Published online Jun 7, 2026. doi: 10.3748/wjg.v32.i21.117971
Revised: January 27, 2026
Accepted: March 10, 2026
Published online: June 7, 2026
Processing time: 154 Days and 19.8 Hours
Symptomatic gallstone disease (SGD) is a leading cause of gastrointestinal hospitalizations with the incidence and severity positively correlated with age. Although early cholecystectomy is the recommended treatment, elderly patients are often managed conservatively due to comorbidities and surgical risk. There is limited data on the recurrence patterns of SGD in the elderly population.
To characterize the clinical features, recurrence patterns, and predictors of recurrence in elderly patients with SGD who were managed non-operatively.
A post hoc analysis was conducted using data from the multicenter RELAPSTONE cohort. The cohort included 3016 patients admitted with the first episode of SGD and did not undergo cholecystectomy during the index admission. Patients with prior biliary events or previous cholecystectomy were excluded. We defined elderly as an age ≥ 80 years. Demographic, clinical, laboratory, and imaging data were collected. Recurrence-free survival was analyzed using Kaplan-Meier curves. Multivariable Cox regression was utilized to identify independent predictors of recurrence.
Among the 3016 patients, 1087 (36.0%) were ≥ 80 years (median 86.5). At the index admission elderly patients had a higher comorbidity burden and more severe acute cholecystitis and cholangitis. Recurrence was less frequent in elderly patients (hazard ratio = 0.70; 95%CI: 0.61-0.80; P = 0.001), and recurrences occurred later in elderly patients (median 3.4 months vs 1.8 months; P < 0.001). However, elderly patients experienced more frequent multiple (51.7% vs 39.7%; P < 0.001) and more severe episodes, particularly for acute cholecystitis and cholangitis. The recurrence pattern differed between the elderly and non-elderly patients. The most frequent recurrence among the elderly patients was acute cholecystitis (29.7%). Independent protective factors against recurrence included prior endoscopic retrograde cholangiopancreatography with sphincterotomy and a higher level of white blood cell at the index admission.
SGD in elderly patients exhibited distinct clinical patterns with fewer but more severe episodes and age-specific recurrence patterns. Our findings could enable risk stratification to guide age-adapted interventions.
Core Tip: Recurrence patterns after symptomatic gallstone disease in elderly patients is scarce. This multicenter study showed that patients ≥ 80 years who were managed conservatively after the index admission followed a distinct clinical course. Although the elderly patients experienced less frequent recurrences, they did experience multiple episodes more frequently that tended to occur later and be more severe. Prior endoscopic retrograde cholangiopancreatography with sphincterotomy was associated with a reduced risk of recurrence. These findings provided novel age-specific data to improve risk stratification that can tailor management strategies in this growing population.
- Citation: Oyón D, Velamazán R, Arnau A, López-Guillén P, Martínez-Domínguez SJ, Abad Baroja D, Ruiz-Belmonte LM, Tejedor-Tejada J, Zapater R, Martín-Vicente N, Julián Gomara AB, Sastre Lozano V, Manzanares García JJ, Cañamares-Orbis P, García-Rayado G, Millastre Bocos J, Garcia de Paredes AG, Vaamonde Lorenzo M, Izagirre Arostegi A, Sirtl S, de-Madaria E. Recurrence patterns and outcomes of symptomatic gallstone disease in the elderly. World J Gastroenterol 2026; 32(21): 117971
- URL: https://www.wjgnet.com/1007-9327/full/v32/i21/117971.htm
- DOI: https://dx.doi.org/10.3748/wjg.v32.i21.117971
Symptomatic gallstone disease (SGD) is a leading cause for hospitalization of all gastrointestinal diseases. Its incidence increases significantly with age[1,2]. Among the elderly population the overall prevalence of gallstones is 14%-23%. Overall, 30% of cases become symptomatic, making SGD the most common cause of acute abdominal pain in this age group[3,4]. SGD in elderly patients frequently presents as atypical features with poor clinical outcomes[5,6]. There is an urgent need to understand the clinical behavior and management challenges of SGD in elderly patients because current projections indicate a 56% increase in the 75-84 years age group by 2050 in Western populations[7].
Current clinical guidelines recommend early cholecystectomy to prevent recurrence and reduce the risk of gallstone-related complications[8-11]. However, management in elderly populations tends to be conservative because of multiple comorbidities, patient preference, and surgical risk[12]. Consequently, many elderly patients do not undergo surgery after the initial SGD episode despite growing evidence that conservative management is associated with increased rates of recurrence, complications, and mortality. These studies have demonstrated that age itself should not be a contraindication for early cholecystectomy[13,14]. Balancing surgical risks with the benefits of preventing recurrence remains a significant clinical challenge and highlights the need for more accurate risk stratification[14-16].
Data describing predictors and patterns of recurrence in elderly patients remain limited[17]. This knowledge gap limits clinicians’ ability to appropriately select the elderly patients who may benefit from early cholecystectomy or from a conservative approach.
To address these gaps, we aimed to provide a comprehensive characterization of the clinical features, recurrence patterns, and predictors of recurrent SGD in elderly patients compared with younger adults to optimize treatment strategies and improve outcomes in the elderly population.
This study was a post hoc analysis of the RELAPSTONE cohort[18]. This data was collected in an international, mul
The cohort included consecutive patients admitted with a first episode of SGD between January 1, 2018 and April 30, 2020. The inclusion criteria were as follows: (1) Patients aged ≥ 18 years; (2) Hospital admission due to SGD including acute biliary pancreatitis (AP); (3) Acute calculous cholecystitis (ACC); (4) Acute calculous cholangitis (ACL); (5) Symptomatic choledocholithiasis (SC); (6) Biliary colic (BC); and (7) Any combination of these. Patients were excluded when the following conditions were satisfied: (1) Previous admission or visit to the emergency room for SGD; (2) Previous or same-admission cholecystectomy; (3) Previous biliary sphincterotomy; (4) Same-admission death; (5) Previous biliary-pancreatic surgery; (6) Biliary; (7) Pancreatic; (8) Duodenal cancer; and (9) Benign biliary stricture. This design captured real-world management pathways and recurrence patterns across diverse clinical settings.
A comprehensive set of variables was analyzed, including demographic characteristics, clinical data, and laboratory parameters measured at admission (first 24 hours), at discharge (final 48 hours), and at the highest recorded value during hospitalization, imaging findings, and the occurrence of SGD recurrence defined as any new episode of AP, ACC, ACL, SC, or BC requiring medical evaluation or hospitalization. All variable definitions are provided in the Supplementary material. Data collection and follow-up were conducted through a systematic review of electronic health records at each participating center. Follow-up concluded on the date of cholecystectomy, death, or the last documented clinical encounter through April 30, 2020. To ensure data quality and consistency, all records were reviewed by experienced clinicians at each site using a standardized data collection protocol. All data were pseudonymized and stored in a centralized secure database for analysis.
The World Health Organization, clinical research, healthcare systems, and government policies typically define elderly as a chronological age of ≥ 65[19]. Due to the increasing global life expectancy, particularly in Western countries[20], we defined elderly in this study as individuals ≥ 80 years[21]. This threshold was selected to represent individuals at the highest risk of age-related complications and to align with the objectives of the study.
The primary outcome of the study was to compare the recurrence-free survival rates between the study groups, defined as < 80 years and ≥ 80 years. The secondary outcomes included characterization of the recurrence patterns according to each type of SGD and identification of factors that increased the risk of recurrence among patients ≥ 80 years.
The statistical methods for this study were designed and reviewed by our biomedical statistician. Categorical variables are presented as absolute values and relative frequencies. Continuous variables are summarized as means and SD for normal distributions and by median and interquartile range (first and third quartiles) for non-normal distributions. Bivariable and multivariable analyses were conducted to determine the factors influencing the recurrence rate. Missing data were imputed (median values for continuous variables and mode values for categorical variables) for independent variables with less than 5% missing data. Recurrence or censored times (recurrence-free survival, cholecystectomy, or death) were calculated from the hospital discharge date to April 30, 2020. This included patients lost to follow-up and led to the follow-up being censored.
Kaplan-Meier survival curves with log-rank testing were used for bivariable analysis to compare recurrence-free survival during the 24 months following the first episode of SGD. Crude and adjusted hazard ratio and 95%CI were calculated using simple or multivariable Cox proportional regression models. Covariables with a P value ≤ 0.20 in the bivariable analysis or with established associations in the literature were included in the multivariable model using a backward exclusion strategy. The proportionality of hazards was assessed using Schoenfeld residuals plot.
The level of statistical significance was 5% (two-sided; P < 0.05). IBM SPSS Statistics v.28 (IBM Corporation®, Armonk, NY, United States) and Stata v.14 (StataCorpLP®, College Station, TX, United States) were used for statistical analysis.
A total of 3016 patients from the RELAPSTONE cohort met the inclusion criteria and were analyzed. Among them, 1087 patients (36.0%) were ≥ 80 years old with a median age of 86.5 years (interquartile range: 83.3, 90.1 years) (Supple
| 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 |
Significant differences were observed in the type of index SGD episode when stratified by age group (Table 2). ACC was the most frequent initial presentation in the elderly group, whereas AP was the most common presentation in the non-elderly group. The elderly group presented with more severe ACC and were more prone to develop acute renal and cardiovascular dysfunction than the non-elderly group. Additionally, the hospital length of stay was significantly longer in the elderly group.
| 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 |
Notable differences were also observed in the diagnostic and therapeutic approaches in the two groups. The elderly group was more likely to undergo elective cholecystectomy with a shorter time to surgery and a greater likelihood of laparoscopic surgery than the non-elderly group. The surgical complication rates were similar in both groups (Supplementary Table 2). Laboratory differences during index admission between the two groups are detailed in Supple
The elderly group had a longer interval between the index admission and the first recurrence compared with the non-elderly group (median 3.4 months vs 1.8 months; P < 0.001). This pattern was consistent across all SGD types except ACL in which the difference was not statistically significant (Table 3). The most frequent recurrence in the non-elderly group was BC (34.7%), whereas ACC recurred most often in the elderly group (29.7%).
| Index admission cause | Age | Total recurrences | 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 | |
The recurrence pattern differed substantially between age groups. Among the non-elderly group, the most frequent forms of recurrence were the same disease at the index presentation or BC. In contrast, ACC was the predominant form of recurrence in the elderly group except when the initial presentation was AP or SC. In these cases, the recurrence was most commonly the same disease as the initial presentation (Table 3). Multiple recurrences after the initial SGD episode was more common in the elderly group than in the non-elderly group (50.7% vs 39.7%; P < 0.01) (Supplementary Table 4). The severity of ACC or ACL recurrence was greater in the elderly group, whereas the severity of recurrent AP was similar in both groups (Supplementary Table 5). Overall, the patients in the elderly group displayed a distinct recurrence phenotype that was characterized by delayed but severe recurrence with a predominance of ACC.
The elderly group experienced fewer recurrent episodes. They showed significantly higher recurrence-free survival following the initial SGD episode with rates of 0.84, 0.77, and 0.69 at 3 months, 6 months, and 12 months, respectively, compared with 0.76, 0.68, and 0.59 in the non-elderly group (hazard ratio = 0.70; 95%CI: 0.61-0.80; P = 0.001; Figure 1). No significant differences were observed within the elderly group when they were further stratified into 5-year age intervals (Table 4).
| 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 |
In the bivariable analysis recurrence was more frequent in patients without a dilated biliary tract and those who did not undergo endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy. The highest risk of recurrence was observed after an initial presentation of BC and ACC. The use of ursodeoxycholic acid was associated with a lower risk of SGD recurrence although the difference did not reach statistical significance (Table 4 and Supple
The multivariable analysis (Table 5) showed that only three variables remained independently associated with a lower risk of recurrence: (1) ERCP with sphincterotomy; (2) Leucocyte levels > 11000/mm3 during index admission; and (3) CCI.
| 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 |
This study provided a comprehensive analysis of the recurrence patterns in SGD and its predictive factors in elderly patients who did not undergo cholecystectomy after the index admission. Recurrence-free survival rates were higher in the elderly group. Recurrence was less frequent and appeared later in the elderly group. However, they did experience multiple episodes more often. Importantly, recurrence in the elderly group predominantly presented as ACC, and when recurrence manifested as ACC or ACL, the episode was more severe than in the non-elderly group. ERCP with sphincterotomy was a main factor that reduced the risk of recurrence.
Patients ≥ 80 years represented more than one-third of the RELAPSTONE cohort, reflecting contemporary life expectancy and clinical practice more accurately than traditional cutoffs at 65 years for elderly patients. This population exhibited a distinct clinical profile compared with the non-elderly population. The elderly group comprised a higher proportion of females, reflecting the longer average life expectancy of females compared with males in Western countries[7]. The elderly group also had a significantly higher burden of comorbidities. This aligns with previous literature underscoring the complexity of managing biliary diseases in older adults[13,22].
In this cohort ACC was the most frequent index event in the elderly group, whereas AP was the most common index event in the non-elderly group. This difference likely reflects age-related variations in clinical presentation[23,24]. Moreover, elderly patients experienced more severe forms of ACC and ACL. This finding reflects atypical symptomatology, delayed diagnosis, and less aggressive early management[6]. However, in contrast to other studies, the severity of AP did not differ significantly with age[25], suggesting that this entity follows a similar clinical course regardless of age in the absence of comorbid decompensation.
We observed a notable age-dependent variability in diagnostic and therapeutic approaches. The non-elderly group frequently underwent advanced imaging techniques, such as magnetic resonance imaging and endoscopic ultrasonography. The elderly group was more likely to undergo ERCP and percutaneous cholecystostomy. This difference reflects the clinical preference for less invasive and more symptom-directed strategies in elderly patients. These approaches also have risk-based considerations that influence patient selection.
This study provided novel insights into the recurrence patterns of SGD in elderly patients with important implications for clinical decision-making. Similar to previous studies[18], the elderly group had a decreased likelihood of recurrence but were more likely to experience a severe recurrence compared with the non-elderly group. However, these differences may be partially explained by under-recognition of mild symptoms by elderly patients. These mild symptoms do not prompt medical evaluation, leading to an underestimation of less severe recurrence. Additionally, the interval between the index episode and the first recurrence was longer in the elderly group (3.4 months vs 1.8 months). This period allowed a longer therapeutic window during to determine definitive management of the index presentation.
Elderly patients who initially presented with ACC, BC, or ACL primarily recurred with ACC. Thus, cholecystectomy is the preferred therapy because it can prevent and resolve all types of SGD[26]. Endoscopic gallbladder drainage te
We identified several predictors of recurrence. In the bivariable analysis a non-dilated common bile duct was associated with a higher risk of recurrence. Physiologically, the bile duct typically dilates with age, partially explaining the differences in the prevalence and clinical presentation of SGD in elderly patients. Dilation of the common bile duct dissipates intrabiliary pressure, leading to fewer symptoms and possibly preventing recurrence. Elderly patients without this dilation may be predisposed to recurrence[31,32]. These findings emphasize the role of both anatomical factors and therapeutic interventions for understanding the risk of recurrence.
Another important preventive factor for SGD recurrence was ERCP with sphincterotomy. Sphincterotomy reduces intraductal pressure and clears residual lithiasis. This procedure is similar to common bile duct dilation in that both effectively prevent biliary obstruction. Sphincterotomy is a viable option for patients who are at high risk for recurrence but are not candidates for cholecystectomy[29,30]. Because our methods may have selected patients with severe SGD or a specific SGD to undergo ERCP, we do not necessarily recommend all patients with SGD to undergo ERCP. Integrating our observations into current management algorithms, such as the Tokyo Guidelines, could refine the management of SGD in elderly patients, particularly those with poor performance status or those in whom cholecystectomy must be delayed.
Interestingly, certain laboratory parameters appeared to exert a protective effect on the risk of recurrence. Elevated WBC levels were inversely associated with recurrence. To our knowledge this observation has not been previously reported. This association may indicate a vigorous inflammatory response or a complete resolution of the initial episode. Leukocytosis may also indicate intense gallbladder inflammation that leads to fibrosis and hypomotility, resulting in a decreased risk of further gallstones. Alternatively, elevated WBC levels may represent a marker of severe pancreatic inflammation, resulting in fibrotic remodeling and scarring that would decrease the likelihood of recurrent episodes of AP. Nevertheless, this association requires confirmation in prospective studies before the mechanism can be determined.
We observed that mild comorbidity (CCI 2) increased recurrence risk and a higher comorbidity burden (CCI ≥ 3) did not. This likely reflects the heterogeneous clinical conditions and the broad spectrum of medications in the patients in this cohort. In the absence of prior evidence linking comorbidity burden to recurrence in SGD, this finding should be interpreted cautiously.
Different models, such as the American College of Surgeons National Surgical Quality Improvement Program model, have been validated in the elderly population to support surgical decision-making in patients ≥ 80 years. However, the American College of Surgeons National Surgical Quality Improvement Program does not include cholecystectomy or stratification for the risk of recurrence[33]. Our data can identify patients at a higher risk of recurrence and predict the most probable recurrence phenotype, thereby guiding the selection of preventive strategies. Because we found that most elderly patients recur with ACC, future research should explore the role of endoscopic gallbladder drainage, particularly endoscopic ultrasound-guided cholecystostomy, as a potential modality to prevent recurrence in this population.
Despite the promising findings in our study, limitations of this work should be acknowledged. The inherent nature of a retrospective design potentially introduced selection bias (Supplementary Table 8). The exclusion of patients who died during the index admission may have led to underrepresentation of the most severe cases. However, the overall impact was likely minimal because the in-hospital mortality associated with biliopancreatic disease is low. Additionally, only patients who were hospitalized at the initial presentation were included. Therefore, patients with BC may have been underrepresented because this disease presentation typically does not lead to hospitalization. Our findings may not be fully generalizable to all care settings. Our conclusions should be applied to countries with a high life expectancy, universal healthcare, and broad access to interventions like ERCP. Caution should be exercised when extrapolating to geographic regions with different age distributions, healthcare access, or clinical practices.
Despite these limitations, the study had important strengths, including its large sample size and the largest reported cohort of patients ≥ 80 years. This age threshold accurately reflects real-world clinical practice in Western countries where life expectancy continues to increase. These features enhance the robustness and external validity of our findings. Finally, the definition of elderly should be standardized in clinical research to facilitate comparison between studies and the translation of findings into clinical practice[19].
This study provided a detailed characterization of recurrence patterns in patients ≥ 80 years and identified a distinct age-related recurrence phenotype of SGD. Although recurrence was less frequent in elderly patients, this group experienced severe recurrence, emphasizing the need for proactive and age-adapted management strategies. The potential protective role of ERCP with sphincterotomy underscores its value as a preventive strategy in selected elderly patients. Together, these findings support the need for individualized, age-adapted management approaches to optimize the prevention of recurrence and clinical outcomes in the elderly population.
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