Gallbladder and Biliary Tract Carcinoma: A Comprehensive Update, Part 1
By Vandana Rajagopalan, MD1, William P. Daines2, Michael L. Grossbard, MD3, Peter Kozuch, MD4 |
June 1, 2004
1Fellow in Hematology/Oncology, St. Luke's-Roosevelt Hospital Center and Beth Israel Medical Center
2Harvard University, Boston, Massachusetts
3Chief of Hematology/Oncology, St. Luke's-Roosevelt Hospital Center and Beth Israel Medical Center; Associate Professor of Clinical Medicine, Columbia University College of Physicians and Surgeons
4Attending Physician, St. Luke's-Roosevelt Hospital Center; Assistant Professor of Clinical Medicine, Columbia University College of Physicians and Surgeons, New York, New York
The symptoms related to gallbladder carcinoma and cholangiocarcinoma are relatively nonspecific, which in part accounts for the often delayed diagnosis. With a high index of suspicion and the advent of better imaging techniques, a preoperative diagnosis of gallbladder carcinoma may be reached in 75% to 88% of cases.
The presentation of gallbladder or cholangiocarcinomas can be divided into five syndromes:
(1) Acute cholecystitis: About 5% of patients operated upon for acute cholecystitis have occult gallbladder neoplasms. An incidence of 6% to 8% has been reported in elderly patients with acute cholecystitis, especially when associated with abnormal liver enzymes. Therefore, it may be reasonable to consider offering patients with abnormal liver function tests an open cholecystectomy instead of a laparoscopic procedure.
(2) Chronic cholecystitis: Recurrent cholecystitis in a patient over age 50 with known gallstone disease should raise suspicion for gallbladder cancer.
(3) Biliary tract disease: Symptoms of biliary obstruction such as jaundice, right upper quadrant pain, nausea, vomiting, and in later stages, pruritus are often associated with unresectable disease. Mirizzi syndrome—obstructive jaundice due to compression of the common hepatic duct by an impacted stone in the gallbladder neck—has been associated with a high incidence of gallbladder cancer, and in such circumstances, intraoperative frozen section is recommended.
(4) Nonspecific symptomatology: Anorexia, weight loss, and generalized weakness are common symptoms related to gallbladder cancer. Symptoms can also result from local complications such as fistula formation, invasion of an adjacent organ presenting with hemobilia, gastrointestinal bleeding, or intestinal obstruction. The presence of a palpable right upper quadrant mass indicates unresectability in most cases of gallbladder carcinoma.
(5) Symptoms and signs related to metastatic disease Patients with gallbladder cancer can present with ascites, hepatomegaly, and paraneoplastic syndromes such as acanthosis nigricans. Most of these symptoms can be caused by gallstone disease alone.
Common Diagnostic Procedures in the Diagnosis of Gallbladder Carcinoma
Imaging studies guide preoperative diagnosis, determine stage, and help assess resectability (Table 3). Multiple discontiguous liver metastasis, ascites, peritoneal metastasis, distant metastasis, extensive involvement of the hepatoduodenal ligament, encasement or occlusion of major vessels, biliary involvement not amenable to reconstruction, and poor performance status are indications of unresectable disease. Direct involvement of duodenum, liver, or colon is not a contraindication to surgery.
Laparoscopic staging should be considered prior to laparotomy in potentially resectable disease because of high rates of occult metastatic disease. The overall accuracy of laparoscopy in detecting unresectable disease is 50% to 56%, which is more the result of detecting peritoneal metastasis than for locally advanced disease.[ 28,29] If the patient has radiologically unresectable disease, pathologic diagnosis can be obtained by needle biopsy to proceed with palliative therapy.
Ultrasonography is the most common radiologic study used to assess gallbladder disease. Findings suggestive of gallbladder cancer are discontinuous gallbladder mucosa, mural thickening, mural calcifications, a mass protruding into the lumen, a fixed mass in the gallbladder, loss of the interface between the gallbladder and the liver, or direct liver infiltration. All gallbladder polyps larger than 1 cm, sessile polyps, and those with eroded mucosa are suspicious for carcinoma and should be resected.[31-33] Duplex and B-mode ultrasonography may be able to delineate biliary, vascular, or nodal involvement, but the sensitivity is only around 50%.[34,35]
Ultrasonography can evaluate potential cholangiocarcinomas by revealing dilatation of intrahepatic and/or extrahepatic ducts, which in the absence of gallstones and in the presence of any discrete narrowing is extremely suggestive of an obstructing malignancy. The diagnostic accuracy of ultrasonography for cholangiocarcinoma is limited in the setting of primary sclerosing cholangitis or cirrhosis.
Endoscopic ultrasound may be useful in predicting the depth of tumor involvement, defining the lymph nodal involvement at the porta hepatic or peripancreatic region, and obtaining biliary cytology.[35,37] Endoscopic ultrasound-guided fine-needle aspiration is safe and effective in providing a definitive diagnosis of gallbladder and biliary tract carcinomas.[38,39]
Computed tomography (CT) scans are inferior to ultrasonography in the detection or evaluation of primary gallbladder tumors but are more useful in determining resectability by better assessing extent of disease. Helical CT scans can predict resectability with 93.3% accuracy. CT scanning is a poor modality for evaluation of contiguous spread of gallbladder cancer and detection of omental spread.[42,43] CT scans are sensitive in the detection of intrahepatic bile duct carcinomas but limited in predicting resectability of cholangiocarcinoma, with accuracy ranging from 60% to 70%.
Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) are useful in obtaining biliary cytology for diagnosis. Biliary cytology may be positive in about 75% cases of gallbladder cancer, but the procedure involves the risk of biliary contamination, cholangitis, and sepsis. ERCP and PTC are often used as therapeutic measures to relieve biliary obstruction by placement of a stent. Noninvasive procedures such as magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) have generally replaced these procedures, as they better define resectability.
MRI with MRCP is effective in preoperative evaluation of gallbladder carcinoma and cholangiocarcinoma.[ 46,47] The sensitivity of MRI and MRCP in studies has ranged from 67% to 100% for direct liver invasion and 56% to 92% for lymph node metastasis.[46,48]
Elevated carcinoembryonic antigen (CEA) and CA19-9 in the presence of biliary obstruction and nonspecific symptoms raises the suspicion of gallbladder cancer, but the sensitivity of CEA is only 50% and that of CA19-9 is approximately 80%.[49,50]
Surgical Management of Gallbladder Carcinoma
The only potentially curative therapy for gallbladder cancer is complete surgical resection (Table 4). Historical data on the results of curative surgical resections have been disappointing until the last decade. A review of all cases of gallbladder cancer reported in the English literature up until 1978 (5,836 cases) reported a 5-year survival rate of less than 5%, with a median survival of 5 to 8 months. For the 25% who were treated with curative-intent surgery, 5-year survival was only 16.5%. Similar results were seen in a French Surgical Association survey of 724 cases of gallbladder cancers, with a median survival of 3 months and survival rates of only 14% at 1 year and 5% at 5 years.
In the past decade, however, better understanding of the patterns of tumor spread and progress in preoperative radiologic evaluation have led to better patient selection and an appreciation of the need for aggressive surgical resection for cure. Complete resection must include removal of the cancerous gallbladder, any adjacent organ invaded by tumor, and any potentially involved lymph nodes. Prognostic factors predicting successful resection include tumors limited to subserosal mucosa, hepatic infiltration of 5 mm or less, papillary or well-differentiated adenocarcinomas, absence of venous, lymphatic, or perineural invasion, and lymph node metastasis limited to the hepatoduodenal ligament.
• Guidelines by Tumor Stage—T1 tumors are typically diagnosed incidentally after simple cholecystectomy for presumed gallstones. If a T1 tumor is discovered intraoperatively, the cystic lymph node should be excised and the portal lymph nodes carefully evaluated, although they are unlikely to be involved. If a T1 tumor is identified pathologically after conclusion of the operation, no further surgery is warranted. Simple cholecystectomy is usually curative for T1 tumors, with 5-year survival rates ranging from 85% to 100%.[54-57] Pathologic findings should be reviewed to make certain surgical margins are clear. If the cystic duct margin is positive, patients should undergo a common bile duct excision and biliary reconstruction. In a case of laparoscopic cholecystectomy for unsuspected gallbladder carcinoma, frozen sections may be effective in predicting T2 or greater lesions for which conversion to radical cholecystectomy would be required.
For patients undergoing exploration, a full abdominal exam should be performed looking for peritoneal metastasis, as this would preclude radical surgery. Because of the tendency of gallbladder cancer to recur in laparoscopic port sites, these should be excised at the time of reexploration.[60,61]
Simple cholecystectomy is inadequate surgery for T2 lesions. The standard subserosal plane for surgical excision during routine cholecystectomy often violates a T2 tumor leading to positive margins.[57,62] Furthermore, lymph node metastases are found accompanying 33% of T2 tumors. Appropriate surgical care for a T2 tumor is radical cholecystectomy, which involves removal of the gallbladder with at least 2 cm of the surrounding liver (segments IVB and V), and en bloc lymphadenectomy of the hepatoduodenal ligament lymph nodes, with or without bile duct excision.[51,57,63-66] Radical re-resection for a pathologic T2 lesion discovered after a simple cholecystectomy significantly improves survival.[54,67,68] In some studies, the survival benefit is limited to tumors associated with cancer cells within 5 mm of the excised margin at the initial cholecystectomy.[69,70]
Radical resection for T3 and T4 gallbladder disease-especially in the absence of nodal metastasis-has gathered support in recent years, with data confirming 5-year survival rates of 15% to 67% and 7% to 33% for T3 and T4 tumors, respectively.[65,69-74]
• Lymph Node Involvement—For patients with N1 disease, regional lymphadenectomy may cure metastasis to cystic, portal, and portocaval lymph nodes. Five-year survival rates ranging from 45% to 60% have been reported for patients with regional N1 disease after radical resection.[71,75] Radical lymphadenectomy for N2 disease, which involves removal of retropancreatic, periduodenal, periportal, superior mesenteric, aortocaval, or celiac lymph nodes, has been advocated by few investigators. Surgery includes a hepatopancreaticoduodenectomy in addition to radical cholecystectomy. However, this approach has been associated with high morbidity and mortality rates. Therefore, radical resection should be reserved for patients with stage I to III disease-ie, tumor invasion up to T3, with nodal involvement confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, and along the common hepatic artery.
Complete excision of the tumor with bilioenteric anastomosis offers the only hope for long-term survival in cholangiocarcinoma. The rates of curative resection for intrahepatic, perihilar, and distal cholangiocarcinomas are approximately 60%, 56%, and 91%, respectively. Resection rates increase with more distal lesions. Surgery for hilar cholangiocarcinomas requires excision of the supraduodenal bile duct, cholecystectomy, portal lymphadenectomy, and restoration of bilioenteric continuity. Management of more distal cancers includes pancreaticoduodenectomy.
Criteria for Unresectability of Hilar Cholangiocarcinoma
Curative resection with histologically negative margins (R0) has been associated with a substantially improved 5-year survival of about 30%, as compared to only a 2-year median survival in the presence of histologically positive margins (R1). Performance of a partial hepatectomy, often but not necessarily with caudate lobectomy, seems necessary to achieve histologically negative margins for hilar cholangiocarcinomas. Recently, the postoperative morbidity and mortality associated with partial hepatectomy has fallen to less than 10%, making the operation feasible. Table 5 summarizes the criteria of unresectablity for a cholangiocarcinoma.[77,78]
Financial Disclosure: Dr. Kozuch receives grant support from Pfizer (irinotecan) and Sanofi-Synthelabo.
Gallbladder and Biliary Tract Carcinoma: A Comprehensive Update
We would like to acknowledge
Dr. Warren Enker, chief of
colorectal surgery at Beth Israel Medical Center
and professor of surgery at the Albert
Einstein College of Medicine in New York, and
Dr. Ronald Chamberlain, chief of hepatobiliary
and pancreatic surgery at Beth Israel and assistant
professor of surgery at the Albert
Einstein College of Medicine, for their critical
review of this manuscript
1. de Groen PC, Gores GJ, LaRusso NF, et
al: Biliary tract cancers. N Engl J Med
2. Gores GJ: Cholangiocarcinoma: Current
concepts and insights. Hepatology 37:961-969,
3. Fong Y, Malhotra S: Gallbladder cancer:
Recent advances and current guidelines for
surgical therapy. Adv Surg 35:1-20, 2001.
4. Lazcano-Ponce EC, Miquel JF, Munoz N,
et al: Epidemiology and molecular pathology
of gallbladder cancer. CA Cancer J Clin
5. Misra S, Chaturvedi A, Misra NC, et al:
Carcinoma of the gallbladder. Lancet 4:167-
6. Pandey M, Shukla VK: Lifestyle, parity,
menstrual and reproductive factors and risk of
gallbladder cancer. Eur J Cancer Prev 12:269-
7. Yee K, Sheppard BC, Domreis J, et al:
Cancers of the gallbladder and biliary ducts.
Oncology 16:939-946, 2002.
8. Zatonski WA, Lowenfels AB, Boyle P, et
al: Epidemiologic aspects of gallbladder cancer:
A case-control study of the SEARCH program
of the International Agency for Research
on Cancer. J Natl Cancer Inst 89:1132-1138,
9. Jarnagin WR: Cholangiocarcinoma of the
extrahepatic bile ducts. Semin Surg Oncol
10. Henson DE, Albores-Saavedra J, Corle
D: Carcinoma of the extrahepatic bile ducts,
stage of disease, grade and survival rates. Cancer
11. Nakeeb A, Pitt HA, Sohn TA, et al:
Cholangiocarcinoma: A spectrum of intrahepatic
perihilar, and distal tumors. Ann Surg
12. Yamaguchi K, Enjoji M: Carcinoma of
the gallbladder-a clinicopathology of 103
patients and a newly proposed staging. Cancer
13. Sumiyoshi K, Nagai E, Chijiiwa K, et
al: Pathology of carcinoma of the gallbladder.
World J Surg 15:315-321,1991.
14. Kimura W, Nagai H, Kuroda A, et al:
Clinicopathologic study of asymptomatic gallbladder
carcinoma found at autopsy. Cancer
15. Perpetuo MD, Valdivieso M, Heilbrun
LK, et al: Natural history study of gallbladder
cancer: A review of 36 years experience at MD
Anderson Hospital and Tumor Institute. Cancer
16. Nevin JE, Moran TJ, Kay S, et al: Carcinoma
of the gallbladder: Staging, treatment,
and prognosis. Cancer 37:141, 1976.
17. Greene FL, Page DL, Fleming ID, et al:
Gallbladder cancer, in AJCC Cancer Staging
Manual, 6th ed, pp 155-161. New York,
18. Weinbren K, Mutum SS: Pathological
aspects of cholangiocarcinoma. J Pathol
19. Yen S, Hseieh CC, MacMagon B: Extra-
hepatic bile duct cancer and smoking, beverage
consumption, past medical history and
oral contraceptive use. Cancer 59:2112-2116,
20. Farrell JJ, Chung RT: Carcinoma of the
Gallbladder and Extrahepatic Biliary Tree in
Gastrointestinal Cancers, pp 623-653. New
York, Saunders, 2003.
21. Chijiiwa K, Sumiyoshi K, Nakayama F:
Impact of recent advances in hepatobiliary
imaging techniques on the preoperative diagnosis
of carcinoma of the gallbladder. World J
Surg 15:322-325, 1991.
22. Piehler JM, Crichlow RW: Primary carcinoma
of the gallbladder. Surg Gynecol Obstet
23. Liu KJ, Richter HM, Cho MJ, et al: Carcinoma
involving the gallbladder in elderly
patients presenting with acute cholecystitis.
Surgery 122:748-754, 1997.
24. Rodriguez Otero JC, Rainoldi J, Celoria
G, et al: Acute cholecystitis and cancer of the
gallbladder in the aged. Acta Gastroenterol
Latinoam 15:123-125, 1985.
25. Xiaodong H, Yi X, Chaoji Z, et al: Overview
for the diagnosis and treatment of gallbladder
carcinoma. Chin Med Sci J 15:115-118,
26. Redaelli CA, Buchler MW, Schilling
MK, et al: High coincidence of Mirizzi syndrome
and gallbladder carcinoma. Surgery
27. Thorbjarnarson B, Glenn F: Carcinoma
of the gallbladder. Cancer 12:1009-1013, 1959.
28. Weber SM, DeMatteo RP, Fong Y, et al:
Staging laparoscopy in patients with extrahepatic
biliary carcinoma. Analysis of 100 patients.
Ann Surg 235:392-399, 2002.
29. Callery MP, Strasberg SM, Doherty GM,
et al: Staging laparoscopy with laparoscopic
ultrasonography: Optimizing resectability in
hepatobiliary and pancreatic malignancy. J Am
Coll Surg 185:33-39, 1997.
30. Wibbenmeyer LA, Sharafuddin MJ,
Wolverson MK, et al: Sonographic diagnosis
of unsuspected gallbladder cancer: Imaging
findings in comparison with benign gallbladder
conditions. AJR Am J Roentgenol
31. Boulton RA, Adams DH: Gallbladder
polyps: When to wait and when to act. Lancet
32. Shinkai H, Kimura W, Muto T: Surgical
indications for small polypoid lesions of the
gallbladder. Am J Surg 175:114-117, 1998.
33. Pandey M, Sood BP, Shukla RC, et al:
Carcinoma of the gallbladder: Role of
sonography in diagnosis and staging. J Clin
Ultrasound 28:227-232, 2000.
34. Bach AM, Loring LA, Hann LE, et al:
Gallbladder cancer: Can ultrasonography
evaluate extent of disease? J Ultrasound Med
35. Sugiyama M, Atomi Y, Yamato T: Endoscopic
ultrasonography for differential diagnosis
of polypoid gallbladder lesions: Analysis
in surgical and follow up series. Gut 46:250-
36. Saini S: Imaging of the hepatobiliary
tract. N Engl J Med 336:1889-1894, 1997.
37. Azuma T,Yoshikawa T, Araida T, et al:
Differential diagnosis of polypoid lesions of
the gallbladder by endoscopic ultrasonography.
Am J Surg 181:65-70, 2001.
38. Jacobson BC, Pitman MB, Brugge WR:
EUS-guided FNA for the diagnosis of gallbladder
masses. Gastrointest Endosc 57:251-254,
39. Sugiyama M, Hagi H, Atomi Y, et al:
Diagnosis of portal venous invasion by
pancreatobiliary carcinoma: Value of endoscopic
ultrasonography. Abdom Imaging
40. Kaneko K, Matsuo Y, Mizuguchi M, et
al: Diagnostic imaging of gallbladder carcinomas
with special reference to ultrasonographic
findings. Retrospective review with emphasis
on diagnostic problems in preoperatively undiagnosed
gallbladder carcinomas [Japanese].
Nippon Igaku Hoshasen Gakkai Zasshi Nippon
Acta Radiologica 49:1009-1016, 1989.
41. Kumaran V, Gulati S, Paul B, et al: The
role of dual-phase helical CT in assessing respectability
of carcinoma of the gallbladder.
Eur Radiol 12:1993-1999, 2001
42. Ohtani T, Shirai Y, Tsukada K, et al:
Carcinoma of the gallbladder: CT evaluation
of lymphatic spread. Radiology 189:875-880,
43. Kumar A, Aggarwal S: Carcinoma of the
gallbladder: CT findings in 50 cases. Abdom
Imaging 8:785-790, 1994.
44. Valls C, Guma A, Puig I, et al: Intrahepatic
cholangiocarcinoma: CT evaluation.
Abdom Imaging 25:490-495, 2000.
45. Tillich M, Mischinger HJ, Preisegger
KH, et al: Multi-phasic helical CT in diagnosis
and staging of hilar cholangiocarcinoma.
AJR Am J Roentgenol 171:651-657, 1998.
46. Schwartz LH, Black J, Fong Y, et al:
Gallbladder carcinoma: Findings at MR imaging
with MR cholangiopancreatography. J
Comput Assist Tomogr 26:405-410, 2002.
47. Yeh TS, Jan YY, Tseng JH, et al: Malignant
perihilar biliary obstruction: Magnetic
resonance cholangiopancreatographic findings.
Am J Gastroenterol 95:432-438, 2000.
48. Kim JH, Kim TK, Eun HW, et al: Preoperative
evaluation of gallbladder carcinoma:
Efficacy of combined use of MR imaging, MR
cholangiography, and contrast-enhanced dualphase
three-dimensional MR angiography. J
Magn Resn Imaging 16:676-684, 2002.
49. Strom BL, Maislin G, West SL, et al:
Serum CEA and CA19-9: Potential future diagnostic
or screening tests for gallbladder cancer?
Int J Cancer 45:821-824,1990.
50. Ritts RE Jr, Nagorney DM, Jacobsen DJ,
et al: Comparison of preoperative serum CA
19-9 levels with results of diagnostic imaging
modalities in patients undergoing laparotomy
for suspected pancreatic or gallbladder disease.
Pancreas 9:707-716, 1994.
51. Piehler JM, Crishlow RW: Primary carcinoma
of the gallbladder. Surg Gynecol Obstet
52. Cubertafond P, Gainant A, Cucchiaro G:
Surgical treatment of 724 carcinomas of the
gallbladder. Results of the French Surgical
Association Survey. Ann Surg 219:275-
53. Dawes LG: Gallbladder cancer. Cancer
Treat Res 109:145-155, 2001.
54. Shirai Y, Yoshida K, Tsukuda K, et al:
Inapparent carcinoma of the gallbladder: An
appraisal of a radical second operation after
simple cholecystectomy. Cancer 62:1422-
55. de Aretxabala XA, Roa IS, Burgos LA,
et al: Curative resection in potentially resectable
tumors of the gallbladder. Eur J Surg
56. Tsukuda K, Kurosaki I, Uchida K, et al:
Lymph node spread from carcinoma of the gallbladder.
Cancer 80:661-667, 1997.
57. Yamaguchi K, Tsuneyoshi M: Subclinical
gallbladder carcinoma. Am J Surg 163:382-
58. Aoki T, Tsuchida A, Kasuya K, et al: Is
frozen section effective for diagnosis of unsuspected
gallbladder cancer during laparoscopic
cholecystectomy? Surg Endosc16:197-200,
59. Matsumoto Y, Fujii H, Aoyama H, et al:
Surgical treatment of primary carcinoma of the
gallbladder based on histologic analysis of 48
surgical specimens. Am J Surg 163:239-245,
60. Winston CB, Chen JW, Fong Y, et al:
Recurrent gallbladder carcinoma along
laparoscopic cholecystectomy port tracks: CT
demonstration. Radiology 212:439-444, 1999.
61. Drouard F, Delamarre J, Capron J: Cutaneous
seeding of gallbladder cancer after
laparoscopic cholecystectomy. N Engl J Med
62. Chijiwa K, Nakano K, Ueda J, et al:
Surgical treatment of patients with T2 gallbladder
carcinoma invading the subserosal layer. J
Am Coll Surg 192:600-607, 2001.
63. Fong Y, Jarnaglin W, Blumgart LH: Gallbladder
cancer: Comparison of patients presenting
initially for definitive operation with those
presenting after prior non-curative intervention.
Ann Surg 232:557-569, 2000.
64. Oertli D, Herzog U, Tondelli P: Primary
carcinoma of the gallbladder: Operative experience
during a 16-year period. Eur J Surg
65. Bartlett DL, Fong Y, Fortner JG, et al:
Long-term results after resection of gallbladder
cancer: Implications for staging and management.
Ann Surg 224:639-646, 1996.
66. Wise PE, Shi YY, Washington MK, et
al: Radical resection improves survival for patients
with pT2 gallbladder carcinoma. Am Surg
67. Fong Y, Heffernan N, Blumgart LH:
Gallbladder carcinoma discovered during
laparoscopic cholecystectomy: Agressive reresection
is beneficial. Cancer 82:423-427,
68. Wakai T, Shirai Y, Hatakeyama K: Radical
second resection provided survival benefit
for patients with T2 gallbladder carcinoma first
discovered after laparoscopic cholecystectomy.
World J Surg 26:867-871, 2002.
69. Toyonaga T, Chijiwa K, Nakano K, et
al: Completion radical surgery after cholecystectomy
for accidentally undiagnosed gallbladder
carcinoma. World J Surg 27:266-271, 2003.
70. Gall FP, Kockerling F, Scheele J, et al:
Radical operations for carcinoma of the gallbladder:
Present status in Germany. World J
Surg 15:328-336, 1991.
71. Onoyama H, Yamamoto M, Tseng A, et
al: Extended cholecystectomy for carcinoma
of the gallbladder. World J Surg 19:758-763,
72. Ogura Y, Mizomoto R, Isaji S, et al: Radical
operations for carcinoma of the gallbladder:
Present status in Japan. World J Surg
73. Matsumoto Y, Fujii H, Aoyama H, et al:
Surgical treatment of primary carcinoma of the
gallbladder based on histologic analysis of 48
surgical specimens. Am J Surg 163:239-245,
74. Donahue JH, Nagorney DM, Grant CS,
et al: Carcinoma of the gallbladder—does radical
resection improve outcome. Arch Surg
75. Shirai Y, Yoshida K, Tsukuda K, et al:
Radical surgery for gallbladder carcinoma-
long term results. Ann Surg 216:565, 1992.
76. Chijiiwa K, Noshiro H, Nakano K, et al:
Role of surgery for gallbladder carcinoma with
special reference to lymph node metastasis and
stage using western and Japanese classification
systems. World J Surg 24:1271-1276, 2000.
77. Chamberlain RS, Blumgart LH: Hilar
cholangiocarcinoma: A review and commentary.
J Surg Oncol 7:55-66, 2000.
78. Burke EC, Jarnagin WR, Hochwald SN,
et al: Hilar cholangiocarcinoma: Patterns of
spread, the importance of hepatic resection for
curative operation, and a presurgical clinical
staging system. Ann Surg 228:385-394, 1998.
SearchMedica Search Result
Find peer-reviewed literature and websites for practicing medical professionals