Analysis of risk factors of lymph node metastasis and comparison of endoscopic resection methods in rectal neuroendocrine neoplasm

doi:10.19401/j.cnki.1007-3639.2022.09.007

Abstract

Abstract:

Background and purpose: In recent years, the incidence of rectal neuroendocrine neoplasm (R-NEN) has been on the rise. However, its treatment remains controversial, especially for tumors of 10-20 mm in diameter. In this study, the clinicopathological characteristics of R-NEN were analyzed, the risk factors for lymph node metastasis were discussed, and the effects of different endoscopic resection were compared, so as to ascertain the indications and methods of endoscopic treatment of R-NEN. Methods: Clinical data of patients with R-NEN treated in the Fourth Hospital of Hebei Medical University from February 2007 to December 2020 were collected and retrospectively analyzed. The risk factors of lymph node metastasis were analyzed, and the safety and effectiveness of different endoscopic resection methods were compared. Results: The clinicopathological features of 190 patients with R-NEN were analyzed, suggesting that tumor size ≥12.5 mm (OR = 69.081, 95% CI: 11.385-419.155, P<0.001) and lymphovascular invasion (OR = 11.732, 95% CI: 1.028-84.567, P = 0.015) were independent risk factors for lymph node metastasis. The clinical data of 114 patients with R-NEN treated with endoscopic mucosal resection with cap (EMR-c) and endoscopic submucosal dissection (ESD) respectively were compared. The results showed that the duration of operation was significantly shorter in EMR-c group than in ESD group [(10.23±1.99) min vs (24.78±8.09) min, P<0.001]. There was no significant difference in rate of endoscopic en bloc resection, pathological complete resection rate and complication rate between the two groups (P>0.05). Conclusion: Tumor size ≥12.5 mm in diameter and presence of lymphovascular invasion are independent risk factors for lymph node metastasis in patients with R-NEN. Both EMR-c and ESD are safe and effective treatments for R-NEN of <12.5 mm in diameter and without lymph node metastasis.

Key words: Rectal neuroendocrine neoplasms, Lymph node metastasis, Endoscopic resection

CLC Number:

R735.3+7

ZHENG Xiuli, YAO Zhiyuan, WU Mingli, ER Limian, LI Shengmian. Analysis of risk factors of lymph node metastasis and comparison of endoscopic resection methods in rectal neuroendocrine neoplasm[J]. China Oncology, 2022, 32(9): 800-806.

Figures/Tables 7

Fig. 1

Tab. 1

Tab. 2

Fig. 2

Fig. 3

Tab. 3

Tab. 4

References 14

[1]	FOLKERT I W, SINNAMON A J, CONCORS S J, et al. Grade is a dominant risk factor for metastasis in patients with rectal neuroendocrine tumors[J]. Ann Surg Oncol, 2020, 27(3): 855-863. doi: 10.1245/s10434-019-07848-0 pmid: 31701298
[2]	FAN J H, ZHANG Y Q, SHI S S, et al. A nation-wide retrospective epidemiological study of gastroenteropancreatic neuroendocrine neoplasms in China[J]. Oncotarget, 2017, 8(42): 71699-71708. doi: 10.18632/oncotarget.17599
[3]	WOOD D E. National Comprehensive Cancer Network (NCCN) clinical practice guidelines for lung cancer screening[J]. Thorac Surg Clin, 2015, 25(2): 185-197. doi: 10.1016/j.thorsurg.2014.12.003 pmid: 25901562
[4]	AL-SUKHNI E, MILOT L, FRUITMAN M, et al. Diagnostic accuracy of MRI for assessment of T category, lymph node metastases, and circumferential resection margin involvement in patients with rectal cancer: a systematic review and meta-analysis[J]. Ann Surg Oncol, 2012, 19(7): 2212-2223. doi: 10.1245/s10434-011-2210-5
[5]	NAGTEGAAL I D, ODZE R D, KLIMSTRA D, et al. The 2019 WHO classification of tumours of the digestive system[J]. Histopathology, 2020, 76(2): 182-188. doi: 10.1111/his.13975 pmid: 31433515
[6]	GLEESON F C, LEVY M J, DOZOIS E J, et al. Endoscopically identified well-differentiated rectal carcinoid tumors: impact of tumor size on the natural history and outcomes[J]. Gastrointest Endosc, 2014, 80(1): 144-151. doi: 10.1016/j.gie.2013.11.031 pmid: 24462168
[7]	MODLIN I M, LYE K D, KIDD M. A 5-decade analysis of 13, 715 carcinoid tumors[J]. Cancer, 2003, 97(4): 934-959. doi: 10.1002/cncr.11105
[8]	DUAN X L, ZHAO M, ZHANG S L, et al. Effects of tumor distance from anal verge on survival outcomes for rectal NENs and lymphatic metastasis risk score for colorectal NENs[J]. Int J Colorectal Dis, 2020, 35(7): 1255-1264. doi: 10.1007/s00384-020-03596-w pmid: 32314191
[9]	SHIM K N, YANG S K, MYUNG S J, et al. Atypical endoscopic features of rectal carcinoids[J]. Endoscopy, 2004, 36(4): 313-316. pmid: 15057680
[10]	KONISHI T, WATANABE T, KISHIMOTO J, et al. Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years[J]. Gut, 2007, 56(6): 863-868. pmid: 17213340
[11]	AHMED Y, OTHMAN M. EMR/ESD: techniques, complications, and evidence[J]. Curr Gastroenterol Rep, 2020, 22(8): 39. doi: 10.1007/s11894-020-00777-z pmid: 32542462
[12]	DĄBKOWSKI K, RUSINIAK-ROSSIŃSKA N, MICHALSKA K, et al. Endoscopic treatment of rectal neuroendocrine tumors in a 13-year retrospective single-center study: are we following the guidelines?[J]. Pol Arch Intern Med, 2021, 131(3): 241-248.
[13]	YANG D H, PARK Y, PARK S H, et al. Cap-assisted EMR for rectal neuroendocrine tumors: comparisons with conventional EMR and endoscopic submucosal dissection (with videos)[J]. Gastrointest Endosc, 2016, 83(5): 1015-1022;quiz1023-.e6. doi: 10.1016/j.gie.2015.09.046
[14]	CHA J H, JUNG D H, KIM J H, et al. Long-term outcomes according to additional treatments after endoscopic resection for rectal small neuroendocrine tumors[J]. Sci Rep, 2019, 9(1): 4911. doi: 10.1038/s41598-019-40668-6 pmid: 30894571

Feature	Patients (n=190) n	Lymph node metastasis (n=17) n (%)	No lymph node metastasis (n=173) n (%)	P value	Feature	Patients (n=190) n	Lymph node metastasis (n=17) n (%)	No lymph node metastasis (n=173) n (%)	P value
Gender					Lymphovascular invasion
Male	107	7 (6.5)	100 (93.5)		Negative	174	6 (3.4)	168 (96.6)
Female	83	10 (12.0)	73 (88.0)	0.208	Positive	16	11 (68.8)	5 (31.2)	<0.001
Age/year					Ki-67 proliferation index
<52	90	5 (5.6)	85 (94.4)		<5%	174	9 (5.2)	165 (94.8)
≥52	100	12 (12.0)	88 (88.0)	0.135	≥5%	16	8 (50.0)	8 (50.0)	<0.001
Tumor size/mm					CgA
<12.5	167	2 (1.2.0)	165 (98.8)		Negative	152	14 (9.2)	138 (90.8)
≥12.5	23	15 (65.2)	8 (34.8)	<0.001	Positive	38	3 (7.9)	35 (92.1)	NA
Tumor location (distance from the anus)/cm					Syn
<5	76	7 (9.2)	69 (90.8)		Negative	7	1 (14.3)	6 (85.7)
≥5	114	10 (8.8)	104 (91.2)	NA	Positive	183	16 (8.7)	167 (91.3)	NA

Characteristic	EMR-c (n=60)	ESD (n=54)	P value	Characteristic	EMR-c (n=60)	ESD (n=54)	P value
Gender				Location group
Male	40 (59.7)	27 (40.3)		Upper rectum	3 (100)	0 (0)
Female	20 (42.6)	27 (57.4)	0.087	Middle rectum	38 (56.7)	29 (43.3)
Age/year				Lower rectum	19 (43.2)	25 (56.8)	0.082
<55	36 (58.1)	26 (41.9)		EUS
≥55	24 (46.2)	28 (53.8)	0.259	Mucosal layer	21 (50.0)	21 (50.0)
Lesion size/mm $\bar{x}\pm s$	6.37±1.85	6.93±2.22	0.146	Submucosa	33 (52.4)	30 (47.6)
Lesion size group/mm				Unknown	6 (66.7)	3 (33.3)	0.652
<7	22 (55.0)	18 (45.0)		Histopathological grade
≥7	38 (51.4)	36 (48.6)	0.844	NET G1	54 (52.4)	49 (47.6)
				NET G2	6 (54.5)	5 (45.5)	NA

Outcome	EMR-c (n = 60)	ESD (n = 54)	P value
Duration of procedure/min $\bar{x}\pm s$	10.23±1.99	24.78±8.09	<0.001
En bloc resection n (%)	59 (98.3%)	54 (100.0%)	NA
P-CR rate n (%)	53 (88.3%)	42 (77.8%)	0.208
Complication n (%)	2 (3.3%)	2 (3.7%)	NA
Post-procedural bleeding	2	0
Perforation	0	2

[1]	JIANG Chaoyang , WANG Juan , ZHANG Ling , GAO Hui , ZHANG Tao , LI Zhihui . Correlation analysis of neck node levels in 709 cases of nasopharyngeal carcinoma [J]. China Oncology, 2021, 31(7): 629-634.
[2]	YU Lei , DAI Zhi , WANG Zheng , ZHANG Yong , CHEN Qing . The impact of lymph node metastasis on the clinical parameters and prognosis of intrahepatic cholangiocarcinoma patients after curative resection [J]. China Oncology, 2020, 30(9): 694-700.
[3]	LI Menglei , ZHANG Jing , DAN Yibo , YANG Guang , YAO Yefeng , TONG Tong . Development and validation of a clinical-radiomics nomogram for preoperative prediction of lymph node metastasis in colorectal cancer [J]. China Oncology, 2020, 30(1): 49-56.
[4]	MA Xiaokai,HUANG Jiankang,ZHU Bo,PENG Defeng,ZHOU Rui,WANG Shengying . Clinical characteristics of papillary thyroid microcarcinoma and risk factors for cervical lymph node metastasis: a clinical analysis of 228 cases [J]. China Oncology, 2019, 29(8): 590-594.
[5]	LU Chenghui, LI Jiao, LIU Xinfeng, WANG Guoqiang, WANG Zenghua, WANG Xufu. Clinical outcome after ¹³¹I treatment in differentiated thyroid cancer with negative stimulated thyroglobulin and lymph node metastasis [J]. China Oncology, 2019, 29(6): 429-433.
[6]	LIU Mengjun, LI Yuzhi, WANG Lihua, CHANG Mengran. Clinical significance of squamous cell carcinoma antigen combined with magnetic resonance imaging in diagnosing pelvic lymph node metastasis of early cervical cancer [J]. China Oncology, 2019, 29(2): 136-141.
[7]	JI Qinghai, SUN Guohua, WANG Yu, et al. The importance of clinical practice in papillary thyroid cancer with lymph node metastasis between sternocleidomastoid and sternohyoid muscles [J]. China Oncology, 2018, 28(7): 487-490.
[8]	SHEN Haoyuan, HU Chaohua, HAN Yuntao, et al. The exploration of clinical pathological characteristics and the diagnosis and treatment strategy of 56 patients with occult breast cancer [J]. China Oncology, 2018, 28(6): 429-434.
[9]	WANG Fen, CHANG Cai. Diagnostic value of ultrasound-guided fine needle aspiration in assessment of cervical lymph node in head and neck carcinoma [J]. China Oncology, 2017, 27(6): 421-424.
[10]	ZHAO Teng, GAO Wen, LIANG Jun, et al. The relationship between the number of dissected central lymph nodes and clinical outcome in pN_1apapillary thyroid carcinoma [J]. China Oncology, 2017, 27(4): 256-261.
[11]	KONG Xiangchong, CHENG Wen, GUO Cunli, et al. Correlation between axillary lymph node metastases and ultrasonographic characteristics of axillary lymph node combined with immunohistochemistry in breast cancer patients [J]. China Oncology, 2016, 26(2): 155-160.
[12]	ZHANG Lei, YANG Jinbao, FAN Yufang, et al. Risk factors of lymph node metastasis in cN₀papillary thyroid carcinoma [J]. China Oncology, 2016, 26(1): 73-79.
[13]	ZHANG Qiongyan, ZHAO Shengnan, WANG Lei, et al. The clinical significance of tumor budding in predicting lymph node metastasis of T1 colorectal cancer [J]. China Oncology, 2015, 25(11): 865-870.
[14]	HE Rong, LIU Yongyu. Expression of OPN protein in lung squamous cell carcinoma tissue and its clinical significance [J]. China Oncology, 2015, 25(10): 812-816.
[15]	ZHANG Yi-liang, ZHANG Jie, CHEN Hai-quan, XIANG Jia-qing, ZHANG Ya-wei, CHEN Su-feng, LI He-cheng, ZHOU Jia-hua, SUI Yi-hua, HU Hong, MIAO Long-sheng, MA Long-fei. Endoscopic resection using the new duette multiband mucosectomy kit for esophageal disease [J]. China Oncology, 2013, 23(7): 530-534.