J Gastrointest Surg DOI 10.1007/s11605-014-2472-x
CASE REPORT
Coexistence of Gallbladder Agenesis and Cholangiocarcinoma: Report of a Case O. Yoldas & P. Yazıcı & I. Ozsan & T. Karabuga & O. Alpdogan & E. Sahin & U. Aydın
Received: 17 December 2013 / Accepted: 22 January 2014 # 2014 The Society for Surgery of the Alimentary Tract
Abstract Gallbladder agenesis (GA) is a rare condition and was first described by Lemary in 1701. Nearly 400 cases of GA is described in the literature and it is associated with various congenital abnormalities and malformations in some cases. Cholangiocarcinoma (CCA) is the malignant tumor arising from bile ducts. A wide range of risk factors have been identified for cholangiocarcinoma. A case of cholangiocarcinoma in which gallbladder agenesis was found incidentally was described in this study. Keywords Gallbladder agenesis . Cholangiocarcinoma
Case
O. Yoldas : I. Ozsan : T. Karabuga : O. Alpdogan : U. Aydın (*) Department of Surgery, Izmir University Faculty of Medicine, Yeni Girne Bulv. 1825sk no 12 Karşıyaka, Izmir, Turkey e-mail: [email protected]
A 35-year-old male patient was referred to our institution with the diagnosis of hepatic mass formative cholangiocarcinoma. The patient was admitted to the previous hospital with gastric complaints. An abdominal ultrasound was performed, and a 12 cm mass was detected in the left hepatic lobe. In our institution, magnetic resonance imaging (MRI) revealed a mean mass of 11×8.5 cm in diameter and two satellite nodules in the central hepatic area (including segments 4a, 4b, 5, and 8) (Fig. 1). Coronal T2-weighted HASTE sequences of abdominal MRI showed the absence of the cystic duct and the gallbladder (Fig. 2). Aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin levels were within normal ranges; carbohydrate antigen 19-9 was over 1000 U/ml. With respect to his family history, her father had nephrectomy at the age of 48 due to renal tuberculosis, his older brother had cholecystectomy due to gallbladder polyps, and his mother had psoriasis. No malignant disorders were detected in his family history. During the operation, common bile duct was demonstrated, and neither cystic duct nor the gallbladder was observed in the gallbladder fossa (Fig. 3). Left trisegmentectomy was performed (Fig. 4), and the patient was discharged without any complication on postoperative day 6.
P. Yazıcı Department of General Surgery, Şişli Hamidiye Etfal Hospital, Istanbul, Turkey
Discussion
E. Sahin Department of Radiology, Izmir University Faculty of Medicine, Izmir, Turkey
Cholangiocarcinoma is a malignant tumor arising from biliary epithelium at any part of the bile duct system, from bile
Introduction Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver after hepatocellular carcinoma. Biliary diseases, surgery, parenchymal liver diseases, gastrointestinal diseases, alcohol intake, and smoking are some of the evaluated risk factors for CCA. Gallbladder agenesis (GA) is a rare congenital anomaly of the biliary system and was first described by Lemary in 1701.1 It is thought that approximately 70 % of cases are usually isolated anomalies, although some cases appear to be familial and are associated with more severe anomalies.2–4 Here, we represent a case of gallbladder agenesis representing with CCA of the liver. To best of our knowledge, this is the first case in which gallbladder agenesis is associated with cholangiocarcinoma.
J Gastrointest Surg Fig. 1 Postcontrast axial T1 A-weighted MRI image demonstrating a mean mass of 11 × 8.5 cm in segments 8 and 4 and two satellite nodules; one in segment 8 with a 15-mm size and the other in segment 4 with a 22- mm size
ductules to ampulla of Vater. A wide range of risk factors have been identified among patients with cholangiocarcinoma including advanced age, male gender, primary sclerosing cholangitis, choledochal cyst, inflammatory bowel disease, chronic pancreatitis, and alcoholic and non-alcoholic cirrhosis. Agenesis of the gallbladder is a rare condition resulting from failure of development or canalisation of the cystic bud in the fourth week of intrauterine life. Any ectopic locations must be excluded before the diagnosis of gallbladder agenesis.5 Ectopic gallbladders may be located intrahepatically, between the
Fig. 2 T2-weighted coronal MRI image demonstrating a normal caliber extrahepatic biliary duct (arrow) and the absence of the cystic duct and the gallbladder
leaves of the lesser omentum, in the retroperitoneum and the retrohepatic region, within the falciform ligament, or in the retroduodenal and retropancreatic areas. Nearly 400 cases of gallbladder agenesis have been described in the medical literature. GA occurs alone in 70–82 % of cases (31.6 % asymptomatic cases and 55.6 % symptomatic cases). It occurs in association with additional malformations in the remaining 12.8–30 % of cases that fall into two subgroups: one with atresia of the bile ducts or choledochal cyst (9 %) and the other with normal bile ducts but with distant multiple fetal anomalies (12.8–21 %).6–8 GA is often associated with other congenital abnormalities (12.8 %–30 %). It has been reported to be associated with gastrointestinal, cardiovascular, genitourinary, and skeletal malformations, such as duodenal atresia, malrotation of the gut, pancreas divisum, imperforate anus, hypoplasia of the right hepatic lobe, duplication cysts of the hepatic flexure, ventricular septal defect, renal agenesis, undescended testes, and syndactyly.3 In particular, some authors report genitourinary anomalies as most frequently associated
Fig. 3 Intraoperative image demonstrating the empty gallbladder fossa
J Gastrointest Surg
Fig. 4 The image of the liver and extra-hepatic and intra-hepatic biliary ducts after resection
with GA.9 GA has also been reported in association with congenital syndromes, trisomy 18, and with congenital malformations caused by thalidomide.10 Bennion et al.11 suggested a classification system for AG based on a review of cases worldwide. They identified three groups: (1) multiple fetal anomalies, the most common malformations being cardiovascular, followed by gastrointestinal and genitourinary, (2) asymptomatic cases, in which agenesis of the gallbladder was found at autopsy or laparotomy for another reason and, in some cases, there was a familial association, and (3) symptomatic cases, with the most common associated symptoms being biliary colic (54 %), dyspepsia (34 %), and jaundice (27 %).11,12 A recent case series suggests that an autosomal recessive trait may cause a hereditary syndrome that causes gallbladder agenesis and biliary atresia, among numerous other abnormalities. However, no specific genetic mutations have yet been identified, although mutations in the HNF6 (hepatocyte nuclear factor 6) gene have been shown to cause biliary abnormalities.13 Medline search revealed only three reports of synchronous gallbladder agenesis and choledochal cyst despite both conditions being rare.14–16 Alagille syndrome is an autosomal dominant condition, caused by a mutation in the JAG 1 (jagged 1) gene. It results in abnormalities of the bile ducts among other abnormalities. It is possible that a part of the role of this gene may contribute to both gallbladder agenesis and choledochal cysts; however, there is no supporting evidence for this at the present time.17 Gallbladder agenesis has been noted to occur in familial clusters suggesting a genetic predisposition.18 Recent research by Yamashita et al. showed that Lgr4 (leucine-rich repeat-containing G protein-coupled receptor 4) gene-trapped mice demonstrated gallbladder agenesis during gestation. These mice developed without any other abnormality to the hepatic primordium or pancreatic buds, with normal common and intrahepatic bile ducts. Therefore, only the gallbladder and cystic duct were absent, apparently failing to elongate or proliferate without the Lgr4 gene.19 Kım et al. reported a case of intrahepatic biliary intraductal papillary mucinous neoplasm (IPMN) with gallbladder agenesis. Multifocal high grade dysplasia was found in the resected cystic
lesion. They suggested that bile stasis due to GA may have caused chronic inflammation of the bile duct, and this resulted in IPMN.20 Shen et al. shared the cases of non-visualization of the fetal gallbladder in the second trimester.21 In four of their five cases with associated anomalies, the anomalies were severe, and the pregnancies were terminated for aneuploidy (two cases of trisomy 18 and one triploidy) or for the severity of the anomalies. When prenatal non-visualization of the gallbladder is non-isolated, it is associated with an increased risk for fetal chromosomal abnormalities.22–24 In conclusion, despite several reports of synchronous diseases and congenital anomalies with gallbladder agenesis, there is no reported case of malignancy in association with gallbladder agenesis. To the best of our knowledge, this is the first case of synchronous gallbladder agenesis and cholangiocarcinoma.
References 1. Praseedom RK, Mohammed R. Two cases of gall bladder agenesis and review of the literature. 1998 Hepato- Gastroenterology;45 (22): 954–5 2. Stephenson JA, Norwood M, Al-Leswas D, Al-Taan O, Beable R, Lloyd DM, Dennison AR. Hepatic haemangioma masquerading as the gallbladder in a case of gallbladder agenesis: a case report and literature review. HPB Surg 2010;2010. 3. Fiaschetti V, Calabrese G, Viarani S, Bazzocchi G, Simonetti G: Gallbladder agenesis and cystic duct absence in an adult patient diagnosed by magnetic resonance cholangiography: report of a case and review of the literature. Case Report Med 2009;2009:674768. 4. Demir MK, Kilicoglu G: Rare coincidence of congenital short and annular pancreas with gallbladder agenesis and splenic malrotation. Br J Radiol 2008; 81: 204–6. 5. Sherson ND. The absent adult gallbladder. Aust N Z J Surg.1970; 39: 255–8. 6. Singh B, Satyapal KS, Moodley J, Haffejee AA. Congenital absence of the gall bladder. Surgical and Radiologic Anatomy, 1999; 21(3): 221–4. 7. Goel AK, Seenu V, Khosla NK, Gupta A, Sarda AK. Agenesis of gallbladder with choledochal cyst—an unusual combination. Tropical Gastroenterology 1994; 15(1): 33–6 8. Coughlin JP, Rector FE, Klein MD. Agenesis of the gallbladder in duodenal atresia: two case reports. Journal of Pediatric Surgery, 1992; 27(10): 1304. 9. Turkel SB, Swanson V, Chandrasoma P. Malformations associated with congenital absence of the gall bladder. J Med Genet 1983; 20: 445–9. 10. Faure JP, Doucet C, Scepi M, Rigoard P, Carretier M, Richer JP. Abnormalities of the gallbladder, clinical effects. Surg Radiol Anat 2008; 30: 285–90. 11. Bennion RS, Thompson JE, Tompkins RK. Agenesis of the gallbladder without extrahepatic biliary atresia. Archives of Surgery, 1988; 123 (10): 1257–60. 12. Richards RJ, Taubin H, Wasson D. Agenesis of the gallbladder in symptomatic adults: a case and review of the literature. Journal of Clinical Gastroenterology,1993; 16(3):231–3. 13. Chappell L, Gorman S, Campbell F. A further example of a distinctive autosomal recessive syndrome comprising neonatal diabetes mellitus, intestinal atresias and gall bladder agenesis. Am J Med Genet A 2008; 146: 1713–17.
J Gastrointest Surg 14. Bedi N, Smith GB, Kumar S, Hutchins R. Gallbladder agenesis with choledochal cyst—a rare association: a case report and review of possible genetic or embryological links. BMJ Case Reports, 2013 15. Goel AK, Seenu V, Khosla NK, et al. Agenesis of gallbladder with choledochal cyst—an unusual combination. Trop Gastroenterol 1994;15:33–6. 16. Tabibian JH, Tabibian N, Aguet JC. Choledochal cyst complications presenting as duodenal obstruction in an 82-year-old patient with gallbladder agenesis. Dig Dis Sci 2009; 54:184–7. 17. Oda T, Elkahloun AG, Pike BL, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16: 235–42. 18. Wilson JE, Deitrick JE. Agenesis of the gallbladder: case report and familial investigation. Surgery 1986; 99:106–9. 19. Yamashita R, Takegawa Y, Sakumoto M, et al. Defective development of the gallbladder and cystic duct in Lgr4-hypomorphic mice. Dev Dyn 2009; 238: 993–1000.
20. Kım BS, Joo SH, Lim SJ, Joo KR. Intrahepatic biliary intraductal papillary mucinous neoplasm with gallbladder agenesis: case report. Surg Laparosc Endosc Percutan Tech. 2013; 23(2) : 61–4. 21. Shen O, Rabinowitz R, Yagel S, Gal M. Absent gallbladder on fetal ultrasound: prenatal findings and postnatal outcome. Ultrasound Obstet Gynecol. 2011;37: 673–7 22. Blazer S, Bronshtein M, Zimmer E. Nonvisualization of the fetal gallbladder in early pregnancy: comparison with clinical outcome. Radiology 2002; 224: 379 – 382. 23. Boughanim M, Benachi A, Dreux S, Delahaye S, Muller F. Nonvisualization of the fetal gallbladder by second-trimester ultrasound scan: strategy of clinical management based on four examples. Prenat Diagn 2008; 28: 46–48. 24. Ochshorn Y, Rosner G, Barel D, Bronshtein M, Muller F, Yaron Y. Clinical evaluation of isolated nonvisualized fetal gallbladder. Prenat Diagn 2007; 27: 699 – 703.
CASE REPORT
Coexistence of Gallbladder Agenesis and Cholangiocarcinoma: Report of a Case O. Yoldas & P. Yazıcı & I. Ozsan & T. Karabuga & O. Alpdogan & E. Sahin & U. Aydın
Received: 17 December 2013 / Accepted: 22 January 2014 # 2014 The Society for Surgery of the Alimentary Tract
Abstract Gallbladder agenesis (GA) is a rare condition and was first described by Lemary in 1701. Nearly 400 cases of GA is described in the literature and it is associated with various congenital abnormalities and malformations in some cases. Cholangiocarcinoma (CCA) is the malignant tumor arising from bile ducts. A wide range of risk factors have been identified for cholangiocarcinoma. A case of cholangiocarcinoma in which gallbladder agenesis was found incidentally was described in this study. Keywords Gallbladder agenesis . Cholangiocarcinoma
Case
O. Yoldas : I. Ozsan : T. Karabuga : O. Alpdogan : U. Aydın (*) Department of Surgery, Izmir University Faculty of Medicine, Yeni Girne Bulv. 1825sk no 12 Karşıyaka, Izmir, Turkey e-mail: [email protected]
A 35-year-old male patient was referred to our institution with the diagnosis of hepatic mass formative cholangiocarcinoma. The patient was admitted to the previous hospital with gastric complaints. An abdominal ultrasound was performed, and a 12 cm mass was detected in the left hepatic lobe. In our institution, magnetic resonance imaging (MRI) revealed a mean mass of 11×8.5 cm in diameter and two satellite nodules in the central hepatic area (including segments 4a, 4b, 5, and 8) (Fig. 1). Coronal T2-weighted HASTE sequences of abdominal MRI showed the absence of the cystic duct and the gallbladder (Fig. 2). Aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin levels were within normal ranges; carbohydrate antigen 19-9 was over 1000 U/ml. With respect to his family history, her father had nephrectomy at the age of 48 due to renal tuberculosis, his older brother had cholecystectomy due to gallbladder polyps, and his mother had psoriasis. No malignant disorders were detected in his family history. During the operation, common bile duct was demonstrated, and neither cystic duct nor the gallbladder was observed in the gallbladder fossa (Fig. 3). Left trisegmentectomy was performed (Fig. 4), and the patient was discharged without any complication on postoperative day 6.
P. Yazıcı Department of General Surgery, Şişli Hamidiye Etfal Hospital, Istanbul, Turkey
Discussion
E. Sahin Department of Radiology, Izmir University Faculty of Medicine, Izmir, Turkey
Cholangiocarcinoma is a malignant tumor arising from biliary epithelium at any part of the bile duct system, from bile
Introduction Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver after hepatocellular carcinoma. Biliary diseases, surgery, parenchymal liver diseases, gastrointestinal diseases, alcohol intake, and smoking are some of the evaluated risk factors for CCA. Gallbladder agenesis (GA) is a rare congenital anomaly of the biliary system and was first described by Lemary in 1701.1 It is thought that approximately 70 % of cases are usually isolated anomalies, although some cases appear to be familial and are associated with more severe anomalies.2–4 Here, we represent a case of gallbladder agenesis representing with CCA of the liver. To best of our knowledge, this is the first case in which gallbladder agenesis is associated with cholangiocarcinoma.
J Gastrointest Surg Fig. 1 Postcontrast axial T1 A-weighted MRI image demonstrating a mean mass of 11 × 8.5 cm in segments 8 and 4 and two satellite nodules; one in segment 8 with a 15-mm size and the other in segment 4 with a 22- mm size
ductules to ampulla of Vater. A wide range of risk factors have been identified among patients with cholangiocarcinoma including advanced age, male gender, primary sclerosing cholangitis, choledochal cyst, inflammatory bowel disease, chronic pancreatitis, and alcoholic and non-alcoholic cirrhosis. Agenesis of the gallbladder is a rare condition resulting from failure of development or canalisation of the cystic bud in the fourth week of intrauterine life. Any ectopic locations must be excluded before the diagnosis of gallbladder agenesis.5 Ectopic gallbladders may be located intrahepatically, between the
Fig. 2 T2-weighted coronal MRI image demonstrating a normal caliber extrahepatic biliary duct (arrow) and the absence of the cystic duct and the gallbladder
leaves of the lesser omentum, in the retroperitoneum and the retrohepatic region, within the falciform ligament, or in the retroduodenal and retropancreatic areas. Nearly 400 cases of gallbladder agenesis have been described in the medical literature. GA occurs alone in 70–82 % of cases (31.6 % asymptomatic cases and 55.6 % symptomatic cases). It occurs in association with additional malformations in the remaining 12.8–30 % of cases that fall into two subgroups: one with atresia of the bile ducts or choledochal cyst (9 %) and the other with normal bile ducts but with distant multiple fetal anomalies (12.8–21 %).6–8 GA is often associated with other congenital abnormalities (12.8 %–30 %). It has been reported to be associated with gastrointestinal, cardiovascular, genitourinary, and skeletal malformations, such as duodenal atresia, malrotation of the gut, pancreas divisum, imperforate anus, hypoplasia of the right hepatic lobe, duplication cysts of the hepatic flexure, ventricular septal defect, renal agenesis, undescended testes, and syndactyly.3 In particular, some authors report genitourinary anomalies as most frequently associated
Fig. 3 Intraoperative image demonstrating the empty gallbladder fossa
J Gastrointest Surg
Fig. 4 The image of the liver and extra-hepatic and intra-hepatic biliary ducts after resection
with GA.9 GA has also been reported in association with congenital syndromes, trisomy 18, and with congenital malformations caused by thalidomide.10 Bennion et al.11 suggested a classification system for AG based on a review of cases worldwide. They identified three groups: (1) multiple fetal anomalies, the most common malformations being cardiovascular, followed by gastrointestinal and genitourinary, (2) asymptomatic cases, in which agenesis of the gallbladder was found at autopsy or laparotomy for another reason and, in some cases, there was a familial association, and (3) symptomatic cases, with the most common associated symptoms being biliary colic (54 %), dyspepsia (34 %), and jaundice (27 %).11,12 A recent case series suggests that an autosomal recessive trait may cause a hereditary syndrome that causes gallbladder agenesis and biliary atresia, among numerous other abnormalities. However, no specific genetic mutations have yet been identified, although mutations in the HNF6 (hepatocyte nuclear factor 6) gene have been shown to cause biliary abnormalities.13 Medline search revealed only three reports of synchronous gallbladder agenesis and choledochal cyst despite both conditions being rare.14–16 Alagille syndrome is an autosomal dominant condition, caused by a mutation in the JAG 1 (jagged 1) gene. It results in abnormalities of the bile ducts among other abnormalities. It is possible that a part of the role of this gene may contribute to both gallbladder agenesis and choledochal cysts; however, there is no supporting evidence for this at the present time.17 Gallbladder agenesis has been noted to occur in familial clusters suggesting a genetic predisposition.18 Recent research by Yamashita et al. showed that Lgr4 (leucine-rich repeat-containing G protein-coupled receptor 4) gene-trapped mice demonstrated gallbladder agenesis during gestation. These mice developed without any other abnormality to the hepatic primordium or pancreatic buds, with normal common and intrahepatic bile ducts. Therefore, only the gallbladder and cystic duct were absent, apparently failing to elongate or proliferate without the Lgr4 gene.19 Kım et al. reported a case of intrahepatic biliary intraductal papillary mucinous neoplasm (IPMN) with gallbladder agenesis. Multifocal high grade dysplasia was found in the resected cystic
lesion. They suggested that bile stasis due to GA may have caused chronic inflammation of the bile duct, and this resulted in IPMN.20 Shen et al. shared the cases of non-visualization of the fetal gallbladder in the second trimester.21 In four of their five cases with associated anomalies, the anomalies were severe, and the pregnancies were terminated for aneuploidy (two cases of trisomy 18 and one triploidy) or for the severity of the anomalies. When prenatal non-visualization of the gallbladder is non-isolated, it is associated with an increased risk for fetal chromosomal abnormalities.22–24 In conclusion, despite several reports of synchronous diseases and congenital anomalies with gallbladder agenesis, there is no reported case of malignancy in association with gallbladder agenesis. To the best of our knowledge, this is the first case of synchronous gallbladder agenesis and cholangiocarcinoma.
References 1. Praseedom RK, Mohammed R. Two cases of gall bladder agenesis and review of the literature. 1998 Hepato- Gastroenterology;45 (22): 954–5 2. Stephenson JA, Norwood M, Al-Leswas D, Al-Taan O, Beable R, Lloyd DM, Dennison AR. Hepatic haemangioma masquerading as the gallbladder in a case of gallbladder agenesis: a case report and literature review. HPB Surg 2010;2010. 3. Fiaschetti V, Calabrese G, Viarani S, Bazzocchi G, Simonetti G: Gallbladder agenesis and cystic duct absence in an adult patient diagnosed by magnetic resonance cholangiography: report of a case and review of the literature. Case Report Med 2009;2009:674768. 4. Demir MK, Kilicoglu G: Rare coincidence of congenital short and annular pancreas with gallbladder agenesis and splenic malrotation. Br J Radiol 2008; 81: 204–6. 5. Sherson ND. The absent adult gallbladder. Aust N Z J Surg.1970; 39: 255–8. 6. Singh B, Satyapal KS, Moodley J, Haffejee AA. Congenital absence of the gall bladder. Surgical and Radiologic Anatomy, 1999; 21(3): 221–4. 7. Goel AK, Seenu V, Khosla NK, Gupta A, Sarda AK. Agenesis of gallbladder with choledochal cyst—an unusual combination. Tropical Gastroenterology 1994; 15(1): 33–6 8. Coughlin JP, Rector FE, Klein MD. Agenesis of the gallbladder in duodenal atresia: two case reports. Journal of Pediatric Surgery, 1992; 27(10): 1304. 9. Turkel SB, Swanson V, Chandrasoma P. Malformations associated with congenital absence of the gall bladder. J Med Genet 1983; 20: 445–9. 10. Faure JP, Doucet C, Scepi M, Rigoard P, Carretier M, Richer JP. Abnormalities of the gallbladder, clinical effects. Surg Radiol Anat 2008; 30: 285–90. 11. Bennion RS, Thompson JE, Tompkins RK. Agenesis of the gallbladder without extrahepatic biliary atresia. Archives of Surgery, 1988; 123 (10): 1257–60. 12. Richards RJ, Taubin H, Wasson D. Agenesis of the gallbladder in symptomatic adults: a case and review of the literature. Journal of Clinical Gastroenterology,1993; 16(3):231–3. 13. Chappell L, Gorman S, Campbell F. A further example of a distinctive autosomal recessive syndrome comprising neonatal diabetes mellitus, intestinal atresias and gall bladder agenesis. Am J Med Genet A 2008; 146: 1713–17.
J Gastrointest Surg 14. Bedi N, Smith GB, Kumar S, Hutchins R. Gallbladder agenesis with choledochal cyst—a rare association: a case report and review of possible genetic or embryological links. BMJ Case Reports, 2013 15. Goel AK, Seenu V, Khosla NK, et al. Agenesis of gallbladder with choledochal cyst—an unusual combination. Trop Gastroenterol 1994;15:33–6. 16. Tabibian JH, Tabibian N, Aguet JC. Choledochal cyst complications presenting as duodenal obstruction in an 82-year-old patient with gallbladder agenesis. Dig Dis Sci 2009; 54:184–7. 17. Oda T, Elkahloun AG, Pike BL, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16: 235–42. 18. Wilson JE, Deitrick JE. Agenesis of the gallbladder: case report and familial investigation. Surgery 1986; 99:106–9. 19. Yamashita R, Takegawa Y, Sakumoto M, et al. Defective development of the gallbladder and cystic duct in Lgr4-hypomorphic mice. Dev Dyn 2009; 238: 993–1000.
20. Kım BS, Joo SH, Lim SJ, Joo KR. Intrahepatic biliary intraductal papillary mucinous neoplasm with gallbladder agenesis: case report. Surg Laparosc Endosc Percutan Tech. 2013; 23(2) : 61–4. 21. Shen O, Rabinowitz R, Yagel S, Gal M. Absent gallbladder on fetal ultrasound: prenatal findings and postnatal outcome. Ultrasound Obstet Gynecol. 2011;37: 673–7 22. Blazer S, Bronshtein M, Zimmer E. Nonvisualization of the fetal gallbladder in early pregnancy: comparison with clinical outcome. Radiology 2002; 224: 379 – 382. 23. Boughanim M, Benachi A, Dreux S, Delahaye S, Muller F. Nonvisualization of the fetal gallbladder by second-trimester ultrasound scan: strategy of clinical management based on four examples. Prenat Diagn 2008; 28: 46–48. 24. Ochshorn Y, Rosner G, Barel D, Bronshtein M, Muller F, Yaron Y. Clinical evaluation of isolated nonvisualized fetal gallbladder. Prenat Diagn 2007; 27: 699 – 703.
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