Tomoyuki Tsuzuki

National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan

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Publications (24)127.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: A phase II study was performed to investigate the safety and efficacy of concurrent chemoradiotherapy (CCRT) combined with an orally active fluoropyrimidine, S-1, plus cisplatin for locally advanced esophageal cancer (LAEC). Methods: CCRT comprised 2 courses, a 30-Gy radiotherapy over 3 weeks plus daily oral S-1 (80 mg/m(2)/day) for 2 weeks and a 24-hour cisplatin infusion (70 mg/m(2)) on day 8, and an identical course administered after a 2-week break. Results: One hundred and sixteen patients, 12 with stage II, 71 with stage III, and 33 with stage IVa LAEC participated, and 106 of them (91.4%) completed the CCRT course. The most serious toxicity was myelosuppression: grade 3 and 4 neutropenia occurred in 28.4 and 9.5% of patients, respectively. Nonhematologic toxicity was moderate. Complete response rates in patients with stage II, III, and IVa LAEC were 91.7, 67.6, and 36.4%, respectively. The overall median survival time was 2.3 years and that of patients with stage II, III, and IVa cancer was 7.0, 2.6, and 1.3 years, respectively. Conclusions: CCRT combined with S-1 plus cisplatin showed promising safety and efficacy. Potentially, this combination therapy could become a baseline medication for patients with LAEC.
    Oncology 05/2013; 84(6):342-349. · 2.17 Impact Factor
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    ABSTRACT: At Nagoya Medical Center, 10 patients co-infected with HIV and HCV received peginterferon α (PEG-IFNα) plus ribavirin therapy. Three of the cases were HCV genotype 1b, 2 cases were HCV 3b, and 1 case each were 2b, 2c, 3a, 4a and 6n. Nine patients received anti HIV therapy from the beginning. In 5 of these patients, anti HIV therapy was modified when PEG-IFNα plus ribavirin treatment was started. Of the above, 7 patients completed the protocol. No patients had severe adverse effects. Sustained virological response was achieved in 1 of 4 (25%) of the patients with genotypes 1 or 4, and in 5 of 6 (83%) of the patients with other genotypes. PEG-IFNα plus ribavirin therapy is considered a safe and efficacious treatment for patients co-infected with HIV and HCV.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2012; 109(7):1186-96.
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    ABSTRACT: Objectives: To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer. Methods: A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m2) was administered by infusion for 3 h on the first day. S-1 (70 mg/m2/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m2) was administered intravenously over 24 h on day 14 of every 28-day cycle. Results: All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1–10). Grade 3–4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3–4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months. Conclusions: Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.
    Oncology 01/2011; 80:76-83. · 2.17 Impact Factor
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2009; 69(5).
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    ABSTRACT: Standard leukocytapheresis (LCAP) protocols recommend the processing of a 3 L blood volume. In this study, we evaluated the clinical effects of LCAP with 1.5 L of blood processing (1.5L-LCAP) in patients with active ulcerative colitis (UC). Ten patients with moderate to severe UC were enrolled. Their clinical and endoscopic responses, the kinetics of the peripheral blood counts and cytokine responses were evaluated. Clinical and endoscopic effects were assessed using the clinical activity index described by Rachmilewitz, and by Matts' endoscopic classification, respectively. The 1.5L-LCAP induced clinical remission in 8 out of 10 patients (80%). Endoscopic improvement was noted in 6 out of 7 patients (85.7%). Prednisolone (PSL) was used in 8 patients; the PSL dose could be reduced in 6 patients, and weaning was possible in one patient. Adverse effects were not observed during 1.5L-LCAP therapy. During the 1.5L-LCAP session, the leukocyte count reached the minimum at 1.0 L of blood processing, but promptly increased after completion of the session, and reached a maximum after 30 min. Interleukin (IL)-1beta-induced IL-8 and IL-6 secretion by peripheral blood mononuclear cells were both significantly reduced by 1.5L-LCAP therapy. 1.5L-LCAP was clinically effective for active UC patients. Cellular responses induced by 1.5L-LCAP were similar to those induced by a standard LCAP session.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 11/2008; 12(5):368-73. · 1.53 Impact Factor
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    ABSTRACT: The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD) and the preliminary antitumor activity of S-1, oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimide, in combination with cisplatin and paclitaxel for advanced gastric cancer. Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1 and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160 and 180 mg/m2). Twenty patients were enrolled. The toxicities were generally mild no grade 4 hematological toxicity or grade 3 non-hematological toxicity were observed. Level 4 was considered as the MTD because of a treatment delay of more than 2 weeks in 3 out of 6 patients. The RD of paclitaxcel was 160 mg/m2. The overall response rate was 75%. A triple combination chemotherapy consisting of S-1, cisplatin and paclitaxel showed a tolerable level of adverse reactions and favorable antitumor activity.
    Anticancer research 01/2006; 26(2B):1605-9. · 1.87 Impact Factor
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    ABSTRACT: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 microg/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori (H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26,695 or recombinant human (rh) IL-17. All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2,499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P< 0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1,356 pg/mg/protein, range 121-1,3730; antrum: median 761 pg/mg/protein, range 24-7,620, P< 0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62, P< 0.0001; antrum: r = 0.61, P< 0.0001) in GU patients. RhIL-17 and H pylori strain 26,695 each stimulated IL-8 production from AGS cells. IL-17 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.
    World Journal of Gastroenterology 11/2005; 11(40):6305-11. · 2.43 Impact Factor
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    ABSTRACT: The long-term benefit of Helicobacter pylori eradication treatment that includes metronidazole on peptic ulcer disease in Japan is unclear. We investigated the rate of H. pylori re-infection and ulcer relapse after H. pylori eradication. A total of 266 patients with endoscopically confirmed peptic ulcer disease and H. pylori infection were treated with triple therapy of omeprazole 40 mg (20 mg b.i.d.), clarithromycin 800 mg (400 mg b.i.d.), and tinidazole 1000 mg (500 mg b.i.d.) for 7 days. Endoscopy with gastric biopsy was performed before and 1 month, 6 months, 1.5 years, and 3.5 years after therapy. H. pylori status was determined by H. pylori culture, rapid urease test, and histopathology. 13C-urea breath test was done at 6 months after eradication therapy. Treatment was deemed successful when all tests were negative at 6 months after therapy by endoscopic biopsy. Successful H. pylori eradication was achieved in 262/266 (98.5%) patients with peptic ulcer. Total relapse of peptic ulcer occurred in 8/262 (3%) patients after eradication, with 3/262 (1.1%) occurring within 1.5 years after treatment and 5/262 (1.9%) within 3.5 years. All relapsed patients were found to be H. pylori-positive at the time of relapse. Of the 262 patients who experienced eradication, 20 (7.6%) were subsequently re-infected, six (2.3%) within 1.5 years and 14 (5.3%) within 3.5 years. Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) is useful for H. pylori eradication in Japan, but there is an appreciable re-infection rate in this population.
    Helicobacter 11/2005; 10(5):379-84. · 2.99 Impact Factor
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    ABSTRACT: Background: Assessment of the response of esophageal cancer to chemoradiotherapy is difficult. We investigated the value of a transendoscopic miniature ultrasonic probe (USP) in assessing response to chemoradiotherapy in patients with locally advanced esophageal cancer.Methods: A total of 33 patients were entered in this prospective study. Response to treatment was evaluated according to World Health Organization criteria. According to the sonographic image, complete response (CR) of the primary lesion was divided into two subcategories: confirmed CR (cCR) and unconfirmed CR (uCR).Results: Initial sonographic criteria for evaluating tumor depth and lymph nodes in the 33 patients before therapy showed two cases of T2N0, four of T3N0, 15 of T3N1, four of T4N0, and eight of T4N1. Following chemoradiotherapy, CR was obtained in 18 (54.5%): seven cCR and 11 uCR. Eleven were partial response (PR) (33.3%), while three were stable disease (SD) and one was progressive disease (PD). High frequency USP (20 MHz) was able to detect tumor disappearance and restoration of the esophageal wall. One-year survival rates among CR (cCR + uCR), PR and SD + PD were 100%, 70% and 0%, respectively. A significant difference in survival was evident among CR, PR and SD + PD (P < 0.001). Three-year survival rates between cCR and uCR were 100% and 40%, respectively. A significant difference in survival was evident between cCR and uCR (P < 0.001). In seven cases of uCR, local recurrence and distant metastasis appeared within 1 year, and five died of disease progression. Not one cCR case has relapsed.Conclusion: USP, which can be accomplished with a standard endoscopy, including biopsy, in one procedure, is a useful method for objectively assessing the response to chemoradiotherapy in patients with locally advanced esophageal cancer.
    Digestive Endoscopy 03/2005; 17(2):159 - 163. · 1.61 Impact Factor
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    ABSTRACT: We investigated the possible roles of the interleukin (IL)-15 and IL-15 receptor (IL-15R) system in a heightened state of B-cell activation and differentiation in intestinal mucosa with inflammatory bowel disease (IBD). The expression of IL-15 and IL-15Ralpha mRNA and protein in inflamed colonic mucosal tissues with IBD, and in control tissues was examined by reverse transcriptase-polymerase chain reaction and immunohistological methods. The effects of recombinant (r)IL-15 on the expression of IL-15Ralpha on lamina propria B cells and the production of immunoglobulin G (IgG) were analyzed in vitro, using lamina propria mononuclear cells (LPMCs) isolated from control tissues. The intensity of IL-15 and IL-15Ralpha mRNA was greater in the mucosal tissues of patients with IBD, especially in those of patients with ulcerative colitis (UC), than in control tissues. Compared to control tissues, mononuclear cells positive for IL-15Ralpha protein were observed in greater proportions in tissue sections from patients with IBD, especially in those from patients with UC, where IL-15Ralpha protein was localized to CD20-positive B cells to a significant degree. There were increases in the proportions of IL-15Ralpha-positive B cells and IgG-producing cells in rIL-15- or rCD40L-stimulated cultures of LPMCs, with stimulatory effects being greater in the presence of their combination. These data suggest that the IL-15 and IL-15R system may play important roles in the activation and differentiation of lamina propria B cells in patients with IBD, especially in those with UC.
    Journal of Gastroenterology 03/2005; 40(2):128-36. · 4.02 Impact Factor
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    ABSTRACT: A 51-year-old man was hospitalized for evaluation of dysphagia and bloody stool. Gastrointestinal endoscopy showed esophageal cancer invading the gastric fundus. A metastatic lesion was demonstrated in the sigmoid colon. The patient agreed to have concurrent chemoradiotherapy for the primary lesion, followed by additional chemotherapy. The first course included 30 Gy of radiotherapy given over 3 weeks, together with daily oral administration of S-1 (80 mg/m2 per day) for 2 weeks, and a 24-h infusion of cisplatin (70 mg/m2) on day 8. After a second course of chemoradiotherapy, four additional courses of chemotherapy with S-1 and cisplatin were administered, at 4-week intervals. After the additional chemotherapy, gastroscopy and colonoscopy showed disappearance of both the primary and the metastatic lesions. One year after his initial hospitalization, no recurrence of either the primary or the metastatic tumor lesions is evident.
    International Journal of Clinical Oncology 11/2004; 9(5):398-402. · 2.17 Impact Factor
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    ABSTRACT: The association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been reported widely. We investigated the prevalence of H. pylori infection, its virulence profile and the effectiveness of its eradication in patients with ITP. Twenty patients with ITP, 20 with peptic ulcer (10 gastric ulcer (GU), 10 duodenal ulcer (DU)) and 20 with NUD were studied. The virulence profile of the strains was assessed by genotyping for cagA, vacA, iceA, and hpyIIIR/hrgA and by assaying for IL-8 and DNA fragmentation after incubation with AGS cells. Infected patients and two uninfected ITP patients received triple therapy and platelets were counted before and 1 month, 6 months, 1 year, and 2 years after eradication therapy. H. pylori infection was found in 17 ITP (85%), 20 ulcer (100%) and 13 NUD (65%) patients. Biopsies and strains were collected from five ITP, 20 ulcer and 13 NUD patients. The ITP patients had a pangastritis or corpus-predominant gastritis pattern. All H. pylori isolates, from ITP, ulcer and NUD patients, were cagA(+) and vacA s1/m1, and did not differ in levels of IL-8 induction or DNA fragmentation. Fifteen ITP (88%) and 17 ulcer (85%) patients had successful eradication of H. pylori. Ten of these 15 (67%) H. pylori-eradicated ITP patients had platelet recovery. There was no significant change in platelet count in the two ITP patients in whom eradication failed or in the two originally H. pylori-uninfected ITP patients, or in the treated ulcer patients. Age at onset of ITP was the main determinant of platelet recovery: 100% of patients diagnosed after the age of 60 recovered compared with only 22% of those diagnosed before 50. H. pylori-infected ITP patients have a corpus-predominant pattern of gastritis but the virulence profile of their strains does not differ from that of ulcer or NUD patients. Eradication of H. pylori infection is a good therapeutic option for some patients with chronic ITP, especially for those who develop ITP in older age.
    Helicobacter 11/2004; 9(5):443-52. · 2.99 Impact Factor
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    ABSTRACT: A 51-year-old male patient with esophageal cancer and cervical, thoracic and celiac artery lymph node metastases was treated by combination chemotherapy of TS-1 and cisplatin. TS-1 (80 mg/m2/day) was administered for 14 days followed by 14 days rest as 1 course. Cisplatin (70 mg/m2/day) was administered in 24-hour continuous intravenous infusion at day 8 after the start of TS-1. Before treatment, the tumor marker, CEA showed 27,060 ng/ml. After 5 courses of chemotherapy, endoscopy revealed that the primary tumor had disappeared and no cancer cells were detected by endoscopic biopsy. Chest and abdominal CT scan also showed almost total disappearance of the lymph nodes metastases. CEA decreased to 710 ng/ml. No high-grade toxicities (WHO grade 3 or 4) were seen during the chemotherapy. He is now very well. This TS-1/cisplatin chemotherapy regimen might be a useful treatment for metastatic esophageal cancer.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2004; 31(5):755-8.
  • The Japanese journal of antibiotics 05/2003; 56 Suppl A:51-3.
  • Gastroenterology 04/2003; 124(4). · 12.82 Impact Factor
  • Journal of Gastroenterology 02/2003; 38(4):412-3. · 4.02 Impact Factor
  • Gastroenterology 01/2003; 124(4). · 12.82 Impact Factor
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    ABSTRACT: Little information is available on the relative contribution of peptide growth factors and leukocyte-derived proteinases to the repair processes in inflammatory bowel disease (IBD). We investigated their possible roles in epithelial cell restitution and proliferation in patients with IBD. The expression of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), transforming growth factor-beta (TGF-beta), and neutrophil elastase (NE) was examined in colonic mucosal tissues. The effects of organ culture supernatants of mucosal tissues on epithelial cell restitution and proliferation were analyzed in vitro using an intestinal cell line, IEC-6 cells. Most organ cultures detected the presence of measurable levels of HGF, with a relative paucity of KGF and TGF-beta activity. Greater levels of HGF were obtained in the mucosa involved with IBD, especially in patients with ulcerative colitis (UC). The mucosa involved with UC also showed higher amounts of NE. The supernatants from the mucosa involved with UC possessed a prominent stimulatory effect on the restitution of IEC-6 cells. By contrast, significant suppression beyond baseline levels was observed for the proliferation of IEC-6 cells when they were incubated with recombinant HGF plus the supernatants from the mucosa involved with UC. This suppression was diminished considerably by preincubation of the supernatants with the anti-NE antibody. HGF produced in the intestinal mucosa may be an important stimulator acting on epithelial cell restitution in patients with IBD. However, NE released in situ may impair mucosal repair through inhibiting epithelial cell proliferation in patients with UC.
    Journal of Gastroenterology 12/2002; 37 Suppl 14:22-32. · 4.02 Impact Factor
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    ABSTRACT: An intravenous infusion of cyclosporine A (CsA) shows clinical benefits in patients with steroid-resistant ulcerative colitis (UC). To clarify its mechanisms, we investigated the ability of CsA to inhibit the functions of neutrophils and T cells. The cytotoxic activity by mucosal T cells was analyzed by anti-CD3-triggered cytotoxicity after lamina propria mononuclear cells were cultured with recombinant interleukin (IL)-2. The chemotactic response, the generation of superoxide, and the production of chemokines, IL-8, and macrophage inflammatory protein-1alpha by neutrophils were examined using a multiple-well chamber assay, a chemiluminescence method, and an enzyme-linked immunosorbent assay (ELISA), respectively. Mucosal chemokine activity was determined by an ELISA using the organ culture supernatant of mucosal biopsy tissues. Pretreatment with CsA caused consistent inhibitions of cytotoxic activity by mucosal T cells and chemotactic migration, superoxide generation, and chemokine production by neutrophils mostly in a dose-dependent manner. In patients who received an intravenous infusion of CsA, mucosal chemokine activity decreased after therapy in parallel with decreases in the numbers of neutrophils and mononuclear cells in the biopsy tissues. These results suggest that suppressive effects of CsA on neutrophils and T cells may be related to therapeutic benefits in patients with steroid-resistant UC.
    Inflammatory Bowel Diseases 02/2002; 8(1):1-9. · 5.48 Impact Factor
  • Gastroenterology 04/2001; 120(5). · 12.82 Impact Factor

Publication Stats

144 Citations
127.22 Total Impact Points


  • 2006–2012
    • National Hospital Organization Nagoya Medical Center
      Nagoya, Aichi, Japan
  • 2005
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan