Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm

Yang, Fan; Wang, Jianhong; Rao, Yuansheng; Feng, Yanjun; Meng, Lingzhao; Fang, Jugao

doi:10.20945/2359-3997000000537

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Archives of Endocrinology and Metabolism

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Original Article • Arch. Endocrinol. Metab. 67 (3) • May-Jun 2023 • https://doi.org/10.20945/2359-3997000000537 copy

Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

The recurrent laryngeal nerve (RLN) may be involved by papillary thyroid carcinoma ≤ 1 centimeter (PTC ≤ 1 cm). Current study investigated the predictive factors of RLN invasion in PTC ≤ 1 cm, the risk factors of disease recurrence in RLN invaded cases and the results of surgical management for RLN invasion.

Materials and methods:

Data of 374 PTC ≤ 1 cm patients were retrospectively collected. We performed univariate and multivariate analysis to identify predictive factors of RLN invasion and risk factors of disease recurrence. The abilities of factors in predicting RLN invasion were evaluated. Surgical outcomes and recurrence free survival (RFS) of patients were analyzed.

Results:

A total of 28 patients suffered RLN invasion, among which seven had disease recurrence. Preoperative vocal cord palsy (VCP), gross extrathyroidal extension, larger tumor size and tumor on the dorsal side of thyroid were verified as predictive factors of RLN invasion. RLN involved patients had poorer RFS, but better than those who also had upper-aerodigestive tract invasion. Upper-aerodigestive tract invasion, lateral neck lymph nodes metastasis (LNM) and BRAF V600E mutation were independent risk factors of disease recurrence in RLN invaded cases. Tumor shaving showed better RLN function preservation without increasing recurrent risk.

Conclusions:

Current study confirmed the rarity of RLN invasion in PTC ≤ 1 cm. Various aggressive features were verified as predictive factors of RLN invasion. Tumor shaving showed superiority in preserving nerve function without increasing recurrent risk. Special attentions should be paid for disease recurrence when RLN invasion accompanied by upper-aerodigestive tract invasion, lateral neck LNM or BRAF V600E mutation.

Keywords
Papillary thyroid carcinoma; recurrent laryngeal nerve; surgical management; recurrence; predictive factor

Characteristics		All n (%)	RLN invasion
Characteristics		All n (%)	RLN-n (%)	RLN+n (%)	p value
Sex					0.249^b b Chi-square test.
	Female	275 (73.5%)	257 (74.3%)	18 (64.3%)
	Male	99 (26.5%)	89 (25.7%)	10 (35.7%)
Age					0.572^b b Chi-square test.
	<55 years	277 (74.1%)	255 (73.7%)	22 (78.6%)
	≥55 years	97 25.9%)	91 (26.3%)	6 (21.4%)
Body mass index					0.260^b b Chi-square test.
	<25	216 (57.8%)	197 (56.9%)	19 (67.9%)
	≥25	158 (42.2%)	149 (43.1%)	9 (32.1%)
Hashimoto thyroiditis					0.488^b b Chi-square test.
	Yes	57 (15.2%)	54 (15.6%)	3 (10.7%)
	No	317 (84.8%)	292 (84.4%)	25 (89.3%)
Multifocality					0.035 ^b b Chi-square test.
	Yes	144 (38.5%)	128 (37.0%)	16 (57.1%)
	No	230 (61.5%)	218 (63.0%)	12 (42.9%)
Bilateral tumor					0.466^b b Chi-square test.
	Yes	86 (23.0%)	78 (22.5%)	8 (28.6%)
	No	288 (77.0%)	268 (77.5%)	20 (71.4%)
Central neck LNM					<0.001 ^b b Chi-square test.
	Yes	145 (38.8%)	124 (35.8%)	21 (75.0%)
	No	229 (61.2%)	222 (64.2%)	7 (25.0%)
Lateral neck LNM					<0.001 ^b b Chi-square test.
	Yes	36 (9.6%)	26 (7.5%)	10 (35.7%)
	No	338 (90.4%)	320 (92.5%)	18 (64.3%)
Preoperative VCP					<0.001 ^b b Chi-square test.
	Yes	11 (2.9%)	2 (0.6%)	9 (32.1%)
	No	363 (97.1%)	344 (99.4%)	19 (67.9%)
Extrathyroidal extension					0.01 ^c c Kruskal-Wallis test.
	None	295 (78.9%)	279 (80.6%)	16 (57.1%)
	Micro ETE	18 (4.8%)	16 (4.6%)	2 (7.1%)
	Gross ETE	61 (16.3%)	51 (14.7%)	10 (35.7%)
BRAF V600E mutation					0.069^b b Chi-square test.
	Yes	249 (66.6%)	226 (65.3%)	23 (82.1%)
	No	125 (33.4%)	120 (34.7%)	5 (17.9%)
Average tumor size (cm)		0.60±0.28	0.59±0.27	0.82±0.31	<0.001 ^d d Student's t test.
Average tumor number		1.51±0.75	1.49±0.73	1.79±0.92	0.055^c c Kruskal-Wallis test.
Number of central neck lymph nodes excised		7.04±5.31	6.88±4.90	9.00±8.82	0.561^c c Kruskal-Wallis test.
Number of central neck LNM		1.13±2.00	1.00±1.83	2.86±3.04	<0.001 ^c c Kruskal-Wallis test.
Number of lateral neck lymph nodes excised		32.40±21.15	32.74±22.05	31.50±19.48	0.865^d d Student's t test.
Number of lateral neck LNM		5.51±4.23	4.32±3.19	8.58±5.13	0.002 ^d d Student's t test.
Tumor depth^a a Based on the characteristics of tumors.					<0.001 ^b b Chi-square test.
	Ventral side of thyroid	310 (54.9%)	304 (56.6%)	6 (21.4%)
	Dorsal side of thyroid	255 (45.1%)	233 (43.4%)	22 (78.6%)
Tumor location^a a Based on the characteristics of tumors.					0.125^c c Kruskal-Wallis test.
	Upper 1/3	205 (36.3%)	189 (35.2%)	16 (57.1%)
	Middle 1/3	173 (30.6%)	167 (31.1)	6 (21.4%)
	Lower 1/3	179 (31.7%)	173 (32.2%)	6 (21.4)
	Isthmus	8 (1.4%)	8 (1.5%)	0 (0%)

Characteristics	OR	95% CI	p value^a a Logistic regression analysis.	Sensitivity	Specificity	PPV	NPV	LR+	LR-
Preoperative VCP	27.484	4.197-179.990	0.001	17.9	99.4	70.75	93.7	30.89	0.83
Gross extrathyroidal extension	2.96	1.244-7.046	0.014	42.9	80.6	15.2	94.6	2.21	0.71
Large tumor size	12.533	3.545-44.303	<0.001	82.1	52.9	12.4	97.3	1.74	0.34
Tumor on the dorsal side of thyroid	4.784	1.909-11.989	0.001	78.6	56.6	8.7	98	1.81	0.38
Multifocality	1.869	0.818-4.270	0.138	-	-	-	-	-	-

Characteristics	HR	95% CI	p value^a a Cox proportional hazards model.
Esophageal invasion	8.015	1.442-44.543	0.017
Laryngotracheal invasion	7.688	1.362-43.189	0.021
Lateral Neck LNM	11.57	1.299-95.805	0.028
BRAF V600E mutation	8.288	1.010-67.977	0.049

Characteristics		HR	95% CI	p value^a a: Cox proportional hazards model, only those p < 0.05 were further included for multivariate analysis; HR, hazard ratio; CI, confidence interval, LNM, lymph node metastasis; RLN, recurrent laryngeal nerve; VCP, vocal cord palsy.
Sex
	Female	Reference	-	-
	Male	.278	0.033-2.311	0.236
Age
	< 55 years	Reference	-	-
	≥ 55years	.032	0.0-47.587	0.355
Body mass index
	< 25	Reference	-	-
	≥ 25	1.756	0.392-7.869	0.462
Hashimoto thyroiditis
	No	Reference	-	-
	Yes	0.041	0.0-755.584	0.523
Multifocality
	No	Reference	-	-
	Yes	1.014	0.227-4.537	0.985
Gross strap muscle invasion
	No	Reference	-	-
	Yes	2.064	0.247	17.245
Central neck LNM
	No	Reference	-	-
	Yes	0.921	0.178-4.758	0.922
Lateral neck LNM
	No	Reference	-	-
	Yes	6.036	1.160-31.402	0.033
Esophageal invasion
	No	Reference	-	-
	Yes	10.505	2.008-54.966	0.005
Laryngotracheal invasion
	No	Reference	-	-
	Yes	6.234	1.180-32.936	0.031
BRAF V600E mutation
	No	Reference	-	-
	Yes	6.179	1.179-32.386	0.031
RLN invasion type
	Direct invasion	Reference	-	-
	LNM	1.349	0.261-6.958	0.721
Tumor depth
	Ventral side of thyroid	Reference	-	-
	Dorsal side of thyroid	0.932	0.180-4.818	0.933
Tumor location
	Upper 1/3	Reference	-	-
	Middle 1/3	1.208	0.221-6.601	0.828
	Lower 1/3	0.668	0.075-5.977	0.718

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[1] Correspondence to: Jugao Fang, fangjugao19651110@163.com