Although there have been significant advances in the early detection and treatment of gallbladder cancer (GBC), it is still considered a leading cause of morbidity and mortality. Molecular profiling of tumors is generally performed using samples obtained during surgery or biopsy. However, tissue genotyping has its limitations as it only provides a single snapshot and is susceptible to spatial selection bias due to the tumor heterogeneity. Over the past decade, there has been a remarkable transition from invasive diagnostic methods to non-invasive alternatives, including liquid biopsy, for cancer diagnosis and monitoring. Liquid biopsies have ushered in a new era in clinical oncology, enabling convenient tumor sampling, continuous monitoring through repeated analysis, development of personalized treatment regimens, and assessment of therapy resistance. While peripheral blood is the primary medium for these biopsies, other biological fluids, including urine, saliva, and bile, also serve as valuable sources of information. Currently, the focus of blood-based biopsy analyses is on four main sources of biomarkers for cancer detection and stratification: circulating tumor DNA (ctDNA) or circulating free DNA (cfDNA), circulating tumor cells (CTCs), and extracellular vesicle (EVs). There are over 300 clinical trials either ongoing or actively recruiting participants to investigate the diagnostic and prognostic applications of ctDNA/cfDNA in the context of cancer. This review outlines the current standard of care for individuals with GBC, anticipates future treatment developments, and evaluates the potential applications of liquid biopsies in various clinical contexts. The review addresses ctDNA/cfDNA, CTC, and circulating microRNA and highlights their prospective roles in management of GBC.

The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is based on the gender, geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer (GC) is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly.

Intraoperative diagnosis of resection margins in the biliary tract and pancreas tumors is important in deciding extent of resection; however, diagnosis based solely on frozen sections is sometimes difficult. Therefore, we investigated the usefulness of intraoperative cytology (IC) combined with frozen section (FS) histology. We present the results with a discussion of the value of this combination and its associated problems.

We examined 80 bile duct resection margin specimens from 42 patients, and 34 pancreatic resection margin specimens from 29 patients, who underwent intraoperative diagnosis of resection margins during surgery for biliary tract or pancreatic tumors between October 2012 and January 2014. IC was performed on imprint specimens prepared from surfaces of margins being examined. The results were compared with FS and final histology of operative materials.

In IC, excluding cases with insufficient material, the results for bile duct margins; sensitivity was 96.7%, specificity 100% and accuracy 98.7%. The results for pancreatic margins; sensitivity was 100%, specificity 92.9%, and accuracy 93.3%. In FS, the results for bile duct margins; sensitivity was 96.8%, specificity 100%, and accuracy 98.8%. The results for pancreatic margins; sensitivity was 66.7%, specificity 100%, and accuracy 97.1%.

IC is quick, highly accurate and very easy to perform. This study even included a specimen for which only IC led to an accurate diagnosis. IC used in combination with FS can achieve intraoperative diagnosis with high overall accuracy.

Gallbladder cancer (GBC) is a rather uncommon disease, but at the time when it gives symptoms it has usually reached no longer curable stage. Therefore, all attempts must be made to make the diagnosis earlier to have better opportunity for cure. The author searched PubMed, and reviewed literatures on diagnoses and treatment of GBC.