Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion.

Background: Direct liver invasion (DI) is a predominant pathway of gallbladder cancer (GBC) metastasis, but the molecular alterations associated with DI remain addressed. This study identified specific genes correlated with DI, which may offer a potential biomarker for the diagnosis and prognosis of advanced GBC. Methods: RNA samples from 3 patients with DI of GBC were used for RNA-seq analysis. Differentially expressed genes and metabolic pathways between primary tumor (T) and DI tissue was used to analyze aberrant gene expressions. Immunohistochemistry (IHC) of fatty acid binding protein 1 (FABP1) in 62 patients with DI was engaged to evaluate its association with clinicopathological characteristics and prognosis. IHC of CD3+ and CD8+ T cells was analyzed for their correlation with FABP1 expression, clinicopathological features and prognosis. Univariate and multivariate Cox hazards regression analyses were performed to identify independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: FABP1 mRNA levels were significantly upregulated in DI region compared to T tissue. IHC results showed identical results with elevated FABP1 (p < 0.0001). Expression of FABP1 in DI region was significantly associated with lymph node metastasis (P = 0.028), reduced DFS (P = 0.013) and OS (P = 0.022); in contrast, its expression in T region was not associated with clinicopathological characteristics and prognosis (P > 0.05). The density of CD8+ T cells in DI region with higher FABP1 expression was significantly lower than that with lower FABP1 expression (p = 0.0084). Multivariate analysis unveiled those hepatic metastatic nodules (HR = 3.35, 95%CI: 1.37-8.15, P = 0.008) and FABP1 expression in DI region (HR = 2.01, 95%CI: 1.05-3.88, P = 0.036) were high risk factors for OS, and FABP1(HR = 2.05, 95%CI: 1.04-4.06, P = 0.039) was also a high risk factor for DFS. Conclusions: Elevated expression of FABP1 in DI region serves as a potential prognostic biomarker for advanced GBC with DI.

[Expert consensus on the laparoscopic radical resection of gallbladder cancer(2023)].

The incidence of gallbladder cancer has been increasing. Radial resection is still the most promising curable treatment for patients with gallbladder cancer. Although the techniques required for laparoscopic radical resection of gallbladder cancer have matured, the number of reports is also on the rise, and laparoscopic radical resection of gallbladder cancer is still controversial. To standardize laparoscopic radical resection of gallbladder cancer, the Biliary Surgery Branch, Chinese Society of Surgery, Chinese Medical Association, together with the Chinese Medical Doctor Association in Chinese Committee of Biliary Surgeons, gathered experts to formulate recommendations and consensus on laparoscopic radical resection of gallbladder cancer. This consensus includes several parts: safety, preoperative evaluation, indications, surgical team, positioning of patient and trocars, intraoperative frozen examination, lymph node dissection, liver resection,bile duct resection, etc. Furthermore, suggestions on the principle of treatment, surgical procedures, and precautions were also provided for patients with delayed diagnoses of gallbladder cancer undergoing resection. This consensus aims to offer valuable suggestions for the standardization of laparoscopic radical resection of gallbladder cancer.

SIRT7: A potential prognostic marker and therapeutic target in gallbladder cancer.

Gallbladder cancer (GBC) is a highly aggressive malignancy with limited treatment options and poor prognosis. In this study, we aimed to investigate the role of SIRT7, a member of the sirtuin family, in GBC and its potential as a prognostic marker and therapeutic target. Through immunohistochemistry analysis of GBC tissue samples, we observed elevated levels of SIRT7, which were correlated with worse clinicopathological parameters and shorter overall survival in GBC patients. Additionally, through cellular and animal experiments, we have discovered that interfering with SIRT7 can effectively suppress the proliferation, migration, and invasive capabilities of GBC cells. Conversely, overexpressing SIRT7 yields the opposite outcome. Furthermore, interference with SIRT7 triggers cell cycle arrest and enhances apoptosis in GBC cells. Mechanistically, we found that SIRT7 inhibition led to reduced activation of the NF-κB signaling pathway, suggesting its involvement in modulating GBC cell behavior. Our findings shed light on the oncogenic role of SIRT7 in GBC and highlight its potential as a promising prognostic marker and therapeutic target. Further research is warranted to explore the therapeutic implications of targeting SIRT7 in GBC treatment.

Survival analysis in association with GST gene polymorphism and Treatment outcomes of Gemcitabine and Cisplatin/Carboplatin-based chemotherapy among patients with Gallbladder Carcinoma.

PURPOSE: Majority of the gallbladder cancer (GBC) cases are diagnosed at an advanced stage where chemotherapy alone (or in combination with other treatment methods) is mainly opted as therapeutic approach. However, success or failure of this approach largely depends on the interindividual genetic differences. Careful consideration on the genetic association could assist in the evaluation of patient's treatment response and survival rate. Hence, the present study aims to investigate the survival of patients with GBC and their treatment response to gemcitabine and cisplatin/carboplatin-based chemotherapy in association with Glutathione S-transferase (GSTs) gene polymorphism. MATERIAL AND METHODS: A total of 216 histologically confirmed cases of gallbladder cancer were recruited. A total of 180 patients were treated with gemcitabine and cisplatin/carboplatin-based chemotherapy. GSTM1, GSTT1, and GSTP1 genotypes were determined by multiplex PCR and by PCR restriction fragment length polymorphism (PCR-RFLP), respectively. The influence of genetic polymorphism on overall survival was analyzed by Kaplan-Meier method, survival rate difference was analyzed by log-rank test, and hazard ratio for mortality outcomes was estimated using Cox regression method. RESULTS: GBC patients having genotype GSTP1 (AG + GG) showed poor 3-year survival rate of 0.8% compared to 10.9% of GSTP1 (AA) genotype (χ2 = 6.456, P = 0.011). The multivariate Cox regression results showed that the death risk was significantly higher in GSTP1 (AG + GG) genotype (HR = 3.858, P = 0.050). We found no association of GSTM1 and GSTT1 gene polymorphism with the survival; however, the combined genotypes of GSM1/GSTP1, GSTT1/GSTP1, and GSTM1/GSTT1/GSTP1 were associated with survival (P = 0.053, 0.006, and 0.058, respectively). Increased death hazard was noted by the genotype combinations of GSTM1+/GSTP1AG + GG (HR = 3.484, P = 0.024), GSTM1-/GSTP1AG + GG (HR = 2.721, P = 0.014), GSTT1+/GSTP1AG + GG (HR = 20.690, P = 0.001), and GSTT1-/GSTP1AA (HR = 26.111, P < 0.0001). Our findings indicate that chemotherapy treatment response of GSTP1 (AG + GG) has 1.62-fold increased risk for progression compared to GSTP1 (AA) genotype (p = 0.018); however, none of the genotypes showed association with overall survival and death risk after chemotherapeutic treatment. CONCLUSION: We found that the presence of GSTP1 (AG + GG) genotype showed survival disadvantage and poor treatment outcomes in response to gemcitabine and cisplatin/carboplatin-based chemotherapy. This could serve as biomarker, and future research in pharmacogenomics will definitely pave the way for the development of better treatment approach for GBC.

Clinicopathological and prognostic significance of VEGF, PDGF-B, and HER2/neu expression in gallbladder cancer.

AIM: Gallbladder cancer (GBC) is usually diagnosed in advanced stages with poor survival. The molecular mechanisms of GBC still remain unexplored. Several angiogenesis factors play a pivotal role in tumor progression. We aimed to study the expression of VEGF, PDGF-B, and human epidermal growth factor receptor 2 (HER2/neu) and its association with clinicopathological features and survival in GBC. MATERIALS AND METHODS: VEGF, PDGF-B, and HER2/neu expression was studied by immunohistochemistry (IHC) after histological evaluation in 91 GBC cases. The relationship between these markers and clinicopathological features and survival was explained through the Cox regression model and Kaplan-Meier method. RESULTS: VEGF, PDGF-B, and HER2/neu overexpressed in 45, 79, and 68% GBC cases, respectively. VEGF was significantly overexpressed in GBC without gall stones (GS) (p = 0.007) and with moderately and poorly differentiated tumors (p = 0.012). HER2/neu was significantly overexpressed in GBC with GS (p = 0.022). Median overall survival (OS) was 39 months (95% CI: 23-55). In univariate analysis, histological type (adenocarcinoma and papillary) vs. others (signet ring/mucinous/adenosquamous) (p = 0.004), depth of tumor infiltration (p = 0.017), distant metastasis (p = 0.012), and adjuvant therapies (chemotherapy/radiotherapy) (p = 0.083) were associated with poor prognosis. Multivariate survival analysis showed histological type (p = 0.004) and distant metastasis (p = 0.032) to be independent prognostic factors for OS. Histological type (p = 0.002), distant metastasis (p = 0.003), and depth of tumor infiltration (T3-T4) (p = 0.012) showed poor median survival. Poor survival was seen in VEGF and HER2/neu positive cases. CONCLUSION: Overexpression of VEGF, PDGF-B, and HER2/neu might be possible prognostic biomarkers in GBC. Poor survival of VEGF and HER2/neu positive cases indicates the possibilities of using their blockers as therapeutic agents.

Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway.

BACKGROUND: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking. METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1. RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect. CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.

Metabolomics and miRNA profiling reveals feature of gallbladder cancer-derived biliary extracellular vesicles.

BACKGROUND: Although there are several studies in the development of various human cancers, the role of exosomes is poorly understood in the progression of gallbladder cancer. This study aims to characterize the metabolic changes occurring in exosomes obtained from patients with gallbladder cancer compared with those from other gallbladder disease groups. METHODS: Biliary exosomes were isolated from healthy donors (n = 3) and from patients with gallbladder cancer (n = 3), gallbladder polyps (n = 4), or cholecystitis (n = 3) using a validated exosome isolation kit. Afterward, we performed miRNA profiling and untargeted metabolomic analysis of the exosomes. The results were validated by integrating the results of the miRNA and metabolomic analyses. RESULTS: The gallbladder cancer group exhibited a significant reduction in the levels of multiple unsaturated phosphatidylethanolamines and phosphatidylcholines compared to the normal group, which resulted in the loss of exosome membrane integrity. Additionally, the gallbladder cancer group demonstrated significant overexpression of miR-181c and palmitic acid, and decreased levels of conjugated deoxycholic acid, all of which are strongly associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: Our findings demonstrate that the contents of exosomes are disease-specific, particularly in gallbladder cancer, and that altered metabolites convey critical information regarding their phenotype. We believe that our metabolomic and miRNA profiling results may provide important insights into the development of gallbladder cancer.

Nomograms to predict long-term survival for patients with gallbladder carcinoma after resection.

BACKGROUND: Surgical resection remains the primary treatment option for gallbladder carcinoma (GBC). However, there is a pressing demand for prognostic tools that can refine patients' treatment choices and tailor personalized therapies accordingly. AIMS: The nomograms were constructed using the data of a training cohort (n = 378) of GBC patients at Eastern Hepatobiliary Surgery Hospital (EHBH) between 2008 and 2018. The model's performance was validated in GBC patients (n = 108) at Guangzhou Centre from 2007 to 2018. METHODS AND RESULTS: The 5-year overall survival (OS) rate in the training cohort was 24.4%. Multivariate analyses were performed using preoperative and postoperative data to identify independent predictors of OS. These predictors were then incorporated into preoperative and postoperative nomograms, respectively. The C-index of the preoperative nomogram was 0.661 (95% CI, 0.627 to 0.694) for OS prediction and correctly delineated four subgroups (5-year OS rates: 48.1%, 19.0%, 15.6%, and 8.1%, p < 0.001). The C-index of the postoperative nomogram was 0.778 (95%CI, 0.756 -0.800). Furthermore, this nomogram was superior to the 8th TNM system in both C-index and the net benefit on decision curve analysis. The results were externally validated. CONCLUSION: The two nomograms showed an optimally prognostic prediction in GBC patients after curative-intent resection.

Referral rate of patients with incidental gallbladder cancer and survival: outcomes of a multicentre retrospective study.

BACKGROUND: Treatment outcomes of incidental gallbladder cancer generally stem from tertiary referral centres, while many patients are initially diagnosed and managed in secondary care centres. Referral patterns of patients with incidental gallbladder cancer are poorly reported. This study aimed to evaluate incidental gallbladder cancer treatment in secondary centres, rates of referral to tertiary centres and its impact on survival. METHODS: Medical records of patients with incidental gallbladder cancer diagnosed between 2000 and 2019 in 27 Dutch secondary centres were retrospectively reviewed. Patient characteristics, surgical treatment, tumour characteristics, referral pattern and survival were assessed. Predictors for overall survival were determined using multivariable Cox regression. RESULTS: In total, 382 patients with incidental gallbladder cancer were included. Of 243 patients eligible for re-resection (pT1b-pT3, M0), 131 (53.9%) were referred to a tertiary centre. The reason not to refer, despite indication for re-resection, was not documented for 52 of 112 non-referred patients (46.4%). In total, 98 patients underwent additional surgery with curative intent (40.3%), 12 of these in the secondary centre. Median overall survival was 33 months (95% c.i. 24 to 42 months) in referred patients versus 17 months (95% c.i. 3 to 31 months) in the non-referred group (P = 0.019). Referral to a tertiary centre was independently associated with improved survival after correction for age, ASA classification, tumour stage and resection margin (HR 0.60, 95% c.i. 0.38 to 0.97; P = 0.037). CONCLUSION: Poor incidental gallbladder cancer referral rates were associated with worse survival. Age, performance status, resection margin or tumour stage should not preclude referral of a patient with incidental gallbladder cancer to a tertiary centre.

Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis.

BACKGROUND: The progression of gallbladder cancer (GBC) is accompanied by abnormal fatty acid ß-oxidation (FAO) metabolism. Different types of lipids perform various biological functions. This study aimed to determine the role of acyl carnitines in the molecular mechanisms of GBC progression. METHODS: Distribution of lipids in GBC was described by LC-MS-based lipidomics. Cellular localization, expression level and full-length of lncBCL2L11 were detected using fluorescence in situ hybridization (FISH) assays, subcellular fractionation assay and 5' and 3' rapid amplification of the cDNA ends (RACE), respectively. In vitro and in vivo experiments were used to verify the biological function of lncBCL2L11 in GBC cells. Methylated RNA Immunoprecipitation (MeRIP) was performed to detect the methylation levels of lncBCL2L11. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were used to identify lncBCL2L11 interacting proteins. Co-Immunoprecipitation (Co-IP) and Western blot assay were performed to validate the regulatory mechanism of lncBCL2L11 and THO complex. RESULTS: Acylcarnitines were significantly up-regulated in GBC tissues. High serum triglycerides correlated to decreased survival in GBC patients and promoted tumor migration. LncBCL2L11 was identified in the joint analysis of highly metastatic cells and RNA sequencing data. LncBCl2L11 prevented the binding of THOC6 and THOC5 and causes the degradation of THOC5, thus promoting the accumulation of acylcarnitines in GBC cells, leading to the malignant progression of cancer cells. In addition, highly expressed acylcarnitines stabilized the expression of lncBCL2L11 through N6-methyladenosine methylation (m6A), forming a positive feedback regulation in tumor dissemination. CONCLUSIONS: LncBCL2L11 is involved in gallbladder cancer metastasis through FAO metabolism. High lipid intake is associated with poor prognosis of GBC. Therefore, targeting lncBCL2L11 and its pathway-related proteins or reducing lipid intake may be significant for the treatment of GBC patients.

Risk prediction and analysis of gallbladder polyps with deep neural network.

The aim of this study is to analyze the risk factors associated with the development of adenomatous and malignant polyps in the gallbladder. Adenomatous polyps of the gallbladder are considered precancerous and have a high likelihood of progressing into malignancy. Preoperatively, distinguishing between benign gallbladder polyps, adenomatous polyps, and malignant polyps is challenging. Therefore, the objective is to develop a neural network model that utilizes these risk factors to accurately predict the nature of polyps. This predictive model can be employed to differentiate the nature of polyps before surgery, enhancing diagnostic accuracy. A retrospective study was done on patients who had cholecystectomy surgeries at the Department of Hepatobiliary Surgery of the Second People's Hospital of Shenzhen between January 2017 and December 2022. The patients' clinical characteristics, lab results, and ultrasonographic indices were examined. Using risk variables for the growth of adenomatous and malignant polyps in the gallbladder, a neural network model for predicting the kind of polyps will be created. A normalized confusion matrix, PR, and ROC curve were used to evaluate the performance of the model. In this comprehensive study, we meticulously analyzed a total of 287 cases of benign gallbladder polyps, 15 cases of adenomatous polyps, and 27 cases of malignant polyps. The data analysis revealed several significant findings. Specifically, hepatitis B core antibody (95% CI -0.237 to 0.061, p < 0.001), number of polyps (95% CI -0.214 to -0.052, p = 0.001), polyp size (95% CI 0.038 to 0.051, p < 0.001), wall thickness (95% CI 0.042 to 0.081, p < 0.001), and gallbladder size (95% CI 0.185 to 0.367, p < 0.001) emerged as independent predictors for gallbladder adenomatous polyps and malignant polyps. Based on these significant findings, we developed a predictive classification model for gallbladder polyps, represented as follows, Predictive classification model for GBPs = -0.149 * core antibody - 0.033 * number of polyps + 0.045 * polyp size + 0.061 * wall thickness + 0.276 * gallbladder size - 4.313. To assess the predictive efficiency of the model, we employed precision-recall (PR) and receiver operating characteristic (ROC) curves. The area under the curve (AUC) for the prediction model was 0.945 and 0.930, respectively, indicating excellent predictive capability. We determined that a polyp size of 10 mm served as the optimal cutoff value for diagnosing gallbladder adenoma, with a sensitivity of 81.5% and specificity of 60.0%. For the diagnosis of gallbladder cancer, the sensitivity and specificity were 81.5% and 92.5%, respectively. These findings highlight the potential of our predictive model and provide valuable insights into accurate diagnosis and risk assessment for gallbladder polyps. We identified several risk factors associated with the development of adenomatous and malignant polyps in the gallbladder, including hepatitis B core antibodies, polyp number, polyp size, wall thickness, and gallbladder size. To address the need for accurate prediction, we introduced a novel neural network learning algorithm. This algorithm utilizes the aforementioned risk factors to predict the nature of gallbladder polyps. By accurately identifying the nature of these polyps, our model can assist patients in making informed decisions regarding their treatment and management strategies. This innovative approach aims to improve patient outcomes and enhance the overall effectiveness of care.

Comparing robotic and open surgical techniques in gallbladder cancer management: a detailed systematic review and meta-analysis.

This meta-analysis aims to evaluate the safety and oncological outcomes of robotic surgery compared to open surgery in treating gallbladder cancer (GBC). In October 2023, we performed a literature search across major global databases such as PubMed, Embase, and the Cochrane Library. We employed a Review Manager for parameter comparisons. This study has been registered with PROSPERO under the identifier CRD42023476686. Our final meta-analysis incorporated 5 cohort studies, encompassing a total of 353 patients. Compared to the Open Group (OG), the Robotic Group (RG) had reduced intraoperative blood loss (WMD - 217.72 ml, 95% CI - 371.08 to - 64.35; p = 0.005), shorter hospital stay (WMD - 1.80 days, 95% CI - 2.66 to - 0.95; p < 0.0001), and fewer overall complications (OR 0.31, 95% CI 0.10-0.97; p = 0.04). However, there was no significant difference between the two groups in terms of operation duration, postoperative inpatient days, readmission rate, major complications, 1-year postoperative survival, 2-year postoperative survival, and mortality rates. In our study, we found that for patients with gallbladder cancer, robotic radical cholecystectomy offers certain potential advantages over open radical cholecystectomy. This suggests that robotic radical cholecystectomy might be the optimal choice for treating gallbladder cancer. However, further validation from high-quality randomized clinical trials is required.

Functional relevance of MMP2 promoter variants in gallbladder cancer: A case-control study in an Eastern Indian Population.

Gallbladder cancer (GBC) is a prevalent and deadly form of bile duct cancer, associated with poor prognosis. This study aimed to investigate the genetic factors contributing to the high incidence of GBC in certain geographical regions, particularly in the Northern and Eastern parts of India. The present case-control study focused on MMP2, a gene involved in tumor progression and metastasis, as a potential candidate in GBC pathogenesis. We scanned MMP2 promoter for twelve SNPs using Sanger's sequencing and carried out a case-control study in 300 cases and 300 control samples. We found five rare variants (rs1961998763, rs1961996235, rs1391392808, rs1488656253, and rs17859816) and one nonpolymorphic SNP (rs17859817). Our results revealed a significant association between GBC and MMP2 promoter SNPs, rs243865 (Allelic-Padjusted = 0.0353) and g.55477735G > A (Allelic-Padjusted = 9.22E-05). Moreover, the haplotype "C-C-A-C-C" exhibited a significant association with GBC (P = 4.23E-05). Genotype-phenotype correlation for variant rs243865, in the GBC patient tissue samples, established that 'T' risk allele carriers had higher expression levels of MMP2. Additionally, luciferase reporter assay in HEK293T cells revealed the probable regulatory role of rs243865 variant allele 'T' in MMP2 expression. Our study uncovers the association of MMP2 promoter SNPs with GBC and their role in regulating its expression.

Accuracy of preoperative T2 gallbladder tumor localization and the adequate surgical resection.

INTRODUCTION: The agreement between the radiologic and histopathologic tumor locations in T2 gallbladder cancer is critical. There is no consensus regarding the extent of curative resection by tumor locations. METHODS: Between January 2010 and December 2019, a consecutive series of 118 patients with pathological T2 gallbladder cancer who underwent surgery were retrospectively analyzed in terms of the accordance between radiologic and histopathologic tumor locations, the extents of hepatic resection and the numbers of harvested lymph nodes. Radical resection was defined as liver resection with harvesting of at least four lymph nodes. RESULTS: The accuracy of preoperative tumor localization was only 68%. After radical resection, the 5-year overall survival (OS) was 59.4%; after nonradical resection, the figure was 46.1% (p = 0.092). In subanalyses, the 5-year OS was marginally better for patients who underwent liver resection or from whom at least four lymph nodes were harvested than those who did not undergo liver resection or from whom three or fewer lymph nodes were harvested (58.2% vs. 39.4%, p = 0.072; 59.9% vs. 50.0%, p = 0.072, respectively). In patients with peritoneal side tumor, the 5-year OSs of those who did and did not undergo liver resection were 67% and 41.2%, respectively (p = 0.028). In multivariate analysis, perineural invasion and radical resection were independently prognostic of OS. CONCLUSION: The accuracy of preoperative tumor localization was 68%. Hepatic resection, lymph node dissection harvesting of at least four lymph nodes are required for curative resection for gallbladder cancer, regardless of tumor location.

Decoding the role of long non-coding RNAs in gallbladder cancer pathogenesis: A review focus on signaling pathways interplay.

Gallbladder cancer (GBC) is one of the most aggressive types of biliary tree cancers and the commonest despite its rarity. It is infrequently diagnosed at an early stage, further contributing to its poor prognosis and low survival rate. The lethal nature of the disease has underlined a crucial need to discern the underlying mechanisms of GBC carcinogenesis which are still largely unknown. However, with the continual evolution in the research of cancer biology and molecular genetics, studies have found that non-coding RNAs (ncRNAs) play an active role in the molecular pathophysiology of GBC development. Dysregulated long non-coding RNAs (lncRNAs) and their interaction with intracellular signaling pathways contribute to malignancy and disease development. LncRNAs, a subclass of ncRNAs with over 200 nucleotides, regulate gene expression at transcriptional, translational, and post-translational levels and especially as epigenetic modulators. Thus, their expression abnormalities have been linked to malignancy and therapeutic resistance. lnsRNAs have also been found in GBC patients' serum and tumor tissue biopsies, highlighting their potential as novel biomarkers and for targeted therapy. This review will examine the growing involvement of lncRNAs in GBC pathophysiology, including related signaling pathways and their wider clinical use.

[Can laparoscopic surgery be the preferred strategy for gallbladder cancer?]

Gallbladder cancer, notoriously known for its high malignancy, predominantly requires radical surgery as the treatment of choice. Although laparoscopic techniques have become increasingly prevalent in abdominal surgeries in recent years, the progress of laparoscopic techniques in gallbladder cancer is relatively slow. Due to the anatomical complexity, technical difficulty, and biological features of gallbladder cancer that is prone to metastasis and dissemination, traditional open surgery is still the main surgical approach. This study aims to reappraisal the current state of laparoscopic surgery for gallbladder cancer by appraising clinical practice and research evidence. Laparoscopic surgery for various stages of gallbladder cancer, including early, advanced, incidental, and unresectable gallbladder cancer were discussed. The promise and limitations of laparoscopic techniques are systematically explored.

[The impact of modified T3 sub-staging on the prognosis of gallbladder cancer patients].

Objective: To explore the value of a new modified T3 sub-staging for the prognosis evaluation in gallbladder cancer patients. Methods: This is a retrospective case-series study. The clinical data of patients with pathologically confirmed stage T3 gallbladder cancer who were admitted to the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2021 were retrospectively analyzed. A total of 190 patients were enrolled in this study, 67 males and 123 females, with an age (M(IQR)) of 63(14) years (range:17 to 88 years). The stage T3 was divided into four sub-stages according to the site of tumor invasion: (1) T3a:tumor perforates the serosa,but not invading the liver and one other adjacent structure; (2) T3b:tumor perforates the serosa and invades one other adjacent structure,but not the liver; (3) T3c:tumor perforates the serosa and invades the liver,but not one other adjacent structure; (4) T3d:tumor perforates the serosa,invades the liver and one other adjacent structure. To evaluate the application value of this modified sub-staging,the Kaplan-Meier method was used to draw the survival curve,univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results: According to the modified T3 sub-staging method,34 patients (17.9%) were in stage T3a,24 cases(12.6%) were in stage T3b, 97 cases (51.1%) were in stage T3c, and 35 cases (18.4%) were in stage T3d. The median survival time of patients in stages T3a,T3b,T3c and T3d after radical resection was 72.0 months, 32.0 months, 12.0 months and 10.0 months, respectively. The 1-, 3-, and 5-year survival rates of patients in stage T3a, T3b, T3c and T3d were 79.4%, 53.3%, and 53.3%; 79.2%, 44.6%, and 26.0%;49.5%,27.5%,and 18.1%;42.9%,15.9%, and 15.9% (χ2=18.349,P<0.01),respectively. Univariate analysis showed that gallbladder stones,pathological differentiation,perineural invasion, N stage,postoperative adjuvant therapy and modified T3 substage were factors affecting patient prognosis(all P<0.05). Cox multivariate analysis showed that modified sub-stages with T3c (HR=2.043, 95%CI:1.176 to 3.549) and T3d(HR=2.419, 95%CI:1.284 to 4.555), accompanied by gallbladder stones (HR=1.661,95%CI:1.150 to 2.398),pathological differentiation with poorly differentiated(HR=1.709,95%CI:1.198 to 2.438), and the N stage with N1 and N2(HR=1.602, 95%CI:1.090 to 2.355, 2.714, 95%CI: 1.621 to 4.544) were independent prognostic risk factors for patients in stage T3,while postoperative adjuvant chemotherapy(HR=0.351) was a protective factor for prognosis. There was no statistically significant difference in survival between patients with stage T3a and T3b who underwent hepatic wedge resection and liver segment or major resection (P=0.402). For patients with stage T3c and T3d with liver invasion,the survival difference after hepatic wedge resection and segmental or major resection was statistically significant (P=0.008). Conclusion: The modified T3 sub-staging system based on the depth and direction of tumor invasion maybe helpful to further stratify the prognosis of patients with gallbladder cancer.