Takehiro Tanaka

Okayama University, Okayama, Okayama, Japan

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Publications (67)196.07 Total impact

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    ABSTRACT: Background and study aims: Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time - intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time - intensity curve parameters and tumor microvessel density. Patients and methods: Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time - intensity curve analysis were evaluated retrospectively. Time - intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time - intensity curve parameters was evaluated. Results: The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (P < 0.05); the accuracies of these parameters were 80 %, 86.7 %, and 93.3 %, respectively. The microvessel density of the mural nodule was significantly higher in the HGD/invasive carcinoma group (P = 0.002). There was a strong positive, linear correlation between the echo intensity change of the mural nodule and the microvessel density (r = 0.803, P < 0.001). Conclusions: CH-EUS with time - intensity curve analysis is potentially useful for quantitatively evaluating the blood flow of IPMN microvasculature, and for differentiating between HGD/invasive carcinoma and LGD/IGD.
    No preview · Article · Nov 2015 · Endoscopy
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    ABSTRACT: A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion; however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features.
    No preview · Article · Oct 2015 · Acta medica Okayama
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    ABSTRACT: Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising from mesothelial cells. Evidence suggests that the major pathology associated with asbestos-induced mesothelioma is local iron overload. In the present study, we induced iron-induced mesothelioma in rats based on previous reports. Ten Wistar rats were administered ferric saccharate and nitrilotriacetate intraperitoneally for 5 days a week. Five of the 10 rats exhibited widespread mesotheliomas in the peritoneum and tunica vaginalis. The tumor cells showed positive immunostaining for calretinin, wilms tumor-1, podoplanin, and the oxidative DNA marker 8-hydroxy-2'-deoxyguanosine. In three of the five rats with mesothelioma, array-based comparative genomic hybridization analysis identified a common chromosomal deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene. Downregulation of the TBXAS1 gene was confirmed using quantitative polymerase chain reaction. TBXAS1 gene expression was also reduced in three of four human malignant pleural mesothelioma cell lines compared with normal bronchial epithelial cells. Immunohistochemistry revealed that TBXAS1 expression was weakly positive and positive in five and three out of eight human malignant mesothelioma samples, respectively. In conclusion, TBXAS1 gene expression was downregulated in rats with iron-induced mesothelioma. The relationship between iron overload and TBXAS1 downregulation should be pursued further. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2015 · Cancer Science
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    ABSTRACT: A 78-year-old Japanese man underwent routine esophagogastroduodenoscopy, during which a reddish, flat elevated lesion was observed in the middle third of the esophagus. A bright red area of protrusion appeared in the center of the elevated lesion three months later, and the protruded nodule grew to be a blood blister six months after the initial endoscopy examination. The morphology of the lesion changed from a protruded nodule to a mass with two humps that subsequently returned to a single hump during the three-year observation period. A histological diagnosis of pyogenic granuloma was made based on a biopsy performed at six months. This report illustrates a rare case of an esophageal pyogenic granuloma presenting with a unique endoscopic appearance and morphologic changes. Endoscopic ultrasonography images are also presented.
    Preview · Article · Jul 2015 · Internal Medicine
  • Hiroyuki Kohno · Hiroyuki Okada · Sakiko Hiraoka · Takehiro Tanaka
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    ABSTRACT: A 67-year-old woman was diagnosed with ileocolic Crohn's disease at 61 years of age. Remission had been induced by the monoclonal antibody adalimumab, and maintenance therapy had continued since her diagnosis. However, she developed respiratory symptoms, including a dry cough. A chest CT scan revealed interstitial shadows in the lower pulmonary lobes. Although no sicca symptoms were noted, she was serologically positive for both anti-Sjögren's syndrome-related antigen A and B antibodies, and salivary gland biopsy showed lymphocytic infiltration. Consequently, she was diagnosed as having asymptomatic Sjögren's syndrome. Infection or drug-induced pulmonary disease was considered unlikely, and the interstitial pneumonia was considered an extra-glandular presentation of Sjögren's syndrome. Thus, interstitial shadows, which appear during immunotherapy for Crohn's disease, could indicate asymptomatic Sjögren's syndrome; clinicians should consider this rare clinical picture when assessing such a patient.
    No preview · Article · Jul 2015 · Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology
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    ABSTRACT: The gene expressions of netrin-1 dependence receptors, DCC and UNC5C, are frequently downregulated in many cancers. We hypothesized that downregulation of DCC and UNC5C has an important growth regulatory function in gastric tumorigenesis. In the present study, a series of genetic and epigenetic analyses for DCC and UNC5C were performed in a Japanese cohort of 98 sporadic gastric cancers and corresponding normal gastric mucosa specimens. Loss of heterozygosity (LOH) analyses and microsatellite instability (MSI) analysis was applied to determine chromosomal instability (CIN) and MSI phenotypes, respectively. More than 5 % methylation in the DCC and UNC5C promoters were found in 45 % (44/98) and 32 % (31/98) gastric cancers, respectively, and in 9 % (9/105) and 5 % (5/105) normal gastric mucosa, respectively. Overall, 70 % (58 of 83 informative cases) and 51 % (40 of 79 informative cases) of gastric cancers harbored either LOH or aberrant methylation in the DCC and UNC5C genes, respectively. In total, 77 % (51 of 66 informative cases) of gastric cancers showed cumulative defects in these two dependence receptors and were significantly associated with chromosomal instability. Both DCC and UNC5C were inactivated in 97 % of CIN-positive gastric cancers and in 55 % of CIN-negative gastric cancers. Defect in netrin receptors is a common feature in gastric cancers. DCC alterations are apparent in the early stages, and UNC5C alterations escalate with the progression of the disease, suggesting that the cumulative alterations of netrin-1 receptors was a late event in gastric cancer progression and emphasizing the importance of this growth regulatory pathway in gastric carcinogenesis.
    Full-text · Article · Jul 2015
  • Masaya Iwamuro · Keisuke Hori · Takehiro Tanaka · Hiroyuki Okada

    No preview · Article · Jun 2015 · Gastrointestinal endoscopy
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    ABSTRACT: Although there are some new criteria for human epidermal growth factor receptor 2 (HER2) expression with immunohistochemistry/fluorescence in situ hybridisation (IHC/FISH) in gastric cancer, the method is still ambiguous and is somewhat dependent on the subjective qualities of the evaluator. We used droplet digital polymerase chain reaction (ddPCR) to evaluate HER2 amplification in formalin-fixed and paraffin-embedded (FFPE) samples and cell-free serum circulating tumour DNA (ctDNA) in 25 patients with gastric cancer. The concordance rate of HER2 amplification examined in FFPE samples with ddPCR and IHC/FISH was 92% (23 out of 25). The concordance rate of FFPE with ctDNA was not high (62.5%); however, patients who were HER2-positive by ctDNA had significantly shorter survival compared with HER2-negative patients. Our results demonstrated that this ddPCR method was as effective as IHC/FISH and therefore might become a standard method for analysing not only FFPE but also ctDNA.British Journal of Cancer advance online publication, 21 April 2015; doi:10.1038/bjc.2015.129 www.bjcancer.com.
    No preview · Article · Apr 2015 · British Journal of Cancer
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    ABSTRACT: A 36-year-old Japanese woman presented with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the stomach. The gastric lesions only partially improved after eradication therapy for Helicobacter pylori. A fluorescence in situ hybridization analysis revealed no fusion genes of API2-MALT1, although trisomy of chromosome 18 was identified. Radiation therapy was initiated to treat the gastric lymphoma lesions, resulting in complete remission. However, MALT lymphoma recurred in the stomach 16 months later. This case indicates that intensive follow-up is required for MALT lymphoma associated with chromosomal aberrations in order to detect early relapse.
    No preview · Article · Apr 2015 · Internal Medicine
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    ABSTRACT: Composite tumors in the stomach composed of adenocarcinoma and neuroendocrine carcinoma are rare. We herein report a case of intramucosal gastric mixed adenoneuroendocrine carcinoma (MANEC) that was treated with endoscopic submucosal dissection (ESD). A 77-year-old man who had previously received ESD for early gastric adenocarcinoma underwent esophagogastroduodenoscopy for screening, which showed a depressed lesion on the lesser curvature of the antrum. The tumor was removed en bloc via ESD and pathologically diagnosed as MANEC. The tumor was located within the mucosal layer, and no lymphovascular invasion was evident. Seven months after the ESD procedure, the patient is currently feeling well without recurrence or metastasis.
    No preview · Article · Apr 2015 · Internal Medicine
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    ABSTRACT: A 32-year-old Japanese man presented with a gastric submucosal tumor. Esophagogastroduodenoscopy showed a sessile submucosal tumor measuring approximately 10 mm in diameter on the greater curvature of the gastric antrum. Endoscopic ultrasonography examination revealed a solid tumor with a diameter of 11.8 mm, which was located in the deep mucosal and submucosal layers. The internal echogenicity was homogenous and hypoechoic. Biopsy examinations were performed twice but were not diagnostic since only the intact mucosal layer was obtained. The patient was subsequently diagnosed with ectopic pancreas in the stomach by endoscopic submucosal dissection (ESD). This case underscores the usefulness of the ESD technique for the pathological diagnosis of gastric submucosal tumors.
    Preview · Article · Apr 2015 · Case Reports in Medicine
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    ABSTRACT: We previously showed that a quantitative fecal immunochemical test (FIT) can predict mucosal healing (MH) in ulcerative colitis (UC). Fecal calprotectin (Fcal) has also been reported as an important biomarker of UC activity. The aim of this study was to compare the predictive ability of these two fecal markers for MH in UC. FIT and Fcal were examined in stool samples from consecutive UC patients who underwent colonoscopy. Mucosal status was assessed via the Mayo endoscopic subscore (MES). In total, 105 colonoscopies in 92 UC patients were evaluated in conjunction with the FIT and Fcal results. Both FIT and Fcal results were significantly correlated with MES (Spearman's rank correlation coefficient: 0.61 and 0.58, respectively). The sensitivity and specificity of the FIT values (<100 ng/ml) for predicting MH (MES 0 alone) were 0.95 and 0.62, respectively, whereas those of Fcal (<250 μg/g) were 0.82 and 0.62, respectively. The sensitivities became similar when MH was defined as MES 0 or 1 (0.86 vs. 0.86). Although the predictability of MH evaluated by the area under the receiver operating characteristics curve was similar for the two fecal markers (FIT 0.83 vs. Fcal 0.82 for MES 0 alone), the FIT results were relatively robust regardless of the cutoff value selected. Both FIT and Fcal can efficiently predict MH in UC, but FIT appears to be more sensitive than Fcal for predicting MES 0 alone.Am J Gastroenterol advance online publication, 31 March 2015; doi:10.1038/ajg.2015.66.
    No preview · Article · Mar 2015 · The American Journal of Gastroenterology
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    ABSTRACT: The sensitivity and specificity of magnified endoscopic features for differentiating follicular lymphoma from other diseases with duodenal whitish lesions have never been investigated. Here we compared the magnified endoscopic features of duodenal follicular lymphoma with those of other whitish lesions. We retrospectively reviewed the cases of patients with follicular lymphoma (n=9), lymphangiectasia (n=7), adenoma (n=10), duodenitis (n=4), erosion (n=1), lymphangioma (n=1), and hyperplastic polyp (n=1). The magnified features of the nine follicular lymphomas included enlarged villi (n=8), dilated microvessels (n=5), and opaque white spots of various sizes (n=9). The lymphangiectasias showed enlarged villi, dilated microvessels, and white spots, but the sizes of the white spots were relatively homogeneous and their margin was clear. Observation of the adenoma and duodenitis revealed only whitish villi. Although the lymphangioma was indistinguishable from the follicular lymphomas by magnified features, it was easily diagnosed based on the macroscopic morphology. In conclusion, magnified endoscopic features, in combination with macroscopic features, are useful for differentiating follicular lymphomas from other duodenal diseases presenting whitish lesions.
    No preview · Article · Feb 2015 · Acta medica Okayama
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    ABSTRACT: We report a case of intraocular relapse of extranodal NK/T-cell lymphoma with anterior chamber hypopyon and retinal infiltrates. A 55-year-old man developed fever, malaise, anorexia, and hepatosplenomegaly, and was diagnosed with NK/T-cell lymphoma by liver biopsy. He underwent 2 courses of SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy, followed by myeloablative peripheral blood stem cell transplantation, donated by his brother. Two months later, he developed high-grade fever, hepatosplenomegaly, and peritoneal lymphadenopathy, and the relapse with hemophagocytic syndrome was diagnosed by bone marrow biopsy. He underwent 2 courses of SMILE salvage chemotherapy, followed by non-myeloablative peripheral blood stem cell transplantation, donated by his son. Two months later, he noticed blurred vision in both eyes. The right eye had aqueous cells and keratic precipitates, but no retinal lesions. The left eye had hypopyon in the anterior chamber with numerous aqueous cells, and retinal white infiltrates with retinal hemorrhages. The aqueous cells, obtained by anterior chamber paracentesis, were positive for CD3, CD56, and Epstein-Barr virus-encoded RNA, but negative for CD20 by immunocytochemical staining. Head magnetic resonance imaging demonstrated white matter lesions in the anterior to parietal lobes on the right side. The patient underwent intrathecal methotrexate injection and external beam radiation at 40 Gy, covering the entire brain and both eyes. The retinal lesions and hypopyon disappeared. Two months later, the patient died of renal failure, and autopsy demonstrated multi-organ involvement of lymphoma cells. In conclusion, we report a case of NK/T-cell lymphoma relapse with intraocular lesions, after combined chemotherapy and hematopoietic stem cell transplantation. [J Clin Exp Hematop 55(3) : 157-161, 2015]
    Preview · Article · Jan 2015 · Journal of Clinical and Experimental Hematopathology
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    ABSTRACT: Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation. Recently, in addition to Th2 cells, Th1 and Th17 cells have been shown to contribute to chronic GVHD progression. IL-12 induces Th1 cells and IL-23 plays a role in stabilizing and/or amplifying Th17 cells, as well as in inducing IFN-γ/IL-17 double-producing cells. Because mAb targeting the p40 subunit common to both IL-12 and IL-23 can inhibit both IL-12R and IL-23R-mediated signaling, we investigated the effects of anti-p40 mAb on a well-defined chronic GVHD mice model. Treatment of anti-p40 mAb in allogeneic recipients significantly reduced the severity of clinical and pathological chronic GVHD. Intracellular staining revealed that IFN-γ single-positive (IL-17(-)) and IFN-γ/IL-17 double-positive cells were suppressed in anti-p40 mAb-treated allogeneic recipients compared with control recipients. The cytokine levels of IFN-γ and IL-17 were also decreased in serum from anti-p40 mAb-treated allogeneic recipients. T-bet expression of donor IL-17(+) CD4(+) T cells was reduced significantly in anti-p40 mAb-treated recipients, and this reduction in T-bet expression was associated with IL-22 production by donor T cells. These results suggested that anti-p40 mAb attenuated chronic GVHD via suppression of IFN-γ/IL-17-producing cells, and that targeting the IL-12/IL-23 pathway may represent a promising therapeutic strategy for preventing and treating chronic GVHD. Copyright © 2014 by The American Association of Immunologists, Inc.
    No preview · Article · Dec 2014 · The Journal of Immunology
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    ABSTRACT: A 6 2-year-old man with advanced gastric cancer was referred to our hospital. A gastroscopy revealed a type 3 tumor invading the esophagus in the lesser curvature of the stomach cardia. We diagnosed the tumor as cStageIIIB(T4bN1M0) gastric cancer. For the best chance of a pathological complete response, we selected neoadjuvant chemotherapy(NAC)with S-1+CDDP(SP therapy). A total gastrectomy with lymph node dissection was performed after 2 courses of SP therapy. Pathological evaluation of the resected stomach and lymph nodes indicated an absence of cancerous cells, confirming a pathological complete response(pCR). The patient has been followed up for 4 months without evidence of recurrence.
    No preview · Article · Nov 2014 · Gan to kagaku ryoho. Cancer & chemotherapy
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    ABSTRACT: A cell line named PRU-1, derived from a Langerhans cell (LC) histiocytosis (LCH) skull lesion of a 7-year-old boy, was established and characterized. PRU-1 is an adherent spindle-shaped cell line that shows no Birbeck granules on electron microscopy. Flow cytometric analysis of cells collected from the early seventh passage showed no LC phenotypes of CD1a and S100 protein. Immunostaining of PRU-1 cells also revealed no expression of LC markers but showed expression of CD11c, CD54 (ICAM-1) and CD68, which was also observed in some peripherally located cells of the original LCH lesion. The PRU-1 cells stained positive for factor XIIIa and negative for CD34, suggesting a dermal dendritic cell phenotype. Cytogenetic analyses revealed abnormalities such as 39,XY,-2,-4,-8,-12,-12,-14,add(18)(q21),20,+mar and 44,XY,-11,-14,add(18)(q21). TCRγ rearrangement in the PRU-1 cells was not amplified by PCR. Tumorigenicity was not proven by xenografting into SCID mice. A conditioned medium from PRU-1 culture induced the proliferation of peripheral blood lymphocytes as well as the activation of monocytes from a healthy donor into CD1a-positive LC-like cells. Because the phenotypic characteristics of PRU-1 differed from those of CD1a-positive abnormal LC-like cells (LCH cells), it was likely that the PRU-1 cells were derived from peripherally located cells of the LCH lesion rather than LCH cells. LCH has been regarded as a type of granulomatous neoplasm with several intermingled inflammatory cells and influenced by stimuli such as Merkel cell polyomavirus (MCPyV) infection or cigarette smoking. However, in the PRU-1 cells, MCPyV-DNA was not detected by PCR. Stromal cell-like PRU-1 cells are likely to produce some growth or differentiation factors, which may play important roles in LCH lesion formation, cell maintenance and LC-like cell induction.
    No preview · Article · Oct 2014 · Oncology Reports
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    ABSTRACT: Background: Differentiating sessile serrated adenoma/polyp (SSA/P) from hyperplastic polyp (HP) is clinically important in determining the necessity of endoscopic resection or recommending appropriate surveillance. There are few reports of characterization of SSA/P using narrowband imaging and chromoendoscopy with and without magnification. We aimed to establish imaging criteria to aid real-time diagnosis of SSA/P. Methods: Patients with pale sessile or flat lesions of 6 mm or greater were prospectively enrolled in this multicenter trial. Nine endoscopic criteria, determined in real time, were investigated for possible association with SSA/P. Endoscopic mucosal resection was performed; specimens were retrieved and analyzed by histopathological examination. Results: In 63 patients, 89 lesions were detected, including 41 HP, 38 SSA/P, five mixed polyps, and five other lesions. Right-side colon location, lesion size of 10 mm or greater, excessive mucus, the presence of a varicose microvascular vessel (VMV) noted with high-magnification narrowband imaging, and type III(H) pit pattern were each commonly associated with SSA/P compared with HP. Multivariate analysis substantiated three independent endoscopic criteria for SSA/P: the presence of VMV (p = 0.001), lesion size of 10 mm or greater (p = 0.0017), and right-side location (p = 0.0041), with odds ratios of 8.2, 7.2, and 6.1, respectively. The presence of VMV had a significantly higher specificity (87.8%) than the other two independent endoscopic criteria (p = 0.0007 and p = 0.0008, respectively), but a lower sensitivity (57.9%), whereas a combination of the three criteria (two or more positive) increased the sensitivity significantly (89.5% and p = 0.0033) and had a higher degree of accuracy (82.3%). Conclusions: Three endoscopic criteria individually and in combination were effective in predicting a diagnosis of SSA/P without the need for chromoendoscopy.
    No preview · Article · Oct 2014 · Journal of Gastroenterology
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    ABSTRACT: A 45-year-old female who presented with loss of consciousness and a cold sweat was found to have a pancreatic tumor and multiple liver metastases. Laboratory studies showed marked hypoglycemia and inappropriately elevated serum insulin, C-peptide, and serum tumor markers. Fine needle aspiration revealed Grade 3 small-cell type primary pancreatic neuroendocrine carcinoma. Consequently, the diagnosis of malignant insulinoma was made. Transarterial embolization (TAE) for hepatic metastases resulted in the reduction of tumor volume and prompt resolution of hypoglycemic attacks, whereas diazoxide and systemic chemotherapy had been ineffective for controlling blood glucose levels, and octreotide was unavailable due to the allergic effect. This case report highlights the potential usefulness of TAE for malignant insulinomas in the management of hypoglycemia.
    No preview · Article · Oct 2014 · Acta medica Okayama
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    ABSTRACT: A 55-year-old woman underwent a total thyroidectomy for carcinoma showing thymus-like differentiation (CASTLE). The patient was referred to our hospital after the tumor was found to have directly invaded the cervical esophagus and the entire circumference of the trachea. A total thyroidectomy was performed, followed by end-to-end anastomosis of the trachea, suprahyoid release and dissection of bilateral pulmonary ligaments. No major complications, including anastomotic dehiscence or stenosis, were observed. The patient experienced some swallowing disturbances and hoarseness during the perioperative period but fully recovered. Radiotherapy to the neck was performed as an adjuvant therapy. Eleven months after surgery, lower back pain and right leg numbness developed and led to gait inability. Multiple lung and bone recurrences were observed, but no local recurrence. Palliative radiotherapy to the bone metastasis was performed. The patient died of pleural metastasis 14 months after the initial diagnosis of CASTLE.
    Full-text · Article · Sep 2014 · Case Reports in Oncology

Publication Stats

763 Citations
196.07 Total Impact Points

Institutions

  • 2003-2015
    • Okayama University
      • • Department of Pathology and Oncology
      • • Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
      Okayama, Okayama, Japan