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Effects of an oral iron chelator, deferasirox, on advanced hepatocellular carcinoma

World Journal of Gastroenterology 2016年第40期22卷 8967-8977页

作者： Issei Saeki Naoki Yamamoto takahiro Yamasaki Taro Takami Masaki Maeda Koichi Fujisawa Takuya Iwamoto Toshihiko Matsumoto Isao Hidaka Tsuyoshi Ishikawa Koichi Uchida Kenji Tani Isao Sakaida Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine Yamaguchi 755-8505 Japan yamaguchi University Health Administration Center Yamaguchi 755-8511 Japan Department of Oncology and Laboratory Medicine Yamaguchi University Graduate School of Medicine Yamaguchi 755-8505 Japan Department of Human Nutrition Faculty of Nursing and Human Nutrition Yamaguchi 755-8502 Japan Center of Research and Education for Regenerative Medicine Yamaguchi University Graduate School of Medicine Yamaguchi Prefectural University Yamaguchi 755-8505 Japan Department of Veterinary Surgery Joint Faculty of Veterinary Medicine Yamaguchi University Yamaguchi 755-8511 Japan

AIM To evaluate the inhibitory effects of deferasirox(DFX) against hepatocellular carcinoma(HCC) through basic and clinical *** In the basic study, the effect of DFX was investigated in three hepatoma cell lines(Hep G2, Hep3 B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity(according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was *** Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro. In the murine model, DFX treatment significantly suppressed the development of liver tumors(P < 0.01), and significantly upregulated the mR NA expression levels of hepcidin(P < 0.05), transferrin receptor 1(P < 0.05), and hypoxia inducible factor-1α(P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%.CONCLUSION We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities.

关键词： Liver tumor Hepatocellular carcinoma Advanced stage Iron-chelator Deferasirox

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A Case of Simultaneous Triple Primary Cancers of the Hypopharynx, Esophagus, and Stomach Which Were Dissected by Endoscopic Laryngo-Pharyngeal Surgery Combined with Endoscopic Submucosal Dissection

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Open Journal of Gastroenterology 2018年第3期8卷 94-102页

作者： Kenro Kawada Taro Sugimoto Ryuhei Okada Kazuya yamaguchi Yuudai Kawamura Masafumi Okuda Yuuichiro Kume Andres Mora Tairo Ryotokuji Takuya Okada Akihiro Hoshino Yutaka Tokairin Yasuaki Nakajima Yusuke Kiyokawa Fuminori Nomura Yoshuke Ariizumi Shohei Tomii Takashi Ito takahiro Asakage Yusuke Kinugasa Tatsuyuki Kawano Department of Gastrointestinal Surgery Tokyo Medical and Dental University Tokyo Japan Department of Head and Neck Surgery Tokyo Medical and Dental University Tokyo Japan Department of Human Pathology Tokyo Medical and Dental University Tokyo Japan

A 65-year-old man was admitted to our hospital following 6 months of dysphagia. At first, conventional endoscopy showed a reddish and depressed lesion in the stomach and an elevated lesion in the posterior wall of the hypopharynx. An endoscopic biopsy showed adenocarcinoma in the stomach, and squamous cell carcinoma in the hypopharynx. On the further examination, trans-nasal endoscopy with narrow band imaging (NBI) was performed. During the trumpet maneuver, a huge protruded lesion was observed and it reached to the orifice of the esophagus. Other superficial lesion located at left pyriform sinus was detected by NBI system as brownish area with brown dots. Furthermore, superficial esophageal cancer in the cervical esophagus was detected. Finally, 4 carcinomas in upper gastrointestinal tract were detected. Among them, the hypopharyngeal cancer was the most advanced (T3N0). The patient hoped to preserve his voice and swallowing function, endoscopic laryngo-pharyngeal surgery (ELPS) was performed for the hypopharyngeal cancer. Endoscopic mucosal resection (EMR) was performed for the esophageal cancer, and Endoscopic submucosal dissection (ESD) was performed for the gastric cancer. Under collaboration between a head and neck surgeon and an endoscopist, the tumor was resected en-bloc. The histopathological findings of hypopharyngeal cancer were squamous cell carcinoma, subeipthelial invasion, 29 × 28 × 4.2 mm. The others were diagnosed as mucosal cancers. The patient is currently alive with no recurrence at 28 months after the surgery;there is no stricture at the cervical esophagus. Endoscopic laryngopharyngeal surgery for the tumor of pharyngo-esophageal junction can provide a less invasive treatment.

关键词： Endoscopic Laryngopharyngeal Surgery Hypopharyngeal Cancer Multiple Primary Cancer Trumpet Maneuver Endoscopic Submucosal Dissection

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Zoledronic acid combined with androgendeprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naı¨ve metastatic prostate cancer patients e A propensity scoring approach

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Asian Journal of Urology 2016年第1期3卷 33-38页

作者： Kazuhiro Nagao Hideyasu Matsuyama Masahiro Nozawa Isao Hara Tsukasa Nishioka takahiro Komura Atsunobu Esa Shigeya Uejima Masaaki Imanishi Yasunari Uekado Takatoshi Ogawa Hiroshi Kajikawa Hirotsugu Uemura Department of Urology Graduate School of MedicineYamaguchi UniversityJapan Department of Urology Kinki University Faculty of MedicineJapan Department of Urology Wakayama Medical University School of MedicineJapan Department of Urology Sakai HospitalKinki University Faculty of MedicineJapan Department of Urology Naga HospitalJapan Department of Urology NTT Osaka HospitalJapan Department of Urology National Hospital Organization Osaka Minami Medical CenterJapan Department of Urology Nara Hospital Kinki University Faculty of MedicineJapan Department of Urology Tondabayashi HospitalJapan Department of Urology Wakayama Rosai HospitalJapan Department of Urology Kainan Municipal HospitalJapan Department of Urology Izumiotsu Municipal HospitalJapan

Objective:To clarify the oncological benefit of zoledronic acid for hormone-naive metastatic prostate cancer,patient outcome of androgen deprivation therapy with zoledronic acid(ADT+Z)and androgen deprivation therapy alone(ADT)was ***:Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade(goserelin and bicalutamide)with zoledronic acid(4 mg every 4 weeks for 24 months).A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts(both from ADT+Z and from historical control cohorts who had undergone ADT alone),and patient outcomes were ***:Patients with ADT+Z had significantly longer time to progression(TTP)than those with ADT(median TTP;24.2 vs.14.0 months,p=0.0092),while no significant difference of overall survival between two groups(p=0.1502).Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor(HR:1.724,95%CI:1.06-2.86,p=0.0297).Conclusion:Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

关键词： Zoledronic acid Hormone-naive prostate cancer Biochemical recurrence Propensity scorematch analysis

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Treatment strategies for advanced hepatocellular carcinoma:Sorafenib vs hepatic arterial infusion chemotherapy

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World Journal of Hepatology 2018年第9期10卷 571-584页

作者： Issei Saeki takahiro Yamasaki Masaki Maeda Takuro Hisanaga Takuya Iwamoto Koichi Fujisawa Toshihiko Matsumoto Isao Hidaka Yoshio Marumoto Tsuyoshi Ishikawa Naoki Yamamoto Yutaka Suehiro Taro Takami Isao Sakaida Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of MedicineYamaguchi 755-8505Japan Department of Oncology and Laboratory Medicine Yamaguchi University Graduate School of MedicineYamaguchi 755-8505Japan Department of Medical Education Yamaguchi University Graduate School of MedicineYamaguchi 755-8505Japan Center of Research and Education for Regenerative Medicine Yamaguchi University Graduate School of MedicineYamaguchi755-8505Japan Center for Clinical Research Yamaguchi University HospitalYamaguchi 755-8505Japan yamaguchi University Health Administration Center Yamaguchi 753-8511Japan

Sorafenib is used worldwide as a first-line standardsystemic agent for advanced hepatocellular carcinoma(HCC) on the basis of the results of two large-scale Phase Ⅲ trials. Conversely,hepatic arterial infusion chemotherapy(HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC,several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib,whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization,good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally,sorafenib is generally used to treat patients with Child-Pugh A,while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings,we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A,while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.

关键词： Treatment strategy Hepatic arterial infusion chemotherapy Sorafenib Hepatocellular carcinoma

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Investigation of Well-Balanced kV X-Ray Imaging Conditions between Skin Dose and Image Noise for Dynamic Tumor Tracking Irradiation

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2017年第4期6卷 410-420页

作者： takahiro Nakai Akira Sawada Hiroaki Tanabe Masaki Sueoka Sho Taniuchi Kenji Takayama Takehiro Shiinoki Yoshitomo Ishihara Masaki Kokubo Department of Radiological Technology Kobe City Medical Center General Hospital Kobe Japan Faculty of Medical Science Kyoto College of Medical Science Nantan Japan Department of Radiological Technology Institute of Biomedical Research and Innovation Kobe Japan Department of Radiation Oncology and Image-Applied Therapy Kyoto University Kyoto Japan Department of Radiation Oncology Yamaguchi University Ube Japan Division of Radiation Oncology Institute of Biomedical Research and Innovation Kobe Japan Department of Radiation Oncology Kobe City Medical Center General Hospital Kobe Japan

Purpose: The purposes of this study were to estimate accumulated kV X-ray imaging dose throughout dynamic tumor tracking (DTT) irradiation by Vero 4DRT system and to address an analytical skin dose formula for well-balanced kV X-ray imaging conditions between skin dose and image noise. Method: First, skin dose was measured using kV X-ray tube, chamber, and water-equivalent phantoms. Next, imaging dose for six patients in DTT treatment was computed using log files. Subsequently, scattered dose ratio was calculated by amount of ionization in front of flat panel detector (FPD) for fields with size of maximum and the chamber for 0 - 200 mm-thickness phantoms and tube voltage of 60, 80, 100, 120 kV, respectively. Furthermore, image noise was computed from FPD images. Results: The skin dose was greater by a factor of 1.4 - 1.6 than those in Synergy XVI system. The image noise in FPD, ?was expressed as N = 0.045×(1/QFPDen)0.479, where QFPDen denotes amount of ionization in front of FPD. Then, skin dose, D (N, t, v) was formulated as (0.045/N)(1/0.479)/QFPDen/mAs (t, v) ×D/mAs (v), where QFPDen/mAs (t, v) and D/mAs (v) denote amount of ionization in front of FPD and skin dose per mAs, respectively. Using the formulae, it has been demonstrated that skin dose with 120 kV has become lower than any other tube voltage in this study. Conclusion: Using skin doses for the phantom, the skin dose throughout DTT irradiation was estimated as 0.50 Gy. Furthermore, skin dose by kV X-ray imaging was described as a function of image noise, phantom thickness, and tube voltage, suggesting image noise may be reduced with higher X-ray tube voltage in this phantom study.

关键词： Dynamic Tumor Tracking Irradiation Skin Dose Vero4DRT

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