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INTRAHEPATIC STONES -A CLINICAL STUDY
OF 317 CASES IN SOUTHERN
Chung-Yin YUAN
Departrnent of Surgery, Yuan's General Hospital Kaohsiung, Taiwan, R.O.C. (Received Aug, 19th 1987)
Abstract
Intrahepatic stones (IHS) are prevalent in East Asia and Taiwan. A review of clinical data on 317 patients with confirmed IHS for a seven and one half year period is reported. There were 138 males and 179 females in our study, with a ratio of O.77:1 (male to female). The peak age was the third to fifth decade with a mean age of 46 years.
Pain over the right upper quadrant and
epigas-tralgia were the most common symptoms with a frequency of 82.3% and 58% respectively.
Ten-derness in the right upper quadrant (90.2%) and epigastric tenderness (50.5%) were found in pa-tients with IHS. Location of the stones were as follows: left lobe 164 cases (51.7%) right lobe 57 cases (18%) and bilaterally 96 patients (30.3%). A
popular combination is left hepatic stones and
common bile duct stones 84 cases (26.5%).
The frequency of abnormal levels of gamma-glutarmyl transpeptidase, alkaline phosphate,
GOT, GPT, total bilirubin, and direct bilirubin was 77.6%, 69.7%, 67.4%, 68.5%, 59.2% and 61.2% respectively. Leukocytosis and anemia occurred in
65.6% and 38.6% of cases with IHS.･Serum
amylase and lipase were elevated in 25.2% and 17.0% respectively. Serum levels of GOT, GPT,
and total and direct bilirubin were significantly higher in cases with coexisting common bile duct than those without.
With IHS E. coli was isolated in 18 cases (39.1%)
For reprints: Dr. CY Yuan, Department of surgery, Yuan's General Hospitai, No.162, Sec. 1. Cheng-Kong
Rd. Kaohsiung, Taiwan, R.O.C. Telephone: (07)
3351121-31
of 40 blood cultures and 140 cases (39.9%) of 217 bile cultures, it was the most prominent micro-organism found. Sensitivities of abdominal ultra-sonography (US), endoscopic retrograde cholangi-opancreatography (ERCP) and percutaneous trans-hepatic cholangiography (PTC), were 87.5%, 88.5% and 100% respectively. Sepsis, liver abscess and pancreatitis were complicated with hepatic stones iR the frequency of 1896, 8.596 and 5.7{>6 respec-tively. Seven cases (2.2%) had coexisting
clonor-chiasis and 2 cases (O.6%) has ascariasis. An
association exist between IHS and cholangiocar-cinoma there were 9 cancers in 317 IHS cases.
Medical treatment was given in 75 cases
(23.7%), the balance (76.3%) underwent surgery.
Extended choledocholithotomy with or without cholecystectomy were performed in 203 cases, while left hepatic segmentectomy or lobectomy
were done in 36 cases. Postoperative
choledocho-scopy was required in 93.8% of the cases for
removal of residual stones. The over qll mortality of IHS was 5.4% during hospitalization.
IHS usually affects young females with
recur-rent attacks of cholangitis. US, ERCP and PTC
can correctly diagnose the disease and help local-ize stones. Surgery is the treatment of choice in addition postoperative choledochoscopy is usually required for the removal of residual stones. Mor-tality of IHS is decreasing, however morbidity still remain a serious problem in Southern Taiwan.
Introduction
It is known.that the incidence of IHS is high
throughout East Asia in comparison to Europe and the United Statesi). In Taiwan and other
parts of East Asia, IHS is manifested by recurrent - 1585
cholangitis and liver abscess2}3). Since this condi-tion is responsible for much of the serious
mor-bidity and mortality of gallstone disease in
Taiwan3)"'6}, we retrospectively reviewed the clin-ical information, including age, sex, signs and
symptoms, modes of diagnosis, treatment and
outcomes, of 3l7 patients with verified IHS in our hospital during a peirod of 7.5 years.Materials and Methods
The present data was obtained from Yuan's
General Hospital in Kaohsiung, Taiwan, during a seven and one half year period Uanuary, 1980 to June, 1987), 1,515 cases of proven gallstone disease were found and of these 317 cases (20.9%) had IHS. The diagnosis 'of IHS was verified by surgery in 242 cases (76.3%), and by endoscopic retrogradecholangiopancreatography (ERCP) and/or
percu-taneous transhepatic cholangiography (PTC) with compatible clinical course in 75 cases. Patients diagnosed with ultrasonography (US) alone were excluded from the study. The definition of IHS was stones involving the right and ･left intra-hepatic ducts distal to their junction, and their
branches. Abdominal US was conducted with a
realtime US scanner (Aloka SSD 256) with a
transducer of 3.5 MHz. The results of laboratoryexaminations at admission and discharge were
recorded and calculated. Bile cultures were done
during operation using a sterile technique.
Student's t-test was used for statistics. A p value less than O.05 was considered significant.
Result
Age and sex
As shown in Table 1, there were 138 males and 179 females with a mean age of 46.0 years. The
male to female ratio O.77:1. The peak age was the third to fifth decade. There is no difference of peak age between males and females.
Symptoms and signs
The frequency of symptoms and signs of 317
patients with IHS are listed in Table 2. Among them, pain over right upper quadrant (82.3%), epigastralgia (58%) and fever (52.4%) were the
most common symptoms. Tenderness over the
Table 1 Age and sex distribution of 317 patients with intrahepatic stones
Age Male Female Total
10-19 o(oo/.) 1(o.6o/,) 1(o.3o/.)
20-29 13(9.40/o) 10(5.6%o) 23(7.30/o)
30-39 34(24.60/o) 52(29.0%o) 86(27.10/o)
40-49 43(31.20/.) 39(21.8%) 82(25,9%) 50-59 29(21.00/.) 48(26.sO%) 77(24.3%) 60-69 14(10.2%) 20(11.2%) 34(10.7%) >70 5(3.60%) 9(5.0%) 14(4.4%)
Total 138(1000%) 179(100%.) 317(10oO%)
M(eya,n.,a,ge 45.4 46.4 46,O
Table 2 Symptorns and signs of 317 patients with intrahepatic stones
Symptom No.ofpatient(%) Sign No.o(fggetient
RUQpain
261(82,3) RUQtenderness 286(90.2) Epigastralgia 184(58,O) Epigastrictenderness 160(50,5)Fever 166(52.4) Jaundice 123(38.8) Radiationpain 120(37.9) Knockingpain 121(38.2) Chillness 96(30,3) Charcot'striad 72(22.7) Nausea 94(29,7) Reboundtenderness 60(18.9) Vomiting 64(20.2) Murphy'ssign 54(17.0) Tea-coloredurine 63(19.9) Abdominalrigidity 38(12.0) Clay-coloredstool 42(13.3) Hepatomegaly 30(9.5) Anorexia 36(11,4) Palpablegallbladder 5(1.6)
Malaise 30(9,5) Others* 3(O.9)
RUQ : Right upper quadrant
Table 3 The location of gall stones
LocationofIHDstone Combinationof
location Leftonly
(o/o) Rightonly(o/o) Left+Right(o/o)
Total (%) IHDonly 37(22.6) 9(15.8) 13(13.6) 59(18.6)
IHD+GB
10(6.1) 1(1,8) 3(3.1) 14(4.4)IHD+CBD
84(51.2) 26(45.6) 56(58.3) 166(52.4)IHD+GB+CBD
33(20.1) 21(36.8) 24(25,O) 78(24.6) Total 164(100) 57(100) 96(100) 317(100)IHD : Intrahepatic ducts, CBD : Common bile duct, GB : Gallbladder
right upper quadrant (90.2%), epigastric
tender-ness (50.5%), and jaundice (38.8%) were found
during physical examinations.
Locations of stones
The location of intrahepatic stones was subdi-vided into the left, right and both lobes. As shown in Table 3, there were 164 (51.7%) patients with left IHS (Fig. 1), 57 (18.0%) with right IHS (Fig. 2), and 96 (30.3%) with IHS of both lobes (Fig. 3). The various combinations of IHS, gallbladder stoens, and common bile duct stones are also listed in Table 3. The most frequent combination was left
IHS and common bile duct stones (84 cases,
26.5%).Laboratory examination
As shown in Table 4. The frequency of
abnor-mal levels of gammaglutamyl transpeptidase (r-GT), alkaline phosphatase (Alk-p), GOT, and GPT was 77.6%, 69.7%, 67.4%, and 68.5%, respectively.
Fig. 1 Leftintrahepaticstones.
Fig. 2 Right intrahepatic stones.
Fig. 3 Intrahepatic stones of both lobes.
-1587-Table 4 Biochemical tests of 317 patients with intrahepatic stones Biochemistry Normalvalue No.ofpatientsexamined No.withofpatientsabnormal
result Percentile (o/o)
GOT
<35UIL 310 209 67.4GPT
<30UIL 308 211 68.7 Alk-P(before1985) (after1985)<13KAU/L
<272U/L 2ig),,7 i2g)is6 67 81 .o ,6 )69.7 Bilirubin(T) <1.2mg/dl 306 181 59,2 Bilirubin(D) <O.4mg/dl 308 190 61.7 Albumin >3.9g/dl 307 199 64.8 Globulin <3.9gldl 307 57 ' 19.2 r-GT <100U/L 58 45 77.6 Amylase <200SU/dl 206 52 25,2 Lipase (before1986) (after1986) <1.5U/ml <249U/L iig)i6s 2i)2s 18 13 ,7 ,2 )17.o Leukocytecount <100001cumm 305 200 65.6 Hemoglobulin >12gmldl 308 119 38,6Alk-P : Alkaline phosphotase, (T) : Total, r-GT : gamma-glutarmyl transpeptidase
(D):Direct
Table 5 Comparison of biochemical findings without coexisted common bile duct stone
between patlents with and
Intrahepaticstones
Biochemistry Pvalue""
withCBD'stone withoutCBDstone
GOT
85,O±5.6*.*(N=235) 55,5±7.5(N=75) <O.005GPT
104.3±6.7(N=233) 74.2±10.1(N:=75) <O.O05 Alk-P(before1985) 37.9±8.3(N=:155) 29.1±11,O(N=63) N.S.
(after1985) 563.6±61.8(N=[44) 361,4±121.1(N=5) N.S.
Bilirubin(T) 4.4±O.3(N=i233) 3,2±O.5(N:=73) <O.05 Bilirubin(D) 2.8±O.2(N]:234) 1,8±O,3(N=:74) <O.025 Albumin 3,6±O.1(N=232) 3.6±O.1(N==75) N.S. Globulin 3,O±O.1(N=232) 3.0±O.1(N=:75) N,S. r-GT 276.3±27,8(N=50) 245.1±117.0(N=:8) N,S.
Amylase 193,8±20.6(N=[163) 171.6±30,8(N=43) N.S.
Lipase
(before1986) 1,7±O.4(N=93) 2.2±O.8(N=:30) N,S.
(after1986) 68,2±55.4(N[35) 124.9±124(N==3) N.S. Leukocytecount 13329.5±698.8(N=233) 12408,3±674.1(N==72) N,S. Hemoglobulin 13,4±O.5(N=235) 13±O.2(Ni=73) N,S.
*CBD : Common bile duct "Test with Student's t-test
"'Mean±standard error of mean (SEM)
All abbreviations and units are the same as shown in Table 4.
Total and direct bilirubin were abnormaly ele- IHS. Two hundred (65.6%) patients had
leuko-vated in the frequency of 59.2% and 61.7%, respec- cytosis and 119 (38.6) patients had anemia. Thetively. The serum levels of amylase and lipase comparison of biochemical findings of IHS with were raised in 25.2% and 17.0% of patients with and without common cile duct stones was shown
-Table 6 Microorganisms isolated from blood intrahepatic stones
and bile of patients with
Microorgamism Bloodculture"(N=40) Bile(N=217)culture"
E.coli 18(39.1%) 140(36.90/o)
Klebsiella 9(19.6e/,) 79(20.80/o)
Pseudomonas 2(4,4%) 23( 6 ,10/o)
CNFGram(-)bacilli' 3(6.50/o) 23( 6.10/o)
Enterobacter 1(2,20/o) 20( 5 ,30/o)
Proteus 13( 3･4o%)
17( 4 .50/o)
Morganella 12( 3.20/o)
Streptococcus 4(8･7%o) 8( 2 .10/o)
Bacteroides 5(10.9%) 15( 4,o%) Serratia 6( 1 ,60/o) Enterococcus 6( 1 .6O?6) Staphylococcus 1( o,3%) Providencia 3( o,8%) Pectobacterium 3( o .80/o) Hafnia 2( 0･5o%) Aeromenashydrephila 2(o.so/.) Edwardsiella 1( o .30/o) AnaerobicGram(+)coccus 3(6.5%) 1( o .30/o) AnaerobicGram(+)bacillus 1(2.2%) 4( 1 .10/o)
Total"' 46(looo/o) 37g(looe/.)
'Glucose non-fermentation gram (-) bacilli
"*Mixed infection 6 eases in blood culture 120 cases in bile culture
**'Total genuses of microorganism
in Table 5. The serum levels of GOT, GPT, total and direct bilirubin of patients with coexistent
stones in the common bile duct. The results of microorganisms isolated from bile cultures and
blood cultures are listed in Table 6. E. coli was the leading microorganism both in blood (18/46) and bile (140/379) cultures. Klebsiella was less com-mon in the blood (9/46) and bile (79/379) cultures.
Diagnosis
Table 7 shows the sensitivities of various diag-nostic modalities. The sensitivity is the highest in PTC (100%), and similar in both ERCP (88.5%) and
US (87.5%). PTC provides the best informaiton and have higher diagnostic abi･lity even when
there is a stricture in the intrahepatic ducts, which precluded successful visualization of intra-hepatic ducts by ERCP (Fig. 4).
Complications
As shown in Table 8, clinical sepsis manifested as chillness, fever, and leukocytosis, occurred in
Table 7 The modalities stones Sensitivities of in the diagnosis varlous lmagmg of intrahepatic Imaging
modalities examinedNo, No.positivelydiagnosed
Sensitivity (%)
us
ERCP
PTC
305 296 41 263 262 41 87.5 88.5 100.0 US : UltrasonographyERCP: Endoscopic retrograde cholangiopancreatogra-phy
PTC : Percutaneous transhepatic cholangiography,
1896 (57/317) of cases. Liver abscess, pancreatitis, and pleural effusion were complications in 8.5%, 5.7%, and O.9% of patients with ･IHS (Fig. 5).
Associated diseases
Heart disease, diabetes, hypertension, and liver cirrhosis commonly coexisted with IHS (Table 9). There were 7 (2.2%) of 317 patients with clon-orchiasis (Fig. 6) and 2 (O.696) patients had asca 1589 asca
-a
b
Fig. 4 a: ERCP shows dilated intrahepatic ducts and common bile duct, A stricture was shown in the lst
branch of right intrahepatic duct (arrows), but stones are poorly visualized.
b: PTC show multiple filling defects in the distal part of lst branch of right intrahepatic duct, the stricture was clearly demonstrated (arrows).
Table 8 Complications of 317 patients with
intrahepatic stones
Complication No.ofpatients Percentile (o/o)
Sepsis' 57 18.0 Liverabscess 27 8.5 Leftlobe 15 4.7 Rightlobe 7 2.2 Bothlobes 5 !.6 Pancreatitis 18 Pleuraleffusion 3 O.9
'Positive blood culture in 40 cases
g
riasis. A significant association does exist be-tween IHS and cholangiocarcinoma (9 cancers in 317 IHS) (Fig. 7).
Treatment
As shown in Table 10, 75 patients (23.7%)
received medical treatment including
sympto-matic treatment (70 cases), endoscopic
papillo-Fig. 5 Intrahepatic stone extirpated during operation.
It was muddy in nature, blackish in color. The major
chemical composition was calcium bilirubinate.
Table 9 Associated diseases in 317 patients with intrahepatic stones Associated disease No.of. patlents Percentile(%) Heartdisease 15 4.7 Diabetesmellitus 14 4.4 Cirrhosis 10 3.2 Cholangiocarcinoma 9 2.8 Hypertension 8 2.5 Pulrnonarydisease 8 2.5 Hematologicdisease 5 1.6 Parasites 14 4.4 Clonorchiasis 7 2,2 Ascariasis 2 O.6 Ankylostomiasis 2 O.6 Trichuriasis 3
O.9-Othermalignancy' 8 2.5'include hepatoma (3), pancreatic cancer (1), gastric cancer (1), colonic cancer (1), 1ung cancer (1), and cancer of underrnined origin (1)
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Table 10 . patlc stones Medical treatment (N= 75, 23.7%) Symptomatic treatment (N=70, 22.4%) Endoscopic papillotomy (N=4, li3%) PTCD and PTCDS' (N= 1, O.3%) Surgical treatment" (N=242, 76.3%) Extended choledocholithotomy (N=150, 47.3%) +cholecystectomy Extended choledocholithotomy (N=53, 16.7%) Extended choledocholithotomy (N=36, 11.4%) +cholecystectomy+left hepatic segmentectorny Transhepatolithotomy (N=3, O.9%)
6 Intrahepaticstoneswithcloronchiasis.
'Percutaneous transhepatic choledocho drainage and percutaneous transhepatic choledochoscopy for extirpation of stone.
"Drainage procedures including tomy (125 cases), hepatojejunostomy (Roux-en-Y procedure, 6 cases), choledochojejunostomy en-Y procedure, 2 cases), and oplasty (1 case).
Ske
Fig. 7 Intrahepaticstoneswithcholangiocarcinoma.
' Table 11 Postoperative complications operated intrahepatic stones
in 242 Complication No.of. patlents Percentile (o/o) Woundinfection 93 38.3 Biliarytractinfection 29 12.0 Pleuraleffusion 9 3.7 Ventralhernia 6 2.5 Hemobilia 4 1.7 Miscellaneous' 13 5.4
'Including subphrenic abscess (3), pneumonia (2), gastrointestinal bleeding (2), pancreatitis (2), bile
duct injury (2), intestinal obstruction (1), intraper-itoneal abscess (1).
tomy (4 cases) and percutaneous transhepatic
choledochoscopy (1 case). The remaining 242 cases (76.3%) received operative therapy. Most common
procedure for removal the stones was extended cholechodolithotomy with cholecystectomy (150 cases, 47.3%). In patients with contracted or
atrophic left lobes and 1ocalized stones in the left intrahepatic ducts, left hepatic segmentectomy or
lobectomy was sometimes performed (36 cases,
11.4%). Postoperative choledochoscopy was done in 227 cases (93.8%) for removal of retained stones.
Table 12 Mortality of 317 patients with .
patlc stones
Operative cause (N=11, 3.5%) Sepsis (N=7, 2.2%) Heart failure (N=1, O.3%) AMI. (N=1, O.3%)
Gastrointestinal bleeding (N= 1, O.3%) Disseminated intravascular
coagulation (N=1, O.3%) Non-operative cause (N=6, 1.9%) Sepsis (N=5, 1.6%)
Heart failure (N=1, O.3%) 'AMI : Acute myocardial infarction
-Nevertheless, there were 22 cases (9.1%) with
residual stoens after a follow-up period of 2 years.
Postoperative complication
Among 242 patients receiving operation, 93
(38.4%) had wound infection and 29 (12.0%) had biliary tract infection (Table 11).
Outcome
As shown in Table 12, 17 patients (5.4%) died during hospitalization. Eleven patients died with postoperative complications and the remaining 6 patients died of non-surgical causes. Sepsis was the leading causes of death (12/17, 70.6%).
Discussion
The pathogenesis of stone formation in the
biliary tract is not completely understood. It has been attributed to metabolic disturbance, stasis or infection. Gallstones are predominantly found in
the gallbladder and common bile duct. However for centuries both surgeons and pathologists
noticed another type of stone in the intrahepatic biliary ducts. The location, consistency, composi-tion, number and clinical manifestations of these stones were entirely different from cholelithiasis of gallbladder origin. The earliest and most de-tailed report of IHS was described by Vachell and Stevens in 19067}. The true prevalence of IHS was difficult to evaluate and usually depended on the method and thoroughness of the search for stones.
Autopsy is not a reliable method because of
detailed and specific search of the intrahepatic ducts is usually not required. The relative opera-tive prevalence of IHS compared to all surgical cholelithiasis is a more reliable and feasible method to indirectly reflect the true prevalence of IHS.The relative prevalence of IHS in Western
countries is extremely low8). Recently, Lindstr6mreported only 5 (O.6%) cases of IHS among 763
cases of cholelithiasis8). On the contrary, IHS is common in East Asia and remain to be a special problemi). Even in East Asia, the prevalence of IHS varied in different regions. The prevalence of IHS was highest in Taiwan9). HuangiO} found that
30% of 110 primary bile duct stones were IHS,
while Ker et al.`) discovered (IHS) in 5I.6% (163 in
316) of all gallstones operated in Southern
Taiwan.
In other areas of Taiwan, the relative preva-lence of IHS was as high as 30%3>5). In 1986; a retrospective study of IHS in Japan, Taiwan, Hong
Kong and Singapore was conducted by Nakayama
et al.9). The relative prevalence of IHS in all operated gallstones was highest in Taiwan (53.5%) and lowest in Singapore (1.7%). The prevalence in
Hong Kong (3.1%) and Japan (4.6%). The great difference between Taiwan, Singapore and Hong
Kong is surprising because the majority of popula-tion in these areas is of Chinese descent.
There-fore, the major difference must be sought in
environmental rather than ethnic factors.
Among the environmental factors, parasites
and bacterial infection were commonly
consid-ered. Clonorchis sinesis was proposed to be one
cause of IHSii), however, the infestation in Taiwan was only endemic and not as common as
in Hong Kong and Southern China3}. In this study, there only 7 cases (2.2%) with IHS had coexisting clonorchiasis. Ascaris lumbricodies was once
con-sidered to be responsible for the formation of
calcium bilirubin stones2). However, infestation
rate of ascaris declined remarkably in Taiwan
since 1950, but IHS persisted.
In 1984, a prospective epidemiological survey of
gallstoens and parasital infestation was con-ducted in Southern Taiwan'2). IHS was detected
in 28 (O.93%) out of 3004 subjects by ultrasonic examination. No direct relationship can be con-ciuded between IHS and parasital infestationi2). Bacterial infection jn the biliary tree was also proposed as the etiology of calcium bilirubinate stones, the major component of IHSi3). However,
whether IHS per se is a preexisted anomaly or secondary to recurrent infection needs further investigationi3}.
The increased incidence of gallbladder stones
with age was an universal phenomenon in all
studiesi4). Glenn reported that the incidence ofcholedocholithiasis increased with the age and
reached a high incidence of 25% in patients over 60i5). Nevertheless, Hsu et al. reported muddy IHS tended to affect the younger age groupi6}. In our
study, the peak age was the third to fifth decade with a mean of 46 years. The result was in line with that of Ker and Sheen (mean age: 39 years)'6},
and Hsu et al. (mean age: 43.6 years)i6). As
described by Change and Passaro, the disease can occur before the age of 15i7}. It has been partially
explained by the different mechanisms of stone formations among IHS, gall bladder stones and
common bile duct stones. IHS were proposed to be associated with parasital infestation such as clo-norchiasis and ascariasis which occurred in the early aldolencence2), while gali bladder stones commonly occurred in the older age group due to impaired cholesterol metabolism and desaturated
bile.
Female predominance of IHS in our series (maie: female=O.77:1) was in accord with the observation of Hsu et al.6}, Ker and Sheeni6), Wen and Leei8)
and Change and Passaroi7). The mechanism was
still unclear. IHS were frequently presented with extrahepatic stones. In this series, 81.4% of IHS had coexisted extrahepatic stones, including gall bladder stones and common bile duct stones. 18.6
percent had only IHS. Although Bolton and
LeQuesne reported that almost all calculi in thecommon bile duct were originating from stones migrating from the gall bladder via the cystic
ducti9), there is definitely some cases (52.4%) who had intrahepatic and common bile duct stones but no gall bladder stones. Therefore, stones in the common bile duct may originate from intrahepatic
ducts rather than the gall bladder. Comparison
between the left and right lobe involvement in the
IHS was shown in Tabel 3. The left lobe was
involved more than the right lobe. This same
relationship holds true in Japan9}. About 82% of our cases involved the left intrahepatic duct. The explanation of left lobe predominance is still not
clear.
The common symptoms of IHS in this series
were right upper quadrant pain, fever and epigas-tralgia. It seemed more severe than the symptoms of gall bladder stones which usually have silent ormild symptoms. In the study of Change and
Passaroi7}, cholangitis manifested as fever, chil-lness, pain over right upper quadrant andjaun-dice presented in 40% of IHS, Our observation
confirmed their results. Biochemical tests espec-ially the biliary enzymes and biiirubin, tended to be elevated in patients with IHS. Moreover, pa-tients with coexisted common bile duct stones had higher levels of serum GOT, GPT, bilirubin and gamma-glutarmyl transpeptidase (Table 5). It
sug-gested that profund or severe cholestasis and
cholangitis occurred when IHS impacted the
common bile duct.E. coli was the leading microorgarism in the bile and blood culture in our study. A similar result
was reported by Wen and Leei8}. Maki proposed
that E. coli produces beta-glucuronidase which deconjugated bilirubin glucuronide to free bil-irubin and plays an important role in formation of calcium bilirubinate gallsones in the intrahepatic ducts20). Nevertheless, most authors believed the existence of E. coli in the bile were the result of ascending infection rather than the cause of IHS.
Ultrasonography (US) is a safe, noninvasive,
and accurate diagnostic modality in the detection of liver and biliary diseases. The diagnostic ability of US in detecting IHS was reported as high as 90%2i}. It provides a good way for screening IHS and also detecting coexistent anomalies in the liver, such as liver abscess and choiangiocar-cinoma. Only pneumobilia and intrahepatic calci-fication need to be differentiated from IHS by US.
However, the acutural anatomatic locations of
stones in the intrahepatic ducts and common bile duct cannot be accurately plotted by US alone.
ERCP and PTC provides better information
con-cerning the stricture, dilatation, fistula and other anormalies of the intrahepatic ducts which is very important for surgical intervention. CT, although of similar sensitivity in detecting IHS as US, it is more expensive with a hazard of irradiation ex-posure. It's usually adopted as a supplementary tool for detecting coexisting liver abscess or cholangiocarcinoma.
The major complication of IHS in our study was
sepsis although some cases had negative blood
cultures. Clinical evidence of sepsis occurred in the frequency of 37 to 60%i6)i8). It's sometimes combined with liver abscess. These complications, 1593
-were rarely seen in the gallbladder stones, How-ever, pancreatitis rarely complicates with IHS alone, but occurs when the stones are impacted in the common bile duct. The association of clornor-chiasis and IHS has been described previously,
Cholangiocarcinoma was proposed as one of the
sequeles of IHS22}. In our study, there were 9 patients with coexisted cholangiocarcinoma and IHS. It's reasonable that chronic irritation of stones in the intrahepatic ducts causes inflam-mation, dysplasia, metapiasia and eventually ne-oplasia of the ducts. However, preexisted
malig-nancy in the bile ducts may result in stasis,
stagnation and infection of the bile, along with
secondary stone formation in' the intrahepatic
ducts23). Our observation confirmed the
coexis-tence of IHS and cholangiocarcinoma, but the
proposed hypothesis needs further investigation. The treatment of IHS is usually unsatisfactory.
Medical treatment by symptomatic therapy and
endoscopic palpillotomy provided temporary relief of symptoms of cholangitis5). Medical dissolution
of IHS by ursodeoxycholic acid or
chenodeoxy-choic acid is impossible at present because the major components of IHS are not cholesterol but calcium bilirubinate24).
Surgery remains the treatment of choice for the IHS. Operative procedure is essential except for high risk patients who can be only treated with choledochoscope via a PTC fistula. Nevertheless,
the disease has a high incidence of repeated
attacks of cholangitis due to residual stones.
Therefore, reoperation is often required. The
choice of operation is based on the location of stones and the existence of pathologic stricutre or dilatation of bile ducts. The basic procedures for
lithotomy include choledocholithotomy,
trans-hepatic lithotomy and trans-hepatic segmentectomy or
lobectomy25)26}. The additional drainage pro
cedure includes T-tube drainage, choledochojeju nostomy, hepatojejunostomy, and
choledochoduo-denostomy.
In patients with IHS involving only the left lobe, or IHS coexisting with cholangiocarcinoma, hep-atic segmentectomy or even lobectomy was under-taken. A procedure of postoperative
choledocho-scopy was performed on evey surgical patients for extraction of the retained stones in the bile duct.
However, the incidence of residual IHS remains high in Taiwan26) and non-surgical removal of
residual stones by postoperative choledochoscopy is accepted by most surgeons27}.
Wound infection (38.3%) was the most frequent postoperative complication, the infections
re-sponded well to antibiotic therapy. The mortality rate of IHS cases in our series was 5.4%. With the administration of sensitive antibiotics successful
'
removal of stone either during surgery or by
postoperative choledochoscope, and adequate
drainage of iiver abscess, the mortality of IHS is less severe than in the past.In summary, IHS usually affects young females with repeated cholangitis. The imaging
modal-ities, including US, ERCP and PTC, can correctly
diagnose the disease and localize the stones.
Surgery remains the treatment of choice although postoperative choledochoscopy is usually required for removal of residual stoens. The mortality is decreasing but the morbidity and compiications of
this disease remained to be a big problem in Southern Taiwan.
Acknowledgement
The authors thank miss Y.C. Liang for her excellent secretarial work and preparing this manuscript.
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