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Background: Gallbladder carcinoma (GBC) is an extremely aggressive tumor of the biliary tract with a bleak prognosis, and the evidence supporting the benefit of available systemic therapy for advanced GBC is scarce. Herein, this study intended to investigate the real-world outcome of chemotherapy combined with programmed death-1 (PD-1) inhibitor for the management of unresectable or recurrent GBC. Methods: From January 2018 to December 2023, consecutive patients who were treated with systematic treatment, including chemotherapy or the combination of chemotherapy plus PD-1 inhibitor, for unresectable or recurrent GBC were retrospectively identified. Clinical data regarding baseline characteristics, therapeutic response, adverse events (AEs), and oncological outcomes were collected. Results: The eligible patients were allocated to combination therapy arm (n = 46) and mono-chemotherapy arm (n = 19). After propensity score matching (PSM), 16 patients were allocated in each arm. The overall survival (OS) and progression-free survival (PFS) of combination therapy were marginally superior to mono-chemotherapy both before and after PSM. The combination therapy exhibited advantage over mono-chemotherapy in regards to partial response (PR) (before PSM: P = 0.009; after PSM: P = 0.037) and objective response rate (ORR) (before PSM: P = 0.006; after PSM: P = 0.015). In combined therapy cohort, 1 patient achieve a complete response, and 13 patients were assessed as appropriate for surgical excision, among which 1 patient refused further surgical intervention. Conclusions: In patients with unresectable or recurrent GBC, the combination of chemotherapy and PD-1 inhibitor as first-line therapy exhibited prolonged OS and PFS, and increased PR and ORR over those receiving chemotherapy alone, with an acceptable toxicity profile. The combination therapy may be a potential conversion therapy in unresectable GBC patients. [ABSTRACT FROM AUTHOR]

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

Abstract Objective We aimed to develop a preoperative clinical radiomics survival prediction model based on the radiomics features via deep learning to provide a reference basis for preoperative assessment and treatment decisions for patients with gallbladder carcinoma (GBC). Methods A total of 168 GBC patients who underwent preoperative upper abdominal enhanced CT from one high-volume medical center between January 2011 to December 2020 were retrospectively analyzed. The region of interest (ROI) was manually outlined by two physicians using 3D Slicer software to establish a nnU-Net model. The DeepSurv survival prediction model was developed by combining radiomics features and preoperative clinical variables. Results A total of 1502 radiomics features were extracted from the ROI results based on the nnU-Net model and manual segmentation, and 13 radiomics features were obtained through the 4-step dimensionality reduction methods, respectively. The C-index and AUC of 1-, 2-, and 3-year survival prediction for the nnU-Net based clinical radiomics DeepSurv model was higher than clinical and nnU-Net based radiomics DeepSurv models in the training and testing sets, and close to manual based clinical radiomics DeepSurv model. Delong-test was performed on the AUC of 1-, 2-, and 3-year survival prediction for the two preoperative clinical radiomics DeepSurv prediction models in the testing set, and the results showed that the two models had the same prediction efficiency (all P > 0.05). Conclusions By using the DeepSurv model via nnU-Net segmentation, postoperative survival outcomes for individual gallbladder carcinoma patients could be assessed and stratified, which can provide references for preoperative diagnosis and treatment decisions.

Krukenberg tumour is defined by the development of metastasis in both ovaries, characterised by the presence of mucine secreting cells, hence the name carcinoma mucocellular; However, the term “Krukenberg” has often been broadly applied to any metastases to the ovaries, irrespective of the site of origin. It is uncommon representing about 1%-2% of all ovarian tumours. It is in general secondary to a gastric adenocarcinoma but other sites have been found to be responsible of krukenberg's tumour, notably large bowels adenocarcinoma, pancreas, breast cancer, lung adenocarcinoma and biliary tract cholangiocarcinoma. In this article we will report the case of a 29 years old patient presenting with metachronous krukenberg tumour and peritoneal carcinosis with a history of surgery for a gallbladder adenocarcinoma 9 month prior. This case study sheds light on this pathology, familiarizing us with its clinical and radiological picture, as well as its prognosis.

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]

Objective: The differentiation between reactive atypical changes and dysplasia/ carcinoma in the daily cases of cholecystectomies is a routine histopathological challenge. Up to our knowledge, no immunohistochemical marker can definitely differentiate between these two changes. Many promising markers have been proposed to be helpful tools in this situation. One of them is B-cell lymphoma-2 (BCL-2) immunohistochemical stain. Therefore, this study aims to evaluate its usefulness as a marker that might be helpful in such challenging cases. Methods: From the archive of the histopathology laboratories of Qassim University Medical City and King Fahad Specialist Hospital in Qassim, five dysplastic/neoplastic gallbladder cases were collected (in the shape of formalin-fixed, paraffin-embedded blocks) as well as five cholecystitis with reactive atypical changes cases. Two slides from each block were prepared: One was stained with H&E and the other was stained immunohistochemically with BCL-2. The slides were evaluated by two histopathologist consultants in the same sitting using multiheaded microscope to confirm the original diagnosis and to evaluate the BCL-2 staining. Results: Five dysplastic/carcinoma cases and five cholecystitis with reactive atypia were collected. The original diagnoses were confirmed by two pathologists. They also confirmed that all the BCL-2 stained slides (with the exception of one reactive case) were negative for BCL-2 immunohistochemical stain. Conclusion: BCL-2 immunohistochemical stain is not a promising marker in the differentiation between reactive epithelium and dysplasia/carcinoma in the gallbladder. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been shown to play important roles in tumour development and tumour immunology. However, genome‐wide characterisation of circRNAs and their roles in the immunology and immunotherapy of gallbladder carcinoma (GBC) has been lacking. We present a comprehensive characterisation of the circRNA landscape in GBC, revealing GBC‐specific circRNAs. Our analysis found that circRNAs are significantly enriched in cell proliferation and are involved in cancer‐related hallmarks. In particular, circAATF was upregulated in GBC, which was positively correlated with AATF mRNA expression, and promoted GBC cell growth. Through integrating computational and experimental approaches, we revealed that circAATF is positively associated with the CD4+ T cell abundance and PD‐L1 level, and enhances the clinical benefits of anti‐PD‐L1 immunotherapy for GBC. We further demonstrate that circAATF elevates the PD‐L1 level by activating phosphorylated AKT and acting as a sponge for miR‐142‐5p. CircAATF is positively associated with CD4+ T cells and PD‐L1 levels and shows potential to aid anti‐PD‐L1 immunotherapy for GBC. Our study provides insights into roles of circAATF in the tumour development and immunology of GBC and accelerates the development of therapeutic strategies for GBC immunotherapy. Highlights: We present a comprehensive characterisation of circRNA landscape in gallbladder carcinoma (GBC).CircAATF is positively associated with CD4+ T cell abundance and PD‐L1 expression and is shown to promote PD‐L1 treatment in mouse model.CircAATF can elevate PD‐L1 level through phosphorylated AKT and linear AATF, which upregulates PD‐L1 by acting as a sponge of miR‐142‐5p. [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]

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

Background. Undifferentiated gallbladder carcinoma is a rare type of cancer with poor prognosis, due to the absence of specific clinical manifestations, and the final diagnosis depends on pathological and immunohistochemical examinations. However, only a few reports of SMARCA4-deficient undifferentiated gallbladder tumor have been published to date. Therefore, we report the diagnosis and treatment of an undifferentiated gallbladder carcinoma with SMARCA4 deficiency. Case Presentation. A 65-year-old woman with undifferentiated gallbladder carcinoma was treated using traditional Chinese medicine and underwent palliative surgery in our hospital. The postoperative pathology showed SMARCA4-deficient undifferentiated gallbladder carcinoma with metastasis to the abdominal lymph nodes. Conclusions. This case report contributes to the limited literature regarding undifferentiated carcinoma without SMARCA4 in the gallbladder. [ABSTRACT FROM AUTHOR]

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

Gallbladder carcinoma (GBC) is a common malignancy and is usually diagnosed in the late stages of the disease. The identification of new effective early diagnostic biomarkers could represent an effective approach in reducing mortality in GBC. Altered expression of long non-coding RNAs (lncRNAs) is believed to be associated with the emergence and development of GBC. Our study aims to identify the expression of a range of circulating lncRNAs, including HOTAIR, ANRIL, H19, CCAT1 and MEG3, in matched serum and tissues of GBC for diagnosis and its association with clinicopathological features. The case and control study included matched serum and tissues from 63 GBC, 19 cholecystitis (CC), and 46 normal controls (NC). RNA extraction and cDNA synthesis from serum and fresh tissue match were performed using commercially available kits. Relative expression was assessed using SYBR Green real-time quantitative polymerase chain reaction. Circulating lncRNA levels including HOTAIR, ANRIL and H19 were upregulated in serum samples, while MEG3 and CCAT1 were downregulated in GBC compared to controls. The trend towards upregulation and downregulation was comparable in the tissue. HOTAIR and MEG3 levels were significantly different between serum CC and early-stage GBC (p = 0.0373, 0.0020), while H19 was significantly upregulated comparing early-stage GBC to advanced-stage GBC (p = 0.018). The expression of ANRIL was significant with M stage (p = 0.0488), H19 with stage (p = 0.009), M stage (p=

Abstract Background The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. Methods According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. Results Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P0.05). Conclusion The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

Background: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. Methods: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2 × 103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. Results: The normal group (n= 179 patients) and the normalization group (n= 73 patients) had better OS and RFS than the nonnormalization group (n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003). Conclusions: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients. [ABSTRACT FROM AUTHOR]

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

Objective: To investigate the effect of M2 macrophages on the proliferation, migration and invasion of gallbladder carcinoma cells by regulating the expression of interleukin-10 (IL-10). Methods: Human monocyte line THP-1 was induced into M2 macrophages in vitro, and the expression of corresponding markers and IL-10 was detected by RT-qPCR. The expression of IL-10 in cell supernatant was detected by ELISA. GBC cell lines NOZ and GBC-SD were divided into the Control group (serum-free medium), the M2-CM group (M2 macrophage conditioned medium), the M2-CM+anti-IL-10 group (M2-CM containing anti-IL-10) and the M2-CM + IgG group (M2-CM containing IL-10 isotype control antibody). The cell proliferation rate of each group was measured by CCK-8 test, the cell migration rate of each group was detected by cell scratch test and the change in cell invasive ability of each group was detected by Transwell test; and Western blot assay was used to detect the expression of epithelial-mesenchymal transformation markers (E-cadherin and Vimentin) in each group. Results: M2 macrophages were successfully induced in vitro. Compared with uninduced THP-1, IL-10 was highly expressed in M2 macrophages and M2 macrophages supernatant (P<0.05). M2 macrophages could promote the proliferation, migration and invasion of GBC cells, as well as inhibit the expression of E-cadherin and promote the expression of Vimentin. Blocking IL-10 could inhibit the effect of M2 macrophages (P<0.05) . Conclusion: M2 macrophages can promote the proliferation, migration, invasion and epithelial-mesenchymal transformation of GBC cells by secreting IL-10. [ABSTRACT FROM AUTHOR]

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.

Abstract 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

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

Background Carcinoma of the gallbladder is a malignant neoplasm, which is associated with a poor prognosis due to its often-asymptomatic nature and late-stage diagnosis. Non-invasive imaging techniques play a key role in the early detection and characterization of gallbladder carcinoma. This thesis presents a comprehensive analysis of the utility of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping in the magnetic resonance imaging (MRI) evaluation of carcinoma of the gallbladder. The primary objective of this research was to investigate the exact diagnostic accuracy and potential clinical applications of DWI and ADC in assessing carcinoma of the gallbladder and related tumour aggressiveness. A systematic review of existing literature was conducted to establish a foundation for this study with efforts to acquire relevant imaging data. The results of this study demonstrate the efficacy of DWI and ADC in the detection of carcinoma of the gallbladder when compared to conventional MRI sequences. These advanced imaging techniques hold promise in increasing the accuracy of diagnosis, ultimately leading to improved patient outcomes and more informed clinical decision making. The potential of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping in the evaluation of gallbladder cancer using magnetic resonance imaging (MRI) is thoroughly analysed in this thesis. Methods A descriptive prospective study will be done at Acharya Vinoba Bhave Rural Hospital, Sawangi, involving 20 patients with clinically suspected carcinoma gallbladder, who are referred to the department of Radiodiagnosis. These patients will be subjected to study-purposive sampling. Conclusion After an appropriate statistical analysis, we expect to assess the role of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping in the magnetic resonance imaging (MRI) evaluation of carcinoma of the gallbladder. CTRI registration This trial has been submitted to Clinical Trials Registry-India (CTRI) for Review. Registration Number: REF/2023/09/072780 Registration date:01/05/2023 URL of trial: https://www.ctri.nic.in/

Introduction: Cholelithiasis is known to cause a spectrum of changes, including inflammation in the gallbladder wall, cholesterolosis, atrophy, metaplasia, dysplasia, polyps, and eventually cancer. Gallbladder Carcinoma (GBC) is a rare and highly fatal malignancy. Aim: To determine the frequency of preneoplastic and neoplastic lesions, along with demographic and clinical aspects of different gallbladder lesions. Materials and Methods: This cross-sectional study was performed on 788 patients who underwent elective cholecystectomy for gallbladder disease at Hind Medical College, Sitapur, Uttar Pradesh, India, from August 2017 to October 2021. All patients underwent a history and physical examination, followed by routine laboratory tests and other investigations, including full abdominal ultrasound. Histopathologic evaluation of the gallbladder specimen was also performed after surgical resection. Categorical variables were presented as numbers and percentages (%), while continuous variables were presented as mean ± Standard Deviation (SD). Results: A total of 788 cholecystectomy specimens were analysed. The mean age of the patients was 42.49±1.39 years with female predominance 640 (82.05%). The majority of cases were between 40-49 269 (34.13%) and 60-69 399 (50.63) years of age. Preneoplastic changes were found in 764 (96.96%) cases, while neoplastic pathology was evident in 24 (3.04%) cholecystectomy specimens. The most commonly observed preneoplastic change was chronic cholecystitis in 532 (67.54%) cases. Other lesions associated with chronic cholecystitis were cholesterolosis in 76 cases (9.64%), xanthogranulomatous cholecystitis in 34 cases (4.31%), follicular cholecystitis in 30 cases (3.80%), and GBC in 24 cases (3.04%). Conclusion: This study observed that chronic cholecystitis and cholesterolosis, followed by xanthogranulomatous cholecystitis, were associated with metaplastic changes in gallbladder pathologies. It is believed that metaplasia-dysplasia could be linked to GBC. Therefore, routine microscopic examination is required for all cholecystectomies. However, further studies on gallbladder carcinogenesis are needed.

Abstract 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 Background Gallbladder carcinoma (GBC) is a highly malignant tumor with a poor overall prognosis. This study aimed to identify the characteristic microRNAs (miRNAs) of GBC and the competing endogenous RNA (ceRNA) regulatory mechanisms. Methods The microarray data of GBC tissue samples and normal gallbladder (NGB) tissue samples from the Gene Expression Omnibus (GEO) database was downloaded. GBC-related differentially expressed miRNAs (DE-miRNAs) were identified by inter-group differential expression analysis and weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were used to screen the characteristic miRNA based on the intersect between least absolute shrinkage and selection operator (LASSO) and Support vector machine-recursive feature elimination (SVM-RFE). Based on the differential expression analysis of GEO database, the ceRNA network of characteristic miRNA was predicted and constructed. The biological functions of the ceRNA network were revealed by carrying out the gene enrichment analysis was implemented. We further screened the key genes of ceRNA network and constructed a protein-protein interaction (PPI) network, and predicted and generated the transcription factors (TFs) network of signature miRNAs. The expression of characteristic miRNA in clinical samples was verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results A total of 131 GBC-related DE-miRNAs were obtained. The hsa-miR-4770 was defined as characteristic miRNA for GBC. The ceRNA network containing 211 mRNAs, one miRNA, two lncRNAs, and 48 circRNAs was created. Gene enrichment analysis suggested that the downstream genes were mainly involved in actin filament organization, cell-substrate adhesion, cell-matrix adhesion, reactive oxygen species metabolic process, glutamine metabolic process and extracellular matrix (ECM)-receptor interaction pathway. 10 key genes in the network were found to be most correlated with disease, and involved in cell cycle-related processes, p53, and extrinsic apoptotic signaling pathways. The qRT-PCR result demonstrated that hsa-miR-4770 is down-regulated in GBC, and the expression trend is consistent with the public database. Conclusions We identified hsa-miR-4770 as the characteristic miRNA for GBC. The ceRNA network of hsa-miR-4770 may play key roles in GBC. This study provided some basis for potential pathogenesis of GBC.

Background: Xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma (GBC) share similar imaging and serological profiles, posing significant challenges in accurate preoperative diagnosis. This study aimed to identify reliable indicators and develop a predictive model to differentiate between XGC and GBC. Methods: This retrospective study involved 436 patients from Zhejiang Provincial People's Hospital and The Affiliated Lihuili Hospital of Ningbo University. Comprehensive preoperative imaging, including ultrasound, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and blood tests, were analyzed. Machine learning (Random Forest method) was employed for variable selection, and a multivariate logistic regression analysis was used to construct a nomogram for predicting GBC. Statistical analyses were performed using SPSS and RStudio software. Results: The study identified gender, Murphy's sign, absolute neutrophil count, glutamyl transpeptidase level, carcinoembryonic antigen level, and comprehensive imaging diagnosis as potential risk factors for GBC. A nomogram incorporating these factors demonstrated high predictive accuracy for GBC, outperforming individual or combined traditional diagnostic methods. External validation of the nomogram showed consistent results. Conclusion: The study successfully developed a predictive nomogram for distinguishing GBC from XGC with high accuracy. This model, integrating cmultiple clinical and imaging indicators, offers a valuable tool for clinicians in making informed diagnostic decisions. The findings advocate for the use of comprehensive preoperative evaluations combined with advanced analytical tools to improve diagnostic accuracy in complex medical conditions. [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]

Abstract Objective 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. Methods 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. Results 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

Abstract Background Multiple-organ primary tumors can invade the ovary through lymphatic and hematogenous routes, presenting as ovarian Krukenberg tumors, but these rarely originate from the gallbladder. Krukenberg tumors can present similar to primary ovarian tumors; however, their treatments are completely different. Patient concerns A 62-year-old Chinese woman presented with abdominal distension for six months and weight loss of five kilograms for two months. Diagnoses Based on multiple imaging examinations, the patient was preliminarily diagnosed with a malignant tumor of unknown origin with multiple metastases (omentum). To identify the origin of the malignancy, the patient underwent real-time contrast-enhanced ultrasound-guided percutaneous biopsy. The results revealed a perihepatic hypoechoic lesion and right adnexal mass that were both metastatic adenocarcinomas from the gallbladder. Interventions The patient initially received chemotherapy with gemcitabine and cisplatin instead of surgery. However, the tumor increased in size on re-examination after two cycles, so the treatment was shifted to a combination regimen with durvalumab for six cycles. Outcomes The treatment proceeded smoothly, with no recurrence or obvious progression of the cancer during follow-up. Conclusions Differentiating between primary and metastatic ovarian tumors is important. Early diagnosis and effective treatment options are essential for patient survival. CEUS-guided percutaneous biopsy is a valuable procedure for patients with multiple metastases who cannot tolerate surgery.

Biliary tract cancers (BTC) are rare and aggressive tumors with poor prognosis. Radical surgery offers the best chance for cure; however, most patients present with unresectable disease, and among those receiving curative-intent surgery, recurrence rates remain high. While other locoregional therapies for unresectable disease may be considered, only select patients may be eligible. Consequently, systemic therapy plays a significant role in the treatment of BTC. In the adjuvant setting, capecitabine is recommended following curative-intent resection. In the neoadjuvant setting, systemic therapy has mostly been explored for downstaging in borderline resectable tumours, although evidence for its routine use is lacking. For advanced unresectable or metastatic disease, gemcitabine-cisplatin plus durvalumab has become the standard of care, while the addition of pembrolizumab to gemcitabine-cisplatin has also recently demonstrated improved survival compared to chemotherapy alone. Following progression on gemcitabine-cisplatin, several chemotherapy combinations and biomarker-driven targeted agents have been explored. However, the optimum regimen remains unclear, and access to targeted agents remains challenging in Canada. Overall, this article serves as a practical guide for the systemic treatment of BTC in Canada, providing valuable insights into the current and future treatment landscape for this challenging disease.

Abstract Background Surgical resection remains the primary treatment option for gallbladder carcinoma (GBC). However, there is a pressing demand for prognostic tools that can refine patients' treatment choices and tailor personalized therapies accordingly. Aims The nomograms were constructed using the data of a training cohort (n = 378) of GBC patients at Eastern Hepatobiliary Surgery Hospital (EHBH) between 2008 and 2018. The model's performance was validated in GBC patients (n = 108) at Guangzhou Centre from 2007 to 2018. Methods and results The 5‐year overall survival (OS) rate in the training cohort was 24.4%. Multivariate analyses were performed using preoperative and postoperative data to identify independent predictors of OS. These predictors were then incorporated into preoperative and postoperative nomograms, respectively. The C‐index of the preoperative nomogram was 0.661 (95% CI, 0.627 to 0.694) for OS prediction and correctly delineated four subgroups (5‐year OS rates: 48.1%, 19.0%, 15.6%, and 8.1%, p

Synchronous primary cancers are very rare. Due to their low incidence rate and insidious onset, they may be easily overlooked or misdiagnosed. In addition, there is currently no international consensus for their clinical diagnosis and treatment. Three exceedingly unusual synchronous primary malignancies, carcinoma gallbladder with renal cell carcinoma, carcinoma gallbladder with carcinoma colon, and carcinoma gallbladder with carcinoma breast, are presented here. Together with their clinical presentation, therapeutic options and outcomes are also presented. Curative radical surgery of each particular tumor, along with postoperative chemotherapy or radiotherapy improves disease-free survival. [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]