Prognostic value of lymph nodes count on survival of patients with distal cholangiocarcinomas

Table 1 Characteristics of patients and tumors

Variable	No. of patients, n (%) n = 449
Race
White	321 (71.5)
Black	35 (7.8)
Other	93 (20.7)
Sex
Male	286 (63.7)
Female	163 (36.3)
Age at diagnosis, in yr
≤ 60	128 (28.5)
60-70	171 (38.1)
> 70	150 (33.4)
Marital status
Married	302 (67.3)
Divorced	33 (7.3)
Separated or single	58 (12.9)
Widowed	40 (8.9)
Unknown	16 (3.6)
Year of diagnosis
2004-2010	110 (24.5)
2011-2012	160 (35.6)
2013-2014	179 (39.9)
Tumor size, in mm
≤ 20	203 (45.2)
20-50	191(42.5)
> 50	15 (3.3)
Unknown	40 (8.9)
Grade
Well differentiated	54 (12.0)
Moderately differentiated	204 (45.4)
Poorly differentiated	158 (35.2)
Undifferentiated	3 (0.7)
Unknown	30 (6.7)
Stage
IA	44 (9.8)
IB	60 (13.7)
IIA	89 (19.8)
IIB	161 (35.9)
III	95 (21.2)
T stage
T1	49 (10.9)
T2	85 (18.9)
T3	220 (49.0)
T4	95 (21.2)
pN stage
pN0	226 (50.3)
pN1	223 (49.7)
Surgery type
Local excision	102 (22.7)
Extensive surgery	347 (77.3)
Adjuvant radiotherapy
No/Unknown radiotherapy	298 (66.3)
Beam radiation	151 (33.7)
Adjuvant chemotherapy
No/Unknown chemotherapy	204 (45.4)
Chemotherapy performed	245 (54.6)
No. of LNs retrieved
1-10	196 (43.7)
11-20	151 (33.6)
> 20	102 (22.7)

LNs: Lymph nodes.

Table 2 Impact of the number of retrieved lymph nodes on survival rates

Retrieved LNs counts	No.	3-yr OS	95%CI	3-yr CSS	95%CI
For all patients
1	26	29.51%	10.90-51.07	29.51%	10.90-51.07
3	23	35.33%	13.50-58.23	43.64%	18.10-66.88
5	18	46.55%	16.40-72.36	51.20%	17.95-77.03
7	22	63.31%	35.24-81.81	63.31%	35.24-81.84
9	16	57.29%	27.94-78.40	66.20%	32.37-86.00
11	16	37.09%	11.27-63.72	40.46%	12.19-67.77
13	11	28.41%	4.52-59.96	28.41%	4.52-59.96
15	13	16.46%	0.90-50.11	16.46%	0.90-50.11
17	15	15.80%	0.82-49.22	17.01%	0.84-51.90
19	9	34.29%	4.81-68.55	34.29%	4.81-68.55
21	12	47.62%	19.35-71.52	47.62%	19.35-71.52
23	5	33.86%	5.73-66.35	33.86%	5.73-66.35
25	15	37.50%	9.37-66.61	37.50%	9.37-66.61
For N0 patients
1	17	40.38%	14.15-65.68	40.38%	14.15-65.68
3	18	43.65%	17.20-67.68	47.01%	18.51-71.34
5	11	30.00%	1.23-71.92	37.50%	1.10-80.80
7	16	76.15%	42.67-91.65	76.15%	42.67-91.65
9	5	66.67%	5.41-94.52	66.67%	5.41-94.52
11	9	50.79%	15.67-78.07	59.26%	18.59-84.95
13	4	37.50%	1.10-80.80	37.50%	1.10-80.80
15	6	26.67%	0.97-68.61	26.67%	0.97-68.61
17	4	-	-	-	-
19	2	-	-	-	-
21	6	55.56%	7.34-87.61	55.56%	7.34-87.61
23	1	-	-	-	-
25	7	42.00%	7.01-75.34	52.50%	8.42-84.55
For N1 patients
1	9	14.29%	0.71-46.49	14.29%	0.71-46.49
3	5	33.33%	0.90-77.41	33.33%	0.90-77.41
5	7	53.57%	13.20-82.50	53.57%	13.20-82.50
7	6	55.56%	7.34-87.61	55.56%	7.34-87.61
9	11	45.00%	13.88-72.41	58.33%	18.02-84.41
11	7	25.00%	1.23-64.59	25.00%	1.23-64.59
13	7	41.67%	5.60-76.65	41.67%	5.60-76.65
15	7	35.71%	1.41-77.98	35.71%	1.41-77.98
17	11	17.05%	0.84-51.92	18.94%	0.87-55.82
19	7	26.67%	0.97-68.61	26.67%	0.97-68.61
21	6	43.64%	11.29-72.96	43.64%	11.29-72.96
23	4	-	-	-	-
25	8	28.57%	4.11-61.15	28.57%	4.11-61.15

CI: Confidence interval; CSS: Cancer-specific survival; LNs: Lymph nodes; OS: Overall survival.

Table 3 Univariate and multivariate survival analyses of factors associated with overall and cancer-specific survival of all patients with distal cholangiocarcinoma

Variables	Overall survival					Cancer-specific survival
	Univariate analysis			Multivariate analysis		Univariate analysis			Multivariate analysis
	3-yr OS	χ2	P value	HR (95%CI)	P value	3-yr OS	χ2	P value	HR (95%CI)	P value
Race		2.22	0.329				1.95	0.377
White	33.3%					36.1%
Black	34.8%					36.9%
Other	38.9%					42.1%
Sex		0.44	0.507				0.54	0.463
Male	35.3%					38.3%
Female	37.7%					40.9%
Age at diagnosis, in yr		1.89	0.387				0.48	0.783
≤ 60	31.2%					35.8%
60-70	39.1%					41.4%
> 70	30.7%					36.8%
Marital status		5.02	0.285				5.98	0.201
Married	37.3%					39.6%
Divorced	-					-
Separated or single	31.4%					35.3%
Widowed	34.1%					-
Unknown	-
Year of diagnosis		1.82	0.402				3.25	0.197
2004-2010	37.3%					41.4%
2011-2012	30.9%					33.2%
2013-2014	-					-
Tumor size, in mm		8.04	0.045		0.230		8.76	0.032		0.249
≤ 20	40.8%			Reference		44.0%			Reference
20-50	29.9%			1.25 (0.94-1.67)		33.2%			1.23 (0.91-1.68)
> 50	0.0%			1.67 (0.86-3.23)		0.0%			1.76 (0.91-3.43)
Unknown	37.7%			0.95 (0.57-1.58)		46.3%			0.96 (0.56-1.65)
Grade		6.77	0.079				6.92	0.074
Well differentiated	48.6%					52.4%
Moderately differentiated	32.6%					38.9%
Poorly or undifferentiated	30.3%					32.6%
Unknown	43.2%					43.2%
T stage		5.57	0.018		0.270		11.16	< 0.001		0.037
T1/T2	44.3%			Reference		51.6%			Reference
T3/T4	29.6%			1.19 (0.87-1.64)		32.6%			1.45 (1.02-2.07)
N stage		10.64	0.001		0.020		12.27	< 0.001		0.022
N0	44.5%			Reference		47.4%			Reference
N1	26.9%			1.40 (1.05-1.86)		30.3%			1.42 (1.05-1.92)
Surgery type		1.20	0.272				0.73	0.393
Local excision	44.0%					45.3%
Extensive surgery	34.4%					37.9%
Adjuvant radiotherapy		0.16	0.683				0.79	0.372
No/Unknown radiotherapy	39.9%					44.3%
Beam radiation	29.5%					30.5%
Adjuvant chemotherapy		1.10	0.293				2.92	0.087
No/Unknown chemotherapy	41.2%					47.5%
Chemotherapy performed	32.2%					33.3%
No. of LNs retrieved		2.91	0.233				3.90	0.141
1-2	23.6%					29.9%
3-6	35.6%					39.4%
> 6	36.0%					39.0%

CI: Confidence interval; HR: Hazard ratio; LNs: Lymph nodes; OS: Overall survival.

Table 4 Univariate and multivariate survival analyses of factors associated with overall and cancer-specific survival of patients with node-negative distal cholangiocarcinoma

Variable	Overall survival					Cancer-specific survival
	Univariate analysis			Multivariate analysis		Univariate analysis			Multivariate analysis
	3-yr OS	χ2	P value	HR (95%CI)	P value	3-yr OS	χ2	P value	HR (95%CI)	P value
Race		0.82	0.663				0.13	0.939
White	44.3%					46.8%
Black	49.4%					49.4%
Other	40.4%					44.0%
Sex		1.32	0.250				0.77	0.377
Male	39.5%					46.0%
Female	47.0%					49.8%
Age at diagnosis, in yr		3.85	0.049		0.056		2.73	0.097
≤ 70	49.8%			Reference		51.8%
> 70	31.4%			1.51 (0.98-2.33)		35.7%
Marital status		6.30	0.177				6.52	0.163
Married	42.9%					48.5%
Divorced	-					-
Separated or single	31.8%					39.6%
Widowed	46.9%					46.9%
Unknown	-					-
Year of diagnosis		3.41	0.181				4.05	0.131
2004-2010	50.0%					52.1%
2011-2012	36.5%					41.4%
2013-2014	48.8%					54.0%
Tumor size, in mm		7.47	0.058				9.11	0.027		0.036
≤ 20	47.3%					49.6%			Reference
20-50	36.9%					40.0%			1.57 (0.98-2.53)
> 50	0.0%					0.0%			3.08 (1.16-8.21)
Unknown	46.8%					60.8%			0.72 (0.30-1.71)
Grade		9.65	0.021		0.014		12.56	0.005		0.003
Well differentiated	56.8%			Reference		63.3%			Reference
Moderately differentiated	43.5%			1.59 (0.84-2.99)		51.8%			1.44 (0.70-2.97)
Poorly or undifferentiated	26.0%			2.35 (1.24-4.46)		30.5%			2.90 (1.43-5.88)
Unknown	57.0%			0.76 (0.27-2.16)		57.0%			1.14 (0.37-3.50)
T stage		1.35	0.244				4.63	0.031		0.030
T1/T2	48.7%					58.4%			Reference
T3/T4	37.1%					38.7%			1.69 (1.05-2.71)
Surgery type		0.10	0.748				0.23	0.631
Local excision	45.7%					48.2%
Extensive surgery	44.1%					47.0%
Adjuvant radiotherapy		1.64	0.199				1.53	0.215
No/Unknown radiotherapy	48.2%					53.2%
Beam radiation	35.5%					37.2%
Adjuvant chemotherapy		1.31	0.251				1.48	0.222
No/Unknown chemotherapy	46.3%					53.8%
Chemotherapy performed	38.5%					42.1%
No. of LNs retrieved		7.24	0.026		0.013		6.47	0.039		0.008
1-3	35.1%			Reference		40.9%			Reference
4-9	52.3%			0.39 (0.20-0.74)		60.0%			0.32 (0.15-0.66)
> 9	39.3%			0.85 (0.53-1.36)		44.9%			0.62 (0.36-1.07)

CI: Confidence interval; CSS: Cancer-specific survival; HR: Hazard ratio; LNs: Lymph nodes; OS: Overall survival.

Table 5 Stratified analyses of overall and cancer-specific survival according to the number of retrieved LNs for N0 patients

Variable	4-9 retrieved LNs (1-3 retrieved LNs as the reference)				> 9 retrieved LNs (1-3 retrieved LNs as the reference)
	Overall survival		Cancer-specific survival		Overall survival		Cancer-specific survival
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age, in yr
≤ 70	0.33 (0.13-0.86)	0.023	0.34 (0.13-0.89)	0.030	1.02 (0.49-2.14)	0.940	0.93 (0.46-1.88)	0.848
> 70	0.32 (0.11-0.98)	0.047	0.33 (0.11-1.04)	0.059	0.63 (0.26-1.49)	0.294	0.40 (1.55-1.04)	0.059
Tumor size, in mm
≤ 20	0.55 (0.21-1.46)	0.232	0.61 (0.22-1.68)	0.340	1.34 (0.60-2.97)	0.472	0.96 (0.41-2.23)	0.921
20-50	0.22 (0.07-0.69)	0.010	0.12 (0.03-0.55)	0.007	0.54 (0.24-1.21)	0.134	0.48 (0.21-1.12)	0.090
> 50	-	-	-	-	-	-	-	-
Grade
Well or moderately differentiated	0.56 (0.24-1.30)	0.180	0.47 (0.18-1.20)	0.114	0.99 (0.49-2.01)	0.994	0.74 (0.34-1.62)	0.454
Poorly or undifferentiated	0.23 (0.07-0.79)	0.020	0.26 (0.07-0.89)	0.032	0.69 (0.31-1.58)	0.389	0.75 (0.32-1.78)	0.514
T stage
T1/T2	0.30 (0.11-0.85)	0.024	0.30 (0.09-0.94)	0.039	0.79 (0.39-1.59)	0.501	0.76 (0.36-1.59)	0.467
T3/T4	0.34 (0.13-0.85)	0.022	0.31 (0.12-0.79)	0.016	0.66 (0.31-1.41)	0.285	0.65 (0.30-1.39)	0.267

CI: Confidence interval; HR: Hazard ratio; LNs: Lymph nodes.