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Keywords = gallbladder dysplasia

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14 pages, 257 KiB  
Review
Environmental and Metabolic Risk Factors Linked to Gallbladder Dysplasia
by Andrei Bojan, Catalin Pricop, Manuela Ciocoiu, Maria Cristina Vladeanu, Iris Bararu Bojan, Oana Viola Badulescu, Minerva Codruta Badescu, Carmen Elena Plesoianu, Dan Iliescu Halitchi and Liliana Georgeta Foia
Metabolites 2024, 14(5), 273; https://doi.org/10.3390/metabo14050273 - 8 May 2024
Cited by 1 | Viewed by 1746
Abstract
Gallbladder disorders encompass a spectrum from congenital anomalies to inflammatory and neoplastic conditions, frequently requiring surgical intervention. Epithelial abnormalities like adenoma and metaplasia have the potential to progress to carcinoma, emphasizing the importance of histopathological assessment for early detection of malignancy. Gallbladder cancer [...] Read more.
Gallbladder disorders encompass a spectrum from congenital anomalies to inflammatory and neoplastic conditions, frequently requiring surgical intervention. Epithelial abnormalities like adenoma and metaplasia have the potential to progress to carcinoma, emphasizing the importance of histopathological assessment for early detection of malignancy. Gallbladder cancer (GBC) may be incidentally discovered during cholecystectomy for presumed benign conditions, underscoring the need for a thorough examination. However, the lack of clarity regarding the molecular mechanisms of GBC has impeded diagnostic and therapeutic advancements. Timely detection is crucial due to GBC’s aggressive nature and poor prognosis. Chronic inflammation plays a central role in carcinogenesis, causing DNA damage and oncogenic alterations due to persistent insults. Inflammatory cytokines and microRNAs are among the various mediators contributing to this process. Gallbladder calcifications, particularly stippled ones, may signal malignancy and warrant preemptive removal. Molecular pathways involving mutations in oncogenes and tumor suppressor genes drive GBC pathogenesis, with proposed sequences such as gallstone-induced inflammation leading to carcinoma formation. Understanding these mechanisms, alongside evaluating mucin characteristics and gene mutations, can deepen comprehension of GBC’s pathophysiology. This, in turn, facilitates the identification of high-risk individuals and the development of improved treatment strategies, ultimately enhancing patient outcomes. Thus, in this review, our aim has been to underscore the primary mechanisms underlying the development of gallbladder dysplasia and neoplasia. Full article
(This article belongs to the Special Issue New Biomarkers for Diagnostics in Metabolic Diseases)
13 pages, 7280 KiB  
Review
Gallbladder Pancreatic Heterotopia—The Importance of Diagnostic Imaging in Managing Intraoperative Findings
by Crenguţa Sorina Şerboiu, Cătălin Aliuș, Adrian Dumitru, Dana Țăpoi, Mariana Costache, Adriana Elena Nica, Mihăilescu Alexandra-Ana, Iulian Antoniac and Sebastian Grădinaru
Medicina 2023, 59(8), 1407; https://doi.org/10.3390/medicina59081407 - 1 Aug 2023
Cited by 8 | Viewed by 2847
Abstract
Pancreatic heterotopy is a rare entity defined as the presence of abnormally located pancreatic tissue without any anatomical or vascular connection to the normal pancreas. Heterotopic pancreatic tissue can be found in various regions of the digestive system, such as the stomach, duodenum, [...] Read more.
Pancreatic heterotopy is a rare entity defined as the presence of abnormally located pancreatic tissue without any anatomical or vascular connection to the normal pancreas. Heterotopic pancreatic tissue can be found in various regions of the digestive system, such as the stomach, duodenum, and upper jejunum, with the less commonly reported location being the gallbladder. Gallbladder pancreatic heterotopia can be either an incidental finding or diagnosed in association with cholecystitis. Pancreatitis of the ectopic tissue has also been described. In this context, we report three cases of heterotopic pancreatic tissue in the gallbladder with different types of pancreatic tissue according to the Heinrich classification. One patient was a 24-year-old male who presented with acute pancreatitis symptoms and an ultrasonographical detected mass in the gallbladder, which proved to be heterotopic pancreatic tissue. The other two cases were female patients aged 24 and 32, respectively, incidentally diagnosed on histopathological examination after cholecystectomy for symptomatic cholelithiasis. Both cases displayed chronic cholecystitis lesions; one of them was also associated with low grade dysplasia of the gallbladder. Although a rare occurrence in general, pancreatic heterotopia should be acknowledged as a possible incidental finding in asymptomatic patients as well as a cause for acute cholecystitis or pancreatitis. Full article
(This article belongs to the Special Issue Diagnostic and Interventional Imaging in Various Diseases)
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Figure 1

Figure 1
<p>Modified Heinrich Classification for pancreatic heterotopia.</p>
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<p>Ultrasonography reveals pancreatic heterotopia Type 1 (red arrow).</p>
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<p>Gross appearance of the heterotopic pancreatic tissue in the wall of the gallbladder (red arrow). Note the Mascagni lymph node in the vicinity (blue arrow).</p>
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<p>Heterotopic pancreatic tissue of the gallbladder. Hematoxylin and Eosin staining, 4× magnification. It can be observed in serous acini (red arrows) and exocrine ducts (blue arrows).</p>
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<p>Type 1 gallbladder pancreatic heterotopia according the de modified Heinrich classification. All three histological elements of the pancreas can be observed: serous acini (red arrows), endocrine cells (yellow arrow) and exocrine ducts (blue arrow).</p>
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<p>Histological features and IHC (imunohistochemistry) features of type I pancreatic heterotopia.</p>
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<p>Langerhans islets are strongly positive for Insulin antibodies in heterotopic pancreatic tissue of the gallbladder. IHC staining with DAB chromogen, 20× magnification.</p>
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<p>Microscopic aspects suggestive of chronic cholecystitis. Observe a cholesterol calculus included in a Rokitansky-Aschoff sinus. Hematoxylin and Eosin staining, 10× magnification.</p>
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<p>Ultrasonography reveals the site of pancreatic ectopy type 2 (red arrow), opposite the macro calculus with posterior shadow cone.</p>
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<p>Histological features and IHC features of type II pancreatic heterotopia.</p>
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<p>Small foci of heterotopic pancreatic tissue of the gallbladder (red arrow) in the vicinity of pseudo-pyloric metaplasia (blue arrow). Hematoxylin and Eosin staining, 10× magnification.</p>
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<p>Small foci of heterotopic pancreatic tissue of the gallbladder (red arrow) in the vicinity of pseudo-pyloric metaplasia (blue arrow). High power magnification showing serous acini and exocrine ducts only in the heterotopic pancreatic tissue of the gallbladder (type 2 heterotopic pancreatic tissue according to the Heinrich classification). Hematoxylin and Eosin staining, 40× magnification.</p>
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<p>Ultrasonography of a case with type 3 pancreatic heterotopy (red arrow).</p>
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<p>Heterotopic pancreatic tissue (serous acini only-red arrow) in the neck region of the gallbladder. Hematoxylin and Eosin staining, 4× magnification, Leica stitch image software resolution.</p>
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<p>The serous pancreatic acini were strongly positive for Ck8/18 antibody. IHC staining with DAB (Diaminobenzidine) chromogen, 10× magnification.</p>
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<p>Histological features and IHC features of type I pancreatic heterotopia.</p>
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<p>Low grade biliary intraepithelial neoplasia (BilIN1): flat architecture, basal nuclei, pseudo-stratification within lower two thirds of epithelium (green arrows). Note the mild nuclear abnormalities and frequent mitotic figures (black circles). Hematoxylin and Eosin staining, 10× and 40× magnifications.</p>
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<p>Histological features and IHC features of pancreatic atypia.</p>
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15 pages, 3077 KiB  
Article
Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression
by Alice Blandino, Dominique Scherer, Trine B. Rounge, Sinan U. Umu, Felix Boekstegers, Carol Barahona Ponce, Katherine Marcelain, Valentina Gárate-Calderón, Melanie Waldenberger, Erik Morales, Armando Rojas, César Munoz, Javier Retamales, Gonzalo de Toro, Olga Barajas, María Teresa Rivera, Analía Cortés, Denisse Loader, Javiera Saavedra, Lorena Gutiérrez, Alejandro Ortega, Maria Enriqueta Bertrán, Fernando Gabler, Mónica Campos, Juan Alvarado, Fabrizio Moisán, Loreto Spencer, Bruno Nervi, Daniel E. Carvajal-Hausdorf, Héctor Losada, Mauricio Almau, Plinio Fernández, Ivan Gallegos, Jordi Olloquequi, Macarena Fuentes-Guajardo, Rolando Gonzalez-Jose, Maria Cátira Bortolini, Carla Gallo, Andres Ruiz Linares, Francisco Rothhammer and Justo Lorenzo Bermejoadd Show full author list remove Hide full author list
Cancers 2022, 14(3), 634; https://doi.org/10.3390/cancers14030634 - 27 Jan 2022
Cited by 4 | Viewed by 9773
Abstract
Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both [...] Read more.
Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04–1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk. Full article
(This article belongs to the Collection The Role of Non-coding RNA in Cancer)
Show Figures

Graphical abstract

Graphical abstract
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<p>Flowchart representing the three-stage approach used in the study.</p>
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<p>LncRNA preselection. (<b>A</b>) PCA based on normalized log2 expression counts for lncRNAs with a nonzero MAD expression in the preselection dataset. (<b>B</b>) Volcano plot for the lncRNAs with nonzero MAD expression investigated in the lncRNA preselection dataset. The <span class="html-italic">y</span>-axis shows −log10 <span class="html-italic">p</span>-values from J–T tests. The black line represents the applied threshold (FDR = 0.05). The red dots highlight lncRNAs preselected according to both J–T tests and ML, which showed low expression variability (MAD = 0) in serum samples. The blue dots show the six candidates that fulfilled both J–T and ML preselection criteria, with nonzero MAD expression in serum samples. (<b>C</b>) Dot-and-box plots of log2 expression in GS, Dys, and <span class="html-italic">GBC</span> tissue samples for the three preselected lncRNAs.</p>
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<p>LncRNA-eQTL validation. (<b>A</b>) Genetic PCA based on LD-pruned genotypes from the lncRNA-eQTL validation dataset. (<b>B</b>,<b>C</b>) Measured vs. predicted log2 expression for LINC00662 and C22orf34, respectively.</p>
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<p>Predicted genotype-based log2 LINC00662 expression in the lncRNA-<span class="html-italic">GBC</span> association dataset. Rhombuses represent the average genotype-based log2 expression in population-based controls and <span class="html-italic">GBC</span> patients.</p>
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