Faculty Profiles - FUJIWARA Toshiyoshi

MISC - FUJIWARA Toshiyoshi

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Cancer associated fibroblasts promote tumor metastasis coexisting with cancer cells in blood circulation

Hajime Kashima, Kazuhiro Noma, Hiroaki Sato, Yuki Katsura, Takuya Kato, Toshiaki Ohara, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

Novel theranostic strategy against scirrhous gastric cancer; combination of chemotherapy and fluorescence oncolytic adenovirus

Wataru Ishikawa, Satoru Kikuchi, Hiroshi Tazawa, Shinji Kuroda, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

Fluorescence-guided spatiotemporal dynamics of epithelial-mesenchymal transition under inflammatory microenvironment during colorectal cancer progression

Takeshi Ieda, Hiroshi Tazawa, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Takeshi Imamura, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

Clinicopathological significance of endometrial cancer with MSH2 deficiency

Junko Haraga, Takeshi Nagasaka, Keiichirou Nakamura, Tomoko Haruma, Takeshi Nishida, Akihiro Nyuya, Kazuya Yasui, Hisashi Masuyama, Toshiyoshi Fujiwara, Yuji Hiramatsu

CANCER RESEARCH 77 2017.7

Hyperthermia at the single-cell level for disseminated cancer disease with immuno-magnetic nanoparticles

Tetsuya Kagawa, Hiroyuki Kishimoto, Toshiaki Ohara, Hiroshi Tazawa, Shunsuke Kagawa, Takeshi Nagasaka, Satoshi Nohara, Ichiro Kato, Adarsh Sandhu, Hiromichi Aono, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

Primary pancreatic-type acinar cell carcinoma of the jejunum with tumor thrombus extending into the mesenteric venous system: a case report and literature review

Kosei Takagi, Takahito Yagi, Takehiro Tanaka, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Toshiyoshi Fujiwara

BMC SURGERY 17 ( 1 ) 237 - 243 2017.6

Language：English Publisher：BIOMED CENTRAL LTD

Background: Although ectopic pancreatic tissue is common in the upper gastrointestinal tract, the incidence of ectopic pancreatic tissue in the jejunum is low, and malignant transformation in ectopic pancreatic tissue is rare. Furthermore, pancreatic-type acinar cell carcinoma (ACC) developing in the jejunum and ACC accompanied by tumor thrombus are extremely rare.
Case presentation: A 78-year-old-woman presented with melena. Abdominal computed tomography images and endoscopic examination revealed a submucosal jejunal mass with tumor thrombus extending into a jejunal vein. The patient underwent a curative resection combined with a partial jejunectomy and partial pancreatectomy. Histopathological examination of the resected tissue showed tumor cells with a homogeneous acinar architecture identical to pancreatic-type ACC and tumor thrombus. Postoperatively, she was followed for 10 months and had no recurrence.
Conclusion: We present an extremely rare case of pancreatic-type ACC in the jejunum with extensive tumor thrombus invading into the mesenteric venous system. This type of cancer has not been reported previously but should be considered in the differential diagnosis of a jejunal mass.

DOI： 10.1186/s12893-017-0273-3

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Management of early gastric cancer that meet the indication for radical lymph node dissection following endoscopic resection: a retrospective cohort analysis

Satoru Kikuchi, Shinji Kuroda, Masahiko Nishizaki, Tetsuya Kagawa, Hiromitsu Kanzaki, Yoshiro Kawahara, Shunsuke Kagawa, Takehiro Tanaka, Hiroyuki Okada, Toshiyoshi Fujiwara

BMC SURGERY 17 ( 1 ) 687 - 694 2017.6

Language：English Publisher：BIOMED CENTRAL LTD

Background: Endoscopic resection (ER) has been widely accepted as the standard treatment for early gastric cancer (EGC). However, in patients considered to have undergone non-curative ER due to their potential risk of lymph node metastasis (LNM), additional gastrectomy is recommended. The aim of the present study was to identify EGC patients after non-curative ER at high risk of LNM.
Methods: A total of 150 patients who had undergone ER for EGC were diagnosed as non-curative ER due to their potential risk of LNM. Clinicopathological data and clinical outcomes were examined retrospectively.
Results: Additional gastrectomy with lymph node dissection was performed in 73 patients, and the remaining 77 patients were followed-up without additional gastrectomy. In patients who underwent additional gastrectomy, 8 patients had local residual tumor, and 8 patients had LNM, which were limited in the peritumoral nodes. Only lymphatic invasion (p = 0.012) was a statistically significant factor for LNM. The 5-year overall survival and recurrence-free survival were not significantly different between patients with and without additional gastrectomy.
Conclusion: Additional gastrectomy with lymph node dissection is recommended for patients who were diagnosed as non-curative ER with lymphatic invasion, and minimizing the extent of lymph node dissection may be allowed for these patients.

DOI： 10.1186/s12893-017-0268-0

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Radiographic sarcopenia predicts postoperative infectious complications in patients undergoing pancreaticoduodenectomy

Kosei Takagi, Ryuichi Yoshida, Takahito Yagi, Yuzo Umeda, Daisuke Nobuoka, Takashi Kuise, Toshiyoshi Fujiwara

BMC SURGERY 17 ( 1 ) 453 - 466 2017.5

Language：English Publisher：BIOMED CENTRAL LTD

Background: Recently, skeletal muscle depletion (sarcopenia) has been reported to influence postoperative outcomes after certain procedures. This study investigated the impact of sarcopenia on postoperative outcomes following pancreaticoduodenectomy (PD).
Methods: We performed a retrospective study of consecutive patients (n = 219) who underwent PD at our institution between January 2007 and May 2013. Sarcopenia was evaluated using preoperative computed tomography. We evaluated postoperative outcomes and the influence of sarcopenia on short-term outcomes, especially infectious complications. Subsequently, multivariate analysis was used to assess the impact of prognostic factors (including sarcopenia) on postoperative infections.
Results: The mortality, major complication, and infectious complication rates for all patients were 1.4%, 16.4%, and 47.0%, respectively. Fifty-five patients met the criteria for sarcopenia. Sarcopenia was significantly associated with a higher incidence of in-hospital mortality (P = 0.004) and infectious complications (P < 0.001). In multivariate analyses, sarcopenia (odds ratio = 3.43; P < 0.001), preoperative biliary drainage (odds ratio = 2.20; P = 0.014), blood loss (odds ratio = 1.92; P = 0.048), and soft pancreatic texture (odds ratio = 3.71; P < 0.001) were independent predictors of postoperative infections.
Conclusions: Sarcopenia is an independent preoperative predictor of infectious complications after PD. Clinical assessment combined with sarcopenia may be helpful for understanding the risk of postoperative outcomes and determining perioperative management strategies.

DOI： 10.1186/s12893-017-0261-7

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Nonexposure laparoscopic and endoscopic cooperative surgery (closed laparoscopic and endoscopic cooperative surgery) for gastric submucosal tumor

Satoru Kikuchi, Masahiko Nishizaki, Shinji Kuroda, Shunsuke Tanabe, Kazuhiro Noma, Shunsuke Kagawa, Yasuhiro Shirakawa, Hiroshi Kato, Hiroyuki Okada, Toshiyoshi Fujiwara

GASTRIC CANCER 20 ( 3 ) 553 - 557 2017.5

Language：English Publisher：SPRINGER

Laparoscopic and endoscopic cooperative surgery (LECS) is increasingly applied for gastric submucosal tumors (SMTs) such as gastrointestinal stromal tumors. However, the conventional LECS procedure has the potential risk that gastric contents and even tumor cells could spread into the abdominal cavity because the gastric wall has to be opened during the resection. To avoid this problem, we have developed a modified LECS procedure named "closed LECS." Ten patients underwent closed LECS for the resection of gastric SMTs. Closed LECS consists of the following steps: endoscopic submucosal layer dissection around the tumor, laparoscopic marking of a resection line on the serosal surface along submucosal dissection line, seromuscular suturing with the marked lesion inverted into the inside of the stomach, endoscopic circumferential seromuscular dissection, and peroral retrieval. In three of the initial five cases, the closed LECS procedure was not completed as planned because of the tumor size and endoscopic inappropriate seromuscular dissection. After modification of the procedure, the entire procedure was successful in all five cases. The mean resected tumor diameter was 24.1 +/- 7.6 mm. The mean operation time was 253 +/- 45 min. One patient experienced an intra-abdominal abscess potentially related to delayed perforation as a postoperative complication. The closed LECS procedure for gastric SMTs can theoretically be applied without contamination and tumor cell dissemination into the abdominal cavity.

DOI： 10.1007/s10120-016-0641-1

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Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer

Yasuhiro Shirakawa, Kazuhiro Noma, Naoaki Maeda, Shunsuke Tanabe, Shinji Kuroda, Shunsuke Kagawa, Kuniaki Katsui, Norihisa Katayama, Susumu Kanazawa, Toshiyoshi Fujiwara

ACTA MEDICA OKAYAMA 71 ( 2 ) 127 - 133 2017.4

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

Currently, chemoradiation is the most widely used nonsurgical treatment for esophageal cancer. However, some patients, particularly the very elderly or those with severe vital organ dysfunction, face difficulty with the chemotherapy component. We therefore examined the outcome of radiation therapy (RT) alone for patients with esophageal cancer at our facility. Between January 2005 and December 2014, 84 patients underwent RT at our hospital, and 78 of these patients received concomitant chemotherapy. The remaining 6 patients underwent RT alone; these patients were considered to be high-risk and to have no lymph node metastasis (stage I). Five of them received irradiation up to a curative dose: 4 showed a complete response (CR) and 1 showed a partial response (PR). Of the patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient underwent endoscopic submucosal dissection (ESD) as salvage therapy for local recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer patients can be treated radically with RT alone under certain conditions. In the future, to broaden the indications for RT monotherapy to include some degree of advanced cancers, a novel concurrent therapy should be identified.

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Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk breast cancers as reliably as genomic markers

Takayuki Iwamoto, Toyomasa Katagiri, Naoki Niikura, Yuichiro Miyoshi, Mariko Kochi, Tomohiro Nogami, Tadahiko Shien, Takayuki Motoki, Naruto Taira, Masako Omori, Yutaka Tokuda, Toshiyoshi Fujiwara, Hiroyoshi Doihara, Balazs Gyorffy, Junji Matsuoka

ONCOTARGET 8 ( 16 ) 26122 - 26128 2017.4

Language：English Publisher：IMPACT JOURNALS LLC

Background: The purpose of this study was to test whether immunohistochemical (IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67) predict similar numbers of patients with favorable prognoses as genomic markers.
Results: Thirty paired cases (60 samples) were enrolled in this study. Post-Ki67 levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). PostKi67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate signature(GSS) (66.7%: 20/30), but the difference in predictive power was not significant (P = 0.233). Proliferation (MKI67, STK15, Survivin, CCNB1, and MYBL2) and estrogen (ER, PGR, BCL2, and SCUBE2) related signatures were significantly downregulated after therapy (P < 0.001 and 0.041, respectively).
Materials and Methods: Core needle biopsy specimens of primary breast cancer were collected at Okayama University Hospital from hormone receptor-positive and human epidermal growth factor 2-negative patients that subsequently received two weeks of neoadjuvant hormone therapy. Paired post-treatment specimens from surgical samples were also collected. IHC Ki67 levels and GSS were compared between pre-and post-hormone treatment samples. Changes of gene expression pattern in short-term hormone therapy were also assessed.
Conclusions: IHC based post-Ki67 levels may have distinct predictive power compared with the naive IHC Ki67. Future studies with larger cohorts and longer follow-up periods may be needed to validate our results.

DOI： 10.18632/oncotarget.15385

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High-metastatic triple-negative breast-cancer variants selected in vivo become chemoresistant in vitro

Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M. Hoffman

IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL 53 ( 4 ) 285 - 287 2017.4

IDENTIFICATION OF A CIRCULATING MIRNA DIAGNOSTIC SIGNATURE IN PANCREATIC DUCTAL ADENOCARCINOMA

Kazuhiro Yoshida, Shusuke Toden, Haiyong Han, Susan Tsai, Murtaza Muhammed, Scott Celinski, Carlos Becerra, Takeshi Nagasaka, Toshiyoshi Fujiwara, Douglas B. Evans, Danniel V. Hoff, Ajay Goel

GASTROENTEROLOGY 152 ( 5 ) S273 - S273 2017.4

Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models

Shuya Yano, Kiyoto Takehara, Hiroshi Tazawa, Hiroyuki Kishimoto, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M. Hoffman

JOURNAL OF CELLULAR BIOCHEMISTRY 118 ( 3 ) 559 - 569 2017.3

Language：English Publisher：WILEY-BLACKWELL

We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. (c) 2016 Wiley Periodicals, Inc.

DOI： 10.1002/jcb.25735

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Early Chimerism After Liver Transplantation Reflects the Clinical Course of Recurrent Hepatitis C

Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C. Napier, Nobukazu Watanabe, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Takahiro Oto, Motoo Araki, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi

ANNALS OF TRANSPLANTATION 22 156 - 165 2017.3

Language：English Publisher：INT SCIENTIFIC LITERATURE, INC

Background: Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C.
Material/Methods: We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined.
Results: Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism.
Conclusions: Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

DOI： 10.12659/AOT.900494

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A Novel "Shrug Technique" for Totally Implantable Venous Access Devices via the External Jugular Vein: A Consecutive Series of 254 Patients

Tetsuya Kagawa, Satoshi Ueyama, Tatsunori Kobayashi, Hiroki Okabayashi, Shinji Kuroda, Toshiyoshi Fujiwara

JOURNAL OF SURGICAL ONCOLOGY 115 ( 3 ) 291 - 295 2017.3

Language：English Publisher：WILEY

Background: The external jugular vein (EJV) approach for totally implantable venous access devices (TIVADs) is safe. However, the success rate is unsatisfactory because of the difficulty in catheterization due to the acute angle between the EJV and the subclavian vein (SCV). A novel "shrug technique" to overcome this difficulty was developed, and its efficacy was assessed in a consecutive case series.
Methods: TIVAD placement was performed via the EJV cut-down approach. "Shrug technique," a simple way to straighten the EJV-SVC angle by shrugging the patient's shoulder, was applied to facilitate the passage of the guidewire and sheath-introducer when there was acute angulation between the EJV and SCV.
Results: A total of 254 patients underwent TIVAD implantation by the EJV cut-down approach. The " shrug technique" was applied in 51 cases (20%), and catheterization was successful in all cases. Thus, TIVAD implantation was successfully completed in all 254 cases (100%) in a single operative setting. The median operating time was 38 [IQR 30-45] min. Eleven complications (4%) were observed, but none of them were EJV-specific.
Conclusion: The " shrug technique" is simple but very useful to achieve a higher success rate and safer insertion of TIVADs from the EJV. (C) 2016 Wiley Periodicals, Inc.

DOI： 10.1002/jso.24504

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A Novel "Shrug Technique" for Totally Implantable Venous Access Devices via the External Jugular Vein: A Consecutive Series of 254 Patients

Tetsuya Kagawa, Satoshi Ueyama, Tatsunori Kobayashi, Hiroki Okabayashi, Shinji Kuroda, Toshiyoshi Fujiwara

JOURNAL OF SURGICAL ONCOLOGY 115 ( 3 ) 291 - 295 2017.3

Language：English Publisher：WILEY

DOI： 10.1002/jso.24504

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OBP-401-GFP telomerase-dependent adenovirus illuminates and kills high-metastatic more effectively than low-metastatic triple-negative breast cancer in vitro

S. Yano, K. Takehara, H. Kishimoto, H. Tazawa, Y. Urata, S. Kagawa, M. Bouvet, T. Fujiwara, R. M. Hoffman

CANCER GENE THERAPY 24 ( 2 ) 45 - 47 2017.2

Language：English Publisher：NATURE PUBLISHING GROUP

We previously described the development of a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of MDA-MB-231 human breast cancer in nude mice. The isolated variant is highly invasive in the mammary gland and Metastasized to lymph nodes in 10 of 12 mice compared with 2 of 12 of the parental cell line. OBP-401 is a telomerase-dependent cancer-specific, green fluorescent protein (GFP)-expressing adenovirus. OBP-401 was used to infect parental MDA-MB-231P cells and high-metastatic MDA-MB-231H and MDA-MB-231HLN isolated from a lymph node metastasis and MDA-MB-231HLM isolated from a lung metastasis. Time-course imaging showed that OBP-401 labeled MDA-MB-231HP, MDA-MB-231HLN, and MDA-MB-231HLM cells more brightly than MDA-MB-231 parental cells. OBP-401 killed MDA-MB-231H, MDA-MB-231HLN, and MDA-MB-231HLM cells more efficiently than MDA-MB-231P parental cells. These results indicate that OBP-401 could infect, label and then kill high-metastatic MDA-MB-231 more efficiently than low-metastatic MDA-MB-231.

DOI： 10.1038/cgt.2016.67

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Comparison of in vitro invasiveness of high- and low-metastatic triple-negative human breast cancer visualized by color-coded imaging

Shuya Yano, Kiyoto Takehara, Hiroshi Tazawa, Hiroyuki Kishimoto, Shunsuke Kagawa, Toshiyoshi Fujiwara, Robert M. Hoffman

IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL 53 ( 2 ) 96 - 98 2017.2

Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Liver Transplantation

Kosei Takagi, Takahito Yagi, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Nobuyuki Watanabe, Takashi Kuise, Tomokazu Fuji, Hiroyuki Araki, Toshiyoshi Fujiwara

ACTA MEDICA OKAYAMA 71 ( 1 ) 85 - 89 2017.2

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an extremely rare cause of hyponatremia post-liver transplantation. A 15-year-old Japanese girl with recurrent cholangitis after Kasai surgery for biliary atresia underwent successful living donor liver transplantation. Peritonitis due to gastrointestinal perforation occurred. Hyponatremia gradually developed but improved after hypertonic sodium treatment. One month later, severe hyponatremia rapidly recurred. We considered the hyponatremia's cause as SIADH. We suspected that tacrolimus was the disease's cause, so we used cyclosporine instead, plus hypertonic sodium plus water intake restriction, which improved the hyponatremia. Symptomatic hyponatremia manifested by SIADH is a rare, serious complication post-liver transplantation.

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