Gallbladder cancer is the development of cancerous cells in the lining of the gall bladder, a small pear-shaped organ below the liver. It can develop anywhere in the gallbladder, but primarily occurs within the body of the organ. Although it is typically regarded as a rare disease, gallbladder cancer accounts for 80–95% of biliary tract tumors and is the most frequent biliary cancer. It is the 23rd most common cancer worldwide with more than 1,15,000 new cases reporting every year. Geographical variation significantly affects the occurrence. More than 50% of newly discovered cases are identified in developing nations.

Gallbladder cancer is the development of cancerous cells in the lining of the gallbladder, which is part of the digestive system.

Symptoms

The majority of patients do not experience any symptoms when gallbladder cancer is in its early stages. However, symptoms only appear when the disease has progressed significantly. The most prevalent signs and symptoms include:

• Unintentional weight loss

• Persistent abdominal (belly) pain

• Bloating  in the stomach

• Nausea

• Vomiting

• Loss of appetite

• Minor stomachache

• Yellowing of the skin and eyes(Jaundice).

Diagnosis

The medical history, physical examination, and imaging tests can be suggestive of the diagnosis of gallbladder cancer. Nonetheless, the diagnosis must be confirmed by histopathological examination of the biopsy specimen. The various steps employed for the diagnosis of gallbladder cancer include:

• General history taking and physical examination: The patient is interviewed about their symptoms as well as their medical, familial, and occupational histories. They are also checked for any indications of the illness, such as the presence of lumps or anything that appears unusual.

• Endoscopic retrograde cholangiopancreatography (ERCP): In this procedure, an endoscope is introduced into the stomach  through the mouth, down the esophagus. Through this endoscope, a tiny tube or catheter is inserted into the bile ducts. Later, a dye is injected into the biliary ducts, to evaluate the extent of the tumor in the gallbladder. It can be used to detect gallbladder cancer at an early stage.

• Percutaneous cholangiography: In this procedure, a thin needle is inserted through the skin and into the gallbladder area. A dye is injected through the needle to evaluate the tumor in the gallbladder.

• Imaging modalities: These include endoscopic ultrasound (the most accurate and sensitive diagnostic procedure for patients suspecting gall bladder cancer), computed tomography (CT, used for staging gallbladder cancer), magnetic resonance imaging (MRI, used in the clinical diagnosis and treatment of gallbladder cancer), and 18FFluorodeoxyglucose (FDG) -positron emission tomography (PET, used to evaluate the extent of cancer).

• Staging laparoscopy (SL): It is a quick, minimally invasive procedure that needs a small incision. An endoscope is used to look for the gall bladder and other internal organs.

• Routine blood investigations: Routine lab tests can be carried out to determine the patient immunological status and the presence of risk factors. They include complete blood count, blood glucose tests, lipid profiles, thyroid function testing, and urine analysis. Levels of bilirubin are also checked which are elevated in gallbladder  cancer.

• Histopathological examination of the biopsy specimen: It involves the removal of cells or tissues of the suspicious area. A tissue sample may be collected from regions where cancer may have spread and tested for the presence of tumor cells. Biopsy can also be done with the help of laparoscopy and endoscopy.

Treatment

A multidisciplinary treatment approach prior to making any treatment decision is mandatory for gallbladder cancer patients which comprises of :

• Surgery: Surgery is frequently used to treat gallbladder cancer at all stages which include simple cholecystectomy (removal of the gall bladder), extended cholecystectomy(removal of the gall bladder, adjacent 1mm of liver tissue and surrounding lymph nodes), radical gallbladder resection(removal of the gallbladder, bile duct, ligaments between the liver and the intestine) and palliative surgery (surgery done to remove the blockage of the bile duct or the intestine).

• Endoscopic mucosal resection: Endoscopic mucosal resection is a minimally invasive technique that removes the tumor through the lumen of the stomach.

• Laparoscopic surgery: Laparoscopic surgery is a minimally invasive procedure utilized in gallbladder cancer patients who cannot go for conventional  treatment. It has less postoperative discomfort, better cosmetic outcomes, and quicker recovery time.

• Radiotherapy : In patients with advanced gallbladder cancer, preoperative radiation therapy is primarily employed to reduce tumor burden. It has been utilized, primarily as an adjuvant treatment along with chemotherapy.

• Chemotherapy: The most frequently prescribed drug for the treatment of gallbladder cancer is fluorouracil (5-FU), gemcitabine, cisplatin,oxaliplatin, and nab-paclitaxel. Chemotherapeutic drugs are coupled with tumor antigen-specific antibodies to enable direct delivery of the medications to the tumor.

• Chemoradiation: Combining chemotherapy and radiation therapy increases the effectiveness of both treatments. Adjuvant chemoradiation may compensate for inadequate surgery.

• Targeted therapy: Targeted therapies for the treatment of gallbladder cancer include ivosidenib and pemigatinib. They are used to treat end stage gallbladder cancer that cannot be surgically removed or has recurred.

• Immunotherapy: For the treatment of high-risk, early-stage gallbladder carcinoma, immune checkpoint inhibitors are recommended. Examples are pembrolizumab, nivolumab and durvalumab. These medications inhibit several kinase proteins that aid in tumor cell growth, either directly or by encouraging angiogenesis (formation of new blood vessels).

The understanding and treatment of gallbladder cancer have generally advanced significantly. Its occurrence can be influenced by a variety of environmental and genetic variables. Greater knowledge of these elements holds the prospect of preventing gallbladder cancer and producing cutting-edge treatments.