Factors contributing to diagnostic delay of Caroli syndrome: a single-center, retrospective study

Abstract

Background Caroli syndrome (CS) is a rare congenital disorder without pathognomonic clinical symptoms or laboratory findings; therefore, the diagnosis is often delayed. The objective of this study was to investigate the diagnostic delay and associated risk factors in CS patients. Methods This was a retrospective analysis of 16 CS patients admitted to a single tertiary medical center on mainland China. The diagnostic timelines of CS patients were reviewed to demonstrate the initial findings of CS at diagnosis, the risk factors associated with diagnostic delay, and potential clues leading to early diagnosis. Results The median diagnostic delay was 1.75 years (range: 1 month to 29 years, interquartile range: 6.2 years) in 16 enrolled CS patients. Sex, age, and initial symptoms were not associated with diagnostic delay. 87.5% of CS patients were diagnosed by imaging, and the accuracies of ultrasonography, computed tomography (CT), and magnetic resonance cholangiopancreatography were 25, 69.2, and 83.3%, respectively. The median diagnostic delays for patients with or without CT performed at the first hospital visited according to physician and radiologist suspicion of the diagnosis were 7.4 months and 6 years, respectively (p = 0.021). Hepatic cysts with splenomegaly were detected by ultrasound in over half of CS patients. Conclusions The majority of CS patients were not diagnosed until complications of portal hypertension had already developed. Recognition and early suspicion of the disease were important factors influencing diagnostic delay of CS. Hepatic cysts plus splenomegaly detected by US might raise the clinical suspicion to include CS in the differential diagnosis.

Caroli's Syndrome: A Case Report and Literature Review

“…Though the etiology and pathophysiology are still not very well known, CS is inherited in an autosomal recessive pattern. It is associated with genetic mutations in PKHD1 gene, which encodes a protein fibrocystin that helps build bile ducts and involves ductal plate malformation and consequent peri-portal fibrosis [1,3,4].…”

“…There are no pathognomonic signs or symptoms associated with CS. Affecting both genders equally, with a male-to-female ratio in both CD and CS of 1:1.8, the clinical manifestations may be insidious, and patients mainly present in one of the following two ways: 'intra-hepatic ductal ectasia and stagnation of bile' (recurrent cholangitis and/or choledocholithiasis) or 'portal hypertension' (gastrointestinal (GI) bleed, splenomegaly, ascites) [3,5]. Physical examination findings include either no findings or hepatosplenomegaly, peripheral edema, ascites, splenomegaly, hepatomegaly, hepatic insufficiency, and/or portal hypertension.…”

“…Laboratory findings are mostly non-specific [6]. CS is also associated with pancreatic cysts, cavernomatous portal vein transformation, choledochal cysts, renal tubular ectasias, cortical cysts, renal medullary spongiosis, medullary cystic disease, autosomal recessive polycystic kidney disease (ARPKD), or even autosomal dominant polycystic kidney disease (ADPKD), nephrolithiasis, hypertension, or pyelonephritis in infants and an increased risk of cholangiocarcinoma [3,5,6]. The risk of cholangiocarcinoma is 2.5-17.5% in CS, 100 times higher than in patients with normal hepatobiliary ducts and 10 times higher than in those with calculi [7].…”

“…While generally diagnosed within the first 20 years of life, CS may also remain asymptomatic for the entire life of the individual, or it can be diagnosed as late as the fifth decade [4,5]. A definitive diagnosis can be established by histopathology, but the first-line diagnostic investigation methods used because of their convenience and non-invasiveness are ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) [3].…”

“…The first step to timely intervention, complication control, and surveillance of CS is an early diagnosis [3].…”