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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Locally advanced, inoperable, or metastatic gallbladder cancers (GBC) are treated with either gemcitabine-platinum combinations or gemcitabine alone based on physician discretion. However, the combination of gemcitabine, cisplatin, and nab-paclitaxel (GCNP) has shown increased response rates and prolonged survival in a phase II trial of biliary tract patients. Materials and Methods: Consecutive series of patients diagnosed with locally advanced (liver infiltration > 5 cm, large nodes at porta, abutting duodenum), inoperable, and metastatic biliary tract patients between January 2018 and August 2022 were evaluated for first-line chemotherapy GCNP, in the multidisciplinary joint clinic (MDJC). The primary endpoint was ORR, and the major secondary endpoint was event-free survival (EFS). Results: A total of 142 patients received GCNP during the specified time period. The median age of the cohort was 52 years (range: 21–79), the majority were females (61.3%), and the majority were GB (81.7%). Response rates were available in 137 patients. Complete response, partial response, and stable disease were seen in 9 (6.3%), 87 (61.3%), and 24 (16.9%), respectively, for an ORR of 67.6% and a clinical benefit rate of 84.5%. The median EFS was 9.92 (95% CI, 7.69–12.14) months. Of the 52 patients in whom GCNP was given with NACT intent for locally advanced GBC, 17 patients underwent surgery (34%). Conclusion: Our study indicates that GCNP leads to improved response rates, increased chances of resectability, and possibly better survival in patients with GBC. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: 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. Results: 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. Conclusion: The combination of NLR and PDW may serve as a significant prognostic biomarker for GBC patients superior to either NLR or PDW alone. [ABSTRACT FROM AUTHOR]

Background: Gallbladder carcinoma (GC) is a rare malignant tumor. Laparoscopic technology has revolutionized the reality of surgery. However, whether laparoscopic surgery is suitable for GC has not been clarified. We aimed to analyze the safety, feasibility, and oncological outcomes of laparoscopic surgery in GC. Methods: The medical records of patients with GC treated at our hospital between January 2016 and December 2021 were retrospectively reviewed. Patients who underwent laparoscopic and open surgery were compared. Propensity score matched analysis was performed to balance the basic characteristics of the two groups. Kaplan–Meier curves were used to describe and compare the overall and disease-free survival rates between the groups. Results: A total of 163 patients with GC were included. Cholelithiasis was detected in 64 (39.3%) patients. Seventy patients were matched after propensity score matching. The laparoscopic group was significantly better than the open group in terms of operation time (p < 0.001), blood loss (p = 0.002), drain time (p = 0.001), and hospital stay (p < 0.001). After a median follow-up time of 19 (12, 35) months, there was no significant difference in the cumulative overall (p = 0.650) and disease-free (p = 0.663) survival rates between the laparoscopic and open groups according to Kaplan–Meier curves. Conclusion: Laparoscopic surgery can reduce the operation time and blood loss, and shorten drain time and hospital stay without increasing the incidence of complications. Patients undergoing laparoscopic and open surgery have a similar prognosis. Laparoscopic surgery is worth promoting in patients with GC. [ABSTRACT FROM AUTHOR]

Background: Thick wall gallbladder (TWGB) is not an uncommon finding on ultrasonography especially in region with high prevalence of gall stones disease like north India. On most occasion, these thickening could be because of benign disorders but malignancy are not a rare cause of it. Preoperative distinction between benign and malignant causes of TWGB is important as the surgical treatment entirely differ. Despite after thorough evaluation with various imaging modalities, a definitive diagnosis cannot be reached on many occasion. The aim of our study was to review the literature for the diagnosis and management approach in patients with TWGB. Methods: We perform a thorough online search of full text articles related with thick wall GB published in English literature. After doing a critical appraisal of available literature, a comprehensive narrative review was described. Conclusions: In this review, the authors have described a clinical algorithmic approach by detailing the diagnostic utility of various imaging modalities and also different surgical options for treatment especially in cases of ambiguity. [ABSTRACT FROM AUTHOR]

Background: The 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. Methods: From 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). Results: The 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). Conclusions: LNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. Methods: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. Results: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). Conclusion: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is the most common malignancy of the biliary system, often associated with a poor prognosis in its advanced stages. The GB-RADS (Gallbladder Reporting and Data System) was recently developed to standardize the interpretation of ultrasound findings and evaluate the risk of malignancy. This study aims to assess the role of GB-RADS in predicting malignancy in cases of gallbladder wall thickening. All patients aged 18 years and above with gallbladder wall thickening > 3 mm in screening USG were included between August 2022 to March 2024. GB-RADS score was then compared to histopathological diagnosis of surgical specimen for resectable disease and FNAC/core needle biopsy for unresectable disease. A total of 150 patients were assessed in this study, all of whom underwent evaluation of GB-RADS via ultrasonography. Among them, 14 (9.2%) had a GB-RADS score of 2, 26 (17.5%) had a score of 3, 31 (20.8%) had a score of 4, and 79 (52.5%) had a score of 5. Following histopathological evaluation, 34 (22.5%) were found to be benign and 116 (77.5%) were malignant. The area under the ROC curve for GB-RADS scoring in predicting histopathology as malignant versus benign was 0.957 (95% CI: 0.926—0.987), indicating excellent diagnostic accuracy with a statistically significant result (p < 0.001). Ultrasonography (USG) has long been a key diagnostic tool for detecting gallbladder cancer (GBC), offering high sensitivity and specificity, particularly in the absence of mass-forming lesions. GB-RADS can serve as an excellent method for predicting carcinoma in patients with gallbladder wall thickening. [ABSTRACT FROM AUTHOR]

The article discusses the "rosary sign" in abdominal radiology, which is used to differentiate adenomyomatosis of the gallbladder from gallbladder carcinoma. The rosary sign is characterized by hyper-enhanced gallbladder epithelium with intramural fluid-filled diverticula, resembling the beads of a rosary. Adenomyomatosis is a benign condition that can mimic gallbladder malignancy, and the presence of the rosary sign on contrast-enhanced CT scans helps increase diagnostic accuracy. Surgical resection may be necessary in symptomatic patients or when gallbladder carcinoma cannot be excluded by imaging. [Extracted from the article]

There are highly conflicting data on relative frequency (2–32%), prognosis, and management of pT1b-gallbladder carcinoma (GBC), with 5-year survival ranging from > 90% in East/Chile where cholecystectomy is regarded as curative, versus < 50% in the West, with radical operations post-cholecystectomy being recommended by guidelines. A total of 473 in situ and invasive extensively sampled GBCs from the USA (n = 225) and Chile (n = 248) were re-evaluated histopathologically per Western invasiveness criteria. 349 had invasive carcinoma, and only 24 were pT1. Seven cases previously staged as pT1b were re-classified as pT2. There were 19 cases (5% of all invasive GBCs) qualified as pT1b and most pT1b carcinomas were minute (< 1mm). One patient with extensive pTis at margins (but pT1b focus away from the margins) died of GBC at 27 months, two died of other causes, and the remainder were alive without disease (median follow-up 69.9 months; 5-year disease-specific survival, 92%). In conclusion, careful pathologic analysis of well-sampled cases reveals that only 5% of invasive GBCs are pT1b, with a 5-year disease-specific survival of > 90%, similar to findings in the East. This supports the inclusion of pT1b in the "early GBC" category, as is typically done in high-incidence regions. Pathologic mis-staging of pT2 as pT1 is not uncommon. Cases should not be classified as pT1b unless extensive, preferably total, sampling of the gallbladder to rule out a subtle pT2 is performed. Critical appraisal of the literature reveals that the Western guidelines are based on either SEER or mis-interpretation of stage IB cases as "pT1b." Although the prognosis of pT1b-GBC is very good, additional surgery (radical cholecystectomy) may be indicated, and long-term surveillance of the biliary tract is warranted. [ABSTRACT FROM AUTHOR]

Purpose: To analyze diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder (GBC) and to establish its possible impact on post-recurrence survival. Method: FDG PET/CT studies of suspected recurrent GBC were retrospectively analyzed alongside tumor markers serum CEA and CA 19-9. Abnormal FDG-avid lesions and abnormal morphological lesions were considered positive for recurrence, and were categorized as isolated abdominal wall recurrence, loco-regional recurrence, and distant metastatic disease. Histopathology, definite progression on imaging and positive response to treatment was considered as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used as diagnostic performance parameters. Post-recurrence survival was calculated whenever appropriate follow-up was available, based on the abovementioned categories of sites of recurrence using survival curves and log-rank test. Results: Out of 117 PET/CT studies, 93 (79.5%) were positive and 24 (20.5%) were negative for recurrence. 86 out of 93 were true positive and 23 of 24 were true negative. PET/CT demonstrated sensitivity, specificity, PPV, NPV and accuracy of 98.8%, 76.7%, 92.5%, 95.8% and 93.1%, respectively. Diagnostic performance of PET/CT was significantly better than combination tumor markers. Of 66 cases with available follow-up, isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence demonstrated significantly higher post-recurrence survival as compared to distant metastasis; median survival being 39, 25 and 12 months, respectively. Conclusion: F-18 FDG PET/CT has better diagnostic performance than tumor markers combination. Isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence on PET/CT demonstrated better survival than non-regional metastatic disease. These results suggest a possible role of PET/CT as a surveillance modality, as well as a guide to therapeutic decision-making in cases of recurrent GBC. [ABSTRACT FROM AUTHOR]

Background: It is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8–15 mm based on preoperative ultrasound. Methods: The independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables. Results: Independent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0–0.2), [0.2–0.5), [0.5–0.8) and [0.8–1] according to the total points of [− 337, − 234], [− 197, − 145], [− 123, − 108], and [− 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively. Conclusion: A BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8–15 mm undergoing cholecystectomy based on preoperative ultrasound. [ABSTRACT FROM AUTHOR]

Objectives: Gallbladder carcinoma (GBC) is the most common and aggressive biliary tract malignancy with high postoperative recurrence rates. This single-center study aimed to develop and validate a radiomics signature to estimate GBC recurrence-free survival (RFS). Methods: This study retrospectively included 204 consecutive patients with pathologically diagnosed GBC and were randomly divided into development (n = 142) and validation (n = 62) cohorts (7:3). The radiomics features of tumor were extracted from preoperative contrast-enhanced CT imaging for each patient. In the development cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression was employed to develop a radiomics signature for RFS prediction. The patients were stratified into high-score or low-score groups according to their median value of radiomics score. A nomogram was established using multivariable Cox regression by incorporating significant pathological predictors and radiomics signatures. Results: The radiomics signature based on 12 features could discriminate high-risk patients with poor RFS. Multivariate Cox analysis revealed that pT3/4 stage (hazard ratio, [HR] = 2.691), pN2 stage (HR = 3.60), poor differentiation grade (HR = 2.651), and high radiomics score (HR = 1.482) were independent risk variables associated with worse RFS and were incorporated to construct a nomogram. The nomogram displayed good prediction performance in estimating RFS with AUC values of 0.895, 0.935, and 0.907 at 1, 3, and 5 years, respectively. Conclusions: The radiomics signature and combined nomogram may assist in predicting RFS in GBC patients. Key Points: • A radiomics signature extracted from preoperative contrast-enhanced CT can be a useful tool to preoperatively predict RFS of GBC. • T3/T4 stage, N2, poor tumor differentiation, and high radiomics score were positively associated with postoperative recurrence. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the utility of combining clinical and contrasted-enhanced tomography (CECT) parameters for the preoperative evaluation of perineural invasion (PNI) in gallbladder carcinoma (GBC).A total of 134 patients with GBC (male/female, 52/82; age, 64.4 ± 9.7 years) were divided into PNI-positive (n = 63) and PNI-negative groups (n = 71). Clinical characteristics (demographic information, liver function indicators and tumor markers) and CECT parameters (tumor type, tumor size, gallbladder stone, invasion of gallbladder neck/cystic duct, clinical T stage and N stage) were collected and compared between two groups. Binary logistic regression analysis, receiver operating characteristic curves analyses and Delong test were used in further statistical analyses in clinical T3-4 stage (cT3-4) GBC patients. Overall survival (OS) rates after surgery were compared between PNI-negative group and PNI-positive group of cT3-4 GBC patients.The majority of GBC patients with PNI were classified as cT3-4 (61/63, 96.8%), while only 3.2% (2/63) of PNI-positive cases were identified at cT1-2. Among cT3-4 GBC, OS was significantly lower in the PNI-positive group than the PNI-negative group after surgery (HR,1.661; 95% CI, 1.044–2.643; P = 0.032). Gender and gallbladder neck/cystic duct invasion were independent predictive factors for cT3-4 GBC patients with PNI. A combination of gender and gallbladder neck/cystic duct invasion showed the best diagnostic performance than that of individual parameters (all P < 0.05).Preoperative T staging using CECT enables the initial assessment of PNI status in GBC patients. A combination of gender and gallbladder neck/cystic duct invasion may effectively predict PNI in GBC, particularly in cT3-4 GBC.Methods: To investigate the utility of combining clinical and contrasted-enhanced tomography (CECT) parameters for the preoperative evaluation of perineural invasion (PNI) in gallbladder carcinoma (GBC).A total of 134 patients with GBC (male/female, 52/82; age, 64.4 ± 9.7 years) were divided into PNI-positive (n = 63) and PNI-negative groups (n = 71). Clinical characteristics (demographic information, liver function indicators and tumor markers) and CECT parameters (tumor type, tumor size, gallbladder stone, invasion of gallbladder neck/cystic duct, clinical T stage and N stage) were collected and compared between two groups. Binary logistic regression analysis, receiver operating characteristic curves analyses and Delong test were used in further statistical analyses in clinical T3-4 stage (cT3-4) GBC patients. Overall survival (OS) rates after surgery were compared between PNI-negative group and PNI-positive group of cT3-4 GBC patients.The majority of GBC patients with PNI were classified as cT3-4 (61/63, 96.8%), while only 3.2% (2/63) of PNI-positive cases were identified at cT1-2. Among cT3-4 GBC, OS was significantly lower in the PNI-positive group than the PNI-negative group after surgery (HR,1.661; 95% CI, 1.044–2.643; P = 0.032). Gender and gallbladder neck/cystic duct invasion were independent predictive factors for cT3-4 GBC patients with PNI. A combination of gender and gallbladder neck/cystic duct invasion showed the best diagnostic performance than that of individual parameters (all P < 0.05).Preoperative T staging using CECT enables the initial assessment of PNI status in GBC patients. A combination of gender and gallbladder neck/cystic duct invasion may effectively predict PNI in GBC, particularly in cT3-4 GBC.Results: To investigate the utility of combining clinical and contrasted-enhanced tomography (CECT) parameters for the preoperative evaluation of perineural invasion (PNI) in gallbladder carcinoma (GBC).A total of 134 patients with GBC (male/female, 52/82; age, 64.4 ± 9.7 years) were divided into PNI-positive (n = 63) and PNI-negative groups (n = 71). Clinical characteristics (demographic information, liver function indicators and tumor markers) and CECT parameters (tumor type, tumor size, gallbladder stone, invasion of gallbladder neck/cystic duct, clinical T stage and N stage) were collected and compared between two groups. Binary logistic regression analysis, receiver operating characteristic curves analyses and Delong test were used in further statistical analyses in clinical T3-4 stage (cT3-4) GBC patients. Overall survival (OS) rates after surgery were compared between PNI-negative group and PNI-positive group of cT3-4 GBC patients.The majority of GBC patients with PNI were classified as cT3-4 (61/63, 96.8%), while only 3.2% (2/63) of PNI-positive cases were identified at cT1-2. Among cT3-4 GBC, OS was significantly lower in the PNI-positive group than the PNI-negative group after surgery (HR,1.661; 95% CI, 1.044–2.643; P = 0.032). Gender and gallbladder neck/cystic duct invasion were independent predictive factors for cT3-4 GBC patients with PNI. A combination of gender and gallbladder neck/cystic duct invasion showed the best diagnostic performance than that of individual parameters (all P < 0.05).Preoperative T staging using CECT enables the initial assessment of PNI status in GBC patients. A combination of gender and gallbladder neck/cystic duct invasion may effectively predict PNI in GBC, particularly in cT3-4 GBC.Conclusions: To investigate the utility of combining clinical and contrasted-enhanced tomography (CECT) parameters for the preoperative evaluation of perineural invasion (PNI) in gallbladder carcinoma (GBC).A total of 134 patients with GBC (male/female, 52/82; age, 64.4 ± 9.7 years) were divided into PNI-positive (n = 63) and PNI-negative groups (n = 71). Clinical characteristics (demographic information, liver function indicators and tumor markers) and CECT parameters (tumor type, tumor size, gallbladder stone, invasion of gallbladder neck/cystic duct, clinical T stage and N stage) were collected and compared between two groups. Binary logistic regression analysis, receiver operating characteristic curves analyses and Delong test were used in further statistical analyses in clinical T3-4 stage (cT3-4) GBC patients. Overall survival (OS) rates after surgery were compared between PNI-negative group and PNI-positive group of cT3-4 GBC patients.The majority of GBC patients with PNI were classified as cT3-4 (61/63, 96.8%), while only 3.2% (2/63) of PNI-positive cases were identified at cT1-2. Among cT3-4 GBC, OS was significantly lower in the PNI-positive group than the PNI-negative group after surgery (HR,1.661; 95% CI, 1.044–2.643; P = 0.032). Gender and gallbladder neck/cystic duct invasion were independent predictive factors for cT3-4 GBC patients with PNI. A combination of gender and gallbladder neck/cystic duct invasion showed the best diagnostic performance than that of individual parameters (all P < 0.05).Preoperative T staging using CECT enables the initial assessment of PNI status in GBC patients. A combination of gender and gallbladder neck/cystic duct invasion may effectively predict PNI in GBC, particularly in cT3-4 GBC. [ABSTRACT FROM AUTHOR]

Genomic instability and mutability are a prominent character of tumor. The whole-exosome sequence reveals that ERBB2 mutations are the representative mutations of gallbladder carcinoma, which takes potential targets for gallbladder carcinoma therapy. However, the roles of ERBB2 mutations are unclear in gallbladder carcinoma. We identified S310F mutation is the hottest mutation of ERBB2 mutations from TCGA PanCancer Altas data with 10,967 samples and our previous study with 157 gallbladder carcinoma samples. S310F mutation located in ERBB2 extracellular domain, promoted ERBB2 homodimerization and consequent auto-phosphorylation to activate the downstream PI3K/AKT and MAPK pathways, which was independent on ERBB1, ERBB3, and ERBB4. ERBB2 S310F mutation up-regulated aerobic glycolysis and promoted gallbladder carcinoma growth. Our study reveals the roles of ERBB2 S310F mutation, which is beneficial to ERBB2 S310F mutant gallbladder carcinoma therapy. [ABSTRACT FROM AUTHOR]

Background: Locally advanced gallbladder cancer (GBC) may require extended hepatectomy. Portal vein embolization (PVE) can lead to hypertrophy of future liver remnant (FLR), and neoadjuvant chemotherapy (NACT) can be used in this cohort, with additional advantage of downstaging tumors as well as preventing progression while waiting for liver regeneration. Here, we share our experience of combining NACT along with PVE in locally advanced GBC requiring major hepatectomy. Methods: Retrospective analysis of prospectively maintained database was conducted for patients with locally advanced GBC who underwent PVE and received NACT between 2012 and 2018. Results: Fourteen patients with locally advanced GBC underwent PVE and NACT. Median baseline FLR volume was 25.09% with a median degree of hypertrophy of 8.8% after PVE. Out of 14 patients, 7 (50%) underwent curative resection. Median overall survival in resectable and unresectable patients was 27 months and 15 months respectively. Conclusion: PVE along with NACT made curative surgery feasible in half of the patients who were deemed unresectable initially. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to validate the safety and feasibility of pure laparoscopic extended cholecystectomy (LEC) by comparing the outcome with that of open extended cholecystectomy (OEC). Moreover, on the basis of our experience, we also aimed to investigate the learning curve of pure LEC. Methods: This single-center study enrolled patients who were diagnosed primary gallbladder cancer with pathologically confirmed and underwent R0 resection with curative intent between January 2016 and December 2019. A total of 31 patients who underwent OEC and 17 patients who underwent LEC were selected. Propensity score matching analysis was performed in a 1:1 ratio using the nearest-neighbor matching method, and clinical information was retrospectively collected from medical records and analyzed. Results: The postoperative hospital stay was statistically shorter in the LEC group (7 days) than in the OEC group (12 days). The overall surgical complication rate did not differ between the two groups. The 1- and 3-year disease-free survival rates were 82.4% and 82.4% in the OEC group and 94.2% and 71.5% in the LEC group, respectively (P = 0.94). Considering the correlation between the number of cumulative cases and the operation time and between the number of cumulative cases and the number of retrieved lymph nodes in the LEC group, as the cases were accumulated, both the operation time and the number of retrieved lymph nodes had a statistically significant correlation with the number of cases. Conclusions: LEC showed a significant advantage in terms of achieving shorter postoperative hospital stay and similar results to OEC with respect to overall complications and pathological outcomes. The present results confirm that laparoscopy can be considered a safe treatment for primary gallbladder cancer in selected patients. [ABSTRACT FROM AUTHOR]

Gallbladder (GB) carcinoma is a relatively rare malignancy and is associated with poor prognosis. Numerous risk factors have been associated with the development of GB carcinoma. GB carcinomas may present as mass lesions replacing the GB, focal or diffuse thickening of the GB wall, and intraluminal mass in the GB. Various benign conditions can mimic GB carcinoma. This article reviews the epidemiology, pathology, clinical findings, imaging features, and management of GB carcinomas. [ABSTRACT FROM AUTHOR]

AIM: To assess how laparoscopy has altered the presentation of patients with gallbladder cancer and determine whether radical resection in patients with gallbladder cancer is benefi cial. METHOD: 47 patients underwent surgery because of suspected gallbladder cancer. Cancer was found incidentally in 29 patients (61.7 %) during routine laparoscopic cholecystectomy using frozen biopsy. Gallbladder cancer had been diagnosed preoperatively in the other 18 patients (38.3 %). RESULTS: Patients in whom carcinoma was found incidentally at laparoscopic cholecystectomy had a signifi cant increase in survival when compared with those who were admitted electively with a known diagnosis. All patients who presented with a known diagnosis had stage II or higher, and 38.3 % of these were in stage IV. However, 58.6 % of those patients who were found incidentally were in stage I or II. The overall 2-year survival for all patients was 45 %; those discovered incidentally at laparoscopic cholecystectomy (Tis-T2) had a 2-year survival of 87 %. CONCLUSION: Laparoscopic cholecystectomy resulted in an earlier discovery of gallbladder cancer in some patients, resulting in increased probability of survival. Adjunctive radical surgical resection, either at the time of cholecystectomy or subsequently, increases survival signifi cantly in early stage disease (Tab.2, Fig. 2, Ref. 24). [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma (GBC) is a lethal biliary tract malignant neoplasm. Patient-derived primary cancer cell lines (PDPCs) are appropriate models to explore biological characteristics and potential therapeutics; however, there is a lack of PDPCs in GBC. In this study, we aimed to establish and characterize the GBC PDPCs, and further investigated the intra-tumor heterogeneity (ITH). Multi-region sampling (3–9 regions) of the operable tumor tissue samples was used to establish PDPCs. Short tandem repeat genotyping for cell authentication and karyotyping was performed, followed by whole-exome sequencing and RNA sequencing to assess the ITH at the genetic and transcriptional levels, respectively. Thirty-eight PDPCs were successfully established from seven GBC patients and characterized. ITH was observed with a median of 38.3% mutations being heterogeneous (range, 26.6–59.4%) across all patients. Similar with other tumor types, TP53 mutations were always truncal. In addition, there were three genes, KMT2C, CDKN2A, and ARID1A, with truncal mutations in at least two patients. A median of 370 differentially expressed genes (DEGs) was identified per patient. Distinct expression patterns were observed between major histocompatibility complex (MHC) class I and II genes. We found the expression of MHC class II genes in the PDPC samples was closely regulated by CIITA, while that of MHC class I genes were not correlated with CIITA expression. The PDPCs established from GBC patients can serve as novel in vitro models to identify the ITH, which may pave a crucial molecular foundation for enhanced understanding of tumorigenesis and progression. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasonography (EUS) has excellent spatial resolution and allows more detailed examination than abdominal ultrasonography (US) in terms of qualitative diagnosis of tumors and evaluation of tumor invasion depth. To understand the role of EUS in gallbladder disease, we need to understand the normal gallbladder wall structure and how to visualize it on EUS. In addition, gallbladder lesions can be classified into two broad categories: protuberant and wall-thickening lesions. Here, the features on EUS were outlined. We also outlined the current status of EUS-FNA for gallbladder lesions as there have been scattered reports of EUS-FNA in recent years. [ABSTRACT FROM AUTHOR]

Diseases associated with gallbladder wall thickening include benign entities such as adenomyomatosis of the gallbladder, acute and chronic cholecystitis, and hyperplasia associated with pancreaticobiliary maljunction, and also cancer. Unique conditions such as sclerosing cholecystitis and cholecystitis associated with immune checkpoint inhibitor treatment can also manifest as wall thickening, as in some systemic inflammatory conditions. Gallbladder cancer, the most serious disease that can show wall thickening, can be difficult to diagnose early and to distinguish from benign causes of wall thickening, contributing to a poor prognosis. Differentiating between xanthogranulomatous cholecystitis and gallbladder cancer with wall thickening can be particularly problematic. Cancers that thicken the wall while coexisting with benign lesions that cause wall thickening represent another potential pitfall. In contrast, some benign gallbladder lesions that can cause wall thickening, such as adenomyomatosis and acute cholecystitis, typically show characteristic ultrasonographic features that, together with clinical findings, permit easier diagnosis. In this review of the literature, we describe B-mode abdominal ultrasonographic diagnosis of gallbladder lesions showing wall thickening. [ABSTRACT FROM AUTHOR]

Introduction: Many cases of gallbladder cancer (GBC) were made incidentally after cholecystectomy for presumed benign disease. The aim of this review is to assess the preoperative predictor factors of gallbladder cancer. Methods: This systematic review was conducted according to PRISMA guidelines when it was applicable. We conducted bibliographic researches on October 2nd, 2019, in the following sources: The National Library of Medicine through PubMed, Cochrane database, and Google scholar. We have assessed the univariate and multivariate analysis outcomes. Results: We included ten studies. Incidence of incidental GBC was 0.36%. Seven studies reported age as a significant predictive factor of iGBC. Comorbidities were the second significant predictor. One study found that iGBC group was more likely to have elevated TB, DB, PAL, and ALT. Another study reported a significantly higher rate of TB, PAL, and AST. One study concluded that elevated CA19-9 combined with CEA or CA-125 was significantly more frequent in the group with iGBC. Polyps, porcelain GB, GB wall thickness, and CBD dilation were reported to be associated with iGBC. iGBC group were more likely to have solitary and larger GS and gallbladder wall thickening, essentially focal. Conclusion: Incidence of iGBC was 0.365% varying between 0.19 and 1.6% of laparoscopic cholecystectomy and about 50% of GBC cases. This highlights the deficiency of preoperative diagnostic features. Despite the efforts made, the rate of this condition is still high, underlining the need of new radiological technologies. [ABSTRACT FROM AUTHOR]

S-adenosylmethionine (SAM) is a naturally occurring physiologic molecule found ubiquitously in all mammalian cells and an essential compound in many metabolic pathways. It has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, the precise molecular mechanism involved in its anticancer effect is not yet clear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of SAM on human gallbladder cancer cells (GBC-SD and SGC-996) in vitro and in vivo. Cells were dealt with SAM and subjected to cell viability, colony formation, Hoechst staining, apoptosis, cycle arrest, western blot, and xenograft tumorigenicity assay. Experimental results showed that SAM could significantly inhibit the growth and proliferation and induce the apoptosis as well as cell cycle arrest in G0/G1 phase of GBC-SD and SGC-996 cells in a dose-dependent manner in vitro. The expression levels of p-JAK2, p-STAT3, Mcl-1, and Bcl-XL were significantly downregulated. In addition, inhibition of the JAK2/STAT3 pathway significantly enhanced the anti-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. More importantly, our in vivo studies demonstrated that administration of SAM could significantly decrease the tumor weight and volume and immunohistochemistry analysis proved the downregulation of p-JAK2 and p-STAT3 in tumor tissues following SAM treatment, consistent with our in vitro results. In summary, our findings indicated that SAM can inhibit cell proliferation and induce apoptosis as well as cycle arrest of GBC cells by suppression of JAK2/STAT3 pathways and the dramatic effects of SAM hinting that SAM might be a useful therapeutic option for patients suffering from gallbladder cancer. [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma (GBC) is more frequent after 60 years of age; its behavior in young adults has not been much studied. A retrospective analysis was performed in patients who underwent a cholecystectomy procedure between the years 2001 to 2016. A group of young patients (< 45) were compared with elderly patients (> 60 years) with reference to various clinical, histomorphologic, and immunohistochemical parameters. Statistical analysis was performed using t test and Fisher's test. Survival curves were calculated by Kaplan-Meier actuarial survival curves and log-rank tests. One hundred and one patients with GBC were observed during the study period. Of these, 14 patients (13.9%) belonged to the study group (age range 20 to 45 years) and 43 patients (42.6%) constituted the comparison elderly control group (age range 60 to 80 years). Forty-four pts. were in the middle-aged group (46 to 59 years) and were thus excluded from the study. With reference to age (< 45 and > 60), no significant difference was found in sex (females 64.3% vs 69.8%, p = 0.7), presence of gall stones (64% vs 60%, p = 0.8), advanced disease at presentation (T4) (14.3% vs 7%, p = 0.40), incidental detection of gallbladder carcinoma (28.5% vs 28%, p = 0.9), tumor stage at presentation (stage I/II) (35.7% vs 49%, p = 0.39), and poor differentiation (tumor grades G3) (14% vs 12%, p = 0.79). Full-length involvement (28.5% vs 11.6%, p = 0.015) of the gallbladder and abundant tumor necrosis (43% vs 14%, p = 0.021) were more common in the younger patients group whereas adenosquamous and pure squamous cell carcinoma were predominantly observed in elderly patients. Immunohistochemical studies showed higher percentage of overexpression of p53 and Ki-67 proliferation indices in the younger population. Overall survival in younger patients was 48 months whereas in elderly patients it was 36 months. Histological markers denoting aggressive tumor behavior were observed in gallbladder carcinomas of younger individuals; further studies are needed to delineate the differences in molecular mechanisms involved in progression of the tumor in the two groups. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4 (IgG4)-related cholecystitis (IgG4-C) is often difficult to distinguish from gallbladder carcinoma (GBC). This study aimed to determine a practical strategy for differentiating between IgG4-C and GBC to avoid unnecessary surgical resection. The expression of IgG4 in the gallbladder was detected by immunohistochemistry. The clinicopathological and radiological characteristics of IgG4-C patients and GBC patients were analyzed retrospectively. Immunohistochemistry revealed that IgG4 was upregulated in the plasma cells of IgG4-C tissues. The median serum total bilirubin levels were significantly higher in the patients with IgG4-C than in those with GBC (45.8 µmol L−1 vs. 29.9 µmol L−1). The serum γ-GGT levels were higher in IgG4-C patients than in GBC patients, whereas the serum levels of CA125 were significantly higher in GBC patients than in IgG4-C patients. The imaging scans were helpful for differentiating IgG4-C from GBC based on the presence of a layered pattern and Rokitansky-Aschoff sinuses in the gallbladder wall. There were no statistically significant differences in age, presence of abdominal pain, level of emaciation between the two groups. Our study demonstrated that the combination of imaging with serum total bilirubin, γ-GGT and CA125 levels can offer added preoperative diagnostic value and reduce the rate of IgG4-C misdiagnosis. [ABSTRACT FROM AUTHOR]

Background: In patients with malignant perihilar biliary strictures, preoperative biliary drainage (PBD) of the hepatic lobe to be resected may decrease the liver volume of the future liver remnant (FLR) after percutaneous transhepatic portal vein embolization (PVE). However, evidence of its application is insufficient. This study aimed to clarify the effects of PBD on liver hypertrophy after PVE.Methods: Between January 2008 and December 2017, 169 patients with malignant perihilar biliary strictures underwent major hepatectomy or palliative surgery at our hospital. Of these, 76 patients who underwent PVE were categorized into two groups: group A (n = 29) who received unilateral PBD of the FLR and group B (n = 47) who received bilateral PBD, including that of the hepatic lobe to be resected. FLR ratios after PVE and liver hypertrophy ratios were retrospectively compared in both groups.Results: Group B exhibited significantly severe biliary stenosis (p = 0.0038) and high serum bilirubin before biliary drainage (p = 0.0037). After PVE, the total liver volumes were 1287 ± 260 ml and 1340 ± 257 ml (p = 0.39), respectively. FLR volumes were 555 ± 135 and 577 ± 113 ml (p = 0.45), respectively. FLR ratios were 43.4 ± 8.2% and 43.4 ± 6.4%, respectively (p = 0.98). Liver hypertrophy ratios were 124.2 ± 17.7% and 129.2 ± 20.9%, respectively (p = 0.28). In addition, an examination which excluded patients with Bismuth type I obtained similar result.Conclusions: PBD of the hepatic lobe to be resected did not decrease the FLR ratios and hypertrophy ratios. Thus, in patients with poor biliary drainage, additional PBD of the target lobe is acceptable. [ABSTRACT FROM AUTHOR]

Background: Gallbladder carcinoma (GBC) is one of the most aggressive and lethal tumors, with extremely high metastatic activity and poor prognosis. Previously we have studied miRNAs that promote metastasis and progression of GBC, the aim of present study was to systematically elucidate the metastasis suppressor miRNAs in GBC.Methods: A novel designed high-throughput screening method that combined high content screening (HCS) and miRNA microarray analysis was conducted to filter out anti-metastatic miRNAs of GBC. Frozen samples were analyzed for the expression of goal miRNAs by real-time PCR. The biological functions of miRNAs were studied by transwell, immunoblot. Liver metastasis model via spleen injection was further examined in nude mice. Kaplan-Meier and Cox regression analyses were used to analyze the effect of goal miRNAs on overall survival. The target genes and interaction network of goal miRNAs were determined by whole transcriptome genome sequencing.Results: Out of the miRNAs library, a series of prominent metastatic suppressor miRNA candidates were filtered out. Among them, miR-7-2-3p and miR-29c-3p were discovered downregulated in GBC, and upregulation of them could reverse epithelial-mesenchymal transition and decrease the metastasis ability of GBC cells in vitro and in vivo, which was dominated by the miRNA-mRNA-lncRNA co-expression network. And DCLK1 and SLC36A1 are the direct target genes of miR-7-2-3p and miR-29c-3p. Moreover, the deficiency of miR-7-2-3p and miR-29c-3p was closely associated with poor prognosis of GBC patients.Conclusions: Our findings indicate that miR-7-2-3p and miR-29c-3p play crucial roles in the pathogenesis and worse prognosis of GBCs, which may serve as prognosis biomarkers and promise potential therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

Background: Ultrasound (US) has been widely used in screening and differential diagnosis of gallbladder wall thickening (GWT). However, the sensitivity and specificity for diagnosing wall-thickening type gallbladder cancer are limited, leading to delayed treatment or overtreatment. We aim to explore the value of high frame rate contrast enhanced ultrasound (H-CEUS) in distinguishing wall-thickening type gallbladder cancer (malignant) from GWT mimicking malignancy (benign)., Methods: This retrospective study enrolled consecutive patients with non-acute GWT who underwent US and H-CEUS examination before cholecystectomy. Clinical information, US image and H-CEUS image characteristics between malignant and benign GWT were compared. The independent risk factors for malignant GWT on H-CEUS images were selected by multivariate logistic regression analysis. The diagnostic performance of H-CEUS in determining malignant GWT was compared with that of the gallbladder reporting and data system (GB-RADS) score., Results: Forty-six patients included 30 benign GWTs and 16 malignant GWTs. Only mural layering and interface with liver on US images were significantly different between malignant and benign GWT (P < 0.05). Differences in enhancement direction, vascular morphology, serous layer continuity, wash-out time and mural layering in the venous phase of GWT on H-CEUS images were significant between malignant and benign GWT (P < 0.05). The sensitivity, specificity and accuracy of H-CEUS based on enhancement direction, vascular morphology and wash-out time in the diagnosis of malignant GWT were 93.75%, 90.00%, and 91.30%, respectively. However, the sensitivity, specificity and accuracy of the GB-RADS score were only 68.75%, 73.33% and 71.74%, respectively. The area under ROC curve (AUC) of H-CEUS was significantly higher than that of the GB-RADS score (AUC = 0.965 vs. 0.756)., Conclusions: H-CEUS can accurately detect enhancement direction, vascular morphology and wash-out time of GWT, with a higher diagnostic performance than the GB-RADS score in determining wall-thickening type gallbladder cancer. This study provides a novel imaging means with high accuracy for the diagnosis of wall-thickening type gallbladder cancer, thus may be better avoiding delayed treatment or overtreatment., (© 2024. The Author(s).)

The ovary is a common site of metastasis from various organs. However, little is known about gallbladder carcinoma metastasising to the ovaries and presenting as a primary ovarian tumour. We report a case of a metastatic gallbladder carcinoma which mimicked a primary ovarian tumour in a 31-year-old woman who presented with menstrual symptoms and an ovarian mass without obvious signs and symptoms related to gallbladder carcinoma. Postoperatively histopathological examination diagnosed primary ovarian germ cell tumour for further chemotherapy. However, postoperative re-evaluation with radiology suggested the possibility of a primary gallbladder carcinoma. Exact diagnosis could only be made after repeat histopathological evaluation of the ovarian mass. [ABSTRACT FROM AUTHOR]

Oxymatrine extracted from Sophora flavescens Ait as a natural polyphenolic phytochemical has been demonstrated to exhibit anti-tumor effects on various cancers, including Gallbladder carcinoma (GBC). However, its underlying mechanisms of function are largely unknown in GBC cells. The present study is conducted to investigate the antitumor effects and the underlying mechanisms of oxymatrine on GBC cells in vitro and in vivo. The results showed that oxymatrine inhibited cell viability, metastatic ability and induced cell apoptosis in dose-dependent manners. Furthermore, we found that the expression of p-AKT, MMP-2, MMP-9 and the ratio of Bcl-2/Bax were significantly down-regulated, while the expression of PTEN was up-regulated in GBC cells. In addition, pretreatment with a specific PI3K/AKT activator (IGF-1) significantly antagonized the oxymatrine-mediated inhibition of GBC-SD cells. Subsequently, our in vivo studies showed that administration of oxymatrine induced a significant dose-dependent decrease in tumor growth. In conclusion, these findings indicated that the inhibition of cells proliferation, migration, invasion and the induction of apoptosis in response to oxymatrine in GBC cells, may function through the suppression of PTEN/PI3K/AKT pathway, which was considered as the vital signaling pathway in regulating tumorigenesis. These results suggested that oxymatrine might be a novel effective candidate as chemotherapeutic agent against GBC. [ABSTRACT FROM AUTHOR]

Background: CCK1 (cholecystokinin receptor 1) and protein lysine acetylation were associated with several cancers, respectively. However, whether they are involved in the alternation of gallbladder carcinoma is unknown. Aims: This study investigated the characteristics of CCK1 and protein lysine acetylation in GBC-SD cells and carcinoma of gallbladder. Methods: The expression and localization of CCK1 were detected by western blot analysis and indirect immunofluorescence. GBC-SD cells were treated with CCK-8 and CCK-8+CCK1 inhibitor. The protein lysine acetylation from cells, as well as tissues of gallbladder carcinoma, was examined by western blotting. Results: CCK1 receptor was expressed and localized in the GBC-SD cells. The synthetic octapeptide of CCK (CCK-8) could accelerate the lysine acetylation of a subset of proteins in dose-dependent manners in GBC-SD cells. Further investigation demonstrated that the specific inhibitor (CR1409) of CCK1 receptor could attenuate the CCK8-induced increase of protein lysine acetylation. In addition, we revealed that the rise of CCK1 receptor expression is associated with the increase of protein lysine acetylation in tissues from carcinoma of gallbladder. Conclusions: CCK might regulate protein lysine acetylation via CCK1 receptor. [ABSTRACT FROM AUTHOR]

Background: Although surgical resection is the only curative treatment for gallbladder cancer (GBC), concomitant peritoneal dissemination is considered far beyond the scope of resection. We report a long-term survivor with a residual GBC with multiple peritoneal disseminations who underwent an extended resection after effective chemotherapy. Case presentation: A 59-year-old male underwent an open cholecystectomy for Mirizzi syndrome at a local hospital. Because of severe inflammation, the gallbladder was perforated during surgery, ending in a piecemeal resection. A pathological examination revealed GBC with positive margins, and the patient was referred to our hospital 1 month after surgery for further treatment. A multidetector-row computed tomography (MDCT) showed three hypoattenuated tumours: a tumour (3.9 cm) at the left medial segment corresponding to the gallbladder bed, a tumour (1.8 cm) around the hepatic flexure of the transverse colon, and a tumour (1.0 cm) at the stump of the cystic duct. Percutaneous needle biopsy was performed, which provided histologic evidence of adenocarcinoma. Thus, the patient had a rapidly progressive local relapse with limited peritoneal dissemination, labelled ycT3N0M1, stage IVB disease according to the UICC system. After the administration of 3 cycles of gemcitabine plus cisplatin combination chemotherapy, the size of all tumours and the CA19-9 level decreased significantly. Since the patient's general condition and liver function reserve were satisfactory, we decided the initial unresectable scenario to perform surgical therapy. After portal vein embolization, right hepatectomy, resection of the extrahepatic bile duct, partial duodenectomy, and partial colectomy were performed. Operative time was 555 min, and intraoperative blood loss was 1654 mL. Pathologic diagnosis of residual gallbladder carcinoma with peritoneal dissemination was confirmed, and the surgical margins were tumour-free. The patient was discharged on postoperative day 29, with a Clavien-Dindo IIIa complication (abdominal wall abscess). Postoperative adjuvant chemotherapy with tegafur/gimeracil/oteracil was administered during 1 year after surgery. The patient is doing well 6 years after the second surgery without evidence of disease. Conclusions: Although specific clinical factors were associated with a favourable outcome in this patient, the present report suggests that multidisciplinary therapy may be a promising option in selected patients with distant metastatic GBC. [ABSTRACT FROM AUTHOR]

Background: The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. Methods: 98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated. Results: Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis. Conclusions: The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC. [ABSTRACT FROM AUTHOR]

Background: Carcinoembryonic antigen (CEA) can be used to screen for biliary tract cancer in patients with primary sclerosing cholangitis (PSC).Aim: To study the influence of benign dominant strictures (DS), superimposed bacterial cholangitis (SBC), smoking status, and inflammatory bowel disease on CEA serum levels.Methods: A retrospective analysis of CEA values in cancer-free PSC patients was performed. We included the maximal CEA value obtained during follow-up and information on the presence of DS and SBC at that time, and we analyzed the CEA values in the presence and absence of DS and SBC. Results are reported as medians with the interquartile range (IQR).Results: The median maximal CEA level, which was 1.8 ng/mL (IQR 1.2-2.9) in the final 270 PSC patients included in the study, was not influenced by the presence of either DS or SBC (P = 0.320). Moreover, in 49 patients, the first CEA value available at the time of DS (1.5 ng/mL; IQR 1.2-2.1) and that at a time without DS (1.6 ng/mL; IQR 1.1-2.3) did not differ significantly (P = 0.397). Lastly, in 24 patients, the median CEA values at a time without SBC (1.8 ng/mL; IQR 1.2-2.5) and at the time of SBC (1.8 ng/mL; IQR 1.0-3.0) were comparable (P = 0.305). Smoking did not influence CEA-based cancer screening.Conclusions: Serum CEA level is not influenced by the presence of DS or SBC and might therefore serve as a favorable parameter for improving cancer screening in PSC patients. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is one of the lethal diseases of digestive system. Increasing evidence prompt that microRNAs (miRs) might provide a novel therapeutical target for malignant disease. The antitumor effect of miR-122 to GBC is worth to be investigated. miR-122 expression level in GBC tissue sample and cell lines were assayed by qRT-PCR. miR-122 mimics were transfected for upregulation of miR-122 expression. Cell function was assayed by CCK8, flow cytometry, wound healing assay, migration assay, and invasion assay. The target genes of miR-122 were predicated by TargetScan online program and verified by western blot and luciferase report gene assay. miR-122 was decreased in GBC tissue and cell lines. The exogenous introduction of miR-122 exhibits multiple antitumor effect in GBC cell proliferation, invasion, and metastasis. Further studies revealed that the PKM2 was a regulative target of miR-122 in GBC cell. miR-122 also inhibits TGF-β-induced epithelium mesenchymal transformation of GBC cell by downregulating PKM2 expression. These findings suggest that miR-122 plays an important role in tumorigenesis of GBC through interfering PKM2, highlighting its usefulness as a potential therapeutic agent in GBC. [ABSTRACT FROM AUTHOR]

The pretreatment nutritional and immunological status play indispensable roles in predicting the outcome of patients with various types of malignancies. The aim of the study was to investigate whether preoperative prognostic nutritional index (PNI), which simply accounts for nutritional and immunological status, was associated with overall survival (OS) in patients with gallbladder carcinoma (GBC). The retrospective study included a total of 315 GBC patients after surgery between 2002 and 2012. PNI was calculated according to the following formula: 10× serum albumin (g/dl) +0.005× total lymphocyte count (per mm). A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff value for LMR, which was set at 46.14. According the value, patients were categorized into two different groups, namely high-PNI group ( n = 133) and low-PNI group ( n = 182). The univariate and multivariate Cox regression models were used to identify the independent prognostic factors. The results showed that low pretreatment PNI value was significantly associated with elderly age, partial surgery procedure, and advanced tumor status such as tumor stage, node stage, and tumor-node-metastasis stage ( P < 0.05). The low-PNI group had a worse OS compare with the high-PNI group ( P < 0.05). Via univariate and multivariate analyses, pretreatment PNI was identified as an independent prognostic factor for OS [HR: 0.613; 95%CI: 0.448-0.838; P < 0.001]. Subgroup analyses further revealed that PNI was significantly associated with postoperative OS independent of tumor node metastasis stage and surgical procedure. In conclusion, pretreatment PNI might serve as an effective predictor to evaluate prognosis of GBC patients after surgery. Based on the findings, PNI, characterized with accessibility, objectivity and noninvasiveness, should be included in the routine assessment of GBC. [ABSTRACT FROM AUTHOR]

Purpose: Gallbladder carcinoma (GBC) is characterized by a dismal prognosis owing to the paucity of early signs and symptoms. North India reports high incidence of GBC possibly due to environmental, dietary and reproductive factors. Understanding the epidemiology of gallbladder cancer has and will continue to provide valuable insights into determining causes and risk factors for gallbladder cancer. Methods: Prospective study of gallbladder carcinoma patients, presenting in our department, was undertaken over three year period to evaluate the epidemiological profile of gallbladder carcinoma patients from our region. Results: The peak incidence of GBC was in 31-50 years age group (58 %). Male to female ratio was 1:4.83, with mean age for females (mean 49.1 years) significantly lower than male counterpart (mean 54.9 years) ( p value = 0.000423). Majority of patients were non-vegetarians (67 %) and 84 % of them consumed mustard oil (home made/loose packed) as predominant cooking medium. Majority of the patients of GBC in our study were from low socioeconomic strata (68 %) (Kuppuswamy classes IV, V (lower class)). GBC was more commonly seen in females with the age of menarche less than 14 years (83 %) and the age of the first child birth less than 20 years (56 %). Females with more than two children had higher incidence (57 %). Majority of the female patients (71 %) were postmenopausal. Gallstones were present in 390 out of 490 patients (80 %). Incidental gallbladder carcinoma was detected in 158 out of 490 patients (32 %). Pain abdomen was the most common presenting complaint (98 %). Significant proportion of the patients with GBC presented with distant metastasis (stage IVB) (52 %). The most common histological subtype was adenocarcinoma (78 %). Conclusion: Current data suggest that the epidemiology of gallbladder cancer is constantly evolving, with much of this change caused by lifestyle, cultural and dietary factors. Balanced diet, prevention of malnutrition/adulteration, tobacco prevention and early intervention for cholelithiasis may help in decreasing the incidence of this dreaded disease. More structured studies need to be carried out to ascertain risk factors for GBC in our population subgroup. [ABSTRACT FROM AUTHOR]

The cytostatic drug from fruits and other plant derived products have acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Lupeol, a dietary triterpene, present in many fruits and medicinal plants, has been shown to possess many pharmacological properties including anti-cancer effect in both in vitro and in vivo assay systems. However, the cancer proliferative and invasive inhibitory effects and molecular mechanisms on gallbladder carcinoma GBC-SD cells have not been studied. In the present study, GBC-SD cells were treated by lupeol and subjected to methyl thiazolyl tetrazolium analysis, Hoechst 33342 staining, annexin V/propidium iodide double-staining, transwell chamber assay and Western blot analysis. In addition, GBC-SD xenograft tumors were established in male nude BALB/c mice, and lupeol was intravenously administered to evaluate the anti-cancer capacity in vivo. Our results showed that lupeol inhibited the proliferation, migration, invasion and induced apoptosis of GBC-SD cells in a dose-dependent manner in vitro. Furthermore, the expression of p-EGFR, p-AKT and MMP-9 levels were significantly down-regulated. These protein interactions may play a pivotal role in the regulation of apoptosis and invasion. More importantly, our in vivo studies showed that administration of lupeol decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the down-regulation of p-EGFR and MMP-9 in tumor tissues following lupeol treatment, consistent with the in vitro results. Taken together, our findings indicated that lupeol can induce apoptotic cell death and inhibit the migration as well as invasion of GBC-SD cells. The mechanism may be associated with the suppression of EGFR/MMP-9 signaling. These results might offer a therapeutic potential advantage for human gallbladder carcinoma chemoprevention or chemotherapy. [ABSTRACT FROM AUTHOR]

Background: This study evaluated our new strategy for treating suspected T2 gallbladder carcinoma (GBC) using a laparoscopic approach.Methods: We examined 19 patients with suspected T2 GBC who were treated laparoscopically (LS group) between December 2007 and December 2013; these patients were compared with 14 patients who underwent open surgery (OS group). Laparoscopic staging was initially performed to exclude factors making the patients ineligible for curative resection. Intraoperative pathological examination of the surgical margin of the cystic duct was performed prior to laparoscopic gallbladder bed resection, and pathological examination was again performed to confirm the presence of carcinoma and the depth of tumor invasion. Surgery was completed when the pathological findings indicated that the patient was cancer free. Lymph node dissection was performed according to the depth of tumor invasion.Results: None of the patients required conversion to laparotomy. For three patients with benign lesions, only gallbladder bed resection was required. Additional regional lymph node dissection was performed in 16 patients in the LS group. The mean operative time (309 vs. 324 min, p = 0.755) and mean number of dissected lymph nodes (12.6 vs. 10.2, p = 0.361) were not significantly different between the LS and OS groups. The intraoperative blood loss was significantly lower (104 vs. 584 mL, p = 0.002) and the postoperative hospital stay was significantly shorter (9.1 vs. 21.6 days, p = 0.002) for LS patients than for those in the OS group. In the LS group, one patient developed postoperative pneumonia, but all patients survived without recurrence after a mean follow-up of 37 months.Conclusion: Our strategy for suspected T2 gallbladder GBC is safe and useful, avoids unnecessary procedures, and is associated with similar oncologic outcomes as the open method. [ABSTRACT FROM AUTHOR]

Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the MYC and TP53 copy numbers in gallbladder tumors and their possible association with protein expression. We also investigated whether MYC may be controlled by mutations and DNA promoter methylation. In the present study, 15 samples of invasive gallbladder carcinomas and six control samples were analyzed. On the other hand, the expression of MYC and p53 was more frequent in gallbladder carcinomas than in control samples ( p = 0.002, p = 0.046, respectively). Gain of copies of the MYC and TP53 genes was detected in 86.7 and 50 % of gallbladder carcinomas, respectively. MYC and TP53 amplifications were associated with immunoreactivity of their protein ( p = 0.029, p = 0.001, respectively). MYC hypomethylation was only detected in tumoral samples and was associated with its protein expression ( p = 0.029). MYC mutations were detected in 80 % of tumor samples. The G allele at rs117856857 was associated with the presence of gallbladder tumors ( p = 0.019) and with MYC expression ( p = 0.044). Moreover, two tumors presented a pathogenic mutation in MYC exon 2 (rs28933407). Our study highlights that the gain of MYC and TP53 copies seems to be a frequent finding in gallbladder cancer. In addition, gain of copies, hypomethylation and point mutations at MYC may contribute to overexpression of its protein in this type of cancer. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery has been widely employed in the field of digestive surgery, since the minimally invasive procedure provides a significant benefit to patients. However, laparoscopic curative surgery for gallbladder cancer has been rarely described. The aim of this study was to evaluate the effectiveness and validity of laparoscopic radical cholecystectomy with lymph node dissection (Lap-RC) to treat with T1b/T2 gallbladder carcinoma. Methods: A total of 11 patients underwent Lap-RC for gallbladder carcinoma from November 2001 until June 2013. While 4 patients were preoperatively diagnosed with T1b/T2 gallbladder carcinoma, 7 patients were diagnosed with incidental T1b/T2 gallbladder carcinoma by postoperative pathological examination after laparoscopic cholecystectomy. Common bile duct resection and biliary tract reconstruction were performed in 2 cases. End points in this clinical study were tumor recurrence and survival of patients. Results: Mean operative time was 196 min, and average hospital stay after surgery was 6.4 days, excluding 2 cases with biliary tract reconstruction. One patient died of recurrence of cancer 89 months after surgery, and another patient died of other reason with local recurrence 39 months after the operation. The other 9 patients were all alive without recurrence at this writing. The 5-year survival rate was 100 % for T1b patients and 83.3 % for T2. These results indicate that almost equivalent outcomes compared with open surgery in terms of curability were achieved. Conclusions: We conclude that pure laparoscopic radical cholecystectomy with lymph node dissection is safe and beneficial for the patients with T1b/T2 gallbladder carcinoma. [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma (GBC) is the most common cancer of the biliary tract. Lymph node metastasis (LNM) is the major diffusion route of GBC and is a prognosis factor. The aim of study was to assess the potential of the serum VEGF-C and VEGF-D (sVEGF-C/D) levels to predict the presence of LNM and the survival of GBC patients. The preoperative sVEGF-C/D levels of 31 patients with GBC, 10 patients with cholesterol polyps, and 10 healthy volunteers were measured by enzyme-linked immunoadsorbent assay (ELISA). The sVEGF-C/D levels of patients with GBC were significantly higher than those of people with healthy gallbladders ( p < 0.001 and p = 0.001, respectively) and cholesterol polyp ( p = 0.032 and p = 0.004, respectively). In GBC, the sVEGF-C levels were associated with LNM ( p = 0.011), distant metastasis ( p = 0.018), and stage ( p = 0.045), but the sVEGF-D levels had a significant association with the tumor depth ( p = 0.001), LNM ( p = 0.001), distant metastasis ( p = 0.047), and stage ( p = 0.002). The sVEGF-C/D diagnostic values for the presence of GBC were sensitivity of 71.0 and 74.2 % and specificity of 80.0 and 85.0 %, respectively. With respect to the diagnosis of LNM, the diagnostic values of sVEGF-C/D were as follows: sensitivity 81.2 and 87.5 % and specificity 73.3 and 80.0 %, respectively. The mean survival time with high sVEGF-C was significantly shorter than that with low sVEGF-C ( p < 0.001), which was also true for low sVEGF-D ( p = 0.032). The preoperative sVEGF-C/D levels might be reliable biomarkers for the presence of disease and LNM in patients with GBC. The sVEGF-C/D levels may be prognosis factors that can predict a poor outcome for GBC patients. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a frequently progressive and fatal disease. Death from cancer occurs in a significant subset of patients with PSC. Patients with PSC have a 10 to 15 % lifetime risk of developing cholangiocarcinoma (CCA). About one third of CCAs are present in the first year after a diagnosis of PSC; the remainder are present with a frequency of about 1.5 % each year. Patients with concomitant PSC and inflammatory bowel disease (IBD) have a 4-fold higher risk of colorectal cancer (CRC) than patients with IBD alone and a 10-fold higher risk of CRC than the general population. The risk does not diminish with liver transplantation. This patient population also has a high frequency of carcinoma in gallbladder mass lesions. The risk for hepatocellular carcinoma (HCC) in the presence of cirrhosis is uncertain-two large cohort studies suggest that HCC is not as common as in other causes of cirrhosis. Although AASLD guidelines do not recommend routine screening for liver tumors in patients with PSC, we recommend MRI/MRCP and serum CA 19-9 levels in patients with PSC every 6 months to screen for CCA, HCC, pancreatic cancer, and gallbladder cancer. Screening colonoscopy at the diagnosis of PSC and surveillance colonoscopies every 1-2 years should be performed in those with PSC and IBD. [ABSTRACT FROM AUTHOR]

The genetic abnormalities involved in the pathogenesis of gallbladder carcinoma (GBC) remain unclear. Microsatellite instability (MSI) has been described in many carcinomas, but little is known about the significance of mismatch repair in gallbladder carcinogenesis. Additionally, methylation status of long interspersed element-1 (LINE-1), a surrogate marker of global DNA methylation, has defined distinct subsets of other cancer types but has not been explored in GBC. Immunohistochemical expression of MSH2, MSH6, MLH1, and PMS2 and LINE-1 mRNA in situ hybridization was evaluated in 67 primary and 15 metastatic GBCs from 77 patients. Amplification of human epidermal growth factor receptor 2 ( HER2) was evaluated by fluorescence in situ hybridization. Genotyping for 24 genes involved in carcinogenesis was performed using a multiplex PCR-based platform. MSI was present in 6 of 77 GBCs (7.8 %). Loss of MSH2/MSH6 was detected in five cases and loss of MLH1/PMS2 in one case. MSI status was not associated with Lynch syndrome, tumor grade, extracellular mucin, or tumor-infiltrating lymphocytes. There was no significant difference in mean overall survival of patients with and without MSI. Strong LINE-1 staining was identified in none of the GBC with MSI and in 36 of 69 (52 %) of those without MSI ( p = 0.005), suggesting that LINE-1 in the former cohort was hypermethylated. All MSI tumors were negative for HER2 amplification, and TP53 and NRAS mutations were only found in GBC without MSI. MSI was identified in a minority of GBC cases. The strong correlation between global DNA methylation as measured by LINE-1 and loss of mismatch repair proteins suggests that methylation may account for the loss of these proteins. These hypermethylated tumors appear to represent a genetically unique cohort of gallbladder neoplasms, and the data suggests that demethylating agents may have a therapeutic value in this class of tumors. [ABSTRACT FROM AUTHOR]

Background: No previous studies have compared cytology obtained under endoscopic transpapillary gallbladder drainage (ETGD) and EUS-guided fine needle aspiration (EUS-FNA) for thick-walled gallbladders. Aim: The present study investigated the diagnostic yield of bile cytology under ETGD and EUS-FNA for gallbladder tumors. Methods: A total of 69 patients were diagnosed as having gallbladder wall thickening. Among these patients, 28 patients were diagnosed by clinical follow-up, solely by imaging such as computed tomography or by histological examination of surgical specimens. The remaining 41 patients underwent ETGD and/or EUS-FNA. In these 41 patients, the clinical data collected included gender, age, diameter of gallbladder wall, site of gallbladder wall thickening, final diagnosis, adverse events, and diagnostic yield of ETGD and EUS-FNA. Results: Cyto-histological diagnosis with EUS-FNA was higher than that with ETGD, with a sensitivity of 100 versus 71 %, specificity of 100 versus 94 %, and accuracy of 100 versus 88 %, respectively, in the two groups. In addition, the sampling adequacy of EUS-FNA was 100 %. Adverse events were seen in five patients in the ETGD group (mild pancreatitis), although no adverse events were seen in the EUS-FNA group ( P = 0.08). Conclusion: Our results suggest that EUS-FNA can be safely performed for the diagnosis of gallbladder lesions. Further, this procedure may be the diagnostic method of choice over cytology of bile juice obtained via ETGD to obtain histological evidence of gallbladder cancer. [ABSTRACT FROM AUTHOR]

Background and Aims: Differentiation of gallbladder (GB) carcinoma from benign GB wall thickening is challenging. The recent introduction of second-generation ultrasonic contrast agents has made contrast harmonic imaging with EUS possible. The aim of our study was to evaluate the utility of contrast-enhanced harmonic EUS (CH-EUS) for the differential diagnosis of GB wall thickening. Methods: Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then underwent surgery were enrolled in this study. After the lesions were observed with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C: experienced gastroenterologist with expertise in transabdominal ultrasound but no EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS. The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was compared. Results: Final diagnoses based on surgical histology were GB carcinoma in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3. Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98 % ( p < 0.001) and 73.1 versus 94.4 % ( p < 0.001). The inter-observer agreement for H-EUS was moderate ( κ = 0.51), whereas that for CH-EUS was substantial ( κ = 0.77). The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of malignant GB wall thickening. Conclusion: CH-EUS has the potential to improve the preoperative diagnostic accuracy and inter-observer agreement in the differential diagnosis of GB wall thickening. [ABSTRACT FROM AUTHOR]