[Clinical analysis of the correlation between gallbladder adenomyomatosis and occult pancreaticobiliary reflux].

Objective: To explore the association between gallbladder adenomyomatosis (GA) and occult pancreaticobiliary reflux (OPBR). Methods: A total of 81 patients with GA who underwent cholecystectomy in Shanghai East Hospital from December 2020 to January 2022 were enrolled, including 48 cases of fundal type, 28 cases of segmental type and 5 cases of diffuse type. Patient's intraoperative bile was coltected and tested for amylase. According to gallbladder bile amylase level, patients were divided into OPBR group (bile amylase>110 U/L) and the control group (bile amylase≤110 U/L). Results: Among 81 patients, 32 were male and 49 were female, and aged (49.1±13.2) years; there were 66 cases in control group, including 27 males and 39 females, and aged (50.0±12.9)years; there were 15 patients in the OPBR group, including 5 males and 10 females, and aged (45.1±14.2) years. In terms of the clinical features of the two groups, there was no significant difference (all P>0.05), except for a significant increase in biliary amylase in the OPBR group compared with the control group (P<0.001). However, the incidence of OPBR was significantly different in the three types of GA, with a lower incidence of OPBR in the fundal type (10.4%, 5/48) than in the segmental type (28.6%, 8/28) and diffuse type (2/5) (P=0.038). In addition, segmental GA was more likely to be combined with gallbladder stones (85.7%, 24/28) than fundal GA (58.3%, 28/48) and diffuse GA (3/5) (P=0.031). Univariate and multivariate logistic regression analyses showed OPBR [OR (95%CI)=3.410 (1.010 to 11.513), P=0.048] and combined gallbladder stones [OR (95%CI)=2.974 (1.011 to 8.745), P=0.048] indepenclently correlated with segmental and diffuse GA. Conclusions: The incidence of OPBR is higher in segmental and diffuse GA, and gallstones and OPBR are independently associated with the occurrence of segmental and diffuse GA. These results suggest that OPBR may be the initiating factor for the occurrence and carcinogenesis of segmental and diffuse GA.

Paraganglia of the Gallbladder: An Underrecognized Incidental Finding and Potential Diagnostic Pitfall.

CONTEXT.­: The identification of paraganglia (PG) in the gallbladder (GB) is infrequent, and easily overlooked as it is not something routinely reported. Occasionally they may be misinterpreted as neoplastic cells, such as low-grade carcinomas, germ cell tumors, or because of their close resemblance to neuroendocrine cells, as low-grade neuroendocrine neoplasms. OBJECTIVE.­: To evaluate the incidence and histological features of PG of the GB in patients that underwent cholecystectomy, and discuss the potential misinterpretation of these benign structures as clusters of neoplastic cells. DESIGN.­: A retrospective study of cholecystectomy specimens performed during a 6-month period were reviewed for identification of PG. Immunohistochemical studies for chromogranin, synaptophysin, S100, and cytokeratin AE1/AE3 were performed in selected cases. RESULTS.­: A total of 365 GBs were reviewed and in 16 cases (4.4%) PG was identified within the subserosal connective tissue of the GB wall or cystic duct adjacent to small capillaries, nerves, and ganglia. They consisted of well-demarcated, lobular structures ranging in size from 0.2 to 0.5 cm, which were predominantly composed of chief cells, with strong expression for chromogranin and synaptophysin and negative CKAE1/AE3, and a minor component of S100-positive sustentacular cells. CONCLUSIONS.­: PG is an uncommon finding with a prevalence of 4.4% in our study. Awareness of their location, histologic features, and immunohistochemical profile may help practicing pathologists to confirm their benign nature, avoid a misdiagnosis of malignancy, and prevent unnecessary diagnostic work-up and treatment.

Surface Modification of Polypropylene Mesh with a Porcine Cholecystic Extracellular Matrix Hydrogel for Mitigating Host Tissue Reaction.

Polypropylene (PP) meshes are widely used for repairing skeletal muscle defects like abdominal hernia despite the chances of undesirable pro-inflammatory tissue reactions that demand revision surgeries in about 45% of cases. Attempts have been made to address the problem by modifying the mesh surface and architecture. These procedures have yielded only incremental improvements in the management of overall postoperative complications, and the search for a clinically viable therapeutic strategy continues. This study deployed a tissue engineering approach for mitigating PP-induced adverse tissue reaction by dip-coating the mesh with a hydrogel formulation of the porcine cholecystic extracellular matrix (CECM). The biomaterial properties of the CECM hydrogel-coated PP (C-PP) meshes were studied and their biocompatibility was evaluated by in vitro and in vivo tests based on ISO standards. Further, the nature of tissue reactions induced by the hydrogel-coated mesh and a commercial PP hernia repair graft was compared in a rat model of partial-thickness abdominal wall defect. Histomorphologically, in comparison with the PP graft-induced tissue reaction, C-PP caused a favorable graft-acceptance response characterized by reduced numbers of pro-inflammatory M1 macrophages and cytotoxic lymphocytes. Remarkably, the differential inflammatory response of the C-PP graft-assisted healing was associated with a fibrotic reaction predominated by deposition of type I collagen rather than type III collagen, as desired during skeletal muscle repair. It was concluded that the CECM hydrogel is a potential biomaterial for surface modification of polymeric biomedical devices.

Feasibility of Voltage-Applied SERS Measurement of Bile Juice as an Effective Analytical Scheme to Enhance Discrimination between Gall Bladder (GB) Polyp and GB Cancer.

A unique surface-enhanced Raman scattering (SERS) measurement scheme to discriminate gall bladder (GB) polyp and GB cancer by analysis of bile juice is proposed. Along with the high sensitivity of SERS, external voltage application during SERS measurement was incorporated to improve sample discriminability. For this purpose, Au nanodendrites were constructed on a screen-printed electrode (referred to as AuND@SPE), and Raman spectra of extracted aqueous phases from raw bile juice samples were acquired using the AuND@SPE at voltages from -300 to 300 mV. The sample spectra resembled that of bilirubin, possessing an open chain tetrapyrrole, showing that bilirubin derivatives in bile juice were mainly responsible for the observed peaks. Discrimination of GB polyp and GB cancer using just the normal SERS spectra was not achieved but became apparent when the spectra were acquired at a voltage of -100 mV. When voltage-applied SERS spectra of bilirubin and urobilinogen (one of bilirubin's derivatives) were examined, a sudden intensity elevation occurring at -100 mV was observed for urobilinogen but not bilirubin. Based on examination of corresponding cyclic voltammograms, the potential-driven strong adsorption of urobilinogen (no faradaic charge transfer) on AuND occurring at -100 mV induced a substantial increase in SERS intensity. It was presumed that the content of urobilinogen in the bile juice of a GB cancer patient would be higher than that of a GB polyp patient, and the contained urobilinogen was sensitively highlighted by applying -100 mV during SERS measurement, allowing clear discrimination of GB cancer against GB polyp.

Pioglitazone prevents cholesterol gallstone formation through the regulation of cholesterol homeostasis in guinea pigs with a lithogenic diet.

BACKGROUND: The cholesterol gallstones diseases (CGD) is highly correlated with metabolic syndrome and type 2 diabetes. The present study aimed to investigate preventive effects of pioglitazone (PIO), an antidiabetic drug, on the CGD in guinea pigs fed with a lithogenic diet (LD). METHODS: The guinea pigs were fed with the LD for 8 weeks. All guinea pigs were grouped as follows: low fat diet; LD; LD plus PIO (4 mg/kg); LD plus PIO (8 mg/kg); LD plus ezetimibe (EZE) (2 mg/kg). Gallbladder stones were observed using microscopy. The profile of biliary composition, and blood glucose, insulin and lipid were analyzed. The liver or ileum was harvested for determinations of hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8), bile salt export pump (BSEP), Niemann-Pick C1-Like 1 (NPC1L1) and acetyl-coenzyme A cholesterol acyltransferase (ACAT2) by Western blot. The gallbladders were used for histological examination. RESULTS: The LD successfully induced gallstone. Both pioglitazone and ezetimibe prevented gallstone formation, as well as hepatic and cholecystic damages. Pioglitazone significantly decreased HMGCR and SREBP2, but increased CYP7A1, ABCG5, ABCG8, and BSEP in the liver. Pioglitazone also remarkably decreased NPC1L1 and ACAT2, while increased ABCG5/8 in the intestine. The beneficial alterations of cholesterol and bile acids in the bile, as well as profile of glucose, insulin and lipid in the blood were found in the guinea pigs treated with pioglitazone. CONCLUSION: Pioglitazone has a noticeable benefit towards the CGD, which is involved in changes of synthesis, transformation, absorption, and transportation of cholesterol.

Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry.

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10-5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10-8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10-7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

Radiation effect on cathodoluminescence and thermoluminescence emission of Ca-rich oxalates from the human body.

The radiation effect of luminescence emission of Ca-rich oxalate biogenic materials (gallbladder and renal calculi) and a commercial standard sample (CaC2 O4 ·H2 O) is reported. The samples were characterized by environmental scanning electron microscopy, energy dispersive X-ray spectroscopy, thermogravimetric and differential thermal analyses, display complex cathodoluminescence (CL) and thermoluminescence (TL) glow emissions. CL spectra (in the UV-infrared range) displayed non-well defined peaks, and exhibited emission at: (i) higher energies (300-490 nm) mainly associated with non-bridging oxygen hole centers, oxygen-deficient centers and peroxy intrinsic defects, regardless of the sample; and (ii) higher, narrow and sharp wavebands, in the red region, probably induced by the presence of traces of Sm3+ (4 G5/2 →6 H9/2 transition) and/or Tb3+ (5 D4 →7 F3 transition) only for mineral-like materials in the human body. The UV-blue TL emission showed low-intensity maxima in which it was possible to distinguish at least four groups of components in each sample.

Differential proteomics analysis of bile between gangrenous cholecystitis and chronic cholecystitis.

To establish human biliary protein expression profiles of gangrenous cholecystitis, chronic cholecystitis, and to discover differently expressed proteins for gangrenous cholecystitis by comparative proteomics, we gathered human gallbladder bile samples from gangrenous cholecystitis and chronic cholecystitis patients, respectively After removing the bile salts and lipid peptide fragments were identified by the iTRAQ-coupled LC-MS/MS technology,then identified in SwissProt with Mascot software. A total of 2251 proteins from chronic cholecystitis patients and 2180 proteins from gangrenous cholecystitis patients were identified. A total of 575 differential proteins were found between gangrenous cholecystitis and chronic cholecystitis, 159 proteins were over-expressed and 416 proteins were under-expressed in gangrenous cholecystitis. By bio-informatics analysis, in gangrenous cholecystitis, cell death, necrosis,immune response of neutrophils, apoptosis and degranulation of cells were activated; while cell survival, fatty acid metabolism, transport of molecular and proliferation of cells were inhibited, which might reflect the de-compensatory phase. Pathway analysis showed acute phase proteins were changed, indicating the role of the inflammatory response in the pathogenesis of gangrenous cholecystitis. Six acute phase proteins were found up-regulated,implying a close linkage to gangrenous gallbladder. Our study could be applicable in the biomarker discovery of gangrenous cholecystitis.

Cross-Linked Cholecyst-Derived Extracellular Matrix for Abdominal Wall Repair.

Abdominal wall repair frequently utilizes either nondegradable or biodegradable meshes, which are found to stimulate undesirable biological tissue responses or which possess suboptimal degradation rate. In this study, a biologic mesh prototype made from carbodiimide cross-linked cholecyst-derived extracellular matrix (EDCxCEM) was compared with small intestinal submucosa (Surgisis®), cross-linked bovine pericardium (Peri-Guard®), and polypropylene (Prolene®) meshes in an in vivo rabbit model. The macroscopic appearance and stereological parameters of the meshes were evaluated. Tailoring the degradation of the EDCxCEM mesh prevents untimely degradation, while allowing cellular infiltration and mesh remodeling to take place in a slower but predictable manner. The results suggest that the cross-linked biodegradable cholecyst-derived biologic mesh results in no seroma formation, low adhesion, and moderate stretching of the mesh. In contrast to Surgisis, Peri-Guard, and Prolene meshes, the EDCxCEM mesh showed a statistically significant increase in the volume fraction (Vv) of collagen (from 34% to 52.1%) in the central fibrous tissue region at both day 28 and 56. The statistically high length density (Lv), of blood vessels for the EDCxCEM mesh at 28 days was reflected also by the higher cellular activity (high Vv of fibroblast and moderate Vv of nuclei) indicating remodeling of this region in the vicinity of a slowly degrading EDCxCEM mesh. The lack of mesh area stretching/shrinkage in the EDCxCEM mesh showed that the remodeled tissue was adequate to prevent hernia formation. The stereo-histological assays suggest that the EDCxCEM delayed degradation profile supports host wound healing processes including collagen formation, cellular infiltration, and angiogenesis. The use of cross-linked CEM for abdominal wall repair is promising.

Asbestos fibre burden in gallbladder: A case study.

The methods conventionally used to determine the burden of asbestos fibres inhaled/incorporated in lung require chemical digestion of the biological matrix before counting/characterising the inorganic fibrous phases under scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS). Asbestos fibres can also be present in extra-pulmonary organs, and we set out to quantify the fibres in gallbladder. Although the standardised procedure requires approximately 5 × 10-1 g of wet tissue, this amount of tissue is not always available. We applied the procedure on about 9 × 10-4 g of gallbladder from a patient with known environmental and workplace exposure to asbestos. The patient died of malignant pleural mesothelioma and was also affected by severe bile-tract problems. The traditional procedure of digesting tissue samples in NaClO and filtering the resulting suspension was carried out. The filter was then examined under SEM/EDS using two methods 1. following the standardised procedure to assess the fibre burden in lung by investigating only 2 mm2 of the filter (660 microscopic fields), and 2. analysing all the microscopic fields in one-quarter of the filter (about 82 mm2). In parallel, histological sections (prepared in the usual way for medical diagnosis) were analysed without digestion or manipulation of the sample using variable pressure SEM/EDS. The fibre counts obtained using the two methods were of the same order of magnitude, i.e., ∼105 fibres/g of wet tissue. We showed that the counting of fibres in human tissue may be successfully carried out even when a limited amount of tissue is available. We also found that, when exposure to asbestos is considerable, the number of asbestos fibres accumulating in the gallbladder may be significant.

Crocodiles and alligators: Antiamoebic and antitumor compounds of crocodiles.

Crocodiles exist in unsanitary environments, feed on rotten meat, are often exposed to heavy metals such as arsenic, cadmium, cobalt, chromium, mercury, nickel, lead, selenium, tolerate high levels of radiation, and are amid the very few species to survive the catastrophic Cretaceous-Tertiary extinction event, nonetheless they can live for up to a 100 years. Moreover, as they live in unhygienic conditions, they regularly come across pathogens. Logically, we postulate that crocodiles possess mechanisms to defend themselves from noxious agents as well as protecting themselves from pathogens. To test this hypothesis, various organ lysates and serum of Crocodylus palustris were prepared. Amoebicidal assays were performed using Acanthamoeba castellanii belonging to the T4 genotype. Cytotoxicity assays were performed using Prostate cancer cells culture by measuring lactate dehydrogenase release as a marker for cell death. Growth inhibition assays were performed to determine the growth inhibitory effects of various organ lysates. Serum and heart lysates of Crocodylus palustris exhibited powerful anti-tumor activity exhibiting more than 70% Prostate cancer cell death (P < 0.05). Additionally, lysates from gall bladder and bile also showed significant host cell cytotoxicity, however intestine, lungs and brain showed partial cytotoxicity. Both sera and heart lysates of Crocodylus palustris abolished Prostate cells growth. Moreover, serum completely abolished A. castellanii viability. For the first time, these findings showed that the organ lysates of Crocodylus palustris exhibit potent anti-amoebic and anti-tumor activity. The discovery of antimicrobial and antitumor activity in crocodile will stimulate research in finding therapeutic molecules from unusual sources, and has potential for the development of novel antitumor/antimicrobial compound(s) that may also overcome drug resistance. Nevertheless, rigorous research in the next few years will be necessary to realize these expectations.

Retrospective analysis of canine gallbladder contents in biliary sludge and gallbladder mucoceles.

The pathophysiology of canine gallbladder diseases, including biliary sludge, gallbladder mucoceles and gallstones, is poorly understood. This study aimed to evaluate the component of gallbladder contents and bacterial infection of the gallbladder in order to elucidate the pathophysiology of biliary sludge and gallbladder mucoceles. A total of 43 samples of canine gallbladder contents (biliary sludge, 21 and gallbladder mucoceles, 22) were subjected to component analysis by infrared spectroscopy, and the resultant infrared spectra were compared with that of swine mucin. Of the 43 samples, 41 were also evaluated by aerobic and anaerobic bacterial culture. The contents of 20 (95.2%) biliary sludge and 22 (100%) gallbladder mucocele samples exhibited similar infrared spectra as swine mucin. Although biliary sludge and gallbladder mucocele contents exhibited similar infrared spectra, one sample of biliary sludge (4.8%) was determined to be composed of proteins. The rate of bacterial infection of the gallbladder was 10.0% for biliary sludge and 14.3% for gallbladder mucoceles. Almost all of the identified bacterial species were intestinal flora. These results indicate that the principal components of gallbladder contents in both gallbladder mucoceles and biliary sludge are mucins and that both pathophysiologies exhibit low rates of bacterial infection of the gallbladder. Therefore, it is possible that gallbladder mucoceles and biliary sludge have the same pathophysiology, and, rather than being independent diseases, they could possibly represent a continuous disease. Thus, biliary sludge could be considered as the stage preceding the appearance of gallbladder mucoceles.

Traditional serrated adenomas of the upper digestive tract.

For many years, it was generally accepted that the vast majority of the colorectal carcinomas (CRCs) evolved from conventional adenomas, via the adenoma-carcinoma sequence. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas (TSAs)) have emerged as an alternative pathway of colorectal carcinogenesis. It has been estimated that about 30% of the CRC progress via the serrated pathway. Recently, TSAs were also detected in the upper digestive tract. In this work, we review the literature on TSA in the oesophagus, the stomach, the duodenum, the pancreatic main duct and the gallbladder. The review indicated that 53.4% (n=39) out of the 73 TSA of the upper digestive tract now in record showed a simultaneously growing invasive carcinoma. As a corollary, TSAs of the upper digestive tract are aggressive adenomas that should be radically excised, either endoscopically or surgically, to rule out the possibility of a synchronously growing invasive adenocarcinoma or to prevent cancer progression. The present findings substantiate a TSA pathway of carcinogenesis in the upper digestive tract.

Identification of the anti-oxidant components in a two-step solvent extract of bovine bile lipid: Application of reverse phase HPLC, mass spectrometry and fluorimetric assays.

An ether extract of nine different bacterial metabolites in combination with two solvent extract (ether followed by ethanol) of bile lipids from ox gall bladder is used as an immune stimulator drug. Over the years bile acids are discussed regarding their anti-oxidant and lipid peroxidation properties. Since some of the bile acids are known to be potent antioxidants, presence of similar activity in the solvent extract of ox bile lipid was investigated using TLC and reverse phase HPLC systems. Fractions from HPLC were analyzed with mass spectrometry using electrospray ionization. The presence of twelve different bile acids along with other substances in small proportions including fatty acids, sulfate conjugates and bile pigments were confirmed. The twelve separated peaks had similar retention times as those of tauroursodeoxycholic acid, glycoursodeoxycholic acid, taurocholic acid, glycocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, cholic acid, ursodeoxycholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid. Subsequently, all fractions were tested for their anti-oxidative property on HepG2 cells exposed to H2O2 that served as an oxidative injury model. Four fluorescent dyes H2DCF DA, MitoSOX red, Amplex red and DAF-2 DA were used for estimation of reactive radicals in the HepG2 cells. Among the separated bile acids, tauroursodeoxycholic acid, glycoursodeoxycholic acid and ursodeoxycholic acid prevented the HepG2 cells from H2O2-induced oxidative stress.

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.

BACKGROUND: N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the ß1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments. METHODS: Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA. RESULTS: Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis. CONCLUSIONS: GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.

Guanylin and functional coupling proteins in the hepatobiliary system of rat and guinea pig.

Guanylin, a bioactive intestinal peptide, is involved in the cystic fibrosis transmembrane conductance (CFTR)-regulated electrolyte/water secretion in various epithelia. In the present work we report on the expression and cellular localization of guanylin and its affiliated signaling and effector proteins, including guanylate cyclase C (Gucy2c), Proteinkinase GII (Pkrg2), CFTR and the solute carrier family 4, anion exchanger, member 2 (Slc4a2) in the hepatobiliary system of rat and guinea pig. Localization studies in the liver and the gallbladder revealed that guanylin is located in the secretory epithelial cells of bile ducts of the liver and of the gallbladder, while Gucy2c, Pkrg2, CFTR, and Slc4a2 are confined exclusively to the apical membrane of the same epithelial cells. Based on these findings, we assume that guanylin is synthesized as an intrinsic peptide in epithelial cells of the hepatobiliary system and released luminally into the hepatic and cystic bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.

Expression of ezrin, HGF and c-met and its clinicopathological significance in the benign and malignant lesions of the gallbladder.

BACKGROUND/AIMS: To investigate the expression of ezrin, HGF and c-met in the benign and malignant lesions of the gallbladder. METHODOLOGY: Ezrin, HGF and c-met expression was detected by immunohistochemistry. RESULTS: The positive ezrin, HGF and c-met expression was significantly higher in gallbladder adenocarcinoma than in benign lesions. The benign lesions with positive ezrin, HGF and/or c-met expression showed moderately- or severely-atypical hyperplastic epithelium. The positive expression of ezrin, HGF and c-met was significantly associated with differentiation, tumor mass, lymph node metastasis and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that increased expression of ezrin, HGF and c-met was associated with decreased overall survival. Multivariate Cox regression analysis showed that increased expression of ezrin, HGF or c-met was an independent bad-prognostic predictor in gallbladder adenocarcinoma. CONCLUSIONS: The expression of ezrin, HGF and/or c-met might be closely related to the carcinogenesis, progression, clinical biological behaviors and prognosis of gallbladder adenocarcinoma.

The gallbladder of Uranoscopus scaber L. (teleost perciform fish) is lined by specialized cholecystocytes.

The gallbladder of Uranoscopus exhibits a mucosal surface layer of simple columnar epithelium composed of specialized cholecystocytes. The apices show storage and mucous secretions, typical microvilli, and very apical projections extending deep into the luminal contents. Many organelles and heterogeneous vesicles of diverse size fill the cytoplasm, including neutral mucins, mitochondria, peroxisomes, lysosomal bodies, and lipid-rich deposits with cholesterol inclusions. The fibromuscular layer shows little blood supply and contains scattered lymph-like walls with minute cholesterol inclusions. The remaining muscular, subserosal, and serosal or adventitial layers of this species do not show any histologic differences to those of other vertebrates. It was unexpected to find cholesterol inclusions in the fatty deposits of the cholecystocytes, similar to those noted in human cholesterolosis and in some forms of hypercholesterolemia, in this teleostean. In addition, aggregations of mitochondria and anomalous mitochondrial morphologies were found that resemble oncocytoma-like changes.

Hepcidin is an antibacterial, stress-inducible peptide of the biliary system.

BACKGROUND/AIMS: Hepcidin (gene name HAMP), an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections. METHODS: Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and -blotting, while prohepcidin levels in human bile were determined by ELISA. RESULTS: Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC) patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03). In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively). In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p<0.05). CONCLUSION: Hepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections.