Management of childhood cholelithiasis: experience at a third-level pediatric surgical center

Management of childhood cholelithiasis: experience at a third-level pediatric surgical center | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Management of childhood cholelithiasis: experience at a third-level pediatric surgical center Davina Scalise, Alessandro Boscarelli, Manuela Giangreco, Daniela Codrich, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4144989/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Cholelithiasis is increasing in the pediatric population. While its etiology is primarily idiopathic, it is often related to underlying diseases, and a significant number of patients may be asymptomatic. There are currently no guidelines for the management of asymptomatic patients with both cholelithiasis and a predisposing condition. Therefore, this study seeks to highlight situations where prophylactic cholecystectomy may be desirable based on pre, intra, and postoperative complications, length of hospital stay, and disease recurrence. Methods: We retrospectively reviewed the medical records of patients who underwent elective laparoscopic cholecystectomy between October 2011 and September 2022. Data, including clinical presentation at the time of diagnosis and admission, imaging, treatments, complications, and length of hospital stay, were collected. Results: Thirty-two patients (21 females and 11 males) were included in the study. The median age was 14 years (range <1–17). Five different groups of patients were identified based on associated pathologies. Ten patients had hematologic disease (31.25%), four had cystic fibrosis (12.5%), six were overweight or obese (18.75%), two had an autoimmune disease (6.25%), and ten had no underlying disease (31.25%). Twenty-six patients were symptomatic (81.25%), and six were asymptomatic (18.75%). The idiopathic etiology group was entirely symptomatic. All patients underwent a laparoscopic cholecystectomy. There was one patient (in the idiopathic etiology group) who required conversion from laparoscopy to open surgery and a reintervention (3.13%). Hematologic and cystic fibrosis patients with asymptomatic cholelithiasis had a shorter length of hospital stay than patients with the same condition who progressed from asymptomatic to symptomatic gallstone disease. Conclusions: Patients with cystic fibrosis and hematologic diseases who have concomitant asymptomatic cholelithiasis may benefit from early laparoscopic cholecystectomy, which could reduce the probability of surgical and postsurgical complications and shorten the length of hospital stays. Pediatrics Cystic fibrosis Hematological disorders Symptomatic cholelithiasis Children Management BACKGROUND Cholelithiasis is a rare pediatric disease, but its incidence is increasing. It is idiopathic in 40–65% of patients, but in the remaining cases, it is associated with hemolytic disorders, obesity, and diseases such as cystic fibrosis (CF). Children with cholelithiasis are asymptomatic in 33–40% of cases. Otherwise, they may present with classic biliary colic or nonspecific abdominal pain. Possible complications include acute cholecystitis, acute pancreatitis, hydrops of the gallbladder, obstructive jaundice, cholangitis, and cancerous lesions 1 – 3 . Treatment options include a conservative approach using ursodeoxycholic acid (UDCA), but results have been neither satisfactory nor definitive. In contrast, laparoscopic cholecystectomy (LC) is an effective and safe procedure, even in pediatric patients. In particular, LC has led to a reduction in the length of hospital stays and is associated with a low rate of postoperative complications 1 , 2 , 4 . The management of pediatric cholelithiasis remains controversial. In the absence of standardized guidelines, patients with clinical manifestations of disease generally undergo LC as adults, whereas the management of asymptomatic patients is not standardized and varies from center to center 2 , 5 . Therefore, this study seeks to highlight situations where a prophylactic cholecystectomy may be desirable based on pre, intra, and postoperative complications, length of hospital stay (LoS), and recurrences. MATERIALS AND METHODS We retrospectively reviewed the records of patients < 18 years of age admitted to our Pediatric Surgery Unit who underwent a cholecystectomy between 2011 and 2022. Data were extrapolated from the departmental database, and clinical notes were reviewed. Personal data (age and sex), anamnestic data (weight, BMI, and associated pathologies), presentation of cholelithiasis (asymptomatic or symptomatic), presurgery laboratory parameters (white blood cells, neutrophil percentage, C-reactive protein (CRP), hemoglobin, total bilirubin, direct bilirubin, indirect bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)), diagnostic and presurgical ultrasound imaging (evaluating the gallbladder, biliary tract, liver, pancreas, spleen, kidneys and any additions), type of surgery (laparoscopic, open, conversion), time of surgery, intraoperative complications, length of hospitalization, follow-up, postoperative complications and reoperations were examined. Ultrasounds were conducted in all patients for diagnostic purposes. Elective surgery was suggested for patients with symptomatic manifestations of cholelithiasis (biliary colic, acute cholecystitis, hepatocholangitis, hydrops of the gallbladder, acute pancreatitis, or cholangitis) and in asymptomatic patients with associated pathologies (thalassemia, CF, hereditary spherocytosis, sclerosing cholangitis, overweight and obesity). The outcomes measured included intraoperative complications, length of hospitalization, postoperative complications, and reinterventions. Five patient groups were created based on the presence or absence of cholelithiasis-associated disorders. The groups were: idiopathic/unknown etiology, hematologic (suffering from spherocytosis, thalassemia, leukemia, Gilbert syndrome or sickle cell disease), the CF group, the autoimmune group (due to the presence of celiac disease or sclerosing cholangitis), and the overweight/obese patient group. Statistical Analysis We conducted descriptive analyses stratified by disease group. Frequencies and percentages are reported for categorical variables The distribution of continuous variables by percentiles was assessed, specifically the median (50th percentile) and interquartile range (25th–75th percentile). SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) was for the statistical analyses. RESULTS Thirty-two patients, 21 females (65.63%) and 11 males (34.38%) admitted to our Pediatric Surgery Unit for elective cholecystectomy were included in the study. The median age was 14 years (range <1–17 years). Ten patients were idiopathic (31.25%), ten had hematological diseases (31.25%), four had CF (12.50%), two had autoimmune diseases (6.25%), and six patients were overweight or obese (18.75%). The associated pathologies are shown in Table 1 . The laboratory parameters were within the normal range in most idiopathic patients, with only the median CRP value being slightly increased (5.4 mg/L). In the autoimmune patients, the parameters were also within the normal range, except for a slight increase in the median values of ALT (39.5 U/L) and GGT (26 U/L). In the hematology patients, the median values of CRP (6.7 mg/dL), hemoglobin (9.55 g/dL), total bilirubin (2.99 mg/dL), direct bilirubin (0.53 mg/dL) and indirect bilirubin (2.45 mg/dL) were outside the normal ranges. In the overweight/obese group and patients with CF, the median values of the laboratory parameters were within normal ranges ( Table 2 ). Out of thirty-two patients, 26 were symptomatic (81.25%) and primarily presented with biliary colic, including recurrent episodes (53.12%). Severe manifestations of disease such as jaundice (6.25%), choledocholithiasis (6.25%), acute cholecystitis (6.25%), acute pancreatitis (3.13%), cholangitis (3.13%), and hydrops (3.13%) also occurred. In the idiopathic group, all ten patients were symptomatic, and six had biliary colic (60%). There was one case each of cholelithiasis, acute cholecystitis, acute pancreatitis, and gallbladder hydrops. Within the autoimmune group, one patient was symptomatic with biliary colic (50%), and the other was asymptomatic. In the group of ten hematologic patients, two were asymptomatic (20%), five manifested biliary colic (50%), two patients had jaundice (20%), and one had acute cholecystitis (10%). Of the four patients with CF, one was asymptomatic (25%), two presented with biliary colic (50%), and there was one case of cholangitis (25%). In the six overweight/obese patients, two were asymptomatic (33.3%), three presented with biliary colic (50%), and there was one case of choledocholithiasis (16.7%) ( Table 3 ). All patients underwent an abdominal ultrasound for the diagnosis of cholelithiasis. In addition to the presence of gallstones in all subjects, there were twenty-one cases of gallbladder distention (65.62%), four cases of a thickened gallbladder wall (12.5%), eight patients had dilated bile ducts (25%), there were eight cases of splenomegaly (25%), and four cases of hepatomegaly (12.5%). Among the ten idiopathic patients, there were eight cases of a distended gallbladder (80%), two cases of gallbladders with thickened walls (20%), and one case of splenomegaly (10%). Of the two autoimmune patients, one presented with gallbladder distention (50%), and the other had gallbladder wall thickening (50%). Among the ten hematologic patients, gallbladder distention was found in six patients (60%), a thickened gallbladder wall in one (10%), dilated bile ducts in five (50%), splenomegaly in five (50%), and hepatomegaly in two patients (20%). Among the patients with CF, three had gallbladder distention (75%), two had splenomegaly (50%), and one had hepatomegaly (25%). Within the overweight/obese group, gallbladder distention was found in three patients (50%) and hepatomegaly in one patient (16.7%). Ultrasound data are listed in Table 4 . Regarding the surgical complications ( Table 5 ), there were six cases of intraoperative complications (18.75%) due to adhesions between the gallbladder and adjacent organs, making removal difficult. These complications included one case of hydrops. For one patient, the LC was converted to open surgery (3.13%). Similarly, there was only one case of postoperative complications and the need for reoperation (3.13%). The median LoS for the entire sample was four days. Of the ten idiopathic patients, there were three cases with intraoperative complications (30%), one case requiring conversion from laparoscopic to open surgery (10%), and one patient requiring postoperative reoperation (10%). The median LoS for the idiopathic patients was four days. There were no surgical complications in the autoimmune group, and their median LoS was 3.5 days. Among the ten hematologic patients, there was one intraoperative complication (10%), and the median LoS for this group was six days. Among the four patients with CF, there were two cases of intraoperative complications (50%). The median LoS for this group was 8.5 days. No intraoperative complications were observed in the overweight/obese patients, who had a median LoS of 3.5 days. Surgical outcomes between the 26 symptomatic and 6 asymptomatic patients were compared. Among the symptomatic patients, there were five cases of intraoperative complications (19.2%), one case of conversion from laparoscopic to open surgery (3.84%), and one case with postoperative complications requiring reoperation (3.84%). The median LoS was four days. Among the asymptomatic patients, there were two cases with intraoperative complications (33.3%), and the median LoS was four days ( Table 6 ). DISCUSSION Compared to adults, cholelithiasis is rare in the pediatric population and idiopathic in 40% to 65% of cases 1 . While, several pathologies represent risk factors for pediatric cholelithiasis, in our study, idiopathic cases represented 31.25% of patients. However, we also found the presence of hematologic diseases (31.25%), CF (12.5%), and obesity (18.75%), which are similar to the results of a recent review 2 . Children with cholelithiasis tend to be asymptomatic in 33% to 40% of cases. The classic manifestation is biliary colic, but complications such as obstructive jaundice, choledocholithiasis, acute cholecystitis, acute pancreatitis, and cholangitis may also occur 3 . In our study, 18.75% of the patients were asymptomatic, and in the symptomatic patients, the most common manifestation was biliary colic. According to our analyses, patients with the most clinical manifestations and complications were idiopathic. This could be due to the prolonged and asymptomatic presence of the gallstones, which would have increased complications. These findings are aligned with a 2020 study, which concluded that symptomatic cholelithiasis is associated with a higher risk of complications (thus supporting early surgical treatment) 6 . Cholelithiasis is clinical diagnosed and confirmed by ultrasound 1,2 . In our study, an ultrasound was performed on every patient at the time of the diagnosis and before surgery. Among the ultrasound findings, numerous alterations were consistent with the presentation of cholelithiasis in the hematologic and CF groups. Pediatric cholelithiasis can be treated conservatively with UDCA, which is reserved primarily for asymptomatic patients but has shown limited results in stone dissolution 4 . For symptomatic patients, the gold standard is LC. Other indications for surgery include conservative treatment failure, choledocholithiasis, and the presence of one or more complications 1 . The principal issue in cholelithiasis management is the lack of standardized guidelines. Typically, symptomatic patients undergo surgery, but there is a notable gap in guidance regarding the treatment and optimal timing of surgery for asymptomatic patients. While recommendations for elective cholecystectomy are emerging for asymptomatic patients with risk factors, such as hemolytic diseases 1 and the presence of cholelithiasis at a very young age 3,7 , standardized guidelines have not yet been defined, even for patients with risk factors. Moreover, there is no recognized consensus regarding the indications for LC in asymptomatic children without specific risk factors 1 . In this study, 68.75% of patients had risk factors for cholelithiasis, and most progressed from being asymptomatic to symptomatic (72.7%). Hematologic disorders represented the largest group (31.25%). Despite the small number of cases, we found that most hematological patients were symptomatic with manifestations such as jaundice and acute cholecystitis. They also had ultrasound abnormalities consistent with cholelithiasis, and their intraoperative complications indicated chronic inflammation. Two asymptomatic hematologic patients in our study underwent elective LC and, aside from the absence of complications, we observed a reduction in the median LoS for these patients (5 days) compared to the hematologic group (6 days). These data are compatible with the idea that patients with hematologic diseases and asymptomatic cholelithiasis could benefit from prophylactic LC to reduce clinical symptoms, intraoperatively difficult situations, complications, and LoS. Several studies have suggested using preventive cholecystectomy in patients with hematologic disorders. Goodwin et al. found a reduced LoS and fewer surgical complications in patients with sickle cell disease who underwent elective/asymptomatic cholecystectomy than those who underwent emergency cholecystectomy 8 . Liu and colleagues found that surgical interventions for asymptomatic gallstones in patients with hereditary spherocytosis necessitating splenectomy were linked to a reduced risk of adverse outcomes 9 . Premawardhena et al. strongly advocated that elective LC should be considered in patients with thalassemia to prevent the onset of serious complications associated with LC in symptomatic patients 10 . The benefits of prophylactic LC in hematologic patients may also apply to the CF patients in our study. We observed the presence of ultrasound abnormalities and intraoperative difficulties due to chronic inflammatory conditions, even though LC was well tolerated by all CF patients in our study. Notably, one patient with CF and asymptomatic cholelithiasis who underwent elective surgery had a significant reduction in hospitalization duration (4 days) compared to the median of the CF group (8.5 days). Considering the clinical, ultrasound, and intraoperative findings, prophylactic LC in CF patients with asymptomatic cholelithiasis appears to be a feasible option for preventing complications and reducing hospital stays. Other reasons for considering prophylactic LC include the fact that CF patients may undergo lung transplantation and immunosuppressive therapy, which, in the case of chronic cholelithiasis, would pose an increased risk of cancer and cholecystitis 11,12 . Cholelithiasis alone also carries a risk of cancerous lesions, especially in association with a very young patient age 3,7 .Assis and colleagues found an increased risk of gallbladder and bile duct cancer in CF patients 13 . It has also been observed that lung transplant patients experience a significant incidence of cholecystitis with posttransplant gallstones. Hence, prophylactic treatment could be beneficial 12 . Similarly, Graham et al. observed that pretransplant cholecystectomy patients experience no morbidity or mortality. In contrast, those who underwent cholecystectomy after transplantation had significantly higher rates of morbidity, mortality, and graft loss 14 .Finally, several studies have shown patient improvement in lung function and quality of life following a cholecystectomy— after excluding patients with highly compromised lung functions from surgery 13,15 . As guidelines are currently lacking for asymptomatic patients, we would like to emphasize that 18.75% of the operated patients in our study were asymptomatic (two hematologic, one CF, one autoimmune, and two obese cases). In these patients, we found ultrasound signs consistent with cholelithiasis. Moreover, during surgery, 33.3% of asymptomatic patients had adhesions, indicating a chronic inflammatory state that could make removal of the bladder more difficult. In addition, unlike symptomatic patients, asymptomatic ones did not experience postoperative complications. While the median LoS was similar between the two groups, we observed LoS reductions in asymptomatic patients with CF and hematologic disorders. Study limitations Our study has several limitations, including its retrospective nature and the small cohort of patients. Further prospective research with more patients is needed to establish evidence-based guidelines for treating cholelithiasis in pediatric populations. CONCLUSIONS Patients with conditions predisposing them to the formation of gallstones, such as hematologic diseases and CF, should be considered for prophylactic cholecystectomy upon detection of gallstones to avoid facing complications and/or challenges during surgery. Furthermore, specific guidelines for managing asymptomatic patients with and without defined risk factors are needed, as medical therapeutic approaches have shown limited resolution outcomes. Abbreviations LC = Laparoscopic Cholecystectomy; CF = Cystic Fibrosis; UDCA = ursodeoxycholic acid; LOS = Length of Stay Declarations Statement of ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the (Burlo Garofolo) institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The (Burlo Garofolo) Institutional research committee waived the approval requirement due to the retrospective nature of the study. Conflicts of Interest: The authors declare no conflict of interest. Funding: This research received no external funding. Availability of data and material: The data that support the findings of this study are available on request from the corresponding author. Informed Consent Statement: Patient consent was waived due to the retrospective nature of the study. Statement of ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. References Wong MCY, Incerti F, Avanzini S, Palo F, Sertorio F, Damasio MB, Arrigo S, Gandullia P, Mattioli G. Cholelithiasis management in a third-level pediatric center: case series and literature review. Updates Surg. 2022 Jun;74(3):963-968. doi: 10.1007/s13304-021-01227-9. Epub 2022 Jan 30. PMID: 35094309. Papparella P, Nino F, Ferrante I, Cavaiuolo S. (2015). Colelitiasi. In M. Lima & G. Ruggeri (Eds.), Chirurgia Pediatrica (pp. 301-308). Edises Bhaumik K. Asymptomatic Cholelithiasis in Children: Management Dilemma. J Indian Assoc Pediatr Surg. 2021 Jul-Aug;26(4):228-233. doi: 10.4103/jiaps.JIAPS_107_20. Epub 2021 Jul 12. PMID: 34385765; PMCID: PMC8323576. Della Corte C, Falchetti D, Nebbia G, Calacoci M, Pastore M, Francavilla R, Marcellini M, Vajro P, Iorio R. Management of cholelithiasis in Italian children: a national multicenter study. World J Gastroenterol. 2008 Mar 7;14(9):1383-8. doi: 10.3748/wjg.14.1383. PMID: 18322952; PMCID: PMC2693686. Diez S, Müller H, Weiss C, Schellerer V, Besendörfer M. Cholelithiasis and cholecystitis in children and adolescents: Does this increasing diagnosis require a common guideline for pediatricians and pediatric surgeons? BMC Gastroenterol. 2021 Apr 21;21(1):186. doi: 10.1186/s12876-021-01772-y. PMID: 33882844; PMCID: PMC8061037. Cabrera Chamorro CC, Pabón Arteaga JS, Caicedo Paredes CA, Cabrera Bravo N, Villamil Giraldo CE, Chávez Betancourt G, Zarama Márquez RA, Rincón Torres CA. Cholelithiasis and associated complications in pediatric patients. Cir Pediatr. 2020 Oct 1;33(4):172-176. English, Spanish. PMID: 33016656. Kapoor VK. Cholecystectomy in patients with asymptomatic gallstones to prevent gall bladder cancer--the case against. Indian J Gastroenterol. 2006 May-Jun;25(3):152-4. PMID: 16877831. Goodwin EF, Partain PI, Lebensburger JD, Fineberg NS, Howard TH. Elective cholecystectomy reduces morbidity of cholelithiasis in pediatric sickle cell disease. Pediatr Blood Cancer. 2017 Jan;64(1):113-120. doi: 10.1002/pbc.26179. Epub 2016 Sep 19. PMID: 27643455. Liu Y, Jin S, Li Y, Xu R, Pang W, Wang K, Wang Z, Chen Y. Treatment of asymptomatic gallstones in children with hereditary spherocytosis requiring splenectomy. J Pediatr Surg. 2023 Apr;58(4):756-761. doi: 10.1016/j.jpedsurg.2022.11.012. Epub 2022 Nov 25. PMID: 36588038. Premawardhena A, Fernando R, Kumarage S, Nishad N, Goonatilleke D, Silva I, Mettananda S. Place for elective cholecystectomy for patients with severe thalassaemia: a retrospective case control study. BMC Res Notes. 2019 Apr 29;12(1):245. doi: 10.1186/s13104-019-4285-1. PMID: 31036075; PMCID: PMC6489186. Naderi AS, Farsian FN, Lee WM. Cholangiocarcinoma after lung transplantation in a patient with cystic fibrosis. Eur J Gastroenterol Hepatol. 2008 Nov;20(11):1115-7. doi: 10.1097/MEG.0b013e3282f4de7e. PMID: 19047845. Grass F, Schäfer M, Cristaudi A, Berutto C, Aubert JD, Gonzalez M, Demartines N, Ris HB, Soccal PM, Krueger T. Incidence and Risk Factors of Abdominal Complications After Lung Transplantation. World J Surg. 2015 Sep;39(9):2274-81. doi: 10.1007/s00268-015-3098-1. PMID: 26013207. Assis DN, Debray D. Gallbladder and bile duct disease in Cystic Fibrosis. J Cyst Fibros. 2017 Nov;16 Suppl 2:S62-S69. doi: 10.1016/j.jcf.2017.07.006. PMID: 28986023. Graham SM, Flowers JL, Schweitzer E, Bartlett ST, Imbembo AL. The utility of prophylactic laparoscopic cholecystectomy in transplant candidates. Am J Surg. 1995 Jan;169(1):44-8; discussion 48-9. doi: 10.1016/s0002-9610(99)80108-1. PMID: 7817997. Cogliandolo A, Patania M, Currò G, Chillè G, Magazzù G, Navarra G. Postoperative outcomes and quality of life in patients with cystic fibrosis undergoing laparoscopic cholecystectomy: a retrospective study. Surg Laparosc Endosc Percutan Tech. 2011 Jun;21(3):179-83. doi: 10.1097/SLE.0b013e318219a2b5. PMID: 21654302. Tables Table 1 : Pathologies associated with cholelithiasis detected in our study. ASSOCIATED PATHOLOGIES N° (%) Hematologic Diseases 10 (31.25) Cystic Fibrosis 4 (12.5) Autoimmune Diseases 2 (6.5) Overweight/Obesity None (idiopathic) 6 (18.75) 10 (31.25) N: number Table 2 : Laboratory parameters of the various groups using the 50th percentile value. Laboratory parameters Idiopathic n=10 Autoimmune n=2 Hematologic n=10 CF n=4 Obesity n=6 WBC (mm3) 8760 6040 8540 7500 8760 Neu (%) 58.75 58.9 58.2 63.75 58.75 PCR (mg/L) 5.4↑ 1.2 6.7↑ 1.2 5.4 Hb (g/dL) 13.8 12.3 9.55↓ 12.95 13.8 Bil-tot (mg/dL) 0.80 0.3 2.99↑ 0.68 0.80 Bil-dir (mg/dL) 0.21 0.11 0.53↑ 0.18 0.21 Bil-ind (mg/dL) 0.59 0.21 2.45↑ 0.5 0.59 AST-GOT (U/L) 19.5 32.5 30.5 21 19.5 ALT-GPT (U/L) 21 39.5 ↑ 15 17.5 21 GGT (U/L) 17 26 ↑ 24 12.5 17 ALP (U/L) 71 165.5 224 177.5 71 CF: Cystic Fibrosis; n: number Table 3 : Clinical Characteristics of Children with Cholelithiasis Clinical characteristics Total n=32 n (%) Idiopathic n=10 n (%) Autoimmune n=2 n (%) Hematologic n=10 n (%) CF n=4 n (%) Obesity n=6 n (%) Asymptomatic 6 (18.75) — 1 (50.0) 2 (20.0) 1 (25.0) 2 (33.3) Biliary Colic only 17 (53.12) 6 (60.0) 1 (50.0) 5 (50.0) 2 (50.0) 3 (50.0) Complications Jaundice 2 (6.25) — — 2 (20.0) — — Choledocholithiasis 2 (6.25) 1 (10.0) — — — 1 (16.7) Acute Cholecystitis 2 (6.25) 1 (10.0) — 1 (10.0) — — Acute Pancreatitis 1 (3.13) 1 (10.0) — — — — Cholangitis 1 (3.13) — — — 1 (25.0) — Hydrops 1 (3.13) 1 (3.13) — — — — CF: Cystic Fibrosis; n: number Table 5: Surgical Outcomes Surgical complications Total n=32 n (%) Idiopathic n=10 n (%) Autoimmune n=2 n (%) Hematologic n=10 n (%) CF n=4 n (%) Obesity n=6 n (%) Intraoperative complications 6 (18.75) 3 (30.0) — 1 (10.0) 2 (50.0) — Conversions from lap to open 1 (3.13) 1 (10.0) — — — — Postoperative complications 1 (3.13) 1 (10.0) — — — — Median length of stay (days) 4 4 3.5 6 8.5 3.5 CF: Cystic Fibrosis; n: number Table 6: Comparison of outcomes between symptomatic and asymptomatic patients Symptomatic n (%) Asymptomatic n (%) Numerosity 26 6 Intraoperative complication 5 (19.2) 2 (33.3) Conversion from lap to open 1 (3.84) — Postoperative complication 1 (3.84) — Median length of stay (days) 4 4 n: number Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4144989","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":282368731,"identity":"b77c1cd2-1ab0-4fca-8f37-a9f0fc553e21","order_by":0,"name":"Davina Scalise","email":"","orcid":"","institution":"University of Trieste, Faculty of Medicine and Surgery, Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Davina","middleName":"","lastName":"Scalise","suffix":""},{"id":282368732,"identity":"e5018b60-ba28-4cb3-9127-6810ae2969c0","order_by":1,"name":"Alessandro Boscarelli","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYDACCQglZwCmDCwY2Ajp4IFqMTZgYAZpkWBgI6QHpiVxA1gLyFJCWuylmw9/+FFzL307e//RDT8KJBj45BsI2CJzLE2y51hx7s6ew2w3e4hzWI4ZMwNbQu6GG8lsN3iI1GL8meFfQroBUMvNP0RqMZBmbEtIAGm5TZwtd4B+6e1LMNxw5rDZbRkDCR42tgT8Wthng0LsW4K8wfHGZzff/LGRk28+QMAaDGtJVD8KRsEoGAWjABsAADteOYC/dAhtAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-1934-1764","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":true,"prefix":"","firstName":"Alessandro","middleName":"","lastName":"Boscarelli","suffix":""},{"id":282368733,"identity":"c091490e-69eb-4aa0-ad68-7385f2537b50","order_by":2,"name":"Manuela Giangreco","email":"","orcid":"https://orcid.org/0000-0002-4479-3087","institution":"Clinical Epidemiology and Public Health Research Unit, Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Manuela","middleName":"","lastName":"Giangreco","suffix":""},{"id":282368734,"identity":"124b415f-1b0f-431e-8cbd-4c1b2631ae51","order_by":3,"name":"Daniela Codrich","email":"","orcid":"https://orcid.org/0000-0003-2925-8876","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Daniela","middleName":"","lastName":"Codrich","suffix":""},{"id":282368735,"identity":"325e4d5c-1038-489e-b043-db3637bb0896","order_by":4,"name":"Maria-Grazia Scarpa","email":"","orcid":"","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Maria-Grazia","middleName":"","lastName":"Scarpa","suffix":""},{"id":282368736,"identity":"480ab3d5-7bc5-4901-af8c-871f7100e18e","order_by":5,"name":"Marianna Iaquinto","email":"","orcid":"","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Marianna","middleName":"","lastName":"Iaquinto","suffix":""},{"id":282368737,"identity":"7105f51e-19a6-45df-a922-14c384ad0f8d","order_by":6,"name":"Camilla Pagliara","email":"","orcid":"","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Camilla","middleName":"","lastName":"Pagliara","suffix":""},{"id":282368738,"identity":"e702a92d-9407-48ae-aab3-057ee95770e2","order_by":7,"name":"Damiana Olenik","email":"","orcid":"","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Damiana","middleName":"","lastName":"Olenik","suffix":""},{"id":282368739,"identity":"a747776b-6f56-43c2-98a7-bbd0ea6522e8","order_by":8,"name":"Edoardo Guida","email":"","orcid":"https://orcid.org/0000-0003-4901-2515","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Edoardo","middleName":"","lastName":"Guida","suffix":""},{"id":282368740,"identity":"0d7e8d61-052f-4db1-bd71-b6fad2d88b88","order_by":9,"name":"Jurgen Schleef","email":"","orcid":"https://orcid.org/0000-0001-9754-2479","institution":"Department of Pediatric Surgery and Urology, Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", 34137 Trieste, Italy","correspondingAuthor":false,"prefix":"","firstName":"Jurgen","middleName":"","lastName":"Schleef","suffix":""}],"badges":[],"createdAt":"2024-03-21 16:52:40","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4144989/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4144989/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53357252,"identity":"e38dfe3f-00de-460e-96f8-74ede18da6dd","added_by":"auto","created_at":"2024-03-25 03:38:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":275902,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4144989/v1/6134b041-00aa-475d-8199-d6e04d767acc.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eManagement of childhood cholelithiasis: experience at a third-level pediatric surgical center\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCholelithiasis is a rare pediatric disease, but its incidence is increasing. It is idiopathic in 40\u0026ndash;65% of patients, but in the remaining cases, it is associated with hemolytic disorders, obesity, and diseases such as cystic fibrosis (CF). Children with cholelithiasis are asymptomatic in 33\u0026ndash;40% of cases. Otherwise, they may present with classic biliary colic or nonspecific abdominal pain. Possible complications include acute cholecystitis, acute pancreatitis, hydrops of the gallbladder, obstructive jaundice, cholangitis, and cancerous lesions\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Treatment options include a conservative approach using ursodeoxycholic acid (UDCA), but results have been neither satisfactory nor definitive. In contrast, laparoscopic cholecystectomy (LC) is an effective and safe procedure, even in pediatric patients. In particular, LC has led to a reduction in the length of hospital stays and is associated with a low rate of postoperative complications\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe management of pediatric cholelithiasis remains controversial. In the absence of standardized guidelines, patients with clinical manifestations of disease generally undergo LC as adults, whereas the management of asymptomatic patients is not standardized and varies from center to center\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Therefore, this study seeks to highlight situations where a prophylactic cholecystectomy may be desirable based on pre, intra, and postoperative complications, length of hospital stay (LoS), and recurrences.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eWe retrospectively reviewed the records of patients\u0026thinsp;\u0026lt;\u0026thinsp;18 years of age admitted to our Pediatric Surgery Unit who underwent a cholecystectomy between 2011 and 2022. Data were extrapolated from the departmental database, and clinical notes were reviewed. Personal data (age and sex), anamnestic data (weight, BMI, and associated pathologies), presentation of cholelithiasis (asymptomatic or symptomatic), presurgery laboratory parameters (white blood cells, neutrophil percentage, C-reactive protein (CRP), hemoglobin, total bilirubin, direct bilirubin, indirect bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)), diagnostic and presurgical ultrasound imaging (evaluating the gallbladder, biliary tract, liver, pancreas, spleen, kidneys and any additions), type of surgery (laparoscopic, open, conversion), time of surgery, intraoperative complications, length of hospitalization, follow-up, postoperative complications and reoperations were examined. Ultrasounds were conducted in all patients for diagnostic purposes. Elective surgery was suggested for patients with symptomatic manifestations of cholelithiasis (biliary colic, acute cholecystitis, hepatocholangitis, hydrops of the gallbladder, acute pancreatitis, or cholangitis) and in asymptomatic patients with associated pathologies (thalassemia, CF, hereditary spherocytosis, sclerosing cholangitis, overweight and obesity). The outcomes measured included intraoperative complications, length of hospitalization, postoperative complications, and reinterventions.\u003c/p\u003e \u003cp\u003eFive patient groups were created based on the presence or absence of cholelithiasis-associated disorders. The groups were: idiopathic/unknown etiology, hematologic (suffering from spherocytosis, thalassemia, leukemia, Gilbert syndrome or sickle cell disease), the CF group, the autoimmune group (due to the presence of celiac disease or sclerosing cholangitis), and the overweight/obese patient group.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eWe conducted descriptive analyses stratified by disease group. Frequencies and percentages are reported for categorical variables The distribution of continuous variables by percentiles was assessed, specifically the median (50th percentile) and interquartile range (25th\u0026ndash;75th percentile). SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) was for the statistical analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThirty-two patients, 21 females (65.63%) and 11 males (34.38%) admitted to our Pediatric Surgery Unit for elective cholecystectomy were included in the study. The median age was 14 years (range \u0026lt;1–17 years). Ten patients were idiopathic (31.25%), ten had hematological diseases (31.25%), four had CF (12.50%), two had autoimmune diseases (6.25%), and six patients were overweight or obese (18.75%). The associated pathologies are shown in \u003cem\u003eTable 1\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eThe laboratory parameters were within the normal range in most idiopathic patients, with only the median CRP value being slightly increased (5.4 mg/L). In the autoimmune patients, the parameters were also within the normal range, except for a slight increase in the median values of ALT (39.5 U/L) and GGT (26 U/L). In the hematology patients, the median values of CRP (6.7 mg/dL), hemoglobin (9.55 g/dL), total bilirubin (2.99 mg/dL), direct bilirubin (0.53 mg/dL) and indirect bilirubin (2.45 mg/dL) were outside the normal ranges. In the overweight/obese group and patients with CF, the median values of the laboratory parameters were within normal ranges (\u003cem\u003eTable 2\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eOut of thirty-two patients, 26 were symptomatic (81.25%) and primarily presented with biliary colic, including recurrent episodes (53.12%). Severe manifestations of disease such as jaundice (6.25%), choledocholithiasis (6.25%), acute cholecystitis (6.25%), acute pancreatitis (3.13%), cholangitis (3.13%), and hydrops (3.13%) also occurred. In the idiopathic group, all ten patients were symptomatic, and six had biliary colic (60%). There was one case each of cholelithiasis, acute cholecystitis, acute pancreatitis, and gallbladder hydrops. Within the autoimmune group, one patient was symptomatic with biliary colic (50%), and the other was asymptomatic. In the group of ten hematologic patients, two were asymptomatic (20%), five manifested biliary colic (50%), two patients had jaundice (20%), and one had acute cholecystitis (10%). Of the four patients with CF, one was asymptomatic (25%), two presented with biliary colic (50%), and there was one case of cholangitis (25%). In the six overweight/obese patients, two were asymptomatic (33.3%), three presented with biliary colic (50%), and there was one case of choledocholithiasis (16.7%) (\u003cem\u003eTable 3\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eAll patients underwent an abdominal ultrasound for the diagnosis of cholelithiasis. In addition to the presence of gallstones in all subjects, there were twenty-one cases of gallbladder distention (65.62%), four cases of a thickened gallbladder wall (12.5%), eight patients had dilated bile ducts (25%), there were eight cases of splenomegaly (25%), and four cases of hepatomegaly (12.5%).\u003c/p\u003e\n\u003cp\u003eAmong the ten idiopathic patients, there were eight cases of a distended gallbladder (80%), two cases of gallbladders with thickened walls (20%), and one case of splenomegaly (10%). Of the two autoimmune patients, one presented with gallbladder distention (50%), and the other had gallbladder wall thickening (50%). Among the ten hematologic patients, gallbladder distention was found in six patients (60%), a thickened gallbladder wall in one (10%), dilated bile ducts in five (50%), splenomegaly in five (50%), and hepatomegaly in two patients (20%). Among the patients with CF, three had gallbladder distention (75%), two had splenomegaly (50%), and one had hepatomegaly (25%). Within the overweight/obese group, gallbladder distention was found in three patients (50%) and hepatomegaly in one patient (16.7%). Ultrasound data are listed in \u003cem\u003eTable 4\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eRegarding the surgical complications (\u003cem\u003eTable 5\u003c/em\u003e), there were six cases of intraoperative complications (18.75%) due to adhesions between the gallbladder and adjacent organs, making removal difficult. These complications included one case of hydrops. For one patient, the LC was converted to open surgery (3.13%). Similarly, there was only one case of postoperative complications and the need for reoperation (3.13%). The median LoS for the entire sample was four days. Of the ten idiopathic patients, there were three cases with intraoperative complications (30%), one case requiring conversion from laparoscopic to open surgery (10%), and one patient requiring postoperative reoperation (10%). The median LoS for the idiopathic patients was four days. There were no surgical complications in the autoimmune group, and their median LoS was 3.5 days. Among the ten hematologic patients, there was one intraoperative complication (10%), and the median LoS for this group was six days. Among the four patients with CF, there were two cases of intraoperative complications (50%). The median LoS for this group was 8.5 days. No intraoperative complications were observed in the overweight/obese patients, who had a median LoS of 3.5 days.\u003c/p\u003e\n\u003cp\u003eSurgical outcomes between the 26 symptomatic and 6 asymptomatic patients were compared. Among the symptomatic patients, there were five cases of intraoperative complications (19.2%), one case of conversion from laparoscopic to open surgery (3.84%), and one case with postoperative complications requiring reoperation (3.84%). The median LoS was four days. Among the asymptomatic patients, there were two cases with intraoperative complications (33.3%), and the median LoS was four days (\u003cem\u003eTable 6\u003c/em\u003e).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eCompared to adults, cholelithiasis is rare in the pediatric population and idiopathic in 40% to 65% of cases\u003csup\u003e1\u003c/sup\u003e. While, several pathologies represent risk factors for pediatric cholelithiasis, in our study, idiopathic cases represented 31.25% of patients. However, we also found the presence of hematologic diseases (31.25%), CF (12.5%), and obesity (18.75%), which are similar to the results of a recent review\u003csup\u003e2\u003c/sup\u003e. Children with cholelithiasis tend to be asymptomatic in 33% to 40% of cases. The classic manifestation is biliary colic, but complications such as obstructive jaundice, choledocholithiasis, acute cholecystitis, acute pancreatitis, and cholangitis may also occur\u003csup\u003e3\u003c/sup\u003e. In our study, 18.75% of the patients were asymptomatic, and in the symptomatic patients, the most common manifestation was biliary colic. According to our analyses, patients with the most clinical manifestations and complications were idiopathic. This could be due to the prolonged and asymptomatic presence of the gallstones, which would have increased complications. These findings are aligned with a 2020 study, which concluded that symptomatic cholelithiasis is associated with a higher risk of complications (thus supporting early surgical treatment)\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eCholelithiasis is clinical diagnosed and confirmed by ultrasound\u003csup\u003e1,2\u003c/sup\u003e. In our study, an ultrasound was performed on every patient at the time of the diagnosis and before surgery. Among the ultrasound findings, numerous alterations were consistent with the presentation of cholelithiasis in the hematologic and CF groups.\u003c/p\u003e\n\u003cp\u003ePediatric cholelithiasis can be treated conservatively with UDCA, which is reserved primarily for asymptomatic patients but has shown limited results in stone dissolution\u003csup\u003e4\u003c/sup\u003e. For symptomatic patients, the gold standard is LC. Other indications for surgery include conservative treatment failure, choledocholithiasis, and the presence of one or more complications\u003csup\u003e1\u003c/sup\u003e. The principal issue in cholelithiasis management is the lack of standardized guidelines. Typically, symptomatic patients undergo surgery, but there is a notable gap in guidance regarding the treatment and optimal timing of surgery for asymptomatic patients. While recommendations for elective cholecystectomy are emerging for asymptomatic patients with risk factors, such as hemolytic diseases\u003csup\u003e1\u003c/sup\u003e and the presence of cholelithiasis at a very young age\u003csup\u003e3,7\u003c/sup\u003e, standardized guidelines have not yet been defined, even for patients with risk factors. Moreover, there is no recognized consensus regarding the indications for LC in asymptomatic children without specific risk factors\u003csup\u003e1\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn this study, 68.75% of patients had risk factors for cholelithiasis, and most progressed from being asymptomatic to symptomatic (72.7%). Hematologic disorders represented the largest group (31.25%). Despite the small number of cases, we found that most hematological patients were symptomatic with manifestations such as jaundice and acute cholecystitis. They also had ultrasound abnormalities consistent with cholelithiasis, and their intraoperative complications indicated chronic inflammation. Two asymptomatic hematologic patients in our study underwent elective LC and, aside from the absence of complications, we observed a reduction in the median LoS for these patients (5 days) compared to the hematologic group (6 days). These data are compatible with the idea that patients with hematologic diseases and asymptomatic cholelithiasis could benefit from prophylactic LC to reduce clinical symptoms, intraoperatively difficult situations, complications, and LoS.\u003c/p\u003e\n\u003cp\u003eSeveral studies have suggested using preventive cholecystectomy in patients with hematologic disorders. Goodwin et al. found a reduced LoS and fewer surgical complications in patients with sickle cell disease who underwent elective/asymptomatic cholecystectomy than those who underwent emergency cholecystectomy\u003csup\u003e8\u003c/sup\u003e. Liu and colleagues found that surgical interventions for asymptomatic gallstones in patients with hereditary spherocytosis necessitating splenectomy were linked to a reduced risk of adverse outcomes\u003csup\u003e9\u003c/sup\u003e. Premawardhena et al. strongly advocated that elective LC should be considered in patients with thalassemia to prevent the onset of serious complications associated with LC in symptomatic patients\u003csup\u003e10\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe benefits of prophylactic LC in hematologic patients may also apply to the CF patients in our study. We observed the presence of ultrasound abnormalities and intraoperative difficulties due to chronic inflammatory conditions, even though LC was well tolerated by all CF patients in our study. Notably, one patient with CF and asymptomatic cholelithiasis who underwent elective surgery had a significant reduction in hospitalization duration (4 days) compared to the median of the CF group (8.5 days).\u0026nbsp;Considering the clinical, ultrasound, and intraoperative findings, prophylactic LC in CF patients with asymptomatic cholelithiasis appears to be a feasible option for preventing complications and reducing hospital stays. Other reasons for considering prophylactic LC include the fact that CF patients may undergo lung transplantation and immunosuppressive therapy, which, in the case of chronic cholelithiasis, would pose an increased risk of cancer and cholecystitis\u003csup\u003e11,12\u003c/sup\u003e. Cholelithiasis alone also carries a risk of cancerous lesions, especially in association with a very young patient age\u003csup\u003e3,7\u003c/sup\u003e.Assis and colleagues found an increased risk of gallbladder and bile duct cancer in CF patients\u003csup\u003e13\u003c/sup\u003e. It has also been observed that lung transplant patients experience a significant incidence of cholecystitis with posttransplant gallstones. Hence, prophylactic treatment could be beneficial\u003csup\u003e12\u003c/sup\u003e. Similarly, Graham et al. observed that pretransplant cholecystectomy patients experience no morbidity or mortality. In contrast, those who underwent cholecystectomy after transplantation had significantly higher rates of morbidity, mortality, and graft loss\u003csup\u003e14\u003c/sup\u003e.Finally, several studies have shown patient improvement in lung function and quality of life following a cholecystectomy— after excluding patients with highly compromised lung functions from surgery\u003csup\u003e13,15\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAs guidelines are currently lacking for asymptomatic patients, we would like to emphasize that 18.75% of the operated patients in our study were asymptomatic (two hematologic, one CF, one autoimmune, and two obese cases). In these patients, we found ultrasound signs consistent with cholelithiasis. Moreover, during surgery, 33.3% of asymptomatic patients had adhesions, indicating a chronic inflammatory state that could make removal of the bladder more difficult. In addition, unlike symptomatic patients, asymptomatic ones did not experience postoperative complications. While the median LoS was similar between the two groups, we observed LoS reductions in asymptomatic patients with CF and hematologic disorders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study has several limitations, including its retrospective nature and the small cohort of patients. Further prospective research with more patients is needed to establish evidence-based guidelines for treating cholelithiasis in pediatric populations.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003ePatients with conditions predisposing them to the formation of gallstones, such as hematologic diseases and CF, should be considered for prophylactic cholecystectomy upon detection of gallstones to avoid facing complications and/or challenges during surgery. Furthermore, specific guidelines for managing asymptomatic patients with and without defined risk factors are needed, as medical therapeutic approaches have shown limited resolution outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eLC = Laparoscopic Cholecystectomy; CF = Cystic Fibrosis; UDCA = ursodeoxycholic acid; LOS = Length of Stay\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatement of ethics approval:\u003c/strong\u003e All procedures performed in studies involving human participants were in accordance with the ethical standards of the (Burlo Garofolo) institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The (Burlo Garofolo) Institutional research committee waived the approval requirement due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u003c/strong\u003e The data that support the findings of this study are available on request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement:\u003c/strong\u003e Patient consent was waived due to the retrospective nature of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of ethics approval:\u003c/strong\u003e All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and\u003c/p\u003e\n\u003cp\u003ewith the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWong MCY, Incerti F, Avanzini S, Palo F, Sertorio F, Damasio MB, Arrigo S, Gandullia P, Mattioli G. Cholelithiasis management in a third-level pediatric center: case series and literature review. Updates Surg. 2022 Jun;74(3):963-968. doi: 10.1007/s13304-021-01227-9. Epub 2022 Jan 30. PMID: 35094309.\u003c/li\u003e\n \u003cli\u003ePapparella P, Nino F, Ferrante I, Cavaiuolo S. (2015). Colelitiasi. In M. Lima \u0026amp; G. Ruggeri (Eds.), Chirurgia Pediatrica (pp. 301-308). Edises\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBhaumik K. Asymptomatic Cholelithiasis in Children: Management Dilemma. J Indian Assoc Pediatr Surg. 2021 Jul-Aug;26(4):228-233. doi: 10.4103/jiaps.JIAPS_107_20. Epub 2021 Jul 12. PMID: 34385765; PMCID: PMC8323576.\u003c/li\u003e\n \u003cli\u003eDella Corte C, Falchetti D, Nebbia G, Calacoci M, Pastore M, Francavilla R, Marcellini M, Vajro P, Iorio R. Management of cholelithiasis in Italian children: a national multicenter study.\u0026nbsp;World J Gastroenterol. 2008 Mar 7;14(9):1383-8. doi: 10.3748/wjg.14.1383. PMID: 18322952; PMCID: PMC2693686.\u003c/li\u003e\n \u003cli\u003eDiez S, M\u0026uuml;ller H, Weiss C, Schellerer V, Besend\u0026ouml;rfer M. Cholelithiasis and cholecystitis in children and adolescents: Does this increasing diagnosis require a common guideline for pediatricians and pediatric surgeons? BMC Gastroenterol. 2021 Apr 21;21(1):186. doi: 10.1186/s12876-021-01772-y. PMID: 33882844; PMCID: PMC8061037.\u003c/li\u003e\n \u003cli\u003eCabrera Chamorro CC, Pab\u0026oacute;n Arteaga JS, Caicedo Paredes CA, Cabrera Bravo N, Villamil Giraldo CE, Ch\u0026aacute;vez Betancourt G, Zarama M\u0026aacute;rquez RA, Rinc\u0026oacute;n Torres CA.\u0026nbsp;Cholelithiasis and associated complications in pediatric patients. Cir Pediatr. 2020 Oct 1;33(4):172-176. English, Spanish. PMID: 33016656.\u003c/li\u003e\n \u003cli\u003eKapoor VK. Cholecystectomy in patients with asymptomatic gallstones to prevent gall bladder cancer--the case against. Indian J Gastroenterol. 2006 May-Jun;25(3):152-4. PMID: 16877831.\u003c/li\u003e\n \u003cli\u003eGoodwin EF, Partain PI, Lebensburger JD, Fineberg NS, Howard TH. Elective cholecystectomy reduces morbidity of cholelithiasis in pediatric sickle cell disease. Pediatr Blood Cancer. 2017 Jan;64(1):113-120. doi: 10.1002/pbc.26179. Epub 2016 Sep 19. PMID: 27643455.\u003c/li\u003e\n \u003cli\u003eLiu Y, Jin S, Li Y, Xu R, Pang W, Wang K, Wang Z, Chen Y. Treatment of asymptomatic gallstones in children with hereditary spherocytosis requiring splenectomy. J Pediatr Surg. 2023 Apr;58(4):756-761. doi: 10.1016/j.jpedsurg.2022.11.012. Epub 2022 Nov 25. PMID: 36588038.\u003c/li\u003e\n \u003cli\u003ePremawardhena A, Fernando R, Kumarage S, Nishad N, Goonatilleke D, Silva I, Mettananda S. Place for elective cholecystectomy for patients with severe thalassaemia: a retrospective case control study. BMC Res Notes. 2019 Apr 29;12(1):245. doi: 10.1186/s13104-019-4285-1. PMID: 31036075; PMCID: PMC6489186.\u003c/li\u003e\n \u003cli\u003eNaderi AS, Farsian FN, Lee WM. Cholangiocarcinoma after lung transplantation in a patient with cystic fibrosis. Eur J Gastroenterol Hepatol. 2008 Nov;20(11):1115-7. doi: 10.1097/MEG.0b013e3282f4de7e. PMID: 19047845.\u003c/li\u003e\n \u003cli\u003eGrass F, Sch\u0026auml;fer M, Cristaudi A, Berutto C, Aubert JD, Gonzalez M, Demartines N, Ris HB, Soccal PM, Krueger T. Incidence and Risk Factors of Abdominal Complications After Lung Transplantation. World J Surg. 2015 Sep;39(9):2274-81. doi: 10.1007/s00268-015-3098-1. PMID: 26013207.\u003c/li\u003e\n \u003cli\u003eAssis DN, Debray D. Gallbladder and bile duct disease in Cystic Fibrosis. J Cyst Fibros. 2017 Nov;16 Suppl 2:S62-S69. doi: 10.1016/j.jcf.2017.07.006. PMID: 28986023.\u003c/li\u003e\n \u003cli\u003eGraham SM, Flowers JL, Schweitzer E, Bartlett ST, Imbembo AL. The utility of prophylactic laparoscopic cholecystectomy in transplant candidates. Am J Surg. 1995 Jan;169(1):44-8; discussion 48-9. doi: 10.1016/s0002-9610(99)80108-1. PMID: 7817997.\u003c/li\u003e\n \u003cli\u003eCogliandolo A, Patania M, Curr\u0026ograve; G, Chill\u0026egrave; G, Magazz\u0026ugrave; G, Navarra G. Postoperative outcomes and quality of life in patients with cystic fibrosis undergoing laparoscopic cholecystectomy: a retrospective study. Surg Laparosc Endosc Percutan Tech. 2011 Jun;21(3):179-83. doi: 10.1097/SLE.0b013e318219a2b5. PMID: 21654302.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cem\u003eTable\u0026nbsp;\u003c/em\u003e\u003cem\u003e1\u003c/em\u003e\u003cem\u003e:\u003c/em\u003e\u003cem\u003e\u0026nbsp;Pathologies associated with cholelithiasis detected in our study.\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"284\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eASSOCIATED PATHOLOGIES\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u0026deg; (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHematologic Diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (31.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCystic Fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAutoimmune Diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOverweight/Obesity\u003c/p\u003e\n \u003cp\u003eNone (idiopathic)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 (18.75)\u003c/p\u003e\n \u003cp\u003e10 (31.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;N: \u0026nbsp;number\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable\u0026nbsp;\u003c/em\u003e\u003cem\u003e2\u003c/em\u003e\u003cem\u003e:\u003c/em\u003e\u003cem\u003e\u0026nbsp;Laboratory parameters of the various groups using the 50th percentile value.\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"85%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eLaboratory parameters\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eIdiopathic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=10\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAutoimmune\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; n=2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eHematologic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=10\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eCF\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=4\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eObesity\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=6\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eWBC (mm3)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e8760\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e6040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e8540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e7500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e8760\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eNeu (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e58.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e58.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e58.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e63.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e58.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePCR (mg/L)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e5.4\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e6.7\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eHb (g/dL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e13.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e9.55\u0026darr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e12.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eBil-tot (mg/dL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e0.80\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e2.99\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eBil-dir (mg/dL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e0.53\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eBil-ind (mg/dL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e0.59\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e2.45\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAST-GOT (U/L)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e19.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e32.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e30.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e19.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eALT-GPT (U/L)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e39.5\u0026nbsp;\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eGGT (U/L)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e26\u0026nbsp;\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eALP (U/L)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e165.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e177.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eCF: Cystic Fibrosis; n: number \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable\u0026nbsp;\u003c/em\u003e\u003cem\u003e3\u003c/em\u003e\u003cem\u003e:\u003c/em\u003e\u003cem\u003e\u0026nbsp;Clinical Characteristics of Children with Cholelithiasis\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"85%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eClinical characteristics\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eTotal\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=32\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eIdiopathic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=10\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAutoimmune\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eHematologic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=10\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eCF\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=4\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eObesity\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=6\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAsymptomatic\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e6 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eBiliary Colic only\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e17 (53.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e6\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e5\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e2 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e3\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eComplications\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eJaundice\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e2 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eCholedocholithiasis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e2 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAcute Cholecystitis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e2 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAcute Pancreatitis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eCholangitis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eHydrops\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cem\u003eCF: Cystic Fibrosis; n: number\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cimg 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\"\u003e\u003c/em\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eTable 5: Surgical Outcomes\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"101%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eSurgical complications\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eTotal\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=32\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eIdiopathic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=10\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAutoimmune\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eHematologic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=10\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eCF\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=4\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eObesity\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en=6\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eIntraoperative\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ecomplications\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e6 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e3 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e2 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eConversions\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003efrom lap to open\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePostoperative\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ecomplications\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMedian length of stay (days)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eCF: Cystic Fibrosis; n: number\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;Table 6: Comparison of outcomes between symptomatic and asymptomatic patients\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"76%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.29896907216495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eSymptomatic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAsymptomatic\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.29896907216495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eNumerosity\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e26\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.29896907216495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eIntraoperative complication\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e5 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e2 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.29896907216495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eConversion from lap to open\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.29896907216495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePostoperative complication\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.29896907216495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMedian length of stay (days)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;n: number\u003c/em\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"IRCCS Materno Infantile Burlo Garofolo","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cystic fibrosis, Hematological disorders, Symptomatic cholelithiasis, Children, Management","lastPublishedDoi":"10.21203/rs.3.rs-4144989/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4144989/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCholelithiasis is increasing in the pediatric population. While its etiology is primarily idiopathic, it is often related to underlying diseases, and a significant number of patients may be asymptomatic. There are currently no guidelines for the management of asymptomatic patients with both cholelithiasis and a predisposing condition. Therefore, this study seeks to highlight situations where prophylactic cholecystectomy may be desirable based on pre, intra, and postoperative complications, length of hospital stay, and disease recurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe retrospectively reviewed the medical records of patients who underwent elective laparoscopic cholecystectomy between October 2011 and September 2022. Data, including clinical presentation at the time of diagnosis and admission, imaging, treatments, complications, and length of hospital stay, were collected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThirty-two patients (21 females and 11 males) were included in the study. The median age was 14 years (range \u0026lt;1–17). Five different groups of patients were identified based on associated pathologies. Ten patients had hematologic disease (31.25%), four had cystic fibrosis (12.5%), six were overweight or obese (18.75%), two had an autoimmune disease (6.25%), and ten had no underlying disease (31.25%). Twenty-six patients were symptomatic (81.25%), and six were asymptomatic (18.75%). The idiopathic etiology group was entirely symptomatic. All patients underwent a laparoscopic cholecystectomy. There was one patient (in the idiopathic etiology group) who required conversion from laparoscopy to open surgery and a reintervention (3.13%). Hematologic and cystic fibrosis patients with asymptomatic cholelithiasis had a shorter length of hospital stay than patients with the same condition who progressed from asymptomatic to symptomatic gallstone disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003ePatients with cystic fibrosis and hematologic diseases who have concomitant asymptomatic cholelithiasis may benefit from early laparoscopic cholecystectomy, which could reduce the probability of surgical and postsurgical complications and shorten the length of hospital stays.\u003c/p\u003e","manuscriptTitle":"Management of childhood cholelithiasis: experience at a third-level pediatric surgical center","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-25 03:30:06","doi":"10.21203/rs.3.rs-4144989/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4bacb0c8-b2b4-415d-be57-2d1dd352f863","owner":[],"postedDate":"March 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29733276,"name":"Pediatrics"}],"tags":[],"updatedAt":"2024-03-25T03:30:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-25 03:30:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4144989","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4144989","identity":"rs-4144989","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}