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Background Congenital intrahepatic bile duct dilatation without fibrosis is called Caroli disease (CD), and is called Caroli syndrome (CS) when it has fibrotic and cirrhotic liver morphology. The development of intrahepatic carcinoma is described in both conditions, but the reported incidence varies extensively. Potential risk factors for the malignant transformation were not described. Furthermore, conservative or surgical treatment is performed depending on the extent of cystic malformation, hepatic dysfunction and structural hepatic changes, but little is known about which treatment should be offered to patients with CD or CS and cancer. Aim To further investigate the malignant transformation in these conditions. Methods A systematic review of the current literature until January 2019 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A search using Medline (PubMed) was performed using a combination of Medical Subject Headings terms "caroli disease", "caroli syndrome", "tumor", "malignant", and "cholangiocarcinoma". Only human studies published in English were used for this systematic review. The following parameters were extracted from each article: year of publication, type of study, number of patients, incidence of malignant tumor, duration of symptoms, age, sex, diagnostics, identification of tumor, surgical therapy, survival and tumor recurrence. Results Twelve retrospective studies reporting the courses of 561 patients (53% females) were included in this systematic review. With a mean age of 41.6 years old (range 23 to 56 years old), patients were younger than other populations undergoing liver surgery. Depending on the size of the study population the incidence of cholangiocarcinoma varied from 2.7% to 37.5% with an overall incidence of 6.6%. There were only few detailed reports about preoperative diagnostic work-up, but a multimodal work-up including ultrasound of the liver, computed tomography, magnetic resonance imaging and endoscopic retrograde cholangiopancreatography was used in most studies. Disease duration was variable with up to several years. Most patients had episodes of cholangitis, sepsis, fever or abdominal pain. Tumor detection was an incidental finding of the surgical specimen in most cases because it is currently often impossible to detect tumor manifestation during preoperative diagnostics. Liver resection or liver transplantation was performed depending on the extent of the biliary pathology and additional alterations of the liver structure or function. No postoperative adjuvant chemotherapy was reported, but chemotherapy was administered in selected cases of tumor recurrence. Overall survival rates after one year were low at 36% and a high recurrence rate of up to 75% during the observation period. Conclusion Only few retrospective studies reported a low tumor incidence. Despite the high rate of mortality and tumor recurrence, definite surgical treatment should be offered as soon as possible.

Summary Introduction Caroli disease (CD) is a congenital dilatation of the intrahepatic bile ducts. In combination with liver fibrosis or cirrhosis, it is called Caroli syndrome (CS). Infectious complications and intrahepatic cholangiocarcinoma are secondary problems. The aim of this study was to analyse the clinical pattern and outcome in patients with CD/CS who underwent liver surgery. Methods Between January 2004 and December 2016, 21 patients with CD/CS were treated with liver resection or transplantation (LTX) and post-operative data of patients with CD/CS were retrospectively analysed in a database. Results Two patients underwent LTX, and 19 patients underwent liver resection due to CD/CS. During follow-up, one patient developed lung cancer nine years after LTX. Patients resected due to CD/CS were predominantly females (74%) with an overall low incidence of co-morbidities. The median post-operative Clavien-Dindo score was 1 (range: 0–3). There was no death during a median follow-up period of over five years. In four patients, cholangiocarcinoma was confirmed. Tumor recurrence was seen in three patients, and was treated with chemotherapy or repeated liver resection. Conclusions LTX and liver resections due to CD/CS are rare and associated with an acceptable post-operative morbidity and low mortality. Surgical treatment should be performed as early as possible to avoid recurrent episodes of cholangitis or carcinogenesis.

Polycystic kidney disease (PKD) is a genetic disorder leading to end-stage renal disease more commonly in the fourth to sixth decades of life. Cyst formation in the kidneys and other organs such as the liver and pancreas is the main characteristic of this disease. A significant number of patients with PKD undergo kidney transplantation and receive significant immunosuppression, predisposing them to comorbidities such as infections and malignancies. The link between these cystic syndromes and Caroli disease (which is radiologically demonstrated as bile duct ectasia, segmental cystic dilation of intrahepatic bile ducts, with a normal common bile duct and absence of hepatic fibrosis or portal hypertension), is extremely important. Suspicion, screening, and timely diagnosis of the presence of Caroli disease in patients with PKD prior or post receiving a kidney transplant will reduce morbidity in these patients and possibly prolong both graft and patient survival. We describe a patient with autosomal dominant polycystic kidney disease who underwent recurrent admissions for presumed cholangitis and was eventually diagnosed with Caroli disease.

International audience; OBJECTIVE. The purpose of this multicenter retrospective study was to assess the MRCP features of Caroli disease (CD).MATERIALS AND METHODS. Sixty-six patients were identified from 2000 to 2019. The inclusion criteria were diagnosis of diffuse or localized CD mentioned in an imaging report, presence of intrahepatic bile duct (IHBD) dilatation, and having undergone an MRCP examination. The exclusion criteria included presence of obstructive proximal biliary stricture and having undergone hepatobiliary surgery other than cholecystectomy. Histopathology records were available for 53 of the 66 (80%) patients. Diffuse and localized diseases were compared by chi-square and t tests and Kaplan-Meier model.RESULTS. Forty-five patients had diffuse bilobar CD ((five pediatric patients [three girls and two boys] with a mean [± SD] age of 8 ± 5 years [range, 1–15 years] and 40 adult patients [26 men and 14 women] with a mean age of 35 ± 11 years [range, 20–62 years]) and 21 patients had localized disease (12 men and 9 women; mean age, 54 ± 14 years). Congenital hepatic fibrosis was found only in patients with diffuse CD (35/45 [78%]), as was a “central dot” sign (15/35 [43%]). IHBD dilatation with both saccular and fusiform features was found in 43 (96%) and the peripheral “funnel-shaped” sign in 41 (91%) of the 45 patients with diffuse CD but in none of the patients with localized disease (p < .001). Intrahepatic biliary calculi were found in all patients with localized disease but in only 16 of the 45 (36%) patients with diffuse CD (p < .001). Left liver atrophy was found in 18 of the 21 (86%) patients with localized disease and in none of the patients with diffuse CD (p < .001). The overall survival rate among patients with diffuse CD was significantly lower than that among patients with localized disease (p = .03).CONCLUSION. Diffuse IHBD dilatation with both saccular and fusiform features associated with the peripheral funnel-shaped sign can be used for the diagnosis of CD on MRCP. Localized IHBD dilatation seems to be mainly related to primary intrahepatic lithiasis.

Herein we present a clinical case of the Caroli syndrome caused by the compound heterozygous mutation in the PKHD1 gene. Histopathological assessment of liver detected biliary cirrhosis, numerous dilated bile ducts of various sizes, hyperplastic cholangiocytes containing a large amount of acid mucopolysaccharides, decreased s-tubulin expression and increased proliferation of cholangiocytes. A significant proportion of hepatic tissue was composed of giant cysts lined with a single layer of cholangiocytes, containing pus and bile in its lumen and surrounded by granulation tissue. An accumulation of neutrophils in the lumen of the bile ducts was observed, as well as an infiltration of the ducts and cysts surrounding connective tissue by CD4+ and to a lesser extent CD8+ lymphocytes. This may be caused by the expression of HLA-DR by cholangiocytes. Atrophy and desquamation of the epithelium of collecting tubules with the formation of microcysts were detected in the kidneys without a clinically significant loss of renal function. Morphopathogenetic mechanisms of the Caroli syndrome can be targets for a potential pathogenetic therapy and prevention of its manifestations and complications.

This case report is about one genetically specified diagnosed infant case of Caroli syndrome with autosomal recessive polycystic kidney disease (ARPKD) in China. The patient in this case report was an eight-month infant boy with an atypical onset and the main clinical manifestation was non-symptomatic enlargement of the liver and kidneys. The imaging study demonstrated a diffused cystic dilatation of intrahepatic bile ducts as well as polycystic changes in bilateral kidneys. The basic blood biochemical tests indicated a normal hepatorenal function. Four serum biomarkers of hepatic fibrosis were all elevated and the urine test for an early detection of the renal injury was positive. The genetic sequencing proved two heterozygous missense mutations of polycystic kidney and hepatic disease 1 (PKHD1) gene, c.9292GA and c.2507TC, inherited from each of his parents respectively. The former was a novel mutation that had been verified as disease causing through the predicting software while the latter had been reported from one recent case study on Chinese twins, which was possibly unique among Chinese population. The relations between the gene type and the clinical phenotype were not clarified yet. Up till a follow-up eleven months later after the discharge, the patient had a normal hepatorenal function without occurrence of any severe complication yet. The clinical symptoms of Caroli syndrome with ARPKD at infant stage were atypical and the enlargement of liver and kidney was usually the sole symptom. From the above systematic retrospective clinical analysis, as well as the relevant literature review, it's been concluded that the features of the hepatorenal images in patients with Caroli syndrome and ARPKD were distinctive. Genetic testing combined with the imaging study benefits a definite diagnosis as well as a differentiation from other hepatorenal fibrocystic diseases. Specific to the long-term management of this kind of patients, it's necessary to schedule a regular follow-up to monitor the hepatorenal function and the occurrence of various complications for an appropriate intervention, meantime to devote efforts to the genetic counseling work for the patients' family.

Nephronophthisis 13 (NPHP 13) is associated with mutations in the WDR19 gene, which encodes for a protein in the intraflagellar transport complex. Herein, we describe six additional cases accompanied by Caroli syndrome or disease.Targeted exome sequencing covering 96 ciliopathy-related genes was performed for 48 unrelated Korean patients with a clinical suspicion of NPHP. Mutations were confirmed by Sanger sequencing. We evaluated the expression of WDR19 in the biopsied kidney by immunohistochemistry in patients and controls.We detected three (3/48, 6.3 %) unrelated index cases with WDR19 mutations. One of the cases involved two siblings with the same mutation. Later, we detected an additional index case with a similar phenotype of kidney and liver involvement by Sanger sequencing of WDR19. The p.R1178Q mutation was common in all patients. All of the six affected patients from four families progressed to chronic kidney disease. Of note, all six patients had Caroli syndrome or disease. Immunohistochemistry for WDR19 showed localized expression along the luminal borders of the renal tubular epithelium in controls, whereas it showed diffuse cytoplasmic staining in the affected patients.Caroli disease is a major extra-renal phenotype associated with mutations in WDR19 in the Korean population. In this study, we visually validated the expression pattern of mutant WDR19 protein in the kidneys of NPHP 13 patients. More data are needed to identify the true frequency of p.R1178Q. Functional studies including transfection assay will provide solid grounds for the pathogenicity of each mutation.

We report the first case of a male child with both Caroli disease and vein of Galen malformation. The neonate presented to our department with congestive heart failure as a result of the intracranial arteriovenous high-flow shunt. Over time, several endovascular embolizations led to a complete angiographic occlusion of the shunt. Additionally, the diagnosis of Caroli disease was made at the age of 2 months. He developed choledocholithiasis necessitating endoscopic sphincterotomy and stone extraction. As a prolonged medical treatment he received ursodeoxycholic acid and antibiotics. A coincidence of Caroli disease and vein of Galen malformation has not yet been described. Both diseases are very rare, leading to the question of whether there is a link in the pathogenesis. Based on the few previously described underlying mechanisms, we develop hypotheses about the relationship between both rare diseases. We consider overexpression of vascular endothelial growth factor and its receptors as a possible common molecular mechanism in their pathogenesis. We also highlight the critical role of increased expression of the Notch ligand Jagged 1 both in the development of cerebral arteriovenous malformations in general and in the formation of dilated intrahepatic bile ducts (eg, in Caroli disease).

Background Caroli disease (CD) is characterized by dilation of the intrahepatic biliary tree, which may result in malignancy. Treatments include management of symptoms and hepatic resection to decrease disease burden. In patients with CD not amenable to these treatments, orthotopic liver transplantation (OLT) has been used. This study examines if OLT is a reasonable treatment for patients with CD. Materials and methods The United Network of Organ Sharing/Organ Procurement and Transplantation Network database between September 30, 1987 and March 31, 2011 was queried. Cases without patient or allograft survival time or without a diagnosis were excluded from analysis. Patients with CD were compared to patients with primary biliary cirrhosis (PBC), secondary biliary cirrhosis (BC), primary sclerosing cholangitis (PSC), and all indications for OLT. Survival analysis was performed by log-rank test and Kaplan-Meier. Results One hundred forty patients with CD were compared to 4797 patients with PBC, 489 patients with secondary BC, 6033 patients with PSC, and 92,210 patients post-OLT. Patient and allograft survivals of CD patients at 1, 3, 5, and 10 y are, respectively, 88.5%, 83.4%, 80.9%, and 77.8%; and 81.2%, 74.8%, 70.6%, and 67.9%. CD patients have significantly improved patient and allograft survivals after OLT compared to patients with secondary BC ( P = 0.003, P = 0.015) and all other patients undergoing OLT ( P = 0.003, P = 0.026). There is a trend towards long-term improved patient and allograft survival in transplanted patients with CD compared to patients with PBC and PSC. Conclusions These results suggest that OLT should be considered an effective treatment modality for patients with CD resulting in excellent long-term outcomes.

Objective To assess the preoperative disease characteristics as well as the rate of postoperative complications, patient survival, and course of symptoms after liver resection or orthotopic liver transplantation (OLT) for Caroli disease (CD) or syndrome (CS). Summary background data The clinical course of monolobar or diffuse CD or CS is often characterized by multiple conservative treatment attempts and interventions with recurrent episodes of cholangitis and a serious reduction in quality of life. The role and effectiveness of surgical treatment is still not well defined. Patients and methods Between June 1989 and December 2002, we treated 44 consecutive patients with CD or CS who had failure of conservative treatment before and were referred for surgical intervention. Demographic and clinical data, operative procedures and related morbidity, course of symptoms, and long-term follow-up were reviewed. Four patients with palliative resection for cholangiocarcinoma and incidental diagnosis of CD were excluded from the analysis. Results Twenty-two women and 18 men had a median period of 26.5 months from onset of symptoms to surgical therapy. Their median age at therapy was 49 years and 80% of the patients had monolobar disease with a left-right ratio of 2.6 to 1. Thirty-three (82.5%) patients underwent liver resection, while 4 (10%) patients received OLT for diffuse disease. Biliodigestive anastomosis alone was performed in 3 (7.5%) patients with contraindications to OLT. Patients (37.5%) had minor postoperative complications, which were treated conservatively, while 2 (5%) transplanted patients had a reoperation due to intraperitoneal bleeding. After a median follow-up of 86.5 months, we observed a favorable patient and graft survival. Three deaths during follow-up were not related to treatment or disease complications. Follow-up of disease-related symptoms, biliary complications, and antibiotic treatment revealed a significant improvement. Conclusion Our data show that liver resection for monolobar CD or CS and OLT for diffuse manifestations can achieve excellent long-term patient survival with marked symptom relief. Because of life-threatening long-term complications such as biliary sepsis and development of cholangiocarcinoma, timely indication for surgical treatment is crucial.

Background Caroli disease is a rare congenital disorder characterized by segmental, nonobstructive dilatation of intrahepatic bile ducts. The term Caroli syndrome is used for the association of Caroli disease with congenital hepatic fibrosis. Study aims To provide an overview of the clinical presentation and imaging features of Caroli disease and syndrome, with an emphasis on magnetic resonance imaging. Patients and methods Retrospective analysis of medical records on eight patients in whom a histologic diagnosis of Caroli disease or syndrome had been made. Results Presenting signs and symptoms were (hepato)splenomegaly, hematemesis and/or melena, cholangitis, jaundice, and recurrent fever. The central dot sign, defined in the literature as a dot or bundle of strong contrast enhancement within dilated intrahepatic ducts, was found in seven cases on various imaging modalities. A ‘dot-like structure’ was found in one case in which only unenhanced studies were available. There was a tendency toward a right hepatic-lobe predominance. Conclusion There is an overlap between the imaging features of Caroli disease and Caroli syndrome. Our findings support earlier reports that the central dot sign is highly specific for the disease, and that it can be reliably detected by current imaging techniques.

Caroli's disease is a cystic disease of the liver, which has been rarely associated with adult onset polycystic kidney disease. Three cases have been reported in the English Medline search. The presentation of this fourth case discusses the issues surrounding the treatment of Caroli's disease in the setting of a renal transplant.

A 12-month-old boy presented with fever, Klebsiellabacteremia, emesis, and abdominal pain. US demonstratedmultiple intrahepatic cysts containing fibrovascular bundles,known as the central dot sign (Fig. 1). Subsequent percuta-neous transhepatic cholangiography showed segmentalsaccular biliary ductal dilation (Fig. 2).Caroli disease is a rare congenital cystic dilatation of theintrahepatic bile ducts. This predisposes to biliary stasis andconsequent lithiasis, cholangitis, abscesses, and septicemia.Additionally, children face increased risk of hepatic fibrosis(termedCarolisyndrome),renaldisease,cholangiocarcinoma,and amyloidosis [2]. The central dot sign on US and CT isindicative of Caroli disease, but can also be seen inperibiliary cysts, obstructive jaundice, and periportal lym-phedema [1]. Cholangiography is the most sensitive radio-graphic study, because communication between bile ductsand cystic loculations is important to differentiate frommultiple liver cysts [2]; the role of magnetic resonancecholangiopancreatography for Caroli disease in children hasnot been systematically studied. Treatment can be achievedby partial hepatectomy in localized disease; however, diffuseliver involvement necessitates eventual transplant.References

연락처: 이상협, 463-707, 경기도 성남시 분당구 구미동 300 분당서울대학교병원 내과 Tel: (031) 787-7042, Fax: (031) 787-4051 E-mail: gidoctor@snubh.org Correspondence to: Sang Hyub Lee, M.D. Department of Internal Medicine, Seoul National University Bundang Hospital, 300, Gumi-dong, Bundang-gu, Seongnam 463-707, Korea Tel: +82-31-787-7042, Fax: +82-31-787-4051 E-mail: gidoctor@snubh.org Fig. 1. Pancreatico-bliliary CT and MRCP findings. (A) Non-contrast image. In segment IV/VIII of left lobe of liver, multiple high attenuated stones were found (arrowhead). (B) Contrast-enhanced image. This image showed focal low attenuated cystic dilatation of right intrahepatic duct (arrowhead). It also showed no definite dilatation of intrahepatic duct in other segments of the liver. 국소 Caroli병

Simultaneous bilateral spontaneous pneumothorax is an uncommon and serious medical problem frequently related to an underlying lung disease such as parenchymal lung disease, inflammatory events or neoplasms. Recurrent pneumothorax associated with persistent air leakage may pose a therapeutic dilemma in patients with underlying lung diseases. Caroli disease (CD) is a very rare congenital disorder characterised by intrahepatic biliary cystic dilatations and frequently associated with polycystic kidney and hepatic fibrosis. To date, no relation between CD and the bilateral diffuse cystic structure of pulmonary parenchyma has been described. In this paper we present a patient with the diagnosis of CD in whom simultaneous bilateral spontaneous pneumothorax was the initial finding due to severe underlying pulmonary disease. Our patient’s demographic and clinical characteristics, laboratory findings and course made us exclude the other aetiologies leading to such diffuse multi-bullous pulmonary involvement. The coincidence of recurrent pneumothorax and severe pulmonary disease has led to a big therapeutic dilemma. Open or minimally invasive surgery could be morbid or even mortal because of the nature of the parenchyma and the operative risk due to CD. Therefore, we suggest a unique conservative management including tube thoracostomy by locating the correct air spaces with the aid of high-resolution computed tomography followed by talc pleurodesis in patients with severe multi-bullous lung disease associated with potential risks due to co-morbidities.

Background Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully established. Methods Whole exome sequencing (WES) was performed on one twin sample with Caroli disease from a Chinese family from Shandong province. Routine Sanger sequencing was used to validate the WES and to carry out segregation studies. We also described the PKHD1 mutation associated with the genotype-phenotype of this twin. Results A combination of WES and Sanger sequencing revealed the genetic defect to be a novel compound heterozygous genotype in PKHD1, including the missense mutation c.2507 T>C, predicted to cause a valine to alanine substitution at codon 836 (c.2507T>C, p.Val836Ala), and the nonsense mutation c.2341C>T, which is predicted to result in an arginine to stop codon at codon 781 (c.2341C>T, p.Arg781*). This compound heterozygous genotype co-segregates with the Caroli disease-affected pedigree members, but is absent in 200 normal chromosomes. Conclusions Our findings indicate exome sequencing can be useful in the diagnosis of Caroli disease patients and associate a compound heterozygous genotype in PKHD1 with Caroli disease, which further increases our understanding of the mutation spectrum of PKHD1 in association with Caroli disease.

The results of surgical treatment of 7 patients, in whom disease of Karoly type I was diagnosed, were analyzed. Ultrasonographic examination, computeric tomography (CT) and retrograde pancreatocholangiography constitute highly informative diagnostic procedures in this disease. The choose of sugical treatment method of the patients depends on volumic cystic affection of intrahepatic biliary ducts and presence of strictured portions in them.

A 68 years old male presented with right hypochondrium abdominal pain and jaundice with no other clinical finding. CAT Scan and Ultrasonography showed right lobe bile duct dilatation. Magnetic Resonance Cholangiopancreatography gave an outstanding vision of a restricted right lobe bile duct dilatation associated to choledocholithiasis. A right hepatectomy and bile duct exploration were performed. The histopathological study disclosed a Caroli disease associated to a primary cholangiocarcinoma. Caroli disease is a congenital disorder characterized by intrahepatic cystic bile duct dilatation with a high risk association with cholangiocarcinoma.

Caroli disease is a rare congenital malformation characterized by cystic dilatations of large bile ducts. There are two forms of Caroli disease. Simple form entails the bile duct dilatation or ectasia. Complex form is copresense of hepatic fibrosis and portal hypertension. Here is presented a case of central diabetes insipidus (CDI) associated with Caroli disease.

We describe a case of Caroli syndrome (Caroli's disease and congenital hepatic fibrosis) in a 10-year-old boy with bilobar involvement and numerous renal cysts. Liver transplantation offers the only hope for such patients.

Hepatic fibrosis with bile duct ectasia and hyperplasia associated with polycystic kidney disease, analogous to Caroli syndrome in humans, was observed in a rat used as a control in a subchronic toxicity study. Light microscopy of liver sections showed multiple cystic and segmental saccular dilatations and hyperplasia of the intrahepatic bile ducts associated with overgrowth of portal connective tissue; the kidneys had diffuse cystic dilatation of cortical renal tubules. The lesions resembled those of human cases of the fibropolycystic disease termed as Caroli syndrome, which is thought to be the result of a pathologic developmental process known as ductal plate malformation. Recently, an animal model of Caroli syndrome has been described in mutant rats from a colony that constantly showed renal and hepatic cysts and an autosomal recessive mode of inheritance. The finding in our case of identical hepatorenal lesions suggests that the same mutation has occurred incidentally in a standard colony.

We describe a case of congenital non-obstructive dilatation of the hepatic bile ducts (Caroli disease). The accuracy of ultrasound for the diagnosis of this syndrome is pointed out. Ultrasound scan can be carried out easily and with a remarkable imaging precision. The ultrasonographic patterns consist of both evident dilatation of the ducts and characteristic protrusions connecting the ductal walls to intraluminal portal branches (bridging). These sonographic findings confirm the etiopathogenetic hypothesis according to which Caroli disease is a result of the blockage of the bile ducts development. Moreover, we underline the efficacy of ursodeoxycholic acid in the treatment of the chronic cholestasis, always present in this disease.

A patient who was studied for portal hypertension had an enlarged liver and multiple hepatic cysts on abdominal CT scan. He underwent hepatobiliary scintigraphy using Tc-99m mebrofenin which documented communication of the cysts with the main biliary tree and allowed a noninvasive diagnosis of Caroli syndrome associated with congenital hepatic fibrosis.

We describe a new case of pure Caroli disease and review of the literature. Although often sporadic, this disease is usually considered an autosomal recessive hereditary disease. It is often either associated with another congenital hepatorenal fibrocystic disease or with extrahepatic bile duct dilatation. The clinical examination and laboratory tests are of not specific if congenital hepatic fibrosis or congenital cysts of the coleduct is lacking. Certain echographic and scan images are however very specific. Complications are related to intrahepatic stone formation and to superinfections. The long-term course appears to involve increased risk of cholangiocarcinoma. Treatment of the localized form includes priority resection. In diffuse disease, treatment may be more medical with antibiotics and sometimes bile solvents. In case of failure, transplantation may be entertained.

17 patients with a Caroli's syndrome are reviewed with emphasis on clinical features and late results (follow-up: 2-10 years). The group consists of 9 women and 8 men ranging in age from 17 to 80 years (mean of 42.6). 14 patients had a diffuse form, 5 of whom had periportal fibrosis with secondary biliary cirrhosis, which in 3 cases resulted in a portal hypertension with hepatic failure. In only 3 cases the dilatation was limited to the left lobe of the liver. 9 of the patients had previously undergone surgery in the form of cholecystectomy and choledocholithotomy elsewhere. The disease was complicated by lithiasis (14 intrahepatic, 9 extrahepatic). Curative treatment was only possible in the 3 patients with unilobar Caroli's syndrome (partial liver resection). In 5 patients we performed a cholecystectomy and choledocholithotomy combined in 2 cases with a transduodenal sphincterotomy. There was no operative death. Endoscopic treatment consisted in removal of stones and decompression of the biliary tree by sphincterotomy in 9 cases and endoscopic retrograde biliary drainage (endoprosthesis) in 5 cases. Excepting the 3 curative operated patients who are asymptomatic respectively 2, 4 and 5 years after surgery, the remaining cases had repeated bouts of acute pains accompanied by recurrent episodes of cholangitis. A late mortality of 23.5% (4 patients) is proof of the poor prognosis of this disease.

The authors report a case of single-lobe Caroli's disease discovered at the radiologic exploration during a laparoscopic cholecystectomy leading to a left hepatic lobectomy 2.5 months later. Localized dilatation of the intrahepatic bile-ducts are infrequent. They may be associated with others pathological conditions such as cystic dilatation of the extrahepatic bile-ducts, congenital hepatic fibrosis of the liver or renal pathology. Hepatic resection is the logical treatment of such localized lesions, but it may have an excessive risk in case of association with a congenital hepatic fibrosis of the liver. The authors insist about the necessity of radiographic exploration during every biliary surgical approach, even with laparoscopic technic.

Caroli's disease is characterized by uni- or bilobar cystic enlargement of the intrahepatic biliary tract. Clinical symptoms include recurrent cholangitis, right upper quadrant abdominal pain and jaundice. The diagnosis is usually established preoperatively based on abdominal ultrasound, computertomography and ERCP. Eight patients suffering from unilobar Caroli's disease underwent liver resection during a period of six years. The postoperative course was uneventful, and after a median follow-up of 39.6 months in one case only a temporary jaundice occurred. Liver resection is the method of choice for Caroli's syndrome when feasible. Apart from the curative intention liver resection represents also a prophylactic method since the risk of malignant transformation to cholangiocellular carcinoma in the cystic walls after draining procedures is considerably high. For diffuse spread of Caroli's disease in the liver orthotopic liver transplantation has emerged as therapeutic option.

Two adults with communicating cavernous ectasia of the biliary tract (Caroli disease) are described. Both patients had the pure form of the disease, characterized by saccular dilatation of intrahepatic bile ducts, multiple intrahepatic calculi, absence of portal hypertension, and associated cystic renal disease. Computed tomographic (CT) scans of the liver showed tiny dots with strong contrast enhancement within dilated intrahepatic bile ducts (the central dot sign). These intraluminal dots on CT scans corresponded to intraluminal portal veins on sonograms, findings indicating portal radicles surrounded by dilated intrahepatic bile ducts.

Two new pediatric examples of Caroli disease are reported; one was diagnosed by operative cholangiography and one by percutaneous transhepatic cholangiography. Although a variety of approaches may lead one to suspect the diagnosis, percutaneous transhepatic cholangiography is now the method of choice to establish the diagnosis.

Two patients are discussed in whom Caroli diseases was diagnosed with the aid of computed tomography (CT). One patient had the pure form of the disease, characterized primarily by saccular dilatation of the intrahepatic bile ducts and clinically manifesting as recurrent cholangitis. The second patient had a form ccharacterized primarily by hepatic fibrosis and clinically manifesting as portal hypertension. These are the first patients studied with CT to be reported to the authors' knowledge; CT is recommended as the optimal noninvasive method to evaluate such patients.

The role of vibrissa sense of touch, sense of smell, and vision in the Ryukyu mice in experiments with the optic boundary and the glass corridor were studied. A total of 20 adult and 20 young mice were used in the experiments. At the first stage, observations on the intact animals were performed; the animals with removed vibrissa and anosmic animals were used at the second and third stages, respectively. Significant similarities were observed between the behavior of adult males and females. More essential differences were found between the young and adult mice. The role of vibrissa sense of touch is important for orientation of Mus caroli, especially in young mice. Adult animals with a great life experience compensate for the absence of vibrissae more successfully through the intensified use of vision. Anosmia markedly reduces the motor activity of animals and leads to a reduced marking behavior. However, it stimulates the intense use of vision to a lesser extent than does vibrissectomy.

Congenital cystic dilatation of the biliary tree (Caroli's disease) is a rare condition that usually presents with ascending cholangitis. This report demonstrates the difficulty of recognizing other complications of Caroli's disease antemortem. A 35-year-old man developed a subphrenic abscess and malignant transformation of the biliary tree; both were clinically undetected. Episodes of pain, pyrexia, or weight loss should be assessed carefully and the complications of Caroli's disease considered before attributing such symptoms to recurrent cholangitis.

Although Mus caroli is being used in a number of laboratories as an experimental animal, basic information concerning its life span, reproductive ability, and age-related pathologies has been unavailable. Here we present this basic information, and discuss the similarities to and differences from the laboratory mouse, Mus musculus domesticus [strains A/StTrWo and (A/StTrWo x C57BL/6NNia)F1] and, from published data, wild-type Mus musculus.

This paper describes the clinical symptomatology, the pathogenesis, diagnosis and therapy of the Caroli'Syndrome with a special reference to differences to other congenital hepatic diseases with similar manifestations. We report on a male infant with a Caroli'Syndrome, which is associated with a chromosomal imbalance and other malformations and discuss the genetical background.

In two men and three women aged 64-89 years on necropsy a localized form of congenital cystic dilatation of the intrahepatic bile ducts (Caroli's disease) was found affecting the left and/or one of the segments of the right liver lobe. There was diffuse fibrosis with striking reduction of the left lobe where the dilated bile ducts were macroscopically apparent only in two subjects with concurrent occlusion of the extrahepatic bile ducts by stones and carcinoma of the head of the pancreas. Segmental dilatation of the bile ducts of the right lobe was not associated with structural changes of the hepatic tissue. On microscopic inspection the wide open or collapsed dilated bile ducts had a fibrohyaline wall of different thickness. In the smaller peripheral bile ducts there were diverticulous deformations of the lumen with persistent inflammation in the deep mucosal folds. No neuroendocrine cells or dysplastic changes were found in the mucosa and glands of the intrahepatic bile ducts.

Caroli's disease was complicated by a Budd-Chiari-like syndrome as a result of enlarged lymph nodes that compressed the vena cava. Histologically the picture was compatible with "sinus histiocytosis with massive lymphadenopathy." We discuss the combination of these two rare disorders.