Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.
Animals ; Bile ; Bile Acids and Salts ; Endothelial Cells/metabolism* ; Hepatic Veno-Occlusive Disease/pathology* ; Inflammation/pathology* ; Liver Cirrhosis/drug therapy* ; Mice ; Powders ; Pyrrolizidine Alkaloids/adverse effects* ; Ursidae

China ; Consensus ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatic Veno-Occlusive Disease/therapy* ; Humans ; Transplantation Conditioning

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT.
Adolescent* ; Astrocytoma ; Brain Neoplasms ; Carboplatin ; Child* ; Cyclophosphamide ; Drug Therapy* ; Etoposide ; Glioblastoma ; Glioma* ; Hepatic Veno-Occlusive Disease ; Humans ; Medical Records ; Melphalan ; Radiotherapy ; Retrospective Studies ; Stem Cell Transplantation* ; Stem Cells* ; Thiotepa

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.
Child* ; Cyclophosphamide* ; Drug Therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Hepatic Veno-Occlusive Disease* ; Humans ; Liver ; Rhabdomyosarcoma* ; Vincristine*

PURPOSE: Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS: Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION: Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.
Colorectal Neoplasms* ; Disease-Free Survival ; DNA ; Drug Therapy ; Fluorouracil ; Hepatic Veno-Occlusive Disease ; Humans ; Leucovorin ; Platelet Count ; Polymorphism, Genetic* ; Spleen ; Splenomegaly* ; Thrombocytopenia ; Treatment Outcome*

OBJECTIVETo summarize the clinical features of sinusoidal obstruction syndrome (SOS) and to improve the understanding of this disease.

METHODSA retrospective study was performed on the clinical data of 12 children with SOS including clinical manifestations, laboratory results, imaging findings, treatment, and prognosis.

RESULTSOf the 12 cases, 8 were secondary to acute lymphoblastic leukemia, and 4 had undergone hematopoietic stem cell transplantation. Manifestations mainly included abdominal distention (4 cases), hepatomegaly with tenderness (9 cases), splenomegaly (6 cases), and weight increase (10 cases). Biochemical tests revealed varying degrees of liver damage in all cases. In the coagulation function test, the activated partial thromboplastin time (APTT) was prolonged in 7 cases. Out of the 7 patients who underwent serum D-dimer test, 4 showed elevated serum level of D-dimer. In routine blood tests, 4 cases showed decreases in both white blood cells and neutrophils. In addition, varying degrees of thrombocytopenia were observed in 9 cases. Eight patients were subjected to color Doppler ultrasound examination, and diffuse hepatomegaly, inhomogeneous liver parenchyma, unclear or thinner hepatic veins, hydrothorax/ascites, or splenomegaly was observed. Sinusoidal dilatation or hepatic cell infiltration was observed in 2 patients who underwent liver biopsy. Treatments were basically symptomatic and supportive therapies, and the prognosis was good in all patients.

CONCLUSIONSSOS should be considered in children who present with hepatomegaly, sudden weight gain, liver dysfunction and coagulation dysfunction after they have received chemotherapy for leukemia and hematopoietic stem cell transplantation.

Child ; Child, Preschool ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Hepatic Veno-Occlusive Disease ; blood ; therapy ; Humans ; Male ; Retrospective Studies ; Tomography, X-Ray Computed

No abstract available.
Antineoplastic Agents/*adverse effects/therapeutic use ; Colorectal Neoplasms/drug therapy/pathology ; Female ; Hepatic Veno-Occlusive Disease/*pathology ; Humans ; Liver Neoplasms/drug therapy/secondary ; Middle Aged ; Organoplatinum Compounds/*adverse effects/therapeutic use ; Tomography, X-Ray Computed

INTRODUCTIONWe aimed to analyse the pregnancy outcome of women with extrahepatic portal vein obstruction.

METHODSThis was a retrospective observational analysis conducted at the Institute of Postgraduate Medical Education and Research, Kolkata, India, between January 2007 and September 2009. A total of 41 pregnancies in 24 women were evaluated.

RESULTSAll women conceived spontaneously (maternal age 20-35 years). 17 women had moderate-to-severe anaemia, and five women had pancytopenia. Variceal bleeding occurred in ten women during pregnancy, which was managed successfully with endoscopic sclerotherapy in eight women and endoscopic variceal ligation in two women. Preterm labour (14.63%), postpartum haemorrhage (7.31%), abortion (4.87%) and pregnancy-induced hypertension (4.87%) were observed in the 41 pregnancies. There were 39 live births and almost all mothers delivered vaginally, except for four who underwent Caesarean section for obstetric indications. Prematurity (15.38%), low birth weight (10.25%), admission to the neonatal intensive care unit (12.82%), stillbirth (2.56%) and neonatal death (2.56%) were noted in the newborns.

CONCLUSIONVariceal bleeding during pregnancy coincided with unfavourable outcomes. Although endoscopic obliteration of varices is a safe and effective method for antenatal management of varices in women, prenatal obliteration results in less morbidity. On rare occasions, obliterated varices can bleed in subsequent pregnancies. Therefore, preconception evaluation of the state of varices prior to each pregnancy and their ligation are important aspects of counselling. A successful foetomaternal outcome is achievable with multidisciplinary backup in a tertiary care centre.

Adult ; Endoscopy, Gastrointestinal ; Female ; Hepatic Veno-Occlusive Disease ; complications ; epidemiology ; therapy ; Humans ; Hypertension, Portal ; complications ; epidemiology ; therapy ; Liver ; blood supply ; Portal Vein ; Pregnancy ; Pregnancy Complications ; epidemiology ; therapy ; Pregnancy Outcome ; Retrospective Studies ; Young Adult

Child ; Female ; Hepatic Veno-Occlusive Disease ; diagnosis ; pathology ; therapy ; Humans ; Liver ; pathology

OBJECTIVETo improve the treatment of drug related childhood hepatic veno-occlusive disease (HVOD), clinical characteristics of 6 children with hematologic neoplasm from 2 hospitals of China Children's Leukemia Group (CCLG) treated with 6-thioguanine (6-TG) complicated with HVOD were analyzed.

METHODAll the drug related HVOD patients were treated with CCLG acute lymphoblastic leukemia (ALL)-2008 protocol. They were from Children's Hospital of Fudan University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from April 2008 to April 2009. The diagnosis was made according to the modified Seattle criteria and Baltimore criteria, including 2 or 3 of the following clinical features: hepatomegaly and upper right abdominal pain, jaundice (bilirubin ≥ 35 µmol/L), ascites or confirmed by pathology. The 6 HVOD patients' clinical manifestations, laboratory finding, imageologic and pathologic data were collected and analyzed.

RESULTOf the 6 patients, 2 were males and 4 females. Mean age of the 6 patients was 3.89 years (range from 3 years 1 month to 4 years 11 months). The original disease was acute lymphoblastic leukemia. HVOD occurred during chemotherapy protocols of CAM (CTX + Ara-C + 6-TG) or maintenance period (MTX + 6-TG). Most of 6 HVOD patients presented with pain in liver area, hepatomegaly on imaging, elevated aminotransferase and bilirubin (often ≥ 35 µmol/L), hydroperitonia was common, one with pleural fluid, illegible hepatic veins. All the patients recovered after being treated with hepatoprotective, jaundice-relieving and supportive therapeutics, some patients were treated with low molecular weight heparin. The prognoses were good.

CONCLUSIONHVOD was a serious complication of chemotherapy with 6-TG. Hepatoprotective and jaundice-relieving and low molecular weight heparin could improve the prognosis.

Antineoplastic Agents ; therapeutic use ; Child, Preschool ; Female ; Hepatic Veno-Occlusive Disease ; drug therapy ; Humans ; Leukemia ; therapy ; Male ; Thioguanine ; therapeutic use