BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy that is usually diagnosed at a late stage. Prior data showed increasing incidence of GBC in the US. However, little is known about race/ethnic-specific incidence and mortality trends of GBC per stage at diagnosis. Therefore, we aimed to conduct a time-trend analysis of GBC incidence and mortality rates categorized by race/ethnicity and stage-at-diagnosis.
METHODS: Age-adjusted GBC incidence and mortality rates were calculated using SEER*Stat software from the United States Cancer Statistics database (covers ~98% of US population between 2001 and 2020) and NCHS (covers ~100% of the US population between 2000 and 2020) databases, respectively. Race/Ethnic groups were Non-Hispanic-White (NHW), Non-Hispanic-Black (NHB), Hispanic, Non-Hispanic-Asian/Pacific-Islander (NHAPI), and Non-Hispanic-American-Indian/Alaska-Native (NHAIAN). Stage-at-diagnoses were all stages, early, regional, and distant stages. Joinpoint regression was used to generate time-trends [annual percentage change (APC) and average APC (AAPC)] with parametric estimations and a two-sided t-test (p-value cut-off 0.05).
RESULTS: 76,873 patients were diagnosed with GBC with decreasing incidence rates in all races/ethnicities except NHB who experienced an increasing trend between 2001 and 2014 (APC = 2.08, p < 0.01) and plateauing afterward (APC = -1.21, p = 0.31); (AAPC = 1.03, p = 0.03). Among early-stage tumors (9927 patients), incidence rates were decreasing only in Hispanic (AAPC = -4.24, p = 0.006) while stable in other races/ethnicities (NHW: AAPC = -2.61, p = 0.39; NHB: AAPC = -1.73, p = 0.36). For regional-stage tumors (29,690 patients), GBC incidence rates were decreasing only in NHW (AAPC = -1.61, p < 0.001) while stable in other races/ethnicities (NHB: AAPC = 0.73, p = 0.34; Hispanic: AAPC = -1.58, p = 0.24; NHAPI: AAPC = -1.22, p = 0.07). For distant-stage tumors (31,735 patients), incidence rates were increasing in NHB (AAPC = 2.72, p < 0.001), decreasing in Hispanic (AAPC = -0.64, p = 0.04), and stable in NHW (AAPC = 0.07, p = 0.84) and NHAPI (AAPC = 0.79, p = 0.13). There were 43,411 deaths attributed to GBC with decreasing mortality rates in all races/ethnicities except NHB who experienced a stable trend (AAPC = 0.25, p = 0.25).
CONCLUSIONS: Nationwide data over the last two decades show that NHB patients experienced increasing GBC incidence between 2001 and 2014 followed by stabilization of the rates. This increase was driven by late-stage tumors and occurred in the first decade. NHB also experienced non-improving GBC mortality, compared to other race and ethnic groups who had decreasing mortality. This can be due to lack of timely-access to healthcare leading to delayed diagnosis and worse outcomes. Future studies are warranted to investigate contributions to the revealed racial and ethnic disparities, especially in NHB, to improve early detection.

暂无摘要。

Gallbladder cancer (GBC) is one of the commonest biliary malignancies seen in India, Argentina, and Japan. The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs. Early detection is the only way to improve the outcome. There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC. Therefore, it is important and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis, early diagnosis, treatment, and prognostication. As India being one of the largest hubs for GBC in the world, it is important to know how the country has progressed on GBC. In this review, we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.

BACKGROUND: Perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, and gall bladder cancer are difficult malignancies to treat, and are characterized by a tendency for local recurrence and a generally unfavorable prognosis. Surgical resection offers the only potential cure, conventionally performed via the open approach. While minimally invasive approaches show promise, data remains limited.
METHODS: With IRB approval, we prospectively followed 100 patients between 2013-2023 who underwent robotic surgical resection for perihilar, intrahepatic (IHCC) and gallbladder cholangiocarcinoma. Data are presented as median (mean ± standard deviation). Significance was accepted at p≤0.05.
RESULTS: The median patient age was 70 years, and the median operative duration was 333minutes, with an estimated blood loss of 200mL. Importantly, there were no unplanned conversions, and only 1 intraoperative complication occurred within the IHCC cohort. The median length of stay was 4 days. There was a total of 19 postoperative complications and 19 readmissions within 30 days. Additionally, there were three in-hospital mortalities and five 90-day mortalities. R0 resection was achieved in 87% of patients, and R1 resection in 13%. At a median follow-up of 36 months, 62% of patients demonstrated disease-free survival, while 6% continued to live with the disease and 32% did not survive.
CONCLUSIONS: Our experience demonstrates the feasibility and safety of robotic resection for these complex malignancies, yielding promising short-term outcomes. Further investigation is required to ascertain the long-term oncological outcomes.

Aberrant expression of G protein-coupled receptor class C group 5 member A (GPRC5A) has been reported in multiple cancers and is closely related to patient prognosis. However, the mechanistic role of GPRC5A in gallbladder cancer (GBC) remains unclear. Here, we determined tumor expression levels of GPRC5A and the molecular mechanisms by which GPRC5A regulates gallbladder cancer metastasis. We found that GPRC5A was significantly upregulated in GBC, correlating with poorer patient survival. Knocking down GPRC5A inhibited GBC cell metastasis both in vitro and in vivo. GRPRC5A knockdown resulted in downregulation of TNS4 expression through the JAK2-STAT3 axis. Clinically, GPRC5A expression positively correlated with TNS4. Finally, STAT3 bound to TNS4\'s promoter region, inducing its expression. Overall, GPRC5A showed high expression in GBC tissues, associated with poor patient prognosis. Our findings first demonstrate that the GPRC5A-JAK2-STAT3-TNS4 pathway promotes GBC cell metastasis, suggesting potential therapy targets.

BACKGROUND: Helicobacter pylori (H. pylori) infection is widely recognized for its association with gastric diseases. Prior studies on the relationship between H. pylori infection and biliary diseases have faced constraints, including inadequate control of confounding factors and small sample sizes. This study aims to explore the association between H. pylori infection and biliary diseases using a large, population-based sample with adequate control for various covariates.
METHODS:  The National Inpatient Sample (NIS) from 2016 to 2020 was used to investigate the association between H. pylori infection and biliary diseases. We identified patients with H. pylori infection using the International Classification of Diseases, Tenth Revision (ICD-10) code (B96.81). Descriptive analysis and inferential statistics, including univariate and multivariate regression, were performed to explore the relationship between H. pylori and selected biliary diseases.  Results: Overall, 32,966,720 patients were analyzed. Among them, 736,585 patients had biliary diseases (n=1,637 with H. pylori and n=734,948 without H. pylori). The baseline characteristics revealed notable differences in demographics and healthcare variables between both groups. Univariate regression analysis demonstrated significant associations between H. pylori infection and various biliary diseases such as gallbladder stones, gallbladder cancer, cholangitis, acute cholecystitis, and biliary pancreatitis, with the highest risk for chronic cholecystitis (odds ratio: 5.21; 95% confidence interval: 4.1-6.62; p<0.0001). Multivariate regression analysis, after adjusting for various covariates, confirmed these associations, providing insights into the potential causal relationship between H. pylori and biliary diseases.
CONCLUSIONS:  This study strengthens the evidence suggesting a potential association between H. pylori infection and biliary diseases. The findings need to be validated in prospective clinical studies.

Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.

暂无摘要。

暂无摘要。

BACKGROUND: Among cancers, carcinoma gallbladder has one of the most dismal prognosis. Early lesions are difficult to biopsy because of proximity to luminal structures and risk of biliary peritonitis. However, early surgery offers the only chance of a complete cure. Utilizing a risk score would allow characterization of the risk of malignancy and early referral to an oncology centre thereby resulting in better outcomes for patients with carcinoma gallbladder.
METHODS: The aim of this study was to develop a risk score for carcinoma in patients with suspicious gallbladder lesions based on clinical presentation and imaging. All patients with suspicious gallbladder lesions on radiological imaging who underwent surgery were analyzed. Patients were considered for scoring if the ultrasound showed the gallbladder wall thickening (more than 4 mm) and computed tomography scan showed operable disease. Statistical analysis was done to derive a score for malignancy.
RESULTS: Total 175 patients underwent an operation for suspicious gallbladder lesions from January 2005 to December 2014. The factors analyzed were clinical biochemical and imaging findings. Of these, 71 were benign on the final histopathology and 104 were malignant. The score was constructed with the following variables: female sex, high total bilirubin (≥ 1 mg/dL), presence of a mass, focal location of the lesion, presence of gallbladder stones and nodal involvement in the hepatoduodenal region on imaging. A model score and modified score were obtained. In this modified score, score of more than 8 out of 20 predicted malignancy with a sensitivity of 78% and specificity of 70.4%. Receiver operating characteristic (ROC) curve constructed with these variables had an area under curve of 0.828. There was no statistically significant difference between the model score and the modified score.
CONCLUSIONS: A pre-operative risk score was obtained for carcinoma gallbladder, which needs to be validated prospectively in future.