Publications by authors named "Tomoya Kato"

34 Publications

Real-Time Identification of Two Substrate-Binding Intermediates for the Light-Driven Sodium Pump Rhodopsin.

J Biol Chem 2021 May 18:100792. Epub 2021 May 18.

Faculty of Advanced Life Science, Hokkaido University, Sapporo, 060-0810, Japan; Global Station for Soft Matter, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, 001-0021, Japan. Electronic address:

Membrane transport proteins undergo critical conformational changes during substrate uptake and release, as the substrate-binding site is believed to switch its accessibility from one side of the membrane to the other. Thus, at least two substrate-binding intermediates should appear during the process, that is, after uptake and before the release of the substrate. However, this view has not been verified for most transporters due to the difficulty in detecting short-lived intermediates. Here, we report real-time identification of these intermediates for the light-driven outward current-generating Na pump rhodopsin (NaR). We triggered the transport cycle of NaR using a short laser pulse, and subsequent formation and decay of various intermediates was detected by time-resolved measurements of absorption changes. We used this method to analyze transport reactions, and elucidated the sequential formation of the Na-binding intermediates O1 and O2. Both intermediates exhibited red-shifted absorption spectra and generated transient equilibria with short-wavelength intermediates. The equilibria commonly shifted toward O1 and O2 with increasing Na concentration, indicating that Na is bound to these intermediates. However, these equilibria were formed independently; O1 reached equilibrium with preceding intermediates, indicating Na uptake on the cytoplasmic side. In contrast, O2 reached equilibrium with subsequent intermediates, indicating Na release on the extracellular side. Thus, there is an irreversible switch in "accessibility" during the O1 to O2 transition, which could represent one of the key processes governing unidirectional Na transport.
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http://dx.doi.org/10.1016/j.jbc.2021.100792DOI Listing
May 2021

Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer.

Oncol Lett 2021 Jun 23;21(6):490. Epub 2021 Apr 23.

Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama 641-8510, Japan.

Currently, gastric cancer is the third most common cause of cancer-associated mortality worldwide. Oncolytic virotherapy using herpes simplex virus (HSV) has emerged as a novel therapeutic strategy against cancer. Telomerase is activated in >90of malignant tumors, including gastric cancer, and human telomerase reverse transcriptase (hTERT) is one of the major components of telomerase enzyme. Therefore, in oncolytic HSV, placing the essential genes under the regulation of the hTERT promoter may enhance its antitumor efficacy. The present study examined the antitumor effect of fourth-generation oncolytic HSVs, which contain the gene under the regulation of the hTERT promoter (T-hTERT). To examine the association between hTERT expression and prognosis in patients with gastric cancer, immunohistochemical analysis of resected tumor specimens was performed. The enhanced efficacy of T-hTERT was determined in human gastric cancer cell lines and in human gastric adenocarcinoma specimens . In experiments, enhanced cytotoxicity of T-hTERT was observed in MKN1, MKN28 and MKN45 cells compared with that of a third-generation oncolytic HSV, T-null. In particular, the cytotoxicity of T-hTERT was markedly enhanced in MKN45 cells. Furthermore, experiments demonstrated that 36.7 and 54.9% of cells were found to be lysed 48 h after infection with T-null or T-hTERT viruses at 0.01 pfu/cell, respectively. The T-hTERT-treated group exhibited considerably lower cell viability than the control [phosphate-buffered saline (-)] group. Therefore, employing oncolytic HSVs that contain the gene under the regulation of the hTERT promoter may be an effective therapeutic strategy for gastric cancer. To the best of our knowledge, the present study was the first to describe the effect of an oncolytic HSV with expression regulated by the hTERT promoter on gastric cancer cells.
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http://dx.doi.org/10.3892/ol.2021.12751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100961PMC
June 2021

Effect of ankle joint fixation on tibialis anterior muscle activity during split-belt treadmill walking in healthy subjects: A pilot study.

Turk J Phys Med Rehabil 2021 Mar 4;67(1):11-16. Epub 2021 Mar 4.

Department of Rehabilitation, Fujita Health University Bantane Hospital, Nagoya, Japan.

Objectives: This study aims to examine the characteristics of muscle activity change of the tibialis anterior (TA) muscle in healthy adults while they walked on a split-belt treadmill with one fixed ankle.

Patients And Methods: This randomized controlled trial was conducted between November 2017 and July 2018. Fourteen healthy male individuals (mean age 31.4 years; range, 23 to 50 years) were divided into two groups: right ankle joint fixed by ankle-foot orthosis (fixation group) and no orthosis (control group). Both groups were asked to walk on a treadmill with the same belt speed. After familiarizing with walking on both belts at 5.0 km/h, they walked for 6 min with the right belt slower (2.5 km/h) and the left faster (5.0 km/h). For analysis, the 6 min were divided equally among three time periods. The TA muscle activity was calculated at first and last time periods. We compared muscle activities in time periods (early and late phase) and in groups (fixation and control) using two-way mixed analysis of variance.

Results: The TA muscle activity decreased in the late phase regardless of ankle joint fixation, and also decreased in the fixation group regardless of the time periods. There was an interaction between these factors.

Conclusion: These data show that changes in the TA muscle activity were smaller in the fixation group, suggesting that the ankle joint fixation reduces the adaptation.
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http://dx.doi.org/10.5606/tftrd.2021.4980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088797PMC
March 2021

Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.

Front Endocrinol (Lausanne) 2021 22;12:625663. Epub 2021 Feb 22.

Department of Ophthalmology and Visual Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.

Background: Orbital metastases from cancers of various organs can arise the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.

Case Presentation: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.

Conclusion: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.
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http://dx.doi.org/10.3389/fendo.2021.625663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937957PMC
February 2021

Oncolytic virotherapy with SOCS3 enhances viral replicative potency and oncolysis for gastric cancer.

Oncotarget 2021 Feb 16;12(4):344-354. Epub 2021 Feb 16.

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.

Oncolytic virotherapy is an encouraging treatment using herpes simplex virus (HSV) for gastric cancer patients. To treat gastric cancer, we generated and evaluated the efficacy of an attractive type of oncolytic HSV expressing the suppressor of cytokine signaling 3 (SOCS3). We constructed a third-generation type of oncolytic HSV (T-SOCS3) arming with SOCS3 by a bacterial artificial chromosome (BAC) system. We examined the viral replicative intensification and oncolysis of T-SOCS3 for human gastric cancer cell lines . T-SOCS3 enhanced its replication and potentiated its cell-killing effect for MKN1 human gastric cancer cell lines, which are resistant to a non-armed third-generation type of oncolytic HSV (T-01) . T-SOCS3 also induced the destruction within human gastric cancer specimens. Armed oncolytic HSVs expressing SOCS3 may be an efficacious therapeutic agent for gastric cancer treatment.
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http://dx.doi.org/10.18632/oncotarget.27873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899552PMC
February 2021

Pleomorphic Carcinoma with Exophthalmos and a Subsequent Diagnosis of Paraneoplastic Syndrome.

Intern Med 2021 Feb 30;60(4):605-609. Epub 2020 Sep 30.

Department of Thoracic Surgery, Gifu Prefectural General Medical Center, Japan.

The patient was a 75-year-old man who developed polyopia and exophthalmos. Chest computed tomography (CT) revealed a mass in the left upper lobe. A CT-guided biopsy suggested lung adenocarcinoma. He was treated by neoadjuvant chemotherapy followed by left upper lobectomy. He was diagnosed with stage IIB pleomorphic carcinoma postoperatively. Preoperative head magnetic resonance imaging revealed exophthalmos and bilateral swelling of the extraocular muscles. The thyroid function of the patient was within the normal range, and he tested negative for autoantibodies. As his symptoms and swelling of the extraocular muscles improved postoperatively, he was diagnosed with paraneoplastic syndrome.
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http://dx.doi.org/10.2169/internalmedicine.5286-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946491PMC
February 2021

A Patient with Lung Adenocarcinoma Accompanied by Whole Right Lung Torsion Induced by the Accumulation of a Large Amount of Pleural Effusion.

Intern Med 2021 Feb 30;60(4):595-599. Epub 2020 Sep 30.

Department of Pulmonary Medicine, Gifu Prefectural General Medical Center, Japan.

A 68-year-old man visited a physician with a chief complaint of difficulty breathing. Right pleural effusion was noted, and he was referred to our department for a close examination and treatment. Thoracoscopy was performed under local anesthesia, and pleural dissemination of lung adenocarcinoma was noted, so a chest drain was placed. Since poor right lung inflation persisted and whole right lung torsion was observed on computed tomography, thoracoscopy-assisted thoracotomic reduction of lung torsion was performed. In this patient, the right middle lobe and anterior chest wall were adhered, suggesting that whole right lung torsion occurred when atelectasis was formed due to pleural effusion.
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http://dx.doi.org/10.2169/internalmedicine.5277-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946505PMC
February 2021

Novel lateral transfer assist robot decreases the difficulty of transfer in post-stroke hemiparesis patients: a pilot study.

Disabil Rehabil Assist Technol 2020 Sep 15:1-5. Epub 2020 Sep 15.

Department of Rehabilitation Medicine I, School of Medicine, Fujita Health University, Toyoake, Japan.

Purpose: The purpose of this study was to clarify whether the novel lateral transfer assist robot facilitates easier transfers compared with a wheelchair in post-stroke hemiparesis patients.

Methods: This cross-sectional study enrolled 20 post-stroke hemiparesis patients, and the task difficulty of transfers was compared between a wheelchair and lateral transfer assist robot. All participants were asked to transfer from either wheelchair or lateral transfer assist robot to a platform table and back. The primary outcome was the transfer score of the Functional Independence Measure. The secondary outcome was the time required for transfer.

Results: The transfer score of the Functional Independence Measure was significantly higher with lateral transfer assist robot than with wheelchair ( < .001). The transfer times from these devices to a platform table and back showed no significant differences (to device from platform table: 7.8 s, lateral transfer assist robot vs 7.6 s, wheelchair,  > .05: device to platform table: 7.1 s, lateral transfer assist robot vs 8.0 s, wheelchair, > .05).

Conclusions: Transfer with a lateral transfer assist robot is easier than with wheelchair and facilitates independence in post-stroke hemiparesis patients.IMPLICATIONS FOR REHABILITATIONTransfer skill influences the functional independence and quality of life of a wheelchair userA novel structural mobility device-the lateral transfer assist robot (LTAR)-can facilitate transfersThe LTAR could improve the degree of independence for transfers than the wheelchair, without any time loss, in post-stroke hemiparesis patientsThe LTAR could potentially reduce the risk for falls in various medical and care facilities.
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http://dx.doi.org/10.1080/17483107.2020.1818136DOI Listing
September 2020

Comparative study of HO-1 expressing synovial lining cells between RA and OA.

Mod Rheumatol 2021 Jan 22;31(1):133-140. Epub 2020 Jan 22.

Faculty of Medicine, Department of Pathological Diagnostics, Yamagata University, Yamagata, Japan.

Objectives: We aimed to clarify the characteristics of heme oxygenase (HO)-1 expressing cells in the synovium from rheumatoid arthritis (RA) and osteoarthritis (OA), and to investigate the co-expression of HO-1 and IgG-Fc/HLA-DR complex.

Methods: The characteristics of HO-1 expressing cells in the synovium were investigated by using immunohistochemistry. The co-expression of HO-1 and IgG-Fc/HLA-DR complex was examined by an proximity ligation assay (PLA) with immunofluorescence. HO-1 mRNA was investigated by reverse transcription-polymerase chain reaction.

Results: The number of HO-1 cells from the RA synovium is higher than that from OA synovium. The double positive cells of HO-1 and IgG-Fc/HLA-DR complex were detected by the PLA with immunofluorescence in RA synovium. HO-1 mRNA was detected in both RA and OA synovium.

Conclusion: A portion of HO-1 cells with IgG-Fc/HLA-DR complex in lining layer of RA may be concluded as one of antigen presenting cells in RA and may be involved in production of RF.
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http://dx.doi.org/10.1080/14397595.2019.1704976DOI Listing
January 2021

Lateral Transfer Assist Robot (LTAR): Development of a proof-of-concept prototype.

Technol Health Care 2020 ;28(2):175-183

Faculty of Rehabilitation, School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan.

Background: Falls during transfer to and from a wheelchair are associated with numerous problems. Factors responsible for difficulty in transferring include horizontal/vertical gaps between surfaces; obstacles, such as armrests; and complicated brake/footrests configurations before transferring. Moreover, controlling a wheelchair sufficiently close to the transfer surface within the confined home space is difficult.

Objective: We described the design of the novel Lateral Transfer Assist Robot (LTAR) for solving problems during transfer. Furthermore, the effectiveness and usability of the robot were preliminary examined in healthy adults.

Method: The transfer problems and basic designs were organized. The effectiveness of the prototype was measured by three-dimensional motion analysis and questionnaire.

Results: The prototype LTAR was developed. With just a push on a button, the footplate lowers to the floor and the seat and armrest lowers to the height of the seating surface to fill the gap between the surfaces. Using these features, users can transfer by simply shifting their buttocks sideways. Additionally, LTAR has omnidirectional wheels that help move it within a narrow space. The LTAR was confirmed to reduce the physical and subjective burden, except for maneuverability.

Conclusion: The LTAR was found to be effective for home use and reducing burden of transfer.
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http://dx.doi.org/10.3233/THC-191762DOI Listing
January 2021

Expression of TRPM8 in human reactive lymphoid tissues and mature B-cell neoplasms.

Oncol Lett 2018 Nov 3;16(5):5930-5938. Epub 2018 Sep 3.

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Yamagata 990-9585, Japan.

Transient receptor potential melastatin 8 (TRPM8) is a member of the transient receptor potential superfamily of Ca channels. The aim of the present study was to clarify TRPM8 expression in reactive lymphoid tissues and mature B-cell neoplasms. Reactive and neoplastic lymphoid tissues were used to evaluate TRPM8 expression by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). TRPM8 cells were frequently detected in the follicular light zone and marginal zone of reactive lymphoid tissues. Double immunostaining revealed that TRPM8 cells co-expressed cluster of differentiation (CD) 38, CD79a, CD138, interferon regulatory factor 4/melanoma associated antigen (mutated) 1, B cell CLL/lymphoma 6 and transmembrane activator and CAML interactor. TRPM8 neoplastic cells were frequently detected in plasma cell myeloma. The positive band of TRPM8 mRNA was confirmed by RT-PCR in cases of myeloma. The present study is, to the best of our knowledge, the first to demonstrate the expression of TRPM8 in reactive lymphoid tissues and mature B-cell neoplasms, revealing that TRPM8 is frequently expressed in pre-plasmablasts, plasmablasts, plasma cells and mature B-cell lymphomas that are likely to differentiate into plasma cells.
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http://dx.doi.org/10.3892/ol.2018.9386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176370PMC
November 2018

Conversion Surgery for Gastric Cancer with Peritoneal Metastasis Based on the Diagnosis of Second-Look Staging Laparoscopy.

J Gastrointest Surg 2019 09 27;23(9):1758-1766. Epub 2018 Sep 27.

Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.

Background: Patients with positive peritoneal cytology (CY1) or peritoneal dissemination (P1) have significantly poor prognosis. We performed pre-therapeutic staging laparoscopy (SL) to diagnose peritoneal metastasis for patients with advanced gastric cancer. When peritoneal metastasis disappears by chemotherapy for patients with CY1 or P1, we have intention to perform conversion surgery (CS). This study aims to clarify the clinical significance of CS for such patients.

Methods: We retrospectively analyzed clinical outcomes of 115 patients with advanced gastric cancer (large type 3, type 4, serosa-invasion) who underwent SL between 2005 and 2014. Disappearance of peritoneal metastasis was confirmed by second-look SL.

Results: CY0P0, CY1P0, and P1 were found in 56, 26, and 33 patients, respectively. In patients with CY1P0, 12 patients (66.7%) underwent CS (R0) as peritoneal cytology turned negative. All cases received S-1-based regimens, with median five treatment courses. The survival of patients with CS was significantly longer than those without CS (median survival time (MST); 41 vs. 11 months, respectively, P < 0.001). We observed no difference in overall survival between patients who underwent CS and patients with CY0P0 at the first SL (P = 0.913). All patients with P1 received chemotherapy. As peritoneal metastasis of five patients (15.2%) disappeared by chemotherapy, those patients underwent the CS (R0). The survival of patients who underwent CS was significantly longer than those who did not (MST; 31 vs. 10 months, respectively, P = 0.034).

Conclusion: This study suggests that conversion surgery contributes to improvement in survival of patients with peritoneal metastasis.
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http://dx.doi.org/10.1007/s11605-018-3983-7DOI Listing
September 2019

Detection of Minimal Bone Marrow involvement of Blastic Plasmacytoid Dendritic Cell Neoplastic Cells - CD303 immunostaining as a diagnostic tool.

J Clin Exp Hematop 2018 Mar 8;58(1):1-9. Epub 2018 Feb 8.

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.

Blastic plasmacytoid dendritic cell (pDC) neoplasm (BPDCN) is a relatively rare hematological malignancy with significantly complex clinicopathological features that are still unclear. This study aimed to analyze the clinicopathological data of BPDCN and evaluate immunohistochemical detection of minimal bone marrow (BM) involvement. In this study, we examined skin and BM lesions from 6 patients with BPDCN. Neoplastic cells tested positive for CD303 (polyclonal, 100%; monoclonal, 40%) in the skin lesions and for CD303 (polyclonal, 100%; monoclonal, 67%) in the BM clots. Although immunostaining of CD4, CD56, CD123, CD303, and TCLl detected minimal BM involvement in 3 patients, morphological identification was challenging in the BM clots stained with hematoxylin-eosin. In conclusion, our results demonstrate the significance of observing BM smears to detect neoplastic cells and that immunohistochemical examination, including CD303 antibodies, is useful to detect minimal BM involvement. This study is the first to report the expression of thymic stromal lymphopoietin (TSLP) and its receptor in BPDCN cells. Therefore, the TSLP/TSLP receptor axis may be associated with the proliferation of BPDCN, and consequently, the survival of patients.
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http://dx.doi.org/10.3960/jslrt.17030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144195PMC
March 2018

Internal Hernia After Laparoscopic Total Gastrectomy for Gastric Cancer.

Surg Laparosc Endosc Percutan Tech 2017 Dec;27(6):470-473

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.

Purpose: The aim of this study was to clarify internal hernia (IH) characteristics after laparoscopic gastrectomy.

Materials And Methods: This was a retrospective study of 1943 consecutive gastric cancer patients who underwent surgery at our institute between 2004 and 2015. Since 2013, our technique includes antecolic Roux-en-Y (RY) with closure of all mesenteric defects during laparoscopic total gastrectomy (LTG) as standard.

Results: Postoperative IH was only detected in patients who underwent total gastrectomy with RY reconstruction. Furthermore, the incidence of IH was significantly higher after LTG than after open total gastrectomy (4.9% vs. 1.0%; P=0.005). IH after LTG occurred in 8.0% of patients before standardization with closure of the mesenteric defects, but no IH was observed after standardization (P=0.047).

Conclusions: Closure of all mesenteric defects is recommended for gastric cancer patients who undergo LTG with antecolic RY. Registration number: UMIN000009163/000025029 (www.umin.ac.jp/ctr/).
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http://dx.doi.org/10.1097/SLE.0000000000000481DOI Listing
December 2017

Circular stapling versus triangulating stapling for the cervical esophagogastric anastomosis after esophagectomy in patients with thoracic esophageal cancer: A prospective, randomized, controlled trial.

Surgery 2017 07 18;162(1):131-138. Epub 2017 Mar 18.

Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan. Electronic address:

Background: Several studies have reported that the triangulating stapling method decreases the incidence of anastomotic stricture after esophagectomy, but no randomized, controlled trial has confirmed the efficacy of the triangulating stapling method for cervical esophagogastrostomy. We compared triangulating stapling and circular stapling for cervical esophagogastric anastomosis regarding the decrease in anastomotic stricture after esophagectomy for thoracic esophageal cancer.

Methods: Between August 2010 and April 2014, 100 patients enrolled in this randomized, controlled trial at the Wakayama Medical University Hospital were allocated randomly to either the circular stapling group (n = 49) or the triangulating stapling group (n = 51). The primary end point was the incidence of anastomotic stricture within 12 months postoperatively. This randomized, controlled trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000004848).

Results: There were no differences between the circular stapling and triangulating stapling groups in terms of clinical data. The amount of time required for esophagogastric anastomosis was slightly greater for the triangulating stapling group (22 minutes) than for the circular stapling group (18 minutes) (P = .028). Anastomotic stricture occurred in 8 patients (17%) in the circular stapling group and 9 patients (19%) in the triangulating stapling group (P = .935). The rate of anastomotic leakage was 11% for the circular stapling group and 2% for the triangulating stapling group (P = .073).

Conclusion: The triangulating stapling method for cervical anastomosis for thoracic esophageal cancer does not decrease the incidence of anastomotic stricture compared with the circular stapling method within 12 postoperative months but may affect the rate of anastomotic leakage.
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http://dx.doi.org/10.1016/j.surg.2017.01.013DOI Listing
July 2017

Expression of Extracellular Signal-regulated Kinase 5 and Ankyrin Repeat Domain 1 in Composite Pheochromocytoma and Ganglioneuroblastoma Detected Incidentally in the Adult Adrenal Gland.

Intern Med 2016;55(24):3611-3621. Epub 2016 Dec 15.

Department of Urology, Yamagata University Faculty of Medicine, Japan.

Composite pheochromocytoma (cPC) is extremely rare, arising in the adrenal medulla as a mixture of PC and other tumors of neural origin. We herein report on a case of adrenal incidentaloma post-operatively diagnosed as cPC with ganglioneuroblastoma (GNBL). The PC component had 7 points on the PASS, a Ki-67 index of 5.1%, a focal absence of sustentacular cells, and no genetic aberrations in succinate dehydrogenase subunit B. The GNBL component exhibited no N-myc amplification. Tumor cells of both components were stained positively for extracellular signal-regulated kinase 5 and ankyrin repeat domain 1. The aberrant activation of growth signaling may play a role in the marginal malignancy of cPC.
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http://dx.doi.org/10.2169/internalmedicine.55.7293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283962PMC
April 2017

Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates with elevated serum immunoglobulin A titer by promoting tonsillar immunoglobulin A class switching in immunoglobulin A nephropathy.

Transl Res 2016 10 30;176:1-17. Epub 2016 Apr 30.

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan. Electronic address:

Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Previous studies suggest that elevated serum IgA partly originates from the tonsils. Here, we investigated the mechanisms of IgA production in the tonsils of patients with IgAN. Immunohistochemistry revealed that the number and relative percentage of IgA-bearing cells were significantly increased in the tonsils of IgAN patients. Compared with non-IgAN patients, enhanced IgA class switching and overexpression of thymic stromal lymphopoietin (TSLP), TSLP receptor (TSLPR), activation-induced cytidine deaminase (AID), transforming growth factor-β1 (TGF-β1), B cell-activating factor of the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL) were detected in follicular dendritic cells (FDCs) of tonsillar germinal centers from IgAN patients. Importantly, TSLP correlated with IgA production in isolated FDC-associated clusters. Serum TSLP levels were increased and correlated with IgA overexpression in the tonsils and serum of IgAN patients. These data indicated that TSLP overexpression in tonsillar FDCs may promote IgA class switching in IgAN patients through the cooperative roles of AID, TGF-β1, BAFF, and APRIL. Therefore, interactions between TSLP in FDCs and IgA production in tonsils may be an important mechanism contributing to the pathogenesis of IgAN.
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http://dx.doi.org/10.1016/j.trsl.2016.04.008DOI Listing
October 2016

Specific Neuropilins Expression in Alveolar Macrophages among Tissue-Specific Macrophages.

PLoS One 2016 22;11(2):e0147358. Epub 2016 Feb 22.

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan.

In the immune system, neuropilins (NRPs), including NRP-1 and NRP-2, are expressed in thymocytes, dendritic cells, regulatory T cells and macrophages. Their functions on immune cells around the neoplastic cells vary into pro-angiogenesis, tumor progression and anti-angiogenesis according to their ligands. Even though NRPs expression on malignant tumors and immune system has studied, a PubMed-based literature query did not yield any articles describing NRPs expression on tissue-specific macrophages. The aims of this study were (i) to detect NRPs expression on tissue-specific macrophages in the brain, liver, spleen, lymph node and lung; (ii) to observe NRPs expression in classes of macrophages, including alveolar macrophages (AMs), bronchial macrophages (BMs), interstitial macrophages (IMs), intravascular macrophages (IVMs) and macrophage subsets (M1, M2 and Mox) in lung; and (iii) to detect the co-expression of NRPs and dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in AMs. Both NRPs were specifically detected in AMs among tissue-specific macrophages by immunohistochemistry (IHC). NRPs mRNA expression levels were characterized in normal lung by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ-polymerase chain reaction (in situ-PCR). The expression of both NRPs was detected in AMs, BMs and IVMs by IHC. The frequency of NRPs+ AMs in lung tissue adjacent to the cancer margin was significantly higher than the frequencies in inflamed and normal lung tissue. Double and triple IHC demonstrated that NRPs are expressed on all macrophage subsets in lung. Double IHC showed co-expression of DC-SIGN and NRPs in AMs. This study demonstrated for the first time the specific expression of both NRPs in AMs among tissue-specific macrophages and their expression on M1, M2 and Mox macrophages. Furthermore, the possible origin of AMs from blood monocytes could be suggested from a co-expression of NRPs and DC-SIGN.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764655PMC
July 2016

Neoadjuvant Chemotherapy with Divided-dose Docetaxel, Cisplatin and Fluorouracil for Patients with Squamous Cell Carcinoma of the Esophagus.

Anticancer Res 2016 Feb;36(2):829-34

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan

Background: The aim of this phase II study was to evaluate the feasibility of a neoadjuvant chemotherapy regimen consisting of divided-dose docetaxel and cisplatin, with 5-fluorouracil (NAC-DCF), for treatment of patients with stage II/III squamous cell carcinoma of the esophagus (SCCE).

Patients And Methods: The NAC-DCF regimen, consisting of 2-h infusion of docetaxel at 35 mg/m(2) on days 1 and 8, 4-h infusion of cisplatin at 12 mg/m(2) on days 1-5, and continuous infusion of 5-fluorouracil at 600 mg/m(2) on days 1-5, was administered. We compared NAC-DCF with conventional NAC-CF.

Results: The DCF group comprised of 45 patients, and the CF group comprised of 28 patients. The incidence of grade 3/4 neutropenia was significantly higher in the DCF group (56%) than in the CF group (0%). Grade 2/3 pathological response was attained in a significantly higher percentage of patients in the DCF group (40%) than in the CF group (11%) (p=0.0153).

Conclusion: This DCF regimen led to a high frequency of pathological responses among patients with advanced SCCE.
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February 2016

Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues.

Leuk Lymphoma 2016 07 24;57(7):1687-96. Epub 2015 Dec 24.

a Department of Pathological Diagnostics , Yamagata University Faculty of Medicine , Yamagata , Japan.

The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II(+) FRCs/CD35(+) FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas.
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http://dx.doi.org/10.3109/10428194.2015.1107907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926777PMC
July 2016

Decreased expression of follicular dendritic cell-secreted protein correlates with increased immunoglobulin A production in the tonsils of individuals with immunoglobulin A nephropathy.

Transl Res 2015 Sep 17;166(3):281-91. Epub 2015 Apr 17.

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan. Electronic address:

Immunoglobulin A nephropathy (IgAN) is characterized by a qualitative abnormality of IgA in the circulation and IgA deposition in the renal mesangium. Recent research has indicated that pathogenic IgA may originate from affected tonsils. Follicular dendritic cell-secreted protein (FDC-SP), a small novel secretory protein that may regulate the induction of B-cell responses, has been suggested to control IgA production. Given this background, this study investigated the expression of FDC-SP and its correlation with IgA production in the tonsils of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to compare the expression of FDC-SP in the tonsils of IgAN patients with tonsillitis and of non-IgAN patients with chronic tonsillitis. The location of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. We found that FDC-SP expression significantly decreased and was correlated negatively with enhanced IgA production in the tonsils of IgAN patients. FDC-SP secreted by follicular dendritic cells may act on germinal center B cells and participate in the modulation of IgA generation in the tonsils. Our study demonstrated that FDC-SP may be involved in IgA production in the tonsils of IgAN patients, making this protein an attractive candidate immunomodulator, and highlighting a promising strategy for therapeutic intervention in IgAN.
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http://dx.doi.org/10.1016/j.trsl.2015.04.004DOI Listing
September 2015

Immunoglobulin and CD8⁺ T-cell distribution in histologically distinctive tonsils of individuals with tonsillar focal infection.

Acta Otolaryngol 2015 Mar;135(3):264-70

Department of Pathology, Harbin Medical University Cancer Hospital , Harbin , PR China.

Conclusion: This study demonstrated that the common immunological mechanism, which involves aberration of immunoglobulin and T-cell distribution in histologically distinctive tonsils, may be associated with the pathogenesis of tonsillar focal infection.

Objectives: Tonsillar focal infection comprises a group of relatively common diseases combined with chronic tonsillar infection, is associated with unusual immune responses in tonsils, and may cause lesions in another distant target organ. This study aimed to investigate the distribution of inflammatory T cells and T-cell regulatory elements, such as programmed cell death-1 (PD-1) and Fork head box protein 3 (Foxp3), immunoglobulin production, and histological characteristics in tonsils from patients with tonsillar focal infection.

Methods: Immunohistochemistry and reverse transcription-polymerase chain reaction (PCR) were used to compare the expression of CD8(+) T cells, immunoglobulins, and cytokines associated with immunoglobulin production in the tonsils of patients with IgA nephropathy (IgAN), palmoplantar pustulosis (PPP), rheumatoid arthritis (RA), and chronic tonsillitis.

Results: The overexpression of CD8(+) T cells combined with decreased expression of Foxp3 and PD-1 and the aberration of immunoglobulin production, which may be due to the elevated expression of activation-induced deaminase (AID), B-cell-activating factor of the TNF family (BAFF), supporting isotype switching, and B-cell survival in the histologically distinctive tonsils.
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http://dx.doi.org/10.3109/00016489.2014.968802DOI Listing
March 2015

Reconstruction after proximal gastrectomy for early gastric cancer in the upper third of the stomach: an analysis of our 13-year experience.

Surgery 2014 Jul 28;156(1):57-63. Epub 2014 Feb 28.

Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan. Electronic address:

Background: Fundoplication during esophagogastrostomy (EG) after proximal gastrectomy (PG) is a useful procedure to prevent reflux esophagitis, but it is unclear how much of the remnant stomach should be wrapped around the esophagus.

Methods: We analyzed data from 101 patients who underwent PG for upper third early gastric cancer between 1999 and 2011. In all, 64 patients underwent EG, 25 underwent jejunal interposition (JI), and 12 underwent jejunal pouch interposition (JPI). We compared intraoperative details and postoperative outcomes, and investigated the relationships between the degree of the fundoplication during EG and endoscopic findings.

Results: The length of the operation was significantly shorter in the EG group than in the other 2 groups (P < .05), and the intraoperative blood loss was significantly less in the EG group (P < .05). The JI and the JPI groups had significantly greater rates of early complications than did the EG group (P = .01). Reflux esophagitis was present in 22% of patients in the EG group, 8% in the JPI group, and none in the JI group. In the EG group, reflux esophagitis was significantly less common in patients with a >180° wrap of the remnant stomach around the esophagus than in patients with a smaller wrap (P = .0008). The rate of body weight loss was significantly less in the EG group compared with the other 2 groups (P < .05).

Conclusion: Considering the low invasiveness of the procedure and postoperative outcomes, we consider that EG with a >180° wrap as the optimal reconstructive procedure.
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http://dx.doi.org/10.1016/j.surg.2014.02.015DOI Listing
July 2014

New prognostic score for the survival of patients with esophageal squamous cell carcinoma.

Surg Today 2014 May 20;44(5):875-83. Epub 2013 Jun 20.

Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.

Purpose: Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS.

Methods: One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP.

Results: Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000-9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021-7.112, p = 0.0449).

Conclusions: The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.
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http://dx.doi.org/10.1007/s00595-013-0628-zDOI Listing
May 2014

Relapsing polychondritis complicated by giant cell myocarditis and myositis.

Intern Med 2013 ;52(12):1397-402

Department of Respiratory Medicine, Saiseikai Yamagata Saisei Hospital, Japan.

An 83-year-old man presented with a three-week history of dyspnea. The clinical features suggested a diagnosis of relapsing polychondritis (RP); however, the patient died of heart failure. An autopsy revealed active chondritis of the tracheal and bronchial cartilage. Furthermore, giant cell myocarditis (GCM) and myositis were detected. To the best of our knowledge, this represents the first report of RP complicated by GCM and myositis. In patients with RP, GCM and myositis, CD163-positive macrophages and T-cells are most common, and the T-cell subset exhibits CD8 predominance. Common mechanisms of tissue damage caused by cytotoxic T-cells are likely to contribute to RP, GCM and myositis.
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http://dx.doi.org/10.2169/internalmedicine.52.9080DOI Listing
February 2014

Myoepithelial carcinoma of the breast with focal rhabdoid features.

Breast J 2013 Jan-Feb;19(1):100-3. Epub 2012 Dec 17.

Department of Diagnostic Pathology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Myoepithelial carcinoma of the breast is extremely rare and only 33 cases have been reported in the English literature. Herein, we report a case of myoepithelial carcinoma of the breast with focal rhabdoid features. The patient was a 67-year-old woman, who presented with a lump of the left breast that rapidly grew to 3 cm in diameter within 3 months. Lumpectomy revealed a solid and whitish colored tumor, which was composed mainly of elongated spindle-shaped cells with mild atypia, focal necrosis, and infiltrative margin. In a small area of the lesion, ovoid tumor cells exhibited eccentric nuclei with centrally located nucleoli and plump cytoplasm including round eosinophilic inclusions, resembling a rhabdoid tumor. Immunohistochemically, both types of tumor cells exhibited a myoepithelial phenotype. MIB-1 index was 30%. The cytoplasmic inclusion of the ovoid cells exhibited immunopositivity for both vimentin and cytokeratin. From these findings, this tumor was diagnosed as a myoepithelial carcinoma with focal rhabdoid features. Although rhabdoid features have been reported in some types of malignant and benign tumors, this is the first report of such features in myoepithelial carcinoma of the breast.
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http://dx.doi.org/10.1111/tbj.12058DOI Listing
June 2013

[Two cases of mixed infection following 2009 H1N1 influenza pneumonia].

Nihon Kokyuki Gakkai Zasshi 2011 Mar;49(3):226-31

Department of Internal Medicine, Yamagata Prefectural Shinjo Hospital

Case 1 was a 73-year-old woman admitted to our hospital due to bilateral pneumonia with respiratory failure. Real-time reverse transcription polymerase chain reaction (RRT-PCR) analysis confirmed 2009 H1N1 influenza infection. Streptococcus pneumoniae was confirmed from sputum culture and a urine antigen test on admission. She was treated with antiviral drugs and antibiotics, and improved gradually. Case 2 was a 66-year-old woman admitted to our hospital due to suspected acute exacerbation of interstitial pneumonitis. RRT-PCR analysis confirmed 2009 H1N1 influenza infection, and methicillin-resistant Staphylococcus aureus was cultured from her sputum. Mixed pneumonia due to influenza virus, bacteria and fungus was suspected. Although she was treated with medicines for these pathogens, she died from respiratory failure. An autopsy confirmed primary viral pneumonia, Pseudomonas aeruginosa pneumonia and invasive pulmonary aspergillosis. Not only viral pneumonia, but also mixed infections due to bacteria or fungus, might influence the prognosis of 2009 H1N1 influenza infection. These cases indicate the importance of early identification of complicating pathogens and treatment in 2009 H1N1 influenza infection.
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March 2011

Angioimmunoblastic T-cell lymphoma with dual genotype of TCR and IgH genes.

Pathol Res Pract 2011 May 5;207(5):317-21. Epub 2011 Mar 5.

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

A 70-year-old man complained of fever and sore throat accompanied by hoarseness of voice. On physical examination, there was no systemic abnormality but a mild lymphadenopathy of cervical lymph nodes. With laryngoscopy, there was a marked outgrowth of the bilateral palatine tonsils proximal to the vocal cord. The histology of the resected tumor was compatible with angioimmunoblastic T cell lymphoma (AITL), revealing the effacement of normal tonsillar architecture and small to medium-sized neoplastic cell proliferation around marked vascular proliferation and atrophic lymphoid follicles. Tumor cells were positive for conventional T-cell antigens as well as for the follicular helper T-cell marker, PD-1, and CXCL13. Large hodgkinoid cells, but no tumor cells, were positive for latent membrane protein-1 and Epstein-Barr virus-encoded small RNA (EBER)-1 (in situ hybridization). Non-neoplastic, double positive cells for EBER-1 and CD20 were also scattered. Southern blot analysis revealed dual TCR-Cβ1 and IGH-JH gene rearrangements. Although the swelling of bilateral inguinal and perigastric lymph nodes developed later, the radical resection of tumor and chemotherapy appeared to be effective for the treatment of AITL with clinical stage IIIa. We here report a rare case of AITL involving palatine tonsil as primary site and give a review of the literature.
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http://dx.doi.org/10.1016/j.prp.2011.01.004DOI Listing
May 2011