World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 4, August 2024, pages 579-591

Impact of Lymph Node Dissection for Patients With Clinically Node-Negative Intrahepatic Cholangiocarcinoma: A Multicenter Cohort Study

Figure 2. Patients with different lymph node status of ICC. (a) A patient with clinically node-positive ICC received left hemi-hepatectomy and lymph node dissection. (b) A patient with clinically node-negative ICC underwent both liver resection and lymph node dissection based on suspicion of lymph node metastasis at multidisciplinary team discussion. Postoperative pathology confirmed no lymph node metastasis. (c) A patient with clinically node-negative ICC underwent liver resection only. Yellow arrows: tumor; red arrows: lymph node.

Figure 3. The lymph node dissection map of patients with suspected positive lymph nodes. Including: 1) Lymph nodes located around the hepatoduodenal ligament and the common hepatic artery (stations 12 and 8); 2) Retro-pancreatic lymph nodes (station 13, for right-sided tumors); and 3) Lymph nodes around the cardiac portion of the stomach and along the lesser curvature (station 7, for left-sided tumors).

Figure 4. Recurrence-free (a) and overall (b) survival of patients receiving lymph node dissection or not after propensity score matching (PSM). LND: lymph node dissection.

Figure 5. Recurrence-free (a) and overall (b) survival of patients with lymph node metastasis (LNM (+)) and no lymph node metastasis (LNM (-)). Recurrence-free (c) and overall (d) survival of patients with hepatectomy alone (non-LND) and LNM (-). LND: lymph node dissection.

Figure 6. (a-d) Recurrence-free survival of patients in total, with non-LND, LNM (-) and LNM (+) receiving postoperative adjuvant therapy or not after PSM. LND: lymph node dissection; LNM: lymph node metastasis; PSM: propensity score matching.

Figure 7. (a-d) Overall survival of patients in total, with non-LND, LNM (-) and LNM (+) receiving postoperative adjuvant therapy or not after PSM. LND: lymph node dissection; LNM: lymph node metastasis; PSM: propensity score matching.

**Table 1.** Correlation Between Lymph Node Dissection and Clinicopathological Characteristics in Patients Matched by LND Before and After PSM
Characteristics	Before PSM	After PSM
P values were calculated using Chi-square test for categorical variables. PSM: propensity score matching; LND: lymph node dissection; KPS: Karnofsky Performance Status; HBV: hepatitis B virus; CA 19-9: carbohydrate antigen 19-9.
Gender
Female	39 (38.2%)	19 (33.3%)	0.538	17 (33.3%)	17 (33.3%)	1.000
Male	63 (61.8%)	38 (66.7%)		34 (66.7%)	34 (66.7%)
Age
≤ 50 years	18 (17.6%)	13 (22.8%)	0.431	13 (25.5%)	11 (21.6%)	0.641
> 50 years	84 (82.4%)	44 (77.2%)		38 (74.5%)	40 (78.4%)
HBV infection
Absent	65 (63.7%)	43 (75.4%)	0.129	39 (76.5%)	37 (72.5%)	0.650
Present	37 (36.3%)	14 (24.6%)		12 (23.5%)	14 (27.5%)
KPS score
> 60	88 (86.3%)	50 (87.7%)	0.796	43 (84.3%)	45 (88.2%)	0.565
≤ 60	14 (13.7%)	7 (12.3%)		8 (15.7%)	6 (11.8%)
Cirrhosis
Absent	74 (72.5%)	55 (96.5%)	< 0.001	48 (94.1%)	49 (96.1%)	0.647
Present	28 (27.5%)	2 (3.5%)		3 (5.9%)	2 (3.9%)
CA 19-9 level
≤ 55 U/mL	54 (52.9%)	30 (52.6%)	0.970	26 (51.0%)	27 (52.9%)	0.843
> 55 U/mL	48 (47.1%)	27 (47.4%)		25 (49.0%)	24 (47.1%)
Tumor diameter
≤ 5 cm	59 (57.8%)	27 (47.4%)	0.204	22 (43.1%)	23 (45.1%)	0.842
> 5 cm	43 (42.2%)	30 (52.6%)		29 (56.9%)	28 (54.9%)
Tumor number
Single	84 (82.4%)	45 (78.9%)	0.599	40 (78.4%)	42 (82.4%)	0.618
Multiple	18 (17.6%)	12 (21.1%)		11 (21.6%)	9 (17.6%)
Vascular invasion
Absent	76 (74.5%)	35 (61.4%)	0.084	36 (70.6%)	34 (66.7%)	0.670
Present	26 (25.5%)	22 (38.6%)		15 (29.4%)	17 (33.3%)
Differentiation
Well and moderate	51 (50.0%)	36 (63.2%)	0.110	30 (58.8%)	32 (62.7%)	0.685
Poor	51 (50.0%)	21 (36.8%)		21 (41.2%)	19 (37.3%)
Perineural invasion
Absent	84 (82.4%)	51 (89.5%)	0.229	47 (92.2%)	45 (88.2%)	0.505
Present	18 (17.6%)	6 (10.5%)		4 (7.8%)	6 (11.8%)
Postoperative adjuvant therapy
Absent	55 (53.9%)	29 (50.9%)	0.712	29 (56.9%)	28 (54.9%)	0.842
Present	47 (46.1%)	28 (49.1%)		22 (43.1%)	23 (45.1%)

Table 1. Correlation Between Lymph Node Dissection and Clinicopathological Characteristics in Patients Matched by LND Before and After PSM

Characteristics

Before PSM

After PSM

Non-LND (n = 102)

LND (n = 57)

P value

Non-LND (n = 51)

LND (n = 51)

P value

P values were calculated using Chi-square test for categorical variables. PSM: propensity score matching; LND: lymph node dissection; KPS: Karnofsky Performance Status; HBV: hepatitis B virus; CA 19-9: carbohydrate antigen 19-9.

Gender

Female

39 (38.2%)

19 (33.3%)

0.538

17 (33.3%)

1.000

Male

63 (61.8%)

38 (66.7%)

34 (66.7%)

Age

≤ 50 years

18 (17.6%)

13 (22.8%)

0.431

13 (25.5%)

11 (21.6%)

0.641

> 50 years

84 (82.4%)

44 (77.2%)

38 (74.5%)

40 (78.4%)

HBV infection

Absent

65 (63.7%)

43 (75.4%)

0.129

39 (76.5%)

37 (72.5%)

0.650

Present

37 (36.3%)

14 (24.6%)

12 (23.5%)

14 (27.5%)

KPS score

> 60

88 (86.3%)

50 (87.7%)

0.796

43 (84.3%)

45 (88.2%)

0.565

≤ 60

14 (13.7%)

7 (12.3%)

8 (15.7%)

6 (11.8%)

Cirrhosis

Absent

74 (72.5%)

55 (96.5%)

< 0.001

48 (94.1%)

49 (96.1%)

0.647

Present

28 (27.5%)

2 (3.5%)

3 (5.9%)

2 (3.9%)

CA 19-9 level

≤ 55 U/mL

54 (52.9%)

30 (52.6%)

0.970

26 (51.0%)

27 (52.9%)

0.843

> 55 U/mL

48 (47.1%)

27 (47.4%)

25 (49.0%)

24 (47.1%)

Tumor diameter

≤ 5 cm

59 (57.8%)

27 (47.4%)

0.204

22 (43.1%)

23 (45.1%)

0.842

> 5 cm

43 (42.2%)

30 (52.6%)

29 (56.9%)

28 (54.9%)

Tumor number

Single

84 (82.4%)

45 (78.9%)

0.599

40 (78.4%)

42 (82.4%)

0.618

Multiple

18 (17.6%)

12 (21.1%)

11 (21.6%)

9 (17.6%)

Vascular invasion

Absent

76 (74.5%)

35 (61.4%)

0.084

36 (70.6%)

34 (66.7%)

0.670

Present

26 (25.5%)

22 (38.6%)

15 (29.4%)

17 (33.3%)

Differentiation

Well and moderate

51 (50.0%)

36 (63.2%)

0.110

30 (58.8%)

32 (62.7%)

0.685

Poor

51 (50.0%)

21 (36.8%)

21 (41.2%)

19 (37.3%)

Perineural invasion

Absent

84 (82.4%)

51 (89.5%)

0.229

47 (92.2%)

45 (88.2%)

0.505

Present

18 (17.6%)

6 (10.5%)

4 (7.8%)

6 (11.8%)

Postoperative adjuvant therapy

Absent

55 (53.9%)

29 (50.9%)

0.712

29 (56.9%)

28 (54.9%)

0.842

Present

47 (46.1%)

28 (49.1%)

22 (43.1%)

23 (45.1%)

**Table 2.** Intra- and Postoperative Outcomes in Patients Matched by LND Before and After PSM
Characteristics	Before PSM	After PSM
Data were median (interquartile range) and n (%) for continuous and categorical variables. P values were calculated using nonparametric test and Chi-square test for continuous and categorical variables. PSM: propensity score matching; LND: lymph node dissection.
Surgical time (min)	160 (100, 180)	160 (120, 190)	0.319	180 (140, 200)	170 (130, 200)	0.521
Blood loss (mL)	200 (50, 300)	200 (100, 300)	0.752	200 (100, 300)	200 (100, 200)	0.454
Postoperative hospital stays (days)	9 (7, 11)	10 (8, 12)	0.021	9 (8, 11)	10 (8, 13)	0.049
Major complications	13 (12.7%)	8 (14.0%)	0.818	8 (15.7%)	7 (13.7%)	0.780
Postoperative adjuvant therapy	47 (46.1%)	28 (49.1%)	0.712	22 (43.1%)	23 (45.1%)	0.842

Table 2. Intra- and Postoperative Outcomes in Patients Matched by LND Before and After PSM

Characteristics

Before PSM

After PSM

Non-LND (n = 102)

LND (n = 57)

P value

Non-LND (n = 51)

LND (n = 51)

P value

Data were median (interquartile range) and n (%) for continuous and categorical variables. P values were calculated using nonparametric test and Chi-square test for continuous and categorical variables. PSM: propensity score matching; LND: lymph node dissection.

Surgical time (min)

160 (100, 180)

160 (120, 190)

0.319

180 (140, 200)

170 (130, 200)

0.521

Blood loss (mL)

200 (50, 300)

200 (100, 300)

0.752

200 (100, 300)

200 (100, 200)

0.454

Postoperative hospital stays (days)

9 (7, 11)

10 (8, 12)

0.021

9 (8, 11)

10 (8, 13)

0.049

Major complications

13 (12.7%)

8 (14.0%)

0.818

8 (15.7%)

7 (13.7%)

0.780

Postoperative adjuvant therapy

47 (46.1%)

28 (49.1%)

0.712

22 (43.1%)

23 (45.1%)

0.842

**Table 3.** Univariate and Multivariate Analysis of Prognosis Factors for Recurrence-Free Survival in Patients Who Underwent Resection for ICC After PSM
Characteristics	Univariate analysis	Multivariate analysis
KPS: Karnofsky Performance Status; HBV: hepatitis B virus; CA19-9: carbohydrate antigen 19-9; HR: hazard ratio; CI: confidence interval.
Age (≤ 50 vs. > 50)	1.608	0.914 - 2.830	0.099
Gender (male vs. female)	1.491	0.913 - 2.437	0.111
HBV infection (absent vs. present)	0.807	0.471 - 1.384	0.436
KPS score (> 60 vs. ≤ 60)	1.509	0.758 - 2.618	0.278
Cirrhosis (absent vs. present)	1.576	0.574 - 4.326	0.377
Preoperative CA19-9 (U/mL) (≤ 55 vs. > 55)	1.187	0.759 - 1.858	0.452
Tumor diameter (≤ 50 mm vs. > 50 mm)	2.353	1.461 - 3.789	< 0.001	2.027	1.231 - 3.338	0.005
Tumor number (single vs. multiple)	1.754	1.018 - 3.021	0.043	1.493	0.860 - 2.591	0.154
Vascular invasion (absent vs. present)	1.772	1.110 - 2.827	0.016	1.517	0.940 - 2.447	0.088
Histologic differentiation (well/moderate vs. poor)	1.465	0.930 - 2.309	0.100
Perineural invasion (absent vs. present)	1.386	0.690 - 2.784	0.358
Lymph node dissection (absent vs. present)	1.222	0.778 - 1.919	0.385
Postoperative adjuvant therapy (absent vs. present)	0.619	0.392 - 0.978	0.040	0.623	0.393 - 0.987	0.044

Table 3. Univariate and Multivariate Analysis of Prognosis Factors for Recurrence-Free Survival in Patients Who Underwent Resection for ICC After PSM

Characteristics

Univariate analysis

Multivariate analysis

95% CI

P value

95% CI

P value

KPS: Karnofsky Performance Status; HBV: hepatitis B virus; CA19-9: carbohydrate antigen 19-9; HR: hazard ratio; CI: confidence interval.

Age (≤ 50 vs. > 50)

1.608

0.914 - 2.830

0.099

Gender (male vs. female)

1.491

0.913 - 2.437

0.111

HBV infection (absent vs. present)

0.807

0.471 - 1.384

0.436

KPS score (> 60 vs. ≤ 60)

1.509

0.758 - 2.618

0.278

Cirrhosis (absent vs. present)

1.576

0.574 - 4.326

0.377

Preoperative CA19-9 (U/mL) (≤ 55 vs. > 55)

1.187

0.759 - 1.858

0.452

Tumor diameter (≤ 50 mm vs. > 50 mm)

2.353

1.461 - 3.789

< 0.001

2.027

1.231 - 3.338

0.005

Tumor number (single vs. multiple)

1.754

1.018 - 3.021

0.043

1.493

0.860 - 2.591

0.154

Vascular invasion (absent vs. present)

1.772

1.110 - 2.827

0.016

1.517

0.940 - 2.447

0.088

Histologic differentiation (well/moderate vs. poor)

1.465

0.930 - 2.309

0.100

Perineural invasion (absent vs. present)

1.386

0.690 - 2.784

0.358

Lymph node dissection (absent vs. present)

1.222

0.778 - 1.919

0.385

Postoperative adjuvant therapy (absent vs. present)

0.619

0.392 - 0.978

0.040

0.623

0.393 - 0.987

0.044

**Table 4.** Univariate and Multivariate Analysis of Prognosis Factors for Overall Survival in Patients Who Underwent Resection for ICC After PSM
Characteristics	Univariate analysis	Multivariate analysis
KPS: Karnofsky Performance Status; HBV: hepatitis B virus; CA19-9: carbohydrate antigen 19-9; HR: hazard ratio; CI: confidence interval.
Age (≤ 50 vs. > 50)	1.863	1.000 - 3.471	0.050
Gender (male vs. female)	1.360	0.818 - 2.262	0.236
HBV infection (absent vs. present)	0.826	0.466 - 1.462	0.511
KPS score (> 60 vs. ≤ 60)	1.692	0.923 - 3.100	0.089
Cirrhosis (absent vs. present)	1.865	0.675 - 5.151	0.229
Preoperative CA19-9 (U/mL) (≤ 55 vs. > 55)	1.342	0.838 - 2.149	0.221
Tumor diameter (≤ 50 vs. > 50 mm)	2.383	1.443 - 3.936	0.001	2.172	1.304 - 3.618	0.003
Tumor number (single vs. multiple)	2.330	1.349 - 4.022	0.002	2.130	1.223 - 3.711	0.008
Vascular invasion (absent vs. present)	1.389	0.841 - 2.295	0.199
Histologic differentiation (well/moderate vs. poor)	1.605	0.997 - 2.583	0.051
Perineural invasion (absent vs. present)	1.527	0.757 - 3.082	0.237
Lymph node dissection (absent vs. present)	1.189	0.740 - 1.909	0.474
Postoperative adjuvant therapy (absent vs. present)	0.578	0.357 - 0.936	0.026	0.585	0.359 - 0.952	0.031

Table 4. Univariate and Multivariate Analysis of Prognosis Factors for Overall Survival in Patients Who Underwent Resection for ICC After PSM

Characteristics

Univariate analysis

Multivariate analysis

95% CI

P value

95% CI

P value

KPS: Karnofsky Performance Status; HBV: hepatitis B virus; CA19-9: carbohydrate antigen 19-9; HR: hazard ratio; CI: confidence interval.

Age (≤ 50 vs. > 50)

1.863

1.000 - 3.471

0.050

Gender (male vs. female)

1.360

0.818 - 2.262

0.236

HBV infection (absent vs. present)

0.826

0.466 - 1.462

0.511

KPS score (> 60 vs. ≤ 60)

1.692

0.923 - 3.100

0.089

Cirrhosis (absent vs. present)

1.865

0.675 - 5.151

0.229

Preoperative CA19-9 (U/mL) (≤ 55 vs. > 55)

1.342

0.838 - 2.149

0.221

Tumor diameter (≤ 50 vs. > 50 mm)

2.383

1.443 - 3.936

0.001

2.172

1.304 - 3.618

0.003

Tumor number (single vs. multiple)

2.330

1.349 - 4.022

0.002

2.130

1.223 - 3.711

0.008

Vascular invasion (absent vs. present)

1.389

0.841 - 2.295

0.199

Histologic differentiation (well/moderate vs. poor)

1.605

0.997 - 2.583

0.051

Perineural invasion (absent vs. present)

1.527

0.757 - 3.082

0.237

Lymph node dissection (absent vs. present)

1.189

0.740 - 1.909

0.474

Postoperative adjuvant therapy (absent vs. present)

0.578

0.357 - 0.936

0.026

0.585

0.359 - 0.952

0.031