the controls and the low-Zn groups. In contrast, in the rats that received islets from the high-Zn groups, these were maintained within a reference range (P < 0.01). These data indicate that a Zn-rich diet for donor rats improves the function of islet grafts in chemically induced diabetic rats.
    Pancreas 03/2014; 43(2):236-9. DOI:10.1097/MPA.0000000000000093 · 3.01 Impact Factor
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    ABSTRACT: Abstract Background: The improvement of quality of life is of great importance in managing patients with far-advanced gastric cancer. We report a new secure and less invasive method of creating a stomach-partitioning gastrojejunostomy in reduced-port laparoscopic surgery for unresectable gastric cancers with gastric outlet obstruction. Materials and Methods: A 2.5-cm vertical intraumbilical incision was made, and EZ Access (Hakko Co., Ltd., Tokyo, Japan) was placed. After pneumoperitoneum was created, an additional 5-mm trocar was inserted in the right upper abdomen. A gastrojejunostomy was performed in the form of an antiperistaltic side-to-side anastomosis, in which the jejunal loop was elevated in the antecolic route and anastomosed to the greater curvature of the stomach using an endoscopic linear stapler. The jejunal loop together with the stomach was dissected with additional linear staplers just proximal to the common entry hole so that a functional end-to-end gastrojejunostomy was completed. At the same time, the stomach was partitioned using a linear stapler to leave a 2-cm-wide lumen in the lesser curvature. Subsequently, jejunojejunostomy was performed 30 cm distal to the gastrojejunostomy, and the stomach-partitioning gastrojejunostomy resembling Roux-en Y anastomosis was completed. Results: All patients resumed oral intake on the day of operation. Neither anastomotic leakage nor anastomotic stricture was observed. Conclusions: Our less invasive palliative operation offers the utmost priority to improve quality of life for patients with unresectable gastric cancer.
    Journal of Laparoendoscopic & Advanced Surgical Techniques 02/2014; DOI:10.1089/lap.2013.0417 · 1.19 Impact Factor
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    ABSTRACT: Background: This study evaluated the tolerability and efficacy of intermittent oxaliplatin treatment based on mFOLFOX6 using oral uracil-tegafur(UFT) and leucovorin(LV) maintenance therapy in the treatment of elder-ly patients with advanced colorectal cancer. Methods: Ten non-elderly patients (<70 years) and 8 elderly patients (>70 years) with advanced/recurrent colorectal cancer were enrolled in this prospective, multicenter cooperative group clinical trial. The mFOLFOX6 regimen was administered for eight cycles with maintenance therapy with oral UFT/LV treatment until progression. In cases with disease progression, mFOLFOX6 was reintroduced. Re-sults: Grade 2 peripheral neuropathy was noted in 30.0% and 25.0% of the elderly and non-elderly patients, re-spectively. The observed time to treatment failure (TTF) was 6.3 months in the elderly patients and 6.4 months in the non-elderly patients. The disease control rate was 83.3% in each group. Conclusion: Our new stop-and-go strategy using oral UFT/LV is well-tolerated and effective even in elderly patients.
    Journal of Cancer Therapy 01/2014; 5(02):146-153. DOI:10.4236/jct.2014.52018
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    ABSTRACT: Pancreaticoduodenectomy (PD) is the only curative treatment for periampullary carcinomas, including the ampulla of Vater, the distal common bile duct, and the pancreas. Because positive resection margin and insufficient lymph node dissection around the superior mesenteric artery (SMA) result in a dismal outcome, we devised a new surgical technique called “total meso-pancreatoduodenum excision (tMPDe)” when performing a PD. Between June 2009 and July 2011, 24 consecutive patients with periampullary carcinoma underwent PD with tMPDe and the surgical outcomes were evaluated. Cancer-free resection was achieved in all patients, except for one with R1 in the retropancreatic tissue. Lymph node metastasis around the SMA was found in 5 patients (21%), while no loco-regional recurrence was recognized during a median follow-up period of 18.2 months. From the results, it was found that PD performed with tMPDe is the most effective surgical-oncological treatment for patients with periampullary carcinoma.
    Shimane journal of medical science 01/2014; 30(2):59-68.
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    ABSTRACT: Background: This study aimed to evaluate the safety and feasibility of a pancreaticoduodenectomy with total meso-pancreatoduodenum excision (tMPDe) as an new anatomical concept. Methods: A total of 90 patients underwent PD for various periampullary diseases. Of these, 52 patients received a conventional PD (cPD), while 38 patients underwent a tMPDe. Surgical outcomes were compared between the two study groups. Results: Operative time was equivalent in the two groups; however, the estimated blood loss (cPD, 1360ml ; tMPDe, 995ml; median, P=0.026) and blood transfusion rate (cPD, 63%; tMPDe, 31% ; P=0.001) were significantly decreased in tMPDe. Morbidity had no significant difference between cPD and tMPDe, and tMPDe showed no characteristic complications. With regard to oncological aspects, tMPDe was superior to cPD. Risk factors analysis revealed the operative time (P=0.003), estimated blood loss (P<0.001), and blood transfusion (P<0.001) to be significant predictive risk factors for postoperative morbidity but not tMPDe procedure (P=0.794). Conclusions: tMPDe is safe and superior to cPD because it is a bloodless operation with a good oncological outcome. We concluded that tMPDe should be adaptable to various periampullary diseases, including benign and low-grade malignant disorders.
    Hepato-gastroenterology 01/2014; 61(131):821-826. · 0.91 Impact Factor
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    ABSTRACT: The aim of this study is to identify an adequate surgical management for early ampullary carcinoma (AC).
    Hepato-gastroenterology 01/2014; 61(129):12-7. · 0.91 Impact Factor
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    ABSTRACT: A gastric conduit is commonly used to reconstruct the alimentary tract after esophagectomy. When the posterior mediastinum is applied to a reconstruction route, the gastric conduit created has been protected by an echo probe cover and, then blindly elevated to the neck. However, using this elevation method, the gastric conduit has the potential to catch on the vessels and nerves, posing a risk of major bleeding. We report a safe method of gastric conduit pull-through procedure to avoid unexpected technical complications. Two approximately 60-cm-long polyester tapes are prepared and ligated at both ends forming a loop. A 50-cm-long echo probe cover of 10 cm in diameter is prepared, and the closed end of the echo probe cover is cut to make an open-ended echo probe cover. A line parallel to the long axis of the echo probe cover is drawn across the echo probe cover with a sterile surgical marking pen. The looped polyester tape is inserted into the echo probe cover. The looped polyester tape and echo probe cover are ligated with 2-0 silk, approximately 5 cm in front of the knots on both sides. After dissection is carried out according to practice, the previously crafted polyester tape is inserted into the chest cavity. The echo probe cover is placed to connect the distal and proximal ends of the esophagus, and its torsion is corrected using the line marked with the pen and a crease, both of which are parallel to the long axis of the echo probe cover. One end of polyester tape is fixed to the distal esophageal stump by using the clips, with the opposite end fixed to the proximal esophageal stump. Either one of the 2 lengths of polyester tape is connected to the gastric conduit. By pulling up this length of polyester tape from the neck, the gastric conduit can pass through the echo probe cover and be elevated to the neck.
    Surgical laparoscopy, endoscopy & percutaneous techniques 08/2013; 23(4):e141-4. DOI:10.1097/SLE.0b013e31828b81a7 · 0.88 Impact Factor
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    ABSTRACT: This report describes the case of an 85-year-old male with inflammatory breast cancer. The patient presented with diffuse erythema and induration over the right anterior chest wall. Ultrasonography and mammography demonstrated an ill-defined small mass, 8 mm in diameter, in the right breast with skin thickening. A core needle biopsy of the breast mass confirmed the presence of invasive ductal carcinoma. A skin biopsy revealed a diffuse tumor cell infiltration with dermal lymphatic emboli. These findings were compatible with the diagnosis of inflammatory breast cancer. The tumor cells were triple negative for estrogen receptor, progesterone receptor, and HER2/neu. His bone scintigraphy showed multiple bone metastases. Systemic chemotherapy using capecitabine was introduced, but it failed to control the disease. TS-1, as second-line systemic chemotherapy, also resulted in treatment failure. Third-line chemotherapy using docetaxel and cyclophosphamide was then administered and was effective. However, he developed pneumonia due to febrile neutropenia after two cycles of treatment and the chemotherapy was discontinued. The patient died of carcinomatous lymphangiosis 2 years and 3 months after the initial onset of the disease. Male inflammatory breast cancer is challenging because of its rarity, biological uncertainness, diagnostic difficulty, and the fact that it is associated with a very poor prognosis. The establishment of a reliable diagnostic and treatment strategy for male inflammatory breast cancer is therefore needed.
    07/2013; 2(3):183-187. DOI:10.1007/s13691-013-0087-9
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    ABSTRACT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of various types of cancers with little cytotoxicity to normal cells through the stimulation of death receptors. In this study, after confirming that heat shock protein (HSP) 70 and autophagy play protective roles in antitumor effects of TRAIL, we examined a sensitizing effect of pifithrin-μ, which is an HSP70 and autophagy inhibitor, on TRAIL-induced antitumor effects on pancreatic cancer cell lines. TRAIL decreased the cell viability and induced apoptosis in three out of four cell lines tested. Regarding TRAIL-sensitive MiaPaca-2 and Panc-1, knockdown of HSP70 or Beclin-1, a key molecule for autophagy, with RNA interference significantly enhanced TRAIL-induced antitumor effects, i.e., decreased the cell viability and colony-forming capacity. Pifithrin-μ had the potential to induce both apoptosis and cell growth arrest. In addition, pifithrin-μ seemed to inhibit I κBα degradation in TRAIL-treated cancer cells probably via inhibition of the autophagy-lysosome pathway, thereby resulting in inhibition of NF-κB activation in TRAIL-treated cancer cells. In a xenograft mouse model, combination therapy with TRAIL plus pifithrin-μ significantly inhibited MiaPaca-2 tumor growth compared to treatment with either agent alone. These results suggest that pifithrin- μ is a promising agent for use in therapies intended to enhance the antitumor effects of TRAIL on pancreatic cancer.
    Gastroenterology 05/2013; 144(5):S-868. · 13.93 Impact Factor
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    ABSTRACT: Objectives: To identify the risk factors for clinically relevant pancreatic fistula after distal pancreatectomy with a flexible cartridge stapler, TL60. Methods: Forty consecutive patients who underwent a distal pancreatectomy by the TL60 stapler were retrospectively reviewed in association with postoperative complications. Results: The overall morbidity rate was 43% (17 patients), and mortality was null. Pancreatic fistula was the most frequent postoperative complication, seen in 11 patients (27.5%): grade A in 4 (10%) and grade B in 7 (17.5%). No grade C pancreatic fistula was observed. Univariate analyses of risk factors demonstrated that pancreas-related factors, including diabetes mellitus, thickness and texture of the pancreatic parenchyma, transection line for the pancreas, pancreatic duct ligation, and use of artificial patches had no impact on the occurrence of pancreatic fistula. A multivariable logistic regression analysis identified operative time (≥300 min) as the only notable predictor of clinically relevant pancreatic fistula (odds ratio = 3.253, 95% confidence interval 1.739-5.752; p = 0.031). Conclusion: Distal pancreatectomy with the use of the TL60 stapler eliminated the risk of pancreas-related factors for the occurrence of clinically relevant pancreatic fistula.
    European Surgical Research 04/2013; 50(2):71-79. DOI:10.1159/000349977 · 1.43 Impact Factor
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    ABSTRACT: Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor (CM101). PSK is a biological response modifier (BRM), and its mechanism of action is partly mediated by modulating host immune systems; however, recent studies showed antiproliferative activity of PSK. Therefore, we examined the mechanism underlying the antiproliferative activity of PSK using seven different human malignant cell lines (WiDr, HT29, SW480, KATOⅢ, AGS, HL-60 and U937), and PSK was found to inhibit the proliferation of HL-60 cells most profoundly. Therefore, HL-60 cells were used to elucidate the mechanism of the antiproliferative activity. Western blotting was performed to detect phosphorylated p38 mitogen-activated protein kinase (MAPK). A p38 MAPK inhibitor, SB203580, was used to examine the roles in PSK-induced apoptosis and growth inhibition. Flow cytometry was performed for mitochondrial membrane potential detection. PSK activated caspase-3 and induced p38 MAPK phosphorylation. Co-treatment with SB203580 blocked PSK-induced apoptosis, caspase-3 activation and growth inhibition. PSK induced apoptosis via the mitochondrial pathway. The depolarization of mitochondria induced by PSK was reversed by co-treatment with SB203580. The present study revealed that PSK induced apoptosis in HL-60 cells via a mitochondrial and p38 MAPK-dependent pathway.
    Oncology Reports 04/2013; 30(1). DOI:10.3892/or.2013.2412 · 2.19 Impact Factor
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    ABSTRACT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and agonistic death receptor-specific antibodies can induce apoptosis in cancer cells with little cytotoxicity to normal cells. To improve TRAIL-induced antitumor effects, we tested its effectiveness in combination with pifithrin-μ, which has the potential to inhibit HSP70 function and autophagy, both of which participate in TRAIL resistance in cancer cells. Among the four human pancreatic cancer cell lines tested, MiaPaca-2, Panc-1, and BxPC-3 cells showed varying sensitivities to TRAIL. In MiaPaca-2 and Panc-1 cells, knockdown of HSP70 or Beclin-1, the latter an autophagy-related molecule, by RNA interference augmented TRAIL-induced antitumor effects, decreasing cell viability and increasing apoptosis. Based on these findings, we next determined whether the TRAIL-induced antitumor effects could be augmented by its combination with pifithrin-μ. The combination of TRAIL plus pifithrin-μ significantly decreased the viability and colony-forming ability of MiaPaca-2 and Panc-1 cells compared to cells treated with either agent alone. When applied alone, pifithrin-μ increased Annexin V+ cells in both caspase-dependent and caspase-independent manners. It also promoted TRAIL-induced apoptosis and arrested cancer cell growth. Furthermore, pifithrin-μ antagonized TRAIL-associated NF-κB activation in cancer cells. In a xenograft mouse model, combination therapy significantly inhibited MiaPaca-2 tumor growth compared to treatment with either agent alone. The results of this study suggest protective roles for HSP70 and autophagy in TRAIL resistance in pancreatic cancer cells and suggest that pifithrin-μ is a promising agent for use in therapies intended to enhance the antitumor effects of TRAIL.
    Molecular Cancer Therapeutics 01/2013; 12(4). DOI:10.1158/1535-7163.MCT-12-0954 · 5.60 Impact Factor
  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2013; 74(11):3045-3050. DOI:10.3919/jjsa.74.3045

Publication Stats

975 Citations
370.02 Total Impact Points


  • 2011–2014
    • Shimane University
      • • Department of Digestive and General Surgery
      • • Department of Surgery
      Matsu, Shimane, Japan
  • 2004–2012
    • Nagasaki University
      • Department of Surgery
      Nagasaki, Nagasaki, Japan
  • 2007–2010
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
    • Numazu City Hospital
      Sizuoka, Shizuoka, Japan
  • 1986–2008
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 1996
    • Kawasaki Medical University
      Kurasiki, Okayama, Japan