Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and...Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and the main risk factors are:chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree.While the incidence of intra-hepatic CC is increasing,the incidence of extra-hepatic CC is trending down.The only curative treatment for CC is surgical resection with negative margins.Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy.Magnetic resonance imaging/magnetic resonance cholangiopancreatography,positron emission tomography scan,endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging.Adjuvant therapy,palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC.For most of these patients biliary stenting provides effective palliation.Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief,improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization,hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.展开更多
It has long been appreciated that there is a direct relationship between the intensity and duration of inflammatory bowel diseases (IBD) and increasing intestinal cancer risk but which elements of the inflammatory res...It has long been appreciated that there is a direct relationship between the intensity and duration of inflammatory bowel diseases (IBD) and increasing intestinal cancer risk but which elements of the inflammatory response are responsible have not been identified. Anti-TNF drugs have been successful at treating IBD but considering the presumed anti-tumor activity of TNF, it is important to understand whether the treatment impacts on the patients’ intestinal cancer risk. We modeled this relationship by “treating mice lacking TNF receptors with a colon cancer causing combination of azoxymethane followed by repeated dextran sulphate sodium exposures (AOM + DSS regime). TNF receptor type1 gene deficient (TNFR1-/-) and TNFR2-/- mice experienced similar clinical illnesses and colonic inflammation as C57BL/6 wildtype controls during the AOM + DSS regime. Despite the inflammation, TNFR1-/- mice developed significantly fewer colon tumors than the other strains. The reduced tumor incidence was a product of the combined lack of receptor expression on hematopoietic and nonhematopoietic cells, shown using bone marrow cell chimeras of wildtype and TNFR1-/- mice. As oxidative damage is a potent contributing factor to tumorigenesis and inflammatory leukocytes make copious amounts of reactive oxygen radicals, we measured oxidative damage in the animals’ colons. TNFR1-/- mice showed less damage compared to the other strains. We subsequently examined mice deficient in their leukocyte NADPH oxidative pathway (Nox2-/-) for their cancer incidence using the AOM + DSS regime. Nox2-/- mice became inflamed but had fewer tumors than wildtype mice. We conclude that TNF promotes colon cancer including through promoting oxidative processes utilizing TNFR1 in leukocytes. Moreover, the C57BL/6 strain can be used to dissociate mechanisms of colon inflammation from tumorigenic processes. We interpret our results to mean that IBD patients on TNF antagonist therapies will potentially benefit with reduced colon cancer risk even if they do not respond with reduced inflammation.展开更多
Most studies revealed that ischemic time has substantial role in occurrence of delayed graft function (DGF) after deceased donor kidney transplantation. However, less is known about the potential impact of surgical ti...Most studies revealed that ischemic time has substantial role in occurrence of delayed graft function (DGF) after deceased donor kidney transplantation. However, less is known about the potential impact of surgical times on early outcomes following live donor kidney transplantation. A retrospective cohort of 189 consecutive laparoscopic live donor kidney transplant (LDKT) recipients from January 2006 to August 2012 was analyzed to reveal the impact of pneumoperitoneum time (PT) and anastomosis time (AT) on donor and recipient length of hospital stay and early graft function (EGF). DGF was observed in 13 (6.8%) patients while slow graft function (SGF) was seen in 27 (14%) of the recipients. The median AT was 28 minutes (interquartile range 23, 35 minutes). AT was associated with DGF (Odds Ratio [OR] 1.044, per minute, 95% CI 1.007, 1.082, p = 0.018). Median recipient length of hospital stay was 8 (interquartile range 7, 11) days. Every 13.5 minutes of longer AT was associated with 1 extra day in hospital. The median PT was 180 minutes (interquartile range 144, 234 minutes). PT was associated with both DGF (OR 1.013 per minute, 95% CI 1.005, 1.021, p = 0.001) and SGF (OR 1.009 per minute, 95% CI 1.002, 1.016, p = 0.016). Every extra hour of PT was associated with 0.42 more days in hospital for the donor. Surgical times may be underestimated variables in dictating use of hospital resources. The effect of surgical times on long term hard outcomes entails further study.展开更多
Background: Patients with advanced heart disease are at risk from sudden death; however, benefit from implantable cardioverter defibrillators(ICDs) may be limited as a result of early mortality from other causes. The ...Background: Patients with advanced heart disease are at risk from sudden death; however, benefit from implantable cardioverter defibrillators(ICDs) may be limited as a result of early mortality from other causes. The objective of this study was to develop a model to predict mortality within the first year after ICD implantation. Methods and Results: A retrospective analysis was performed of 469 consecutive patients who underwent ICD implantation at a single tertiary- care center from 1999 to 2002. Vital status was determined from the Social Security Death Index. Patients were randomized into prediction and validation cohorts. A risk score was derived from the prediction cohort by multivariate logistic regression and applied to the validation cohort. One point was assigned for each variable in the risk score(age>80 years, history of atrial fibrillation, creatinine> 1.8 mg/dL,New York Heart Association class III or IV). One- year mortality significantly increased with increasing risk score in both the prediction and validation cohorts. Validation cohort mortality was 3.4% for 0 points, 4.3% for 1 point, 17% for 2 points, and 33% for ≥ 3 points(P for trend< .0001). A risk score ≥ 2 predicted a 1- year mortality rate of 21% , whereas a risk score< 2 predicted a mortality rate of 4% at 1 year(P< .0001). Conclusion: A risk score using simple clinical criteria may identify patients at high risk of early mortality after ICD implantation. This may be helpful in consideration of ICD risk/benefit for individual patients. Further studies conducted in a prospective manner using these clinical criteria are warranted.展开更多
Background: Although hepatitis C virus (HCV) transmission through tissue transplantation has been rarely reported, a donor with undetected viremia may infect several recipients. A patient developed acute hepatitis C s...Background: Although hepatitis C virus (HCV) transmission through tissue transplantation has been rarely reported, a donor with undetected viremia may infect several recipients. A patient developed acute hepatitis C shortly after tissue transplantation. Ninety-one tissues or organs had been recovered from the donor. Objective: To determine whether the donor was the source of infection and the extent of transmission to other organ and tissue recipients. Design: Descriptive epidemiologic study; serum testing for HCV infection. Setting: Recipients were located in 16 states and 2 other countries. Participants: Donor and graft recipients. Measurements: Hepatitis C virus infection was defined as the presence of anti-HCV or HCV RNA. The authors determined the genetic relatedness of viral isolates from the donor and recipients by genotype comparison and quasi-species analysis. Results: The donor was anti-HCV-negative but was HCV RNA-positive (genotype 1a). Forty persons received transplants during 22 months. Five persons were HCV-infected before transplantation or had a genotype other than 1a, and 5 persons had no post-transplantation serum specimens available. Of the remaining 30 recipients, HCV infection occurred in 8 recipients: 3 of 3 organ recipients, 1 of 2 saphenous vein recipients, 1 of 3 tendon recipients, and 3 of 3 tendon with bone recipients. These 8 recipients had viral isolates genetically related to those of the donor. No cases occurred in recipients of skin (n = 2), cornea (n = 1), or irradiated bone (n = 16). Limitations: Post-transplantation serum specimens were unavailable for 5 recipients. Conclusions: An anti-HCV-negative donor was the source of HCV infection for 8 recipients of organs or tissues. Although HCV transmission from anti-HCV-negative donors is probably uncommon, changes in donor screening to include routine testing for HCV RNA merit further consideration to improve the safety of transplantation.展开更多
Introduction Nitrate-induced headache is common and may signify responsive cerebral vasculature.We assessed the relationship between nitrate headache and outcome in patients with acute stroke.Materials and methods Pat...Introduction Nitrate-induced headache is common and may signify responsive cerebral vasculature.We assessed the relationship between nitrate headache and outcome in patients with acute stroke.Materials and methods Patients were those randomised to glyceryl trinitrate(GTN)versus no GTN in the efficacy of nitric oxide in stroke trial.Development of headache by end of treatment(day 7),and functional outcome(modified Rankin Scale,primary outcome)at day 90,were assessed.Analyses are adjusted for baseline prognostic factors and give OR and mean difference(MD)with 95%CI.Results In 4011 patients,headache was more common in GTN than control(360,18.0% vs 170,8.5%;p<0.001).Nitrate-related headache was associated with:younger age,female sex,higher diastolic blood pressure,non-total anterior circulation syndrome,milder stroke and absence of dysphasia(p<0.05).Nitrate headache was not associated with improved functional outcome(OR 0.90,95% CI 0.73 to 1.10,p=0.30)or death(day 90)(HR 0.64,95% CI 0.40 to 1.02,p=0.062),but reduced death or deterioration(day 7)(OR 0.45,95% CI 0.25 to 0.82),death in hospital(OR 0.44,95% CI 0.22 to 0.88)and improved activities of daily living(Barthel index,MD 3.7,95% CI 0.3 to 7.1)and cognition(telephone interview cognitive screen,MD 2.0,95% CI 0.7 to 3.3)(day 90).Non-nitrate headache was not associated with death,disability or cognition.Discussion and conclusion Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90,which was not seen with non-nitrate headache.展开更多
文摘Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and the main risk factors are:chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree.While the incidence of intra-hepatic CC is increasing,the incidence of extra-hepatic CC is trending down.The only curative treatment for CC is surgical resection with negative margins.Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy.Magnetic resonance imaging/magnetic resonance cholangiopancreatography,positron emission tomography scan,endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging.Adjuvant therapy,palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC.For most of these patients biliary stenting provides effective palliation.Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief,improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization,hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.
文摘It has long been appreciated that there is a direct relationship between the intensity and duration of inflammatory bowel diseases (IBD) and increasing intestinal cancer risk but which elements of the inflammatory response are responsible have not been identified. Anti-TNF drugs have been successful at treating IBD but considering the presumed anti-tumor activity of TNF, it is important to understand whether the treatment impacts on the patients’ intestinal cancer risk. We modeled this relationship by “treating mice lacking TNF receptors with a colon cancer causing combination of azoxymethane followed by repeated dextran sulphate sodium exposures (AOM + DSS regime). TNF receptor type1 gene deficient (TNFR1-/-) and TNFR2-/- mice experienced similar clinical illnesses and colonic inflammation as C57BL/6 wildtype controls during the AOM + DSS regime. Despite the inflammation, TNFR1-/- mice developed significantly fewer colon tumors than the other strains. The reduced tumor incidence was a product of the combined lack of receptor expression on hematopoietic and nonhematopoietic cells, shown using bone marrow cell chimeras of wildtype and TNFR1-/- mice. As oxidative damage is a potent contributing factor to tumorigenesis and inflammatory leukocytes make copious amounts of reactive oxygen radicals, we measured oxidative damage in the animals’ colons. TNFR1-/- mice showed less damage compared to the other strains. We subsequently examined mice deficient in their leukocyte NADPH oxidative pathway (Nox2-/-) for their cancer incidence using the AOM + DSS regime. Nox2-/- mice became inflamed but had fewer tumors than wildtype mice. We conclude that TNF promotes colon cancer including through promoting oxidative processes utilizing TNFR1 in leukocytes. Moreover, the C57BL/6 strain can be used to dissociate mechanisms of colon inflammation from tumorigenic processes. We interpret our results to mean that IBD patients on TNF antagonist therapies will potentially benefit with reduced colon cancer risk even if they do not respond with reduced inflammation.
文摘Most studies revealed that ischemic time has substantial role in occurrence of delayed graft function (DGF) after deceased donor kidney transplantation. However, less is known about the potential impact of surgical times on early outcomes following live donor kidney transplantation. A retrospective cohort of 189 consecutive laparoscopic live donor kidney transplant (LDKT) recipients from January 2006 to August 2012 was analyzed to reveal the impact of pneumoperitoneum time (PT) and anastomosis time (AT) on donor and recipient length of hospital stay and early graft function (EGF). DGF was observed in 13 (6.8%) patients while slow graft function (SGF) was seen in 27 (14%) of the recipients. The median AT was 28 minutes (interquartile range 23, 35 minutes). AT was associated with DGF (Odds Ratio [OR] 1.044, per minute, 95% CI 1.007, 1.082, p = 0.018). Median recipient length of hospital stay was 8 (interquartile range 7, 11) days. Every 13.5 minutes of longer AT was associated with 1 extra day in hospital. The median PT was 180 minutes (interquartile range 144, 234 minutes). PT was associated with both DGF (OR 1.013 per minute, 95% CI 1.005, 1.021, p = 0.001) and SGF (OR 1.009 per minute, 95% CI 1.002, 1.016, p = 0.016). Every extra hour of PT was associated with 0.42 more days in hospital for the donor. Surgical times may be underestimated variables in dictating use of hospital resources. The effect of surgical times on long term hard outcomes entails further study.
文摘Background: Patients with advanced heart disease are at risk from sudden death; however, benefit from implantable cardioverter defibrillators(ICDs) may be limited as a result of early mortality from other causes. The objective of this study was to develop a model to predict mortality within the first year after ICD implantation. Methods and Results: A retrospective analysis was performed of 469 consecutive patients who underwent ICD implantation at a single tertiary- care center from 1999 to 2002. Vital status was determined from the Social Security Death Index. Patients were randomized into prediction and validation cohorts. A risk score was derived from the prediction cohort by multivariate logistic regression and applied to the validation cohort. One point was assigned for each variable in the risk score(age>80 years, history of atrial fibrillation, creatinine> 1.8 mg/dL,New York Heart Association class III or IV). One- year mortality significantly increased with increasing risk score in both the prediction and validation cohorts. Validation cohort mortality was 3.4% for 0 points, 4.3% for 1 point, 17% for 2 points, and 33% for ≥ 3 points(P for trend< .0001). A risk score ≥ 2 predicted a 1- year mortality rate of 21% , whereas a risk score< 2 predicted a mortality rate of 4% at 1 year(P< .0001). Conclusion: A risk score using simple clinical criteria may identify patients at high risk of early mortality after ICD implantation. This may be helpful in consideration of ICD risk/benefit for individual patients. Further studies conducted in a prospective manner using these clinical criteria are warranted.
文摘Background: Although hepatitis C virus (HCV) transmission through tissue transplantation has been rarely reported, a donor with undetected viremia may infect several recipients. A patient developed acute hepatitis C shortly after tissue transplantation. Ninety-one tissues or organs had been recovered from the donor. Objective: To determine whether the donor was the source of infection and the extent of transmission to other organ and tissue recipients. Design: Descriptive epidemiologic study; serum testing for HCV infection. Setting: Recipients were located in 16 states and 2 other countries. Participants: Donor and graft recipients. Measurements: Hepatitis C virus infection was defined as the presence of anti-HCV or HCV RNA. The authors determined the genetic relatedness of viral isolates from the donor and recipients by genotype comparison and quasi-species analysis. Results: The donor was anti-HCV-negative but was HCV RNA-positive (genotype 1a). Forty persons received transplants during 22 months. Five persons were HCV-infected before transplantation or had a genotype other than 1a, and 5 persons had no post-transplantation serum specimens available. Of the remaining 30 recipients, HCV infection occurred in 8 recipients: 3 of 3 organ recipients, 1 of 2 saphenous vein recipients, 1 of 3 tendon recipients, and 3 of 3 tendon with bone recipients. These 8 recipients had viral isolates genetically related to those of the donor. No cases occurred in recipients of skin (n = 2), cornea (n = 1), or irradiated bone (n = 16). Limitations: Post-transplantation serum specimens were unavailable for 5 recipients. Conclusions: An anti-HCV-negative donor was the source of HCV infection for 8 recipients of organs or tissues. Although HCV transmission from anti-HCV-negative donors is probably uncommon, changes in donor screening to include routine testing for HCV RNA merit further consideration to improve the safety of transplantation.
基金ENOS was funded by the UK Medical Research Council(G0501797)。
文摘Introduction Nitrate-induced headache is common and may signify responsive cerebral vasculature.We assessed the relationship between nitrate headache and outcome in patients with acute stroke.Materials and methods Patients were those randomised to glyceryl trinitrate(GTN)versus no GTN in the efficacy of nitric oxide in stroke trial.Development of headache by end of treatment(day 7),and functional outcome(modified Rankin Scale,primary outcome)at day 90,were assessed.Analyses are adjusted for baseline prognostic factors and give OR and mean difference(MD)with 95%CI.Results In 4011 patients,headache was more common in GTN than control(360,18.0% vs 170,8.5%;p<0.001).Nitrate-related headache was associated with:younger age,female sex,higher diastolic blood pressure,non-total anterior circulation syndrome,milder stroke and absence of dysphasia(p<0.05).Nitrate headache was not associated with improved functional outcome(OR 0.90,95% CI 0.73 to 1.10,p=0.30)or death(day 90)(HR 0.64,95% CI 0.40 to 1.02,p=0.062),but reduced death or deterioration(day 7)(OR 0.45,95% CI 0.25 to 0.82),death in hospital(OR 0.44,95% CI 0.22 to 0.88)and improved activities of daily living(Barthel index,MD 3.7,95% CI 0.3 to 7.1)and cognition(telephone interview cognitive screen,MD 2.0,95% CI 0.7 to 3.3)(day 90).Non-nitrate headache was not associated with death,disability or cognition.Discussion and conclusion Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90,which was not seen with non-nitrate headache.