Immunotherapy: A Modern Treatment For Cancer
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Gallbladder is an important organ of the digestive system. It is located posterior to the liver, about 3-4 inches long and acts as a storage unit of bile. Bile is a yellowish-green fluid produced by the liver that is vital for the digestion of fats or lipids. The gall bladder concentrates and holds the bile, till it is needed for fat digestion, upon receiving signal for fat metabolism, the gall bladder releases the bile into the duodenum.
The wall of the gall bladder has three layers, the innermost mucosal layer, the middle layer or the muscularis and the outer serosa. Primary gallbladder cancer originates in the inner layer and spreads into the outer layers as it grows. It may also spread beyond that to affect the liver, bile duct, and stomach. 85% of GBCs are adenocarcinoma; the remaining 15% are rare types of GBC. There are three types of adenocarcinoma – Non-papillary adenocaricoma, papillary adenocarcinoma and mucinous adenocarcinoma. About 75% of all adenocarcinomas are non-papillary adenocarcinomas. The other types of GBC includes – Squamous cell cancers, Adenosquamous GBC, small cells GBC, Sarcoma of gall bladder, NET (Neuroendocrinal tumor), iInteresting facts about Gall bladder cancer:
1. Gallbladder cancer is a relatively rare cancer among the GI (gastrointestinal) cancers. Yet, it constitutes about 80-90% of the cancers that affect the biliary tracts
2. It is a malignancy with a marked ethnic and geographical variation (7/100,000 cases in India) versus the western countries (1.5/100,000 in USA). With-in India, it is more prevalent in the north and the northeastern states (Bihar, Orissa, West Bengal)
3. Women are twice more likely to be affected by gall bladder cancer than men and the frequency increases in women above 65 years of age.
4. GBC (gall bladder cancer) is the most aggressive of the biliary cancer, with poor prognosis. The survival rate of patients with GBC in advanced stage is a dismal 6 months. The 5 year survival rate is less than 5% in stage IV cancer.
5. Gallbladder cancer incidence is low in south India and its association with gall stones is also low.
6. Currently there are no biochemical tests to detect GBC
One the challenges for early detection of GBC, is that the symptoms of gall bladder cancer can be vague and may mimic other conditions such as cholelithaisis and cholecystitis. There are cases where GBC has been incidentally diagnosed during a laparotomy – a surgical incision into the abdominal cavity in preparation of a major surgery. By the time it presents in a late stage, the disease is characterized by local invasion, extensive regional lymph node metastasis and distant metastasis or spread to other organs. GBC has a high propensity to implant or seed onto peritoneum, laparoscopic or laparotomy wounds. Advanced stage GBC may present with symptoms such as:
1. Jaundice – yellowing of the skin and whites of the eyes
2. Steady abdominal pain, especially in the upper right region
3. Nausea, bile, and vomiting
6. A lump in the abdomen
8. Loss of appetite
10. Unnatural weight loss
Diagnostic tests: Currently there are no biochemical tests for early detection of GBC. One of the first modalities for detection is a transabdominal ultrasound (USG). However USG is user dependent and subtle changes in the gall bladder could be missed. Imaging tests provide better resolution and helpful in identifying structural changes to gall bladder induced by the tumor, such as mass, polyps, parietal thickening etc. Imaging modalities such as CT, PET, MRI, ERCP (endoscopic retrograde cholangiopancreatography) MRCP (magnetic resonance Cholangiopancreatography are used for detection as well as staging of the tumor. Often laparoscopic biopsy is obtained instead of FNAC (fine needle aspiration) in case of GBC as it has a high propensity for seeding. Information on the stage and the pathology of the tumor will be critical in addressing the next steps of treatment in GBC.
It is important to remember that people with gallstones need to be monitored closely for gallbladder cancer.
The following factors can raise a person’s risk of developing gallbladder cancer:
1. Age – Gallbladder cancer usually occurs in older people, over the age of 45 years
2. Gender – The cancer has shown strong links to the female gender
3. Ethnicity – Certain ethnic groups have been observed to be more susceptible to gallbladder cancer. These include Mexican Americans, Native Americans, Indians, Pakistan is, people in certain regions of East Europe, East Asia and South America.
4. Gallstones – This is considered to be the most common risk factor of gallbladder cancer
5. Gallbladder polyp – A type of growth that sometimes forms when small gallstones get embedded in the gallbladder wall
6. Poor lifestyle– Smoking, being overweight, imbalanced diet, and suffering from chronic infections of gallbladder
GBC has a poor outcome and prognosis. When detected in an early stage, complete surgical resection of gall bladder is the best option. Surgical management of GBC is dependent on the extent of spread of GBC (to liver, intra-peritoneal spread, lymphatic and vascular invasion), Depending on the stage of the tumor, the primary treatment may involve simple cholecystectomy or radical surgery, involving removal of gall bladder, liver resection (hepatectomy) or removal of sections of liver, and lymph nodes. If there is a pancreatic or deudenal involvement, additional resection involving pancreas and the deuodenum may be performed (Hepato-pancreaticoduodenectomy, excision of duodenum wall in localized involvement, Pancreaticoduodenectomy for local and peri pancreatic lymph spread).
Radiation therapy modalities including external beam therapy, intraoperative radiotherapy and brachytherapy with or without chemotherapy has been used for adjuvant treatment of GBCvi. Adjuvant treatment is often used in all patients diagnosed post stage II to IVA.
The benefit of adjuvant chemotherapy in GBC has been observed in node positive patients. Some of the common chemotherapeutic agents used for treatment of GBC include-Gemacitabine, Cisplatin, 5-flurouracil, cepacitabine.vii In case of GBC, Chemotherapy is directly injected into the hepatic artery (hepatic artery infusion) unlike injecting it into a vein, to maximize the benefit of chemotherapy. Since the hepatic artery also supplies to the gall bladder tumor, the drug can be effectively delivered in concentration to the tumor. Chemotherapy may also be useful in management of unresectable tumors.
While there is no sure way of preventing gallbladder cancer, and one cannot control natural factors like age, gender and ethnicity, it is recommended that one lead an active and healthy lifestyle. A healthy diet with cereals, whole grains instead of refined, at least two and half cups of fruits and vegetables daily, limiting intake of processed food and red meat have been shown to lower the risk of many cancers including gallbladder cancer.