Recurrence patterns and outcomes of symptomatic gallstone disease in the elderly

Table 1 Clinical characteristics by age group, n (%)/median (interquartile range)

Variables	< 80 years (n = 1929)	≥ 80 years (n = 1087)	P value
Age	65.5 (51.3, 73.6)	86.5 (83.3, 90.1)	< 0.001
Gender			< 0.001
Male	1025 (53.1)	453 (41.7)
Female	904 (46.9)	634 (58.3)
Tobacco			< 0.001
Never	917 (60.0)	556 (73.4)
Previous smoking	334 (21.9)	175 (23.1)
Active smoking	277 (18.1)	27 (3.6)
Alcohol			< 0.001
Never	1056 (72.6)	633 (88)
Previous use	78 (5.4)	24 (3.3)
Active use	320 (22.0)	62 (8.6)
Charlson Comorbidity Index	1 (2)	2 (2)	< 0.001
Low (0-1)	1825 (60.5)	470 (43.2)
Medium (2)	515 (17.1)	246 (22.6)
High (≥ 3)	676 (22.4)	371 (34.1)	< 0.001

Table 2 Symptomatic gallstone disease index admission causes, severity, work-up, and management approaches by age group, n (%)/median (interquartile range)

Variables	< 80 years (n = 1929)	≥ 80 years (n = 1087)	P value
Gallstone disease index admission
Type of gallstone disease			< 0.001
Acute pancreatitis	689 (35.7)	252 (23.2)
Acute cholecystitis	463 (24.0)	368 (33.9)
Acute cholangitis	189 (9.8)	190 (17.5)
Symptomatic choledocholithiasis	208 (10.8)	94 (8.6)
Biliary colic	251 (13.0)	63 (5.8)
Any combination	129 (6.7)	120 (11.0)
Severity of acute pancreatitis1			0.751
Mild	535 (77.6)	194 (77.0)
Moderate	112 (16.3)	45 (17.9)
Severe	42 (6.1)	13 (5.2)
Severity of acute cholecystitis1			< 0.001
Mild	342 (73.9)	217 (59.0)
Moderate	105 (22.7)	116 (31.5)
Severe	16 (3.5)	35 (9.5)
Severity of acute cholangitis1			< 0.001
Mild	116 (61.4)	80 (42.1)
Moderate	59 (31.2)	87 (45.8)
Severe	14 (7.4)	23 (12.1)
Acute renal dysfunction			< 0.001
No	1847 (95.8)	974 (89.6)
Yes	80 (4.2)	113 (10.4)
Acute respiratory dysfunction			0.820
No	1893 (98.2)	1066 (98.1)
Yes	35 (1.8)	21 (1.9)
Acute cardiovascular dysfunction			0.027
No	1893 (98.1)	1053 (96.9)
Yes	36 (1.9)	34 (3.1)
Hospital stay (days)	6 (4, 10)	8 (5, 11)	< 0.001
Intensive care unit stay (days)	4 (3, 7)	3 (2, 6)	0.347
No	1889 (98.0)	1072 (98.7)
Yes	39 (2.0)	14 (1.3)
Follow-up time (months)	4.3 (1.9, 8.4)	8.7 (3.0, 18.4)	< 0.001
Initial diagnostic approach
Transabdominal ultrasonography (yes)	1776 (92.2)	1005 (92.5)	0.773
Computed axial tomography (yes)	702 (36.4)	394 (36.2)	0.920
Magnetic resonance imaging (yes)	539 (28.0)	207 (19.0)	< 0.001
Endoscopic ultrasound (yes)	291 (15.1)	109 (10.0)	< 0.001
Initial therapeutics
ERCP index admission (yes)	481 (24.9)	338 (31.1)	< 0.001
Sphincterotomy (yes)	457 (95.0)	322 (95.3)	0.867
Wirsung cannulation (yes)	104 (21.6)	52 (15.4)	0.025
Wirsung stent (yes)	67 (13.9)	40 (11.8)	0.381
Successful ERCP (yes)	392 (83.1)	279 (82.8)	0.783
Biliary stent (yes)	83 (17.3)	59 (17.5)	0.941
ERCP complications (yes)	79 (16.4)	49 (15.5)	0.455
Percutaneous transhepatic cholangiography (yes)	4 (0.2)	4 (0.4)	0.470
Cholecystostomy (yes)	99 (5.1)	144 (13.3)	< 0.001
Type of cholecystostomy			< 0.001
Endoscopic	5 (0.3)	24 (2.2)
Percutaneous	91 (4.7)	114 (10.5)
Both	3 (0.2)	6 (0.6)
Complications (yes)	5 (5.1)	6 (4.2)	0.761
Elective cholecystectomy (yes)	1329 (68.1)	243 (22.4)	< 0.001
Time to cholecystectomy (months)	4.3 (2.2, 6.8)	4.6 (2.4, 8.0)	0.034
< 3 months	478 (36.5)	73 (30.2)
3-6 months	407 (31.0)	70 (28.9)
> 6 months	426 (32.5)	99 (40.9)	0.032
Type of cholecystectomy			< 0.001
Laparoscopic	1200 (90.6)	197 (81.4)
Open after laparoscopic	64 (4.8)	19 (7.9)
Open	60 (4.5)	26 (10.7)
Complications (yes)	78 (5.9)	21 (8.6)	0.103

¹Severity was graded according to the Atlanta classification (2012) in the cases of acute pancreatitis and the Tokyo classification (2018) in the cases of acute cholecystitis and cholangitis.

ERCP: Endoscopic retrograde cholangiopancreatography.

Table 3 Median time to first recurrence and type of recurrence by each gallstone disease at index admission and age, n (%)/median (interquartile range)

Index admission cause	Age	Total recurrences (n = 1021)	Median time until first recurrence		Type of recurrence
			Months	P value	Acute pancreatitis	Acute cholecystitis	Acute cholangitis	SC	BC	Any combination	P value
Acute pancreatitis	< 80	255 (37.0)	2.1 (0.7, 4.5)		146 (57.3)	16 (6.3)	8 (3.1)	14 (5.5)	59 (23.1)	12 (4.7)
	≥ 80	91 (36.1)	3.5 (1.5, 9.7)	0.002	51 (56.0)	9 (9.9)	5 (5.5)	5 (5.5)	10 (11.0)	11 (12.1)	0.027
Acute cholecystitis	< 80	150 (32.4)	1.9 (0.6, 4.4)		13 (8.7)	56 (37.3)	8 (5.3)	7 (4.7)	62 (41.3)	4 (2.7)
	≥ 80	134 (36.4)	2.8 (0.9, 7.3)	0.001	4 (3.0)	54 (40.3)	20 (14.9)	8 (6.0)	35 (26.1)	13 (9.7)	< 0.001
Acute cholangitis	< 80	62 (32.8)	2 (0.5, 6.2)		3 (4.8)	11 (17.7)	20 (32.3)	7 (11.3)	17 (27.4)	4 (6.5)
	≥ 80	45 (23.7)	3.6 (0.9, 11.5)	0.102	3 (6.7)	16 (35.6)	11 (24.4)	4 (8.9)	10 (22.2)	1 (2.2)	0.368
SC	< 80	63 (30.3)	0.9 (0.5, 2.4)		9 (14.3)	9 (14.3)	7 (11.1)	15 (23.8)	22 (34.9)	1 (1.6)
	≥ 80	22 (23.4)	3.2 (0.5, 12.6)	0.049	1 (4.5)	7 (31.8)	4 (18.2)	8 (36.4)	2 (9.1)	0 (0.0)	0.082
BC	< 80	93 (37.1)	1.6 (0.4, 3.5)		14 (15.1)	13 (14.0)	1 (1.1)	3 (3.2)	61 (65.6)	1 (1.1)
	≥ 80	25 (39.7)	5.8 (2.5, 8.9)	< 0.001	4 (16.0)	8 (32.0)	3 (12.0)	2 (8.0)	7 (28.0)	1 (4.0)	0.004
Any combination	< 80	45 (34.9)	1.4 (4.2, 4.9)		11 (24.4)	8 (17.8)	5 (11.1)	2 (4.4)	11 (24.4)	8 (17.8)
	≥ 80	36 (30.0)	3.8 (0.9, 13.8)	0.038	5 (13.9)	11 (30.6)	6 (16.7)	1 (2.8)	9 (25.0)	4 (11.1)	0.589
All	< 80	668 (35.8)	1.8 (0.6, 4.2)		196 (29.3)	113 (16.9)	49 (7.3)	48 (7.2)	232 (34.7)	30 (4.5)
	≥ 80	353 (32.5)	3.4 (1.1, 9.1)	< 0.001	68 (19.3)	105 (29.7)	49 (13.9)	28 (7.9)	73 (20.7)	30 (8.5)	< 0.001

BC: Biliary colic; SC: Symptomatic choledocholithiasis.

Table 4 Recurrence-free survival at 3 months (S3), 6 months (S3), and 12 months (S12) according to demographic and clinical variables in patients aged 80 years and older

Variables	n (%)	S3	S6	S12	P value	Unadjusted hazard ratio	95%CI
All patients	1087 (100)	0.84	0.77	0.69
Type of gallstone disease					0.004
Acute cholangitis	190 (17.5)	0.90	0.84	0.79		1.00
Acute pancreatitis	252 (23.2)	0.81	0.75	0.68		1.66	1.16-2.37
Acute cholecystitis	368 (33.9)	0.81	0.73	0.63		1.82	1.30-2.55
Symptomatic choledocholithiasis	94 (8.6)	0.89	0.85	0.78		1.08	0.65-1.80
Biliary colic	63 (5.8)	0.87	0.74	0.53		1.85	1.13-3.02
Multiple diseases	120 (11.0)	0.85	0.82	0.77		1.31	0.84-2.03
Age					0.890
80-85 years	405 (37.3)	0.83	0.76	0.69		1.00
85-90 years	397 (36.5)	0.85	0.79	0.70		0.98	0.78-1.25
90-95 years	222 (20.4)	0.84	0.77	0.68		0.96	0.72-1.30
> 95 years	63 (5.8)	0.85	0.76	0.69		1.16	0.75-1.79
Gender					0.853
Female	634 (58.3)	0.84	0.78	0.71		1.00
Male	453 (41.7)	0.84	0.76	0.67		1.02	0.83-1.26
Charlson Comorbidity Index					0.144
Low (0-1)	470 (43.2)	0.85	0.79	0.71		1.00
Medium comorbidity (2)	246 (22.6)	0.82	0.72	0.62		1.27	0.98-1.65
High comorbidity (3)	371 (34.1)	0.84	0.78	0.71		0.99	0.78-1.27
Acute renal dysfunction					0.332
No	974 (89.6)	0.83	0.77	0.69		1.00
Yes	113 (10.4)	0.90	0.82	0.71		0.83	0.58-1.21
Acute respiratory dysfunction					0.749
No	1066 (98.1)	0.84	0.77	0.61		1.00
Yes	21 (1.9)	0.89	0.84	0.77		0.88	0.39-1.96
Acute cardiovascular dysfunction					0.387
No	1053 (96.9)	0.84	0.77	0.69		1
Yes	34 (3.1)	0.85	0.81	0.81		0.75	0.39-1.45
Cholelithiasis					0.560
No multiple cholelithiasis	555 (51.1)	0.85	0.79	0.71		1
Multiple cholelithiasis	532 (48.9)	0.83	0.76	0.68		1.06	0.86-1.31
Biliary tract dilation					< 0.001
Not dilatated	641 (59.0)	0.81	0.73	0.63		1.00
Dilated	444 (41.0)	0.89	0.83	0.78		0.65	0.52-0.81
Duodenal diverticula					0.143
No	636 (85.1)	0.83	0.76	0.68		1.00
Yes	111 (14.9)	0.91	0.84	0.78		0.76	9.53-1.10
Pancreas divisum					0.650
No	731 (98.1)	0.84	0.77	0.69		1.00
Yes	14 (1.9)	1.00	0.91	0.68		1.21	0.54-2.70
Sphincterotomy					< 0.001
No	765 (70.4)	0.81	0.73	0.63		1.00
Yes	322 (29.6)	0.92	0.86	0.83		0.44	0.33-0.58
Cholecystostomy					0.228
No	942 (86.7)	0.84	0.78	0.70		1.00
Yes	144 (13.3)	0.83	0.73	0.64		1.20	0.89-1.62
Ursodeoxycholic acid at discharge					0.072
No	1026 (94.4)	0.84	0.77	0.69		1.00
Yes	61 (5.6)	0.92	0.84	0.79		0.61	0.36-1.04

Table 5 Independent prognostic factors for the probability of recurrence after the first episode of symptomatic gallstone disease

Variables	Adjusted hazard ratio	95%CI	P value
Sphincterotomy			< 0.001
No	1.00
Yes	0.43	0.33-0.57
Leucocytes highest value			0.022
≤ 11000/mm3	1
> 11000/mm3	0.78	0.63-0.96
Charlson Comorbidity Index
Low (0-1)	1.00
Medium (2)	1.35	1.04-1.75	0.023
High (≥ 3)	0.99	0.78-1.28	0.987