Positive relationship between number of negative lymph nodes and duration of gallbladder cancer cause-specific survival after surgery

Figures & data

Table 1 Univariate analysis for the influence of different cutoffs on gallbladder cancer cause-specific survival (GCCS)

Cutoff	N	5-year GCCS	Log-rank χ^2	P-value
<1	490	0.089	255.347	<0.001
≥1	1,264	0.396
<2	969	0.231	85.325	<0.001
≥2	785	0.409
<3	1,167	0.270	37.818	<0.001
≥3	587	0.391
<4	1,290	0.281	27.313	<0.001
≥4	464	0.383
<5	1,377	0.291	17.570	<0.001
≥5	377	0.371
<6	1,449	0.299	7.651	0.006
≥6	305	0.353
<7	1,507	0.306	2.551	0.110
≥7	247	0.324
<8	1,544	0.308	0.471	0.492
≥8	210	0.314
<9	1,575	0.309	0.014	0.905
≥9	179	0.307
<10	1,606	0.307	0.457	0.499
≥10	148	0.327

Table 2 Baseline patient and tumor characteristics of patients with gallbladder cancer from the SEER database according to NLN status

Characteristics	All patients	<2	≥2	P-value
	(N=1,754) n (%)	(N=969) n (%)	(N=785) n (%)
Sex				0.368
Male	526 (30)	282 (29.1)	244 (31.1)
Female	1,228 (70)	687 (70.9)	541 (68.9)
Age				<0.001
<60 years	497 (28.3)	230 (23.7)	267 (34.0)
≥60 years	1,257 (71.7)	739 (76.3)	518 (66.0)
Race				0.423
White	1,288 (73.4)	719(74.2)	569 (72.5)
Black	243 (12.7)	119 (12.3)	104 (13.2)
Othera	243 (13.9)	131 (13.5)	112 (14.3)
Years of diagnosis				0.001
2004–2007	449 (25.6)	277 (28.6)	172 (21.9)
2008–2011	550 (31.4)	307 (31.7)	243 (31.0)
2012–2015	755 (43)	385 (39.7)	370 (47.1)
Histotype				0.035
Adenocarcinoma	1,279 (72.9)	712 (73.5)	567 (72.2)
Squamous cell carcinoma	21 (1.2)	7 (0.7)	14 (1.8)
Adenosquamous carcinoma	59 (3.4)	25 (2.6)	34 (4.3)
Otherb	395 (22.5)	225(23.2)	170 (21.7)
SEER historic stage A				<0.001
Localized	624 (35.6)	278 (28.7)	346 (44.1
Regional	623 (35.5)	383 (39.5)	240 (30.6)
Distant	507 (28.9	308 (31.8)	199 (25.3)
Grade				<0.001
Well/moderate	963 (54.9)	480 (49.5)	483 (61.5)
Poor/anaplastic	709 (40.4)	440 (45.4)	269 (34.3)
Unstage	82 (4.7)	49 (5.1)	33 (4.2)
Tumor size (cm)				0.821
<3	768 (43.8)	420 (43.4)	348 (44.3)
3–5	604 (34.4)	348 (35.9)	256 (32.6)
>5	382 (21.8)	201 (20.7)	181 (23.1)
TNM stage				<0.001
I/II	366 (20.9)	154 (15.9)	212 (27.0)
III/IV	685 (39.0)	391 (40.4)	294 (37.5)
Unstage	703 (40.1)	424 (43.7)	279 (35.5)
No. of TLNs dissected (median)	2.0	1.0	5.0	<0.001
No. of PLNs dissected (median)	1.0	1.0	0.0	<0.001
No. of NLNs dissected (median)	1.0	0.0	4.0	<0.001

Notes:

a Other includes American Indian/Alaskan native, Asian/Pacific Islander, and unknown.

b Other cancers includes signet ring, small cell, giant and spindle cell, non-small cell, carcinoma not otherwise specified, undifferentiated, mucinous adenocarcinoma, papillary adenocarcinoma, and carcinoma, duct, adenocarcinoma with metaplasia, cholangiocarcinoma, neoplasm, and malignant. Data shown as number of patients (%), or median, as indicated.

Abbreviations: NLNs, negative lymph nodes; PLNs, positive lymph nodes; SEER, Surveillance, Epidemiology, and End Results; TLNs, total regional lymph nodes.

Table 3 Univariate and multivariate survival analyses for evaluating the influence on GCSS in data from the SEER database

Variables	5-year GCSS	Univariate analysis		Multivariate analysis
		Log-rank χ^2 test	P-value	HR (95% CI)	P-value
Sex		3.268	0.071		NI
Male	0.266
Female	0.325
Age		30.930	<0.001		<0.001
<60 years	0.386			Reference
≥60 years	0.280			1.494 (1.291–1.730)
Race		5.672	0.059		NI
White	0.298
Black	0.309
Othera	0.379
Years of diagnosis		20.073	<0.001		0.314
2004–2007	0.256			Reference
2008–2011	0.293			0.876 (0.730–1.052)
2012–2015	0.470			0.832 (0.641–1.079)
Histotype		27.137	<0.001		<0.001
Adenocarcinoma	0.281			Reference
Squamous cell carcinoma	0.095			2.475 (1.494–4.100)
Adenosquamous carcinoma	0.269			0.964 (0.696–1.334)
Otherb	0.406			0.777 (0.662–0.911)
SEER historic stage A		354.805	<0.001		<0.001
Localized	0.611			Reference
Regional	0.177			2.439 (1.970–3.020)
Distant	0.104			3.511 (2.803–4.396)
Grade		71.964	<0.001		0.001
Well/moderate	0.358			Reference
Poor/anaplastic	0.223			1.262 (1.107–1.439)
Unstaged	0.450			0.910 (0.663–1.250)
Tumor size (cm)		70.580	<0.001		<0.001
<3	0.395			Reference
3–5	0.263			1.171 (1.011–1.356)
>5	0.192			1.402 (1.186–1.657)
TNM		167.351	<0.001		0.012
I/II	0.649			Reference
III/IV	0.165			0.955 (0.633–1.441)
Unstaged	0.276			1.478 (1.056–2.070)
T stage		139.710	<0.001		<0.001
T1/T2	0.477			Reference
T3/T4	0.112			1.655 (1.334–2.053)
Unstaged	0.276			–
No. of NLNs		85.325	<0.001		0.006
<2	0.231			Reference
≥2	0.409			0.761 (0.627–0.925)
No. of PLNs		133.372	<0.001		0.246
N0	0.533			Reference
N1/N2	0.142			1.164 (0.901–1.503)
Unstaged	0.276			–
No. of TLNs		22.057	<0.001		0.035
≤2	0.280			Reference
>2	0.350			0.814 (0.673–0.985)

Notes:

a Other includes American Indian/Alaskan native, Asian/Pacific Islander, and unknown.

b Other cancers includes signet ring, small cell, giant and spindle cell, non-small cell, carcinoma not otherwise specified, undifferentiated, mucinous adenocarcinoma, papillary adenocarcinoma, and carcinoma, duct, adenocarcinoma with metaplasia, cholangiocarcinoma, neoplasm, and malignant. Data shown as number of patients (%), or median, as indicated.

Abbreviations: GCSS, gallbladder cancer cause-specific survival; NI, not included; NLNs, negative lymph nodes; PLNs, positive lymph nodes; SEER, Surveillance, Epidemiology, and End Results; TLNs, total regional lymph nodes.

Table 4 Univariate and multivariate analyses of effect of NLN count on GCSS according to cancer stage

Variables	5-year GCSS	Univariate analysis	P-value	Multivariate analysis	P-value
		Log-rank χ^2 test		HR (95% CI)
TNM
I/II		14.236	<0.001		<0.001
No. of NLNs
<2	0.542			Reference
≥2	0.733			0.413 (0.256–0.665)
III/IV		18.048	<0.001		<0.001
No. of NLNs
<2	0.137			Reference
≥2	0.200			0.655 (0.563–0.801)
Unstage		34.358	<0.001		<0.001
No. of NLNs
<2	0.207			Reference
≥2	0.381			0.595 (0.498–0.711)
N stage
N1		11.306	0.001		0.001
No. of NLNs
<2	0.140			Reference
≥2	0.173			0.664 (0.520–0.849)
N2					NI
No. of NLNs		0.767	0.381
<2	0.058
≥2	0
Unstage
No. of NLNs		34.358	<0.001		<0.001
<2	0.207			Reference
≥2	0.381			0.595 (0.498–0.711)

Abbreviations: GCSS, gallbladder cancer cause-specific survival; NI, not included; NLNs, negative lymph nodes.

Figure 1 Survival curves in gallbladder cancer patients according to number of NLNs.

Notes: Log-rank tests according to number of NLNs (two or more vs fewer than two) for (A) all TNM stages: 40.9% vs 23.1%, respectively; χ²=85.325, P<0.001; (B) stage I/II: 73.3% vs 54.2%, respectively; χ²=14.236, P<0.001; (C) stage III/IV: 20.0% vs 13.7%, respectively; χ²=18.048, P=0.002; (D) TNM stage unavailable: 38.1% vs 20.7%, respectively; χ²=34.358, P<0.001; (E) stage N1: 17.3% vs 14.0%, respectively; χ²=11.306, P=0.001; and (F) N stage unavailable: 38.1% vs 20.7%, respectively; χ²=34.358, P<0.001. The absolute number of patients at risk is listed below the curve.

Abbreviation: NLNs, negative lymph nodes.