Yasuhiro Ogawa

Kochi Medical School, Kôti, Kōchi, Japan

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Publications (98)195.97 Total impact

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    ABSTRACT: A novel radiosensitization treatment involving the injection of hydrogen peroxide and sodium hyaluronate, using ultrasonic guidance, into a tumor immediately prior to intraoperative radiotherapy (IORT) was established for patients with stage IVa locally advanced unresectable pancreatic cancer. The aim of the present study was to assess the safety and efficacy of this novel treatment, termed Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas-IORT (KORTUC and IORT). In total, 12 patients were treated with KORTUC-IORT, external-beam radiotherapy and systemic chemotherapy using gemcitabine hydrochloride and S-1. For evaluation of the therapeutic and adverse effects, contrast-enhanced computed tomography was conducted prior to the treatment, and one and six months following KORTUC-IORT. Medical examinations were performed every month at the regularly scheduled follow-up visits. The one- and two-year survival rates were 75 and 25%, respectively, and the median survival time was 16 months. All treatments associated with KORTUC-IORT were well-tolerated by the patients, with a small number of adverse effects and no serious complications. It was identified that the delivery of KORTUC-IORT is safe and effective, in combination with external-beam radiotherapy and systemic chemotherapy, for patients with locally advanced unresectable pancreatic cancer.
    Oncology letters 07/2014; 8(1):404-408. · 0.24 Impact Factor
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    ABSTRACT: Severe knee pain associated with osteoarthritis (OA) is one of the most common and troublesome symptoms in the elderly. Recently, local bone denervation by MR-guided focused ultrasound (MRgFUS) has been demonstrated as a promising tool for pain palliation of bone metastases. The purpose of this study was to develop a novel treatment for knee OA using MRgFUS, and to validate its safety and efficacy. Eight patients with medial knee pain and eligible for total knee arthroplasty were included. MR-guided focused sonication treatments were applied to bone surface just below the rim osteophyte of medial tibia plateau with real-time monitoring of the temperature in the target sites. The pain intensity during walking was assessed on a 100 mm visual analog scale (VAS) before and after treatment. Pressure pain thresholds (PPTs) were also evaluated over several test sites adjacent to the sonication area and control sites one month after treatment. Six patients (75%) showed immediate pain alleviation after treatment, and four of them demonstrated long-lasting effect at 6-month follow up (mean VAS reduction; 72.6%). In responders, PPTs in medial knee were significantly increased after treatment (Median; pre- 358 kpa vs post- 534 kpa, p < 0.0001). There were no adverse side effects or complications during and after treatment. These initial results illustrate the safety and efficacy of the newly developing MRgFUS treatment. Significant increase of PPTs on treated area showed successful denervation effect on the nociceptive nerve terminals. MRgFUS is a promising and innovative procedure for noninvasive pain management of knee OA.Trial registration: Trial Registration: UMIN000010193.
    BMC Musculoskeletal Disorders 09/2013; 14(1):267. · 1.88 Impact Factor
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    ABSTRACT: The significance of (18)F-2-deoxy-2-fluoro-glucose positron emission tomography combined with computed tomography imaging (FDG-PET/CT) in the diagnosis of gastric cancer remains controversial. This study aimed to evaluate the efficacy of preoperative FDG-PET/CT in staging of gastric cancer. FDG-PET/CT results for 90 patients with gastric cancer were retrospectively examined. For quantitative PET analysis, FDG uptake was assessed based on the maximum standardized uptake values (SUVmax). FDG-PET/CT detected the primary gastric cancer in 71 of the 90 patients (sensitivity 78.9 %). The median SUVmax was significantly higher in patients with T3/T4 disease than in those with T1/T2 (9.0 vs. 3.8; P < 0.001), in patients with distant metastasis than in those with no metastasis (9.5 vs. 7.7; P = 0.018), and with stage III/IV tumors than in those with stage I/II (9.0 vs. 4.7; P = 0.017). The SUVmax of the primary tumor was significantly correlated with tumor size (r = 0.461, P < 0.001). The sensitivity, specificity, and accuracy of FDG-PET/CT in assessing metastasis to regional lymph nodes were 64.5, 85.7, and 71.1 %, respectively. FDG-PET/CT results are significantly associated with tumor progression in gastric cancer, and such findings can reliably identify cancer cell populations.
    International Journal of Clinical Oncology 07/2013; · 1.41 Impact Factor
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    ABSTRACT: The present study aimed to evaluate the long-term follow-up results of patients with intraductal papillary mucinous neoplasm (IPMN) and to estimate the degree of IPMN malignancy based on pathological and molecular features of resected specimens. The detection rate of IPMN has increased over the last decade; however, the management of this neoplasm remains controversial. This is particularly so for branch duct-type IPMN, which carries a high potential for malignancy and risk of recurrence. We retrospectively reviewed a single institution's prospective pancreatic resection database to identify IPMN patients who underwent pancreatectomy with curative intent. The clinicopathological variables of 100 patients resected for IPMN were analyzed with a detailed review of histopathological results (borderline lesions, non-invasive carcinoma and invasive carcinoma) to determine the grade of IPMN malignancy based on transforming growth factor (TGF)-β/SMAD4 signaling. The incidence of malignant change was significantly higher in patients with main duct-type IPMN (69.7%) compared with branch duct-type IPMN cases (17.9%). However, patients with an invasive carcinoma had a significantly worse outcome if it was derived from branch duct-type IPMN compared with those derived from main duct-type IPMN, and TGF-β mRNA expression was significantly increased in the former patient group. Immunohistochemistry also showed higher numbers of SMAD4-positive cells in patients with carcinoma derived from branch duct-type IPMN. Our results demonstrated that invasive carcinoma derived from branch duct-type IPMN is more aggressive than that derived from main duct-type IPMN, once invasive morphological change takes place. Determining TGF-β and/or SMAD4 status at initial diagnosis may be useful for stratifying IPMN patients into treatment regimens.
    Oncology letters 06/2013; 5(6):1819-1825. · 0.24 Impact Factor
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    ABSTRACT: Insulinomas, the most common cause of hypoglycemia related to endogenous hyperinsulinism, occur in 1-4 people per million of the general population. Common autonomic symptoms of insulinoma include diaphroresis, tremor, and palpitations, whereas neuroglycopenenic symptoms include confusion, behavioural changes, personality changes, visual disturbances, seizure, and coma. Diagnosis of suspected cases is based on standard endocrine tests, especially the prolonged fasting test. Non-invasive imaging procedures, such as computed tomography and magnetic resonance imaging, are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion. Invasive modalities, such as endoscopic ultrasonography and arterial stimulation venous sampling, are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to non-invasive localization techniques. The range of techniques available for the localization of insulinomas means that blind resection can be avoided. Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas. A high proportion of patients with insulinomas can be cured with surgery. In patients with malignant insulinomas, an aggressive medical approach, including extended pancreatic resection, liver resection, liver transplantation, chemoembolization, or radiofrequency ablation, is recommended to improve both survival and quality of life. In patients with unresectable or uncontrollable insulinomas, such as malignant insulinoma of the pancreas, several techniques should be considered, including administration of ocreotide and/or continuous glucose monitoring, to prevent hypoglycemic episodes and to improve quality of life.
    World Journal of Gastroenterology 02/2013; 19(6):829-37. · 2.55 Impact Factor
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    ABSTRACT: Enthesitis, defined as the inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis, and joint capsules, is a hallmark of spondyloarthritis (SpA). New imaging techniques including magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography with computed tomography using (18)F-fluorodeoxyglucose capable of detecting morphological and metabolic abnormalities and monitoring disease activity have improved the assessment and management of enthesitis of SpA.
    Annals of Nuclear Medicine 11/2012; · 1.41 Impact Factor
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    ABSTRACT: Animal studies have demonstrated that liver function parameters affect the degree of liver enhancement by gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA). The present study prospectively investigated whether liver function parameters and liver damage scores similarly correlate with the degree of liver enhancement by Gd-EOB-DTPA in humans with hepatocellular carcinoma (HCC). A total of 41 patients (32 males, 9 females; mean age, 71.9 years; range, 38-86 years) with suspected HCC provided written, informed consent to undergo a Gd-EOB-DTPA (30 μmol/kg of body weight)-enhanced T1-gradient-echo (GRE) magnetic resonance imaging (MRI) study. The signal intensity of the liver parenchyma was quantified at various time points following injection of Gd-EOB-DTPA. We investigated the correlations between maximal relative enhancement (RE) values and liver function parameters, and liver damage scores. Correlations between parameters and maximum RE values were determined using the Student's t-test and univariate regression analyses. The effect of potential confounding factors was controlled by multiple stepwise regression analysis. Two-tailed values of p<0.05 were considered to indicate a statistically significant difference. The RE values were maximal in 8 and 33 patients at 20 and 30 min, respectively, following Gd-EOB-DTPA injection and did not significantly differ between respective liver damage scores. Univariate analyses revealed that maximal RE values were associated with serum aspartate aminotransferase, total bilirubin, albumin and 15-min indocyanine green retention rates. Multiple stepwise regression analyses revealed that serum albumin and total bilirubin remained independently significant. The degree of liver parenchyma enhancement by Gd-EOB-DTPA depends on liver function parameters in humans, as in animals. The results from this study suggest that Gd-EOB-DTPA has potential for use as a liver function test, and for providing a short examination time for liver MRI results in patients with normal liver function.
    Oncology letters 05/2012; 3(5):990-994. · 0.24 Impact Factor
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    ABSTRACT: We report herein the case of a 42-year-old woman in whom a solitary lung metastasis from stromal sarcoma of the breast was effectively treated by radiotherapy. The original breast tumor had been extirpated in a local hospital, and she was subsequently referred to our outpatient clinic for nonsurgical treatment. Pathological examination of the breast tumor had confirmed a diagnosis of stromal sarcoma. Radiation and systemic chemotherapy for the remnant disease were administered at our hospital; however, 8 months later, local recurrence and a solitary lung metastasis were recognized on a chest X-ray. A second lumpectomy of the recurrent breast tumor along with radiation for the lung metastasis and systemic chemotherapy were performed. After a 4-year disease-free period, there is still no sign of recurrence. This case serves to demonstrate the effectiveness of radiotherapy for the treatment of lung metastasis from stromal sarcoma of the breast. Key Wordsstromal sarcoma–breast–lung metastasis–radiotherapy
    Surgery Today 04/2012; 30(3):282-285. · 0.96 Impact Factor
  • Modern Rheumatology 03/2012; · 1.72 Impact Factor
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    ABSTRACT: Aim:  Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD). Therefore, it is important to evaluate disease activity and distinguish NASH from simple steatosis in NAFLD. Technetium-99 m-2-methoxy-isobutyl-isonitrile ((99m) Tc-MIBI) is a lipophilic cation designed for myocardial perfusion scintigraphy in the diagnosis of ischemic heart diseases, and its retention reflects mitochondrial function. It was reported that hepatic mitochondrial abnormalities would be an important predictive factor for NASH disease progression. The aim of this study was to examine the clinical usefulness of (99m) Tc-MIBI liver scintigraphy for evaluating disease activity of NAFLD and distinguishing NASH from simple steatosis in patients with NAFLD. Methods:  Twenty-six patients with biopsy-proven NAFLD were enrolled. Clinicolaboratory tests and (99m) Tc-MIBI liver scintigraphy were performed. To evaluate hepatic uptake, regions of interest were set at the liver and heart, and the uptake ratio of the liver to heart (liver/heart ratio) was calculated. Results:  All patients with NAFLD were classified into three groups according to the NAFLD activity score: non-NASH (simple steatosis) (n = 4), borderline NASH (n = 11), and NASH (n = 11). Liver/heart ratios were significantly lower in NASH than in simple steatosis (P < 0.05). Moreover, liver/heart ratios were significantly correlated with NAFLD activity scores among the patients (r = -0.413, P < 0.05). Conclusions:  The present study indicates that (99m) Tc-MIBI liver scintigraphy would be a useful non-invasive functional imaging method with which to evaluate disease activity of NAFLD and distinguish NASH from simple steatosis.
    Hepatology Research 03/2012; 42(3):273-9. · 2.07 Impact Factor
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    ABSTRACT: Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) method and is considered potentially useful for detecting prostate cancer. We evaluated the clinical value of DWI with apparent diffusion coefficient (ADC) maps in addition to T2-weighted imaging (T2WI) using 3 tesla (3 T) MRI. Thirty-three patients with elevated prostate specific antigen were evaluated by MRI with T2WI and DWI prior to transperineal template-guided mapping biopsy. The MRI findings were compared with the pathology of biopsy specimens in six parts of prostate : both sides of outer peripheral zones, inner peripheral zones, and transition zones. The sensitivities, specificities and accuracies were 42.1, 84.4 and 76.3% in T2WI, 57.1, 84.7 and 80.8% in T2WI/DWI, and 87.5, 85.2 and 85.4% in DWI/ADC using 0.951×10 -3 mm2/s as cutoff ADC value. The hazard ratio of patients whose ADC values were under the cutoff was 25.86 by multivariate analysis. Mean ADC values were significantly different between cancer positive and negative cores (p<0.001). The ADC value showed a negative correlation with increasing tumor length (p=0.0047). Although further study with a large number of patients is necessary, DWI/ADC using 3 T MRI is a useful tool for detecting prostate cancer.
    Hinyokika kiyo. Acta urologica Japonica 03/2012; 58(3):143-8.
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    ABSTRACT: The diagnosis of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy is of great interest to breast physicians. The present study compared the utility of gray-scale sonography standardized by a breast imaging reporting and data system (BI-RADS) and power Doppler sonography for differentiating between benign scar formation and IBTR after breast-conserving therapy. Gray-scale sonography detected 83 solid breast lesions classified as BI-RADS categories 3-5 in 272 patients after breast-conserving therapy, and these lesions were entered into the study (53 lesions as category 3, probably benign; 30 lesions as categories 4-5, suspected malignancy). Power Doppler sonography revealed intratumoral flow in 19 of 83 solid breast lesions. BI-RADS category 3 was accepted as probably benign and BI-RADS categories 4-5 were considered as suspicious for breast tumor recurrence in the gray-scale ultrasound criteria. Positive and negative intratumoral flow were employed as suspicious for breast tumor recurrence and probably benign, respectively, in the power Doppler sonography criteria. Sensitivity was higher for power Doppler sonography (94.7±10.0%) than for gray-scale sonography (57.9±22.2%). Specificity was also higher for power Doppler sonography (98.4±3.0%) than for gray-scale sonography (70.3±0.6%). These results suggest that power Doppler sonography can complement gray-scale sonography standardized by BI-RADS in differentiating between IBTR and benign scar lesions.
    Oncology Reports 09/2011; 26(6):1357-62. · 2.30 Impact Factor
  • Journal of dermatological science 08/2011; 64(2):144-7. · 3.71 Impact Factor
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    ABSTRACT: Linear accelerator-based radiotherapy has little effect on tumors such as malignant melanoma, various types of sarcoma, and most locally-advanced neoplasms that have grown to several centimeters or more. These tumors contain many hypoxic cancer cells or large amounts of anti-oxidative enzymes, and are therefore resistant to low linear energy transfer radiation. Therefore, it was necessary to develop a new radiosensitizer to overcome these situations. We previously developed a new enzyme-targeting radiosensitization treatment named KORTUC I, which uses 3% w/v hydrogen peroxide solution-soaked gauze. We developed a new radiosensitizer for intratumoral injection (KORTUC II), comprising a combination of hydrogen peroxide and sodium hyaluronate. After providing a fully informed written consent, 52 patients with unresectable or recurrent neoplasms (53 lesions) were enrolled in the KORTUC II trial. The present study of 52 patients with unresectable or recurrent neoplasms showed that KORTUC II is safe when injected intratumorally, well tolerated, and can efficiently exert a radiation sensitizing effect. Because this radiosensitizer is safe and less expensive than other methods, and can be applied for almost every type of low-LET radio-resistant neoplasm, it has potential for worldwide and immediate use.
    International Journal of Oncology 06/2011; 39(3):553-60. · 2.66 Impact Factor
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    ABSTRACT: A 31-year-old woman developed polyarthralgia and extension disorder of the right elbow of 2 months' duration without abdominal symptom. Laboratory findings revealed C-reactive protein 2.7 mg/dL. Anti-nuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) antibody were negative. F-18 FDG PET/CT showed elevated pinpoint uptakes of FDG in the entheses. In contrast, MRI revealed no specific findings. Four months after PET/CT, she developed right lower abdominal pain. Colonoscopy showed abscess in ascending colon, which the initial PET/CT finding might mean early image of infective colitis. A diagnosis of early reactive arthritis was made. Treatment with antibiotics improved colitis, colonic abscess, and enthesitis after 2 months. Moreover, F-18 FDG PET/CT showed no accumulation in colon and entheses. These findings suggest that F-18 FDG PET/CT scanning allows enthesitis in the early stage of reactive arthritis, before the possible detection by the other procedures.
    Clinical nuclear medicine 02/2011; 36(2):121-3. · 3.92 Impact Factor
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    ABSTRACT: We introduced non-surgical therapy with a novel enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II) into early stages breast cancer treatment. The purpose of this study was to examine changes in tumor shadows and microcalcifications on mammography (MMG) following KORTUC II for elderly patients with breast cancer. We also sought to determine whether MMG was useful in evaluating the therapeutic effect of KORTUC II. In addition to MMG, positron emission tomography-computed tomography (PET-CT) was performed to detect both metastasis and local recurrence. In all 10 patients, tumor shadows on MMG completely disappeared in several months following the KORTUC II treatment. The concomitant microcalcifications also disappeared or markedly decreased in number. Disappearance of the tumors was also confirmed by the profile curve of tumor density on MMG following KORTUC II treatment; density fell and eventually approached that of the peripheral mammary tissue. These 10 patients have so far have also shown neither local recurrence nor distant metastasis on PET-CT with a mean follow-up period of approximately 27 months at the end of September, 2010. We conclude that breast-conservation treatment using KORTUC II, followed by aromatase inhibitor, is a promising therapeutic method for elderly patients with breast cancer, in terms of avoiding any surgical procedure. Moreover, MMG is considered to be useful for evaluating the efficacy of KORTUC II.
    Cancers. 01/2011; 3(3):3496-505.
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    ABSTRACT: We report 2 cases of primary breast cancer with swelling of the parasternal lymph nodes detected on diffusion-weighted imaging (DWI) as small parasternal nodules. After neoadjuvant chemotherapy, DWI showed disappearance of one node but a focus of subtle signal hyperintensity in the other. DWI findings correlated with the results of conventional breast contrast-enhanced magnetic resonance imaging before and after neoadjuvant chemotherapy.
    Magnetic Resonance in Medical Sciences 01/2011; 10(1):53-7. · 0.75 Impact Factor
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    ABSTRACT: We have previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which markedly enhances radiotherapeutic effects on various types of locally advanced malignant neoplasms. KORTUC II was approved by our local ethics committee for use against various types of malignant neoplasms. A maximum of 6 ml of radiosensitizer was injected into tumor tissue under ultrasonographic guidance just before each administration of radiotherapy. Seventeen patients with locally advanced breast cancer were enrolled to receive KORTUC II with systemic chemotherapy without surgical care. Patients were eligible if they had declined surgical treatment. Median observation period was 13.4 months (range, 1-26 months). This therapy was well tolerated. Contrast-enhanced magnetic resonance imaging revealed complete response in all primary breast tumors, and no patients displayed local recurrence during the follow-up period. Ultrasonography depicted tumor-like findings in 9 of 17 cases after therapy. The existence rate of posterior shadow artifacts behind the tumor was 2/17 before therapy, increasing to 8/17 after therapy. Intratumoral flow signals on color Doppler sonography were seen in 16/17 cases before therapy, but had disappeared from all cases after therapy. The increased rate of posterior shadow artifacts and absence of flow signals after therapy suggest that the tumor-like finding on ultrasonography represents scar tissue. Computed tomography revealed positive axillary nodes metastases in 16/17 and 2/17 cases before and after therapy, respectively. Nodal metastatic failure affected only 1 patient, who refused adjuvant systemic chemotherapy at the end of the observation period. Abnormal lymph node findings on computed tomography remained stable in the other patient. Excellent locoregional control based on accurate radiological evaluation implies that KORTUC II with chemotherapy has the potential to replace surgery in therapy for locally advanced breast cancer.
    Oncology Reports 11/2010; 24(5):1161-8. · 2.30 Impact Factor
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    ABSTRACT: The therapeutic effect of radiotherapy using linear accelerators for relatively large tumors of more than several centimeters in diameter is reduced to one third due to a large number of hypoxic tumor cells and a significant amount of anti-oxidative enzymes including peroxidase/catalase. The most effective method by which to inject hydrogen peroxide into tumor tissue was examined. This proved difficult as 3% w/v hydrogen peroxide solution (Oxydol) is an antiseptic agent for skin lesions. Thus, injection into an affected lesion may result in hydrogen peroxide soaking into a body cavity, possibly causing an intra-arterial oxygen embolism. This study aimed to identify the most effective combination of drugs containing hydrogen peroxide in order to relieve local pain at the injection site and preserve high intratumoral oxygen concentration. Hyaluronate-hydrogen peroxide was identified as the most effective combination of drugs containing hydrogen peroxide for the preservation of high intratumoral oxygen concentration for 24 h following intratumoral injection with the agent. Based on the results, the clinical application of a novel enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC), was initiated for malignant tumors including advanced breast cancer, soft tissue sarcoma and cervical lymph node metastasis. Moreover, we have developed KORTUC III for locally advanced hepatocellular carcinoma and KORTUC IV for locally advanced pancreas cancer (stage IVa).
    Oncology letters 11/2010; 1(6):1025-1028. · 0.24 Impact Factor
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    ABSTRACT: The decision to repeat transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is based on correct evaluation of response to therapy. The purpose of this study was to investigate whether apparent diffusion coefficient (ADC), a quantitative parameter of diffusion-weighted imaging (DWI), can predict early HCC recurrence after TACE. Results obtained using this method were compared with those using iodized-oil computed tomography (CT). DWI was performed on 25 patients with 36 HCCs before and 5-7 days after TACE to calculate the ADC of HCC. Patients were also evaluated with iodized-oil CT immediately after TACE. Contrast-enhanced CT was performed 3 months after TACE to confirm early relapse of HCC lesion. After TACE, the percent change in ADC (%ADC) from before to after therapy was significantly increased in non-relapsed lesions (85.2+/-12.4%) compared to relapsed lesions (8.0+/-56.7%, p=0.0004). However, no difference in area under the curve was seen for receiver operating characteristic analysis to predict early relapse after TACE between %ADC from DWI (95% confidence interval, 0.743-1.026) and iodized-oil CT (95% confidence interval, 0.703-1.016). ADC from DWI can evaluate the efficacy of TACE for HCC as effectively as iodized-oil CT, and may help in deciding whether to repeat TACE.
    Oncology Reports 09/2010; 24(3):727-32. · 2.30 Impact Factor

Publication Stats

428 Citations
195.97 Total Impact Points

Institutions

  • 2002–2014
    • Kochi Medical School
      Kôti, Kōchi, Japan
  • 2013
    • Kochi Health Sciences Center
      Kôti, Kōchi, Japan
  • 2004–2013
    • Kochi University
      • • Department of Radiology
      • • Department of Endocrinology, Metabolism and Nephrology
      • • Department of Medicine
      Kôti, Kōchi, Japan
  • 2008
    • Osaka Medical College
      • Department of Radiology
      Takatuki, Ōsaka, Japan
  • 2005
    • Ehime University
      • Department of Orthopaedic Surgery
      Matuyama, Ehime, Japan