Pediatric cholelithiasis: a comprehensive analysis of clinical characteristics and surgical treatment strategies
Highlight box
Key findings
• The surgical rate of pediatric cholelithiasis is lower than that of adults, and there is still no consensus on the selection of surgical methods.
What is known and what is new?
• The incidence of pediatric cholelithiasis is relatively low, and the etiology is complex. Laparoscopic cholecystectomy (LC) and endoscopic retrograde cholangiopancreatography (ERCP) are safe and feasible procedures for pediatric patients.
• Our study shows that the median age of cholelithiasis patients is presented earlier than reported, which poses a threat to children’s health. Doctors should make a comprehensive diagnosis based on the symptoms, medical history, growth and development status; surgery should not be regarded as the first-line treatment strategy. LC and laparoscopic choledochoscopic cholecystolithotomy are effective for children with gallbladder stones; pediatric ERCP for choledocholithiasis is more dependent on the doctor’s treatment level. These procedures should be performed in compliance with the surgical indications.
What is the implication, and what should change now?
• A comprehensive assessment of the patient’s condition should be made, avoiding treatment delay and unnecessary surgery. Both conservative treatment and minimally invasive surgery have the risk of recurrence. Therefore, identifying the etiology is of utmost significance.
Introduction
Pediatric cholelithiasis refers to the biliary system calculi under various pathological conditions. It is gradually becoming a significant public health challenge, particularly in developed regions. The prevalence is about 0.1–2.0% in pediatric patients (1), but the pathogenesis and therapeutic strategies remain poorly understood. Historical records of pediatric cholelithiasis can be traced back to 1966 (2), while debates have persisted over centuries regarding its etiology, pathology, and optimal treatment. Cholelithiasis is broadly categorized into two types: gallbladder stones and choledocholithiasis (bile duct stones). The incidence has increased significantly in recent years, perhaps attributable to lifestyle modifications and advancements in diagnostic technologies. Current research indicates that the development of cholelithiasis is associated with factors such as obesity, gender, genetics, medication, and primary diseases. However, the demographic characteristics of different cholelithiasis subtypes in Asian pediatric populations, particularly in northern regions, remain inadequately elucidated.
The development of diagnostic techniques for cholelithiasis has been relatively mature, with imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) enabling definitive diagnoses. Despite these advancements, molecular genetic testing remains underutilized in clinical practice. A significant controversy lies in the therapeutic strategy for cholelithiasis. Recent innovations in surgical techniques have expanded therapeutic options and improved procedural efficacy, including minimally invasive approaches such as robot-assisted surgery, endoscopic interventions, and the combination of various applications. However, given the distinct etiological, anatomical, and prognostic differences between pediatric and adult cholelithiasis, directly applying adult guidelines to pediatric patients is inappropriate. Furthermore, therapeutic experience in pediatric populations remains limited, and there is a lack of large-scale clinical studies in Asia to support long-term treatment effects. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-367/rc).
Methods
Study population and data collection
All children clinically diagnosed with cholelithiasis, including gallbladder stones, cholangiolithiasis [common bile duct (CBD) stones and intrahepatic bile duct stones], who were admitted to the Department of Surgery of Tianjin Children’s Hospital between June 2017 and January 2024 and underwent conservative or surgical treatment, were retrospectively included in this study. General data on these pediatric patients were collected, including demographic information such as gender, age, height, and weight, as well as ethnic background. Principal complications and comorbidities associated with cholelithiasis were recorded. Additionally, imaging findings of gallstone features and associated structures, including CBD diameter and portal vein width, were documented.
Patients were divided into three groups based on the anatomical site of the stones: the gallbladder stone group, the cholangiolithiasis group, and the combined group. The body mass index (BMI) of each patient was calculated utilizing the standard formula: BMI = weight (kg)/height (m)2. After BMI calculation, patients were categorized according to the World Health Organization (WHO) Child Growth Standards into four classifications: normal, overweight, obese, and thinness (3). Laboratory indications, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBil), were recorded at two critical time points: preceding surgery and before hospital discharge. These perioperative indicators were subjected to comparative analysis to assess treatment efficacy. Specifically, we have analyzed the basic information of patients undergoing surgery for gallbladder stones, including their age, gender, BMI, imaging features, total inpatient time, etc. Furthermore, all patients who underwent surgical treatment were subjected to telephone follow-up to evaluate the recurrence status of their condition, ensuring a comprehensive assessment of clinical efficacy and long-term prognosis. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Institutional Ethics Committee of Tianjin Children’s Hospital (No. 2022-SYYJCYJ-008). Individual consent for this analysis was waived due to the retrospective nature.
Statistical analysis
Statistical analysis was performed using SPSS 24.0 software. Continuous data were assessed for normality using graphical methods, skewness, kurtosis, or non-parametric tests. Normally distributed data were expressed as mean ± standard deviation, while non-normally distributed data were presented as median (interquartile range). Categorical data were described in rates. For comparisons between groups, non-normally distributed continuous data were analyzed using the Kruskal-Wallis H test, while pairwise comparisons for non-normally distributed data were conducted using the Wilcoxon signed-rank test. Normally distributed data were compared using the t-test. The Bonferroni method was used for multiple comparisons between groups if there were statistical differences between multiple groups. Comparisons of rates between groups were conducted using the χ2 test, corrected χ2 test, or Fisher’s exact probability test, as appropriate. A two-tailed P value less than 0.05 was considered statistically significant.
Results
Demographic characteristics of different types of cholelithiasis
A total of 185 children with cholelithiasis admitted to the department of surgery were reviewed, including 107 patients in the gallstones group, 47 patients in the cholelithiasis group, and 31 patients with both conditions (Table 1). The median age was 7.5 (3.7–11.0) years, and female patients accounted for more than male patients. The height and weight of patients with both conditions were significantly higher than the cholangiolithiasis group according to Bonferroni multiple comparisons (P=0.02 and P=0.03, respectively). For BMI, the results of multiple testing showed that under the test level α=0.05, there was a statistically significant difference in the obese and overweight children between the group of both conditions and the other groups, the proportion was significantly higher than that of the other groups (except thinness in both conditions). There was no statistically significant difference between the other groups.
Table 1
| Characteristics | Overall | Gallstones | Cholangiolithiasis | Both | P value |
|---|---|---|---|---|---|
| Number | 185/185 (100.0) | 107/185 (57.8) | 47/185 (25.4) | 31/185 (16.8) | |
| Gender | 0.42 | ||||
| Male | 77/185 (41.6) | 41/107 (38.3) | 20/47 (42.6) | 16/31 (51.6) | |
| Female | 108/185 (58.4) | 66/107 (61.7) | 27/47 (57.4) | 15/31 (48.4) | |
| Age (years) | 7.5 (3.7, 11.0) | 8.0 (5.0, 11.0) | 4.0 (2.0, 9.0) | 10.0 (3.7, 12.0) | 0.006 |
| Height (cm) | 126.0 (101.0, 150.0) | 133.0 (120.0, 158.0) | 102.0 (89.0, 125.0) | 140.0 (100.0, 157.0) | 0.01 |
| Weight (kg) | 25.0 (15.6, 43.7) | 25.6 (19.5, 45.7) | 15.6 (12.0, 23.5) | 39.7 (16.0, 50.8) | 0.03 |
| BMI | 0.02 | ||||
| Normal | 106/174 (60.9) | 64/99 (64.6) | 27/45 (60.0) | 13/30 (43.3) | |
| Overweight | 18/174 (10.3) | 9/99 (9.1) | 4/45 (8.9) | 5/30 (16.7) | |
| Obesity | 21/174 (12.1) | 10/99 (10.1) | 5/45 (11.1) | 7/30 (23.3) | |
| Thinness | 29/174 (16.7) | 16/99 (16.2) | 9/45 (20.0) | 5/30 (16.7) |
Data are presented as n/N (%) or median (interquartile range). BMI, body mass index.
Imaging diagnostic modalities and characteristics of cholelithiasis in different conditions
All patients were initially diagnosed by B-ultrasound examination. For patients with complex conditions, additional imaging diagnostics should be performed. There was a statistically significant difference in the proportion of MRI and magnetic retrograde cholangiopancreatography (MRCP) examinations in cholelithiasis patients of different groups (P<0.001 and P=0.001, respectively). According to the results of various imaging studies, the calculus’ characteristics were summarized and analyzed. Multiple types of stones accounted for most of cholelithiasis, however, there was no significant difference in the proportion of every group (χ2=13.854, P=0.07). There was a significant difference in CBD width among the three groups (H=24.4, P<0.001). Bonferroni multiple comparisons showed that there was a significant difference in CBD width between the gallbladder stone group and the patients with both conditions group (P=0.004). The width of the latter group was significantly higher than the former group. There was also a significant difference between the gallbladder stone group and the cholangiolithiasis group (P<0.001). The CBD width of the cholangiolithiasis group was significantly higher than that of the gallbladder stone group, and there was no significant difference between the other groups (Table 2).
Table 2
| Clinical diagnosis | Gallstones | Cholangiolithiasis | Both | P value |
|---|---|---|---|---|
| Imaging diagnostic modalities | N=107 | N=47 | N=31 | |
| B-ultrasound | 107 (100.0) | 47 (100.0) | 31 (100.0) | |
| CT | 38 (35.5) | 24 (51.1) | 13 (41.9) | 0.19 |
| Enhanced CT | 2 (1.9) | 2 (4.3) | 1 (3.2) | 0.56 |
| MRI | 5 (4.7) | 12 (25.5) | 1 (3.2) | <0.001 |
| MRCP | 17 (15.9) | 21 (44.7) | 7 (22.6) | 0.001 |
| Imaging features | N=90 | N=15 | Gallbladder (N=20)/ bile duct (N=8) |
0.07 |
| Multiple | 51 (56.7) | 7 (46.7) | 13 (65.0)/3 (37.5) | |
| Sand form | 26 (28.9) | 6 (40.0) | 3 (15.0)/1 (12.5) | |
| Single | 9 (10.0) | 2 (13.3) | 1 (5.0)/4 (50.0) | |
| Gallbladder filled | 4 (4.4) | 0 | 3 (15.0)/0 | |
| Other anatomical structures (mm) | N=90 | N=15 | N=28 | |
| CBD width | 3.0 (2.0, 4.0) | 8.0 (5.2, 9.1) | 5.8 (3.3, 8.2) | <0.001 |
| Portal vein diameter | 7.0 (6.3, 8.0) | 6.5 (5.8, 7.5) | 8.0 (5.0, 8.5) | 0.50 |
| Cyst diameter | – | 45.0 (25.6, 59.5) | –/32.5 (25.5, 39.5) | 0.35 |
Data are presented as median (interquartile range) or n (%). CBD, common bile duct; CT, computed tomography; MRCP, magnetic retrograde cholangiopancreatography; MRI, magnetic resonance imaging.
Symptoms and signs of pediatric cholelithiasis patients who have specific primary diseases
In this study, a total of 39 children had hemolytic diseases, accounting for 21.1% of the total included population. Among them, 32 patients had hereditary spherocytosis (HS). In addition, there was autoimmune hemolytic anemia (AIHA), megaloblastic anemia, Fanconi anemia, and thalassemia, and 1 case in each group, respectively. Among the children with gallstones, 30 (28.0%) had hemolytic disease. In the cholangiolithiasis group, only 2 (1.9%) had hemolytic disease, and 7 (6.5%) had hemolytic disease in patients with both conditions. A total of 21 (21/22 had specific symptoms) children with choledochal cysts (CC), also known as congenital biliary dilatation, accounted for 33.3% of the total included population. Among the children with cholangiolithiasis, 14 (66.7%) had CC. In the gallstones group, only 3 (14.3%) had CC. Among the children with both conditions, 4 (19.0%) had CC. Notably, there were three children with pancreaticobiliary maljunction (PBM), all of whom had bile duct stones, one of whom was diagnosed by MRCP (Figure 1). The other two cases were diagnosed by subsequent endoscopic retrograde cholangiopancreatography (ERCP) treatment. We can confirm that these children had secondary cholelithiasis; however, it is not clear whether the remaining patients were secondary to other factors, because they may have spontaneous remission due to the milder condition.
Because the symptoms and signs of gallstones and cholangiolithiasis often overlap due to complications (such as cholecystitis, cholangitis, etc.) and individual differences in children’s response, clinical guidance is limited. We focused on statistical analysis and comparison between children with specific primary diseases to better identify these conditions while diagnosing cholelithiasis. The results suggest that: of the cholelithiasis patients who had hemolytic disease, 7.7% were asymptomatic. Of the patients who had CC, 66.7% had no obvious signs (Table 3).
Table 3
| Symptoms and signs | Overall | Hemolytic disease | Choledochal cyst | P value |
|---|---|---|---|---|
| Symptoms | 185 | 39 | 21 | |
| Abdominal pain | 151 (81.6) | 22 (56.4) | 17 (81.0) | 0.057 |
| Nausea/vomiting | 105 (56.8) | 10 (25.6) | 13 (61.9) | 0.055 |
| Diarrhea | 7 (3.8) | 0 | 2 (9.5) | 0.12 |
| Jaundice | 54 (29.2) | 29 (74.4) | 1 (4.8) | <0.001 |
| Fever | 24 (13.0) | 6 (15.4) | 1 (4.8) | 0.40 |
| Dizziness/headache/chest tightness/fatigue | 2 (1.1) | 1 (2.6) | 0 | >0.99 |
| No symptom | 6 (3.2) | 3 (7.7) | 0 | 0.55 |
| Sign | ||||
| Abdominal tenderness | ||||
| Overall | 109 (58.9) | 14 (35.9) | 9 (42.9) | 0.60 |
| Right upper quadrant | 55 (29.7) | 5 (12.8) | 4 (19.0) | |
| Epigastric and subxiphoid | 34 (18.4) | 5 (12.8) | 2 (9.5) | |
| Periumbilical | 20 (10.8) | 2 (5.1) | 3 (14.3) | |
| Whole abdomen | 10 (5.4) | 2 (5.1) | 0 | |
| Murphy’s sign (+) | 31 (16.8) | 4 (10.3) | 2 (9.5) | >0.99 |
| Splenomegaly | 25 (13.5) | 23 (59.0) | 0 | <0.001 |
| No obvious sign | 65 (35.1) | 9 (23.1) | 14 (66.7) | 0.001 |
Data are presented as n (%).
The surgical indications for pediatric cholelithiasis
In our study, most patients received a conservative treatment after comprehensive assessments, then had regular outpatient reviews. The surgical indication was strictly followed, not only one specific index, but their symptom, imaging features, anatomical structure and function of the biliary system, primary diseases, site/shape of the stone. Moreover, patients’ advice was fully considered in children whose surgical indications were not completely met. For children with conservative treatment, regular outpatient reviews were performed. Patients with clinical symptom resolution and no imaging abnormalities after surgery were considered cured, but still received regular follow-up.
Gallbladder-preserving surgery could be performed when (I) clinical condition deteriorated, such as aggravated gallbladder swelling, and pain could not be controlled by medicine; (II) calcified stones that could be visualized on X-ray, especially multiple stones and gallbladder filled stones; (III) the gallbladder morphology and function were normal. The gallbladder should be resected when it met the following criteria: (I) acute/chronic severe cholecystitis that caused severe purulent exudation, atrophy, necrosis, and perforation of the gallbladder wall; (II) gallbladder malformation. Pediatric cholangiolithiasis should undergo surgery when: (I) PBM; (II) irreversible dilatation of the distal bile duct caused by obstruction; endoscopic intervention could be performed when (I) clinical symptoms deteriorated and could not be controlled, the condition was too severe to tolerate surgery; (II) stone obstruction in the biliary tract without structural damage. When there were specific primary diseases, such as hemolytic disease or CC, we focused on treating their etiology. The diameter of stones and bile duct dilation should be evaluated according to the patient’s physical size. Finally, there were 29 patients with gallbladder stone (15.7%) who underwent surgery, and 44 patients with cholangiolithiasis (23.8%) underwent surgery, although their conditions may affect both sites (Figure 2).
Surgical treatments for pediatric gallbladder stones and effect analysis
Retrospective analysis was performed on patients with gallbladder stones who underwent surgical treatment. 8 children underwent LC (cholecystectomy group), and 7 children underwent laparoscopic choledochoscopic cholecystolithotomy (gallbladder-preserving group) (Table 4). In the cholecystectomy group, 4 cases (50.0%) were diagnosed as chronic atrophic cholecystitis, and 1 patient (12.5%) had duplication of the gallbladder (Figure 3). In the gallbladder-preserving group, 3 cases (42.9%) were diagnosed as acute cholecystitis, intrahepatic and extrahepatic bile duct dilatation accounted for 14.3%. ALT and AST in the cholecystectomy group were significantly increased shortly after the operation. However, ALP decreased significantly after gallbladder-preserving surgery; all patients recovered well after the operation (Table 5). The postoperative follow-up time was 43.8±33.0 months in the cholecystectomy group and 23.1±12.3 months in the gallbladder-preserving group, there was no recurrence (Table 6).
Table 4
| Characteristics | Laparoscopic cholecystectomy (N=8) | Laparoscopic choledochoscopic cholecystolithotomy (N=7) | P value |
|---|---|---|---|
| Age (years) | 12.0±1.85 | 9.0±3.37 | 0.07 |
| Gender (M/F) | 2/6 | 3/4 | – |
| BMI | – | ||
| Normal | 2 (25.0) | 5 (71.4) | |
| Overweight | 2 (25.0) | 1 (14.3) | |
| Obesity | 2 (25.0) | 1 (14.3) | |
| Thinness | 1 (12.5) | – | |
| Diagnosis | Chronic atrophic cholecystitis: 4 (50.0); gangrenous cholecystitis: 1 (12.5); acute cholecystitis: 2 (25.0); biliary dilatation with calculi, cholangitis: 1 (12.5); gallbladder duplication 1: (12.5) |
Acute cholecystitis: 3 (42.9); choledocholithiasis: 1 (14.3); dilation of intrahepatic and extrahepatic bile ducts: 1 (14.3) |
– |
| Imaging | Multiple: 4 (50.0); single: 2 (25.0) | Multiple: 2 (28.6); gallbladder filled: 2 (28.6); sand form: 2 (28.6) |
– |
Data are presented as mean ± standard deviation or n (%). BMI, body mass index; F, female; M, male.
Table 5
| Group | Laboratory indicators | Pre-operation | Post-operation | Wilcoxon signed rank sum test | |
|---|---|---|---|---|---|
| Z-value | P value | ||||
| Laparoscopic cholecystectomy | ALT (U/L) | 19.0 (10.5, 24.5) | 28.5 (19.3, 34.8) | −2.03 | 0.04 |
| AST (U/L) | 20.5 (12.8, 36.5) | 33.0 (19.5, 40.5) | −2.53 | 0.01 | |
| ALP (U/L) | 127.5 (112.3, 264.0) | 117.5 (98.8, 283.0) | −1.05 | 0.29 | |
| GGT (U/L) | 11.5 (10.3, 35.5) | 13.5 (9.3, 47.0) | −0.21 | 0.83 | |
| TBil (μmol/L) | 9.9 (4.5, 14.0) | 10.7 (6.4, 12.0) | −0.56 | 0.58 | |
| Laparoscopic choledochoscopic cholecystolithotomy |
ALT (U/L) | 10.0 (8.0, 68.0) | 18.0 (9.0, 28.0) | −0.42 | 0.67 |
| AST (U/L) | 23.0 (18.0, 29.0) | 24.0 (16.0, 34.0) | −0.73 | 0.46 | |
| ALP (U/L) | 252.0 (149.0, 267.0) | 178.0 (137.0, 203.0) | −2.37 | 0.02 | |
| GGT (U/L) | 14.0 (3.0, 169.0) | 31.0 (9.0, 90.0) | −1.35 | 0.18 | |
| TBil (μmol/L) | 6.7 (4.5, 9.3) | 7.6 (5.7, 11.8) | −0.34 | 0.74 | |
Data are presented as median (interquartile range). ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; TBil, total bilirubin.
Table 6
| Postoperative conditions | Laparoscopic cholecystectomy (n=8) | Laparoscopic choledochoscopic cholecystolithotomy (n=7) | P value |
|---|---|---|---|
| Postoperative fasting time (days) | 3.0 (2.0, 3.0) | 4.0 (3.0, 4.0) | 0.05 |
| Postoperative inpatient (days) | 7.0±1.15 | 8.71±1.38 | 0.03 |
| Total inpatient (days) | 12.6±3.3 | 13.4±4.0 | 0.67 |
| Follow up (months) | 43.8±33.0 | 23.1±12.3 | 0.20 |
| Recurrence | 0 | 1 (14.3) | 0.47 |
Data are presented as median (interquartile range), mean ± standard deviation or n (%).
The clinical data of 11 patients with hemolytic disease were analyzed. Splenectomy was performed in the majority of patients (45.5%), followed by splenectomy + cholecystectomy (27.3%) and laparoscopic splenectomy + cholecystolithotomy (18.2%). The average postoperative fasting time was 3.4–9.0 days, the postoperative hospital stay was 11.8–13.7 days, and the total length of hospital stay was 15.6–28.0 days. After the operation, the change of platelet was observed, dipyridamole or aspirin was added when the platelet increased to 1,000×109/L, and the highest recorded was 2,201×109/L. No complications occurred after drug treatment. Six patients were followed up for 73.0 (58.5, 81.8) months, and no recurrence of cholelithiasis was found.
Surgical treatments for pediatric cholangiolithiasis and effect analysis
The basic information of children with cholangiolithiasis treated with ERCP was retrospectively analyzed (12/16 patients with complete clinical data), accounting for 20.5% of patients with bile duct stone. There were seven males and five females, aged 3.7–16.0 years, with a median age of 11.5 (5.4, 13.5) years. Among them, two were obese, two were overweight, and one was thinness, the others were normal. There were ten cases of abdominal pain, two cases of jaundice, and two cases were asymptomatic. There were six cases of choledocholithiasis and six cases of choledocholithiasis accompanied by gallstones (Table 7).
Table 7
| Patient No. | Main symptoms | Medical history | Main diagnosis | Other diagnosis |
|---|---|---|---|---|
| 1 | Abdominal pain, nausea and vomiting | Performed right testicular torsion correction surgery 1 year before | Choledocholithiasis, cholangitis, cholecystitis, bile duct dilatation, biliary pancreatitis | Liver function insufficiency, hyperbilirubinemia, hyperlipidemia |
| 2 | Abdominal pain, jaundice | Choledocholithiasis, gallstones, cholangitis | ||
| 3 | Abdominal pain | Choledocholithiasis | Liver function insufficiency, hypothyroidism, sinus bradycardia | |
| 4 | Abdominal pain | Performed splenectomy 21 days before | Choledocholithiasis, gallstones | Hereditary spherocytosis |
| 5 | Asymptomatic (physical examination reveals choledocholithiasis) | Performed liver transplantation 2 years before | Choledocholithiasis, liver transplantation status | |
| Performed ERCP 1.5 years before | ||||
| Performed biliary exploration + bile duct anastomosis 3 months before | ||||
| 6 | Asymptomatic (physical examination reveals abnormal liver function) | Performed liver transplantation 3 years before | Choledocholithiasis, acute pancreatitis | Acute rejection after liver transplantation, hypoproteinemia, electrolyte metabolism disorder |
| 7 | Abdominal pain, jaundice | Choledocholithiasis, cholecystolithiasis, intrahepatic and extrahepatic bile ducts dilatation | Fatty liver disease, splenomegaly, hereditary spherocytosis | |
| 8 | Abdominal pain | Performed cholecystectomy + splenectomy 1 month before | Choledocholithiasis | Hereditary spherocytosis |
| 9 | Abdominal pain | Grandmother suffered from gallstones | Choledocholithiasis, cholecystolithiasis, cholecystitis, common bile duct dilatation, intrahepatic and extrahepatic bile duct dilatation, hilar bile duct constriction | |
| 10 | Abdominal pain | Choledocholithiasis, common bile duct dilatation, abnormal biliopancreatic junction, intrahepatic bile duct dilatation | ||
| 11 | Abdominal pain | Choledocholithiasis, gallstones, cholangitis | Electrolyte metabolism disorder | |
| 12 | Abdominal pain | Choledocholithiasis, common bile duct dilatation, gallstones, cholecystitis | Abnormal liver function, small diverticulum of the descending duodenum |
ERCP, retrograde cholangiopancreatography.
All patients were under general anesthesia and left lateral position, endoscope was inserted through the mouth to the opening of duodenum papilla. The papilla was cut 0.2 cm by arcuate knife in case 1, 12, the papilla was cut 0.2 cm with arcuate knife and dilated to 0.6 cm by balloon in case 3. In cases 5 and 6, the papillae were cut 0.1 cm with arcuate knife and the balloon expanded it to 0.6 cm. In cases 1, 2, 3, 4, 6, 7, 11, 12, stone removal basket and stone removal balloon were used to drag the stones. In cases 3 and 4, a large amount of debris-like stones was removed; in case 5 and 8, massive stones were removed by using a stone extraction endoscopic basket. In case 10, PBM was diagnosed during the operation. An endoscopic nasobiliary drainage (ENBD) catheter was indwelled for postoperative drainage. No special conditions occurred during the operation.
The changes in amylase were closely monitored after the operation. Compared with those indicators before treatment, they showed a trend of improvement (Table 8). Three patients developed pancreatitis after the operation. No tumor cells were found in the case, which was performed by biliary brushing cytology. One patient underwent CC resection 16 days after ERCP. One patient developed cholecystitis and underwent laparoscopic choledochoscope cholecystolithotomy 1 month after ERCP. All patients completed ERCP treatment without complications such as bleeding and perforation. The fasting time after ERCP was 2.0 (1.0, 3.8) days, the ENBD extraction time was 3.0 (3.0, 5.8) days, and the average postoperative hospital stay was 5.6±2.2 days. Two cases recurred at 48 and 3 months after ERCP, respectively.
Table 8
| Laboratory indicators | Pre-operation | Post-operation | Wilcoxon signed rank sum test | |
|---|---|---|---|---|
| Z-value | P value | |||
| ALT (U/L) | 153.8 (93.3, 219.2) | 55.5 (29.1, 115.2) | −2.31 | 0.02 |
| AST (U/L) | 80.8 (40.1, 102.6) | 30.0 (28.6, 64.9) | −1.69 | 0.10 |
| ALP (U/L) | 324.0 (137.8, 485.0) | 189.0 (110.0, 348.5) | −2.22 | 0.02 |
| GGT (U/L) | 185.0 (73.6, 270.3) | 100.0 (38.0, 142.0) | −2.05 | 0.04 |
| TBil (μmol/L) | 39.1 (13.6, 39.1) | 14.2 (11.5, 58.8) | −0.53 | 0.64 |
| DBil (μmol/L) | 18.0 (2.4, 69.6) | 8.2 (4.4, 37.1) | −0.98 | 0.37 |
| Pancreatic AMY (μmol/L) | 25.0 (18.5, 62.0) | 54.8 (40.7, 341.7) | −1.51 | 0.15 |
Data are presented as median (interquartile range). ALP, alkaline phosphatase; ALT, alanine aminotransferase; AMY, amylase; AST, aspartate aminotransferase; DBil, direct bilirubin; ERCP, retrograde cholangiopancreatography; GGT, gamma-glutamyl transferase; TBil, total bilirubin.
We briefly analyzed the clinical data of 22 choledocholithiasis with CC. Among them, CC resection, cholecystectomy, Roux-en-Y hepaticojejunostomy were performed in the majority (21.8%) (5 cases were operated by laparoscopy, and the other were operated by laparotomy), CBD lithotomy and T-tube drainage were performed in 2 cases (2.6%). There was no recurrence of cholelithiasis during the follow-up, but 2 cases had occasional abdominal pain and 1 case had occasional constipation.
Discussion
Pediatric cholelithiasis is mainly classified by its anatomical site and component. In this study, we adopted the anatomical classification to associate with subsequent therapeutic strategies, which is also a widespread classification method in clinical studies. There are three types of stone concerning their components: cholesterol, pigment, and calcium carbonate stone. The median age of cholelithiasis patients in our cohort was 7.5 (3.7–11.0) years, significantly younger than prior studies (10 years) (4,5). Patients with cholangiolithiasis presented at an earlier age, possibly due to anatomical abnormalities that accelerate stone formation and manifest typical symptoms, which leads to earlier diagnosis. Previous studies indicate a higher incidence of pediatric cholelithiasis in females than males (6,7), mainly caused by the secretion of estrogen, consistent with our findings. Oral contraceptive leads to higher odds for gallstones: OR 2.00% (95% CI: 1.66–2.40%) in girls (8), it may also be a pathogenic factor. Hormone level fluctuation may induce bile cholesterol supersaturation, increasing the morbidity in adolescence (9), also causing biliary motility disorders and gallbladder dysfunction. While most cases were reported in infancy and post-adolescence, our study found the highest prevalence in preschool- and school-aged children (57.8%), potentially linked to accelerated growth, unhealthy diets, overnutrition, and rising precocious puberty rates.
The prevalence of obesity in children and adolescents has risen to 8.5% (95% CI: 8.2–8.8%), which is a huge problem in modern society (10). Obesity and high-nutrient diets are significant contributors to cholelithiasis pathogenesis. Additional etiological factors, such as congenital anatomical abnormalities, prior surgical interventions, improper use of cephalosporin antibiotics, and prolonged parenteral nutrition, have also contributed to stone formation. Our study found that most patients had normal BMI, and 16.7% were classified as thinness, highlighting the need to consider cholelithiasis in normal and malnourished children. Genetic factors, particularly ABCB4 mutations, are mostly reported in unexplained recurrent cholesterol stones. Other candidate genes (e.g., ABCG5/G8, NPC1L1, ATP8B1) have also been identified (11,12). Amino acid substitutions due to single-nucleotide polymorphisms also contribute to pediatric cholelithiasis (1). For children with recurrent cholelithiasis, primary disease and family history should be taken into account to make a comprehensive diagnosis.
Abdominal pain was the most common symptom (81.6%), while asymptomatic patients accounted for 3.2% in our study. About 50% of abdominal pain caused by sand-form stones resolves spontaneously, though 10–15% develop symptoms within 3 years (13). These sand-form stones, also known as biliary/gallbladder sludge, are the common type of pediatric cholelithiasis. Although it is classified as a kind of gallstone, we are prone to consider it as “pseudolithiasis”, which is often caused by the use of Ceftriaxone (14). For the diagnosis of suspected choledocholithiasis, US has a 17% false-negative rate compared with MRI (15). MRI is more sensitive and can find the stone in distal bile duct, which could be obstructed by bowel gas. MRI and MRCP utilization were higher in the choledocholithiasis group (25.5% and 44.7%, respectively) than in other groups, indicating the potential underdiagnosis of cholangiolithiasis in patients diagnosed as gallbladder stones. Bile duct dilation was observed in 34.1% of children, with 33.3% attributed to congenital bile duct dilation (also called CC). The critical CBD diameter values have been established: ≤2.26 mm for infants <1 year, 2.99 mm for 4-year-old, 3.03 mm for 7-year-old, and 4.10 mm for 11-year-old (16). For other types of bile duct dilation, particularly CBD dilation, severity should be assessed according to the patient’s growth and developmental status.
Pediatric cholelithiasis therapy aims to achieve long-term symptom relief and fewer complications. We focus on surgical treatment, particularly those with multiple, larger gallstones, which may cause biliary obstruction, secondary bile duct dilation, and intrahepatic cholestasis. There are some differences between our treatment and the existing adult guidelines from the UK, Germany, Denmark, China, and Japan (17-21). For asymptomatic stones, we are prone to perform observational treatment for most children, while adult patients are usually considered the risk of gallbladder cancer (such as the diameter of the stone and the thickness of the gallbladder wall) to receive surgery. Children with symptomatic gallstones initially receive conservative treatment, unlike immediate surgery recommended for adults, LC is only reserved for refractory cases. In terms of surgical methods, gallbladder-preserving surgery is not recommended in the adult guidelines, while we have selected children to perform laparoscopic choledochoscopic cholecystolithotomy. For patients with severe acute cholecystitis, timely surgery and early gallbladder drainage, such as percutaneous transhepatic gallbladder drainage (PTGBD), is recommended for adult patients after systemic antibiotics treatment, while these procedures are hard to tolerate in children.
LC is the gold standard operation for symptomatic pediatric cholelithiasis. LC should be performed when there is gallbladder malformation, severe purulent exudation, atrophy, necrosis, and perforation of the gallbladder wall. Short-term increases in ALT and AST after cholecystectomy may be caused by bile storage capacity impairment, bile circulation balance disruption, and digestive function disorder. In our institution, we also fully evaluate the possibility of preserving the gallbladder, when its structure and function are normal, but symptoms deteriorate which cannot be controlled by medicine, and the stone won’t dissolve spontaneously as estimated. The choledochoscope or duodenoscope has been used in combination with laparoscopic surgery to remove bile duct stones. For younger patients, using ureteroscope instead of choledochoscope also achieves good results. Endoscopic minimally invasive cholecystolithotomy in our study has a recurrence of 14.3%, and still needs a longer observation and follow-up. Laparoscopic robotic-assisted cholecystectomy has been reported in pediatric patients, which has less pain and bleeding. Meanwhile, they have small scars and faster postoperative recovery, over 50% of robotic-assisted cholecystectomies were performed in symptomatic children (22). While considering the strict indication for cholecystectomy and small sample size, the price-performance ratio for patients is a hindrance to the application.
Cholangiolithiasis can be divided into intrahepatic bile duct stones and extrahepatic bile duct stones. Most children suffered from the latter situation derived from gallbladder stones. The majority of intrahepatic bile duct stones are asymptomatic and thus receive conservative treatment. For severe symptoms, bile duct incision, choledochojejunostomy, or hepatectomy could be performed. Symptomatic extrahepatic bile duct stones should be intervened in time, otherwise, secondary obstruction will affect bile drainage and cause cholangitis. Laparoscopic common bile duct exploration (LCBDE), choledocholithotomy, and choledochojejunostomy could be performed. In children with CC, stone extraction should be performed incidentally with Roux-en-Y hepaticojejunostomy. Before surgery, the structure of the aberrant ductal system must be visualized by MRCP/ERCP, avoiding damage to these structures. Endoscopic lithotomy combined with surgical cholecystectomy is recommended in adult cholangiolithiasis, while we have already performed endoscopy in children, no patients have received a combination therapy at the same time. Notably, a clinical practice guideline for the treatment of pediatric choledocholithiasis has been published recently, which recommends a surgery-first (SF) two-stage therapy. This guideline empowers pediatric surgeons to prioritize LC and LCBDE, and to minimize delays of ERCP/MRCP (23). It remains uncertain whether this radical approach will be accepted by parents. We considered that surgery is only performed when necessary.
ERCP is a unique and complex technique, pediatric ERCP has been used since the mid-1970s, and it has been reported that nearly 50% of pediatric ERCP is used for the treatment of cholelithiasis, especially for CBD stones (24). In younger children, the obstruction is typically less rigid due to the predominantly sand-like or debris-like stones, which can often be managed through endoscopic extraction. This approach reduces surgical trauma and may serve as a transitional therapy. For example, biliary obstruction is often caused by protein embolism in CC, and fatty acid calcium stones are rare (25). Most of the stones are composed of a sand-form mixture of bilirubin calcium and cholesterol crystals in viscous bile, which contains high concentrations of protein (26). ERCP can clearly show the expansion range of CC, find out whether there is PBM, and remove the protein plug, to clarify the anatomical structure for subsequent surgical treatment (27). Post-ERCP pancreatitis (PEP) is the most common complication, and it is more likely to occur in children with a history of chronic pancreatitis and pancreatic duct intubation. However, it is difficult to evaluate the clinical manifestation in most children, especially infants, so the level of pancreatic enzymes is routinely monitored after the operation.
In addition to patients who received surgery, this study reviews the clinical characteristics of all patients admitted to a children’s medical center. The single-center retrospective design is an unavoidable limitation. We implemented stringent inclusion and classification criteria to enhance data reliability. Pediatric cholelithiasis has various etiologies and clinical manifestations, with multiple surgical options and evolving techniques. Therefore, it is challenging to evaluate the efficacy of a single operation (e.g., gallbladder-preserving surgery, LC, ERCP) in large cohorts. A comprehensive evaluation is crucial, and the parents’ opinion should also be considered. The improvement of surgical skills, the selection of surgical methods, and the accurate time of surgery are key factors for surgeons to improve in limited patients. Pediatric cholelithiasis involves a dynamic progression between gallbladder and bile duct stones, necessitating long-term clinical monitoring. Current surgical indications remain uncertain due to limited experience, we will carry out research depending on the multi-center platform of pediatric surgery, further enhancing the reliability of our results.
Conclusions
Our study shows that the age of onset for pediatric cholelithiasis appears to be earlier than previously reported. Notably, patients with normal BMI still constituted a significant proportion of cases, while obesity was a predominant risk factor. Hence, we should pay more attention to younger patients and those who have normal body weight. Conservative observation should be the first-line treatment, unless the symptoms are severe and uncontrolled, or structural damage, congenital malformation, specific primary disease is found. Endoscopy is becoming a valuable therapeutic modality, which effectively addresses biliary obstruction caused by stones, resolves secondary bile duct dilatation, and improves liver function. These findings highlight the importance of individualized therapeutic strategies in pediatric cholelithiasis.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-367/rc
Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-367/dss
Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-367/prf
Funding: This study was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-367/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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Institutional Ethics Committee of Tianjin Children’s Hospital (No. 2022-SYYJCYJ-008). Individual consent for this analysis was waived due to the retrospective nature.
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/.
References
- Svensson J, Makin E. Gallstone disease in children. Semin Pediatr Surg 2012;21:255-65. [Crossref] [PubMed]
- Kirtley JA Jr, Holcomb GW Jr. Surgical management of diseases of the gallbladder and common duct in children and adolescents. Am J Surg 1966;111:39-46. [Crossref] [PubMed]
- World Health Organization, WHO child growth standards: Body mass index-for-age. Available online: https://www.who.int/toolkits/child-growth-standards/standards/body-mass-index-for-age-bmi-for-age; https://www.who.int/tools/growth-reference-data-for-5to19-years/indicators/bmi-for-age
- Wang HH, Liu M, Clegg DJ, et al. New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochim Biophys Acta 2009;1791:1037-47. [Crossref] [PubMed]
- Wong MCY, Incerti F, Avanzini S, et al. Cholelithiasis management in a third-level pediatric center: case series and literature review. Updates Surg 2022;74:963-8. [Crossref] [PubMed]
- Wesdorp I, Bosman D, de Graaff A, et al. Clinical presentations and predisposing factors of cholelithiasis and sludge in children. J Pediatr Gastroenterol Nutr 2000;31:411-7. [Crossref] [PubMed]
- Zdanowicz K, Daniluk J, Lebensztejn DM, et al. The Etiology of Cholelithiasis in Children and Adolescents-A Literature Review. Int J Mol Sci 2022;23:13376. [Crossref] [PubMed]
- Koebnick C, Smith N, Black MH, et al. Pediatric obesity and gallstone disease. J Pediatr Gastroenterol Nutr 2012;55:328-33. [Crossref] [PubMed]
- Nakken KE, Labori KJ, Rødningen OK, et al. ABCB4 sequence variations in young adults with cholesterol gallstone disease. Liver Int 2009;29:743-7. [Crossref] [PubMed]
- Zhang X, Liu J, Ni Y, et al. Global Prevalence of Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analysis. JAMA Pediatr 2024;178:800-13. [Crossref] [PubMed]
- Yonem O, Bayraktar Y. Clinical characteristics of Caroli's syndrome. World J Gastroenterol 2007;13:1934-7. [Crossref] [PubMed]
- Vitale G, Gitto S, Raimondi F, et al. Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing. J Gastroenterol 2018;53:945-58. [Crossref] [PubMed]
- Wang HH, Portincasa P, Liu M, et al. Similarities and differences between biliary sludge and microlithiasis: Their clinical and pathophysiological significances. Liver Res 2018;2:186-99. [Crossref] [PubMed]
- Biner B, Oner N, Celtik C, et al. Ceftriaxone-associated biliary pseudolithiasis in children. J Clin Ultrasound 2006;34:217-22. [Crossref] [PubMed]
- Stock MR, Fine RO, Rivas Y, et al. Magnetic resonance imaging following the demonstration of a normal common bile duct on ultrasound in children with suspected choledocholithiasis: what is the benefit? Pediatr Radiol 2023;53:358-66. [Crossref] [PubMed]
- Zhang Y, Wang XL, Li SX, et al. Ultrasonographic dimensions of the common bile duct in Chinese children: results of 343 cases. J Pediatr Surg 2013;48:1892-6. [Crossref] [PubMed]
- Warttig S, Ward S, Rogers G, et al. Diagnosis and management of gallstone disease: summary of NICE guidance. BMJ 2014;349:g6241. [Crossref] [PubMed]
- Gutt C, Jenssen C, Barreiros AP, et al. Updated S3-Guideline for Prophylaxis, Diagnosis and Treatment of Gallstones. German Society for Digestive and Metabolic Diseases (DGVS) and German Society for Surgery of the Alimentary Tract (DGAV) - AWMF Registry 021/008. Z Gastroenterol 2018;56:912-66. [Crossref] [PubMed]
- Shabanzadeh DM, Christensen DW, Ewertsen C, et al. National clinical practice guidelines for the treatment of symptomatic gallstone disease: 2021 recommendations from the Danish Surgical Society. Scand J Surg 2022;111:11-30. [Crossref] [PubMed]
- Hepatobiliary CRHAPancreatic Surgery Professional Committee. National Health Commission Expert Committee of the Public Welfare Industry Research Special Project. Guidelines for minimally invasive surgery for hepatolithiasis (2019 edition). Chinese Journal of Digestive Surgery 2019;18:407-13.
- Fujita N, Yasuda I, Endo I, et al. Evidence-based clinical practice guidelines for cholelithiasis 2021. J Gastroenterol 2023;58:801-33. [Crossref] [PubMed]
- Raymond SL, Sharafeddin F, Sacks MA, et al. Establishment of a successful robotic pediatric general surgery practice. J Robot Surg 2023;17:2427-33. [Crossref] [PubMed]
- Achey MA, Sims JK, Busing J, et al. Shifting the pediatric choledocholithiasis paradigm: Development of a surgery-first clinical practice guideline at a tertiary children's hospital. Semin Pediatr Surg 2025;34:151496. [Crossref] [PubMed]
- Barakat MT, Cholankeril G, Gugig R, et al. Nationwide Evolution of Pediatric Endoscopic Retrograde Cholangiopancreatography Indications, Utilization, and Readmissions over Time. J Pediatr 2021;232:159-165.e1. [Crossref] [PubMed]
- Tsuchiya H, Kaneko K, Itoh A, et al. Endoscopic biliary drainage for children with persistent or exacerbated symptoms of choledochal cysts. J Hepatobiliary Pancreat Sci 2013;20:303-6. [Crossref] [PubMed]
- Issa H, Al-Haddad A, Al-Salem AH. Diagnostic and therapeutic ERCP in the pediatric age group. Pediatr Surg Int 2007;23:111-6. [Crossref] [PubMed]
- Zeng JQ, Deng ZH, Yang KH, et al. Endoscopic retrograde cholangiopancreatography in children with symptomatic pancreaticobiliary maljunction: A retrospective multicenter study. World J Gastroenterol 2019;25:6107-15. [Crossref] [PubMed]

