RESUMO
BACKGROUND: The aim of this study was to establish features of inflammation in histologically normal gallbladders with gallstones and compare the expression of inflammatory markers in acutely and chronically inflamed gallbladders. METHODS: Immunohistochemistry was performed on formalin-fixed paraffin-embedded gallbladders for tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R, and substance p in three groups: Group I (n = 60) chronic cholecystitis, Group II (n = 57) acute cholecystitis and Group III (n = 45) histologically normal gallbladders with gallstones. Expression was quantified using the H-scoring system. RESULTS: Median, interquartile range expression of mucosal IL-2R in Groups I (2.65, 0.87-7.97) and II (12.30, 6.15-25.55) was significantly increased compared with group III (0.40, 0.10-1.35, p < 0.05). Submucosal IL-2R expression in Groups I (2.0, 1.12-4.95) and II (10.0, 5.95-14.30) was also significantly increased compared with Group III (0.50, 0.15-1.05, p < 0.05). There was no difference in the lymphoid cell IL-6 expression between Groups I (5.95, 1.60-18.15), II (6.10, 1.1-36.15) and III (8.30, 2.60-26.35, p > 0.05). Epithelial IL-6 expression of Group III (8.3, 2.6-26.3) was significantly increased compared with group I (0.5, 0-10.2, p < 0.05) as was epithelial TNF-α expression in Group III (85.0, 70.50-92.0) compared with Groups I (72.50, 45.25.0-85.50, p < 0.05) and II (61.0, 30.0-92.0, p < 0.05). Lymphoid cell Substance P expression in Groups I (1.90, 1.32-2.65) and II (5.62, 2.50-20.8) was significantly increased compared with Group III (1.0,1.0-1.30, p < 0.05). Epithelial cell expression of Substance P in Group III (121.7, 94.6-167.8) was significantly increased compared with Groups I (75.7, 50.6-105.3, p < 0.05) and II (78.9, 43.5-118.5, p < 0.05). CONCLUSION: Histologically normal gallbladders with gallstones exhibited features of inflammation on immunohistochemistry.
Assuntos
Cálculos Biliares , Imuno-Histoquímica , Humanos , Cálculos Biliares/patologia , Cálculos Biliares/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/análise , Colecistite/patologia , Colecistite/metabolismo , Substância P/metabolismo , Vesícula Biliar/patologia , Vesícula Biliar/metabolismo , Receptores de Interleucina-2/metabolismo , Idoso , Doença Crônica , Biomarcadores/metabolismo , Biomarcadores/análise , Colecistite Aguda/patologia , Colecistite Aguda/metabolismo , Colecistite Aguda/cirurgiaRESUMO
OBJECTIVE: Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention. DESIGN: We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc. Further molecular mechanism was demonstrated with in vitro and in vivo studies. RESULTS: The cell atlas unveiled an altered immune landscape across different pathological states of gallbladder diseases. GBC featured a more suppressive immune microenvironment with distinct T-cell proliferation patterns and macrophage attributions in different GBC subtypes. Notably, mutual exclusivity between stromal and immune cells was identified and remarkable stromal ecosystem (SC) heterogeneity during GBC progression was unveiled. Specifically, SC1 demonstrated active interaction between Fibro-iCAF and Endo-Tip cells, correlating with poor prognosis. Moreover, epithelium genetic variations within adenocarcinoma (AC) indicated an evolutionary similarity between adenoma and AC. Importantly, our study identified elevated olfactomedin 4 (OLFM4) in epithelial cells as a central player in GBC progression. OLFM4 was related to T-cell malfunction and tumour-associated macrophage infiltration, leading to a worse prognosis in GBC. Further investigations revealed that OLFM4 upregulated programmed death-ligand 1 (PD-L1) expression through the MAPK-AP1 axis, facilitating tumour cell immune evasion. CONCLUSION: These findings offer a valuable resource for understanding the pathogenesis of gallbladder diseases and indicate OLFM4 as a potential biomarker and therapeutic target for GBC.
Assuntos
Neoplasias da Vesícula Biliar , Análise de Célula Única , Microambiente Tumoral , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/imunologia , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Humanos , Microambiente Tumoral/imunologia , Adenoma/patologia , Adenoma/genética , Adenoma/imunologia , Adenoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Masculino , Macrófagos/imunologia , Macrófagos/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Colecistite/patologia , Colecistite/metabolismo , Perfilação da Expressão Gênica/métodos , Pólipos/patologia , Pólipos/genética , Pólipos/imunologia , Fator Estimulador de Colônias de GranulócitosRESUMO
Relatively little is known about the relationship between Th1/Th2 cytokines and calculus cholecystitis (CC). The purpose of this study was to investigate the correlation between serum Th1 and Th2 cytokine expression and CC, including both acute and chronic cases. In total, 102 patients with chronic calculous cholecystitis (CCC), 64 patients with acute calculous cholecystitis (ACC), and 55 healthy controls (HCs) were recruited for the study. Serum concentration of Th1 (IL-2, TNF-α, IFN-γ) and Th2 cytokines (IL-4, IL-6, IL-10) was measured at admission and on the fifth day after cholecystectomy using flow cytometry. In addition, the ratio of IL-6/IL-10 was calculated. Correlation of the corresponding factors was then analysed, and univariate and multivariate Cox regression analyses were performed to identify independent markers of ACC severity. Compared to HCs, CCC patients exhibited significantly elevated expression levels of IL-6 and IL-10, while ACC patients demonstrated higher expression of IL-2, TNF-α, and IL-6/ IL-10 in addition to IL-6, and IL-10. In ACC patients, there was a strong positive correlation between IL-6 and IL-10 concentration, the expression of IL-2 was observed to positively correlate with serum ALT and AST concentration, and TNF-α expression positively correlated with the duration of hospitalization. Moreover, patients with moderate-to-severe ACC presented with higher expression of IL-10 compared to those with mild ACC. Cox regression analysis confirmed that IL-10 and IL-6 were independent factors for the severity of ACC. Following surgery, the levels of IL-6 and IL-6/IL-10 significantly decreased but did not fully return to baseline levels in ACC patients. Our study reveals atypical Th1/Th2 cytokine expression profiles in patients with acute and chronic CC, and further highlights the significant potential of these cytokines, particularly IL-6 and IL-10, in assessing the severity and progression of CC.
Assuntos
Colecistite , Interleucina-10 , Humanos , Interleucina-10/metabolismo , Células Th1 , Células Th2/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-2 , Citocinas/metabolismo , Colecistite/metabolismoRESUMO
Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have explored the mechanism of GBC, thus far, few molecules have been discovered that can be utilized as specific biomarkers for the early diagnosis and therapeutic treatment of GBC. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry specific information that can define multiple cancer types. The present study investigated the expression profiles of coding (or messenger) ribonucleic acids (mRNAs) and non-coding RNAs (ncRNAs, including long non-coding RNAs [lncRNAs] and circular RNAs [circRNAs]) in plasma-derived exosomes from GBC patients. Using high-throughput RNA sequencing and subsequent bioinformatic analysis, a number of differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in GBC exosomes, compared to their expressions in xantho-granulomatous cholecystitis (XGC) exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were then conducted to investigate the potential functions of these DE RNAs. Furthermore, the interaction networks and competing endogenous RNA networks of these DE RNAs and their target genes were investigated, revealing a complex regulatory network among mRNAs and ncRNAs. In summary, this study demonstrates the diagnostic value of plasma-derived exosomes in GBC and provides a new perspective on the mechanism of GBC.
Assuntos
Colecistite/metabolismo , Exossomos/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , RNA , Transcriptoma/genética , Xantomatose/metabolismo , Colecistite/sangue , Colecistite/diagnóstico , Colecistite/genética , Exossomos/química , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/genética , Humanos , Mapas de Interação de Proteínas/genética , RNA/sangue , RNA/genética , RNA/metabolismo , Xantomatose/sangue , Xantomatose/diagnóstico , Xantomatose/genéticaRESUMO
ABSTRACT: 68Ga-FAPI PET/CT has been used in the evaluation of a variety of malignancies. An increasing number of case studies on FAPI uptake in nonmalignant diseases is also gaining support and enthusiasm. We present a case of asymptomatic chronic cholecystitis and degenerative osteophyte detected incidentally by 68Ga-FAPI PET/CT.
Assuntos
Colecistite/metabolismo , Osteófito/metabolismo , Osteófito/patologia , Quinolinas/metabolismo , Transporte Biológico , Colecistite/diagnóstico por imagem , Doença Crônica , Humanos , Osteófito/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
Recent studies suggested that calreticulin (CRT) has an important role in the progression of various types of cancer. Our previous study suggested that CRT was upregulated and acted as an oncogene in hepatocellular carcinoma. However, the role of CRT in gallbladder cancer (GBC) remains unclear. The expression level of CRT was upregulated in GBC tissues in comparison with adjacent non-tumor tissues and chronic cholecystitis tissues. Moreover, CRT expression was found to be correlated with the tumor size. Knockdown of CRT inhibited cell proliferation, induced apoptosis, arrested cell cycle and resulted in decreased resistance to gemcitabine, which was mediated by the inactivation of the PI3K/Akt pathway. Collectively, the present results suggested a potential role of CRT in GBC progression and provided novel insights into the mechanism underlying the CRT-mediated chemosensitivity in GBC cells.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Calreticulina/metabolismo , Desoxicitidina/análogos & derivados , Neoplasias da Vesícula Biliar/metabolismo , Animais , Antimetabólitos Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Calreticulina/antagonistas & inibidores , Calreticulina/genética , Linhagem Celular Tumoral , Colecistite/metabolismo , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/genética , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Oncogenes , Prognóstico , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto , GencitabinaRESUMO
NOP2/Sun domain family, member 2 (NSUN2) is a nuclear RNA methyl-transferase catalyzing 5-methylcytosine formation. Evidence shows that NSUN2 is correlated with cell unlimited proliferation. However, its functional role in gallbladder carcinoma (GBC), which is the most common biliary tract malignancy and has a poor prognosis, remains to be determined. Here we found that NSUN2 was highly expressed in GBC tissues as well as cell lines. NSUN2 silencing repressed GBC cell proliferation and tumorigenesis both in vitro and in vivo. Conversely, upregulation of NSUN2 enhanced GBC cell growth and colony formation. We further discovered that RPL6 was a closely interacting partner with NSUN2. Silencing RPL6 resulted in insufficient NSUN2 translational level and accumulative NSUN2 transcriptional level. Exogenous expression of NSUN2 partially rescued the effect of RPL6 in gallbladder cancer progression. Taken together, our data provided novel mechanic insights into the function of NSUN2 in GBC, thus pointing to NSUN2 as a potential and effective therapeutic approach to GBC treatment.
Assuntos
Carcinoma/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Metiltransferases/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Ribossômicas/metabolismo , Animais , Carcinoma/patologia , Carcinoma/terapia , Linhagem Celular Tumoral , Proliferação de Células , Colecistite/metabolismo , Progressão da Doença , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Metiltransferases/antagonistas & inibidores , Camundongos , Camundongos Nus , Ensaio Tumoral de Célula-Tronco , Regulação para CimaRESUMO
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.
Assuntos
Bile/química , Colecistite Aguda/diagnóstico , Colecistite/diagnóstico , Gangrena/diagnóstico , Proteômica/métodos , Apoptose , Proliferação de Células , Sobrevivência Celular , Colecistite/metabolismo , Colecistite Aguda/metabolismo , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Biologia Computacional , Ácidos Graxos/metabolismo , Vesícula Biliar/química , Gangrena/metabolismo , Humanos , Neutrófilos/metabolismo , Peptídeos/química , Proteoma , Software , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Little is known about the turnover of crystalloid fluids infused in patients with acute systemic inflammation. We hypothesised that systemic inflammation would be associated with altered distribution and elimination of Ringer's lactate solution (volume kinetics). METHODS: Ringer's lactate solution (15 ml kg-1) was infused intravenously over 35 min in patients undergoing cholecystectomy (n=20) or appendectomy (n=20) starting before induction of general anaesthesia. Blood samples and urine were collected over the following 2 h. Plasma concentrations of inflammatory (tumour necrosis factor-α, interleukin-10, and C-reactive protein) and endothelial damage (syndecan-1) biomarkers were quantified by enzyme-linked immunosorbent assay. The volume kinetics was studied using mixed-effect modelling. RESULTS: Ongoing surgery (duration: 30-45 min) increased the rate constant for fluid transfer from the plasma to the extravascular space (k12; from 32 to 57×10-3 min-1; P<0.001), and decreased the elimination rate constant (k10; from 5.3 to 0.6×10-3 min-1; P<0.001). A lower mean arterial pressure was associated with reduced elimination, independent of conscious/anaesthetised state. The redistribution of fluid back to the plasma occurred more slowly in the group with appendicitis (P<0.02), in whom higher plasma concentrations of C-reactive protein were measured [median: 38.1 (range 1.8-143.6) vs 1.3 (0.1-159.0) µg ml-1; P<0.001]. However, no biomarkers for inflammation or endothelial damage were significantly associated covariates in the kinetic model. CONCLUSIONS: No association was found between the volume kinetics of Ringer's lactate solution and the degree of inflammation as indicated by established biomarkers in patients with cholecystitis or appendicitis. However, the rate of elimination was greatly retarded by general anaesthesia in both groups. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-15006063.
Assuntos
Lactato de Ringer/farmacocinética , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Adolescente , Adulto , Anestesia Geral/métodos , Apendicectomia , Apendicite/metabolismo , Apendicite/fisiopatologia , Apendicite/cirurgia , Biomarcadores/metabolismo , Pressão Sanguínea/fisiologia , Colecistectomia Laparoscópica , Colecistite/metabolismo , Colecistite/fisiopatologia , Colecistite/cirurgia , Feminino , Hidratação/métodos , Humanos , Mediadores da Inflamação/metabolismo , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Lactato de Ringer/administração & dosagem , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/cirurgia , Adulto JovemRESUMO
Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7µm particle size reversed-phase C18 LC column at a flow rate of 200µL/min with negative electrospray ionization MS. A significant difference (p=0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups.
Assuntos
Adenocarcinoma/metabolismo , Ácidos e Sais Biliares/análise , Bile/química , Colecistite/metabolismo , Neoplasias Pancreáticas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
This study aimed to evaluate the radiologist's ability to identify excreted gadoxetate disodium within the gallbladder on CT scan. Thirty three healthy adults underwent imaging of the liver during work-up for potential liver donation. Three patients had undergone prior cholecystectomy and therefore were excluded. Imaging consisted of gadoxetate disodium-enhanced magnetic resonance cholangiography (MRC) and multiphase contrast-enhanced CT scan of the abdomen and pelvis. Two fellowship-trained abdominal imaging radiologists, who were blinded to the MRC images and the contrast agent used during MRC, independently reviewed the CT scans of the 30 patients that were included. The scans were evaluated for the presence or absence of abnormal hyperdensity within the gallbladder. Three patients did not receive intravenous gadoxetate disodium, 4 patients had their MRC after the CT scan, and 1 patient had the CT scans 5 days following the MRC. Twenty two patients had the CT scan within 24 h following the gadoxetate disodium-enhanced MRC. Of the 22 patients expected to have gadolinium in the gallbladder, both reviewers identified hyperdensity in the same 20 patients (90%). Both reviewers reported no abnormal hyperdensity within the gallbladder in the remaining 10 patients. CT scan can reveal excreted gadoxetate disodium within the gallbladder lumen and therefore gadoxetate disodium-enhanced CT scan can potentially play a role in the evaluation of cystic duct patency and work-up of acute cholecystitis.
Assuntos
Colangiopancreatografia por Ressonância Magnética/métodos , Colecistite/diagnóstico por imagem , Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Vesícula Biliar/diagnóstico por imagem , Meglumina/análogos & derivados , Compostos Organometálicos/farmacocinética , Tomografia Computadorizada por Raios X/métodos , Adulto , Colecistite/metabolismo , Feminino , Vesícula Biliar/metabolismo , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Meglumina/farmacocinética , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: Gallstone pathogenesis is linked to mucin hypersecretion and bacterial infection. Several mucin genes have been identified in gallbladder epithelial cells (GBECs). We investigated MUC expression in cholesterol-associated gallbladder disease and evaluated the relationship between mucin and bacterial infection. METHODS: The present study involved 20 patients with cholesterol stones with cholecystitis, five with cholesterol stones with cholesterolosis, six with cholesterol polyps, two with gallbladder cancer, and six controls. Canine GBECs treated with lipopolysaccharide were also studied. MUC3, MUC5AC, MUC5B, and MUC6 antibodies were used for dot/slot immunoblotting and immunohistochemical studies of the gallbladder epithelial tissues, canine GBECs, and bile. Reverse-transcription polymerase chain reaction was performed to evaluate MUC3 and MUC5B expression. RESULTS: MUC3, MUC5AC, MUC5B, and MUC6 were expressed in the normal gallbladder epithelium, and of those, MUC3 and MUC5B exhibited the highest expression levels. Greatly increased levels of MUC3 and MUC5B expression were observed in the cholesterol stone group, and slightly increased levels were observed in the cholesterol polyp group; MUC3 and MUC5B mRNA was also upregulated in those groups. Canine GBECs treated with lipopolysaccharide also showed upregulation of MUC3 and MUC5B. CONCLUSIONS: The mucin genes with the highest expression levels in gallbladder tissue in cholesterol-associated diseases were MUC3 and MUC5B. Cholesterol stones and gallbladder infections were associated with increased MUC3 and MUC5B expression.
Assuntos
Colecistite/metabolismo , Células Epiteliais/metabolismo , Doenças da Vesícula Biliar/metabolismo , Mucinas Gástricas/metabolismo , Hipercolesterolemia/metabolismo , Animais , Estudos de Casos e Controles , Colecistite/etiologia , Cães , Vesícula Biliar/citologia , Doenças da Vesícula Biliar/etiologia , Humanos , Hipercolesterolemia/complicações , Mucina-5AC/metabolismo , Mucina-3/metabolismo , Mucina-5B/metabolismo , Mucina-6/metabolismoRESUMO
PURPOSE OF THE STUDY: To assess the state of the hepatobiliary system in psoriasis andpsoriatic arthritis in order to establish a causal relationship and to identify clinical and functional predictors of psoriatic disease progression. METHODS: The study includedpatients with extensive psoriasis vulgaris (n = 175) aged 18 to 66 years old and healthy donors (n = 30), matched by sex and age: Group 1--patients with psoriasis (PS, n = 77), group 2--patients with psoriatic arthritis (PsA, n = 98), group 3--control. The evaluation of functional state of the hepatobiliary system was performed by the analysis of the clinical and anamnestic data and by the laboratory-instrumental methods. RESULTS: We identified predictors of psoriasis: triggers (stress and nutritionalfactor), increased total bilirubin, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, eosinophilia, giardiasis, carriers of hepatitis C virus, ductal changes andfocal leisons in the liver, thickening of the walls of the gallbladder detected by ultrasound. Predictors ofpsoriatic arthritis: age over 50 years, dyspeptic complaints, the presence of hepatobiliary system diseases, the positive right hypochondrium syndrome, the clinical symptoms of chronic cholecystitis, excess body weight, high levels of bilirubin, cholesterol and low density lipoprotein, hepatomegaly, non-alcoholic fatty liver disease. CONCLUSION: High activity of hepatocytes cytolysis, cholestasis, inflammation, metabolic disorders let us considerpsoriatic arthritis as a severe clinical stage psoriatic disease when the hepatobiliary system, in turn, is one of the main target organs in systemic psoriatic process. Non-alcoholic fatty liver disease and chronic cholecystitis are predictors of psoriatic disease progression.
Assuntos
Artrite Psoriásica , Colecistite , Hepatopatia Gordurosa não Alcoólica , Psoríase , Adulto , Idoso , Artrite Psoriásica/complicações , Artrite Psoriásica/metabolismo , Artrite Psoriásica/fisiopatologia , Colecistite/complicações , Colecistite/diagnóstico , Colecistite/metabolismo , Progressão da Doença , Feminino , Eliminação Hepatobiliar , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Valor Preditivo dos Testes , Prognóstico , Psoríase/complicações , Psoríase/metabolismo , Psoríase/fisiopatologia , Fatores de RiscoRESUMO
PURPOSE: To detect the expression and prognostic clinical significance of heat-shock protein gp96 (HSP gp96) in gallbladder cancer. METHODS: Immunohistochemistry was used to detect and compare the rate of HSP gp96 expression in 107 samples of gallbladder cancer, 70 of gallbladder adenoma and 67 of chronic cholecystitis. The association of clinicopathological factors and patients' survival were calculated by univariate and multivariate (Cox proportional hazard regression method) analysis. RESULTS: The expression positive rate of HSP gp96 was 90.7% (97/107) in gallbladder cancer, 71.4% (50/70) in gallbladder adenoma and 47.76% (32/67) in chronic cholecystitis respectively. The positive rate of HSP gp96 in gallbladder cancer tissues was significantly higher than that in gallbladder adenoma and chronic cholecystitis tissues (P < 0.01). Multivariate and Cox regression analysis showed that positive of HSP gp96 (P = 0.026) expression was an independent poor prognostic predictor in gallbladder cancer. CONCLUSIONS: HSP gp96-positive expression is closely correlated with poor survival in gallbladder cancer.
Assuntos
Adenocarcinoma/metabolismo , Adenoma/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Proteínas de Choque Térmico/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenoma/mortalidade , Adenoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Colecistite/metabolismo , Colecistite/mortalidade , Colecistite/patologia , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
INTRODUCTION: Cholecystectomy is one of the most common surgical procedures. Postoperative investigation of cholecystectomy specimen has a great value since histopathological reports may document some entities with significant clinical consequences. The aim of this study was to evaluate the association between cholesterolosis and the reports indicating some histopathological alterations in symptomatic cholecystitis. METHODS: This paper is based on a retrospective study. Histopathological reports of 432 cholecystectomy specimens between January 2011 and June 2013 were reviewed. Three reports were excluded due to perioperative diagnosis of cancer. Reports of 429 cholecystectomy specimens of the acute and symptomatic chronic cholecystitis patients were analyzed. Standardization of the reporting was questioned. Age, gender, histopathological wall thickness of gallbladder, reporting rates of acute inflammation, cholesterolosis, polypoid lesions, epithelial hyperplasia, gastric or intestinal metaplasia, dysplasia and incidental cancer were investigated and compared between patients with and without cholesterolosis. Reported rates of histopathological findings were comparable between patients under and over 60 years old and patients with and without reported cholesterolosis. RESULTS: Reported histopathological findings were presented as acute inflammation in 46 (10.7%), cholesterolosis in 79 (18.4%), gallbladder polypoid lesions in 7 (1.6%), epithelial hyperplasia in 16 (3.7%), metaplasia of any type in 34 (7.9%) of 429 patients. Dysplasia was excluded whereas one incidental gallbladder carcinoma was reported. Epithelial hyperplasia and metaplasia were found to be related to age. Gallbladder wall thickness was decreased with cholesterolosis. However, only a correlation between cholesterolosis and gender or metaplasia was noted. CONCLUSION: Recent study suggests that cholesterolosis is somehow associated with metaplasia. Thus, surgeons should carefully interpret the histopathology reports based on unusual or exceptional findings corresponding to the cholecystectomy specimens. Any abnormal finding in the reports should be investigated in terms of the progress of the pathology and also its clinical consequences.
Assuntos
Colecistectomia , Colecistite/patologia , Colecistite/cirurgia , Colesterol/metabolismo , Prontuários Médicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistite/metabolismo , Doença Crônica , Feminino , Humanos , Hiperplasia , Masculino , Metaplasia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Results of investigation of collagen metabolism in Dupuitren's contracture (DC) were summarized. The patients were operated for calculous cholecystitis and DC stages II - III. The changes revealed witnessed about more expressed degradation of collagen and affection of the elastin components of connective tissue. On background of the pathological process progress in palmar aponeurosis in patients, suffering DC, a content of oxyproline have enhanced trustworthy in urine and reduced in tissue of a changed palmar aponeurosis.
Assuntos
Colecistite/metabolismo , Colágeno/metabolismo , Contratura de Dupuytren/metabolismo , Fáscia/metabolismo , Hidroxiprolina/urina , Cirrose Hepática/metabolismo , Idoso , Aminoácidos/sangue , Colecistite/complicações , Colecistite/cirurgia , Tecido Conjuntivo/metabolismo , Contratura de Dupuytren/complicações , Contratura de Dupuytren/cirurgia , Elastina/metabolismo , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Sonic hedgehog (Shh) signaling has been extensively studied and is implicated in various inflammatory diseases and malignant tumors. We summarized the clinicopathological features and performed immunohistochemistry assays to examine expression of Shh signaling proteins in 10 normal mucosa, 32 gallbladder carcinoma (GBC), and 95 chronic cholecystitis (CC) specimens. The CC specimens were classified into three groups according to degree of inflammation. Compared with normal mucosa, CC, and GBC specimens exhibited increased expression of Shh. The immunoreactive score of Shh in the GBC group was higher than that in the mild to moderate CC groups but lower than that in the severe CC group (P < .05). Expression of Patched (Ptch) and Gli1 gradually increased from non-malignant cholecystitis to malignant tumors. Compared with CC specimens, GBC specimens showed higher cytoplasmic and membranous expression for Ptch (P < .05). Gli1 staining showed cytoplasmic expression of Gli1 in both CC (60% for mild, 77% for moderate, and 84% for severe) and GBC specimens (97%). Nuclear expression of Gli1 was detected in 16% of severe CC specimens with moderate to poor atypical hyperplasia, and in 62.5% of GBC specimens. Shh expression strongly correlated with expression of Ptch and Gli1. Furthermore, patients with strongly positive Gli1 staining had significantly lower survival rates than those with weakly positive staining. Our data indicate that the Shh signaling pathway is aberrantly activated in CC and GBC, and altered Shh signaling may be involved in the course of development from CC to gallbladder carcinogenesis.
Assuntos
Carcinoma/metabolismo , Colecistite/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Vesícula Biliar/metabolismo , Proteínas Hedgehog/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Colecistite/mortalidade , Colecistite/patologia , Feminino , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/metabolismo , Mucosa/patologia , Transdução de Sinais/fisiologia , Taxa de SobrevidaRESUMO
Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The molecular mechanisms involved in the pathogenesis of GBC remain poorly understood. The vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and is an attractive target for cancer therapy. We characterized VEGF-A expression in advanced GBC and its relation to clinicopathologic features. VEGF-A expression was examined by immunohistochemistry in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 chronic cholecystitis. The cases were classified as low or high expression to evaluate the association of VEGF-A expression level with clinicopathologic variables. The Kaplan-Meier method was used to estimate survival as a function of time, and survival differences were analyzed by the log-rank test. High expression of VEGF-A was observed in 81% (183/224) of tumors and 5.1% (2/39) of chronic cholecystitis (P<0.0001). The VEGF-A expression had a significant relationship with histologic grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF-A is associated with a poor prognosis in patients with advanced GBC (P=0.0116). Our results indicate that VEGF-A is highly expressed in GBC and correlates with poor prognosis, suggesting that VEGF-A expression could be used as a biomarker for predicting malignant behavior and for identifying a subset of patients who may benefit from anti-VEGF-A therapies.
Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Vesícula Biliar , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Idoso , Colecistite/genética , Colecistite/metabolismo , Colecistite/mortalidade , Colecistite/patologia , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND/AIMS: To investigate the expressions and prognostic value of stem cell markers, EpCAM and CD133, in benign and malignant lesions of gallbladder. METHODOLOGY: Expression of EpCAM and CD133 was assessed in gallbladder adenocarcinoma (n = 100), peritumoral tissues (n = 46), adenoma (n = 30), polyp (n = 15), and chronic cholecystitis (n = 35) by using immunohistochemistry. RESULTS: The positive rates of EpCAM and CD133 expression were significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues (χ2(EpCAM7) = 15.36, χ2(CD133) =16.05; Ps < 0.01), adenoma (χ2 (EpCAM) =10.92, χ2(CD133) = 11.09; Ps < 0.01), polyp (χ2(EpCAM) = 8.88, χ2(CD133) = 10.43; Ps < 0.01) and chronic cholecystitism (χ2(EpCAM) = 28.58, χ2(CD133) =25.57; Ps < 0.01). In adenocarcinoma, the positive expression of EpCAM and CD133 was significanctly associated with differentiation, tumor mass, lymph node metastasis, invasion and overall survival. Notably, the benign lesions with positive EpCAM or /and CD133 expression showed moderately or severely atypical hyperplasia in gallbladder epithelium. The high consistence was found between the expressive levels of EpCAM and CD133 in gallbladder adenocarcinoma (χ2 = 10.02, P < 0.01). Unitivariate Kaplan-Meier analysis showed that high level of EpCAM (P = 0.004) and CD133 (P = 0.012) were associated with poor overall survival. CONCLUSIONS: The elevated expression of EpCAM and/or CD133 is closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.
Assuntos
Adenocarcinoma/química , Antígenos CD/análise , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Moléculas de Adesão Celular/análise , Neoplasias da Vesícula Biliar/química , Glicoproteínas/análise , Células-Tronco Neoplásicas/química , Peptídeos/análise , Antígeno AC133 , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenoma/química , Adenoma/patologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Colecistite/metabolismo , Colecistite/patologia , Doença Crônica , Progressão da Doença , Molécula de Adesão da Célula Epitelial , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Células-Tronco Neoplásicas/patologia , Pólipos/química , Pólipos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
AIMS AND BACKGROUND: Over 90% of patients with gallbladder cancer have invasion and/or metastasis when they are diagnosed at the clinic. Such patients usually have an extremely poor prognosis. The molecular mechanism responsible for the high prevalence of invasion and metastasis remains unknown. METHODS: We investigated the expression of two metastasis-suppression genes--KAI-1 and KiSS-1--and a metastasis-associated gene--MTA1--in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using in situ hybridization or immunohistochemistry. RESULTS: We demonstrated that positive MTA1 expression was significantly higher whereas positive expressions of KAI-1 and KiSS-1 genes were significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, polyps, and chronic cholecystitis. Positive MTA1 expression was significantly lower, but positive KAI-1 and KiSS-1 expressions were significantly higher in cases with well-differentiated adenocarcinoma, smaller tumor mass, no metastasis of lymph node, and no invasion of regional tissues than in cases having poorly differentiated adenocarcinoma, larger tumor mass, metastasis and invasion. Univariate Kaplan-Meier analysis showed that increased expression of MTA1 and lowered expression of KAI-1 and KiSS-1 were significantly associated with decreased overall survival. Cox regression analysis showed that tumor mass, lymph node metastasis, invasion, and MTA1 expression levels negatively correlated with survival. CONCLUSIONS: Our study suggested that KAI-1, KiSS-1, and MTA1 might be important biological markers involved in the carcinogenesis, metastasis, and invasion of gallbladder adenocarcinoma, but MTA1 is an independent factor of prognosis.