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| 1 | Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review显示文摘AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. 'Neural networks' as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the 'feature selection and root cause analysis', was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206 ± 0.6249 vs SCC: 4.1356 ± 0.4038, P < 0.05). The odds for re-classification of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC, respectively. Local tumor recurrence was best predicted by grade 3 differentiation and piecemeal resection, metachronous cancer development by the carcinoma in situ component, and lymph node positivity by lymphovascular invasion. With regard to surgically resected patients: Significant differences in patients with positive lymph nodes were observed between ADC and SCC [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P<0.01). In contrast, lymphovascular and microvascular invasion and grade 3 patients between histologic types were comparable, the respective rank order of the predictors of lymph node positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type (ADC/SCC) was not included in the model. The best predictors for SCC lymph node positivity were Sm3 invasion and (V+). For ADC, the most important predictor was (L+). CONCLUSION: Local tumor recurrence is predicted by grade 3, metachronous cancer by the carcinoma insitu component, and lymph node positivity by L+. T1b cancer should be treated with surgical resection. | George Sgourakis Ines Gockel Hauke Lang | 2013 | World Journal of Gastroenterology2013，19，9： | 40 |
| 2 | High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells显示文摘AIM: To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis. METHODS: The impact of miR-196a on the restriction targets HoxA7, HoxB8, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction (RT-PCR) after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectal cancer samples, mucosa samples and diverse cancer cell lines was quantifi ed by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo. RESULTS: HoxA7, HoxB8, HoxC8 and HoxD8 were restricted by miR-196a in a dose-dependent and gene-specific manner. High levels of miR-196a activated the AKT signaling pathway as indicated by increased phosphorylation of AKT. In addition, high levels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towards platin derivatives but did not impact on proliferation or apoptosis. Furthermore, miR-196a increased the development of lung metastases in mice after tail vein injection. CONCLUSION: miR-196a exerts a pro-oncogenic influence in colorectal cancer. | Carl Christoph Schimanski Kirsten Frerichs Fareed Rahman Martin Berger Hauke Lang Peter R Galle Markus Moehler Ines Gockel | 2009 | World Journal of Gastroenterology2009，15，17： | 40 |
| 3 | Multidisciplinary management of gastric and gastroesophageal cancers显示文摘Carcinomas of the stomach and gastroesophageal junction are among the fi ve top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer,surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer (UICC) stages in Western countries because of the high risk of recurrence and metachronous metastases. However,recent large phase-Ⅲ Studies improved the diagnostic and therapeutic options in gastric cancers,indicating a more multidisciplinary management of the disease. Multimodal strategies combining dif-ferent neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular,the perioperative (neoadjuvant,adjuvant) chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection,mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastro-esophageal cancer,and discusses future strategies toimprove locoregional failures. | Markus Moehler Orestis Lyros Ines Gockel Peter R Galle Hauke Lang | 2008 | World Journal of Gastroenterology2008，14，24： | 17 |
| 4 | VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab显示文摘AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab. | Markus Moehler Christian Frings Annett Mueller Ines Gockel Carl C Schimanski Stefan Biesterfeld Institute of Pathology Johannes Gutenberg University Mainz 55101 Germany Peter R Galle Martin H Holtmann | 2008 | World Journal of Gastroenterology2008，14，26： | 15 |
| 5 | Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus显示文摘瞄准:C 反应的蛋白质(CRP ) 是尖锐阶段的反应物和瘤的恶意的潜力的已知的指示物。这研究的目的是作为起作用的仙子的一个参数调查外科手术前的 CRP 的意义在有有鳞的房间癌和食道的腺癌的病人的路线和长期的预后。方法:浆液 CRP 在从 1989 年 12 月为癌症经历 oesophagectomy 到 2004 年 3 月的 371 个病人中的 291 个外科手术前地被决定。中部的耐心的年龄是 59 (28-79 ) 年, 82.5% 病人是男性。有鳞的房间癌在 151 被诊断(51.9%) 并且在 122 个病人的腺癌。Transhiatal oesophagectomy 在 151 被做(51.9%) 病人并且 134 (46.0%) 病人们经历了腹胸的过程。结果:(43.6%) 在 127,外科手术前的浆液 CRP 集中在正常以内的病人变化(<
5 mg/dL ) ,提高的 CRP 层次在 164 被测量(56.4%) 病人。瘤扩展(P <
0.0005 ) 并且淋巴节点的数字由变形传播影响了(P = 0.015 ) 显著地与提高的 CRP 层次在这个组被增加。在起作用的仙子之中参数两输血的数字(P = 0.006 ) 并且一般复杂并发症率(P = 0.002 ) 在有提高的外科手术前的 CRP 层次的病人是更高的。13.6 的长期的幸存率(0-109.8 ) 瞬间在有与 18.9 相比的提高的 CRP 层次的组是更差的(0-155.4 ) 在有正常 CRP 的组的瞬间铺平(木头等级测试:P = 0.107 ) 。有向后的变量选择的 Multivariate 分析与食道的癌在病人作为长期的预后的一个独立预示的因素识别了外科手术前的 CRP,与 1.182 的危险比率(95% 信心间隔:1.030-1.356 ) 。结论:外科手术前的浆液 CRP 水平是在有有鳞的房间癌和食道的腺癌的病人的一个容易坚定的独立预示的标记。 | Ines Gockel Kathrin Dirksen Claudia M Messow Theodor Junginger | 2006 | World Journal of Gastroenterology2006，12，23： | 12 |
| 6 | Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model显示文摘AIM: To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning (IP) as well as pharmacologic pretreatment by α-lipoic acid (LA). METHODS: Several groups of rats were compared: sham operated animals, non-pretreated animals (nt), animals receiving IP (10 min of ischemia by clamping of the portal triad and 10 min of reperfusion) prior to sustained ischemia, animals receiving selective ischemic preconditioning (IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 min of reperfusion) prior to sustained ichemia, and animals receiving 500 μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS: Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA (19 ± 2 vs 10 ± 1, P < 0.05 and 29 ± 5 vs 12 ± 1, P < 0.05). Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment (3.1 ± 0.3 vs 1.8 ± 0.2, P < 0.05). Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation (LPO) in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towardsanti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION: IP, consisting of 10 min of ischemia and 10 min of reperfusion, protects only partly against ischemia/reperfusion injury of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax. | Friedrich Duenschede Kirsten Erbes Nina Riegler Patrick Ewald Achim Kircher Stefanie Westermann Arno Schad Imke Miesmer Simon Albrecht-Schck Ines Gockel Alexandra K Kiemer Theodor Junginger | 2007 | World Journal of Gastroenterology2007，13，27： | 8 |
| 7 | Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?显示文摘AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3,PDGFRα/b and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition,IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%),VEGFR2 (80%),VEGFR3 (67%),PDGFRα (82%) and PDGFRβ(82%) expression,whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells,accompanied by an additional nuclear staining for VEGFR3 ,EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes,which also depicted a PDGFRα expression.receptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy. | Daniel Drescher Markus Moehler Ines Gockel Kirsten Frerichs Annett Müller Friedrich Dünschede Thomas Borschitz Stefan Biesterfeld Martin Holtmann Thomas Wehler Andreas Teufel Kerstin Herzer Thomas Fischer Martin R Berger Theodor Junginger Peter R Galle Carl C Schimanski | 2007 | World Journal of Gastroenterology2007，13，26： | 4 |
| 8 | Achalasia: will genetic studies provide insights?显示文摘 | Henning R. Gockel Johannes Schumacher Ines Gockel Hauke Lang Thomas Haaf Markus M. N?then | 2010 | Human Genetics2010，，4： | 3 |
| 9 | Endoscopic findings in patients with Schatzki rings:Evidence for an association with eosinophilic esophagitis显示文摘AIM:To investigate endoscopic findings in patients with Schatzki rings(SRs) with a focus on evidence for eosinophilic esophagitis(EoE).METHODS:We consecutively approached all adult patients scheduled for elective outpatient upper endoscopy for a variety of indications at the German Diagnostic Clinic,Wiesbaden,Germany between July 2007 and July 2010.All patients with endoscopically diagnosed SRs,defined as thin,symmetrical,mucosal structures located at the esophagogastric junction,were prospectively registered.Additional endoscopic findings,clinical information and histopathological findings with a focus on esophageal eosinophilia(≥ 20 eosinophils/high power field) were recorded.The criteria for active EoE were defined as:(1) eosinophilic tissue infiltration ≥ 20 eosinophils/hpf;(2) symptoms of esophageal dysfunction;and(3) exclusion of other causes of esophageal eosinophilia.Gastroesophageal reflux disease was excluded by proton pump inhibitor treatment prior to endoscopy.The presence of ≥ 20 eosinophils/hpf in esophageal biopsies in patients that did not fulfil the criteria of EoE was defined as esophageal hypereosinophilia.RESULTS:A SR was diagnosed in 171(3.3%;128 males,43 females,mean age 66 ± 12.9 years) of the 5163 patients that underwent upper gastrointestinalendoscopy.Twenty of the 116 patients(17%) from whom esophageal biopsies were obtained showed histological hypereosinophilia(≥ 20 eosinophils/hpf).Nine of these patients(8 males,1 female,mean age 49 ± 10 years) did not fulfill all diagnostic criteria of EoE,whereas in 11(9%) patients with ≥ 20 eosinophils/hpf,a definite diagnosis of EoE was made.Three of the 11 patients(27%) with definite EoE had no suspicious endoscopic features of EoE.In contrast,in the 25 patients in whom EoE was suspected by endoscopic features,EoE was only confirmed in 7(28%) patients.Patients with EoE were younger(mean age 41.5 ± 6.5 vs 50.5 ± 11.5 years,P = 0.012),were more likely to have a history of allergies(73% vs 29%,P = 0.007) and complained more often of dysphagia(91% vs 34%,P = 0.004) and food impaction(36% vs 6%,P = 0.007) than patients without EoE.Endoscopically,additional webs were found significantly more often in patients with EoE than in patients without EoE(36% vs 11%,P = 0.04).Furthermore,the SR had a tendency to be narrower in patients with EoE than in those without EoE(36% vs 18%,P = 0.22).The percentage of males(73% vs 72%,P = 1.0) and frequency of heartburn(27% vs 27%,P = 1.0) were not significantly different in both groups.The 9 patients with esophageal hypereosinophilia that did not fulfil the diagnostic criteria of EoE were younger(mean age 49 ± 10 years vs 58 ± 6 years,P = 0.0008) and were more likely to have a history of allergies(78% vs 24%,P = 0.003) than patients with < 20 eosinophils/hpf.Predictors of EoE were younger age,presence of dysphagia or food impaction and a history of allergies.CONCLUSION:A significant proportion of patients with SRs also have EoE,which may not always be suspected according to other endoscopic features. | Michaela Müller Alexander J Eckardt Annette Fisseler-Eckhoff Susanne Haas Ines Gockel Till Wehrmann | 2012 | World Journal of Gastroenterology2012，18，47： | 2 |
| 10 | Is the schatzki ring a unique esophageal entity?显示文摘AIM:To study,whether the association of Schatzki rings with other esophageal disorders support one of the theories about its etiology.METHODS:From 1987 until 2007,all patients with newly diagnosed symptomatic Schatzki rings (SRs) were prospectively registered and followed.All of them underwent structured interviews with regards to clinical symptoms,as well as endoscopic and/or radiographic examinations.Endoscopic and radiographic studies determined the presence of an SR and additional morphological abnormalities.RESULTS:One hundred and sixty-seven patients (125 male,42 female) with a mean age of 57.1±14.6 years were studied.All patients complained of intermittent dysphagia for solid food and 113 (79.6%) patients had a history of food impaction.Patients experienced symptoms for a mean of 4.7±5.2 years before diagnosis.Only in 23.4% of the 64 patients who had endoscopic and/or radiological examinations before their first presentation to our clinic,was the SR previously diagnosed.At presentation,the mean ring diameter was 13.9±4.97 mm.One hundred and sixty-two (97%) patients showed a sliding hiatal hernia.Erosive reflux esophagitis was found in 47 (28.1%) patients.Twenty-six (15.6%) of 167 patients showed single or multiple esophageal webs;five (3.0%) patients exhibited eosinophilic esophagitis;and four (2.4%) had esophageal diverticula.Four (7%) of 57 patients undergoing esophageal manometry had nonspecific esophageal motility disorders.CONCLUSION:Schatzki rings are frequently associated with additional esophageal disorders,which support the assumption of a multifactorial etiology.Despite typical symptoms,SRs might be overlooked. | Michaela Müller Ines Gockel Philip Hedwig Alexander J Eckardt Kathrin Kuhr Jochem Knig Volker F Eckardt | 2011 | World Journal of Gastroenterology2011，17，23： | 2 |
| 11 | Endoscopic adrenaleetomy : an analysis of the transperitoneal and retroperitoneal approaches and results of a prospective follow-up study 显示文摘 | Gockel I Kneist W Heintz A | 2005 | Surg Endosc2005，19，4： | 1 |
| 12 | Retinoic acid receptor beta silences human papillomavirus-18 oncogene expression by induction of de novo methylation and heterochromatinization of the viral control region显示文摘 | De-Castro Arce J Gockel KE Rosl F | 2007 | J Biol Chem2007，282，28： | 1 |
| 13 | Genetic algorithm for variable ordering of OBDDs 显示文摘 | Drechsler R Becker B Gockel N | 1996 | IEE Proceedings of Computers and Digital Techniques1996，143，6： | 1 |
| 14 | Chemokine receptor CCR7 enhances intrahepatic and lymphatic dissemination of human hepatocellular cancer显示文摘 | Schimanski CC Bahre R Gockel I | 2006 | Oncol Rep2006，16，1： | 1 |
| 15 | The use of self - expanding stents in esophageal and gastroesophageal junction cancer pallia- tion:a meta - analysis and meta - regression analysis of outcomes 显示文摘 | Sgourakis G Gockel I Radtke A | 2010 | Dig Dis Sci2010，55，11： | 1 |
| 16 | Transoral thyroid and parathyroid surgery-development of a new transoral technique显示文摘 | Karakas E Steinfeldt T Gockel A | 2011 | Surgery2011，150，1： | 1 |
| 17 | Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone显示文摘 | Beagley KW Gockel CM | | 0，，： | 1 |
| 18 | Prospective,open,multi-centre phase Vll trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction显示文摘 | Moehler M Gockel I Roessler HP | 2013 | BMC Cancer2013，11，13： | 1 |
| 19 | Transoral thyroid and parathyroid surgery显示文摘 | Karakas E Steinfeldt T Gockel A | 2010 | Surg Endosc2010，24，： | 1 |
| 20 | Thalidomide induces apoptosis in human monocytes by using a cytochrome c-dependent pathway显示文摘 | Gockel HR Lugering A Heidemann J | 2004 | Immunol2004，172，8： | 1 |
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