Impact of elective laparoscopic cholecystectomy on symptom improvement: a cross-sectional study

Introduction

Background

The rates of cholecystectomy have been on the rise globally, with some nations showing particularly sharp increases. For example, in Korea from 2003 to 2017, the age-standardized rate of cholecystectomy rose from 67.7 to 211.4 per 100,000 people (1). Gallbladder disease treatment with laparoscopic cholecystectomy (LC) is both safe and effective. The reported range for bile duct injury is 0.32–0.52% and 1.6–5.3% for overall morbidity in LC (2).

Current knowledge and gaps

However, some individuals who undergo the procedure may still experience similar feelings afterward, indicating that success is not guaranteed. Therefore, it brings forth the question of whether further research is necessary to determine if excision is the optimal treatment for specific patients. Notably, patients found that LC effectively alleviated their symptoms, although one-fifth of the patients may still experience them (3). An analysis of 38 studies on post-cholecystectomy syndrome (PCS) revealed that most patients experienced relief from upper abdominal pain following cholecystectomy (4). PCS refers to the reappearance of symptoms that are akin to those encountered prior to the cholecystectomy, typically presenting as upper abdominal pain, primarily in the right upper quadrant, along with dyspepsia, and may include jaundice. The leading causes of extra-biliary sources of PCS are unnoticed reflux oesophagitis, peptic ulcer disease, irritable bowel syndrome, or pancreatitis, while the biliary reasons include remnant large cystic stump, collection, fallen or retained stone, bile leakage, Sphincter of Oddi stenosis or dyskinesia, and bile salt-induced diarrhoea (3). Various predictors were examined to determine which patients are likely to experience symptom persistence following cholecystectomy. According to certain research, pre-operative biliary symptoms and dyspeptic symptoms, such as bad taste and flatulence, are significant indicators of unfavourable outcomes following cholecystectomy, particularly in female patients (5). Age and sex have minimal influence, although some studies suggest an increased incidence of bile duct injury in men, which is associated with symptom persistence post-LC (6). Some studies suggested that individuals with prior cholecystitis face an elevated risk of complications such as wound infection, collection, and bile leakage, potentially resulting in PCS (7). Other studies investigated the role of weight and using intraoperative cholangiography as predictors in PCS (6-8). Although a recent meta-analysis and other studies (9-11) evaluated the procedural risk factors for PCS, including the roles of ERCP, sphincterotomy, and stenting, there remains limited evidence on long-term patient-reported symptom outcomes and on how the pre-operative symptom duration or severity may influence recovery.

Objective

Our study aimed to bridge this gap by focusing on these patient-centred factors and examining their relationship with post-operative symptom persistence. We present this article in accordance with the STROBE reporting checklist (available at https://ales.amegroups.com/article/view/10.21037/ales-2025-1-49/rc).

Methods

Demographic, clinical presentation, diagnosis, and surgical data and symptoms during the follow-up period of the patients were gathered retrospectively from their electronic records from January 1, 2019, to December 30, 2021. The procedures performed on the patient, such as ERCP and magnetic resonance cholangiopancreatography (MRCP), were retrieved from their medical records to reduce the recall bias from the patients. The flowchart of patient inclusion and grouping is demonstrated in Figure 1. The patients were divided into two groups for comparison. Patients whose symptoms improved after surgery were designated as having symptoms alleviated (SA). Individuals exhibiting persistent symptoms are classified as having symptoms persist (SP).

Figure 1 Flowchart of patient’s inclusion and grouping. COVID-19, coronavirus disease 2019; LC, laparoscopic cholecystectomy; SA, symptoms alleviated; SP, symptoms persist.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia (No. 366/IRB/2022) and informed consent was taken from all the patients.

Statistical analysis

The mean and standard deviation were calculated for continuous variables. The median and inter-quartile ranges were calculated in case of continuous variables following a non-normal distribution. Normality of data was checked with the Shapiro-Wilk test. Those variables following normal distribution were compared using an unpaired Student’s t-test, and those variables, which did not follow normal distribution, were subjected to the Mann-Whitney U test. The Chi-squared test and Fisher’s exact test were used to compare the outcomes between groups. We performed a Spearman correlation between selected pre-operative factors and post-operative symptom persistence.

All P values reported in this study are two-sided with the statistical significance set at <0.05. The entire data analysis was performed using SPSS software (version 25, SPSS Inc., Chicago, IL, USA).

Questionnaire

We conducted a descriptive cross-sectional study among patients who underwent cholecystectomy in the period between 2019 and 2021. Patient-reported symptoms were assessed using a structured questionnaire adapted from previously published instruments addressing postoperative symptoms after cholecystectomy (12). The questionnaire evaluated abdominal pain characteristics, gastrointestinal symptoms (such as heartburn and diarrhoea), and overall symptom persistence following surgery. The patients answered the questionnaire in Arabic with the help of bilingual professionals who translated the questions both ways. The International Society for Quality-of-Life Research defines patient-reported outcomes as any health status information reported directly by the patients without clinician interpretation. The questionnaire aligns fully with this definition.

The patients were contacted personally and were requested to answer the survey between January 1^st and March 30^th, 2023. Notably, abdominal pain was evaluated using a validated questionnaire designed to reflect the patient’s predominant symptom experience, acknowledging that the measure captures the overall pain perception rather than disease-specific pain characteristics.

Definitions

Pre-operative complaint duration: the number of weeks between the patient’s first experience of biliary symptoms and date of their cholecystectomy.

Symptom severity: symptom severity was classified based on the questionnaire into two categories: vague abdominal discomfort or intense upper abdominal pain, reflecting the patient’s predominant pre-operative symptom.

SA: defined as the patient reporting that their pre-operative abdominal symptoms had completely resolved after surgery.

SP: defined as the continued presence of the same abdominal symptoms experienced before surgery, lasting for at least 1 month post-operatively, as indicated in the questionnaire.

Patient satisfaction: measured using a four-point scale (very satisfied, satisfied, no effect, or worse). For statistical analysis, these responses were grouped into ‘satisfied’ vs. ‘not satisfied’.

Results

Demographics, clinical features, and indication of surgery of the study patients

Overall, 220 patients completed the survey. Most respondents were female, accounting for 68.6% (151/220), with an average age of 38 years at the time of surgery. The average patient’s body mass index (BMI) was 30 kg/m². The most frequent indication of surgery was acute cholecystitis 61.2% (135/220), followed by biliary colic 18.2% (40/220), obstructive jaundice 8.6% (19/220), chronic cholecystitis 6% (13/220), and biliary pancreatitis 6% (13/220). Post-operatively, the patients were observed for 30.7±7.8 months. Following cholecystectomy, abdominal pain persisted at 18.2% (40/220). The patients’ age, sex, comorbidities, BMI, diagnosis, and emergency room visit were not statistically significant different between the SA and SP groups. Table 1 represents the patients’ demographic and clinical data.

Symptoms duration and acuity

The patients whose symptoms improved had a significantly shorter duration of symptoms compared to those whose symptoms did not improve (23.7±18 vs. 45.9±31 weeks, P=0.050). More than half of the studied patients, 58% (128/220), exhibited symptoms with an acuity duration of <6 weeks. Table 1 represents the demographic and clinical data of the patients.

Procedures, surgery setting, and approach

Approximately 14.5% (32/220) and 33.6% (74/220) of the patients received ERCP or MRCP, respectively, as part of the workup and management for biliary pancreatitis or obstructive jaundice. Despite not reaching significance, the SP group did more ERCPs compared to the SA group, 22.5% vs. 14.4%, respectively. Surgery setting, approaches, and ERCP did not show a statistically significant difference between the SP and SA groups. Table 1 represents the patients’ demographic and clinical data.

Patient response to the questionnaire and satisfaction rate

Pre-operative complaints such as abdominal pain, discomfort, intense pain, and emergency visits were not statistically different between the two groups.

The SP group had more 30-day complications compared to the SA group, with 45% (18/45) vs. 23.3% (42/180), P=0.001, respectively. The complications range from wound infection, fever, collection, pain, diarrhoea, retained stone after surgery, discomfort, hernia, acid reflux, shortness of breath, and fatigue.

Post-surgery, 18.2% (40/220) had abdominal pain, 1.8% (4/220) had wound infection, 21.8% (48/220) had persistent scar pain, 4.5% (10/220) biliary stones, 26.8% (59/220) heartburn, 30.4% (67/220) had diarrhoea, and 5% (11/220) incisional hernia. The abdominal pain remains the dominant symptom in the SP group, present in 100% of the patients. The frequent symptoms after surgery include heartburn, diarrhoea, scar pain, stone persistence, and incisional hernia, with rates of 52%, 40%, 25%, 12.5%, 2.5%, respectively. Approximately 8.6% (19/220) of cohort patients were unhappy with the result of their surgery. The patients in the SP group were not significantly satisfied with the surgery results compared with the patients in the SA group, with 27.5% (11/40) vs. 4.4% (8/180), P=0.001, respectively. Table 2 represents the patients’ outcomes and satisfaction rate.

Correlation analysis

A comprehensive Spearman correlation analysis was performed, including all the relevant pre-operative and clinical variables. The analysis demonstrated that a longer symptom duration showed a borderline association with post-operative symptom persistence [rho=−0.132; P=0.050; 95% confidence interval (CI): −0.26 to 0.00], while the post-operative complications were significantly correlated with symptom persistence (rho=−0.198; P=0.003; 95% CI: −0.32 to 0.06). All other pre-operative factors, including age, BMI, diagnosis, and pre-operative ERCP, showed no significant correlation. Table 3 represents the Spearman correlation between selected preoperative factors and postoperative symptom persistence.

Discussion

Principal findings

In a previous cohort study from our institution (10), we investigated the incidence and causes of PCS during the first post-operative year, concentrating primarily on the biliary and non-biliary aetiologies identified through clinical assessment and imaging. Although that study provided important diagnostic insights, it did not explore the long-term patient-reported symptom patterns or examine the pre-operative factors that might predict persistent post-operative symptoms. The present study extends this earlier work by analysing a larger cohort and incorporating patient-reported outcomes collected 2–4 years after surgery. In doing so, we evaluated symptom persistence, overall satisfaction, and the potential predictive role of factors such as symptom duration, symptom severity, and pre-operative ERCP. This complementary approach allows for a broader understanding of the post-operative symptom trajectories and offers new perspectives on the long-term outcomes that were not captured in our previous study.

This study found that 30 months after LC, 18.2% of patients still had symptoms.

Comparison with other studies

In some reviews, as many as 40% of the patients encounter ongoing or novel symptoms following cholecystectomy, such as abdominal pain, diarrhoea, and dyspepsia (3,11). Patients who have mild pre-operative symptoms are more likely to report persistent symptoms post-operatively, although this is not always the case. The severity and frequency of pre-operative symptoms can impact the persistence of symptoms after surgery (12-15). Although the pre-operative evaluation focused on gallbladder-related disease, non-biliary causes of abdominal pain may persist post-operatively. Among 342 surveyed patients, 40% reported enduring the symptoms, and those with symptoms lasting ≤1 year had a higher likelihood of being pain-free post-cholecystectomy (16).

Interpretation of finding

In this cohort, there was no significant difference between the two groups regarding mild and intense pain; however, the duration did differ. The persistence of symptoms averages 45.9±31 weeks; yet, they defer their decision to undergo surgery. Despite some variations in the surgical indications, both groups had a comparable distribution of underlying diagnoses. Therefore, it is unlikely that diagnosis alone accounted for the continued post-operative symptoms.

A surgeon’s choice could also account for the length of time a patient complains before a cholecystectomy. The surgeon may be unsure whether to recommend gallbladder removal because these patients may be experiencing unusual gallstone symptoms.

Although a longer duration of pre-operative symptoms and post-operative complications was associated with persistent post-operative complaints, this relationship should not be interpreted as a reason to withhold surgery from such patients. Rather, it underscores the importance of a careful and comprehensive pre-operative evaluation, thoughtful discussion about the expected outcomes, and consideration of alternative or functional gastrointestinal causes that may contribute to their symptoms. In this context, the symptom duration may serve as a helpful component of pre-operative counselling, guiding shared decision-making; however, it should not be viewed as a determinant of surgical eligibility.

ERCP can diagnose the underlying reasons for PCS, including sphincter of Oddi dysfunction (SOD), stricture, or retained stones. It can also offer therapeutic interventions like sphincterotomy or balloon dilation (17). Despite that, ERCP with sphincterotomy does not produce a statistically significant decrease in the pain-related disability in patients suffering from post-cholecystectomy pain linked to SOD (18).

The procedure may induce pain from the injection of contrast medium, potentially mimicking or intensifying post-cholecystectomy discomfort (19). Serial follow-up studies suggest that ERCP can assist in diagnosing genuine PCS; however, it may not consistently yield a conclusive diagnosis or alleviate pain (19,20). The potential risk factors of PCS include sphincterotomy and pre-operative ERCP with stenting. It has been found that pre-operative ERCP increases the risk of surgical site infection after LC by a factor of three (21). Other studies mention the low morbidity rate if papillotomy is not done during ERCP (22). In this cohort, more patients in the SP group underwent pre-operative ERCP compared with patients in the SA group (22.5% vs. 14.4%).

Because some patients in the SP group had clear post-operative causes for their symptoms, such as retained bile duct stones or new-onset reflux, their persistent complaints may not fully reflect classical PCS. While it would have been ideal to analyse the outcomes after excluding these patients, a meaningful subgroup analysis was limited by the small sample size. We have now acknowledged this as a limitation and recommend that future studies explore this distinction more thoroughly.

These complications can arise from several factors. SOD may explain abdominal pain in 14% of patients with PCS (23). This muscular valve regulates the flow of bile and pancreatic secretions into the duodenum. ERCP may irritate or damage the sphincter, resulting in spasm, obstruction, pancreatitis, or dysfunction. The procedure might alter the pancreatic duct and lead to chronic unexplained abdominal pain related to pancreatic dysfunction. Manipulation of the bile ducts may occasionally exacerbate inflammation or result in incomplete stone removal, leading to ongoing symptoms. The continuous flow of bile into the intestines may precipitate bile acid diarrhoea. Although ERCP does not directly cause this condition, it may exacerbate the symptoms by disrupting the bile duct system or sphincter function after sphincterotomy, causing sphincter incontinence.

Approximately 95.6% (172/220) of cohort patients were happy with the result of their surgery. The results from two randomized controlled trials on symptomatic noncomplicated gallstone disease and acute cholecystitis indicate that many patients continue to experience pain even 5 years after gallbladder removal. Generally, younger women with simple gallstone disease are more likely to report non-specific persistent abdominal pain. Nevertheless, 88% of the patients expressed satisfaction with the outcome of the procedure (14).

Study limitations

This study has certain limitations that should be considered. Its cross-sectional design and the long interval between surgery and follow-up introduce the possibility of recall bias, and some patient-reported symptoms may not perfectly match what is documented in the medical records. Although abdominal pain is a broad and heterogeneous clinical symptom, our study relied on a validated patient-reported questionnaire to capture each patient’s overall symptom experience. We recognize that the symptom patterns may vary by an underlying diagnosis; however, meaningful subgroup comparisons were limited by the uneven distribution of diagnostic categories in our cohort. Our ability to perform detailed subgroup analyses was also limited by the relatively small number of patients who continued to experience symptoms after surgery. In addition, because we did not collect the baseline PROM scores, we were unable to quantify how much the individual symptoms changed over time. Finally, the study was conducted at a single tertiary centre, which may limit the generalizability of the findings to other settings.

Conclusions

Approximately one-fifth of the patients continue to experience symptoms following cholecystectomy for benign gallbladder disease. This phenomenon underscores the necessity for enhanced predictive tools and a more comprehensive understanding of the factors influencing these outcomes. Prolonged symptom duration prior to surgery and post-operative complication appears to correlate with less favourable post-operative results; however, pre-operative ERCP shows no association with symptom persistence, emphasizing the need for refined pre-operative assessments, thereby guiding tailored treatments aimed at alleviating persistent symptoms and enhancing patient quality of life following surgery.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://ales.amegroups.com/article/view/10.21037/ales-2025-1-49/rc

Data Sharing Statement: Available at https://ales.amegroups.com/article/view/10.21037/ales-2025-1-49/dss

Peer Review File: Available at https://ales.amegroups.com/article/view/10.21037/ales-2025-1-49/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ales.amegroups.com/article/view/10.21037/ales-2025-1-49/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia (No. 366/IRB/2022) and informed consent was taken from all the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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