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CASE REPORTS
CAROLI’S DISEASE WITH MEDULLARY SPONGE KIDNEY AND PORTAL HYPERTENSION.... FEATURES OF CAROLI’S SYNDROME :
A CASE REPORT AND REVIEW OF LITERATURE
VAISHALI NIMBKAR*, AJITA NAWALE**, ANAGHA JOSHI***, SHASHANK S PRASAD*
We report a case of portal hypertension presenting with recurrent episodes of haematemesis, who on ultrasound was diagnosed to be a case of Caroli’s syndrome with intrahepatic biliary ectasia, medullary sponge kidney and nephrocalcinosis. The diagnosis of this syndrome is essential for the management of not only the patient in case but also of his family, as this syndrome is genetically inherited in an autosomal recessive or dominant mode. The aetiopathology of this rare entity is discussed here along with the role of newer non-invasive diagnostic modalities like ultrasound, spiral CT, MRI and MRCP, which has made conventional diagnostic methods like cholangiography outdated. We also discuss the management of this syndrome along with review of literature.
CASE REPORTA 29 yr old man presented with abdominal pain, distension and recurrent haematemesis for which he had multiple blood transfusions. No other significant history was available. He was referred to us with a provisional diagnosis of portal hypertension.
Plain x-ray of the abdomen was unremarkable. Ultrasound (USG) of the abdomen revealed the true nature and full extent of the disease. Abdominal sonography showed hepatosplenomegaly, an elongated and tortuous splenic vein suggestive of portal hypertension which explained his haematemesis. However, that was not all. The interesting finding was the presence of multiple dilated, interconnecting intrahepatic biliary radicles with a normal extrahepatic bile duct (Fig. 1). On further scanning, the kidneys showed multiple medullary cysts with nephrocalcinosis (Fig. 2). The full spectrum of is disease was thus diagnosed as Caroli’s syndrome, which is Caroli’s disease with medullary sponge kidneys and nephrocalcinosis. This diagnosis was important not only for his management but also for the screening of his family members, considering that this syndrome is inherited in an autosomal dominant or recessive mode. Computed Tomography (CT) confirmed the findings. Splenectomy was performed to relieve the haematemesis.
DISCUSSION
Caroli’s disease, also known as communicating cavernous ectasia of the biliary tract, was reported as early as 1906 but became better known as a distinct clinical syndrome after Jacques Caroli reported a case in 1958.
Caroli’s disease is a developmental anomaly and there are many theories explaining its pathogenesis. It is postulated to be due to a combination of disproportionate overgrowth of biliary epithelium and of its supporting connective tissue. Alternately it may be due to ductal plate malformation in which there is arrest in foetal organogenesis of the biliary tree. Another interesting hypothesis is that the cystic dilatation is a result of ischaemic infarction secondary to peripheral hepatic artery occlusion. Development of communicating biliary cysts in women with polyarteritis nodosa and hepatic artery occlusion, and also in 13 monkeys subjected to hepatic artery embolisation, supports this theory. On a genetic level, unbalanced translocation between chromosome 3 and 8 or the structural rearrangement of genes located therein seems to be responsible. This explains the familial clustering and its association with polycystic kidney disease.1 Caroli’s disease, which is classified as type 5 choledochal cyst by Todani,2 is considered to be a part of a spectrum of related conditions with multiple hepatic and renal cysts like polycystic kidney disease. Caroli described two forms of this disease : the so called pure form of Caroli’s disease which occurs in a focal or diffuse manner, characterized by saccular, communicating intrahepatic bile duct dilatation and the second form, called as Caroli’s syndrome which has relatively less
bile duct dilatation but is associated with hepatic fibrosis that results in portal hypertension and terminal liver failure. It is unclear whether the two types described by Caroli represent separate entities or a single disorder distinguished by hepatic fibrosis. Most (75%) of the pts are males and asymptomatic. If symptomatic, they present in childhood or early adulthood, generally less than 30 yrs of age due to the various complications associated with it. The symptoms depend on whether predominant abnormality is duct dilatation or hepatic fibrosis. The former group usually presents with episodic abdominal pain, fever and jaundice secondary to bile stone disease, ascending cholangitis and liver abscesses. The latter group presents with portal hypertension including haematemesis and lower GI bleed. Cholangiocarcinoma is seen in 7% of the pts and can complicate both types.
Associated cystic dilatation of kidneys is seen in 60-80% of the cases, most frequent is medullary sponge kidney. These pts are usually asymptomatic from a renal standpoint but may develop renal stone disease and infections. Congenital hepatic fibrosis is also associated with renal cysts but here renal failure dominates the picture. Caroli’s disease can be associated with choledochal cyst, this type is however inherited in an autosomal dominant pattern, there is no associated hepatic fibrosis or renal anomalies and the ductal dilatation is usually confined to one lobe.
Diagnosis
With the rapid advances in non-invasive techniques like USG, CT and Magnetic resonance imaging (MRI), Caroli’s disease and syndrome are nowadays more frequently diagnosed. The combination of endoscopic retrograde cholangiopancreaticography (ERCP) and USG leads to a more reliable diagnosis to the extent of the disease3 which is essential for appropriate management. CT serves as a useful preoperative roadmap if insufficient data is obtained on USG, however with advent of MRI and MRCP, invasive procedures like ERCP and biopsy are rarely indicated.4
USG is the initial investigation of choice. The pure form shows diverticulum like sacculi of intrahepatic biliary tree, more pronounced towards the center and can be segmental or generalised. Presence of dilatation in the periphery is indicative of development of complications like cholangiocarcinoma. These cystic spaces often contain amorphous debris and/or calculi. There can also be bulging of bile duct walls, causing cystic dilatation to resemble septated hepatic cysts. One finding considered pathognomonic of Caroli’s disease is “intraluminal portal vein sigh” which consists of portal vein radicles surrounded by the dilated bile duct. Awareness of this sign allows us to make a more or less accurate diagnosis without resorting to other expensive, invasive investigative means.5 However, this sign is seen in some other entities like peribiliary cysts and hence should not be considered as an absolutely specific sign for Caroli’s disease.6 Doppler demonstrates the absence of signals on range gating or colour sampling in these cystic spaces. With advanced portal hypertension, there is a “no flow” state in the intracavitary part of portal vein and a strong arterial signal related to disturbed haemodynamics in the liver. Considering the portal haemodynamic changes over time, Doppler monitoring of the
portal system can be used to indirectly follow the progression of the disease and may be an effective alternative to liver biopsy.7 Kidney may be normal or of variable echogenicity, depending on the extent of involvement by polycystic renal disease. In the second form, changes of periportal fibrosis and portal hypertension dominate the picture.
CT scan is an excellent way to demonstrate the extent of disease. “Central dot sign” corresponding to intraluminal portal vein sign on USG can be seen on CT.
The appearance of Caroli’s disease on CT/MRI can be confused with polycystic liver disease or obstructive bile duct dilatation. Whereas the cystic spaces in Caroli’s are irregular in shape and communicate with biliary tree, cysts in polycystic liver disease are rounder and smoother and they deform but do not communicate with bile ducts. Morever in Caroli’s disease, dilated bile ducts have a random, bizarre pattern and there are focal areas of cystic ectasia. This differs from appearance in obstructive bile duct dilatation where dilatation is most marked centrally, tapers towards periphery in an organized pattern and lacks focal areas of cystic dilatation.
Radionuclide studies using Tech-99mIDA shows focal defects in the hepatic phase representing dilated bile ducts and a gradual increase in activity as the radionuclide concentrates in these ducts.
Cholangiography which was absolutely essential previously to delineate the biliary anatomy and determine the surgical approach, is now rarely indicated with the availability of non-invasive diagnostic methods. Caroli’s disease can be diagnosed antenatally on USG, by late second or third trimester. The earliest reported cysts are at 25 wks of gestation. Because these cysts may be initially asymptomatic, prenatal diagnosis facilitates early treatment and prevention of the potential complications by regular follow-up. The natural history of Caroli’s disease diagnosed antenatally is unclear and there is an instance of regression of antenatally diagnosed localized Caroli’s disease. Hence a period of observation appears warranted.8
Management
The management depends on the clinical severity of the symptoms. Whereas choledochal cyst is treated by surgical excision and Roux-en-Y anastomosis, Caroli’s disease, due to the primary intrahepatic nature cannot be treated by surgery as a blanket management. The treatment is primarily aimed at managing the associated complications of recurrent cholangitis, hepatic abscesses, biliary calculi and carcinoma. Recurrent cholangitis requires drainage which can be done by open surgery, positioning of an open stent or by percutaneous drainage. However this treatment is just palliative and presents bad results on follow-up. If the disease is confined to one lobe, partial lobectomy is the surgical treatment of choice.9 In view of development of cholangiocarcinoma in 7% of these pts, the patients with bilobar disease should have regular clinical follow-up with ultrasound, and biopsy if required. Orthotopic liver transplantation appears to be an effective curative option for the treatment of these patients who cannot be operated radically.10 It gives good results on follow-up not only in cholangitis but also in carcinoma when it is localized in the liver.10
REFERENCES
1. Parada LA, Hallen M, Hagerstrand I, Tranberg KG, et al. Clonal chromosomal abnormalities in congenital bile duct dilatation. Gut 1999; 45 (5) : 780-2.
2. Todani T, Watanabe Y, Narusue M, et al. Congenital bile cysts : classification, operative procedures and review of 37 cases including cancer arising from choledochal cyst. Am J Surg 1977; 124 : 263-9.
3. Rickes S, Neye H, Wirth J, et al. Improved accuracy in diagnosis of intrahepatic bile duct ectasia in Carolis disease by combination of ultrasound and ERCP. Ultraschall Med 2000; 21 (5) : 223-5.
4. Hussain SZ, Bloom DA, Tolia V. Carolis disease diagnosed in a child by MRCP. Clin Imaging 2000; 24 (5) : 289-91.
5. Seth AK, Chawla Y, Dhiman RK, et al. Carolis disease : a central dot means a lot. Trop Gastroenterol 1997; 18 (4) : 165-6.
6. Ahmadi T, Itai Y, Minami M. Central dot sign in entities other than Carolis disease. Radiat Med 1997; 15 (6) : 381-4.
7. Gorka W, Lewall DB. Value of Doppler sonography in assessment of patients with Carolis disease. J Clin Ultrasound 1998; 26 (6) : 283-7.
8. Bratu I, Laberge JM, Khalife S, et al. Regression of antenatally diagnosed localized Carolis disease. J Pediatr Surg 2000; 35 (9) : 1390-3.
9. Ammori BJ, Jenkins BL, Lim PC, et al. Surgical strategy for cystic diseases of liver in a western hepatobiliary centre. World J Surg 2002; 26 (4) : 462-9.
10. Waechter FL, Sampaio JA, Pinto RD, et al. The role of liver transplantation in patients with Carolis disease.
Hepatogastroenterology 2001; 48 (39) : 672-4.
