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

Abstract 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.

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Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190725122400 ◽

2020 ◽

Vol 19 (16) ◽

pp. 2019-2033 ◽

Cited By ~ 2

Author(s):

Pratibha Pandey ◽

Mohammad H. Siddiqui ◽

Anu Behari ◽

Vinay K. Kapoor ◽

Kumudesh Mishra ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cell Growth ◽

Gall Bladder ◽

Growth Inhibition ◽

Cell Cycle Arrest ◽

Gall Bladder Cancer ◽

Cell Growth Inhibition ◽

Cycle Arrest ◽

Apoptotic Induction

Background: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. Objective: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. Methods: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. Results: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5μM) in combination with Jab1-siRNA. Conclusion: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of gall bladder cancer.

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Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190206124120 ◽

2019 ◽

Vol 19 (6) ◽

pp. 826-837 ◽

Cited By ~ 3

Author(s):

Pratibha Pandey ◽

Preeti Bajpai ◽

Mohammad H. Siddiqui ◽

Uzma Sayyed ◽

Rohit Tiwari ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Gall Bladder ◽

Cancer Cells ◽

Caspase 3 ◽

Annexin V ◽

Gall Bladder Cancer ◽

Apoptosis Induction ◽

Bladder Cancer Cells ◽

Hoechst Staining

Background:Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.Objective:In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.Methods:In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.Results:Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.Conclusion:Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

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Anatomical segment 4b/5 resection for gall bladder cancer using intraoperative ultrasound

Journal of Visceral Surgery ◽

10.1016/j.jviscsurg.2021.04.003 ◽

2021 ◽

Author(s):

S. Singh ◽

S. Goel ◽

A. Iqbal

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Intraoperative Ultrasound ◽

Gall Bladder Cancer

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Descriptive epidemiology of gall-bladder cancer in Europe

Journal of Cancer Research and Clinical Oncology ◽

10.1007/bf01229532 ◽

1993 ◽

Vol 119 (3) ◽

pp. 165-171 ◽

Cited By ~ 29

Author(s):

Witold Zatonskí ◽

Carlo La Vecchia ◽

Fabio Levi ◽

Eva Negri ◽

Franca Lucchini

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Gall Bladder Cancer ◽

Descriptive Epidemiology

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Role of Combination Chemotherapy with 5-Fluorouracil, Cisplatin and Paclitaxel for Advanced Gall Bladder Cancer

Journal of Cancer Therapy ◽

10.4236/jct.2014.53032 ◽

2014 ◽

Vol 05 (03) ◽

pp. 246-252 ◽

Cited By ~ 1

Author(s):

Mumtaz Ahmad Ansari ◽

Satyendra K. Tiwary ◽

Uday Pratap Shahi ◽

Vijay K. Shukla

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Combination Chemotherapy ◽

Gall Bladder Cancer ◽

Advanced Gall Bladder Cancer

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The role of H. pylori infection in gall bladder cancer: clinicopathological study

Tumor Biology ◽

10.1007/s13277-015-3444-9 ◽

2015 ◽

Vol 36 (9) ◽

pp. 7093-7098 ◽

Cited By ~ 10

Author(s):

Ehsan Hassan Hassan ◽

Shawkat S. Gerges ◽

Kamal A. El-Atrebi ◽

Hala T. El-Bassyouni

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Gall Bladder Cancer ◽

Clinicopathological Study ◽

H Pylori

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Sudden Cardiac Death Due to Coronary Artery Involvement by IgG4-Related Disease: A Rare, Serious Complication of a Rare Disease

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0614-cr ◽

2014 ◽

Vol 138 (6) ◽

pp. 833-836 ◽

Cited By ~ 31

Author(s):

Nimesh R. Patel ◽

Mary L. Anzalone ◽

L. Maximilian Buja ◽

M. Tarek Elghetany

Keyword(s):

Sudden Cardiac Death ◽

Coronary Arteries ◽

Cardiac Death ◽

Plasma Cells ◽

Severe Stenosis ◽

Immunoglobulin G4 ◽

Emergency Center ◽

Related Disease ◽

Igg4 Related Disease ◽

Systemic Disorder

Immunoglobulin G4–related disease (IgG4-RD) is a systemic disorder characterized by multiorgan fibrosis with IgG4-producing plasma cells, increased IgG4 serum concentration, and responsiveness to steroid therapy. Involvement of the pancreas, salivary glands, orbit, aorta, and other sites has been well documented in the literature; however, there have been limited reports of cases involving the coronary arteries. We report the case of a 53-year-old Hispanic man who was brought to the emergency center and diagnosed with sudden cardiac death. Autopsy was subsequently performed, revealing multiorgan involvement by IgG4-RD, including involvement of the coronary arteries. The inflammation and fibrosis, in combination with concomitant atherosclerotic disease, resulted in severe stenosis of the coronary arteries. Two of the coronary arteries were further occluded by thrombosis. These factors led to cardiac hypoperfusion, myocardial infarction and, ultimately, sudden cardiac death. Fatal involvement of the coronary arteries has not been previously reported, raising a new concern for a severe complication of IgG4-RD.

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