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| 1 | Recent advances in the surgical treatment of hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection(LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation(LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. | Zenichi Morise Norihiko Kawabe Hirokazu Tomishige Hidetoshi Nagata Jin Kawase Satoshi Arakawa Rie Yoshida Masashi Isetani | 2014 | World Journal of Gastroenterology2014，20，39： | 24 |
| 2 | Pure laparoscopic hepatectomy for hepatocellular carcinoma with chronic liver disease显示文摘Pure laparoscopic hepatectomy is a less invasive procedure than conventional open hepatectomy for the resection of hepatic lesions. Increases in experiences with the technique, in combination with advances in technology, have promoted the popularity of pure laparoscopic hepatectomy. However, indications for usage and potential contraindications of the procedure remain unresolved. The characteristics and specific advantages of the procedure, especially for hepatocellular carcinoma(HCC) patients with chronic liver diseases,are reviewed and discussed in this paper. For cirrhotic patients with liver tumors, pure laparoscopic hepatectomy minimizes destruction of the collateral blood and lymphatic flow from laparotomy and mobilization, and mesenchymal injury from compression. Therefore, pure laparoscopic hepatectomy has the specific advantage of minimal postoperative ascites production that leads to lowering the risk of disturbance in water or electrolyte balance and hypoproteinemia. It minimizes complications that routinely trigger postoperative serious liver failure. Under adequate patient positioning and port arrangement, the partial resection of the liver in the area of subphrenic space, peri-inferior vena cava area or next to the attachment of retro-peritoneum is facilitated in pure laparoscopic surgery by providing good vision and manipulation in the small operative field.Furthermore, the features of reduced post-operative adhesion, good vision, and manipulation within the small area between the adhesions make this procedure safer in the context of repeat hepatectomy procedures.These improved features are especially advantageous for patients with liver cirrhosis and multicentric and/or metachronous HCCs. | Zenichi Morise Norihiko Kawabe Jin Kawase Hirokazu Tomishige Hidetoshi Nagata Hisanori Ohshima Satoshi Arakawa Rie Yoshida Masashi Isetani | 2013 | World Journal of Hepatology2013，5，9： | 21 |
| 3 | Diagnostic and therapeutic single-operator cholangiopancreatoscopy in biliopancreatic diseases:Prospective multicenter study in Japan显示文摘AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy(SOCPS) using the Spy Glass system in widespread clinical application for biliary and pancreatic diseases.METHODS: This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. RESULTS: A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2%(135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5%(84/89) and 88.2%(15/17), respectively. Diagnosis: the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS(bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7%(53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5%(14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2%(23/31) and 42.9%(3/7) of the patients, respectively. Others: SOCPS using the Spy Glass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both SOCPS-guided therapies. The incidence of procedure-related adverse events was 5.4%(8/148). CONCLUSION: SOCPS with direct visualization and biopsy for diagnosis and SOCPS-directed therapy for biliary and pancreatic diseases can be safely performed with a high success rate. | Toshio Kurihara Ichiro Yasuda Hiroyuki Isayama Toshio Tsuyuguchi Taketo Yamaguchi Ken Kawabe Yoshinobu Okabe Keiji Hanada Tsuyoshi Hayashi Takao Ohtsuka Syuhei Oana Hiroshi Kawakami Yoshinori Igarashi Kazuya Matsumoto Kiichi Tamada Shomei Ryozawa Hiroki Kawashima Yutaka Okamoto Iruru Maetani Hiroyuki Inoue Takao Itoi | 2016 | World Journal of Gastroenterology2016，22，5： | 20 |
| 4 | Continuous regional arterial infusion therapy with gabexate mesilate for severe acute pancreatitis显示文摘AIM: To evaluate the effi cacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulf illed clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy (non-CRAI). CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate (2400 mg/d) was continuously administered for 3 to 5 d. The clinical outcome including serum infl ammation-related parameters were examined. RESULTS: The duration of abdominal pain in the CRAI group was 1.9 ± 0.26 d, whereas that in the non-CRAI group was 4.3 ± 0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared signifi cantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization signifi cantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4 ± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION: The present results suggest that CRAI using gabexate mesilate was effective against SAP. | Yoshifumi Ino Yoshiyuki Arita Tetsuro Akashi Toshinari Kimura Hisato Igarashi Takamasa Oono Masayuki Furukawa Ken Kawabe Keiichiro Ogoshi Jiro Ouchi Toshihiko Miyahara Ryoichi Takayanagi Tetsuhide Ito | 2008 | World Journal of Gastroenterology2008，14，41： | 20 |
| 5 | Pure laparoscopic hepatectomy as repeat surgery and repeat hepatectomy显示文摘AIM:To assess clinical outcomes of laparoscopic hepatectomy(LH) in patients with a history of upper abdominal surgery and repeat hepatectomy.METHODS:This study compared the perioperative courses of patients receiving LH at our institution that had or had not previously undergone upper abdominal surgery.Of the 80 patients who underwent LH,22 had prior abdominal surgeries,including hepatectomy(n = 12),pancreatectomy(n = 3),cholecystectomy and common bile duct excision(n = 1),splenectomy(n = 1),total gastrectomy(n = 1),colectomy with the involvement of transverse colon(n = 3),and extended hysterectomy with extensive lymph-node dissection up to the upper abdomen(n = 1).Clinical indicators including operating time,blood loss,hospital stay,and morbidity were compared among the groups.RESULTS:Eighteen of the 22 patients who had undergone previous surgery had severe adhesions in the area around the liver.However,there were no conversions to laparotomy in this group.In the 58 patients without a history of upper abdominal surgery,the median operative time was 301 min and blood loss was 150 m L.In patients with upper abdominal surgical history or repeat hepatectomy,the operative times were 351 and 301 min,and blood loss was 100 and 50 m L,respectively.The median postoperative stay was 17,13 and 12 d for patients with no history of upper abdominal surgery,patients with a history,and patients with repeat hepatectomy,respectively.There were five cases with complications in the group with no surgical history,compared to only one case in the group with a prior history.There were no statistically significant differences in the perioperative results between the groups with and without upper abdominal surgical history,or with repeat hepatectomy.CONCLUSION:LH is feasible and safe in patients with a history of upper abdominal surgery or repeat hepatectomy. | Masashi Isetani Zenichi Morise Norihiko Kawabe Hirokazu Tomishige Hidetoshi Nagata Jin Kawase Satoshi Arakawa | 2015 | World Journal of Gastroenterology2015，21，3： | 13 |
| 6 | NF-κB and ERK-signaling pathways contribute to the gene expression induced by cag PAI-positive-Helicobacter pylori infection显示文摘AIM: To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Hellcobacter pylori (Hpylon) as a model of H pylori-infected gastric epithelium, and to further examine the contribution of cag-pathogenicity islands (cagPAI)-coding type Ⅳ secretion system and the two pathways, nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinases (ERK) on wild-type H pylori-induced gene expression. METHODS: Gene expression profiles induced by H pylori were evaluated in AGS gastric epithelial cells using cDNA microarray, which were present in the 4 600 independent clones picked up from the human gastric tissue. We also analyzed the contribution of NF-κB and ERK signaling on H pylori-induced gene expression by using inhibitors of specific signal pathways. The isogenic mutant with disrupted capE (△cagE) was used to elucidate the role of capPAI-encoding type Ⅳ secretion system in the gene expression profile. RESULTS: According to the expression profile, the genes were classified into four clusters. Among them, the clusters characterized by continuous upregulation were most conspicuous, and it contained many signal transducer activity-associated genes. The role of cagPAI on cultured cells was also investigated using isogenic mutant cagE, which carries non-functional cagPAI. Then the upregulation of more than 80% of the induced genes (476/566) was found to depend on cagPAI. Signal transducer pathway through NF-κB or ERK are the major pathways which are known to be activated by cagPAI-positive H pylori. The role of these pathways in the whole signal activation by cagPAI- positive H pylori was analyzed. The specific inhibitors against NF-κB or ERK pathway blocked the activation of gene expression in 65% (367/566) or 76% (429/566) of the genes whose activation appealed to depend on cagPAI. CONCLUSION: These results suggest that more than half of the genes induced by cagPAI-positive H pylori depend on NF-κB and ERK signaling activation, and these pathways may play a role in the gene expression induced by host-bacterial interaction which may associate with H pylori-related gastro-duodenal diseases. | Wataru Shibata Yoshihiro Hirata Haruhiko Yoshida Motoyuki Otsuka Yujin Hoshida Keiji Ogura Shin Maeda Tomoya Ohmae Ayako Yanai Yuzo Mitsuno Naohiko Seki Takao Kawabe Masao Omata | 2005 | World Journal of Gastroenterology2005，11，39： | 12 |
| 7 | Acute pancreatitis associated with peroral double-balloon enteroscopy: A case report显示文摘人有的一个 58 岁的日本人逗留凳子和严重贫血症。既不上面也不更低胃肠(官方补给) 内视镜检查法显示出任何局部性的损害。因此,他的官方补给的流血的来源被怀疑在小肠,并且他用 EN-450T5 每口头的双汽球肠寄生物(DBE ) 经历了(Fujinon 东芝 ES 系统公司,东京,日本) 。没有损害,考虑是官方补给的流血的来源。在过程以后,病人开始经历了腹的疼痛。实验室测试揭示了血淀粉酶过多,腹的计算断层摄影术揭示了胰和仙子胰的发炎。他因此被诊断有尖锐胰腺炎。保守疗法导致了临床并且实验室改善。他没有白酒摄取,胆石疾病或胰腺炎的历史。磁性的回声 cholangiopancreatography 没在 pancreatobiliary 管的系统表明结构的改变和没有石头。当他的腹的疼痛在过程以后开始了,他的尖锐胰腺炎因此被认为与 per 有关是口头的 DBE。这是可能与联系的尖锐胰腺炎的首先报导的案例每口头的 DBE。 | Kuniomi Honda Takahiro Mizutani Kazuhiko Nakamura Naomi Higuchi Kenji Kanayama Yorinobu Sumida Shigetaka Yoshinaga Soichi Itaba Hirotada Akiho Ken Kawabe Yoshiyuki Arita Tetsuhide Ito | 2006 | World Journal of Gastroenterology2006，12，11： | 11 |
| 8 | Factors correlating with acoustic radiation force impulse elastography in chronic hepatitis C显示文摘AIM: To investigate the factors other than fibrosis stage correlating with acoustic radiation force impulse(ARFI) elastograpy in chronic hepatitis C. METHODS: ARFI elastograpy was performed in 108 consecutive patients with chronic hepatitis C who underwent a liver biopsy. The proportion of fibrosis area in the biopsy specimens was measured by computerassisted morphometric image analysis. RESULTS: ARFI correlated significantly with fibrosis stage(β = 0.1865, P < 0.0001) and hyaluronic acid levels(β = 0.0008, P = 0.0039) in all patients by multiple regression analysis. Fibrosis area correlated significantly with ARFI by Spearman's rank correlation test but not by multiple regression analysis. ARFI correlated significantly with body mass index(BMI)(β =-0.0334, P = 0.0001) in F 0 or F 1, with γ-glutamyltranspeptidase levels(β = 0.0048, P = 0.0012) in F 2, and with fibrosis stage(β = 0.2921, P = 0.0044) and hyaluronic acid levels(β = 0.0012, P = 0.0025) in F 3 or F 4. The ARFI cutoff value was 1.28 m/s for F ≥ 2, 1.44 m/s for F ≥ 3, and 1.73 m/s for F 4. CONCLUSION: ARFI correlated with fibrosis stage and hyaluronic acid but not with inflammation. ARFI was affected by BMI, γ-glutamyltranspeptidase, and hyaluronic acid in each fibrosis stage. | Toru Nishikawa Senju Hashimoto Naoto Kawabe Masao Harata Yoshifumi Nitta Michihito Murao Takuji Nakano Yuko Mizuno Hiroaki Shimazaki Toshiki Kan Kazunori Nakaoka Yuka Takagawa Masashi Ohki Naohiro Ichino Keisuke Osakabe Kentaro Yoshioka | 2014 | World Journal of Gastroenterology2014，20，5： | 7 |
| 9 | A new index for non-invasive assessment of liver fibrosis显示文摘AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS,platelet count and prothrombin time. The values of the Fibro-Stiffness index differed signif icantly between neighboring f ibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F≥2 (0.90), F≥ 3 (0.90) and F= 4(0.92) in the estimation group and those for F≥ 3 (0.93) and F =4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F≥2, F≥3 and F=4 in both the estimation and validation groups. The diagnostic performance for F= 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F ≥ 2,3 and 4. | Naohiro Ichino Keisuke Osakabe Toru Nishikawa Hiroko Sugiyama Miho Kato Shiho Kitahara Senju Hashimoto Naoto Kawabe Masao Harata Yoshifumi Nitta Michihito Murao Takuji Nakano Yuko Arima Hiroaki Shimazaki Koji Suzuki Kentaro Yoshioka | 2010 | World Journal of Gastroenterology2010，16，38： | 7 |
| 10 | Caudal approach to pure laparoscopic posterior sectionectomy under the laparoscopy-specific view显示文摘AIM:To study our novel caudal approach laparoscopic posterior-sectionectomy with parenchymal transection prior to mobilization under laparoscopy-specific view.METHODS:Points of the procedure are:(1) Patients are put in left lateral position and posterior sector is not mobilized;(2) Glissonian pedicle of the sector is encircled and clamped extra-hepatically and divided afterward during the transection;(3) Dissection of inferior vena cava(IVC) anterior wall behind the liver is started from caudal.Simultaneously,liver transection is performed to search right hepatic vein(RHV) from caudal;(4) Liver transection proceeds to the bifurcation of the vessels from caudal to cranial,exposing the surfaces of IVC and RHV.Since the remnant liver sinks down,the cutting surface is well-opend;and(5) After the completion of transection,dissection of the resected liver from retroperitoneum is easily performed using the gravity.This approach was performed for a 63 years old woman with liver metastasis close to RHV.RESULTS:RHV exposure is required for R0 resection of the lesion.Although the cutting plane is horizontal in supine position and the gravity obstructs the exposure in the small subphrenic space,the use of specific characteristics of laparoscopic hepatectomy,such as the good vision for the dorsal part of the liver and IVC and facilitated dissection using the gravity with the patient positioning,made the complete RHV exposure during the liver transection easy to perform.The operation time was 341 min and operative blood loss was 1356 mL.Her postoperative hospital stay was uneventfull and she is well without any signs of recurrences 14 mo after surgery.CONCLUSION:The new procedure is feasible and useful for the patients with tumors close to RHV and the need of the exposure of RHV. | Hirokazu Tomishige Zenichi Morise Norihiko Kawabe Hidetoshi Nagata Hisanori Ohshima Jin Kawase Satoshi Arakawa Rie Yoshida Masashi Isetani | 2013 | World Journal of Gastrointestinal Surgery2013，5，6： | 7 |
| 11 | Endoscopic approach through the minor papilla for the management of pancreatic diseases显示文摘AIM:To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases.METHODS:This study included 44 endoscopic retrograde cholangiopancreatography(ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012.We retrospectively evaluated the clinical profiles of the patients,the endoscopic interventions,short-term outcomes,and complications.RESULTS:Of 44 ERCPs,26 were diagnostic ERCP,and 18 were therapeutic ERCP.The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung's duct.The overall success rate of minor papilla cannulation was 80%(35/44),which was significantly improved by wire-guided cannulation(P = 0.04).Endoscopic minor papillotomy(EMP) was performed in 17 of 34 patients(50%) using a needle-knife(13/17) or a pull-type papillotome(4/17).EMP with pancreatic stent placement,which was the main therapeutic option for patients with chronic pancreatitis,recurrent acute pancreatitis,and pancreatic pseudocyst,resulted in short-term clinical improvement in 83% of patients.Mild post-ERCP pancreatitis occurred as an early complication in 2 cases(4.5%).CONCLUSION:The endoscopic minor papilla approach is technically feasible,safe,and effective when the procedure is performed in a high-volume referral center by experienced endoscopists. | Nao Fujimori Hisato Igarashi Akira Asou Ken Kawabe Lingaku Lee Takamasa Oono Taichi Nakamura Yusuke Niina Masayuki Hijioka Masahiko Uchida Kazuhiro Kotoh Kazuhiko Nakamura Tetsuhide Ito Ryoichi Takayanagi | 2013 | World Journal of Gastrointestinal Endoscopy2013，5，3： | 6 |
| 12 | Lysophosphatidic acid induced nuclear translocation of nuclear factor-κB in Panc-1 cells by mobilizing cytosolic free calcium显示文摘AIM: To clarify whether Lysophosphatidic acid (LPA) activates the nuclear translocation of nuclear factor-κB (NF-κB) in pancreatic cancer. METHODS: Panc-1, a human pancreatic cancer cell line, was used throughout the study. The expression of LPA receptors was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). Cytosolic free calcium was measured by fluorescent calcium indicator fura-2, and the localization of NF-κB was visualized by immunofluorescent method with or without various agents, which effect cell signaling. RESULTS: Panc-1 expressed LPA receptors, LPA1, LPA2 and LPA3. LPA caused the elevation of cytosolic free calcium dose-dependently. LPA also caused the nuclear translocation of NF-κB. Cytosolic free calcium was attenuated by pertussis toxin (PTX) and U73122, an inhibitor of phospholipase C. The translocation of NF-κB was similarly attenuated by PTX and U73122, but phorbol ester, an activator of protein kinase C, alone did not translocate NF-κB. Furthermore, the translocation of NF-κB was completely blocked by Ca2+ chelator BAPTA-AM. Thapsigargin, an endoplasmic- reticulum Ca2+-ATPase pump inhibitor, also promoted the translocation of NF-κB. Staurosporine, a proteinkinase C inhibitor, attenuated translocation of NF-κB induced by LPA. CONCLUSION: These findings suggest that protein kinase C is activated endogenously in Panc-1, and protein kinase C is essential for activating NF-κB with cytosolic calcium and that LPA induces the nuclear translocation of NF-κB in Panc-1 by mobilizing cytosolic free calcium. | Yoshiyuki Arita Tetsuhide Ito Takamasa Oono Ken Kawabe Terumasa Hisano Ryoichi Takayanagi | 2008 | World Journal of Gastroenterology2008，14，28： | 5 |
| 13 | Mutations in carboxy-terminal part of E2 including PKR/eIF2αphosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b:Their correlation with response to interferon monotherapy and viral load显示文摘AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-lb-infected patients treated with IFN. METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2a phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to IFN (25.0% vs 6.9 %, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P < 0.0001) and sustained response to IFN (85.7% vs 2.9%, P < 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P < 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independent predictors for small viral load, and ISDR (OR = 39.0, P < 0.0001) was selected as the only independent predictor for sustained response. CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load. | Koji Ukai Masatoshi Ishigami Kentaro Yoshioka Naoto Kawabe Yoshiaki Katano Kazuhiko Hayashi Takashi Honda Motoyoshi Yano Hidemi Goto | 2006 | World Journal of Gastroenterology2006，12，23： | 5 |
| 14 | Familial pancreatic cancer: Concept, management and issues显示文摘Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome(HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (<20%) and the familial aggregation is usually modest. However, an ethnic deviation (Ashkenazi Jewish>Caucasian) and a younger onset are common also in FPC. In European countries, 'anticipation' is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (Pan IN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society. | Hiroyuki Matsubayashi Kyoichi Takaori Chigusa Morizane Hiroyuki Maguchi Masamichi Mizuma Hideaki Takahashi Keita Wada Hiroko Hosoi Shinichi Yachida Masami Suzuki Risa Usui Toru Furukawa Junji Furuse Takamitsu Sato Makoto Ueno Yoshimi Kiyozumi Susumu Hijioka Nobumasa Mizuno Takeshi Terashima Masaki Mizumoto Yuzo Kodama Masako Torishima Takahisa Kawaguchi Reiko Ashida Masayuki Kitano Keiji Hanada Masayuki Furukawa Ken Kawabe Yoshiyuki Majima Toru Shimosegawa | 2017 | World Journal of Gastroenterology2017，23，6： | 5 |
| 15 | Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver显示文摘AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment. | Motoyuki Kohjima Tsuyoshi Yoshimoto Munechika Enjoji Nobuyoshi Fukushima Kunitaka Fukuizumi Tsukasa Nakamura Miho Kurokawa Nao Fujimori Yusuke Sasaki Yasushi Shimonaka Yusuke Murata Susumu Koyama Ken Kawabe Kazuhiro Haraguchi Yorinobu Sumida Naohiko Harada Masaki Kato Kazuhiro Kotoh Makoto Nakamuta | 2015 | World Journal of Gastroenterology2015，21，11： | 4 |
| 16 | Fractalkine and TGF-β1 levels reflect the severity of chronic pancreatitis in humans显示文摘AIM: To clarify whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of chronic pancreatitis (CP). This study aimed at clarifying whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of CP. METHODS: Serum monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta-1 (TGF-β1), and soluble type fractalkine (s-fractalkine) concentrations were examined in patients with CP (n = 109) and healthy controls (n = 116). Severity of disease was classified in patients with CP by a staging system. Relationships between stage-specifi c various clinical factors and serum MCP-1, TGF-β1, and s-fractalkine levels were investigated. Furthermore, 57 patients with non-alcoholic CP were similarly evaluated in order to exclude in? uence of alcohol intake. RESULTS: Patients with CP showed signifi cant higher levels of serum TGF-β1 and s-fractalkine, but not MCP-1, compared to the controls. Serum TGF-β1 in the severe stage and s-fractalkine in the mild and thesevere stage of CP significantly increased compared to those of controls. However, it was observed that both TGF-β1 and s-fractalkine levels were affected by alcohol intake. In patients with non-alcoholic CP, serum TGF-β1 showed significant increase in the moderate stage of CP, and serum s-fractalkine revealed signifi cant increase in the early stage of CP. CONCLUSION: It is suggested that the measurement of serum F-fractalkine is useful to diagnose early-stage CP. Moreover, the combined determination of both, s-fractalkine and TGF-β1, in human sera may be helpful in evaluating the severity status of CP. | Mikihiko Yasuda Tetsuhide Ito Takamasa Oono Ken Kawabe Toyoma Kaku Hisato Igarashi Taichi Nakamura Ryoichi Takayanagi | 2008 | World Journal of Gastroenterology2008，14，42： | 4 |
| 17 | Safety and efficacy of lamivudine after radiofrequency ablation in patients with hepatitis B virus-related hepatocellular carcinoma显示文摘 | Hideo Yoshida Haruhiko Yoshida Eriko Goto Takahisa Sato Takamasa Ohki Ryota Masuzaki Ryosuke Tateishi Tadashi Goto Shuichiro Shiina Takao Kawabe Masao Omata | 2008 | Hepatology International2008，，1： | 3 |
| 18 | Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer显示文摘AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases. | Hisato Igarashi Tetsuhide Ito Ken Kawabe Terumasa Hisano Yoshiyuki Arita Toyoma Kaku Ryoichi Takayanagi | 2008 | World Journal of Gastroenterology2008，14，34： | 3 |
| 19 | Rectosigmoid findings are not associated with proximal colon cancer: Analysis of 6 196 consecutive cases undergoing total colonoscopy显示文摘AIM: To review the risk of proximal colon cancer in patients undergoing colonoscopy.METHODS: We estimated the risk of advanced proximal adenomas and cancers in 6 196 consecutive patients that underwent colonoscopy (mean age 60 years, 65% males,without prior history of colorectal examination). Neoplasms were classified as diminutive adenoma (5 mm or less),small adenoma (6-9 mm), advanced adenoma (10 mm or more, with villous component or high-grade dysplasia)and cancer (invasive adenocarcinoma). The sites of neoplasms were defined as rectosigmoid (rectum and sigmoid colon) and proximal colon (from cecum to descending colon).RESULTS: The trend of the prevalence of advanced proximal adenoma was to increase with severe rectosigmoid findings, while the prevalence of proximal colon cancer did not increase with severe rectosigmoid findings. Among the 157 patients with proximal colon cancer, 74% had no neoplasm in the rectosigmoid colon. Multivariate logisticregression analysis revealed that age was the main predictor of proximal colon cancer and existence of rectosigmoid adenoma was not a predictor of proximal colon cancer.CONCLUSION: Sigmoidoscopy is inadequate for colorectal cancer screening, especially in older populations. | Makoto Okamoto Takao Kawabe Yutaka Yamaji Jun Kato Tsuneo Ikenoue Goichi Togo Haruhiko Yoshida Yasushi Shiratori Masao Omata | 2005 | World Journal of Gastroenterology2005，11，15： | 3 |
| 20 | Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis显示文摘AIM:To explore the pathological flndings in the entire esophagus in rats with reflux esophagitis, and the effects of ecabet sodium(ES).METHODS:A rat model of chronic acid reflux esophagitis was used.In the treatment group, ES was administered after surgery(n = 16).No drug was administered postoperatively to the esophagitis group(n = 9).Shamoperated rats were used as a control group(n = 5).Rats were sacriflced on day 7 after the operation.The epithelial thickness and leukocyte inflltration were examined in the upper, middle and lower areas of the esophagus.The survival rate, incidence of esophageal ulcer, and mean surface area and number of esophageal ulcers were determined in the esophagitis and ES groups.Esophageal histology was assessed in all three groups.RESULTS:Leukocyte infiltration in the esophagitis group was 26.3 ± 22.0 in the middle esophagus and 8.2 ± 4.9 in the upper esophagus, which was signiflcantly greater than that in the controls(1.3 ± 1.1 and 1.4 ± 1.0, respectively)(P < 0.05).The thickness of the epithelium in the esophagitis group was 210.8 ± 47.7 μm in the lower esophagus and 204.2 ± 60.1 μm in the middle esophagus, which was significantlygreater than that in the controls(26.0 ± 5.5 and 21.0 ± 6.5 μm, respectively)(P < 0.05).The mean number of ulcers per animal in the ES group in the entire esophagus was 5.4 ± 2.5, which was signiflcantly less than that in the esophagitis group(9.0 ± 3.5)(P < 0.05).The epithelial thickness in the ES group was 97.5 ± 32.2 μm in the lower esophagus, which was decreased compared with that in the esophagitis group(210.8 ± 47.7 μm)(P < 0.05).CONCLUSION:Mucosal inflammation extended to the upper esophagus close to the hypopharynx.Our study suggested that ES may have a useful defensive role in reflux esophagitis. | Daisuke Asaoka Akihito Nagahara Masako Oguro Yuko Izumi Akihiko Kurosawa Taro Osada Masato Kawabe Mariko Hojo Michiro Otaka Sumio Watanabe | 2009 | World Journal of Gastroenterology2009，15，28： | 2 |
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