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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 | 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 |
| 4 | 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 |
| 5 | 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 |
| 6 | 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 |
| 7 | Prognostic significance of perioperative tumor marker levels in stage Ⅱ/Ⅲ gastric cancer显示文摘AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9) levels in stage Ⅱ/Ⅲ gastric cancer.METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage Ⅱ/Ⅲ gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival.Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy. | Yasuhito Suenaga Mitsuro Kanda Seiji Ito Yoshinari Mochizuki Hitoshi Teramoto Kiyoshi Ishigure Toshifumi Murai Takahiro Asada Akiharu Ishiyama Hidenobu Matsushita Chie Tanaka Daisuke Kobayashi Michitaka Fujiwara Kenta Murotani Yasuhiro Kodera | 2019 | World Journal of Gastrointestinal Oncology2019，11，1： | 7 |
| 8 | ARID1A expression in gastric adenocarcinoma:Clinicopathological significance and correlation with DNA mismatch repair status显示文摘AIM:To analyze the mismatch repair(MMR)status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.METHODS:We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas.The results were further correlated with clinicopathological variables.RESULTS:The loss of any MMR protein expression,indicative of MMR deficiency,was observed in 38cases(7.8%)and was significantly associated with an older age(68.6±9.2 vs 60.4±11.7,P<0.001),a female sex(55.3%vs 31.3%,P=0.004),an antral location(44.7%vs 25.7%,P=0.021),and a differentiated histology(57.9%vs 39.7%,P=0.023).Abnormal ARID1A expression,including reduced or loss of ARID1A expression,was observed in 109 cases(22.3%)and was significantly correlated with lymphatic invasion(80.7%vs 69.5%,P=0.022)and lymph node metastasis(83.5%vs 73.7%,P=0.042).The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency(47.4%vs 20.2%,P<0.001).A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor(HR=1.36,95%CI:1.01-1.84;P=0.040).CONCLUSION:Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion,lymph node metastasis,poor prognosis,and MMR deficiency in gastric adenocarcinomas. | Ryo Inada Shigeki Sekine Hirokazu Taniguchi Hitoshi Tsuda Hitoshi Katai Toshiyoshi Fujiwara Ryoji Kushima | 2015 | World Journal of Gastroenterology2015，21，7： | 7 |
| 9 | 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 |
| 10 | 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 |
| 11 | 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 |
| 12 | Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium显示文摘AIM:To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial cells.METHODS:We developed three kinds of artificial milk with different amounts of glutamine;Complete amino acid milk (CAM),which is based on maternal mouse milk,glutamine-depleted milk (GDM),and glutaminerich milk (GRM).GRM contains three-fold more glutamine than CAM.Eighty-seven newborn mice were divided into three groups and were fed with either of CAM,GDM,or GRM via a recently improved nipple-bottle system for seven days.After the feeding period,the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation,and for cleaved-caspase-3 as a marker of apoptosis.Moreover,IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay,flow cytometry,and western blotting to examine the biological effect of glutamine on cell growth and apoptosis.RESULTS:During the feeding period,we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%),but not in the GRM-fed mice,with no differences in body weight gain between each group.Microscopic examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed mice.Intake of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining;GRM:13.8%,CAM:10.7%,GDM:1.14%,GRM vs GDM:P < 0.001,CAM vs GDM:P < 0.001) and Ki-67 labeling index (the average percentage of Ki67-positive staining;GRM:24.5%,CAM:22.4% GDM:19.4%,GRM vs GDM:P=0.001,CAM vs GDM:P =0.049),suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial cells.Glutamine deprivation further caused the deformation of the nuclear membrane and the plasma membrane,accompanied by chromatin degeneration and an absence of fat droplets from the colonic epithelia,indicating that the cells underwent apoptosis.Moreover,immunohistochemical analysis revealed the appearance of cleaved caspase-3 in colonic epithelial cells of GDM-fed mice.Finally,when IEC6 rat intestinal epithelial cells were cultured without glutamine,cell proliferation was significantly suppressed after 24 h (relative cell growth;4 mmol/L:100.0% ± 36.1%,0 mmol/L:25.3% ± 25.0%,P < 0.05),with severe cellular damage.The cells underwent apoptosis,accompanied by increased cell population in sub-G0 phase (4 mmol/L:1.68%,0.4 mmol/L:1.35%,0 mmol/L:5.21%),where dying cells are supposed to accumulate.CONCLUSION:Glutamine is an important alimentary component for the maintenance of intestinal mucosa.Glutamine deprivation can cause instability of the intestinal epithelial alignment by increased apoptosis. | Takayuki Motoki Yoshio Naomoto Junji Hoshiba Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka Yasuko Tomono Yasuhiro Fujiwara Hiroshi Tsuchita Mehmet Gunduz Hitoshi Nagatsuka Noriaki Tanaka Toshiyoshi Fujiwara | 2011 | World Journal of Gastroenterology2011，17，6： | 4 |
| 13 | 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 |
| 14 | 使用ATP酶敏感钾离子通道开放剂——尼可地尔静脉给药用于冠状动脉腔内血管成形术介入治疗的药学证据显示文摘1前言动物实验研究表明,反复短暂的冠脉闭塞导致心脏抗心肌缺血的发作,这种现象被称为缺血性预处理。一些研究表明,这种预处理的效果是由于ATP敏感性钾通道的激活(KATP通道)。人类涉及经皮冠状动脉成形术(PTCA)的临床研究发现KATP通道的关闭与格列本脲防止预处理的效果通常出现在反复球囊扩张期间血管成形术模型中,表明ATP敏感性钾通道在预处理中发挥了核心作用。 | Hitoshi Matsuo Sachiro Watanabe Tomonori Segawa Shinji Yasuda Takeshi Hirose Makoto Iwama Shinichiro Tanaka Takahiko Yamaki Yukihiko Matsuno Masaaki Tomita Shinya Minatoguchi Hisayoshi Fujiwara 魏丽莎 | 2015 | 首都食品与医药2015，0，8： | 3 |
| 15 | Questionnaire survey regarding the current status of superextended lymph node dissection in Japan显示文摘AIM To verify the current status of super-extended lymph node dissection for advanced gastric cancer according to a questionnaire survey.METHODS One-hundred and five institutions responded to the questionnaire.The survey included the following items: Number of experiences,whether performed prophylactically and/or therapeutically,whether preoperative chemotherapy was provided,number of preoperative chemotherapy rounds,and therapeutic options after chemotherapy.RESULTS Eighty-seven of the 105 institutions(83%) had performed D3 gastrectomy in the past or continued to perform D3 gastrectomy at present.However,D3 gastrectomy was rarely performed prophylactically in clinical practice.Seventy-eight institutions(74%) indicated that preoperative chemotherapy with curative intent was required for patients suspected of having para-aortic node(PAN) metastases.After chemotherapy,a D3 gastrectomy was scheduled for patients with a complete or partial response,stable disease,and progressive disease at 36(46%),28(36%),and 13(17%) of the institutions,respectively.CONCLUSION For patients with apparent PAN metastasis,a D3 gastrectomy is typically planned if a few courses of preoperative chemotherapy yield at least a stable disease condition. | Shinji Morita Takeo Fukagawa Hisataka Fujiwara Hitoshi Katai | 2016 | World Journal of Gastrointestinal Oncology2016，8，9： | 3 |
| 16 | Inhibition of TRPC6 Channel Activity Contributes to the Antihypertrophic Effects of Natriuretic Peptides-Guanylyl Cyclase-A Signaling in the Heart显示文摘 | Hideyuki Kinoshita Koichiro Kuwahara Motohiro Nishida Zhong Jian Xianglu Rong Shigeki Kiyonaka Yoshihiro Kuwabara Hitoshi Kurose Ryuji Inoue Yasuo Mori Yuhao Li Yasuaki Nakagawa Satoru Usami Masataka Fujiwara Yuko Yamada Takeya Minami Kenji Ueshima Kazuwa | 2010 | Circulation Research2010，，12： | 2 |
| 17 | Induction of ischemic tolerance in rat liver via reduced nicotinamide adenine dinucleotide phosphate oxidase in Kupffer cells显示文摘AIM: To elucidate the mechanisms of hepatocyte preconditioning by H2O2 to better understand the pathophysiology of ischemic preconditioning. METHODS: The in vitro effect of H2O2 pretreatment was investigated in rat isolated hepatocytes subjected to anoxia/reoxygenation. Cell viability was assessed with propidium iodide fluorometry. In other experiments, rat livers were excised and subjected to warm ischemia/ reperfusion in an isolated perfused liver system to determine leakage of liver enzymes. Preconditioning was performed by H2O2 perfusion, or by stopping the perfusion for 10 min followed by 10 min of reperfusion. To inhibit Kupffer cell function or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gadolinium chloride was injected prior to liver excision, or diphenyleneiodonium, an inhibitor of NADPH oxidase, was added to the perfusate, respectively. Histological detection of oxygen radical formation in Kupffer cells was performed by perfusion with nitro blue tetrazolium. RESULTS: Anoxia/reoxygenation decreased hepatocyte viability compared to the controls. Pretreatment with H2O2 did not improve such hepatocyte injury. In liver perfusion experiments, however, H2O2 preconditioning reduced warm ischemia/reperfusion injury, which wasreversed by inhibition of Kupffer cell function or NADPH oxidase. Histological examination revealed that H2O2 preconditioning induced oxygen radical formation in Kupffer cells. NADPH oxidase inhibition also reversed hepatoprotection by ischemic preconditioning. CONCLUSION: H2O2 preconditioning protects hepato- cytes against warm ischemia/reperfusion injury via NADPH oxidase in Kupffer cells, and not directly. NADPH oxidase also mediates hepatoprotection by ischemic preconditioning. | Kazuaki Tejima Masahiro Arai Hitoshi Ikeda Tomoaki Tomiya Mikio Yanase Yukiko Inoue Takako Nishikawa Naoko Watanabe Natsuko Ohtomo Masao Omata Kenji Fujiwara | 2007 | World Journal of Gastroenterology2007，13，38： | 2 |
| 18 | Surgical Outcomes of Gastrectomy for Elderly Patients with Gastric Cancer显示文摘 | Hiroki Takeshita Daisuke Ichikawa Shuhei Komatsu Takeshi Kubota Kazuma Okamoto Atsushi Shiozaki Hitoshi Fujiwara Eigo Otsuji | 2013 | World Journal of Surgery2013，，12： | 2 |
| 19 | Immunotherapy of solid cancer using dendritic cells pulsed with the HLA-A24-restricted peptide of carcinoembryonic antigen显示文摘 | Tsuyoshi Itoh Yuji Ueda Ichiro Kawashima Ikuei Nukaya Hitoshi Fujiwara Nobuaki Fuji Tetsuro Yamashita Tetsunori Yoshimura Kaori Okugawa Tomoko Iwasaki Mitsuko Ideno Kazutoh Takesako Masakazu Mitsuhashi Kunzo Orita Hisakazu Yamagishi | 2002 | Cancer Immunology,Immunotherapy2002，，2： | 2 |
| 20 | Differences of the Lymphatic Distribution and Surgical Outcomes Between Remnant Gastric Cancers and Primary Proximal Gastric Cancers显示文摘 | Shuhei Komatsu Daisuke Ichikawa Kazuma Okamoto Daito Ikoma Masahiro Tsujiura Atsushi Shiozaki Hitoshi Fujiwara Yasutoshi Murayama Yoshiaki Kuriu Hisashi Ikoma Masayoshi Nakanishi Toshiya Ochiai Yukihito Kokuba Eigo Otsuji | 2012 | Journal of Gastrointestinal Surgery2012，，3： | 2 |
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