Síndrome obstructivo sinusoidal hepático secundario al consumo de nitritos de alquilo. Presentación de caso / Hepatic sinusoidal obstructive syndrome due to the consumption of alkyl nitrites. A case report

El síndrome obstructivo sinusoidal es una causa de hipertensión portal hepática postsinusoidal. Se produce como consecuencia de agentes hepatotóxicos que lesionan el endotelio de la vénula central, lo que lleva a un bloqueo del flujo sanguíneo y congestión que generan hipertensión portal postsinusoidal. Esta patología es muy rara y su principal causa es el trasplante de células hematopoyéticas, aunque también se han descrito otras causas como el uso de agentes hepatotóxicos que incluyen quimioterapia, radioterapia e ingesta de alcaloides. La clínica de estos pacientes no varía significativamente con respecto a la clínica de los pacientes con otras causas de hipertensión portal por lo que las imágenes diagnósticas juegan un papel clave en el enfoque de estos pacientes. Se describe el caso de un paciente de 16 años de edad con antecedente de consumo de sustancias psicoactivas, quien se presenta con hipertensión portal hepática postsinusoidal por consumo de nitritos de alquilo.

The sinusoidal obstructive syndrome is a cause of post-sinusoidal hepatic portal hypertension. Caused by hepatotoxic agents that damage the endothelium of the central venule, which results in obstruction of the blood flow and congestion, leading to post-sinusoidal portal hypertension. This pathology is very rare, and its main etiology is hematopoietic cell transplantation, although other etiologies have been described such as the use of hepatotoxic agents that include chemotherapy, radiotherapy, and intake of alkaloids. The clinical presentation of these patients does not vary significantly with respect to the other causes of portal hypertension, and therefore diagnostic images play a key role in the initial approach of these patients. We present the case of a 16 year old patient with a history of consumption of psychoactive substances, who showed portal hypertension due to the consumption of alkyl nitrites.

Bear bile powder attenuates senecionine-induced hepatic sinusoidal obstruction syndrome in mice / 中国天然药物

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.

Gynura segetum induces hepatic sinusoidal obstruction syndrome in mice by impairing autophagy

ABSTRACT Purpose: To investigate the underlying mechanism of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum by measuring autophagy in mouse models. Methods: The model group was administered G. segetum (30 g/kg/d) by gavage, while the normal control group was administered an equal volume of saline daily for five weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic histopathological examinations, and Masson staining were performed to evaluate liver injury. Liver intercellular adhesion molecule-1 (ICAM-1) and P-selectin were evaluated by immunohistochemistry. Hepatocellular apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Protein expression levels of autophagy markers were measured using Western blot analysis. Results: Gynura segetum was found to significantly induce liver injury compared with control mice, as evidenced by the increase of serum transaminases, a decrease in triglyceride levels, and histopathological changes in mice. Gynura segetum remarkably induced hepatocellular apoptosis and upregulated the expressions of ICAM-1 and P-selectin and also downregulated the protein expression levels of LC3, Atg12 and cytoplasmic polyadenylation element binding protein. Conclusions: Our results suggested that G. segetum induced liver injury with HSOS, and it was partly due to its ability to impair the autophagy pathway.

Conservation of both hematocrit and liver regeneration in hepatectomies: a vascular occlusion approach in rats / Hepatectomia hemoconservadora no rato: preservação do hematócrito e da regeneração hepática

ABSTRACT Background: Hepatectomies promote considerable amount of blood loss and the need to administrate blood products, which are directly linked to higher morbimortality rates. The blood-conserving hepatectomy (BCH) is a modification of the selective vascular occlusion technique. It could be a surgical maneuver in order to avoid or to reduce the blood products utilization in the perioperative period. Aim: To evaluate in rats the BCH effects on the hematocrit (HT) variation, hemoglobin serum concentration (HB), and on liver regeneration. Methods: Twelve Wistar rats were divided into two groups: control (n=6) and intervention (n=6). The ones in the control group had their livers partially removed according to the Higgins and Anderson technique, while the rats in the treatment group were submitted to BCH technique. HT and HB levels were measured at day D0, D1 and D7. The rate between the liver and rat weights was calculated in D0 and D7. Liver regeneration was quantitatively and qualitatively evaluated. Results: The HT and HB levels were lower in the control group as of D1 onwards, reaching an 18% gap at D7 (p=0.01 and p=0.008, respectively); BCH resulted in the preservation of HT and HB levels to the intervention group rats. BCH did not alter liver regeneration in rats. Conclusion: The BCH led to beneficial effects over the postoperative HT and serum HB levels with no setbacks to liver regeneration. These data are the necessary proof of evidence for translational research into the surgical practice.

RESUMO Racional: As hepatectomias compreendem considerável perda sanguínea e utilização de hemoderivados, o que diretamente estão relacionados com maior morbimortalidade. A hepatectomia hemoconservadora (HH) é modificação da técnica de oclusão vascular seletiva em hepatectomia. Ela pode ser alternativa cirúrgica para evitar ou diminuir o uso de hemoderivados no perioperatório. Objetivo: Avaliar os efeitos da HH sobre o volume globular (VG), concentração de hemoglobina (HB) e sobre a regeneração hepática em ratos. Métodos: Dois grupos de ratos Wistar foram constituídos: controle (n=6) e intervenção (n=6). Os do grupo controle foram submetidos à hepatectomia parcial de Higgins e Anderson e os do grupo Intervenção à HH. VG e HB foram medidos nos dias D0, D1 e D7. A relação peso do fígado/peso do rato foi calculada em D0 e D7. A regeneração hepática foi analisada qualitativamente e quantitativamente. Resultados: Houve diminuição dos níveis de VG e HB nos ratos do grupo controle a partir de D1, atingindo decréscimo de 18% em D7 (p=0,01 e p=0,008 respectivamente); a HH permitiu a manutenção dos níveis de VG e HB nos ratos do grupo intervenção. A HH não alterou a regeneração hepática. Conclusão: HH resultou em níveis maiores de VG e HB pós-operatórios sem alterar a regeneração hepática. Pode-se considerar estes dados como a prova necessária para a translação à pesquisa clinicocirúrgica.

Quantitative Imaging in Pediatric Hepatobiliary Disease

Pediatric hepatobiliary imaging is important for evaluation of not only congenital or structural disease but also metabolic or diffuse parenchymal disease and tumors. A variety of ultrasonography and magnetic resonance imaging (MRI) techniques can be used for these assessments. In ultrasonography, conventional ultrasound imaging as well as vascular imaging, elastography, and contrast-enhanced ultrasonography can be used, while in MRI, fat quantification, T2/T2* mapping, diffusion-weighted imaging, magnetic resonance elastography, and dynamic contrast-enhanced MRI can be performed. These techniques may be helpful for evaluation of biliary atresia, hepatic fibrosis, nonalcoholic fatty liver disease, sinusoidal obstruction syndrome, and hepatic masses in children. In this review, we discuss each tool in the context of management of hepatobiliary disease in children, and cover various imaging techniques in the context of the relevant physics and their clinical applications for patient care.

Caso clínico: Enfermedad Veno-Oclusiva Hepática secundaria a Quimioterapia en un paciente con Sarcoma de Ewing / Case report: Veno-Occlusive liver disease secondary to Chemotherapy in a patient with Ewing's Sarcoma

Introducción: La enfermedad veno-oclusiva hepática o síndrome de obstrucción sinusoidal se caracteriza clínicamente por presentar hepatomegalia dolorosa, ictericia, ascitis, edema y aumento de peso, que generalmente ocurre como una complicación del trasplante de médula ósea. Caso clínico: Se trata de un escolar masculino de 9 años de edad con Sarcoma de Ewing quien presentó una Enfermedad Veno-oclusiva Hepática secundaria a la administración de quimioterapia con ciclofosfamida y vincristina. Evolución: Se realizó el diagnóstico diferencial con daño hepático por causas infecciosas y autoinmunes a través de pruebas serológicas y biopsia. Conclusión: Siendo este el primer reporte que describe la asociación entre la enfermedad Veno-oclusiva Hepática con Sarcoma de Ewing.

Introduction: Hepatic Veno-occlusive Disease or Sinusoidal Obstruction Syndrome is a clinical syndrome characterized by painful hepatomegaly, jaundice, ascites, edema and weight gain, which usually occurs as a complication of bone marrow transplantation. Clinical Case: We describe a new case of male school age 9 with Ewing Sarcoma who had Hepatic Veno-occlusive Disease secondary to chemotherapy with cyclophosphamide and vincristine. Evolution: We set the differential diagnosis from liver damage due to infection and autoimmune diseases through serological tests and biopsy. Conclusion: This is the first report that describes the association between Ewing Sarcoma and Hepatic Veno-occlusive Disease.

Effects of Parenteral Nutrition in Pediatric Patients with Hematopoietic Stem Cell Transplantation

PURPOSE: This study examined the effects of parenteral nutrition (PN) on the nutritional status, clinical improvement, and PN-related complications in pediatric patients who had undergone hematopoietic stem cell transplantation (HSCT). METHODS: A retrospective audit of 110 pediatric patients (age≤18), who underwent HSCT from March 2015 to February 2017 was undertaken. The patients were divided into 3 groups based on the ratio of daily calorie supplementation to the daily calorie requirement (ROCS). The clinical factors related to the nutritional status, such as difference in body weight (BW), body mass index (BMI), percent ideal body weight (PIBW), total protein (T.protein), and albumin; the early clinical outcome, such as PN-duration, length of hospitaliaztion (LOH), engraftment day (ED), graft-versus-host disease, sepsis, pneumonia and mucositis; and PN-related complications, including elevation of total bilirubin (T.bil), direct bilirubin (D.bil), aspartate aminotransferase, alanine aminotransferase, glucose and cholesterol levels, and hepatic veno-occlusive disease were analyzed using the electronic medical records. Additional analysis subject to auto-HSCT and allo-HSCT patients was also performed. RESULTS: The very-low-ROCS, low-ROCS, and satisfied-ROCS group were 30 (27.3%), 47 (42.7%), and 33 (30.0%) patients, respectively. The PN-duration (P=0.005, z=−2.271), LOH (P=0.023, z=−2.840), ED (P < 0.001, z=−3.695), T.bil elevation (P < 0.001, z=−3.660), and D.bil elevation (P=0.002, z=−3.064) tended to decrease with increasing ROCS. The difference in the PN-duration (P=0.017), ED (P=0.001), T.bil elevation (P=0.001), and D.bil elevation (P=0.011) in the 3 groups was statistically significant. In the auto-HSCT patients, the change in BW (P=0.031, z=+2.154), PIBW (P=0.029, z=+2.187), and BMI (P=0.021, z=+2.306) tended to increase. In the allo-HSCT patients, the change in T.protein (P=0.022, z=+2.286) increased but the ED (P=0.021, z=−2.304) decreased. CONCLUSION: Aggressive PN supplementation has an effect on maintaining the nutritional status and achieving better early outcomes in pediatric HSCT patients, whereas it has no effect on increasing the PN-related complications.

Enfermedad Veno-oclusiva Hepática/Síndrome de Obstrucción Sinusoidal: actualización de los aspectos fisiopatológicos, criterios diagnósticos y opciones terapéuticas / Venous-Occlusive Hepatic Disease / Sinusoidal Obstruction Syndrome: update of the pathophysiological aspects, diagnostic criteria and therapeutic options

La enfermedad veno-oclusiva hepática o síndrome de obstrucción sinusoidal se caracteriza clínicamente por presentar hepatomegalia dolorosa, ictericia, ascitis, edema, aumento de peso y/o trombocitopenia refractaria, que generalmente ocurre como una complicación del trasplante de médula ósea y la quimioterapia en algunos tumores sólidos. La fisiopatología es compleja y se relaciona con daño endotelial en los sinusoides hepáticos que condiciona un estado proinflamatorio, protrombótico e hipofibrinolítico. El tratamiento varía de acuerdo a la severidad de cada caso, cuando son cuadros leves a moderados se presenta una resolución espontánea requiriendo medidas de soporte y tratamiento sintomático; mientras que en los casos severos o muy severos se requiere adicionar tratamiento específico debido a la alta mortalidad que presentan estos pacientes. Considerando la alta mortalidad y las escasas opciones terapéuticas aprobadas actualmente, la identificación de factores de riesgo sigue siendo la principal estrategia para disminuir la incidencia de esta enfermedad, de ahí la importancia de esta revisión.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome is clinically characterized by painful hepatomegaly, jaundice, ascites, edema, weight gain and / or refractory thrombocytopenia, which usually occurs as a complication of bone marrow transplantation and chemotherapy in some solid tumors. The pathophysiology is complex and is related to endothelial damage in the hepatic sinusoids that conditions a proinflammatory, prothrombotic and hypofibrinolytic state. The treatment depends on the severity of each case, when there are mild to moderate cases a spontaneous resolution is presented requiring support measures and symptomatic treatment; while in severe or very severe cases it is necessary to add specific treatment due to the high mortality that these patients present. Considering the high mortality and the scarce therapeutic options currently approved, the identification of risk factors remains the main strategy to reduce the incidence of this disease.

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

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.

Radiation-induced liver disease: current understanding and future perspectives

Although radiotherapy (RT) is used for the treatment of cancers, including liver cancer, radiation-induced liver disease (RILD) has emerged as a major limitation of RT. Radiation-induced toxicities in nontumorous liver tissues are associated with the development of numerous symptoms that may limit the course of therapy or have serious chronic side effects, including late fibrosis. Although the clinical characteristics of RILD patients have been relatively well described, the understanding of RILD pathogenesis has been hampered by a lack of reliable animal models for RILD. Despite efforts to develop suitable experimental animal models for RILD, current animal models rarely present hepatic veno-occlusive disease, the pathological hallmark of human RILD patients, resulting in highly variable results in RILD-related studies. Therefore, we introduce the concept and clinical characteristics of RILD and propose a feasible explanation for RILD pathogenesis. In addition, currently available animal models of RILD are reviewed, focusing on similarities with human RILD and clues to understanding the mechanisms of RILD progression. Based on these findings from RILD research, we present potential therapeutic strategies for RILD and prospects for future RILD studies. Therefore, this review helps broaden our understanding for developing effective treatment strategies for RILD.

Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX / Journal of the Korean Cancer Association, 대한암학회지

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.

Delayed Hepatic Veno-Occlusive Disease after Haploidentical Hematopoietic Stem Cell Transplantation:A Report of Six Cases / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the morbidity, risk factors, clinical characterisitics, treatments and prognosis of delayed hepatic veno-occlusive disease(HVOD) after haploidentical hematopoietic stem cell transplantation (hi-HSCT).</p><p><b>METHODS</b>The clinical data of 208 patients undergoing hi-HSCT were retrospectively analyzed.</p><p><b>RESULTS</b>Six patients were diagnosed with delayed VOD, among them 4 patients were moderate VOD and 2 patients were severe VOD. The incidence of VOD after hi-HSCT was 2.88%, the median onset time was 44.5(30-57) days after transplant, 2 patients died of multiple organ failure (MOF) due to rapid progress of disease. With intravenous administration of defibrotide, 4 patients displayed encouraging response, but 2 patients died of hepatic acute graft-versus-host disease (aGVHD), 1 had bone marrow relapse and the other one was cured.</p><p><b>CONCLUSION</b>Norethindrone is one of the high risk factors, while sex, age and disease status are irrelevant to the occurrence of VOD. Unfractionated heparin (UH) can effectively decrease the morbidity. Pretransplant hepatic function reserve, high dose preconditioning regimens and pharmacotherapy may result in delayed VOD onset. The delayed VOD has the same clinical features and treatment-response as early VOD, but a poorer prognosis is usually observed. A larger amount of samples (patients) is needed to research the relationship of the delayed VOD with hi-HSCT. Defibrotide can effectively increase the survival rate of VOD patients.</p>

Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide / Journal of the Korean Cancer Association, 대한암학회지

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.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Síndrome de DIOS en dos pacientes con fibrosis quística: revisión de la literatura / Case Studies of Two Cystic Fibrosis Patients with distal intestinal obstruction syndrome (DIOS) and a Literature review

En los pacientes con fibrosis quística (FQ) el íleo meconial, el síndrome de obstrucción distal y la constipación conforman un grupo de manifestaciones gastrointestinales con una gravedad variable como consecuencia del incremento en la viscosidad del moco y el tiempo prolongado del tránsito intestinal. El grupo de trabajo de fibrosis quística de la Sociedad Europea de Gastroenterología, Hepatología y Nutrición Pediátrica realizó un consenso en 2010 y definió el síndrome de obstrucción intestinal distal (DIOS) como un cuadro agudo de obstrucción intestinal que puede ser completo o incompleto. El DIOS completo se define como un cuadro de vómito bilioso y/o niveles hidroaéreos en el intestino delgado observados en la radiografía de abdomen, masa fecal a nivel ileocecal, y dolor y/o distensión abdominal; el incompleto se define como el cuadro de dolor abdominal y/o distensión y masa fecal a nivel ileocecal, pero sin los otros signos de obstrucción completa. La frecuencia de presentación de esta entidad en pacientes con FQ es variable y depende de las definiciones utilizadas; se ha considerado que la prevalencia va del 7% a 8% en niños y en adultos puede ser tan alta como de 23,3 episodios por 1000 pacientes/año, con una prevalencia que varía entre el 14% y el 16%. Dadas las dificultades que se presentan en estos pacientes para definir y establecer el diagnóstico, quisimos ilustrar este síndrome con 2 niños que consultaron a nuestra institución; además, se realizó una revisión del tema para generar sensibilización sobre el diagnóstico temprano y su manejo.

Patients with cystic fibrosis (CF) have greater than normal mucosal viscosity and prolonged intestinal transit times which can result in meconium ileus, distal intestinal obstruction syndrome (DIOS) and constipation of varying severity. The cystic fibrosis working group of the European Society of Gastroenterology, Hepatology and Pediatric Nutrition produced a consensus in 2010 that defined distal intestinal obstruction syndrome (DIOS) as acute intestinal obstruction which may be complete or incomplete. Fully developed DIOS is defined as bilious vomiting and/or sufficient amounts of fluid and air in the small intestine to be observed in an abdominal X-ray, a fecal mass in the ileocecal area, pain and/or bloating. Incomplete DIOS is defined as abdominal pain and/or bloating and fecal mass in the ileocecal area, but without the other signs of complete obstruction. The incidence of this condition in cystic fibrosis patients varies. Depending on the definition used, the prevalence of DIOS has been measured between 7% and 8% in children with cystic fibrosis, but has been reported to be as high as 23.3 episodes per 1,000 patients per year for adult cystic fibrosis patients with a prevalence ranging between 14% and 16%. Given the difficulties of establishing this diagnosis in these patients, we wanted to illustrate this syndrome with two children who were treated in our institution and to review this subject in order to generate awareness about early diagnosis and management.

Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation

BACKGROUND: The outcome of hematopoietic stem cell transplantation (HSCT) is poor in patients with secondary iron overload (SIO). We evaluated the relationship between SIO and veno-occlusive disease (VOD) in an animal model with radiation for HSCT. METHODS: We used a 6-week-old female BDF1 (H-2b/d) and a male C57/BL6 (H-2b) as recipient and donor, respectively. Recipient mice were injected intraperitoneally with 10 mg of iron dextran (cumulative doses of 50 mg, 100 mg, and 200 mg). All mice received total body irradiation for HSCT. We obtained peripheral blood for alanine transaminase (ALT) and liver for pathologic findings, lipid hyperoxide (LH) as reactive oxygen species (ROS), and liver iron content (LIC) on post-HSCT day 1 and day 7. The VOD score was assessed by pathologic findings. RESULTS: ALT levels increased depending on cumulative iron dose, with significant differences between days 1 and 7 for mice loaded with 200 mg of iron (P<0.01). LH levels significantly increased in mice loaded with 200 mg of iron compared to those in other groups (P<0.01). For mice loaded with 100 mg of iron, the LH level depended on the radiation dose (P<0.01). There was a statistically significant relationship among ALT, LH, and LIC parameters (P<0.05). Pathologic scores for VOD correlated with LIC (P<0.01). CONCLUSION: Livers with SIO showed high ROS levels depending on cumulative iron dose, and correlations with elevated liver enzyme and LIC. The pathologic score for VOD was associated with the LIC. Our results suggest that SIO may induce VOD after HSCT with irradiation.

Biomarkers for hepatic sinusoidal obstruction syndrome after hematopoietic cell transplantation

No abstract available.

Hematologic toxicity of Gynura segetum and effects on vascular endothelium in a rat model of hepatic veno-occlusive disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the effects ofGynura segetum in rats with hepatic veno-occlusive disease (HVOD).</p><p><b>METHODS</b>Sixty Sprague-Dawley rats were assigned to a blank control group, one of three Gynura segetum treatment groups (low-dose group, 5.0 g/kg; mid-dose group, 10 g/kg; high-dose group, 20 g/kg), or a pseudo-drug group (10 g/kg of pseudo-ginseng). After 28 days of treatment, effects on white blood cell count, coagulation, secreted factors from vascular endothelium, and histopathology of the spleen were observed and inter-group differences were statistically assessed.</p><p><b>RESULTS</b>After the 4-week administration, all rats in the Gynura segetum treatment groups showed decrease in body weight, increases in numbers of leukocytes, neutrophils, lymphocytes, monocytes and eosinophils.decreases in platelets and platelet hematocrit, and increases in mean platelet volume and platelet distribution.In addition, the Gynura segetum treatments increased the prothrombin time, activated partial thromboplastin time, thrombin time, prothrombin ratio and international normalized ratio, but decreased the PT%, fibrinogen level and platelet aggregation.Serum levels of endothelin and nitric oxide were also elevated by the Gynura segetum treatments.All measured parameters showed significant differences from the control group (P less than 0.01 or less than 0.05).Finally, the splenic follicles were significantly reduced and the spleens showed an absence of germinal centers along with a large number of diffuse lymphocytes and reduced red pulp sinusoids.</p><p><b>CONCLUSION</b>The Gynura segetum treatment has some toxic effects; it can reduce platelet count and platelet hematocrit, inhibit blood clotting time and platelet aggregation, increase the secretion of factors from the vascular endothelium and disrupt spleen histology.</p>

Clinical analysis of acute heart failure's risk factor for chronic myelogenous leukemia patient during the early stage of allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>The study was to analyze the acute heart failure's risk factors and clinical characteristics for the patient with chronic myelogenous leukemia (CML) during the early stage (within 100 d) of allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>A total of 106 cases of CML received allo-HSCT were retrospectively studied in Nanfang Hospital from May 2003 to May 2013. On the basis of existence or absence of acute heart failure during early stage of allo-HSCT (100 d), the patients were divided into heart failure (15 cases) and control group (91 cases). Using Logistic univariate analysis, Fisher' exact test and Pearson X(2) test, the acute heart failure's risk factors and clinical characteristics of both groups were analyzed.</p><p><b>RESULTS</b>The median occurrence time of acute heart failure was 3 d (1 d before transplantation to 84 d after transplantation). Logistic univariate analysis indicated that the imatinib treatment history and time, and the prophylaxis regimens for GVHD with anti-thymocyte globulin (ATG) were all the poor prognostic factors for acute heart failure. Incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and adverse prognostic events including death in the heart failure group patients were statistically higher than that in control group (P < 0.05).</p><p><b>CONCLUSION</b>Acute heart failure mostly happened in the early stage after allo-HSCT, imatinib treatment and GVHD prophylaxis regimens with ATG are the poor prognostic factors for acute heart failure. The patients of heart failure group seem to have higher incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and deaths.</p>