M Ono

National Cancer Center, Tokyo, Tokyo-to, Japan

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Publications (7)19.16 Total impact

  • Article: Highly proliferative intratumoral fibroblasts and a high proliferative microvessel index are significant predictors of tumor metastasis in T3 ulcerative-type colorectal cancer.
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    ABSTRACT: Fibroblast and endothelial cell mitotic figures are seen in some areas of colorectal cancers, and the purpose of this study was to investigate whether the proliferative activity of fibroblasts and endothelial cells plays an important role in tumor progression of T3 ulcerative-type colorectal cancer. The tumor area of 157 colorectal cancers was divided into marginal elevated area and central depressed area (CDA), and at half the depth of the depression the CDA was in turn divided into CDA upper area (CDAU) and CDA lower area (CDAL). The proliferative activity of the tumor cells, fibroblasts, and endothelial cells was assessed immunohistochemically by double CD31/MIB-1 (anti--Ki-67 antigen) staining. The proliferative microvessel index was estimated as the percentage of microvessels lined by MIB-1-positive endothelial cells relative to the total microvessel count. Proliferative activities of tumor cells showed significant associations with those of fibroblasts and the proliferative microvessel indices in all of the corresponding areas. Proliferative activities of fibroblasts also showed significant associations with proliferative microvessel indices in all of the corresponding areas. Colorectal cancers with nodal metastasis showed significantly higher proliferative activities of fibroblasts in the CDAU than those without nodal metastasis (P <.001). The high proliferative activities of fibroblasts and proliferative microvessel indices in the CDAU showed significant associations with short distant organ metastasis-free periods in colorectal cancers without nodal metastasis (P <.001 and P =.010, respectively) and those with nodal metastasis (P =.024 and P =.036, respectively). Multivariate analysis showed that the highly proliferative fibroblasts in the CDAU significantly increased hazard rates of distant organ metastasis of colorectal cancer patients with nodal metastasis (P =.018). Proliferative activities of fibroblasts and endothelial cells in the CDAU are useful parameters for predicting tumor metastasis in patients with T3 ulcerative-type colorectal cancer. HUM PATHOL 32:401-409.
    Human Pathlogy 05/2001; 32(4):401-9. · 2.88 Impact Factor
  • Article: Macroscopic typing with wall stricture sign may reflect tumor behaviors of advanced colorectal cancers.
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    ABSTRACT: No appropriate macroscopic classification of advanced colorectal cancers (A-CRC) is available for assessing their tumor behavior. In the present study, A-CRC were classified macroscopically as either stricture or nonstricture type, and the differences in clinicopathological features, mode of recurrence, and prognosis between the two types were investigated. The subjects were 166 patients with A-CRC invading beyond the muscular layer who had undergone curative surgical resection. Fresh resected specimens from these patients were used for the study. The A-CRC were classified as of stricture or nonstricture type according to whether or not they showed marked fold convergence and/or stricture of the intestinal tract (more than 30% wall shrinkage) that had the appearance of a "bow tie". Of the 166 A-CRC, 47 (28%) were classified as stricture type. This type was significantly more frequent in the colon (37%; 37/101) than in the rectum (15%; 10/65) (P = 0.003). The stricture type was more frequently associated with an abundance of fibrosis than the nonstricture type (76%; 28/37 vs 39%; 25/64 in colon; P < 0.001; 100%, 10/10 vs 42%, 23/55 in rectum; P < 0.001). The recurrence rate was also higher in the stricture type than in the non-stricture type in both the colon (51%, 19/37 vs 17%, 11/64; P = 0.003) and rectum (80%, 8/10 vs 38%, 21/55; P = 0.01). The time to recurrence was significantly shorter for the stricture type in both the colon (P < 0.001) and rectum (P = 0.02). These results indicate that the macroscopic typing of A-CRC according to the presence or absence of wall stricture sign may reflect their tumor behavior, although this behavior appears to be complex and related to tumor progression. This classification could be important clinically to assess tumor behavior in a simple way.
    Journal of Gastroenterology 03/2001; 36(3):158-65. · 4.16 Impact Factor
  • Article: Phase II study of sequential high-dose methotrexate and fluorouracil combined with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer.
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    ABSTRACT: The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer. Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m2, day 1) fluorouracil (1.5 g/m2, day 1), leucovorin (15 mg/m2, days 2-4), and doxorubicin (30 mg/m2, day 15), repeated at a 28-day interval, and followed by radical surgery. A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls. Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate.
    Gastric Cancer 02/2001; 4(4):192-7. · 2.42 Impact Factor
  • Article: Tumor thickness is a histopathologic predictive parameter of tumor metastasis and prognosis in patients with Dukes stage C ulcerative-type colorectal carcinoma. A two-hospital-based study.
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    ABSTRACT: Metastasis to the liver or lymph nodes is an important prognostic factor in patients with colorectal carcinoma. The purpose of the current study was to estimate the power of tumor thickness in predicting metachronous liver metastasis (MLM), lymph node metastasis (LNM), or overall survival (OS) in patients at two hospitals (the National Cancer Center Hospital [NCCH] and the National Cancer Center Hospital East [NCCHE]) to confirm the reproducibility of the study. The subjects of this study were 74 and 186 consecutive patients with ulcerative-type colorectal carcinoma treated at the NCCH and NCCHE, respectively. Tumor thickness was measured in three areas: 1) the marginal elevated area (MEA), 2) the central depressed area (CDA), and 3) the most thickened area (MTA). Studies were performed with well known histologic parameters to compare the predictive power of tumor thickness on MLM, LNM, and OS using the Cox proportional hazards regression model or analysis of variance. A significant correlation between tumor thickness and MLM was observed only in the CDA in the NCCH patients (P = 0.005). The authors applied a tumor thickness cutoff value in the CDA of 10 mm (</= 10 mm and > 10 mm) for further study. Multivariate analyses demonstrated that a tumor CDA thickness > 10 mm was associated significantly with MLM, multiple LNMs, and OS in NCCH patients with Dukes Stage C disease (P = 0.002, P = 0.023, and P = 0.002, respectively). A significant predictive power for tumor CDA thickness for MLM, multiple LNMs, and OS was confirmed by multivariate analysis in NCCHE patients with Dukes Stage C disease (P = 0.008, P = 0.021, and P = 0.010, respectively). The CDA thickness of the tumor was found to be a useful predictive parameter for MLM, multiple LNMs, and OS in patients with Dukes Stage C ulcerative-type colorectal carcinoma who were being treated in two independent hospitals.
    Cancer 07/2000; 89(1):35-45. · 4.77 Impact Factor
  • Article: The fibrotic focus in advanced colorectal carcinoma: a hitherto unrecognized histological predictor for liver metastasis.
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    ABSTRACT: A fibrotic focus (FF) is a clearly defined area consisting of fibroblasts and/or collagen fibres arranged in irregular or storiform patterns within tumours. We looked to see whether FF in advanced colorectal carcinoma was associated with distant organ metastasis especially to the liver. The correlation between FF and the presence of synchronous or total (synchronous and/or metachronous) liver metastasis and tumour recurrence was assessed in 77 patients with Dukes B and C advanced colorectal carcinoma treated by resection. The median follow-up period was 21 months. In multivariate analysis, FF significantly increased the relative risk (RR) of synchronous liver metastasis (RR=4.9, P<0.05) and total liver metastasis (RR=4.6, P<0.05). FF also increased the RR of tumour recurrence (RR=2.4), but the increase was not statistically significant. FF is a newly recognized histological indicator of liver metastasis in advanced colorectal carcinoma.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 12/1998; 433(6):517-22. · 2.49 Impact Factor
  • Article: Growth patterns and genetic changes of colorectal carcinoma.
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    ABSTRACT: Recent Japanese studies have shown that histogenesis of small colorectal carcinomas can be divided into two groups: polypoid growth arising from polypoid neoplasia, and nonpolypoid growth arising from flat or depressed neoplasia. This classification should be verified with genetic as well as morphologic characteristics. In order to classify our subject into polypoid growth and nonpolypoid growth types both histologically and endoscopically, we selected 42 colorectal carcinomas < 2 cm in size (35 submucosal and seven more advanced). Clinicopathological findings, presence or absence of Ki-ras gene mutation and overexpression of p53 protein were compared between the two types. Histologically, the cases were divided into 27 of the polypoid growth type and 15 of the nonpolypoid growth type. None of the nonpolypoid growth cases contained adenomatous remnant, wheras this was found in 75% of the polypoid growth cases. No Ki-ras mutation was observed in any of the nonpolypoid growth cases, although it appeared in 44% of the polypoid growth cases. Regarding the overexpression of p53 protein, no significant difference was observed between the two types. The histological and the colonoscopic polypoid growth-nonpolypoid growth classifications correlated well with each other (agreement rate 98%), except for one lesion, which was classified as polypoid growth type endoscopically but as nonpolypoid growth type histologically. The histologically defined polypoid growth-nonpolypoid growth classification may indicate a difference in pathway of colorectal carcinogenesis. Also, colonoscopic polypoid growth-nonpolypoid growth classification is available for preoperative estimation of the genetic characteristics of small carcinomas.
    Japanese Journal of Clinical Oncology 04/1998; 28(3):196-201. · 1.78 Impact Factor
  • Article: Primary squamous cell carcinoma of the stomach: a case report with a review of Japanese and Western literature.
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    ABSTRACT: A case of a 75 year-old male with primary squamous cell carcinoma of the stomach is reported. It is extremely rare to see squamous cell carcinoma developing in the stomach, without being accompanied by a component of adenocarcinoma. Up to the present, 18 Japanese and 62 Western cases of this type of carcinoma have been reported in the literature. The origin of this malignancy has not been well elucidated yet and thus, several plausible hypotheses have been proposed. In this presented case, the tumor consisted of only squamous cell carcinoma and the focus of squamous metaplasia was not found histologically in the adjacent mucosa. Therefore, it may be considered that the carcinoma arises from misplaced squamous cell nests of the stomach.
    Hepato-gastroenterology 46(29):3015-8. · 0.66 Impact Factor