Highlights
- •Only one previous study published in Spanish have investigated post-cholecystectomy syndrome in pediatric patients.
- •Our study shows that post-cholecystectomy syndrome is not uncommon in pediatric patients.
- •Moreover, the vast majority of the patients had a total recovery from their abdominal pain and were satisfied with the result after cholecystectomy.
Abstract
Background
Post-cholecystectomy syndrome (PCS) refers to persistent or new abdominal symptoms after cholecystectomy. As there are very few reports on PCS in pediatric patients, we aimed to examine whether it was a frequent finding and which symptoms the affected children experienced.
Method
This is a retrospective cross sectional study of pediatric patients, who underwent cholecystectomy during 2003–2019 at Oslo University Hospital. The PedsQL™ gastrointestinal symptoms scale questionnaire and a self-designed questionnaire exploring satisfaction after surgery and current medical conditions were mailed to all eligible patients. Patient/parental consent and approval from the local data protection officer (19/09054) were obtained.
Results
Questionnaires were sent to 82 patients of whom 44 (54%) answered. There were no significant demographic differences between the responders and the non responders. We identified 16 (36.7%) patients to have PCS. The most common symptoms were diarrhea (25%), bloating (16%), and heartburn/reflux (16%). Overweight was more common in patients with PCS (31%) than in patients without PCS (4%) (p = 0.014). Altogether 34/44 (77.3%) patients were satisfied with the result of the cholecystectomy; 92,6% of patients without PCS and 56.6% of those with PCS (p = 0.012).
Conclusion
PCS is not uncommon in pediatric patients, and they report a wide range of gastrointestinal symptoms. We identified overweight as a potential risk factor for developing PCS. Nonetheless, most patients got total relief of abdominal pain and were satisfied with outcome after cholecystectomy.
Level of evidence
Level 3
Keywords
1. Introduction
The prevalence of gallstones in children is reported to vary from 0.1 to 1.9% [
1
, 2
, 3
]. There are several risk factors for developing gallstones in childhood. These include hemolytic disease, long-term parenteral nutrition, genetic disorders, trauma, sepsis, antibiotics, and obesity [[4]
]. Cholecystectomy is the standard treatment for symptomatic gallstone disease in both adults and children. Unfortunately, not all patients experience total relief of symptoms after cholecystectomy, and some even develop new gastrointestinal symptoms postoperatively. Post-cholecystectomy syndrome (PCS) is a term used to describe the persistence or occurrence of abdominal symptoms after cholecystectomy [[5]
].PCS symptoms are often divided into biliary and non biliary symptoms. Undiagnosed extra-biliary diseases, such as irritable bowel syndrome or functional dyspepsia are the most common causes of non biliary symptoms [
[6]
]. Increased bile flow into the upper gastrointestinal tract may lead to duodeno-gastric biliary reflux, which may play a significant role in the pathogenesis of symptoms like dyspepsia, gastric/ duodenal ulcer, and nausea [[7]
]. Biliary etiologies of PCS include bile salt-induced diarrhea, retained calculi, bile leak, biliary strictures, long remnant cystic duct, and dyskinesia of the sphincter Oddi [[8]
].In adults, PCS occurs in 5–47% and is significantly more common in women than in men [
[5]
,9
, 10
, 11
. It is only one previous published study on PCS in the pediatric population. This study, published in Spanish, including 33 patients found that 48% experienced PCS [[12]
]. We performed this study to expand current knowledge about PCS in children, and our primary objective was to explore the frequency of PCS in these patients. Our secondary aims were to investigate the spectrum of PCS symptoms and patient/ parent satisfaction after cholecystectomy.2. Patients and methods
This is a retrospective cross sectional study of patients <18 years who underwent cholecystectomy during 2003–2019 at Oslo University Hospital, which serves as a local, regional, and tertiary referral center in pediatric surgery. Patients who underwent cholecystectomy as a part of liver resection, resection of choledochal cysts, or Kasai portoenterostomy were excluded. Clinical details such as age at surgery, gender, comorbidities, body mass index, indication for cholecystectomy, surgical method (open/ laparoscopic operation), and postoperative complications were recorded retrospectively from medical records. Postoperative complications were graded according to the Clavien-Dindo classification of complications [
[13]
]. A more detailed description of the majority of the patients’ demographics and perioperative results has been described previously [[14]
].The PedsQL™ gastrointestinal symptoms scale (GSS) questionnaire and a self-designed questionnaire were mailed to the patients and their parents. The PedsQL™ GSS questionnaire includes a total of 58 items divided into 10 different domains: Stomach Pain (6 items), stomach discomfort when eating (5 items), trouble swallowing (3 items), food and drink limits (6 items), heartburn and reflux (4 items), nausea and vomiting (4 items), gas and bloating (7 items), constipation (14 items), blood in stool (2 items), and diarrhea (7 items). Answers are graded as 0=never a problem, 1=almost never a problem, 2=sometimes a problem, 3=often a problem, 4=almost always a problem. To generate the total score, answers are transformed reversely from a 0–4 scale to a 0–100 scale, where 0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0. A high score indicates high gastrointestinal quality of life and few gastrointestinal symptoms. Scores are presented as the mean score of the items within each domain and the mean total score for all items. If > 50% of items in one scale were missing, the scale score was not computed [
[15]
]. The non validated self-designed questionnaire included questions on satisfaction with the cholecystectomy (yes/no/do not know), current medications, any abdominal surgery after cholecystectomy, and any health contacts related to abdominal pain after cholecystectomy. In patients < 12 years parents were instructed to answer the questionnaire, patients 12–17 were instructed to answer together with their parents and patients >18 years were instructed to answer independently.We defined the patients to have an abdominal symptom if they had a PedsQL™ GSS score lower than two standard deviations from the mean score in a healthy control group [
[16]
,[17]
for one or more domains. The patient`s body mass index was adjusted for age and gender, and a body mass index >25 was categorized as being overweight.Data were registered in EpiData Manager (version 4.6.0.2), and the statistical analysis was performed by use of SPSS statistics 28 (IBM corp. Armonk, NY). Numerical variables are presented as median and range for not normally distributed data and as the mean and standard deviation (SD) for normally distributed data. Chi-Square test was applied for comparison of all categorical variables. Continuous variables were analyzed with parametric test (Student T-Test) and non parametric test (Mann-Whitney-U test) used as appropriate. All age groups were analyzed together because of the low sample size. Patient/parental consent and approval from the local data protection officer (19/09054) were obtained.
3. Results
We identified 86 eligible patients. Four patients were deceased at follow-up. They had serious underlying neurological or syndromic conditions and died mean four years after surgery of causes unrelated to the cholecystectomy. Thus, questionnaires were sent to 82 patients of which 44 (54%) returned the questionnaires. All patients returning questionnaires were included. Twenty-two (50%) were girls, and mean age at surgery was 8.6 (SD=3.9) years. All patients had gallstones demonstrated on ultrasound preoperatively, and 18 (42%) had complicated gallstone disease (previous or current cholecystitis, choledochal stones, biliary pancreatitis, and/or cholangitis). The indication for cholecystectomy was pain in 25 (61%), common bile duct stones in seven (17%), and cholecystitis in three (7%). Three patients did not have symptoms of gallstone disease, but had the gallbladder removed concomitantly with (7%) other procedures, and none were operated for biliary dyskinesia alone. Fifteen (37%) patients had no other disease, ten (25%) had hemolytic disease (hereditary spherocytosis (9 patients), hereditary hemolytic anemia (1 patient)), four (9%) had gastrointestinal dysmotility disorders, four (9%) had neurological disorders, four (9%) had a syndrome, and 15 (34%) had a variety of other disorders. Laparoscopic cholecystectomy was performed in 40 (86%) patients, 34 (78%) underwent elective surgery, and seven (15%) had a concomitant splenectomy. Seven (15%) patients experienced postoperative complications. Two (5%) patients experienced Clavien Dindo 3b complications; one common bile duct injury and one postoperative bleeding. The median time from operation to follow-up was five (0.5–16) years, and the mean age at follow-up was 14.9 (SD=6.1) years. There were no demographic differences between the patients who returned the questionnaires and those who did not (Table 1).
Table 1Responders versus non responders. A comparison of demographic and clinical data in 81 responders and non responders of questionnaires sent after cholecystectomy. Being overweight was defined as an age and gender-adjusted body mass index >25.
| Responders (n = 44) | Non responders (n = 37) | p value | |
|---|---|---|---|
| Age, mean (SD) | 8.6 (3.9) | 10.2 (4.6) | 0.088 |
| Gender, girls | 22 (50%) | 30 (71.4%) | 0.074 |
| Body mass index, median (min-max) | 16.4 (13−32) | 18.3 (11−37) | 0.127 |
| Comorbidity | |||
| No comorbidity | 15 (34.1%) | 15 (40.5%) | 0.646 |
| Hemolytic disease | 10 (22.7%) | 10 (27.0%) | 0.796 |
| Being overweight | 6 (13.6%) | 8 (21.6%) | 0.230 |
| Syndromic disease | 4 (9.1%) | 2 (5.4%) | 0.685 0.819 |
| Other | 17 (38.6%) | 13 (35.1%) | |
| Complicated gallstone disease | 17 (38.6%) | 16 (43.2%) | 0.820 |
| Long-term parenteral nutrition | 4 (9.1%) | 3 (8.1%) | 1.000 |
| Years from cholecystectomy to being invited to participate, median (min-max) | 5 (0–16) | 5 (0–16) | 1.000 |
Overall gastrointestinal quality of life was good (Table 2). Sixteen (37%) patients had abdominal symptoms fulfilling the definition of PCS. These patients presented a variety of symptoms; diarrhea (11 patients), gas and bloating (7 patients) heartburn/reflux (7 patients), stomach pain (5 patients), stomach discomfort when eating (5 patients), nausea and vomiting (4 patients), food and drink intolerance (4 patients), constipation (3 patients), trouble swallowing (3 patients), and blood in stool (1 patient). The individual patients with PCS reported from one to six different abdominal symptoms (1 symptom: 6 patients, 2 symptoms: 3 patients, 3 symptoms: 2 patients, 4 symptoms: 3 patients, 6 symptoms: 2 patients).
Table 2Gastro PedsQL™ gastrointestinal symptom scale score in patients with and without post-cholecystectomy syndrome (PCS) in patients undergoing cholecystectomy in a pediatric department during 2003–2019.
| Domain | Patients without PCS score (SD), n = 28 | Patients with PCS score (SD), n = 16 | All patients score (SD), n = 44 |
|---|---|---|---|
| Total score | 90.6 (7.4) | 66.5 (12.8) | 82.7 (14.1) |
| Stomach Pain | 85.4 (13.8) | 49.6 (17.8) | 72.9 (22.9) |
| Stomach Discomfort When Eating | 89.3 (11.7) | 65.1 (20.1) | 80.8 (18.9) |
| Food and Drink Limits | 89.1 (13.8) | 68.3 (29.8) | 81.9 (22.8) |
| Trouble Swallowing | 97.0 (6.5) | 87.2 (18.6) | 93.6 (12.8) |
| Heartburn and Reflux | 88.6 (13.7) | 67.4 (22.6) | 80.8 (20.1) |
| Nausea and Vomiting | 94.4 (10.3) | 77.1 (21.0) | 88.4 (16.8) |
| Gas and Bloating | 78.8 (18.0) | 38.8 (13.8) | 64.4 (25.2) |
| Constipation | 85.8 (13.6) | 64.3 (17.6) | 78.9 (17.4) |
| Blood in Poop | 98.2 (5.6) | 87.5 (13.9) | 94.6 (10.4) |
| Diarrhea | 94.3 (9.4) | 66.8 (18.3) | 84.9 (18.5) |
The majority (80%) were satisfied with the result of the cholecystectomy. Four (10%) were not satisfied, and four (10%) patients were unsure. Two (4.5%) patients had undergone additional gastrointestinal surgery after the cholecystectomy (liver resection and appendectomy), and fifteen (34%) patients had been examined by a doctor because of abdominal symptoms since the cholecystectomy. Among patients with PCS, significantly more patients were overweight (Table 3). Fewer patients with PCS were satisfied with the postoperative result than those without PCS (Table 3). The frequency of health contacts because of abdominal pain was also higher among patients with PCS (Table 3).
Table 3Patients with and without post-cholecystectomy syndrome. A comparison of demographic and clinical data in patients with and without post-cholecystectomy syndrome (PCS) after cholecystectomy in a pediatric department. The patient's body mass index was adjusted for age and gender, and body mass index >25 was categorized as overweight.
| With PCS, n = 16 | Without PCS, n = 28 | p value | |
|---|---|---|---|
| Gender, girls | 7 (43.8%) | 13 (51.9) | 0.607 |
| No comorbidity | 5 (31.3%) | 10 (37%) | 0.700 |
| Age at operation, median years (min-max) | 8 (2–13) | 10 (0.2–17) | 0.217 |
| Overweight at operation | 5 (31.3%) | 1 (3.7%) | 0.014 |
| Elective surgery | 12 (75.0%) | 23 (85.2%) | 0.666 |
| Complicated gallstone disease | 6 (37.5%) | 11 (40.7%) | 0.834 |
| Age at follow-up (median, min-max) | 14.5 (3–25) | 13.75 (6–29) | 0.659 |
| Follow-up time, median years (min-max) | 5.5 (0–16) | 5 (0–16) | 0.785 |
| Being overweight at follow-up | 7 (43.8%) | 3 (11.1%) | 0.010 |
| Overall satisfied with the result after the cholecystectomy | 9 (56.6%) | 25 (92.6%) | 0.012 |
| Examined by a doctor for abdominal pain after discharge | 13 (81.3%) | 2 (7.4%) | <0.001 |
4. Discussion
The main finding in this study is that PCS defined as new or persisting abdominal symptoms after cholecystectomy is not uncommon in pediatric patients as around one-third of the patients reported abdominal symptoms after the cholecystectomy. Only one previous study published in Spanish including 33 patients has examined how often PCS occurs in children [
[12]
]. The Spanish study found a similar rate of PCS as we did. The prevalence of PCS in the present study is within the same range as reported in adults, although at the higher end [[5]
,9
, 10
, 11
. The small study populations in both pediatric studies make it difficult to make any firm conclusion about the prevalence of PCS in children. That many of the children had comorbidities has most likely contributed to the relatively high rate of PCS. Moreover, how abdominal symptoms are defined and recorded may also affect how often PCS is reported.Diarrhea, bloating, and reflux/ heartburn were the most common symptoms after cholecystectomy. This is in line with what is reported in adults [
[10]
,[11]
. Both diarrhea and bloating may be a consequence of loss of the gallbladder's reservoir function and may therefore be caused by the cholecystectomy. Reflux and dyspeptic symptoms have been reported both before cholecystectomy and to increase postoperatively in many adult patients [18
, 19
, 20
]. Thus, reflux/ heartburn may both be a consequence of cholecystectomy and a persisting symptom. It is interesting that postoperative symptoms are similar in children and adults in spite of children often having a different pathogenesis and preoperative symptoms compared to adults [[21]
].Abdominal pain was the most common indication for cholecystectomy, and about 90% of the patients in this study had total relief of their abdominal pain postoperatively. This is within the same range as reported in adults, where the rate of total recovery from abdominal pain varies between 60% and 100% [
[10]
,[11]
,[22]
. As mentioned earlier, pediatric patients undergoing cholecystectomy often have comorbidities that may cause abdominal symptoms. Therefore, it is positive that the cholecystectomy had such a good effect on abdominal pain in nine out of ten patients. This finding suggests that cholecystectomy is a good treatment for gallstone-related pain in pediatric patients.- van Dijk A.H.
- Wennmacker S.Z.
- de Reuver P.R.
- Latenstein C.S.S.
- Buyne O.
- Donkervoort S.C.
- et al.
Restrictive strategy versus usual care for cholecystectomy in patients with gallstones and abdominal pain (SECURE): a multicentre, randomised, parallel-arm, non-inferiority trial.
Lancet. 2019; 393: 2322-2330
The majority of the patients were satisfied with the result of the cholecystectomy. This is in line with findings from studies on patient satisfaction after cholecystectomy in adults [
[23]
,[24]
. As expected, patients with PCS were less satisfied with the postoperative result than patients without PCS. Nonetheless, more than half of the patients with PCS were satisfied with the postoperative result. We interpret this finding as PCS patients had an overall reduction in abdominal symptoms after cholecystectomy.More patients with PCS were overweight at the time of surgery and at follow-up compared to those without PCS. Similar results have not been found in adults. We do not have any obvious explanation for this finding, and further research is needed. PCS is reported more frequently among adult women than men [
[5]
,9
, 10
, 11
. In contrast, we did not demonstrate any gender difference. That many of the patients in this study were prepubertal may be one explanation for the lack of gender difference in the frequency of PCS.Since there were no demographic differences between the group returning the questionnaires and those who did not, we think this patient population is representative of pediatric patients undergoing cholecystectomy in a university hospital. The use of a validated gastrointestinal quality of life questionnaire and recording of patient/parent satisfaction is an important strength of this study as many studies in pediatric surgery are based on chart reviews only. The limitations with a retrospective cross sectional study are that we were not able to directly compare pre and postoperative symptoms. Consequently, we are unable to report whether PCS symptoms were new or persisting. A prospective study investigating both pre and post operative symptoms are needed to address this, and results from such a study may provide important information for patients and surgeons. Another limitation is that the time from surgery to follow-up differed among the patients. Furthermore, patients with symptoms may be more likely to respond to the questionnaire than those without symptoms or the other way around, causing a possible responders bias. Finally, the number of patients was too low to do any sub analysis.
To conclude, PCS is not uncommon in pediatric patients, and a wide range of abdominal symptoms was reported. Even so, most patients had complete relief of their preoperative abdominal pain and were overall satisfied with outcome of the cholecystectomy. This study highlights that preoperative counseling should include information about the possibility of PCS.
Declaration of Competing Interest
The authors do not have any conflicts of interest or have received any external financial support.
References
- Prevalence of gallstone disease in a general population of Okinawa, Japan.Am J Epidemiol. 1988; 128: 598-605
- Gallstone prevalence and gallbladder volume in children and adolescents: an epidemiological ultrasonographic survey and relationship to body mass index.Am J Gastroenterol. 1989; 84: 1378-1382
- Clinical presentations and predisposing factors of cholelithiasis and sludge in children.J Pediatr Gastroenterol Nutr. 2000; 31: 411-417
- The spectrum of biliary tract disorders in infants and children. Experience with 300 cases.Arch Surg. 1994; 129 (discussion 8-20): 513-518
- A systematic review of the aetiology and management of post cholecystectomy syndrome.Surgeon. 2018; 17: 33-42
- Post-cholecystectomy syndrome and sphincter of Oddi dysfunction: past, present and future.Expert Rev Gastroenterol Hepatol. 2016; 10: 1359-1372
- The postcholecystectomy syndrome. A role for duodenogastric reflux.J Clin Gastroenterol. 1996; 22: 197-201
- Etiologies of long-term postcholecystectomy symptoms: a systematic review.Gastroenterol Res Pract. 2019; 20194278373
- Postcholecystectomy syndrome (PCS).Int J Surg. 2010; 8: 15-17
- Abdominal symptoms: do they disappear after cholecystectomy?.Surg Endosc. 2003; 17: 1723-1728
- Persistent and de novo symptoms after cholecystectomy: a systematic review of cholecystectomy effectiveness.Surg Endosc. 2013; 27: 709-718
- Postcholecystectomy syndrome in children, fact or fiction?.Cir Pediatr. 2016; 29 (organo oficial de la Sociedad Espanola de Cirugia Pediatrica): 115-119
- Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.Ann Surg. 2004; 240: 205-213
- Few serious complications after cholecystectomy in paediatric patients.Acta Paediatr. 2019; 109 (630-630)
- Interpretability of the PedsQL™ gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with functional and organic gastrointestinal diseases.J Pediatr Psychol. 2015; 40: 591-601
- Interpretability of the PedsQL™ gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with functional and organic gastrointestinal diseases.J Pediatr Psychol. 2015; 40: 591-601
- PedsQL gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with inflammatory bowel disease in comparison with healthy controls.Inflamm Bowel Dis. 2015; 21: 1115-1124
- Gastroduodenoscopy: a routine examination of 2,800 patients before laparoscopic cholecystectomy.Surg Endosc. 2005; 19: 1103-1108
- Cholecystectomy and duodenogastric reflux: interacting effects over the gastric mucosa.SpringerPlus. 2016; 5: 1970
- Increased risk of peptic ulcers following a cholecystectomy for gallstones.Sci Rep. 2016; 6: 30702
- Postcholecystectomy syndrome with special regard to children–a review.Eur J Pediatr Surg. 2004; 14: 221-225
- Restrictive strategy versus usual care for cholecystectomy in patients with gallstones and abdominal pain (SECURE): a multicentre, randomised, parallel-arm, non-inferiority trial.Lancet. 2019; 393: 2322-2330
- Quality and patient satisfaction after ambulatory laparoscopic management of non-severe and uncomplicated gallbladder pathology.Cir Cir. 2019; 87: 656-661
- Patient-centered outcomes after laparoscopic cholecystectomy.Surg Endosc. 2013; 27: 4491-4498
Article info
Publication history
Published online: July 14, 2022
Accepted:
July 10,
2022
Received in revised form:
July 5,
2022
Received:
March 16,
2022
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