BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs ...BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.展开更多
Non-alcoholic fatty liver disease（NAFLD） comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associ...Non-alcoholic fatty liver disease（NAFLD） comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associated with a significant increase in mortality rates, hepatic inflammation is, as this augments the risk of terminal liver disease, i.e.,cirrhosis, hepatic decompensation（liver failure） and/or hepatocellular carcinoma. Disease progression is usually slow, over a decade or more and, for the most part, remains asymptomatic. Recent estimates suggest that the global prevalence of NAFLD is high, about one in four. In most cases, NAFLD overlaps with overweight, obesity,cardiovascular disease and the metabolic syndrome with numerous contributing parameters including a dysregulation of adipose tissue, insulin resistance, type 2 diabetes, changes in the gut microbiome, neuronal and hormonal dysregulation and metabolic stress. NAFLD is diagnosed incidentally, despite its high prevalence. Non-invasive imaging techniques have emerged, making it possible to determine degree of steatosis as well asfibrosis. Despite this,the benefit of routine diagnostics remains uncertain. A better understanding of the（molecular） pathogenesis of NAFLD is needed combined with long-term studies where benefits of treatment can be assessed to determine costbenefit ratios. This review summarizes the current state of knowledge and possible areas of treatment.展开更多
AIM: To evaluate the ability of the McGill Brisbane Symptom Score (MBSS) to predict survival in resectable pancreatic head adenocarcinoma (PHA) patients.
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive te...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients,namely controlled attenuation parameter(CAP)and the serum biomarker cytokeratin 18(CK-18).We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018.Serial measurements of CK-18 and CAP were recorded.NAFLD and NASH were diagnosed by CAP≥270 dB/m,and a combination of CAP≥270 dB/m with CK-18>130.5 U/L,respectively.Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.RESULTS Overall,40 liver transplant recipients(mean age 57 years;70%males)were included.During a median follow-up of 16.8 mo(interquartile range 15.6-18.0),63.0%and 48.5%of patients developed NAFLD and NASH,respectively.On multivariable analysis,after adjusting for sex and alanine aminotransferase,body mass index was an independent predictor of development of NAFLD[adjusted hazard ratio(aHR):1.21,95%confidence interval(CI):1.04-1.41;P=0.01]and NASH(aHR:1.26,95%CI:1.06-1.49;P<0.01).Compared to liver histology,CAP had a 76%accuracy to diagnose NAFLD,while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo.Close follow-up and nutritional counselling should be planned in overweight patients.展开更多
基金the Human Resources Development Program for the Outstanding Talents in The Fifth People’s Hospital of Shanghai,Fudan University,No.2017WYRCJY09the Key Medical Speciality of The Fifth People’s Hospital of Shanghai,Fudan University,No.2017WY202K08
文摘BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.
文摘Non-alcoholic fatty liver disease（NAFLD） comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associated with a significant increase in mortality rates, hepatic inflammation is, as this augments the risk of terminal liver disease, i.e.,cirrhosis, hepatic decompensation（liver failure） and/or hepatocellular carcinoma. Disease progression is usually slow, over a decade or more and, for the most part, remains asymptomatic. Recent estimates suggest that the global prevalence of NAFLD is high, about one in four. In most cases, NAFLD overlaps with overweight, obesity,cardiovascular disease and the metabolic syndrome with numerous contributing parameters including a dysregulation of adipose tissue, insulin resistance, type 2 diabetes, changes in the gut microbiome, neuronal and hormonal dysregulation and metabolic stress. NAFLD is diagnosed incidentally, despite its high prevalence. Non-invasive imaging techniques have emerged, making it possible to determine degree of steatosis as well asfibrosis. Despite this,the benefit of routine diagnostics remains uncertain. A better understanding of the（molecular） pathogenesis of NAFLD is needed combined with long-term studies where benefits of treatment can be assessed to determine costbenefit ratios. This review summarizes the current state of knowledge and possible areas of treatment.
文摘AIM: To evaluate the ability of the McGill Brisbane Symptom Score (MBSS) to predict survival in resectable pancreatic head adenocarcinoma (PHA) patients.
基金the Canadian Donation and Transplantation Research Program of the Canadian Society of Transplantation(grant competition 2014)Sebastiani G is supported by a Senior Salary Award from Fonds de la Recherche en Santédu Quebéc(FRQS)(No.#296306).
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients,namely controlled attenuation parameter(CAP)and the serum biomarker cytokeratin 18(CK-18).We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018.Serial measurements of CK-18 and CAP were recorded.NAFLD and NASH were diagnosed by CAP≥270 dB/m,and a combination of CAP≥270 dB/m with CK-18>130.5 U/L,respectively.Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.RESULTS Overall,40 liver transplant recipients(mean age 57 years;70%males)were included.During a median follow-up of 16.8 mo(interquartile range 15.6-18.0),63.0%and 48.5%of patients developed NAFLD and NASH,respectively.On multivariable analysis,after adjusting for sex and alanine aminotransferase,body mass index was an independent predictor of development of NAFLD[adjusted hazard ratio(aHR):1.21,95%confidence interval(CI):1.04-1.41;P=0.01]and NASH(aHR:1.26,95%CI:1.06-1.49;P<0.01).Compared to liver histology,CAP had a 76%accuracy to diagnose NAFLD,while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo.Close follow-up and nutritional counselling should be planned in overweight patients.
