MRNA Profiling Involved in Triggering of STAT1 with Regulatory Involvement of IRF7, PTPRF, and miR-145p in Patients Suffering from Gall Bladder Carcinoma

Background. Gall Bladder Cancer (GBC) is a type of extremely malignant tumor, which has high incidences of mortality. There is rare information about its mechanisms of invasion and gene expression regulations. microRNA-155 (miR-155) has mostly been reported to be over expressed in cases of solid tumors and hematopoietic malignancies. In this study, we have investigated the role and clinical significance of miR-155 in a Chinese population suffering from GBC and compared the results with nonneoplastic inflammation. Methods. Tissue specimens were collected on 50 patients of Gall Bladder Carcinoma and 10 patients suffering from nonneoplastic inflammation who have undergone surgeries at the Department of Pathology, Renji Hospital, Shanghai, from January 2019 to January 2020. We performed profiling of miR-155 expression in both nonneoplastic and gall bladder carcinoma tissues by QRT-PCR. Results. Expression levels of miR-155 were found to be extremely high in GBC patients in comparison to the nonneoplastic tissues ( ∗ P < 0.05 ), as high miRNA is correlated with TNM stages. Further results noted were that miR-145-5p expressed genes mimic the gene expression of STAT1, a downregulation of IRF7 was noted in the GBC, and an activation of STAT1 was significantly noted in carcinoma cells of the gallbladder. Downregulation of PTPRF was also noted during the expression of miR-145. Conclusions. As downregulation of IRF7 is linked with low rates of survival, it was found that gall bladder carcinoma patients may face high mortality. The STAT-1 expression of unregulated in GBC patients was also noted.

Reiterating the Emergence of Noncoding RNAs as Regulators of the Critical Hallmarks of Gall Bladder Cancer

Gall bladder cancer (GBC) is a rare and one of the most aggressive types of malignancies, often associated with a poor prognosis and survival. It is a highly metastatic cancer and is often not diagnosed at the initial stages, which contributes to a poor survival rate of patients. The poor diagnosis and chemoresistance associated with the disease limit the scope of the currently available surgical and nonsurgical treatment modalities. Thus, there is a need to explore novel therapeutic targets and biomarkers that will help relieve the severity of the disease and lead to advanced therapeutic strategies. Accumulating evidence has correlated the atypical expression of various noncoding RNAs (ncRNAs), including circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNA) with the increased cell proliferation, epithelial–mesenchymal transition (EMT), invasion, migration, metastasis, chemoresistance, and decreased apoptosis in GBC. Numerous reports have indicated that the dysregulated expression of ncRNAs is associated with poor prognosis and lower disease-free and overall survival in GBC patients. These reports suggest that ncRNAs might be considered novel diagnostic and prognostic markers for the management of GBC. The present review recapitulates the association of various ncRNAs in the initiation and progression of GBC and the development of novel therapeutic strategies by exploring their functional and regulatory role.

Immunoglobulin (IgG4) Sclerosing Cholecystitis- Camouflaging Gall Bladder Cancer- A Case Report and Review of Literature

Background: IgG4 related disease is a rare systemic disorder having an underlying autoimmune cause. These disorders mainly affects pancreatico biliary tree i.e. pancreas, gall bladder and biliary tree (extrahepatic as well intrahepatic),but can also affect other part of body.Majority of disorders involving biliary tree are associated with autoimmune pancreatitis component.These disorders are difficult to diagnose clinically as they can mimic inflammatory as well malignancy and poses a real diagnostic challenge to manage and treat.Case presentation: 64 years old female known diabetic evaluated for pain in right hypochondrium. Gall bladder cancer was suspected clinically as well on radiologically basis. Patient underwent extended cholecystectomy as it was a resectable disease.Final histopathology revealed immunoglobulin G4 (IgG4) related cholecystitis which was confirmed after immunohistochemistry for CD 138 and IgG4.This disease could be managed conservatively by giving oral steroids ,if it has been picked up preoperatively and major surgical intervention have been avoided. No defined blood test or tumour markers are currently available to diagnose this entity except serum immunoglobulin G4 which is costly and not feasible to get done in all patients especially in developing nations like India.Conclusion: IgG4 cholecystitis is an immune mediated disease whose pathophysiology is still not completely understood. Every clinician should keep possibility of IgG4 cholecystitis in mind whenever any patient with abnormal gall bladder thickening or gall bladder mass is encountered in their clinical practice, as both these entities have completely different options of treatment. We should not rely solely upon clinical and radiological picture.

Retrospective analysis of the efficacy of percutaneous transhepatic biliary drainage in palliation of obstructive jaundice in patients with carcinoma gall bladder: Experience from tertiary care center in Northern India

Background: Percutaneous Transhepatic Biliary Drainage (PTBD) is a minimally invasive procedure to palliate the biliary obstruction caused by unresectable malignancy. Aims and Objective: To analyze the outcome of PTBD in patients of unresectable gall bladder cancer presenting with obstructive jaundice in terms of reduction in serum bilirubin levels, symptomatic improvement, and overall survival (OS) at 4 weeks and 12 weeks following the procedure. Materials and Methods: In this retrospective study, PTBD was attempted on 30 patients diagnosed with inoperable gall bladder cancer. Various patient and procedure-related variables were analyzed and recorded both pre and post-PTBD. Outcome data on OS was collected at 4 weeks and 12 weeks. Results: Technical success was achieved in 29 (99.66%) patients. The mean fall in the serum bilirubin at the 7th post-procedural day was 41.5% after the successful PTBD. The most common complication in our study was cholangitis noted in six (21%) patients. OS at 4 weeks and 12 weeks was 79% and 41%, respectively. Conclusion: Younger age and good performance status favored better survival rate in our study.

Rare case of gall bladder squamous cell carcinoma in pacient with cholelithic illness

The clinical case of the patient with squamous cell carcinoma of gall bladder in a combination with cholelithic illness is described. Presurgical diagnostics of gall bladder cancer is difficult, demands a complex and careful assessment of disease anamnesis, a clinical sings, results of laboratory and tool analysis. At impossibility to exclude gall bladder cancer in the presence of a cholelithic illness in all cases operative treatment is needed.

DIAGNOSTIC SIGNIFICANCE OF SERUM CA242, CA19.9 AND CEA IN DIAGNOSIS OF GALL BLADDER CANCER

Background: Tremendous progress of imaging technique does not result in early diagnosis of gall bladder cancer. In search of effective, inexpensive and non-invasive tool tumour markers shows promise. Serum CA242, CA19.9 and CEA are evaluated for this purpose. Aim and objective: To evaluate diagnostic signicance of serum CA242, CA19.9 and CEAin gall bladder cancer either alone or in combination. Material and methods: It was an analytical cross sectional study done in Indira Gandhi Institute of medical Sciences. These markers were measured in 70 cases of gall bladder cancer and 70 healthycontrols. Serum CA242 was done by ELISA assay as per instruction given in pack insert (CD diagnostic). Serum CA19.9 and CEA were done by CLIA technique by Assess 2 analyser. Results: Mean value of these tumour marker were increased in gall bladder cancer group (p<0.001). CA19.9 was most sensitive tumourmarker (79.5%). Serum CA 242 was most specic test (83.3%) for diagnosis of gall bladder cancer among the three-tumour marker. On combination of tumour marker sensitivity (87.5%) and specicity (89.5%) were increased. In ROC curve analysis area under curve (AUC) for CA242 was highest. Conclusion: Combination of these tumour markers can be used as screening tool for gall bladder cancer.

A histopathological evaluation of gall bladder cancer with special reference to HER2/neu and E-cadherin in Southern part of Assam

Background/Objective: Gall bladder carcinoma (GBC) is an aggressive malignancy with high mortality and aggressive course, with palliation as the only available option. The signs and symptoms of gall bladder arcinoma are not specific and often present late. Diagnosis is, therefore, often made at advanced stage with poorer outcomes. Identifying biomarkers and cancer specific cellular targets, that will pave the way for novel therapeutic approaches and early diagnosis for gall bladder carcinoma, is urgently needed. Proto-oncogenes (HER-2) and E-Cadherin are commonly deregulated in gallbladder cancer (GBC). This study evaluates the prognostic significance of HER-2 and E-Cadherin in GBC patients in Silchar Medical College.Our main objective was to evaluate frequency of HER-2/neu overexpression in GBC and to seek its correlation, if any with conventional clinicopathological parameters and survival.Methods: A total of 168 cases were received and evaluated for Gall Bladder cancer and control specimens were prospectively collected from 2018-2020. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and E-Cadherin protein expression. The criterion for HER-2 and E-Cadherin positivity was set at 10% and >5% tumor cells showing complete, membranous staining. Clinicopathological correlations were drawn with major clinical outcomes. Results: It was observed that out of 168 cases the male to female ratio is 1:5 with highest number of cases in the age group of 50-59 , i.e., 70 cases with 41.7%. The most common location in this study was fundus with 69% of cases (116 out 0f 168), most commonly presented as biliary colic with 56 number of cases. Grading was also done in 168 cases where most number of cases were moderately differentiated with 86 number of cases with a percentage of 51%. Expression of Her2Neu and E-Cadherin was evaluated where highest number of cases were seen with 1+ score in the IHC expressions of both the markers with 81 and 61 number of cases respectively. Conclusion: The increasing global incidence, late presentation leading to poor prognosis and lack of effective therapy make the management of gall bladderv carcinoma really challenging. Our study shows the abnormal expression of HER-2 and E-Cadherin expression in gall bladder carcinoma patients in Southern Assam and suggests that these two markers can be used for potential tool for early detection of gall bladder carcinoma and also can be used for targeted therapy in gall bladder carcinoma.