With estimated incidence rates of 3 per 100,000 individuals in the United States, gallbladder carcinoma is rarely encountered in clinical practice [1]. Still, it encompasses up to 90% of all neoplastic processes arising from the biliary tree [1] [2]. Risk factors are increasing age, female gender, certain ethnic (native American ancestry) and geographic predispositions (southeast Asia has a significantly higher incidence rate compared to the rest of the world), the presence of gallstones and chronic inflammation, as well as parasitic infections, congenital abnormalities of the biliary tract, and genetics [1] [2] [3] [4] [5]. The 5-year survival rate of patients suffering from gallbladder carcinoma from the time of diagnosis is less than 5% [3], and the poor overall prognosis occurs due to two reasons. Firstly, the gallbladder lacks a serosal layer at the site where it is in contact with the liver, thus allowing rapid dissemination and metastatic spread of the tumor [3]. And secondly, the clinical presentation is often nonspecific and mimics other more common pathologies of the biliary tree (cholelithiasis, cholecystitis, other abdominal tumors, etc.) [1] [2] [4] [5] [6] [7]. Right upper quadrant abdominal pain, fever, jaundice, nausea, vomiting, pruritus, anorexia, and weight loss are the most important complaints in the literature when it comes to gallbladder carcinoma [1] [2] [4] [6] [8].

Because of the very low survival rate of patients with gallbladder carcinoma, physicians must raise clinical suspicion toward a malignant disorder in the presence of nonspecific abdominal complaints. A detailed patient history and a complete physical examination, which will assess the course and progression of symptoms, but also their potential origin (through abdominal inspection and palpation), are vital steps in the workup. Laboratory tests are of limited benefit in the raising suspicion toward gallbladder carcinoma [4] [8]. Serum tumor markers, however, mainly carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), are frequently elevated in this patient group, suggesting their important role in the workup [9] [10]. Imaging studies are the cornerstone in making the diagnosis. Various techniques are recommended, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (particularly high-resolution), positron emission tomography (fludeoxyglucose (FDG)-PET and PET-CT), endoscopic ultrasonography (EUS), and magnetic resonance cholangiopancreatography (MRCP) [1] [2] [6] [7]. A large space-occupying mass in the gallbladder that is frequently infiltrating the liver is a typical finding, while asymmetric and extensive gallbladder wall thickening is also an important sign used to discriminate this tumor from other etiologies [1] [2]. Once the initial diagnosis is made, often through high-resolution US, CT, or MRI (all used to assess nodal or metastatic spread as well), EUS is vital in determining the exact stage of the tumor, as it provides the ability to perform a biopsy (through fine-needle aspiration) and subsequent histopathological examination [3] [11].

Treatment for gallbladder carcinoma depends on the stage of the disease at diagnosis. Surgical removal of the gallbladder (cholecystectomy) is the primary treatment for early-stage cancer. If the cancer has spread, more extensive surgery may be required. In cases where surgery is not possible, chemotherapy and radiation therapy may be used to control the disease and alleviate symptoms. Targeted therapies and clinical trials may also be options for some patients.

The prognosis for gallbladder carcinoma is generally poor, largely due to late diagnosis. The five-year survival rate is low, especially for advanced stages. However, early detection and treatment can significantly improve outcomes. Factors influencing prognosis include the cancer's stage at diagnosis, the patient's overall health, and the cancer's response to treatment.

The exact cause of gallbladder carcinoma is not well understood, but several risk factors have been identified. These include gallstones, chronic inflammation of the gallbladder, obesity, and certain genetic predispositions. Other factors such as age, gender (more common in women), and geographic location (higher incidence in certain regions) also play a role.

Gallbladder carcinoma is relatively rare, accounting for a small percentage of all cancer cases. It is more prevalent in certain parts of the world, such as South America and Asia. The disease is more common in older adults, with a higher incidence in women compared to men. The reasons for these demographic differences are not fully understood but may relate to genetic and environmental factors.

Gallbladder carcinoma typically begins in the innermost layer of the gallbladder and can invade deeper layers as it progresses. The most common type is adenocarcinoma, which originates in the glandular cells lining the gallbladder. Chronic inflammation, often due to gallstones, is thought to contribute to the development of cancer by causing cellular changes over time.

Preventing gallbladder carcinoma involves managing risk factors. Maintaining a healthy weight, eating a balanced diet, and managing conditions like gallstones and chronic gallbladder inflammation can reduce risk. Regular medical check-ups and monitoring for those with a family history of gallbladder disease may also be beneficial.

Gallbladder carcinoma is a rare but serious cancer with a poor prognosis due to its often late diagnosis. Understanding the risk factors, symptoms, and treatment options is crucial for early detection and management. While prevention focuses on lifestyle modifications and managing underlying conditions, ongoing research aims to improve diagnostic and therapeutic strategies.

If you or someone you know is experiencing symptoms such as persistent abdominal pain, jaundice, or unexplained weight loss, it is important to seek medical evaluation. Early detection of gallbladder carcinoma can significantly impact treatment outcomes. Discuss any concerns with your healthcare provider, who can guide you through the necessary diagnostic tests and potential treatment options.

1. Furlan A, Ferris JV, Hosseinzadeh K, Borhani AA. Gallbladder carcinoma update: Multimodality imaging evaluation, staging, and treatment options. Am J Roentgenol. 2008;191:1440–1447.
2. Andrén-Sandberg Å. Diagnosis and Management of Gallbladder Cancer. N Am J Med Sci. 2012;4(7):293-299.
3. Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol. 2014;6:99-109.
4. Graff AE, Lewis SL, Bear JR, Van Echo DC, Dainer HM. Gallbladder Carcinoma, the Difficulty of Early Detection: A Case Report. Cureus. 2016;8(2):e493.
5. Hsing AW, Gao YT, Han TQ, et al. Gallstones and the risk of biliary tract cancer: a population-based study in China. Br J Cancer. 2007;97:1577–1582.
6. Rodríguez-Fernádez A, Gómez-Río M, Medina-Benitez A, et al. Application of modern imaging methods in diagnosis of gallbladder cancer. J Surg Oncol 2006; 93:650–664.
7. Joo I, Lee JY, Kim JH, Kim SJ, Kim MA, Han JK, Choi BI. Differentiation of adenomyomatosis of the gallbladder from early-stage, wall-thickening-type gallbladder cancer using high-resolution ultrasound. Eur Radiol. 2012;23(3):730–738.
8. Löhe F, Meimarakis G, Schauer C, Angele M, Jauch KW, Schauer RJ. The time of diagnosis impacts surgical management but not the outcome of patients with gallbladder carcinoma. Eur J Med Res. 2009;14:345–351.
9. Strom BL, Maislin G, West SL, et al. Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer. Int J Cancer. 1990;45:821–824.
10. Ritts RE Jr, Nagorney DM, Jacobsen DJ, Talbot RW, Zurawski VR Jr. Comparison of preoperative serum CA19-9 levels with results of diagnostic imaging modalities in patients undergoing laparotomy for suspected pancreatic or gallbladder disease. Pancreas. 1994;9:707–716.
11. Kim HJ, Lee SK, Jang JW, et al. Diagnostic role of endoscopic ultrasonography-guided fine needle aspiration of gallbladder lesions. Hepatogastroenterology. 2012;59(118):1691–1695.