AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human...AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.展开更多
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
AIM: To investigate the role of TIP30 in apoptotic signal pathway in hepatoblastoma cells and to provide a basis for TIP30 as a gene therapy candidate in the regression of hepatoblastoma cells. METHODS: Apoptosis of h...AIM: To investigate the role of TIP30 in apoptotic signal pathway in hepatoblastoma cells and to provide a basis for TIP30 as a gene therapy candidate in the regression of hepatoblastoma cells. METHODS: Apoptosis of human hepatoblastoma cell lines HepG2 (p53 wild), Hep3B (p53 null) and PLC/RPF/5 (p53 mutant) infected with Ad-TIP30 (bearing a wild type human Tip30 gene) were analyzed and p53, Bax and Bcl-xl expression levels were compared among these cells. MTT assay, DNA fragmentation, in situ 3' end labeling of DNA, annexin-V FITC staining were used to detect cell death and apoptosis in cells at various time intervals subsequent to infection, and to determine whether TIP30 had an effect on the expression levels of some apoptosis-related gene products such as Bax, p53 and Bcl-xl. A similar time course experiment was performed by Western blotting. RESULTS: In MTT assay, the viability of HepG2 cells decreased significantly from 99.7% to 10% and displayed more massive cell death within 5-8 d than Hep3B and PLC/ RPF/5 cells, with their viability decreased from 97.8% to 44.3% and 98.1% to 50.4%, respectively. In annexin-V FITC assay, the percentage of apoptosis cells in HepG2 cells was two to three-fold higher than that in control cells (infected with Ad-GFP), two-fold higher than that in Hep3B cells and 1.4-fold higher than that in PLC/RPF/5 cells 36 h after infection, respectively. Moreover, in HepG2 cells, the p53 began to increase 6-8 h after infection, reaching a maximum level between 8 and 12 h after infection and then dropped. Bax showed a similar increase in the cells as p53 reached the maximum at 8-12 h and subsequently decreased. Interestingly, Bcl-xl protein levels were down regulated during 24 to 36 h after Ad-TIP30 infection. In contrast, ectopic expression of TIP30 in Hep3B and PLC/ RPF/5 cells had no effect on the regulation of Bax expression, but had an effect on Bcl-xl levels. In comparison with HepG2 cells, these data suggested that up-regulation of p53 levels by TIP30 might be a pre-requisite for Ba展开更多
Background:Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children.Due to limited epidemiological data,therapy for hepatoblastoma tends to be individualized.This ...Background:Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children.Due to limited epidemiological data,therapy for hepatoblastoma tends to be individualized.This study aimed to evaluate incidence trends of hepatoblastoma and to develop a nomogram to predict the survival of children with newly diagnosed hepatoblastoma on a population-based level.Methods:Individuals up to 18 years of age with hepatoblastoma recorded in 18 registries of the Surveillance,Epi-demiology,and End Results(SEER)database between 2004 and 2015 were examined.Joinpoint regression analyses were applied to assess incidence trends in annual percentage change(APC).Multivariable Cox regression was used to identify factors associated with overall survival(OS).A nomogram was constructed to predict OS in individual cases based on independent predictors.Concordance index(C-index)and calibration curves were used to evaluate predic-tive performance.Results:Between 2004 and 2015,hepatoblastoma incidence increased significantly(APC,2.2%;95%confidence interval[CI]0.5%to 3.8%,P<0.05).In particular,this increase was observed among 2-to 4-year-old patients,males,and African-Americans.The 5-and 10-year OS rates were 81.5%and 81.0%,respectively.Age of 2 to 4 years,Afri-can-American ethnicity,and no surgery were independent predictors for short OS.Distant disease at presentation was found not to be an independent factor of survival.The nomogram had a C-index of 0.79(95%CI 0.74-0.84)with appropriate calibration curve fitting.Conclusions:We constructed a nomogram that integrates common factors associated with survival for hepatoblas-toma patients.It provides accurate prognostic prediction for children with hepatoblastoma.展开更多
During the first year of life, most of the liver neoplasms are benign in origin, but some of these histologically benign lesions may be challenging in their management. Although most hepatic hemangiomas can be safely ...During the first year of life, most of the liver neoplasms are benign in origin, but some of these histologically benign lesions may be challenging in their management. Although most hepatic hemangiomas can be safely observed until involution is documented, some patients will need treatment due to progressive hepatomegaly, hypothyroidism and/or cardiac failure. Large mesenchymal hamartomas may require extensive hepatic resection and an appropriate surgical plan is critical to obtain good results. For malignant neoplasms such as hepatoblastoma, complete surgical resection is the mainstay of curative therapy. The decision about whether to perform an upfront or delayed resection of a primary liver malignant tumor is based on many considerations, including the ease of resection, surgical expertise, tumor histology and stage, and the likely chemosensitivity of the tumor. This article reviews the initial management of the more common hepatic tumors of infancy, focusing on the differential diagnosis and treatment options.展开更多
BACKGROUND Hepatoblastoma(HB) is the most common hepatic malignant tumour in children,accounting for approximately 50%-60% of primary hepatic malignant tumours in children, mostly in children under 3 years old. In Wes...BACKGROUND Hepatoblastoma(HB) is the most common hepatic malignant tumour in children,accounting for approximately 50%-60% of primary hepatic malignant tumours in children, mostly in children under 3 years old. In Western countries, the incidence of hepatoblastoma is approximately 1-2/100000. Da Vinci surgical system is fast becoming a key instrument in microinvasive surgery. The past decade has seen the rapid development of robot-assisted laparoscopy, which expends many fields including the liver surgery. This paper discusses the significance and feasibility of robot-assisted gallbladder-preserving hepatectomy for treating S5 hepatoblastoma in children. The aim of this essay is to compare the safety and effectiveness of robotic surgery with conventional laparoscopic surgery, and explore the meaning of preservation of the gallbladder by sharing this case.CASE SUMMARY A 3-year-old child with a liver mass in the 5 th segment was treated using the Da Vinci surgical system, and the gallbladder was retained. The child was admitted to the hospital for 20 d for the discovery of the right hepatic lobe mass.Ultrasonography revealed a low echo mass, 46 mm × 26 mm × 58 mm in size,indicating hepatoblastoma in the right lobe, and enhanced computed tomography showed continuous enhancement of iso-low-density lesions with different sizes and nodules and unclear boundaries, without the dilation of the intrahepatic bile duct, no enlargement of the gallbladder, and uniform thickness of the wall. The diagnosis was "liver mass, hepatoblastoma". It was decided to perform S5 liver tumour resection. During surgery, the tumour and gallbladder were isolated first, and the gallbladder could be completely separated from the tumour surface without obvious infiltration; therefore, the gallbladder was preserved. The cutting line was marked with an electric hook. The hepatic duodenal ligament was blocked with a urethral catheter using the Pringle method, and the tumour and part of the normal liver tissue were completely resected with an ultra展开更多
文摘AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.
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AIM: To investigate the role of TIP30 in apoptotic signal pathway in hepatoblastoma cells and to provide a basis for TIP30 as a gene therapy candidate in the regression of hepatoblastoma cells. METHODS: Apoptosis of human hepatoblastoma cell lines HepG2 (p53 wild), Hep3B (p53 null) and PLC/RPF/5 (p53 mutant) infected with Ad-TIP30 (bearing a wild type human Tip30 gene) were analyzed and p53, Bax and Bcl-xl expression levels were compared among these cells. MTT assay, DNA fragmentation, in situ 3' end labeling of DNA, annexin-V FITC staining were used to detect cell death and apoptosis in cells at various time intervals subsequent to infection, and to determine whether TIP30 had an effect on the expression levels of some apoptosis-related gene products such as Bax, p53 and Bcl-xl. A similar time course experiment was performed by Western blotting. RESULTS: In MTT assay, the viability of HepG2 cells decreased significantly from 99.7% to 10% and displayed more massive cell death within 5-8 d than Hep3B and PLC/ RPF/5 cells, with their viability decreased from 97.8% to 44.3% and 98.1% to 50.4%, respectively. In annexin-V FITC assay, the percentage of apoptosis cells in HepG2 cells was two to three-fold higher than that in control cells (infected with Ad-GFP), two-fold higher than that in Hep3B cells and 1.4-fold higher than that in PLC/RPF/5 cells 36 h after infection, respectively. Moreover, in HepG2 cells, the p53 began to increase 6-8 h after infection, reaching a maximum level between 8 and 12 h after infection and then dropped. Bax showed a similar increase in the cells as p53 reached the maximum at 8-12 h and subsequently decreased. Interestingly, Bcl-xl protein levels were down regulated during 24 to 36 h after Ad-TIP30 infection. In contrast, ectopic expression of TIP30 in Hep3B and PLC/ RPF/5 cells had no effect on the regulation of Bax expression, but had an effect on Bcl-xl levels. In comparison with HepG2 cells, these data suggested that up-regulation of p53 levels by TIP30 might be a pre-requisite for Ba
基金This work was supported by the China Scholarship Council[File No.201708080137]We acknowledge additional financial support by the Deutsche Forschungsgemeinschaft,within the funding program Open Access Publishing+1 种基金by the Baden-Württemberg Ministry of Science,Researchthe Arts,and by Ruprecht-Karls-Universität Heidelberg
文摘Background:Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children.Due to limited epidemiological data,therapy for hepatoblastoma tends to be individualized.This study aimed to evaluate incidence trends of hepatoblastoma and to develop a nomogram to predict the survival of children with newly diagnosed hepatoblastoma on a population-based level.Methods:Individuals up to 18 years of age with hepatoblastoma recorded in 18 registries of the Surveillance,Epi-demiology,and End Results(SEER)database between 2004 and 2015 were examined.Joinpoint regression analyses were applied to assess incidence trends in annual percentage change(APC).Multivariable Cox regression was used to identify factors associated with overall survival(OS).A nomogram was constructed to predict OS in individual cases based on independent predictors.Concordance index(C-index)and calibration curves were used to evaluate predic-tive performance.Results:Between 2004 and 2015,hepatoblastoma incidence increased significantly(APC,2.2%;95%confidence interval[CI]0.5%to 3.8%,P<0.05).In particular,this increase was observed among 2-to 4-year-old patients,males,and African-Americans.The 5-and 10-year OS rates were 81.5%and 81.0%,respectively.Age of 2 to 4 years,Afri-can-American ethnicity,and no surgery were independent predictors for short OS.Distant disease at presentation was found not to be an independent factor of survival.The nomogram had a C-index of 0.79(95%CI 0.74-0.84)with appropriate calibration curve fitting.Conclusions:We constructed a nomogram that integrates common factors associated with survival for hepatoblas-toma patients.It provides accurate prognostic prediction for children with hepatoblastoma.
文摘During the first year of life, most of the liver neoplasms are benign in origin, but some of these histologically benign lesions may be challenging in their management. Although most hepatic hemangiomas can be safely observed until involution is documented, some patients will need treatment due to progressive hepatomegaly, hypothyroidism and/or cardiac failure. Large mesenchymal hamartomas may require extensive hepatic resection and an appropriate surgical plan is critical to obtain good results. For malignant neoplasms such as hepatoblastoma, complete surgical resection is the mainstay of curative therapy. The decision about whether to perform an upfront or delayed resection of a primary liver malignant tumor is based on many considerations, including the ease of resection, surgical expertise, tumor histology and stage, and the likely chemosensitivity of the tumor. This article reviews the initial management of the more common hepatic tumors of infancy, focusing on the differential diagnosis and treatment options.
文摘BACKGROUND Hepatoblastoma(HB) is the most common hepatic malignant tumour in children,accounting for approximately 50%-60% of primary hepatic malignant tumours in children, mostly in children under 3 years old. In Western countries, the incidence of hepatoblastoma is approximately 1-2/100000. Da Vinci surgical system is fast becoming a key instrument in microinvasive surgery. The past decade has seen the rapid development of robot-assisted laparoscopy, which expends many fields including the liver surgery. This paper discusses the significance and feasibility of robot-assisted gallbladder-preserving hepatectomy for treating S5 hepatoblastoma in children. The aim of this essay is to compare the safety and effectiveness of robotic surgery with conventional laparoscopic surgery, and explore the meaning of preservation of the gallbladder by sharing this case.CASE SUMMARY A 3-year-old child with a liver mass in the 5 th segment was treated using the Da Vinci surgical system, and the gallbladder was retained. The child was admitted to the hospital for 20 d for the discovery of the right hepatic lobe mass.Ultrasonography revealed a low echo mass, 46 mm × 26 mm × 58 mm in size,indicating hepatoblastoma in the right lobe, and enhanced computed tomography showed continuous enhancement of iso-low-density lesions with different sizes and nodules and unclear boundaries, without the dilation of the intrahepatic bile duct, no enlargement of the gallbladder, and uniform thickness of the wall. The diagnosis was "liver mass, hepatoblastoma". It was decided to perform S5 liver tumour resection. During surgery, the tumour and gallbladder were isolated first, and the gallbladder could be completely separated from the tumour surface without obvious infiltration; therefore, the gallbladder was preserved. The cutting line was marked with an electric hook. The hepatic duodenal ligament was blocked with a urethral catheter using the Pringle method, and the tumour and part of the normal liver tissue were completely resected with an ultra
