SEMINARS IN LIVER DISEASE-VOL.
10, NO. 2, 1990
Carcinoma of the Hepatic Confluence 25 Years After Klatskin's Description: Diagnosis and Endoscopic Management
'Twenty-five years have passed since the late Gerald Klatskin, Professor of Internal Medicine at Yale University, published his article "Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatis."' The tumor was described by others, including Altemeier, as reviewed by Bengmark and Tranberg.? However, the characteristics of the hilar tumors were reported in such a way that they have often eponymously been called Klatskin tumors. Since his description, major diagnostic improvements have been made with respect to tests to diagnose viral hepatitis and primary biliary cirrhosis, as well as the imaging of the biliary tree by means of ultrasound, endoscopic retrograde cholangiopancreatography (ERCP) percutaneous transhepatic cholangeography (PTC). These improvements have greatly facilitated diagnosis and contributed to a more individualized therapy. Although some of his statements are outdated now, others have remained apt, like "the tumor is readily overlooked unless the surgeon recognizes the possibility of its existence, . . . tumors of this type tend to be small and to remain sharply localized; they seldom metastasize, and ultimately give rise to fatal hepatocellular failure andlor suppurative cholangitis as a consequence of unrelieved biliary obstruction . . . , palliative surgery aimed at relieving biliary obstruction is remarkably effective in allaying symptoms and prolonging life."' This article discusses the current diagnostic approach toward patients with assumed malignancies at the level of the liver hilus. The application of the available diagnostic tools is often during the same session followed by temporary or definitive stent insertion. This aspect will be addressed also, mainly focused on endoscopic drainage, whereas Lameris et al discuss the role of the percutaneous approach elsewhere in this issue of Seminars. At this stage, it should be mentioned that the rarity of the tumor, the enormous variety in initial approaches toward the problem, and further management,
Frorn the Depcrrtrnent of Hepcrto~cr.srroc~ntc~ro/o,q~ trtld the Hr~xitopur~crrc~tic~ohilic~ry litlit qf the, Ac.udc,mic. Mrdic~rlC m t r r of the Ur~iversityof'Atnsrrrdmn. Amsterdam, The Netlzc~rltrt~ds. Reprint requests: Dr. Van Leeuwen. Department of Hepatogastroenterology (CEOI). Academic Medical Center. Meibergdreef 9 , 1105 AZ. The Netherlands. 102
as well as mixtures of data and results of diverse clinical groups limit the possibility of making firm recommendations based on properly conducted clinical trials. Any proposed approach toward the problem is at least partly based on local expertise.
DEFINITION, ETIOLOGY, ANATOMIC CLASSIFICATION
Definitions Primary cholangiocarcinomas arising from the part of the common bile duct between the cystic duct junction (common hepatic duct) and the confluence of the hepatic ducts at the liver hilus are called biliary hepatic confluence (Klatskin) tumors. Cholangiocarcinoma is grouped with the hepatocellular carcinomas (HCC) as classified by World Health Organization WHO3 and is not distinguished from them in the ICD classification (rubric 155.0). Cholangiocarcinoma may account for only an estimated 10% of all HCC; hilar (Klatskin) tumors represent 15 to 53% of these.'-7 The rarity of extrahepatic bile duct tumors was demonstrated in autopsy studies, being present in 0.12% of 129,57 1 cases.' Various histopathologic aspects of Klatskin tumors are addressed by Bosma elsewhere in this issue of Seminurs. Many reviews of the pathologic aspects have been published.'.'-1J The main characteristics of these tumors are the usually slow-growing behavior of the tumor, the sclerosing or fibrosing characteristics in a majority of cases, and the late occurrence of metastasis.'
Etiology The etiology of these tumors has remained unclear. The disease has been associated with congenital fibropolycystic disease,15." sclerosing cholangitis,17 typhoid carrier state," flukes,"-" chronic ch~langitis,'~biliary cirrhosis," hepatolithia~is,".~possibly secondary to malignancy," and ulcerative colitis." Chronic inflammatory activity and bile acid alterations could be common denominator^.^' Occurrence in combination with
Copyright 0 1990 by Thieme Medical Publishers, lnc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
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D I R K J. V A N LEEUWEN, M.D., KEES HUIBREGTSE, M.D., and GUlDO N.J. TYTGAT, M.D.
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LEEUWEN, HUIBREGTSE, TYTGAT
HCC has been described." An assumed association with methyldopa was not confirmed.'"
TABLE 1. Differential Diagnosis of Obstruction at the Hilar Confluence of the Liver Cause, of'Ohstruc.tion"
Anatomic Classification Based on the anatomic location of the tumor Bisclassified them as: muth and C~rlette'~' unobstructed primary confluence (tumor Type I: located in the main hepatic duct) Type 11: obstruction limited to the primary confluence (tumor located exactly at the confluence) Type 111: obstruction of the primary confluence with extension to the right or left secondary confluence. The types reflect increasingly difficult treatment options.
DIFFERENTIAL DIAGNOSIS Cholangiocarcinoma of the Klatskin type needs to be discriminated from various other conditions because of its prognostic and therapeutic implications. Table I summarizes conditions that may mimic this malignancy. There are various important clues and pitfalls to the diagnosis. Direct cholangiography will greatly contribute to the diagnosis. The appearances may be highly suggestive and some examples of proved cholangiocarcinoma are shown in Figures 1 through 4. However, features preoperatively thought to be fully compatible with hilar cholangiocarcinoma may, after a thoroughly performed pathologic examination of the resected specimens, show nonmalignant fibrosing processes only. Such cases were recently described3' and are in keeping with our own experience. Figure 5 presents a typical example of gallbladder carcinoma invading the liver hilus. Cholangiography in ultrasothis condition has been reviewed in nography was described in detail as we11.3J.3SFigure 6 shows an example of benign inflammation (evidence obtained after laparotomy) invading the liver hilus. Ultrasound (US) and US-guided cytologic puncture of the wall of the gallbladder may help to avoid needless laparotomy. Patients with gallbladder carcinoma are unlikely to benefit from surgery. However, it should be recognized that it may be impossible even during surgery to obtain definite proof of the malignant character of a process. This is due to various factors, including the fact that, within the biliary tract, substantial fibrosis may accompany a small tumor. Conversely, changes in the biliary tract secondary to obstruction can easily be interpreted as malignant in the frozen specimen. Endoscopic "probing" of the stricture may provide an indication of the primary problem. Strictures due to primary cholangiocarcinoma and benign postoperative strictures tend to be very tough. They may be difficult to pass, usually in contrast to strictures due to secondary tumor compression of the hilus. The presence of features of sclerosing cholangitis and the history of sudden worsening of jaun-
C1ur.s to Ditrn.t~osis"
Primary cholangiocarcinoma of upper CBDIhepatic duct confluence (Klatskin tumor)
US, ERCP or PTC, brush cytology
Hilar invasion o f gallbladder carcinoma
ERCPIPTS US (gallbladder) with cytology
Cholangiocarcinoma or PSC
Sudden worsening of PSC or UC patients
Benign biliary stricture (stricture\ may be congenital or of unknown origin)
Surgical history, preferential locali~ation,ERCP or PTC (interval may be many years)
Biliary stone5 or sludge
ERCP o r PTC renloval (nasobiliary drain)
Metastatic carcinoma
History. cholanglographic appearance, tumor markers
Lymphoma Benign (reactive)
Malignant
May be impressive after even short perlod of obstruction; may accompany malignancy History, lymphoma elsewhere, upper abdominal US
Other type tumors. including primary liver cell carcinoma obstructing the biliary tree (alpha,-fetoprotein levels). *US: ultrasound; ERCP: endoscopic retrograde choliangiopancreatography: PTC: percutaneous transhepatic cholangiography: CBD: common bile duct; PSC: primary sclerosing cholangitis; UC: ulcerative colitis.
dice fit in with the diagnosis of hilar cholangiocarcinoma associated with long-standing primary sclerosing cholangitis (PSC) often occurring in patients with ulcerative ~ o l i t i s " ~(Fig. ' ~ 7). However, a previous history of sclerosing cholangitis may be absent (Fig. 3). Repeated sampling for cytologic examination can be helpful if positive.37.3x Figure 8 shows intrahepatic spread of metastatic pancreas head carcinoma. The designation of Klatskin tumor probably should be limited to proved cholangiocarcinoma of the liver hilus. The occasional surprise underlines this. We have seen patients with a clinically "typical" Klatskin tumor who finally proved to have undifferentiated small cell (oat cell) carcinoma3' or, in a comparable case, nonHodgkin lymphoma without any localization elsewhere. In a recent series of patients who were referred to our unit for obstructive jaundice, 4 to 5 % of the patients had signs of hilar obstruction. As will be discussed later in this article, we obtained histologic or cytologic confirmation in 55% of the patients only. Figures 9 a and b show examples of benign strictures. According to Klatskin, any stricture diagnosed in patients without previous biliary tract disease or surgery should be considered neoplastic until proved otherwise.'
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10, NUMBER 2, 1990
FIG. 1. ERCP in a 74-year-old woman in excellent condition with a 2-week history of obstructive jaundice. Note a subhilar stenosis (a) extending to the right and the left hepatic duct (arrows, b). Initial drainage of this type II tumor was obtained endoscopically. A 10 endoprosthesis was inserted into the left system but only a smaller 7 endoprosthesis could be inserted into the right system (c). She was keen to be operated on and had an uncomplicated hilar resection followed by intraluminal and external radiotherapy, which was well tolerated. She remained in good condition without jaundice or chills during the following year. She then presented with general malaise, tumor recurrence, and progressive, fatal liver failure. Autopsy revealed necrotic intrahepatic tumor masses.
CLINICAL APPROACH TOWARD MALIGNANT HlLAR OBSTRUCTION Clinical Presentation Obstructive jaundice is often the presenting symptom of hilar cholangiocarcinoma. However, in case of one-sided hilar occlusion other symptoms may be present in the absence of jaundice. The previous history is usually unremarkable except for weight loss and general malaise. In retrospect this often may have existed over a
period of months. The patient may be known to have PSC or malignancy elsewhere. Physical examination may show liver enlargement. Laboratory investigations show obstructive liver disease (increased alkaline phosphatase and gamma glutamyl transferase), but are otherwise not helpful in the differential diagnosis. In the past, unexplained liver function test abnormalities led more often to liver biopsies. These then suggested bile duct obstruction which, at that time, could not be demonstrated by other methods." Viral hepatitis and primary biliary cirrhosis presenting as jaundice are usually
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LEEUWEN, HUIBREGTSE, TYTGAT
FIG. 2. Another example of a type 11 tumor. Note that there is regular filling of the cystic duct and gallbladder. Adenomal carcinoma of the bifurcation was confirmed.
FIG. 4. ERCP in a 48-year-old man with a recent history of severe itching followed by overt jaundice. Note intraductal subhilar tumor growth with dilation of the right system but no filling of the left system. A hilar resection was carried out confirming moderately differentiated carcinoma with peri- and intraneural growth. The resection margin of the left hepatic duct was tumor positive. Postoperative radiotherapy was well tolerated and the patient did satisfactorily during the next 12 months. Progressive malaise developed and severe cholangitis responded during a few months only to external percutaneous transhepatic biliary drainage (PTBD). Eighteen months after surgery the patient died from tumor recurrence and cholangitis.
suggested by further symptoms. In some cases viral markers, antimitochondrial antibodies and the alpha,fetoprotein level may point to an underlying diagnosis. Drugs should be excluded as a cause of the symptoms. A history of typical colic or known stones, particularly in the elder patient group, may lead to the recognition of stones either as the main problem or as a concomitant problem only, where malignant or benign stricture or strictures have developed.
Biliary Tract Imaging
FIG. 3. Type Ill tumor in a 52-year-old man with longstanding history of ulcerative colitis. The features, however, are not typical for sclerosing cholangitis. Note multiple strictures (arrows) representing extensive tumor growth. This patient had surgical U-tube drainage, which provided palliation for jaundice and itching during the last 4 months of his life.
A major diagnostic breakthrough was the introduction of the fine flexible (Chiba) needle technique for percutaneous transhepatic cholangiography (PTC) introduced in the late 1960s by workers at Chiba University." This technique increased the safety of the procedure and permitted high quality cholangiography to be performed in the x-ray suite rather than in the operating room, which usuallv in anv case offered voorer imaging. During the 970i cholang&graphy (fR&) was introduced and became the alternative way for performing direct chO1angiOgra~h~. purposes, phisticated US techniques became the primary method
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CARCINOMA O F HEPATIC CONFLUENCE-VAN
FIG. 5. Cholangiography in a 35-year-old woman who had a history of recent general malaise and jaundice. Ultrasound suggested tumor of the gallbladder and the cholangiographic appearance fit in with extensive growth of gallbladder carcinoma. Brush cytology confirmed adenocarcinoma. After insertion of an endoprosthesis, she did reasonably well and was seen 6 months later for change of endoprosthesis, which had clogged.
TABLE 2.
Ultrasound Appearances in Liver Hilus Obstruction
Mass to be identified? Sizeidiall~eterirelationshipwith surrounding structures, including gallbladder? Extent into right or left liver lobe'! lntrahepatic rnasses (tumor? abscess'.') Vessels, including intra- and extrahepatic portal vein (flow pattern'!)
of assessing the cause of obstructive jaundice in the 1980s, since they show much more than dilated bile ducts. Combined with the Doppler facility, US has become a superb tool in experienced hands. Table 2 and Figure 10 show relevant data that can be obtained from a carefully performed US study. In our experience, computed tomography (CT) scan is less helpful in diagnosing hilar masses and their extension into the liver. This is due to the fact that these tumors are often isodense, and bile duct dilation will already have been shown on US. This experience is shared by others."." It remains unclear whether contrary experiences are related to a different expertise.13 CT may help to demonstrate liver atrophy in case of portal vein compre~sion.~' A recent editorial addressed further aspects of liver atrophy.j5Hilar obstruction can be assumed
10, NUMBER 2, 1990
FIG. 6. Cholangiography in a 55-year-old woman teacher with a recent history of general malaise, weight loss, and abnormal liver function test. Ultrasound suggested a mass of the gallbladder with stones extending toward the liver hilus. The preoperative diagnosis was gallbladder carcinoma invading the liver hilus. The final pathologic diagnosis, however, was inflamed gallbladder with abscesses and fibrosis invading the liver hilus. Surgical drainage was followed by an uneventful recovery.
if intrahepatic bile ducts show dilation in the presence of a nondilated common bile duct and, if distances between the cuts are small enough, lack of fusing of the left and right biliary systems. US endoscopy has not yet been shown to have major advantages in diagnosis compared with other modalities, with the exception of the obese patient or those in whom upper abdominal gas hinders external imaging. In our experience, it is more helpful compared with CT scan, as discussed by Tio and colleagues elsewhere in this issue of Seminars. Magnetic resonance imaging has been suggested to discriminate normal liver tissue from cholangio~arcinoma.~~ The assessment of the patient with possible liver hilus obstruction should be closely linked to options available to the individual patient. As will be discussed by Van der Heyde et al in this issue of Seminars, curative resection of hilar tumors can be achieved only rarely. The first aim is to limit the differential diagnosis and to place the patients in one of four categories: I: Inoperable patient (age, major risk factors) 11: Operable, but nonresectable process (major involvement of left and right intrahepatic biliary tree, major vascular involvement, extensive metastatic disease)
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FIG. 7. Details of the cholangiography in a 31-year-old man. During childhood he had ulcerative colitis (pancolitis) responding to conservative treatment. When 27 years old, he presented for the first time with abnormal liver function tests including elevated alkaline phosphatase and gamma glutamyl transferase. He was admitted with a historv of aeneral malaise and jaundice. Under antibiotic cover, ERCP was performed. Note the irregular stenosis at the hilar level with intrahepatic irregularities as well. He underwent extended right hemihepatectomy. Pathology report: Nonradically resected cholangiocarcinoma in primary sclerosing cholangitis. He recovered after an episode of severe liver failure. Postoperative radiotherapy was given. In spite of some major complications (radiation stenosis, bleeding radiation ulcer), he had two satisfactory years and traveled abroad. Progressive liver failure has occurred 2 % years after initial treatment and the patient needs increasingly supportive care.
111: Operable with limited option (surgical drainage of one lobe, no tumor resection) IV: Operable with the option of maximum resection (with or without partial hepatectomy) It should be realized that drainage options available to patients with a mid or distal common bile duct obstruction are easier for the surgeon, endoscopist, and radiologist compared with the proximal obstructions. Whereas a biliodigestive anastomosis is usually feasible or one stent suffices to provide adequate drainage in case of more distal obstruction, all specialists are faced with major problems as soon as various hepatic ducts or various liver segments have to be drained adequately. Sooner or later, any part of the biliary tree that has not been drained, especially if contrast has entered but no drainage was obtained, will become an intrahepatic empyema before that part of the liver has atrophied. However, even before any instrumental contamination could have occurred, the biliary tree appears to be contaminated in as many as 36% of cases.47-" Most specialists agree that more patients with obstruction at the hilar level might be and should be eligible for surgical drain-
FIG. 8. A 60-year-old man with progressive intrahepatic abnormalities in the Course of general deterioration due to Pancreatic head carcinoma. Note the Presence of a mid common bile duct stenosis (arrow) and completely irregular intrahepatic cholangiography.
age compared with patients with a malignant mid or distal common bile duct obstruction, who may be dealt with endoscopically. The primary reason is the fact that stenting is extremely difficult if multiple stenoses have to be passed, as discussed later. Launois et alx' and Blumgart et a15 I .s? have become the leading advocates of this approach. This approach is partly followed by our group, although major differences are present, partly related to a different local expertise. An idealized diagnostic and therapeutic flow chart is given in Figure I I . It takes into account the categorization of the patients. Adhering to this scheme will reduce unnecessary or risky procedures in patients unlikely to benefit from these.i3 Major factors that limit the local surgical options are: (1) a compromised vascular supply (in case of involvement of the artery, cutting off portal venous drainage will mean liver necrosis); and (2) major tumor ingrowth, which limits surgical anastomotic possibilities. Both aspects need careful preoperative study, but in case of doubt imaging techniques should not replace surgical exploration. Intrahepatic metastasis will not always exclude the patient from surgical treatment because drainage is the first aim and further treatment may follow (see Gonzalez et al in this issue of Seminars).
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FIG. 9. a: Typical aspect of a benign subhilar stenosis 6 years after cholecystectomy in a 55-year-old man. These stenoses are thought to be caused by sutures or ischemia. b: Cholangiography in 73-year-old woman with a common bile duct str~cture3 months after cholecystectomy with severe inflammation. The very irregular stenosis was resected and proved to be benign. She did well after reoperation (hepaticojejunostomy).
NONSURGICAL BlLlARY DRAINAGE General Aspects Because of the higher complication rate of PTC,54-" ERCP has become the modality of choice for cholangiography and nonsurgical drainage. Some advantages and disadvantages of both techniques have been summarized in Table 3. Traditionally it has been said that injecting contrast into the biliary tree should be avoided in patients with hilar obstruction who could still be surgical candid a t e ~ . ~Indeed. " severe septicemia may follow PTC or ERCP, although the procedures per se are not the only factors for colonizing the biliary tree with pathogens (see before). In addition, we know of cases in which surgery confirmed that an endoscopically drained lobe was without pus, whereas a part occluded by tumor contained pure pus. However, to avoid septicemia and shock, high quality US is required to diagnose hilar obstruction. In such patients further precautions (adequate drip, antibiotics. bile cultures, plasma expanders) can be taken. er, this may prevent problems only partly. Unfor-
tunately, at the Academic Medical Center in Amsterdam, a surprisingly large number of patients who were outside referrals for diagnostic or therapeutic ERCP had hilar obstruction diagnosed by that procedure. This finding requires the immediate start of antibiotics, which should be given more often as single-dose prophylaxis and definitely before the procedure if hilar obstruction or PSC has been diagnosed at an earlier stage.54 If possible, an endoprosthesis is inserted during the same procedure. It should be realized that for 80 to 85% of the patients the insertion of stents is the final palliation as well, occasionally followed by percutaneous drainage or combined techniques, because other factors exclude them from surgical therapy. In 100 consecutive patients with hilar tumors only 16% were found to be suitable for surgical exploration." Thus, the operable minority that develops severe cholangitis is the group most likely to experience the disadvantages rather than the advantages of cholangiography without feasibility of drainage. One liver lobe with appropriate drainage (surgical or nonsurgical) may suffice to relieve jaundice and itching. Nonsurgical drainage of hilar obstruction can be im-
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TABLE 3. Pros and Cons of PTC or PTBD Versus ERCP in Patients with Obstruction of the Liver Hilus* PTCIPTBD Positive Siniple diagnostic procedure lncreasinzlv difficult if drainage has to be established (PTBD) c. Limited sophisticated equipment required N o introduction of bowel pathogens into the biliary tract (but colonization may have occurred spontaneously) Change of clogged drains relativelv, easv in external or external and internal drains Only with external and internal drainage will bile reach bowels Negative High risk of early and late conlplications (septicemia, bile leakage, abdominal abscesses) Discomfort (and loss of bile or electrolytes) if external drains need to be left
TABLE 5.
--
A
ERCP Positive Occasionally simple method to establish drainage Complication rate much lower compared with PTC ~ o n i f o r tto patients higher if succekful (including food absorption) Internal bile flow restored Negative Considerable endoscopic experience required Failure of drainage more frequent High risk of failure to establish drainage of contrast-filled parts of the biliary tree *PTBD: Percutaneous transhepatic biliary drainage. See Table I for other abbreviations.
TABLE 4.
Success of Endoprosthesis Insertion*
I o r 2 stents Right side only Left side only Both sides *Adapted from H u i b r e g ~ s e . ' ~
portant in emergencies in which surgical therapy may follow, but at least temporary relief of obstruction or severe cholangitis requires treatment to diminish surgical risks. The optimal use of the percutaneous and endoscopic treatment modalities is determined by various factors; local expertise is the most important. Table 4 summarizes the pros and cons of the various techniques. As mentioned, Lameris et a1 discuss PTC and percutaneous transhepatic biliary drainage in detail in their contribution in this issue of Seminars in Liver Disease.
RESULTS OF ENDOSCOPIC DRAINAGE OF HILAR OBSTRUCTION We have recently summarized the results of endoscopic drainage of bifurcation tumors occluding both left and right hepatic ducts in 300 patients seen in the period 1980 to 1986.58 This series illustrates the previously mentioned point that in a considerable number of pa-
Survival Data After Endoprosthesis Insertion 30-Dtr~ Morttrlit~ No. Purir11t.s
2
-
109
LEEUWEN, HUIBREGTSE, TYTGAT
Total group 2 endoprosthesis endoprosthesis Failures
300 40
253 47
No.
%
75 2 5.. 1 22
25 5 20 47
Surr,r~.tr/( D t r ~ s ) Medicr~~lMrtrrrIRtrrrgr 87117711-1566 17013 1819- 128 1 871 17612- 1566
j'Adapted from Huibregtse."
tients and particularly those of category I, malignant obstruction of the hilus is diagnosed on cholangiographic appearances only. In fact, some patients may have had "benign" disease. However, benign fibrosing disease may behave in a malignant way. Our series included 122 men and 178 women, with a mean age of 69 years (range, 19 to 94). Of the 300 patients, 193 were thought to have primary tumors (Klatskin-type), 27 had a primary gallbladder carcinoma, and 80 had hilar metastases from various sites or conditions, including breast ( l7), colon (28), lymphoma (6), pancreas (7), cervix (9), stomach (6), melanoma (4), and hepatoma (3). Histologic or cytologic confirmation of the malignancy was obtained in 166 of 300 (55%) patients. The results of stenting are summarized in Table 4 and the survival data after endoprosthesis insertion, in Table 5. Because we could not observe a difference in the cholangitis rate in patients with one versus two endoprostheses, we are uncertain whether to adhere to the recommendation of immediate endoscopic or percutaneous drainage of all obstructed part^.^" Many patients with a diseased biliary tree and attacks of chills or fever may benefit from antibiotic maintenance therapy. This applies both to stented patients and patients after reconstructive biliary tract surgery. In this respect, cotrimoxazole once daily is in our experience an effective drug that can be taken by mouth.
CONCLUDING REMARKS It should be clear from this review that major progress over the last 25 years has been made with respect to a more accurate diagnosis of hilar obstruction and recognition of therapeutic options, including nonsurgical drainage. However, it should be stressed that an important role has remained for surgery, not-as in the pastto discover that something is wrong, but usually to diagnose what exactly is wrong (malignancy, stones) or to confirm nonresectability already assumed after preoperative imaging. Surgical drainage should follow whenever feasible. The diagnostic pitfalls and uncertainties have been illustrated and justify this view. Klatskin likely would agree that it remains dangerous to give la-
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FIG. 10. This 67-year-old man who underwent cholecystectomy 17 years ago developed itching and jaundice with cholestatic liver function tests. A liver biopsy and ERCP (a) in another hospital were thought to be compatible with advanced biliary cirrhosis. Patient was referred to a liver transplant center and a new ERCP was performed 3 months later. There is now obvious dilation of the right system with multiple hilar stenoses (b). Ultrasound findings (c and d) were highly abnormal. At the origin of the left portal vein branch, narrowing was seen with a Doppler signal in one direction compatible with nearly complete occlusion (c). d: At a slightly different place turbulence with strong poststenotic dilation of the left portal vein branch is seen. The turbulence is illustrated by the positive and negative signals of the flow registration. It was thought that right-sided operative drainage was the best surgical approach. However, the extent of tumor made this impossible. The left system could be drained and jaundice and itching disappeared. Three months later there was recurrence of complaints of obstruction and percutaneous drainage of the left system was carried out.
CARCINOMA O F HEPATIC CONFLUENCE-VAN
LEEUWEN, HUIBREGTSE, TYTGAT Physical examinatlon
I
+
Hilar obstruction (ultrasound)
/; \ I II
Operable patient
-
Evldence of tumor elsewhere (lymphoma, breast carclnorna, etc.)?
I
Treat accordingly (radiotherapylchemotherapy)
IV. Operable patient
(a) exclude treatable extrahepatic cause
(b) attempt for cytological confirmation of malignancy
I I . Locally non resectable process
Non-Surglcal drainage
I l l . Limited surglcal optlon due
IV. Attempt for curative resection
to extent of disease
I
Limited surg~calexploration
lntended palliat~on
Diagnost~c& therapeutic ERCP andlor PTC drainage procedure
I
Resection liver hilus
lntended cure
For all patients: conslder radiotherapy, conslder need for maintenance antlb~otlctreatment (*) for limited transplant options s e e Van Th~elet al, 1989 (ref 60)
FIG. 11. Recommended diagnostic and therapeutic approach towards patients with assumed malignant hilar obstruction.
bels to patients without definite proof of the benign or malignant character of the disease. The current approach to these patients may need reconsideration if major breakthroughs (sophisticated baby endoscopes, further improvement of adjuvant therapy. laser therapy, improved antibiotic therapy) are developed. Improvement should be defined by feasibility of these approaches, prolonged survival, and acceptable quality of life. Acknow,lrdgment. The authors thank Dr. J.W.A.J. Reeders and Dr. N.J. Smits (Department of Radiology) for their help in obtaining ultrasound and x-ray images.
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3.
4.
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I
ary fibropolycystic d~sease:A clinical and histolog~calreview of 51 patients. J Hepatol 2:141-156. 1986. Wee A, Ludwig J. Coffey RJ. et al: Hepatob~liarycarcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hum Pathol 16:7 19-726. 1985. Welton JC. Marr JS, Friedman SM: Association between hepatobiliary cancer and typhoid carrier state. Lancet 1:791794, 1979. Belamaric J: lntrahepatic bile duct carcinoma and C . s~nensis infection in Hong Kong. Cancer 3 1 :468-473. 1973. Kurathong S. Lerdverasirikul P. Wongpaitoon V. et al: Opisthorchis viverrini infection and cholangiocarcinonia. A prospective case controlled study. Gastroenterology 89: 15 1 1 5 6 . 1985. Schwartz DA: Cholangiocarcinon~aassoclated with liver fluke infection: A preventable source of morbidity in Asian immigrants. Am J Gastroenterol 8 1 :76-79, 1986. Smith R : Surgery of the gallbladder and bile ducts. London. Butterworths, 1964. Okuda K. Kubo Y. O k a ~ a k iN. ct al: Cl~nlcalaspects of intrahepatic b ~ l educt carcinoma including hilar carcinoma: A study of 57 autopsy-proven cases. Cancer 39:232-246, 1977. Koga A, Yarnanchi S. lzumi Y. Hamanaka N: Ultrasonographic detection of early and curable carcinomas of the gallbladder. Br J Surg 72:372-378. 1980. Nakanuma Y. Tevada T. Tanaka Y, Ohta G: Are hepatolithiasi.. and cholangiocarcinoma aetiologically related'! A morphological study of 12 cases of hepatolithiasis assoclated with cholangiocarcinonia: Virchows Arch [ A ]406:45-58. 1985. Kimura W. S h ~ m a d aH. Kuroda A, Morioka Y: Carcinoma of the gall-bladder and extrahepatic bile duct in autopsy cases ol the aged, wlth special reference to its relationship to gallstones. Am J Gastroenterol 84:386-390. 1989. Scott. J. Shousha S. Thomas HC. et al: Bile duct carcinoma: A late complication of congenital hepatic fibrosis Case report and review of the literature. Am J Gastroenterol 73: 1 1 7 1 19. 1980. Goodman ZD, lshak KG. Langloss JM. et al: Combined hepatocellular cholangiocarcinoma: A histologic and inimunohistochemical study. Cancer 55:124-135, 1985. Soiva M, Aro K, Pamilo M. et al: Ultrasonography in carcinoma of the gallbladder. Acta Radiol [DlagnJ (Stockh) 28:711-714. 1987. Bismuth H, Corlette MB: lntrahepatic cholang~o-enteric anastomosis in carcinoma of the hilus of the liver. Surg Gynecol Obstet 140: 170-178. 1975. Hadjis NS. Collien NA. Blumgart LH: Malignant masquerades at the hilus of the liver. Br J Surg 7:659-661, 1985. Okuda K, Tanikawa. Emura T. et al: Nonsurgical. percutaneous transhepatic cholangiography-diagnostic significance in medical problems of the liver. Dig Dis 19:21. 1974. Kuno N: Carcinoma of the biliary tract. In: Takemoto T, et al (Eds): Endoscopic retrograde cholangiopancreaticography. Tokyo. Igaku-shoin. 1979. pp 229-2518, Yeh HC: Ultrasonography and computed tomography of carclnoma o f the gallbladder. Radiology 133: 167-173. 1979. Soiva M. Aro K, Panilo M, et al: Ultrasonography in carcinoma of the gallbladder. Acta Radiol IDiagnj (Stockh) 28:71 1-714, 1987. McCarty RL, LaRusso NF, May GR, et al: Cholangiocarcinoma complicating primary sclerosing cholangitis: Cholangiographic appearances. Radiology 156:43, 1985. Cohan RH, lllescas FF, Newman GE. et al: Biliary cytodiagnosis. Bile sampling for cytology. Invest Radiol 20: 177. 1985.
10, NUMBER 2, 1990
Floyd WN, Cobb C: Cholangiography and b ~ l ecytopathology in the diagnosis of biliary tract obstruction. South Med J 73: 134. 1986. Wal AJ van der, van Leeuwen DJ, Walton N: Small cell neurocndocrine (oat cell) tumor of the common bile duct. Histopathology 1989. In press. Sherlock S. Dick R, van Leeuwen DJ: Liver biopsy today. The Royal Free Hospital experience. J Hepatol 1 :75-85. 1984. G ~ b s o nRN, Yeung E. Thompson JN, ct al: Bile duct obstruction: Radiologic evaluation of level. cause and tumor resectability. Radiology 160:43-47. 1986. Benjamin IS. Blumgart LH: Assessment of diagnostic technique for biliary obstruction and liver masses. In: Blurngart LH (Ed): Surgery of the Liver and Blliary Tract. Edinburgh. Churchill L~vingstone,1988. pp 337-347. Nesbit GM. Johnson CD, James EM, et al: Cholangiography and pancreaticography. Tokyo, Igaku-shoin. 1978. Takayasu K. Muramatau Y, Shinia Y. et al: Hepatic lobar atrophy following obstruction of the ipsilateral portal vein from hilar cholangiography. Radiology 160:389-393, 1986. Hadjis NS, Blumgart LH. Cl~nicalaspects of liver atrophy. (Editorial.) J Clin Gastroenterol 11:3-7. 1989. Dooms GC. Kerler RR. Hricak H. et al: Cholangiocarcino~l~~~: Imaging by MR. Radiology 159:89-94, 1986. Keighley MRB: Microorganisms in the bile: A preventable cause of sepsis after b~liarysurgery. Ann R Coll Surg 59:329334. 1977. McPherson GAD. Blenkharn JI. Nathanson B. et al: Significance of bacteria in external biliary drainage systems: A possiblc role for antisepsis. J Clin Surg 1:22-26. 1982. Wells GR. Taylor EW. Lindsay G . et al: Relationship between b ~ l ecolonisation. high-risk factors and postoperative sepsis in patients undergoing biliary tract operations while receiving a prophylactic antibiotic. Br J Surg 76:374-377. 1989. Launois B, Camion J-P, Brissot R, Gossel~nM: Carc~nomaol the hepat~chilus: Surgical treatment and the case for resection. Ann Surg 190:151-157. 1979. Blumgart LH. Hadjis NS, Benjam~nIS. Beazley R: Surgical approaches to cholangiocarcinoma at the confluence of hepatic ducts. Lancet 1 :66-70, 1984. Blumgart LH: Cancer of the bile ducts. In: Blumgart LH (Ed): Surgery of the Liver and Biliary Tract. Edinburgh. Churchlll Livingstone. 1988. pp 829-853. van Leeuwen DJ. Reeders JWAJ: Imaging in hepatohiliary and pancreatic rnalignancies. In: Lygidakis N. Tytgat GNJ (Eds): Hepatobil~aryand Pancreatic Malignancies. Stuttgart, Georg Thieme Verlag. 19x9. pp 47-50. Harbin WP, Muella PR. Ferruci JT: Transhepat~ccholangiography: Complications and use pattern of the fine needle technlque. Radiology 135: 15-22, 1980. Ricniann JF: Complications of percutaneous b ~ l edrainage. In: Classen M. Geenen J. Kawai K. (Eds): Non Surglcal Biliary Drainage. Berlin. 1984. p 29-35. van Leeuwen DJ: Antibiotic prophylaxis and treatment of inl'ect~on of the biliary tract. In: Tytgat GNJ. Huibregtse K ( E d ) : Bile and Bile Duct Abnormalities. Georg Thieme Verlag. Stuttgart 1989. pp 55-62. Verbeek PCM. van der Heyde MN, Lygidakis NJ, Huibregtse K: How many patients with a Klatskin tumor are candidates for surgery'! (Abstr.) Neth J Surg 1988: PO 090 Huibregtse K. Malignant strictures. In: Endoscopic Biliary and Pancreatic Drainage. Georg Thieme Verlag, Stuttgart, 1988 pp 93-1 20.
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Deviere J , Baize M , de Toeuf J , Cremer M: Long-term followup of patients with hilar malignant stricture treated by endoscopic internal biliary drainage. Gastrointest Endosc 2:95101, 1988.
60.
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van Thiel DH, Dindzans V, Gavaler JS, et al: Liver transplantation for hepatocellular carcinoma In: Bannasch P, Keppler D, Weber G (Eds): Liver Cell Carcinoma. Dordrecht, Kluwer Academic Publishers, 1989, pp 499-508.
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Carcinoma of the Hepatic Confluence 25 Years After Klatskin's Description: Diagnosis and Endoscopic Management
'Twenty-five years have passed since the late Gerald Klatskin, Professor of Internal Medicine at Yale University, published his article "Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatis."' The tumor was described by others, including Altemeier, as reviewed by Bengmark and Tranberg.? However, the characteristics of the hilar tumors were reported in such a way that they have often eponymously been called Klatskin tumors. Since his description, major diagnostic improvements have been made with respect to tests to diagnose viral hepatitis and primary biliary cirrhosis, as well as the imaging of the biliary tree by means of ultrasound, endoscopic retrograde cholangiopancreatography (ERCP) percutaneous transhepatic cholangeography (PTC). These improvements have greatly facilitated diagnosis and contributed to a more individualized therapy. Although some of his statements are outdated now, others have remained apt, like "the tumor is readily overlooked unless the surgeon recognizes the possibility of its existence, . . . tumors of this type tend to be small and to remain sharply localized; they seldom metastasize, and ultimately give rise to fatal hepatocellular failure andlor suppurative cholangitis as a consequence of unrelieved biliary obstruction . . . , palliative surgery aimed at relieving biliary obstruction is remarkably effective in allaying symptoms and prolonging life."' This article discusses the current diagnostic approach toward patients with assumed malignancies at the level of the liver hilus. The application of the available diagnostic tools is often during the same session followed by temporary or definitive stent insertion. This aspect will be addressed also, mainly focused on endoscopic drainage, whereas Lameris et al discuss the role of the percutaneous approach elsewhere in this issue of Seminars. At this stage, it should be mentioned that the rarity of the tumor, the enormous variety in initial approaches toward the problem, and further management,
Frorn the Depcrrtrnent of Hepcrto~cr.srroc~ntc~ro/o,q~ trtld the Hr~xitopur~crrc~tic~ohilic~ry litlit qf the, Ac.udc,mic. Mrdic~rlC m t r r of the Ur~iversityof'Atnsrrrdmn. Amsterdam, The Netlzc~rltrt~ds. Reprint requests: Dr. Van Leeuwen. Department of Hepatogastroenterology (CEOI). Academic Medical Center. Meibergdreef 9 , 1105 AZ. The Netherlands. 102
as well as mixtures of data and results of diverse clinical groups limit the possibility of making firm recommendations based on properly conducted clinical trials. Any proposed approach toward the problem is at least partly based on local expertise.
DEFINITION, ETIOLOGY, ANATOMIC CLASSIFICATION
Definitions Primary cholangiocarcinomas arising from the part of the common bile duct between the cystic duct junction (common hepatic duct) and the confluence of the hepatic ducts at the liver hilus are called biliary hepatic confluence (Klatskin) tumors. Cholangiocarcinoma is grouped with the hepatocellular carcinomas (HCC) as classified by World Health Organization WHO3 and is not distinguished from them in the ICD classification (rubric 155.0). Cholangiocarcinoma may account for only an estimated 10% of all HCC; hilar (Klatskin) tumors represent 15 to 53% of these.'-7 The rarity of extrahepatic bile duct tumors was demonstrated in autopsy studies, being present in 0.12% of 129,57 1 cases.' Various histopathologic aspects of Klatskin tumors are addressed by Bosma elsewhere in this issue of Seminurs. Many reviews of the pathologic aspects have been published.'.'-1J The main characteristics of these tumors are the usually slow-growing behavior of the tumor, the sclerosing or fibrosing characteristics in a majority of cases, and the late occurrence of metastasis.'
Etiology The etiology of these tumors has remained unclear. The disease has been associated with congenital fibropolycystic disease,15." sclerosing cholangitis,17 typhoid carrier state," flukes,"-" chronic ch~langitis,'~biliary cirrhosis," hepatolithia~is,".~possibly secondary to malignancy," and ulcerative colitis." Chronic inflammatory activity and bile acid alterations could be common denominator^.^' Occurrence in combination with
Copyright 0 1990 by Thieme Medical Publishers, lnc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
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HCC has been described." An assumed association with methyldopa was not confirmed.'"
TABLE 1. Differential Diagnosis of Obstruction at the Hilar Confluence of the Liver Cause, of'Ohstruc.tion"
Anatomic Classification Based on the anatomic location of the tumor Bisclassified them as: muth and C~rlette'~' unobstructed primary confluence (tumor Type I: located in the main hepatic duct) Type 11: obstruction limited to the primary confluence (tumor located exactly at the confluence) Type 111: obstruction of the primary confluence with extension to the right or left secondary confluence. The types reflect increasingly difficult treatment options.
DIFFERENTIAL DIAGNOSIS Cholangiocarcinoma of the Klatskin type needs to be discriminated from various other conditions because of its prognostic and therapeutic implications. Table I summarizes conditions that may mimic this malignancy. There are various important clues and pitfalls to the diagnosis. Direct cholangiography will greatly contribute to the diagnosis. The appearances may be highly suggestive and some examples of proved cholangiocarcinoma are shown in Figures 1 through 4. However, features preoperatively thought to be fully compatible with hilar cholangiocarcinoma may, after a thoroughly performed pathologic examination of the resected specimens, show nonmalignant fibrosing processes only. Such cases were recently described3' and are in keeping with our own experience. Figure 5 presents a typical example of gallbladder carcinoma invading the liver hilus. Cholangiography in ultrasothis condition has been reviewed in nography was described in detail as we11.3J.3SFigure 6 shows an example of benign inflammation (evidence obtained after laparotomy) invading the liver hilus. Ultrasound (US) and US-guided cytologic puncture of the wall of the gallbladder may help to avoid needless laparotomy. Patients with gallbladder carcinoma are unlikely to benefit from surgery. However, it should be recognized that it may be impossible even during surgery to obtain definite proof of the malignant character of a process. This is due to various factors, including the fact that, within the biliary tract, substantial fibrosis may accompany a small tumor. Conversely, changes in the biliary tract secondary to obstruction can easily be interpreted as malignant in the frozen specimen. Endoscopic "probing" of the stricture may provide an indication of the primary problem. Strictures due to primary cholangiocarcinoma and benign postoperative strictures tend to be very tough. They may be difficult to pass, usually in contrast to strictures due to secondary tumor compression of the hilus. The presence of features of sclerosing cholangitis and the history of sudden worsening of jaun-
C1ur.s to Ditrn.t~osis"
Primary cholangiocarcinoma of upper CBDIhepatic duct confluence (Klatskin tumor)
US, ERCP or PTC, brush cytology
Hilar invasion o f gallbladder carcinoma
ERCPIPTS US (gallbladder) with cytology
Cholangiocarcinoma or PSC
Sudden worsening of PSC or UC patients
Benign biliary stricture (stricture\ may be congenital or of unknown origin)
Surgical history, preferential locali~ation,ERCP or PTC (interval may be many years)
Biliary stone5 or sludge
ERCP o r PTC renloval (nasobiliary drain)
Metastatic carcinoma
History. cholanglographic appearance, tumor markers
Lymphoma Benign (reactive)
Malignant
May be impressive after even short perlod of obstruction; may accompany malignancy History, lymphoma elsewhere, upper abdominal US
Other type tumors. including primary liver cell carcinoma obstructing the biliary tree (alpha,-fetoprotein levels). *US: ultrasound; ERCP: endoscopic retrograde choliangiopancreatography: PTC: percutaneous transhepatic cholangiography: CBD: common bile duct; PSC: primary sclerosing cholangitis; UC: ulcerative colitis.
dice fit in with the diagnosis of hilar cholangiocarcinoma associated with long-standing primary sclerosing cholangitis (PSC) often occurring in patients with ulcerative ~ o l i t i s " ~(Fig. ' ~ 7). However, a previous history of sclerosing cholangitis may be absent (Fig. 3). Repeated sampling for cytologic examination can be helpful if positive.37.3x Figure 8 shows intrahepatic spread of metastatic pancreas head carcinoma. The designation of Klatskin tumor probably should be limited to proved cholangiocarcinoma of the liver hilus. The occasional surprise underlines this. We have seen patients with a clinically "typical" Klatskin tumor who finally proved to have undifferentiated small cell (oat cell) carcinoma3' or, in a comparable case, nonHodgkin lymphoma without any localization elsewhere. In a recent series of patients who were referred to our unit for obstructive jaundice, 4 to 5 % of the patients had signs of hilar obstruction. As will be discussed later in this article, we obtained histologic or cytologic confirmation in 55% of the patients only. Figures 9 a and b show examples of benign strictures. According to Klatskin, any stricture diagnosed in patients without previous biliary tract disease or surgery should be considered neoplastic until proved otherwise.'
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FIG. 1. ERCP in a 74-year-old woman in excellent condition with a 2-week history of obstructive jaundice. Note a subhilar stenosis (a) extending to the right and the left hepatic duct (arrows, b). Initial drainage of this type II tumor was obtained endoscopically. A 10 endoprosthesis was inserted into the left system but only a smaller 7 endoprosthesis could be inserted into the right system (c). She was keen to be operated on and had an uncomplicated hilar resection followed by intraluminal and external radiotherapy, which was well tolerated. She remained in good condition without jaundice or chills during the following year. She then presented with general malaise, tumor recurrence, and progressive, fatal liver failure. Autopsy revealed necrotic intrahepatic tumor masses.
CLINICAL APPROACH TOWARD MALIGNANT HlLAR OBSTRUCTION Clinical Presentation Obstructive jaundice is often the presenting symptom of hilar cholangiocarcinoma. However, in case of one-sided hilar occlusion other symptoms may be present in the absence of jaundice. The previous history is usually unremarkable except for weight loss and general malaise. In retrospect this often may have existed over a
period of months. The patient may be known to have PSC or malignancy elsewhere. Physical examination may show liver enlargement. Laboratory investigations show obstructive liver disease (increased alkaline phosphatase and gamma glutamyl transferase), but are otherwise not helpful in the differential diagnosis. In the past, unexplained liver function test abnormalities led more often to liver biopsies. These then suggested bile duct obstruction which, at that time, could not be demonstrated by other methods." Viral hepatitis and primary biliary cirrhosis presenting as jaundice are usually
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FIG. 2. Another example of a type 11 tumor. Note that there is regular filling of the cystic duct and gallbladder. Adenomal carcinoma of the bifurcation was confirmed.
FIG. 4. ERCP in a 48-year-old man with a recent history of severe itching followed by overt jaundice. Note intraductal subhilar tumor growth with dilation of the right system but no filling of the left system. A hilar resection was carried out confirming moderately differentiated carcinoma with peri- and intraneural growth. The resection margin of the left hepatic duct was tumor positive. Postoperative radiotherapy was well tolerated and the patient did satisfactorily during the next 12 months. Progressive malaise developed and severe cholangitis responded during a few months only to external percutaneous transhepatic biliary drainage (PTBD). Eighteen months after surgery the patient died from tumor recurrence and cholangitis.
suggested by further symptoms. In some cases viral markers, antimitochondrial antibodies and the alpha,fetoprotein level may point to an underlying diagnosis. Drugs should be excluded as a cause of the symptoms. A history of typical colic or known stones, particularly in the elder patient group, may lead to the recognition of stones either as the main problem or as a concomitant problem only, where malignant or benign stricture or strictures have developed.
Biliary Tract Imaging
FIG. 3. Type Ill tumor in a 52-year-old man with longstanding history of ulcerative colitis. The features, however, are not typical for sclerosing cholangitis. Note multiple strictures (arrows) representing extensive tumor growth. This patient had surgical U-tube drainage, which provided palliation for jaundice and itching during the last 4 months of his life.
A major diagnostic breakthrough was the introduction of the fine flexible (Chiba) needle technique for percutaneous transhepatic cholangiography (PTC) introduced in the late 1960s by workers at Chiba University." This technique increased the safety of the procedure and permitted high quality cholangiography to be performed in the x-ray suite rather than in the operating room, which usuallv in anv case offered voorer imaging. During the 970i cholang&graphy (fR&) was introduced and became the alternative way for performing direct chO1angiOgra~h~. purposes, phisticated US techniques became the primary method
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FIG. 5. Cholangiography in a 35-year-old woman who had a history of recent general malaise and jaundice. Ultrasound suggested tumor of the gallbladder and the cholangiographic appearance fit in with extensive growth of gallbladder carcinoma. Brush cytology confirmed adenocarcinoma. After insertion of an endoprosthesis, she did reasonably well and was seen 6 months later for change of endoprosthesis, which had clogged.
TABLE 2.
Ultrasound Appearances in Liver Hilus Obstruction
Mass to be identified? Sizeidiall~eterirelationshipwith surrounding structures, including gallbladder? Extent into right or left liver lobe'! lntrahepatic rnasses (tumor? abscess'.') Vessels, including intra- and extrahepatic portal vein (flow pattern'!)
of assessing the cause of obstructive jaundice in the 1980s, since they show much more than dilated bile ducts. Combined with the Doppler facility, US has become a superb tool in experienced hands. Table 2 and Figure 10 show relevant data that can be obtained from a carefully performed US study. In our experience, computed tomography (CT) scan is less helpful in diagnosing hilar masses and their extension into the liver. This is due to the fact that these tumors are often isodense, and bile duct dilation will already have been shown on US. This experience is shared by others."." It remains unclear whether contrary experiences are related to a different expertise.13 CT may help to demonstrate liver atrophy in case of portal vein compre~sion.~' A recent editorial addressed further aspects of liver atrophy.j5Hilar obstruction can be assumed
10, NUMBER 2, 1990
FIG. 6. Cholangiography in a 55-year-old woman teacher with a recent history of general malaise, weight loss, and abnormal liver function test. Ultrasound suggested a mass of the gallbladder with stones extending toward the liver hilus. The preoperative diagnosis was gallbladder carcinoma invading the liver hilus. The final pathologic diagnosis, however, was inflamed gallbladder with abscesses and fibrosis invading the liver hilus. Surgical drainage was followed by an uneventful recovery.
if intrahepatic bile ducts show dilation in the presence of a nondilated common bile duct and, if distances between the cuts are small enough, lack of fusing of the left and right biliary systems. US endoscopy has not yet been shown to have major advantages in diagnosis compared with other modalities, with the exception of the obese patient or those in whom upper abdominal gas hinders external imaging. In our experience, it is more helpful compared with CT scan, as discussed by Tio and colleagues elsewhere in this issue of Seminars. Magnetic resonance imaging has been suggested to discriminate normal liver tissue from cholangio~arcinoma.~~ The assessment of the patient with possible liver hilus obstruction should be closely linked to options available to the individual patient. As will be discussed by Van der Heyde et al in this issue of Seminars, curative resection of hilar tumors can be achieved only rarely. The first aim is to limit the differential diagnosis and to place the patients in one of four categories: I: Inoperable patient (age, major risk factors) 11: Operable, but nonresectable process (major involvement of left and right intrahepatic biliary tree, major vascular involvement, extensive metastatic disease)
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FIG. 7. Details of the cholangiography in a 31-year-old man. During childhood he had ulcerative colitis (pancolitis) responding to conservative treatment. When 27 years old, he presented for the first time with abnormal liver function tests including elevated alkaline phosphatase and gamma glutamyl transferase. He was admitted with a historv of aeneral malaise and jaundice. Under antibiotic cover, ERCP was performed. Note the irregular stenosis at the hilar level with intrahepatic irregularities as well. He underwent extended right hemihepatectomy. Pathology report: Nonradically resected cholangiocarcinoma in primary sclerosing cholangitis. He recovered after an episode of severe liver failure. Postoperative radiotherapy was given. In spite of some major complications (radiation stenosis, bleeding radiation ulcer), he had two satisfactory years and traveled abroad. Progressive liver failure has occurred 2 % years after initial treatment and the patient needs increasingly supportive care.
111: Operable with limited option (surgical drainage of one lobe, no tumor resection) IV: Operable with the option of maximum resection (with or without partial hepatectomy) It should be realized that drainage options available to patients with a mid or distal common bile duct obstruction are easier for the surgeon, endoscopist, and radiologist compared with the proximal obstructions. Whereas a biliodigestive anastomosis is usually feasible or one stent suffices to provide adequate drainage in case of more distal obstruction, all specialists are faced with major problems as soon as various hepatic ducts or various liver segments have to be drained adequately. Sooner or later, any part of the biliary tree that has not been drained, especially if contrast has entered but no drainage was obtained, will become an intrahepatic empyema before that part of the liver has atrophied. However, even before any instrumental contamination could have occurred, the biliary tree appears to be contaminated in as many as 36% of cases.47-" Most specialists agree that more patients with obstruction at the hilar level might be and should be eligible for surgical drain-
FIG. 8. A 60-year-old man with progressive intrahepatic abnormalities in the Course of general deterioration due to Pancreatic head carcinoma. Note the Presence of a mid common bile duct stenosis (arrow) and completely irregular intrahepatic cholangiography.
age compared with patients with a malignant mid or distal common bile duct obstruction, who may be dealt with endoscopically. The primary reason is the fact that stenting is extremely difficult if multiple stenoses have to be passed, as discussed later. Launois et alx' and Blumgart et a15 I .s? have become the leading advocates of this approach. This approach is partly followed by our group, although major differences are present, partly related to a different local expertise. An idealized diagnostic and therapeutic flow chart is given in Figure I I . It takes into account the categorization of the patients. Adhering to this scheme will reduce unnecessary or risky procedures in patients unlikely to benefit from these.i3 Major factors that limit the local surgical options are: (1) a compromised vascular supply (in case of involvement of the artery, cutting off portal venous drainage will mean liver necrosis); and (2) major tumor ingrowth, which limits surgical anastomotic possibilities. Both aspects need careful preoperative study, but in case of doubt imaging techniques should not replace surgical exploration. Intrahepatic metastasis will not always exclude the patient from surgical treatment because drainage is the first aim and further treatment may follow (see Gonzalez et al in this issue of Seminars).
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FIG. 9. a: Typical aspect of a benign subhilar stenosis 6 years after cholecystectomy in a 55-year-old man. These stenoses are thought to be caused by sutures or ischemia. b: Cholangiography in 73-year-old woman with a common bile duct str~cture3 months after cholecystectomy with severe inflammation. The very irregular stenosis was resected and proved to be benign. She did well after reoperation (hepaticojejunostomy).
NONSURGICAL BlLlARY DRAINAGE General Aspects Because of the higher complication rate of PTC,54-" ERCP has become the modality of choice for cholangiography and nonsurgical drainage. Some advantages and disadvantages of both techniques have been summarized in Table 3. Traditionally it has been said that injecting contrast into the biliary tree should be avoided in patients with hilar obstruction who could still be surgical candid a t e ~ . ~Indeed. " severe septicemia may follow PTC or ERCP, although the procedures per se are not the only factors for colonizing the biliary tree with pathogens (see before). In addition, we know of cases in which surgery confirmed that an endoscopically drained lobe was without pus, whereas a part occluded by tumor contained pure pus. However, to avoid septicemia and shock, high quality US is required to diagnose hilar obstruction. In such patients further precautions (adequate drip, antibiotics. bile cultures, plasma expanders) can be taken. er, this may prevent problems only partly. Unfor-
tunately, at the Academic Medical Center in Amsterdam, a surprisingly large number of patients who were outside referrals for diagnostic or therapeutic ERCP had hilar obstruction diagnosed by that procedure. This finding requires the immediate start of antibiotics, which should be given more often as single-dose prophylaxis and definitely before the procedure if hilar obstruction or PSC has been diagnosed at an earlier stage.54 If possible, an endoprosthesis is inserted during the same procedure. It should be realized that for 80 to 85% of the patients the insertion of stents is the final palliation as well, occasionally followed by percutaneous drainage or combined techniques, because other factors exclude them from surgical therapy. In 100 consecutive patients with hilar tumors only 16% were found to be suitable for surgical exploration." Thus, the operable minority that develops severe cholangitis is the group most likely to experience the disadvantages rather than the advantages of cholangiography without feasibility of drainage. One liver lobe with appropriate drainage (surgical or nonsurgical) may suffice to relieve jaundice and itching. Nonsurgical drainage of hilar obstruction can be im-
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TABLE 3. Pros and Cons of PTC or PTBD Versus ERCP in Patients with Obstruction of the Liver Hilus* PTCIPTBD Positive Siniple diagnostic procedure lncreasinzlv difficult if drainage has to be established (PTBD) c. Limited sophisticated equipment required N o introduction of bowel pathogens into the biliary tract (but colonization may have occurred spontaneously) Change of clogged drains relativelv, easv in external or external and internal drains Only with external and internal drainage will bile reach bowels Negative High risk of early and late conlplications (septicemia, bile leakage, abdominal abscesses) Discomfort (and loss of bile or electrolytes) if external drains need to be left
TABLE 5.
--
A
ERCP Positive Occasionally simple method to establish drainage Complication rate much lower compared with PTC ~ o n i f o r tto patients higher if succekful (including food absorption) Internal bile flow restored Negative Considerable endoscopic experience required Failure of drainage more frequent High risk of failure to establish drainage of contrast-filled parts of the biliary tree *PTBD: Percutaneous transhepatic biliary drainage. See Table I for other abbreviations.
TABLE 4.
Success of Endoprosthesis Insertion*
I o r 2 stents Right side only Left side only Both sides *Adapted from H u i b r e g ~ s e . ' ~
portant in emergencies in which surgical therapy may follow, but at least temporary relief of obstruction or severe cholangitis requires treatment to diminish surgical risks. The optimal use of the percutaneous and endoscopic treatment modalities is determined by various factors; local expertise is the most important. Table 4 summarizes the pros and cons of the various techniques. As mentioned, Lameris et a1 discuss PTC and percutaneous transhepatic biliary drainage in detail in their contribution in this issue of Seminars in Liver Disease.
RESULTS OF ENDOSCOPIC DRAINAGE OF HILAR OBSTRUCTION We have recently summarized the results of endoscopic drainage of bifurcation tumors occluding both left and right hepatic ducts in 300 patients seen in the period 1980 to 1986.58 This series illustrates the previously mentioned point that in a considerable number of pa-
Survival Data After Endoprosthesis Insertion 30-Dtr~ Morttrlit~ No. Purir11t.s
2
-
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LEEUWEN, HUIBREGTSE, TYTGAT
Total group 2 endoprosthesis endoprosthesis Failures
300 40
253 47
No.
%
75 2 5.. 1 22
25 5 20 47
Surr,r~.tr/( D t r ~ s ) Medicr~~lMrtrrrIRtrrrgr 87117711-1566 17013 1819- 128 1 871 17612- 1566
j'Adapted from Huibregtse."
tients and particularly those of category I, malignant obstruction of the hilus is diagnosed on cholangiographic appearances only. In fact, some patients may have had "benign" disease. However, benign fibrosing disease may behave in a malignant way. Our series included 122 men and 178 women, with a mean age of 69 years (range, 19 to 94). Of the 300 patients, 193 were thought to have primary tumors (Klatskin-type), 27 had a primary gallbladder carcinoma, and 80 had hilar metastases from various sites or conditions, including breast ( l7), colon (28), lymphoma (6), pancreas (7), cervix (9), stomach (6), melanoma (4), and hepatoma (3). Histologic or cytologic confirmation of the malignancy was obtained in 166 of 300 (55%) patients. The results of stenting are summarized in Table 4 and the survival data after endoprosthesis insertion, in Table 5. Because we could not observe a difference in the cholangitis rate in patients with one versus two endoprostheses, we are uncertain whether to adhere to the recommendation of immediate endoscopic or percutaneous drainage of all obstructed part^.^" Many patients with a diseased biliary tree and attacks of chills or fever may benefit from antibiotic maintenance therapy. This applies both to stented patients and patients after reconstructive biliary tract surgery. In this respect, cotrimoxazole once daily is in our experience an effective drug that can be taken by mouth.
CONCLUDING REMARKS It should be clear from this review that major progress over the last 25 years has been made with respect to a more accurate diagnosis of hilar obstruction and recognition of therapeutic options, including nonsurgical drainage. However, it should be stressed that an important role has remained for surgery, not-as in the pastto discover that something is wrong, but usually to diagnose what exactly is wrong (malignancy, stones) or to confirm nonresectability already assumed after preoperative imaging. Surgical drainage should follow whenever feasible. The diagnostic pitfalls and uncertainties have been illustrated and justify this view. Klatskin likely would agree that it remains dangerous to give la-
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10, NUMBER 2, 1990
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FIG. 10. This 67-year-old man who underwent cholecystectomy 17 years ago developed itching and jaundice with cholestatic liver function tests. A liver biopsy and ERCP (a) in another hospital were thought to be compatible with advanced biliary cirrhosis. Patient was referred to a liver transplant center and a new ERCP was performed 3 months later. There is now obvious dilation of the right system with multiple hilar stenoses (b). Ultrasound findings (c and d) were highly abnormal. At the origin of the left portal vein branch, narrowing was seen with a Doppler signal in one direction compatible with nearly complete occlusion (c). d: At a slightly different place turbulence with strong poststenotic dilation of the left portal vein branch is seen. The turbulence is illustrated by the positive and negative signals of the flow registration. It was thought that right-sided operative drainage was the best surgical approach. However, the extent of tumor made this impossible. The left system could be drained and jaundice and itching disappeared. Three months later there was recurrence of complaints of obstruction and percutaneous drainage of the left system was carried out.
CARCINOMA O F HEPATIC CONFLUENCE-VAN
LEEUWEN, HUIBREGTSE, TYTGAT Physical examinatlon
I
+
Hilar obstruction (ultrasound)
/; \ I II
Operable patient
-
Evldence of tumor elsewhere (lymphoma, breast carclnorna, etc.)?
I
Treat accordingly (radiotherapylchemotherapy)
IV. Operable patient
(a) exclude treatable extrahepatic cause
(b) attempt for cytological confirmation of malignancy
I I . Locally non resectable process
Non-Surglcal drainage
I l l . Limited surglcal optlon due
IV. Attempt for curative resection
to extent of disease
I
Limited surg~calexploration
lntended palliat~on
Diagnost~c& therapeutic ERCP andlor PTC drainage procedure
I
Resection liver hilus
lntended cure
For all patients: conslder radiotherapy, conslder need for maintenance antlb~otlctreatment (*) for limited transplant options s e e Van Th~elet al, 1989 (ref 60)
FIG. 11. Recommended diagnostic and therapeutic approach towards patients with assumed malignant hilar obstruction.
bels to patients without definite proof of the benign or malignant character of the disease. The current approach to these patients may need reconsideration if major breakthroughs (sophisticated baby endoscopes, further improvement of adjuvant therapy. laser therapy, improved antibiotic therapy) are developed. Improvement should be defined by feasibility of these approaches, prolonged survival, and acceptable quality of life. Acknow,lrdgment. The authors thank Dr. J.W.A.J. Reeders and Dr. N.J. Smits (Department of Radiology) for their help in obtaining ultrasound and x-ray images.
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