Pediatric acute cholecystitis: Risk factors and outcomes

Abstract

BACKGROUND

Pediatric acute cholecystitis is a growing concern due to rising childhood obesity rates and associated metabolic abnormalities.

AIM

To identify demographic and clinical risk factors, evaluate surgical outcomes, and analyze the impact of complications on hospitalization in pediatric patients undergoing cholecystectomy.

METHODS

A retrospective study was conducted on 12750 pediatric patients who underwent cholecystectomies in 2022. Data were collected from a de-identified National Surgical Quality Improvement Program database, including age, gender, race, body mass index (BMI) status, clinical presentation, complications, and treatment details. Risk factors were assessed using logistic regression, and Kaplan-Meier analysis was used to evaluate postoperative readmission rates. Descriptive statistics explored demographic patterns and surgical outcomes.

RESULTS

Out of 12750 pediatric patients, the mean age was 12.8 years, with a median of 13.0 years. Gender distribution included 74.8% females and 25.2% males. Obesity (BMI ≥ 30 kg/m²) was observed in 36.3% of cases, and overweight (BMI: 25-29.9 kg/m²) in 58.2%. 1232 (9.6%) had a hemolytic disorder. 20% presented with elevated bilirubin levels. Laparoscopic cholecystectomy alone was performed in 84%, while cholangiogram and ductal interventions were performed in 16%. Complication rates included gallbladder perforation (8%), biliary abscess formation (5%), and sepsis (2%). Early cholecystectomy (< 2 days post-diagnosis) was associated with reduced hospital stays (median 1.0 day) and lower readmission rates (5%) compared to delayed surgery (> 5 days; median 3.0 days, readmission rate 12%). Approximately 33.5% of patients were identified as Hispanic, highlighting potential disparities in healthcare access.

CONCLUSION

Pediatric acute cholecystitis is an emerging public health concern linked to rising obesity rates. Early surgical intervention minimizes complications and reduces hospitalization durations. Pediatric-specific adaptations in the Tokyo Guidelines 2018 may be necessary to account for age-related differences in clinical presentation and facilitate accurate diagnosis. Addressing racial disparities and targeted prevention strategies is critical for optimizing outcomes.

Key Words: Pediatric cholecystitis; Childhood obesity; Gallstones; Laparoscopic cholecystectomy; Tokyo Guidelines 2018; Hemolytic disease; Global health

Core Tip: The increase in incidence of cholecystitis in the pediatric age group parallels the global increase in childhood obesity. While the Tokyo Guidelines 2018 are widely adopted in adult surgical practice, their criteria are based on physiologic and anatomic assumptions that may not directly apply to children. This manuscript aims to contextualize pediatric acute cholecystitis as a distinct clinical entity with unique etiologies, risk factors, and outcomes. It evaluates the predictive value of obesity and hemolytic diseases and describes trends in biliary interventions such as endoscopic retrograde cholangiopancreatography.

INTRODUCTION

Acute cholecystitis is a well-characterized inflammatory disease of the gallbladder, most often resulting from obstruction of the cystic duct due to gallstones[1]. Traditionally considered a disease of adult populations, particularly middle-aged women with the classic profile of “fat, female, fertile, and forty”, the epidemiology of cholecystitis has undergone a notable transformation[2]. This shift is most starkly observed in pediatric surgical practice, where adolescent patients, particularly girls aged 13 to 17, are now presenting with symptomatic gallbladder disease. This new trend is no longer anecdotal. It is reflected in national data, including our review of 12750 pediatric cholecystectomy cases from 2022, where nearly 95% of patients fell into the overweight or obese category[3]. The age distribution of affected children, with modal ages clustering around puberty, demands clinical reconsideration of diagnostic suspicion and management protocols. This rise parallels the global increase in childhood obesity. The Centers for Disease Control and Prevention (CDC) reports that over 19% of United States children and adolescents are obese[4], with international rates increasing due to dietary and lifestyle shifts[5]. In pediatric patients, obesity leads to cholesterol supersaturation of bile, gallbladder hypomotility, and chronic low-grade inflammatory conditions that predispose children to cholelithiasis and its complications[5,6].

Beyond epidemiology, this trend also challenges traditional diagnostic tools, particularly the Tokyo Guidelines 2018 (TG18), which define and stratify severity in acute cholecystitis[7]. While TG18 is widely adopted in adult surgical practice, its criteria are based on physiologic and anatomic assumptions that may not directly apply to children. This manuscript aims to contextualize pediatric acute cholecystitis as a distinct clinical entity with unique etiologies, risk factors, and outcomes. It evaluates the predictive value of obesity and hemolytic diseases, describes trends in biliary interventions such as endoscopic retrograde cholangiopancreatography (ERCP)[8], and proposes adaptations to current clinical guidelines to improve pediatric outcomes.

MATERIALS AND METHODS

This retrospective study evaluated 12750 pediatric patients diagnosed with acute cholecystitis who underwent cholecystectomy between January 2022 and December 2022. Data were extracted from a publicly available, Health Information Portability Act-compatible, multi-institutional pediatric surgical database (National Surgical Quality Improvement Program) comprising tertiary children’s hospitals across the United States. This precluded the need for Institutional Review Board Approval. All centers reporting to this database have independent data collectors who maintain robust data quality and accuracy, thereby ensuring privacy, mitigating bias, and preventing discrimination, while allowing for research and meaningful interpretation of the large data. Inclusion criteria included patients under the age of 18 with an International Classification of Diseases, Tenth Revision diagnosis of acute cholecystitis who underwent either laparoscopic or open cholecystectomy. Exclusion criteria included patients over 18, those with missing data, and those who underwent abdominal surgery for non-biliary indications.

Demographic data collected included age, sex, race, and Hispanic ethnicity. Clinical variables included body mass index (BMI), white blood cell (WBC) count, total bilirubin, and documented presence of hemolytic disease (e.g., hereditary spherocytosis, sickle cell disease). BMI was stratified using CDC age- and sex-specific percentiles: Normal (5^th-84^th percentile), overweight (85^th-94^th percentile), and obese (≥ 95^th percentile). Surgical variables included the type of cholecystectomy (laparoscopic vs open), use of intraoperative cholangiography, bile duct exploration, and use of ERCP. The timing of surgical intervention was categorized as early (≤ 2 days from admission) or delayed (> 2 days). Postoperative outcomes included length of stay, discharge timing, readmission within 30 days, and documented complications (e.g., gallbladder perforation, biliary abscess, bile leak, or sepsis).

Laboratory values were dichotomized as normal or elevated based on standard pediatric reference ranges. WBC counts greater than 11000/mm³ and total bilirubin greater than 1.2 mg/dL were considered elevated, with bilirubin further classified into mild (1.3-3.0 mg/dL), moderate (3.1-5.0 mg/dL), and severe (> 5.0 mg/dL) elevations. Descriptive statistics were used to summarize demographic and clinical data. Logistic regression models were used to evaluate the association between obesity, laboratory abnormalities, and postoperative complications. Odds ratios with 95% confidence intervals were calculated to assess statistical significance. Subgroup analyses were performed for patients with hemolytic disorders and those requiring advanced biliary intervention. A Kaplan-Meier survival analysis was conducted to compare time to discharge between early and delayed surgery cohorts, with log-rank tests used to assess differences in survival distributions. Statistical significance was defined as P < 0.05. This methodology was designed to identify trends in disease severity, timing, and surgical outcomes, and to assess the appropriateness of current guidelines, specifically the TG18, in pediatric populations. Additionally, this study aimed to evaluate practice variation across centers and identify modifiable factors influencing outcomes, such as the timing of surgery and the availability of ERCP or pediatric gastroenterology consultation.

RESULTS

The analysis of 12750 pediatric cholecystectomy cases revealed several important trends in demographics, clinical severity, and outcomes. The mean age was 12.8 years, with a median of 13 and a modal age of 16. A majority (74.8%) were female (Figure 1A), and 58% were classified as either overweight or obese based on CDC percentile criteria (Figure 1B). Hemolytic disorders were identified in 9.7% of patients (n = 1232), with hereditary spherocytosis and sickle cell disease representing the majority of this subgroup. These patients typically presented earlier in life and more frequently underwent open cholecystectomy or bile duct exploration, consistent with known risks of pigment stone formation.

Figure 1 Clinical characteristics of gall bladder pathology in the pediatric population. A: Sex distribution. The sex distribution among the 12750 pediatric patients undergoing cholecystectomy demonstrated a significant female predominance, with 74.8% of the cohort identifying as female (9530 cases), 25.2% male (3208 cases), and 0.01% non-binary (12 cases), suggesting a gender-based disparity in disease incidence; B: Body mass index classification. Among the 12750 pediatric patients who underwent cholecystectomy, 4628 were classified as obese, 2711 as overweight, 3280 as normal weight, and 2131 as underweight. 58% of the patients were either overweight or obese, establishing a strong association between elevated body mass index and pediatric gallbladder disease; C: Laboratory abnormalities (white blood cell and bilirubin). Elevated white blood cell was present in 62% of patients, while 20% had hyperbilirubinemia, with subcategories of mild (12.7%), moderate (4.2%), and severe (3.5%) elevations. These values correlated with more invasive biliary interventions; D: Surgical approach breakdown. Laparoscopic cholecystectomy was performed in 10710 cases. Cholecystectomy with cholangiography in 2040 cases, common bile duct exploration in 1785 cases, sphincterotomy/sphincteroplasty in 765 cases, and open surgery in 128 cases, highlighting the predominance of minimally invasive techniques; E: Kaplan-Meier discharge survival curve. Over 85% of patients were discharged within the first two days. The curve plateaus for patients with delayed surgery or complications, emphasizing the benefit of early intervention. BMI: Body mass index; WBC: White blood cell; CBD: Common bile duct.

Laboratory data indicated elevated WBC counts in 62% and elevated bilirubin in about 20% of patients. Of these, 12.7% had mild elevations (1.3-3.0 mg/dL), 4.2% moderate (3.1-5.0 mg/dL), and 3.5% severe (> 5.0 mg/dL). Children with moderate to severe hyperbilirubinemia had significantly higher rates of bile duct procedures, including cholangiography and bile duct exploration. A subset of these patients also required ERCP, most often in centers with pediatric gastroenterology capabilities (Figure 1C). Laparoscopic cholecystectomy was the primary operative approach in 84% of cases, while 1% required open cholecystectomy due to complications or anatomy. Of the laparoscopic cases, 4.8% were converted to open, most commonly due to intraoperative findings, perforation, or significant adhesions (Figure 1D).

Postoperative complication rates were low overall, but increased with obesity and inflammatory markers. Gallbladder perforation occurred in 1.9%, biliary abscess in 1.4%, and bile leak in 0.8% of all patients. Sepsis was documented in 0.5% of cases, disproportionately affecting those with delayed intervention and severe laboratory abnormalities. The timing of surgery strongly influenced the length of stay and readmission rates (Table 1). Patients undergoing early cholecystectomy (within 2 days of diagnosis) had a median stay of 1 day and a 5% readmission rate, while delayed surgery (beyond 5 days) resulted in a median stay of 3 days and a 12% readmission rate. Figure 1E illustrates the Kaplan-Meier survival analysis of time to discharge, showing a steep drop within the first two hospital days, with over 85% discharged by day 2. However, this curve flattened substantially among those with delayed intervention, laboratory derangements, or complications. Taken together, these results highlight the clinical benefit of timely diagnosis and intervention, the predominant role of obesity in disease pathogenesis, and the emerging complexity of pediatric gallbladder surgery, including the increasing use of ERCP and bile duct exploration in children.

Table 1 Timing of surgery and readmission rates¹.

Timing of surgery	Number of patients	Number readmitted	Readmission rate
Early (≤ 2 days)	10838	542	5.0%
Delayed (> 5 days)	1912	229	12.0%
Total	12750	771	6.0% overall

¹This table illustrates the correlation between the timing of surgical intervention and 30-day readmission rates in pediatric patients undergoing cholecystectomy. Of the 12750 patients, 10838 underwent early surgery (defined as within ≤ 2 days of diagnosis), while 1912 had delayed surgery (> 5 days). Readmission occurred in 542 early cases (5%) and 229 delayed cases (12%). These findings underscore the benefits of prompt surgical management, with early intervention associated with significantly reduced readmissions and shorter hospital stays.

DISCUSSION

This study reinforces pediatric acute cholecystitis as a rising public health and surgical concern, closely linked to the ongoing global childhood obesity epidemic[4,5]. The finding that a majority of patients were overweight or obese reaffirms metabolic dysfunction as the predominant driver of gallbladder pathology in youth, shifting the disease profile away from historically hemolysis-centered etiologies[3,9]. Hemolytic disorders such as hereditary spherocytosis and sickle cell disease remain important but now account for less than 10% of cases[8,9]. These patients, while fewer in number, presented with a distinct clinical course, earlier onset, pigment stones, and increased rates of open procedures, highlighting the need for ongoing vigilance and tailored surgical planning.

The TG18 provides diagnostic and severity criteria widely used in adult populations[7]. However, our data suggest these thresholds may inadequately capture pediatric disease severity. Several children with only modest elevations in WBC count or bilirubin developed serious complications, including biliary abscess or required bile duct exploration[1]. These findings argue for refinement or pediatric-specific adaptation of the guidelines to improve triage and decision-making. The TG18 proposed three criteria for severity grading in acute cholecystitis based on local signs of inflammation (Murphy’s sign; Right Upper Quadrant mass, pain, or tenderness); systemic signs of inflammation [fever, elevated C-reactive protein (CRP), elevated WBC count], and imaging findings (pericholecystic fluid and gallstones/debris)[7]. Clinical presentation in the adult population is classified as grade 1: Mild; grade 2: Moderate; and grade 3: Severe, with dysfunction of one or more organ systems. Early surgical intervention is recommended in grades 1 and II, and resuscitative measures with early gallbladder drainage are recommended in patients with grade III who are not suitable for cholecystectomy. In the pediatric population, severely inflamed and technically challenging gallbladder pathology can be present with a normal WBC count or CRP, and biliary ductal evaluation and intervention are often necessary. Imaging findings may not correlate with intraoperative findings. Further, organ dysfunction is not commonly seen in the pediatric population. We propose that one should consider prophylactic antibiotic use when treating pediatric gallbladder pathology is present. Further, we propose that all pediatric gall bladder pathology be managed at higher-volume pediatric centers due to the need for multimodal management. Postoperative complications, while infrequent overall, demonstrated clear patterns. Gallbladder perforation, bile leak, and abscess formation were most common in patients with delayed intervention and laboratory markers of inflammation[9]. These data support early surgery, as endorsed by the TG18, and raise the question of whether pediatric guidelines should mandate similar timing targets[7]. Currently, in many countries, surgeons prefer waiting until the gallbladder inflammation resolves before surgical intervention. In this study, early intervention appeared to improve outcomes and decrease complication rates.

Obesity was associated not only with a higher risk of developing cholecystitis but also with increased surgical complexity[6,10]. Obese children were more likely to require conversion from laparoscopic to open surgery and to have longer hospital stays. These associations persisted despite statistical limitations in logistic regression modeling and warrant further prospective validation. The role of bile duct procedures, particularly ERCP, is emerging in the pediatric realm[8]. Although use remains limited to specialized centers, our cohort demonstrated that a subset of children required advanced intervention for choledocholithiasis or obstructive jaundice. This underscores the need for pediatric surgical and gastroenterology teams to coordinate early in cases of suspected ductal involvement.

From a systems perspective, hospitals should ensure that perioperative protocols accommodate high-BMI children, and surgical teams should be trained in both technical and psychosocial management of these patients. This study highlights the importance of cross-disciplinary collaboration amongst pediatric surgeons, gastroenterologists, primary care providers, and public health leaders. Stakeholders must work together to identify at-risk children earlier and implement preventive measures. School-based interventions, family counseling, and systemic changes to food and activity environments will be essential in reversing this trend[4,5]. Overall, this work confirms that pediatric cholecystitis is not simply an earlier onset of adult disease but a distinct clinical phenomenon requiring its own diagnostic algorithms, treatment strategies, and public health urgency.

Study limitations

This study is subject to some limitations. First, it is a retrospective analysis using data derived exclusively from institutions within the United States, which may limit the generalizability of the findings to international settings with differing healthcare systems, surgical resources, and population demographics. Second, although this dataset captures a large volume of pediatric cases, clinical variability in diagnosis, documentation, and surgical decision-making may exist across participating centers. The reliance on administrative coding and retrospective abstraction also poses inherent risks of selection and information bias. Lastly, despite the high prevalence of obesity, other confounding factors such as socioeconomic status, diet composition, and access to preventive care were not captured in this dataset and may influence disease incidence and outcomes.

Future directions

Given the rising global burden of pediatric obesity reported by the World Health Organization[5], future studies should expand to include international cohorts across diverse socioeconomic and geographic contexts. This would allow for comparative analysis of incidence, risk factors, and treatment modalities and help identify population-specific protective or exacerbating trends. Further research is also needed to refine the TG18 for pediatric applicability. Our findings suggest that existing severity criteria based on WBC count, bilirubin level, and physical findings may not adequately predict outcomes in children. Prospective multicenter trials should aim to validate pediatric-specific thresholds and explore the predictive accuracy of additional variables such as BMI category, puberty status, and inflammatory markers, including CRP. An international pediatric gallbladder disease registry would support more robust epidemiologic surveillance and improve standardization in care. Such a registry could facilitate the development of risk prediction models and inform best practices in the timing of surgery, especially in resource-limited environments. Lastly, the emerging use of ERCP in the pediatric population warrants further evaluation. As access to pediatric gastroenterology services expands, the safety, success rates, and long-term outcomes of ERCP in children with choledocholithiasis or biliary obstruction should be carefully studied and compared with alternative surgical approaches.

CONCLUSION

Pediatric acute cholecystitis is no longer a rare diagnosis but a predictable consequence of the global childhood obesity epidemic[4,5]. Our review of 12750 cases shows that nearly 95% of affected children are overweight or obese, representing a dramatic shift in the etiology of gallbladder disease from predominantly hemolytic causes to lifestyle-driven metabolic dysfunction[3]. This evolving landscape demands a reevaluation of current diagnostic and management strategies. The TG18 offers a valuable framework[7], but our findings underscore the need for pediatric-specific adaptations, particularly given the elevated complication rates observed in patients with only modest elevations in WBC or bilirubin[1]. Timely surgical intervention is paramount. Early cholecystectomy, defined as within two days of diagnosis, was associated with significantly shorter hospital stays and lower readmission rates[9]. Prospective studies should be considered to validate the safety and efficacy of early intervention in pediatric acute cholecystitis. Laparoscopic cholecystectomy remains the standard of care[10,11], but our data show an increasing need for advanced biliary procedures, including cholangiography and ERCP, as pediatric disease complexity rises[8].