Surg Radiol Anat (2008) 30:285290 DOI 10.

1007/s00276-008-0332-7

R EV IE W

Abnormalities of the gallbladder, clinical eVects

J. P. Faure C. Doucet M. Scepi P. Rigoard M. Carretier J. P. Richer

Received: 30 April 2007 / Accepted: 25 February 2008 / Published online: 11 March 2008 Springer-Verlag 2008

Abstract The aim of this review of the literature was to present and discuss the anatomical and embryological basis of congenital abnormalities of the gallbladder, based on a case of volvulus. In the rare cases of ectopic gallbladder, diagnosis of a biliary disease could be diYcult. In such cases surgery can also be dangerous, especially when it is associated with abnormalities of the intra-hepatic biliary and vascular tree. This study, based on the embryology of the extra hepatic bile duct, focused on the most frequent gallbladder abnormalities to keep them in mind. Keywords Ectopic gallbladder Gallbladder volvulus Congenital anomaly Anatomic variation

Materials and methods Case report A 84-year-old woman was admitted to our hospital with the complain of right upper quadrant pain of approximately 48 h in duration. She had no relevant past history. Pain was not preceded by jaundice. Murphys sign and a palpable mass were detected in the abdominal examination. Laboratory data only showed a leukocytes count of 10,300/mm3. Abdominal ultrasound (US) demonstrated a distended, thick-walled gallbladder, but no stones. A computed tomography (CT) examination of the abdomen demonstrated a large dilated gallbladder, measuring approximately 67.9 mm 47.4 mm. Additionally, the enhanced CT was characterized by the non-enhanced wall of the gallbladder (Fig. 1). The diagnosis of gallbladder volvulus was supposed. She underwent a laparoscopy, Wndings included a distended and gangrenous gallbladder, and closer examination revealed a clockwise torsion of 360 on the gallbladder mesentery. De-torsion and cholecystectomy were easily performed. The histopathology report showed necrosis and hemorrhage of the gallbladder without evidence of lithiasis. Two days after the operation she was discharged with no complications.

Introduction Volvulus of the gallbladder is a rare phenomenon, which may mimick cholelithiasis disease. Based on one reported case, the aim of our study was to present and discuss the anatomical and embryological basis of congenital abnormalities of the gallbladder. We focused on ectopic gallbladder to highlight the associated abnormalities of the intra-hepatic biliary and vascular tree when they are present.

J. P. Faure (&) C. Doucet M. Carretier J. P. Richer Service Chirurgie Viscrale Digestive et Endocrinienne, Hpital Jean Bernard, CHU Poitiers, Universit de Poitiers, 2 rue de la Miletrie, BP 577, 86021 Poitiers Cedex, France e-mail: j.p.faure@chu-poitiers.fr J. P. Faure C. Doucet M. Scepi P. Rigoard J. P. Richer Laboratoire Anatomie, Centre de Don de Corps, Facult de Mdecine et de Pharmacie, Universit de Poitiers, 6 rue de la Miletrie, BP 199, 86034 Poitiers Cedex, France

Discussion First reported in 1898 by Wendel [41], volvulus of the gallbladder is a relatively uncommon phenomenon, with no more than 300 cases reported in the literature. It occurs in all age groups, with the highest incidence in elderly women, and a female-to-male ratio of 3:1. The incidence could increase with a longer life expectancy rate [12, 22, 36].

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Fig. 1 Computed tomography of the abdomen, sagittal view gating on the gallbladder hilum. a Dilated gallbladder but a non-enhanced gallbladder wall. b Cystic artery

Gallstones are unlikely to be the cause of gallbladder torsion, as gallstones are not uniformly present in all patients reported with torsion: only in 24.4% of the cases [27]. In the literature, 51% of cases developed a clockwise torsion rotation. Although supportive evidence is lacking, inferences have been made in the literature linking gastric peristalsis to clockwise gallbladder torsion and colonic peristalsis to counterclockwise torsion [17]. This congenital anomaly of the gallbladder can result in the development of an abnormally long mesentery suspending the gallbladder from the liver bed, thus increasing the propensity for rotational instability. In conjunction with this anomalous anatomic conWguration, a subsequent triggering event must occur to initiate torsion. Theories have focused on liver atrophy, loss of visceral fat and elasticity, weight loss as causes, particularly found in the aging population, as impetuses for gallbladder torsion [32]. Spinal deformities are also associated with volvulus of the gallbladder, in such cases we can hypothesized that peritoneal tensile strength on the liver and also the gallbladder in the abdominal cavity could increase the risk of volvulus. Further suppositions include arteriosclerosis and tortuosity of the cystic duct acting as rigid fulcrums for torsion [32]. Other anomalies of the gallbladder Gallbladder ectopia has been classiWed into four types: transverse, intrahepatic, left-sided, and retroplaced [6, 12]. Retroposition of the gallbladder may also be found: it may

be retroperitoneal or retrohepatic. This position might be produced by hypoplasia of the right hepatic lobe. The abnormal gallbladder might have originated from abnormal migration of the gallbladder bud. Another possibility is that it might have originated from a second bud with atrophy of the Wrst. Triplication of Gallbladder is an extremely rare congenital anomaly (only eleven reported cases to date) [24]. In such cases there was no intra hepatic biliary duct (IHBD) abnormality. So diagnosis of a biliary disease and surgery may be a challenge. The absence of gallbladder (AG) is an unusual anomaly, mimicking a biliary stone disease in 23% of cases. This condition must be kept in mind in the diVerential diagnosis of ultrasonographically undetected or scleroatrophic gallbladder, this congenital malformation should be suspected [29]. Absence of gallbladder can be observed in both children and adults, with a median age of 46 at the time of diagnosis [29]. It is almost always a fortuitous Wnding during abdominal surgery or at autopsy. The prevalence range is 0.007 0.13%. The incidence of this malformation is slightly lower in surgical cholecystectomy series (0.0070.027%) [29] than that in autopsy reports (0.040.13%) [23]. The male to female ratio is equal in autopsy reports [23] but seems to reach the same ratio (23 women for 1 man) in the clinical group as other biliary tract diseases [29]. AG occurs in association with other malformations in 4065% of cases [23]. It is then found above all in children, leading in most cases to death in the Wrst year of life [23]. Two congenital syndromes with multiple anomalies including gallbladder agenesis have been described: cerebrotendinous xanthomatosis is a rare, inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts. Large deposits of cholesterol and cholestanol can be found in virtually every tissue [42], and the G syndrome or Opitz BBB/G syndrome is characterized by association of crania-facials and urogenitals abnormalities. Two types of this syndrome are described: one autosomic dominant and one associated to X [39]. AG has been occasionally mentioned with trisomy 18 and the KlippelFeil syndrome witch is a rare disorder characterized by failure in the normal segmentation of the cervical vertebrae during the early weeks of fetal development. Associated abnormalities may include scoliosis and spina biWda, anomalies of the kidneys and the ribs, cleft palate, respiratory problems, and heart malformations [29]. Some authors [15, 33] reported this anomaly in children with congenital malformations caused by thalidomide (up to 10% in Mnnls series [20]). This anomaly is explained by an embryological disturbance occurring during the third week of gestation and concerning the caudal portion of the anterior diverticulum of the primitive gut. It is an anomaly of the development of vessels located on each side of the

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gallbladder bud (sinus venosus cordis, omphaloenteric, and umbilical veins) [5]. This may explain the association of this anomaly with cardiac, vascular, gastro-intestinal, and abdominal wall malformations observed in the multiple fetal anomaly groups. AG may be inherited, with several familial cases observed, including across two generations. These series suggest a non-sex-linked heredity with variable penetration [29, 34]. Multiseptate gallbladder, characterized by the presence of multiple septa dividing the gallbladder lumen, is a very extremely rare congenital anomaly of the gallbladder. To our knowledge, only 30 cases have been reported in the literature [44]. A review of the cases showed a female predominance; 21 of the patients were females. A mean age was 29.4 years (range 370 years), and pediatric patients in 4 cases [30, 37]. Most patients usually present with right upper abdominal pain, epigastralgia, and back pain, in the literature, only six cases were asymptomatic [30, 37, 44]. Though the symptoms of multiseptate gallbladder patients were relieved after cholecystectomy, histological Wndings of the resected gallbladder in patients were usually of normal size with smooth surface and not always recognized as acute cholecystitis or cholecystolithiasis, and the exact mechanism of the biliary symptoms of multiseptate gallbladder is unknown. In nearly all literatures, pathological Wndings of multiseptate gallbladder reveal numerous septa, which consisted of anormal muscularis layer of the gallbladder wall, like a honeycomb appearance. Though the septa usually existed in the whole of the gallbladder, in some cases, the septations were conWned to the neck, the body and the fundus alone [1, 28, 44]. Situs inversus totalis (SIT) is a very uncommon entity. It was Wrst reported by Fabricius in 1600 [43]. The incidence is thought to be in the range of 1:10,0001:20,000 [2]. Transposition of the organs may also aVect thoracic organs, besides abdominal organs. Intrahepatic biliary tree, arterial and venous systems are in the mirror-image conWguration of the normal anatomy. The hepatoduodenal ligament is the same as seen in the orthotopic patients [18]. Arterial system anomalies are in the mirror-image conWguration of the orthotopic patients [14]. There is no evidence for increased incidence of cholelithiasis in SIT [8]. Since Mouret Wrst performed it in 1987, laparoscopic cholecystectomy has become the standard operative procedure for cholelithiasis in SIT [3, 10]. Concerning these previous described abnormalities location of the gallbladder, we were unable to Wnd any reference in the literature suggesting increased chances of anomalous biliary anatomy in patients. But that is not the case of another interesting abnormality, which is the left sided gallbladder or right sided round ligament. In such cases, the gallbladder is located in the plane of the round ligament and the bifurcation of the portal vein in two main

branches may not exist. The Wrst reported cases were thought to be published in 1886 by Hochstetter [13]. Very few cases have been described in the literature: Asonuma et al. [4] reported an incidence of 4 in 379 (1.1%), and Nagai et al. [25] reported an incidence of 3 in 1,621 (0.2%). Yamasaki et al. [45] listed 5 patients among 2,210 patients studied by ultrasonography (0.2%); Maetani et al. [21] 4 in 327 (1.2%); and Kuwayama et al. [16] 7 in 1,025 patients (0.7%). But recently a new concept for this anatomic entity named fusion of the plane has been proposed by Savier et al. [31]: two liver lobes separated by a unique plane containing the portal axis, without true bifurcation. They hypothesized that the origin of fusion of the planes (Fig. 2), as observed in adults, would correspond to an embryologic step of liver development. Portal and hepatic veins of 20 24 mm embryos resemble fusion of the planes [19], the central portion of the liver develops secondarily between two primitive lateral lobes [7] and there is variability in the position of the anterior sectorial branch [7]. In the case of incomplete development of the central part of the liver, the left intersectional plane resembles the midplane, which could not yet be clearly identiWed between the outlines of the portal branches for the future segment 4 and the future right sector. The absence of growth of segment 4 prevented shift of the round ligament toward the left, the formation of the horizontal part of the left bile duct, the formation of the quadrate lobe between the round ligament and the gallbladder, and the curving of its anterior branch [31]. When reviewing the literature, with the exception of AG (in those cases the diagnosis proposed was almost always cystic duct obstruction or a small contracted gallbladder) [29], the preoperative investigations always demonstrated the diagnosis of ectopic gallbladder which automatically induced an entire exploration of the biliary tree [3, 8, 9, 17, 31, 44]. Ectopic gall bladder is a rare entity mandating caution by the laparoscopic surgeon. The surgeon must locate the gallbladder accurately and map out the biliary tract preoperatively with appropriate investigations (Ultrasonography, CT scan, MRI and Endoscopic Retrograde CholangioPancreatography). Appropriate modiWcations of surgical approach and technique are required in these patients [29]. Ultrasonography is actually the investigation method of choice for the diagnosis of common gallbladder bile stones, with a sensitivity of 9598% [29]. Development of the biliary tract [11] The development of the biliary tract in humans has been and is still being actively studied [7, 38]. It is well-known that an endodermal bud develops from the foregut (duodenum) during the Wrst 3 weeks of gestation. The bud separates into two partshepatic and biliary. The hepatic part is

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288 Fig. 2 According to Savier et al. [31] relation between fusion of the planes of the liver and normal anatomy. a Fusion of the planes. b Development of the central region separates the medial plane and the left intersectional planes. c The central area is the place of development of the horizontal part of the left portal branch and the right anterior branch, with its known variations. d Normal hepatic architecture

Surg Radiol Anat (2008) 30:285290

a collection of rapidly proliferating cells (liver precursor cells) which penetrate the adjacent mesodermal tissue (the septum transversum) and are met by an in growing capillary plexus around the bile duct and umbilical veins, followed by the formation of the hepatic lobules and sinusoids. Development of the extrahepatic biliary tract [26] (Fig. 3) The extrahepatic bile ducts (EHBD) develop from the caudal part of the hepatic diverticulum [35, 38]. The lining biliary epithelium is continuous at its caudal end with the duodenal epithelium and at the cranial end with the proliferating precursor liver cells. The caudal segment develops into the gallbladder, part of the cystic duct and the common bile duct. The extrahepatic segments of the right and left hepatic ducts, which are recognizable from 12 weeks of
Fig. 3 According to Shiojiri [35] development of the extra hepatic bile duct. Mid-sagittal sections of the anterior intestinal area. The hepatic diverticulum is formed at 9 days of gestation and is divided into cranial and caudal portions at 9.5 days. Hepatic cord from the cranial portion then invades the septum transversum Mesenchyme

gestation and continuous with the common hepatic duct, and part of the cystic duct, develop from the cranial end of the diverticulum. The common hepatic duct and distal parts of both hepatic ducts are known to connect to several converging ductules in the hilar mesenchyme, which in turn are in direct communication with the ductal plate. Variations in the remodeling process of the common hepatic duct and distal parts of both hepatic ducts could explain, in part, the many recognized branching variants of large bile ducts [38]. It is well known that bile begins to Xow at about 12 weeks, so that this connection should be completed before 12 weeks of gestation but not as a solid stage as primary described but as a functional duct. This fact is well demonstrated by Vijayan and Tan [40] in a 3D radiological study of EHBD in embryos and fetuses at 5.516 weeks of gestation. They were able to show too that the gallbladder is already present with a lumen. Throughout infancy and

Day 9

Day 9.5
Hepatic cord

Day 10.5
Cranial Ventral

Mesenchyme

Cranial Caudal

liver

Hepatic diverticulum

Extra hepatic bile duct Gallbladder

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289 17. Levene A (1955) Acute torsion of the gallbladder. Post mortem Wndings in two cases. Br J Surg 45:338340 18. McDermott JP, Caushaj PF (1994) ERCP and laparoscopic cholecystectomy for cholangitis in a 66-year-old male with situs inversus. Surg Endosc 8:12271229 19. Mall FP (1906) A study of the structural unit of the liver. Am J Anat 5:227308 20. Mannl HF (1978) Gallbladder agenesis. Med Welt 29:19691974 21. Maetani Y, Itoh K, Kojima N et al (1998) Portal vein anomaly associated with deviation of the ligamentum teres to the right and malposition of the gallbladder. Radiology 207:723728 22. Matsuhashi N, Satake S, Yawata K et al (2006) Volvulus of the gall bladder diagnosed by ultrasonography, computed tomography, coronal magnetic resonance imaging and magnetic resonance cholangio-pancreatography. World J Gastroenterol 12(28):4599 4601 23. Monroe SE, Ragen FJ (1956) Congenital absence of the gallbladder. Calif Med 85:422423 24. Mottin CC, Toneto MG, Padoin AV (2004) Laparoscopic triple cholecystectomy. Surg Laparosc Endosc Percutan Tech 14:163 164 25. Nagai M, Kubota K, Kawasaki S et al (1997) Are left-sided gallbladders really located on the left side? Ann Surg 225:274280 26. Nakanuma Y, Hoso M, Sanzen T, Sazaki M (1997) Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply. Microsc Res Tech 38:552570 27. Nakao A, Matsuda T, Funabiki S et al (1999) Gallbladder torsion: case report and review of 245 cases reported in the Japanese literature. J Hepatobiliary Pancreat Surg 6:418421 28. Naritomi G, Kimura H, Konomi H, Takeda T, Ogawa Y, Chijiiwa K (1994) Multiseptate gallbladder as a cause of biliary pain. Am J Gastroenterol 89:18911892 29. Peloponissios N, Gillet M, Cavin R, Halkic N (2005) Agenesis of the gallbladder: a dangerously misdiagnosed malformation. World J Gastroenterol 11(39):62286231 30. Pery M, Kaftori JK, Marvan H, Sweed Y, Kerner H (1985) Ultrasonographic appearance of multiseptate gallbladder: report a case with coexisting choledochal cyst. J Clin Ultrasound 13:570573 31. Savier E, Taboury J, Lucidarme O, Kitajima K, Cadi M, Vaillant JC, Hannoun L (2005) Fusion of the planes of the liver: an anatomic entity merging the midplane and the left intersectional plane. J Am Coll Surg 200:711719 32. Shaikh AA, Charles A, Domingo S, Schabd G (2005) Gallbladder volvulus: report of two original cases and review of the literature. Am Surg 71:8789 33. Schinzel A (1990) Phocomelia and additional anomalies in two sisters. Hum Genet 84:539541 34. Shing B et al (1999) Congenital absence of the gallbladder. Surg Radiol Anat 21:221224 35. Shiojiri N (1997) Development and diVerentiation of bile ducts in the mammalian liver. Microsc Res Tech 39:328335 36. Short AR, Paul RG (1934) Torsion of gall-bladder. Brit J Surg 22:301309 37. Strauss S, Starinsky R, Alon Z (1993) Partial multiseptate gallbladder: sonographic appearance. J Ultrasound Med 12:201 203 38. Tan CEL, Moscoso GJ (1994) The developing human intrahepatic biliary system at the porta hepatis level between 29 days and 8 weeks of gestation: a way to understanding biliary atresia. Part 1. Pathol Int 44:587599 39. Turkel SB, Swanson V, Chandrasoma P (1983) Malformations associated with congenital absence of the gall bladder. J Med Genet 20:445449 40. Vijayan V, Tan CE (1997) Developing human biliary system in three dimensions. Anat Rec 249(3):389398

early childhood, the lumen (diameter and surface area) and the wall of the common bile duct increase progressively and reach mature proportions in adulthood [38].

Conclusion Congenital anomalies of the gallbladder are a relatively uncommon phenomenon. But in the rare cases associated with an intra-hepatic biliary abnormalities, anatomical knowledge is capital to recognize and understand these conWgurations. So before all biliary surgery, a good exploration of the extra and intra hepatic duct biliary is required to avoid injuries.

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