Figure 62-16. Cholangiogram of a patient with cholangiohepatitis with diffuse bile duct dilatation. The biliary tree is filled with

sludge (Sl) and stones.

References

1. Hall JG, Pappas TN. Current management of biliary strictures. J Gastrointest Surg 2004;8:1098–

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2. Brooks KR, Scarborough JE, Vaslef SN, et al. No need to wait: an analysis of the timing of

cholecystectomy during admission for acute cholecystitis using the American College of Surgeons

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3. Joseph M, Phillips MR, Farrell TM, et al. Single incision laparoscopic cholecystectomy is asscoaited

with a higher bile duct injury rate: a review and word of caution. Ann Surg 2012;256:1–6.

4. Branum G, Schmitt C, Baillie J, et al. Management of major biliary complications after laparoscopic

cholecystectomy. Ann Surg 1993;217:532–540; discussion 540–541.

5. Flum DR, Dellinger EP, Cheadle A, et al. Intraoperative cholangiography and risk of common bile

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6. Sheffield KM, Riall TS, Kuo YF, et al. Association between cholecystectomy with vs without

intraoperative cholangiography and risk of common duct injury. JAMA 2013;310:812.

7. Massaruch NN, Devlin A, Elrod JA, et al. Surgeon knowledge, behavior and opinions regarding

intraoperative cholangiography. J Am Coll Surg 2008; 207:821–820.

8. Way LW, Stewart L, Gantert W, et al. Causes and prevention of laparoscopic bile duct injuries:

analysis of 252 cases from a human factors and cognitive psychology perspective. Ann Surg

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9. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic

cholecystectomy. J Am Coll Surg 1995;180:101–125.

10. Alves A, Farges O, Nicolet J, et al. Incidence and consequence of an hepatic artery injury in patients

with postcholecystectomy bile duct strictures. Ann Surg 2003;230:93–96.

11. Strasberg SM, Helton WS. An analytical review of vasculobiliary injury in laparoscopic and open

cholecystectomy. HPB(Oxford) 2011;13:1–14.

12. Pitt HA, Miyamoto T, Parapatis SK, et al. Factors influencing outcome in patients with

postoperative biliary strictures. Am J Surg 1982;144:14–21.

13. Pellegrini CA, Thomas MJ, Way LW. Recurrent biliary stricture: patterns of recurrent and outcome

of surgical therapy. Am J Surg 1984;147:175–180.

14. Lillemoe KD, Martin SA, Cameron JL, et al. Major bile duct injuries during laparoscopic

cholecystectomy: follow-up after combined surgical and radiologic management. Ann Surg

1977;225:459–471.

15. Mercado MA, Chan C, Jacinto JC, et al. Voluntary and involuntary ligature of the bile duct in

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iatrogenic injuries: a nonadvisable approach. J Gastrointest Surg 2008;12:1029–1032.

16. Lillemoe KD. Treatment of laparoscopic bile duct injuries. Curr Tech Gen Surg 1997;6:1.

17. Warren KW, Christophi C, Armendari ZR. The evolution and current perspectives of the treatment

of benign bile duct strictures: a review. Surg Gastroenterol 1982;1:141.

18. Sicklick JK, Camp MS, Lillemoe KD, et al. Surgical management of bile duct injuries sustained

during laparoscopic cholecystectomy: perioperative results in 200 patients. Ann Surg 2005;241:786–

792; discussion 793–795.

19. Pitt HA, Kaufman SL, Coleman J, et al. Benign postoperative biliary strictures: operate or dilate?

Ann Surg 1989;210:417–425; discussion 426–427.

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outcome in the 1990s. Ann Surg 2000;232:430–441.

22. Walsh RM, Henderson JM, Voglt DP, et al. Long-term outcome of biliary reconstruction for bile

duct injuries from laparoscopic cholecystectomies. Surgery 2007;142:450–456; discussion 456–457.

23. Pitt HA, Sherman S, Johnson MS, et al. Improved outcomes of bile duct injuries in the 21st century.

Ann surg2013;258:490–499.

24. Stewart L, Way LW. Bile duct injuries during laparoscopic cholecystectomy. Arch Surg

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25. Murr MM, Gigot JI, Nagorney DM, et al. Long-term results of biliary reconstruction after

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injuries associated with laparoscopic cholecystectomy: a decade of experience. J Am Coll Surg

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injuries: long term outcomes and predictors of success. Gut 2007;56:1599–1605.

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Gastrointest Endosc 1989;35:367–371.

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41. Warshaw AL, Schapiro RH, Ferrucci JT Jr, et al. Persistent obstructive jaundice, cholangitis, and

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biliary cirrhosis due to common bile duct stenosis in chronic pancreatitis. Gastroenterology

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Chapter 63

Biliary Neoplasms

Kaitlyn J. Kelly, Yuman Fong, and Sharon Weber

Key Points

1 Surgery remains the only curative option for biliary malignancies.

2 Gallbladder cancer is a rare malignancy with a dismal prognosis because of its insidious onset,

propensity for local invasion, and rapid disease progression.

3 The association of gallstones with carcinoma is probably related to chronic inflammation.

4 Patients with choledochal cysts have an increased risk of carcinoma developing anywhere in the

biliary tree, but the incidence is highest in the gallbladder.

5 The only curative option in patients with gallbladder cancer is complete surgical resection.

6 Nonoperative palliative biliary decompression can be accomplished with percutaneous or endoscopic

stenting, depending on the level of obstruction.

INTRODUCTION

1 Tumors arising in the gallbladder and biliary tree are rare, with approximately 10,650 cases per year

in the United States and 140,000 per year worldwide.1,2 These tumors are often asymptomatic until late

in the course of the disease. Consequently, these tumors commonly present in an advanced, often

unresectable stage. Surgery remains the only curative option for biliary malignancies. Complete

resection of biliary neoplasms, however, often requires radical resections and complex biliary

reconstructions that are only routinely safe at specialized, high-volume centers. Surgery also offers

potential for effective palliation of these cancers, including biliary bypasses for jaundiced patients with

unresectable tumors. Both the late diagnosis and the complex operative techniques required for

potentially curative resection contribute to the challenge of these cases. In addition, there are no proven

effective options for adjuvant treatment. This chapter reviews the incidence, diagnosis, and therapy of

these malignancies as well as the outcomes of treatment.

GALLBLADDER CARCINOMA

2 Gallbladder cancer is a rare malignancy with a dismal prognosis because of its insidious onset,

propensity for local invasion, and rapid disease progression. Overall, most series report a 5-year

survival of less than 5%.

Incidence

Gallbladder cancer is the most common biliary tract malignancy, but there are only 6,000 to 7,000 new

cases diagnosed nationally each year. Attesting to the rarity of this lesion, after routine screening of

abdominal ultrasounds in asymptomatic patients in Japan, only 19 out of 194,767 patients (0.01%) were

found to have gallbladder cancer.3 This tumor occurs more frequently in women (female:male ratio =

3:1), and peak incidence is in the seventh decade.4 There is a tremendously increased risk of gallbladder

cancer, in particular indigenous populations, including Mapuche Indians in South America (12.3

cases/100,000 males and 27.3/100,000 females, and Native Americans in New Mexico (8.9

cases/100,000 people).5,6

The increased risk of gallbladder cancer with cholelithiasis is well established; 70% to 90% of all

patients with carcinoma also have gallstones. However, less than 0.5% of patients with gallstones are

found to have gallbladder cancer.5 In recent series of patients undergoing elective cholecystectomy for

gallstones, gallbladder cancer is found incidentally in <0.5% of patients.7 The association of gallstones

with carcinoma is probably related to chronic inflammation. Larger stones (>3 cm) are associated with

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a 10-fold increased risk of cancer.6,8

3 The association of gallbladder cancer with gallstone disease has led some investigators to question

whether all patients with gallstones should undergo cholecystectomy. The argument against this

approach is that the use of cholecystectomy only for symptomatic patients, thus leaving the gallbladder

in place in patients with asymptomatic gallstones, has not led to an increase in the prevalence of

gallbladder cancer over time. Also, epidemiologic studies have found that the 20-year risk of developing

cancer in patients with gallstones is less than 0.5% for the overall population and 1.5% for high-risk

groups.5 Thus, routine cholecystectomy for asymptomatic gallstones because of concern for gallbladder

cancer does not appear to be warranted.

In the past, the finding of a calcified gallbladder wall, called “porcelain gallbladder” (Fig. 63-1), was

associated with a high risk of cancer, in some series ranging from 25% to 60%.9 Thus, the

recommendation was for all patients with porcelain gallbladder to undergo open cholecystectomy, even

if asymptomatic. Recent series evaluating this issue, however, suggest that the risk of gallbladder cancer

in patients with porcelain gallbladder has likely been greatly overestimated. In fact, although patients

with limited areas of calcification of the wall may have a higher incidence of gallbladder cancer (7%),

patients with diffuse calcification of the gallbladder wall, the classic presentation for porcelain

gallbladder, do not appear to have an increased risk of gallbladder cancer.10,11

4 Patients with choledochal cysts have an increased risk of carcinoma developing anywhere in the

biliary tree, but the incidence is highest in the gallbladder. This risk increases with age. Therefore,

cholecystectomy is recommended for all patients with choledochal cysts at the time of diagnosis.

Figure 63-1. Unresectable gallbladder cancer demonstrating palliative transhepatic percutaneous stent placed to relieve jaundice.

Porcelain gallbladder is present (arrows).

Pathology and Staging

More than 80% of gallbladder cancers are adenocarcinomas; there are several histologic subtypes,

including papillary, nodular, and tubular. Papillary tumors, which grow predominantly into the

gallbladder lumen, have an improved prognosis compared with the other subtypes.12 Poor prognostic

signs in gallbladder cancer include grade, and vascular invasion.12,13 The most important prognostic

factor may be lymph node status, although 5-year survivors with nodal involvement have been

documented.14,15 Less than 5% of cases are squamous cell carcinomas, with the remaining 10% being

anaplastic lesions.

Gallbladder cancer spreads via the lymphatic and venous drainage. Because of drainage of the

cholecystic veins directly into the adjacent liver, these tumors often involve hepatic parenchyma, most

often portions of segments IV and V. Lymphatic spread is first to the cystic duct (Calot) node, then to

pericholedochal and hilar nodes, and finally to peripancreatic, duodenal, periportal, celiac, and superior

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