Hepatoblastoma(HB) is the most common primary liver tumor in children and accounts for two-thirds of all malignant liver neoplasms in the pediatric population. For patients with advanced HB(unresectable or unresponsiv...Hepatoblastoma(HB) is the most common primary liver tumor in children and accounts for two-thirds of all malignant liver neoplasms in the pediatric population. For patients with advanced HB(unresectable or unresponsive to chemotherapy), combined treatment with chemotherapy and liver transplantation is an excellent option. The etiology of HB is mostly obscure because of its extreme rarity although some inherited syndromes and very low birth weight have been associated with it. The prognosis for children with HB has significantly improved in the past three decades thanks to advancements in chemotherapy, surgical resection and postoperative care. In 2002 a surgical staging system called pretreatment extent of disease(PRETEXT) was designed to allow a universal, multidisciplinary approach to patients with HB. Between one-third to two-thirds of patients initially present with unresectable tumors or distant metastases, but up to 85% of these tumors become operable after neoadjuvant chemotherapy. Patients with PRETEXT categories 1, 2, and some 3 are referred for neoadjuvant chemotherapy followed by surgical resection with the goal of complete tumor removal. Classic treatments regimens include a combination of cisplatin, fluorouracil, and vincristine or cisplatin and doxorubicin. Liver transplantation is the only treatment option for unresectable HB. In 2010 the pediatric end-stage liver disease, a pediatric-specific scoring system that determines a patient's ranking on the liver transplant list, began to award additional "exception" points for patients with HB. We analyzed the Standard Transplant Analysis and Research dataset to assess the impact of changes in exception point criteria for HB on outcomes after liver transplantation at Texas Children's Hospital in Houston, Texas. We found that patients who were listed for transplantation with current HB exception criteria experienced a shorter waitlist time but survival was similar between the two eras.展开更多
Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the ...Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.展开更多
AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by...AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.展开更多
The number of children affected by the hepatitis C virus (HCV) in the United States is estimated to be between 23000 to 46000. The projected medical cost for children with HCV in the United States is upwards of 200 mi...The number of children affected by the hepatitis C virus (HCV) in the United States is estimated to be between 23000 to 46000. The projected medical cost for children with HCV in the United States is upwards of 200 million over the next decade. The implementation of routine screening of blood supply has virtually eliminated transmission via transfusion and vertical transmission is now the most common mode of infection in children. Infections acquired during infancy are more likely to spontaneously resolve and fibrosis of the liver tends to increase with age suggesting slow progressive histologic injury. Anti-viral treatment may be warranted in children with persistently elevated liver enzymes or with significant fibrosis on liver biopsy. Current standard of care includes weekly pegylated interferon and ribavirin twice daily. Predictors of high sustained viral response include genotype 2 and 3 and low viral load in children with genotype 1 (< 600000 IU/mL). Triple therapy is associated with a significantly higher rate of sustained virologic response (> 90%). Only 34 pediatric patients were transplanted with hepatitis C between January 2008 and April 2013. The majority of pediatric patients were born prior to universal screening of blood products and, as of June 2013, there are only two pediatric patients awaiting liver transplantation for end-stage liver disease secondary to hepatitis C. Pediatric survival rates post-transplant are excellent but graft survival is noticeably reduced compared to adults (73.73% for pediatric patients at one year compared to 87.69% in adult patients). New safe potent, and all-oral effective antiviral therapies for recurrent HCV should help increase graft survival.展开更多
BACKGROUND Recurrent hepatitis C virus(HCV)infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation.Direct-acting antiviral(DAA)therapy has been ad...BACKGROUND Recurrent hepatitis C virus(HCV)infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation.Direct-acting antiviral(DAA)therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting.However,there are insufficient data regarding its efficacy in liver transplant(LT)recipients with a history of hepatocellular carcinoma(HCC),and the risk of HCC recurrence after DAA therapy is unknown.predictors of DAA treatment failure and HCC recurrence in LT recipients.METHODS A total of 106 LT recipients given DAAs for recurrent HCV infection from 2015 to 2019 were identified(68 with and 38 without HCC).Descriptive statistics and logistic regression models were used to estimate the multivariate odds ratios and respective 95%confidence intervals for predictors of treatment failure and HCC recurrence.RESULTS Six patients(6%)experienced DAA therapy failure post-LT and 100(94%)had a sustained virologic response at follow-up week 12.A high alanine transaminase level>35 U/L at treatment week 4 was a significant predictor of treatment failure.Relapse to pre-LT DAA therapy is a predictor of post-LT HCC recurrence,P=0.04.DAA relapse post-LT was also associated with post-transplantation HCC recurrence,P=0.05.CONCLUSION DAAs are effective and safe in the treatment of recurrent HCV infection in LT recipients with history of HCC.Relapse to pre-and post-LT DAA therapy is associated with post-transplantation HCC recurrence.展开更多
AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years ...AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival(P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival(P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific(Br Ca) and other cause(OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1(IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-OH vitamin D were associated with(1) all cause mortality, and if so; and(2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models.RESULTS: The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447(82%) < 70 years and 120(18%) ≥ 70 years. There were 170 deaths: 106(62.3%) BrC a; 55(32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9(5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrC a and OC deaths were not significantly different by treatment arm(P = 0.40): tamoxifen patients experienced 50 BrC a and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 Br Ca and 23 OC deaths. Proportionately more deaths(P = 0.004) were from BrC a for patients< 70 years, where 70% of deaths were due to Br Ca, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index(BMI)(P = 0.02). Higher pathologic T and N were associated with more BrC 展开更多
Predictors of performance can aid coaches and trainers in prescribing exercise programs for rowing athletes. To date, most of the prediction models have been developed for runners and cyclists. Purpose: The aim of thi...Predictors of performance can aid coaches and trainers in prescribing exercise programs for rowing athletes. To date, most of the prediction models have been developed for runners and cyclists. Purpose: The aim of this study was to develop a regression model to predict performance of a simulated 2 kilometer rowing ergometer time trial. Methods: A group of mixed gender rowing athletes (n = 12) completed in a counterbalanced order a 2 kilometer rowing time trial and a continuous progressively incremented graded exercise test on a rowing ergometer. Subjects were 23.91 ± 4.99 years old, weighed 79.14 ± 12.85 kg, were 187.38 ± 12.60 cm, had a VO2max of 55.48 ± 10.32 mL/kg/min and had 3.17 ± 2.79 years of rowing experience. Physiological measures were recorded during both testing protocols. Results: Maximum power/stroke ratio (r =-0.96, p < 0.001), power/stroke ratio at the ventilatory breakpoint (r =-0.90, p < 0.001), maximal oxygen uptake (r =-0.84, p < 0.001) and oxygen uptake at the ventilatory breakpoint (r =-0.82, p < 0.001) were found to be strong and significant predictors of 2 kilometer rowing performance. Conclusion: The four significant predictors of rowing performance suggest training should focus on improving both aerobic capacity and strength. Practical Application: Rowing training should focus on developing hip and leg aerobic and anaerobic capacities to improve performance. Developing strength improves mechanical efficiency as well as raising anaerobic thresholds allowing athletes to utilize a larger portion of their aerobic capacity.展开更多
文摘Hepatoblastoma(HB) is the most common primary liver tumor in children and accounts for two-thirds of all malignant liver neoplasms in the pediatric population. For patients with advanced HB(unresectable or unresponsive to chemotherapy), combined treatment with chemotherapy and liver transplantation is an excellent option. The etiology of HB is mostly obscure because of its extreme rarity although some inherited syndromes and very low birth weight have been associated with it. The prognosis for children with HB has significantly improved in the past three decades thanks to advancements in chemotherapy, surgical resection and postoperative care. In 2002 a surgical staging system called pretreatment extent of disease(PRETEXT) was designed to allow a universal, multidisciplinary approach to patients with HB. Between one-third to two-thirds of patients initially present with unresectable tumors or distant metastases, but up to 85% of these tumors become operable after neoadjuvant chemotherapy. Patients with PRETEXT categories 1, 2, and some 3 are referred for neoadjuvant chemotherapy followed by surgical resection with the goal of complete tumor removal. Classic treatments regimens include a combination of cisplatin, fluorouracil, and vincristine or cisplatin and doxorubicin. Liver transplantation is the only treatment option for unresectable HB. In 2010 the pediatric end-stage liver disease, a pediatric-specific scoring system that determines a patient's ranking on the liver transplant list, began to award additional "exception" points for patients with HB. We analyzed the Standard Transplant Analysis and Research dataset to assess the impact of changes in exception point criteria for HB on outcomes after liver transplantation at Texas Children's Hospital in Houston, Texas. We found that patients who were listed for transplantation with current HB exception criteria experienced a shorter waitlist time but survival was similar between the two eras.
文摘Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.
基金Supported by Grants from the American Liver Foundation, Naomi Judd Liver Scholar Award, The American Surgical Association Career Development Fellowship, and National Ⅰ
文摘AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.
文摘The number of children affected by the hepatitis C virus (HCV) in the United States is estimated to be between 23000 to 46000. The projected medical cost for children with HCV in the United States is upwards of 200 million over the next decade. The implementation of routine screening of blood supply has virtually eliminated transmission via transfusion and vertical transmission is now the most common mode of infection in children. Infections acquired during infancy are more likely to spontaneously resolve and fibrosis of the liver tends to increase with age suggesting slow progressive histologic injury. Anti-viral treatment may be warranted in children with persistently elevated liver enzymes or with significant fibrosis on liver biopsy. Current standard of care includes weekly pegylated interferon and ribavirin twice daily. Predictors of high sustained viral response include genotype 2 and 3 and low viral load in children with genotype 1 (< 600000 IU/mL). Triple therapy is associated with a significantly higher rate of sustained virologic response (> 90%). Only 34 pediatric patients were transplanted with hepatitis C between January 2008 and April 2013. The majority of pediatric patients were born prior to universal screening of blood products and, as of June 2013, there are only two pediatric patients awaiting liver transplantation for end-stage liver disease secondary to hepatitis C. Pediatric survival rates post-transplant are excellent but graft survival is noticeably reduced compared to adults (73.73% for pediatric patients at one year compared to 87.69% in adult patients). New safe potent, and all-oral effective antiviral therapies for recurrent HCV should help increase graft survival.
基金Supported by Ministry of Higher Education,Egypt,No.JS-3787.
文摘BACKGROUND Recurrent hepatitis C virus(HCV)infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation.Direct-acting antiviral(DAA)therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting.However,there are insufficient data regarding its efficacy in liver transplant(LT)recipients with a history of hepatocellular carcinoma(HCC),and the risk of HCC recurrence after DAA therapy is unknown.predictors of DAA treatment failure and HCC recurrence in LT recipients.METHODS A total of 106 LT recipients given DAAs for recurrent HCV infection from 2015 to 2019 were identified(68 with and 38 without HCC).Descriptive statistics and logistic regression models were used to estimate the multivariate odds ratios and respective 95%confidence intervals for predictors of treatment failure and HCC recurrence.RESULTS Six patients(6%)experienced DAA therapy failure post-LT and 100(94%)had a sustained virologic response at follow-up week 12.A high alanine transaminase level>35 U/L at treatment week 4 was a significant predictor of treatment failure.Relapse to pre-LT DAA therapy is a predictor of post-LT HCC recurrence,P=0.04.DAA relapse post-LT was also associated with post-transplantation HCC recurrence,P=0.05.CONCLUSION DAAs are effective and safe in the treatment of recurrent HCV infection in LT recipients with history of HCC.Relapse to pre-and post-LT DAA therapy is associated with post-transplantation HCC recurrence.
基金Supported by the Canadian Cancer Society through a grant to the NCIC Clinical Trials Group from the Canadian Cancer Society Research InstituteNovartis provided the NCIC CTG MA.14 drug octreotide LAR
文摘AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival(P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival(P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific(Br Ca) and other cause(OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1(IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-OH vitamin D were associated with(1) all cause mortality, and if so; and(2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models.RESULTS: The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447(82%) < 70 years and 120(18%) ≥ 70 years. There were 170 deaths: 106(62.3%) BrC a; 55(32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9(5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrC a and OC deaths were not significantly different by treatment arm(P = 0.40): tamoxifen patients experienced 50 BrC a and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 Br Ca and 23 OC deaths. Proportionately more deaths(P = 0.004) were from BrC a for patients< 70 years, where 70% of deaths were due to Br Ca, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index(BMI)(P = 0.02). Higher pathologic T and N were associated with more BrC
文摘Predictors of performance can aid coaches and trainers in prescribing exercise programs for rowing athletes. To date, most of the prediction models have been developed for runners and cyclists. Purpose: The aim of this study was to develop a regression model to predict performance of a simulated 2 kilometer rowing ergometer time trial. Methods: A group of mixed gender rowing athletes (n = 12) completed in a counterbalanced order a 2 kilometer rowing time trial and a continuous progressively incremented graded exercise test on a rowing ergometer. Subjects were 23.91 ± 4.99 years old, weighed 79.14 ± 12.85 kg, were 187.38 ± 12.60 cm, had a VO2max of 55.48 ± 10.32 mL/kg/min and had 3.17 ± 2.79 years of rowing experience. Physiological measures were recorded during both testing protocols. Results: Maximum power/stroke ratio (r =-0.96, p < 0.001), power/stroke ratio at the ventilatory breakpoint (r =-0.90, p < 0.001), maximal oxygen uptake (r =-0.84, p < 0.001) and oxygen uptake at the ventilatory breakpoint (r =-0.82, p < 0.001) were found to be strong and significant predictors of 2 kilometer rowing performance. Conclusion: The four significant predictors of rowing performance suggest training should focus on improving both aerobic capacity and strength. Practical Application: Rowing training should focus on developing hip and leg aerobic and anaerobic capacities to improve performance. Developing strength improves mechanical efficiency as well as raising anaerobic thresholds allowing athletes to utilize a larger portion of their aerobic capacity.
