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| 1 | Liver metastasis is the only independent prognostic factor in AFP-producing gastric cancer显示文摘AIM:To investigate differences between common gastric cancer andα-fetoprotein(AFP)-producing gastric cancer according to the presence or absence of liver metastasis.METHODS:Between 1997 and 2011,1299 patients underwent gastrectomy for gastric cancer(GC)at our institute and their hospital records were reviewed retrospectively.Patients were immunohistochemically divided into two groups:23 patients(1.8%)with AFPproducing GC and 1276 patients(98.2%)without it.RESULTS:AFP-producing GC patients had a significantly higher incidence of deeper tumors,venous invasion,lymphatic invasion,lymph node metastasis,and liver metastasis and a poorer prognosis(P<0.005)than those without AFP-producing GC.However,multi-variate analysis revealed that AFP-positivity was not an independent prognostic factor.The prognosis of AFPproducing GC was similar to that of AFP-non producing GC according to the presence or absence of liver metastasis.Concerning recurrence,47.8%of patients(11/23)with AFP-producing GC and 20.0%of patients(256/1276)without AFP-producing GC exhibited recurrence.Liver metastasis[90.9%(10/11)]was the most prevalent in AFP-producing GC patients.Multivariate analysis revealed that liver metastasis was the only independent prognostic factor in AFP-producing GC(HR=17.6,95%CI:2.1-147.1;P=0.0081).CONCLUSION:AFP-producing GC is similar to common GC without liver metastasis,which should be specifically targeted in an effort to improve the prognosis of AFP-producing GC patients. | Shoji Hirajima Shuhei Komatsu Daisuke Ichikawa Takeshi Kubota Kazuma Okamoto Atsushi Shiozaki Hitoshi Fujiwara Hirotaka Konishi Hisashi Ikoma Eigo Otsuji | 2013 | World Journal of Gastroenterology2013，19，36： | 33 |
| 2 | Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy显示文摘AIM: To re-evaluate the recent clinicopathological features of remnant gastric cancer (RGC) and to develop desirable surveillance programs. METHODS: Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan. Of these, 33 patients underwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gastric cancer. The hospital records of these patients were reviewed retrospectively. RESULTS: Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter interval [P < 0.05; gastric cancer vs benign disease: 12 (2-22) vs 30 (4-51) years] and were more frequently reconstructed by Billroth-Ⅰ procedure than those following benign lesions (P < 0.001). Regarding reconstruction, RGC following Billroth-Ⅱ reconstruction showed a longer interval between surgical procedures [P < 0.001; Billroth-Ⅱ vs Billroth-Ⅰ: 32 (5-51) vs 12 (2-36) years] and tumors were more frequently associated with benign disease (P < 0.001) than those following Billroth-Ⅰ reconstruction. In tumor location of RGC, after Billroth-Ⅰ reconstruction, RGC occurred more frequently near the suture line and remnant gastric wall. After Billroth-Ⅱ reconstruction, RGC occurred more frequently at the anastomotic site. The duration of follow-up was significantly associated with the stage of RGC (P < 0.05). Patients diagnosed with early stage RGC such as stage Ⅰ-Ⅱ tended to have been followed up almost every second year. CONCLUSION: Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC. | Shuhei Komatsu Daisuke Ichikawa Kazuma Okamoto Daito Ikoma Masahiro Tsujiura Yukihisa Nishimura Yasutoshi Murayama Atsushi Shiozaki Hisashi Ikoma Yoshiaki Kuriu Masayoshi Nakanishi Hitoshi Fujiwara Toshiya Ochiai Yukihito Kokuba Eigo Otsuji | 2012 | World Journal of Gastroenterology2012，18，22： | 25 |
| 3 | Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids显示文摘Hepatocellular carcinoma(HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called 'liquid biopsy' is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma. | wataru okajima shuhei komatsu daisuke ichikawa mahito miyamae takuma ohashi taisuke imamura jun kiuchi keiji nishibeppu tomohiro arita hirotaka konishi atsushi shiozaki ryo morimura hisashi ikoma kazuma okamoto eigo otsuji | 2017 | World Journal of Gastroenterology2017，23，31： | 22 |
| 4 | Optimal duration of the early and late recurrence of hepatocellular carcinoma after hepatectomy显示文摘AIM: To determine the best cut-off value between the early and late recurrence periods after the initial recurrence of hepatocellular carcinoma(HCC).METHODS: The clinical records of 404 patients who underwent macroscopic curative hepatectomy for HCC between 1980 and 2010 were retrospectively examined. We divided the 252 patients experienced a recurrence of HCC into two groups, the early and late recurrence groups using the 'minimum P-value' approach. Factors for early recurrence were investigated using all 404 patients, and factors related to late recurrence were investigated in the patients who were confirmed to be recurrence free at the end of the early recurrence period.RESULTS: For the 252 patients who experienced a recurrence, the optimal cut-off value for differentiating early and late recurrence based on the overall survival after initial recurrence was 17 mo(5-year overall survival after initial recurrence: 15.4% vs 36.3%, P = 0.000018). Cox proportional hazard analysis identified early recurrence(P = 0.003) as one of the independent prognostic factors associated with overall survival after initial recurrence. A logistic regression model showed that an alpha-fetoprotein level > 100 ng/m L(P < 0.001), multiple HCC(P < 0.001), serosal invasion(P = 0.031), and microvascular invasion(P = 0.012) were independent factors associated with early recurrence, whereas the only independent factor related to late recurrence was liver cirrhosis(P = 0.002).CONCLUSION: Seventeen months after hepatectomy is a useful cut-off value between early and late recurrence of HCC based on the prognosis and different etiologies. | Yusuke Yamamoto Hisashi Ikoma Ryo Morimura Hirotaka Konishi Yasutoshi Murayama Shuhei Komatsu Atsushi Shiozaki Yoshiaki Kuriu Takeshi Kubota Masayoshi Nakanishi Daisuke Ichikawa Hitoshi Fujiwara Kazuma Okamoto Chouhei Sakakura Toshiya Ochiai Eigo Otsuji | 2015 | World Journal of Gastroenterology2015，21，4： | 14 |
| 5 | Risk factors to predict severe postoperative pancreatic fistula following gastrectomy for gastric cancer显示文摘AIM:To allow the identification of high-risk postoperative pancreatic fistula(POPF)patients with special reference to the International Study Group on Pancreatic Fistula(ISGPF)classification.METHODS:Between 1997 and 2010,1341 consecutive patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery,Kyoto Prefectural University of Medicine,Japan.Based on the preoperative diagnosis,total or distal gastrectomy and sufficient lymphadenectomy was performed,mainly according to the Japanese guidelines for the treatment of gastric cancer.Of these,35 patients(2.6%)were diagnosed with Grade B or C POPF according to the ISGPF classification and were treated intensively.The hospital records of these patients were reviewed retrospectively.RESULTS:Of 35 patients with severe POPF,17(49%)and 18(51%)patients were classified as Grade B and C POPF,respectively.From several clinical factors,the severity of POPF according to the ISGPF classification was significantly correlated with the duration of intensive POPF treatments(P=0.035).Regarding the clinical factors to distinguish extremely severe POPF,older patients(P=0.035,65 years≤vs<65 years old)and those with lower lymphocyte counts at the diagnosis of POPF(P=0.007,<1400/mm3vs 1400/mm3≤)were significantly correlated with Grade C POPF,and a low lymphocyte count was an independent risk factor by multivariate analysis[P=0.045,OR=10.45(95%CI:1.050-104.1)].CONCLUSION:Caution and intensive care are required for older POPF patients and those with lower lymphocyte counts at the diagnosis of POPF. | Shuhei Komatsu Daisuke Ichikawa Kingo Kashimoto Takeshi Kubota Kazuma Okamoto Hirotaka Konishi Atsushi Shiozaki Hitoshi Fujiwara Eigo Otsuji | 2013 | World Journal of Gastroenterology2013，19，46： | 13 |
| 6 | Surgical treatment of hepatocellular carcinoma with severe intratumoral arterioportal shunt显示文摘We report a case of hepatocellular carcinoma (HCC) that caused a severe arterioportal shunt (APS). A 49-year-old man was admitted to hospital due to esophagogastric variceal hemorrhage and HCC, and underwent endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). He was then referred to our hospital. Abdominal computed tomography revealed a lowdensity lesion in the posterior segment of the liver and an intratumoral APS, which caused portal hypertension. Although the patient underwent EVL, EIS, Hassab’s operation, and transcatheter arterial embolization for APS, he vomited blood due to rupture of esophagogastric varices. Right hepatectomy was performed for the treatment of HCC and APS, although the indocyanine green retention value at 15 min after intravenous injection was poor (30%). The patient’s postoperative course was uneventful. Eventually, APS disappeared and the esophagogastric varices improved. | Hiromichi Ishii Teruhisa Sonoyama Shingo Nakashima Hiroyuki Nagata Atsushi Shiozaki Yoshiaki Kuriu Hisashi Ikoma Masayoshi Nakanishi Daisuke Ichikawa Hitoshi Fujiwara Kazuma Okamoto Toshiya Ochiai Yukihito Kokuba Chohei Sakakura Eigo Otsuji | 2010 | World Journal of Gastroenterology2010，16，25： | 11 |
| 7 | Liquid biopsy in patients with pancreatic cancer: Circulating tumor cells and cell-free nucleic acids显示文摘Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called 'liquid biopsy' has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field. | Taisuke Imamura Shuhei Komatsu Daisuke Ichikawa Tsutomu Kawaguchi Mahito Miyamae Wataru Okajima Takuma Ohashi Tomohiro Arita Hirotaka Konishi Atsushi Shiozaki Ryo Morimura Hisashi Ikoma Kazuma Okamoto Eigo Otsuji | 2016 | World Journal of Gastroenterology2016，22，25： | 10 |
| 8 | Medical management of gastric cancer:A 2014 update显示文摘Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy(United States),pre-and post-operative chemotherapy(Europe),and adjuvant chemotherapy after a D2 resection(Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population,the treatments remain limited.In the first line setting,the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy,with or without epirubicin or docetaxel.The results of targeted therapy trials have by and large been disappointing,but none of these trials looked at an appropriately enriched population.Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting,with either irinotecan,docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial. | Elena Elimova Hironori Shiozaki Roopma Wadhwa Kazuki Sudo Qiongrong Chen Jeannelyn S Estrella Mariela A Blum Brian Badgwell Prajnan Das Shumei Song Jaffer A Ajani | 2014 | World Journal of Gastroenterology2014，20，38： | 10 |
| 9 | Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis显示文摘AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P < 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) > 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis. | Yusuke Yamamoto Hisashi Ikoma Ryo Morimura Katsutoshi Shoda Hirotaka Konishi Yasutoshi Murayama Shuhei Komatsu Atsushi Shiozaki Yoshiaki Kuriu Takeshi Kubota Masayoshi Nakanishi Daisuke Ichikawa Hitoshi Fujiwara Kazuma Okamoto Chouhei Sakakura Toshiya Ochiai Eigo Otsuji | 2015 | World Journal of Gastroenterology2015，21，1： | 9 |
| 10 | Evolution of gastric surgery techniques and outcomes显示文摘Surgical management of gastric cancer improves survival.However,for some time,surgeons have had diverse opinions about the extent of gastrectomy.Researchers have conducted many clinical studies,making slow but steady progress in determining the optimal surgical approach.The extent of lymph node dissection has been one of the major issues in surgery for gastric cancer.Many trials demonstrated that D2 dissection resulted in greater morbidity and mortality than D1 dissection.However,long-term outcomes demonstrated that D2 dissection resulted in longer survival than D1 dissection.In 2004,the Japan Clinical Oncology Group reported a pivotal trial which was performed to determine whether para-aortic lymph node dissection combined with D2 dissection was superior to D2 dissection alone and found no benefit of the additional surgery.Gastrectomy with pancreatectomy,splenectomy,and bursectomy was initially recommended as part of the D2 dissection.Now,pancreas-preserving total gastrectomy with D2 dissection is standard,and ongoing trials are addressing the role of splenectomy.Furthermore,the feasibility and safety of laparoscopic gastrectomy are well established.Survival and quality of life are increasingly recognized as the most important endpoints.In this review,we present perspectives on surgical techniques and important trials of these techniques in gastric cancer patients. | Hironori Shiozaki Yusuke Shimodaira Elena Elimova Roopma Wadhwa Kazuki Sudo Kazuto Harada Jeannelyn S.Estrella Prajnan Das Brian Badgwell Jaffer A.Ajani | 2016 | Chinese Journal of Cancer2016，35，8： | 9 |
| 11 | Liquid biopsy of gastric cancer patients:Circulating tumor cells and cell-free nucleic acids显示文摘To improve the clinical outcomes of cancer patients,early detection and accurate monitoring of diseases are necessary.Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression,and analyses of these changes have been increasingly utilized for diagnostic,prognostic and therapeutic purposes in malignant diseases including gastric cancer(GC).Surgical and/or biopsy specimens are generally used to understand the tumor-associated alterations;however,those approaches cannot always be performed because of their invasive characteristics and may fail to reflect current tumor dynamics and drug sensitivities,which may change during the therapeutic process.Therefore,the importance of developing a non-invasive biomarker with the ability to monitor real-time tumor dynamics should be emphasized.This concept,so called'liquid biopsy',would provide an ideal therapeutic strategy for an individual cancer patient and would facilitate the development of'tailor-made'cancer management programs.In the blood of cancer patients,the presence and potent utilities of circulating tumor cells(CTCs)and cell-free nucleic acids(cfNAs)such as DNA,mRNA and microRNA have been recognized,and their clinical relevance is attracting considerable attention.In this review,we discuss recent developments in this research field as well as the relevance and future perspectives of CTCs and cfNAs in cancer patients,especially focusing on GC. | Masahiro Tsujiura Daisuke Ichikawa Hirotaka Konishi Shuhei Komatsu Atsushi Shiozaki Eigo Otsuji | 2014 | World Journal of Gastroenterology2014，20，12： | 8 |
| 12 | Clinicopathological characteristics of clinical early gastric cancer in the upper-third stomach显示文摘AIM: To elucidate the clinicopathological characteristics of clinically early gastric cancer in the upper-third stomach and to clarify treatment precautions.METHODS: A total of 683 patients with clinical early gastric cancer were enrolled in this retrospective study, 128 of whom had gastric cancer in the upper-third stomach(U group). All patients underwent a double contrast barium examination, endoscopy, and computed tomography(CT), and were diagnosed preoperatively based on the findings obtained. The clinicopathological features of these patients were compared with those of patients with gastric cancer in the middle- and lower-third stomach(ML group). We also compared clinicopathological factors between accurate-diagnosis and under-diagnosis groups in order to identify factors affecting the accuracy of a preoperative diagnosis of tumor depth.RESULTS: Patients in the U group were older(P = 0.029), had a higher ratio of males to females(P = 0.015), and had more histologically differentiated tumors(P = 0.007) than patients in the ML group. A clinical under-diagnosis occurred in 57 out of 683 patients(8.3%), and was more frequent in the U group than in the ML group(16.4% vs 6.3%, P < 0.0001). Therefore, the rates of lymph node metastasis and lymphatic invasion were slightly higher in the U group than in the ML group(P = 0.071 and 0.082, respectively). An under-diagnosis was more frequent in histologically undifferentiated tumors(P = 0.094) and in those larger than 4 cm(P = 0.024). The medianfollow-up period after surgery was 56 mo(range, 1-186 mo). Overall, survival and disease-specific survival rates were significantly lower in the U group than in the ML group(P = 0.016 and 0.020, respectively). However, limited operation-related cancer recurrence was not detected in the U group in the present study.CONCLUSION: Clinical early gastric cancer in the upper-third stomach has distinguishable characteristics that increase the risk of a clinical under-diagnosis, especially in patients with larger or undifferentiated tumors. | Daisuke Ichikawa Shuhei Komatsu Toshiyuki Kosuga Hirotaka Konishi Kazuma Okamoto Atsushi Shiozaki Hitoshi Fujiwara Eigo Otsuji | 2015 | World Journal of Gastroenterology2015，21，45： | 6 |
| 13 | Intracellular chloride regulates the G_1/S cell cycle progression in gastric cancer cells显示文摘Recent studies show that ion channels/transporters play important roles in fundamental cellular functions. Several reports indicating the important roles of Cl- channels/transporters on cell proliferation suggest that the intracellular chloride concentration ([Cl-]i) regulated by them would be one of critical messengers. We investigated whether the [Cl-]i controls cell proliferation and cell cycle progression in human gastric cancer cells. Our studies indicated that furosemide, a blocker of Na+ /K+ /2Cl- cotransporter (NKCC), diminished cell growth by delaying the G1-S phase progression in gastric cancer cells with high expression and activity of NKCC. Furthermore, we found that the culture in the low Cl- medium (replacement of Cl- by NO3-) decreased the [Cl-]i and inhibited cell growth of gastric cancer cells and that this inhibition of cell growth was due to cell cycle arrest at the G0/G1 phase caused by diminutionof CDK2 and phosphorylated Rb. The culture of cells in the low Cl- medium significantly increased expressions of p21 mRNA and protein. In addition, the low Cl- medium induced phosphorylation of mitogen activated protein kinases (MAPKs). Treatment with an inhibitor of p38 or JNK significantly suppressed p21 upregulation caused by culture in a low Cl- medium and rescued gastric cancer cells from the low Cl- -induced G1 cell cycle arrest. These findings revealed that the [Cl-]i affects the cell proliferation via activation of MAPKs through upregulation of p21 in gastric cancer cells. Our results suggest that the [Cl-]i regulates important cellular functions in gastric cancer cells, leading to the development of novel therapeutic strategies. | Atsushi Shiozaki Eigo Otsuji Yoshinori Marunaka | 2011 | World Journal of Gastrointestinal Oncology2011，3，8： | 6 |
| 14 | Complete response to preoperative chemoradiotherapy in highly advanced gastric adenocarcinoma显示文摘This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underwent FDG positron emission tomography (PET) during a routine health examination. The patient was found to have swollen paraaortic lymph nodes. Shortly thereafter, he was diagnosed with gastric carcinoma with a type 2 tumor in the antrum with paraaortic lymph node metastases based on FDG-PET, endoscopic examination and abdominal computed tomography. After the completion of chemoradiation therapy (CRT), the tumor and the paraaortic lymph node metastases disappeared. The patient underwent surgery 5 wk after the completion of CRT, including a subtotal gastrectomy with Rouxen-Y reconstruction, D3 lymph node dissection and a left adrenalectomy. No cancer cells were detected in the resected specimen either in the primary lesion or lymph nodes, thus confirming a pathologically CR to CRT (CR grade 3). The patient has been stable and well without any evidence of recurrence for 48 mo after surgery. Such a preoperative CRT regimen might therefore be very effective for treatment of some advanced gastric cancers. | Hironori Shigeoka Haruhiko Imamoto Yasumasa Nishimura Taro Shimono Hiroshi Furukawa Hiroshi Imamura Takushi Yasuda Hitoshi Shiozaki | 2010 | World Journal of Gastrointestinal Oncology2010，2，6： | 6 |
| 15 | Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells显示文摘AIM:To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha(TNF-α)-induced gene expression in human gastric adenocarcinoma cells.METHODS:Knockdown experiments were conducted with claudin 1 small interfering RNA(si RNA),and theeffects on the cell cycle,apoptosis,migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells.The gene expression profiles of cells were analyzed by microarray and bioinformatics.RESULTS:The knockdown of claudin 1 significantly inhibited cell proliferation,migration and invasion,and increased apoptosis.Microarray analysis identified 245genes whose expression levels were altered by the knockdown of claudin 1.Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway,which involved MMP7,TNF-SF10,TGFBR1,and CCL2.Furthermore,TNFand nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1.TNF-αtreatment increased claudin 1 expression and cell migration in MKN28 cells.Microarray analysis indicated that the depletion of claudin1 inhibited 80%of the TNF-α-induced m RNA expression changes.Further,TNF-αdid not enhance cell migration in the claudin 1 si RNA transfected cells.CONCLUSION:These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells.A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer. | Atsushi Shiozaki Hiroki Shimizu Daisuke Ichikawa Hirotaka Konishi Shuhei Komatsu Takeshi Kubota Hitoshi Fujiwara Kazuma Okamoto Daisuke Iitaka Shingo Nakashima Yoshito Nako Mingyao Liu Eigo Otsuji | 2014 | World Journal of Gastroenterology2014，20，47： | 6 |
| 16 | Histological mixed-type as an independent prognostic factor in stageⅠgastric carcinoma显示文摘AIM: To evaluate the clinicopathological features of mixed-type gastric cancer and their influence on prognosis of mixed-type stageⅠgastric cancer.METHODS: We analyzed 446 patients who underwent curative gastrectomy for stageⅠgastric cancer between 1999 and 2009. The patients were divided into two groups: those with differentiated or undifferentiated cancer(non-mixed-type, n = 333) and those with a mixture of differentiated and undifferentiated cancers(mixed-type, n = 113).RESULTS: The overall prevalence of mixed-type gastric cancer was 25.3%(113/446). Compared with patients with non-mixed-type gastric cancer, those with mixedtype gastric cancer tended to be older at onset(P = 0.1252) and have a higher incidence of lymph node metastasis(P = 0.1476). They also had significantly larger tumors(P < 0.0001), more aggressive lymphatic invasion(P = 0.0011), and deeper tumor invasion(P < 0.0001). In addition, they exhibited significantly worse overall survival rates than did patients with non-mixedtype gastric cancer(P = 0.0026). Furthermore, mixedtype gastric cancer was independently associated with a worse outcome in multivariate analysis [P = 0.0300, hazard ratio = 11.4(1.265-102.7)].CONCLUSION: Histological mixed-type of gastric cancer contributes to malignant outcomes and highlight its usefulness as a prognostic indicator in stageⅠgastric cancer. | Shuhei Komatsu Daisuke Ichikawa Mahito Miyamae Hiroki Shimizu Hirotaka Konishi Atsushi Shiozaki Hitoshi Fujiwara Kazuma Okamoto Mitsuo Kishimoto Eigo Otsuji | 2015 | World Journal of Gastroenterology2015，21，2： | 6 |
| 17 | Detection of fusion gene in cell-free DNA of a gastric synovial sarcoma显示文摘Synovial sarcoma(SS) is genetically characterized by chromosomal translocation, which generates SYT-SSX fusion transcripts. Although SS can occur in any body part, primary gastric SS is substantially rare. Here we describe a detection of the fusion gene sequence of gastric SS in plasma cell-free DNA(cf DNA). A gastric submucosal tumor was detected in the stomach of a 27-year-old woman and diagnosed as SS. Candidate intronic primers were designed to detect the intronic fusion breakpoint and this fusion sequence was confirmed in intron 10 of SYT and intron 5 of SSX2 by genomic polymerase chain reaction(PCR) and direct sequencing. A locked nucleic acid(LNA) probe specificto the fusion sequence was designed for detecting the fusion sequence in plasma and the fusion sequence was detected in preoperative plasma cfD NA, while not detected in postoperative plasma cfD NA. This technique will be useful for monitoring translocation-derived diseases such as SS. | Shinpei Ogino Hirotaka Konishi Daisuke Ichikawa Junichi Hamada Katsutoshi Shoda Tomohiro Arita Shuhei Komatsu Atsushi Shiozaki Kazuma Okamoto Sanae Yamazaki Satoru Yasukawa Eiichi Konishi Eigo Otsuji | 2018 | World Journal of Gastroenterology2018，24，8： | 5 |
| 18 | Use of barbed suture for peritoneal closure in transabdominal preperitoneal hernia repair显示文摘AIM:To investigate the use of the V-Loc wound closure device for transabdominal preperitoneal hernia repair. METHODS:We performed conventional transabdominal preperitoneal hernia repair in 19 patients, including one single incisional case using V-Loc. Except for the use of V-Loc for peritoneal closure, the procedures were the same as those used in conventional techniques. RESULTS:Although the operators included 2 residents who have no experience in laparoscopic herniorrhaphy and intracorporeal suture, the operations were completed. We believe that V-Loc is especially suitable for inexperienced surgeons and the use of V-Loc reduces the operative time by a small amount but reduces operator stress significantly. CONCLUSION:We conclude that V-Loc is the ideal peritoneal closure device for transabdominal preperitoneal hernia repair. | Satoru Takayama Nozomu Nakai Midori Shiozaki Ryo Ogawa Masaki Sakamoto Hiromitsu Takeyama | 2012 | World Journal of Gastrointestinal Surgery2012，4，7： | 4 |
| 19 | Clinical characteristics of hepatoduodenal lymph node metastasis in gastric cancer显示文摘AIM: To assess the clinical features of hepatoduodenal lymph node(HDLN) metastasis and to clarify the optimal indication of HDLN dissection.METHODS: We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy,including HDLN dissection,for gastric cancer between 1999 and 2012. Of these,26 patients(9.4%) had HDLN metastasis. First,we investigated the clinicopathological characteristics,their perioperative clinical outcomes,such as postoperative complications,and prognostic outcomes between patients with and without HDLN metastasis. Second,we detected the prognostic factors,particularly in patients with HDLN metastasis. Third,we assessed the therapeutic value of HDLN dissection to determine its optimal indication.RESULTS: The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location(the middle or lower stomach [P = 0.005,OR = 5.88(95%CI: 1.61-38.1)] and p T category [T3 or T4,P = 0.017,OR = 4.45(95%CI: 1.28-21.3)] were independent risk factors for HDLNmetastasis. Cox proportional hazard analysis identified p N3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021,HR = 5.17(95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection,HDLN metastasis was a prognostic indicator in p N3 gastric cancer(P < 0.0001),but not p N1-2(P = 0.602). Furthermore,the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0,respectively.CONCLUSION: We suggest that HDLN dissection should be indicated for p N1 or p N2 gastric cancers located at the middle or lower stomach. | Taisuke Imamura Shuhei Komatsu Daisuke Ichikawa Toshiyuki Kosuga Kazuma Okamoto Hirotaka Konishi Atsushi Shiozaki Hitoshi Fujiwara Eigo Otsuji | 2015 | World Journal of Gastroenterology2015，21，38： | 4 |
| 20 | A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia or severely head injured patients with low intracranial pressure显示文摘 | Shiozaki T Hayakata T Tanoda M | 2001 | J Neurosurg2001，94，： | 2 |
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