Gallbladder cancer explained

Gallbladder cancer
Field:Gastroenterology Hepatology Oncology
Symptoms:Abdominal pain, Bloating, Fever, Unexplained weight loss, Nausea, Yellowing of the skin, although some people may have no symptoms[1]
Complications:Cancer spreading to other parts of the body
Onset:Above 65 years old[2]
Types:Adenocarcinoma (most common), Squamous cell carcinoma (more rare)[3]
Causes:Unknown
Risks:History of Gallstones and other Gallbladder diseases
Diagnosis:Blood tests, medical imaging, examination of the Bile duct
Differential:Other types of cancer in the Digestive system
Treatment:Surgery, Radiation therapy, Chemotherapy[4]
Prognosis:Five-year survival rate ~19% (USA) (January, 2020)[5]
Frequency:~3,700 cases per year (USA)[6]
Deaths:~2,000 deaths per year (USA)

Gallbladder cancer is a relatively uncommon cancer, with an incidence of fewer than 2 cases per 100,000 people per year in the United States.[7] It is particularly common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics.[8] If it is diagnosed early enough, it can be cured by removing the gallbladder, part of the liver and associated lymph nodes. Most often it is found after symptoms such as abdominal pain, jaundice and vomiting occur, and it has spread to other organs such as the liver.

It is a rare cancer that is thought to be related to gallstones building up, which also can lead to calcification of the gallbladder, a condition known as porcelain gallbladder. Porcelain gallbladder is also rare. Some studies indicate that people with porcelain gallbladder have a high risk of developing gallbladder cancer, but other studies question this. The outlook is poor for recovery if the cancer is found after symptoms have started to occur, with a 5-year survival rate of close to 3%.

Signs and symptoms

Early symptoms mimic gallbladder inflammation due to gallstones. Later, the symptoms may be that of biliary and stomach obstruction.

Of note, Courvoisier's law states that in the presence of a palpably enlarged gallbladder which is nontender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones. This implicates possible malignancy of the gallbladder or pancreas, and the swelling is unlikely due to gallstones due to the chronic inflammation associated with gallstones leading to a shrunken, non-distensible gallbladder. However, the original observations of Ludwig Georg Courvoisier, published in Germany in 1890, were not originally cited as a law, and no mention of malignancy or pain (tenderness) was made. These points are commonly misquoted or confused in the medical literature.[9]

Risk factors

Diagnosis

Early diagnosis is not generally possible. People at high risk, such as women or Native Americans with gallstones, are evaluated closely. Transabdominal ultrasound, CT scan, endoscopic ultrasound, MRI, and MR cholangio-pancreatography (MRCP) can be used for diagnosis. A large number of gallbladder cancers are found incidentally in patients being evaluated for cholelithiasis, or gallstone formation, which is far more common.[14] A biopsy is the only certain way to tell whether or not the tumorous growth is malignant.[15]

Differential diagnosis

Xanthogranulomatous cholecystitis (XGC) is a rare form of gallbladder disease which mimics gallbladder cancer although it is not cancerous.[16] [17] It was first discovered and reported in the medical literature in 1976 by J.J. McCoy Jr., and colleagues.[16] [18]

Treatment

If detected early in a stage where it has not spread, gallbladder cancer can be treated by surgery. Surgery for gallbladder cancer is called radical cholecystectomy or extended cholecystectomy.[19] It entails the removal of gallbladder along with adequate removal of its liver bed to the healthy tissue. The lymph nodes in the vicinity are also removed. Sometimes removal of a large part of the liver called hepatectomy is required to completely remove the tumor. The bile duct if involved also needs to be removed. However, with gallbladder cancer's extremely poor prognosis, most patients will die within a year of surgery. If surgery is not possible, endoscopic stenting or percutaneous transhepatic biliary drainage (PTBD) of the biliary tree can reduce jaundice and a stent in the stomach may relieve vomiting. Chemotherapy and radiation may also be used with surgery. If gallbladder cancer is diagnosed after cholecystectomy for stone disease (incidental cancer), re-operation to remove part of liver and lymph nodes is required in most cases. When it is done as early as possible, patients have the best chance of long-term survival and even cure.[20]

Epidemiology

Most tumors are adenocarcinomas, with a small percent being squamous cell carcinomas.

Prognosis

The prognosis still remains poor. The cancer commonly spreads to the liver, bile duct, stomach, and duodenum.[24]

Research

A better understanding of the biology of biliary tract cancers, including gallbladder cancer, is being achieved by advances in genomic profiling.[25] This research is providing insight into deficiencies in the tumor cell's ability to accurately repair damages in their own DNA. The tumors in about 25% of patients with biliary tract cancer have some form of DNA damage repair deficiency.[25] Knowledge of such deficiencies can be exploited to potentially increase response to treatment strategies that are currently available such as chemotherapy, radiotherapy, or immunotherapy.

External links

Notes and References

  1. Web site: Gallbladder cancer - Symptoms and causes. Mayo Clinic.
  2. Web site: Risk Factors for Gallbladder Cancer. www.cancer.org.
  3. Web site: Types of gallbladder cancer | Gallbladder cancer | Cancer Research UK.
  4. Web site: Gallbladder cancer - Diagnosis and treatment - Mayo Clinic. Mayo Clinic.
  5. Web site: Gallbladder Cancer - Statistics. 25 June 2012.
  6. Gallbladder Cancer Incidence and Mortality, United States 1999–2011. 10.1158/1055-9965.EPI-15-0199. 2015. Henley. S. Jane. Weir. Hannah K.. Jim. Melissa A.. Watson. Meg. Richardson. Lisa C.. Cancer Epidemiology, Biomarkers & Prevention. 24. 9. 1319–1326. 26070529. 886615.
  7. CDC - Gallbladder Cancer Incidence and Death Rates. 2018-09-27. Cancer Epidemiology, Biomarkers & Prevention. 24. 9. 1319–1326. 10.1158/1055-9965.EPI-15-0199. en-us. 2018-12-10. Henley. S. Jane. Weir. Hannah K.. Jim. Melissa A.. Watson. Meg. Richardson. Lisa C.. 26070529. 886615.
  8. Kapoor VK, McMichael AJ . Gallbladder cancer: an 'Indian' disease . Natl Med J India . 16 . 4 . 209–13 . 2003 . 14606770 .
  9. Fitzgerald . J Edward F . White Matthew J . Lobo Dileep N . Apr 2009 . Courvoisier's gallbladder: law or sign? . . 33 . 4 . 886–91 . United States. 0364-2313. 19190960 . 10.1007/s00268-008-9908-y . 21799234 .
  10. Folseraas. T. Boberg. KM. Cancer Risk and Surveillance in Primary Sclerosing Cholangitis. Clinics in Liver Disease. February 2016. 20. 1. 79–98. 10.1016/j.cld.2015.08.014. 26593292.
  11. Book: 10.1007/978-94-007-2585-0_5. Salmonella typhi and Gallbladder Cancer. Bacteria and Cancer. 117–137. 2012. Ferreccio . C. . 978-94-007-2584-3.
  12. Srivastava K, Srivastava A, Sharma KL, Mittal B. Candidate gene studies in gallbladder cancer: a systematic review and meta-analysis. Mutat Res. 2011 Jul–Oct;728(1–2):67–79.
  13. Web site: Gallbladder Cancer: Symptoms, Causes & Treatment Dr. Nikhil Agrawal. 2020-10-11. Dr.Nikhil Agrawal. en.
  14. Duffy. A.. Capanu. M.. Abou-Alfa. G. K.. Huitzil. D.. Jarnagin. W.. Fong. Y.. D'Angelica. M.. Dematteo. R. P.. Blumgart. L. H.. 2008-12-01. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). Journal of Surgical Oncology. 98. 7. 485–489. 10.1002/jso.21141. 1096-9098. 18802958. 43595860.
  15. Web site: Tests for gallbladder cancer. Cancer Research UK. live. https://web.archive.org/web/20111010001647/http://cancerhelp.cancerresearchuk.org/type/gallbladder-cancer/diagnosis/tests-for-gallbladder-cancer. 10 October 2011. 17 September 2012.
  16. Makino I, Yamaguchi T, Sato N, Yasui T, Kita I . Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma with a false-positive result on fluorodeoxyglucose PET . World J. Gastroenterol. . 15 . 29 . 3691–3 . August 2009 . 19653352 . 2721248 . 10.3748/wjg.15.3691 . free .
  17. Rao RV, Kumar A, Sikora SS, Saxena R, Kapoor VK . Xanthogranulomatous cholecystitis: differentiation from associated gall bladder carcinoma . Trop Gastroenterol . 26 . 1 . 31–3 . 2005 . 15974235 .
  18. McCoy JJ, Vila R, Petrossian G, McCall RA, Reddy KS . Xanthogranulomatous cholecystitis. Report of two cases . J S C Med Assoc . 72 . 3 . 78–9 . March 1976 . 1063276 .
  19. Web site: Cholecystectomy: Approaches and Technique. The Lecturio Medical Concept Library . 8 July 2021.
  20. Web site: Gallbladder Cancer Treatment (PDQ®)–Patient Version. National Cancer Institute. 24 March 2004. 8 July 2021.
  21. Carriaga. M. T.. Henson. D. E.. 1995-01-01. Liver, gallbladder, extrahepatic bile ducts, and pancreas. Cancer. 75. 1 Suppl. 171–190. 0008-543X. 8000995. 10.1002/1097-0142(19950101)75:1+<171::AID-CNCR2820751306>3.0.CO;2-2. free.
  22. Hsing AW, Gao YT, Han TQ, etal . Gallstones and the risk of biliary tract cancer: a population-based study in China . Br. J. Cancer . 97 . 11 . 1577–82 . December 2007 . 18000509 . 2360257 . 10.1038/sj.bjc.6604047 .
  23. National Cancer Registry Programme (2013).Three-year report of population based cancer registries:2009-2011. NCDIR-ICMR, Bangalore.
  24. Goetze . T.O . 21 November 2015 . Gallbladder carcinoma: Prognostic factors and therapeutic options . World Journal of Gastroenterology . 21. 43 . 12211–12217 . 10.3748/wjg.v21.i43.12211 . 26604631 . 4649107 . free .
  25. Lamarca A, Barriuso J, McNamara MG, Valle JW. Biliary Tract Cancer: State of the Art and potential role of DNA Damage Repair. Cancer Treat Rev. 2018 Nov;70:168-177. doi: 10.1016/j.ctrv.2018.09.002. Epub 2018 Sep 8. PMID 30218788

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