Follow-up study of gallbladder stones in 44 children

Abstract

BACKGROUND

Cholesterol stones affect a certain subpopulation of children. Concerns have been raised on the impact of gallbladder surgery on the growth of children and adolescents.

AIM

To study the population characteristics, clinical features, treatment, and prognosis of gallstones in children.

METHODS

The clinical data of 44 children with gallstones admitted to The First Affiliated Hospital of Naval Medical University from August 2009 to August 2021 were collected, the children were followed up by telephone to monitor their prognoses. The follow-up ended in August 2023. The shortest follow-up time was 2 years and 6 months, whereas the longest was 13 years and 11 months. The population characteristics, general clinical characteristics, and treatments were retrospectively analyzed. The children were divided according to whether they underwent surgical gallbladder removal into an operation group (n = 28) and a non-operation group (n = 16), The effects of surgical gallbladder resection on the growth and development of children were analyzed.

RESULTS

The male–female ratio in the population was 6:5 and 84.09% of the children had onset in adolescence. Furthermore, 29.55% of the children were overweight or obese. The study identified 26 cases with metabolic abnormalities, 9 with hemolytic anemia, and 4 with choledochal cyst. Of the population, 68.18% had recurrent symptomatic cholecystolithiasis. Surgical treatment accounted for 63.64%, with laparoscopic cholecystectomy accounting for 71.43% of surgical treatment. No significant differences were observed in symptoms and complications between the surgery and non-surgery groups. Furthermore, no significant differences were found between the two groups in the attainment of genetic height target and the rightward shift of height curve during follow-up.

CONCLUSION

The sex characteristics of gallstones in children were not observed. Most gallstones occurred in adolescents and rarely in young children. A considerable proportion of children have inborn causes, which are often concurrent with metabolic abnormalities and hemolytic anemia. Most children had recurrent symptomatic gallstones. Surgical treatment, especially laparoscopic cholecystectomy, is still the main treatment for gallstones in children. Surgical treatment did not affect the growth and development of children who underwent gallstone removal.

Key Words: Gallstones in children, Clinical characteristics, Growth and development, Operation, Clinical features

Core Tip: In this study, we investigated the population of children with gallstones to determine the population characteristics, clinical features, treatment, and prognosis. The sex characteristics of gallstones in children were not observed, and most gallstones occurred in older children. Relevant symptoms may be recurrent. Surgical treatment, especially laparoscopic cholecystectomy, is still the main treatment for gallstones in children. However, surgical treatment did not affect the growth and development of children who underwent gallstone removal.

INTRODUCTION

Gallstones are a common disorder of the hepatobiliary system, which mainly manifests as the formation of stones in the gallbladder. Gallstones are usually composed of cholesterol, bile pigment, or calcium salts. This condition can be caused by the supersaturation of certain substances in the bile, the crystallization of stones, or gallbladder movement dysfunction. Gallstones can cause no symptoms and are thus referred to as “silent gallstones”; however, in some cases they can cause biliary colic, which is a sudden and intense pain in the upper abdomen. If stones obstruct the flow of bile, they can induce cholecystitis, an acute inflammation of the gallbladder characterized by persistent abdominal pain, fever, and weakness. In more severe cases, gallstones can also cause jaundice, bile duct infections, bile duct stones, pancreatic duct stones, or pancreatitis. A high-fat, high-cholesterol diet may increase the risk of gallstones, whereas eating a balanced diet and maintaining a healthy weight can help reduce this risk. In adults, the development of gallstones is associated with multiple factors, such as age, sex (women are more susceptible), obesity, pregnancy, genetic factors, certain diseases (such as diabetes), and certain medications[1]. However, in children, the development of gallstones may be closely related to the rising rate of childhood obesity[2]. Obesity not only increases the risk of gallstones in adults, but is now increasingly affecting children. In addition, the increase in high-fat, high-cholesterol, and high-sugar foods in children’s diets may also contribute to the increased incidence of gallstones in children. This type of diet may induce the supersaturation of cholesterol, increasing the risk of gallstone formation. Therefore, extensive research on gallstones in children is very important. This not only contributes to a better understanding of the pathogenesis of gallstones in children, but it can also aid in the development of preventive measures and treatment strategies, especially in terms of diet and lifestyle modification. Furthermore, health education for children and promotion of a healthy lifestyle can prevent the development of gallstones at an early stage.

This study retrospectively collected data on children and adolescents with gallstones admitted to our hospital in the last 12 years and conducted telephone follow-up to analyze the population characteristics, general clinical characteristics, treatment, and effects of cholecystectomy on the children’s growth and development. This study aimed to provide relevant clinical data for the surgical treatment of gallstones in children, especially symptomatic gallstone formation.

MATERIALS AND METHODS

Study design

The clinical data of 44 children with gallstones admitted to The Firs Affiliated Hospital of Naval Medical University from August 2009 to August 2021 were selected. All patients underwent at least one abdominal ultrasound, abdominal computed tomography, magnetic resonance cholangiopancreatography, retrograde cholangiopancreatography, endoscopic ultrasound, and postoperative pathological analysis. The diagnosis was confirmed using the relevant clinical diagnostic criteria. The children were divided according to whether they underwent cholecystectomy into the operation group (28 cases) and non-operation group (16 cases). In the operation group, the children were further subdivided into the laparoscopic cholecystectomy group (20 cases) and open cholecystectomy group (8 cases) according to the surgical method undergone. The inclusion criteria were patients with clinically diagnosed gallstones and age 0–18 years old. The exclusion criteria were incomplete clinical data and cases complicated with congenital diseases that seriously affect the growth and development of children.

Collection of data

Detailed information on onset age, age at first diagnosis, sex, height, weight, clinical symptoms and signs, laboratory examination results, treatment, and outcome were collected by consulting the previous case data and telephone follow-up. The deadline of the follow-up was August 2023. The shortest follow-up time was 2 years and 6 months, whereas the longest was 13 years and 11 months. No deaths occurred during the follow-up period. The main assessment points of the follow-up included subsequent morbidity, treatment, survival, and growth and development of the children after discharge.

Statistical analysis

SPSS 25.0 statistical software (IBM, Armonk, NY, United States) was used for data analysis. Count data are expressed as number and percentage (%). The chi-square test and its correction formula were used to compare between groups. P < 0.05 was considered statistically significant.

RESULTS

Baseline information

The population characteristics of the enrolled children with gallstones were distributed according to sex and included 20 girls (45.45%) and 24 boys (54.55%). According to the age distribution of onset, 5 patients were 18 years old; 8 patients were 17 years old; 5 patients were 16 years old; 8 patients were 15 years old; 1 patient was 14 years old; 4 patients were 13 years old; 4 patients were 12 years old; 2 patients were 11 years old; 2 patients were 10 years old; 1 patient was 9 years old; 1 patient was 8 years old; 1 patient was 7 years old; 1 patient was 6 years old; 1 patient was 5 years old; most of them were adolescents (37 patients were > 10 years old, accounting for 84.09%). According to the body size distribution as assessed using the overweight and obesity screening standard for school-age children and adolescents[3], 31 patients (70.45%) had a normal body size, 9 patients (20.45%) were overweight, and 4 patients (9.09%) were obese (Table 1).

Table 1 Demographics of children with gallstones.

Demographic	Frequency or median (n = 44, %)
Sex
Female	45.45
Male	54.55
Age (yr)
Adolescence (> 10 yr)	84.09
Preschool and school-age children (≤ 10 yr)	15.91
Shape
Normal	70.45
Overweight	20.45
Obesity	9.09

Clinical characteristics of children with gallstones

In terms of gallstone etiology, 26 patients had metabolic abnormalities (including overweight, obesity, dyslipidemia, fatty liver, and diabetes); 9 with hemolytic anemia (3 diagnosed with hereditary spherocytosis, 1 with hereditary glucose-6-phosphate dehydrogenase deficiency, and 5 diagnosed based merely on clinical features without a specific type of hemolytic anemia); and 4 with choledochal cyst. Five patients had metabolic abnormalities and lytic anemia, 1 had metabolic abnormalities and a choledochal cyst, and 1 had lytic anemia and a choledochal cyst. No definite etiology was found in the relevant medical history of 12 patients.

Based on symptoms, 42 patients had symptomatic gallstones, whereas 2 had asymptomatic ones. The main manifestations of symptomatic gallstones were abdominal pain, accompanied by nausea, vomiting, radiating pain, fever, and jaundice, among others. Forty-one cases were accompanied by complications, including cholecystitis, pancreatitis, bile duct stones, and pancreatic duct stones. At the end of follow-up, only 12 patients had one recurrence of symptomatic gallstones, 6 had two recurrences, and 24 cases had multiple recurrences.

Twenty-eight cases were treated surgically (20 cases of laparoscopic surgery, 8 cases of open surgery), and 16 cases were treated conservatively. Four cases underwent emergency cholecystectomy, whereas the remaining 24 cases underwent elective cholecystectomy. In the 8 cases of open cholecystectomy, 4 were due to a complicated biliary structure, whereas the other 4 were due to other abdominal procedures. Laparoscopic cholecystectomy was the main surgical method performed (Table 2).

Table 2 Clinical comparisons of children with gallstones.

Clinical features	Frequency or median (n = 44, %)
Possible causes
Suspected etiology exists	72.73
No cause found	27.27
Any symptom onset
Yes	95.45
No	4.55
Treatment methods
Laparoscopic cholecystectomy	45.45
Open cholecystectomy	18.18
Conservative treatment	36.36

Comparison between the surgical and conservative treatment groups on symptom onset

No significant differences were found in the frequency of symptoms or complications between the surgical and conservative treatment groups (Tables 3 and 4).

Table 3 Comparison between the surgical and conservative treatment groups on symptom onset, n (%).

Symptom frequency	≥ 2	< 1	P value
Conservative treatment group	10 (62.5)	6 (37.5)	0.54
Surgical treatment group	20 (71.43)	8 (28.57)

Table 4 Comparison between the surgical and conservative treatment groups on complication onset, n (%).

Complication frequency	≥ 2	< 1	P value
Conservative treatment group	11 (68.75)	5 (31.35)	0.26
Surgical treatment group	13 (46.43)	15 (53.57)

Comparison between the surgical and conservative treatment groups on genetic height

Most of the children in the two groups achieved their genetic height, and no significant difference in height was observed between the two groups (Table 5). During the follow-up period, the tendency of a rightward shift in the height curve was low, and no significant difference in the height curve was found between the two groups (Table 6).

Table 5 Comparison between the surgical and conservative treatment groups on genetic height, n (%).

If genetic height reached	Reached	Not reached	P value
Conservative treatment group	11 (68.75)	5 (32.25)	0.52
Surgical treatment group	23 (82.14)	5 (27.86)

Table 6 Comparison between the surgical and conservative treatment groups on the height curve recorded during the follow-up period, n (%).

If shifted to the right	Yes	No	P value
Conservative treatment group	1 (6.25)	15 (93.75)	1
Surgical treatment group	3 (10.71)	25 (89.29)

DISCUSSION

Gallstones can be classified into cholesterol stones and pigment stones[4]. Cholesterol stones account for the majority of gallstones removed in adults[1,5]. The composition of gallstones in children changes with the obesity epidemic in children[6]. Cholesterol stones have specific population characteristics. The prevalence of gallstones gradually increases with age and is higher in women than in men. Gallstone formation is also more common in people who are overweight and obese[1,7]. These characteristics have been mostly observed in adult population studies. Cholecystolithiasis can be asymptomatic or manifest in various forms. Most patients with cholecystolithiasis may have exhibited no symptoms their whole life[2]. The common clinical complications of symptomatic cholelithiasis include cholecystitis, bile duct stones, pancreatic duct stones, pancreatitis, and obstructive jaundice, among others. One state may transition into the other under certain conditions. The disease status of gallstones in children and adolescents can affect their physical health[8], nutritional status, and growth and development. Cholecystectomy is currently the first choice of treatment for symptomatic gallstones[9]. Delayed or no surgery may cause related symptoms and complications, affecting the quality of life. However, concerns have been raised about the impact of surgical gallbladder removal on the growth of children and adolescents.

This study analyzed the data of 44 children and adolescents with gallstones admitted to our hospital in the last 12 years. Analysis of population characteristics revealed a comparable proportion of boys and girls with gallstones, which may be due to the sex ratio of children and adults with gallstones. Furthermore, the nearly equal ratio may be related to the different hormone levels in men and women at different ages but may also be due to other factors, such as body size, eating habits, and complications. The nearly equal male–female ratio may also be related to pigment gallstones, which accounted for a considerable proportion of gallstone cases in the present study. Relevant studies on adult patients have shown that cholesterol gallstones occur more frequently in women[1,10]. In the present study, the onset age was mainly around adolescence (approximately 84.09%), and school-age children accounted for only a small proportion (approximately 15.91%), which confirms that the prevalence of gallstones increases with age.¹ In terms of body shape, a considerable number of children in the study were overweight and obese, and children with an abnormal body mass index (BMI) was 29.55%, which was much higher than the percentage reported in the 2020 Chinese statistics. However, an increase in BMI is a decisive risk factor for gallstone formation and a pathogenic risk factor for symptomatic gallstone disease[11-14].

In the etiological analysis, 26 cases had metabolic abnormalities, 9 had hemolytic anemia, 4 had choledochal cyst, and 12 had an unknown etiology. This indicates that most pediatric gallstone cases have underlying causes, and that treatment of the causes can mitigate the disease or prevent it completely. However, some studies have shown that a considerable proportion of patients continue to experience abdominal pain after cholecystectomy[15]. In terms of the onset of symptoms, the majority of children (95.45%) in this study had symptomatic gallstones, and only 2 cases were asymptomatic, which were diagnosed after further examination of initial findings of a benign pancreatic mass and hemolytic anemia, respectively.

The necessity of early surgical decision-making for gallstones in children is especially significant for children with symptomatic gallstones and gallstones complicated with hemolytic anemia[16]; thus, almost all children included in this study had surgical indications. In particular, the patients with recurrent symptoms would have had their health negatively impacted and faced a heavy economic burden, highlighting the necessity and urgency of the surgical treatment of symptomatic gallstones. In this study, 63.64% of children with cholecystolithiasis were treated surgically, mostly by laparoscopic surgery, which involved less trauma and a quicker recovery. Only 8 cases underwent open cholecystectomy, including 4 with a complex biliary structure and 4 that underwent combined surgery. Previous studies have shown that laparoscopic cholecystectomy and small-incision open cholecystectomy had comparable efficacy; however, the short-term quality of life after open cholecystectomy is slightly worse, making laparoscopic cholecystectomy the first choice for cholecystectomy in patients with gallstones[11,17].

Despite previous findings, the surgical treatment of symptomatic gallstone remains controversial[6,18]. A young age is the main reason most pediatricians choose conservative treatment. The main concerns about surgery are postoperative complications and possible effects on the growth and development of pediatric patients. Previous studies have suggested that the gallbladder may function as a metabolic organ[11,19]. In the present study, only 1 patient who underwent combined distal pancreatectomy and splenectomy developed pancreatic fistula, which confirms previous reports on the rarity of serious complications after cholecystectomy in pediatric patients[20,21]. Furthermore, no significant differences in symptoms and complications were found between the surgical and non-surgical treatment groups, indicating that the surgical indication for children with gallstones may not only depend on the symptoms and complications but may also be influenced by family’s wishes, doctors’ treatment preferences, and other social, familial, and personal factors.

CONCLUSION

No significant differences were observed between the surgical and non-surgical groups in the attainment of genetic height and the rightward shift of the height curve during the follow-up period. The results indicate that surgical treatment of gallstones in children may not affect their subsequent growth and development. This confirmation may relieve some parents’ and doctors’ concerns about this and related issues. However, due to the limitations of small sample size and retrospective, single-center study design, the above conclusions may need to be confirmed by further large-sample, multi-center, randomized controlled studies to confirm the current findings.