{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:24:46Z","timestamp":1791347086229,"version":"4.3.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["surg case rep"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Immune checkpoint inhibitors (ICIs) are emerging agents used for the treatment of various malignant tumors. As ICIs are generally used for unresectable malignant tumors, there have been only a few reports of patients who underwent surgery after receiving these drugs. Therefore, it remains unclear how immune-related adverse events (irAEs) affect the postoperative course. Here, we report a patient with advanced gastric cancer who underwent laparoscopic hepatectomy for liver metastases after an objective response with lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism as irAEs in the immediate postoperative period.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 73-year-old man had undergone total gastrectomy for pT4aN2M0 gastric cancer followed by adjuvant chemotherapy with S-1 and docetaxel, and developed liver metastases in segments 6 and 7. He was enrolled in phase 2 clinical trial of lenvatinib plus pembrolizumab. He continuously achieved a partial response with the study treatment, and the liver metastases were decreased in size on imaging. The tumors were judged to be resectable and the patient underwent laparoscopic partial hepatectomy for segments 6 and 7. From the 1st postoperative day, the patient continuously presented with fever and general fatigue, and his fasting blood glucose level remained slightly lower than that before the surgery. On the 4th postoperative day, laboratory examination revealed hypothyroidism and hypopituitarism, which were suspected to be irAE caused by lenvatinib plus pembrolizumab after surgery. He received hydrocortisone first, followed by levothyroxine after adrenal insufficiency was recovered. Subsequently, his fever, general fatigue, and any abnormality regarding fasting blood glucose level resolved, and he was discharged on the 12th postoperative day. After discharge, his laboratory data for thyroid and pituitary function remained stable while receiving hydrocortisone and levothyroxine without recurrence of gastric cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We present a case of laparoscopic hepatectomy after receiving lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism after surgery. Regarding surgery after ICI therapy, it is important to recognize that irAEs might occur in the postoperative period.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40792-021-01346-w","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T10:03:12Z","timestamp":1639994592000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hypothyroidism and hypopituitarism as immune-related adverse events due to lenvatinib plus pembrolizumab therapy in the immediate postoperative period after laparoscopic hepatectomy for liver metastases from gastric cancer: a case report"],"prefix":"10.1186","volume":"7","author":[{"given":"Kimimasa","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-8452","authenticated-orcid":false,"given":"Shin","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motokazu","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Kawazoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Shitara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Gotohda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"1346_CR1","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1093\/annonc\/mdw373.04","volume":"27","author":"M Taylor","year":"2016","unstructured":"Taylor M, Dutcus CE, Schmidt E, Bagulho T, Li D, Shumaker R, et al. A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEM) in patients with selected solid tumors. Ann Oncol. 2016;27:266\u201395.","journal-title":"Ann Oncol"},{"key":"1346_CR2","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/S1470-2045(19)30020-8","volume":"20","author":"V Makker","year":"2019","unstructured":"Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20:711\u20138.","journal-title":"Lancet Oncol"},{"key":"1346_CR3","volume-title":"TNM classification of malignant tumours","author":"JD Brierley","year":"2017","unstructured":"Brierley JD, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 8th ed. Hoboken: Wiley-Blackwell; 2017.","edition":"8"},{"key":"1346_CR4","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/S1470-2045(20)30271-0","volume":"21","author":"A Kawazoe","year":"2020","unstructured":"Kawazoe A, Fukuoka S, Nakamura Y, Kuboki Y, Wakabayashi M, Nomura S, et al. Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020;21:1057\u201365.","journal-title":"Lancet Oncol"},{"key":"1346_CR5","unstructured":"Takeuchi S, et al. Early prediction of immune checkpoint inhibitor treatment efficacy in patients with untreated advanced non-small-cell lung cancer. University hospital Medical Information Network 2019 UMIN000037614. https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000042868."},{"key":"1346_CR6","unstructured":"Minami Y, Yamauchi N, Fuse N, et al. Phase II study of Nivolumab in patients with relapsed\/refractory hematologic malignancies. University hospital Medical Information Network 2019 UMIN000033794. https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000037955."},{"key":"1346_CR7","unstructured":"Izumo T. Prospective study of anti-PD-L1 antibody therapy in advanced non-small cell lung cancer patients who previously treated with anti-PD-1 antibody. University hospital Medical Information Network 2018 UMIN000037867. https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000037867."},{"key":"1346_CR8","doi-asserted-by":"publisher","first-page":"R153","DOI":"10.1530\/EJE-13-0434","volume":"169","author":"F Torino","year":"2013","unstructured":"Torino F, Barnabei A, Paragliola RM, Marchetti P, Salvatori R, Corsello SM. Endocrine side-effects of anti-cancer drugs: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses. Eur J Endocrinol. 2013;169:R153\u201364.","journal-title":"Eur J Endocrinol"},{"key":"1346_CR9","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.wneu.2019.06.024","volume":"129","author":"AR Patel","year":"2019","unstructured":"Patel AR, Connors S, Wardak Z, Brugarolas J, Patel TR. Inflammatory reaction secondary to immune checkpoint inhibitor therapy mimicking a post-operative brain abscess. World Neurosurg. 2019;129:354\u20138.","journal-title":"World Neurosurg"},{"key":"1346_CR10","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","volume":"4","author":"R Barroso-Sousa","year":"2018","unstructured":"Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol. 2018;4:173\u201382.","journal-title":"JAMA Oncol"},{"key":"1346_CR11","doi-asserted-by":"publisher","first-page":"3888","DOI":"10.1210\/jc.2016-2118","volume":"101","author":"M Fleseriu","year":"2016","unstructured":"Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:3888\u2013921.","journal-title":"J Clin Endocrinol Metab"},{"key":"1346_CR12","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1158\/1078-0432.CCR-14-2353","volume":"21","author":"L Min","year":"2015","unstructured":"Min L, Hodi FS, Giobbie-Hurder A, Ott PA, Luke JJ, Donahue H, et al. Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study. Clin Cancer Res. 2015;21:749\u201355.","journal-title":"Clin Cancer Res"},{"key":"1346_CR13","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1111\/cen.13297","volume":"86","author":"DL Morganstein","year":"2017","unstructured":"Morganstein DL, Lai Z, Spain L, Diem S, Levine D, Mace C, et al. Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf). 2017;86:614\u201320.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"1346_CR14","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2016-214603","author":"B McMillen","year":"2016","unstructured":"McMillen B, Dhillon MS, Yong-Yow S. A rare case of thyroid storm. BMJ Case Rep. 2016. https:\/\/doi.org\/10.1136\/bcr-2016-214603.","journal-title":"BMJ Case Rep"},{"key":"1346_CR15","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nrendo.2016.205","volume":"13","author":"DJ Byun","year":"2017","unstructured":"Byun DJ, Wolchok JD, Rosenberg LM, Girotra M. Cancer immunotherapy-immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol. 2017;13:195\u2013207.","journal-title":"Nat Rev Endocrinol"},{"key":"1346_CR16","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1097\/PPO.0000000000000186","volume":"22","author":"R Dadu","year":"2016","unstructured":"Dadu R, Zobniw C, Diab A. Managing adverse events with immune checkpoint agents. Cancer J. 2016;22:121\u20139.","journal-title":"Cancer J"},{"key":"1346_CR17","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1002\/pds.5108","volume":"29","author":"S Hasegawa","year":"2020","unstructured":"Hasegawa S, Ikesue H, Nakao S, Shimada K, Mukai R, Tanaka M, et al. Analysis of immune-related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database. Pharmacoepidemiol Drug Saf. 2020;29:1279\u201394.","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"1346_CR18","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1093\/annonc\/mdv383","volume":"26","author":"J Naidoo","year":"2015","unstructured":"Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26:2375\u201391.","journal-title":"Ann Oncol"},{"key":"1346_CR19","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1210\/jc.2012-4075","volume":"98","author":"SM Corsello","year":"2013","unstructured":"Corsello SM, Barnabei A, Marchetti P, De Vecchis L, Salvatori R, Torino F. Endocrine side effects induced by immune checkpoint inhibitors. J Clin Endocrinol Metab. 2013;98:1361\u201375.","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"1346_CR20","doi-asserted-by":"publisher","first-page":"3106","DOI":"10.1093\/annonc\/mdx497","volume":"28","author":"K Otsubo","year":"2017","unstructured":"Otsubo K, Nakatomi K, Furukawa R, Ashida K, Yoneshima Y, Nakanishi Y, Okamoto I. Two cases of late-onset secondary adrenal insufficiency after discontinuation of nivolumab. Ann Oncol. 2017;28(12):3106\u20137.","journal-title":"Ann Oncol"},{"key":"1346_CR21","doi-asserted-by":"publisher","first-page":"3888","DOI":"10.1210\/jc.2016-2118","volume":"101","author":"M Fleseriu","year":"2016","unstructured":"Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad M, Salvatori R, Samuels MH. Hormonal replacement in hypopituitarism in adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:3888\u2013921.","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"1346_CR22","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1002\/pds.5108","volume":"29","author":"S Hasegawa","year":"2020","unstructured":"Hasegawa S, Ikesue H, Nakao S, et al. Analysis of immune-related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database. Pharmacoepidemiol Drug Saf. 2020;29(10):1279\u201394.","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"1346_CR23","doi-asserted-by":"publisher","first-page":"4078","DOI":"10.1210\/jc.2014-2306","volume":"99","author":"AT Faje","year":"2014","unstructured":"Faje AT, Sullivan R, Lawrence D, Tritos NA, Fadden R, Klibanski A, et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab. 2014;99:4078\u201385.","journal-title":"J Clin Endocrinol Metab"},{"key":"1346_CR24","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1530\/ERC-13-0499","volume":"21","author":"M Ryder","year":"2014","unstructured":"Ryder M, Callahan M, Postow MA, Wolchok J, Fagin JA. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer. 2014;21:371\u2013481.","journal-title":"Endocr Relat Cancer"},{"key":"1346_CR25","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1530\/EJE-09-0884","volume":"162","author":"S Hahner","year":"2010","unstructured":"Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010;162:597\u2013602.","journal-title":"Eur J Endocrinol"},{"key":"1346_CR26","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s40425-019-0805-8","volume":"7","author":"S Das","year":"2019","unstructured":"Das S, Johnson DB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer. 2019;7:306.","journal-title":"J Immunother Cancer"}],"container-title":["Surgical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40792-021-01346-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40792-021-01346-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40792-021-01346-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T10:43:20Z","timestamp":1639997000000},"score":1,"resource":{"primary":{"URL":"https:\/\/surgicalcasereports.springeropen.com\/articles\/10.1186\/s40792-021-01346-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1346"],"URL":"https:\/\/doi.org\/10.1186\/s40792-021-01346-w","relation":{},"ISSN":["2198-7793"],"issn-type":[{"value":"2198-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"21 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Because of the retrospective nature of the study and the absence of invasive interventions, patients\u2019 personal written consents were waived.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"There are no competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"267"}}