Diagnosis Of Gallbladder Cancer Research Articles

Exploring the Potential of Robotic Single-Port Surgery for Gallbladder Cancer: Initial Insights and Future Prospects.

Robotic surgery has demonstrated outcomes comparable or superior to open and laparoscopic surgeries for extended cholecystectomy.1-8 Despite its advantages, the minimally invasive robotic single-port (SP) system remains underutilized in complex hepatobiliary pancreatic surgery due to instrument limitations and retraction issues.9,10 This study evaluated the feasibility, safety, and effectiveness of the da Vinci SP system in gallbladder cancer surgery. The study was approved by the Ethics Committee of OOO University Hospital (IRB no. DAUH IRB-24-081) and conducted in accordance with the principles of the Declaration of Helsinki. The requirement for informed consent was waived due to the study's retrospective design. A 62-year-old woman with a diagnosis of gallbladder cancer was referred for surgery. Preoperative computed tomography (CT) scans showed no evidence of metastasis (T2N0). Therefore, a robotic SP extended cholecystectomy was planned. Figure 1 shows a 30-mm SP port and a 1-mm assistant port inserted for the procedure. Due to the absence of an energy device for the liver wedge resection, Maryland bipolar forceps were used, mimicking the Kelly clamp crushing technique. A monopolar cautery hook was used for lymph node resection of stations 7, 8, 12, and 13 (Fig. 2). Fig. 1 Port placement for robotic extended cholecystectomy using the da Vinci Xi system Fig. 2 Demonstration of full lymph node dissection RESULTS: The total duration of the operation was 226 min, with an estimated blood loss of 200 ml. The CT scan on day 5 showed no abnormalities, and the patient was discharged routinely on day 7 (Fig. 3). The pathologic examination confirmed adenocarcinoma (T2a) with clear resection, and all six lymph nodes tested negative for malignancy. Fig. 3 The wound 2 weeks after surgery CONCLUSIONS: This study underscores the adequacy of robotic surgeries and emphasizes the potential of the da Vinci SP system in hepatobiliary surgery. Despite current challenges related to instrument limitations, the authors are confident that the SP system will evolve into a crucial asset for hepatobiliary surgical practices in the foreseeable future.

Prognostic Factors in Patients Diagnosed with Gallbladder Cancer over a Period of 20 Years: A Cohort Study.

Gallbladder cancer (GBC) is an uncommon cancer. This study aimed to determine the outcomes of GBC in relation to geographic, demographic, and clinical factors in a Canadian province from 2000 to 2019. This population-based retrospective cohort study included all patients diagnosed with gallbladder cancer (GBC) in Saskatchewan, Canada, from 2000 to 2019. Cox proportional multivariate regression analysis was conducted to identify factors associated with poorer outcomes. In total, 331 patients with a median age of 74 years and male-female ratio of 1:2 were identified. Of these patients, 305 (92%) had a pathological diagnosis of GBC. Among patients with documented staging data, 64% had stage IV disease. A total of 217 (66%) patients were rural residents, and 149 (45%) were referred to a cancer center. The multivariate analysis for patients with stage I-III GBC showed that stage III disease [hazard ratio (HR), 2.63; 95% confidence interval (CI), 1.09-6.34)] and urban residence (HR, 2.20; 95% CI, 1.1-4.39) were correlated with inferior disease-free survival. For all patients, stage IV disease (HR, 3.02; 95% CI, 1.85-4.94), no referral to a cancer center (HR, 2.64; 95% CI, 1.51-4.62), lack of surgery (HR, 1.63; 95% CI, 1.03-2.57), a neutrophil-lymphocyte ratio of >3.2 (HR, 1.57; 1.05-2.36), and age of ≥70 years (HR, 1.51; 95% CI, 1.04-2.19) were correlated with inferior overall survival. In this real-world context, the majority of patients with GBC were diagnosed at a late stage and were not referred to a cancer center. For those with early-stage GBC, living in an urban area and having stage III disease were linked to worse outcomes. Across all stages of GBC, stage IV disease, older age, absence of surgery, lack of referral to a cancer center, and a high neutrophil-to-lymphocyte ratio were associated with poorer survival.

Early Diagnosis of Gall Bladder Cancer: An Appeal

A team of gastroenterologists, oncologists, pathologists, radiologists, and surgeons from a university teaching hospital in western India make an appeal, through the Journal, to the statutory bodies and the scientific societies related to surgery, oncology, gastroenterology, radiology, and pathology for considering measures, which, if implemented, can help in early diagnosis of gallbladder cancer, the most common nongender organ cancer in women in some parts of India.

Texture and color enhancement imaging and red dichromatic imaging for diagnosis of gallbladder cancer by using peroral cholecystoscopy through an EUS-guided gallbladder drainage route (with video)

Texture and color enhancement imaging and red dichromatic imaging for diagnosis of gallbladder cancer by using peroral cholecystoscopy through an EUS-guided gallbladder drainage route (with video)

Risk prediction and analysis of gallbladder polyps with deep neural network

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

EUS-guided FNA and biopsy for cytohistologic diagnosis of gallbladder cancer: a multicenter retrospective study

EUS-guided FNA and biopsy (EUS-FNAB) is a standard diagnostic procedure for pancreatic masses but not gallbladder (GB) cancer (GBC). The aim of this study was to investigate the efficacy and safety of EUS-FNAB for patients with suspected GBC. Data were analyzed from patients who underwent EUS-FNAB for suspected GBC in 3 hospitals between 2010 and 2023. The diagnostic performance and safety of EUS-FNAB according to characteristic factors were calculated and compared. Of 170 patients, 163 had GBC. EUS-FNAB samples were obtained from the GB in 125 patients and sites other than the GB in 45 patients. The overall sensitivity, specificity, and accuracy were 83.4%, 100%, and 84.1%, respectively. The sensitivity and accuracy for patients with GB samples were 80.8% and 81.6%; for patients without GB samples, these values were 90.7% and 91.1%. The sensitivity and accuracy were higher with fine-needle biopsy needles than with FNA needles and with≤22-gauge needles than with 25-gauge needles. However, no significant differences were observed between the GB and lymph node samples. GB lesions<40mm in size, wall-thickening type, fundal location, absence of extensive liver invasion, and distant metastasis were more frequent in patients without GB samples than in patients with GB samples. Four mild bleeding events were the only reported adverse events. EUS-FNAB was safe and showed high diagnostic performance for patients with suspected GBC, regardless of the target site. When appropriate GB targeting is difficult, targeting the lymph nodes would be a good strategy with comparable outcomes.

Construction of a Human Immune Library from Gallbladder Cancer Patients for the Single-Chain Fragment Variable (scFv) Antibody Selection against Claudin 18.2 via Phage Display.

Gallbladder cancer (GBC) is a very aggressive malignant neoplasm of the biliary tract with a poor prognosis. There are no specific therapies for the treatment of GBC or early diagnosis tools; for this reason, the development of strategies and technologies that facilitate or allow an early diagnosis of GBC continues to be decisive. Phage display is a robust technique used for the production of monoclonal antibodies (mAbs) involving (1) the generation of gene libraries, (2) the screening and selection of isoforms related to an immobilized antigen, and (3) the in vitro maturation of the affinity of the antibody for the antigen. This research aimed to construct a human immune library from PBMCs of GBC patients and the isolation of scFv-phage clones with specificity against the larger extracellular loop belonging to claudin 18.2, which is an important biomarker overexpressed in GBC as well as gastric cancer. The immune-library-denominated GALLBLA1 was constructed from seven GBC patients and has a diversity of 6.12 × 1010pfu mL-1. After three rounds of panning, we were able to identify clones with specificity against claudin 18.2. GALLBLA1 can contribute to the selection, isolation, and recombinant production of new human mAbs candidates for the treatment of gastrointestinal cancers.

JAUNDICE IN PATIENTS WITH GALL BLADDER CANCER- A SURROGATE MARKER OF ADVANCED DISEASE

Background: Gall bladder cancer (GBC) is most common cancer of biliary tract. R0 resection is the most important predictor of survival. Patients with GBC and jaundice do worse than those without jaundice.Methods: Retrospective analysis of prospectively kept data of patients with GBC admitted to the department of Surgical Gastroenterology at a tertiary care hospital in northern India over10 years from 2011 to 2020. Data on patient demography, clinical profile, imaging characteristics, clinical course, staging, and operative procedures was extracted and analyzed to compare the experience of patients with GBC with jaundice and GBC without jaundice.Results: There were 401 patients with GBC; 75 with jaundice and 326 without jaundice. Patients with GBC and jaundice had a significantly higher incidence of pain abdomen, loss of appetite, loss of weight and presence of an abdominal lump, gastric outlet obstruction and hypoalbuminemia, a shorter duration of symptoms, more number of hospital admissions, a less frequent (4% vs 10.7%) incidental diagnosis of GBC and a higher incidence of GB neck tumors (80% vs 20%). In patients with GBC and jaundice detection of metastatic or locally advanced unresectable disease on imaging (31%), laparoscopy (11%) or laparotomy (31%) precluded resection in majority of patients. Only 2.6% patients with GBC and jaundice could undergo definitive surgery as compared to 71.2% of patients without jaundice.Conclusion: Patients with GBC and jaundice are very likely to have advanced, unresectable disease. Chances of complete resection are slim even after extensive preparation requiring more extensive, time-consuming, costly, multidisciplinary interventions.

Downregulated circRNA_CDKN1A promotes gallbladder cancer progression through activation of the NF-κB pathway.

This study uncovered the potential clinical value and molecular driving mechanisms of circular RNAs (circRNAs) in gallbladder cancer (GBC). Differentially expressed circRNAs in GBC cells were screened by high-throughput sequencing. CircRNA_CDKN1A (circBase ID: hsa_circ_0076194) was knocked out in BGC-SD cells through transfection with sh-circRNA_CDKN1A. Then, proliferation was investigated via CCK8 and EdU assays, apoptosis via flow cytometry, migration via wound healing assays, and invasion via Transwell assays. Bioinformatics analysis of circRNA_CDKN1A-related signaling pathways was performed using MetScape and g:Profiler. Results showed that the knockdown of circRNA_CDKN1A enhanced the proliferation, migration, and invasion of GBC cells and inhibited apoptosis. In addition, knocking out circRNA_CDKN1A promoted GBC cell proliferation and enhanced the dry indices of the OCT4 protein and CD34 expression levels. The knockdown of circRNA_CDKN1A activated the epithelial-mesenchymal transition pathway. Bioinformatics analysis revealed that the biological role of circRNA_CDKN1A in GBC cells involved the NF-κB pathway. LY2409881, which is an NF-κB inhibitor, reversed the effects induced by the knockdown of circRNA_CDKN1A in GBC-SD cells. In summary, the knockdown of circRNA_CDKN1A promoted the progression of GBC by activating the NF-κB signaling pathway. For the first time, this study revealed the mechanism of circRNA_CDKN1A-mediated regulatory action in GBC and identified the newly discovered circRNA_CDKN1A-NF-κB signaling axis as a potentially important candidate for clinical therapy and prognostic diagnosis of GBC.

Prognostic factors of gallbladder cancer (GBC) in patients diagnosed over a period of 20 years: A Canadian province experience.

437 Background: GBC is an uncommon but often fatal gastrointestinal cancer. The poor prognosis of GBC may in part be due to lack of effective screening tools and a delay in diagnosis that leads to presentation in the latter stages of the disease. The current study aims to determine outcomes of patients with GBC in relation to contextual, demographic and clinical factors in a Canadian province over a span of 20 years. Methods: In this population-based retrospective cohort study patients with GBC diagnosed in Saskatchewan, Canada from 2000-2019 were evaluated. Cox proportional multivariate regression analyses was performed to determine factor correlated with inferior outcomes. Results: 331 patients with median age of 74 yrs and M:F of 1:2 were identified. 92% had a pathological diagnosis of GBC &amp; 80% had adenocarcinoma. 49% were diagnosed &gt;year 2010. 217 (66%) of those diagnosed with GBC were rural residents. 149 (45%) patients were referred to a cancer center. In patients with documented stage, 64% had stage IV disease &amp; &gt;90% were symptomatic with a median time from the onset of symptoms to the diagnosis of 7 months. Rural residents have a significantly high rate of smoking history whereas urban residents have significantly high rates of pathological diagnosis, low serum albumin and elevated platelet count. Median overall survival (OS) of patients with stage I-III GBC was 20 months (95% CI:10.9-29.1) vs. 4.0 months (3.0-5.0) with stage IV GBC (&lt;0.001). No significant differences were noted in OS in relation to residence and time-period of diagnosis. Patients who were not referred for a cancer center had a median OS of 3 months (1.98-4.0) vs. 13 months (9.9-16.1), p&lt;0.001. Median disease-free survival (DFS) of patients with stage I-III GBC was 20 months (95%CI: 10-30.1) with 5-year DFS of 36%. Patients with stage I-III GBC who received adjuvant chemotherapy had 5-yr DFS of 43% vs. 33% without adjuvant chemotherapy (p=0.73). 5-year DFS of urban patients was 25% vs. 42% of rural patients (p=0.016). On multivariate analysis for patients with Stage I-III GBC, stage III disease, HR (hazard ratio), 2.63 (1.09-6.34) and urban residence, HR, 2.20 (1.1-4.39) were correlated with inferior DFS whereas for all patients, stage IV disease, HR, 3.02 (1.85-4.94); no referral to cancer center, HR, 2.64 (1.51-4.62); lack of surgery, HR, 1.63 (1.03-2.57); neutrophil:lymphocyte of &gt;3.2, HR, 1.57 (1.05-2.36); and age ≥70, HR, 1.51 (1.04-2.19) were correlated with inferior OS. Conclusions: In a real-world setting, most patients with GBC are diagnosed with late-stage disease and were not referred to cancer center. For early-stage GBC, urban residence and stage III disease were correlated with inferior outcome, whereas for all stage GBC, stage IV disease, old age, lack of surgery, lack of referral to cancer center, and high neutrophil to lymphocyte ratio were correlated with inferior survival.

Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors.

Risk factors of gallbladder cancer (GBC) are not well-defined resulting in greater than 60% of GBCs being diagnosed incidentally following cholecystectomy performed for presumed benign indications. As most localized GBCs require more extensive oncologic surgery beyond cholecystectomy, this study aims to examine factors associated with incidentally found GBC to improve preoperative and intraoperative diagnoses. The American College of Surgeons National Surgical Quality Improvement Program Database from 2007 to 2017 was used to identify cholecystectomies performed with and without a final diagnosis of GBC. Univariate and multivariable logistic regressions were used to compare demographic, intraoperative, and postoperative characteristics among those with and without a diagnosis of GBC. The incidence of GBC was observed to be 0.11% (441/403,443). Preoperative factors associated with risk of GBC included age > 60 (OR 6.51, p < .001), female sex (OR 1.75, p < .001), history of weight loss (2.58, p < .001), and elevated preoperative alkaline phosphatase level (OR 1.67, p = .001). Open approach was associated with 7 times increased risk of GBC compared to laparoscopic approach (OR 7.33, p < .001). In addition to preoperative factors and surgical approach, longer mean operative times (127min vs 70.7min, p < .001) were significantly associated with increased risk of GBC compared to benign final pathology. This study demonstrates that those with incidentally discovered GBC at cholecystectomy are unique from those undergoing cholecystectomy for benign indications. By identifying predictors of GBC, surgeons can choose high risk individuals for pre-operative oncologic evaluation and consider better tools for identifying GBC such as intraoperative frozen pathology.

Effective Combination of 3D-DenseNet's Artificial Intelligence Technology and Gallbladder Cancer Diagnosis Model

Gallbladder cancer is the most common malignant tumor in the biliary system. It has the characteristics of low early diagnosis rate, strong invasiveness and high lymphatic metastasis rate. In recent years, with the rapid development of artificial intelligence technology, relevant technologies based on machine learning and deep learning algorithms have been applied to the diagnosis and treatment of malignant tumors, prognosis assessment and medical image processing, bringing revolutionary changes to the diagnosis and treatment mode of malignant tumors. At present, artificial intelligence technology has been preliminarily studied in the early screening and diagnosis of gallbladder cancer, preoperative lymph node status assessment, intraoperative lymph node dissection, surgical treatment and prognosis assessment, showing certain clinical value. In this paper, in order to assist clinical diagnosis of gallbladder cancer, an improved 3D-DenseNet was used to establish an assisted diagnosis model of gallbladder cancer based on enhanced CT images of patients. Firstly, multiple arterial CT images of patients were converted into 3D images, and the regions of interest were cut out using the gallbladder area marked by doctors. Then, the traditional Dense Net network is optimized, the Dropout mechanism and Soft max loss function are improved, and the cross-entropy function is replaced by Focal loss in the output part for imbalance correction, so as to establish the auxiliary diagnosis model of gallbladder cancer.

Рак желчного пузыря: заболеваемость, факторы риска, диагностика

Aim. To analyze current data on the incidence, risk factors, diagnostic methods and prevention of gallbladder cancer (GBC). Key points. GBC is a malignant tumor arising from the epithelium of the gallbladder, characterized by local and vascular invasion, extensive regional lymphogenous and hematogenous metastasis. GBC is the most common malignant tumor of the biliary tract, characterized by high malignancy and low 5-year survival rate. In international recommendations, gastrointestinal tract is considered as a natural stage of the course of biliary pathology: dyskinesia — cholecystitis — cholelithiasis — GBC. Globally, the incidence of GBC varies significantly among different geographic regions, reaching 27 per 100,000 population in Chile. In Russia, according to the Federal State Statistics Service, the incidence of GBC in 2019 was 1.4 per 100 thousand among men, and 2.5 per 100 thousand among women. The incidence of GBC is associated with female gender and increasing age. In the pathogenesis of gallstones, decisive importance is attached to long-term inflammatory changes in the epithelium due to mechanical trauma to the mucous membrane of the gallbladder by stones and a probable increase in the proportion of secondary bile acids in the bile. In the diagnosis of GBC, the recommendations of the Japanese Society of Hepato-Biliary-Pancreatic Surgery, in the first step, particular importance is attached to ultrasound examination of the abdominal organs and biochemical blood test. For a more detailed study, computed tomography, magnetic resonance imaging, magnetic resonance cholangiopancreatography, endosonography, retrograde cholangiopancreatography, oral cholangioscopy and positron emission tomography are useful. Gallstone disease is one of the five most significant risk factors. The remaining 4 leading risk factors for GBC — ethnicity, genetic predisposition, lifestyle factors (excess weight) and biliary tract infections — are common risk factors for patients with cholelithiasis. The risk of developing GBC increases significantly in patients with stones larger than 2 cm and with the duration of the pathology for more than 5 years. Another significant risk factor for GBC is patients with gallbladder polyps, therefore the article presents the main recommendations of European associations for the management of patients with gallbladder polyps. Conclusion. GBC is currently considered as a possible and natural stage in the course of cholelithiasis. The risk of developing GBC increases significantly in patients with cholelithiasis and gallbladder polyps. Considering the above, diagnosis of possible complications in elderly patients with cholecystitis and gallstone disease should include a thorough clinical, laboratory and instrumental examination. Preventive measures for people with risk factors for GBC should include optimizing diet, weight loss, and, if possible, expanding the physical activity regime. Taking ursodeoxycholic acid preparations helps reduce the content of hydrophobic bile acids in bile and reduces the likelihood of complications of biliary pathology. Keywords: gallbladder cancer, cholelithiasis, gallbladder polyps, diagnosis, morbidity.

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

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

Different Tumour Marker Kinetics as Prognosticators in Patients with Adenocarcinoma of Gall Bladder Undergoing Chemotherapy: A Cohort Study

Introduction: Gallbladder Cancer (GBC) is the most common malignancy of the biliary tract worldwide. Patients do not have specific symptoms, and therefore, GBC is usually diagnosed at an advanced stage. Carbohydrate Antigen (CA)-242, CA 19-9, and Cancer Antigen 125 (CA-125) have been found to be effective in the diagnosis and prognosis of GBC. Aim: To determine the significance of tumour markers as prognosticators in adenocarcinoma of GBC with chemotherapy. Materials and Methods: The present cohort study was conducted in the Department of Biochemistry, Murshidabad Medical College and Hospital, Baharampur, West Bengal, India, between December 2021 and November 2022. Thirty patients with pathologically confirmed adenocarcinoma of the gallbladder who were treated with gemcitabine-based chemotherapy were included in the study. Differences in serum CA-125 and CA 19-9 levels before and after chemotherapy (KINETICS) were measured along with haemoglobin, serum urea, creatinine, total bilirubin and Neutrophil-Lymphocyte Ratio (NLR). Receiver Operating Characteristic (ROC) curve analysis and Kaplan-Meier analyses of CA-125, CA 19-9, and combined changes were performed to assess survival rates and their statistical relevance as prognosticators in correlation with disease progression. Results: The mean±Standard Deviation (SD) age was 52.4±5.275 years. A total of 25 (83.3%) patients were females. The associations of CA 19-9 change with other baseline variables were analysed, and there were significant associations with baseline Carbohydrate Antigen (CA19-9) levels (p-value=0.003) and metastatic changes (p-value &lt;0.001). Patients with decreased tumour markers had significantly better Progression- Free Survival (PFS) than patients with increased tumour markers. The pre- and post-chemotherapy CA 19-9 ratio had the highest area-under-the-curve values (AUC 0.910) for predicting 6-month PFS, whereas for predicting metastatic changes, the combined pre- and post-chemotherapy marker ratio had the highest AUC 0.842. In the multivariate analysis, CA 19-9 ≥100 U/mL at diagnosis (p-value &lt;0.001) and NLRchange ≥1.0 (p-value=0.003) were independent prognosticators of PFS, with hazard ratios of 1.007 (p-value &lt;0.001) and 15.4 (p-value=0.003), respectively. Conclusion: CA 19-9 kinetics proved to be a reliable prognosticator of metastatic changes in patients with adenocarcinoma of the gallbladder undergoing chemotherapy. The significant decline in tumour markers that were seen throughout the follow-up phase emphasises how important it is to use these markers as primary indicators of treatment response. To validate the present study findings, larger-scale studies involving a longer follow-up period and a greater number of patients are needed.

Deep-learning enabled ultrasound based detection of gallbladder cancer in northern India: a prospective diagnostic study

Gallbladder cancer (GBC) is highly aggressive. Diagnosis of GBC is challenging as benign gallbladder lesions can have similar imaging features. We aim to develop and validate a deep learning (DL) model for the automatic detection of GBC at abdominal ultrasound (US) and compare its diagnostic performance with that of radiologists. In this prospective study, a multiscale, second-order pooling-based DL classifier model was trained (training and validation cohorts) using the US data of patients with gallbladder lesions acquired between August 2019 and June 2021at the Postgraduate Institute of Medical Education and research, a tertiary care hospital in North India. The performance of the DL model to detect GBC was evaluated in a temporally independent test cohort (July 2021-September 2022) and was compared with that of two radiologists. The study included 233 patients in the training set (mean age, 48 ± (2SD) 23 years; 142 women), 59 patients in the validation set (mean age, 51.4±19.2 years; 38 women), and 273 patients in the test set (mean age, 50.4±22.1 years; 177 women). In the test set, the DL model had sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of 92.3% (95% CI, 88.1-95.6), 74.4% (95% CI, 65.3-79.9), and 0.887 (95% CI, 0.844-0.930), respectively for detecting GBC which was comparable to both the radiologists. The DL-based approach showed high sensitivity (89.8-93%) and AUC (0.810-0.890) for detecting GBC in the presence of stones, contracted gallbladders, lesion size <10mm, and neck lesions, which was comparable to both the radiologists (p=0.052-0.738 for sensitivity and p=0.061-0.745 for AUC). The sensitivity for DL-based detection of mural thickening type of GBC was significantly greater than one of the radiologists (87.8% vs. 72.8%, p=0.012), despite a reduced specificity. The DL-based approach demonstrated diagnostic performance comparable to experienced radiologists in detecting GBC using US. However, multicentre studies are warranted to explore the potential of DL-based diagnosis of GBC fully. None.

ZFP64 Promotes Gallbladder Cancer Progression through Recruiting HDAC1 to Activate NOTCH1 Signaling Pathway.

The lack of meaningful and effective early-stage markers remains the major challenge in the diagnosis of gallbladder cancer (GBC) and a huge barrier to timely treatment. Zinc finger protein 64 (ZFP64), a member of the zinc finger protein family, is considered to be a promising predictor in multiple tumors, but its potential effect in GBC still remains unclear. Here, we identified that ZFP64 was a vital regulatory protein in GBC. We found that ZFP64 expressed higher in GBC gallbladder carcinoma tissues than in normal tissues and was positively correlated with poor prognosis. Furthermore, ZFP64 was responsible for the migration, invasion, proliferation, anti-apoptosis, and epithelial mesenchymal transition (EMT) of GBC cells in vitro and in vivo. Mechanistically, through Co-IP assay, we confirmed that ZFP64 recruits HDAC1 localized to the promoter region of NUMB for deacetylation and therefore inhibits NUMB expression. The downregulation of NUMB enhanced the activation of the Notch1 signaling pathway, which is indispensable for the GBC-promotion effect of ZFP64 on GBC. In conclusion, ZFP64 regulated GBC progression and metastasis through upregulating the Notch1 signaling pathway, and thus ZFP64 is expected to become a new focus for a GBC prognostic marker and targeted therapy.

Non cancer causes of death after gallbladder cancer diagnosis: a population-based analysis

Mortality from non cancer causes in patients with gallbladder cancer (GBC) still unclear. This study evaluated the causes and risk factors of non cancer death during different follow-up periods after GBC diagnosis. Non cancer causes of death for GBC patients diagnosed between 2000 and 2017 in Surveillance, Epidemiology and End Results database were analyzed and standardized mortality rates (SMR) for each non cancer death were calculated. Predictors for non cancer death were identified through multivariate competing risk analysis. A total 11,927 GBC patients were identified for further analysis, 9393 died during follow up. The largest proportion of non cancer deaths occurred > 3 years after diagnosis (39.4%). Most common non cancer cause were cardiovascular disease (43.3%), followed by other cause of death (34.4%) and infectious diseases (8.6%). Compared with US general population, GBC patients has higher risk of death from disease of heart (SMR, 1.58; 95%CI, 1.41–1.75), septicemia (SMR,3.21; 95%CI, 2.27–4.40), diabetes mellitus (SMR,1.97; 95%CI, 1.43–2.63), alone with other causes. Non cancer causes accounted for a significant proportion of deaths during the follow-up period after GBC diagnosis. The risk of non cancer death is higher in GBC patients than in the general population. Our study provides comprehensive assessment of death from non cancer cause in GBC patients, which has important implications for health management in GBC patients.

Billiary Tract Obstruction due to Gallbladder Carcinoma at Prof. Dr. R. D. Kandou General Hospital: Two Case Reports

Abstract: Gallbladder cancer is the fifth most common gastrointestinal malignancy with a high mortality rate. Detection of gallbladder carcinoma in early stages can be difficult, despite improvements in ultrasound and CT-Scan imaging. It is possible to cure gallbladder cancer surgically at an early stage. We reported two cases of gall bladder carcinoma, 65-year-old and 52-year-old females, with the chief complaints of abdominal pain in the right upper quadrant (RUQ) and obstructive jaundice in both cases. The abdominal CT-scans showed circumferentially irregular focal thickening of gallbladder wall, and severe intra and extrahepatic cholestasis. Endoscopic preoperative biliary drainage using biliary stent was performed in one case. Open cholecystectomy with in toto common bile duct resection and portal lymphadenectomy followed by roux en-y hepaticojejunostomy reconstruction were performed for both cases. Both patients are still well with no cancer recurrences over two-year follow-up. The symptoms of gall bladder cancer were non-specific, and commonly included RUQ abdominal pain, weight loss, anorexia, nausea or vomiting, jaundice, and pruritus. Imaging with ultrasound and CT-Scan had improved preoperative diagnosis of gallbladder cancer. Outcomes of patient with incidental finding of gallbladder cancer had better prognosis since it provided the patient to be staged and managed appropriately with resection. In conclusion, early detection of gallbladder cancer results in better surgical outcome and less patient morbidity and mortality which shows its importance. Keywords: gallbladder carcinoma; early-stage detection; common bile duct resection

Label-free surface-enhanced Raman spectroscopy of serum with machine-learning algorithms for gallbladder cancer diagnosis

Gallbladder cancer (GBC) is a rare but frequently fatal biliary tract malignancy that is typically discovered when it is already advanced. In this study, we investigated a novel technique for the quick and non-invasive diagnosis of GBC based on serum surface-enhanced Raman spectroscopy (SERS). SERS spectra of serum from 41 patients with GBC and 72 normal subjects were recorded. Principal component analysis-linear discriminant analysis (PCA-LDA), and PCA-support vector machine (PCA-SVM), Linear SVM and Gaussian radial basis function-SVM (RBF-SVM) algorithms were used to establish the classification models, respectively. When the Linear SVM was used, the overall diagnostic accuracy for classifying the two groups could achieve 97.1%, and when RBF-SVM was used, the diagnostic sensitivity of GBC was 100%. The results demonstrated that SERS combination with a machine learning algorithm is a promising candidate to be one of the diagnostic tools for GBC in the future.