Gallbladder Cancer: Practice Essentials, Background, Pathophysiology
Gallbladder Cancer: Practice Essentials, Background, Pathophysiology
Gallbladder cancer is a rare disease that often arises in the setting of chronic inflammation. The American Cancer Society estimates that approximately 10,000 new cases of gallbladder cancer and other biliary cancers will be diagnosed in 2013.
The image below is a schematic drawing of the extent of lymphadenectomy for gallbladder cancer.
A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.
Signs and symptoms are usually not present until the later stages of gallbladder cancer and may include the following:
Jaundice, anorexia, and weight loss often indicate more advanced disease.
See Clinical Presentation for more detail.
Gallbladder cancer is difficult to detect and diagnose. Signs and symptoms are not usually seen in the early stages of disease and often overlap with the symptoms of gallstones and biliary colic.
Laboratory studies
Some tests that may prove helpful in diagnosing gallbladder cancer include the following:
Imaging studies
Ultrasonography (US) is a standard initial study in patients with right upper quadrant pain. A mass can be identified in 50-75% of patients with gallbladder cancer.
Computed tomography (CT) scans also may be useful in patients with upper abdominal pain and can demonstrate tumor invasion outside of the gallbladder and identify metastatic disease elsewhere in the abdomen or pelvis.
Percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangiography (ERCP) may establish the diagnosis of gallbladder cancer by bile cytology. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive way to take images of the bile ducts using the same type of machine used for standard MRI scans.
Staging
The following stages are used for gallbladder cancer:
See Workup for more detail.
The main types of treatments used for gallbladder cancer include the following:
Although complete surgical resection is the only therapy to afford a chance of cure, en bloc resections of the gallbladder and portal lymph nodes carry a high morbidity and mortality (similar to bile duct carcinoma). Nodal metastases outside of the regional area (ie, porta hepatis, gastrohepatic ligament, retroduodenal area) are not resectable.
See Treatment and Medication for more detail.
Cancers of the biliary tract include cholangiocarcinoma (cancers arising from the bile duct epithelium), ampulla of Vater cancer, and gallbladder cancer. All subtypes of biliary tract cancers are rare and have an overall poor prognosis. They are also difficult to diagnose. These diseases are often discussed together and are mingled in therapeutic trials. However, this leads to significant confusion. Gallbladder cancer is the fifth most common GI cancer in the United States and the most common hepatobiliary cancer. According to 1992-2000 data from the Surveillance, Epidemiology, and End Results (SEER) program, gallbladder cancer accounts for 46% of the biliary tract cancers in the United States.About 20% arise from the extrahepatic biliary tract and 20% arise from the ampulla of Vater.Despite some similarities, gallbladder cancer is a distinct clinical entity and will be discussed exclusively in this article.
Gallbladder cancer arises in the setting of chronic inflammation. In the vast majority of patients (>75%), the source of this chronic inflammation is cholesterol gallstones. The presence of gallstones increases the risk of gallbladder cancer 4- to 5-fold.Other more unusual causes of chronic inflammation are also associated with gallbladder cancer. These causes include primary sclerosing cholangitis, ulcerative colitis,liver flukes, chronic Salmonella typhi and paratyphi infections,and Helicobacter infection.
However, chronic gallbladder inflammation is likely only part of the cause of the malignant transformation seen in gallbladder cancer. Many other factors have been identified. Ingestion of certain medications (eg, oral contraceptives, INH, methyldopa) can increase the risk of gallbladder cancer. Likewise, certain chemical exposures (eg, pesticides, rubber, vinyl chloride) and occupational exposures associated with working in the textile, petroleum, paper mill, and shoemaking industries increase the risk of gallbladder cancer. In addition, exposures through water pollution (organopesticides, eg, dichlorodiphenyltrichloroethane and benzene hexachloride); heavy metals (eg, cadmium, chromium, lead); and radiation exposure (eg, radon in miners) are associated with gallbladder cancer. Obesitymay contribute to gallbladder cancer through its association with gallstones, its association with increased endogenous estrogens, or through the ability of fat cells to secrete alargenumberofinflammatorymediators.
An increased incidence of gallbladder cancer also occurs in hereditary syndromes including Gardner syndrome, neurofibromatosis type I, and hereditary nonpolyposis colon cancer.The role of various oncogenic mutations in gallbladder cancer is an area of active research. For example, a small study of gallbladder cancer from Japan reported an excess risk associated with polymorphism of the cytochrome P450 1A1 gene (CYP1A1), which encodes a protein involved in catalyzing the synthesis of cholesterol and other lipids.Another study looked at polymorphisms within the apolipoprotein B gene.
Wu et al retrospectively analyzed surgical specimens from 97 consecutive gallbladder cancer patients treated in Taiwan between 1993 and 2005 at 2 tertiary medical centers for alpha-methylacyl coenzyme A racemase (AMACR) expression. The authors found that overexpression of this enzyme in gallbladder cancer was associated with a more advanced T stage, a higher histologic grade and vascular invasion. Overexpression of AMACR was also found to be an independent predictor of decreased disease-specific survival in this group of patients.
Abnormal anatomy such as congenital defects with anomalous pancreaticobiliary duct junctions and choledochal cysts increase the risk of gallbladder cancer.The tumor is usually located in the fundus of the gallbladder. Local spread through the gallbladder wall can lead to direct liver invasion, or, if in the opposite direction, leads to transperitoneal spread (20% of patients at presentation), with implants on the liver, on the bowel, and in the pelvis. Tumor may also directly invade other adjacent organs such as the stomach, duodenum, colon, pancreas, and extrahepatic bile duct. At diagnosis, the gallbladder is often replaced or destroyed by the cancer, and approximately 50% of patients have regional lymph node metastases.
See the Gallbladder and Biliary Disease Resource Center for more information about related conditions.
Approximately 10,000 new cases of gallbladder cancer and other biliary cancers are predicted for 2013 according to the American Cancer Society.Gallbladder cancer incidence increases with age and is more common in women. According to the American Cancer Society 2013 statistic projections, the number of new cases of gallbladder and other biliary cancers in the United States in men is predicted to be 4740 and in women is predicted to be 5570. The number of deaths projected for 2013 is 1260 and 21970 for men and women, respectively.
In the United States, incidence varies substantially with racial and ethnic group and sex. Gallbladder cancer rates are the highest among American Indians/Alaska Natives and among white Hispanic peoples. Within both groups, incidence of gallbladder cancer is significantly higher in women.The white Hispanic female incidence rate is 4.2 per 100,000 person-years. The American Indian/Alaskan Native female incidence rate is 4.1 per 100,000 person-years. The corresponding male rates are 1.4 and 3,3 per 100,000 person-years, respectively. The lowest incidence rate for gallbladder cancer is among non-Hispanic white males and is 0.7 per 100,000 person-years.
The incidence of gallbladder cancer rises with age. Seventy-five percent of patients with gallbladder cancer are older than 64 years.In non-Hispanic whites and blacks, the rate of gallbladder cancer rises more slowly than among Hispanic whites and American Indian/Alaskan Natives. The rates for gallbladder cancer are higher among women than men in all age groups.
Overall, the incidence (cases per year) has dropped by more than 50% in the general population since 1973. In Native American women, the incidence has decreased by 70%.
Considerable variation exists in the incidence of gallbladder cancer throughout the world. Areas with the highest incidence rates include India, Korea, Japan, Czech Republic, Slovakia, Spain, Columbia, Chile, Peru, Bolivia, and Ecuador. The high incidence rates reported in Peru and Chile are thought to reflect the Hispanic populations with Indian heritage. Females from India have the highest international rate of gallbladder cancer at between 8.8 per 100,000 person-years and 21.2 per 100,000 person-years.The United Kingdom, Denmark, and Norway have the lowest international incidence rates. Gallbladder cancer is the most common cancer affecting women in Chile.
Survival is correlated with staging based on the American Joint Committee on Cancer (AJCC) tumor, node, metastases (TNM) staging system.Most patients have regional disease or distant metastases at presentation. Therefore, the prognosis in gallbladder disease is poor, with 5-year survival rates of 15-20%.
Patients with stage IA disease (T1N0M0) should be cured with a simple cholecystectomy. In selected surgical series, patients with stage IB (T2N0M0) disease treated with extended cholecystectomy have a 5-year survival rate of 70-90%, and patients with stage IIB (T1-3N1M0) treated with extended cholecystectomy have a 5-year survival of 45-60%. Stage III (T4, any N, M0) gallbladder cancer is generally not surgically curable. The 1-year survival rate for advanced gallbladder cancer is less than 5%. The median survival is 2-4 months.
The SEER registry from 1995-2001 shows 5-year survival rates for localized gallbladder cancer of approximately 40%. The 5-year survival rate for regional disease is listed at approximately 15%, and the 5-year survival rate for distant metastatic disease is reported at less than 10%.However, survival data are variable from institution to institution for each stage.
Unfortunately, only about 10-20% of patients present with tumor confined to the gallbladder wall. At diagnosis, 40-60% of patients have lesions that perforate the gallbladder wall and invade adjacent organs (T3) and 45% of patients have regional lymph node involvement (N1). Approximately 30% of patients present with metastatic disease.
The highest rates of gallbladder cancer in the US are found in the US Native American and Hispanic, especially Mexican, populations.
A substantial female predominance exists worldwide, with female-to-male ratios of approximately 2.5:1 to 3:1.
Gallbladder cancer is most typically diagnosed in the seventh decade of life, with a median age of 62-66 years.
Clinical Presentation
Mary Denshaw-Burke, MD, FACP Clinical Assistant Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Clinical Assistant Professor, Affiliated Clinical Faculty of the Lankenau Institute for Medical Research; Program Director of Hematology/Oncology Fellowship, Education Coordinator for Oncology, Lankenau Medical Center
Mary Denshaw-Burke, MD, FACP is a member of the following medical societies: American College of Physicians
Coauthor(s)
Andrew Scott Kennedy, MD Physician-in-Chief, Radiation Oncology
Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society for Radiation Oncology, Radiological Society of North America, Americas Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology
Jessica Katz, MD, PhD, FACP Medical Director, BMS, Global Clinical Research, Lankenau Medical Center
Jessica Katz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, Phi Beta Kappa, American Society of Clinical Oncology
Disclosure: Received salary from BMS for employment.
Specialty Editor Board
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Benjamin Movsas, MD
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology
Chief Editor
Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center
Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology
References
A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.
Practice Essentials
Gallbladder cancer is a rare disease that often arises in the setting of chronic inflammation. The American Cancer Society estimates that approximately 10,000 new cases of gallbladder cancer and other biliary cancers will be diagnosed in 2013.
The image below is a schematic drawing of the extent of lymphadenectomy for gallbladder cancer.
A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected. Signs and symptoms
Signs and symptoms are usually not present until the later stages of gallbladder cancer and may include the following:
- Jaundice
- Pain above the stomach
- Fever
- Nausea and vomiting
- Bloating
- Lumps in the abdomen
Jaundice, anorexia, and weight loss often indicate more advanced disease.
See Clinical Presentation for more detail.
Diagnosis
Gallbladder cancer is difficult to detect and diagnose. Signs and symptoms are not usually seen in the early stages of disease and often overlap with the symptoms of gallstones and biliary colic.
Laboratory studies
Some tests that may prove helpful in diagnosing gallbladder cancer include the following:
- Liver function tests
- CA 19-9 assay
- Carcinoembryonic antigen (CEA) assay
Imaging studies
Ultrasonography (US) is a standard initial study in patients with right upper quadrant pain. A mass can be identified in 50-75% of patients with gallbladder cancer.
Computed tomography (CT) scans also may be useful in patients with upper abdominal pain and can demonstrate tumor invasion outside of the gallbladder and identify metastatic disease elsewhere in the abdomen or pelvis.
Percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangiography (ERCP) may establish the diagnosis of gallbladder cancer by bile cytology. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive way to take images of the bile ducts using the same type of machine used for standard MRI scans.
Staging
The following stages are used for gallbladder cancer:
- Stage 0 (carcinoma in Situ) : Abnormal cells are found in the inner (mucosal) layer of the gallbladder; these abnormal cells may become cancer and spread into nearby normal tissue [#Keypoint11]
- Stage I : Cancer has formed and has spread beyond the inner (mucosal) layer to a layer of tissue with blood vessels or to the muscle layer
- Stage II : Cancer has spread beyond the muscle layer to the connective tissue around the muscle.
- Stage IIIA : Cancer has spread through the thin layers of tissue that cover the gallbladder and/or to the liver and/or to one nearby organ (eg, stomach, small intestine, colon, pancreas, or bile ducts outside the liver)
- Stage IIIB : Cancer has spread to nearby lymph nodes and [#Section_218] beyond the inner layer of the gallbladder to a layer of tissue with blood vessels or to the muscle layer; or beyond the muscle layer to the connective tissue around the muscle; or through the thin layers of tissue that cover the gallbladder and/or to the liver and/or to one nearby organ
- Stage IVA : Cancer has spread to a main blood vessel of the liver or to 2 or more nearby organs or areas other than the liver. Cancer may have spread to nearby lymph nodes.
- Stage IVB : Cancer has spread to either lymph nodes along large arteries in the abdomen and/or near the lower part of the backbone or to organs or areas far away from the gallbladder.
See Workup for more detail.
Management
The main types of treatments used for gallbladder cancer include the following:
- Surgery
- Radiation therapy
- Chemotherapy
- Palliative therapy
Although complete surgical resection is the only therapy to afford a chance of cure, en bloc resections of the gallbladder and portal lymph nodes carry a high morbidity and mortality (similar to bile duct carcinoma). Nodal metastases outside of the regional area (ie, porta hepatis, gastrohepatic ligament, retroduodenal area) are not resectable.
See Treatment and Medication for more detail.
Background
Cancers of the biliary tract include cholangiocarcinoma (cancers arising from the bile duct epithelium), ampulla of Vater cancer, and gallbladder cancer. All subtypes of biliary tract cancers are rare and have an overall poor prognosis. They are also difficult to diagnose. These diseases are often discussed together and are mingled in therapeutic trials. However, this leads to significant confusion. Gallbladder cancer is the fifth most common GI cancer in the United States and the most common hepatobiliary cancer. According to 1992-2000 data from the Surveillance, Epidemiology, and End Results (SEER) program, gallbladder cancer accounts for 46% of the biliary tract cancers in the United States.About 20% arise from the extrahepatic biliary tract and 20% arise from the ampulla of Vater.Despite some similarities, gallbladder cancer is a distinct clinical entity and will be discussed exclusively in this article.
Pathophysiology
Gallbladder cancer arises in the setting of chronic inflammation. In the vast majority of patients (>75%), the source of this chronic inflammation is cholesterol gallstones. The presence of gallstones increases the risk of gallbladder cancer 4- to 5-fold.Other more unusual causes of chronic inflammation are also associated with gallbladder cancer. These causes include primary sclerosing cholangitis, ulcerative colitis,liver flukes, chronic Salmonella typhi and paratyphi infections,and Helicobacter infection.
However, chronic gallbladder inflammation is likely only part of the cause of the malignant transformation seen in gallbladder cancer. Many other factors have been identified. Ingestion of certain medications (eg, oral contraceptives, INH, methyldopa) can increase the risk of gallbladder cancer. Likewise, certain chemical exposures (eg, pesticides, rubber, vinyl chloride) and occupational exposures associated with working in the textile, petroleum, paper mill, and shoemaking industries increase the risk of gallbladder cancer. In addition, exposures through water pollution (organopesticides, eg, dichlorodiphenyltrichloroethane and benzene hexachloride); heavy metals (eg, cadmium, chromium, lead); and radiation exposure (eg, radon in miners) are associated with gallbladder cancer. Obesitymay contribute to gallbladder cancer through its association with gallstones, its association with increased endogenous estrogens, or through the ability of fat cells to secrete alargenumberofinflammatorymediators.
An increased incidence of gallbladder cancer also occurs in hereditary syndromes including Gardner syndrome, neurofibromatosis type I, and hereditary nonpolyposis colon cancer.The role of various oncogenic mutations in gallbladder cancer is an area of active research. For example, a small study of gallbladder cancer from Japan reported an excess risk associated with polymorphism of the cytochrome P450 1A1 gene (CYP1A1), which encodes a protein involved in catalyzing the synthesis of cholesterol and other lipids.Another study looked at polymorphisms within the apolipoprotein B gene.
Wu et al retrospectively analyzed surgical specimens from 97 consecutive gallbladder cancer patients treated in Taiwan between 1993 and 2005 at 2 tertiary medical centers for alpha-methylacyl coenzyme A racemase (AMACR) expression. The authors found that overexpression of this enzyme in gallbladder cancer was associated with a more advanced T stage, a higher histologic grade and vascular invasion. Overexpression of AMACR was also found to be an independent predictor of decreased disease-specific survival in this group of patients.
Abnormal anatomy such as congenital defects with anomalous pancreaticobiliary duct junctions and choledochal cysts increase the risk of gallbladder cancer.The tumor is usually located in the fundus of the gallbladder. Local spread through the gallbladder wall can lead to direct liver invasion, or, if in the opposite direction, leads to transperitoneal spread (20% of patients at presentation), with implants on the liver, on the bowel, and in the pelvis. Tumor may also directly invade other adjacent organs such as the stomach, duodenum, colon, pancreas, and extrahepatic bile duct. At diagnosis, the gallbladder is often replaced or destroyed by the cancer, and approximately 50% of patients have regional lymph node metastases.
See the Gallbladder and Biliary Disease Resource Center for more information about related conditions.
Frequency
United States
Approximately 10,000 new cases of gallbladder cancer and other biliary cancers are predicted for 2013 according to the American Cancer Society.Gallbladder cancer incidence increases with age and is more common in women. According to the American Cancer Society 2013 statistic projections, the number of new cases of gallbladder and other biliary cancers in the United States in men is predicted to be 4740 and in women is predicted to be 5570. The number of deaths projected for 2013 is 1260 and 21970 for men and women, respectively.
In the United States, incidence varies substantially with racial and ethnic group and sex. Gallbladder cancer rates are the highest among American Indians/Alaska Natives and among white Hispanic peoples. Within both groups, incidence of gallbladder cancer is significantly higher in women.The white Hispanic female incidence rate is 4.2 per 100,000 person-years. The American Indian/Alaskan Native female incidence rate is 4.1 per 100,000 person-years. The corresponding male rates are 1.4 and 3,3 per 100,000 person-years, respectively. The lowest incidence rate for gallbladder cancer is among non-Hispanic white males and is 0.7 per 100,000 person-years.
The incidence of gallbladder cancer rises with age. Seventy-five percent of patients with gallbladder cancer are older than 64 years.In non-Hispanic whites and blacks, the rate of gallbladder cancer rises more slowly than among Hispanic whites and American Indian/Alaskan Natives. The rates for gallbladder cancer are higher among women than men in all age groups.
Overall, the incidence (cases per year) has dropped by more than 50% in the general population since 1973. In Native American women, the incidence has decreased by 70%.
International
Considerable variation exists in the incidence of gallbladder cancer throughout the world. Areas with the highest incidence rates include India, Korea, Japan, Czech Republic, Slovakia, Spain, Columbia, Chile, Peru, Bolivia, and Ecuador. The high incidence rates reported in Peru and Chile are thought to reflect the Hispanic populations with Indian heritage. Females from India have the highest international rate of gallbladder cancer at between 8.8 per 100,000 person-years and 21.2 per 100,000 person-years.The United Kingdom, Denmark, and Norway have the lowest international incidence rates. Gallbladder cancer is the most common cancer affecting women in Chile.
Mortality/Morbidity
Survival is correlated with staging based on the American Joint Committee on Cancer (AJCC) tumor, node, metastases (TNM) staging system.Most patients have regional disease or distant metastases at presentation. Therefore, the prognosis in gallbladder disease is poor, with 5-year survival rates of 15-20%.
Patients with stage IA disease (T1N0M0) should be cured with a simple cholecystectomy. In selected surgical series, patients with stage IB (T2N0M0) disease treated with extended cholecystectomy have a 5-year survival rate of 70-90%, and patients with stage IIB (T1-3N1M0) treated with extended cholecystectomy have a 5-year survival of 45-60%. Stage III (T4, any N, M0) gallbladder cancer is generally not surgically curable. The 1-year survival rate for advanced gallbladder cancer is less than 5%. The median survival is 2-4 months.
The SEER registry from 1995-2001 shows 5-year survival rates for localized gallbladder cancer of approximately 40%. The 5-year survival rate for regional disease is listed at approximately 15%, and the 5-year survival rate for distant metastatic disease is reported at less than 10%.However, survival data are variable from institution to institution for each stage.
Unfortunately, only about 10-20% of patients present with tumor confined to the gallbladder wall. At diagnosis, 40-60% of patients have lesions that perforate the gallbladder wall and invade adjacent organs (T3) and 45% of patients have regional lymph node involvement (N1). Approximately 30% of patients present with metastatic disease.
Race
The highest rates of gallbladder cancer in the US are found in the US Native American and Hispanic, especially Mexican, populations.
Sex
A substantial female predominance exists worldwide, with female-to-male ratios of approximately 2.5:1 to 3:1.
Age
Gallbladder cancer is most typically diagnosed in the seventh decade of life, with a median age of 62-66 years.
Clinical Presentation
Mary Denshaw-Burke, MD, FACP Clinical Assistant Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Clinical Assistant Professor, Affiliated Clinical Faculty of the Lankenau Institute for Medical Research; Program Director of Hematology/Oncology Fellowship, Education Coordinator for Oncology, Lankenau Medical Center
Mary Denshaw-Burke, MD, FACP is a member of the following medical societies: American College of Physicians
Coauthor(s)
Andrew Scott Kennedy, MD Physician-in-Chief, Radiation Oncology
Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society for Radiation Oncology, Radiological Society of North America, Americas Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology
Jessica Katz, MD, PhD, FACP Medical Director, BMS, Global Clinical Research, Lankenau Medical Center
Jessica Katz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, Phi Beta Kappa, American Society of Clinical Oncology
Disclosure: Received salary from BMS for employment.
Specialty Editor Board
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Benjamin Movsas, MD
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology
Chief Editor
Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center
Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology
References
- What are the key statistics about gallbladder cancer?. American Cancer Society. Available at http://www.cancer.org/cancer/gallbladdercancer/detailedguide/gallbladder-key-statistics. Accessed: August 21, 2013.
- National Cancer Institute. Cancer Statistics. SEER Surveillance, Epidemiology, and End Results. Available at http://seer.cancer.gov/. Accessed: 2008.
- Schottenfeld D and Fraumeni J. Cancer. Epidemiology and Prevention. 3rd. Oxford University Press; 2006. 787-800.
- Lowenfels AB, Maisonneuve P, Boyle P, Zatonski WA. Epidemiology of gallbladder cancer. Hepatogastroenterology. 1999 May-Jun. 46(27):1529-32. [Medline].
- Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer. 2001 Feb 15. 91(4):854-62. [Medline].
- Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006 Apr 1. 118(7):1591-602. [Medline].
- Matsukura N, Yokomuro S, Yamada S, Tajiri T, Sundo T, Hadama T, et al. Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. Jpn J Cancer Res. 2002 Jul. 93(7):842-7. [Medline].
- Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003 Apr 24. 348(17):1625-38. [Medline].
- Tsuchiya Y, Sato T, Kiyohara C, Yoshida K, Ogoshi K, Nakamura K. Genetic polymorphisms of cytochrome P450 1A1 and risk of gallbladder cancer. J Exp Clin Cancer Res. 2002 Mar. 21(1):119-24. [Medline].
- Singh MK, Pandey UB, Ghoshal UC, Srivenu I, Kapoor VK, Choudhuri G. Apolipoprotein B-100 XbaI gene polymorphism in gallbladder cancer. Hum Genet. 2004 Feb. 114(3):280-3. [Medline].
- Wu LC, Chen LT, Tsai YJ, Lin CM, Lin CY, Tian YF, et al. Alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confers an independent prognostic indicator. J Clin Pathol. 2012 Apr. 65(4):309-14. [Medline].
- Benjamin IS. Biliary cystic disease: the risk of cancer. J Hepatobiliary Pancreat Surg. 2003. 10(5):335-9. [Medline].
- Hu B, Gong B, Zhou DY. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study. Gastrointest Endosc. 2003 Apr. 57(4):541-5. [Medline].
- American Joint Committee on Cancer. Staging Resources. AJCC Staging Resources. Available at http://www.cancerstaging.org/staging/index.html. Accessed: 2008.
- Mohandas KM, Swaroop VS, Gullar SU, Dave UR, Jagannath P, DeSouza LJ. Diagnosis of malignant obstructive jaundice by bile cytology: results improved by dilating the bile duct strictures. Gastrointest Endosc. 1994 Mar-Apr. 40(2 Pt 1):150-4. [Medline].
- Gupta P, Chitalkar P, Sen A, et al. Combination of gemcite and cisplatin chemotherapy in unresectable gallbladder cancer. J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007. 25, No18s (June 20 Supplement):15166.
- Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010 Oct 20. 28(30):4581-6. [Medline].
- Valle JS, Wasan HS, Palmer DD, et al. Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial (the UK ABC-02 trial). J Clin Oncol. 2009 (suppl; abstr 4503). 27:15s. [Full Text].
- Iqbal S, Rankin C, Lenz HJ, et al. A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202. Cancer Chemother Pharmacol. 2011 Dec. 68(6):1595-602. [Medline].
- Malka D, Trarbach T, Fartoux L, et al. A multicenter, randomized phase II trial of gemcitabine and oxaliplatin (GEMOX) alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: interim analysis of the BINGO trial. J Clin Oncol. 2009. 27(15 Suppl):Abstr 4520.
- Gruenberger B, Schueller J, Heubrandtner U, et al. Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol. 2010 Dec. 11(12):1142-8. [Medline].
- Gallardo J, Rubio B, Ahumada M, et al. Therapy for advanced gallbladder cancer: Improving survival. J Clin Oncol. 2008 (May 20 suppl; abstr 15566). 26:[Full Text].
- Dixon E, Vollmer CM Jr, Sahajpal A, et al. An aggressive surgical approach leads to improved survival in patients with gallbladder cancer: a 12-year study at a North American Center. Ann Surg. 2005 Mar. 241(3):385-94. [Medline]. [Full Text].
- Ito H, Ito K, D'Angelica M, Gonen M, Klimstra D, Allen P. Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment. Ann Surg. 2011 Aug. 254(2):320-5. [Medline].
- Jensen EH, Abraham A, Jarosek S, Habermann EB, Al-Refaie WB, Vickers SA, et al. Lymph node evaluation is associated with improved survival after surgery for early stage gallbladder cancer. Surgery. 2009 Oct. 146(4):706-11; discussion 711-3. [Medline].
- Abdalla EK, Vauthey JN. Biliary tract cancer. Curr Opin Gastroenterol. 2001 Sep. 17(5):450-7. [Medline].
- American Cancer Society. Facts and Figures. Available at www.cancer.org/docroot/stt/stt_0.asp.. Accessed: March 29, 2008.
- Barone JE. Gallbladder Cancer Outcomes May Improve With Radiation. Available at http://www.medscape.com/viewarticle/809215. Accessed: August 20, 2013.
- Bartlett DL, Ramanathan RK, Ben-Josef E. Cancer of the Biliary Tree. DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008. 1156-86.
- Benson AB, Curley SA, Langnas AN. Hepatobiliary Cancers. NCCN Clinical Practice Guidelines in Oncology. 2005. 1:
- Chang BB, Thomas MB, Wolff RA. Pancreatic Cancer and Hepatobiliary Malignancies. Kantarjian HM, Wolff RA, Koller CA. MD Anderson Manual of Medical Oncology. 2nd ed. New York, NY: McGraw-Hill Medical Publishing Division; 2006. 383-393.
- Czito BG, Hurwitz HI, Clough RW, Tyler DS, Morse MA, Clary BM. Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys. 2005 Jul 15. 62(4):1030-4. [Medline].
- Dawes LG. Gallbladder cancer. Cancer Treat Res. 2001. 109:145-55. [Medline].
- Dingle BH, Rumble RB, Brouwers MC,. The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer: a systematic review. Can J Gastroenterol. 2005 Dec. 19(12):711-6. [Medline].
- Douglas HO, Tepper JE, Leichman L. Neoplasms of the Gallbladder. Holland JF, et al, eds. Cancer Medicine. 3rd ed. Philadelphia, Pa: Lea & Febiger; 1993. 1448-1454.
- Doval DC, Sekhon JS, Gupta SK, Fuloria J, Shukla VK, Gupta S. A phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer. Br J Cancer. 2004 Apr 19. 90(8):1516-20. [Medline].
- Gallardo JO, Rubio B, Fodor M, Orlandi L, Yanez M, Gamargo C. A phase II study of gemcitabine in gallbladder carcinoma. Ann Oncol. 2001 Oct. 12(10):1403-6. [Medline].
- Gunderson LL, Haddock MG, Foo ML, Todoroki T, Nagorney D. Conformal irradiation for hepatobiliary malignancies. Ann Oncol. 1999. 10 Suppl 4:221-5. [Medline].
- Gunderson LL, Willett CG. Pancreas and Hepatobiliary Tract. Perez CA, Brady LW, eds. Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1997. 1467-1488.
- Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH, Fong Y. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 2004 Mar. 11(3):310-5. [Medline].
- Houry S, Haccart V, Huguier M, Schlienger M. Gallbladder cancer: role of radiation therapy. Hepatogastroenterology. 1999 May-Jun. 46(27):1578-84. [Medline].
- Hyder O, Dodson RM, Sachs T, Weiss M, Mayo SC, Choti MA, et al. Impact of adjuvant external beam radiotherapy on survival in surgically resected gallbladder adenocarcinoma: A propensity score-matched Surveillance, Epidemiology, and End Results analysis. Surgery. 2013 Jul 19. [Medline].
- Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg. 2004 Feb. 8(2):183-90. [Medline].
- Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. 2005 Apr 1. 23(10):2332-8. [Medline].
- Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. 2005 Apr 1. 23(10):2332-8. [Medline].
- Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys. 2002 Jan 1. 52(1):167-75. [Medline].
- Lillemoe K, Kennedy AS, Picus J. Clinical Management of Carcinoma of the Biliary Tree. Kelsen, et al, eds. Principles and Practice of Gastrointestinal Oncology. Philadelphia, Pa: JB Lippincott Co; 2000. 1:
- Lotze MT, Flickinger JC, Carr BI. Hepatobiliary Neoplasms. Devita VT, Hellman S, Rosenberg SA, eds. Principles and Practice of Oncology. 4th ed. Philadelphia, Pa: JB Lippincott Co; 1993. 883-907.
- Malik IA, Aziz Z, Zaidi SH, Sethuraman G. Gemcitabine and Cisplatin is a highly effective combination chemotherapy in patients with advanced cancer of the gallbladder. Am J Clin Oncol. 2003 Apr. 26(2):174-7. [Medline].
- Malka D, Boige V, Dromain C, Debaere T, Pocard M, Ducreux M. Biliary tract neoplasms: update 2003. Curr Opin Oncol. 2004 Jul. 16(4):364-71. [Medline].
- Scheingraber S, Justinger C, Stremovskaia T, et al. The standardized surgical approach improves outcome of gallbladder cancer. World J Surg Oncol. 2007. 5:55. [Medline].
- Stuver S, Trichopoulos D. Cancer of the Liver and Biliary Tract. Adami H, Hunter D, Trichopoulos D, eds. Textbook of Cancer Epidemiology. 2nd ed. New York, NY: Oxford University Press; 2008. 308-332/12.
- Taner CB, Nagorney DM, Donohue JH. Surgical treatment of gallbladder cancer. J Gastrointest Surg. 2004 Jan. 8(1):83-9; discussion 89. [Medline].
A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.
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