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| 1 | A rare case of hyaline-type Castleman disease in the liver显示文摘Castleman disease often develops in the neck, mediastinum and pulmonary hilum. Its onset in the peritoneal cavity is very rare. The patient, a woman in her 70s, was referred to our department for a detailed examination of an abdominal mass. On abdominal ultrasonography, computed tomography scan, magnetic resonance imaging and positron emission tomography, a mass approximately 15 mm in diameter was noted in the hepatic S6. We attempted radical treatment and conducted a laparoscope-assisted right lobectomy. On the basis of histopathological findings, the patient was diagnosed as having hyaline type Castleman disease in the liver, a very rare condition. | Hisaaki Miyoshi Shima Mimura Takako Nomura Joji Tani Asahiro Morishita Hideki Kobara Hirohito Mori Hirohito Yoneyama Akihiro Deguchi Takashi Himoto Naoki Yamamoto Keiichi Okano Yasuyuki Suzuki Tsutomu Masaki | 2013 | World Journal of Hepatology2013,5,7: | 14 |
| 2 | RAPDs和RFLPs分析甘蓝型杂交油菜亲本的遗传多样性显示文摘利用RAPD和RFLP分子标记技术对甘蓝型杂交油菜亲本遗传多样性的分析结果表明 :(1) 2 0个亲本间具有丰富的遗传多样性 ,4 0个引物扩增出 2 77条多态性带 ,其中 2 1条带为 10个亲本所特有 ,12个探针得到了 117条多态性杂交带 ,其中 7条带为 5个亲本所特有 ;(2 )不育系与恢复系之间的遗传差异大于不育系内和恢复系内的遗传差异 ;(3)依RAPDs与RFLPs估计的亲本遗传多样性存在有一定的差异 ,这种差异由估计时所用多态性带的数目不同而引起 ;(4)NJT聚类方法将 2 0份亲本分为 3组 :不育系组、恢复系组和混合组。杂交种“秦油 2号”和“华杂 3号”的双亲都被聚在不同的组内。 | 马朝芝 Sakai Takako 傅廷栋 孟金陵 杨光圣 涂金星 | 2003 | 作物学报2003,29,5: | 12 |
| 3 | Vitamin D and calcium are required at the time of denosumab administration during osteoporosis treatment显示文摘To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group(18 cases) or a denosumab plus vitamin D supplementation group(combination group; 23 cases). We measured serum bone alkaline phosphatase(BAP), tartrate-resistant acid phosphatase(TRACP)-5 b and urinary N-terminal telopeptide of type-I collagen(NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We also measured bone mineral density(BMD) of L1–4 lumbar vertebrae(L)-BMD and bilateral hips(H)-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5 b and urinary NTX were significantly suppressed in both groups from 1 week to 12 months(except at 12 months for NTX). In the combination group, TRACP-5 b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months(P < 0.05).BAP was significantly suppressed in both groups at 2–12 months. L-BMD significantly increased at 8 and12 months(8.9%) in the combination group and at 4, 8 and 12 months(6.0%) in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group(3.6%) compared with the denosumab group(1.2%) at 12 months(P < 0.05). Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD(especially at the hips). | Yukio Nakamura Takako Suzuki Mikio Kamimura Kohei Murakami Shota Ikegami Shigeharu Uchiyama Hiroyuki Kato | 2017 | Bone Research2017,5,4: | 11 |
| 4 | Diabetes mellitus and metformin in hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects. The search for biological links between cancer and diabetes has revealed intracellular pathways that are shared by cancer and diabetes. The signal transduction mechanisms by which metformin suppresses carcinogenesis in cell lines or xenograft tissues and improves chemoresistance in cancer stem cells have also been elucidated. This review addresses the clinical and biological links between HCC and diabetes mellitus and the anti-cancer activity of metformin in clinical studies and basic experiments. | Koji Fujita Hisakazu Iwama Hisaaki Miyoshi Joji Tani Kyoko Oura Tomoko Tadokoro Teppei Sakamoto Takako Nomura Asahiro Morishita Hirohito Yoneyama Tsutomu Masaki | 2016 | World Journal of Gastroenterology2016,22,27: | 7 |
| 5 | Different natural courses of chronic hepatitis B with genotypes B and C after the fourth decade of life显示文摘AIM: To investigate the different impact of genotypes B and C on the development of liver cirrhosis (LC) among different age groups of patients with chronic hepatitis B (CH-B). METHODS: We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC. RESULTS: In patients < 30 years old, there were no significant predictors for development of LC. However, in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12 patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis (7 patients were positive for HBeAg). In the genotype B group, 4 of 8 patients who developed LC were ≥ 50 years old at initial diagnosis and were HBeAg-negative. CONCLUSION: The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at < 30 years old. However, CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs. | Tatsuji Maeshiro Shingo Arakaki Takako Watanabe Hajime Aoyama Joji Shiroma Tsuyoshi Yamashiro Tetsuo Hirata Akira Hokama Fukunori Kinjo Tomofumi Nakayoshi Tomokuni Nakayoshi Masashi Mizokami Jiro Fujita Hiroshi Sakugawa | 2007 | World Journal of Gastroenterology2007,13,34: | 7 |
| 6 | Bleeding duodenal hemangioma: Morphological changes and endoscopic mucosal resection显示文摘Recently, the development of endoscopic procedures has increased the availability of minimally invasive treatments; however, there have been few case reports of duodenal hemangioma treated by endoscopic mucosal resection. The present report describes a case of duodenal hemangioma that showed various endoscopic changes over time and was treated by endoscopic mucosal resection. An 80-year-old woman presented with tarry stools and a loss of appetite. An examination of her blood revealed severe anemia, and her hemoglobin level was 4.2 g/dL. An emergency upper gastrointestinal endoscopy was performed. A red, protrusive, semipedunculated tumor (approximately 20 mm in diameter) with spontaneous bleeding on its surface was found in the superior duodenal angle. Given the semipedunculated appearance of the tumor, it was suspected to be an epithelial tumor with a differential diagnosis of hyperplastic polyp. The biopsy results suggested a telangiectatic hemangioma. Because this lesion was considered to be responsible for her anemia, endoscopic mucosal resection was performed for diagnostic and treatment purposes after informed consent was obtained. A histopathological examination of the resected specimen revealed dilated and proliferated capillary lumens of various sizes, which confirmed the final diagnosis of duodenal hemangioma. Neither anemia nor tumor recurrence has been observed since the endoscopic mucosal resection (approximately 1 year). Duodenal hemangiomas can be treated endoscopically provided that sufficient consideration is given to all of the possible treatment strategies. Interestingly, duodenal hemangiomas show morphological changes that are influenced by various factors, such as mechanical stimuli. | Noriko Nishiyama Hirohito Mori Hideki Kobara Shintarou Fujihara Takako Nomura Mitsuyoshi Kobayashi Tsutomu Masaki | 2012 | World Journal of Gastroenterology2012,18,22: | 7 |
| 7 | Two distinct pathways of p16 gene inactivation in gallbladder cancer显示文摘AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder cancer,and to investigate p16 alterations and their correlation with clinicopathological features. METHODS: Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression,loss of heterozygosity (LOH),homozygous deletion and promoter hypermethylation using immunohistochemistry,microsatellite analysis,quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR,respectively. In addition,mutations were examined by direct DNA sequencing. RESULTS: Homozygous deletions of the p16 gene exon2,LOH at 9p21-22,p16 promoter hypermethylation,and loss of p16 protein expression were detected in 26.0% (13/50),56.9% (29/51),72.5% (37/51) and 62.7% (32/51),respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene,a combination LOH and promoter hypermethylation,and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene,respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION: Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion,a combination of LOH and promoter hypermethylation,and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer. | Hiroyuki Tadokoro Takako Shigihara Tomomi Ikeda Masaru Takase Masafumi Suyama | 2007 | World Journal of Gastroenterology2007,13,47: | 6 |
| 8 | Transnasal endoscopic retrograde chalangiopancreatography using an ultrathin endoscope: A prospective comparison with a routine oral procedure显示文摘AIM: To investigate if transnasal endoscopic retrograde cholangiopancreatography (n-ERCP) using an ultrathin forward-viewing scope may overcome the disadvantages of conventional oral ERCP (o-ERCP) related to the large- caliber side-viewing duodenoscope. METHODS: The study involved 50 patients in whom 25 cases each were assigned to the o-ERCP and n-ERCP groups. We compared the requirements of esophagogastroduodenoscopy (EGD) prior to ERCP, rates and times required for successful cannulation into the pancreatobiliary ducts, incidence of post-procedure hyperamylasemia, cardiovascular parameters during the procedure, the dose of a sedative drug, and successful rates of endoscopic naso-biliary drainage (ENBD). RESULTS: Screening gastrointestinal observations were easily performed by the forward-viewing scope and thus no prior EGD was required in the n-ERCP group. There was no significant difference in the rates or times for cannulation, or incidence of hyperamylasemia between the groups. However, the cannulation was relatively difficult in n-ERCP when the scope appeared U-shape under fluoroscopy. Increments of blood pressure and the amount of a sedative drug were significantly lower in the n-ERCP group. ENBD was successfully performed succeeding to the n-ERCP in which mouth-to-nose transfer of the drainage tube was not required. CONCLUSION: n-ERCP is likely a well-tolerable methodwith less cardiovascular stress and no need of prior EGD or mouth-to-nose transfer of the ENBD tube. However, a deliberate application is needed since its performance is difficult in some cases and is not feasible for some endoscopic treatments such as stenting. | Akihiro Mori Noritsugu Ohashi Takako Maruyama Hideharu Tatebe Katsuhisa Sakai Takashi Shibuya Hiroshi Inoue Shoudou Takegoshi Masataka Okuno | 2008 | World Journal of Gastroenterology2008,14,10: | 6 |
| 9 | Shikonin Promotes Skin Cell Proliferation and Inhibits Nuclear Factor-κB Translocation via Proteasome Inhibition In Vitro显示文摘 | Yan Yan Minao Furumura Takako Gouya Atsufumi Iwanaga Kwesi Teye Sanae Numata Tadashi Karashima Xiao-Guang Li Takashi Hashimoto | 2015 | Chinese Medical Journal2015,,16: | 6 |
| 10 | A Combined Computational and Experimental Study on the Structure-Regulation Relationships of Putative Mammalian DNA Replication Initiator GINS显示文摘GINS, a heterotetramer of SLD5, PSF1, PSF2, and PSF3 proteins, is an emerging chromatin factor recognized to be involved in the initiation and elongation step of DNA replication. Although the yeast and Xenopus GINS genes are well docu- mented, their orthologous genes in higher eukaryotes are not fully characterized. In this study, we report the genomic structure and transcriptional regulation of mammalian GINS genes. Serum stimulation increased the GINS mRNA levels in human cells. Reporter gene assay using putative GINS promoter sequences revealed that the expression of mammalian GINS is regulated by 17β-Estradiol- stimulated estrogen receptor α, and human PSF3 acts as a gene responsive to transcription factor E2F1. The goal of this study is to present the current data so as to encourage further work in the field of GINS gene regulation and functions in mammalian cells. | Reiko Hayashi Takako Arauchi Moe Tategu Yuya Goto Kenichi Yoshida | 2006 | Genomics, Proteomics & Bioinformatics2006,4,3: | 4 |
| 11 | Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011显示文摘 | Hisanori Umehara Kazuichi Okazaki Yasufumi Masaki Mitsuhiro Kawano Motohisa Yamamoto Takako Saeki Shoko Matsui Tadashi Yoshino Shigeo Nakamura Shigeyuki Kawa Hideaki Hamano Terumi Kamisawa Toru Shimosegawa Akira Shimatsu Seiji Nakamura Tetsuhide Ito Kenji | 2012 | Modern Rheumatology2012,,1: | 4 |
| 12 | gastrointestinal symptom prevalence depends on disease duration and gastrointestinal region in type 2 diabetes mellitus显示文摘AIM To unravel relationships between gastrointestinal(GI)symptoms impairing quality of life(QOL)and clinical profiles of diabetes mellitus(DM)patients. METHODS We enrolled 134 outpatients with type 2 DM.Mean age was 64.7 years,mean body mass index was 24.7 RESULTS Lower abdominal symptoms were found to be more frequent than those affecting the upper abdomen.Diabetic duration and medications showed associations with GI symptoms.We identified differences in peak prevalences of the five symptoms.Gastralgia(P=0.02vs 10-14 years)and total GI symptoms(P=0.01 and P=0.02 vs 5-9 years and 10-14 years,respectively)peaked at a diabetes duration of 15-19 years.Heartburn(P=0.004)and postprandial fullness(P=0.03)tended to increase with disease duration.Constipation and diarrhea showed bimodal peaks,with the first early and the second late(e.g.,P=0.03 at 15-19 years vs 10-14years for diarrhea)in the disease course.Finally,GI symptoms showed clustering that reflected the region of the GI tract affected,i.e.,constipation and diarrhea had similar frequencies(P<0.0001). CONCLUSION Our study highlights the importance of questioning patients about QOL impairment due to abdominal symptoms,especially in the early and the late periods of diabetes. | Midori Fujishiro Akifumi Kushiyama Hiroki Yamazaki Sunao Kaneko Yuko Koketsu Takeshi Yamamotoya Takako Kikuchi Hideyuki Sakoda Ryo Suzuki Takashi Kadowaki | 2017 | World Journal of Gastroenterology2017,23,36: | 4 |
| 13 | A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details显示文摘 | Hisanori Umehara Kazuichi Okazaki Yasufumi Masaki Mitsuhiro Kawano Motohisa Yamamoto Takako Saeki Shoko Matsui Takayuki Sumida Tsuneyo Mimori Yoshiya Tanaka Kazuo Tsubota Tadashi Yoshino Shigeyuki Kawa Ritsuro Suzuki Tsutomu Takegami Naohisa Tomosugi Nozo | 2012 | Modern Rheumatology2012,,1: | 4 |
| 14 | Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy显示文摘AIM To determine the clinical characteristics of elderly patients of hemorrhagic gastroduodenal ulcer on low-dose aspirin(LDA)therapy.METHODS A total of 1105 patients with hemorrhagic gastroduodenal ulcer treated in our hospital between January 2000 and March 2016 were grouped by age and drugs used,and these groups were compared in several factors.These groups were compared in terms of length of hospital stay,presence/absence of hemoglobin(Hb)decrease,presence/absence of blood transfusion,Forrest Ⅰ,percentage of Helicobacter pylori infection,presence/absence of underlying disease,and percentage of severe cases.RESULTS The percentage of blood transfusion(62.6%vs 47.7%,P<0.001),Hb decrease(53.8% vs 40.8%,P<0.001),and the length of hospital stay(23.5 d vs 16.7 d,P<0.001)were significantly greater in those on drug therapy.The percentage of blood transfusion(65.3%vs 47.8%,P<0.001),Hb decrease(54.2%vs 42.1%,P<0.001),and length of hospital stay(23.3 d vs 17.5 d,P<0.001)were significantly greater in the elderly.In comparison with the LDA monotherapy group,the percentage of severe cases was significantly higher in the LDA combination therapy group when elderly patients were concerned(16.1%vs34.0%,P=0.030).Meanwhile,among those on LDA monotherapy,there was no significant difference between elderly and non-elderly(16.1%vs 16.0%,P=0.985).CONCLUSION A combination of LDA with antithrombotic drugs or nonsteroidal anti-inflammatory drugs(NSAIDs)contributes to aggravation.And advanced age is not an aggravating factor when LDA monotherapy is used. | Koh Fukushi Keiichi Tominaga Kazunori Nagashima Akira Kanamori Naoya Izawa Mimari Kanazawa Takako Sasai Hideyuki Hiraishi | 2018 | World Journal of Gastroenterology2018,24,34: | 3 |
| 15 | Effect of the anti-diabetic drug metformin in hepatocellular carcinomain vitro and in vivo显示文摘 | Hisaaki Miyoshi Kiyohito Kato Hisakazu Iwama Emiko Maeda Teppei Sakamoto Koji Fujita Yuka Toyota Joji Tani Takako Nomura Shima Mimura Mitsuyoshi Kobayashi Asahiro Morishita Hideki Kobara Hirohito Mori Hirohito Yoneyama Akihiro Deguchi Takashi Himoto Kazut | 2014 | International Journal of Oncology2014,,1: | 3 |
| 16 | Clinical importance of colonoscopy in patients with gastric neoplasm undergoing endoscopic submucosal dissection显示文摘AIM To evaluate the usefulness of total colonoscopy(TCS) for patients undergoing gastric endoscopic submucosal dissection(ESD) and to assess risk factors for colorectal neoplasms.METHODS Of the 263 patients who underwent ESD at our department between May 2010 and December 2013, 172 patients undergoing TCS during a one-year period before and after ESD were targeted. After excluding patients with a history of surgery or endoscopic therapy for colorectal neoplasms, 158 patients were analyzed. Of the 868 asymptomatic patients who underwent TCS during the same period because of positive fecal immunochemical test(FIT) results, 158 patients with no history of either surgery or endoscopic therapy for colorectal neoplasms who were matched for age and sex served as the control group for comparison.RESULTS TCS revealed adenoma less than 10 mm in 53 patients(33.6%), advanced adenoma in 17(10.8%), early colorectal cancer in 5(3.2%), and advanced colorectalcancer in 4(2.5%). When the presence or absence of adenoma less than 10 mm, advanced adenoma, and colorectal cancer and the number of adenomas were compared between patients undergoing ESD and FITpositive patients, there were no statistically significant differences in any of the parameters assessed. The patients undergoing ESD appeared to have the same risk of colorectal neoplasms as the FIT-positive patients. Colorectal neoplasms were clearly more common in men than in women(P = 0.031). Advanced adenoma and cancer were significantly more frequent in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus(P = 0.019).CONCLUSION In patients undergoing gastric ESD, TCS appears to be important for detecting synchronous double neoplasms. Advanced adenoma and cancer were more common in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus. Caution is therefore especially warranted in patients with these risk factors. | Chieko Tsuchida Naoto Yoshitake Hitoshi Kino Yoshihito Kaneko Masakazu Nakano Kohei Tsuchida Keiichi Tominaga Takako Sasai Hironori Masuyama Hidetsugu Yamagishi Yasuo Imai Hideyuki Hiraishi | 2017 | World Journal of Gastroenterology2017,23,23: | 3 |
| 17 | Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as melena with long-term survival: A case report and review of literature显示文摘BACKGROUND Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is a rare primary intestinal T-cell lymphoma,previously known as enteropathy-associated T-cell lymphoma type II.MEITL is an aggressive T-cell lymphoma with a poor prognosis and high mortality rate.The known major complications of MEITL are intestinal perforation and obstruction.Here,we present a case of MEITL that was diagnosed following upper gastrointestinal bleeding from an ulcerative duodenal lesion,with recurrence-free survival for 5 years.CASE SUMMARY A 68-year-old female was admitted to our hospital with melena and mild anemia.An urgent esophagogastroduodenoscopy(EGD)revealed bleeding from an ulcerative lesion in the transverse part of the duodenum,for which hemostatic treatment was performed.MEITL was diagnosed following repeated biopsies of the lesion,and cyclophosphamide,doxorubicin,vincristine,and prednisone(CHOP)chemotherapy was administered.She achieved complete remission after eight full cycles of CHOP therapy.At the last follow-up examination,EGD revealed a scarred ulcer and 18Fluorodeoxyglucose(18FDG)positron emission tomography/computed tomography showed no abnormal FDG accumulation.The patient has been in complete remission for 68 mo after initial diagnosis.CONCLUSION To rule out MEITL,it is important to carefully perform histological examination when bleeding from a duodenal ulcer is observed. | Sotaro Ozaka Kunimitsu Inoue Tomoya Okajima Takako Tasaki Shimpei Ariki Hideki Ono Takeaki Ando Tsutomu Daa Kazunari Murakami | 2021 | World Journal of Gastroenterology2021,27,38: | 3 |
| 18 | Perspectives of Science and Technology in Disaster Risk Reduction of Asia显示文摘Science and technology innovation has always been present in Asia,but its application in disaster risk reduction(DRR) has been differential.In Asia,globally significant hotspots of disasters and economic development have emerged in which the application of science and technology in DRR has become an essential requirement for informed decision making.Science has supported establishment and implementation of major international initiatives in DRR,including the Hyogo Framework for Action 2005-2015.The more recent Sendai Framework for DRR 2015-2030 recognizes the importance of science and technology in all of its priority action areas,and subsequent global and regional forums and conferences have reconfirmed science and technology's importance.To perceive and monitor the progress of science and technology in DRR,a qualitative assessment of different countries is made using three major attributes:(1) science-based decision making;(2) investment in science and technology;and(3) the intensity of science's link to the public.This assessment exercise points out several strengths and weaknesses in science and technology application;the method can be employed to develop future multistakeholder and multidisciplinary science and technology plans at the country level.To implement regional and national activities,a set of 15 recommendations is put forward,which will strengthen the collective regional 'science voice' in DRR. | Rajib Shaw Takako Izumi Peijun Shi | 2016 | International Journal of Disaster Risk Science2016,7,4: | 2 |
| 19 | Brassinosteroid functions in a broad range of disease resistance in tobacco and rice 显示文摘 | Hideo N Michiko Y Takako N | 2003 | The Plant Journal2003,33,5: | 2 |
| 20 | Metachronous gastric cancers after endoscopic resection: how effective is annual endoscopic surveillance?显示文摘 | Takeshi Nakajima Ichiro Oda Takuji Gotoda Hisanao Hamanaka Takako Eguchi Chizu Yokoi Daizo Saito | 2006 | Gastric Cancer2006,,2: | 2 |