Hitoshi Katai

National Hospital Organization Kyushu Cancer Center, Hukuoka, Fukuoka, Japan

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Publications (165)605.3 Total impact

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    ABSTRACT: An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Two years after the initial ESD, a 0-IIc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum. The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma. ESD was performed for this lesion and en bloc resection with negative margins was achieved. Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer (1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection. Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection. Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD. Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known. The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer.
    04/2015; 21(14):4385-90. DOI:10.3748/wjg.v21.i14.4385
  • World Journal of Gastroenterology 04/2015; 14(21):4385-4390. · 2.43 Impact Factor
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    ABSTRACT: The dormancy of tumor cells is a major problem in chemotherapy, since it limits the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One potential way to overcome chemo-resistance is to "wake up" these dormant cells. Here we show that the opioid antagonist methylnaltrexone (MNTX) enhances the effect of docetaxel (Doc) by blocking a cell growth-suppressive pathway. We found that PENK, which encodes opioid growth factor (OGF) and suppresses cell growth, is predominantly expressed in diffuse-type gastric cancers (GCs). The blockade of OGF signaling by MNTX releases cells from their arrest and boosts the effect of Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX significantly prolongs survival, alleviates abdominal pain, and diminishes Doc-resistant spheroids on the peritoneal membrane in model mice. These results suggest that blockade of the pathways that suppress cell growth may enhance the effects of anti-tumor drugs.
    PLoS ONE 04/2015; 10(4):e0123407. DOI:10.1371/journal.pone.0123407 · 3.53 Impact Factor
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    ABSTRACT: The aim of this study was to clarify the significance of DNA methylation alterations during gastric carcinogenesis. Single-CpG-resolution genome-wide DNA methylation analysis using the Infinium assay was performed on 109 samples of non-cancerous gastric mucosa (N) and 105 samples of tumorous tissue (T). DNA methylation alterations in T samples relative to N samples were evident for 3,861 probes. Since N can be at the precancerous stage according to the field cancerization concept, unsupervised hierarchical clustering based on DNA methylation levels was performed on N samples (βN) using the 3,861 probes. This divided the 109 patients into three clusters: A (n=20), B1 (n=20) and B2 (n=69). Gastric carcinomas belonging to Cluster B1 showed tumor aggressiveness more frequently than those belonging to Clusters A and B2. The recurrence-free and overall survival rates of patients in Cluster B1 were lower than those of patients in Clusters A and B2. Sixty hallmark genes for which βN characterized the epigenetic clustering were identified. We then focused on DNA methylation levels in T samples (βT) of the 60 hallmark genes. In 48 of them, including the ADAM23, OLFM4, AMER2, GPSM1, CCL28, DTX1 and COL23A1 genes, βT was again significantly correlated with tumor aggressiveness, and the recurrence-free and/or overall survival rates. Multivariate analyses revealed that βT was a significant prognostic factor, being independent of clinicopathological parameters. These data indicate that DNA methylation profiles at the precancerous stage may be inherited by gastric carcinomas themselves, thus determining tumor aggressiveness and patient outcome. © The Author 2015. Published by Oxford University Press.
    Carcinogenesis 03/2015; 74(19 Supplement). DOI:10.1093/carcin/bgv013 · 5.27 Impact Factor
  • Hitoshi Katai
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    ABSTRACT: More than 20 years after the introduction of laparoscopic gastrectomy, two ongoing, large-scale randomized controlled trials are currently being conducted in Japan: JCOG0912 for patients with stage I disease and JLSSG0901 for patients with advanced cancer. Both trials are designed to evaluate the non-inferiority of laparoscopic-assisted distal gastrectomy to its open counterpart. The primary end-point of JCOG0912 is overall survival, whereas that of JLSSG0901 is relapse-free survival. Quality control for the surgeries is being strictly performed in each study; eligibility criteria apply to participating surgeons and a central review of the surgical procedure has been conducted. The accrual of patients for JCOG0912 and for JLSSG0901 (phase II) is complete, and the disclosure of level I evidence is being awaited.
    Asian Journal of Endoscopic Surgery 03/2015; 8(2). DOI:10.1111/ases.12171
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    ABSTRACT: To analyze the mismatch repair (MMR) status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas. We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas. The results were further correlated with clinicopathological variables. The loss of any MMR protein expression, indicative of MMR deficiency, was observed in 38 cases (7.8%) and was significantly associated with an older age (68.6 ± 9.2 vs 60.4 ± 11.7, P < 0.001), a female sex (55.3% vs 31.3%, P = 0.004), an antral location (44.7% vs 25.7%, P = 0.021), and a differentiated histology (57.9% vs 39.7%, P = 0.023). Abnormal ARID1A expression, including reduced or loss of ARID1A expression, was observed in 109 cases (22.3%) and was significantly correlated with lymphatic invasion (80.7% vs 69.5%, P = 0.022) and lymph node metastasis (83.5% vs 73.7%, P = 0.042). The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency (47.4% vs 20.2%, P < 0.001). A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor (HR = 1.36, 95%CI: 1.01-1.84; P = 0.040). Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion, lymph node metastasis, poor prognosis, and MMR deficiency in gastric adenocarcinomas.
    World Journal of Gastroenterology 02/2015; 21(7):2159-68. DOI:10.3748/wjg.v21.i7.2159 · 2.43 Impact Factor
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    ABSTRACT: Tumor samples are unavoidably contaminated with coexisting normal cells. Here, we aimed to establish a DNA methylation marker to estimate the fraction of gastric cancer (GC) cells in any DNA sample by isolating genomic regions specifically methylated in GC cells. Genome-wide and gene-specific methylation analyses were conducted with an Infinium HumanMethylation450 BeadChip array and by quantitative methylation-specific PCR, respectively. Purified cancer and noncancer cells were prepared by laser-capture microdissection. TP53 mutation data were obtained from our previous study using next-generation target sequencing. Genome-wide DNA methylation analysis of 12 GC cell lines, 30 GCs, six normal gastric mucosae, one sample of peripheral leukocytes, and four noncancerous gastric mucosae identified OSR2, PPFIA3, and VAV3 as barely methylated in normal cells and highly methylated in cancer cells. Quantitative methylation-specific PCR using 26 independent GCs validated that one or more of them was highly methylated in all of the GCs. Using four pairs of purified cells, we confirmed the three genes were highly methylated (85 % or more) in cancer cells and barely methylated (5 % or less) in noncancer cells. The cancer cell fraction assessed by the panel of the three genes showed good correlation with that assessed by the TP53 mutant allele frequency in 13 GCs (r = 0.77). After correction of the GC cell fraction, unsupervised clustering analysis of the genome-wide DNA methylation profiles yielded clearer clustering. A DNA methylation marker-namely, the panel of the three genes-is useful to estimate the cancer cell fraction in GCs.
    Gastric Cancer 02/2015; DOI:10.1007/s10120-015-0475-2 · 4.83 Impact Factor
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    ABSTRACT: Diffuse-type solid tumors are often composed of a high proportion of rarely proliferating (i.e., dormant) cancer cells, strongly indicating the involvement of cancer stem cells (CSCs) Although diffuse-type gastric cancer (GC) patients have a poor prognosis due to high-frequent development of peritoneal dissemination (PD), it is limited knowledge that the PD-associated CSCs and efficacy of CSC-targeting therapy in diffuse-type GC. In this study, we established highly metastatic GC cell lines by in vivo selection designed for the enrichment of PD-associated GC cells. By microarray analysis, we found C-X-C chemokine receptor type 4 (CXCR4) can be a novel marker for highly metastatic CSCs, since CXCR4-positive cells can grow anchorage-independently, initiate tumors in mice, be resistant to cytotoxic drug, and produce differentiated daughter cells. In clinical samples, these CXCR4-positive cells were found from not only late metastasis stage (accumulated ascites) but also earlier stage (peritoneal washings). Moreover, treatment with transforming growth factor-β enhanced the anti-cancer effect of docetaxel via induction of cell differentiation/asymmetric cell division of the CXCR4-positive gastric CSCs even in a dormant state. Therefore, differentiation inducers hold promise for obtaining the maximum therapeutic outcome from currently available anti-cancer drugs through re-cycling of CSCs.
    PLoS ONE 01/2015; 10(6):e0130808. DOI:10.1371/journal.pone.0130808 · 3.53 Impact Factor
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    ABSTRACT: A field for cancerization, or a field defect, is formed by the accumulation of genetic and epigenetic alterations in normal-appearing tissues, and is involved in various cancers, especially multiple cancers. Epigenetic alterations are frequently present in chronic inflammation-exposed tissues, but information on individual genes involved in the formation of a field defect is still fragmental. Here, using non-cancerous gastric tissues of cancer patients, we isolated 16 aberrantly methylated genes, and identified chromatin remodelers ACTL6B and SMARCA1 as novel genes frequently methylated in non-cancerous tissues. SMARCA1 was expressed at high levels in normal gastric tissues, but was frequently silenced by aberrant methylation in gastric cancer cells. Moreover, somatic mutations of additional chromatin remodelers, such as ARID1A, SMARCA2, and SMARCA4, were found in 30% of gastric cancers. Mutant allele frequency suggested that the majority of cancer cells harbored a mutation when present. Depletion of a chromatin remodeler, SMARCA1 or SMARCA2, in cancer cell lines promoted their growth. These results showed that epigenetic and genetic alterations of chromatin remodelers are induced at an early stage of carcinogenesis and are frequently involved in the formation of a field defect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Cancer Letters 11/2014; 357(1). DOI:10.1016/j.canlet.2014.11.038 · 5.02 Impact Factor
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    ABSTRACT: Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms of borderline malignancy that generally affect children and young adults.1 IMTs most commonly occur in the lung, mesentery, and retroperitoneum.1 Gastric IMTs are extremely rare, with less than 10 cases reported in English-language literature.2This article is protected by copyright. All rights reserved.
    Histopathology 10/2014; 66(4). DOI:10.1111/his.12575 · 3.30 Impact Factor
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    ABSTRACT: Prognostic markers are urgently needed to optimize the postoperative treatment strategies for gastrointestinal stromal tumor (GIST). GISTs of the small intestine (I-GISTs) show more aggressive behavior than those of the stomach (S-GISTs), and the molecular background of the malignancy in I-GISTs may include potential prognostic biomarkers. We conducted integrated proteomic and transcriptomic analysis to identify genes showing differential expressions according to the tumor site. We generated protein expression profiles for 4 cases each of surgically resected I-GISTs and S-GISTs using label-free proteomic analysis. For proteins showing differential expressions, global mRNA expression was compared between 9 I-GISTs and 23 S-GISTs. Among the 2555 genes analyzed, we found that promyelocytic leukemia (PML), a tumor suppressor gene, was significantly down-regulated in I-GISTs at both the protein and mRNA levels (P <0.01; fold difference ≥2.0). Immunohistochemistry of 254 additional cases from multiple clinical facilities showed that PML-negative cases were significantly frequent in the I-GIST group (P <0.001). The 5-year recurrence-free survival rate was significantly lower in the PML-negative than in the PML-positive cases (60.1% versus 91.7%; P <0.001). Multivariate analysis revealed that down-regulation of PML was an independent unfavorable prognostic factor (HR = 2.739; P = 0.001). Our study indicated that prognostication based on PML expression may have potential for optimizing the treatment strategy for GIST patients. Further validation studies of PML for clinical application, and the investigation for the mechanistic significance of PML to clarify the molecular backgrounds of malignancy in GIST seem warranted.This article is protected by copyright. All rights reserved.
    Cancer Science 10/2014; 106(1). DOI:10.1111/cas.12565 · 3.53 Impact Factor
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    ABSTRACT: The efficacy of 5-fluorouracil (5FU)-based therapy, which remains the cornerstone of gastrointestinal cancer treatment, depends upon the expression of enzymes involved in pyrimidine metabolism, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT). We analyzed the expression of these genes in patients enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) and their possible roles as biomarkers for treatment outcomes.
    Gastric Cancer 08/2014; DOI:10.1007/s10120-014-0413-8 · 4.83 Impact Factor
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    ABSTRACT: Background and Objectives The optimal surgical procedure for gastric remnant carcinoma (GRC) remains debatable. The aim of this study was to retrospectively evaluate the surgical treatments for T2-4 GRC developing after distal gastrectomy for gastric cancer.Methods Between 1970 and 2012, a total of 50 patients underwent R0 resection for T2-4 GRC. The clinicopathologic features, therapeutic methods, and follow-up data of these patients were reviewed.ResultsThe tumor was located at a non-anastomotic site of the remnant stomach in 43 of the 50 patients. Total gastrectomy was performed in 48 patients and partial gastrectomy was in two patients. Lymph node metastasis was found in 19 patients. Major postoperative complications occurred in 16 patients. The overall 1-, 3-, and 5-year survival rates of the 50 patients were 90%, 66%, and 44%, respectively. Presence of small intestinal or esophageal infiltration and postoperative complications was independently associated with poorer survival. Dissection of the perigastric and splenic hilar/artery nodes was found to have potential therapeutic benefit.Conclusions Surgical resection for T2-4 GRC developing after distal gastrectomy for gastric cancer can be invasive, but is feasible and effective. Total gastrectomy with splenectomy is one of the recommendable procedures for this disease. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 08/2014; 111(2). DOI:10.1002/jso.23774 · 2.84 Impact Factor
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    ABSTRACT: Background We recently reported that the presence of a papillary adenocarcinoma (pap) component was an independent risk factor for lymphatic involvement in endoscopically resected early gastric cancer (EGC). This study aimed to investigate the potential association between the presence of a pap component in EGC and lymph node metastasis (LNM). Methods In order to evaluate the association between LNM and clinicopathological features, including a pap component, we reviewed 628 surgically resected EGCs at our institution between 2009 and 2012. Clinicopathological features included age, gender, tumor location, macroscopic type, tumor size, histological type, depth, ulcerative findings, and lymphatic and venous involvement. In addition, the association between clinicopathological features and lymphatic involvement was also evaluated. Results LNM was observed in 52 cases (8.3%). Univariate analyses revealed a significant correlation between a pap component and LNM as well as tumor size, depth, macroscopic type, a poorly differentiated adenocarcinoma component, and lymphatic and venous involvement. The percentage of positive LNM among the EGC cases with a pap component was significantly higher than in those without the component (18.2 vs. 7.3%, P = 0.010). Via multivariate analyses lymphatic involvement was identified as the strongest risk factor for LNM [odds ratio (OR) 14.1] and a pap component was revealed as an independent risk factor for lymphatic involvement (OR 3.1). Conclusion Our study revealed that EGC cases with a pap component were at higher risk of lymphatic involvement and showed a higher percentage of positive LNM. More attention should be paid to a pap component in EGC.
    Journal of Gastroenterology 08/2014; 50(4). DOI:10.1007/s00535-014-0991-6 · 4.02 Impact Factor
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    ABSTRACT: Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival.
    Gastric Cancer 07/2014; DOI:10.1007/s10120-014-0398-3 · 4.83 Impact Factor
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    ABSTRACT: HER2 protein overexpression and gene amplification are important biomarkers for identifying gastric cancer patients who may respond to HER2-targeted therapy using trastuzumab. The aim of this study was to evaluate the concordance between HER2 protein expression and gene amplification in both surgically resected tumors and matched biopsy specimens of gastric cancer. Formalin-fixed, paraffin-embedded sections of 207 surgically resected tumors and 158 biopsy specimens from 207 cases of invasive intestinal-type gastric cancer were analyzed. Protein expression was assessed using immunohistochemistry and graded by the modified scoring criteria for gastric cancer. Gene amplification was evaluated by fluorescence in situ hybridization (FISH). HER2 overexpression was observed in 17 % of both surgically resected tumors (35/207) and biopsy specimens (26/158). HER2 gene amplification was detected in 31 % (61/200) of surgically resected tumors and 32 % (47/147) of biopsy specimens. Except for immunohistochemistry (IHC) equivocal (2+) cases, the concordance rates between IHC and FISH was 90.9 % in surgically resected tumors and 90.2 % in biopsy specimens. In IHC 2+ cases, the rate of HER2 gene amplification was 56 and 38 % in surgically resected tumors and biopsy specimens, respectively. IHC-FISH discordance was mainly due to intratumoral heterogeneity and low-level gene amplification. The concordance rate of IHC results between surgically resected specimens and the corresponding biopsy specimen was 57.0 % (κ = 0.224), and in discordant cases, HER2 positivity in biopsies and HER2 negativity in surgically resected tumors were most common. The concordance rate of FISH results between surgically resected tumors and biopsy specimens was 72.7 % (κ = 0.313). Polysomy 17 was detected in 5.5 and 7.5 % of surgically resected tumors and biopsy specimens and significantly correlated with IHC score, but polysomy 17 could explain one IHC score 3+ and FISH-negative tumor only. Although high concordance rates between HER2-protein expression and gene amplification were observed in both surgically resected tumors and biopsy specimens, the agreement levels were evaluated to be fair. Polysomy 17 was infrequent and seemed to have limited impact on gastric HER2 testing. Further investigations are required for an appropriate biopsy method to reduce false results of HER2 testing and to clarify the clinical significance of intratumoral heterogeneity in HER2 status.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2014; 465(2). DOI:10.1007/s00428-014-1597-3 · 2.56 Impact Factor
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    ABSTRACT: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). Of 39,859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5,196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3,085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2,111 patients who underwent surgery in 2003 were used as an external validation set. Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 vs. 0.61; p<0.001). Moreover, calibration was accurate. We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.
    Annals of Oncology 03/2014; 25(6). DOI:10.1093/annonc/mdu125 · 6.58 Impact Factor
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    ABSTRACT: Chromosomal abnormalities are good guideposts when hunting for cancer-related genes. We analyzed copy number alterations of 163 primary gastric cancers using array-based comparative genomic hybridization and simultaneously performed a genome-wide integrated analysis of copy number and gene expression using microarray data for 58 tumors. We showed that chromosome 6p21 amplification frequently occurred secondary to ERBB2 amplification, was associated with poorer prognosis and caused overexpression of half of the genes mapped. A comprehensive small interfering RNA knockdown of 58 genes overexpressed in tumors identified 32 genes that reduced gastric cancer cell growth. Enforced expression of 16 of these genes promoted cell growth in vitro, and six genes showing more than two-fold activity conferred tumor-forming ability in vivo. Among these six candidates, GLO1, encoding a detoxifying enzyme glyoxalase I (GLO1), exhibited the strongest tumor-forming activity. Coexpression of other genes with GLO1 enhanced growth-stimulating activity. A GLO1 inhibitor, S-p-bromobenzyl glutathione cyclopentyl diester, inhibited the growth of two-thirds of 24 gastric cancer cell lines examined. The efficacy was found to be associated with the mRNA expression ratio of GLO1 to GLO2, encoding glyoxalase II (GLO2), another constituent of the glyoxalase system. GLO1 downregulation affected cell growth through inactivating central carbon metabolism and reduced the transcriptional activities of nuclear factor kappa B and activator protein-1. Our study demonstrates that GLO1 is a novel metabolic oncogene of the 6p21 amplicon, which promotes tumor growth and aberrant transcriptional signals via regulating cellular metabolic activities for energy production and could be a potential therapeutic target in gastric cancer.Oncogene advance online publication, 24 March 2014; doi:10.1038/onc.2014.57.
    Oncogene 03/2014; 34(9). DOI:10.1038/onc.2014.57 · 8.56 Impact Factor
  • Hiroharu Yamashita, Hitoshi Katai
    Annals of surgery 03/2014; 261(3). DOI:10.1097/SLA.0000000000000589 · 7.19 Impact Factor
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    ABSTRACT: The profiles of genetic and epigenetic alterations in cancer-related pathways are considered to be useful for selection of patients likely to respond to specific drugs, including molecular-targeted and epigenetic drugs. In this study, we aimed to characterize such profiles in gastric cancers (GCs). Genetic alterations of 55 cancer-related genes were analyzed by a benchtop next-generation sequencer. DNA methylation statuses were analyzed by a bead array with 485,512 probes. The WNT pathway was activated by mutations of CTNNB1 in 2 GCs and potentially by aberrant methylation of its negative regulators, such as DKK3, NKD1, and SFRP1, in 49 GCs. The AKT/mTOR pathway was activated by mutations of PIK3CA and PTPN11 in 4 GCs. The MAPK pathway was activated by mutations and gene amplifications of ERBB2, FLT3, and KRAS in 11 GCs. Cell-cycle regulation was affected by aberrant methylation of CDKN2A and CHFR in 13 GCs. Mismatch repair was affected by a mutation of MLH1 in 1 GC and by aberrant methylation of MLH1 in 2 GCs. The p53 pathway was inactivated by mutations of TP53 in 19 GCs and potentially by aberrant methylation of its downstream genes in 38 GCs. Cell adhesion was affected by mutations of CDH1 in 2 GCs. Genes involved in cancer-related pathways were more frequently affected by epigenetic alterations than by genetic alterations. The profiles of genetic and epigenetic alterations are expected to be useful for selection of the patients who are likely to benefit from specific drugs.
    Gastric Cancer 02/2014; DOI:10.1007/s10120-014-0348-0 · 4.83 Impact Factor

Publication Stats

3k Citations
605.30 Total Impact Points

Institutions

  • 2006–2015
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 1995–2015
    • National Cancer Center, Japan
      • • Endoscopy Division
      • • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
  • 2012–2014
    • Hyogo College of Medicine
      • Department of Surgery
      Nishinomiya, Hyōgo, Japan
  • 2001
    • The University of Tokyo
      Tōkyō, Japan
  • 1994
    • Hospital Dos de Mayo
      Λίμα, Provincia de Lima, Peru