Hirokazu Taniguchi

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

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Publications (138)526.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Endoscopic resection (ER) has been increasingly used for the treatment of rectal neuroendocrine tumors (NETs); however, only limited data are available on its long-term outcomes. This study analyzed the long-term outcomes of rectal NETs treated by ER and characterized potential risk factors for metastasis in these cases, with emphasis on lymphovascular invasion. We retrospectively analyzed the clinicopathological features and outcomes of 86 patients with 90 rectal NETs who had been treated by ER. Lymphovascular invasion was reevaluated using elastic-staining and double-staining immunohistochemistry. En bloc resection with tumor-free margins was achieved in 87 lesions (96.7 %). The median tumor size was 5 mm (range 2-13), and all the lesions were confined to the submucosal layer. The Ki-67 index was less than 3 % in all the lesions, which were therefore classified as NET G1. Elastic-staining and double-staining immunohistochemistry revealed the presence of lymphatic and venous invasion in 23 (25.6 %) and 35 lesions (36.7 %), respectively. Collectively, lymphatic and/or vascular invasion was identified in 42 lesions (46.7 %). All cases were followed up without additional surgery, and no metastasis or recurrence was detected during the median follow-up period of 67.5 months. This study showed an excellent long-term prognosis following ER of patients with rectal NETs, confirming that ER is a valid treatment option for small rectal NETs. The present study also revealed highly prevalent lymphovascular invasion even in minute rectal NETs; this observation raises a question regarding its significance as a risk factor for metastasis.
    Journal of Gastroenterology 05/2015; DOI:10.1007/s00535-015-1079-7 · 4.02 Impact Factor
  • Gastrointestinal Endoscopy 05/2015; 81(5):AB274-AB275. DOI:10.1016/j.gie.2015.03.1382 · 4.90 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-746. DOI:10.1016/S0016-5085(15)32551-8 · 13.93 Impact Factor
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    ABSTRACT: A sessile serrated adenoma/polyp (SSA/P) is a common type of colorectal polyp that possesses malignant potential. Although narrow-band imaging (NBI) can easily differentiate neoplastic lesions from hyperplastic polyps (HPs), SSA/Ps can be a challenge to distinguish from HPs. To investigate specific endoscopic features of SSA/Ps by using NBI with optical magnification. Retrospective study. Single high-volume referral center. A total of 289 patients with histopathologically proven SSA/Ps or HPs obtained from colonoscopic polypectomy. Endoscopic images obtained by using NBI with optical magnification of 242 lesions (124 HPs, 118 SSA/Ps) removed between January 2010 and December 2012 were independently evaluated by 2 experienced endoscopists. Three external experienced endoscopists systematically validated the diagnostic accuracies by using 40 lesions (21 HPs and 19 SSA/Ps) removed between January and March 2013. Specific endoscopic features of SSA/Ps by using 5 potential characteristics: dilated and branching vessels (DBVs), irregular dark spots, a regular network pattern, a disorganized network pattern, and a dense pattern. Multivariate analysis demonstrated that DBV had a 2.3-fold odds ratio (95% confidence interval, 0.96-5.69) among SSA/Ps compared with HPs (sensitivity, 56%; specificity, 75%; accuracy, 65%). Interobserver and intraobserver agreement indicated almost perfect agreement for DBVs in both the evaluation and validation studies. When DBVs, proximal location, and tumor size (≥10 mm) were combined, the positive predictive value was 92% and the area under the curve was 0.783 in the receiver-operating characteristics by using the validation group. Retrospective study. The current study suggests that a DBV is a potentially unique endoscopic feature of a colorectal SSA/P. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
    Gastrointestinal endoscopy 03/2015; DOI:10.1016/j.gie.2014.12.037 · 4.90 Impact Factor
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    ABSTRACT: Detection of immunoglobulin light chain restriction (LCR) by flow cytometry (FCM) is a useful tool for B-cell non-Hodgkin lymphoma (B-NHL) diagnosis. Here, we identified B-NHLs without LCR by FCM and investigated the pathological causes for lack of LCR. 89/471 cases (19%) of B-NHL were LCR-negative. The incidence of lack of LCR was 30% both in diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), and was 6% in follicular lymphoma (FL). In DLBCL cases, low expression of surface membrane light chain (33%), low proportion of lymphoma cells (11%), CD45 negativity (9%), and destruction or sampling error were suggested as reasons for lack of LCR. In MZL cases, low proportion of lymphoma cells owing to admixture of many reactive germinal centres, and non-detection of plasmacytoid lymphoma cells by CD45 gating might be the reasons. Based on pathological subtypes, the frequency and reasons for lack of LCR by FCM varied.
    Leukemia & lymphoma 03/2015; DOI:10.3109/10428194.2015.1034702 · 2.61 Impact Factor
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    ABSTRACT: Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds. We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS, KRAS, and BRAF mutations. Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS-mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation. A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours.British Journal of Cancer advance online publication, 24 March 2015; doi:10.1038/bjc.2015.104 www.bjcancer.com.
    British Journal of Cancer 03/2015; 112(8). DOI:10.1038/bjc.2015.104 · 4.82 Impact Factor
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    ABSTRACT: Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome caused by a germline APC mutation. A recent study showed the enrichment of pyloric gland adenomas (PGAs) of the stomach, in addition to fundic gland polyps (FGPs) and foveolar-type adenomas (FAs), in patients with FAP. In the present study, we analyzed the genetic alterations in these FAP-associated gastric lesions. Mutational statuses of GNAS and KRAS, which are frequently mutated in sporadic PGAs, as well as those of APC, were examined in PGAs, FAs and FGPs in patients with FAP, using Sanger sequencing. Our analysis identified GNAS mutations in five of six PGAs (83%), but in none of the three FAs or the 40 FGPs examined. KRAS mutations were identified in four PGAs (67%), one FA (33%), and one FGP (3%). Somatic truncating APC mutations were found in all PGAs (100%), two FAs (67%), and 14 FGPs (47%). We additionally analyzed sporadic PGAs of the stomach and duodenum and identified truncating APC mutations in 11 of 25 lesions (44%). FAP-associated and sporadic PGAs not only show similar morphologies, but also share common genetic aberrations, including mutations of GNAS, KRAS and APC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 03/2015; DOI:10.1111/his.12705 · 3.30 Impact Factor
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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.
  • Pathology International 12/2014; 64(12). DOI:10.1111/pin.12220 · 1.59 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: We here report on two rare cases of intrafollicular classical Hodgkin lymphoma (CHL). Case 1 was a 34-year-old man who underwent left supraclavicular lymph node biopsy. Case 2 was a 28-year-old woman who underwent surgical resection of an anterior mediastinal mass. The histology and microenvironment of both specimens resembled those of nodular lymphocyte predominant Hodgkin lymphoma. Nodular architecture was observed, which comprised normal-appearing small lymphocytes and scattered lymphocyte predominant (LP)-like cells. CD23(+) follicular dendritic cell meshworks were present in the nodules, surrounded by a mantle zone containing IgD(+) B cells. The LP-like cells were ringed by CD3(+) and PD-1(+) T cells, and numerous CD20(+) B cells were present in the background. However, the immunophenotypes of the LP-like cells resembled those of Hodgkin/Reed-Sternberg cells of CHL; they were positive for CD15, CD30, and PAX5, and negative for CD20, Bcl6, Oct2, and Bob1. These histopathological findings indicate that CHL can be derived from the germinal center.
    Pathology International 11/2014; 64(12). DOI:10.1111/pin.12221 · 1.59 Impact Factor
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    ABSTRACT: ABSTRACT This study aimed to indicate the patients' outcomes and pathological characteristics of follicular lymphoma (FL) with peripheral blood (PB) involvement. Of 533 patients with FL, 56 (11%) had PB involvement. Of the patients treated with rituximab, 39 patients with PB involvement had significantly shorter progression-free survival than 107 patients with stage IV disease without PB involvement (P = .021), but the overall survival was not different (P = .804). The histopathology of the primary sites was usually nodal (95%) low-grade (86%) FL with IGH/BCL2 fusion (75%). Flow cytometric and immunohistochemical analyses revealed that the incidence of CD10 positivity was lower in the bone marrow (55% and 58%) and PB (41% and not available) than in the primary site (86% and 93%) (P = .004 and P = .0001, respectively). Therefore, even if small lymphoma cells in the bone marrow and PB are negative for CD10, FL cannot be ruled out.
    Leukemia and Lymphoma 10/2014; DOI:10.3109/10428194.2014.963578 · 2.61 Impact Factor
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    ABSTRACT: Background and study aims: Compared with any other location in the gastrointestinal tract, the duodenum presents the most challenging site for endoscopic resection. The aim of this study was to analyze the clinical outcomes of duodenal endoscopic resection and to assess the feasibility of the technique as a therapeutic procedure. Patients and methods: A total of 113 consecutive patients with 121 nonampullary duodenal tumors underwent endoscopic resection by endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), or polypectomy between January 2000 and September 2013. Long-term outcomes were investigated in patients with more than 1 year follow-up. Results: The median tumor size was 12 mm (range 3 - 50 mm). Lesions consisted of 63 adenocarcinomas/high-grade intraepithelial neoplasias (53 %) and 57 adenomas/low-grade intraepithelial neoplasias (48 %). Endoscopic resection included 106 EMRs (87 %), 8 ESDs (7 %), and 7 polypectomies (6 %). En bloc resection was achieved in 77 lesions (64 %), and 43 lesions (35 %) underwent piecemeal resection; one procedure was discontinued due to perforation. There were 14 cases of delayed bleeding after EMR (12 %), 1 perforation (1 %) during ESD, and 1 delayed perforation (1 %) after ESD, which required emergency surgery. Of the 76 patients who were followed for more than 1 year, none of the patients died from a primary duodenal neoplasm, and there were no local recurrences during the 51-month median follow-up period (range 12 - 163 months). Conclusions: Duodenal endoscopic resection was feasible as a therapeutic procedure, but it should only be performed by highly skilled endoscopists because of its technical difficulty. Piecemeal resection by EMR is acceptable for small lesions, based on these excellent long-term outcomes.
    Endoscopy 10/2014; 47(02). DOI:10.1055/s-0034-1390774 · 5.20 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: To investigate the clinicopathological and prognostic significance of a nodular pattern and immunophenotypes in primary mediastinal large B-cell lymphoma (PMBL), histopathological features, including a nodular pattern and immunophenotypes, were analyzed in 58 Japanese PMBL patients. The patients were 23 men and 35 women with a median age of 31 years. The 4-year progression free survival (PFS) rate was 78%, and the 4-year overall survival (OS) rate was 89%. Among the histopathological and immunohistochemical features, Bcl6+ (P = 0.013), MUM1+ (P = 0.091), and pale cytoplasm (P = 0.064) were favorable prognostic indicators of PFS, and Bcl6+ (P = 0.051) and MUM1+ (P = 0.07) were favorable prognostic indicators of OS. Patients with Bcl2 negativity (n = 11) had 4-year PFS and OS rates of 100%. Histologically, a nodular pattern, resembling nodular sclerosis classical Hodgkin lymphoma (CHL), was observed in 22 patients (38%). However, this was not a significant prognostic indicator. In conclusion, Bcl6+, MUM1+, Bcl2-, and pale cytoplasm are candidate favorable prognostic indicators for PMBL and should be further examined in larger studies. We suggest that PMBL with a nodular pattern may belong to the same histological spectrum as nodular sclerosis CHL.
    Pathology International 08/2014; 64(8). DOI:10.1111/pin.12186 · 1.59 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: Pathological response rate (pathRR) is a common endpoint used to assess the efficacy of preoperative therapy for gastric cancer. PathRR is estimated based on the percentage of the residual tumor area in the primary tumorous bed. Various cutoff definitions used in previous trials (e.g., 10, 33, 40, 50, 67 %) often impair the comparability of pathRRs between trials.
    Gastric Cancer 06/2014; DOI:10.1007/s10120-014-0401-z · 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: Biomarkers associated with anti-EGFR antibodies therapy have been investigated in metastatic colorectal cancer (CRC). We conducted this study to evaluate the clinical utility of a combined assessment of EGFR status and genomic mutations of the EGFR downstream signal pathway in predicting the efficacy of anti-EGFR antibody treatment. We collected formalin-fixed paraffin-embedded tumor tissues and evaluated the EGFR status by immunohistochemistry (IHC), dual color in situ hybridization (DISH) and genomic analyses of KRAS, BRAF, PIK3CA and NRAS by direct sequencing. A total of 129 patients were evaluated in our study. Among KRAS wild-type patients, EGFR DISH positivity was associated with a higher response rate than DISH negativity (56.3 vs. 21.1%, p = 0.011). A subgroup with EGFR DISH positivity plus IHC3+ and wild-type of EGFR downstream gene mutations achieved higher response rate and disease control rate. EGFR DISH positivity, KRAS codon 146 mutation and NRAS codon 61 mutation were prognostic factors in both progression-free survival and overall survival by multivariate analyses. Combined assessment of DISH plus IHC and EGFR downstream gene mutations was useful to predict the response to anti-EGFR antibodies treatment in metastatic colorectal cancer patients in our study.
    Archives of medical research 05/2014; 45(5). DOI:10.1016/j.arcmed.2014.05.004 · 2.41 Impact Factor
  • Gastrointestinal Endoscopy 05/2014; 79(5):AB558-AB559. DOI:10.1016/j.gie.2014.02.932 · 4.90 Impact Factor

Publication Stats

1k Citations
526.99 Total Impact Points


  • 2011–2015
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
    • Richard L. Roudebush VA Medical Center
      Indianapolis, Indiana, United States
  • 2006–2015
    • National Cancer Center, Japan
      • • Endoscopy Division
      • • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
  • 2013
    • Kinki University
      • Faculty of Medicine
      Ōsaka-shi, Osaka-fu, Japan
  • 2012
    • Kyorin University
      Edo, Tōkyō, Japan
    • Nippon Medical School
      • Department of Internal Medicine
      Edo, Tōkyō, Japan
  • 2007–2010
    • Clinical Research Hospital, Tokyo
      Edo, Tōkyō, Japan
  • 1992–1993
    • Kansai Medical University
      • First Department of Internal Medicine
      Moriguchi, Ōsaka, Japan