A New Technique of Biliary Reconstruction After ''High Hilar Resection ...

Annals of Surgical Oncology 15(7):1871–1879

DOI: 10.1245/s10434-008-9926-x

A New Technique of Biliary Reconstruction After ‘‘High Hilar Resection’’ of Hilar Cholangiocarcinoma with Tumor Extension to Secondary and Tertiary Biliary Radicals Unal Aydin, MD,1 Suleyman Yedibela, MD,1 Pinar Yazici, MD,1 Bulent Aydinli, MD,2 Murat Zeytunlu, MD,1 Murat Kilic, MD,1 and Ahmet Coker, MD1

1

Organ Transplantation and Research Center, Ege University School of Medicine, Izmir, Turkey 2 Department of General Surgery, Medical Faculty, Ataturk University, Erzurum, Turkey

Background: Radical operation for hilar cholangiocellular carcinoma, including extended hepatic resection, seems to improve prognosis by increasing the surgical curability rate. Nevertheless, high postoperative morbidity and mortality have been reported in patients with obstructive jaundice. We describe the technique of ‘‘high hilar resection’’ and a modification of bilioenteric anastomosis for drainage of the multiple secondary or tertiary biliary radicals. Methods: Ten patients with advanced hilar cholangiocellular carcinoma underwent a high hilar resection with complete parenchymal preservation, and the biliary drainage was reconstructed by a sheath-to-enteric hepaticojejunostomy. Because of the technical difficulty caused by anastomosis line in the range of the biliary sheath, a modification was performed by dividing the biliary apertures of segments 5 and 4b. Results: A high hilar resection was successfully performed, and all patients were discharged from the hospital in good condition. No patient died postoperatively. The proximal resection margin was tumor-free in all patients. One patient died after 29 months of peritoneal carcinomatosis. None of the patients developed local recurrence around the hepaticojejunostomy. The remaining nine patients are alive after a mean follow-up of 28.8 months after surgery without any signs of recurrence. Conclusion: In highly selected patients with advanced hilar cholangiocellular carcinoma, a high hilar resection is technically safe and oncologically justifiable. In combination with our new technique of sheath-to-enteric anastomosis, the patients considerably benefit from the preservation of liver parenchyma with low postoperative morbidity and very short in-hospital stay. Key Words: Hilar cholangiocarcinoma—High hilar resection—Hepaticojejunostomy—Surgical technique.

Worldwide, cholangiocarcinoma accounts for 3% of all gastrointestinal cancers and is the second most common primary hepatic tumor.1 Cholangiocellular carcinoma arises from the ductular epithelium of the biliary tree, either within the liver [intrahepatic

cholangiocarcinoma (ICC)] or more commonly from the extrahepatic bile ducts [extrahepatic cholangiocarcinoma (ECC)]. About 50–60% of tumors occur at the bifurcation of the left and right hepatic ducts [hilar cholangiocarcinoma (HiCC), ‘‘Klatskin’’ tumor], 10% are intrahepatic, and 20–30% of the tumors are extrahepatic distal bile duct tumors.2 Based on the tumor location, hilar lesions are further classified by Bismuth-Corlette (Fig. 1).3 HiCC leads to progressive biliary obstruction, sepsis, secondary

Published online May 3, 2008. Address correspondence and reprint requests to: Unal Aydin, MD; E-mail: drunalaydin@gmail.com Published by Springer Science+Business Media, LLC 2008 The Society of Surgical Oncology, Inc.

1871

1872

U. AYDIN ET AL.

FIG. 1. Bismuth-Corlette classification, three patients with type IIIa, three patients with IIIb, and four with type IV classification.

biliary cirrhosis, and hepatic failure. However, resectability rates and long-term survival rates remain low because of the difficulty and late diagnosis, as these neoplasms tend to grow slowly and infiltrate surrounding structures such as intrahepatic bile ducts and the hepatic pedicle. The treatment of hilar cholangiocarcinoma has changed markedly over the last decades. Since the 1990s, more aggressive approaches including extensive liver resections were established. Especially, data from Japanese surgeons, who performed hilar resection combined with partial hepatectomy including caudate lobe resection, showed a higher tumor-free margin resection rate (R0).4,5 The anatomic location of HiCC determines the optimal diagnostic and therapeutic strategy. Besides infiltration of portal vein or hepatic artery, extent of the intrahepatic bile duct invasion with impossibility of biliary drainage limits a surgical procedure with curative intent. Bilateral tumor extension to secondary or tertiary biliary radicals was defined as criteria of unresectability by several authors.6–8 In this contribution, we describe a modified practical technique of Roux-en-Y biliary-enteric anastomosis after ‘‘high hilar resection (HHiR)’’ for HiCC, which allows drainage of multiple secondary biliary radicals, without the need of ligation of any bile duct.

METHODS Patients Ten patients with advanced HiCC without any satellite nodules or skip metastasis and distant metastatic spread, but invasion of secondary and/or tertiary biliary ducts underwent a high hilar resection, and the bilioenteric continuity was reestablished with a modified Roux-en-Y bilioenteric anastomosis, according to the surgical procedure detailed below (Fig. 2). Furthermore, two patients, with intraoperatively detected skip lesions in the proximal part of Ann. Surg. Oncol. Vol. 15, No. 7, 2008

the bile ducts to segments 3 and 4b of the liver, underwent a partial hepatectomy and were excluded from analysis. All patients were jaundiced on admission, and seven patients underwent percutaneous transhepatic biliary drainage before surgery. Most patients were referred after at least a partial radiographic evaluation had been completed, usually consisting of a computed tomography (CT) scan and either endoscopic or percutaneous cholangiography. After referral, further evaluation of biliary tumor extent and assessment of possible vascular involvement or metastatic disease were performed with magnetic resonance cholangiopancreatography and duplex sonography. In addition to Bismuth-Corlette classification,3 we also used the morphologic classification of the tumor according to the Liver Cancer Study Group of Japan.9 After preoperative evaluation, 10 patients were considered to have a potentially resectable disease with a high hilar resection without any hepatic segmentectomy or lobectomy. Patients were identified from a prospective database and retrospectively reviewed. Statistical calculations were performed using SPSS, version 14.0 (Statistical Package for the Social Sciences, Chicago, IL). Survival was estimated by the Kaplan-Meier method. A P value \ 0.05 was considered statistically significant. Surgical Procedure After laparatomy through an upper midline incision with bilateral subcostal extensions (Mercedes incision), a careful exploration was performed for assessment of resectability by exclusion of peritoneal implants, hepatic metastases, regional lymph node involvement, and vascular invasion. A Doppler ultrasonography was used in all cases for detection of all aforementioned criteria. In the first step, an early mobilization of the gallbladder was performed for exposition of the extrahepatic biliary tree and the hepatic duct confluence. Accordingly, the exposure of the biliary confluence and assessment for vascular

A HIGH HILAR RESECTION FOR KLATSKIN TUMOR

1873

FIG. 2. Inverted transverse ‘‘S’’-figure of the biliary sheath and the anatomical localization of the apertures of the segmental biliary branches.

involvement was accomplished by transection of the common bile duct from the level of duodenum upward, taking along with it lymphatic tissue of the hepatoduodenal ligament to the celiac trunk. Finally, careful assessment of the extent of tumor along the bile duct was completed. The distal extrahepatic bile duct was sutured closed, and the proximal bile duct was mobilized from the portal vein and hepatic artery under direct vision. Subsequently, a skeletonization of hepatic duct confluence and the intrahepatic biliary tree to the level of secondary and/or tertiary biliary radicals was performed under palpation to determine a tumor-free segment. If a tumor-free segment was found, the intrahepatic bile ducts were divided at the level of secondary and/or tertiary biliary radicals. The numbers of divided biliary radicals accounts from 6 to 12 (Table 1, Fig. 2). To determine margin-negative R0 resection, we performed parenchymal resection including about 1–1.5 cm of the hilar part of the segments 5 and 4b. A partial resection of segment 1 was also carried out in all cases. Frozen section assessments of proximal and distal bile duct surgical margins were performed during operation. In three patients, the portal vein was adherent to and could not be freed from the tumor during skeletonization and resection of the hepatoduodenal ligament. Thus, we performed a partial portal vein resection and reconstruction by a continuous suture (Table 1). In one patient, an infiltration of the hepatic

artery was detected; after a partial resection of the artery, an end-to-end anastomosis was performed. All biliary radicals were probed to exclude any stricture in the proximal parts of any biliary radical and were separately suture marked. The biliary continuity was reestablished by an end-to-side anastomosis of the entire biliary sheath to an upper portion of a 70-cm retrocolic Roux-en-Y jejunal limb (Fig. 3). None of the biliary radicals had to be ligated in our series; the biliary ducts met during caudate lobe resection as well. The biliary-enteric anastomosis was performed with continuous No. 5.0 synthetic absorbable sutures. Because of the anatomic ‘‘inverted transverse S’’ figure (Fig. 2) of the biliary sheath around the right and left portal vein branch with the difficulty to suture to the distal part of ‘‘inverted transverse S,’’ a technical modification was used. The apertures of the divided bile ducts to the segments 4b and 5 were probed and then split each 1 cm across the liver parenchyma as shown in Fig. 3. Thus, a straight layer above the deep part of the ‘‘inverted transverse S’’ was created. As shown in Fig. 3, we began the anastomosis at the level of the biliary aperture of segment 3 and continuously sutured the posterior part of the biliary sheath up to the level of the biliary aperture of segment 6 and accomplished the ventral part of the biliary sheath from the left side along the split bile ducts of segments 4b and 5 to the right side. All biliary radicals were drained into Ann. Surg. Oncol. Vol. 15, No. 7, 2008

1874

U. AYDIN ET AL.

TABLE 1. Surgical data of the patients Patient No. 1 2 3 4 5 6 7 8 9 10

Bismuth-Corlette classification IIIb IV IIIb IV IV IV IIIa IIIb IIIa IIIa

PVI

HAI

Duration of operation, minutes

Blood loss, mL

Number of biliary radicals

130 165 150 170 175 210 155 180 110 135

200 150 100 300 250 800** 250 100 100 150

6 9 5 12 8 10 7 6 7 7

+* +*

+

+*

PVI, portal vein invasion; HAI, hepatic artery invasion. * All three patients underwent partial portal vein resection and reconstruction. ** 1 unit blood transfusion was delivered.

this ‘‘biliary pool’’ without the need of any stent implantation. Intraoperative photos before and after the anastomosis are shown in Fig. 4(a) and (b).

RESULTS There were seven male and three female patients with a mean age of 55.9 years (range, 34–77 years). All patients were jaundiced on admission with a mean total bilirubin of 16.4 mg/dL (range, 4.8–31.3 mg/ dL). Mean size of tumors was determined to be 35 mm (range, 25–52 mm). According to BismuthCorlette classification,3 there were four patients with type IV, three patients with type IIIa, and three patients with type IIIb. On the other hand, according to classification of the Liver Cancer Study Group of Japan,9 there were five patients with intraductal type, of which the largest tumor detected was 52 mm in size. Of the remainder, three patients had periductal-infiltrating type, which extends longitudinally along the bile duct, often resulting in dilatation of the peripheral ducts. The other two patients had mass-forming type tumor. A high hilar resection was performed without any hepatic segmentectomy or lobectomy and without any intraoperative complications. The operating time ranged from 110 to 210 minutes, and the blood loss was from 100 to 800 mL (Table 1). Concomitant vascular resection was performed because of macroscopic involvement with partial portal vein resection in two patients and hepatic artery resection in one patient. Serum aspartate transaminase and alanine transaminase levels were moderately elevated with a mean value of 46.2 U/L (range, 21–90 U/L) and 45.1 U/L (range, 20–84 U/L), respectively. While gamma-glutamyl transferase levels were partly at high levels with a mean value of 254.8 U/L (range, 63– 859 U/L), the total bilirubin levels returned to nearly Ann. Surg. Oncol. Vol. 15, No. 7, 2008

normal range 1.8 mg/dL (range, 0.4–4.6 mg/dL) within 1 week (Table 2). Three patients presented postoperative complications. One patient developed a transient insufficiency of the hepaticojejunostomy, which was treated conservatively. Under postoperative antibiotic coverage, no fever or other septic complications occurred. While one patient developed self-limiting hemobilia, wound infection occurred in a third patient. Mean length of hospital stay was 8.6 days (range, 5–21 days). Histologically, all patients were diagnosed as having advanced cholangiocarcinoma of the invasive type with lymphatic permeation in five patients and perineural invasion in eight patients. According to the frozen sections as well as the definite histological examination, curative resection was performed in all patients. In three patients, a tumor spread to the hilar lymph nodes was present (Table 3). As to long-term follow-up after a mean of 28.8 months (range, 16– 44 months), none of the patients developed local recurrence around the hepaticojejunostomy. One patient (patient 5) died after 29 months due to peritoneal carcinomatosis. The remaining nine patients have been well without any sign of recurrence after a mean follow-up of 27.6 months after surgery (Fig. 5).

DISCUSSION Although diagnostic techniques for hepatobiliary disease did significantly improve over last couple of years, hilar cholangiocarcinoma is still diagnosed at an advanced stage, and most of the patients have been treated using palliative surgical procedures or nonsurgical techniques. The prognosis of patients undergoing palliative treatment is poor, and adjuvant treatments do not prolong survival.10 In an effort to increase the resectability rate and prolong survival,


1875

FIG. 3. End-to-side anastomosis of the biliary sheath to a retrocolic Roux-en-Y jejunal limb.

many surgeons have recently adopted a more aggressive resection than palliative surgical drainage, with varying degrees of success.11,12 Nevertheless, recent improvement in preoperative management and staging as well as technical development in hepatobiliary surgery have decreased operative morbidity and mortality and increased the curative resection rate.7,13

There is some discordance among various series regarding the indications and the contraindications to resection and the extent of resection. As a general agreement distant metastases, extensive intrahepatic spread, or lymph node involvement outside the hepatic pedicle contraindicate resection.8,14 In all remaining patients, local resection (LR), parenAnn. Surg. Oncol. Vol. 15, No. 7, 2008

1876

U. AYDIN ET AL.

FIG. 4. Intraoperative photos before and after anastomosis. (a) BS: percutaneous biliary drainage catheter placed before operation; r-HA: right hepatic artery; yellow arrows (B): biliary channels: B1-l: biliary branch of the left caudate lobe, B1-r: biliary branch of the right caudate lobe. (b) AL: anastomosis line.

TABLE 2. Postoperative course Patient No. 1 2 3 4 5 6 7 8 9 10

AST (U/L)*

ALT (U/L)*

GGT (U/L)*

Total bilirubin (mg/dL)*

Hospital stay (days)

Postoperative complication (early period)

Follow-up (months)

21 45 38 25 90 23 30 71 54 65

20 51 38 29 84 29 22 84 43 55

221 234 268 63 327 88 224 859 124 140

1.1 2.2 2.1 2.2 1.2 0.4 4.6 1.2 1.8 2.4

8 8 21 7 5 6 8 7 7 9

– – Biliary leakage – – – Wound infection – – Hemobilia

44 33 23 25 29** 21 30 35 22 16

AST, aspartate transaminase; ALT, alanine transaminase; GGT, gamma-glutamyl transferase. * At the end of the hospital stay. ** Died of peritoneal recurrence.

TABLE 3. Pathological examination Patient No. 1 2 3 4 5 6 7 8 9 10

Resection margin

Histological grade

Lymph node metastasis

R0 R0 R0 R0 R0 R0 R0 R0 R0 R0

G2 G1 G2 G3 G1 G2 G2 G2 G2 G3

+ +

Microscopically venous invasion

+

+

LVI

PNI

+

+

+ +

+ + +

+ + +

+

+ + + +

LVI, lymphovascular invasion; PNI, perineural invasion.

chyma-preserving hepatectomy (PPH), or an extended hepatectomy (EH) is indicated, whereas localization of the lesions and its intrahepatic invasion of the biliary tract determines each of the surgical procedures.13,15–19 Regarding its pattern of infiltration, the best treatment for hilar cholangiocarcinoma is extrahepatic bile duct resection plus hepatectomy and regional lymphadenectomy. Limited resections such as PPH and in fact LR are not favored, because of the complexity of the surgical Ann. Surg. Oncol. Vol. 15, No. 7, 2008

procedure and the difficulty of biliary reconstruction.20 As a result of this difficulty, in these cases a less aggressive resection leads to a high incidence of positive margins.15 In well-selected patients without metastatic spread and without infiltration of liver parenchyma, we were able to perform a curative resection (R0) in all patients who underwent a HHiR. Glisson’s capsule extends into the liver as tissue sheaths around the hepatic ducts, hepatic arteries, and portal tributaries.21 After dividing the intrahepatic bile


FIG. 5. 3-year survival curve of high hilar resected patients.

ducts beyond the proximal part of the tumor (HiHR), up to 12 or more biliary radicals can be localized within the biliary sheath, depending on the depth of the resection level. In conventional surgery for hilar cholangiocellular carcinoma, biliary continuity could only be performed in these cases by ligating multiple biliary radicals (\1–2 mm), because the number of end-toside biliary-enteric anastomoses is technically restricted. On the other hand, biliary dilatation compresses the portal vein within the confines of the Glissonian sheath, causing portal hypertension and persisting cholestasis, increasing the risk of cholangitis and septic events in the postoperative course.22 The postoperative bacteremic risk for patients having obstructive jaundice is increased 12.7 times after extended hepatectomy.23 Through our new technique of biliary reconstruction as described previously and seen in Fig. 3, all biliary radicals drain into the ‘‘biliary pool’’ without the necessity of ligation of any biliary radical and implantation of biliary drainage. Additionally, without major parenchymal resection such as hepatic lobectomy or segmentectomy, resection of biliary ducts was performed resulting in lower biluribin levels in the early postoperative period with a mean value of 1.8 mg/dL. Elective liver resection for liver metastases and hepatocellular carcinoma (HCC) can be performed with an acceptable mortality.24–26 However, large resection volumes and underlying parenchymal disease such as obstructive jaundice correlate with increased morbidity and mortality rates.4,13,27–29 It is because of the fact that cholestasis itself may affect the function of Kupffer cells, decreasing the effectiveness

1877

of bacteria clearance and increasing susceptibility to systemic infection and sepsis.30–33 However, in these cholestatic patients, when extended hepatic resection is done, the number of Kupffer cells with already impaired function will be decreased. In these series, as reserve of the hepatocyte and Kupffer cells are preserved, prompt decrease of bilirubin levels due to preservation of whole bile ducts was also maintained. Thus, the infection risk was decreased, and because of the excellent biliary drainage no cholangitis with fever or septic episodes occurred in any of the patients. Inadequate remnant liver function leading to liver failure after liver resection is a dreaded complication. Postoperative morbidity and mortality in the reported series vary between 42–85% and 0–46%.7,13,15,17,19,34 The most frequent postoperative complications are reported to be biliary leakage, liver or intra-abdominal abscesses, and bleeding.7,13,15,17,19,34 In our series, biliary leakage was seen in one patient, but this could be managed conservatively. Dinant et al. reported on a bile leakage rate of 25% and reoperation in 22% of the patients.34 Through high hilar resection and biliary sheath-enteric anastomosis as described here, we avoided the resection of hepatic parenchyma in these highly selected patients. Absence of postoperative cholestasis due to adequate biliary drainage and preservation of parenchyma led to a good and quick anastomotic healing with a minimum of unspecific postoperative complications. Although there is similarity between Kasai procedure and our reconstruction technique with part of the anastomosis duct to mucosa and a large part of it not duct to mucosa, there are some different points between two anastomosis techniques. In the Kasai procedure, dissection is performed to discover any bile duct,35 whereas in the surgical procedure for Klatskin tumor, dissection is performed to ensure R0 resection. In the pediatric cases with biliary atresia, the problem is the lack of or few bile ducts, but in the patients with Klatskin tumor, it is the opposite, large and multiple bile ducts. At this point, our surgical technique for biliary reconstruction has advantages. The guidance of this approach for the surgical treatment of cholangiocarcinoma is the reconstruction technique of the multiple bile ducts using sheath of the bile duct we performed during live donor liver transplantation (LDLT). High hilar dissection (HHD) is routinely performed for all recipients, graft liver with multiple bile ducts are anastomosed in continuous manner using the biliary sheath. Because we have experienced good results with this technique in LDLT, we have also planned to use this technique for surgical management of Klatskin tumors. HowAnn. Surg. Oncol. Vol. 15, No. 7, 2008

1878

U. AYDIN ET AL.

ever, in transplant patients, there are a lot of potential risk factors such as cold ischemia of the graft, rejection episodes, bile duct \ 2 mm in size etc.,36 whereas in the patients with Klatskin tumor, the bile ducts were dilated ([5 mm) due to tumoral obstruction. Additionally, continuous suturing of the sheath of bile ducts shaped as ‘‘S’’ letter allowed a low complication rate including local recurrence. CONCLUSION In conclusion, high hilar resection at the level of secondary and tertiary biliary radicals with complete preservation of liver parenchyma and subsequent biliary-enteric anastomosis along the biliary sheath as described previously can be performed in highly selected patients with advanced hilar cholangiocellular carcinoma. The technical difficulties of biliary reconstruction after division of secondary and tertiary bile ducts with multiple biliary radicals can be solved by our technique. Furthermore, there are other advantages: • Postoperative cholestasis caused by ligation of (multiple) biliary radicals with cholangitis and septic episodes is reduced or eliminated. • Implantation of drainage is not necessary due to excellent drainage of the biles into the ‘‘biliary pool.’’ • The healing of the patients’ anastomoses is very fast because liver parenchyma can be preserved and the in-hospital stay can be reduced significantly. • Postoperative morbidity is low compared with the literature; no patient died in the postoperative period. • There is a high curative resection rate (100%) and no local recurrence after a follow-up of mean 29 months. • Due to a proportionally short duration of the operation and short in-hospital stay, the costs were significantly reduced. • The increased surgical curability rate with HHiR allows to establish an extended operability criteria for the patients with advanced hilar cholangiocarcinoma

REFERENCES 1. Vautey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis 1994; 14:109–14. 2. Khan SA, Davidson BR, Goldin R, et al. Guidelines for the diagnosis and treatment of cholangiocellular carcinoma: consensus document. Gut 2002; 51:1–9.

Ann. Surg. Oncol. Vol. 15, No. 7, 2008

3. Bismuth H, Nakache R, Diamont T. Management strategies in resection for hilar cholangiocarcinoma. Ann Surg 1992; 215:31–8. 4. Tsao JI, Nimura Y, Kamiya J, et al. Management of hilar cholangiocarcinoma: comparison of an American and Japanese experience. Ann Surg 2000; 232:166–74. 5. Kawasaki S, Imamura H, Kobayashi A, et al. Results of surgical resection for patients with hilar bile duct cancer: application of extended hepatectomy after biliary drainage and hemihepatic portal vein embolization. Ann Surg 2003; 238:84– 92. 6. Jarnagin WR, Fong Y, DeMatteo RP, et al. Staging, respectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 2001; 234:507–19. 7. Silva MA, Tekin K, Aytekin F, et al. Surgery for hilar cholangiocarcinoma; a 10 year experience of a tertiary referral centre in the UK. EJSO 2005; 31:533–9. 8. Jarnagin WR, Bownw W, Klimstra DS, et al. Papillary phenotype confers improved survival after resection of hilar cholangiocarcinoma. Ann Surg 2005; 241:703–14. 9. Liver Cancer Study Group of Japan (2000) The General Rules for the Clinical and Pathological Study of Primary Liver Cancer, 4th edition. Tokyo: Kanehara. 10. Cameron JL, Pitt HA, Zinner MJ, et al. Management of proximal cholangiocarcinoma by surgical resection and radiotherapy. Am J Surg 1990; 159:91–8. 11. Fortner JG, Vitelli CE, Maclean BJ. Proximal extrahepatic bile duct tumors; analysis of a series of 52 consecutive patients treated over a period of 13 years. Arch Surg 1989; 124:1275–9. 12. Sugiura Y, Nakamura S, Iida S, et al. Extensive resection of the bile ducts combined with liver resection for cancer of the main hepatic junction: A cooperative study of the Keio Bile Duct Cancer Study Group. Surgery 1994; 115:445–51. 13. Seyama Y, Kubota K, Sano K, et al. Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with no mortality and high survival rate. Ann Surg 2003; 238:73–83. 14. Bismuth H, Castaing D, Traynor O. Resection or palliation: Priority of surgery in the treatment of hilar cancer. World J Surg 1988; 12:39–47. 15. Miyazaki M, Ito H, Nakagawa K, et al. Parenchyma-preserving hepatectomy in the surgical treatment of hilar cholangiocarcinoma. J Am Coll Surg 1999; 189:575–83. 16. Nagino M, Kamiya J, Arai T, et al. ‘‘Anatomic’’ right hepatic trisectionectomy (extended right hepatectomy) with caudate lobectomy for hiloär cholangiocarcinoma. Ann Surg 2006; 243:28–32. 17. Baton O, Azoulay D, Adam DVR, et al. Major hepatectomy for hilar cholangiocarcinoma type 3 and 4: prognostic factors and longterm outcomes. J Am Coll Surg 2007; 204:250–60. 18. Kosuge T, Yamamoto J, Shimada K, et al. Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection. Ann Surg 1999; 230:663–71. 19. Liu CL, Fan ST, Lo CM, et al. Improved operative and survival outcomes of surgical treatment for hilar cholangiocarcinoma. Br J Surg 2006; 93:1488–94. 20. Seyama Y, Makuuchi M. Current surgical treatment for bile duct cancer. World J Gastroenterol 2007; 13:1505–15. 21. Launois B, Jamieson GG. The importance of Glisson’s capsule and its sheath in the intrahepatic approach to resection of the liver. Surg Gynecol Obstet 1992; 174:7–10. 22. Khan AZ, Makuuchi M. Trends in the surgical management of Klatskin tumours. Br J Surg 2007; 94:393–4. 23. Shigeta H, Nagino M, Kamiya J, et al. Bacteremia after hepatectomy: an analysis of single center, 10-year experience with 407 patients. Langenbecks Arch Surg 2002; 387:117–24. 24. Yedibela S, Gohl J, Graz V, et al. Changes in indication and results after resection of hepatic metastases from noncolorectal primary tumors: a single-institutional review. Ann Surg Oncol 2005; 12:778–85.


25. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999; 30:1434–40. 26. Poon RT, Fan ST, Lo CM, et al. Improving perioperative expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database. Ann Surg 2004; 240:698– 708. 27. Pichlmayr R, Weimann A, Klempnauer J, et al. Surgical treatment in proximal bile duct cancer; a single-center experience. Ann Surg 1996; 224:628–38. 28. Neuhaus P, Jonas S, Bechstein WO, et al. Extended resection for hilar cholangiocarcinoma. Ann Surg 1999; 230:808–19. 29. Kondo S, Hirano S, Ambo Y, et al. Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins. Ann Surg 2004; 240:95–101. 30. Tomioka M, Iinuma H, Okinaga K. Impaired Kupffer cell function and effect of immunotherapy in obstructive jaundice. J Surg Res 2000; 92:276–82.

1879

31. Clements WD, McCaigue M, Erwin P, et al. Biliary decompression promotes Kupffer cell recovery in obstructive jaundice. Gut 1996; 38:925–31. 32. Katz S, Yang R, Rodefeld MJ, et al. Impaired hepatic bacterial clearance is reversed by surgical relief of obstructive jaundice. J Pediatr Surg 1991; 26:401–5. 33. Vane DW, Redlich P, Weber T, et al. Impaired immune function in obstructive jaundice. J Surg Res 1988; 45:287–93. 34. Dinant S, Gerhards MF, Rauws EAJ, et al. Improved outcome of resection of hilar cholangiocarcinoma (klatskin tumor). Ann Surg 2006; 13:872–80. 35. Kasai M, Kimura S, Asakura Y, et al. Surgical treatment of biliary atresia. J Pediatr Surg 1968; 3:665–75. 36. Icoz G, Kilic M, Zeytunlu M, et al. Biliary reconstructions and complications encountered in 50 consecutive right-lobe living donor liver transplantations. Liver Transpl 2003; 9:575–80.

Ann. Surg. Oncol. Vol. 15, No. 7, 2008