Prevalence, Risk Factors And Location Of Skip Metastasis In Papillary Thyroid Carcinoma: A Systematic Review And Meta-Analysis

Figures & data

Table 1 Characteristics Of The 18 Included Studies

Author	Year	Country	Study Period	Study Design	Study Population	Case	Age	Male	Female	Surgical Extent	LND Extent	NOS-Gen
Jin WX^Citation24	2018	P.R.China	2014/1-2016/12	Retrospective	PTC	355	48.8±12.51^§(15–85)*	112	243	TT+ CND + LND	Selective	8
Lei JY^Citation26	2017	P.R.China	na	Retrospective	PTC	450	40.5±13.7^§	120	330	TT + CND + LND	Selective	7
Likhterov L^Citation27	2017	U.S.	2006/6-2015/10	Retrospective	PTC	80	45.8 (16–98)*	24	56	TT + CND + LND	Selective	8
Nie XL^Citation25	2017	P.R.China	2008/1-2011/12	Retrospective	PTC	271	44.8 (12–85)*	64	207	TT + CND + LND	Modified radical	9
Lee YS^Citation9	2013	South Korea	2004/1-2009/6	Retrospective	PTC	131	50.4 (12–76)*	26	105	TT + CND + LND	Selective	8
Shi L^Citation28	2013	P.R.China	2003/6-2007/6	Retrospective	PTC	165	39.7 (14–76)*	36	129	TT + CND ± LND	Selective	8
Park JH^Citation11	2012	South Korea	2006/1-2009/12	Retrospective	PTC	147	41.9±11.6^§	21	126	TT + CND + LND	Selective	8
Kim YS^Citation30	2012	South Korea	2007/5-2010/9	Retrospective	PTMC	490	45.95±10.56^§	62	428	TT + CND ± LND	Selective	8
Kliseska E^Citation29	2012	Croatia	2007-2011	Retrospective	PTC	42	na	na	na	TT + CND + LND	Na	6
Lim YC^Citation10	2011	South Korea	2004/3-2010/5	Retrospective	PTC	90	47±13.9^§	20	70	TT + CND + LND	Modified radical	9
Xiao GZ^Citation32	2010	P.R.China	2001/12-2007/9	Retrospective	PTC	121	43.5 (6–73)*	25	96	TT + CND + LND	Selective	8
Koo BS^Citation31	2010	South Korea	2003/3-2009/5	Retrospective	PTC	70	47 (22–78)*	15	55	TT + CND + LND	Selective	8
Chung YS^Citation8	2009	South Korea	2006/1-2008/1	Retrospective	PTMC	245	48.2 (23–76)*	34	211	TT + CND ± LND	Selective	8
Roh JL^Citation34	2008	South Korea	2003-2006	Retrospective	PTC	52	46.9±14.4^§	12	40	TT + CND + LND	Selective	7
Lee BJ^Citation36	2007	South Korea	2000/3-2006/4	Retrospective	PTC	46	37.8 (12–86)*	8	38	TT + CND + LND	Modified radical	7
Roh JL^Citation35	2007	South Korea	2002-2004	Retrospective	PTC	22	50.6±16.4^§(29–76)*	5	17	CND + LND	Modified radical	7
Wada N^Citation33	2007	Japan	1986-2006	Retrospective	PTC	231	51.3±15.9^§(15–85)*	58	173	TT or ST or LT + CND + LND	Modified radical	8
Machens A^Citation37	2004	Germany	1994/11-2002/11	Retrospective	PTC&MTC	66	na	na	na	TT + CND + LND or CND + LND	Selective	7

Notes: ±, with or without; §, Mean ± SD; *Mean (range).

Abbreviations: na, not reported; PTC, papillary thyroid cancer; PTMC, papillary thyroid microcarcinoma; MTC, medullary thyroid cancer; TT, total thyroidectomy; ST, sub thyroidectomy; LT, lobectomy; CND, central neck dissection; LND, lateral neck dissection.

Figure 1 PRISMA flow chart of the included studies.

Figure 2 Prevalence of skip metastasis in patients with lateral lymph node metastasis.

Table 2 Risk Factors For Skip Metastasis

	RR	95% CI	P	P value Of Q-test	I^2
Multifocality of tumor	0.95	0.65–1.40	0.8047	0.0849	46.0%
Gender (male)	0.94	0.68–1.30	0.4578	0.4578	0.0%
Tumor location (upper pole)	3.35	1.65–6.79	0.0008	0.0019	73.7%
Age (<45 years)	0.84	0.63–1.14	0.2685	0.3293	13.3%
Tumor size (≤1 cm)	2.65	1.50–4.70	0.0008	0.0027	72.5%
Lymphovascular invasion	0.33	0.15–0.75	0.0083	0.9872	0.0%
Tumor bilaterality	1.08	0.74–1.56	0.6989	0.7504	0.0%
Thyroiditis	1.36	0.88–2.10	0.1646	0.2048	37.8%
Extrathyroidal extension (ETE)	1.20	0.88–1.65	0.2469	0.2488	24.7%
Capsule invasion	1.02	0.32–3.28	0.9734	0.0004	83.5%

Abbreviations: RR, risk ratio; 95% CI, 95% confidence interval.

Figure 3 Forest plot of tumor location (upper pole).

Figure 4 Forest plot of tumor size (≤1 cm).

Figure 5 Forest plot of lymphovascular invasion.

Table 3 Location Of Skip Metastasis

Level	No. Of Studies	Proportion %	95% CI	P value Of Q-test	I^Citation2
II	4	56.29	39.77–72.16	0.0162	70.9%
III	4	68.85	42.11–90.46	<0.001	89.2%
IV	4	15.95	0.66–42.34	<0.001	90.8%
V	4	3.67	0.72–8.11	0.2348	29.6%

Jin WX, Jin YX, Ye DR, et al. Predictive factors of skip metastasis in papillary thyroid cancer. Med Sci Monit. 2018;24:2744.29722351

 PubMed Web of Science ®Google Scholar

Lei J, Zhong J, Jiang K, Li Z, Gong R, Zhu J. Skip lateral lymph node metastasis leaping over the central neck compartment in papillary thyroid carcinoma. Oncotarget. 2017;8(16):27022–27033.28223546

 PubMedGoogle Scholar

Likhterov I, Reis LL, Urken ML. Central compartment management in patients with papillary thyroid cancer presenting with metastatic disease to the lateral neck: anatomic pathways of lymphatic spread. Head Neck. 2017;39(5):853.28252836

 PubMed Web of Science ®Google Scholar

Nie X, Tan Z, Ge M. Skip metastasis in papillary thyroid carcinoma is difficult to predict in clinical practice. BMC Cancer. 2017;17(1):702.29070029

 PubMedGoogle Scholar

Paek SH, Lee YM, Min SY, Kim SW, Chung KW, Youn YK. Risk factors of hypoparathyroidism following total thyroidectomy for thyroid cancer. World J Surg. 2013;37(1):94–101.23052805

 PubMed Web of Science ®Google Scholar

Shi L, Song H, Zhu H, Li D, Zhang N. Pattern, predictors, and recurrence of cervical lymph node metastases in papillary thyroid cancer. Contemp Oncol. 2013;17(6):504–509.

 Google Scholar

Park JH, Lee YS, Kim BW, Chang HS, Park CS. Skip lateral neck node metastases in papillary thyroid carcinoma. World J Surg. 2012;36(4):743–747.22354485

 PubMed Web of Science ®Google Scholar

Kim YS. Patterns and predictive factors of lateral lymph node metastasis in papillary thyroid microcarcinoma. Otolaryngol Head Neck Surg. 2012;147(1):15.22399280

 PubMed Web of Science ®Google Scholar

Kliseska E, Makovac I. Skip metastases in papillary thyroid cancer. Coll Antropol. 2012;36 Suppl 2(36 Suppl 2):59–62.

 PubMedGoogle Scholar

Lim YC, Koo BS. Predictive factors of skip metastases to lateral neck compartment leaping central neck compartment in papillary thyroid carcinoma. Oral Oncol. 2012;48(3):262–265.22047924

 PubMed Web of Science ®Google Scholar

Xiao GZ, Gao L. Central lymph node metastasis: is it a reliable indicator of lateral node involvement in papillary thyroid carcinoma? World J Surg. 2010;34(2):237.20041247

 PubMed Web of Science ®Google Scholar

Koo BS, Choi EC, Park YH, Kim EH, Lim YC. Occult contralateral central lymph node metastases in papillary thyroid carcinoma with unilateral lymph node metastasis in the lateral neck. J Am Coll Surg. 2010;210(6):895.20510797

 PubMed Web of Science ®Google Scholar

Chung YS, Kim JY, Bae JS, et al. Lateral lymph node metastasis in papillary thyroid carcinoma: results of therapeutic lymph node dissection. Thyroid. 2009;19(3):241–246.19265495

 PubMed Web of Science ®Google Scholar

Roh JL, Kim JM, Park CI. Lateral cervical lymph node metastases from papillary thyroid carcinoma: pattern of nodal metastases and optimal strategy for neck dissection. Ann Surg Oncol. 2008;15(4):1177–1182.18253801

 PubMed Web of Science ®Google Scholar

Lee BJ, Wang SG, Lee JC, Son SM, Kim IJ, Kim YK. Level IIb lymph node metastasis in neck dissection for papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2007;133(10):1028.17938327

 PubMedGoogle Scholar

Roh JL, Park JY, Rha KS, Park CI. Is central neck dissection necessary for the treatment of lateral cervical nodal recurrence of papillary thyroid carcinoma? Head Neck. 2007;29(10):901–906.17405173

 PubMed Web of Science ®Google Scholar

Wada N, Masudo K, Nakayama H, et al. Clinical outcomes in older or younger patients with papillary thyroid carcinoma: impact of lymphadenopathy and patient age. Eur J Surg Oncol. 2008;34(2):202.18023321

 PubMed Web of Science ®Google Scholar

Machens A, Holzhausen HJ, Dralle H. Skip metastases in thyroid cancer leaping the central lymph node compartment. Arch Surg. 2004;139(1):43.14718274

 PubMedGoogle Scholar

Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;140(4):317–322.24557566

 PubMed Web of Science ®Google Scholar