Diseases of the Gallbladder and Bile Ducts - part 7 pdf

258 Section 3: Specific conditions 1997. Patients with a margin-negative (R0) resection fol- lowed by adjuvant EBRT plus 5-FU had a favorable 5-year survival rate of 64%. However, similar to the findings of Jar- nagin et al. [58], 67% of the patients suffered distant failure, emphasizing the need for more effective adjuvant chemo- therapy for this disease. Intraoperative radiation therapy (IORT) has been advoca- ted as a means to deliver high-dose, small-field therapy di- rectly to the tumor bed without the dose l imitations associated with EBRT. Todoroki et al. [66] have reported the most sub- s t a nt i a l ex per i ence w it h IORT i n 85 p atients wit h A J CC st age IV gallbladder cancer who underwent aggressive surgical re- section with or without IORT at a mean dose of 21 Gy. Forty- s e v e n p a t i e n t s i n t o t a l r e c e i v e d s o m e f o r m o f r a d i a t i o n t h e r a p y (EBRT and/or IORT). The local control rate was signifi cantly higher after adjuvant radiotherapy (59%) than after resec- tion alone (36%). Moreover, the 5-year survival rate was sig- nifi cantly higher after adjuvant radiotherapy (9%) than after resection alone (3%), with the most pronounced improve- ment in 5-year survival rate (17%) in patients with only microscopic residual disease (R1 resection). The role of radiation therapy for the palliation of symptoms such as jaundice, pain, and pruritus in patients with unre- sectable disease is difficult to ascertain as published studies consist of small numbers of patients with the signifi cant con- founding variable that most patients also underwent a biliary drainage procedure [59,67,68]. Chemotherapy Most published studies concerning the role of chemotherapy in patients with locally advanced or metastatic gallbladder carcinoma are limited by the small numbers of patients and by the inclusion of patients with biliary tract cancers. Unfor- tunately, no single chemotherapeutic agent or combination of agents has been identified to be effective in the treatment of this disease (Table 15.4). Though overall response rates range as high as 64%, complete responses are rare and median overall survival rates range from only 20 weeks to 15 months. 5-fluoruracil (5-FU), administered either alone or in com- bination, is the most extensively studied chemotherapeutic agent for this disease. In a prospective, randomized study of 53 patients with advanced gallbladder cancer treated with oral 5-FU alone or in combination with either streptozocin or methyl-CCNU, objective response rates ranged from 5 to 12% in the three treatment arms [69]. 5-FU administered in combination with doxorubicin and mitomycin C (FAM) or in combination with cisplatin and epirubicin (CEF) has yielded response rates of 8% and 33%, respectively [70]. Better re- sponse rates have been published in patients treated with combinations of 5-FU with hydroxyurea (30%) [71] or inter- feron alpha-2b (34%) [72]. Other chemotherapeutic agents have exhibited variable success in the treatment of advanced gallbladder cancer (Table 15.4). Cisplatin [73], mitomycin C [74], paclitaxel [75], and CPT-11 [76,77] have produced response rates of Table 15.4 Systemic chemotherapy for advanced gallbladder carcinoma. Study (phase) Agent(s) Number of Response rate Median overall patients survival Falkson et al. [69] 5-FU ± steptozocin or methyl-CCNU 53 9% (PR 5; CR 0) – Taal et al. (II) [74] MMC 30 a (13 GBCa) 10% (PR 3; CR 0) – Okada et al. (II) [73] Cisplatin 13 a (6 GBCa) 8 % ( PR 1; C R 0 ) – Jones et al. (II) [75] Paclitaxel 15 a (4 GBCa) 0% N/A Gebbia et al. (II) [71] 5-FU/LV/hydroxyurea 70 a (30 GBCa) 30% b (PR 9; CR 0) 8 months Patt et al. (II) [72] 5-FU/IFN-alpha-2b 35 a (10 GBCa) 34% (PR 12; CR 0) 12 months Sanz-Altamira et al. (II) [77] CPT-11 25 a (10 GBCa) 8% (PR 2; CR 0) 10 months Alberts et al. (II) [76] CPT-11 36 a 8% (PR 2; CR 1) – Kuhn et al. [83] Gemcitabine/docetaxel 43 a (26 GBCa) 9% (PR 4; CR 0) 12 months Malik (II) et al. [82] Gemcitabine/cisplatin 11 64% (PR 6; CR 1) 42 weeks Kim (II) et al. [88] Cisplatin/xeloda 42 a (19 GBCa) 32% b (PR 5; CR 1) 9.1 months Malik et al. [89] 5-FU/folinic acid 30 7% (PR 2; CR 0) 14.8 months Doval (II) et al. [81] Gemcitabine/cisplatin 30 36% (PR 7; CR 4) 20 weeks Ishii et al. [70] Cisplatin/epirubicin/5-FU 21 33% (PR 7; CR 0) – 5-FU/doxorubicin/MMC 25 8% (PR 2; CR 0) – Knox et al. [85] Gemcitabine/5-FU 27 a (7 GBCa) 71% b (PR 5; CR 0) 5.3 months Patt et al. [78] Xeloda 63 a (8 GBCa) 50% b (PR 2; CR 2) 9.9 months Alberts et al. (II) [84] Gemcitabine/5-FU/leucovorin 42 a (14 GBCa) 21% b (PR 3; CR 0) 9.7 months a These studies include patients with both extrahepatic biliary tract carcinoma as well as patients with gallbladder carcinoma (GBCa). The response rates are for all of the patients included in the study unless indicated by b , in which case the response rate is for the subset of patients with GBCa. 5-FU = 5-fluorouracil; MMC = mitomycin-C; LV = leucovorin; IFN = interferon; PR = partial response; CR = complete response; N/A = not applicable. Chapter 15: Benign and malignant gallbladder tumors 259 10% or less as single agents. In contrast, four of eight patients with gallbladder carcinoma treated with single-agent oral capecitabine had either a complete (n = 2 ) o r p a r t i a l ( n =2) re- sponse [78]. Several case reports have shown that gemcita- bine is active in the treatment of patients with gallbladder carcinoma [79,80]. Accordingly, several phase II studies of gemcitabine in combination with other agents have subse- quently been reported. Gemcitabine in combination with cisplatin has yielded response rates of 36 to 64% [81,82]; in combination with docetaxel yielded a response rate of only 9% [83]; and in combination with 5-FU has produced response rates of 9 to 33% [84,85] (Table 15.3). Based on these studies, it appears that gemcitabine is an important component of the systemic therapy of gallbladder carcinoma, but additional studies of gemcitabine in combination with other agents are warranted, as the survival benefit with ex- isting regimens is modest at best. Hepatic arterial infusion chemotherapy has been studied in a few patients with locally unresectable gallbladder can- cer. Partial response rates of up to 60% have been reported, but the median duration of response was only 3 months and all patients developed progressive disease [86,87]. The medi- an overall survival rates of 12 to 14 months in these studies is comparable to that achieved with intravenous chemo- therapy, providing little impetus to recommend this more complicated mode of drug delivery. Conclusions Gallbladder carcinoma is an aggressive, rapidly fatal disease unless discovered at an early stage. Complete surgical resec- tion offers the only chance for cure, but only 10 to 30% of pa- tients have surgically resectable disease. Radical resection is indicated for early stage (T2) tumors and can result in long- term survival even in patients with locally advanced (T3 or T4) tumors. Radical reresection should be offered to patients who are incidentally discovered to have gallbladder carcin- oma at the time of cholecystectomy. Nonetheless, there is a high incidence of recurrence, particularly distant recurrence, in patients who undergo a complete surgical resection, em- phasizing the need for effective adjuvant therapies. Given the rarity of this cancer, prospective, multi-institutional studies will be necessary to accrue sufficient numbers of patients to make meaningful progress in the treatment of this disease. Questions 1. Which of the following is NOT a risk factor for malignancy in a gallbladder polyp? a. concurrent gallstones b. age less than 50 years c. polyp diameter greater than 10 mm d. solitary polyp e. symptomatic polyp 2. Which of the following is TRUE with respect to the incidence of gallbladder carcinoma? a. it increases steadily with age b. it is decreasing in the United States c. women are affected three times as frequently as men d. american Indian natives are affected more frequently than African Americans e. all of the above 3. Which of the following is NOT a risk factor for gallbladder carcinoma? a. concurrent gallstones b. gallstone size <1 cm c. anomalous pancreaticobiliary junction d. chronic typhoid infection e. cholecystoenteric fistula 4. What is the depth of invasion of a T1b gallbladder carcinoma? a. mucosa b. submucosa c. muscle d. serosa e. liver 5. What is the incidence of nodal metastasis in a T2 gallbladder carcinoma? a. 2.5% b. 15% c. 50 to 60% d. 80 to 90% 6. A wedge resection of the gallbladder fossa includes which segments of the liver? a. I and IVb b. IVb and V c. V and VIII d. IVb and VIII 7. The term “extended cholecystectomy” may encompass a resection of all of the following structures EXCEPT a. gallbladder b. common bile duct c. hepatoduodenal lymph nodes d. hepatic bisegments IVb and V e. all of the above 8. The most significant prognostic factor in gallbladder cancer is a. degree of tumor differentiation b. tumor size c. lymph node status d. CEA level e. none of the above 260 Section 3: Specific conditions 9. Which is the most common pattern of failure after a potentially curative surgical resection of gallbladder cancer? a. locoregional recurrence b. distant metastasis 10. Which of the following is TRUE concerning the adjuvant treatment of gallbladder carcinoma? a. several large, randomized trials have established that postoperative external beam radiation therapy prolongs survival in patients after a margin-negative resection b. single-agent 5-FU has produced response rates of 50% c. hepatic arterial infusion chemotherapy yields a durable response in patients with unresectable disease d. no single treatment regimen has been shown to be effective in the treatment of this disease 11. What is the approximate median overall survival of patients with advanced gallbladder carcinoma receiving chemotherapy? a. 3 to 4 months b. 6 to 12 months c. 18 to 24 mo nt hs d. 3 to 5 years References 1. Christensen AH, Ishak KG. Benign tumors and pseudotumors of the gallbladder. Report of 180 cases. Arch Pathol 1970;90: 423–32. 2. Jorgensen T. Prevalence of gallstones in a Danish population. Am J Epidemiol 1987;126:912–21. 3. Segawa K, Arisawa T, Niwa Y, et al. 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SECTION 3.2 The intrahepatic and extrahepatic bile ducts Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment, Second Edition Edited By Pierre-Alain Clavien, John Baillie Copyright © 2006 by Blackwell Publishing Ltd CHAPTER 16 Acute cholangitis Suyi Chang and Joseph Leung 16 OBJECTIVES • Describe common etiologies of acute cholangitis • Understand the pathogenic mechanisms in the development of acute cholangitis • Describe the bacteriology of bile and blood cultures in the setting of acute cholangitis • Recognize clinical presentations and complications of acute cholangitis • Understand the principles in the management of acute cholangitis and the different interventional strategies, in particular the endoscopic interventions Introduction Acute cholangitis is a common cause for emergency hospital admissions. It occurs as a result of bacterial contamination and overgrowth within an obstructed biliary system, often secondary to bile duct stones. Over the past two decades, nonsurgical therapy has evolved to become the mainstay in the treatment of cholangitis with a signifi cant reduction in overall morbidity and mortality compared to surgery. With the advances in therapeutic endoscopy and interventional radiology, many patients can now be managed acutely with- out surgery, with a better clinical outcome. The acute man- agement of cholangitis includes empiric broad-spectrum antibiotic therapy, and urgent biliary decompression is nec- essary for those who failed conservative management. Over- all, 80% of patients will respond to conservative management but 20% may progress to suppurative cholangitis because of complete bile duct obstruction and require urgent drainage. Etiology The most common cause of acute cholangitis is stone ob- structing the common bile duct, accounting for 80% of cases seen in the Western world [1]. Secondary common bile duct (CBD) stones which originate from the gallbladder are more likely to be cholesterol or mixed stones. Primary CBD stones are mostly brown pigment stones which form de novo within the bile duct as a result of bacterial infection and biofilm for- mation around a nidus, which may be a surgical clip or suture or a small cholesterol gallstone. In the East, patients with hepatolithiasis or recurrent pyogenic cholangitis (Oriental cholangiohepatitis) have stones that formed in the intrahe- 265 patic system and these can migrate into the CBD [2]. These intrahepatic stones are often black in color, containing calci- um bilirubinate and a relatively high cholesterol content [3]. In endemic areas, intrahepatic stones may form as a result of parasitic infestations, such as Ascariasis and Clonorchiasis, within the biliary system. It is possible that the adult worms of Ascaris lumbricoides [4] or Clonorchis sinensis [5] may cause biliary obstruction and also serve as a nidus for bacterial infection and intrahepatic ductal stone formation. This is supported by the presence of remains of adult worm and ova found in the center of these pigment stones [6]. Other causes of cholangitis include biliary obstruction associated with benign postoperative bile duct stricture, neoplasms, papillary stenosis, chronic pancreatitis, and scle- rosing cholangitis. Infection is more common after nonsur- gical manipulation of t he biliar y system, such as percutaneous transhepatic cholangiogram (PTC) or endoscopic retrograde cholangiopancreatography (ERCP) in which drainage fails. Foreign bodies, such as biliary stents or surgical sutures, may predispose to bacterial contamination and sludge/stone for- mation causing cholangitis. Mirrizi’s syndrome due to ex- trinsic compression of the common hepatic duct caused by an impacted stone in the cystic duct can precipitate concomitant acute cholecystitis and cholangitis. Pathogenesis As discussed above, bacterial contamination and biliary stasis are important factors in the pathogenesis of acute cholangitis [7]. The biliary system is sterile under normal circumstances [8] except for transient bacterobilia. The nat- ural defense mechanisms that protect the biliary system Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment, Second Edition Edited By Pierre-Alain Clavien, John Baillie Copyright © 2006 by Blackwell Publishing Ltd 266 Section 3: Specific conditions against infection include: (1) an intact sphincter of Oddi which guards against ascending infection from duodenobili- ary refl ux, (2) the flushing effects of a unidirectional bile flow, (3) the bacteriostatic effects of bile salts, (4) immuno- globulin IgA secreted by the cholangiocytes, (5) phagocytic activity of the Kupffer cells, and (6) mucinous coating and tight intercellular junctions of the bile duct epithelium [9– 12]. The last two mechanisms play a crucial role in prevent- ing descending infection from the portal circulation. Animal (feline) studies demonstrated that bacteria could gain entry to the bile duct via the portal venous system [10]. Bacterobilia can occur without bacteremia if there is no bile duct obstruction, as seen after sphincterotomy or biliary drainage with a patent stent [12]. Chronic obstruction renders the biliary system more susceptible to infection by causing a raised intrabiliary pressure and bile stasis [10]. The nutrient-rich bile serves as a good culture medium for bacterial multiplication. The raised biliary pressure causes refl ux of bacteria into the lymphatics and hepatic sinusoids (cholangiovenous refl ux), leading to endotoxemia and septicemia. The normal intrabiliary pressure ranges from 8 to 16 c mH 2 O. Cholangiovenous refl ux was demonstrated in a canine model when the intrabiliary pressure exceeded 25 cmH 2 O [13]. In human studies, cholangitis can occur when intrabiliary pressure exceeds 20 cmH 2 O. Bile secretion stops completely when the biliary pressure exceeds 30 cmH 2 O [14]. A continued elevation of bile duct pressure eventually overwhelms the integrity of the biliary epithelium leading to bacterial reflux into the systemic circulation. The clinical severity and mortality of acute cholangitis correlate well with the intraductal pressure [15]. In fact, forceful injection of contrast during direct cholangiography was shown to cause bacteremia [16]. Endotoxin, which is the breakdown product of the cell wall of Gram-negative bacteria, is usually metabolized by the liver and excreted in bile. However, it may refl ux into the sinusoi- dal spaces under high biliary pressure in the presence of bile infection. Relief of biliary obstruction allows endotoxin ex- cretion to be resumed. This is demonstrated by a study of 40 patients with calculous cholangitis. There was a signifi cant association between clinical acute cholangitis and the serum and bile endotoxin levels. Furthermore, signifi cant reduc- tions in bile and serum endotoxin levels were achieved with- in 24 hours after successful endoscopic drainage [17]. Biliary decompression has also been shown to promote biliary ex- cretion of antibiotics [18] and resumption of IgA secretion in bile [19]. Hence, biliary decompression plays a crucial role in the management of acute cholangitis. Bacteriological findings Many clinical studies have reported the bacteriology of bile and blood cultures in patients with acute cholangitis [20,21]. Leung et al. analyzed the bile, biliary stones, and blood cul- tures in 579 patients who presented over a 7-year period [21]. Blood culture was positive in 121 patients (21%) and the ma- jority yielded a single organism (Table 16.1) with Escherichia coli being the predominant one. In contrast, over two-thirds of the bile cultures showed mixed infections with two or more bacteria. Culture of bile duct stones always showed a mixed fl ora. Two-thirds of the patients with bacteremia had similar organisms isolated from both blood and bile. Analysis of the cultures showed that E. coli, Klebsiella sp., Enterobacter sp., Enterococcus sp., and Streptococcus sp. were the most commonly isolated bacteria (Table 16.2). Anaerobic organisms, including Bacteroides sp.andClostrid- ium sp., are found in CBD stones but occur more commonly in intrahepatic bile duct stones [22]. Pseudomonas sp. may be found in patients with prior instrumentation or surgery. Gram-positive organisms are isolated more often following percutaneous drainage of the biliary system [23]. Candida albicans is the most common fungal cause of cholangitis, but is usually associated with an immunocompromised state. Clinical features Most cases of acute cholangitis occur de novo, although pa- tients with recurrent pyogenic cholangitis may have a history of previous attacks. Fifty to 70% of the patients may present with the Charcot’s triad, which includes right upper quad- rant abdominal pain, spiking fever, and increasing jaundice. Fever is the most common presentation, which occurs in over 90% of patients. Abdominal pain ranges from mild to severe, often localized to the right upper quadrant. Jaundice may be absent in the early stages but a profound jaundice may suggest underlying malignant biliary obstruction [24]. Chills and rigor may complicate intermittent bacteremia [25]. Elderly patient may present only with mental confusion and deterioration of general condition. A combination of mental confusion, hypotension, and the Charcot’s triad constitutes the Reynolds’ pentad, which is invariably fatal Table 16. 1 Frequency (%) of polymicrobial infections in bile and blood. (Reproduced from Leung et al. [21] with permission from the American Society for Gastrointestinal Endoscopy.) Number of species Bile (n = 579) Blood (n = 121) 1 29 94 2 33 6 3 29 0 4 8 0 5 1 0 Chapter 16: Acute cholangitis 267 without urgent drainage of the biliary system. The term toxic cholangitis is an alternative term depicting this severe condition. Recurrent pyogenic cholangitis presents with bouts of Charcot’s triad. A typical attack of cholangitis may last for several hours or even days before subsiding spontaneously. Chronic bile duct obstruction may give rise to dilated com- mon duct or segmental branch ducts. Intrahepatic stones may contribute to multiple liver abscesses and associated liver atrophy with prolonged obstruction, and eventually secondary biliary cirrhosis. Patients with recurrent pyogenic cholangitis typically have recurrent attacks of cholangitis and may have undergone multiple operative interventions. However, the incidence of residual stones is over 70% and recurrent stones may occur in 15% of patients after surgery. Silent cholangiocarcinoma is a major concern associated with the intrahepatic strictures, even after complete stone removal [26]. Multiple organ failure may develop in severe acute cholangitis due to septicemia or endotoxemia. Uncontrolled infections can give rise to liver abscesses and secondary scle- rosing cholangitis. Spread of infection or infl ammation into the portal circulation can lead to pyelophlebitis and portal vein thrombosis [27]. Cholecystitis and/or pancreatitis may occur secondary to biliary stones (Table 16.3). Acute cholangitis carries signifi cant morbidity and an overall mortality rate ranging from 10 to 30%. In a multivar- iate analysis [28], seven risk factors were identified which predict mortality in acute cholangitis: (1) age over 50 years, (2) female gender, (3) associated liver abscess, (4) underlying cirrhosis, (5) cholangitis due to a high-grade malignant stricture, (6) cholangitis after percutaneous transhepatic cholangiography, and (7) acute renal failure. In addition, the following risk factors were found to account for therapeutic failure in acute cholangitis: (1) underlying malignancy, (2) bacteremia, (3) two or more bacteria isolated or a pan- resistant species recovered from bile, and (4) an elevated serum bilirubin higher than 2.2 mg/dL. Laboratory fi ndings Complete blood counts often show a leukocytosis with a left shift. Depending on the degree of biliary obstruction, liver function abnormalities could have a cholestatic or a hepato- cellular pattern. Signifi cant elevation in the serum transam- inases can occur due to sudden acute biliary obstruction and infection within the first 24 to 48 hours. Elevated serum alkaline phosphatase and direct hyperbilirubinemia are seen in over 80% of acute cholangitis cases [7]. The presence of a CBD stone can cause coexisting pancreatitis, often as a result of an impacted ampullary stone. In this case, the serum amylase and lipase levels will be elevated. However, mild hy- peramylasemia can occur in 40% of cholangitis patients without any concomitant pancreatitis. Radiologic imaging Plain abdominal film is usually not helpful because most Table 16.2 Species of bacteria isolated from bile, stones, and blood in patients with bacterobilia-cholangitis. (Reproduced from Leung et al. [21] with permission from the American Society for Gastrointestinal Endoscopy.) Organisms isolated Bile (%) a Stone (%) b Blood (%) c E.coli 27 22 71 Klebsiella sp. 17 18 14 Enterobacter sp. 8 8 5 Ps. Aeruginosa 7 9 4 Citrobacter sp. 3 1 2 Proteus sp. 3 1 0 Acinetobacter sp. 1 3 0 Bacteroides sp. 1 1 1 Enterococcus sp. 17 12 0 Streptococcus sp. 8 9 0 Staphylococcus sp. 2 6 3 Clostridium sp. 2 1 0 Candida sp. 4 1 0 Others 0 8 0 a Isolated from 579 patients (1236 species). b Isolated from 70 patients (152 species). c Isolated from 121 patients with septicemia (128 species). Table 16.3 Common complications of cholangitis. (Reproduced from Köksal and Lo. Pyogenic cholangitis. In: Brandt L, ed. Clinical Practice of Gastroenterology. Philadelphia: W.B. Saunders, 1999: 1079–88, with permission from Elsevier.) Local Systemic Liver abscess (solitary or multiple) Disseminated intravascular coagulopathy Secondary sclerosing cholangitis Acute renal failure Secondary bile duct strictures Respiratory failure Cholangiocarcinoma Sepsis/ septic shock Portal vein thrombosis/ pylephlebitis Mental obtundation Cholecystitis Pancreatitis 268 Section 3: Specific conditions gallstones are non radio-opaque. However, the plain film can sometimes reveal the presence of pneumobilia which sug- gests a bilioenteric communication from prior sphincteroto- my, surgical bypass, or spontaneous fistula due to stone passage. Noninvasive imaging studies include abdominal ultra- sound scan (US), computed tomography (CT), and magnetic resonance cholangiography (MRC). Abdominal ultrasound is quick and inexpensive but to some extent is operator de- pendent. It can demonstrate the presence of stones and dilat- ed ducts. It is especially useful to delineate the dilated intrahepatic system with stones. In addition, ultrasound may reveal the presence of an abscess, evidence of acute cholecys- titis, or pancreatitis. The technical limitation to abdominal ultrasound exami- nation is an obese patient or interference from adjacent bowel gas, which makes examination of the distal bile duct more difficult. It is also not a very sensitive test for the detection of small common duct stones. However, because it is readily available and noninvasive, it should be considered the initial imaging of choice for patients with suspected biliary sepsis. The CT scan is noninvasive and can detect the presence of dilated intrahepat ic or extrahepat ic bile duc ts. However, it is not very sensitive in the detection of small common duct stones. The pigment content of intrahepatic stones also makes them less obvious on CT scans. The CT scan produces good images of the liver and pancreas and can define the extent of underlying liver damage, such as segmental atrophy, intra- hepatic abscess formation, or dilated intrahepatic bile ducts. It can demonstrate isolated obstructed intrahepatic bile ducts not seen on direct cholangiography, and is useful in preoper- ative planning. It also plays a role in the detection of silent cholangiocarcinoma or metastatic cancer. It may reveal sple- nomegaly associated with portal hypertension secondary to biliary cirrhosis. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive imaging method of the pancreatobiliary sys- tem. An MRI of the abdomen is taken using a special protocol and high-quality images of the bile duct and pancreatic duct are produced without the injection of contrast. It serves as a good diagnostic tool in cases with failed ERCP, incomplete delineation of the biliary anatomy, or bilioenteric anastomo- sis. Its sensitivity in defining stones and strictures is similar to that of conventional direct cholangiography [29]. Further- more, it is less operator-dependent and its images are easily reproducible. It is especially useful to guide selective drain- age of obstructed bile ducts. In addition, it provides informa- tion on adjacent soft tissue not obtained with ERCP or PTC. The major limitation of MRC is the lack of therapeutic options. Direct cholangiogram involves invasive procedures, that is endoscopic retrograde cholangiography (ERC) or PTC in which contrast is injected into the biliary system for imaging. Direct cholangiography serves to define the cause of bile duct obstruction and has a potential for therapeutic applications. It is used as the gold standard for the diagnosis of acute chol- angitis. The choice between ERCP and PTC depends on the availability of local expertise and the nature and level of bili- ary obstruction. Both imaging can define the extent of ductal i n vol ve me n t . E RC P i s r e l a t i v e l y l e s s i n va s i v e b u t t h e o b s t r u c t- ed ducts upstream may not be visualized unless an occlusion cholangiogram is performed. Upon inflating the occlusion balloon, contrast can be injected under pressure to fill the bile ducts proximal to the obstruction. However, this rise in intrabiliary pressure may precipitate bacteremia by causing cholangiovenous refl ux and worsening of the pre-existing cholangitis. Apart from diagnosing the obstructing patholo- gy, therapeutic ERCP can be applied to remove bile duct stones or bypass the biliary obstruction in the same setting. PTC is useful to define the ductal anatomy and the extent and level of obstruction, especially in cases where ERCP has failed as i n patients with a bilioenteric anastomosis. PTC ca n be performed under ultrasound guidance to define the ob- structed ducts. Once percutaneous access to the biliary sys- tem is established, transhepatic drainage of the bile ducts can be performed using an internal/external drainage catheter or an indwelling stent. PTC is more invasive and carries the risk and complications of hemobilia, hepatic arteriovenous shunting, and bile peritonitis. Management Principles of management for acute cholangitis Untreated acute cholangitis is uniformly fatal. Early recogni- tion of the underlying condition is crucial especially in eld- erly patients. Empiric broad-spectrum antibiotics and prompt biliary decompression is the mainstay of therapy. Approxi- mately 80% of patients will improve with conservative man- agement and antibiotic therapy [30]. Twenty percent of patients may continue to deteriorate despite antibiotic ther- apy and will warrant urgent biliary drainage. These patients continue to spike a temperature despite antibiotic treatment. Mental confusion, hemodynamic instability, and multisys- tem involvement are predictors of poor clinical outcome. Progressive tachycardia, dropping blood pressure, and oligu- ria are warning signs of impending sepsis. The main objec- tive in emergency management of acute cholangitis is focused on reducing the intrabiliary pressure and controlling the underlying infection by biliary drainage. There are three major therapeutic options for urgent bili- ary decompression. Surgery has been the traditional treat- ment. With the advances in technology over the past two decades, therapeutic ERCP has replaced surgical drainage as the treatment of choice for acute cholangitis. A randomized controlled study showed that urgent ERCP and biliary drain- age is superior to emergency surgery in patients with acute cholangitis, with a signifi cantly lower morbidity and overall mortality [31]. The choice between endoscopic decompres- sion and percutaneous transhepatic biliary drainage (PTBD) [...]... Understand the various types of genetic background in polycystic liver disease • Name the classification of cystic diseases of the biliary tract • Understand the premalignant nature of cystic diseases of the biliary tract • Understand the role of liver resection for biliary cystadenoma and cystadenocarcinoma Introduction Cystic lesions of the bile ducts and liver can result from a variety of pathologic... syndrome The abnormal bile ducts are in continuity with the remaining normal bile tree, and therefore contain bile Biliary stasis, leading to stone formation, is commonly seen in the dilated ducts and predisposes to the development of recurrent cholangitis and septicemia [36, 37] Other complications include amyloidosis and cholangiocarcinoma, the latter of which is found in 7 to 10% of the patients [ 37] Caroli’s... because of the assumed role of the intrahepatic biliary epithelium in the origin of the noncommunicating liver cysts, this group of cystic liver diseases will be discussed here as well Cystic lesions of the liver with an infectious origin (e.g echinococcus or hydatid cysts, liver abscesses) and pseudocysts are outside the scope of this chapter and will not be discussed Cysts of the liver and bile ducts. .. No (%) of patients who responded to therapy In a prospective randomized clinical trial of 100 patients with acute cholangitis, ciprofloxacin monotherapy was compared with the triple combination of ampicillin, ceftazidime, and metronidazole [34] Eighty-five percent of patients in the monotherapy group and 77 % of those in the triple therapy group responded to antibiotic treatment The mean durations of fever,... choledochal cysts; type II is a diverticulum of the common bile duct Type III is choledochocele of the distal end of the common bile duct Type IVa is a combination of intra- and extrahepatic cysts, and type IVb is a combination extrahepatic cysts Type V represents multiple cysts of the large intrahepatic bile ducts (Caroli’s disease) Chapter 17: Cystic diseases of the biliary system above 1.5 to 2 cm is... removal of all biliary sludge and concrements d percutaneous transhepatic cholangiodrainage (PTCD) and irrigation of the biliary tree until all sludge and debris is flushed into the duodenum e en-block resection of the extrahepatic bile duct f en-block resection of the extrahepatic bile duct and the left hemiliver g orthotopic liver transplantation Suggested readings Polycystic diseases of the liver... into the common bile duct, leading to damage of the wall and subsequent dilatation [40] Another theory proposes that choledochal cysts are part of the congenital fibropolycystic diseases, or ductal plate malformations [3] This theory is supported by the occasional finding of combinations of intrahepatic and extrahepatic bile disorders, with or without concomitant liver fibrosis [30] (Fig 17. 4) Other factors... Groningen, The Netherlands.) [4,48] Malignancies associated with choledochal cysts may arise within the cyst, but have also been described elsewhere within the liver or the biliary or pancreatic ducts In fact, about one-third of the malignancies occur outside the bile duct cyst itself and they may even develop after cyst excision The current treatment of choice is a complete resection of the cyst and a... Gallbladder and Bile Ducts: Diagnosis and Treatment, Second Edition Edited By Pierre-Alain Clavien, John Baillie Copyright © 2006 by Blackwell Publishing Ltd 17 C H A P T E R 17 Cystic diseases of the biliary system Robert J Porte and Pierre-Alain Clavien OBJECTIVES • List the differential diagnosis of cystic lesions in the liver • Describe the diagnosis and management of polycystic liver disease • Understand... light microscopic features of the tumors were correlated with immunohistochemical and follow-up data Chapter 17: Cystic diseases of the biliary system References 1 Everson G, Taylor M, Doctor R Polycystic disease of the liver Hepatology 2004;40 :77 4–82 2 Landing BH Considerations of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst — the concept of infantile obstructive cholangiopathy . carcinoma of the gallblad- der. The role of adjunctive therapy in its treatment. Am J Surg 1 976 ;132 :70 3–6. 63. Smoron GL. Radiation therapy of carcinoma of gallbladder and biliary tract. Cancer 1 977 ;40:1422–4. 64 therapy in cancer of the extra-hepatic biliary system: an analy- sis of thirteen patients and a review of the literature of the effec- tiveness of surgery, chemotherapy and radiotherapy. Int J Radiat. was com- paredwith the triple combination of ampicillin, ceftazidime, and metronidazole [34]. Eighty-five percent of patients in the monotherapy group and 77 % of those in the triple thera- py