{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:59:16Z","timestamp":1784069956885,"version":"3.55.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Surg Oncol"],"published-print":{"date-parts":[[2020,5]]},"DOI":"10.1245\/s10434-019-08183-0","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T01:31:05Z","timestamp":1579656665000},"page":"1533-1545","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Toxicity of Immune Checkpoint Inhibitors: Considerations for the Surgeon"],"prefix":"10.1245","volume":"27","author":[{"given":"Beth A.","family":"Helmink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Roland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Kiernan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Wargo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"8183_CR1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","volume":"378","author":"MA Postow","year":"2018","unstructured":"Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158\u201368.","journal-title":"N Engl J Med."},{"key":"8183_CR2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","volume":"168","author":"P Sharma","year":"2017","unstructured":"Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168:707\u201323.","journal-title":"Cell."},{"key":"8183_CR3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.it.2019.04.002","volume":"40","author":"KE Pauken","year":"2019","unstructured":"Pauken KE, Dougan M, Rose NR, et al. Adverse events following cancer immunotherapy: obstacles and opportunities. Trends Immunol. 2019;40:511\u201323.","journal-title":"Trends Immunol."},{"key":"8183_CR4","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrclinonc.2016.58","volume":"13","author":"C Boutros","year":"2016","unstructured":"Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016;13:473\u201386.","journal-title":"Nat Rev Clin Oncol."},{"key":"8183_CR5","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","volume":"4","author":"DY Wang","year":"2018","unstructured":"Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4:1721\u20138.","journal-title":"JAMA Oncol."},{"key":"8183_CR6","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1093\/annonc\/mdv182","volume":"26","author":"TW Chen","year":"2015","unstructured":"Chen TW, Razak AR, Bedard PL, et al. A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors. Ann Oncol. 2015;26:1824\u20139.","journal-title":"Ann Oncol."},{"key":"8183_CR7","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.2217\/fon-2017-0218","volume":"13","author":"MS Ernstoff","year":"2017","unstructured":"Ernstoff MS, Gandhi S, Pandey M, et al. Challenges faced when identifying patients for combination immunotherapy. Future Oncol. 2017;13:1607\u201318.","journal-title":"Future Oncol."},{"key":"8183_CR8","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s40425-017-0300-z","volume":"5","author":"I Puzanov","year":"2017","unstructured":"Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5:95.","journal-title":"J Immunother Cancer."},{"key":"8183_CR9","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1200\/JCO.2012.41.6750","volume":"30","author":"JS Weber","year":"2012","unstructured":"Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30:2691\u20137.","journal-title":"J Clin Oncol."},{"key":"8183_CR10","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000455014","volume":"45","author":"R Wanchoo","year":"2017","unstructured":"Wanchoo R, Karam S, Uppal NN, et al. Adverse renal effects of immune checkpoint inhibitors: a narrative review. Am J Nephrol. 2017;45:160\u20139.","journal-title":"Am J Nephrol."},{"key":"8183_CR11","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1126\/science.270.5238.985","volume":"270","author":"P Waterhouse","year":"1995","unstructured":"Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270:985\u20138.","journal-title":"Science."},{"key":"8183_CR12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1126\/science.291.5502.319","volume":"291","author":"H Nishimura","year":"2001","unstructured":"Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319\u201322.","journal-title":"Science."},{"key":"8183_CR13","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1056\/NEJMoa1609214","volume":"375","author":"DB Johnson","year":"2016","unstructured":"Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375:1749\u201355.","journal-title":"N Engl J Med."},{"key":"8183_CR14","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/annonc\/mdw640","volume":"28","author":"JC Osorio","year":"2017","unstructured":"Osorio JC, Ni A, Chaft JE, et al. Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol. 2017;28:583\u20139.","journal-title":"Ann Oncol."},{"key":"8183_CR15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1001\/jamadermatol.2015.2707","volume":"152","author":"C Hua","year":"2016","unstructured":"Hua C, Boussemart L, Mateus C, et al. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol. 2016;152:45\u201351.","journal-title":"JAMA Dermatol."},{"key":"8183_CR16","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","volume":"36","author":"JR Brahmer","year":"2018","unstructured":"Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36:1714\u201368.","journal-title":"J Clin Oncol."},{"key":"8183_CR17","doi-asserted-by":"crossref","first-page":"594","DOI":"10.6004\/jnccn.2018.0047","volume":"16","author":"JA Thompson","year":"2018","unstructured":"Thompson JA. New NCCN Guidelines: recognition and management of immunotherapy-related toxicity. J Natl Compr Cancer Netw. 2018;16:594\u20136.","journal-title":"J Natl Compr Cancer Netw."},{"key":"8183_CR18","doi-asserted-by":"crossref","first-page":"iv264","DOI":"10.1093\/annonc\/mdy162","volume":"29","author":"J Haanen","year":"2018","unstructured":"Haanen J, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2018;29:iv264\u20136.","journal-title":"Ann Oncol."},{"key":"8183_CR19","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1177\/1078155217744872","volume":"25","author":"KJ Williams","year":"2019","unstructured":"Williams KJ, Grauer DW, Henry DW, et al. Corticosteroids for the management of immune-related adverse events in patients receiving checkpoint inhibitors. J Oncol Pharm Pract. 2019;25:544\u201350.","journal-title":"J Oncol Pharm Pract."},{"key":"8183_CR20","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1200\/JCO.2015.60.8448","volume":"33","author":"TZ Horvat","year":"2015","unstructured":"Horvat TZ, Adel NG, Dang TO, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol. 2015;33:3193\u20138.","journal-title":"J Clin Oncol."},{"key":"8183_CR21","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1200\/JCO.2015.66.1389","volume":"35","author":"JS Weber","year":"2017","unstructured":"Weber JS, Hodi FS, Wolchok JD, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol. 2017;35:785\u201392.","journal-title":"J Clin Oncol."},{"key":"8183_CR22","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1158\/1078-0432.CCR-18-2564","volume":"25","author":"J Park","year":"2019","unstructured":"Park J, Kwon M, Kim KH, et al. Immune checkpoint inhibitor-induced reinvigoration of tumor-infiltrating CD8(+) T cells is determined by their differentiation status in glioblastoma. Clin Cancer Res. 2019;25:2549\u201359.","journal-title":"Clin Cancer Res."},{"key":"8183_CR23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/BOR.0b013e3282f51031","volume":"20","author":"AK McDonough","year":"2008","unstructured":"McDonough AK, Curtis JR, Saag KG. The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol. 2008;20:131\u20137.","journal-title":"Curr Opin Rheumatol."},{"key":"8183_CR24","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s40257-017-0336-3","volume":"19","author":"V Sibaud","year":"2018","unstructured":"Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: skin toxicities and immunotherapy. Am J Clin Dermatol. 2018;19:345\u201361.","journal-title":"Am J Clin Dermatol."},{"key":"8183_CR25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s40425-019-0577-1","volume":"7","author":"H Abu-Sbeih","year":"2019","unstructured":"Abu-Sbeih H, Ali FS, Wang X, et al. Early introduction of selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor-induced colitis. J Immunother Cancer. 2019;7:93.","journal-title":"J Immunother Cancer."},{"key":"8183_CR26","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1200\/JCO.2019.37.7_suppl.652","volume":"37","author":"S Abou Aliwi","year":"2019","unstructured":"Abou Aliwi S, Martini DJ XW, Nassar A, Bakouny Z, Steinharter JA, Nuzzo PV, et al. Safety and efficacy of restarting (CPI) after immune-related adverse events (irAEs) in metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2019;37:652.","journal-title":"J Clin Oncol."},{"key":"8183_CR27","doi-asserted-by":"crossref","unstructured":"Santini FC RH, Wilkins O, et al. Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(l)-1 therapy. ASCO 2019. Abstract 9012, 2019.","DOI":"10.1200\/JCO.2017.35.15_suppl.9012"},{"key":"8183_CR28","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/annonc\/mdw443","volume":"28","author":"AM Menzies","year":"2017","unstructured":"Menzies AM, Johnson DB, Ramanujam S, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28:368\u201376.","journal-title":"Ann Oncol."},{"key":"8183_CR29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.12998\/wjcc.v7.i4.405","volume":"7","author":"A Som","year":"2019","unstructured":"Som A, Mandaliya R, Alsaadi D, et al. Immune checkpoint inhibitor-induced colitis: a comprehensive review. World J Clin Cases. 2019;7:405\u201318.","journal-title":"World J Clin Cases."},{"key":"8183_CR30","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1093\/ibd\/izy104","volume":"24","author":"Y Wang","year":"2018","unstructured":"Wang Y, Abu-Sbeih H, Mao E, et al. Endoscopic and histologic features of immune checkpoint inhibitor-related colitis. Inflamm Bowel Dis. 2018;24:1695\u2013705.","journal-title":"Inflamm Bowel Dis."},{"key":"8183_CR31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s40425-018-0411-1","volume":"6","author":"H Abu-Sbeih","year":"2018","unstructured":"Abu-Sbeih H, Ali FS, Luo W, et al. Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis. J Immunother Cancer. 2018;6:95.","journal-title":"J Immunother Cancer."},{"key":"8183_CR32","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.athoracsur.2018.02.030","volume":"106","author":"MJ Bott","year":"2018","unstructured":"Bott MJ, Cools-Lartigue J, Tan KS, et al. Safety and feasibility of lung resection after immunotherapy for metastatic or unresectable tumors. Ann Thorac Surg. 2018;106:178\u201383.","journal-title":"Ann Thorac Surg."},{"key":"8183_CR33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fonc.2017.00121","volume":"7","author":"AW Elias","year":"2017","unstructured":"Elias AW, Kasi PM, Stauffer JA, et al. The feasibility and safety of surgery in patients receiving immune checkpoint inhibitors: a retrospective study. Frontiers Oncol. 2017;7:121.","journal-title":"Frontiers Oncol."},{"key":"8183_CR34","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1245\/s10434-013-2999-1","volume":"20","author":"DE Gyorki","year":"2013","unstructured":"Gyorki DE, Yuan J, Mu Z, et al. Immunological insights from patients undergoing surgery on ipilimumab for metastatic melanoma. Ann Surg Oncol. 2013;20:3106\u201311.","journal-title":"Ann Surg Oncol."},{"key":"8183_CR35","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/s41591-018-0197-1","volume":"24","author":"RN Amaria","year":"2018","unstructured":"Amaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med. 2018;24:1649\u201354.","journal-title":"Nat Med."},{"key":"8183_CR36","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1038\/s41591-018-0198-0","volume":"24","author":"CU Blank","year":"2018","unstructured":"Blank CU, Rozeman EA, Fanchi LF, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24:1655\u201361.","journal-title":"Nat Med."},{"key":"8183_CR37","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1158\/1078-0432.CCR-10-0569","volume":"16","author":"BC Carthon","year":"2010","unstructured":"Carthon BC, Wolchok JD, Yuan J, et al. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res. 2010;16:2861\u201371.","journal-title":"Clin Cancer Res."},{"key":"8183_CR38","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1056\/NEJMoa1716078","volume":"378","author":"PM Forde","year":"2018","unstructured":"Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018;378:1976\u201386.","journal-title":"N Engl J Med."},{"key":"8183_CR39","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.amjsurg.2010.09.018","volume":"201","author":"H Ismael","year":"2011","unstructured":"Ismael H, Horst M, Farooq M, et al. Adverse effects of preoperative steroid use on surgical outcomes. Am J Surg. 2011;201:305\u20138. (discussion 308\u20139).","journal-title":"Am J Surg."},{"key":"8183_CR40","doi-asserted-by":"crossref","first-page":"11984","DOI":"10.1038\/s41598-019-48349-0","volume":"9","author":"H Jeong","year":"2019","unstructured":"Jeong H, Choi JW, Ahn HJ, et al. The effect of preventive use of corticosteroids on postoperative complications after esophagectomy: a retrospective cohort study. Sci Rep. 2019;9:11984.","journal-title":"Sci Rep."},{"key":"8183_CR41","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.2174\/1389450120666190404144048","volume":"20","author":"T Yamamoto","year":"2019","unstructured":"Yamamoto T, Teixeira FV, Saad-Hossne R, et al. Anti-TNF and postoperative complications in abdominal crohn\u2019s disease surgery. Curr Drug Targets. 2019;20:1339\u201348.","journal-title":"Curr Drug Targets."},{"issue":"339","key":"8183_CR42","first-page":"e1","volume":"129","author":"TH Puar","year":"2016","unstructured":"Puar TH, Stikkelbroeck NM, Smans LC, et al. Adrenal crisis: still a deadly event in the 21st century. Am J Med. 2016;129:339 e1\u20139.","journal-title":"Am J Med."},{"key":"8183_CR43","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","volume":"18","author":"J Galon","year":"2019","unstructured":"Galon J, Bruni D. Approaches to treat immune hot, altered, and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18:197\u2013218.","journal-title":"Nat Rev Drug Discov."},{"key":"8183_CR44","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fphar.2018.00185","volume":"9","author":"Y Wang","year":"2018","unstructured":"Wang Y, Deng W, Li N, et al. Combining immunotherapy and radiotherapy for cancer treatment: current challenges and future directions. Front Pharmacol. 2018;9:185.","journal-title":"Front Pharmacol."}],"container-title":["Annals of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-019-08183-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1245\/s10434-019-08183-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-019-08183-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T07:11:55Z","timestamp":1665558715000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1245\/s10434-019-08183-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,21]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["8183"],"URL":"https:\/\/doi.org\/10.1245\/s10434-019-08183-0","relation":{},"ISSN":["1068-9265","1534-4681"],"issn-type":[{"value":"1068-9265","type":"print"},{"value":"1534-4681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,21]]},"assertion":[{"value":"21 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2020","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Beth A. Helmink, MD, PhD, was supported by National Institutes of Health T32 CA 009599 and the MD Anderson Cancer Center support Grant (P30 CA016672). Colleen M. Kiernan, MD, MPH, reports no disclosures. Christina L. Roland, MD, MS, receives research support from Bristol Myers Squibb. Jennifer A. Wargo, MD, MSc, reports compensation for speaker\u2019s bureau and honoraria from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Exelixis, and Bristol-Myers Squibb. She serves as a consultant\/advisory board member for Roche\/Genentech, Novartis, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Biothera Pharmaceuticals, and Microbiome DX; receives research support from GlaxoSmithKline, Roche\/Genentech, Bristol-Myers Squibb, and Novartis; and has a U.S. patent application (PCT\/US17\/53.717) submitted by the University of Texas MD Anderson Cancer Center that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}