Preoperative biliary drainage for biliary tract and ampullary carcinomas

We posed six clinical questions (CQ) on preoperative biliary drainage and organized all pertinent evidence regarding these questions. CQ

# Abstract
We posed six clinical questions (CQ) on preoperative biliary drainage and organized all pertinent evidence regarding these questions. CQ 1. Is preoperative biliary drainage necessary for patients with jaundice? The indications for preoperative drainage for jaundiced patients are changing greatly. Many reports state that, excluding conditions such as cholangitis and liver dysfunction, biliary drainage is not necessary before pancreatoduodenectomy or less invasive surgery. However, the morbidity and mortality of extended hepatectomy for biliary cancer is still high, and the most common cause of death is hepatic failure; therefore, preoperative biliary drainage is desirable in patients who are to undergo extended hepatectomy. CQ 2. What procedures are appropriate for preoperative biliary drainage? There are three methods of biliary drainage: percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary drainage (ENBD) or endoscopic retrograde biliary drainage (ERBD), and surgical drainage. ERBD is an internal drainage method, and PTBD and ENBD are external methods. However, there are no reports of comparisons of preoperative biliary drainage methods using randomized controlled trials (RCTs). Thus, at this point, a method should be used that can be safely performed with the equipment and techniques available at each facility. CQ 3. Which is better, unilateral or bilateral biliary drainage, in malignant hilar obstruction? Unilateral biliary drainage of the future remnant hepatic lobe is usually enough even when intrahepatic bile ducts are separated into multiple units due to hilar malignancy. Bilateral biliary drainage should be considered in the following cases: those in which the operative procedure is diffi cult to determine before biliary drainage; those in which cholangitis has developed after unilateral drainage; and those in which the decrease in serum bilirubin after unilateral drainage is very slow. CQ 4. What is the best treatment for postdrainage fever? The most likely cause of high fever in patients with biliary drainage is cholangitis due to problems with the existing drainage catheter or segmental cholangitis if an undrained segment is left. In the latter case, urgent drainage is required. CQ 5. Is bile culture necessary in patients with biliary drainage who are to undergo surgery? Monitoring of bile cultures is necessary for patients with biliary drainage to determine the appropriate use of antibiotics during the perioperative period. CQ 6. Is bile replacement useful for patients with external biliary drainage? Maintenance of the enterohepatic bile circulation is vitally important. Thus, preoperative bile replacement in patients with external biliary drainage is very likely to be effective when highly invasive surgery (e.g., extended hepatectomy for hilar cholangiocarcinoma) is planned.

# Introduction
In the 1980s, several randomized controlled trials (RCTs) were conducted in Western countries to determine the clinical value of percutaneous transhepatic biliary drainage (PTBD). These RCTs concluded that "preoperative biliary decompression using PTBD did not improve surgical outcomes." However, there were many concerns regarding these RCTs: fi rst, most of the surgeries performed in these studies were bypass or palliative small resections, and few major surgeries such as pancreatoduodenectomy or hepatectomy were included; second, PTBD-related complications were very high; and the drainage period was insuffi cient. Thus, most Japanese surgeons were skeptical about the results of these RCTs, yet they were motivated to reevaluate preoperative biliary drainage in the treatment of obstructive jaundice.
Subsequently, the view of preoperative biliary drainage has changed dramatically, and a consensus has started to form that, in many cases, preoperative biliary drainage is unnecessary, even before pancreatoduodenectomy. Recently, a surprising study was reported suggesting that preoperative biliary drainage is unnecessary even before extended hepatectomy for jaundiced patients.
In this article, we have posed six clinical questions (CQs) on preoperative biliary drainage and organized all pertinent evidence regarding the questions. In the responses to the CQs, recommendations for treatment are noted (grades of these recommendations are defi ned in . Also, levels of evidence are given (in parentheses) for fi ndings in reference citations (see defi nitions of levels in .

## Cq 1 is preoperative biliary drainage necessary for patients with jaundice?

## Preoperative biliary drainage is necessary for patients with cholangitis or patients scheduled to undergo extended hepatectomy (recommendation b).
The proper approach to obstructive jaundice has been debated for a long time. Although research on the pathology of the disease is progressing with time, it is still not well understood. As obstructive jaundice affects the liver, kidneys, gastric mucosa, coagulation, the immune system, and other systems, biliary drainage has been a routine preoperative management for jaundiced patients in Japan. However, RCTs conducted in Western countries raised questions about the effectiveness of preoperative biliary drainage. The results of these trials showed no signifi cant difference in postoperative morbidity and mortality between patients who received preoperative biliary drainage and those who did not. These RCTs concluded that, considering the potential risk related to PTBD, preoperative biliary drainage had no advantage, and was unnecessary 2-4 (level II). These RCT studies included mostly bypass surgeries and palliative small resections, involving few major procedures such as hepectomy for jaundiced liver. In addition, the incidence of PTBD-related complications was extremely high. These fl aws made it diffi cult to accept the conclusions of these RCTs.
There was a time when nationwide RCTs were being considered in Japan as well, but they never came about, for various reasons. Recently, several reports from Western countries have clearly shown that preoperative biliary drainage is unnecessary, except for patients with cholangitis or poor hepatic function, before pancreatoduodenectomy or less invasive surgery, although these studies were retrospective, not RCTs 5-9 (level IV). However, mortality after extended hepatectomy for jaundiced patients is still high, near 10%, and the cause of death is mainly hepatic failure 10 (level IV). These observations indicate that preoperative biliary drainage should be recommended before extended hepatectomy, in spite of a lack of clear evidence based on RCTs.

## Cq 4 what is the best treatment for post-drainage fever?

## Treat with antibiotics and confi rm whether the biliary drainage is effective. if the drainage is effective, suspect cholangitis in the undrained segment (segmental cholangitis; recommendation b).
Segmental cholangitis may occur when an undrained segment is left despite the performance of biliary drainage using PTBD, ERBD, or another procedure. Thus, segmental cholangitis never develops in middle or lower bile duct obstruction and is seen only when there is hilar obstruction such as Bismuth type III and IV 21 hilar cholangiocarcinomas or advanced gallbladder carcinoma involving the hepatic hilus. Segmental cholangitis is a potential cause of posthepatectomy liver failure [bib_ref] Logistic regression and discriminant analyses of hepatic failure after liver resection for..., Nagino [/bib_ref] (level IV) and may worsen the surgical outcome [bib_ref] Preoperative intrahepatic segmental cholangitis in patients with advanced carcinoma involving the hepatic..., Kanai [/bib_ref] [bib_ref] Extended hepatic resection: a 6-year retrospective study of risk factors for perioperative..., Melendez [/bib_ref] (level IV); thus, segmental cholangitis must be treated immediately. When a patient with hilar cholangiocarcinoma who has already undergone biliary drainage suddenly presents with high fever, the most probable cause of the fever is cholangitis due to drainage catheter obstruction or catheter dislodgement, or segmental cholangitis in the undrained segment . If cholangiography demonstrates no problem with the existing catheter, segmental cholangitis should be suspected. After giving antibiotics and identifying the undrained bile duct by computed tomography (CT) or ultrasonography (US), drainage must be urgently performed in the undrained segment 24,25 (level V). Even with a wait-and-see approach when using antibiotics, drainage should be considered if the fever does not come down within 1 or 2 days. Drainage can become effective either through the additional insertion of a new PTBD catheter or, if possible, through inserting the existing catheter into the undrained bile tract. [bib_ref] Preoperative intrahepatic segmental cholangitis in patients with advanced carcinoma involving the hepatic..., Kanai [/bib_ref] [bib_ref] Successful management of preoperative cholangitis by percutaneous transhepatic biliary drainage: case report..., Iyomasa [/bib_ref] [bib_ref] Case of bile duct carcinoma of the hepatic hilus with segmental obstructive..., Sakamoto [/bib_ref] The latter method is less invasive and less painful for the patient. If drainage is done properly, the fever comes down by the following day in most patients, and administration of antibiotics for 2 or 3 days is suffi cient 27 (level IV).

## Cq 3 which is better, unilateral or bilateral biliary drainage, in malignant hilar obstruction?

## In principle, unilateral drainage in the future remnant lobe is enough (recommendation c1).
It is well known that a suffi cient decrease in serum bilirubin can be achieved through unilateral drainage (drainage of either the left or right lobe), as the hepatic reservoir for the excretion of bilirubin is quite large.
The strategy for biliary drainage, i.e., right-side drainage, left-side drainage, or both, is directly linked to the selection of the operative procedure. The advent of Multidetector row computed tomograply (MDCT) has made it possible to determine the surgical procedure for jaundiced patients before biliary drainage [bib_ref] Biliary ductal evaluation of hilar cholangiocarcinoma: threedimensional direct multi-detector row CT cholangiographic..., Kim [/bib_ref] [bib_ref] Preoperative assessment of resectability of hepatic hilar cholangiocarcinoma: combined CT and cholangiography..., Lee [/bib_ref] (level IV). In addition, the types of hepatectomy have changed since the introduction of portal vein embolization; the performance of central hepatectomies, including S1 resection, S1 + 4 resection, S1 + 5 + 8 resection, and S1 + 4 + 5 + 8 resection, has become uncommon, while typical major hepatectomies including right or left hepatectomy, and right or left trisectionectomy have been increasingly performed [bib_ref] Results of surgical resection for patients with hilar bile duct cancer: application..., Kawasaki [/bib_ref] [bib_ref] Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with no..., Seyama [/bib_ref] [bib_ref] Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary..., Nagino [/bib_ref]. Overall, unilat-eral drainage of the future remnant lobe is enough in many patients.
Bilateral biliary drainage should be considered in the following cases: those in which the operative procedure is diffi cult to determine before biliary drainage; those in which cholangitis has developed after unilateral drainage; and those in which the decrease in serum bilirubin after unilateral drainage is very slow. Unilateral or bilateral drainage should be determined on a case-by-case basis considering the operative procedure, liver function, and/or the presence or absence of cholangitis.

## Bile replacement may be useful (recommendation c1).
Maintenance of the enterohepatic circulation of bile is important for host defense function. In humans, it is CQ 5 Is bile culture necessary in patients with biliary drainage who are to undergo surgery?

## Monitoring of bile culture is necessary to select appropriate antibiotics in the perioperative period (recommendation b).
Once biliary drainage has been performed, the bile is contaminated with microorganisms. In recent studies involving patients who underwent pancreatoduodenectomy, the incidence of postoperative infections was signifi cantly higher in patients with biliary infection before surgery than in those without. [bib_ref] Preoperative biliary drainage: Impact on intraoperative bile cultures and infectious morbidity and..., Povoski [/bib_ref] [bib_ref] Effect of bile contamination on immediate outcomes after pancreaticoduodenectomy for tumor, Cortes [/bib_ref] Furthermore, in 30% to 50% of cases, the microorganisms isolated from postoperative infections were identical to those found in the preoperative bile cultures 13,28,29 (level IV). Therefore, identifi cation of microorganisms in bile before surgery is necessary to enable selection of the appropriate prophylactic antibiotics after surgery.
well known that the increased intestinal permeability caused by obstructive jaundice is recovered after internal biliary drainage 30,31 (level IV). A recent study has shown that bile replacement by oral intake during external drainage helps restore intestinal barrier function in patients with biliary obstruction, similar to fi ndings that have been documented in studies of internal drainage 32 (level IV). Internal drainage (ERBD) is more physiological than external drainage (PTBD and ENBD), as the enterohepatic circulation of bile is maintained. Several experimental studies have demonstrated that internal drainage is superior to external drainage, from the viewpoints of intestinal immunity, prevention of bacterial translocation, and liver regeneration. Preoperative bile replacement is recommended for patients scheduled to undergo hepatectomy for biliary cancer, as this type of hepatectomy is still a high-risk procedure. However, further studies are required to assess whether bile replacement can prevent gut-derived bacterial translocation and, in turn, reduce the incidence of postoperative septic complications.
2006 sponsored by the Japanese Ministry of Health, Labour, and Welfare.
We truly appreciate the following active working members who developed the draft of the evidencebased clinical practice Guidelines for the treatment of biliary tract cancer (Japanese version, 2007): Masahiro Kai (Miyazaki), Yasutoshi Kimura (Sapporo), Shigeaki Sawada (Toyama), Hiroaki Shimizu (Chiba), Hisatoshi Nakagawara (Kanazawa), Kohei Nakachi (Kashiwa), and Hiroyuki Yoshitome (Chiba). We also appreciate very much the following members who reviewed and approved the fi nal Japanese version of the guidelines: Hiromitsu Saisyo (Ichikawa), Munemasa Ryu (Chiba), Satoru Shikata (Kyoto), and Yuji Nimura (Nagoya).
[fig] Fig: 1a,b. A patient who had undergone percutaneous transhepatic biliary drainage (PTBD) suddenly presented with high fever. a Abdominal ultrasound demonstrated dilation of the left medial segmental bile duct (B4). A diagnosis of seg-mental cholangitis of this undrained segment was made, and additional PTBD was performed urgently. b Cholangiogram through the PTBD catheter shows typical fi ndings of liver abscess a b CQ 6 Is bile replacement useful for patients with external biliary drainage? [/fig]
[table] Table 1 Table 2: Strength of recommendations 1 A, Strongly recommend performing the clinical action B, Recommend performing the clinical action C1, The clinical action may be considered although there is a lack of high-level scientifi c evidence for its use. May be useful C2, Clinical action not defi nitively recommended because of insuffi cient scientifi c evidence. Evidence insuffi cient to support or deny usefulness D, Recommend not performing the clinical action Levels of evidence 1 [/table]