Research progress on prognostic factors of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma is the most common malignant tumor of the biliary system, and has a poor overall prognosis. Poor prognosis in patients with gallbladder carcinoma is associated with the aggressive nature of the tumor, subtle clinical symptoms, ineffective adjuvant treatment, and lack of reliable biomarkers. PURPOSE: Therefore, evaluating the prognostic factors of patients with gallbladder carcinoma can help improve diagnostic and treatment methods, allowing for tailored therapies that could benefit patient survival. METHODS: This article systematically reviews the factors affecting the prognosis of gallbladder carcinoma, with the aim of evaluating prognostic risk in patients. CONCLUSION: A comprehensive and in-depth understanding of prognostic indicators affecting patient survival is helpful for assessing patient survival risk and formulating personalized treatment plans.

Aberrant Expression of Pneumocytic Markers (TTF-1 and Napsin-A) in Biliary Duct and Gallbladder Adenocarcinomas; A Potential Diagnostic Pitfall.

Cholangiocarcinomas and gallbladder carcinomas are epithelial tumours with biliary differentiation. On histology and immunohistochemistry, they resemble adenocarcinomas and possess overlapping immunohistochemical profiles. Diagnosing these tumours is best done using appropriate imaging and clinical features with compatible immunohistochemistry. Immuno-staining for thyroid transcription factor-1 (TTF-1) and novel aspartic proteinase of pepsin A (Napsin-A) is believed to be specific for primary pulmonary adenocarcinomas. We herein report uncommon instances of strong and diffuse expression of these markers in two examples of adenocarcinomas arising from the bile duct and gallbladder. A review of the literature and a summary of similar studies relating to aberrant TTF-1 and Napsin-A expression in biliary tract adenocarcinomas are presented.

Prognostic Value of Easy Albumin-Bilirubin Score for Radical Surgery in Patients With Gallbladder Carcinoma.

BACKGROUND: To investigate the clinical significance of the easy albumin-bilirubin (EZ-ALBI) score as a prognostic indicator in postoperative patients with gallbladder carcinoma (GBC). METHODS: The comprehensive clinical and pathological records of 140 patients with GBC who underwent radical resection between January 2015 and December 2020 were retrospectively examined. Based on the EZ-ALBI score, the 140 GBC patients were categorized into two groups: a low EZ-ALBI score group (score ≤ -34.4) consisting of 108 patients and a high EZ-ALBI score group (score > -34.4) consisting of 32 patients. The association between the EZ-ALBI score and clinicopathological factors was assessed. Survival analysis was performed using the Kaplan-Meier method, and the Cox proportional hazard model was utilized to evaluate the impact of clinicopathological factors on prognosis. RESULTS: Significant differences were observed between the low EZ-ALBI score group and the high EZ-ALBI score group in terms of serum total bilirubin, serum albumin, CA19-9 levels, liver metastasis, and tumor TNM stage. The 5-year survival rate was significantly lower in the high EZ-ALBI score group compared to the low EZ-ALBI score group. Univariate analysis indicated that serum total bilirubin, lymph node metastasis, TNM stage, and EZ-ALBI score were closely related to overall survival (OS). Multivariate analysis identified TNM stage and EZ-ALBI score as independent prognostic factors for OS. CONCLUSIONS: The EZ-ALBI score is a significant independent prognostic factor for overall survival in GBC patient's post-radical resection, highlighting its potential utility in clinical prognosis and patient management.

Exceptional Response to Pembrolizumab in HER2-Positive Gallbladder Carcinoma with High Tumor Mutational Burden.

PURPOSE: Patients with advanced cholangiocarcinoma, including gallbladder cancer, typically have a poor prognosis owing to limited effective chemotherapy options. The field of genotype-directed therapy in patients with cholangiocarcinoma is advancing. However, limited clinical data are currently available to evaluate the efficacy of molecularly targeted therapy. METHODS: Herein, we report the case of a 67-year-old man diagnosed with human epidermal growth factor receptor-2 (HER2)-positive and tumor mutation burden-high (TMB-H) cholangiocarcinoma. The HER2-positive and TMB-H characteristics were identified using comprehensive genomic profiling after showing resistance to gemcitabine and S-1 therapy. In the absence of clinical trials for HER2-positive cancer at that time, the patient was treated with pembrolizumab, which is used for TMB-H solid tumors in clinical practice. RESULTS: After receiving pembrolizumab, the patient experienced significant shrinkage in the primary tumor and liver metastases. Thus far, the patient has been receiving pembrolizumab for approximately 10 months. CONCLUSION: To our knowledge, this is the first report showing the efficacy of pembrolizumab in a patient with cholangiocarcinoma harboring both HER2-positive and TMB-H.

Comparison of Chemotherapy Combined with Percutaneous Electroporation and Chemotherapy Alone in the Management of Locally Advanced Gallbladder Carcinoma (GBC): A Study Protocol.

PURPOSE: This study aims to evaluate the feasibility and efficacy of chemotherapy combined with irreversible electroporation (IRE) in patients with locally advanced gallbladder carcinoma (GBC) presenting as gallbladder masses. MATERIALS AND METHODS: Patients with unresectable GBC masses of size greater than 2 cm and less than 6 cm without evidence of distant metastases and with no contraindication to general anaesthesia will be enrolled in the study. They will be randomized using computer generated table into two arms with 1:1 allocation ratio to include 15 patients in each group. Group I will be the chemotherapy alone arm and Group II will be the combined image-guided irreversible electroporation of the tumour and chemotherapy arm. The primary outcome assessed shall be the clinical benefit rate (complete response, CR; partial response, PR and stable disease, SD) based on the mRECIST criteria and overall survival. The secondary outcome shall be feasibility and safety of the procedure and quality of life pre and post procedure. The quality of life will be assessed by a questionnaire as given by EORTC-Quality of Life Group before starting therapy and 4 weeks after completion of therapy. EXPECTED GAIN OF KNOWLEDGE: The combined local and systemic effects of irreversible electroporation and systemic chemotherapy respectively may improve the outcomes in inoperable cases of gallbladder carcinoma. TRIAL REGISTRATION: Clinical Trials Registry - India ( https://ctri.nic.in/Clinicaltrials/advancesearchmain.php ). Identifier: CTRI/2021/05/033803. Primary Register of the International Clinical Trials Registry Platform (WHO ICTRP) ( http://www.who.int/ictrp/search/en/ ).

Gallbladder tuberculosis mimicking carcinoma: A case report of a rare entity.

INTRODUCTION: Gallbladder TB (GBTB) is a rare disease with a non-specific presentation, simulating cholecystitis and gallbladder malignancies. We describe a rare case of infiltrative GBTB with biliary strictures in a young female who was initially diagnosed with metastatic gallbladder carcinoma. CASE PRESENTATION: A 33-year-old female presented with recurrent episodes of obstructive jaundice, significant weight loss, fatigue, and oligomenorrhoea. Imaging studies revealed features of locally advanced gallbladder carcinoma with proximal and distal common bile duct strictures. However, biopsy of the liver tissue surrounding the gallbladder mass confirmed necrotizing granulomatous inflammation with similar findings from fine needle aspiration of the cervical lymph node. Along with the histopathological findings, radiological evidence of pulmonary tuberculosis confirmed the diagnosis of infiltrative GBTB. The patient was successfully managed with anti-tubercular drugs along with biliary decompression. DISCUSSION: The rarity of GBTB is attributed to the high alkalinity of bile and bile acids, which afford protection against tubercle bacilli. Patients commonly present with abdominal pain, fever, abdominal lump, anorexia, and weight loss. Biliary strictures, though rare, have been described in GBTB and simulate cholangiocarcinoma. Due to the non-specific findings of pre-operative laboratory and radiological investigations, most patients are taken up for surgery and diagnosed with TB on post-operative histological analysis. CONCLUSION: Gallbladder TB is a rare disease which poses a diagnostic challenge because it lacks any pathognomonic features. A tissue diagnosis must be carried out before confirming gallbladder and biliary tract malignancies. Physicians in TB-endemic regions should possess a high index of suspicion for diagnosing GBTB.

Incidental gallbladder cancer detected during laparoscopic cholecystectomy: conversion to extensive resection is a feasible choice.

Background: Re-resection is recommended for patients with incidental gallbladder carcinoma (iGBC) at T1b stage and above. It is unclear whether continuation of laparoscopic re-resection (CLR) for patients with intraoperatively detected iGBC (IDiGBC) is more beneficial to short- and long-term clinical outcomes than with conversion to radical extensive-resection (RER). Methods: This single-centre, retrospective cohort study of patients with iGBC was conducted between June 2006 and August 2021. Patients who underwent immediate reresection for T1b or higher ID-iGBC were enrolled. Propensity score matching (PSM) was used to match the two groups (CLR and RER) of patients, and differences in clinical outcomes before and after matching were analyzed. Result: A total of 102 patients with ID-iGBC were included in this study. 58 patients underwent CLR, and 44 underwent RER. After 1:1 propensity score matching, 56 patients were matched to all baselines. Patients in the RER group had a lower total postoperative complication rate, lower pulmonary infection rate, and shorter operation time than those in the CLR group did. Kaplan-Meier analysis showed that the overall survival rate of patients who underwent CLR was significantly lower than that of patients who underwent RER. Multivariate analysis showed that CLR, advanced T stage, lymph node positivity, and the occurrence of postoperative ascites were adverse prognostic factors for the overall survival of patients. Conclusion: Patients with ID-iGBC who underwent RER had fewer perioperative complications and a better prognosis than those who underwent CLR. For patients with ID-iGBC, conversion to radical extensive-resection appears to be a better choice.

LncRNA HOXB-AS3 promotes proliferation, migration, and invasion of gallbladder cancer cells by activating the MEK/ERK pathway.

Background: LncRNA HOXB-AS3 are associated with tumor progression in several types of carcinomas, yet, its possibly biological role in gallbladder carcinoma(GBC) remains unclear. Therefore, this study aimed to investigate the biological function of HOXB-AS3 in GBC. Methods: To know the potential function of HOXB-AS3 in gallbladder carcinoma, real-time polymerase chain reaction was used to detected the expression of HOXB-AS3 in gallbladder carcinoma cells. The colony formation assay and cell counting kit-8 assay was performed to measured cell viability. Flow cytometry was to analyse cell apoptosis and cell cycle. Cell invasion and migration were determined by the transwell invasion assay and wound-healing assay. A nude mice xenograft tumor model was performed to investigate the biological function of HOXB-AS3 in vivo. Results: The results indicated that HOXB-AS3 was significantly elevated in gallbladder carcinoma tissues and cell lines. We used siHOXB-AS3 to knockdown the expression levels of HOXB-AS3. And knockdown HOXB-AS3 expression depressed gallbladder cancer cell viability and induced cell apoptosis. In addition, the gallbladder carcinoma cell cycle was obviously arrested at the G1 phase. Cell invasion and migration were markedly suppressed following knockdown HOXB-AS3 expression. Furthermore, the features of siHOXB-AS3 in gallbladder cancer cells could be reversed by the ERK1/2 phosphorylation agonist Ro 67-7476. Finally, we confirmed that HOXB-AS3 promoted the growth of transplanted tumors in vivo. Conclusion: HOXB-AS3 promoted gallbladder carcinoma cell proliferation, invasion and migration by activating the MEK/ERK signaling pathway. HOXB-AS3 contributed to gallbladder cancer tumorigenesis and metastasis, making it a viable therapeutic target for gallbladder cancer treatment.

Role of Magnetic Resonance Spectroscopy in Evaluating Choline Levels in Gallbladder Carcinoma: A Comprehensive Review.

Gallbladder carcinoma (GBC) presents a significant clinical challenge due to its aggressive nature and often asymptomatic progression, resulting in late-stage diagnoses and a poor prognosis. Early detection and accurate staging are pivotal for improving patient outcomes, highlighting the critical role of advanced imaging techniques in oncological practice. Magnetic resonance spectroscopy (MRS) has emerged as a valuable non-invasive tool capable of assessing biochemical changes within tissues, including alterations in choline metabolism-a biomarker indicative of cell membrane turnover and proliferation. This review explores the application of MRS in evaluating choline levels in gallbladder carcinoma, synthesizing current literature to elucidate its potential in clinical settings. By analyzing studies investigating the correlation between choline levels detected via MRS and tumor characteristics, this review underscores MRS's role in enhancing diagnostic precision and guiding therapeutic decision-making. Moreover, it discusses the challenges and limitations associated with MRS in clinical practice alongside future research and technological advancement directions. Ultimately, integrating MRS into the diagnostic armamentarium for gallbladder carcinoma promises to improve early detection and treatment outcomes. This review provides insights into the evolving landscape of MRS in oncology, emphasizing its contribution to personalized medicine approaches aimed at optimizing patient care and management strategies for GBC.

Deep venous thrombosis, as the earliest presenting feature of gallbladder carcinoma: Case report.

Deep venous thrombosis is a common and potentially life-threatening condition that is often associated with various risk factors including underlying malignancy. In this case report, we present a male patient who presented with deep venous thrombosis as the earliest presenting feature of metastatic gallbladder carcinoma. This case report emphasizes the importance of thorough evaluation of patients presenting with unprovoked deep venous thrombosis to early detection of underlying malignancy.

Unmasking the silent killer: The hidden aggressiveness of signet-ring cell carcinoma in gallbladder cancer.

The prognostic significance of the signet-ring cell component in gallbladder carcinoma (GBC) has not been systematically evaluated. The aim of this study was to assess the similarities and differences between gallbladder signet-ring cell carcinoma (GBSRCA) and gallbladder adenocarcinoma (GBAC) in terms of clinicopathological features and long-term survival. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed 6,612 patients diagnosed with gallbladder cancer between 2000 and 2021. The cohort included 147 patients with GBSRCA and 6,465 with GBAC. Patients with GBSRCA were significantly younger, with 33.3% being age 60 or younger compared to 23.9% of patients with GBAC (p = 0.009). There was a higher proportion of females in the GBSRCA group (77.6%) compared to the GBAC group (70.1%, p = 0.049). GBSRCA was associated with a more advanced tumor stage (T3-T4: 56.5% vs. 44.4%, P = 0.004), higher rates of lymph node metastasis (43.5% vs. 28.0%, P < 0.001), and poorer differentiation status (poorly to undifferentiated: 80.3% vs. 29.7%, P < 0.001). Survival analysis revealed that patients with GBSRCA had significantly worse overall survival (OS) and cancer-specific survival (CSS) compared to patients with GBAC (p < 0.001). GBSRCA was an independent prognostic factor for OS (P = 0.001) in the entire cohort, while the T stage and N stage were independent prognostic factors for OS and CSS in patients with GBSRCA. Even after propensity score matching, patients with GBSRCA still had a poorer prognosis.

Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.

The Broad Spectrum of Gallbladder Paraneoplastic Syndromes.

Gallbladder carcinoma (GBC) is a rare gastrointestinal tumor with a reported incidence of 1 in 100,000 in the United States. GBC may present with subtle signs and symptoms that can be missed on routine examination and/or confused with other conditions. Unfortunately, its subtle presentation frequently leads to late diagnosis and, thus, a poor prognosis. Several paraneoplastic syndromes have been associated with GBC. Despite their strong associations with neoplastic disease, the precise pathophysiologic mechanisms underlying the development of these syndromes remain poorly understood. Given the vague nature of their initial signs and symptoms, these syndromes are frequently diagnosed as independent entities and only later associated with occult malignancies that may have already metastasized to other organs. Physicians need to be aware of the signs and symptoms of these paraneoplastic syndromes and include an underlying malignancy as part of the differential diagnosis. This review provides a detailed discussion of the paraneoplastic syndromes associated with GBC.

Multicellular 3D bioprinted human gallbladder carcinoma forin vitromimicry of tumor microenvironment and intratumoral heterogeneity.

Gallbladder carcinoma (GBC) is a malignant hepatobiliary cancer characterized by an intricate tumor microenvironments (TME) and heterogeneity. The traditional GBC 2D culture models cannot faithfully recapitulate the characteristics of the TME. Three-dimensional (3D) bioprinting enables the establishment of high-throughput and high-fidelity multicellular GBC models. In this study, we designed a concentric cylindrical tetra-culture model to reconstitute the spatial distribution of cells in tumor tissue, with the inner portion containing GBC cells, and the outer ring containing a mixture of endothelial cells, fibroblasts, and macrophages. We confirmed the survival, proliferation, biomarker expression and gene expression profiles of GBC 3D tetra-culture models. Hematoxylin-eosin (HE) and immunofluorescence staining verified the morphology and robust expression of GBC/endothelial/fibroblast/macrophage biomarkers in GBC 3D tetra-culture models. Single-cell RNA sequencing revealed two distinct subtypes of GBC cells within the model, glandular epithelial and squamous epithelial cells, suggesting the mimicry of intratumoral heterogeneity. Comparative transcriptome profile analysis among variousin vitromodels revealed that cellular interactions and the TME in 3D tetra-culture models reshaped the biological processes of tumor cells to a more aggressive phenotype. GBC 3D tetra-culture models restored the characteristics of the TME as well as intratumoral heterogeneity. Therefore, this model is expected to have future applications in tumor biology research and antitumor drug development.

A deep unenhanced area on contrast-enhanced ultrasound suggests T2 gallbladder carcinoma.

CE-US (Advanced Dynamic Flow, mechanical index: 1.6) in the perfusion phase (48 s after injection of Sonazoid®, marked with a red underline): A heterogeneously enhanced, sessile elevated lesion with a clearly visible deep unenhanced area (arrowhead), 3 mm in diameter, at the fundus.

Demographic and Clinicopathological Spectrum of Gallbladder Carcinoma in a Tertiary Care Centre in Jharkhand: A Retrospective Study.

Introduction Gallbladder carcinoma is a rare but aggressive cancer of adults that affects females more than males. Its occurrence is more common in the regions of South America and Asia. Chronic inflammation and cholelithiasis are frequently associated risk factors of gallbladder carcinoma. The incidental discovery of a gallbladder carcinoma during cholecystectomy, gross or microscopic examination of the unsuspected gallbladder specimens is termed incidental gallbladder carcinoma (IGBC). Considering the lack of extensive studies on gallbladder carcinoma in the Eastern region of India, especially in Jharkhand, this study has been done to present the demographic and clinicopathological characteristics of gallbladder carcinoma in this region. Methods A retrospective and descriptive study was done at Rajendra Institute of Medical Sciences (RIMS), Ranchi, a tertiary care center in Jharkhand. The study sample comprised 2386 gall bladder cases received in the Department of Pathology over five years, from December 2018 to December 2023. Results Of 2368 specimens, 25 cases (n=25) were reported as primary gallbladder carcinoma. The female-to-male ratio was 4:1. Pain was the most common complaint by the patients. Of the 25 cases, 12 were suspected intra-operatively or diagnosed microscopically (IGBC). Most showed a mass at the neck. In six cases, no gross mass/lesion was seen. Cholelithiasis is present in 19/25 cases. Most cases showed adenocarcinoma (not otherwise specified). Out of the adenocarcinoma cases, most were well differentiated. At the time of diagnosis, most were at the pT2 stage. Twelve cases of IGBC were found. Eight out of 12 IGBC were early-stage carcinoma when diagnosed. Conclusion Twenty-five cases of gallbladder carcinoma were diagnosed in the last five years in our center, with 19 (76%) of them associated with cholelithiasis. Twelve (48%) of the cases were incidentally diagnosed either preoperatively or during gross/microscopic examination, and eight (66%) of those were discovered early, out of which five (62.5%) were observed to be in the T1b stage. At this stage, there is a diversion from the general surgical management of gallbladder carcinoma for a better prognosis. This underscores the significance of routine histopathological examination of gallbladder specimens, even if there is no preoperative suspicion of gallbladder carcinoma.

Treatment Outcomes of Incidental Gallbladder Cancer - Results from a High-Volume Tertiary Care Centre in North India.

Gallbladder cancer (GBC) is a lethal disease. Incidentally detected gallbladder cancer (IGBC) presents a unique opportunity for early management and better outcomes. We present the institutional experience of a high-volume tertiary care center in northern India. Retrospective analysis of a prospectively maintained database was performed and data of all IGBC patients between January 2014 to December 2021 was analyzed. There were 125 patients of IGBC among the 750 patients of GBC seen during the study period. Of these 125 patients, 72 (57.6%) patients were not eligible for surgery. Successful completion radical cholecystectomy (CRC) was possible in 37 (69.8%) of the 53 patients who underwent surgery. On univariate analysis, thickness of gallbladder wall 10 mm or more (p < 0.001, OR 19.0, 95% CI 4.58-78.76), pathological stage (p < 0.001, OR 5.8, 95% CI 2.45-14.98) and median delay of 16 weeks or more (p < 0.001, OR 17.0, 95% CI = 4.08-70.76), were associated with inoperability. However, on multivariate analysis only gallbladder wall thickness of 10 mm or more (p < 0.001, AOR 17.9, 95% CI 3.24-98.78) and median delay of 16 weeks or more (p < 0.001, AOR 32.33, 95% CI 6.05-172.66) remained significant. Median time to recurrence (TTR) and overall survival (OS) was not reached after a median follow up of 30 months in patients undergoing successful CRC. Successful outcomes of IGBC are dependent on several factors. Diligent workup of suspicious thickening before simple cholecystectomy for gallstone disease and timely referral of IGBC to tertiary care are the keystones for good outcomes.

Inhibition of circRNA NGFR promotes ferroptosis in gallbladder carcinoma cells.

Background: Gallbladder carcinoma (GBC) is a formidably aggressive malignancy. Circular RNAs (circRNAs) play crucial regulatory roles in cancer. NGFR is a novel circRNA implicated in various types of cancers. The primary goal of this study was to elucidate the role of NGFR in GBC. Methods: NGFR variants exhibiting discernible discrepancies were identified using RNA sequencing and validated using real-time PCR. Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine and Cell Counting Kit-8 assays. The ferroptotic phenotype was characterized by assessing the reactive oxygen species and Fe2+ levels. Western blotting was used to analyze ferroptosis-associated proteins. Superoxide dismutase, malondialdehyde, and glutathione levels were measured using commercially available reagent kits. The severity of mitochondrial damage was evaluated by assessing JC-1, MitoSOX, and ATP activities. Results: NGFR was upregulated, and its suppression inhibited cell proliferation and increased Fe2+ levels in GBC cells. Furthermore, NGFR downregulation disrupted mitochondrial function. Conclusion: Circular RNA NGFR can impede the advancement of GBC by modulating the ferroptotic phenotype, thereby potentially offering a novel avenue for the clinical diagnosis and treatment strategies of GBC.

Expression Pattern of Estrogen Receptor Alpha and Progesterone Receptor in Gallbladder Carcinoma and Their Association with Clinicopathological Parameters and Overall Survival.

BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignant tumor with a poor prognosis. Despite being first described two centuries ago, there are no targeted therapies available beyond conventional cytotoxic therapy. Epidemiological studies have shown that the incidence of gallbladder cancer is higher in females than males. This suggests that the gallbladder may be a female sex hormone-responsive organ, and these hormones might be involved in the pathogenesis of gallbladder cancer. Therefore, we aimed to analyze the expression of ERα and PR in GBC and correlate their expression with clinicopathological variables and overall survival. PATIENTS AND METHODS: A total of 235 histopathologically diagnosed GBC cases were included in this hospital-based cross-sectional study. Clinicopathological data were collected, and the expression of ERα and PR was evaluated by immunohistochemistry. RESULTS: The mean age of this study population was 55.47 ± 8.45 with range 28-87 years. Females were predominated over male with a male-to-female ratio of 1:3.5. Positive nuclear expression of the ERα and PR was found in 13 (5.5%) and eight (3.4%) cases, respectively. Apart from nuclear staining, cytoplasmic expression of ERα and PR was found in three (1.2%) and 31 (13.2%) cases, respectively. Higher percentage of positive nuclear expression of ER was found in < 50 years age (p value = 0.04), parity > 4 (p value = 0.02), advanced pT stage (T3) (p value = 0.01), lymphovascular invasion (p value = 0.02), and liver invasion (p value = 0.04) which were statistically significant. Higher percentage of PR expression was also observed in < 50 years age (p value = 0.01), and tumor associated with gallstone (p value = 0.04). There was no significant correlation between cytoplasmic expression of ER, PR, and clinicopathological variables. In multivariate analysis, there was no significant correlation between ER or PR positive expression and overall survival. CONCLUSION: Although nuclear expression of ERα was significantly associated with progressive disease factors but the positive expression was found in very small percentage of GBC cases. So anti-hormone therapy might be an option in patient with ER α positive gallbladder carcinoma.

Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.