{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T12:09:46Z","timestamp":1747224586165,"version":"3.40.5"},"reference-count":17,"publisher":"PAGEPress Publications","issue":"2","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Ital Urol Androl"],"abstract":"<jats:p>Objective: To conduct a prospective study of the potential prognostic role of endothelin-1 (ET-1) in a cohort of primary high-grade non-muscle-invasive urothelial bladder cancer patients, who were treated with adjuvant intravesical Bacillus Calmette-Gu\u00e9rin (BCG). Material and methods: Patients with primary high-grade nonmuscle- invasive urothelial bladder cancer, who received postoperatively induction and maintenance BCG therapy, were prospectively included. Recurrence and progression were histologically proven. Immunohistochemical staining for ET-1 was assessed. Epidemiological, pathological and clinical parameters as well as the expression of ET-1 in tumor specimens were statistically analyzed for recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS). Results: ET-1 associates significantly with recurrence (p = 0.000), progression (p = 0.000), RFS (p = 0.000) and PFS (p = 0.000). The patient\u2019s age is also significant for recurrence (p = 0.003, OR = 1.273 95% CI: 1.086-1.492) and RFS (p = 0.013). Conclusions: ET-1 seems to deteriorate prognosis in patients suffering from primary high-grade non-muscle-invasive urothelial bladder cancer, who are treated with adjuvant BCG instillations. Furthermore, the patient\u2019s age associates with an increased likelihood for recurrence.<\/jats:p>","DOI":"10.4081\/aiua.2021.2.143","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T12:59:25Z","timestamp":1624971565000},"page":"143-147","source":"Crossref","is-referenced-by-count":2,"title":["Endothelin-1 indicates unfavorable prognosis in primary high-grade non-muscle-invasive urothelial bladder cancer"],"prefix":"10.4081","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2563-5833","authenticated-orcid":false,"given":"Lampros","family":"Mitrakas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Gravas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Foteini","family":"Karasavvidou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Zachos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasios","family":"Karatzas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios","family":"Oeconomou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Koukoulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasilios","family":"Tzortzis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Papandreou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2549","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"38905","doi-asserted-by":"crossref","unstructured":"Sylvester RJ, Brausi MA, Kirkels WJ, et al. Long-term efficacy results of EORTC Genito-Urinary Group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Gu\u00e9rin, and bacillus Calmette-Gu\u00e9rin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder. Eur Urol. 2010; 57:766-773.","DOI":"10.1016\/j.eururo.2009.12.024"},{"key":"38906","unstructured":"Soloway M, Khoury S. Bladder Cancer. 2nd Edition: ICUD-EAU 2012; 254-261."},{"key":"38907","doi-asserted-by":"crossref","unstructured":"Cambier S, Sylvester RJ, Collette L, et al. EORTC nomograms and risk groups for predicting recurrence, progression, and diseasespecific and overall survival in non-muscle-invasive stage Ta-T1 urothelial bladder cancer patients treated with 1-3 years of maintenance Bacillus Calmette-Gu\u00e9rin. Eur Urol. 2016; 69:60-9.","DOI":"10.1016\/j.eururo.2016.01.055"},{"key":"38908","doi-asserted-by":"crossref","unstructured":"Mitrakas L, Gravas S, Papandreou C, et al. Primary high-grade non-muscle-invasive bladder cancer: high NF-B expression in tumor specimens distinguishes patients who are at risk for disease progression. Pathol Oncol Res. 2019; 25:225-231.","DOI":"10.1007\/s12253-017-0340-1"},{"key":"38909","doi-asserted-by":"crossref","unstructured":"Mitrakas L, Gravas S, Karasavvidou F, et al. Endothelin-1 overexpression: a potential biomarker of unfavorable prognosis in nonmetastatic muscle-invasive bladder cancer. Tumour Biol. 2015; 36:4699-705. Erratum in: Tumour Biol. 2015; 36:3127","DOI":"10.1007\/s13277-015-3118-7"},{"key":"38910","doi-asserted-by":"crossref","unstructured":"Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance bacillus Calmette-Gu\u00e9rin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol. 2000; 163:1124-1129.","DOI":"10.1016\/S0022-5347(05)67707-5"},{"key":"38911","doi-asserted-by":"crossref","unstructured":"Babjuk M, B\u00f6hle A, Burger M, et al. EAU Guidelines on non-muscle- invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017; 71:447-461.","DOI":"10.1016\/j.eururo.2016.05.041"},{"key":"38912","doi-asserted-by":"crossref","unstructured":"Zachos I, Tzortzis V, Mitrakas L, et al. Tumor size and T stage correlate independently with recurrence and progression in high-risk non-muscle-invasive bladder cancer patients treated with adjuvant BCG. Tumour Biol. 2014; 35:4185-4189.","DOI":"10.1007\/s13277-013-1547-8"},{"key":"38913","doi-asserted-by":"crossref","unstructured":"Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006; 49:466-5.","DOI":"10.1016\/j.eururo.2005.12.031"},{"key":"38914","doi-asserted-by":"crossref","unstructured":"Palou J, Sylvester RJ, Faba OR, et al. Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Gu\u00e9rin. Eur Urol. 2012; 62:118-25.","DOI":"10.1016\/j.eururo.2011.10.029"},{"key":"38915","doi-asserted-by":"crossref","unstructured":"Gontero P, Sylvester R, Pisano F, et al. Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Gu\u00e9rin: results of a retrospective multicenter study of 2451 patients. Eur Urol. 2015; 67:74-82.","DOI":"10.1016\/j.eururo.2014.08.062"},{"key":"38916","doi-asserted-by":"crossref","unstructured":"Sahan A, Gerin F, Garayev A, et al. The impact of tumor invasion to muscularis mucosaevascular plexus on patient outcome in pT1 bladder urothelial carcinoma. Arch Ital Urol Androl. 2020; 92:239-243.","DOI":"10.4081\/aiua.2020.3.239"},{"key":"38917","doi-asserted-by":"crossref","unstructured":"Eltze E, Wild PJ, Wu\u0308lfing C, et al. Expression of the endothelin axis in noninvasive and superficially invasive bladder cancer. Relation to clinicopathologic and molecular prognostic parameters. Eur Urol. 2009; 56:837-847.","DOI":"10.1016\/j.eururo.2008.10.003"},{"key":"38918","doi-asserted-by":"crossref","unstructured":"Wu\u0308lfing C, Eltze E, Yamini J, et al. Expression of the endothelin axis in bladder cancer: Relationship to clinicopathologic parameters and long-term survival. Eur Urol. 2005; 47:593-600.","DOI":"10.1016\/j.eururo.2004.12.019"},{"key":"38919","unstructured":"Wu\u0308lfing C, Tiemann A, Persigehl T, et al. In vivo activity of ABT- 627, a selective endothelin-A-receptor antagonist, in bladder cancer xenograft tumors. Proc Am Soc Cancer Res. 2005; 46:abstract 3039."},{"key":"38920","doi-asserted-by":"crossref","unstructured":"Herrmann E, Tiemann A, Eltze E, et al. Endothelin-A-receptor antagonism with atrasentan exhibits limited activity on the KU-19-19 bladder cancer cell line in a mouse model. J Cancer Res Clin Oncol. 2009; 135:1455-1462.","DOI":"10.1007\/s00432-009-0593-5"},{"key":"38921","doi-asserted-by":"crossref","unstructured":"Herrmann E, B\u00f6gemann M, Bierer S, et al. The role of the endothelin axis and microvessel density in bladder cancer - correlation with tumor angiogenesis and clinical prognosis. Oncol Rep. 2007; 18:133-138.","DOI":"10.3892\/or.18.1.133"}],"container-title":["Archivio Italiano di Urologia e Andrologia"],"original-title":[],"link":[{"URL":"https:\/\/www.pagepressjournals.org\/index.php\/aiua\/article\/download\/aiua.2021.2.143\/9409","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pagepressjournals.org\/index.php\/aiua\/article\/download\/aiua.2021.2.143\/9409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T12:59:46Z","timestamp":1624971586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.pagepressjournals.org\/index.php\/aiua\/article\/view\/aiua.2021.2.143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,28]]},"references-count":17,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,6,29]]}},"URL":"https:\/\/doi.org\/10.4081\/aiua.2021.2.143","relation":{},"ISSN":["2282-4197","1124-3562"],"issn-type":[{"type":"electronic","value":"2282-4197"},{"type":"print","value":"1124-3562"}],"subject":[],"published":{"date-parts":[[2021,6,28]]}}}