Seminars in Pediatric Surgery 25 (2016) 225–231

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Seminars in Pediatric Surgery

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Gallbladder disease in children

David H. Rothstein, MD, MSa,b, Carroll M. Harmon, MD, PhDa,b,n a Department of Pediatric Surgery, Women and Children's Hospital of Buffalo, 219 Bryant St, Buffalo, New York 14222 b Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York article info abstract

Biliary disease in children has changed over the past few decades, with a marked rise in incidence— — Keywords: perhaps most related to the parallel rise in pediatric obesity as well as a rise in cholecystectomy rates. In Cholelithiasis addition to stone disease (cholelithiasis), acalculous causes of gallbladder pain such as biliary dyskinesia, Biliary dyskinesia also appear to be on the rise and present diagnostic and treatment conundrums to surgeons. Pediatric biliary disease & 2016 Elsevier Inc. All rights reserved. Gallbladder Acalculous cholecystitis Critical view of safety

Introduction In these patients, the etiology of the gallstones is supersaturation of bile due to excess cholesterol, and this variety is the most The spectrum of pediatric biliary tract disease continues to common type of stone encountered in children today. The prox- change. Although congenital and neonatal conditions such as imate cause of cholesterol stones is bile that is saturated with biliary atresia and choledochal cysts remain relatively constant, cholesterol beyond the point at which it is completely soluble. the incidence of cholelithiasis and biliary dyskinesia have dramat- Other than obesity, another factor which has led to an ically increased over the past several decades.1 This has resulted in increased incidence of cholelithiasis in the pediatric population a significant increase in the number of cholecystectomies per- over time is improved survival of critically ill neonates who have formed by pediatric surgeons.2 received long-term total parenteral nutrition and/or have under- lying abnormalities resulting in short-gut syndrome. In a report by Walker et al.,4 the number of cholecystectomies (for non-pigmented gallstones) performed in children increased by Gallstones 213% over a 9-year period ending in 2012. The incidence of cholecystectomy in England has been reported to have tripled Etiology and incidence since 1997, the increase being primarily in white females.5

Until recently, pediatric gallstones were frequently pigmented stones from hemolytic diseases such as hemolytic anemia, sickle Diagnosis cell disease, hereditary spherocytosis, thalassemia major, pyruvate kinase deficiency, and other processes with red blood cell break- The majority of children and adults with cholelithiasis are down. Hemolysis causes release of hemoglobin, and its degrada- asymptomatic (475%). Right upper quadrant abdominal pain is tion results in increased bilirubin; further conjugation of bilirubin the most common complaint in the remainder, with the classic with calcium leads to pigmented gallstones. As many as half of description of biliary colic being sharp, intermittent, cramping children under 10 years of age with sickle cell disease have pain radiating to the right shoulder, nausea, and vomiting. The gallstones, many asymptomatic. The incidence is lower in heredi- pain occurs most commonly after a fatty meal and may last for 3 tary spherocytosis. The incidence of pigmented hemolytic gall- several hours. Other symptoms include nausea, vomiting, and 4 stones in children has remained stable at 15%. occasionally fever. Ultrasound is the most appropriate imaging In recent decades the incidence of gallstone disease in children study to evaluate the biliary tree. Sonographically, gallstones 4 has risen, principally related to the epidemic of pediatric obesity. appear as hyperechoic, mobile structures with acoustic shadowing. Ultrasound has a sensitivity and specificity greater than 95% in the

n detection of gallstones. Endoscopic ultrasound is being used more Corresponding author at: Department of Pediatric Surgery, Women and Children's Hospital of Buffalo, 219 Bryant St, Buffalo, New York 14222. often in children in the setting of complicated biliary stone disease. E-mail address: [email protected] (C.M. Harmon). Computed tomography has little utility in the diagnosis of http://dx.doi.org/10.1053/j.sempedsurg.2016.05.005 1055-8586/& 2016 Elsevier Inc. All rights reserved. 226 D.H. Rothstein, C.M. Harmon / Seminars in Pediatric Surgery 25 (2016) 225–231

Fig. 1. (A) MRCP with coronal T2 sequence through the dilated common bile duct demonstrates obstructing stone in the distal duct. (B) 3D MIP of the biliary system demonstrates intra- and extra-hepatic ductal dilatation as a result of the obstructing stone in the distal duct (arrow). (Courtesy: Kristin Fickenscher, Kansas City, MO.)

gallstones, since greater than 60% of gallstones are radio-lucent with acute cholangitis, manifested by fever, jaundice, and right and the imaging modality exposes patients to radiation unneces- upper quadrant pain. Acute cholangitis is a surgical emergency and sarily. Though not helpful in the diagnosis of cholelithiasis, prompt biliary decompression is necessary. magnetic resonance imaging (MRI) and magnetic resonance chol- angiopancreatography (MRCP) are useful in identifying common Pancreatitis bile duct (CBD) stones and delineating pancreatic and biliary tract Gallstones are one of the leading causes of acute pancreatitis in anatomy (Figure 1A and B). There are no lab tests specificin adults. Though biliary tract disease is reported to be a cause of diagnosing cholelithiasis; however, liver function tests and amy- pediatric pancreatitis in up to 30% of adult cases, the exact lase and lipase are helpful in screening for CBD stones and incidence of gallstone pancreatitis in children is not clear but pancreatitis. appears to be increasing. A recent report found that 25% of pediatric pancreatitis had a biliary (gallstone) origin.7 Patients Complications of gallstones with gallstone pancreatitis present with epigastric abdominal pain, nausea, and vomiting, and may or may not have a history of Acute calculous cholecystitis previous gallbladder-related symptoms. Amylase and lipase are Inflammation of the gallbladder is most often due to obstruc- elevated, and jaundice/elevated conjugated serum bilirubin is fi tion of the cystic duct by stones. The obstruction results in often present. Ultrasound is again the rst-line imaging study. gallbladder swelling followed by bile acid concentration, wall ischemia and occasionally, bacterial infection. Symptoms of biliary Acute acalculous cholecystitis colic usually precede acute calculus cholecystitis with the addition of increased vomiting and fever. Most patients have significant Acute acalculous cholecystitis (AAC) is an inflammation of the right upper quadrant tenderness on exam and occasionally a gallbladder, which is not associated with the presence of gallstones palpable mass. Ultrasound can identify stones, gallbladder wall and may account for greater than 50% of pediatric cholecystitis thickening (44–5 mm) and edema (double-wall sign), gallbladder cases. Although this pathology was initially described in critically sludge, pericholecystic fluid, and a sonographic Murphy's sign. ill patients, currently most pediatric cases have been observed MRCP may be helpful in selected cases. White blood cell counts during several infectious diseases. Symptoms are abdominal pain and C-reactive protein levels are frequently elevated. (mild to severe), often more pronounced at the right upper quadrant, and fever. The diagnosis of AAC is usually obtained Common bile duct obstruction through abdominal ultrasonography that can reveal increased Common bile duct stones (choledocholithiasis) are identified in gallbladder wall thickness (44–5 mm), pericholecystic fluid, and approximately 10% of adults with cholelithiasis and 5–18% of presence of mucosal membrane sludge (Figure 2A and B). The adults undergoing elective cholecystectomy. The exact incidence presence of at least two of these US criteria, in addition to the of choledocholithiasis in children is unknown, but presumably is absence of gallstones, defines the diagnosis of AAC in the pediatric increasing as cholelithiasis increases. A recent report noted that population. AAC was originally described in complex and often 11% of children undergoing cholecystectomy were found to have critically ill children. Tsakayannis et al.8 described a cohort of 25 CBD stones.6 Associated signs include jaundice, acholic stools, and patients (observed between 1970 and 1994): most children devel- dark urine. Patients with common bile duct stones can present oping AAC presented with an underlying clinical condition, such as D.H. Rothstein, C.M. Harmon / Seminars in Pediatric Surgery 25 (2016) 225–231 227

Fig. 2. (A) Acalculous cholecystitis. Transverse US image through the gallbladder shows diffuse gallbladder wall thickening and pericholecystic fluid. (B) Longitudinal image through the gallbladder shows diffuse wall thickening, anechoic lumen, and no evidence of cholelithiasis. The patient had a positive sonographic Murphy's sign. (Courtesy: Kristin Fickenscher, Kansas City, MO.

cardiac surgery or a systemic medical illness (e.g., leukemia, end- Incidence and epidemiology stage liver disease, hemolytic uremic syndrome, and cystic fib- rosis). The main risk factors for AAC in these children were Cholecystectomy in both adults and children has increased prolonged fasting, total parenteral nutrition, intravenous opiate precipitously in the US population over the past few decades.2 It narcotics, volume depletion (shock), multiple transfusion, and is unclear if this follows a true increase in biliary disease incidence, sepsis. More recently, infectious causes of AAC have been identi- a rise in disease diagnosis, or a more generalized acceptance by fied in otherwise healthy children. A number of bacterial (Salmo- both patients and surgeons of the relative ease of cholecystectomy nella typhi, Streptococcus pyogenes, Acinetobacter baumannii, afforded by minimally invasive surgery. Several studies have Streptococcus pneumoniae, Staphylococcus epidermidis, Burkholderia documented a rise in biliary dyskinesia diagnoses in children cepacia, and Stenotrophomonas maltophilia) and viral (Hepatitis A specifically, with this diagnosis replacing cholelithiasis from and Epstein-Barr) causes have been identified and many can be hemolytic diseases as a leading indication for cholecystectomy.17 treated successfully medically.9 Biliary dyskinesia was found in one recent review to account for more than 20% of cholecystectomies in adults, and up to 60% in children.18 Nonetheless, there is no definitive proof that this rise Biliary dyskinesia represents a true increase in disease incidence. A 2013 study by Bielefeldt et al.19 used indirect measures Definition through the Nationwide Inpatient Sample to suggest a 700% rise over the period of 1997–2010, in cholecystectomies performed for One of the earliest descriptions of what we now call biliary indications other that cholelithiasis and cholecystitis in the pedia- dyskinesia was probably Krukenberg's 1903 article, “Uber Gallen- tric population. Other groups have both suggested a wide discrep- blasenkoliken ohne Gallensteine” (about biliary colic without ancy in the application of cholecystectomy for biliary dyskinesia gallstones).10,11 Subsequent articles describing a syndrome of indications between the United States and other countries,20 and acalculous gallbladder stasis, usually accompanied by post- the inconsistent application of diagnostic criteria prior to oper- prandial pain, populated the medical and surgical literature with ation (in adults).21 increasing frequency throughout the 20th century, until we arrived at a fairly standard definition comprising the association Differential diagnosis of vague right upper quadrant with absence of gallstones or gallbladder wall thickening and an abnormally low gallbladder Because biliary dyskinesia remains in some respects a syn- ejection fraction on hepatobiliary iminodiacetic acid (HIDA) scan. drome of gallbladder or cystic duct dysfunction, it is important to This definition, however, belies the degree of uncertainty that exclude other causes of vague right upper quadrant pain. A list of surrounds this entity vis-à-vis standard definitions, appropriate differential diagnosis can be extensive, but must include chronic and cost-effective workup, and definitive treatment and patient hepatopathies and pancreatopathies, colonic dysfunction, inflam- selection for maximizing positive and durable outcomes with matory bowel disorders, microcholelithiasis (“sludge”) perhaps regard to symptom relief. missed by transabdominal ultrasonography, peptic ulcer disease, Most radiologists endorse a threshold ejection fraction of 35% and psychiatric causes. In addition, one must consider the similarly at 1 h after slow infusion of a cholecystokinin (CCK) analog; this vague sphincter of Oddi dysfunction that has some overlapping cutoff has remained virtually unchanged since an original article characteristics with biliary dyskinesia.14 published in 1991.12 The CCK injection often provokes pain, but early studies suggesting this finding could be used as a predictor of Clinical presentation cholecystectomy success in relief of symptoms were of poor quality and are generally discounted.13–16 The clinical presentation of biliary dyskinesia often mimics that A key component of the definition, in addition to a low ejection of biliary colic. Symptoms may include episodes of right upper fraction and the presence of right upper quadrant pain, is the quadrant pain, sometimes severe enough to limit activities of daily absence of serological or other structural abnormalities that would living or precipitate a visit to the emergency department. Nausea suggest a different diagnosis. may accompany these episodes, which are often self-limiting. 228 D.H. Rothstein, C.M. Harmon / Seminars in Pediatric Surgery 25 (2016) 225–231

In practice, these children often present to the surgeon with an Treatment abnormal gallbladder ejection fraction on HIDA scan and a widely variable clinical history. The family and the patient have frequently After excluding non-biliary causes of right upper quadrant pain, had longstanding abdominal complaints, many missed school and the clinician is left with a decision regarding medical versus work days, and a multitude of specialist visits and diagnostic surgical therapy. Various recommendations regarding the use of studies; all leading to a high level of frustration and a strong desire bile acid modifiers, anti-inflammatory agents, antacids, and pro- to finally “cure” the problem surgically. kinetic agents exist but lack evidence-based backing,25 and vir- tually all are in the adult literature. Some have explored psychopharmaceuticals and behavioral modification,26 again with- Diagnosis out great success. Cholecystectomy for biliary dyskinesia requires no particular After performing a careful history and physical, the clinician description beyond the perhaps obvious observation that these are usually obtains a right upper quadrant transabdominal sonogram to usually morphologically “normal” gallbladders that are easily evaluate the gallbladder for the presence of cholelithiasis or wall removed laparoscopically, and perhaps most amenable to the thickening and to evaluate the common bile and hepatic ducts for single-incision techniques advocated by some groups.27 evidence of obstruction. Sonography may also exclude the rare congenital anomaly such as a choledochal cyst. Usually laboratory Outcomes workup includes a complete blood count, lipase, and a hepatic panel. These may help exclude hemolytic diseases, an obstructive biliary There is a paucity of data regarding long-term outcomes after process, and hepatitis or pancreatitis. Upper endoscopy is often cholecystectomy for biliary dyskinesia, and even less data on recommended to exclude peptic ulcer disease. results in patients with abnormal HIDA scan results and biliary In 2006, an international working group proposed a consensus colic who do not undergo cholecystectomy. Mahida et al.28 pro- definition of a functional gallbladder disorder in adults, termed the vided perhaps the largest retrospective review on long-term Rome III criteria (Table).22 These criteria were right upper quadrant symptom relief by examining records of 156 patients undergoing pain; the presence of a structurally normal gallbladder (including cholecystectomy for biliary dyskinesia, finding short-term symp- absence of gallstones or biliary sludge); normal liver and pancre- tom improvement and complete symptom resolution in 82% and atic enzymes and conjugated bilirubin; pain lasting 30 min or 56% of patients, respectively. Their long-term follow-up percen- longer at different intervals; pain not relieved by postural changes, tages for symptom improvement and complete relief were 85% diet or antacids; and pain disabling enough to interfere with work and 44%, respectively, but only included a quarter of the original or school and leading to a visit to a medical provider. patients. Knott et al.29 conducted a similar study in 105 children. When considering biliary dyskinesia, the 60 min HIDA scan Of the 92 seen in 1-month follow-up, 71% reported pain relief. after CCK infusion remains the most commonly utilized diagnostic The authors were able to interview 56 patients at a median modality. The Society of Nuclear Medicine has published standards of 3.7 years, and 22 reported persistent or new pain; however, for performing HIDA scans in the workup of functional biliary 21 of these 22 patients reported satisfaction at having undergone a disorders23 although some controversy remains in the details of cholecystectomy. CCK administration (widely variable CCK dosages reported, bolus Multiple studies in adults have found similar results, with an versus infusions over different intervals, and interference from initial success rate of 70–80%, dropping off to 50–60% in selected other medications and concurrent illness affecting results—e.g., long-term follow-up.30 As with Knott's study, authors often failed diabetes, celiac disease, irritable bowel syndrome, oral contra- to find correlation between pain relief and ejection fraction on pre- ceptives, calcium channel blockers, benzodiazepines, and operative HIDA scan.28,31 histamine-2 blockers).14,16 An ejection fraction of o35% at 1 h When examining gallbladder pathology after cholecystectomy scanning time is considered abnormally low (Figure 3). for biliary dyskinesia, no correlation appears to exist between pre- Irshad et al.24 reported a high correlation between scintigraphy operative gallbladder ejection fraction, post-operative symptom and dynamic 3D and 4D ultrasound techniques, but this modality relief, and pathology.32,33 Abnormal pathologic changes found has not yet entered into common practice and further investiga- included microcholelithiasis, cholesterolosis, and microscopic tion is likely required to find an alternative to the HIDA scan, cholecystitis. which is costly and requires the use of a radiolabeled tracer. In the end, one can only conclude that we lack reliable data on the efficacy of cholecystectomy (or any intervention) for biliary Table dyskinesia. The frequency with which patients report persistent Rome III criteria for functional gallbladder and sphincter of Oddi disorders pain and the frequency of additional follow-up procedures—which 1 Episodes lasting 30 min or longer include endoscopy, endoscopic retrograde pancreatography, liver 2 Recurrent symptoms occurring at different intervals (not daily) biopsy and others—reinforces not only our incomplete under- 3 The pain builds up to a steady level standing of functional biliary and gastrointestinal disorders, but 4 The pain is moderate to severe enough to interrupt the patient's daily the need for a complete pre-operative workup and honest and activities or lead to an emergency department visit 5 The pain is not relieved by bowel movements thorough pre-operative patient and family counseling. The high 6 The pain is not relieved by postural change incidence and cost of biliary dyskinesia supports the performance 7 The pain is not relieved by antacids of a long-term, multi-institutional prospective study. 8 Exclusion of other structural disease that would explain the symptoms

Must include episodes of pain located in the epigastrium and right upper quadrant and all of the above. Cholecystectomy Supportive criteria: The pain may present with one or more of the following: (1) pain is associated with nausea and vomiting (2) pain radiates to the back and/or For most children with symptomatic cholelithiasis, laparoscopic right infra- and subscapular region (3) pain awakens from sleep in the middle of or open cholecystectomy is the recommend treatment. In select the night. patients, such as those with hemolytic disease including sickle cell Functional gallbladder disorder (must include all of the following): (1) criteria for functional gallbladder and sphincter of Oddi disorder, (2) gallbladder is present, disease, cholecystectomy is recommended for asymptomatic chol- and (3) normal liver enzymes, conjugated bilirubin, and amylase/lipase. elithiasis. For children and adolescents with gallstones and biliary D.H. Rothstein, C.M. Harmon / Seminars in Pediatric Surgery 25 (2016) 225–231 229

Fig. 3. CCK-HIDA scintiscan demonstrating delayed gallbladder emptying after CCK administration, with a 14% ejection fraction. colic, the timing of cholecystectomy is not emergent; however, it successful in children and has similar operative times and com- has been clearly shown in adults that delaying the operation plication rates to the multiple trocar approach.35 Laparoscopic results in complications and other hospital admissions. The timing robotic-assisted cholecystectomy has also been utilized in adults of cholecystectomy in the setting of acute calculous cholecystitis with more enthusiasm than the NOTES approach. The recently has been controversial in adults and children. There is now robust developed single site robotic platform has also produced small evidence in adults that early (o7 days) cholecystectomy is a series of adult patients and has been utilized by some pediatric best practice associated with decreased morbidity and mortality. surgeons (personal communication). Similar recommendations have been made in children and The topic of routine IOC to lessen CBD injuries has been a point adolescents. of debate, its use widely ranging from 2% to 98% among U.S. adult Early cholecystectomy is also warranted for patients with general surgeons. There is little evidence to clarify this issue in symptomatic choledocholithiasis and mild gallstone pancreatitis. adults and none in children. However, IF it is warranted in select For known CBD stones, pre-operative or post-operative endoscopic patients, surgeons may need to attempt routine IOC in order to retrograde cholangiopancreatography (ERCP) with CBD clearance have the technical skill set to use it when needed. is a common approach in older children and adolescents. In adults, pre-operative ERCP clearance or simultaneous cholecystectomy Complications and laparoscopic CBD exploration have been recently shown to be fi 34 equally ef cacious. Laparoscopic CBD exploration has also been A cohort of 6931 children treated at 360 hospitals was eval- 6 successful in children. Hill et al. reported 97% success at perform- uated in a recent article by Kelley-Quon et al.36 Most children ing an intra-operative cholangiogram (IOC) and a 90% success rate underwent cholecystectomy at a non-children's hospital (84%). of laparoscopic CBD exploration. Various methods of stone clear- Intra-operative cholangiogram was performed in 2053 (30%) fl ance are described, including the use of saline ush, balloon children. Of 5101 children tracked through the year after chol- catheters, nitinol stone extractors, and the injection of glucagon. ecystectomy, 153 (3%) required readmission for surgical complica- Depending on patient size, a choledochosope or ureteroscope can tions. Bile duct injury occurred in 25 (0.36%) children, and post- be helpful. operative ERCP was performed in 711 (10%) children. Older age (odds ratio ¼ 0.80; 95% CI: 0.67–0.95) was associated with a Technical considerations decreased risk of bile duct injury. Increased hospital tendency for routine IOC use was associated with an increased likelihood of bile Although open and laparoscopic cholecystectomy are both duct injury (odds ratio ¼ 12.92; 95% CI: 1.31–127.15). Receiving considered acceptable, the laparoscopic approach has become surgical care at a children's hospital was associated with a the most common approach in adults and children. In the United decreased likelihood of post-operative ERCP (odds ratio ¼ 0.39; States, over 90% of elective adult cholecystectomies are performed 95% CI: 0.23–0.66). Choledocholithiasis, cholecystitis, IOC, and laparoscopically. Natural orifice transluminal endosurgery (NOTES) laparoscopic cholecystectomy were associated with increased risk cholecystectomy has been performed in adults, but has not been of post-operative ERCP (p o 0.01). adopted by the pediatric surgery community. However, single- Serious complications and readmissions from pediatric chole- incision transumbilical laparoscopic cholecystectomy has been cystectomy are uncommon. Surgeons performing cholecystectomy 230 D.H. Rothstein, C.M. Harmon / Seminars in Pediatric Surgery 25 (2016) 225–231 in young children must have an elevated concern about bile duct 2. Csikesz NG, Singla A, Murphy MM, Tseng JF, Shah SA. Surgeon volume metrics injury. Neither routine IOC or surgical volumes have been shown in laparoscopic cholecystectomy. Dig Dis Sci. 2010;55(8):2398–2405. http://dx. doi.org/10.1007/s10620-009-1035-6. to correlate with lower bile duct injury rates. 3. Gumiero AP, Bellomo-Brandão MA, Costa-Pinto EA. Gallstones in children with sickle cell disease followed up at a Brazilian hematology center. Arq Gastro- enterol. 2008;45(4):313–318. Alternatives to cholecystectomy 4. Walker SK, Maki AC, Cannon RM, et al. Etiology and incidence of pediatric gallbladder disease. Surgery. 2013;154(4):927–931. http://dx.doi.org/10.1016/j. surg.2013.04.040. Surgeons are occasionally faced with patients with severe 5. Khoo AK, Cartwright R, Berry S, Davenport M. Cholecystectomy in English cholecystitis who are both grievously ill and likely to suffer major children: evidence of an epidemic (1997–2012). J Pediatr Surg. 2014;49(2): – fl 284 288. http://dx.doi.org/10.1016/j.jpedsurg.2013.11.053. operative morbidity, or have such intense pericholecystic in am- 6. Hill SJ, Wulkan ML, Parker PM, Jones TK, Heiss KF, Clifton MS. Management mation and edema to render safe removal of the gallbladder of the pediatric patient with choledocholithiasis in an era of advanced prohibitively challenging. The former appears more likely with minimally invasive techniques. J Laparoendosc Adv Surg Tech A. 2014;24(1): 38–42. http://dx.doi.org/10.1089/lap.2013.0306. acalculous cholecystitis, often in children with multiple coexisting 7. Antunes H, Nascimento J, Mesquita A, Correia-Pinto J. Acute pancreatitis in comorbidities. children: a tertiary hospital report. Scand J Gastroenterol. 2014;49(5):642–647. Cholecystostomy, most often performed transhepatically under http://dx.doi.org/10.3109/00365521.2014.882403. ultrasound guidance, and partial cholecystectomy, which can be 8. Tsakayannis DE, Kozakewich HP, Lillehei CW. Acalculous cholecystitis in children. J Pediatr Surg. 1996;31(1):127–130 [discussion 130-131]. performed laparoscopically as an alternative to conversion to open 9. Poddighe D, Tresoldi M, Licari A, Marseglia GL. Acalculous acute cholecystitis cholecystectomy, are appealing alternatives to proceeding with a in previously healthy children: general overview and analysis of pediatric challenging cholecystectomy in select cases. This may be partic- infectious cases. Int J Hepatol. 2015;2015:459608. http://dx.doi.org/10.1155/ 2015/459608. ularly important in the era of rising experience with cholecystec- 10. Krukenberg H. Ueber gallenblasenkoliken ohne gallenstein. Berl Klin tomy for biliary dyskinesia, an operation that is virtually uniformly Wochenscher. 1903;40:667–668. 11. Strode JE. Biliary dyskinesia from the surgical viewpoint. Ann Surg. 1943;117 straightforward from a technical standpoint due to the lack of – fl (2):198 206. pericholecystic in ammation in such cases. 12. Fink-Bennett D, DeRidder P, Kolozsi WZ, Gordon R, Jaros R. Cholecystokinin The pediatric literature regarding these two alternatives to cholescintigraphy: detection of abnormal gallbladder motor function in cholecystectomy is sparse. Schaefer et al.37 report a series of patients with chronic acalculous gallbladder disease. J Nucl Med. 1991;32(9): 1695–1699. ultrasound-guided percutaneous cholecystostomies in 10 pediatric 13. DiBaise JK, Richmond BK, Ziessman HH, et al. Cholecystokinin- patients with acalculous cholecystitis and severe illness, all per- cholescintigraphy in adults: consensus recommendations of an interdiscipli- formed without incident and with appropriate temporization of nary panel. Clin Gastroenterol Hepatol. 2011;9(5):376–384. http://dx.doi.org/ 10.1016/j.cgh.2011.02.013. biliary obstruction. Several recent reports in the adult literature 14. Cafasso DE, Smith RR. Symptomatic cholelithiasis and functional disorders of suggest that when faced with a difficult cholecystectomy in a the biliary tract. Surg Clin North Am. 2014;94(2):233–256. http://dx.doi.org/ patient with acute, calculous cholecystitis, the surgeon might 10.1016/j.suc.2013.12.001. preferentially choose laparoscopic partial cholecystectomy over 15. Edwards MA, Mullenbach B, Chamberlain SM. Pain provocation and low gallbladder ejection fraction with CCK cholescintigraphy are not predictive of conversion to open. In a review of 214 adult patients, Kaplan chronic acalculous gallbladder disease symptom relief after cholecystectomy. et al.38 found a 7.9% rate of vascular, bile duct or gastrointestinal Dig Dis Sci. 2014;59(11):2773–2778. http://dx.doi.org/10.1007/s10620-014- tract injury among the 141 patients who underwent open chol- 3213-4. 16. Richmond BK, DiBaise J, Ziessman H. Utilization of cholecystokinin cholescin- ecystectomy after conversion from laparoscopic, and a 0% injury tigraphy in clinical practice. J Am Coll Surg. 2013;217(2):317–323. http://dx.doi. rate in those treated with laparoscopic partial cholecystectomy. A org/10.1016/j.jamcollsurg.2013.02.034. recent meta-analysis by Elshaer et al.39 examined different partial 17. Mehta S, Lopez ME, Chumpitazi BP, Mazziotti MV, Brandt ML, Fishman DS. “ fi ” Clinical characteristics and risk factors for symptomatic pediatric gallbladder cholecystectomy techniques for dif cult gallbladders, concluding disease. Pediatrics. 2012;129(1):e82–e88. http://dx.doi.org/10.1542/peds.2011- that these operations yielded morbidities comparable to complete 0579. cholecystectomies for “simple gallbladders.” 18. Bielefeldt K, Saligram S, Zickmund SL, Dudekula A, Olyaee M, Yadav D. Cholecystectomy for biliary dyskinesia: how did we get there? Dig Dis Sci. As most studies regarding alternatives to cholecystectomy lack 2014;59(12):2850–2863. http://dx.doi.org/10.1007/s10620-014-3342-9. durable long-term data, information on cost-effectiveness, and 19. Bielefeldt K. The rising tide of cholecystectomy for biliary dyskinesia. Aliment direct applicability to the younger pediatric population, perhaps Pharmacol Ther. 2013;37(1):98–106. http://dx.doi.org/10.1111/apt.12105. 20. Preston JF, Diggs BS, Dolan JP, Gilbert EW, Schein M, Hunter JG. Biliary the reader would simply add cholecystostomy and partial chol- dyskinesia: a surgical disease rarely found outside the United States. Am J ecystectomy to his or her armamentarium. Surg. 2015;209(5):799–803. http://dx.doi.org/10.1016/j.amjsurg.2015.01.003. 21. Aggarwal N, Bielefeldt K. Diagnostic stringency and healthcare needs in patients with biliary dyskinesia. Dig Dis Sci. 2013;58(10):2799–2808. http://dx.doi.org/ 10.1007/s10620-013-2719-5. Summary 22. Drossman DA. Rome III the new criteria. Chin J Dig Dis. 2006;7(4):181–185. http://dx.doi.org/10.1111/j.1443-9573.2006.00265.x. Pediatric gallbladder disease is increasing in frequency in 23. Tulchinsky M, Ciak BW, Delbeke D, et al. 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