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Title: The role of the interstitial cells of Cajal and the bile lithogenicity in the pathogenesis of gallstone disease

Abstract:

Cholecystectomy is one of the most frequent abdominal operations, and it is general necessitated by the presence of gallstones. Cholesterol stones appear to be the most common type. Cholesterol supersaturation and gallbladder hypomotility are important pathogenetic factors for cholesterol stones. In recent years understanding of the gastrointestinal smooth muscle physiology has changed due to multiple research concerning the interstitial cells of Cajal. ICCs are present in many organs, but their morphology and function have been recognized and described best within the gastrointestinal tract. On the basis of published observations, the following aims of this study were established: 1. Assessment of the quantity and distribution of interstitial cells of Cajal in the gallbladder muscle wall of patients with cholelithiasis, and in the control group. 2. Determination of the relationship between the number of interstitial cells of Cajal and cholesterol saturation index, bile lipid composition in both groups of patients. A total of 55 patients, operated in the 1st Department of the General Surgery, Jagiellonian University Medical College in 2010, were enrolled in the study. 30 consecutive patients operated for symptomatic gallstone disease were enrolled into the study group. Elective laparoscopic cholecystectomies were carried out in the study group. The co ; ntrol group consisted of 25 consecutive patients operated electively for pancreatic head tumours, with no pre- and intraoperative signs of cholelithiasis and jaundice. The study has been conducted, with the Jagiellonian University Bioethical Commitee's consent, according to the Declaration of Helsinki guidelines. The primary aim of this study was to identify and determine the quantity and localization of the interstitial cells of Cajal within the gallbladder muscle wall in patients suffering from cholelithiasis, and in patients from the control group. The second goal was to measure concentrations of the lipid constituents in bile taken from patients in both groups i.e. cholesterol, phospholipids and bile acids. Identification of ICCs within the transverse sections of the gallbladder wall, was performed by means of the double immunofluorescence technique using anti c-kit and anti tryptase antibodies to better distinguish ICCs from mast cells. Assessment of the quantity and distribution of the ICC in the gallbladder was carried out using immunofluorescence microscopy conjoined with an image analysis system (ProgRes Capture Pro v.2.8, ProgRes C12Plus camera (Jenoptik)). Gallbladder bile samples were taken intraoperatively to be subsequently analyzed for cholesterol, phospholipid, as well as, total and individual bile acid concentrations. Cholesterol and ; phospholipid levels were measured by means of enzymatic colorimetric tests. Individual bile acids were measured using high performance liquid chromatography after prior extraction. Total bile acid concentration was obtained by summing up the individual bile acid concentrations. On the basis of individual lipid concentrations in bile, the cholesterol saturation index was calculated for each bile sample, using Carey tables. Regarding the quantitative analysis, the ICCs were qualified as: c-kit-immunopositive and tryptaseimmunonegative concurrently and posing nucleus (to eliminate other non-cellular structures). Interstitial cells of Cajal had a fusiform shape predominantly, 40 - 60 um length, and in some preparations its branches were also visualized. ICCs were seen in the whole area of the gallbladder including its fundus, body and neck. These cells were identified almost exclusively within the gallbladder muscle wall and were oriented parallel to the smooth muscle cells. The following subpopulations of the ICCs were spotted: ICC-IM (ang. intramuscular ICC) localized between smooth muscle fibres forming one muscle bundle and ICC-IB (ang. interbundle ICC) localized within connective tissue separating smooth muscle bundles. Interstitial cells of Cajal typically appeared singly, sometimes in small clusters consisting of 2-3 cells, but they did not form a gl ; obal network. No differences in shape and morphology of interstitial cells of Cajal were found between the study and control groups. The number of interstitial cells of Cajal was statistically significantly lower in patients in the study group as compared to the control group. Statistically significantly higher lithogenic index was also observed in the study group. The study revealed statistically significantly lower mean concentrations of glicocholic and taurocholic acids in the gallbladder bile, as compared to the control group. In summary, the number of interstitial cells of Cajal is diminished in the gallbladder of patients with cholelithiasis and there is a negative correlation between the number of ICCs and lithogenic index of bile. Taking into consideration the role of interstitial cells of Cajal in the regulation of gastrointestinal and extrahepatic bile ducts motility, it appears that a reduction of their number is an important etiopathogenetic factor of gallstone disease. Progress concerning the role of interstitial cells of Cajal in the human gallbladder may contribute to the advancement of new treatment options of disturbances of the gallbladder motility underlying cholelithiasis.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu trawiennego

Degree grantor:

Wydział Lekarski

Promoter:

Matyja, Andrzej

Date issued:

2011

Identifier:

oai:dl.cm-uj.krakow.pl:4748

Call number:

ZB-115209

Language:

pol

Access rights:

tylko w bibliotece

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Last modified:

Mar 17, 2023

In our library since:

Jun 22, 2022

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ZB-115209 Mar 17, 2023
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