Cholecystectomy reduces subsequent cholangiocarcinoma risk in choledocholithiasis patients undergoing endoscopic intervention

Table 1 Comparisons of choledocholithiasis patients who underwent endoscopic sphincterotomy/endoscopic papillary balloon dilatation, endoscopic sphincterotomy/endoscopic papillary balloon dilatation and cholecystectomy, and no intervention

	ES/EPBD, n = 511, n (SD; %)	ES/EPBD and CCY, n = 100, n (SD; %)	Without intervention, n = 1485, n (SD; %)	P value
Age, mean (SD)	67.44 (15.23)	59.96 (16.87)	66.16 (16.02)	< 0.001
Age, yr
18-49	40.08 (6.91)	39.13 (8.43)	39.48 (6.76)
50-69	60.48 (5.43)	58.21 (5.88)	60.14 (5.55)
> 70	79.45 (6.02)	77.58 (4.71)	79.89 (6.43)
Gender				0.450
Male	282 (55.19)	49 (49.00)	824 (55.49)
Female	229 (44.81)	51 (51.00)	661 (44.51)
Follow-up time (mo), mean (SD)	42.77 (22.20)	47.91 (20.86)	36.14 (24.87)	< 0.001
Economic status				0.445
MBS	292 (57.14)	54 (54.00)	867 (58.38)
1-3 times MBS	189 (36.99)	36 (36.00)	536 (36.09)
Above 3 times MBS	29 (5.68)	10 (10.00)	82 (5.52)
Place of residence				0.154
City	288 (56.36)	68 (68.00)	900 (60.61)
Countryside	213 (41.68)	31 (31.00)	551 (37.10)
Remote village	9 (1.76)	1 (1.00)	33 (2.22)
Comorbidity
CHB	50 (9.78)	3 (3.00)	154 (10.37)	0.057
CHC	23 (4.50)	5 (5.00)	103 (6.94)	0.127
DM	172 (33.66)	29 (29.00)	504 (33.94)	0.599
ESRD	8 (1.57)	1 (1.00)	32 (2.15)	0.552
CCDL	12 (2.35)	2 (2.00)	20 (1.35)	0.289
CO	0 (0.00)	0 (0.00)	0 (0.00)	1.000
IBD	8 (1.57)	0 (0.00)	32 (2.15)	0.253
Cholangiocarcinoma
Number of CC	39 (7.63)	4 (4.00)	90 (6.06)	0.279
Number of CC after first 18 mo	12 (2.35)	1 (1.00)	11 (0.74)	0.013
Hazard ratio	3.45 (1.52-7.82)	1.31 (0.17-10.13)	1.00	0.012
Time to diagnosis of CC (excluding case in first 18 mo), month	39.71 (18.93)	25.12 (0.00)	43.27 (17.98)	0.624
Overall mortality rate	146 (28.57)	12 (12.00)	596 (40.13)	< 0.001

ES: Endoscopic sphincterotomy; EPBD: Endoscopic papillary balloon dilatation; CCY: Cholecystectomy; SD: Standard deviation; MBS: Minimum basic salary; CHB: Chronic hepatitis B; CHC: Chronic hepatitis C; HP: Helicobacter infection; DM: Diabetes mellitus; ESRD: End-stage renal disease; CCDL: Congenital cystic disease of liver; CO: Clonorchis/Opisthorchis; IBD: Inflammatory bowel disease; CC: Cholangiocarcinoma.

Table 2 Incidence of cholangiocarcinoma among patients with choledocholithiasis who underwent therapeutic endoscopic retrograde cholangiopancreatography, endoscopic retrograde cholangiopancreatography and cholecystectomy, or no intervention compared with normal population (excluding cholangiocarcinoma in the first 18 mo)

Variable	Person-years at risk in study cohort	Person-years at risk in control cohort	No. of observed cases of cholangiocarcinoma in study cohort	No. of observed cases of cholangiocarcinoma in control cohort	Incidence rate/1000 person-years (95%CI) in study cohort	Incidence rate/1000 person-years (95%CI) in control cohort	P value
ES/EPBD
Total	1659.70	25360.07	12	7	7.23 (3.92-12.29)	0.28 (0.12-0.55)	< 0.001
Gender
Male	889.95	13822.88	4	3	4.50 (1.43-10.84)	0.22 (0.06-0.59)	< 0.001
Female	769.76	11537.20	8	4	10.39 (4.83-19.74)	0.35 (0.11-0.84)	< 0.001
Age, years
18-49	253.84	4392.03	1	0	3.94 (0.20-19.43)	0.00 (0.00-0.00)	< 0.001
50-69	574.78	8631.76	4	5	6.96 (2.21-16.79)	0.58 (0.21-1.28)	< 0.001
> 70	831.08	12336.28	7	2	8.42 (3.68-16.66)	0.16 (0.03-0.54)	< 0.001
ES/EPBD and CCY
Total	393.11	25360.07	1	7	2.54 (0.13-12.55)	0.28 (0.12-0.55)	0.011
Gender
Male	184.36	13822.88	0	3	0.00 (0.00-0.00)	0.22 (0.06-0.59)	0.842
Female	208.75	11537.20	1	4	4.79 (0.24-23.63)	0.35 (0.11-0.84)	0.002
Age, yr
18-49	113.01	4392.03	0	0	0.00 (0.00-0.00)	0.00 (0.00-0.00)	NA
50-69	143.37	8631.76	1	5	6.98 (0.35-34.40)	0.58 (0.21-1.28)	0.004
> 70	136.73	12336.28	0	2	0.00 (0.00-0.00)	0.16 (0.03-0.54)	0.882
Without intervention
Total	4364.45	25360.07	11	7	2.52 (1.35-4.38)	0.28 (0.12-0.55)	< 0.001
Gender
Male	2345.22	13822.88	6	3	2.56 (1.04-5.32)	0.22 (0.06-0.59)	< 0.001
Female	2019.23	11537.20	5	4	2.48 (0.91-5.49)	0.35 (0.11-0.84)	< 0.001
Age, yr
18-49	871.87	4392.03	0	0	0.00 (0.00-0.00)	0.00 (0.00-0.00)	NA
50-69	1528.74	8631.76	6	5	3.93 (1.601-8.16)	0.58 (0.21-1.28)	< 0.001
> 70	1963.84	12336.28	5	2	2.55 (0.93-5.64)	0.16 (0.03-0.54)	< 0.001

ES: Endoscopic sphincterotomy; EPBD: Endoscopic papillary balloon dilatation; CCY: Cholecystectomy; NA: Not applicable.

Table 3 Recurrent biliary event incidence and relationship with cholangiocarcinoma incidence among patients with choledocholithiasis underwent therapeutic endoscopic retrograde cholangiopancreatography, endoscopic retrograde cholangiopancreatography and cholecystectomy, or without intervention (excluding cholangiocarcinoma in the first 18 mo)

Variable	Number of RBE events	Number of RBE patients	RBE per person (SD)	Incidence proportion (person)	Person-years	Cholangiocarcinoma incidence rate/1000 person-years	RBEs incidence rate/1000 person-years	P value
ES/EPBD, n = 511	581	126	1.14 (2.28)	24.66%	1659.70	7.23	350.06	< 0.0011
ES/EPBD and CCY, n = 100	70	14	0.70 (1.36)	14.00%	393.11	2.54	178.07	< 0.0011
Choledocholithiasis without intervention, n = 1485	1213	286	0.82 (1.52)	19.26%	4364.45	2.52	277.93	Reference
Patients had cholangiocarcinoma after 18 mo, n = 24	43	10	1.79 (2.06)	41.67%	81.47	NA	527.79	< 0.001
Patients without cholangiocarcinoma, n = 1963	1812	414	0.92 (1.76)	21.09%	6320.31	NA	286.69	Reference

¹Z-score. ES: Endoscopic sphincterotomy; EPBD: Endoscopic papillary balloon dilatation; CCY: Cholecystectomy; RBE: Recurrent biliary event; NA: Not applicable.