Haruhiko Nose

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

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Publications (15)48.2 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We prospectively evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) with microembolization material, degradable starch microspheres (DSMs), and epirubicin, for treatment of multifocal hepatocellular carcinoma (HCC). Seventeen patients with multifocal HCC were treated. At the first treatment, DSMs were injected alone to determine the dose for embolization of the hepatic artery in each patient. After 4 weeks, TACE was performed every 4 to 6 weeks with a mixture of DSMs and epirubicin at a dose of 40 mg/m2. A necrotic area of more than 50% was produced in 6 patients by DSMs alone, and in 11 patients by TACE. The overall response rate was 52.9% (2 complete and 7 partial responses). The duration of the responses ranged from 4 to 21 months (median: 9 months). Common toxicities were transient abdominal pain, nausea/vomiting, fever, and leukopenia. In four patients, grade III or IV toxicity was observed as gamma-glutamyl transpeptidase elevation. TACE with DSMs had tumor necrosis efficacy with acceptable toxicity. The median survival time was 21.7 months, and the 2-year survival rate was 45.3%. Further investigation of the effects of DSM treatment on survival should be carried out.
    American Journal of Clinical Oncology 05/2003; 26(2):159-64. DOI:10.1097/01.COC.0000018174.53573.67 · 2.61 Impact Factor
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    ABSTRACT: Radiotherapy plus bolus 5-fluorouracil (5-FU) is generally accepted as the standard treatment for locally advanced pancreatic carcinoma. To intensify the antitumor effect of chemotherapy, the authors administered protracted 5-FU infusion with concurrent radiotherapy. The aim of this study was to determine the feasibility and effectiveness of this combined therapy. Twenty patients, all of whom had histologically confirmed exocrine pancreatic carcinoma that was nonresectable but confined to the pancreatic region, were enrolled in a Phase II trial of protracted 5-fluorouracil infusion (200 mg/m2/day) with concurrent radiotherapy (50.4 gray in 28 fractions over 5.5 weeks). Chemotherapy began on the first day of radiation and continued through the entire radiation course. Thereafter, weekly infusions (500 mg/m2) were administered until disease progression. Of the 20 patients, 17 (85%) completed the scheduled course of chemoradiotherapy. Grade 3 or worse toxicity, graded according to World Health Organization criteria, was observed in 4 patients (20%). Two patients (10%) achieved partial response, and disease remained stable in 16 patients (80%). After the completion of combined therapy, serum CA 19-9 levels were reduced by more than 50% in 10 of 12 patients (83%) who had pretreatment CA 19-9 levels of 100 U/mL or greater. The median progression free survival and 1-year progression free survival rate were 4.9 months and 29.5%, respectively. The median overall survival and 1-year overall survival rate were 10.3 months and 41.8%, respectively. This treatment showed moderate activity against locally advanced pancreatic carcinoma and was accompanied by an acceptable toxicity level.
    Cancer 05/1997; 79(8):1516-20. DOI:10.1002/(SICI)1097-0142(19970415)79:83.3.CO;2-5 · 4.90 Impact Factor
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    ABSTRACT: We studied the effect of heavy alcohol intake (ethanol intake ≥80 g/day for ≥5 yr) on long-term results in 53 patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) who had undergone curative hepatic resection. Cell proliferative activity in the tumor and non-tumorous liver was also assessed by counting argyrophilic nucleolar organizer region-associated proteins (Ag-NOR) in the resected specimens. Twenty patients (20 males, 0 females) were positive for heavy alcohol intake [AI(+)] and 33 (28 males, 5 females) were not [AI(-)]. All patients were positive for HCV antibody and negative for hepatitis B surface antigen. Carcinoma recurred within 3 to 51 postoperative months in 42 (79.2%) of the 53 patients. The median disease-free survival time was 12.6 mo in the AI(+) group and 25.4 mo in the AI(-) group (P<0.01). The AI(+) group also had significantly poorer survival than the AI(-) group (P<0.05, 3-year survival rate: 66.7% vs. 93.5%). HCC tumor in the AI(+) group showed significantly increased proliferative activity compared with that in the AI(-) group (P<0.05, Ag-NOR number: 2.3±0.8 vs. 1.9±0.4). However, there was no significant difference between the numbers of Ag-NORs in non-tumorous liver from these two groups (1.5±0.2 vs. 1.5±0.2). Patients with heavy alcohol intake should be followed particularly closely, even if they have received curative surgery, since heavy alcohol intake is closely related to a poor postoperative prognosis.
    Cancer Science 07/1996; 87(8):867 - 873. DOI:10.1111/j.1349-7006.1996.tb02113.x · 3.53 Impact Factor
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    ABSTRACT: Percutaneous ethanol injection (PEI) therapy is now widely used for small hepatocellular carcinomas (HCC). However, only limited information is available regarding local tumor recurrence after PEI treatment. We investigated the relationship of pretreatment clinicopathologic variables (tumor size, tumor cell differentiation and tumor staining) to local recurrence in 170 PEI-treated HCC nodules (measuring 5-39 mm in greatest dimension) in 84 patients. Local recurrence was observed in 17 of 170 PEI-treated nodules. Among these, 13 local recurrences were observed as the first event of progression after PEI. Local recurrence rates at 1, 2, and 4 years were 6.6%, 14.2%, and 14.2%, respectively, and all recurrences were observed within 2 years after PEI. Of the 3 variables investigated, large tumor size (31 mm or larger in greatest dimension) was significantly associated with a higher local recurrence rate. This study demonstrated that tumor size influences the local efficacy of PEI for small HCC. Therefore, we recommend that a reasonable indication for PEI therapy is HCC lesions measuring less than 30 mm in greatest dimension.
    Cancer 05/1996; 77(9):1792-6. DOI:10.1002/(SICI)1097-0142(19960501)77:9<1792::AID-CNCR6>3.0.CO;2-E · 4.90 Impact Factor
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    ABSTRACT: The clinical features of 65 patients with advanced pancreatic cancer treated between 1984 and 1993 were analyzed retrospectively to identify the significant prognostic factors. All the patients had presented unresectable or metastatic disease on imaging diagnostic evaluation and had received systemic chemotherapy. The overall median survival time and 1-year survival rate were 3.9 months and 9.8%, respectively. The independent favorable prognostic factors identified by multivariate analysis using the Cox proportional hazards model were a performance status of 0-1, a serum carcinoembryonic antigen level of < 10 ng/ml, and an absence of distant metastasis. A prognostic index calculated from the regression coefficients for these three factors was used to classify the patients into three groups, with good, intermediate, and poor prognoses. The median survival time for these three groups was 7.4, 3.5, and 2.0 months, respectively (p < 0.001). The results of this study may be useful in the design and analysis of future clinical trials of systemic chemotherapy for advanced pancreatic cancer.
    Pancreas 04/1996; 12(3):267-71. DOI:10.1097/00006676-199604000-00009 · 3.01 Impact Factor
  • Surgery 12/1995; 118(5):909-11. DOI:10.1016/S0039-6060(05)80285-5 · 3.11 Impact Factor
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    ABSTRACT: Intratumoral DNA heterogeneity provides important information regarding biologic and clinical behavior. The purpose of this study was to evaluate the incidence of DNA heterogeneity in small hepatocellular carcinoma (HCC) nodules. The DNA content of 28 surgically resected small HCC nodules (< or = 3.0 cm) was measured using flow cytometry of fresh or frozen samples taken from different parts of each nodule with reference to the macroscopic features. Of the 28 small HCC nodules, 14 (50.0%) had only DNA diploid stemline characteristics. Five nodules (17.9%) manifested DNA diploid and DNA aneuploidy within the same tumor. Of the remaining nine nodules (32.1%) that showed only DNA aneuploidy, two contained tumor tissues with apparently different DNA content. Thus, DNA heterogeneity was found in 7 (25.0%) of 28 nodules. DNA heterogeneity correlated well with macroscopic histologic features. All four early HCC were composed of only DNA diploid cells, whereas three of six nodule-in-nodule lesions were composed of DNA heterogeneous cells, in which the inner obviously cancerous nodule showed DNA aneuploidy and the outer well differentiated HCC portion demonstrated DNA diploid. Four of 18 overt HCC nodules showed DNA heterogeneity; 2 of these 4 nodules showed both diploid and aneuploid peaks, and the other 2 two showed different aneuploid peaks within the same nodule. DNA heterogeneity correlating with macroscopic features is found frequently even in small HCC nodules. Therefore, multiple sampling based on macroscopic features is required for the accurate assessment of DNA ploidy, particularly when the information about DNA ploidy is used as a prognostic indicator.
    Cancer 02/1995; 75(2):444-50. · 4.90 Impact Factor
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    ABSTRACT: A phase II study of cisplatin was performed in 13 previously untreated patients with unresectable biliary tract carcinoma. The drug was given intravenously at a dose of 80 mg/m2/day once every 4 weeks. Of 13 patients evaluated, 1 showed partial response lasting 3 months, while no patients showed complete response. Of 9 patients, whose serum level of carcinoembryonic antigen (CEA) was high (> or = 10 ng/ml) before treatment, 4 showed > or = 50% reduction in serum CEA level after treatment. The current study indicates that cisplatin does not have significant antitumor activity against biliary tract carcinoma.
    Oncology 01/1994; 51(6):515-7. DOI:10.1159/000227396 · 2.61 Impact Factor
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    ABSTRACT: The prognostic significance of the nuclear DNA content of tumors was studied prospectively in 124 patients who underwent hepatic resection for the treatment of hepatocellular carcinoma (HCC). The DNA content was measured by means of flow cytometry (FCM) using fresh or frozen samples. The DNA index (DI) was calculated, and the nuclear DNA content was classified into two types, DNA diploid and DNA aneuploid. The incidence of DNA aneuploid was 55.6%, and the DI ranged from 1.00 to 3.66, with most values falling between 1.00 and 2.00. There. was a significant difference in overall survival between patients with DNA diploid and DNA aneuploid tumors (P < 0.05), with 3-year survival rates being 94.4% and 51.9%, respectively. Among the DNA aneuploid tumor-bearing patients, 55 patients with a high DI (> 1.5) had a worse prognosis than 14 patients with a low DI (≤ 1.5). Of the 98 patients who underwent curative operations, the 43 DNA diploid tumor-bearing patients had more favorable disease-free survival than the 55 DNA aneuploid tumor-bearing patients (P < 0.05, the 3-year disease-free survival rate: 48.4% vs. 0.0%). These results indicate that nuclear DNA content as measured by FCM has prognostic significance for post-operative HCC patients.
    International Hepatology Communications 05/1993; 1(2):109-115. DOI:10.1016/0928-4346(93)90057-M
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    ABSTRACT: A phase 2 study of cisplatin was performed in 28 previously untreated patients with unresectable hepatocellular carcinoma. The drug was given intravenously at a dose of 80 mg/m2/day every 4 weeks. Of 26 patients evaluated, 4 (15.4%) showed partial responses lasting for > 3 months, while no patient achieved a complete response. Of 22 patients whose serum level of alpha-fetoprotein (AFP) was high (> 400 ng/ml) before treatment, 6 (27.3%) showed a > 50% reduction in serum AFP levels after treatment. The current study indicates that cisplatin is an anticancer agent worthy of further testing in patients with this disease.
    Oncology 01/1993; 50(1):22-6. DOI:10.1159/000227142 · 2.61 Impact Factor
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    ABSTRACT: A total of 71 consecutive patients with unresectable hepatocellular carcinoma were analyzed retrospectively to determine the significant prognostic factors. All the patients received systemic chemotherapy in a phase 2 study from 1980 to 1990, with no other anticancer treatment. Median survival time and 1-yr and 2-yr survival rates were 5.6 mo, 23% and 5%, respectively. By the univariate analysis, a performance status of 0-1 and tumor size less than 50% of the liver cross-sectional area were shown to be the factors most significantly favoring a better prognosis. By the multivariate analysis using the Cox proportional hazards model, a performance status of 0-1 (p less than 0.001), absence of tumor thrombus in the main portal trunk (p = 0.003) and age less than 60 yr (p = 0.036) were independent favorable prognostic factors. A prognostic index was calculated from these three factors according to the following equation: 1.8109 x (0 = performance status of 0-1 and 1 = performance status of 2-3) + 0.9322 x (0 = tumor thrombus absent in the main portal trunk and 1 = present) + 0.6996 x (0 = age less than 60 yr and 1 = age greater than or equal to 60 yr). This index was used to classify the patients into three groups with a good, intermediate and poor prognosis. The median survival times for these three groups were 9.8, 3.8 and 1.9 mo, respectively (p less than 0.01). The results of this study may be useful in the design and analysis of future clinical trials of systemic therapy for hepatocellular carcinoma.
    Hepatology 07/1992; 16(1):112-7. DOI:10.1002/hep.1840160119 · 11.19 Impact Factor
  • European Journal of Cancer 02/1992; 28A(8-9):1590. DOI:10.1016/0959-8049(92)90563-H · 4.82 Impact Factor
  • Kanzo 01/1992; 33(1):9-14. DOI:10.2957/kanzo.33.9
  • Kanzo 01/1992; 33(12):987-988. DOI:10.2957/kanzo.33.987
  • Kanzo 01/1991; 32(10):961-962. DOI:10.2957/kanzo.32.961

Publication Stats

469 Citations
48.20 Total Impact Points

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  • 1995–1997
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
    • National Cancer Center, Japan
      • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan