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B cells possess anti-tumor functions mediated by granzyme B, in addition to their role in antigen presentation and antibody production. However, the variations in granzyme B+ B cells between tumor and non-tumor tissues have been largely unexplored. Therefore, we integrated 25 samples from the Gene Expression Omnibus database and analyzed the tumor immune microenvironment. The findings uncovered significant inter- and intra-tumoral heterogeneity. Notably, single-cell data showed higher proportions of granzyme B+ B cells in tumor samples compared to control samples, and these levels were positively associated with disease-free survival. The elevated levels of granzyme B+ B cells in tumor samples resulted from tumor cell chemotaxis through the MIF- (CD74 + CXCR4) signaling pathway. Furthermore, the anti-tumor function of granzyme B+ B cells in tumor samples was adversely affected, potentially providing an explanation for tumor progression. These findings regarding granzyme B+ B cells were further validated in an independent clinic cohort of 40 liver transplant recipients with intrahepatic cholangiocarcinoma. Our study unveils an interaction between granzyme B+ B cells and intrahepatic cholangiocarcinoma, opening up potential avenues for the development of novel therapeutic strategies against this disease.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Trasplante de Hígado , Humanos , Granzimas/genética , Colangiocarcinoma/genética , Colangiocarcinoma/cirugía , Pronóstico , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Microambiente TumoralRESUMEN
BACKGROUND: T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker. METHODS: Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort. RESULTS: Upon activation the expression of TGF-ß and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885-0.964; p = 0.000). CONCLUSIONS: A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.
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Linfocitos B , Rechazo de Injerto , Estudios de Casos y Controles , Granzimas , HígadoRESUMEN
BACKGROUND: Stricture formation at the biliary-enteric anastomosis can cause serious complications after pancreaticoduodenectomy while the anastomotic size is reported to significantly affect stricture formation. In this study, we aimed to determine the effect of a pedicled gallbladder flap used as an alternative to biliary reconstruction during pancreaticoduodenectomy in patients with a nondilated extrahepatic bile duct. METHODS: Data of patients with a nondilated extrahepatic bile duct, who underwent pancreaticoduodenectomy between October 2012 and July 2015 at the Department of Hepatobiliary and Pancreaticosplenic Surgery at Beijing Chaoyang Hospital, were collected. A pedicled gallbladder flap for biliary reconstruction was consecutively performed in patients with morphologically normal gallbladder, whereas patients with abnormal gallbladder morphology accept conventional biliary reconstruction. RESULTS: A total of 29 patients were enrolled in this study with 17 patients using a pedicled gallbladder flap and 12 patients using the conventional technique. Patients of the two groups had similar preoperative and operative parameters as well as similar early complication rates. No patients in the former group experienced biliary stricture or transient episodes of cholangitis over the follow-up period. While in the latter group, one patient had biliary stricture in the 14th month which was cured by intervene treatment. Another two patients had intermittently mild-to-moderate elevations in liver enzymes level from the 11th month and the 18th month, respectively, and were treated with medication. CONCLUSIONS: Biliary reconstruction with a pedicled gallbladder graft can be used as an alternative in patients with a nondilated extrahepatic bile duct during pancreaticoduodenectomy.
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Procedimientos Quirúrgicos del Sistema Biliar/métodos , Pancreaticoduodenectomía/métodos , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/prevención & control , Colgajos Quirúrgicos , Anciano , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Conductos Biliares Extrahepáticos/patología , Conductos Biliares Extrahepáticos/cirugía , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Constricción Patológica/epidemiología , Constricción Patológica/etiología , Constricción Patológica/prevención & control , Femenino , Estudios de Seguimiento , Vesícula Biliar/patología , Vesícula Biliar/cirugía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Pancreatitis Crónica/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
OBJECTIVES: A separate subset of Granzyme B (GrB) producing B-cells regulating T-cell mediated immunity has been identified. In the present study, we investigated the role of GrB+ B-cells in renal transplant patients (RTX). METHODS: 12 healthy controls (HC) and 26 RTX patients were enrolled. In addition, 19 healthy volunteers treated with cyclosporine A (CsA) were enrolled. GrB+ B-cells were determined via flow cytometry. RESULTS: RTX Patients showed a diminished fraction of GrB+ B-cells as compared to HC. CsA treatment of healthy volunteers had no impact on the development of GrB+ B-cells. RTX patients with a history of allograft rejection showed an increased frequency of GrB+ B-cells. RTX patients with at least one episode of CMV viremia tended to have lower GrB+ B-cells as compared to patients without viremic episodes. CONCLUSION: We demonstrate that treatment with CsA does not impair the development of GrB+ B-cells. GrB+ B-cells may have a dual role in renal transplantation as regulatory cells to maintain allospecific tolerance and as effector cells enhancing viral control.
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Linfocitos B/metabolismo , Granzimas/metabolismo , Trasplante de Riñón , Corticoesteroides/uso terapéutico , Anciano , Linfocitos B/efectos de los fármacos , Estudios de Casos y Controles , Ciclosporina/farmacología , Ciclosporina/uso terapéutico , Femenino , Rechazo de Injerto/prevención & control , Granzimas/efectos de los fármacos , Humanos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Interleucinas/farmacología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
BACKGROUND: Stricture formation at the bilioenteric anastomosis is a rare but important postoperative complication. However, information on this complication is lacking in the literature. In the present study, we aimed to assess its prevalence and predictive factors, and report our experience in managing bilioenteric anastomotic strictures over a ten-year period. METHODS: A total of 420 patients who had undergone bilioenteric anastomosis due to benign or malignant tumors between February 2001 and December 2011 were retrospectively reviewed. Univariate and multivariate modalities were used to identify predictive factors for anastomotic stricture occurrence. Furthermore, the treatment of anastomotic stricture was analyzed. RESULTS: Twenty-one patients (5.0%) were diagnosed with bilioenteric anastomotic stricture. There were 12 males and 9 females with a mean age of 61.6 years. The median time after operation to anastomotic stricture was 13.6 months (range, 1 month to 5 years). Multivariate analysis identified that surgeon volume (≤30 cases) (odds ratio: -1.860; P=0.044) was associated with the anastomotic stricture while bile duct size (>6 mm) (odds ratio: 2.871; P=0.0002) had a negative association. Balloon dilation was performed in 18 patients, biliary stenting in 6 patients, and reoperation in 4 patients. Five patients died of tumor recurrence, and one of heart disease. CONCLUSIONS: Bilioenteric anastomotic stricture is an uncommon complication that can be treated primarily by interventional procedures. Bilioenteric anastomosis may be performed by a surgeon in his earlier training period under the guidance of an experienced surgeon. Bile duct size >6 mm may play a protective role.
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Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Colestasis/epidemiología , Colestasis/terapia , Neoplasias del Sistema Digestivo/cirugía , Anciano , Anastomosis Quirúrgica , Procedimientos Quirúrgicos del Sistema Biliar/mortalidad , Distribución de Chi-Cuadrado , China/epidemiología , Colecistectomía/efectos adversos , Coledocostomía/efectos adversos , Colestasis/diagnóstico , Colestasis/mortalidad , Constricción Patológica , Neoplasias del Sistema Digestivo/mortalidad , Neoplasias del Sistema Digestivo/patología , Dilatación , Femenino , Humanos , Yeyunostomía/efectos adversos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Prevalencia , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Early diagnosis of superior mesenteric artery (SMA) involvement is vital for patients with a borderline resectable cancer of the pancreatic head to achieve an R0 resection. We aimed to detect the effect of the inferior infracolic 'superior mesenteric artery first' approach with a no-touch isolation surgical technique in these patients. METHODS: The data of 21 patients who were consecutively diagnosed with a borderline resectable cancer of the pancreatic head and treated with our technique between July 2014 and September 2015 were analyzed. RESULTS: During the exploration, five patients were confirmed to have invasion to the SMA. Fourteen patients underwent a pancreaticoduodenectomy, and two patients underwent a total pancreatectomy due to a positive margin at the pancreatic neck on frozen sections. Ten men and six women, with a mean age of 64.1 years, were included in the study. Pathologic stage was T1, T2, and T3 in 1, 3, and 12 patients, respectively. Venous resection was performed in 8 patients, and an R0 resection was achieved in all patients (16/16). The mean intraoperative blood loss was 532 ml (range 200-1800 ml). At median follow-up time after surgery (12.8 months; range 4.5-18 months), two patients had a recurrence in the liver. The 1-year survival rate was 75 %, and the 1-year tumor-free survival rate was 62.5 %. CONCLUSIONS: Our technique facilitates early diagnosis of arterial involvement and the achievement of an R0 resection. This technique allows the tumor to be resected in situ, and removed en bloc, and is associated with decreased blood loss.
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Carcinoma Ductal Pancreático/cirugía , Neoplasias Hepáticas/secundario , Arteria Mesentérica Superior/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Carcinoma Ductal Pancreático/secundario , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Arteria Mesentérica Superior/patología , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias Pancreáticas/patología , Tasa de SupervivenciaAsunto(s)
Hepatectomía/métodos , Vena Ilíaca/trasplante , Leiomiosarcoma/cirugía , Neoplasias Vasculares/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Vena Cava Inferior/cirugía , Adulto , Femenino , Humanos , Imagenología Tridimensional , Leiomiosarcoma/diagnóstico , Hígado/irrigación sanguínea , Tomografía Computarizada por Rayos X , Trasplante Homólogo , Neoplasias Vasculares/diagnóstico , Vena Cava Inferior/diagnóstico por imagenRESUMEN
BACKGROUND: At the time of diagnosis, most patients with gallbladder cancer are in advanced stage and the cancer is unresectable. Long-term survivors are usually seen in a small number of patients with incidental gallbladder cancer. This study aimed to identify preoperative predictors of incidental gallbladder cancer in elderly patients. METHODS: A total of 4014 patients of more than 44 years old who had undergone cholecystectomy at our department from January 2000 to December 2010 were retrospectively reviewed. Univariate and multivariate modalities were used to identify the predictive factors of incidental gallbladder cancer. RESULTS: Twenty-nine of the 4014 patients who had undergone cholecystectomy for benign gallbladder diseases were histologically diagnosed as having incidental gallbladder cancer. Multivariate analysis identified that elevated carbohydrate antigen 19-9 combined with carcinoembryonic antigen and/or carbohydrate antigen 125 (P=0.045), a gallbladder polyp greater than or equal to 1.2 cm (P=0.043) and focal gallbladder wall thickening of more than or equal to 5 mm (P=0.002) were predictive factors of incidental gallbladder cancer. CONCLUSION: Cholecystectomy is suggested for patients with these predictive factors and intraoperative frozen section should be considered to rule out carcinoma.
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Neoplasias de la Vesícula Biliar/diagnóstico , Hallazgos Incidentales , Adulto , Distribución por Edad , Factores de Edad , Anciano , Antígeno Ca-125/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , China , Colecistectomía , Femenino , Neoplasias de la Vesícula Biliar/sangre , Neoplasias de la Vesícula Biliar/patología , Humanos , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Regulación hacia ArribaAsunto(s)
Síndrome de Budd-Chiari/diagnóstico por imagen , Síndrome de Budd-Chiari/cirugía , Enfermedad Hepática en Estado Terminal/cirugía , Venas Hepáticas , Vena Cava Inferior , Adulto , Síndrome de Budd-Chiari/complicaciones , Circulación Colateral , Enfermedad Hepática en Estado Terminal/etiología , Venas Hepáticas/diagnóstico por imagen , Humanos , Trasplante de Hígado , Imagen por Resonancia Magnética , Masculino , Vena Cava Inferior/diagnóstico por imagenRESUMEN
OBJECTIVE: To investigate the clinical predictors of cytomegalovirus (CMV) infection after liver transplantation. METHODS: The clinical data of 182 patients (146 male and 36 female with a mean age of (50 ± 7) years) receiving liver transplantation in Beijing Chaoyang Hospital between January 2004 and December 2008 were retrospectively analyzed.All patients were divided into two groups, namely the CMV infection group (n=24) and the control group (n=158). Logistic regression was used to identify the predictive factors of postoperative CMV infection. RESULTS: According to univariate analysis results, the factors for CMV infection were acute liver failure (P=0.032), MELD score ≥ 30 (P=0.001), liver retransplantation (P=0.002), acute rejection (P=0.000) and delayed graft function (P=0.022). According to multi-analysis results, MELD score ≥ 30 (P=0.037, 95%CI:1.194-271.461) and acute rejection (P=0.033, 95%CI:1.179-51.863) were proved to be independent predictors by multivariate analysis. CONCLUSION: The study indicates that MELD score ≥ 30 and acute rejection are the independent predictors of CMV infection.
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Infecciones por Citomegalovirus/diagnóstico , Rechazo de Injerto , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/virología , Adulto , Beijing , Enfermedad Hepática en Estado Terminal/diagnóstico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Reoperación , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Purpose: Whether the diagnosis of non-alcoholic fatty liver disease or metabolic dysfunction-associated fatty disease has a different impact on liver transplant recipients with hepatocellular carcinoma is not yet clear. Methods: Data from a two-center retrospective cohort study were collected to compare and investigate the differences between non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in clinicopathologic parameters and prognosis among liver transplant recipients with hepatocellular carcinoma. Results: A total of 268 liver transplant recipients with hepatocellular carcinoma were included. The prevalence among pre- and post-transplant metabolic dysfunction-associated fatty liver disease was 10.82% and 30.22%, while for non-alcoholic fatty liver disease, it was 7.09% and 26.87%, respectively. The clinicopathological parameters were similar between the two pre-transplant groups. In contrast, the post-transplant group with metabolic dysfunction-associated fatty liver disease exhibited a higher prevalence of diabetes mellitus and a greater body mass index. However, the other parameters were similar between the two post-transplant groups (p > 0.05). Factors such as the largest tumor size > 4 cm, microvascular invasion, lack of tumor capsule, post-transplant metabolic dysfunction-associated fatty liver disease, and decreased post-transplant lymphocyte percentage were related to an increased risk of recurrence. Conclusion: In patients undergone liver transplantation for hepatocellular carcinoma, the diagnosis of metabolic dysfunction-associated fatty disease is more strongly associated with metabolic abnormalities than the diagnosis of non-alcoholic fatty liver disease and is an independent predictor of hepatocellular carcinoma recurrence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Trasplante de Hígado/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/cirugía , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Masculino , Femenino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Adulto , AncianoRESUMEN
BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.
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Background: Managing hepatocellular carcinoma (HCC) presents significant clinical challenges, often necessitating orthotopic liver transplantation (OLT). To mitigate the risk of iatrogenic metastasis during OLT and reduce posttransplantation recurrence (PTR), we introduced the "no-touch" left (NTL) approach for recipient hepatectomy in OLT. Methods: In this retrospective cohort study, our aim was to compare the safety and PTR rates in patients undergoing OLT via either the NTL technique or the conventional approach for recipient hepatectomy. We included 106 patients who met the Hangzhou criteria and exhibited a high tumor burden in the right lobe, with 50 patients assigned to the NTL group and 56 to the conventional group. The primary endpoint was the 1-y PTR rate, whereas secondary endpoints encompassed the safety of the NTL approach, PTR rates at 2 and 5 y, and overall survival. Results: Baseline demographics and clinical characteristics showed no significant differences between the groups. The NTL approach exhibited major surgical outcomes similar to those of the conventional approach. The cumulative PTR rates at 1, 2, and 5 y were 14.0% in the NTL group, compared with 24.5%, 35.8%, and 35.8% in the conventional group (Pâ =â 0.013). Cumulative overall survival rates at 1, 2, and 5 y were 94.0%, 91.9%, and 89.7% in the NTL group and 88.7%, 75.5%, and 72.5% in the conventional group (Pâ =â 0.03). Conclusions: This innovative surgical technique enhances safety and significantly reduces the risk of PTR, leading to improved long-term survival. Further prospective studies with larger cohorts and longer follow-up periods are needed to validate our findings and establish the NTL approach as a standard practice in OLT.
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BACKGROUND: Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS: A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS: There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS: Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.
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Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/cirugía , Virus de la Hepatitis B , Neoplasias Hepáticas/etiología , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Inhibidores de la Calcineurina , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Hepatitis B/complicacionesRESUMEN
Pancreatic cancer (PC) is a stubborn malignancy with high lethality and a low 5-year overall survival (OS) rate. Collagen type VII α1 chain (COL7A1), a major component of the extracellular matrix, serves important roles in numerous physiological processes and various illnesses. COL7A1 protein acts as an anchoring fibril between the external epithelial cells and the underlying stroma, and mutation of COL7A1 could cause recessive dystrophic epidermolysis bullosa. Raw data for PC were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus database, and raw data for the normal pancreas were obtained from the Genotype-Tissue Expression database. COL7A1 mRNA expression in PC tissues was compared with that in either paired (GSE15471 dataset) or unpaired (all other data) normal pancreas tissues. The association between COL7A1 mRNA expression and clinicopathological factors was assessed using logistic regression analysis. Cox analysis and Kaplan-Meier analysis were used to evaluate the role of COL7A1 mRNA expression in prognosis and nomograms were constructed. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed to evaluate the relevant functions of COL7A1 and correlation with immune cell infiltration. Furthermore, reverse transcription-quantitative PCR was used to assess the mRNA expression levels of COL7A1 in PC. The present study demonstrated that COL7A1 mRNA expression was higher in PC tissues compared with in normal pancreas tissues. The Kaplan-Meier survival analysis indicated that patients with PC with high COL7A1 mRNA expression had shorter overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) times compared with patients with PC with low COL7A1 mRNA expression. Multivariate analysis demonstrated that COL7A1 mRNA expression was an independent risk factor for OS, DSS and PFI. Nomogram and calibration plots were constructed to predict the prognosis of patients with PC. GSEA demonstrated that high mRNA expression levels of COL7A1 were associated with multiple cancer-related pathways. ssGSEA analysis indicated that COL7A1 expression was positively associated with natural killer CD56bright cells and T helper (Th)2 cells, and negatively associated with Th17 cells and eosinophils. The results of the present study suggested that COL7A1 could be an independent biomarker and an influential moderator of immune infiltration in PC.
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Pancreatic cancer (PC) is notorious for its parallel morbidity and mortality rates. Recently, necroptosis, a form of programmed cell necrosis, has gained popularity for its role in tumorigenesis and metastasis. In this study, we explored the expression of necroptosis-related genes in PC and normal pancreatic tissues and identified 52 differentially expressed genes (DEGs). The Cox regression analysis was applied to construct the prognostic risk model, which divided patients into high- and low-risk groups. PC patients in the low-risk group showed a significantly better overall survival (OS) than those in the high-risk group. We further validated the prognostic role in ICGC cohort. Further, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and tumor microenvironment (TME) analysis were used to explore the underlying mechanisms. Notably, based on the gene signature, we revealed that the risk score was strongly related to the sensitivity of chemotherapy. In conclusion, necroptosis-related genes serve as an important immune mediator, and the risk model could be used to predict the survival and to guide the development of precision drugs for patients with PC.
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Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Necroptosis/genética , Neoplasias Pancreáticas/genética , Pronóstico , Microambiente Tumoral/genética , Neoplasias PancreáticasRESUMEN
BACKGROUND: Tolerance is more easily induced in liver transplant models than in other organs; CD8+CD45RClowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8+CD45RClowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8+CD45RClowTregs effect remains to be investigated. METHODS: A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8+CD45RClowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR). RESULTS: The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8+CD45RClowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8+CD45RClowTregs were positively associated with the frequency of pDCs (P = 0.001, r2 = 0.775). The protein and mRNA expression of IL-10 and TGF-ß in the allograft group were increased, possibly being responsible for tolerance induction. CONCLUSION: CD8+CD45RClowT cells interact with pDCs through the induction of IL-10 and TGF-ß expression and are responsible for inducing immune tolerance in rat liver transplantation.
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Trasplante de Hígado , Linfocitos T Reguladores , Animales , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Células Dendríticas/metabolismo , Rechazo de Injerto , RatasRESUMEN
BACKGROUND: Whether standard lymphadenectomy or extended lymphadenectomy should be performed is still under debate during pancreaticoduodenectomy (PD). We aimed to compare their morbidity and mortality rates among patients with pancreatic head cancer (PHC). METHODS: In this retrospective study, a total of 322 patients were enrolled. According to the scope of intraoperative lymph node dissection, patients were divided into extended lymphadenectomy group (n=120) and standard lymphadenectomy group (n=202). Based on the resectability of the tumor, there were 198 cases of resectable PHC and 124 cases of borderline resectable PHC, respectively, in which further stratified analysis was carried out according to the extent of lymph node dissection. RESULTS: All patients completed the operation successfully, with a perioperative morbidity rate of 27.9% and mortality rate of 0.9%. As for the overall patients, patients in the extended lymphadenectomy group had higher neutrophil-to-lymphocyte ratio (NLR), longer operation time, more intraoperative blood loss, lymph node dissection and patients with borderline resectable pancreatic head cancer (BRPHC) (P<0.05). The 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 71.9%, 50.6%, 30.0% and 70.0%, 32.9%, 21.5%, respectively (P=0.068). With regards to patients with BRPHC, the number of lymph node dissection in the extended lymphadenectomy group was more (P<0.05), and the 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 60.7%, 43.3%, 27.4% and 43.2%, 17.7%, 17.7%, respectively (P=0.007). CONCLUSIONS: Patients with BRPHC tended to have vast lymph node metastasis. Extended lymphadenectomy can improve their long-term survival.
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Little is known about the shift of lymphocytes under the condition of the model for end-stage liver disease score and the follow-up period. Then, we detected the peripheral blood from liver transplant recipients by flow cytometry and compared the results. The model for end-stage liver disease score affected the percentages of T-cell subsets and B cells during the short-term follow-up period, but failed to influence the lymphocyte subsets during the long-term follow-up period. In contrast, the follow-up period not only affected the absolute counts of T-cell subsets and natural killer (NK) cells in patients with the low model for end-stage liver disease scores, but also influenced the percentages and absolute counts of T-cell subsets in patients with the high model for end-stage liver disease scores. In the two-way ANOVA, we further revealed that the model for end-stage liver disease score was associated with the percentages of T cells and CD4+ T cells and the absolute numbers of T-cell subsets and B cells, while the follow-up period was associated with the percentages of T-cell subsets and the absolute numbers of lymphocyte subsets. Therefore, patients with either the low model for end-stage liver disease scores or the long-term follow-up period are in a relatively activated immune condition.