Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Department of Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
J Cancer Res Clin Oncol. 2022 Mar;148(3):697-706. doi: 10.1007/s00432-021-03650-2. Epub 2021 Apr 27.
In patients with metastatic functional gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), it is unknown what degree of tumor reduction is required to eliminate hormonal symptoms. We aimed to reduce hormonal symptoms derived from advanced GEP-NENs by efficient minimal intervention, constructing a hormonal tumor map of liver metastases.
Between 2013 and 2019, we treated 12 insulinoma or gastrinoma patients with liver metastases. Liver segments containing hormone-producing tumors were identified by injecting calcium gluconate via the hepatic arteries and monitoring the change in serum hormone concentration in the three hepatic veins. A greater-than-twofold increase in hormone concentration indicated a tumor-feeding vessel.
Cases included eight insulinomas and four gastrinomas. Primary lesions were functional in three patients and nonfunctional in 9. Nine patients showed hormonal step-up indicating the presence of functional lesions; eight showed step-up in tumor-bearing liver segments, while one with synchronous liver metastases showed step-up only in the pancreatic region. Five patients underwent surgery. Serum hormone concentration decreased markedly after removing the culprit lesions in 3; immediate improvement in hormonal symptoms was achieved in all patients. Three patients with previous surgical treatment who showed step-up underwent transcatheter arterial embolization, achieving temporary improvement of hormonal symptoms. Four patients showed unclear localization of the hormone-producing tumors; treatment options were limited, resulting in poor outcomes.
Hormonal tumor mapping demonstrated heterogeneity in hormone production among primary and metastatic tumors of GEP-NENs. Minimally invasive treatment based on hormonal mapping may be a viable alternative to conventional cytoreduction.
对于转移性功能性胃肠胰腺神经内分泌肿瘤（GEP-NENs）患者，尚不清楚需要多大程度的肿瘤缩小才能消除激素症状。我们旨在通过有效的最小干预来减少源自晚期 GEP-NEN 的激素症状，构建肝转移激素肿瘤图谱。
在 2013 年至 2019 年间，我们治疗了 12 例胰岛素瘤或胃泌素瘤伴肝转移患者。通过肝动脉注射葡萄糖酸钙并监测三条肝静脉中血清激素浓度的变化来识别含有激素产生肿瘤的肝段。激素浓度增加两倍以上表明存在肿瘤滋养血管。
病例包括 8 例胰岛素瘤和 4 例胃泌素瘤。3 例患者的原发病灶具有功能性，9 例为无功能性。9 例患者出现激素上升，表明存在功能性病变；8 例患者在有肿瘤的肝段出现上升，而 1 例同步肝转移患者仅在胰腺区域出现上升。5 例患者接受了手术。3 例切除罪魁祸首病变后血清激素浓度明显下降；所有患者的激素症状均立即改善。3 例先前接受手术治疗且出现上升的患者接受了经导管动脉栓塞术，激素症状暂时得到改善。4 例患者激素产生肿瘤的定位不明确；治疗选择有限，导致预后不良。
激素肿瘤图谱显示 GEP-NEN 的原发和转移肿瘤在激素产生方面存在异质性。基于激素图谱的微创治疗可能是传统细胞减灭术的可行替代方案。
