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Background/Objectives: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated disorder presenting as mass-like lesions with obstructions. An elevated serum IgG4 level is identified in more than half of affected patients and is considered a diagnostic criterion. IgG4-RD is still easily misdiagnosed as neoplastic or infectious disease. We aimed to conduct a hospital-based study to illuminate the association between serum IgG4 levels and pancreatobiliary disorders and cancer. Methods: In this study, serum IgG4 levels were assessed at our hospital's immunology laboratory, utilizing data from the hospital's computer center, and the diagnostic codes used were based on ICD-9-CM. We analyzed IgG4 level data collected between April 2013 and April 2020, including patients' age, gender, and diseases, but excluding the rationale for IgG4 level assessment. Employing propensity score matching (PSM) at a 1:1 ratio to mitigate age and gender confounding, we analyzed 759 patients divided into groups by IgG4 levels (≤140 and >140 mg/dL; and ≤140, 141-280, >280 mg/dL). We explored associations between IgG4 levels and conditions such as pancreatobiliary cancer (the group included cholangiocarcinoma, pancreatic cancer, and ampullary cancer), cholangitis, cholangiocarcinoma, pancreatitis, pancreatic cancer, and ampullary cancer. Results: Our study analyzed the demographics, characteristics, and serum IgG4 levels of participants and found no significant differences in serum IgG4 levels across various pancreatobiliary conditions. Nevertheless, the crude odds ratios (ORs) suggested a nuanced association between a higher IgG4 level > 280 mg/dL and increased risks of cancer and pancreatitis, with crude ORs of 1.52 (p = 0.03) and 1.49 (p = 0.008), respectively. After PSM matching, the further analysis of 759 matched patients showed no significant differences in IgG4 levels > 140 mg/dL between cancerous and non-cancerous groups, nor across other pancreatobiliary conditions. A higher serum IgG4 level > 280 mg/dL was significantly associated with pancreatobiliary cancer and cholangiocarcinoma, with crude ORs of 1.61 (p = 0.026) and 1.62 (p = 0.044), respectively. In addition, IgG4 > 280 mg/dL showed a greater association with pancreatic cancer compared with 141-280 mg/dL, with crude OR of 2.18 (p = 0.038). Conclusions: Our study did not find a clear association between serum IgG4 levels (>140 mg/dL) and pancreatobiliary cancer. We observed that higher IgG4 levels (>280 mg/dL) may be associated with cholangiocarcinoma and pancreatic cancer, as indicated by crude ORs. However, the adjusted analysis did not demonstrate the significant association between IgG4 level > 280 mg/dL and cancer. Considering IgG4-RD as a chronic and persistent inflammatory status, it is more closely associated with inflammatory diseases than with cancer. Therefore, further long-term cohort studies are necessary to evaluate the potential role of IgG4 levels in cancer risk among these patients.
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(1) Background: This study investigates the effects of Ursodeoxycholic acid (UDCA) on NF-κB signaling, farnesoid X receptor (FXR) singling, and microRNA-21 in HepG2 cells. (2) Methods: HepG2 cells were treated with lipopolysaccharide (LPS) to simulate hepatic inflammation. The investigation focused on the expression of NF-κB activation, which was analyzed using Western blot, confocal microscopy, and Electrophoretic Mobility-shift Assays (EMSA). Additionally, NF-κB and farnesoid X receptor (FXR) singling expressions of micro-RNA-21, COX-2, TNF-α, IL-6, cyp7A1, and shp were assessed by RT-PCR. (3) Results: UDCA effectively downregulated LPS-induced expressions of NF-κB/65, p65 phosphorylation, and also downregulated FXR activity by Western blot. Confocal microscopy and EMSA results confirmed UDCA's role in modulating NF-κB signaling. UDCA reduced the expressions of LPS-induced COX-2, TNF-α, and IL-6, which were related to NF-κB signaling. UDCA downregulated LPS-induced cyp7A1 gene expression and upregulated shp gene expression, demonstrating selective gene regulation via FXR. UDCA also significantly decreased micro-RNA 21 levels. (4) Conclusions: This study demonstrates UDCA's potent anti-inflammatory effects on NF-κB and FXR signaling pathways, and thus its potential to modulate hepatic inflammation and carcinogenesis through interactions with NF-κB and FXR. The decrease in micro-RNA 21 expression further underscores its therapeutic potential.
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Background: The therapeutic options for hepatocellular carcinoma (HCC) have greatly expanded recently, and current first-line therapies include sorafenib, lenvatinib, and atezolizumab-bevacizumab. The aim of this study was to investigate the therapeutic efficacy of sequential systemic treatments after progressing to the first-line agent in patients with unresectable HCC. Methods: Data were collected from subjects with HCC, BCLC stage B or C, who received first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab from September 2020 to December 2022. The patients who progressed after first-line therapy were evaluated according to individual clinical status in order to decide whether or not to accept sequential therapy. The clinical baseline characteristics and overall survival (OS) of enrolled patients were collected and further analyzed. Results: Among the 127 enrolled patients, percentage of sequential therapy was 67.9%, 21.6%, and 37.5% in those with tumor progression after first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab, respectively. Acceptance of sequential therapy (HR 0.46, p = 0.041) and presentation of ALBI grade I (HR 0.36, p = 0.002) had a significantly positive impact on OS. Pre-treatment ALBI grade had a significant impact on the decision to accept sequential therapy in patients with progressed HCC. Conclusions: The patients who were able to undergo sequential therapy had a better survival outcome compared to those who received only one agent, and the pre-treatment ALBI level might be regarded as a cornerstone tool to assess survival outcomes in patients undergoing treatment for HCC.
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Hepatic events can occur after discontinuing antiviral therapy. We investigated factors associated with hepatitis flares and hepatic decompensation after discontinuing tenofovir disoproxil fumarate (TDF) and entecavir (ETV). Hepatitis flares within 6 months and hepatic decompensation were compared between non-cirrhotic hepatitis B e antigen-negative patients after discontinuing TDF or ETV by using the Cox proportional hazard model. The cumulative rates of hepatitis flare at 6 months after discontinuing ETV and TDF were 2% and 19%, respectively (p < 0.001). The respective rates of hepatic decompensation at 6 months were 0% and 7% (p = 0.009). Higher alanine aminotransferase (ALT) (AASLD criteria) at the end of treatment (EOT) (HR = 4.93; p = 0.001), an off-therapy dynamic change in HBV DNA (rapid rebound of HBV DNA from the nadir, ≥1 log10 IU/mL per month) (HR = 10.7; p < 0.001), and the discontinuation of TDF (HR = 6.44; p = 0.006) were independently associated with hepatitis flares within 6 months. Older age (HR = 1.06; p < 0.001) and an off-therapy dynamic change in HBV DNA (HR = 3.26; p = 0.028) were independently associated with hepatic decompensation after the discontinuation of antiviral therapy. In summary, we demonstrated several factors associated with hepatitis flares and hepatic decompensation after discontinuing antiviral therapy in non-cirrhotic hepatitis B e antigen-negative patients.
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BACKGROUND: Transarterial chemoembolization (TACE) is a recommended treatment for patients with intermediate stage hepatocellular carcinoma (HCC) but with variable treatment outcomes. AIM: To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC. METHODS: Patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. Patients were assigned to either the objective responder (OR) group or the non-OR group according to mRECIST criteria. Clinical and radiological characteristics were compared between the 2 groups. The overall survival of enrolled subjects was analyzed. RESULTS: In 128 enrolled patients, 66 (51.6%) were in the OR group and 62 (48.4%) in the non-OR group. Compared with the non-OR group, the OR group had a significantly smaller HCC size (6.55 cm vs 9.50 cm, P = 0.001) and was within the up-to-7 criteria (50% vs 26.7%, P = 0.001). After multivariable analyses, these significant associations still existed. Overall survival rate of all the subjects averaged 20.65 ± 13.26 mo. The survival rate at 1-year was 64.8%, 2-year was 46.9%, and 3-year was 31.2%. For those patients with OR to TACE, smaller tumor size and within up-to-7 criteria were associated with significantly better overall survival. Those patients with subgroup B1 had the highest OR ratio (75%) and better overall survival (26.70 ± 12.07 mo) after TACE. CONCLUSION: BCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE. BCLC stage B subgroup is useful to predict refractoriness to TACE.
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(1) Background: The complication rates for nonagenarians receiving therapeutic endoscopic retrograde cholangiopancreatography (ERCP) remain poorly understood. We aimed to determine whether nonagenarians were at an increased risk of ERCP-related complications. (2) Methods: We performed a retrospective study on therapeutic ERCP in nonagenarians from 2011 to 2016 at Taichung Veterans General Hospital. A control group comprising patients aged 65 to 89 years was used to compare demographic data and the outcomes of therapeutic ERCP with the nonagenarians. The risk factors for complications were determined by logistic regression model. (3) Results: There were 35 nonagenarians and 111 patients in the control group. Overall, complication rates were not statistically different between the two groups. However, advanced age was an independent predictor of complications in the multivariate analysis (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.01-1.12; p = 0.049). End stage renal disease (ESRD) was another independent predictor of complications (OR = 4.87; 95% CI = 1.11-21.36; p = 0.036). Post-ERCP pancreatitis and bleeding were more common in ESRD patients than patients without ESRD. (4) Conclusions: Although nonagenarians receiving ERCP did not have more complications compared to elderly patients younger than 90 years, advanced age and comorbidity still affect the outcome of therapeutic ERCP in the elderly patients.
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AIM: Hepatocellular carcinoma (HCC) is one of the most common cancers. Tyrosine kinase inhibitors (TKIs), including sorafenib (SOR) and lenvatinib (LEN), as well as immune checkpoint inhibitors (ICIs), including nivolumab (NIVO) and pembrolizumab (PEMBRO), have been approved for the treatment of advanced HCC. The aim of the study is to determine whether advanced-stage HCC patients should receive a combination of TKI and ICI as first-line therapy. METHODS: Data for subjects with BCLC stage C HCC, who were receiving combining TKI and ICI as first-line therapy at Taichung Veterans General Hospital from April 2019 to July 2021, were evaluated. The general and therapeutic outcome data were collected and analyzed. RESULTS: A total of 33 patients were enrolled (8 SOR/NIVO, 4 SOR/PEMBRO, 11 LEN/NIVO, and 10 LEN/PEMBRO). All cases belonged to Child-Pugh class A. The objective response rate was 48.5%, and disease control rate was 72.7%. The average progression-free survival (PFS) and overall survival (OS) of all patients was 9.2 and 17.0 months, respectively. The use of PEMBRO, when compared with NIVO, had a significantly positive impact towards achieving an objective response, defined as either complete response or partial response (OR 5.54, p = 0.045). PFS and OS between the different TKIs or ICIs had no differences. The most adverse event was fatigue (36.4%), and most cases were mild and manageable. CONCLUSION: Combining TKI and ICI provides an acceptable antitumor efficacy in first-line therapy for advanced-stage HCC patients. The survival outcomes between different TKIs or ICIs display no differences.
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OBJECTIVES: To evaluate the impact of Helicobacter pylori eradication on venous thromboembolism (VTE) events, and the differences between early and late treatment timing. DESIGN: A population-based cohort study. SETTING: Taiwan's National Health Insurance Research Database. PARTICIPANTS: A total of 6736 patients who received H. pylori eradication therapy from 2000 to 2010 were identified. We randomly selected 26 944 subjects matching in gender, age and baseline year as comparison cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence rate ratios of VTE in the H. pylori eradication cohorts to that of the control cohort were examined. Multivariable Cox proportional hazard regression analysis was used to estimate the relative HRs and 95% CI of VTE development. RESULTS: The total incidence rate of VTE was observed in the late H. pylori eradication cohort, the early H. pylori eradication cohort and the control cohort (15.2, 3.04 and 2.91 per 1000 person-years, respectively). An age-specific trend was found in the late H. pylori eradication cohort, with a greater rate of VTE in the 50-65 years and more than 65 years age groups (adjusted HR 5.44; 95% CI 4.21 to 7.03 and 3.13; 95% CI 2.46 to 3.99). With comorbidities, the late H. pylori eradication cohort seemed to have the highest VTE incidence rate and adjusted HR (4.48, 95% CI 3.78 to 5.30). CONCLUSIONS: Late H. pylori eradication was associated with a significantly increased risk of VTE, and there was a significantly greater risk of VTE in patients with female gender, age more than 50 years and with comorbidities.
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Infecciones por Helicobacter , Helicobacter pylori , Úlcera Péptica , Tromboembolia Venosa , Antibacterianos/uso terapéutico , Estudios de Cohortes , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/epidemiología , Tromboembolia Venosa/inducido químicamenteRESUMEN
Severe acute cholangitis is a life-threatening medical emergency. Endoscopic biliary drainage (EBD) or percutaneous transhepatic biliary drainage (PTBD) is usually used for biliary decompression. However, it can be risky to transport a critical patient to the radiology unit. We aimed to compare clinical outcomes between bedside, radiation-free EBD and fluoroscopic-guided PTBD in patients under critical care. METHODS: A retrospective study was conducted on critically ill patients admitted to the intensive care unit with biliary obstruction and cholangitis from January 2011 to April 2020. RESULTS: A total of 16 patients receiving EBD and 31 patients receiving PTBD due to severe acute cholangitis were analyzed. In the EBD group, biliary drainage was successfully conducted in 15 (93.8%) patients. Only one patient (6.25%) encountered post-procedure pancreatitis. The 30-day mortality rate was no difference between the 2 groups (32.72% vs. 31.25%, p = 0.96). Based on multivariate analysis, independent prognostic factors for the 30-day mortality were a medical history of malignancy other than pancreatobiliary origin (HR: 5.27, 95% confidence interval [CI]: 1.01-27.57) and emergent dialysis (HR: 7.30, 95% CI: 2.20-24.24). CONCLUSIONS: Bedside EBD is safe and as effective as percutaneous drainage in critically ill patients. It provides lower risks in patient transportation but does require experienced endoscopists to perform the procedure.
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AIM: Currently, atezolizumab combined with bevacizumab is the standard first-line treatment for unresectable hepatocellular carcinoma (HCC), but lenvatinib or sorafenib are still recommended for these patients for some reasons. The aim of the study was to determine the outcomes of Taiwanese patients with advanced-stage HCC who received lenvatinib or sorafenib. METHODS: Data on patients with BCLC stage C HCC who were receiving lenvatinib or sorafenib as the first-line therapy from May 2018 to August 2020 was collected. The individuals with lenvatinib and sorafenib were propensity score-matched at a ratio of 1:2. RESULTS: A total of 22 patients with lenvatinib and 44 patients with sorafenib were enrolled. The ORR (36.4% vs. 11.4%, p = 0.023) and DCR (81.9% vs. 56.9%, p = 0.039) were both higher in the lenvatinib group compared with the sorafenib group. The median overall survival (OS) of the lenvatinib group and the sorafenib group was 9.36 months and 8.36 months, respectively. The best median OS was detected in patients receiving lenvatinib and having an objective tumor response (11.29 months), with a significant difference (p = 0.031) compared with the other groups. CONCLUSION: Lenvatinib, compared to sorafenib, had better ORR and DCR, but similar OS, in Taiwanese patients with advanced-stage HCC. The patients with an objective tumor response had a better OS.
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Isoamylamine (IA) is an aliphatic monoamine molecule present in cheese, eggs, and wine. It belongs to the family of polyamines and also can be synthesized endogenously. It has been known that regulation of polyamines in cells is related to cell cycle and tumor formation. Malignant melanoma is difficult to treat and easily resistant to chemotherapy/radiotherapy through autophagy. In this study, we aim to clarify whether IA has a growth control effect on melanoma tumor cells and the regulatory mechanism. We treated B16-F1 melanoma cells with IA at concentrations of 0, 200, 400, and 600 ppm for 24 h. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was checked for cell viability and results showed that IA has an inhibitory effect on B16-F1 melanoma cells. The signaling molecules, which included Raf/MEK/ERK, were activated, while MSK1 and protein kinase B (AKT) were suppressed. Autophagy was also confirmed to be induced by IA. The acridine orange stain-positive cells were increased and BECN-1/LC3 upregulated. The data also showed that the autophagy regulatory molecule, 5'-adenosine monophosphate-activated protein kinase (AMPK), was induced after IA treatment, so we used dorsomorphin to inhibit AMPK and found that it could suppress autophagy. In conclusion, IA has an effect of inducing autophagy in B16-F1 cells and it is regulated through AMPK.
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Proteínas Quinasas Activadas por AMP , Aminas , Autofagia , Regulación hacia Arriba , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Aminas/farmacología , Animales , Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Ratones , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity; the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway.
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Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Cognición/efectos de los fármacos , Glucosamina/farmacología , Regulación hacia Arriba/efectos de los fármacos , Animales , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Fosforilación/efectos de los fármacos , Proteínas Tirosina Quinasas/metabolismoRESUMEN
OBJECTIVE: Transarterial chemoembolization (TACE) is the treatment modality for intermediate, or Barcelona Clinic Liver Cancer stage B, hepatocellular carcinoma (HCC), but its beneficial effect on outcomes is still unsatisfactory. This study aimed to assess the outcomes of combined TACE and sorafenib for patients with intermediate HCC. METHODS: Patients with intermediate HCC who were receiving TACE alone (the monotherapy group), or combined TACE and sorafenib (the combined therapy group) from January 2013 to June 2018 were enrolled. RESULTS: Altogether 64 patients were enrolled, of whom 34 were assigned to the monotherapy group and 30 to the combined therapy group. A prolonged time-to-progression (TTP) (mean 14.46 mo vs 6.39 mo, P = 0.001) was noted in the combined therapy group compared with the monotherapy group. Overall survival (OS) (mean 18.96 mo vs15.44 mo, P = 1.000) between the two groups did not differ significantly. After adjustment, there were no significant differences in the 12-18 month mortality rate between the two groups. CONCLUSION: Patients with intermediate HCC receiving combined TACE and sorafenib had a better TTP, but not OS, than those receiving TACE alone.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Sorafenib/administración & dosificación , Anciano , Carcinoma Hepatocelular/patología , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: Systemic therapy, such as sorafenib, has been used clinically to treat patients with advanced stage or Barcelona Clinic Liver Cancer staging system (BCLC) stage C hepatocellular carcinoma (HCC). The aim of the study was to evaluate the therapeutic benefit of combined sorafenib and transarterial chemoembolization (TACE) in this group of patients. METHODS: Data on patients with HCC at BCLC stage C from August 2012 to September 2017 were collected. Patients who were given sorafenib alone were classified as the monotherapy group and those taking sorafenib and TACE were classed as the combined therapy group. RESULTS: A total of 118 patients were enrolled. There were 65 and 53 patients in the monotherapy and the combined therapy group, respectively. The groups' general characteristics were similar. Compared with the monotherapy group the combined therapy group experienced prolonged time-to-progression (TTP) (mean 6.42 mo vs 3.63 mo, P = 0.003) and overall survival (OS) (mean 11.21 mo vs 5.98 mo, P = 0.001). A subgroup analysis found that patients with macroscopic vascular invasion (MVI) also had prolonged TTP and OS in the combined therapy group than the monotherapy group (mean TTP, 7.93 mo vs 3.43 mo, P = 0.007; mean OS, 13.41 mo vs 5.50 mo, P = 0.001), however, these significant differences did not exist for those with extrahepatic spread (EHS). CONCLUSION: Combined sorafenib and TACE therapy has significant better outcomes than sorafenib alone in patients with stage C HCC, particularly those with MVI.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Sorafenib/uso terapéutico , Anciano , Carcinoma Hepatocelular/irrigación sanguínea , Terapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk. MATERIALS AND METHODS: A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location. CONCLUSION: MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.
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Neoplasias Colorrectales/genética , Metaloproteinasa 9 de la Matriz/genética , Metástasis de la Neoplasia/genética , Polimorfismo de Nucleótido Simple , Índice de Masa Corporal , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Regiones Promotoras Genéticas , TaiwánRESUMEN
Sorafenib is of proven efficacy in treating patients of hepatocellular carcinoma (HCC). Our study was aimed to determine the factors influence the sorafenib efficacy.We evaluated data of HCC patients receiving sorafenib from June 2012 to October 2016. All HCC cases were of the Barcelona Clinic Liver Cancer (BCLC) classification stage C. The exclusion criteria: those of BCLC classification stage A or B, with the absence or co-infection of hepatitis B (HBV) and hepatitis C (HCV). The presence of HBV, HCV, macoscopic vascular invasion (MVI) or extrahepatic spread (EHS) was recorded for each patient. Time-to-progression (TTP) and overall survival (OS) were analyzed.Among a total of 90 HCC patients, 48 (53.3%) had HBV infection, 42 (46.7%) had HCV infection, 51 (56.7%) had MVI, and 39 (43.3%) had EHS. Patients with HCV infection showed better TTP and OS than those with HBV infection. Patients with EHS had a longer TTP and OS than those with MVI. For patients with HBV infection, those with EHS had a longer TTP (mean 4.60 vs 2.64 months, Pâ=â.002) and OS (mean 6.65 vs 4.53 months, Pâ=â.045) compared to those with MVI. Among those with MVI, patients with HBV infection had a poorer TTP (mean 2.64 vs 4.74 months, Pâ=â.019) and shorter OS (mean 4.53 vs 7.00 months, Pâ=â.059) compared to those with HCV infection.HCC patients with HCV infection or with the presence of EHS showed better sorafenib efficacy.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , Anciano , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Femenino , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND & AIMS: To evaluate virological breakthrough (VBT) and the risk of hepatocellular carcinoma (HCC) in HBeAg-positive chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment. METHODS: A retrospective cohort study was conducted in a tertiary referral hospital and a total of 228 HBeAg-positive CHB patients treated with ETV for more than 48 weeks were enrolled. Clinical outcome measures included HBeAg seroclearance, maintained virological response and the development of HCC. RESULTS: During a median follow-up period of 197 weeks, VBT developed in 26 (11.4%) patients (VBT group), and the other 202 patients without VBT (non-VBT group). The overall cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group were 23.1% and 23.8%, 27.1% and 37.9%, 27.1% and 55.1%, 27.1% and 74.1%, 27.1% and 76.7% from week 48 to 240, respectively(p = 0.013). The cumulative probability of maintained virological responses from week 48 to 240 were 7.69% and 21.78%, 7.69% in the VBT groups and 36.85%, 7.69% and 51.68%, 7.69% and 64.97%, 7.69% and 72.1% in the non-VBT groups, respectively (p<0.001). In the multivariate analysis, age (p<0.001) and virological response at week 24 (p = 0.005) were independently associated with VBT. Cox regression analysis showed that cirrhosis had carried the highest risk for HCC (HR = 4.99, CI = 1.14-21.81, p = 0.033). Subgroup survival analysis by Kaplan-Meier method showed that patients with VBT had higher incidence of developing HCC than without VBT in cirrhotic patients (50% (95%CI = 1-99%) vs 9% (95% CI = 1-9%); p = 0.048). CONCLUSIONS: VBT was associated with adverse clinical outcomes, including a low probability of HBeAg seroclearance, failure to achieve maintained virological responses, and a risk of developing HCC. Patients, particularly with cirrhosis, who had experienced VBT during ETV treatment, more likely developed HCC.
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Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B , Hepatitis B Crónica/mortalidad , Hepatitis B Crónica/virología , Carga Viral , Adulto , Antivirales/administración & dosificación , Antivirales/efectos adversos , Antivirales/uso terapéutico , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Femenino , Guanina/administración & dosificación , Guanina/efectos adversos , Guanina/análogos & derivados , Guanina/uso terapéutico , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Hepatocellular carcinoma (HCC) is associated with a poor prognosis and a low chemotherapeutic efficiency except for when sorafenib is administered. The aim of this study was to evaluate the efficacy and adverse events (AEs) of sorafenib therapy in a Chinese population diagnosed with HCC. METHOD: Data for the subjects with HCC receiving sorafenib at Taichung Veterans General Hospital from June 2012 to October 2016 were evaluated. All enrolled cases belonged to the HCC Barcelona Clinic Liver Cancer (BCLC) classification stage C. The AEs were defined as appearances of hand-foot syndrome reaction (HFSR), hypertension (HTN), or diarrhea. The exclusion criteria included a poor performance status, lack of compliance to drugs, and loss of follow-up within the following day. RESULTS: Of a total of 116 subjects enrolled, there were 43 (37.1%), 13 (11.2%), and 15 (12.9%) cases experiencing HFSR, HTN, and diarrhea, respectively. The cases with AE had both a longer time to progression (TTP) (HFSR 5.16 vs. 3.33 months, P = 0.003; HTN 6.62 vs. 3.68 months, P = 0.001; diarrhea 6.67 vs. 3.61 months, P = 0.001) and overall survival (OS) (HFSR 8.12 vs. 4.75 months, P = 0.001; HTN 9.08 vs. 5.61 months, P = 0.008; diarrhea 8.20 vs. 5.67 months, P = 0.042) than those without. More AEs were correlated with a longer TTP and OS. CONCLUSION: The appearance of sorafenib AEs, including HFSR, HTN, and diarrhea, can predict a positive therapy efficacy to HCC.
RESUMEN
The major papilla of Vater can be ectopically present in the stomach, pyloric canal, duodenal bulb, and third or fourth portion of the duodenum. In this study, we determined the clinical significance of ectopic papilla of Vater by endoscopic retrograde cholangiopancreatogram (ERCP).A retrospective study was conducted by reviewing the medical records of 6133 patients receiving ERCP from 1988 to 2011. The diagnosis was confirmed if both the common bile duct (CBD) and the main pancreatic duct (PD) drained into the same opening, either by ERCP or magnetic resonance cholangiopancreatography.Eight patients with major papilla of Vater in the duodenal bulb were identified among 6133 patients receiving ERCP from 1988 to 2011, with an incidence rate of 0.13%. The mean age was 67 years and patients were predominantly male. Duodenal bulb deformity was noted in all patients and three of them had shallow gastric and/or duodenal ulcers. Hook-shaped CBD configuration was seen only in half of our cases. Three patients with CBD stones were treated successfully after endoscopic sphincterotomy or papillary balloon dilation.Ectopic orifice of papilla is a rare finding of ERCP. Opacification of both the CBD and main PD from the same opening is an essential criterion for diagnosing an ectopic papilla of Vater in the duodenal bulb.