{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:33:33Z","timestamp":1771598013525,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The incidence of venous thromboembolism has been reported as 20% in cancer patients. Anticoagulation therapy is the standard treatment for venous thromboembolism. On the other hand, bleeding should be carefully managed, because advanced cancer, particularly gastrointestinal cancer, carries a high risk of bleeding. However, the optimal management for cancer-associated thromboembolism remains to be clarified.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We retrospectively examined patients with advanced gastrointestinal cancer, including gastric cancer and colorectal cancer, who were treated with chemotherapy between 2014 and 2018 for the incidence and characteristics of venous thromboembolism and bleeding.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In total, 194 patients (120 men, 74 women) were enrolled in this study. The underlying pathology was gastric cancer in 74 cases and colorectal cancer in 120 cases. Of the 194 patients, 40 patients (20.6%) were diagnosed with venous thromboembolism and 10 patients (5.2%) were diagnosed with concomitant pulmonary thromboembolism. Conversely, bleeding was observed in 29 patients (15%). The location of bleeding was the primary tumor in 17 cases, metastatic tumor in 9 and hemorrhagic gastric ulcer in 3. Within the venous thromboembolism group (n\u00a0=\u00a040), bleeding was observed in 10 patients (25%). Multivariate analysis showed that International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding score \u22657 correlated significantly with major bleeding (P\u00a0=\u00a00.01). In patients with a low risk of bleeding, major bleeding was observed in only three patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>IMPROVE bleeding score may predict the risk for bleeding in gastrointestinal cancer patients with venous thromboembolism. Selecting patients with a low risk of bleeding using with IMPROVE bleeding score is expected to contribute to the safer management of anticoagulation therapy for cancer-associated thromboembolism.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jjco\/hyac103","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T09:56:49Z","timestamp":1656496609000},"source":"Crossref","is-referenced-by-count":3,"title":["IMPROVE bleeding score predicts major bleeding in advanced gastrointestinal cancer patients with venous thromboembolism"],"prefix":"10.1093","author":[{"given":"Hitoshi","family":"Kusaba","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michinari","family":"Hieda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"},{"name":"Department of Neuroinflammation and Brain Fatigue Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Ohmura","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taichi","family":"Isobe","sequence":"additional","affiliation":[{"name":"Department of Oncology and Social Medicine, Kyushu University Graduate School of Medical Sciences , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Tsuchihashi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiro","family":"Fukata","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ariyama","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eishi","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Oncology and Social Medicine, Kyushu University Graduate School of Medical Sciences , Fukuoka , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"2022062909560578600_ref1","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.ejca.2012.10.021","article-title":"Incidence of venous thromboembolism in patients with cancer - a cohort study using linked United Kingdom databases","volume":"49","author":"Walker","year":"2013","journal-title":"Eur J Cancer"},{"key":"2022062909560578600_ref2","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1001\/jama.293.6.715","article-title":"Malignancies, prothrombotic mutations, and the risk of venous thrombosis","volume":"293","author":"Blom","year":"2005","journal-title":"JAMA"},{"key":"2022062909560578600_ref3","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1002\/cncr.23062","article-title":"Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients","volume":"110","author":"Khorana","year":"2007","journal-title":"Cancer"},{"key":"2022062909560578600_ref4","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1056\/NEJM200012213432504","article-title":"Prognosis of cancers associated with venous thromboembolism","volume":"343","author":"Sorensen","year":"2000","journal-title":"N Engl J Med"},{"key":"2022062909560578600_ref5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1160\/TH13-02-0131","article-title":"High incidence of venous thromboembolism despite electronic alerts for thromboprophylaxis in hospitalised cancer patients","volume":"110","author":"Lecumberri","year":"2013","journal-title":"Thromb Haemost"},{"key":"2022062909560578600_ref6","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1470-2045(05)70207-2","article-title":"Cancer and venous thromboembolism","volume":"6","author":"Prandoni","year":"2005","journal-title":"Lancet Oncol"},{"key":"2022062909560578600_ref7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000093551","article-title":"Mechanisms of cancer-induced thrombosis in cancer","volume":"35","author":"Rickles","year":"2006","journal-title":"Pathophysiol Haemost Thromb"},{"key":"2022062909560578600_ref8","doi-asserted-by":"crossref","first-page":"4839","DOI":"10.1200\/JCO.2009.22.3271","article-title":"Assessing risk of venous thromboembolism in the patient with cancer","volume":"27","author":"Khorana","year":"2009","journal-title":"J Clin Oncol"},{"key":"2022062909560578600_ref9","first-page":"CD006649","article-title":"Anticoagulation for the initial treatment of venous thromboembolism in people with cancer","volume":"12","author":"Kahale","year":"2021","journal-title":"Cochrane Database Syst Rev"},{"key":"2022062909560578600_ref10","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1200\/JCO.2014.59.7351","article-title":"Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014","volume":"33","author":"Lyman","year":"2015","journal-title":"J Clin Oncol"},{"key":"2022062909560578600_ref11","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1056\/NEJMoa025313","article-title":"Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer","volume":"349","author":"Lee","year":"2003","journal-title":"N Engl J Med"},{"key":"2022062909560578600_ref12","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1182\/blood-2002-01-0108","article-title":"Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis","volume":"100","author":"Prandoni","year":"2002","journal-title":"Blood"},{"key":"2022062909560578600_ref13","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1200\/JCO.2000.18.17.3078","article-title":"Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis","volume":"18","author":"Hutten","year":"2000","journal-title":"J Clin Oncol"},{"key":"2022062909560578600_ref14","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1253\/circj.CJ-20-0223","article-title":"Risk factors for major bleeding during anticoagulation therapy in cancer-associated venous thromboembolism - from the COMMAND VTE registry","volume":"84","author":"Nishimoto","year":"2020","journal-title":"Circ J"},{"key":"2022062909560578600_ref15","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1253\/circj.CJ-88-0010","article-title":"Guidelines for the diagnosis, treatment and prevention of pulmonary thromboembolism and deep vein thrombosis","volume":"75","author":"JCS joint working group","year":"2011","journal-title":"Circ J"},{"key":"2022062909560578600_ref16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1378\/chest.09-3081","article-title":"Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators","volume":"139","author":"Decousus","year":"2011","journal-title":"Chest"},{"key":"2022062909560578600_ref17","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1538-7836.2005.01204.x","article-title":"Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients","volume":"3","author":"Schulman","year":"2005","journal-title":"J Thromb Haemost"},{"key":"2022062909560578600_ref18","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"2022062909560578600_ref19","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/S1470-2045(14)70420-6","article-title":"Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial","volume":"15","author":"Wilke","year":"2014","journal-title":"Lancet Oncol"},{"key":"2022062909560578600_ref20","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(17)31827-5","article-title":"Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"Kang","year":"2017","journal-title":"Lancet"},{"key":"2022062909560578600_ref21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"2022062909560578600_ref22","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1056\/NEJMoa032691","article-title":"Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer","volume":"350","author":"Hurwitz","year":"2004","journal-title":"N Engl J Med"},{"key":"2022062909560578600_ref23","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S1470-2045(15)70127-0","article-title":"Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study","volume":"16","author":"Tabernero","year":"2015","journal-title":"Lancet Oncol"},{"key":"2022062909560578600_ref24","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/j.1538-7836.2007.02374.x","article-title":"Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy","volume":"5","author":"Khorana","year":"2007","journal-title":"J Thromb Haemost"},{"key":"2022062909560578600_ref25","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1253\/circj.CJ-20-0084","article-title":"Direct oral anticoagulant therapy for cancer-associated venous thromboembolism in routine clinical practice","volume":"84","author":"Ogino","year":"2020","journal-title":"Circ J"},{"key":"2022062909560578600_ref26","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.thromres.2005.10.015","article-title":"Chemotherapy-induced thrombosis","volume":"118","author":"Haddad","year":"2006","journal-title":"Thromb Res"},{"key":"2022062909560578600_ref27","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4251\/wjgo.v9.i4.176","article-title":"Incidence of venous thromboembolism and the role of d-dimer as predictive marker in patients with advanced gastric cancer receiving chemotherapy: a prospective study","volume":"9","author":"Park","year":"2017","journal-title":"World J Gastrointest Oncol"},{"key":"2022062909560578600_ref28","doi-asserted-by":"crossref","first-page":"18516","DOI":"10.1038\/s41598-020-75719-w","article-title":"Patterns and predictors of thromboembolic events among patients with gastric cancer","volume":"10","author":"Abdel-Razeq","year":"2020","journal-title":"Sci Rep"},{"key":"2022062909560578600_ref29","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1007\/s12094-020-02339-1","article-title":"Incidence of venous thromboembolism in patients with colorectal cancer according to oncogenic status","volume":"22","author":"Mor\u00e1n","year":"2020","journal-title":"Clin Transl Oncol"},{"key":"2022062909560578600_ref30","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1111\/jth.12910","article-title":"Tumor oncogene (KRAS) status and risk of venous thrombosis in patients with metastatic colorectal cancer","volume":"13","author":"Ades","year":"2015","journal-title":"J Thromb Haemost"},{"key":"2022062909560578600_ref31","first-page":"CD006650","article-title":"Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer","volume":"7","author":"Akl","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2022062909560578600_ref32","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1056\/NEJMoa1711948","article-title":"Edoxaban for the treatment of cancer-associated venous thromboembolism","volume":"378","author":"Raskob","year":"2018","journal-title":"N Engl J Med"},{"key":"2022062909560578600_ref33","first-page":"2017","article-title":"Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D)","volume":"36","author":"Young","year":"2018","journal-title":"Clin Oncol"},{"key":"2022062909560578600_ref34","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1056\/NEJMoa1915103","article-title":"Apixaban for the treatment of venous thromboembolism associated with cancer","volume":"382","author":"Agnelli","year":"2020","journal-title":"N Engl J Med"},{"key":"2022062909560578600_ref35","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1378\/chest.14-2842","article-title":"Validation of the international medical prevention registry on venous thromboembolism bleeding risk score","volume":"149","author":"Hostler","year":"2016","journal-title":"Chest"},{"key":"2022062909560578600_ref36","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1111\/j.1538-7836.2010.04039.x","article-title":"Major bleeding as a predictor of mortality in patients with venous thromboembolism: findings from the RIETE registry","volume":"8","author":"Prandoni","year":"2010","journal-title":"J Thromb Haemost"},{"key":"2022062909560578600_ref37","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1183\/13993003.00280-2016","article-title":"Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment","volume":"48","author":"Klok","year":"2016","journal-title":"Eur Respir J"},{"key":"2022062909560578600_ref38","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1053\/j.gastro.2019.04.041","article-title":"Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and\/or aspirin in a randomized, double-blind, placebo-controlled trial","volume":"157","author":"Moayyedi","year":"2019","journal-title":"Gastroenterology"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/advance-article-pdf\/doi\/10.1093\/jjco\/hyac103\/44277016\/hyac103.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/advance-article-pdf\/doi\/10.1093\/jjco\/hyac103\/44277016\/hyac103.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T09:57:26Z","timestamp":1656496646000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/advance-article\/doi\/10.1093\/jjco\/hyac103\/6619279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":38,"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyac103","relation":{},"ISSN":["1465-3621"],"issn-type":[{"value":"1465-3621","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]},"article-number":"hyac103"}}