Cancer development is essentially a tissue remodeling process in which normal tissue is substituted with cancer tissue. A crucial role in this process is attributed to proteolytic degradation of the extracellular matr...Cancer development is essentially a tissue remodeling process in which normal tissue is substituted with cancer tissue. A crucial role in this process is attributed to proteolytic degradation of the extracellular matrix (ECM). Degradation of ECM is initiated by proteases, secreted by different cell types, participating in tumor cell invasion and increased expression or activity of every known class of proteases (metallo-, serine-, aspartyl-, and cysteine) has been linked to malignancy and invasion of tumor cells. Proteolytic enzymes can act directly by degrading ECM or indirectly by activating other proteases, which then degrade the ECM. They act in a determined order, resulting from the order of their activation. When proteases exert their action on other proteases, the end result is a cascade leading to proteolysis. Presumable order of events in this complicated cascade is that aspartyl protease (cathepsin D) activates cysteine proteases (e.g. cathepsin B) that can activate pro-uPA. Then active uPA can convert plasminogen into plasmin. Cathepsin B as well as plasmin are capable of degrading several components of tumor stroma and may activate zymogens of matrix metalloproteinases, the main family of ECM degrading proteases. The activities of these proteases are regulated by a complex array of activators, inhibitors and cellular receptors. In physiological conditions the balance exists between proteases and their inhibitors. Proteolytic-antiproteolytic balance may be of major significance in the cancer development. One of the reasons for such a situation is enhanced generation of free radicals observed in many pathological states. Free radicals react with main cellular components like proteins and lipids and in this way modify proteolytic-antiproteolytic balance and enable penetration damaging cellular membrane. All these lead to enhancement of proteolysis and destruction of ECM proteins and in consequence to invasion and metastasis.展开更多
AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium. METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and p...AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium. METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and prior endoscopic sphincterotomy (ES) for benign disease formed the fi rst group. The median time from ES was 42 mo (range 8-144 mo). Another 25 patients with a median age of 76 years (range 44-94 mo) and similar characteristics who underwent current endoscopic retrograde cholangio-pancreatography (ERCP) and ES for benign disease formed the second group (control group). Brush cytology of the biliary tree with p53 immunocytology was performed in all patients of both groups. ERCPs and recruitment were conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio Hospital, Athens, from October 2006 to June 2010. RESULTS: No cases were positive or suspicious for malignancy. Epithelial atypia was higher in the first group (32% vs 8% in the second group, P = 0.034). Acute cholangitis and previous biliary operation rates were also higher in the fi rst group (acute cholangitis, 60% vs 24% in the second group, P = 0.01; previous biliary operation, 76% vs 24% in the second group, P = 0.001). Subgroup analysis showed that previous ES was the main causal factor for atypia, which was not related to the time interval from the ES (P = 0.407). Two patients (8%) with atypia in the fi rst group were p53-positive. CONCLUSION: ES causes biliary epithelial atypia that represents mostly reactive/proliferative rather than premalignant changes. The role of p53 immunoreactivity in biliary atypia needs to be further studied.展开更多
TO THE EDITORAlthough the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide[1], and is the most common cancer in East Asian countries such as Korea ...TO THE EDITORAlthough the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide[1], and is the most common cancer in East Asian countries such as Korea and Japan[2].In terms of the genetics of gastric cancer, mutations in CDH1 (E-cadberin) have been associated with hereditary diffuse gastric cancer (HDGC). The first germline mutation in CDH1 was reported in a large Maori HDGC family[1],with subsequent corroborations in Western and Asian HDGC families[3-5], CDH1 mutations are believed to be associated with up to 50% of HDGC families[5], but have not been linked with sporadic or intestinal types of gastric cancer[5].展开更多
AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (...AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (40 male,41 fe-male) who were diagnosed with fatty liver by ultraso-nographic scan and fulfi lled the inclusion criteria. First anamnesis,anthropometric,clinical,laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification. RESULTS:Sixty-nine of the 81 patients had nonalco-holic steatohepatitis (NASH),11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation. Comparisons were made between two groups of NASH patients,those with and without metabolic syndrome. We did not detect statistically significant differences in liver histology between NASH patients with and wit-hout metabolic syndrome. CONCLUSION:NASH can progress without metabolic risk factors or the presence of metabolic syndrome.展开更多
Objective: To identify the possible safety-influencing factors in use of the tonics of Chinese medicine. Methods: The related case reports published in periodicals published from 1949 to 2006 were analyzed with the bi...Objective: To identify the possible safety-influencing factors in use of the tonics of Chinese medicine. Methods: The related case reports published in periodicals published from 1949 to 2006 were analyzed with the bibliometrics method. Possibility on safety assessment of Chinese materia medica was discussed as well with the method of link analysis. Results: The total number of the tonics selected for the present study was 101, including 44 single drugs and 46 set prescriptions with adverse drug reactions (ADR) found in these tonics. It was found that ADR of 10 single drugs and 29 preparations were not specified in authoritative Chinese materia medica monographs. Among all the set prescriptions, the problem of injection has been standing on the top. Statistical analysis on single factor demonstrates that the most frequently referred ADR come from drug abuse (accounting for 29.20%), and overdose (24.54%). Conclusion: The safety problem of injection remains in a trend of robust growth at least for a period of time, thus reappraisal of the safety issue for the tonics of injection is imperative. It is essential for the public to take doctor’s advice to guarantee safe administration of the tonics, especially for the patients with allergic constitution or those suffering from the liver and heart diseases.展开更多
Background:Current guidelines recommend cholecystectomy for patients with mild acute biliary pancreatitis(MABP)during the index admission because it is associated with better outcomes.In this study,we aimed to assess ...Background:Current guidelines recommend cholecystectomy for patients with mild acute biliary pancreatitis(MABP)during the index admission because it is associated with better outcomes.In this study,we aimed to assess national trends in cholecystectomy during index admissions for MABP and to identify factors associated with cholecystectomy completion and 30-day readmission.Methods:Using diagnostic codes and the National Readmissions Database,we identified patients admitted with MABP between 2010 and 2014.Differences in cholecystectomy rates were computed on the basis of various characteristics.We conducted a multivariable analysis to identify factors associated with 30-day readmission and cholecystectomy during the same admission.Results:We identified 255,695 unique index MABP cases(41.3%male)and the 30-day readmission rate was 12.6%.Overall,43.8%underwent cholecystectomy and 25%underwent endoscopic retrograde cholangiopancreatography(ERCP)with sphincterotomy.We observed a decreasing trend in both procedures during the study period(P<0.001).In multivariate analysis,odds of 30-day readmission were reduced for patients undergoing ERCP with sphincterotomy(odds ratio,0.78;95%confidence interval,0.74–0.84)or cholecystectomy(odds ratio,0.37;95%confidence interval,0.35–0.39).Conclusions:For patients with MABP,cholecystectomy or ERCP with sphincterotomy during the index admission decreased the risk of 30-day readmission.Despite this benefit and national guidelines recommending cholecystectomy during the index MABP admission,the rate of cholecystectomies performed nationally decreased during the study period.Further research is needed to understand the implications and reasons underlying this deviation from guidelines.展开更多
基金Supported by Research Grant From the Polish State Committee for Scientific Research (3 PO5B 07922)
文摘Cancer development is essentially a tissue remodeling process in which normal tissue is substituted with cancer tissue. A crucial role in this process is attributed to proteolytic degradation of the extracellular matrix (ECM). Degradation of ECM is initiated by proteases, secreted by different cell types, participating in tumor cell invasion and increased expression or activity of every known class of proteases (metallo-, serine-, aspartyl-, and cysteine) has been linked to malignancy and invasion of tumor cells. Proteolytic enzymes can act directly by degrading ECM or indirectly by activating other proteases, which then degrade the ECM. They act in a determined order, resulting from the order of their activation. When proteases exert their action on other proteases, the end result is a cascade leading to proteolysis. Presumable order of events in this complicated cascade is that aspartyl protease (cathepsin D) activates cysteine proteases (e.g. cathepsin B) that can activate pro-uPA. Then active uPA can convert plasminogen into plasmin. Cathepsin B as well as plasmin are capable of degrading several components of tumor stroma and may activate zymogens of matrix metalloproteinases, the main family of ECM degrading proteases. The activities of these proteases are regulated by a complex array of activators, inhibitors and cellular receptors. In physiological conditions the balance exists between proteases and their inhibitors. Proteolytic-antiproteolytic balance may be of major significance in the cancer development. One of the reasons for such a situation is enhanced generation of free radicals observed in many pathological states. Free radicals react with main cellular components like proteins and lipids and in this way modify proteolytic-antiproteolytic balance and enable penetration damaging cellular membrane. All these lead to enhancement of proteolysis and destruction of ECM proteins and in consequence to invasion and metastasis.
基金Supported by GC Medical Hellas who offered us free cytology brushes
文摘AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium. METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and prior endoscopic sphincterotomy (ES) for benign disease formed the fi rst group. The median time from ES was 42 mo (range 8-144 mo). Another 25 patients with a median age of 76 years (range 44-94 mo) and similar characteristics who underwent current endoscopic retrograde cholangio-pancreatography (ERCP) and ES for benign disease formed the second group (control group). Brush cytology of the biliary tree with p53 immunocytology was performed in all patients of both groups. ERCPs and recruitment were conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio Hospital, Athens, from October 2006 to June 2010. RESULTS: No cases were positive or suspicious for malignancy. Epithelial atypia was higher in the first group (32% vs 8% in the second group, P = 0.034). Acute cholangitis and previous biliary operation rates were also higher in the fi rst group (acute cholangitis, 60% vs 24% in the second group, P = 0.01; previous biliary operation, 76% vs 24% in the second group, P = 0.001). Subgroup analysis showed that previous ES was the main causal factor for atypia, which was not related to the time interval from the ES (P = 0.407). Two patients (8%) with atypia in the fi rst group were p53-positive. CONCLUSION: ES causes biliary epithelial atypia that represents mostly reactive/proliferative rather than premalignant changes. The role of p53 immunoreactivity in biliary atypia needs to be further studied.
文摘TO THE EDITORAlthough the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide[1], and is the most common cancer in East Asian countries such as Korea and Japan[2].In terms of the genetics of gastric cancer, mutations in CDH1 (E-cadberin) have been associated with hereditary diffuse gastric cancer (HDGC). The first germline mutation in CDH1 was reported in a large Maori HDGC family[1],with subsequent corroborations in Western and Asian HDGC families[3-5], CDH1 mutations are believed to be associated with up to 50% of HDGC families[5], but have not been linked with sporadic or intestinal types of gastric cancer[5].
基金Supported by Uludag University Scientific Project Grant
文摘AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (40 male,41 fe-male) who were diagnosed with fatty liver by ultraso-nographic scan and fulfi lled the inclusion criteria. First anamnesis,anthropometric,clinical,laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification. RESULTS:Sixty-nine of the 81 patients had nonalco-holic steatohepatitis (NASH),11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation. Comparisons were made between two groups of NASH patients,those with and without metabolic syndrome. We did not detect statistically significant differences in liver histology between NASH patients with and wit-hout metabolic syndrome. CONCLUSION:NASH can progress without metabolic risk factors or the presence of metabolic syndrome.
基金supported by the Supporting Program of "the National Eleventh Five-year Plan" for Science and Technology Research of China (No.2006BAI08B02-03)
文摘Objective: To identify the possible safety-influencing factors in use of the tonics of Chinese medicine. Methods: The related case reports published in periodicals published from 1949 to 2006 were analyzed with the bibliometrics method. Possibility on safety assessment of Chinese materia medica was discussed as well with the method of link analysis. Results: The total number of the tonics selected for the present study was 101, including 44 single drugs and 46 set prescriptions with adverse drug reactions (ADR) found in these tonics. It was found that ADR of 10 single drugs and 29 preparations were not specified in authoritative Chinese materia medica monographs. Among all the set prescriptions, the problem of injection has been standing on the top. Statistical analysis on single factor demonstrates that the most frequently referred ADR come from drug abuse (accounting for 29.20%), and overdose (24.54%). Conclusion: The safety problem of injection remains in a trend of robust growth at least for a period of time, thus reappraisal of the safety issue for the tonics of injection is imperative. It is essential for the public to take doctor’s advice to guarantee safe administration of the tonics, especially for the patients with allergic constitution or those suffering from the liver and heart diseases.
文摘Background:Current guidelines recommend cholecystectomy for patients with mild acute biliary pancreatitis(MABP)during the index admission because it is associated with better outcomes.In this study,we aimed to assess national trends in cholecystectomy during index admissions for MABP and to identify factors associated with cholecystectomy completion and 30-day readmission.Methods:Using diagnostic codes and the National Readmissions Database,we identified patients admitted with MABP between 2010 and 2014.Differences in cholecystectomy rates were computed on the basis of various characteristics.We conducted a multivariable analysis to identify factors associated with 30-day readmission and cholecystectomy during the same admission.Results:We identified 255,695 unique index MABP cases(41.3%male)and the 30-day readmission rate was 12.6%.Overall,43.8%underwent cholecystectomy and 25%underwent endoscopic retrograde cholangiopancreatography(ERCP)with sphincterotomy.We observed a decreasing trend in both procedures during the study period(P<0.001).In multivariate analysis,odds of 30-day readmission were reduced for patients undergoing ERCP with sphincterotomy(odds ratio,0.78;95%confidence interval,0.74–0.84)or cholecystectomy(odds ratio,0.37;95%confidence interval,0.35–0.39).Conclusions:For patients with MABP,cholecystectomy or ERCP with sphincterotomy during the index admission decreased the risk of 30-day readmission.Despite this benefit and national guidelines recommending cholecystectomy during the index MABP admission,the rate of cholecystectomies performed nationally decreased during the study period.Further research is needed to understand the implications and reasons underlying this deviation from guidelines.
