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Gall Bladder Cancer as a “Silent Killer”


About Author: Rinki Verma (Research fellow)
Institute of Medical science (CEMS)
Banaras Hindu University
Varanasi - 221005

Abstract:
Gallbladder cancer is a comparatively rare cancer and has poor outcome due to their anatomy and location. It has peculiar geographical distribution being 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 (Kapoor VK, McMichael AJ ,2003. It is fifteen uncommon cancers in the world with high mortality rate. The diagnosis is made very late due to its silent course. The majority of patients have advanced disease at the time of presentation which carries a poor prognosis. The modes of spread of gall bladder carcinoma are direct, lymphatic, vascular, neural, intraperitoneal and intraductal. Ultra Sound, CT and MRI are helpful in diagnosis and staging of the disease. Surgery remains the mainstay of treatment and chemotherapy has a very limited role.

Reference Id: PHARMATUTOR-ART-1194

Introduction:
Gall bladder cancer (GBC) is an uncommon but highly fatal malignancy; fewer than 5000 new cases are diagnosed each year in the United States. The majority are found incidentally in patients undergoing exploration for cholelithiasis; a tumor will be found in 1 to 2 percent of such cases [Carriaga M.,et alr 1995; Hamrick RE Jr,et al 1982; Yamaguchi K, et al 1996;A prospective analysis of 1518 laparoscopic cholecystectomies. The Southern Surgeons Club. N Engl J Med 1991]. The gallbladder is a pear-shaped (fig.1) organ that lies just under the liver in the upper abdomen. The gallbladder stores bile, a fluid made by the liver to digest fat. When food is being broken down in the stomach and intestines, bile is released from the gallbladder through a tube called the common bile duct, which connects the gallbladder and liver to the first part of the small intestine.The wall of the gallbladder has 3 main layers of tissue. Mucosal (innermost) layer, Muscularis (middle, muscle) layer and  Serosal (outer) layer.  Between these layers is supporting connective tissue. Primary gallbladder cancer starts in the innermost layer and spreads through the outer layers as it grows.The poor prognosis associated with GBC is thought to be related to advanced stage at diagnosis, which is due both to the anatomic position of the gallbladder, and the vagueness and nonspecificity of symptoms

   
Figure-. Showing the development of tumor blocks in the Gall bladder.

Epidemiology:
Globally, there is a prominent geographic variability in GBC incidence that correlates with the prevalence of cholelithiasis. High rates of GBC are seen in South American countries, particularly Chile, Bolivia, and Ecuador, as well as some areas of India, Pakistan, Japan and Korea [Strom BL et al 1995 & Randi G et al 2006]. In Chile, mortality rates from GBC are the highest in the world. These populations all share a high prevalence of gallstones and/or salmonella infection, both recognized risk factors for GBC [Lazcano-Ponce EC et al 2001; Wistuba II et a 2004 & Miquel JF et al 1998]. Both genetic factors and socioeconomic issues that delay or prevent access to cholecystectomy for gallstones are thought to be contributory [Serra I , 1996 & Randi G et al 2009]. (See 'Risk factors' below and 'Molecular pathogenesis' below.) North America is considered a low incidence area. In the United States, GBC is the most common cancer arising in the biliary tract [Carriaga M.,et alr 1995]. Estimates from the SEER (Surveillance, Epidemiology and End Results) database reveal an incidence of 1 to 2 cases per 100,000 population in the US [Carriaga M.,et alr 1995]. In contrast to the general population, GBC is the most common malignancy in both Southwestern Native Americans and in Mexican Americans [Diehl AK 1980].The incidence of gall bladder disease is high among people living near the Ganga and its tributaries, says the largest-ever study of the local population over six years. In this region the prevalence. Recent study  shows the high rate of gall bladder in the Bihar , located near the river Gandak (journal of the International Hepato-Pancreato-Biliary Association).About 20,000 and 30,000 people develop gall bladder disease each year because of the environmental factors in Uttar Pradesh and Bihar.In addition to geography, there are also age, race, and gender-related differences in the incidence of GBC. Incidence steadily increases with age, women are affected two to six times more often than men [Duffy A  et al  2008 &Konstantinidis IT et al 2009], and GBC is more common in Caucasians than in blacks [Scott TE 1999]. At least some data suggest that the incidence is increasing in younger individuals [Kiran RP 2007].

Risk factor  and Causing symptom:
Inspite of high frequency and grave mortality risk factors for this disease have not been clearly understood (Adson MA 1973). Because of their elevated humanity rate researches found some risk factor such as gallstones, duration of disease, dietary factors including vitamin intake and smoking. Numerous individuals suggested that  the reality may be a corollary of the older age of the population (Khan ZR 1999). Even though, it occurs most often in people with porcelain gall bladders. Due to recurring inflammation and from passing gallstones leads to calcification of the gall bladder.
                Gallstones are the most common risk factor for gallbladder cancer because of these  are so  hard, rock-like formations of cholesterol and other substances that form in the gallbladder and can cause chronic inflammation ultimately developed the growth of undefined cells . Approximately, 3 out of 4 people with gallbladder cancer have gallstones but this is quite rare. Another second condition is, Porcelain gallbladder in which the wall of the gallbladder becomes covered with calcium deposits. It sometimes occurs after long-term inflammation of the gallbladder and this have high possibility to . developing gallbladder cancer .
        According to the report, gallbladder cancer occurs more than twice as often in women. Gallstones and gallbladder inflammation are the 2 important risk factors for gallbladder cancer and are also much more common in women than men. Gallbladder cancer can occur in younger people, but it’s seen mainly in older people. The average age of people when they are diagnosed is 73. Almost 3 out of 4 people with gallbladder cancer are older than age 65 when it is found. Studies also suggested the Obesity or overweight or obese than people without this disease a  risk factor for gallstones, and  link to cancer. Most important risk factor are , Choledochal cysts are bile-filled sacs that are connected to the tube that carries bile from the liver and gallbladder to the small intestine. The cysts can grow over time and may contain as much as 1 to 2 quarts of bile. The cells lining the sac often have areas of pre-cancerous changes, which increase a person's risk for developing gallbladder cancer.
             The pancreas is another organ that releases fluids through a duct into the small intestine to help digestion. This duct normally meets up with the common bile duct just as it enters the small intestine. Due to abnormalities in the bile duct that allow juice from the pancreas to reflux (flow backward) into the bile ducts. This backward flow also prevents the bile from being emptied through the bile ducts as quickly as normal. Abnormalities  passing of bile involved in the DNA damage and initiate the uncontrolled growth of cell.
            A gallbladder polyp is a growth that bulges out from the surface of the inner gallbladder wall. Some polyps are formed by cholesterol deposits in the gallbladder wall. Others may be small tumors (either cancerous or benign) or may be caused by inflammation. Polyps larger than 1 centimeter (almost a half inch) are more likely to be cancerous, so doctors often advise removing the gallbladder in patients with gallbladder polyps that size or larger. Typhoid, chronically infected with salmonella and those who are carriers of the disease having more chance to develop gallbladder cancer than those not infected. But typhoid is rare in the United States. Some chemical have been identified as risk factor for gallbladder cancer nitrosamines, rubber and textile industries but still is not common and clear.
         We know that most of cancers are hereditary but gallbladder cancers are not found in people with a family history of the disease. A history of gallbladder cancer in the family seems to increase a person's chances of developing this cancer, but the risk is still low because this is a rare disease.

Gall bladder act as a silent killer but some condition which are identified as causing symptom of  this carcinoma such as:

  • Jaundice (yellowing of the skin and whites of the eyes).
  • Pain above the stomach.
  • Fever.
  • Nausea and vomiting.
  • Bloating.
  • Lumps in the abdomen. One of the most common and late development is Jaundice  and the other symptoms have been present for a long time. Itching may result from the buildup in the skin of a derivative of bile, bilirubin, which turns the skin yellow. This symptom usually reflects advanced disease.

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