Correlation of gallstone characteristics with mucosal changes in gall bladder

Department of Pathology, Pt. BD Sharma Post Graduate, Institute of Medical Sciences, Rohtak, India.
Tropical gastroenterology: official journal of the Digestive Diseases Foundation 07/2012; 33(1):39-44.
Source: PubMed


Gallstones are known to produce diverse histopathological changes in the gall bladder. Our aim was to correlate various gallstone characteristics (number, size, weight, volume and morphological type) with the type of mucosal response in gall bladder (inflammation, hyperplasia, metaplasia and carcinoma).
The study was conducted on 330 open cholecystectomy specimens with complete gallstones. The stones were assessed for various parameters i.e. number, size, weight, volume and morphological type. For microscopy, sections were obtained from the fundus, body and neck of the gallbladder. Additional sections were taken from abnormal looking areas.
Out of the 330 cases, 194 (59%) had mixed stones, 84 (25%) combined, 30 (9%) pigment and 22 (7%) had cholesterol stones. Number of stones varied from a single calculus in 131 (39.6%) cases, double in 29 (8.8%) and multiple in the remaining 170 (51.6%) cases. Cholecystitis, hyperplasia, metaplasia and carcinoma were more commonly seen with mixed and multiple stones. The average weight of calculi in cholecystitis was 2.551 gm, in hyperplasia 3.619 gm, metaplasia4.549 gm and 17.96 gm in cases with carcinoma. Similarly, average volume of the stone(s) was 2.664 ml in cholecystitis, 3.742 ml in hyperplasia, 4.532 ml in metaplasia and 19.178 ml in carcinoma. The average calculus size (2.147 cm) was found to be maximum in cases with carcinoma, followed by hyperplasia (1.187 cm), metaplasia (1.145 cm) and cholecystitis (1.136 cm).
As the weight, volume and size of the stone increases the changes in the gall bladder mucosa changes from cholecystitis, hyperplasia, metaplasia, dysplasia, to carcinoma.

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    • "However, the present study is the first to demonstrate that early metaplastic changes in the gallbladder epithelium could be more frequent in patients with micro-lithiasis, posing therefore an important question about the role of preventive cholecystectomy in this group of patients, for instance after incidental detection of micro-lithiasis in abdominal imaging investigations, especially in young patients. Previous studies have reported a positive co-relation between the total amount, weight and size of the gallstones with the presence of concurrent metaplastic and dysplastic lesions of the gallbladder [12]; however, to the best of our knowledge, there are no other data examining this question in a “dichotomous” way. "
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    ABSTRACT: Metaplastic features of the gallbladder epithelium are considered to be the precursors of gallbladder cancer. Considering the possible role of chronic inflammatory changes in the development of these lesions and the rationale for performing an early prophylactic cholecystectomy, we performed a retrospective study to assess the prevalence of gallbladder metaplasia in patients who underwent cholecystectomy due to underlying cholelithiasis. We reviewed the routine histopathology reports of 86 patients with chronic cholecystitis, who underwent elective cholecystectomy, to assess the prevalence of gallbladder metaplasia in the course of chronic cholecystitis. We further attempted to evaluate the existence of any correlations between the presence of the gallbladder metaplasia and the type of lithiasis, as well as the gallbladder wall thickness. The overall prevalence of metaplastic features in the resected specimens was 25.6%. Dysplastic changes were more frequent in gallbladder specimens with concurrent metaplasia. Moreover, in presence of metaplastic changes, we observed an increase of the average gallbladder wall thickness. Finally, metaplastic and dysplastic changes were associated with the presence of micro-lithiasis rather than macro-lithiasis. Gallbladder metaplastic changes appear to be more frequent in cases of micro-lithiasis and seem to be associated with a chronic thickening of the gallbladder wall. Taking into account the usually sub-clinical course of this group of patients, when compared to patients with macro-lithiasis, further studies are needed to evaluate a possible role of prophylactic cholecystectomy in this population to prevent the long term evolution of these early changes to cancerous lesions.
    Journal of Clinical Medicine Research 02/2014; 6(1):26-9. DOI:10.4021/jocmr1689w
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    • "Hyperplastic changes in the epithelium of the gallbladder and bile ducts of the liver were frequently noted in mice harboring gallstones, independent of Salmonella infection. This increased cell proliferation as a result of cholelithiasis has been previously reported [76,77]. However, typically this was seen concurrently with hyalinosis in affected tissues and/or inflammation. "
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    ABSTRACT: Salmonella Typhi asymptomatic chronic carriage represents a challenge for the diagnosis and prevention of typhoid fever in endemic areas. Such carriers are thought to be reservoirs for further spread of the disease. Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. In addition, both gallstones and chronic carriage have been associated with chronic inflammation and the development of gallbladder carcinoma. However, the pathogenic relationship between typhoid carriage and the development of pre-malignant and/or malignant lesions in the hepatopancreatobiliary system as well as the host-pathogen interactions occurring during chronic carriage remains unclear. In this study, we monitored the histopathological features of chronic carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging from mild to severe were present in infected mice regardless of the presence of gallstones. Biliary epithelial hyperplasia was observed more commonly in the gallbladder of mice with gallstones (uninfected or infected). However, pre-malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and exocrine pancreas, respectively, were only associated with chronic Salmonella carriage. This study has implications regarding the role of Salmonella chronic infection and inflammation in the development of pre-malignant lesions in the epithelium of the gallbladder and pancreas that could lead to oncogenesis.
    PLoS ONE 12/2013; 8(12):e84058. DOI:10.1371/journal.pone.0084058 · 3.23 Impact Factor
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    ABSTRACT: Although typhoid fever has been intensively studied, chronic typhoid carriage still represents a problem for the transmission and persistence of the disease in endemic areas. This chronic state is highly associated with the presence of gallstones in the gallbladder of infected carriers upon which Salmonella can form robust biofilms. However, we hypothesize that in addition to gallstones, the gallbladder epithelium aids in the establishment/maintenance of chronic carriage. In this work, we present evidence of the role of the gallbladder epithelium in chronic carriage by a mechanism involving invasion, intracellular persistence and biofilm formation. Salmonella was able to adhere to and invade polarized gallbladder epithelial cells apically in the absence and presence of bile in a SPI-1 dependent manner. Intracellular replication of Salmonella was also evident at 12 and 24 hours post-invasion. A flow-through system revealed that Salmonella is able to adhere to and form extensive bacterial foci on gallbladder epithelial cell as soon as 12 hours post-inoculation. In vivo experiments using a chronic mouse model of typhoid carriage showed invasion and damage of the gallbladder epithelium and lamina propria up to 2 months after Salmonella infection with an abundant presence of macrophages, a relative absence of neutrophils, and extrusion of infected epithelial cells. Additionally, micro-colonies of Salmonella cells were evident on the surface of the mouse gallbladder epithelia up to 21 days post-infection. These data reveal a second potential mechanism, intracellular persistence and/or bacterial aggregation in/on the gallbladder epithelium with luminal cell extrusion, for Salmonella maintenance in the gallbladder.
    Infection and immunity 06/2013; 81(8). DOI:10.1128/IAI.00258-13 · 3.73 Impact Factor
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