TY - JOUR
T1 - Enhanced metastatic growth after local tumor resection in the presence of synchronous metastasis in a mouse allograft model of neuroblastoma
AU - Inoue, Maho
AU - Tsuchiya, Yoshiki
AU - Koike, Nobuya
AU - Umemura, Yasuhiro
AU - Inokawa, Hitoshi
AU - Togashi, Yuichi
AU - Maniwa, Junnosuke
AU - Higashi, Mayumi
AU - Fumino, Shigehisa
AU - Tajiri, Tatsuro
AU - Yagita, Kazuhiro
N1 - Funding Information:
This work was supported in part by Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT KAKENHI grant number 18H02600 [KY], 16K19008 [YU] and 15H05000 [TT]). The English used in this manuscript was reviewed by Brian Quinn (Editor-in-Chief, Japan Medical Communication).
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Purpose: We investigated how local tumor resection affects metastatic lesions in neuroblastoma. Methods: MYCN Tg tumor-derived cells were injected subcutaneously into 129+Ter/SvJcl wild-type mice. First, the frequency of metastasis-bearing mice was investigated immunohistochemically (metastatic ratio) at endpoint or post-injection day (PID) 90. Second, the threshold volume of local tumor in mice bearing microscopic lymph node metastasis (mLNM) was investigated at PID 30. Finally, local tumors were resected after exceeding the threshold. Mice were divided into local tumor resection (Resection) and observation (Observation) groups, and the metastatic ratio and volume of LNM were compared between the groups at endpoint or PID 74. Results: The metastatic ratio without local resection was 88% at PID 78–90. The threshold local tumor volume in the mice with mLNM was 745 mm3 at PID 30, so local tumors were resected after exceeding 700 mm3. The metastatic ratio and LNM volume were significantly greater in the Resection group (n = 16) than in the Observation group (n = 16) (94% vs. 38%, p < 0.001; 2092 ± 2310 vs. 275 ± 218 mm3, p < 0.01; respectively) at PID 50–74. Conclusion: Local tumor resection might augment the growth of synchronous microscopic metastases. Our results provide insights into the appropriate timing of local resection for high-risk neuroblastoma.
AB - Purpose: We investigated how local tumor resection affects metastatic lesions in neuroblastoma. Methods: MYCN Tg tumor-derived cells were injected subcutaneously into 129+Ter/SvJcl wild-type mice. First, the frequency of metastasis-bearing mice was investigated immunohistochemically (metastatic ratio) at endpoint or post-injection day (PID) 90. Second, the threshold volume of local tumor in mice bearing microscopic lymph node metastasis (mLNM) was investigated at PID 30. Finally, local tumors were resected after exceeding the threshold. Mice were divided into local tumor resection (Resection) and observation (Observation) groups, and the metastatic ratio and volume of LNM were compared between the groups at endpoint or PID 74. Results: The metastatic ratio without local resection was 88% at PID 78–90. The threshold local tumor volume in the mice with mLNM was 745 mm3 at PID 30, so local tumors were resected after exceeding 700 mm3. The metastatic ratio and LNM volume were significantly greater in the Resection group (n = 16) than in the Observation group (n = 16) (94% vs. 38%, p < 0.001; 2092 ± 2310 vs. 275 ± 218 mm3, p < 0.01; respectively) at PID 50–74. Conclusion: Local tumor resection might augment the growth of synchronous microscopic metastases. Our results provide insights into the appropriate timing of local resection for high-risk neuroblastoma.
UR - http://www.scopus.com/inward/record.url?scp=85074009507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074009507&partnerID=8YFLogxK
U2 - 10.1007/s00383-019-04568-0
DO - 10.1007/s00383-019-04568-0
M3 - Article
C2 - 31555858
AN - SCOPUS:85074009507
SN - 0179-0358
VL - 35
SP - 1403
EP - 1411
JO - Pediatric surgery international
JF - Pediatric surgery international
IS - 12
ER -