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].

• Weight Loss

  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. [symptoma.com]

  A 45-year-old woman came to us with complaints of flatulent dyspepsia associated with weight loss and anorexia. [ncbi.nlm.nih.gov]

  Weight loss: Unexplained or unintentional weight loss may be the first symptom of gallbladder cancer. [verywell.com]

  […] a malignant neoplasm of the bile reservoir, characterized by anorexia, nausea, vomiting, weight loss, progressively worsening right upper quadrant pain, and eventually jaundice. Tumors of the gallbladder are predominantly adenocarcinomas. [medical-dictionary.thefreedictionary.com]

• Painless Jaundice

  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. [en.wikipedia.org]

• Abdominal Pain

  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. [symptoma.com]

  A 72-year-old woman presented with postprandial abdominal pain and was found to have a mass in the body of the gallbladder with direct liver invasion. Histological examination showed an adenosquamous carcinoma with an infiltrate of benign OGCs. [ncbi.nlm.nih.gov]

  Symptoms of Gallbladder Cancer When present, symptoms of gallbladder cancer may include: Abdominal pain: It is estimated that about 50% of people with gallbladder cancer experience abdominal pain as a symptom. [verywell.com]

• Right Upper Quadrant Pain

  A 52-year-old woman presented with right upper quadrant pain and obstructive jaundice. [ncbi.nlm.nih.gov]

  […] a malignant neoplasm of the bile reservoir, characterized by anorexia, nausea, vomiting, weight loss, progressively worsening right upper quadrant pain, and eventually jaundice. Tumors of the gallbladder are predominantly adenocarcinomas. [medical-dictionary.thefreedictionary.com]

  Other symptoms include right upper quadrant pain, weight loss and anorexia. Over 90% of cases of gallbladder cancer are adenocarcinomas, with the majority related to chronic inflammatory metaplasia and dysplasia 15. [radiopaedia.org]

  Symptoms Abdominal pain more diffuse and persistent than the classic right upper quadrant pain of gallstone disease Jaundice Anorexia Weight loss Signs Jaundice Ascites Palpable mass in the right upper quadrant (Courvoisier sign, if this is due to a palpable [clinicaladvisor.com]

• Loss of Appetite

  Loss of appetite: A general loss of appetite often accompanies a diagnosis of gallbladder cancer. Signs of Gallbladder Cancer Signs of cancer differ from symptoms in that you and others may be able to visualize the condition. [verywell.com]

  A patient with gallhbladder cancer may present with signs and symptoms that include, but are not limited to abdominal pain, particularly in the right upper quadrant (RUQ), and bloating, as well as fever, nausea, unintentional weight loss, loss of appetite [news-medical.net]

  […] of appetite unexplained weight loss swollen abdomen Although not necessarily a result of gallbladder cancer, if you have any of these symptoms you should visit your GP. [global.ihi.com]

  Signs and symptoms [ edit ] Steady pain in the upper right abdomen Indigestion Dyspepsia (gas) Bilious vomit Weakness Loss of appetite Weight loss Jaundice and vomiting due to obstruction Early symptoms mimic gallbladder inflammation due to gallstones [en.wikipedia.org]

• Abdominal Mass

  Suspect cancer if patients have an unexplained extrahepatic biliary obstruction or abdominal mass. Diagnose cancers by imaging, beginning with ultrasonography, followed by MRCP. [merckmanuals.com]

  An abdominal mass: An enlarged gallbladder may indicate gallbladder cancer. An enlarged gallbladder is caused by a blockage of the bile ducts. [verywell.com]

• Jaundice

  A 52-year-old woman presented with right upper quadrant pain and obstructive jaundice. [ncbi.nlm.nih.gov]

  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. [symptoma.com]

• Biliary Colic

  Cancer of the gallbladder is a rare gastrointestinal (GI) tract pathology that must be diagnosed by clinical tests as its symptoms overlap with those of other GI tract conditions, such as biliary colic and gallstones. [news-medical.net]

  Pain may resemble that of biliary colic (reflecting biliary obstruction) or may be constant and progressive. Sepsis (secondary to acute cholangitis), although unusual, may be induced by endoscopic retrograde cholangiopathy (ERCP). [merckmanuals.com]

• Hepatomegaly

  Ultrasound of the abdomen revealed hepatomegaly with thick-walled gallbladder with multiple stones and a mass at the fundus, but normal uterus and ovary. [ncbi.nlm.nih.gov]

  Other features include fatigue, acholic stool, a palpable mass, hepatomegaly, or a distended gallbladder (Courvoisier sign, with distal cholangiocarcinoma). [merckmanuals.com]

• Gallbladder Enlargement

  Gallbladder cancer symptoms include: • Nausea and vomiting • Abdominal pain • Jaundice • Gallbladder enlargement • Abdominal swelling • Weight loss • Loss of appetite Who Gets Gallbladder Cancer The American Cancer Society’s estimates for gallbladder [cancertutor.com]

• Irritability

  Its incidence rate in Spain is intermediate. 5,7–9 Both our study and the literature consulted 1–5,7–9 showed that the principal associated risk factor is cholelithiasis (86%), which causes chronic irritation and inflammation of the gallbladder wall. [elsevier.es]

  The properties of the gallstones themselves play a role in the development of GBC, as different types of stones induce different patterns of mucosal irritation and chronic inflammation [ 16 ]. [intechopen.com]

  Chronic bacterial infections also cause irritations and inflammations in the gallbladder. Salmonnela typhi carriers developed GBC and risk increases 10 folds. [medcraveonline.com]

• Dark Urine

  If you have gallbaldder cancer, you may have some of the following symptoms: feeling sick vomiting pain in the upper right side of the abdomen (tummy) which can come and go your skin and the white of your eyes are yellowed (jaundice) dark urine pale coloured [global.ihi.com]

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].

• Salmonella Typhi

  However, direct association and causal mechanisms between Salmonella Typhi infection and GBC have not been established. [ncbi.nlm.nih.gov]

  Epidemiology occurs late in life. gallstones are a risk factor more common in far east associated with chronic Salmonella typhi infection Klatskin's tumor occurs at junction of hepatic ducts and CBD lethal with mean survival of 9-12 mos Presentation Persistent [medbullets.com]

  Simultaneous assay of every Salmonella Typhi gene using one million transposon mutants. Genome Res. 19:2308–2316. [microbewiki.kenyon.edu]

  "Salmonella typhi and Gallbladder Cancer". Bacteria and Cancer. pp. 117–137. doi : 10.1007/978-94-007-2585-0_5. ISBN 978-94-007-2584-3. ^ Srivastava K, Srivastava A, Sharma KL, Mittal B. [en.wikipedia.org]

  Salmonella typhi (~6% of carriers develop GBC: A 12-fold risk increase) and Helicobacter bilis have been implicated in GBC [19,29,45,54-59]. [medcraveonline.com]

Only one patient had no benefit from treatment with gemcitabine. CONCLUSION: We conclude that gemcitabine may be an effective drug in the palliative treatment of gallbladder cancer, and thus its efficiency warrants evaluation in further studies. [ncbi.nlm.nih.gov]

Primary Treatment of Metastatic Disease 1 General Treatment Note: Order of the treatment options below does not indicate preference. [cancertherapyadvisor.com]

CONCLUSION: Preoperative NLR and PLR were closely related to prognosis of patients with GBC and might be useful for the evaluation of prognosis of patients with GBC. [ncbi.nlm.nih.gov]

The etiology was tumor emboli and PTTM from gallbladder carcinoma, which remained elusive prior to her death despite appropriate clinical investigations and was established on autopsy. [ncbi.nlm.nih.gov]

Etiology The exact etiology is unknown. Genetic susceptibility elicited by chronic inflammation of the gallbladder leading to dysplasia and malignant change is one possibility. [orpha.net]

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. [symptoma.com]

In this new 8th edition an outstanding editorial team from world-renowned medical centers continues to hone the leading edge forged in previous editions, with timely information on biology, immunology, etiology, epidemiology, prevention, screening, pathology [books.google.com]

In this review we delve into the epidemiologic, genetic and pathologic characteristics of this enigmatic disease with a special focus on the recent advancements in the field of gallbladder pathology. [ncbi.nlm.nih.gov]

Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin 2001;51(6):349-64. Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol 2014;6:99-109. Eslick GD. [revista.nutricionhospitalaria.net]

Eslick GD (2010) Epidemiology of gallbladder cancer. Gastroenterol Clin North Am 39(2): 307-330. Hundal R, Shaffer EA (2014) Gallbladder cancer: epidemiology and outcome. Clin Epidemiol 6: 99-109. [medcraveonline.com]

The exact pathophysiologic mechanism leading to oedema of the gallbladder wall in these diverse conditions is uncertain, but it is likely due to elevated portal venous pressure, elevated systemic venous pressure, decreased intravascular osmotic pressure [radiologyassistant.nl]

Pathophysiology Gallbladder cancer arises in the setting of chronic inflammation. In the vast majority of patients (>75%), the source of this chronic inflammation is cholesterol gallstones. [emedicine.medscape.com]

Postoperative extra-beam radiation therapy was delivered to the hepatic portal lesion to prevent GBC recurrence. The patient remains disease-free 14 months after the completion of radiation therapy. [ncbi.nlm.nih.gov]

[…] and early detection of cervical cancer: American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. [nccn.org]

External Cancer Epidemiology, Biomarkers and Prevention 2015;24(9):1319–1326. [cdc.gov]

Causes, Risk Factors, and Prevention Learn about the risk factors for gallbladder cancer and what you might be able to do to help lower your risk. Early Detection, Diagnosis, and Staging Know the signs and symptoms of gallbladder cancer. [cancer.org]

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.