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BACKGROUND: Interleukin-17 (IL-17) is a pro-inflammatory cytokine that plays a vital role in the promotion of tumorigenesis in various cancers, including colorectal cancer (CRC). Based on current evidence, IL-17 binds to interleukin-17 receptor A (IL-17RA); however, the role of IL-17RA has not been elucidated in previous studies on CRC. In this study, we explored the role of IL-17RA in human CRC tissues and the progression of CRC in humans and mice. METHODS: The expressions of IL-17RA and epithelial-mesenchymal transition (EMT)-related genes were examined in CRC cells and tissue samples by quantitative real-time polymerase chain reaction. The role of IL-17RA in pathogenesis and prognosis was evaluated using a Chi-squared test, Kaplan-Meier analysis, univariate, and multivariate Cox regression analysis in 133 CRC patients. A tumor-bearing mice model was executed to evaluate the role of IL-17RA in tumor growth, vascularity and population of infiltrating immune cells. RESULTS: IL-17RA expression was found to be significantly higher in CRC tissues than in adjacent normal tissues. The expression of IL-17RA in Stage IV patients was significantly higher than that in Stages I and II patients. Patients with high IL-17RA expression exhibited significantly worse overall and CRC-specific survival than those with low IL-17RA expression. Functional assessment suggested that the knockdown of IL-17RA expression distinctly suppressed cellular proliferation, migration, invasion, and EMT-related gene expression. In a tumor-bearing mouse model, decreased IL-17RA expression significantly repressed tumor growth and vascularity and reduced the population of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). CONCLUSION: Reduced IL-17RA expression also suppressed cellular proliferation, migration, and invasion, and the expression of EMT genes. Knockdown of IL-17RA inhibited tumor growth and vascularity and decreased the population of Tregs and MDSCs in mouse tumors. Overall, IL-17RA expression was identified to be independently associated with the prognosis of patients with CRC.
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Neoplasias Colorretais , Interleucina-17 , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Interleucina-17/genética , Interleucina-17/metabolismo , PrognósticoRESUMO
BACKGROUND: The main etiologies of hepatocellular carcinoma (HCC) were often hepatitis B virus (HBV) or C and alcohol, rarely autoimmune and biliary diseases. Nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis, cirrhosis, and eventually HCC in recent years. The aim of our study is to investigate and compare the clinical features of HCC in patients with NAFLD and HBV, including age, gender, cirrhosis, liver function tests, largest tumor size, and cancer stage at the time of diagnosis. The survival outcome was compared between the two groups and the significant predictors of mortality were also analyzed in all patients with HCC. METHODS: Most patients with HCC were recruited from the database of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017; and the other patients consecutively from the HCC multidisciplinary conference between January 2018 and December 2019. NAFLD was defined as nonviral hepatitis B (negative HBsAg and either positive anti-HBs or negative anti-HBc), nonviral hepatitis C (negative antihepatitis C virus [HCV]), nonalcoholic (alcohol consumption of <30 g/d for men and <20 g/d for women) liver disease, or present or past histological or ultrasonographic evidence of fatty liver. Totally, 23 NAFLD-related and 156 HBV-related HCC patients were enrolled in our study for further analysis. RESULTS: NAFLD-related HCC patients were significantly older (median age: 70.0 [61.0-79.0] years vs. 63.0 [56.0-72.0] years, p = 0.012) and heavier (median body mass index [BMI]: 26.6 [24.2-30] kg/m2 vs. 24.8 [22.0-27.1] kg/m2, p = 0.044) than those with HBV-related HCC. They were also more susceptible to diabetes mellitus (DM), and 60.9% (14 of 23) of them had this comorbidity compared with 29.5% (46 of 156) of those with HBV-related HCC (p = 0.003). Only 34.8% (8 of 23) and 71.2% (111 of 156) of patients with NAFLD- and HBV-related HCC were cirrhotic, respectively (p = 0.001). However, gender, tobacco use, international normalized ratio, albumin, creatinine, and cholesterol levels were not significantly different between the two groups. Tumor characteristics such as the Barcelona clinic liver cancer stage, largest tumor size, tumor number, extrahepatic metastasis, and treatment modalities had no significant difference between such groups.According to the Kaplan-Meier method analysis, the overall survival was not significantly different between these two patient groups (log-rank test, p = 0.101). To evaluate which patient group would lead to poor prognosis, we analyzed the survival of all patients through multivariate Cox proportional hazard regression after controlling other factors that may influence the hazard ratio. The analysis revealed that NAFLD and HBV infection as the cause of HCC are not risk factors of poor prognosis. CONCLUSION: In conclusion, our study showed NAFLD-related HCC patients were older, heavier, and more had DM than HBV-related. In addition, more NAFLD-related HCC patients were noncirrhotic than HBV-related. The survival rate was similar between NAFLD and HBV-related HCC patients.
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Carcinoma Hepatocelular/fisiopatologia , Hepatite B/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Sobrevida , TaiwanRESUMO
Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.
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AIM: To elucidate the variety of ways early-stage hepatocellular carcinoma (HCC) can appear on magnetic resonance (MR) imaging by analyzing T1-weighted, T2-weighted, and gadolinium-enhanced dynamic studies. METHODS: Seventy-three patients with well-differentiated HCC (wHCC) or dysplastic nodules were retrospectively identified from medical records, and new histological sections were prepared and reviewed. The tumor nodules were categorized into three groups: dysplastic nodule (DN), wHCC compatible with Edmondson-Steiner grade I HCC (w1-HCC), and wHCC compatible with Edmondson-Steiner grade II HCC (w2-HCC). The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups. RESULTS: Among the 73 patients, 14 were diagnosed as having DN, 40 were diagnosed as having w1-HCC, and 19 were diagnosed as having w2-HCC. Hyperintensity measurements on T2-weighted axial images (T2WI) were statistically significant between DNs and wHCC (P = 0.006) and between DN and w1-HCC (P = 0.02). The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC. Hyperintensity on both T1W out-phase imaging (P = 0.007) and arterial enhancement on dynamic study (P = 0.005) showed statistically significant differences between w1-HCC and w2-HCC. The other imaging features revealed no significant differences between w1-HCC and w2-HCC. CONCLUSION: In the follow-up for a cirrhotic nodule, increased signal intensity on T2WI may be a sign of malignant transformation. Furthermore, a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.
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Carcinoma Hepatocelular/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Hepatocelular/complicações , Transformação Celular Neoplásica/patologia , Meios de Contraste , Diagnóstico Diferencial , Progressão da Doença , Detecção Precoce de Câncer , Feminino , Gadolínio DTPA , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
Kasabach-Merritt phenomenon (KMP) is a rare and life-threatening disease of vascular tumor combined with severe consumptive coagulopathy. Currently, there is no established effective treatment of KMP. In this case series, from 2006 to 2008, we treated 6 pediatric patients with newly diagnosed KMP using intralesional corticosteroid injections. The severity and progression of the disease were closely monitored with clinical photographs, blood sampling, and tissue biopsies. The 6 pediatric patients (5 females and 1 male) showed tumor regression after treatments. All coagulopathies were corrected. The average duration of treatment was 3.8 months. Complete tumor regression was observed at approximately 3 years. Treatment was complicated in 1 patient with transient growth retardation. Treatment based on intralesional corticosteroid injections is effective for pediatric patients with KMP. Treatment-associated complications seemed to be reversible and acceptable by severity level.
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Corticosteroides/administração & dosagem , Síndrome de Kasabach-Merritt/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Injeções Intralesionais , Masculino , Indução de RemissãoRESUMO
BACKGROUND/PURPOSE: Iron oxide contrast medium (ferucarbotran) shortens both T1 and T2 relaxation time. We used the T2- and the T1-weighted dynamic ferucarbotran-enhanced magnetic resonance (MR) imaging to predict the histologic grade of hepatocellular carcinoma (HCC) and to distinguish HCC from hyperplastic nodules. METHODS: Forty-three patients with 48 representative hepatic lesions (13 well differentiated HCC, 19 moderately differentiated HCC, 4 poorly differentiated HCC, 12 hyperplastic nodules) were included in the study. T1-weighted image, T2-weighted turbo spin echo, and T2*EPI (echo-planar) images were obtained before and after ferucarbotran injection. The percentage T2 signal intensity loss (T2 PSIL) of the tumors was calculated at 5 minutes and 25 minutes after contrast injection. The enhancement in dynamic T1 images was interpreted by two independent radiologists. RESULTS: The T2 PSIL of well differentiated HCC was 39.5 +/- 8.23%, moderately differentiated HCC was 26.4 +/- 13.78%, poorly differentiated HCC was 4.4 +/- 9.42%, and hyperplastic nodules was 44.3 +/- 11.04%. Comparison of T2 PSIL showed significant differences in the three histologically graded HCCs (p < 0.001), but not between the well differentiated HCCs and hyperplastic nodules (p > 0.05). Delayed post-contrast (25 minutes) T2-weighted images were not necessary and shortened the examination time. In the post contrast dynamic T1 study, no significant differences between all the groups was seen. CONCLUSION: Ferucarbotran MR images help in differentiating the different histologic grades of HCC but T2 PSIL could not differentiate hyperplastic nodules from well differentiated HCC. Dynamic post contrast T1-weighted images provide no additional information.
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Carcinoma Hepatocelular/patologia , Meios de Contraste , Hiperplasia Nodular Focal do Fígado/diagnóstico , Ferro , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Óxidos , Adulto , Idoso , Idoso de 80 Anos ou mais , Dextranos , Diagnóstico Diferencial , Feminino , Óxido Ferroso-Férrico , Humanos , Nanopartículas de Magnetita , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos ProspectivosRESUMO
BACKGROUND/AIMS: Mild to moderate iron overload is common in chronic hepatitis C (CHC) and may influence the response to antiviral therapy. The aim of this study was to assess the association among serum iron indices, hepatic iron stores and sustained virological response (SVR) rates of combination therapy with peginterferon alfa and ribavirin in patients with CHC. METHODOLOGY: A total of 36 CHC patients were treated with peginterferon and ribavirin for 6 months. The SVR was defined as undetectable hepatitis C virus RNA by qualitative assay 6 months after the end of therapy. The serum iron indices including ferritin, iron and transferrin saturation were measured. The hepatic iron deposition was graded on Perls' stain. RESULTS: The SVR was obtained in 25/36 (69.44%) patients. The serum iron indices including transferrin saturation and ferritin were not significantly different between patients with the SVR and without. In multivariate logistic regression analysis, cirrhosis (P = 0.010, odds ratio = 0.020) and a positive hepatic iron stain (P = 0.046, odds ratio = 0.065) were both significantly independent predictors of non-SVR. CONCLUSIONS: The findings suggest that the positive hepatic iron stain is an independent predictor of non-response to combination therapy with peginterferon alfa and ribavirin for patients with CHC. Liver cirrhosis also predicts non-responses to the combination therapy.
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Antivirais/uso terapêutico , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ferro/sangue , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Antivirais/administração & dosagem , Quimioterapia Combinada , Feminino , Ferritinas/sangue , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Valor Preditivo dos Testes , Proteínas Recombinantes , Ribavirina/administração & dosagem , Transferrina/metabolismo , Resultado do Tratamento , Carga ViralRESUMO
AIM: To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C (CHC). METHODS: Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Perls' stain. RESULTS: The CHC patients with severe hepatic fibrosis (n = 16) were significantly older than CHC patients with mild fibrosis (n = 16) (P = 0.024). The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis (Odds ratio = 1.312; P = 0.035). The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase (ALT) (P = 0.017), ferritin (P = 0.008), serum iron (P = 0.019) and transferrin saturation (P = 0.003). The ferritin level showed significant correlation with the value of ALT (r = 0.531; P = 0.003), iron (r = 0.467; P = 0.011) and transferrin saturation (r = 0.556; P = 0.002). CONCLUSION: Our findings suggest that the severity of hepatitis C virus (HCV)-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.
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Hepatite C , Ferro/metabolismo , Cirrose Hepática/metabolismo , Adulto , Fatores Etários , Idoso , Biópsia , Feminino , Hepacivirus/metabolismo , Hepatite C/metabolismo , Hepatite C/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
A case of spontaneous regression of hepatocellular carcinoma is reported and compared with the reports published in the English literature. Spontaneous regression of a histologically proven hepatocellular carcinoma was observed in a 42-year-old male patient with chronic hepatitis B. The patient refused to receive any medical therapy. The tumor subsequently regressed without specific treatment, as demonstrated radiologically by computed tomography 22 months and ultrasonography 24 months after initial diagnosis. We review 27 case reports of apparently spontaneous regression of hepatocellular carcinoma that have been published in the English literature from 1982 to 2002. In this report, we present our unusual case and discuss possible causes of spontaneous total necrosis or regression of hepatocellular carcinoma.