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1001
Review
Radiologic Jae Hoon
Findings
of Clonorchiasis
Lirn1
Clonorchiasis
is a trematodiasis
caused
by chronic
infestation
The adult flukes reside in the medium-sized and small intrahepatic bile ducts and, occasionally, in the extrahepatic bile ducts, gallbladder, and pancreatic duct. The result is mechanical obstruction, inflammatory reaction, adenomatous hyperplasia, and periductal fibrosis. Signs and symptoms are usually mild and nonspecific, but heavy infestation results in obstructive jaundice. The disease has a close relationof liver
ship
flukes,
with
In this
Clonorchis
recurrent
article,
the
sinensis.
pyogenic radiologic
cholangitis findings,
and
cholangiocarcinoma.
including
cholangiography,
sonography, and CT of clonorchiasis are reviewed pathophysiology of the disease. The relationship pyogenic
cholangitis
and
to cholangiocarcinoma
in light of the to recurrent is discussed.
The geographic distribution of clonorchiasis is largely confined to the Orient, from Japan to Vietnam. The endemic areas include Japan, Southern Korea, the mainland of China (except the northwest), Taiwan, and Northern Vietnam [1]. There are some 38 million carriers throughout the world [2]. The disease has been encountered in nonendemic areas as well [3-6] and may be recognized with increasing frequency in the Western world, because the flukes live for decades and the infested person may emigrate or travel anywhere in the world. Human infestation depends on eating habits [1]. Persons with a marked preference for raw fish in their diet are infested more often. In Korea, 30- to 50-year-old men are infested most often. This is explained by social customs. Korean men
1
April 20, 1990;
Department
accepted
of Diagnostic
after revision
Radiology,
Kyung
have a tradition of eating raw freshwater fish, soaked simply in vinegar or red-pepper mash, as an appetizer when drinking at social gatherings. Children and women infrequently join in such gatherings, so they have much less exposure to the infestation.
Parasitology
The adult fluke of Clonorchis sinensis is a flat, elongated, leaflike, flabby worm tapered anteriorly and somewhat rounded posteriorly [1] (Fig. 1). The size ranges from 8.0 to
15.0 mm long by 1 .5 to 4.0 mm wide and about 1 .0 mm thick.
Epidemiology
Received
Article
The fluke has two suckers, oral and ventral; it sucks the blood of the host through the mucous membrane of the bile ducts. The fluke may persist for 1 5-20 years or more. Humans are the most suitable definitive hosts. Animal reservoir hosts are dogs, hogs, wildcats, martens, badgers, minks, weasels, and rats [1]. One adult fluke lays approximately 2000-4000 eggs each day. The eggs, laid within the biliary tree of the definitive host, are carried down the common bile duct and passed in the stools. On reaching fresh water, the eggs are eaten by some genus of snail, mostly Parafossarulus, Bithynia, and Alocinma, the first intermediate host. Within the snail, the eggs undergo metamorphosis, after which the cercariae escape. The cercariae penetrate the scales of suitable freshwater fish, mostly the Cyprinidae, the second intermediate host. Within the muscles of the fish, the cercariae encyst and become metacercariae to be ingested
May 30, 1990.
Hoc University
Hospital,
,
1 Hoeki-dong,
Dongdaemun-ku,
Lim. AJR 155:1001-1008,
November
1990 0361-803X/90/1555-1001
© American
Roentgen
Ray Society
Seoul 130-702, Korea. Address reprint requests to J. H.
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1002
LIM
by the final host. When a person ingests the flesh of raw fish containing metacercariae, the cyst is freed from the flesh by the action of gastric juice in the stomach, and the cyst wall is dissolved by trypsin in the duodenum. The larva excyst and migrate from the duodenum via the ampulla of Vater into the bile ducts, where they become mature worms in about 25 days. They usually reside in the intrahepatic bile ducts (Fig.
2) but also occasionally gallbladder,
in the extrahepatic
as well as the pancreatic
ducts
and the
duct.
Pathophysiology
The main factor in pathogenesis is a mechanical obstruction of the biliary tract by the flukes, congestion of bile, and the effects of soluble substances (metabolites) released from the flukes into the ducts and surrounding tissues [1 ]. The severity of the dysfunction depends on the number of flukes present and the repetition and period of infestation. Most human infestation is chronic, perhaps from several years to several decades because of repeated ingestion of raw fish. Adult flukes living within the medium-sized and small intrahepatic ducts (i.e., tertiary, quaternary, and more peripheral tributaries) (Fig. 2) produce mechanical obstruction and inflammatory reaction [7]. In the early stage, edema and desquamation of epithelium, proliferation of bile ducts, and an inflammatory reaction occur. In the later stage, metaplastic squamous cells appear in conjunction with glandular proliferation, resulting in adenomatous hyperplasia [8, 9]. Bile ducts become dilated, thick, and infiltrated with lymphocytes, plasma cells, histiocytes, and fibroblasts. In heavy infestations, the main bile ducts and gallbladder are involved. Later, marked periductal fibrosis occurs with pronounced thickening of the walls of biliary passages [9]. In heavy infestation, flukes may reside in the pancreatic duct, within the main pancreatic duct of the tail portion, and within its tributary ducts [1 1 0]. These ducts are dilated and packed with flukes. Flukes in the ducts produce squamous metaplasia, mucous gland hyperplasia, and fibrous thickening of the ductal wall [10]. ,
AJR:155, November 1990
Clinical
Manifestations
Clinical manifestations depend on the number of flukes, the period of infestation, and complications [1 ]. Lightly infected persons usually have no signs or symptoms. In moderate or progressive cases, the clinical signs and symptoms are loss of appetite, indigestion, fullness of the abdomen, epigastric distress unrelated to meals, discomfort in the right upper quadrant, diarrhea, edema, and some hepatomegaly. In heavy infestations, the signs and symptoms are weakness and lassitude, epigastric discomfort, paresthesia, loss of weight, palpitation, tachycardia, diarrhea, vertigo, tetanic cramps and tremors, and toxemia from liver impairment. Jaundice is caused by obstruction of the intrahepatic biliary trees by worms or inflammatory changes. In patients with complications, such as pericholangitic abscess or recurrent pyogenic cholangitis, the signs and symptoms are those of acute infection, including fever, chills, and abdominal pain. In patients with cholangiocarcinoma, jaundice and pruritus predominate over other minor symptoms because of the obstruction of the passage of bile. Laboratory abnormalities include eosinophilia and an increased level of serum alkaline phosphatase. In cases with significant obstruction of the bile passage, levels of serum bilirubin, cholesterol, aspartate aminotransferase (GOT), and alanine aminotransferase (GPT) are increased [1].
Cholangiographic
Findings
Cholangiography once played a major role in the assessment of the biliary tract in clonorchiasis. With the advent of sonography and CT, the role of cholangiography has decreased because the diagnosis usually is made on the basis of sonographic or CT findings and subsequent examination of the stool for ova. Cholangiography is indicated in heavy infestation as a workup for obstructive jaundice, or in patients with clonorchiasis complicated with recurrent pyogenic cholangitis or cholangiocarcinoma. Cholangiographic findings reflect the basic disease: flukes within the lumen of the bile ducts, gallbladder, and pancreatic duct and resultant obstruction; ductal dilatation; and periduc-
Fig. 1.-Photograph shows gross appearance of adult flukes of Clonorchis sinensis collected from feces of a patient. (Reprinted with permission from Lim et al. [191.)
.-
:4: -.
.
4 1
...
..
.
.
.
Fig. 2.-Photomicrograph of liver specimen shows adult fluke of Clonorchis .
2
.-
sls (solid arrows) within dilated small patic bile duct. Wall of bile duct shows matous hyperplasia of periductal glands, matory cell infiltration, and fibrosis. Note thickening of wall of bile duct (between arrows). (H and E, x40)
biopsy sinenintraheadenoinflamsevere open
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AJR:155,
November
1990
tal tissue reaction, including adenomatous hyperplasia and periductal fibrosis. Okuda and colleagues [1 1] described (1) many round filling defects of several millimeters in diameter, a size compatible with the width of the fluke; (2) dilatation of intrahepatic ducts, which was more pronounced in the peripheral portion; and (3) hazy appearance of the intrahepatic duct. The filling defects within the bile ducts represent adult flukes (Figs. 3 and 4). The defects have been described as linear [3], round [1 1], filamentous [1 2], ricelike [1 3], and oval or elliptic [1 2, 1 4]. The shape of defects depends on whether the flukes are seen en face or in profile, as the flukes are flat and leaflike [1 4]. The size of filling defects varies from 2 to 1 0 mm. These defects occur mostly within the smaller intrahepatic bile ducts and tertiary, quaternary, and more peripheral tributaries [1 1-15]. In mild infestation, the defects are scattered within the dilated bile ducts. In severe infestation, the tributaries of the biliary tree are obstructed, and peripheral filling by contrast medium is interrupted. The tips of these ducts are blunt [5, 1 2]. This is because flukes or aggregates of flukes pack and block the small peripheral intrahepatic bile ducts. The defects often are encountered within the extrahepatic ducts. In heavy infestation, the defects (Fig. 5) are seen in the gallbladder as well [4, 1 1 1 3]. These defects are distinguished from stone by their elliptic or oval appearance, the frequent change of position in the course of examination, and their uniformity in size [1 2]. Sometimes the outline of bile ducts is irregular, singly or in a series, showing a small indentation or hemispherical defects [6, 1 2, 13, 1 5] (Fig. 4). These irregularities reflect filling defects of flukes abutting the margin of the ducts and adenomatous hyperplasia [12]. The small or medium-sized intrahepatic bile ducts are dilated diffusely [1 1 -1 5]. However, the extrahepatic bile ducts ,
Fig. 3.-Endoscopic retrograde cholangiogram shows severe dilatation of intrahepatic ducts with narrowing (curved arrow). Intraductal ovoid or elliptic filling defects (straight white arrows) in medium-sized bile ducts are caused by adult flukes. Peripheralsmall ducts and cystic duct (solid black arrow) are obstructed, resulting in blunt end (open arrows). Note minimally dilated common hepatic duct. (Reprinted with permission from Lim et al. [19].)
1003
CLONORCHIASIS
are not dilated or are slightly dilated (Figs. 3 and 4). Dilatation of smaller bile ducts most likely is caused by the fluke itself. The 8- to 1 5-mm fluke or aggregates of flukes easily could occlude small peripheral ducts, but larger ducts such as right and left hepatic ducts and extrahepatic ducts are wide enough to be patent, even if flukes are lodged within them. However, the mechanism of obstruction cannot be explained on the basis of fluke size alone, as the flukes are flat, 1 .5-5 mm thick. Adenomatous hyperplasia, mucus in the bile ducts caused by cholangitis [1 1], and periductal fibrosis [7] and stricture may play additional roles in the occlusion of ducts and the resultant dilatation of proximal intrahepatic ducts. Uncommonly short segmental stenosis is seen also [1 2, 13, 15] (Fig. 3). Often the peripheral intrahepatic bile ducts are poorly defined (Fig. 4) [1 1 1 5]. Okuda et al. [1 1] attributed this to increased mucous material within the bile ducts. An amount of contrast medium insufficient to visualize the dilated penpheral ducts and poor mixing due to increased secretion within the ducts may play an additional role. Differential diagnosis of clonorchiasis includes cancer along the bile ducts, choledocholithiasis with recurrent pyogenic cholangitis, sclerosing cholangitis, Caroli disease, and Fasdo/a hepatica infestation. In cancer of the bile ducts, including Klastkin tumor, and cancer of the pancreas or ampulla of Vater, the obstructing lesion usually can be visualized, and the entire biliary tree proximal to the obstructing level is dilated diffusely, not just the peripheral small bile ducts as in donorchiasis. In patients who have stones in the bile duct and recurrent pyogenic cholangitis, small crescentic filling defects within the bile ducts easily are distinguished from those caused by the stone on the basis of the defects’ size and shape [1 2]. Furthermore the pattern of dilatation is quite
Fig. 4-Endoscopic retrograde cholangiogram shows severe dilatation of intrahepatic bile ducts and innumerable oval or elliptic filling defects (arrows) of adult flukes in medium-sized and small bile ducts. Peripheral duct filling is interrupted by those filling defects. Contour of bile ducts is irregular and ragged because of defects abutting margin of ducts. Bile ducts in left hepatic lobe are hazy because of poor mixing of contrast medium with mucous material. Note relatively slightly dilated extrahepatic ducts (13 mm).
,
Fig. 5.-Endoscopic retrograde cholangiogram shows opacification of gallbladder. MultipIe elliptic filling defects (arrows) represent aduft flukes. Gallbladder is distended moderately.
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1004
LIM
AJR:155,
November
1990
different. In recurrent pyogenic cholangitis, the intrahepatic bile ducts are not dilated or are dilated minimally, but the extrahepatic bile ducts are much more dilated [1 4, 1 6]. ScIerosing cholangitis usually shows dilatation of the intrahepatic bile duct, but the ducts are much more irregular and serpiginous and appear to be discontinuous, rather than diffusely dilated, and, unlike in clonorchiasis, the extrahepatic ducts
of flukes can be shown as a nonshadowing echogenic focus or cast (Fig. 6A) within the bile ducts [1 9, 21 ]. The bile ducts may be obstructed [5, 1 6] (Fig. 7). Morikawa et al. [22] described linear echoes moving quickly in the peripheral bile ducts; the movements were clearly apparent on M-mode sonograms.
also are involved
The gallbladder may have floating or dependent, discrete, nonshadowing echogenic foci in the lumen (Fig. 8). Usually flukes sink in the dependent portion, but float with a change in position or a light blow on the gallbladder with the transducer; the change in position or the light blow causes swirling movement of bile within the gallbladder, and the flukes float. Flukes occasionally float spontaneously, and these motions
to be saccular
diseases
[1 4]. In Caroli disease,
rather
than diffusely
other than parasitic
the bile ducts appear
dilated
disease,
[1 4]. In biliary
characteristic
tract
oval or
elliptic filling defects of flukes are not encountered. Fasciola hepatica infestation may result in dilatation of bile ducts and similar filling defects on cholangiograms, and thus differentiation can be difficult [1 7, 18].
Flukes within the gallbladder
are considered Sonographic
and
CT Findings
Sonography is usually the first technique used to examine patients with clonorchiasis, as symptoms of clonorchiasis are vague and nonspecific. In severe cases with jaundice or increased levels of alkaline phosphatase, sonography is still the procedure of choice. For this reason, it is important for radiologists to recognize the varied sonographic appearances in order to suggest that clonorchiasis may be present and to recommend additional studies for correct diagnosis. CT is more or less the same, although CT usually is not the initial technique. Sonographic and CT findings are based on the
same pathologic
processes
within
bile ducts
the dilated
Flukes within the bile ducts sonography resolution
as cholangiography and periductal
(i.e., flukes
changes)
usually are difficult
and CT [1 9, 20]. With the advent sonographic equipment, the flukes
[1 9, 20].
to show with of newer highor aggregates
are much easier to see [19].
to be caused by the movement
of living flukes
[1 9]. These discrete, echogenicfoci are not considered stones because they are fusiform, weakly echogenic, and nonshadowing. CT is of little value in the delineation of flukes [20]. To the best of my knowledge, no description concerning CT visualization of flukes in the bile ducts or gallbladder has been published. In my experience, CT of some patients showed high-density foci scattered within the dilated intrahepatic bile ducts, assumed to be aggregates of flukes (Figs. 9 and 1 OA). As with cholangiograms, sonograms [1 9, 21 22] and CT scans [20, 23, 24] show diffuse, uniform dilatation of the small intrahepatic bile ducts with no or minimal dilatation of the large bile ducts and no focal obstructing lesion (Figs. 6A, 9, and 1 OA). This characteristic finding of clonorchiasis is not encountered in other bile duct diseases, such as tumors along the bile duct or choledocholithiasis, as discussed with cholangiography. My colleagues and I, in prospective studies ,
Fig. 6.-Sonograms of patient with severe infestation show dilatation and fibrous thickening of bile ducts. A, Transverse scan of left hepatic lobe shows severe dilatation of bile ducts within which echogenic casts fill lumen (arrows), suggesting adult flukes. Note parallel echogenic bands (between arrowheads) along dilated bile ducts, indicating severe fibrous thickening of wall. B, Longitudinal scan of left lobe shows markedly thickened bile ducts, mimicking echogenic nodules. Hepatic parenchymal echotexture is coarse. Note dilated small bile ducts (arrows) in center of thick echogenic wall. (Reprinted with permission from Lim et al. [19].)
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AJR:155,
November
CLONORCHIASIS
1990
[25], stressed that dlonorchiasis could be suspected with a high degree of confidence on the basis of dilatation of the peripheral intrahepatic bile duct without dilatation of the extrahepatic bile duct. Thickening of the bile ducts can be shown with sonography and CT. Adenomatous hyperplasia, inflammatory cell infiltration, and periductal fibrosis produce diffuse thickening of the bile ducts. Sonograms show diffuse echogenic thickening of bile ducts [1 9, 26]. When the transducer is parallel to the bile ducts, the thick wall of the bile ducts can be seen as echogenic bands (Fig. 6A). When the transducer is tangential to the direction of the bile ducts, the thick bile ducts simulate echo-
Fig. 7.-Oblique
sonogram
of right upper ab-
domen shows mild dilatation of common hepatic duct (D) (8 mm in diameter) filled by echogenic cast (arrows). This may represent an aggregate of adult flukes. v = portal vein. (Reprinted with permission from Lim et al. [19].)
1005
genic nodules (Fig. 6B) [1 9, 26]. However, each nodule has a small echolucent center dilated duct. The overall hepatic echogenicity [19]. Choi et al. [20] reported that CT failed to ening of the bile ductal wall. On the contrary, showed periductal contrast enhancement
cases,
suggesting
several
cases
shown,
suggesting
Not
periductal
in which
infrequently
periductal
show the thickKim et al. [26] in half of their
We have experienced
contrast
fibrosis
the gallbladder
comes thick, and gallstones
Fig. 8.-Sonogram of gallbladder shows several discrete, fusiform, floating and dependent echogenic foci measuring 5-10 mm, representing flukes.
fibrosis.
periductal
in clonorchiasis representing a becomes coarse
enhancement
(Figs.
is distended,
may be present
was
1OB and 1OC). the
wall
be-
[1 9, 20].
Fig. 9.-CT scan shows diffuse, uniform dilatation of intrahepatic ducts in periphery of liver and innumerable tiny hyperdense foci within dilated ducts, apparently due to aggregates of flukes. Extrahepatic duct was dilated minimally.
Fig. 10.-CT scans show liver flukes within dilated bile ducts and severe periductal fibrosis. A, Postcontrast CT scan through middle of liver shows dilatation of intrahepatic ducts up to periphery of liver. Note high-density casts (arrows), assumed to be aggregates of flukes within dilated bile ducts. These intraductal flukes were depicted by cholangiography (Fig. 3) and sonography (Fig. 6A) as well. After administration of praziquantel, a lump of flukes was expelled, intermingled with feces. Flukes were collected and photographed (Fig. 1). B and C, CT scans before (B) and after (C) administration of contrast medium show extensive periductal fibrous thickening. Branching low densities in B decrease in diameter in C, and only lumen of dilated ducts is visualized. Periductal fibrous tissue is enhanced and blends imperceptibly with adjacent liver parenchyma.
LIM
1006
Sclerosing cholangitis bile ducts and concentric
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hepatic
may cause thickening
dilatation of intrahepatic of the intra- and extra-
biliary tree [27], but the thickening
of the bile duct is
more severe than that seen in clonorchiasis, and bile duct dilatation is focal and discontinuous [28]. Thickening of the bile duct may be encountered in cholangitis in AIDS [29]. Infestation of Fasciola hepatica results in biliary dilatation and thickening of the bile ducts, thus sonographic and CT findings are similar [30]. Furthermore, mobile vermiform structures
[30]
within
the gallbladder
echogenic
are virtually
foci in clonorchiasis
Clonorchiasis
In heavy
the same
as the
[19].
of the
Pancreas
infestations,
flukes
may reside
1 0, 31]. Choi and Yang [32] studied
in the pancreas
[7,
699 cases with surgical
AJR:155,
November
1990
passed from the gallbladder and resulting in ascending cholangitis of Western people [36, 37]. The relationship between recurrent pyogenic cholangitis and clonorchiasis has been disputed. In fact, large proportions
of persons
in endemic
areas
are infested
with liver flukes
without ever having the development of recurrent pyogenic cholangitis [5, 39, 40]. Most persons who have clonorchiasis are male [1 9, 20], but there is no sex predilection in recurrent pyogenic cholangitis [36, 38]. Ong [36] suggested that the primary cause is portal septicemia resulting from poor eating habits, and that C. sinensis need not be present in all cases of recurrent pyogenic cholangitis. Carmona et al. [38] suggested low-protein diet and portal bacteremia as causes of recurrent pyogenic cholangitis. This theory was supported by animal experiments [40, 41].
However, evidence is ample that clonorchiasis is closely related to recurrent pyogenic cholangitis, and that a cause-
intervention of the hepatobiliary tract and confirmed pancreatitis in five cases (8%). Hou and Pang [31] reported that 19 of 300 patients with clonorchiasis had pancreatic involvement,
and-effect
relationship
patients
with intrahepatic
and Chan and Teoh [1 0] found involvement in 24 of 64 cases. Patients with clonorchiasis are usually asymptomatic, but 83% of the patients who had acute pancreatitis of unknown cause were found to have a coexistent Clonorchis infestation [33]. The flukes were found in the main and tributary ducts ofthe pancreatic tail, and these ducts were dilated and packed with worms [10].
reported that 26% of patients with chronic cholecystitis, 1 9% of patients with gallstones, and 17% of patients with bile duct stones had clonorchiasis. Recent articles [1 9, 20] have reported that some 15% of persons with clonorchiasis have
Only one paper has been published on pancreatography pancreatic clonorchiasis [34]. On endoscopic retrograde
in pan-
creatograms, the pancreatic are dilated diffusely (Figs.
duct in the tail and its tributaries 1 1A-i 1 C). However, the main duct and its tributaries in the head and body are
pancreatic not dilated.
caused
Sometimes
small
filling
defects
that
might
by adult flukes are found in the main pancreatic
This characteristic in clonorchiasis of tion due to other pancreatic duct is
appearance,
duct
duct.
pattern of dilatation of the pancreatic duct the pancreas is quite different from dilatacauses. In chronic pancreatitis, the main dilated irregularly, resulting in a beaded
whereas
pancreatic
be
in carcinoma
of the pancreas,
frequently
is dilated
to Recurrent
Pyogenic
the main
uniformly.
study
in an endemic
concomitant
gallstones
patic pigment
stone disease,
of pigmented
is characterized
stones
and remissions
of abdominal
jaundice,
and fever [35-38].
chills,
of the disease
with
by intrahepatic
recurrent
pain frequently
that 20 of 31
Choi
In a clinical
and
Yang
[32]
(Fig. 12).
Stagnation
not only
favors
bacterial
infection
consequent
cellular
infiltration
but also
leads
of the bile ducts and
of the portal
spaces
and liver
parenchyma. ducts, offlukes
When pyogenic infection occurs in the bile C. sinensis are killed [1 7]. Bile stasis and the presence ,
and ova or their debris
may be important.
The flukes
and ova or their debris can form a nucleus for the formation of gallstones or bile duct stones [42], and this could instigate all the consequent abnormalities, resulting in a vicious cycle of repeated bouts of cholangitis and stone formation [37]. are composed almost entirely of of bilirubin stones may be attrib-
deconjugation
of insoluble
bilirubin
of bilirubin during
diglucuronide bouts
with
of cholangitis
[43].
The
Relationship
to Cholangiocarcinoma
exacerbation
associated
The geographic
is similar to clonorchiasis.
in Korea,
to reflux of bile into the smaller branches
the formation
Recurrent pyogenic cholangitis, which is also known as Oriental cholangitis, Oriental cholangiohepatitis, or intraheformation
area
Chemically, such stones bilirubin [1]. The formation
Cholangitis
Hou [7] reported
stone had clonorchiasis.
Rim [1 ] and Hou [7] have asserted that C. sinensis infestation causes recurrent pyogenic cholangitis. As adult flukes, eggs, and desquamated epithelial cells block the intrahepatic ducts, partially or completely, bile stasis is sure to follow [7].
uted to bacterial Relationship
exists.
with
distribution
Unlike both suppur-
The close correlation between C. sinensis infestation and bile duct carcinoma has long been emphasized [8, 24, 4348]. Hou [44] reported that in at least 15% of patients with
ative and nonsuppurative cholangitis in the West, recurrent pyogenic cholangitis does not develop as a consequence of obstruction by primary calculi, strictures, or neoplasm. The stones in recurrent pyogenic cholangitis are usually muddy
primary
and claylike extrahepatic
[46] and Chung and Lee [47] also found that the prevalence of dlonorchiasis was significantly higher in cholangiocarcinoma than in hepatocellular carcinoma. In a cholangiographic
bilirubin
and are often multiple, packing the intra- and bile ducts with casts [35-37]. These stones are
stones,
clearly
different
from
cholesterol
stones
carcinoma
of the
liver,
the
cancer
was
caused
by
infestation with C. sinensis. Belamaric [45] found that most patients with cholangiocarcinoma had adenomatous hyperplasia
and ductal
fibrosis
characteristic
of dlonorchiasis.
Kim
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AJR:155,
November
1007
CLONORCHIASIS
1990
Fig. 1 1.-dlonorchiasis
of pancreas.
A, Sonogram of pancreas shows severe dilatation of main pancreatic duct (thick arrow) and tributaries (thin arrows) in tail of pancreas. A = aorta. B, CT scan shows tortuous dilatation of tributary ducts of tail of pancreas. Pancreatic parenchyma is virtually absent. Note diffuse dilatation of intrahepatic bile ducts in periphery of liver. C, Endoscopic retrograde pancreatogram shows marked dilatation of main pancreatic duct and tributaries in tail of pancreas. Oval filling defects (arrows) are presumed to be flukes. Note relatively normal pancreatic duct in head of pancreas.
I
!
Fig.
12.-Recurrent
associated
pyogenic
with clonorchiasis.
cholangitis
Endoscopic
ret-
rograde cholangiogram shows a stone in cornmon bile duct (open arrow). Note obstruction (curvedarrow)and elliptic filling defect caused by flukes (straight solid arrow).
Fig. 13.-Cholangiocarcinoma, peripheral type associated with clonorchiasis. CT scan shows pooriy defined, large, irregular hypodense mass with small enhancing foci in middle of tumor. Pcripheral intrahepatic bile ducts are dilated (arrows).
study of patients with clonorchiasis (Lim et al., unpublished data), seven of 46 patients had cholangiocarcinoma (Figs. 13 and 1 4). In studies in cats and dogs with clonorchiasis, Hou [8, 48] advocated that adenomatous tissue formation of bile ducts regressed and was replaced by fibrous thickening or progressed to malignant change. The considerably higher prevalence of dlonorchiasis in patients with cholangiocarcinoma, the close physical relationship of the main tumor mass to infested ducts, the frequent coexistence in the same duct of focally atypical epithelial hyperplasia and invasive cancer, and the results of animal
experiments tween
Fig.
ing of right hepatic
hilar type asso-
duct,
left hepatic
duct,
and
proximal common hepatic duct due to Infiltrating carcinoma at porta hepatis. Note dilatation of intrahepatic ducts with small elliptic filling defects in peripheral small bile ducts.
all support
dlonorchiasis
14.-Cholangiocarcinoma,
ciated with clonorchiasis. Endoscopic retrograde cholangiogram shows severe segmental narrow-
a cause-and-effect
relationship
be-
and cholangiocarcinoma.
ACKNOWLEDGMENTS I thank
Jong
Kwon
Won
and
Byung
Do Kim
for
sonographic
assistance, Mun Young Roh for preparation of photographs, Ok Yeo for secretarial assistance in manuscript preparation.
and Nan
REFERENCES
1 . Rim HJ. The current pathobiology and chemotherapy Korean J Parasitol 1986;24[suppl]:7-20
of clonorchiasis.
1008
LIM
2. Peters
W. Medical
aspects:
Muller R, eds. The relevance Oxford:
Blackwell
Scientific,
comments and discussion. II. In: Taylor AER, of parasitology to human welfare today. 1978:25-40 Br J Radiol
3. Cremin BJ. Biliary parasites. 1969;42:506-508 4. Hartley JPR, Doughlas AP. A case of clonorchiasis in England. Br Med J
Downloaded from www.ajronline.org by 117.245.41.132 on 08/22/15 from IP address 117.245.41.132. Copyright ARRS. For personal use only; all rights reserved
1975;6:575
5. Ameres JP, Levine MP, DeBlash HP. Acalculous clonorchiasis obstructing the common bile duct: a case report and review of the literature. Am Surg 1976;42:170-172
6. Baker MS, Baker BH, Woo R. Biliary clonorchiasis. Arch Surg 1979; 114:748 7. Hou PC. The pathology of Clonorchis sinensis infestation of the liver. J Pathol 1955;70:53-64
8. Hou PC. Pathological changes in the intrahepatic
bile ducts of cats (Felis catus) infested with Clonorchis sinensis. J Pathol Bacteriol 1965;89: 357-364 9. Lee SH, Shim T5, Lee SM, Chi JG. Studies on pathological changes of the liver in albino rats infected with Clonorchis sinensis. Korean J Parasitol 1978;16:148-155 10. Chan PH, Tech TB. The pathology of Clonorchis sinensis infestation of the pancreas. J Pathol Bacteriol 1967;93:1 85-189 1 1 . Okuda K, Emura T, Morokuma K, Kojima 5, Yokagawa M. Clonorchiasis studied by percutaneous cholangiography and a therapeutic trial of toluene-2, 4-diiso-thiocyanate. Gastroenterology 1973;65:457-461 12. Choi TK, Wong KP, Wong J. Cholangiographic
14.
Saunders, 1977:285-330 15. Kang 1W, Sec H5, Lim OR, Yeon
KM.
CT Ko Soc 26. Kim MJ, Voo
25.
Radiologicalfindings
of clonorchiasis.
pyogenic
cholangitis:
ultra-
sound evaluation compared with endoscopic retrograde cholangiopancreatography. Clin Radiol 1987;38:79-85 1 7. Clemett AR. Radiology of the liver and biliary tract. In: Margulis AR, Burhenne HJ eds. Alimentary tract radiology. St. Louis: Mosby, 1989: 1260-1
20. 21 22. 23.
.
Choi BI, Kim HJ, Han MC, Do YS, Han MH, Lee 5H. CT findings of clonorchiasis. AJR 1989;1 52:281-284 Kim JW, Kim JG, Sol CH, Kim B5. An observation of ultrasonographic findings in clonorchiasis. J Korean Radiol Soc 1983;1 9:538-545 Morikawa P. Ishida H, Niizawa M, Komatsu M, Arakawa H, Masamune 0. Sonographic features of biliary clonorchiasis. JCU 1988;16:655-658 Kim SY, Ko VT, Suh SJ. Computed tomography in evaluation of jaundiced patients due to Clonorchis sinensis. J Korean Radiol Soc 1978;14:
460-464 24.
Choi
BI, Park JH, Kim VI, et al. Peripheral
195-198 35.
Cook J. Hou PC, Ho HC, McFadzean Br J Surg
and don-
AJS. Recurrent
pyogenic
cholangitis.
1954;42:188-203
36. Ong GB. A study of recurrent
pyogenic
cholangitis.
Arch
Surg
1962;
84:199-225
37. Seel DJ, Park VK. Oriental infestational cholangitis. Am J Surg 1983; 146:188-203 38. Carmona RH, Crass RA, Lim RC, Trunkey DO. Oriental cholangitis. Am J Surg 1984;148:1 17-1 24 39.
Sullivan WG, Koep titis in clonorchiasis.
Li. Common bile duct obstruction JAMA 1980;243:2060-2061
40. Chou ST, Chan CW. Recurrent 41
43. 44. 45. 46. 47.
48.
cholangiocarcinoma
of clonorchiasis.
stration of bile duct wall thickening. AJR 1982;139:101 6-1 018 Ferrucci JT, Adson MA, Mueller PR, Stanley RJ, Stewart ET. Advances in the radiology ofjaundice: a symposium and review. AJR 1983;141 :1-20 29. Dolmatch BL, Laing FC, Federie MP, Jeffrey RB, Cello J. AIDS-related cholangitis: radiographic findings in nine patients. Radiology 1987;1 63: 31 3-316 30. van Beers B, Pringot J, Geubel A, Trigaux J-P, Bigaignon G, Dooms G. Hepatobiliary fascioliasis: noninvasive imaging findings. Radiology 1990;1 74:809-810 31 . Hou PC, Pang SC. Clonorchis sinensis infestation in man in Hong Kong. J Pathol Bacteriol 1964;87:245-250 32. Choi JM, Vang OH. Clinical study on clonorchiasis of hepatobiliary tract. J Korean Surg Soc 1974;16:245-253 33. McFadzen PJS, Voung RU. Acute pancreatitis due to Clonorchis sinensis. Trans R Soc Trop Med Hyg 1966;60:466-470 34. Lim JH, Ko VT. Clonorchiasis of the pancreas. C/in Radiol 1990;41:
.
42.
261
1 8. Ham SY, Park CM, Chung KB, et al. A case of fascioliasis in common bile duct. J Korean Radiol Soc 1989;25:783-785 1 9. Lim JH, Ko VT, Lee OH, Kim 5Y. Clonorchiasis: sonographic findings in 59 proved cases. AJR 1989;152:761-764
findings. Radiology 1988;1 69:149-153 VT, Lee OH, Mm VI. Uftrasound findings Med Ultrasound 1987;6: 193-194
1990
28.
J Korean Radiol Soc 1980;16:159-162
1 6. Chau EMT, Leong LLY, Chan FL. Recurrent
orchiasis: Lim JH, J Korean
November
HS, Lee JT, Jung SH. Radiologic imaging of the bile duct changes by clonorchiasis. J Korean Radiol Soc 1988;24:878-882 27. Carrol BA, Oppenheimer DA. Sclerosing cholangitis: sonographic demon-
appearance in clonorchiasis.
Br J Radiol 1984;57:681-684 Lee JI, Yoo JH, Lim GS, Lee CH, Mm VI, Lim JH. ERCP findings in clonorchiasis. J Korean Soc Gastrointest Endosc 1981;1 :29-32 Clemett AR. The interpretation of the direct cholangiogram. In: Berk RN, Clemett AR, eds. Radiology of the gallbladder and bile ducts. Philadelphia:
13.
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pyogenic
cholangitis:
and cholangiohepa-
a necropsy
study.
Pathology 1980;1 2:415-428 Matsushiro T, Susuki N, Sato T, et al. Effects of diet on glucaric acid concentration in bile and the formation of calcium bilirubinate gallstones. Gastroenterology 1977;72:630-633 Tech TB. A study of gallstones and included worms in recurrent pyogenic cholangitis. J Pathol Bacteriol 1963;86: 123-129
Flavell DJ. Liver-fluke
infection as an aetiological
factor in bile-duct carci-
noma of man. Trans R Soc Trop Hyg 1981;75:814-824 Hou PC. The relationship between primary carcinoma of the liver and infestation with Clonorchis sinensis. J Pathol Bacteriol 1956;72:239-246 Belamaric J. Intrahepatic bile duct carcinoma and clonorchiasis infection in Hong Kong. Cancer 1973;31:468-473 Kim VI. Liver carcinoma and liver fluke infection. Arzneimittelforschung 1984;34:1 121-1126 Chung CS, Lee 5K. An epidemiological study of primary liver carcinoma in Busan area with special reference to clonorchiasis. Korean J Pathol 1976;10:33-46
Hou PC. Hepatic clonorchiasis J Pathol
Bacteriol
1965;89;365-367
and carcinoma
of the bile duct in a dog.
1001
Review
Radiologic Jae Hoon
Findings
of Clonorchiasis
Lirn1
Clonorchiasis
is a trematodiasis
caused
by chronic
infestation
The adult flukes reside in the medium-sized and small intrahepatic bile ducts and, occasionally, in the extrahepatic bile ducts, gallbladder, and pancreatic duct. The result is mechanical obstruction, inflammatory reaction, adenomatous hyperplasia, and periductal fibrosis. Signs and symptoms are usually mild and nonspecific, but heavy infestation results in obstructive jaundice. The disease has a close relationof liver
ship
flukes,
with
In this
Clonorchis
recurrent
article,
the
sinensis.
pyogenic radiologic
cholangitis findings,
and
cholangiocarcinoma.
including
cholangiography,
sonography, and CT of clonorchiasis are reviewed pathophysiology of the disease. The relationship pyogenic
cholangitis
and
to cholangiocarcinoma
in light of the to recurrent is discussed.
The geographic distribution of clonorchiasis is largely confined to the Orient, from Japan to Vietnam. The endemic areas include Japan, Southern Korea, the mainland of China (except the northwest), Taiwan, and Northern Vietnam [1]. There are some 38 million carriers throughout the world [2]. The disease has been encountered in nonendemic areas as well [3-6] and may be recognized with increasing frequency in the Western world, because the flukes live for decades and the infested person may emigrate or travel anywhere in the world. Human infestation depends on eating habits [1]. Persons with a marked preference for raw fish in their diet are infested more often. In Korea, 30- to 50-year-old men are infested most often. This is explained by social customs. Korean men
1
April 20, 1990;
Department
accepted
of Diagnostic
after revision
Radiology,
Kyung
have a tradition of eating raw freshwater fish, soaked simply in vinegar or red-pepper mash, as an appetizer when drinking at social gatherings. Children and women infrequently join in such gatherings, so they have much less exposure to the infestation.
Parasitology
The adult fluke of Clonorchis sinensis is a flat, elongated, leaflike, flabby worm tapered anteriorly and somewhat rounded posteriorly [1] (Fig. 1). The size ranges from 8.0 to
15.0 mm long by 1 .5 to 4.0 mm wide and about 1 .0 mm thick.
Epidemiology
Received
Article
The fluke has two suckers, oral and ventral; it sucks the blood of the host through the mucous membrane of the bile ducts. The fluke may persist for 1 5-20 years or more. Humans are the most suitable definitive hosts. Animal reservoir hosts are dogs, hogs, wildcats, martens, badgers, minks, weasels, and rats [1]. One adult fluke lays approximately 2000-4000 eggs each day. The eggs, laid within the biliary tree of the definitive host, are carried down the common bile duct and passed in the stools. On reaching fresh water, the eggs are eaten by some genus of snail, mostly Parafossarulus, Bithynia, and Alocinma, the first intermediate host. Within the snail, the eggs undergo metamorphosis, after which the cercariae escape. The cercariae penetrate the scales of suitable freshwater fish, mostly the Cyprinidae, the second intermediate host. Within the muscles of the fish, the cercariae encyst and become metacercariae to be ingested
May 30, 1990.
Hoc University
Hospital,
,
1 Hoeki-dong,
Dongdaemun-ku,
Lim. AJR 155:1001-1008,
November
1990 0361-803X/90/1555-1001
© American
Roentgen
Ray Society
Seoul 130-702, Korea. Address reprint requests to J. H.
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1002
LIM
by the final host. When a person ingests the flesh of raw fish containing metacercariae, the cyst is freed from the flesh by the action of gastric juice in the stomach, and the cyst wall is dissolved by trypsin in the duodenum. The larva excyst and migrate from the duodenum via the ampulla of Vater into the bile ducts, where they become mature worms in about 25 days. They usually reside in the intrahepatic bile ducts (Fig.
2) but also occasionally gallbladder,
in the extrahepatic
as well as the pancreatic
ducts
and the
duct.
Pathophysiology
The main factor in pathogenesis is a mechanical obstruction of the biliary tract by the flukes, congestion of bile, and the effects of soluble substances (metabolites) released from the flukes into the ducts and surrounding tissues [1 ]. The severity of the dysfunction depends on the number of flukes present and the repetition and period of infestation. Most human infestation is chronic, perhaps from several years to several decades because of repeated ingestion of raw fish. Adult flukes living within the medium-sized and small intrahepatic ducts (i.e., tertiary, quaternary, and more peripheral tributaries) (Fig. 2) produce mechanical obstruction and inflammatory reaction [7]. In the early stage, edema and desquamation of epithelium, proliferation of bile ducts, and an inflammatory reaction occur. In the later stage, metaplastic squamous cells appear in conjunction with glandular proliferation, resulting in adenomatous hyperplasia [8, 9]. Bile ducts become dilated, thick, and infiltrated with lymphocytes, plasma cells, histiocytes, and fibroblasts. In heavy infestations, the main bile ducts and gallbladder are involved. Later, marked periductal fibrosis occurs with pronounced thickening of the walls of biliary passages [9]. In heavy infestation, flukes may reside in the pancreatic duct, within the main pancreatic duct of the tail portion, and within its tributary ducts [1 1 0]. These ducts are dilated and packed with flukes. Flukes in the ducts produce squamous metaplasia, mucous gland hyperplasia, and fibrous thickening of the ductal wall [10]. ,
AJR:155, November 1990
Clinical
Manifestations
Clinical manifestations depend on the number of flukes, the period of infestation, and complications [1 ]. Lightly infected persons usually have no signs or symptoms. In moderate or progressive cases, the clinical signs and symptoms are loss of appetite, indigestion, fullness of the abdomen, epigastric distress unrelated to meals, discomfort in the right upper quadrant, diarrhea, edema, and some hepatomegaly. In heavy infestations, the signs and symptoms are weakness and lassitude, epigastric discomfort, paresthesia, loss of weight, palpitation, tachycardia, diarrhea, vertigo, tetanic cramps and tremors, and toxemia from liver impairment. Jaundice is caused by obstruction of the intrahepatic biliary trees by worms or inflammatory changes. In patients with complications, such as pericholangitic abscess or recurrent pyogenic cholangitis, the signs and symptoms are those of acute infection, including fever, chills, and abdominal pain. In patients with cholangiocarcinoma, jaundice and pruritus predominate over other minor symptoms because of the obstruction of the passage of bile. Laboratory abnormalities include eosinophilia and an increased level of serum alkaline phosphatase. In cases with significant obstruction of the bile passage, levels of serum bilirubin, cholesterol, aspartate aminotransferase (GOT), and alanine aminotransferase (GPT) are increased [1].
Cholangiographic
Findings
Cholangiography once played a major role in the assessment of the biliary tract in clonorchiasis. With the advent of sonography and CT, the role of cholangiography has decreased because the diagnosis usually is made on the basis of sonographic or CT findings and subsequent examination of the stool for ova. Cholangiography is indicated in heavy infestation as a workup for obstructive jaundice, or in patients with clonorchiasis complicated with recurrent pyogenic cholangitis or cholangiocarcinoma. Cholangiographic findings reflect the basic disease: flukes within the lumen of the bile ducts, gallbladder, and pancreatic duct and resultant obstruction; ductal dilatation; and periduc-
Fig. 1.-Photograph shows gross appearance of adult flukes of Clonorchis sinensis collected from feces of a patient. (Reprinted with permission from Lim et al. [191.)
.-
:4: -.
.
4 1
...
..
.
.
.
Fig. 2.-Photomicrograph of liver specimen shows adult fluke of Clonorchis .
2
.-
sls (solid arrows) within dilated small patic bile duct. Wall of bile duct shows matous hyperplasia of periductal glands, matory cell infiltration, and fibrosis. Note thickening of wall of bile duct (between arrows). (H and E, x40)
biopsy sinenintraheadenoinflamsevere open
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AJR:155,
November
1990
tal tissue reaction, including adenomatous hyperplasia and periductal fibrosis. Okuda and colleagues [1 1] described (1) many round filling defects of several millimeters in diameter, a size compatible with the width of the fluke; (2) dilatation of intrahepatic ducts, which was more pronounced in the peripheral portion; and (3) hazy appearance of the intrahepatic duct. The filling defects within the bile ducts represent adult flukes (Figs. 3 and 4). The defects have been described as linear [3], round [1 1], filamentous [1 2], ricelike [1 3], and oval or elliptic [1 2, 1 4]. The shape of defects depends on whether the flukes are seen en face or in profile, as the flukes are flat and leaflike [1 4]. The size of filling defects varies from 2 to 1 0 mm. These defects occur mostly within the smaller intrahepatic bile ducts and tertiary, quaternary, and more peripheral tributaries [1 1-15]. In mild infestation, the defects are scattered within the dilated bile ducts. In severe infestation, the tributaries of the biliary tree are obstructed, and peripheral filling by contrast medium is interrupted. The tips of these ducts are blunt [5, 1 2]. This is because flukes or aggregates of flukes pack and block the small peripheral intrahepatic bile ducts. The defects often are encountered within the extrahepatic ducts. In heavy infestation, the defects (Fig. 5) are seen in the gallbladder as well [4, 1 1 1 3]. These defects are distinguished from stone by their elliptic or oval appearance, the frequent change of position in the course of examination, and their uniformity in size [1 2]. Sometimes the outline of bile ducts is irregular, singly or in a series, showing a small indentation or hemispherical defects [6, 1 2, 13, 1 5] (Fig. 4). These irregularities reflect filling defects of flukes abutting the margin of the ducts and adenomatous hyperplasia [12]. The small or medium-sized intrahepatic bile ducts are dilated diffusely [1 1 -1 5]. However, the extrahepatic bile ducts ,
Fig. 3.-Endoscopic retrograde cholangiogram shows severe dilatation of intrahepatic ducts with narrowing (curved arrow). Intraductal ovoid or elliptic filling defects (straight white arrows) in medium-sized bile ducts are caused by adult flukes. Peripheralsmall ducts and cystic duct (solid black arrow) are obstructed, resulting in blunt end (open arrows). Note minimally dilated common hepatic duct. (Reprinted with permission from Lim et al. [19].)
1003
CLONORCHIASIS
are not dilated or are slightly dilated (Figs. 3 and 4). Dilatation of smaller bile ducts most likely is caused by the fluke itself. The 8- to 1 5-mm fluke or aggregates of flukes easily could occlude small peripheral ducts, but larger ducts such as right and left hepatic ducts and extrahepatic ducts are wide enough to be patent, even if flukes are lodged within them. However, the mechanism of obstruction cannot be explained on the basis of fluke size alone, as the flukes are flat, 1 .5-5 mm thick. Adenomatous hyperplasia, mucus in the bile ducts caused by cholangitis [1 1], and periductal fibrosis [7] and stricture may play additional roles in the occlusion of ducts and the resultant dilatation of proximal intrahepatic ducts. Uncommonly short segmental stenosis is seen also [1 2, 13, 15] (Fig. 3). Often the peripheral intrahepatic bile ducts are poorly defined (Fig. 4) [1 1 1 5]. Okuda et al. [1 1] attributed this to increased mucous material within the bile ducts. An amount of contrast medium insufficient to visualize the dilated penpheral ducts and poor mixing due to increased secretion within the ducts may play an additional role. Differential diagnosis of clonorchiasis includes cancer along the bile ducts, choledocholithiasis with recurrent pyogenic cholangitis, sclerosing cholangitis, Caroli disease, and Fasdo/a hepatica infestation. In cancer of the bile ducts, including Klastkin tumor, and cancer of the pancreas or ampulla of Vater, the obstructing lesion usually can be visualized, and the entire biliary tree proximal to the obstructing level is dilated diffusely, not just the peripheral small bile ducts as in donorchiasis. In patients who have stones in the bile duct and recurrent pyogenic cholangitis, small crescentic filling defects within the bile ducts easily are distinguished from those caused by the stone on the basis of the defects’ size and shape [1 2]. Furthermore the pattern of dilatation is quite
Fig. 4-Endoscopic retrograde cholangiogram shows severe dilatation of intrahepatic bile ducts and innumerable oval or elliptic filling defects (arrows) of adult flukes in medium-sized and small bile ducts. Peripheral duct filling is interrupted by those filling defects. Contour of bile ducts is irregular and ragged because of defects abutting margin of ducts. Bile ducts in left hepatic lobe are hazy because of poor mixing of contrast medium with mucous material. Note relatively slightly dilated extrahepatic ducts (13 mm).
,
Fig. 5.-Endoscopic retrograde cholangiogram shows opacification of gallbladder. MultipIe elliptic filling defects (arrows) represent aduft flukes. Gallbladder is distended moderately.
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1004
LIM
AJR:155,
November
1990
different. In recurrent pyogenic cholangitis, the intrahepatic bile ducts are not dilated or are dilated minimally, but the extrahepatic bile ducts are much more dilated [1 4, 1 6]. ScIerosing cholangitis usually shows dilatation of the intrahepatic bile duct, but the ducts are much more irregular and serpiginous and appear to be discontinuous, rather than diffusely dilated, and, unlike in clonorchiasis, the extrahepatic ducts
of flukes can be shown as a nonshadowing echogenic focus or cast (Fig. 6A) within the bile ducts [1 9, 21 ]. The bile ducts may be obstructed [5, 1 6] (Fig. 7). Morikawa et al. [22] described linear echoes moving quickly in the peripheral bile ducts; the movements were clearly apparent on M-mode sonograms.
also are involved
The gallbladder may have floating or dependent, discrete, nonshadowing echogenic foci in the lumen (Fig. 8). Usually flukes sink in the dependent portion, but float with a change in position or a light blow on the gallbladder with the transducer; the change in position or the light blow causes swirling movement of bile within the gallbladder, and the flukes float. Flukes occasionally float spontaneously, and these motions
to be saccular
diseases
[1 4]. In Caroli disease,
rather
than diffusely
other than parasitic
the bile ducts appear
dilated
disease,
[1 4]. In biliary
characteristic
tract
oval or
elliptic filling defects of flukes are not encountered. Fasciola hepatica infestation may result in dilatation of bile ducts and similar filling defects on cholangiograms, and thus differentiation can be difficult [1 7, 18].
Flukes within the gallbladder
are considered Sonographic
and
CT Findings
Sonography is usually the first technique used to examine patients with clonorchiasis, as symptoms of clonorchiasis are vague and nonspecific. In severe cases with jaundice or increased levels of alkaline phosphatase, sonography is still the procedure of choice. For this reason, it is important for radiologists to recognize the varied sonographic appearances in order to suggest that clonorchiasis may be present and to recommend additional studies for correct diagnosis. CT is more or less the same, although CT usually is not the initial technique. Sonographic and CT findings are based on the
same pathologic
processes
within
bile ducts
the dilated
Flukes within the bile ducts sonography resolution
as cholangiography and periductal
(i.e., flukes
changes)
usually are difficult
and CT [1 9, 20]. With the advent sonographic equipment, the flukes
[1 9, 20].
to show with of newer highor aggregates
are much easier to see [19].
to be caused by the movement
of living flukes
[1 9]. These discrete, echogenicfoci are not considered stones because they are fusiform, weakly echogenic, and nonshadowing. CT is of little value in the delineation of flukes [20]. To the best of my knowledge, no description concerning CT visualization of flukes in the bile ducts or gallbladder has been published. In my experience, CT of some patients showed high-density foci scattered within the dilated intrahepatic bile ducts, assumed to be aggregates of flukes (Figs. 9 and 1 OA). As with cholangiograms, sonograms [1 9, 21 22] and CT scans [20, 23, 24] show diffuse, uniform dilatation of the small intrahepatic bile ducts with no or minimal dilatation of the large bile ducts and no focal obstructing lesion (Figs. 6A, 9, and 1 OA). This characteristic finding of clonorchiasis is not encountered in other bile duct diseases, such as tumors along the bile duct or choledocholithiasis, as discussed with cholangiography. My colleagues and I, in prospective studies ,
Fig. 6.-Sonograms of patient with severe infestation show dilatation and fibrous thickening of bile ducts. A, Transverse scan of left hepatic lobe shows severe dilatation of bile ducts within which echogenic casts fill lumen (arrows), suggesting adult flukes. Note parallel echogenic bands (between arrowheads) along dilated bile ducts, indicating severe fibrous thickening of wall. B, Longitudinal scan of left lobe shows markedly thickened bile ducts, mimicking echogenic nodules. Hepatic parenchymal echotexture is coarse. Note dilated small bile ducts (arrows) in center of thick echogenic wall. (Reprinted with permission from Lim et al. [19].)
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AJR:155,
November
CLONORCHIASIS
1990
[25], stressed that dlonorchiasis could be suspected with a high degree of confidence on the basis of dilatation of the peripheral intrahepatic bile duct without dilatation of the extrahepatic bile duct. Thickening of the bile ducts can be shown with sonography and CT. Adenomatous hyperplasia, inflammatory cell infiltration, and periductal fibrosis produce diffuse thickening of the bile ducts. Sonograms show diffuse echogenic thickening of bile ducts [1 9, 26]. When the transducer is parallel to the bile ducts, the thick wall of the bile ducts can be seen as echogenic bands (Fig. 6A). When the transducer is tangential to the direction of the bile ducts, the thick bile ducts simulate echo-
Fig. 7.-Oblique
sonogram
of right upper ab-
domen shows mild dilatation of common hepatic duct (D) (8 mm in diameter) filled by echogenic cast (arrows). This may represent an aggregate of adult flukes. v = portal vein. (Reprinted with permission from Lim et al. [19].)
1005
genic nodules (Fig. 6B) [1 9, 26]. However, each nodule has a small echolucent center dilated duct. The overall hepatic echogenicity [19]. Choi et al. [20] reported that CT failed to ening of the bile ductal wall. On the contrary, showed periductal contrast enhancement
cases,
suggesting
several
cases
shown,
suggesting
Not
periductal
in which
infrequently
periductal
show the thickKim et al. [26] in half of their
We have experienced
contrast
fibrosis
the gallbladder
comes thick, and gallstones
Fig. 8.-Sonogram of gallbladder shows several discrete, fusiform, floating and dependent echogenic foci measuring 5-10 mm, representing flukes.
fibrosis.
periductal
in clonorchiasis representing a becomes coarse
enhancement
(Figs.
is distended,
may be present
was
1OB and 1OC). the
wall
be-
[1 9, 20].
Fig. 9.-CT scan shows diffuse, uniform dilatation of intrahepatic ducts in periphery of liver and innumerable tiny hyperdense foci within dilated ducts, apparently due to aggregates of flukes. Extrahepatic duct was dilated minimally.
Fig. 10.-CT scans show liver flukes within dilated bile ducts and severe periductal fibrosis. A, Postcontrast CT scan through middle of liver shows dilatation of intrahepatic ducts up to periphery of liver. Note high-density casts (arrows), assumed to be aggregates of flukes within dilated bile ducts. These intraductal flukes were depicted by cholangiography (Fig. 3) and sonography (Fig. 6A) as well. After administration of praziquantel, a lump of flukes was expelled, intermingled with feces. Flukes were collected and photographed (Fig. 1). B and C, CT scans before (B) and after (C) administration of contrast medium show extensive periductal fibrous thickening. Branching low densities in B decrease in diameter in C, and only lumen of dilated ducts is visualized. Periductal fibrous tissue is enhanced and blends imperceptibly with adjacent liver parenchyma.
LIM
1006
Sclerosing cholangitis bile ducts and concentric
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hepatic
may cause thickening
dilatation of intrahepatic of the intra- and extra-
biliary tree [27], but the thickening
of the bile duct is
more severe than that seen in clonorchiasis, and bile duct dilatation is focal and discontinuous [28]. Thickening of the bile duct may be encountered in cholangitis in AIDS [29]. Infestation of Fasciola hepatica results in biliary dilatation and thickening of the bile ducts, thus sonographic and CT findings are similar [30]. Furthermore, mobile vermiform structures
[30]
within
the gallbladder
echogenic
are virtually
foci in clonorchiasis
Clonorchiasis
In heavy
the same
as the
[19].
of the
Pancreas
infestations,
flukes
may reside
1 0, 31]. Choi and Yang [32] studied
in the pancreas
[7,
699 cases with surgical
AJR:155,
November
1990
passed from the gallbladder and resulting in ascending cholangitis of Western people [36, 37]. The relationship between recurrent pyogenic cholangitis and clonorchiasis has been disputed. In fact, large proportions
of persons
in endemic
areas
are infested
with liver flukes
without ever having the development of recurrent pyogenic cholangitis [5, 39, 40]. Most persons who have clonorchiasis are male [1 9, 20], but there is no sex predilection in recurrent pyogenic cholangitis [36, 38]. Ong [36] suggested that the primary cause is portal septicemia resulting from poor eating habits, and that C. sinensis need not be present in all cases of recurrent pyogenic cholangitis. Carmona et al. [38] suggested low-protein diet and portal bacteremia as causes of recurrent pyogenic cholangitis. This theory was supported by animal experiments [40, 41].
However, evidence is ample that clonorchiasis is closely related to recurrent pyogenic cholangitis, and that a cause-
intervention of the hepatobiliary tract and confirmed pancreatitis in five cases (8%). Hou and Pang [31] reported that 19 of 300 patients with clonorchiasis had pancreatic involvement,
and-effect
relationship
patients
with intrahepatic
and Chan and Teoh [1 0] found involvement in 24 of 64 cases. Patients with clonorchiasis are usually asymptomatic, but 83% of the patients who had acute pancreatitis of unknown cause were found to have a coexistent Clonorchis infestation [33]. The flukes were found in the main and tributary ducts ofthe pancreatic tail, and these ducts were dilated and packed with worms [10].
reported that 26% of patients with chronic cholecystitis, 1 9% of patients with gallstones, and 17% of patients with bile duct stones had clonorchiasis. Recent articles [1 9, 20] have reported that some 15% of persons with clonorchiasis have
Only one paper has been published on pancreatography pancreatic clonorchiasis [34]. On endoscopic retrograde
in pan-
creatograms, the pancreatic are dilated diffusely (Figs.
duct in the tail and its tributaries 1 1A-i 1 C). However, the main duct and its tributaries in the head and body are
pancreatic not dilated.
caused
Sometimes
small
filling
defects
that
might
by adult flukes are found in the main pancreatic
This characteristic in clonorchiasis of tion due to other pancreatic duct is
appearance,
duct
duct.
pattern of dilatation of the pancreatic duct the pancreas is quite different from dilatacauses. In chronic pancreatitis, the main dilated irregularly, resulting in a beaded
whereas
pancreatic
be
in carcinoma
of the pancreas,
frequently
is dilated
to Recurrent
Pyogenic
the main
uniformly.
study
in an endemic
concomitant
gallstones
patic pigment
stone disease,
of pigmented
is characterized
stones
and remissions
of abdominal
jaundice,
and fever [35-38].
chills,
of the disease
with
by intrahepatic
recurrent
pain frequently
that 20 of 31
Choi
In a clinical
and
Yang
[32]
(Fig. 12).
Stagnation
not only
favors
bacterial
infection
consequent
cellular
infiltration
but also
leads
of the bile ducts and
of the portal
spaces
and liver
parenchyma. ducts, offlukes
When pyogenic infection occurs in the bile C. sinensis are killed [1 7]. Bile stasis and the presence ,
and ova or their debris
may be important.
The flukes
and ova or their debris can form a nucleus for the formation of gallstones or bile duct stones [42], and this could instigate all the consequent abnormalities, resulting in a vicious cycle of repeated bouts of cholangitis and stone formation [37]. are composed almost entirely of of bilirubin stones may be attrib-
deconjugation
of insoluble
bilirubin
of bilirubin during
diglucuronide bouts
with
of cholangitis
[43].
The
Relationship
to Cholangiocarcinoma
exacerbation
associated
The geographic
is similar to clonorchiasis.
in Korea,
to reflux of bile into the smaller branches
the formation
Recurrent pyogenic cholangitis, which is also known as Oriental cholangitis, Oriental cholangiohepatitis, or intraheformation
area
Chemically, such stones bilirubin [1]. The formation
Cholangitis
Hou [7] reported
stone had clonorchiasis.
Rim [1 ] and Hou [7] have asserted that C. sinensis infestation causes recurrent pyogenic cholangitis. As adult flukes, eggs, and desquamated epithelial cells block the intrahepatic ducts, partially or completely, bile stasis is sure to follow [7].
uted to bacterial Relationship
exists.
with
distribution
Unlike both suppur-
The close correlation between C. sinensis infestation and bile duct carcinoma has long been emphasized [8, 24, 4348]. Hou [44] reported that in at least 15% of patients with
ative and nonsuppurative cholangitis in the West, recurrent pyogenic cholangitis does not develop as a consequence of obstruction by primary calculi, strictures, or neoplasm. The stones in recurrent pyogenic cholangitis are usually muddy
primary
and claylike extrahepatic
[46] and Chung and Lee [47] also found that the prevalence of dlonorchiasis was significantly higher in cholangiocarcinoma than in hepatocellular carcinoma. In a cholangiographic
bilirubin
and are often multiple, packing the intra- and bile ducts with casts [35-37]. These stones are
stones,
clearly
different
from
cholesterol
stones
carcinoma
of the
liver,
the
cancer
was
caused
by
infestation with C. sinensis. Belamaric [45] found that most patients with cholangiocarcinoma had adenomatous hyperplasia
and ductal
fibrosis
characteristic
of dlonorchiasis.
Kim
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AJR:155,
November
1007
CLONORCHIASIS
1990
Fig. 1 1.-dlonorchiasis
of pancreas.
A, Sonogram of pancreas shows severe dilatation of main pancreatic duct (thick arrow) and tributaries (thin arrows) in tail of pancreas. A = aorta. B, CT scan shows tortuous dilatation of tributary ducts of tail of pancreas. Pancreatic parenchyma is virtually absent. Note diffuse dilatation of intrahepatic bile ducts in periphery of liver. C, Endoscopic retrograde pancreatogram shows marked dilatation of main pancreatic duct and tributaries in tail of pancreas. Oval filling defects (arrows) are presumed to be flukes. Note relatively normal pancreatic duct in head of pancreas.
I
!
Fig.
12.-Recurrent
associated
pyogenic
with clonorchiasis.
cholangitis
Endoscopic
ret-
rograde cholangiogram shows a stone in cornmon bile duct (open arrow). Note obstruction (curvedarrow)and elliptic filling defect caused by flukes (straight solid arrow).
Fig. 13.-Cholangiocarcinoma, peripheral type associated with clonorchiasis. CT scan shows pooriy defined, large, irregular hypodense mass with small enhancing foci in middle of tumor. Pcripheral intrahepatic bile ducts are dilated (arrows).
study of patients with clonorchiasis (Lim et al., unpublished data), seven of 46 patients had cholangiocarcinoma (Figs. 13 and 1 4). In studies in cats and dogs with clonorchiasis, Hou [8, 48] advocated that adenomatous tissue formation of bile ducts regressed and was replaced by fibrous thickening or progressed to malignant change. The considerably higher prevalence of dlonorchiasis in patients with cholangiocarcinoma, the close physical relationship of the main tumor mass to infested ducts, the frequent coexistence in the same duct of focally atypical epithelial hyperplasia and invasive cancer, and the results of animal
experiments tween
Fig.
ing of right hepatic
hilar type asso-
duct,
left hepatic
duct,
and
proximal common hepatic duct due to Infiltrating carcinoma at porta hepatis. Note dilatation of intrahepatic ducts with small elliptic filling defects in peripheral small bile ducts.
all support
dlonorchiasis
14.-Cholangiocarcinoma,
ciated with clonorchiasis. Endoscopic retrograde cholangiogram shows severe segmental narrow-
a cause-and-effect
relationship
be-
and cholangiocarcinoma.
ACKNOWLEDGMENTS I thank
Jong
Kwon
Won
and
Byung
Do Kim
for
sonographic
assistance, Mun Young Roh for preparation of photographs, Ok Yeo for secretarial assistance in manuscript preparation.
and Nan
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