Satoru Motoyama

Akita University Hospital, Akita, Akita, Japan

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Publications (148)358.07 Total impact

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    ABSTRACT: Purpose: To evaluate treatment outcomes of chemoradiotherapy for patients with stage IVA esophageal cancer and to estimate prognostic factors. Materials and methods: Patients with stage IVA esophageal cancer treated with chemoradiotherapy between April 2003 and March 2009 were evaluated. Patients received concurrent chemoradiotherapy comprising cisplatin plus 5-fluorouracil and 61.2 Gy of radiotherapy. Therapeutic response, overall survival time, and toxicity were examined and statistical evaluation was performed. Results: Ninety patients were treated using chemoradiotherapy. Among these, 71 patients (78.9 %) received the complete course of chemoradiotherapy. Seventeen patients (18.9 %) showed complete response, 64 patients (71.1 %) had partial response, 7 patients (7.8 %) experienced no change, and 2 patients (2.2 %) exhibited progressive disease. Mean duration of follow-up was 16.1 months (range 2-88 months). Median overall survival was 12.8 months. Two- and 3-year overall survival rates were 35.1 and 18.6 %, respectively. Severe hematological toxicities included Grade 3 leukopenia in 33 patients (36.7 %). Treatment-related death was estimated to have occurred in 7 patients. Performance status and body weight loss were identified as significant prognostic factors. Conclusion: Our treatment outcomes appeared similar to those of previous studies that used chemoradiotherapy for advanced esophageal cancer. This treatment is useful for stage IVA esophageal cancer.
    Japanese journal of radiology 02/2013; 31(4). DOI:10.1007/s11604-013-0180-1 · 0.84 Impact Factor
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    ABSTRACT: Purpose: To develop a simple noninvasive technique for evaluating pleural invasion by using routine preoperative computed tomography (CT). Materials and methods: The institutional review board approved this retrospective study, and written informed consent was obtained for performing the initial and follow-up CT studies. Preoperative CT findings (169 patients with possible pleural invasion) and pathologic diagnoses after surgical resection were evaluated. The length of the interface between the primary tumor and neighboring structures (arch distance) and the maximum tumor diameter were measured on CT images, after which arch distance-to-maximum tumor diameter ratios were calculated. Receiver operating characteristic (ROC) curves were used to analyze the ratios. Results: Median arch distance-to-maximum tumor diameter ratios for pleural invasion categories (pl1, pl2, pl3) assessed by using the Union Internationale Contre le Cancer TNM staging system were as follows: pl1, 0.206 (25th-75th percentile, 0-0.486); pl2, 0.638 (25th-75th percentile, 0.385-0.830); and pl3, 1.092 (25th-75th percentile, 1.045-1.214) (P < .001 between groups). On the basis of the ROC curves, the cut-off value for invasion was an arch distance-to-maximum tumor diameter ratio of 0.9. When the ratio was greater than 0.9, the sensitivity and specificity for thoracic invasion and area under the ROC curve were 89.7%, 96.0%, and 0.976, respectively, which represents an improvement over values obtained by using conventional criteria (radiologists A and B: 46.7% and 74.2% and 91.3% and 84.8%, respectively). Conclusion: When diagnosing T3 or T4 lung cancer based on arch distance-to-maximum tumor diameter ratios, a higher performance level was achieved than that with use of conventional criteria. Measurement of the ratios is a simple noninvasive technique for evaluating pleural invasion at CT.
    Radiology 01/2013; 267(2). DOI:10.1148/radiol.12120864 · 6.87 Impact Factor

  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2013; 74(9):2441-2445. DOI:10.3919/jjsa.74.2441

  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2013; 74(5):1145-1149. DOI:10.3919/jjsa.74.1145
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    ABSTRACT: Background: More than 40 % of patients with submucosal esophageal squamous cell carcinoma (ESCC) have lymph node metastasis. Furthermore, the potential presence of undetectable metastasis before treatment prompts surgeons to be aggressive with respect to lymph node dissection. Extending the indication for endoscopic resection, a minimally invasive treatment, to superficial ESCCs will require more accurate and individualized evaluation of lymph node metastasis. Methods: The study participants were 121 esophageal cancer patients who underwent curative surgery for thoracic submucosal ESCC at three Japanese hospitals. DNA was extracted from blood samples, and the C-reactive protein (CRP) 1846C>T genetic polymorphism (rs1205) was investigated using polymerase chain reaction-restriction fragment length polymorphism. We then evaluated the value of CRP 1846C>T polymorphism for diagnosis of lymph node metastasis. Results: Forty-nine (40 %) patients had lymph node metastasis. The CRP 1846 C/T genotype was C/C in 19 patients, C/T in 57 patients, and T/T in 45 patients. Fisher's exact analysis of the CRP 1846C>T polymorphism showed a significantly higher frequency of lymph node involvement with the T/T genotype. Univariate and multivariate logistic regression models revealed that patients carrying the 1846 T/T genotype had a significantly greater likelihood of developing lymph node metastasis (odds ratio >2.6). Combining the CRP 1846 C/T genotype with clinical diagnosis, mainly using CT, brought a negative predictive value of 80 % to diagnosing lymph node involvement. Conclusions: CRP genetic polymorphism may be a novel predictor of risk of lymph node metastasis in ESCC, which could enable better evaluation of the necessity for lymph node dissection.
    Annals of Surgical Oncology 12/2012; 20(6). DOI:10.1245/s10434-012-2765-9 · 3.93 Impact Factor
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    ABSTRACT: Zinc Finger Homeobox 3 (ZFHX3) was first identified as a suppressor of alpha-fetoprotein gene and is a good candidate for the 16q22 tumor suppressor. In this study we investigated the relationship between tumoral ZFHX3 mRNA expression and the clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). We used semi-quantitative real time reverse transcription polymerase chain reaction to assess expression of ZFHX3 mRNA in tumor samples from 140 patients with NSCLC. We found that the 5-year overall survival rate among patients weakly expressing ZFHX3 was significantly poorer than among those expressing higher levels of ZFHX3 (P< 0.0001 by log-rank test). Multivariate logistic regression analysis revealed being lower ZFHX3 expression are independent predictors of lymph node metastasis. With low-ZFHX3 tumors, there was a significantly (P=0.009) greater (7.39-fold higher) risk of lymph node metastasis. Multivariate Cox proportional hazard analyses revealed that being lower ZFHX3 expression (Hazard ratio, 4.42; 95% CI, 2.09-8.92; p=0.0002) were independent factors affecting 5-year overall survival. Ratio of ZFHX3 mRNA in tumor against normal lung in low-ZFHX3 tumor was lower than in high-ZFHX3 tumor. In conclusion, suppression of ZFHX3 expression in tumor cells decreases the survival rate among patients with NSCLC.
    Cancer biomarkers: section A of Disease markers 11/2012; 11(4):139-46. DOI:10.3233/CBM-2012-00272 · 1.72 Impact Factor
  • K Yoshino · S Motoyama · S Koyota · K Shibuya · Y Sato · T Sasaki · A Wakita · H Saito · Y Minamiya · T Sugiyama · J Ogawa ·
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    ABSTRACT: Identification of reliable markers of radiosensitivity and the key molecules that donate susceptibility to anticancer treatments to esophageal cancer cells would be highly desirable. We found that the mRNA expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was higher in radioresistant TE-5 and TE-9 cells than in radiosensitive TE-12 cloneA1 cells. Conversely, knocking down expression of IGF2BP3 mRNA in TE-5 and TE-9 cells using small interfering RNA significantly enhanced their radiosensitivity. Furthermore, patients with squamous cell esophageal cancers strongly expressing IGF2BP3 tended to respond poorly to chemoradiation. These data suggest that IGF2BP3 may be a key marker of radiosensitivity that diminishes the susceptibility of squamous cell esophageal cancer cells to radiotherapy. IGF2BP3 may, thus, be a useful target for improving radiotherapy for patients with esophageal squamous cell carcinoma.
    Diseases of the Esophagus 09/2012; 27(5). DOI:10.1111/j.1442-2050.2012.01415.x · 1.78 Impact Factor
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    ABSTRACT: Background Cytomegalovirus (CMV) infection is endemic worldwide. Although CMV reactivation often becomes a serious problem in immunocompromised patients, the prevalence of CMV reactivation caused by methylprednisolone therapy for ARDS after esophagectomy has yet to be determined. Method Among 175 consecutive patients with thoracic squamous cell esophageal cancer who underwent esophagectomy with extensive lymph node dissection at Akita University Hospital between 2007 and 2010, 11 patients (6.3 %) diagnosed with ARDS during the acute phase of esophagectomy were enrolled and treated with steroid pulse therapy, high-dose (15–20 mg/kg/day) administration and tapering in this retrospective study. Results Seven of the 11 patients (63.6 %) were diagnosed with CMV reactivation based on CMV antigenemia assayed 19.1 days after the start of methylprednisolone administration and were treated with ganciclovir for 39.6 days. Six of the 7 patients (85.7 %) diagnosed with CMV reactivation were administered a total methylprednisolone dose of more than 4,000 mg. Though there was no significant difference between patients with and without CMV reactivation, there was a tendency that patients with CMV reactivation showed a lower minimum number of lymphocytes during the acute phase of esophagectomy (p = 0.051, Student’s t test, average 223.3 and 298.0/μl, respectively). Conclusion Though the number of study patients is small, the prevalence of CMV reactivation caused by high-dose methylprednisolone therapy for ARDS after esophagectomy is remarkably high. This result strikes a note of warning concerning the management of these patients and suggests the importance of screenings for CMV reactivation so as to make an accurate diagnosis and initiate treatment in a timely manner.
    Esophagus 09/2012; 9(3). DOI:10.1007/s10388-012-0316-x · 0.74 Impact Factor
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    ABSTRACT: C-reactive protein (CRP) produced locally within esophageal cancer is associated with the prognosis and the rate of recurrence. CRP genetic polymorphisms reportedly affect serum CRP concentrations; however, there are no reports of an association between genetic polymorphisms and tumoral CRP expression. This study enrolled 73 Japanese patients classified with Stage IIA-IV thoracic esophageal squamous cell cancer, and also investigated their CRP genetic polymorphisms using DNA extracted from their peripheral blood. The study then assessed the association between CRP genetic polymorphisms and tumoral CRP expression. The results revealed a significant association between the CRP 1846C>T genetic polymorphism and tumoral CRP expression. This finding suggests that tumoral CRP production controlled by CRP genetics significantly influences tumor behavior.
    Surgery Today 08/2012; 43(3). DOI:10.1007/s00595-012-0294-6 · 1.53 Impact Factor
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    ABSTRACT: Purpose: This study investigated the actual rate or extent of lymph node metastasis or the survival outcomes among patients that underwent esophagectomy with lymph node dissection after ESD for clinical mucosal, but pathological submucosal, esophageal cancer. Methods: Seventeen patients that received esophagectomy with two- or three-field lymph node dissection as additional treatment after ESD for clinical mucosal, but pathological submucosal, esophageal cancer between 2006 and 2010 were analyzed. The rate and extent of lymph node metastasis and the patient outcomes were determined. Results: The tumor depths were diagnosed as SM1 in 8 (47 %) patients and SM2 in 9 (53 %), based on the analyses of resected specimens. Lymphatic invasion was evident in 13 (76 %) patients, while venous invasion was detected in 5 (29 %). Five (29 %) patients had pathologically detected lymph node involvement. Seven (0.8 %) of the 890 dissected nodes showed cancer involvement. Three patients had one involved node in the mediastinum or abdomen, and 2 patients had 2 involved nodes in the abdomen. The patients were followed up for 11-71 months (median 23 months), and all were alive without recurrence at the final follow-up. Conclusion: Twenty-nine percent of the patients diagnosed with clinically mucosal, but pathologically submucosal, thoracic squamous cell esophageal cancer after ESD had 1-2 cancer-involved lymph nodes in the lower mediastinum and abdomen. Esophagectomy with lymph node dissection is therefore considered to be a necessary and effective additional treatment for these patients.
    Surgery Today 08/2012; 43(6). DOI:10.1007/s00595-012-0295-5 · 1.53 Impact Factor
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    ABSTRACT: Esophageal diverticula frequently arise from pharyngoesophageal transition area, tracheal bifurcation and epiphrenic region. Carcinoma arising from esophageal diverticulum is rarely seen. We report a patient with a squamous cell carcinoma arising within an esophageal diverticulum below the aortic arch. A 70-year-old man was diagnosed to have a squamous cell carcinoma of the vocal cord with enlarged lymph nodes in the neck, as well as a squamous cell carcinoma arising within an esophageal diverticulum below the aortic arch. There have been no reported cases of esophageal cancer arising from a diverticulum below the aortic arch. Preoperative radiotherapy for the esophageal cancer and pharyngeal cancer was given, followed by surgery. The excised specimen of the esophageal diverticulum and its external appearance revealed that it lacked muscle fibers, with a type 0-IIa lesion arising from the diverticulum. Microscopic examination showed three lymph nodes at the superior mediastinum were positive for malignancy. Bilateral pleural dissemination was detected 7 months after esophagectomy. Cancer arising from an esophageal diverticulum is mainly found at an advanced stage because of delayed diagnosis. The absence of muscularis propia may lead to early invasion. Thus, cancers within an esophageal diverticulum are considered to be at a more advanced stage than similar cancers arising elsewhere. For detecting of cancer arising from an esophageal diverticulum, a high index of awareness is important. Delay in diagnosis makes surgical management difficult.
    International Journal of Surgery Case Reports 08/2012; 3(11):574-6. DOI:10.1016/j.ijscr.2012.07.010
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    ABSTRACT: Purpose: Lymphatic spread of lung carcinoma to the mediastinum is a key determinant of prognosis. The lymph flow often carries metastases from the pulmonary segment directly into the mediastinal lymph nodes, without passing through the hilar nodes. This phenomenon is termed as "skip metastasis." This study investigated the subpleural lymphatic flow to the mediastinum using indocyanine green (ICG) with a near-infrared fluorescence imaging system. Methods: Seventeen patients with lung cancer were enrolled in this study. A 0.3 ml sample of solution containing the fluorescent dye ICG (5 mg/ml) was injected into subpleural sites near the primary tumor. Fluorescence imaging was used to monitor the flow of ICG-containing lymph from the injection site for 5 min. The relationship between the anatomical segment of the primary tumor and the lymphatic flow was assessed. Results: The lymphatic vessels draining from the injection site were revealed by the bright ICG fluorescence in 14 of the patients (82.4 %). A direct lymphatic flow to the mediastinum was confirmed in 3 of those 14 (21.4 %). Conclusions: These findings confirm the direct flow of lymph to the mediastinum without passage through the hilum pulmonis intraoperatively. These preliminary results may provide a valuable clue for further investigations of the mechanisms underlying skip metastasis.
    Surgery Today 06/2012; 43(3). DOI:10.1007/s00595-012-0237-2 · 1.53 Impact Factor
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    ABSTRACT: Xanthine dehydrogenase (XDH), also known as xanthine oxidoreductase (XOR), has long been recognized as the key enzyme in the catabolism of purines, oxidizing hypoxanthine into xanthine and then xanthine into uric acid. In addition, levels of XDH expression are reportedly related to the prognosis of patients with malignant tumors, though the relationship between the clinicopathological features of lung cancer and XDH is not fully understood. We therefore used semiquantitative real-time reverse transcription polymerase chain reaction to assess expression of XDH mRNA in tumor samples from 88 patients with adenocarcinoma of the lung. We then correlated XDH mRNA levels with known clinicopathological factors. We found that the 5-year overall survival rate among patients strongly expressing XDH was significantly poorer than among those expressing lower levels of XDH (P < 0.001; log-rank test). Normal lung tissue does not express XDH. Multivariate Cox proportional hazard analyses revealed that being male (hazard ratio, 3.14; 95 % confidence interval (CI), 1.45-7.07; P = 0.004), nodal metastasis positivity (hazard ratio, 5.74; 95 % CI, 1.94-19.3; P = 0.001), and high XDH expression (hazard ratio, 2.33; 95 % CI, 1.11-5.02; P = 0.026) were all independent factors affecting 5-year disease-free survival. In conclusion, high tumoral XDH expression is an independent predictor of a poor prognosis in patients with adenocarcinoma of the lung.
    Tumor Biology 06/2012; 33(5):1727-32. DOI:10.1007/s13277-012-0431-2 · 3.61 Impact Factor
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    ABSTRACT: Objective: Systemic and/or local interleukin-6 (IL-6) reportedly plays an active role in the progression and prognosis of thoracic esophageal squamous cell carcinoma (TESCC). We assessed the associations between IL-6 and IL-6 receptor (IL-6R) genetic polymorphisms, tumoral IL-6 expression and survival rates following surgery. Methods: The study participants were 63 Japanese patients treated between 2003 and 2008 for T2-T4 advanced TESCC using curative esophagectomy without neoadjuvant treatment. We investigated IL-6 -634G>C (rs1800796) and IL-6R 48892A>C (rs8192284, Asp358Ala) genetic polymorphisms using DNA from peripheral blood samples. In addition, tumoral IL-6 expression was investigated immunohistochemically in resected specimens, and serum IL-6 was measured using a human IL-6 immunoassay. Results: There was a significant difference in survival between patients with the IL-6 -634G/G+G/C genotype and those with the C/C genotype, such that their 5-year overall survival rates were 42 and 72%, respectively. By contrast, the IL-6R 48892A /C genotype and tumoral IL-6 expression had no significant effect on survival among patients. Univariate and multivariate analyses revealed that IL-6 -634G>C polymorphism was an independent prognostic factor with a hazard ratio of 3. Conclusions: IL-6 -634G>C genetic polymorphism may be a predictive prognostic factor in patients receiving esophagectomy for TESCC.
    Digestive surgery 06/2012; 29(3):194-201. DOI:10.1159/000336952 · 2.16 Impact Factor
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    Esophagus 06/2012; 9(2). DOI:10.1007/s10388-012-0328-6 · 0.74 Impact Factor
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    Yusuke Sato · Satoru Motoyama · Junichi Ogawa ·

    Esophageal Cancer - Cell and Molecular Biology, Biomarkers, Nutrition and Treatment, 03/2012; , ISBN: 978-953-51-0223-6
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    ABSTRACT: Cancer cells reportedly produce C-reactive protein (CRP) locally within tumors. The aim of this study was to determine whether tumoral CRP is associated with clinical outcome and recurrence in thoracic esophageal squamous cell cancer. The subjects included 73 Japanese patients with thoracic esophageal squamous cell cancer (pathological Stage IIA-IV) that had not been treated preoperatively with either chemotherapy or radiotherapy. Tumoral CRP expression in resected specimens of tumor tissue was assessed by immunohistochemistry. The survival rate following surgery, the rates and patterns of recurrence, and the serum CRP levels before treatment and at recurrence were analyzed in patients with and without tumoral CRP expression. Fifty-nine percent of the study participants (43/73) were positive for tumoral CRP expression, and the remaining 41% (30/73) were negative. No significant difference in clinicopathological factors was observed between the tumoral CRP-positive and CRP-negative groups; however, patients expressing tumoral CRP showed significantly poorer survival and recurrence rates. A multivariate analysis showed that tumoral CRP expression was an independent factor contributing to the likelihood of a poor outcome. Tumoral CRP is associated with a poor outcome in thoracic esophageal squamous cell cancer. Tumoral CRP could therefore be an important target for the treatment of this disease.
    Surgery Today 02/2012; 42(7):652-8. DOI:10.1007/s00595-012-0147-3 · 1.53 Impact Factor
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    ABSTRACT: Transforming growth factor (TGF)-β is known to be produced by progressor tumors and to immobilize dendritic cells (DCs) within those tumors. Moreover, although TGF-β1 has been shown to promote tumor progression, there is still no direct, in vivo evidence as to whether TGF-β1 is able to directly induce distant metastasis. To address that issue and investigate the mechanism by which TGF-β1 suppresses DC activity, we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing TGF-β1 or empty vector (mock). The numbers of DCs within lymph nodes draining the resultant TGF-β1-expressing tumors was significantly lower than within nodes draining tumors not expressing TGF-β1. We then injected fluorescently labeled bone marrow-derived dendritic cells into the tumors, and subsequent analysis confirmed that the tumors were the source of the DCs within the tumor-draining lymph nodes, and that there were significantly fewer immature DCs within the nodes draining TGF-β1-expressing tumors than within nodes draining tumors not expressing TGF-β1. In addition, 14 days after tumor cell inoculation, lymph node metastasis occurred more frequently in mice inoculated with TGF-β1 transfectants than in those inoculated with the mock transfectants. These findings provide new evidence that tumor-derived TGF-β1 inhibits migration of DCs from tumors to their draining lymph nodes, and this immunosuppressive effect of TGF-β1 increases the likelihood of metastasis in the affected nodes.
    Journal of Experimental & Clinical Cancer Research 01/2012; 31(1):3. DOI:10.1186/1756-9966-31-3 · 4.43 Impact Factor
  • Anbai A · Koga M · Motoyama S · Sato Y · Jin M · Matsuhashi T · Shibata H · Ohtsuka K · Hashimoto M ·

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    ABSTRACT: In cases of thoracic esophageal cancer, multidirectional lymphatic flow from the tumor means that lymph node metastasis can occur in an area extending from the neck to the abdomen. To validate a method for limiting the performance of three-field lymphadenectomy only to patients who need it, we carried out a prospective study in which superparamagnetic iron oxide (SPIO)-enhanced lymphatic mapping was used to determine whether to perform neck lymph node dissection in patients with submucosal thoracic esophageal cancer. A total of 22 patients with clinically submucosal thoracic squamous cell esophageal cancer, without neck lymph node metastasis, were enrolled. SPIO was endoscopically injected into the peritumoral submucosal layer, after which its appearance in lymph nodes in the neck was evaluated using magnetic resonance imaging (MRI). Neck lymph nodes were then dissected based on the SPIO-enhanced MRI lymphatic mapping. Influx of SPIO into lymph nodes was detected in 21 patients (95% detection rate). SPIO flowed to the neck in 8 (36%) patients. Influx of SPIO into neck lymph nodes was unilateral in five patients and bilateral in three patients, and the lymph nodes were dissected accordingly. A cancer-involved node was identified in two of those patients. In 14 patients, we did not dissect neck nodes. Patients were followed up for 6 to 47 months. The neck lymph node recurrence rate was zero, and the overall recurrence rate was 5%. SPIO-enhanced lymphatic mapping may be useful for estimating the need for three-field lymphadenectomy with neck dissection.
    World Journal of Surgery 01/2012; 36(1):83-9. DOI:10.1007/s00268-011-1322-1 · 2.64 Impact Factor

Publication Stats

974 Citations
358.07 Total Impact Points


  • 1999-2015
    • Akita University Hospital
      Akita, Akita, Japan
  • 1999-2014
    • Akita University
      • • Department of Surgery
      • • Department of Chest, Breast and Endocrinologic Surgery
      • • Graduate School of Medicine
      • • School of Medicine
      • • Department of Emergency and Critical Care Medicine
      Akita, Akita, Japan