Gallbladder Carcinoma Patients Research Articles

Prognostic evaluation in gallbladder carcinoma: Introducing a composite risk model integrating nutritional and immune markers.

The importance of evaluating the nutritional status and immune condition prior to surgery has gained significant attention in predicting the prognosis of cancer patients in recent years. The objective of this study is to establish a risk model for predicting the prognosis of gallbladder carcinoma (GBC) patients. Data from GBC patients who underwent radical resection at West China Hospital of Sichuan University (China) from 2014 to 2021 were retrospectively collected. A novel risk model was created by incorporating the prognostic nutritional index and glucose-to-lymphocyte ratio, and each patient was assigned a risk score. The patients were then divided into low- and high-risk cohorts, and comparisons were made between the two groups in terms of clinicopathological features and prognosis. Propensity score matching was conducted to reduce potential bias. A total of 300 GBC patients receiving radical surgery were identified and included in this study. Patients in the high-risk group were older, had higher levels of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and cancer antigen 19-9 (CA19-9), were more likely to experience postoperative complications, and had more aggressive tumor characteristics, such as poor differentiation, lymph node metastasis, and advanced tumor stage. They also had lower overall survival (OS) rates (5-year OS rate: 11.2% vs. 37.4%) and disease-free survival (DFS) rates (5-year DFS rate: 5.1% vs. 18.2%). After propensity score matching, the high-risk population still experienced poorer prognosis (5-year OS rate: 12.7% vs 20.5%; 5-year DFS rate: 3.2% vs 8.2%). The risk model combining prognostic nutritional index and glucose-to-lymphocyte ratio can serve as a standalone predictor for the prognosis and assist in optimizing the treatment approach for GBC patients.

Association of tumor budding and tumor infiltrating lymphocytes with clinicopathological parameters in gallbladder carcinoma.

Gallbladder carcinoma (GBC) poses significant challenges in oncology due to its aggressive nature and limited treatment options. The lack of effective biomarkers for early detection and prognosis exacerbates the prognosis for GBC patients. Tumor budding (TB) and tumor infiltrating lymphocytes (TILs) have emerged as potential prognostic indicators in various cancers, reflecting tumor-host immune interactions and tumor aggressiveness. The study of TB and TILs in GBC is particularly important due to the limited literature available. This retrospective observational study aimed to evaluate the association of TB and TILs with clinicopathological parameters in GBC patients. Clinicopathological data were collected from patients with histologically confirmed GBC who underwent surgical resection. The sections were evaluated for TB and TILs using standardized methods. Statistical analysis was performed to assess associations between these parameters and clinicopathological variables. Tumor stage and grade showed significant associations with TB and TILs, indicating their potential as prognostic markers. High TB correlated with advanced tumor stage and higher grade, while high TIL infiltration was associated with early tumor stage and lower grade. Additionally, TILs exhibited a significant association with lymphovascular invasion. Interestingly, an inverse association was observed between TB and TILs, highlighting the dynamic interplay between tumor aggressiveness and host immune response. TB and TILs hold prognostic significance in GBC, offering insights into its pathogenesis and potential therapeutic targets. Future research exploring the mechanistic underpinnings of tumor-host immune interactions in GBC is crucial for translating these findings into clinical applications and improving outcomes for patients.

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

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. 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. 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. The two nomograms showed an optimally prognostic prediction in GBC patients after curative-intent resection.

Prognostic value of combined preoperative inflammatory marker neutrophil-lymphocyte ratio and platelet distribution width in patients with gallbladder carcinoma.

The neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW) are associated with poor prognosis in various cancers. We aimed to analyze the prognostic value of the combination of preoperative NLR and PDW in patients with gallbladder carcinoma (GBC). A total of 287 GBC patients who underwent curative-intent surgery in our institution was included. The relationship between NLR and PDW and clinicopathological features were analyzed. The receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for NLR and PDW. Overall survival (OS) was estimated using the Kaplan-Meier method. Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. The optimal cutoff value of NLR and PDW was 3.00 and 14.76, respectively. In addition, survival analysis demonstrated that patients with NLR > 3.00 and PDW > 14.76 had a worse prognosis than patients with NLR ≤ 3.00 and PDW ≤ 14.76, respectively. The multivariate analysis showed that NLR and PDW were independent prognostic factors in the patients with GBC. When we combined NLR and PDW, the area under the ROC curve increased from 0.665 (NLR) and 0.632 (PDW) to 0.676. Moreover, the 1-, 3-, and 5-year OS of group A (patients with NLR ≤ 3.00 and PDW ≤ 14.76), group B (patients with either of NLR > 3.00 or PDW > 14.76) and group C (patients with NLR > 3.00 and PDW > 14.76) were 88.7%, 62.6%, 28.1%, 65.1%, 26.9%, 13.1%, and 34.8%, 8.3%, 0%, respectively. The combination of NLR and PDW may serve as a significant prognostic biomarker for GBC patients superior to either NLR or PDW alone.

Efficacy and safety of a combination of sintilimab, bevacizumab plus gemcitabine, and albumin-bound paclitaxel for initially unresectable gallbladder carcinoma: A prospective, single-arm phase II study.

489 Background: Immune checkpoint inhibitors plus chemotherapy had demonstrated important therapeutic advantages in biliary tract cancers (TOP-AZ and Keynote-966). At present the data of gallbladder carcinoma (GBC) is in blank condition almost, and the effectiveness remains to be improved. Further, the addition of bevacizumab to PD-1 inhibitors has improved the clinical results in carcinomas, such as hepatocellular carcinoma, for which therapeutic options have been limited. This study intended to explore the safety and efficacy of sintilimab combined bevacizumab with chemotherapy in the first-line treatment of initially unresectable GBC. Methods: The study was an ongoing open-label, single-arm, phase II trial (Clinical Trial ID: NCT05757336), which consisted of 2 parts: safety-run-in part, where pts received sintilimab (200mg/kg, iv, d1, Q3W) + bevacizumab (7.5mg/kg, iv, d1, Q3W) + gemcitabine (1000mg/m2, iv, d1, Q3W) and albumin-bound paclitaxel (125mg/m2, iv, d1, Q3W), followed by experimental part to evaluate the efficacy and safety of this strategy. The primary endpoint was safety and objective response rate (ORR) assessed by RECIST v1.1. Secondary objectives included disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: No DLT was reported at safety-run-in part. Up to the end of Sept 2023, 15 patients were enrolled with a median age of 60.4 years (range 46-75), 26.7% were male. Median follow-up time was 3.68 months. All patients completed at least one tumor response evaluation, confirmed ORR was 60.0% and DCR was 93.3%. Median PFS and OS was not reached yet. Grade 3 TRAEs occurred in 40.0% of patients (n=6), and the most common TRAEs (incidence≥5%) among them were rash (20.0%), AST elevation (6.7%), fever (6.7%), platelet count decreased (6.7%), fatigue (6.7%), pneumonitis (6.7%). Conclusions: The combination of sintilimab, bevacizumab and AG chemotherapy was tolerable and showed a promising ORR in initially unresectable GBC patients. This regimen could be a feasible and safe option for initially unresectable GBC, but this needs further validation. Clinical trial information: NCT05757336 .

Deep learning nomogram for preoperative distinction between Xanthogranulomatous cholecystitis and gallbladder carcinoma: A novel approach for surgical decision

The distinction between Xanthogranulomatous Cholecystitis (XGC) and Gallbladder Carcinoma (GBC) is challenging due to their similar imaging features. This study aimed to differentiate between XGC and GBC using a deep learning nomogram model built from contrast enhanced computed tomography (CT) scans. 297 patients were included with confirmed XGC (94) and GBC (203) as the training and internal validation cohort from 2017 to 2021. The deep learning model Resnet-18 with Fourier transformation named FCovResnet18, shows most impressive potential in distinguishing XGC from GBC using 3-phase merged images. The accuracy, precision and area under the curve (AUC) of the model were then calculated. An additional cohort of 74 patients consisting of 22 XGC and 52 GBC patients was enrolled from two subsidiary hospitals as the external validation cohort. The accuracy, precision and AUC achieve 0.98, 0.99, 1.00 in the internal validation cohort and 0.89, 0.92, 0.92 in external validation cohort. A nomogram model combining clinical characteristics and deep learning prediction score showed improved predicting value. Altogether, FCovResnet18 nomogram has demonstrated its ability to effectively differentiate XGC from GBC preoperatively, which significantly aid surgeons in making informed and accurate surgical decisions for XGC and GBC patients.

The utility of systemic immune inflammatory index in discriminating between gallbladder cancer and xanthogranulomatous cholecystitis: A single-tertiary center experience.

Xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma (GBC) are rare diseases with several similarities. This study aimed to evaluate the utility of the systemic immune inflammatory index (SII), a novel index that more accurately depicts inflammatory and immunological balance, in distinguishing between XGC and GBC. This retrospective study included 33 XGC, 22 GBC patients diagnosed according to histopathological findings and 33 age-sex-matched healthy controls at Hacettepe University Faculty of Medicine, General Surgery Department. The demographic, clinical and laboratory findings were recorded. Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, monocyte to lymphocyte ratio and SII were calculated from preoperative complete blood count parameters. The receiver operating characteristic curve was performed to evaluate the utility of SII in differentiating GBC and XGC. A P value < .05 was accepted as statistically significant. The preoperative neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, platelet to lymphocyte ratio and SII were significantly higher in patients with GBC compared to XGC patients and healthy controls (P < .001, P = .001, P = .001, P < .001, respectively). When receiver operating characteristic analysis was made, the optimal cutoff value of SII was 640 for differential diagnosis of XGC and GBC preoperatively with a sensitivity of 77.3% and a specificity of 66.7%, among which the positive likelihood ratio was 2.32, and Youden index was 0.44 (P = .006). The positive predictive value was 60.7%, the negative predictive value was 81.5%, and the diagnostic accuracy was 79.9%. SII may be a valuable, practical, and affordable method to differentiate between XGC and GBC, in addition to clinical and radiological signs, prior to surgery. When supported by prospective trials with a larger study population, distinguishing GBC from XGC using SII preoperatively may lead to a change in the management practice of GBC.

Metastatic lymph node ratio as an important prognostic factor in advanced gallbladder carcinoma with at least 6 lymph nodes retrieved

BackgroundThe metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined.MethodsFrom January 2007 to January 2018, 144 advanced GBC patients (T2–4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS).ResultsThe optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195–2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463–0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148–2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589–0.892) were independent prognostic factors for GBC (all P<0.05).ConclusionsLNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved.

EMP3 as a key downstream target of miR-663a regulation interferes with MAPK/ERK signaling pathway to inhibit gallbladder cancer progression

Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, and its molecular pathogenesis remains unclear. Here we explore the functional roles of epithelial membrane protein 3 (EMP3) in GBC progression, which is aberrantly expressed in various types of cancers. The results showed that the expression level of EMP3 was reduced in human GBC tissues compared with non-malignant tissues. Further, the low expression of EMP3 was associated with the poor prognosis of GBC patients by Kaplan-Meier analysis. The ectopic expression of EMP3 inhibited GBC cell proliferation, migration and invasion in vitro and in vivo. Conversely, the depletion of EMP3 promoted GBC cell growth and metastasis. In addition, we found that EMP3 was a target gene of miR-663a, and the downregulation of EMP3 in GBC was attributed to the overexpression of miR-663a. MiR-663a was also shown to be a tumor-promoting factor mediating GBC development. In this study, we demonstrate that downregulation of EMP3 activates MAPK/ERK signaling, which regulates GBC progression. These data reveal the mechanism by which EMP3 inhibits the progression of GBC, suggesting that the miR-663a/EMP3/MAPK/ERK axis may be a new therapeutic target for GBC treatment.

The significance of countable and treatable metastatic liver disease in patients with gallbladder carcinoma after curative-intent surgery: A 10-year experience in China.

Our study was performed to evaluate the significance of countable and treatable metastatic liver disease (CTMLD) in patients with gallbladder carcinoma (GBC) after curative-intent surgery. Resected GBC patients between September 2010 and January 2021 were reviewed. Comparative analyses between patients with CTMLD and those without it were performed. A propensity score matching analysis was conducted for further validation. A total of 326 resected GBC patients were identified (33 with CTMLD). A significantly higher preoperative CA199 level was detected in those with CTMLD (p = 0.0160). Significantly higher incidences of major hepatectomy (p = 0.0010), lymph node metastasis (p < 0.0001), direct liver invasion (p < 0.0001), moderate to poor differentiation status (p < 0.0001), and T3-4 disease (p < 0.0001) were detected in patients with CTMLD. Even sharing comparable surgical margin status, patients with CTMLD still shared a significantly higher recurrence rate (93.9% vs. 57.3%, p < 0.0001) as well as a significantly higher recurrence rate within 6 months after surgery (63.6% vs. 14.7%, p < 0.0001). A significantly worse overall survival (median survival time: 12 vs. 33 months, p < 0.0001) or disease-free survival (median recurrence-free time: 6 vs. 30 months, p < 0.0001) was acquired in patients with CTMLD. After matching, a significantly higher early recurrence rate was still detected. Adjuvant chemotherapy seemed to have survival benefit for patients with CTMLD. CTMLD was an indicator of advanced disease and served as an independent predictor of early recurrence among resected GBC patients. Whether curative-intent surgery is superior to nonsurgical treatment among GBC patients with CTMLD remains to be explored in future prospective studies.

The clinical impact of early recurrence and its recurrence patterns in patients with gallbladder carcinoma after radical resection

BackgroundIt is common for patients with gallbladder carcinoma (GBC) to develop recurrence shortly after radical resection. We aimed to investigate the risk factors of early recurrence (ER) and its recurrence patterns and further analyze the effect of adjuvant chemotherapy (ACT) on ER and non-ER patients for decision-making in clinical practice. MethodsA total of 276 patients who underwent radical resection for GBC were retrospectively analyzed. Factors associated with overall survival (OS) and recurrence free survival (RFS) were identified using the Cox proportional hazard regression model, whereas ER was investigated using univariate and multivariable logistic regression models. ResultsThe results indicated that 23.2% (64/276) of GBC patients developed ER after radical resection. ER was determined to be an independent risk factor for OS in patients with GBC after resection (P < 0.05). CA125, liver invasion, T stage, and N stage were independently associated with ER (P < 0.05). N1/N2 stage disease was an independent risk factor for OS, RFS and ER, and had a better predictive value in identifying ER than the other three variables associated with ER (P < 0.05). The liver and lymph nodes were the main first recurrence sites, and ER patients had a higher proportion of multisite recurrence. The prognosis of GBC patients with ER after radical resection differed significantly depending on whether ACT was provided, with ACT demonstrated to improve their prognosis (P < 0.05). ConclusionsEarly recurrence after radical resection indicates a very poor prognosis in GBC and can be used to identify those who will benefit from ACT.

Microcystin-leucine-arginine promotes the development of gallbladder carcinoma via regulating ELAC2

Gallbladder carcinoma (GBC) is the most prevalent cancer of the bile tract, with unexpected GBC accounting for almost half of all GBC cases in some tertiary medical centers. Although the involvement of microcystin-leucine-arginine (MC-LR) in the development of intrahepatic cholangiocarcinoma has been established, there is a paucity of data regarding its association with GBC. The present study aims to investigate whether MC-LR level in the gallbladder of patients is associated with GBC development and, if so, to characterize the underlying mechanism in GBC cells. Our clinical data revealed that MC-LR level was significantly increased in GBC patients compared to patients with gallbladder stones only (P = 0.009). Moreover, our findings demonstrated that MC-LR could promote the proliferation and metastasis of human GBC cell lines. Furthermore, ELAC2 was identified as a critical mRNA involved in GBC progression through RNA sequencing. Collectively, our study suggests that MC-LR might be involved in the development of GBC by modulating the expression of ELAC2.

Comparison of cfDNA content in different cancer types with different extraction methods.

e15026 Background: ctDNA liquid biopsy technology has been widely used in the whole course of cancer management, from early screening and early diagnosis of tumors to tumor monitoring and medication guidance. However, the performances of ctDNA as a biomarker in these scenarios are different among different cancer types. One possible reason is that different types of cancer release different amounts of ctDNA or cfDNA, therefore, we explored the cfDNA levels in different cancer types in this study. Methods: We collected 15913 peripheral blood samples from 14686 cancer patients with different clinicopathologies, 256 patients with pulmonary nodules, and 971 healthy people. We isolated their plasma and extracted the cfDNA using QIAamp Circulating Nucleic Acid Kit, Apostle MiniMax cfDNA Extraction Kit or HaploX magnetic bead method cfDNA extraction kit. We calculated the average concentration of cfDNA (ng/ml) for different groups. Results: The number of samples of cervical cancer, liver cancer, glioma, colon cancer, prostate cancer, nasopharyngeal carcinoma, gallbladder carcinoma, melanoma, cholangiocarcinoma, colorectal cancer, breast cancer, gastric cancer, endometrial carcinoma, lung cancer, urothelial carcinoma, rectal cancer, ovarian cancer, healthy people, and pulmonary nodule patients are 93, 469, 113, 277, 139, 76, 89, 132, 171, 4010, 407, 547, 68, 7750, 46, 203, 96, 971 and 256, respectively. The cfDNA level of corresponding groups are 88.07, 79.51, 75.57, 63.58, 61.37, 59.09, 57.59, 57.16, 42.67, 34.73, 31.75, 31.37, 31.33, 29.84, 28.72, 28.69, 23.83, 17.82 and 12.54 ng/ml, respectively. The main groups are shown in the table below. Conclusions: The cfDNA concentrations of healthy people or pulmonary nodule patients were significantly lower than that of tumor patients, and there were also significant differences between different types of cancer. What's interesting, the cfDNA concentrations of lung cancer patients, pulmonary nodule patients and healthy people were quite different. What’s more, there were differences between Colon cancer and Rectal cancer patients. So, the cfDNA concentration maybe a good dimention to be used in early cancer screening and tracing of tumor types. [Table: see text]

Textbook outcome in gallbladder carcinoma after curative-intent resection: a 10-year retrospective single-center study.

Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients. A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO. Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05). Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.

Expression of ER, PR, and HER-2 Neu and correlation with tumor markers in gall bladder carcinoma.

Females having a large proportion of gallbladder carcinoma (GBC) and a higher incidence of gallstones pointed toward the role of sex hormones in GBC development. In this study, we evaluated the expression of Estrogen receptor (ER), Progesterone receptor (PR), and Her2/neu and their correlation with tumor markers and clinicopathological parameters in the GBC. A total of 50 patients of GBC and 42 patients in control group undergoing surgery for other conditions were taken. The patient's biopsy sample's paraffin block was tested for ER, PR, and Her2/neu expression by immunohistochemistry. ER and PR had no significant expression in GBC and control group, but Her2/neu had 16% expression in GBC, significantly associated with the degree of differentiation with 62.5% (n-5) being well-differentiated; 75% of Her2/neu positive were in stages III and IV. Her2/neu did not correlate with tumor markers despite expression. Her2/neu amplification is a small step in validating that option so it could be included in the treatment and prognostication of GBC.

The significance of peri-neural invasion in patients with gallbladder carcinoma after curative surgery: a 10year experience in China.

The significance of peri-neural invasion (PNI) in patients with gallbladder carcinoma (GBC) after curative surgery remains unknown. Current study was performed to evaluate the significance of PNI in resected GBC patients in terms of tumor-related biological features and long-term survival. Patients with GBC between September 2010 and September 2020 were reviewed and analyzed. SPSS 25.0 software were used for statistical analysis. A total of 324 resected GBC patients were identified (No. PNI: 64). An elevated preoperative Ca19.9 level (P = 0.001), obstructive jaundice (P = 0.001), liver invasion (P < 0.0001), lymph-vascular invasion (P < 0.0001), lymph-node metastasis (P < 0.0001), and poor or moderate differentiation status (P = 0.036) were more frequently detected in patients with PNI. Major hepatectomy (P = 0.019), bile duct resection (P < 0.0001), combined multi-visceral resections (P = 0.001), and combined major vascular resections and reconstructions (P = 0.002) were also more frequently detected. However, a significantly lower R0 rate (P < 0.0001) was acquired in patients with PNI. Patients with PNI were generally more advanced disease and shared a much worse prognosis even after matching. PNI was an independent prognostic factor of disease-free survival as well as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy has brought an obvious survival benefit in resected GBC patients with PNI. PNI could be regarded as an indicator of worse prognosis and could serve as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy was correlated with an improved survival for resected GBC patients with PNI. Upcoming multicenter studies covering various races are warranted for further validation.

Expression Patterns of PAK4 and PHF8 Are Associated with the Survival of Gallbladder Carcinoma Patients

PAK4 and PHF8 are involved in cancer progression and are under evaluation as targets for cancer therapy. However, despite extensive studies in human cancers, there are limited reports on the roles of PAK4 and PHF8 in gallbladder cancers. Immunohistochemical expression of PAK4 and PHF8 and their prognostic significance were evaluated in 148 human gallbladder carcinomas. PAK4 expression was significantly associated with PHF8 expression in gallbladder carcinomas. Positive expression of nuclear PAK4, cytoplasmic PAK4, nuclear PHF8, and cytoplasmic PHF8 were significantly associated with shorter overall survival and relapse-free survival in univariate analysis. Multivariate analysis showed that nuclear PAK4 expression and nuclear PHF8 expression were independent predictors of overall survival and relapse-free survival in gallbladder carcinomas. Furthermore, coexpression of nuclear PAK4 and nuclear PHF8 predicted shorter overall survival (p < 0.001) and relapse-free survival (p < 0.001) of gallbladder carcinoma in multivariate analysis. This study suggests that the individual and coexpression patterns of PAK4 and PHF8 as the prognostic indicators for gallbladder carcinoma patients.

Intelligent recognition of CTCs from gallbladder cancer by ultrasensitive electrochemical cytosensor and diagnosis of chemotherapeutic resistance

Gallbladder carcinoma (GBC) is one of most aggressive and lethal malignancies. Early diagnosis of GBC is crucial for determining appropriate treatment and improving chances of cure. Chemotherapy represents the main therapeutic regimen for unresectable GBC patients to inhibit tumor growth & metastasis. But, chemoresistance is the major cause of GBC recurrence. Thus, there is an urgent need to explore potentially non-invasive and point-of-care approaches to screen GBC and monitor their chemoresistance. Herein, we established an electrochemical cytosensor to specifically detect circulating tumor cells (CTCs) and their chemoresistance. Trilayer of CdSe/ZnS quantum dots (QDs) were cladded upon SiO2 nanoparticles (NPs), forming Tri-QDs/PEI@SiO2 electrochemical probes. Upon conjugation of anti-ENPP1, the electrochemical probes were able to specifically label captured CTCs from GBC. The detection of CTCs and chemoresistance were realized by square wave anodic stripping voltammetric (SWASV) responses to anodic stripping current of Cd 2+ ion when cadmium in electrochemical probes was dissolved and eventually electrodeposited on bismuth film-modified glassy carbon electrode (BFE). Taking use of this cytosensor, one ensured the screening of GBC and limit of detection for CTCs approaches to ～10 cells/mL. Furthermore, by monitoring phenotypic changes of CTCs after drug treatment, the diagnosis of chemoresistance was achieved by our cytosensor.

Analysis of safety and efficacy of laparoscopic surgery for gallbladder carcinoma

Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ2 test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ2=0.399,P=0.528) and overall(χ2=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.

Development and validation of a nomogram prediction model based on albumin-to-alkaline phosphatase ratio for predicting the prognosis of gallbladder carcinoma.

Gallbladder carcinoma (GBC) is a rare biliary tract cancer with a high recurrence rate and a poor prognosis. Albumin-alkaline phosphatase ratio (AAPR) has been demonstrated to be a prognostic predictor for several cancers, but its predictive value for GBC patients remains unknown. The aim of this study was to investigate the predictive role of AAPR in GBC patients and to develop a novel nomogram prediction model for GBC patients. We retrospectively collected data from 80 patients who underwent surgery at the Hospital of 81st Group Army PLA as a training cohort. Data were collected from 70 patients with the same diagnosis who underwent surgery at the First Affiliated Hospital of Hebei North University as an external verification cohort. The optimal cut-off value of AAPR was determined using X-tile software. A nomogram for the overall survival (OS) based on multivariate Cox regression analysis was developed and validated using calibration curves, Harrell's concordance index, the receiver operating characteristic curves, and decisive curve analyses. The optimal cut-off value of AAPR was .20. Univariate and multivariate Cox regression analyses demonstrated that BMI (p = .043), R0 resection (p = .001), TNM stage (p = .005), and AAPR (p = .017) were independent risk factors for GBC patients. In terms of consistency, discrimination, and net benefit, the nomogram incorporating these four independent risk factors performed admirably. AAPR is an independent predictor of GBC patients undergoing surgery, and a novel nomogram prediction model based on AAPR showed superior predictive ability.