Gallbladder Epithelium Research Articles

Helicobacter Pylori and Metaplastic Changes in Chronic Cholecystitis: A Correlation Study

Abstract Introduction: Various types of metaplastic changes, such as gastric metaplasia (foveolar type or antral type) and intestinal metaplasia, are observed in chronic cholecystitis but not in normal mucosa. Helicobacter species can be detected in the bile and gallbladder tissue of patients with benign gallbladder disease. Objective: The present study aimed to observe the correlation between chronic cholecystitis and the presence of Helicobacter pylori as well as the different types of metaplastic changes in gallbladder mucosa. Materials and Methods: This descriptive, observational study was conducted at the Departments of Pathology and Surgery at a tertiary care medical college and hospital from April 2021 to March 2022, using a cross-sectional design. All confirmed cases of chronic cholecystitis, with or without cholelithiasis, were included in the study. Results: Intestinal metaplasia was the most common type of metaplastic change in the gallbladder epithelium in chronic cholecystitis in this region. PAS and Alcian Blue positivity were significantly higher in cases with metaplasia compared to those without metaplasia. H. pylori was detected in 3 cases (1.55%) of chronic cholecystitis in this study population. Conclusion: Mucin histochemistry may help identify early metaplastic changes in gallbladder epithelium. The use of a combination of methods for the detection of H. pylori in gallbladder tissue may increase the detection of positive cases.

Bitter tastants relax the mouse gallbladder smooth muscle independent of signaling through tuft cells and bitter taste receptors

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors.

Morphological changes in the biliary mucosa in pediatric patients with congenital biliary dilatation are more influenced by the duration of amylase exposure than by amylase levels in the gallbladder.

We investigated the relationship between bile amylase (AMY) levels and biliary epithelial changes in pancreaticobiliary maljunction (PBM), a congenital anomaly characterized by pancreaticobiliary reflux due to duct fusion outside the duodenal wall. We enrolled 43 children with congenital biliary dilatation (CBD) of Todani types Ia, Ic, and IVa who underwent surgery at the Hokkaido Medical Center for Child Health and Rehabilitation between November 2007 and June 2023. We defined total AMY exposure in bile as bile AMY levels multiplied by the patient's age (months), representing amount of estimated AMY exposure until surgery. We retrospectively investigated the relationships between bile AMY levels and clinicopathological findings. All patients exhibited hyperplasia in the gallbladder and bile duct epithelium, with dysplasia observed in 13 cases, but no carcinoma. Exposure to bile AMY ≥ 662,400IU/L × months was an independent risk factor for dysplasia. The amount of estimated AMY exposure in bile rather than AMY levels in the bile is an independent risk factor for dysplasia in the biliary mucosa.

Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder.

Mucocele formation in dogs is a unique and enigmatic muco-obstructive disease of the gallbladder caused by the amassment of abnormal mucus that bears striking pathological similarity to cystic fibrosis. We investigated the role of cystic fibrosis transmembrane conductance regulatory protein (CFTR) in the pathogenesis of this disease. The location and frequency of disease-associated variants in the coding region of CFTR were compared using whole genome sequence data from 2,642 dogs representing breeds at low-risk, high-risk, or with confirmed disease. Expression, localization, and ion transport activity of CFTR were quantified in control and mucocele gallbladders by NanoString, Western blotting, immunofluorescence imaging, and studies in Ussing chambers. Our results establish a significant loss of CFTR-dependent anion secretion by mucocele gallbladder mucosa. A significantly lower quantity of CFTR protein was demonstrated relative to E-cadherin in mucocele compared with control gallbladder mucosa. Immunofluorescence identified CFTR along the apical membrane of epithelial cells in control gallbladders but not in mucocele gallbladder epithelium. Decreases in mRNA copy number for CFTR were accompanied by decreases in mRNA for the Cl-/[Formula: see text] exchanger SLC26A3, K+ channels (KCNQ1, KCNN4), and vasoactive intestinal polypeptide receptor (VIPR1), which suggest a driving force for change in secretory function of gallbladder epithelial cells in the pathogenesis of mucocele formation. There were no significant differences in CFTR gene variant frequency, type, or predicted impact comparing low-risk, high-risk, and definitively diagnosed groups of dogs. This study describes a unique, naturally occurring muco-obstructive disease of the canine gallbladder, with uncanny similarity to cystic fibrosis, and driven by the underlying failure of CFTR function.NEW & NOTEWORTHY Cystic fibrosis transmembrane conductance regulatory protein (CFTR) genomic variants and expression of mRNA, protein, and electrogenic anion secretory activity of CFTR were characterized in dog gallbladder. Acquired inhibition of CFTR expression by gallbladder epithelium was identified as underpinning a naturally occurring muco-obstructive disease of the dog gallbladder that bears striking pathological similarity to animal models of cystic fibrosis.

Increased lipogenesis and lipidosis of gallbladder epithelium in dogs with gallbladder mucocele formation.

Gallbladder disease in people is frequently associated with disorders of lipid metabolism and metabolic syndrome. A recently emergent gallbladder disease of dogs, referred to as mucocele formation, is characterized by secretion of abnormal mucus by the gallbladder epithelium and is similarly associated with hyperlipidemia, endocrinopathy, and metabolic dysfunction. The cause of gallbladder mucocele formation in dogs is unknown. A prospective case-controlled study was conducted to gain insight into disease pathogenesis by characterization of plasma lipid abnormalities in 18 dogs with gallbladder mucocele formation and 18 age and breed matched control dogs using direct infusion mass spectrometry for complex plasma lipid analysis. This analysis was complemented by histochemical and ultrastructural examination of gallbladder mucosa from dogs with gallbladder mucocele formation and control dogs for evidence of altered lipid homeostasis of the gallbladder epithelium. Gallbladder mucocele formation in dogs carried a unique lipidomic signature of increased lipogenesis impacting 50% of lipid classes, 36% of esterified fatty acid species, and 11% of complex lipid species. Broad enrichment of complex lipids with palmitoleic acid (16:1) and decreased abundance within complex lipids of presumptive omega-3 fatty acids eicosapentaenoic (20:5) and docosahexaenoic (22:6) was significant. Severe lipidosis of gallbladder epithelium pinpoints the gallbladder as involved causally or consequently in abnormal lipid metabolism. Our study supports a primary increase in lipogenesis in dogs with mucocele formation and abnormal gallbladder lipid metabolism in disease pathogenesis.

Erratum: Ultrasonographic aspects of the gallbladder mucocele in 30 dogs: retrospective study

Gallbladder mucocele is characterized by hyperplasia of the gallbladder epithelium, increased mucus production, accumulation, and densification of the bile content, which can lead to biliary obstruction, necrosis, and rupture of the gallbladder wall. Its finding may be accidental or related to symptoms. A retrospective study (2016-2019) was carried out based on abdominal ultrasound examinations in dogs, correlating aspects of the gallbladder and biliary system in the mucocele with existing comorbidities. Thirty dogs diagnosed with biliary mucocele were evaluated, of which 46.66% had the disease at an early stage, and 53.33% showed a more advanced stage. Of these, 66.66% were related to endocrinopathies and hyperadrenocorticism. Signs of extrahepatic bile duct obstruction and biliary peritonitis were observed in two animals. Due to their potential risk of complications, follow-up ultrasound assessments are indicated in cases that opt for clinical treatment, not excluding the need for surgical intervention.

Ultrasonographic aspects of the gallbladder mucocele in 30 dogs: retrospective study

Gallbladder mucocele is characterized by hyperplasia of the gallbladder epithelium, increased mucus production, accumulation, and densification of the bile content, which can lead to biliary obstruction, necrosis, and rupture of the gallbladder wall. Its finding may be accidental or related to symptoms. A retrospective study (2016-2019) was carried out based on abdominal ultrasound examinations in dogs, correlating aspects of the gallbladder and biliary system in the mucocele with existing comorbidities. Thirty dogs diagnosed with biliary mucocele were evaluated, of which 46.66% had the disease at an early stage, and 53.33% showed a more advanced stage. Of these, 66.66% were related to endocrinopathies and hyperadrenocorticism. Signs of extrahepatic bile duct obstruction and biliary peritonitis were observed in two animals. Due to their potential risk of complications, follow-up ultrasound assessments are indicated in cases that opt for clinical treatment, not excluding the need for surgical intervention.

Comparative Survival Benefits of Surgery and Adjuvant Chemotherapy in Neuroendocrine Carcinoma of the Gallbladder: A Population-Based Study with Insight into Future Personalized Therapeutic Approach.

Neuroendocrine carcinomas of the gallbladder (NECs-GB) are rare tumors, accounting for <0.2% of all neuroendocrine carcinomas of the gastrointestinal tract. They originate from the neuroendocrine cells of the gallbladder epithelium with associated intestinal or gastric metaplasia. The current study is the largest study from the SEER database on NECs-GB that aims to elucidate the demographic, clinical, and pathologic factors influencing the prognosis and comparative survival analysis of different treatment modalities. The data from 176 patients with NECs-GB was abstracted from the Surveillance Epidemiology and End Result (SEER) database (2000-2018). Multivariate analysis, non-parametric survival analysis, and a chi-square test were used to analyze the data. NECs-GB had a higher incidence amongst females (72.7%) and Caucasians (72.7%). Most patients had surgery only (N = 52, 29.5%), (N = 40) 22.7% had chemotherapy only, and (N = 23) 13.1% had chemotherapy with surgery. Only (N = 17) 9.7% had trimodaltiy (surgery, chemotherapy, and radiation therapy), and for (N = 41) 23.3% the status of chemotherapy was unknown, and these cases had neither radiation nor surgery. NECs-GB more frequently affects Caucasian females after the 6th decade of life. The combination of surgery, radiation, and adjuvant chemotherapy was associated with better long-term (5 years) outcomes, while surgery alone was associated with better short-term (<2 years) outcome survival.

Carcinogenic risk in the biliary epithelium of children with congenital biliary dilatation via the DNA damage repair pathway.

Congenital biliary dilatation (CBD) is a high-risk factor for biliary tract cancer (BTC). We previously reported the potential for carcinogenesis in the biliary epithelium of patients with CBD. In this study, we investigated potential carcinogenetic pathways, focusing on the DNA damage repair response, in children with CBD and compared the findings with those in adults. We enrolled 6 children with CBD and 10 adults with CBD without BTC who underwent extrahepatic bile duct resections, plus 4 control patients who underwent pancreaticoduodenectomy for non-biliary cancer. Levels of phosphorylated histone H2AX (γH2AX), MRE11, and Ku-70 in the biliary tract epithelium were evaluated by immunohistochemistry. The levels of γH2AX, MRE11, and Ku-70 were significantly higher in the gallbladder epithelium and bile duct epithelium of both children and adults than in controls. Children and adults with CBD might develop BTC via the DNA damage repair pathway, as evidenced by increased γH2AX, MRE11, and Ku-70 expression.

Gallbladder microbiota in healthy dogs and dogs with mucocele formation.

To date studies have not investigated the culture-independent microbiome of bile from dogs, a species where aseptic collection of bile under ultrasound guidance is somewhat routine. Despite frequent collection of bile for culture-based diagnosis of bacterial cholecystitis, it is unknown whether bile from healthy dogs harbors uncultivable bacteria or a core microbiota. The answer to this question is critical to understanding the pathogenesis of biliary infection and as a baseline to exploration of other biliary diseases in dogs where uncultivable bacteria could play a pathogenic role. A pressing example of such a disease would be gallbladder mucocele formation in dogs. This prevalent and deadly condition is characterized by excessive secretion of abnormal mucus by the gallbladder epithelium that can eventually lead to rupture of the gallbladder or obstruction of bile flow. The cause of mucocele formation is unknown as is whether uncultivable, and therefore unrecognized, bacteria play any systematic role in pathogenesis. In this study we applied next-generation 16S rRNA gene sequencing to identify the culture-negative bacterial community of gallbladder bile from healthy dogs and gallbladder mucus from dogs with mucocele formation. Integral to our study was the use of 2 separate DNA isolations on each sample using different extraction methods and sequencing of negative control samples enabling recognition and curation of contaminating sequences. Microbiota findings were validated by simultaneous culture-based identification, cytological examination of bile, and fluorescence in-situ hybridization (FISH) performed on gallbladder mucosa. Using culture-dependent, cytological, FISH, and 16S rRNA sequencing approaches, results of our study do not support existence of a core microbiome in the bile of healthy dogs or gallbladder mucus from dogs with mucocele formation. Our findings further document how contaminating sequences can significantly contribute to the results of sequencing analysis when performed on samples with low bacterial biomass.

Spirochaetosis of the gallbladder – a case report

Spirochaetosis is an infection caused by Brachyspira which are Gram-negative bacteria. The disease classically affects the large bowel and appendix and has not been previously described in the gallbladder. Spirochaetosis is diagnosed on histology and has a characteristic microscopic appearance. We report a case of spirochaetosis of the gallbladder, found incidentally in a cholecystectomy specimen, in a 65-year-old male with acute-on-chronic cholecystitis and cholelithiasis. The gallbladder epithelium showed the presence of a thick fuzzy brush border, and a Warthin-Starry stain highlighted the presence of spirochaetes.

Clinicopathological And Prognostic Significance Of Immuno-Expression Of Cyclin D1, E-Cadherin, EGFR, HER- 2, Ki67, And P53 In Gall Bladder Cancer And Its Precursor Lesions-A Review

Gallbladder carcinoma (GBC) is an aggressive and common cancer of the biliary tract. It develops on the epithelia of the gallbladder and is has the ability to rapidly metastasize to nearby organs and distant lymph nodes. It also has the shortest median survival time when compared to other biliary tract cancers [1]. As the disease rarely presents a distinct set of clinical symptoms, delayed diagnosis contributes heavily towards the negative prognosis widely associated with the disease [2]. The molecular mechanisms and underlying changes that bring about carcinogenesis of the gallbladder epithelia, though widely studied have not been fully understood. Chronic inflammation [3], dysplasia [4] and adenoma [5] among other factors have been observed to increase the risk of developing GBC among other risk factors. With current treatment options offering only limited curative capacities, identifying and studying biomarkers with potential to speed up prognostics and having clinical applicability has become a priority. These biomarkers, apart from playing an important role in carcinogenesis, need to be specific for GBC and their levels should vary significantly enough to differentiate between malignant and benign conditions. Though several such molecules have been identified and used in diagnostic trials, the availability of disease-specific and highly sensitive markers for GBC is yet a task to be achieved. Isolation of such prognostic markers will help in understanding disease progression [6]. Further, expression levels of these prognostic markers can be used to aid in the determination of the clinical course of action, patient response to therapy and the need for adjuvant therapy [7]. An ideal prognostic marker should be easily quantifiable with high sensitivity, specificity and its levels should significantly vary to be able to differentiate benign conditions from malignancy. A clinically applicable prognostic marker should be able to predict recurrence, survivability and need for adjuvant therapies. Several categories of markers have been studied to date and include tumour markers such as CA125, CA19-9, CEA, inflammatory markers like CRP, tumour suppressors like p53, E-cadherin etc. In this review we hope to explore the future prospects of some of these markers based on available literature.

Problematic issues of the mucous membrane inflammatory changes of the gallbladder and the features of hormonal expression in the development of dysplasia-carcinoma consequence

Gallbladder carcinoma is the most common tumour of the biliary tract. It is relatively rare in Western countries. However, it is widespread in different regions of the world, especially in developing countries. The most effective treatment method for gallbladder carcinoma is radical cholecystectomy. However, unfortunately, only 10-30% of patients are subject to this treatment method, since 70-90% of cases are diagnosed at an advanced stage. The development of gallbladder carcinoma is associated with various environmental and genetic factors, also the presence of chronic inflammation and/or exposure to specific chemicals, heavy metals, and nutritional factors. The exact mechanism of how gallbladder carcinoma develops in the background of cholelithiasis is still not completely clear. During inflammatory lesions of the gallbladder, changes in the proliferation index of the gallbladder epithelium have not been studied yet. In addition to proliferative markers, it has also been shown that the reduction of cell apoptotic activity plays an important role in the pathogenesis of many tumours. However, literature data on the apoptotic activity of gallbladder carcinomas are incomplete and contradictory.

Anion Transport Across Human Gallbladder Organoids and Monolayers.

Fluid and anion secretion are important functions of the biliary tract. It has been established that cAMP regulates Na+ absorption through NHE3. However, mechanisms of gallbladder anion transport are less defined. We created organoids and organoid-derived monolayers from human gallbladder tissue to measure organoid swelling and transepithelial electrophysiology. In our in vitro models, forskolin-stimulation caused organoid swelling and increased transepithelial anion transport. Full organoid swelling required Cl−while changes in short-circuit current were HCO3 −-dependent. Organoids and monolayers from an individual homozygous for the cystic fibrosis-causing ΔF508 CFTR mutation had no apical expression of CFTR and minimal changes in transepithelial current and conductance with forskolin treatment. However, organoid swelling remained intact. Dilution potential studies revealed that forskolin treatment increased the paracellular permeability to anions relative to cations. These data suggest a novel paracellular contribution to forskolin-stimulated fluid transport across the gallbladder epithelium.

Prominent Pseudo-Angiovascular invasion by benign gallbladder epithelium and bile emboli in a patient with delayed cholecystectomy due to COVID-19 positive test

Lymphovascular invasion is a hallmark of malignant neoplasms, however the presence of benign epithelium within vessels has been reported in benign processes, albeit infrequently. The proposed mechanism to explain this phenomenon entails mechanical displacement of benign epithelium into the vascular spaces during surgical manipulation or diagnostic interventions. We report a case of numerous benign epithelial vascular emboli in a cholecystectomy specimen. A 29-year-old male presented with acute calculous cholecystitis. Surgery was delayed for several weeks due to COVID-19 infection. Histologic examination of the gallbladder showed subacute cholecystitis, widespread vascular epithelial emboli with associated fibrin deposition and bile embolism supporting an in vivo process. The epithelial emboli were localized in small veins and arterioles with D2–40−/CD31+/CD34+ endothelium. The displaced epithelium showed benign cytologic features, was negative for p53 expression, and had a Ki-67 labelling index like the benign background mucosa, supporting a benign process. There was no evidence of dysplasia or malignancy in the specimen after thorough sampling. Persistent inflammation, mucosal ulceration, transmural mucosal herniation (Rokitansky-Aschoff sinuses), and protracted surgical manipulation secondary to adhesive disease are favored to be the underlying causes of this unusual histologic finding. Although we presume an uneventful outcome, clinical follow up was recommended. COVID-19 infection likely contributed to this phenomenon by causing a delay in the surgical management.

Magnetic Resonance Diffusion-Weighted Imaging for Detecting Fundal Intracholecystic Papillary Neoplasm inside Rokitansky-Aschoff Sinuses: A Comparison of Two Cases and a Literature Review

Rokitansky-Aschoff sinuses (RAS) are a common imaging finding in gallbladder adenomyomatosis (ADM), often presenting as fundal cystic spaces. Intracholecystic papillary neoplasm (ICPN) is a relatively uncommon pre-invasive tumor of the gallbladder epithelium that rarely involves RAS mucosa. We compare two cases that showed similar fundal cystic spaces resembling RAS, in which Magnetic Resonance Diffusion-Weighted Imaging (MR-DWI) was valuable for detecting (or ruling out) an underlying malignant ICPN. Evidence from the literature overall supports the role of MR-DWI for detecting intracholecystic malignant tissue.

Impact of DNA double-strand breaks on pancreaticobiliary maljunction carcinogenesis

BackgroundPancreaticobiliary maljunction (PBM) is a condition characterized by chronic inflammation due to refluxed pancreatic juice into the biliary tract that is associated with an elevated risk of biliary tract cancer. DNA double-strand breaks (DSBs) are considered the most serious form of DNA damage. DSBs are provoked by inflammatory cell damage and are recognized as an important oncogenic event in several cancers. This study used γ-H2AX, an established marker of DSB formation, to evaluate the impact of DNA damage on carcinogenesis in PBM.MethodsWe investigated γ-H2AX expression immunohistochemically in gallbladder epithelium samples obtained from 71 PBM cases and 19 control cases.ResultsFourteen PBM cases with gallbladder adenocarcinoma were evaluated at non-neoplastic regions. A wide range of nuclear γ-H2AX staining was detected in all PBM and control specimens. γ-H2AX expression was significantly higher in PBM cases versus controls (median γ-H2AX-positive proportion: 14.4 % vs. 4.4 %, p = 0.001). Among the PBM cases, γ-H2AX expression was significantly higher in patients with carcinoma than in those without (median γ-H2AX-positive proportion: 21.4 % vs. 11.0 %, p = 0.031).ConclusionsDSBs occurred significantly more abundantly in the PBM gallbladder mucosa, especially in the context of cancer, indicating an involvement in PBM-related carcinogenesis.

Gallbladder Interleukins in Children with Calculous Cholecystitis.

Calculous cholecystitis connects to inflammation and various complications. It is a common disease in the paediatric population, yet it is still uncertain how inflammation factors are involved in its morphopathogenesis. Twenty calculous cholecystitis surgery tissue samples were obtained from 20 children. As a control, seven unaffected gallbladders were used. Tissues were immunohistochemically stained for IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, and IL-17A, and the slides were inspected by light microscopy. To evaluate statistical differences and correlations between interleukins, Mann–Whitney U and Spearman’s tests were used. Statistically significant difference between patient and control gallbladder epithelium was for IL-1α and IL-17A, but connective tissue—IL-1α, IL-4, IL-6, IL-7, IL-8, and IL-17A positive structures. A strong positive correlation in patients was detected between epithelial IL-1α and IL-1α in connective tissue, epithelial IL-6 and IL-7, IL-6 and IL-17A, IL-7 and IL-10, IL-7 and IL-17A, as well as between IL-6 and IL-7, IL-7 and IL-10 in connective tissue. The increase of IL-1α, IL-4, IL-6, IL-7, IL-8 and IL-17A positive structures suggests their role in the morphopathogenesis of calculous cholecystitis. The correlations between interleukins in epithelium and in connective tissues prove that the epithelial barrier function and inflammatory response in deeper layers are sustained through intercellular signalling pathways.

Identification of Cilia in Different Mouse Tissues.

Cilia are microtubule-based hair-like organelles that extend from the cell surface. However, the existence and distribution of cilia in each organ and tissue at the postnatal stage in vivo remain largely unknown. In this study, we defined cilia distribution and arrangement and measured the ciliary lengths and the percentage of ciliated cells in different organs and tissues in vivo by using cilium dual reporter-expressing transgenic mice. Cilia were identified by the presence of ARL13B with an mCherry+ signal, and the cilium basal body was identified by the presence of Centrin2 with a GFP+ signal. Here, we provide in vivo evidence that chondrocytes and cells throughout bones have cilia. Most importantly, we reveal that: 1. primary cilia are present in hepatocytes; 2. no cilia but many centrioles are distributed on the apical cell surface in the gallbladder, intestine, and thyroid epithelia; 3. cilia on the cerebral cortex are well oriented, pointing to the center of the brain; 4. ARL13B+ inclusion is evident in the thyroid and islets of Langerhans; and 5. approximately 2% of cilia show irregular movement in nucleus pulposus extracellular fluid. This study reveals the existence and distribution of cilia and centrioles in different tissues and organs, and provides new insights for further comprehensive study of ciliary function in these organs and tissues.

Risk of carcinogenesis in the biliary epithelium of children with congenital biliary dilatation through epigenetic and genetic regulation.

Congenital biliary dilatation (CBD), defined as pancreaticobiliary maljunction (PBM) with biliary dilatation, is a high risk factor for biliary tract cancer (BTC). KRAS and p53 mutations reportedly affect this process, but the mechanisms are unclear, as is the likelihood of BTC later in life in children with CBD. We investigated potential carcinogenetic pathways in children with CBD compared with adults. The subjects of this study were nine children with CBD and 13 adults with PBM (10 dilated, 3 non-dilated) without BTC who underwent extrahepatic bile duct resections, as well as four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. We evaluated expressions of Ki-67, KRAS, p53, histone deacetylase (HDAC) and activation-induced cytidine deaminase (AID) in the biliary tract epithelium immunohistochemically. The Ki-67 labeling index (LI) and expressions of KRAS, p53, HDAC, and AID in the gallbladder epithelium were significantly higher or tended to be higher in both the children with CBD and the adults with PBM than in the controls. BTC may develop later in children with CBD and in adults with PBM, via HDAC and AID expression and through epigenetic and genetic regulation.