Journal of Visceral Surgery (2010) 147, e175—e180

ORIGINAL ARTICLE

Liver resection for intrahepatic stones in congenitalbile duct dilatation

G. Clemente ∗, F. Giuliante, A.M. De Rose, F. Ardito,I. Giovannini, G. Nuzzo

Department of Hepatobiliary Surgery, Faculty of Medicine and Surgery, A. Gemelli, CatholicUniversity of Sacred Heart, Rome, Italy

Available online 14 August 2010

KEYWORDS Summary

Gallstones;Intrahepatic lithiasis;Hepatectomy;Cholangiocarcinoma;Caroli’s disease

Objective: This study reports our clinical experience with liver resection for congenital dilata-tion of the intrahepatic bile duct and intrahepatic gallstones to evaluate results and defineindications for treatment.Patients and methods: We studied the clinical data of patients who underwent hepatic resectionfor intrahepatic lithiasis from January 1992 to December 2008 and assessed the immediate andlong-term results of these interventions.Results: Of 49 treated patients, 47 underwent liver resection. In the majority of cases, the dis-ease was limited to the left lobe and left hepatectomy was the most commonly performedsurgical procedure. The operative mortality was zero with morbidity in 24.5% of patients.Cholangiocarcinoma was diagnosed in six cases (12.2%). In 91.6% of cases the long-term resultswere good or satisfactory.Conclusion: Treatment goals in all cases should be the elimination of intrahepatic stones, theprevention of recurrent lithiasis, and prevention or cure of cholangiocarcinoma. Surgical exci-sion is the best possible treatment for symptomatic patients with localized disease and atrophyof the affected liver.© 2010 Published by Elsevier Masson SAS.

Introduction

Congenital dilatation of the biliary tree was first reported by Caroli and Couinaud [1] whodescribed small ‘‘grape-cluster’’ dilations along the intrahepatic bile ducts. Guntz et al. [2]have classified these expansions into three types: Type 1 corresponding to the grape clusterdilatation initially described by Caroli, Type 2 consisting of fusiform ductal dilatation,and Type 3 to saccular dilatation (Fig. 1). These three anomalies are part of the Type 5

∗ Correspondant author. Epatobiliare Chirurgia, Dipartimento di Scienze Chirurgiche, Università Cattolica, Policlinico Gemelli,00168 Roma, Italy.

E-mail address: gclemente@rm.unicatt.it (G. Clemente).

1878-7886/$ — see front matter © 2010 Published by Elsevier Masson SAS.doi:10.1016/j.jviscsurg.2010.06.005

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igure 1. Types of dilatation of the intrahepatic ducts; Guntz et al. [2

lassification proposed by Todani et al. [3] (Fig. 2), or typeVa, where they are associated with a choledochal cyst. Theisease may remain asymptomatic for a long time through-ut life. Intraductal stone formation due to prolonged biliarytasis can cause pain and biliary infection or repeated boutsf cholangitis. We call this stone formation ‘‘primary intra-epatic lithiasis’’ (PIHL). Primary stone formation must beistinguished from gallstones due to stone migration fromhe gallbladder and from stone formation upstream fromost-operative biliary strictures. PIHL is a very rare condi-ion in Western countries (less than 1% of all gallstones) [4],ut is more common in the Orient (about 4% of gallstones inapan) [5]. Bile stasis and stone formation on the one handnd chronic inflammation and infection on the other resultn progressive atrophy of the involved parenchyma and leado dysplastic transformation of the biliary epithelium, whichay result in the development of cholangiocarcinoma [6].The treatment of lithiasis complicating congenital dilata-

ion of bile ducts is not yet well defined. As with other typesf intrahepatic lithiasis, both surgical and nonsurgical pro-edures have been used with results that are not always

igure 2. Classification of congenital dilatation of intra- and extrahepithiasis may occur in types IVa and V.

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atic bile ducts, according to Todani et al. [3]. Primary intrahepatic

atisfactory. The anomaly is often limited to a single lobe oregment; in this case, liver resection can be curative [4,6,7].e report our experience with hepatic resections for PIHL.

atients and methods

his is a retrospective study of the clinical records ofatients who underwent liver resection on our service forntrahepatic lithiasis in the setting of congenital dilatationf intrahepatic bile ducts between January 1992 and Decem-er 2008.

We documented the age and gender of each patient,he clinical treatments previously performed for lithiasissurgical and non-surgical), and radiological examina-ions/interventions performed prior to surgery, particularlyhe cholangiographic delineation of stone location andhe presence of morphologic anomalies such as intrahep-tic ductal dilatation or stenosis. The operative reportas reviewed to determine gross macroscopic appearance,

ntra-operative diagnostic techniques (ultrasonography and

Liver resection for intrahepatic stones in congenital bile duct dilatation e177

cholangiography), the type of liver resection (using the clas-sification of Couinaud [8]), and type of calculi found withinthe bile ducts. The post-operative course was reviewed. Thepathology report was searched for the presence of cholan-giocarcinoma or mucosal dysplasia.

Long-term results were assessed from the clinical recordof consultations and follow-up examinations. The follow-up period averaged 58 months (range: 12—282 months),and focused on clinical status, laboratory tests, ultrasoundand, in some cases, magnetic resonance cholangiopan-creatograms (MRCP). These results were judged: good(asymptomatic patient with normal laboratory tests); sat-isfactory (fewer than two episodes of pain and/or fever peryear, with no impairment of quality of life), unsatisfactory(more than two episodes of cholangitis per year and abnor-mal laboratory tests).

Results

Between January 1992 and December 2008, 49 patients weretreated for PIHL: 30 men and 19 women, mean age 53.4years (28—74 years). Biliary colic, reported in 23 patients(47%), and episodes of cholangitis in 21 patients (43%) werethe most common presenting symptoms. Three patients (6%)presented with obstructive jaundice without other associ-ated symptoms, while two patients (4%) presented with anepisode of acute gallstone pancreatitis.

Forty patients (82%) had previously received one or moretreatments for gallstones in an interval ranging from 1 monthto 30 years prior to hospitalization. Table 1 reports the pro-cedures performed on 40 patients before hospitalization inour service. Choledochal cyst was diagnosed during chole-cystectomy in three cases.

On admission, all patients underwent testing as specifiedin Table 2. All patients had ductal dilatation and lithiasisproximal to ductal strictures and associated atrophy of theinvolved parenchyma. Table 3 shows the distribution of bil-iary stricture by location. Three patients with stones in thecommon bile duct were treated by endoscopic sphinctero-

Table 1 Previous biliary interventions.

Previous biliary interventions n %

Endoscopic sphincterotomy 85 64Cholecystectomy 29 21Choledochotomy 5 4Bilio-digestive bypass 5 4Percutaneous treatment 5 4Surgical sphincterotomy 4 3

Total 133 100

Table 2 Pre-operative imaging.

Pre-operative imaging n %

Ultrasound 49 100MRCP 40 82CT 36 73Retrograde cholangiopancreatography 3 6Percutaneous cholangiography 2 4

MRCP: magnetic resonance cholangiopancreatograms; CT:computerized thomography.

tomy before surgery. In two patients, magnetic resonanceimaging (MRI) revealed a cholangiocarcinoma associatedwith PIHL.

All patients were symptomatic (pain, fever, episodesof cholangitis). Of the 49 patients who had surgery, 47underwent liver resection and two patients had a simpleexploratory laparotomy for what proved to be unresectablecholangiocarcinoma. Intra-operative ultrasound was rou-tinely performed to confirm the extent of the disease andto guide the resection. Table 4 reports the variety of inter-ventions. In most cases, lithiasis was limited to the leftlobe, and left hepatectomy was the most common sur-gical procedure. Of the 24 patients who underwent lefthepatectomy, the resection was enlarged to include thecaudate lobe in eight patients. Twenty patients who stillhad their gallbladder underwent cholecystectomy. Intra-operative choledochoscopy was performed in four patientswho had stones in the contralateral bile ducts. A contralat-eral segmental resection was performed in one case of leftlobectomy, and left hepatectomy in one case (Table 4).In three patients with a choledochal cyst, cyst excisionwas performed followed by a hepatico-jejunostomy. Intra-operative cholangiography was performed at the end ofsurgery to verify the absence of residual stones and confirmthe anatomy of the biliary tree. External biliary drainage wasperformed in 27 patients and removed after post-operativecholangiography. The gross appearance of the resectedliver always showed atrophy and fibrosis with dilated bileducts; lithiasis was often associated with localized abscessesbeneath Glisson’s capsule (Figs. 3 and 4). The composition ofthe stones was cholesterol in 24 cases, calcium bilirubinatein 22 cases and calcium carbonate in one case.

Table 3 Site of biliary stricture.

Site of biliary stricture n %

Left hepatic duct 24 49Origin segmental ducts segments II and III 15 31Right hepatic duct 5 10Right posterior sectoral canal 2 4Segment IV canal 1 2Segment VI canal 1 2Segment VIII canal 1 2Total 49 100

Table 4 Surgical interventions.

Surgical interventions n %

Left hepatectomya 24 49Left lobectomyb 14 29Right hepatectomy 4 8Right lateral sectoral resectionc 2 4Resection of segment IV 1 2Resection of segment VI 1 2Resection of segment VIII 1 2Exploratory laparotomy 2 4

Total 49 100

a Resection extended to include caudate lobe in eight patients,combined resection of segment VI in one patient.b Associated resection of segment V in one patient.c Associated resection of segment V in one patient.

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Figure 5. Helical CT: atrophy of the left lobe associated withdilatation of the intrahepatic bile ducts.

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igure 3. Surgical specimen (left hepatectomy): multiple browntones within the bile ducts.

A cancer associated with intrahepatic lithiasis was foundn six of 49 (12.2%). The two patients who had an obviousass pre-operatively underwent left hepatectomy in one

ase and right hepatectomy in the other; pathology revealedT1 and a T3 cholangiocarcinoma. Two other cholangio-

arcinomas (T1 and T3), unsuspected pre-operatively, wereiscovered in the resected left hepatectomy specimen. Thether two patients had unresectable cholangiocarcinoma. Inll other cases, pathology exam revealed signs of inflamma-ion and dysplasia in the biliary mucosa.

Operative mortality was zero. Twelve patients (24.5%)ad complications: one patient had bile peritonitis, whichequired reoperation on the first post-operative day, fourbscesses were treated by percutaneous drainage, five bil-ary fistulae were treated conservatively and two patientsad persistent fever, treated with prolonged antibiotic ther-py. In six patients, post-operative cholangiogram throughhe biliary drain revealed residual common duct stones,hich were extracted by ERCP.

Long-term results of surgery were assessed in 36 patientsith follow-up greater than one year (mean: 58 months;

ange: 12 to 182 months); patients with cholangiocarcinomaere not included. Results were good in 29 cases (80.5%),

atisfactory in four cases (11.1%) and unsatisfactory in threeases (8.3%). These last three patients required additionalndoscopic treatment, with placement of stents. In patientsith cholangiocarcinoma, two patients (T3) died 6 monthsfter surgery. The other two patients (T1) are both alive andn very good condition, 116 months and 10 months after theperation. Of the two patients with unresectable cholan-

igure 4. Operative specimen (left hepatectomy): cholesteroltones in the bile ducts.

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igure 6. Magnetic resonance (MR) cholangiopancreatography:ilated left intrahepatic bile duct with multiple stones.

iocarcinoma, one died after 6 months, and the secondnderwent chemotherapy for a year and then was lost toollow-up.

iscussion

ew imaging technologies such as multi-slice helical CTnd MRI have led to increased diagnosis of cystic dilata-ion of the intrahepatic bile ducts and associated PIHLFigs. 5—7) in occidental countries. The characteristic mor-hological changes are a dilated biliary tree with calculiituated upstream from a stenosis of a major bile duct atr near the hilum. CT scan reveals the relative atrophy ofhe involved segment or lobe. MRI may also reveal abnor-alities of the biliopancreatic junction and choledochal cyst

ct di

Liver resection for intrahepatic stones in congenital bile du

Figure 7. Magnetic resonance imaging: dilatation of the intrahep-atic bile ducts of the left liver.

associated with PIHL; this is an indication for simultaneousresection of the extrahepatic bile duct [9].

The Japanese literature, always rich in descriptionsof biliary malformations and intrahepatic lithiasis [3,10],reports an association between these two disorders. Theclassification of congenital malformations of the biliary tractby Todani et al. [3] is the most widely used today [3]. Twentyyears ago, Matsumoto et al. [10] classified the four types ofhilar biliary strictures responsible for intrahepatic lithiasis.They also hypothesized a congenital origin and offered anexplanation of the formation mechanism. Type 1 strictureis localized at the level of convergence of the segmentalducts from segments 2 and 3. Type 2 stricture is localizedat the origin of the left main hepatic duct. These two typescomprise more than two-thirds of the 51 cases reported byMatsumoto and almost 80% of our cases. Type 3 stricture islocalized at the origin of the right anterior sectoral duct.Type 4 stricture is, in turn, divided into three sub-groups;these are the more complex hilar strictures. While agree-ing with the congenital origin of the strictures, the authors

also suggest a mechanism of embryological developmentdue to a mismatch in size between the intrahepatic bileducts, which arise embryologically within the substance ofthe primitive liver and the common hepatic duct originatingfrom the hepatic diverticulum of the foregut. Biliary stasisabove the stricture favors crystallization and calculus for-mation. Curiously, the vast majority of Matsumo’s patientshad a choledochal cyst in addition to stricture and biliarystasis [10]; we found this condition in only 6% of our cases.

Treatment of PIHL, i.e., of intrahepatic lithiasis compli-cating congenital dilatation of intrahepatic bile ducts, mustremove all stones and prevent their recurrence as well asthe risk of cholangiocarcinoma. When PIHL affects only alimited area of the liver, these objectives can be achieved byright or left hepatectomy or by resection of only the hepaticlobes or segments concerned. Careful topographic analysis isessential, to precisely identify the involved bile ducts. Intra-operative diagnosis with ultrasound and cholangiographyaid the intervention. Hepatic atrophy and/or hypertrophymay alter the normal anatomical relations. When the entireintrahepatic biliary tree is affected, hepatectomy and trans-plantation is the only possible treatment.

Comparison of the results of conservative surgical andnonsurgical treatments vs. liver resection is very difficultbased on data from the literature. Much of the reported

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data considers the treatment of choledocholithiasis in gen-eral rather than lithiasis associated with PIHL. Percutaneoustreatment is a good example: recurrence rates of less than10% at 5 years [11] have been reported, while in other series,recurrence rates are 32.6% [12] or above 50% [13]. In PIHL,treatment is individualized according to the nature andlocation of the lithiasis on the one hand and on the anatom-ical changes of the bile ducts and liver function on theother. In our opinion, the type of lithiasis should be definedpre-operatively in every case. While endoscopic treatmentseems most appropriate in cases of distal stone migra-tion, percutaneous treatment is appropriate for stones,which form proximal to a strictured bilio-digestive anasto-mosis, only liver resection can achieve the therapeutic goalsfor patients with LIHP where conservative measures areoften associated with failure and recurrence [14]. Compar-ison between conservative surgery (bilio-digestive bypass)and non-conservative therapy (liver resection), reported byTsunoda et al. [15] and Choi et al. [16], favors hepatic resec-tion.

The risk of cholangiocarcinoma in patients with PIHLshould not be underestimated. Indeed, the literature reportsthe risk of development of cancer in patients with intrahep-atic lithiasis at 5.8 to 17% [17—19]. For this reason, liverresection has been increasingly used as a treatment forPIHL [4,5,7,20—22]. Mabrut et al. [4] recently reported theresults of a multicenter study in which 27 patients under-went liver resection for localized disease with satisfactoryresults in 87% of cases.

Conclusion

In recent years, PIHL has been diagnosed more frequentlyin Western countries and several Western series of liverresections for PIHL have been reported. In our series, allpatients with PIHL showed dilatation of intrahepatic bileducts with stones upstream of a stricture. All symptomaticpatients with localized disease and associated atrophy ofthe involved liver were treated with hepatic resection. Thedisease occurred more commonly in males and the left lobe

was the most often affected. The clinical presentation is thesame as for other forms of choledocholithiasis; this accountsfor the delayed diagnosis in most patients. Surgical excisionof atrophic parenchyma, along with the locus of chronicinfection, is the therapeutic approach that treats the dis-ease most completely and prevents the risk of developingcholangiocarcinoma.

Conflict of interest statement

There are no conflicts of interest.

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