Is Defibrotide Prophylaxis Effective on Graft Versus Host Disease in Patients with Allogeneic Stem Cell Transplantation?

Introduction:Sinusoidal obstruction syndrome (SOS) is one of the complications of allogeneic stem cell transplantation (allo-SCT). Defibrotide(DF) is used effectively in SOS prophylaxis and treatment. Graft versus host disease (GVHD) is a significant cause of morbidity and mortality in allo-SCT. Here, we retrospectively investigated the effect of DF on the development of GVHD in these patients.Methods:We evaluated 81 allo-transplanted patients due to various diagnoses (benign or malignant), retrospectively. Thirty-four patients used DF as prophylaxis while 47 patients did not receive it. Acute and chronic GVHD assessments were performed at +30/100thday and throughout the life of the patients, respectively. Results: Acute GVHDwas more common with DF use (82% vs 61%). There was no statistical significance in terms of the effect on chronic GVHD. We observed that one patient in the non-DF groupdeveloped SOS.Conclusions: DF may be beneficial to prevent acute GVHD. However, we observed that GVHD and mortality were more common in patients using DF. This is probably due to the similarity of high-risk criteria between GVHD and SOS. We have not found a significant association between defibrotide use and the development of chronic GVHD.

The role of serum pyrrole-protein adduct in evaluating the severity and predicting the anticoagulant efficacy in patients with pyrroidine alkaloid-related hepatic sinusoidal obstruction syndrome / 中华消化杂志

Objective:To explore the role of serum pyrrole-protein-adduct (PPA) in evaluating the severity and predicting the anticoagulant efficacy in patients with pyrrolidine alkaloid-related hepatic sinusoidal obstruction syndrome (PA-HSOS).Methods:From April 2018 to December 2019, the data of 48 patients with PA-HSOS admitted and treated at Drum Tower Hospital, Affiliated Medical College of Nangjing University were collected, which included PPA level, portal vein velocity (PVV), ascites grading, PA-HSOS severity grading (according to the new severity grading criteria for suspected hepatic sinusoidal obstruction syndrome in adults by the European Society of Blood and Bone Marrow Transplantation and adjusted) and the outcome of anticoagulation. Patients with acute onset (onset of symptoms within 1 month after consuming pyrrolizidine alkaloid-containing plants) were taken as research subjects. The combination of PPA with PVV or with ascites classification of PA-HSOS severity assessment model was fitted by logistic regression, and the logit values of 2 combination models were calculated, the formula was logit 1=0.034×PPA(nmol/L)+ 0.055×PVV(cm/s)-3.287, logit 2=0.039×PPA(nmol/L)-2.712×ascites grade 2 (Yes=1, No=0)-0.388×ascites grade 3 (Yes=1, No=0)-0.899. The patients received initial anticoagulation therapy at Drum Tower Hospital, Affiliated Medical College of Nanjing University were selected as research subjects. The anticoagulant efficacy prediction model of combination of PPA with serum creatinine (SCR) and with hepatic venous pressure gradient (HVPG) was fitted by logistic regression, and the logit value was calculated, the formula was logit 3=0.013×PPA(nmol/L)+ 0.064×SCR (mol/L)+ 0.542×HVPG (mmHg, 1 mmHg=0.133 kPa)-16.005. The predictive value of PPA in evaluating the severity of PA-HSOS and anticoagulant efficacy was evaluated. Receiver operating characteristic curve analysis was performed for statistical analysis. Results:The serum PPA level of 48 patients was 10.81 nmol/L (3.91 nmol/L, 32.04 nmol/L). Among them, 33 cases (68.8%) were mild PA-HSOS, 3 cases (6.2%) were moderate PA-HSOS, no severe PA-HSOS case and 12 cases (25.0%) were very severe PA-HSOS. Among 23 patients received initial anticoagulant therapy at Drum Tower Hospital, Affiliated Medical College of Nanjing University and with complete data, 8 patients responded and survived, and 15 patients did not respond (5 patients died, 1 patient relieved after continue anticoagulant therapy, and 9 patients survived after switching to anticoagulant therapy and transjugular intrahepatic portosystemic shunt (TIPS) treatment). One patient without initial anticoagulant therapy, survived after TIPS treatment because of the progress of the disease. Area under the curve (AUC) of PPA to assess the severity of acute onset PA-HSOS was 0.75, 95% confidence interval ( CI) was 0.52 to 0.98 ( P=0.047). When PPA≥45.519 nmol/L, the specificity and sensitivity in evaluating severe and very severe PA-HSOS was 100.0% and 57.1%, respectively. AUC of combination of PPA and PVV to assess the severity of PA-HSOS was 0.77, 95% CI was 0.55 to 1.00 ( P=0.032). When the logit of combination model≥0.180, the specificity and sensitivity in evaluating severe and very severe PA-HSOS was 71.4% and 81.8%, respectively. AUC of combination of PPA and ascites grade (grade 1, 2 or 3) to assess the severity of PA-HSOS was 0.85, 95% CI was 0.63 to 1.00 ( P=0.005). When the logit of combination model≥0.347, the specificity and sensitivity in evaluating severe and very severe PA-HSOS was 85.7% and 92.0%, respectively. AUC of combination of PPA, SCR and HVPG to predict anticoagulation efficacy was 0.85, 95% CI was 0.69 to 1.00 ( P=0.009). When the logit≥0.393, the specificity and sensitivity in predicting anticoagulation efficacy was 62.5% and 91.7%, respectively. Conclusions:PPA can be used to assess the severity of acute onset PA-HSOS patients, and combined with ascites grading can significantly improve its efficiency. PPA combined with SCR and HVPG can better predict anticoagulant efficacy.

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.

Pathological Mechanism of HSOS in Rats Induced by Different Doses of Monocrotaline / 中国实验方剂学杂志

ObjectiveTo observe the pathological changes of hepatic sinusoidal obstruction syndrome （HSOS） induced by different doses of monocrotaline （MCT） in rats， investigate the dose and duration of modeling， and elucidate the mechanism. MethodA total of 72 male SD rats were randomized into normal group （n=12）， and low-， medium-， and high-dose MCT groups （n=20 per group， 80，120，160 mg·kg-1， respecctively）. In the model groups， different doses of MCT were intragastrically administered to induce the HSOS in rats. After 48 h and 120 h separately， rats in each group were sacrificed and sampling was performed. The survival rate of rats in each group was calculated， and the body weight， liver weight， and and serum liver function indexes of the rats were examined. The histopathological changes of the liver were observed based on scanning electron microscopy， hematoxylin and eosin （HE） staining， and Sirius red （SR） staining. Glutathione S-transferase （GST） activity， total superoxide dismutase （T-SOD） activity， and malondialdehyde （MDA） content of liver tissue homogenate were measured with microplate method. The expression of liver tissue-related indexes was detected by real-time polymerase chain reaction （PCR）， Western blot， and immunohistochemistry. ResultThe activity of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in MCT groups rose with the increase in MCT dose （P<0.05， P<0.01） compared with that in the normal group. With the extension of modeling time， the activity of serum ALT and AST in the low-dose group decreased （P<0.01）， while the activity of them in the medium-dose and high-dose groups increased （P<0.01）. HE staining showed that hepatocyte necrosis， inflammatory cell infiltration， and erythrocyte accumulation in MCT groups. Electron microscopy demonstrated that fenestrae of liver sinusoidal endothelial cells widened and the sieve plates disappeared. Morever， the injury was worsened with the increase in MCT dose. In addition， the expression of CD44 in MCT groups was significantly reduced compared with that in the normal group （P<0.05， P<0.01）. SR staining showed that no positive staining was found in model groups after 48 h， while collagen deposition in portal areas and liver sinusoids could be seen in model groups after 120 h. MCT groups showed increase in MDA content and GST activity and decrease in T-SOD activity compared with the normal group， particularly the medium-dose and high-dose groups （P<0.01）， and the changes were dose-dependent after 120 h （P<0.01）. The protein expression of CD68 （pro-inflammatory macrophage marker） was raised with the increase in dosage， which was consistent with the results of immunohistochemistry （P<0.01）， while CD163 （anti-inflammatory macrophage marker） protein and mRNA expression was significantly decreased with the increase in dosage （P<0.01）. Western blot results showed that the expression of phosphorylated nuclear factor-κB/nuclear factor-κB （p-NF-κB/NF-κB） and phosphorylated protein kinase B/protein kinase B （p-Akt/t-Akt） was significantly increased in medium-dose and high-dose MCT groups （P<0.05，P<0.01）. The protein expression of α-smooth muscle actin （α-SMA） in liver tissues in MCT groups was significantly increased over time and with the increase in dose， and the mRNA expression of α-SMA， collagen type I α1 （Col1a1）， and collagen type Ⅳ α1 （Col4a1） showed the same trend （P<0.05， P<0.01）. The results of TUNEL staining showed that apoptotic cells were increased with the rise of MCT dose， while B-cell lymphoma-2（Bcl-2） /Bcl-2 associated X protein （Bax） was remarkably decreased （P<0.01）. ConclusionHSOS in rats induced by intragastric administration of different doses of MCT was aggravated with the increase of dosage. In the low-dose （80 mg·kg-1） MCT group， the liver healed spontaneously over time. However， liver damage caused by MCT of 120 mg·kg-1 and 160 mg·kg-1 aggravated over time， and even fibrosis and death occurred. The pathological mechanism of MCT-induced HSOS in rats may be that MCT triggered intense oxidative stress in liver tissue， thus activated pro-inflammatory macrophages to secrete large amounts of inflammatory factors， and further activated the NF-κB/Akt signalling pathway， leading to severe cell damage and death.

Relationship between hepatic venous pressure gradient and parameters of Doppler ultrasound in 68 patients with pyrroidine alkaloid-related hepatic sinusoidal obstruction syndrome / 中华消化杂志

Objective:To investigate the relationship between hepatic venous pressure gradient (HVPG) and parameters of Doppler ultrasound in patients with pyrroidine alkaloid-related hepatic sinusoidal obstruction syndrome (PA-HSOS).Methods:From February 17, 2017 to April 22, 2020, the clinical data of 68 patients with PA-HSOS who underwent HVPG manometry and Doppler ultrasound examination at Drum Tower Hospital, the Affiliated Medical College of Nanjing University were retrospectively analyzed, which included HVPG, Drum Tower severity scoring (DTSS), time from PA-HSOS related symptoms appeared to diagnosis after taking pyrroidine alkaloid (hereinafter referred to as diagnosis time), and parameters of Doppler ultrasound induding portal vein trunk diameter (PD), peak portal vein velocity (PPV), splenic vein trunk diameter (SD) and peak splenic vein velocity (PSV). Receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value of HVPG for predicting non-response to anticoagulation therapy. Binary logistic regression was used to analyze the independent risk factors for non-response to anticoagulation therapy, and Kaplan-Meier survival curve was used to analyze the prognostic survival rate of patients with different HVPG levels. Unitary linear regression was applied to analyze the correlation of HVPG with PD, PPV, SD and PSV in patients with different HVPG levels, patients with mild, moderate and severe DTSS, and patients with diagnosis time >1 month or ≤ 1 month. Chi-square test was used for statistical analysis.Results:The results of ROC analysis showed that the optimal cut-off value of HVPG for predicting non-response to anticoagulant therapy was 20.165 mmHg(1 mmHg=0.133 kPa). The result of multivariate analysis indicated that high HVPG (HVPG>20.165 mmHg) was an independent risk factor for predicting non-response to anticoagulant therapy ( OR (95% confidence interval)=6.039(1.466 to 24.869), P=0.013). Kaplan-Meier survival curve demonstrated that prognostic survival rate of patients with high HVPG was lower than that of patients with low HVPG (HVPG≤20.165 mmHg) (78.4% vs.96.8%), and the difference was statistically significant( χ2=4.74, P=0.030). The results of unitary linear regression analysis showed that there was a negative correlation between HVPG and PPV in 68 patients with PA-HSOS( r=-0.330, P=0.006); HVPG was positively correlated with PD and SD in patients with high HVPG ( r=0.540 and 0.341, P=0.001 and 0.039); there was a negative correlation between HVPG and PSV in patients with mild DTSS ( r=-0.519, P=0.019), HVPG was negatively correlated with PPV in patients with moderate DTSS ( r=-0.400, P=0.014). In patients with diagnosis time ≤1 month, there was a negative correlation between HVPG and PPV ( r=-0.391, P=0.010). Conclusions:HVPG can assist in judging the response to anticoagulation therapy and the prognosis of patients with PA-HSOS. Parameters of Doppler ultrasound can help to assess the degree of HVPG elevation in patients with PA-HSOS under certain conditions.

Clinical impact of transjugular intrahepatic portosystemic shunt on refractory hepatic sinus obstruction syndrome caused by Gynura segetum / 中华肝胆外科杂志

Objective:To study the treatment outcomes of transjugular intrahepatic portal shunt (TIPS) on refractory hepatic sinus obstruction syndrome (HSOS) caused by Gynura segetum.Methods:The clinical data of 15 patients with refractory HSOS caused by Gynura segetum treated at the Department of Vascular Surgery, Henan Provincial People's Hospital from January 2017 to April 2021 were retrospectively analyzed. There were 7 males and 8 females, with ages ranging from 30 to 85 years, mean ± s. d. (61.2±14.1) years. Albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutamyl transferase, and portal vein pressure were compared before and after TIPS. The liver function and renal function of these patients were followed up.Results:When compared with pre-operation, the albumin, alanine aminotransferase, aspartate aminotransferase and other indexes were significantly improved after TIPS (all P<0.05). The portal vein pressure of 15 patients significantly decreased from the preoperative volume of (41.7±3.5) cmH 2O (1 cmH 2O=0.098 kPa) to (28.3±4.4) cmH 2O ( t=10.41, P<0.001). The preoperative liver function was Child-Pugh grade A in 1 patient, grade B in 8 patients, grade C in 6 patients. The postoperative Child-Pugh grading was grade A in 14 patients and grade B in 1 patient. Ascites, gastrointestinal bleeding, abdominal pain, abdominal distention and spontaneous peritonitis all disappeared in these 15 patients. Postoperative hepatic encephalopathy developed in 2 patients and hepatic myelopathy in 1 patient. Conclusion:TIPS for treatment of HSOS caused by Gynura segetum resulted in a rapid recovery of liver function, rapid symptomatic relief, with a low incidence of hepatic encephalopathy/hepatic myelopathy.

Diagnosis and treatment of hepatic sinusoidal obstruction syndrome after liver transplantation: a single-center experience / 器官移植

Objective To summarize the incidence, diagnostic and therapeutic experience of hepatic sinusoidal obstruction syndrome (HSOS) after liver transplantation. Methods Clinical data of 4 patients with HSOS after liver transplantation were retrospectively analyzed. The incidence, clinical manifestations, imaging and pathological characteristics of HSOS after liver transplantation were collected, and the treatment methods and clinical outcomes of patients with HSOS were analyzed. Results The incidence of HSOS after liver transplantation was 0.8%(2/239), and the median time of onset was 4.5(1.7, 9.0) months after liver transplantation. The clinical manifestations of HSOS mainly included abdominal distension, ascites, hepatomegaly, increased bilirubin, and renal insufficiency in partial cases. Enhanced abdominal CT scan of 4 patients with HSOS showed uneven spot-like enhancement and the liver histopathological examination mainly showed the signs of hepatic sinusoidal dilatation complicated with congestion. Four patients were administered with an adjusted regime of immunosuppressant by replacing tacrolimus (Tac) with ciclosporin and adding anticoagulant therapy with warfarin. One patient received transjugular intrahepatic portosystemic shunt (TIPS). After treatment, the symptoms of 3 patients were completely relieved, and 1 patient died. One of the 3 surviving patients died from pulmonary infection and gastrointestinal bleeding. Conclusions HSOS is a rare and fatal complication after liver transplantation. Timely diagnosis and treatment can avoid the incidence of graft failure and improve clinical prognosis of the patients.

Clinical Analysis of Oxaliplatin-related Thrombocytopenia in Patients with Digestive System Malignancy / 肿瘤防治研究

Objective To investigate the changing trend and correlation of platelet count and spleen diameter in patients with digestive system malignancy receiving oxaliplatin-based chemotherapy. Methods We retrospectively analyzed clinical data of 72 patients with digestive system cancer, recorded and analyzed platelet count and spleen diameter during and after oxaliplatin-based chemotherapy. Results The incidence of thrombocytopenia in all patients was 65.3%. The median time of thrombocytopenia after the beginning of chemotherapy was 2.53±0.49 months, and the median cumulative dose of oxaliplatin was 520±35.81 mg/m2; the median time of lowest platelet count after the beginning of chemotherapy was 4.03±0.49 months, and the median cumulative dose of oxaliplatin was 780±36.32 mg/m2. Splenomegaly occurred in 52(72.2%) patients during the follow-up. The median increase rate was (18.82±0.01)%. The median time of splenomegaly after the beginning of chemotherapy was 2.15±0.19 months, the median time for the largest spleen diameter was 4.68±2.89 months; after the end of chemotherapy, the median time for spleen contraction was 3.28±0.44 months, and the median time for spleen recovery was 8.80±1.05 months. Conclusion Oxaliplatin-based chemotherapy can cause thrombocytopenia and splenomegaly, and it is difficult to recover to baseline for a long time after the end of chemotherapy. The increase of spleen diameter was positively correlated with splenomegaly and thrombocytosis.

Kinetic study of pyrrolizidine alkaloid-derived pyrrole-protein adducts in rats after intragastric administration of Gynura japonica / 药学学报

Recently, hepatic sinusoidal obstruction syndrome (HSOS) induced by misuse of Gynura japonica has increased and gained global attention. Large amounts of pyrrolizidine alkaloids (PAs) are present in G. japonica; these PAs are metabolically activated to generate pyrrole-protein adducts (PPAs). In this study, male SD rats were treated orally with a single dose of G. japonica extract (GJE) at 0.062 5, 0.25, 0.5, 1, and 2 g·kg-1. Blood was collected from the orbital venous plexus at 2, 12, 24 and 48 h, and at 48 h after treatment the rats were anesthetized with isoflurane and livers were collected for hematoxylin & eosin staining. The kinetics of PPAs at different doses were studied at 10, 20, 30 min, 1, 2, 4, 6, 12, 24 h, and 48 h, after a single gavage of GJE. The experimental scheme was approved by the ethics committee of animal experiments of Shanghai University of Traditional Chinese Medicine (PZSHUTCM190912019). The concentration of PPAs in serum was determined by liquid chromatography-mass spectrometry (LC-MS). Kinetic data were processed by using the non-compartmental pharmacokinetics data analysis software program PK solutions 2™. The results demonstrate that the concentration of PPAs increased with the dose of GJE and positively correlated with the severity of liver injury. The elimination rate of PPAs in rats was significantly prolonged at higher doses. The level of PPAs and their clearance rate may serve as useful references for the detoxification of PAs-induced injuries.

Efficacy of transjugular intrahepatic portosystemic shunt in treatment of sinusoidal obstruction syndrome caused by gynura segetum / 中华肝胆外科杂志

Ohjective To evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of sinusoidal obstruction syndrome (SOS) caused by gynura segetum.Methods The clinical data of 9 patients with SOS caused by gynura segetum (5 males and 4 females) who underwent TIPS were retrospectively analyzed from February 2017 to June 2018.The Child-Pugh scores were (9.5 ± 1.3) and the MELD scores were (12.5 ± 5.0).The success rates,complications and follow-up results were evaluated.Results TIPS was performed successfully in all the 9 patients.The portal venous pressure gradient dropped from (22.4 ± 2.7) mmHg to (10.4 ± 3.2) mmHg (P ＜ 0.05).There was no complication such as abdominal hemorrhage and biliary peritonitis.Nine patients were followed-up for 1 ～17months,mean 7.8 ± 6.0 months.One month after treatment,the Child-Pugh scores were (7.1 ± 1.8),compared with that of the preoperative scores,the difference was statistically significant (P ＜ 0.05).The MELD scores were (5.3 ± 4.6),compared with that of the preoperative scores,the difference was also statistically significant (P ＜ 0.05).At the end point of the follow-up,color Doppler ultrasound and portal CTA showed that the TIPS shunt was patent and hepatic congestion was relieved in all the 9 patients.All patients were alive.Conclusion TIPS was a safe and efficacious treatment for SOS caused by gynura segetum.

The clinical thinking of diagnosis and treatment of cryptogenic cirrhosis / 医学研究生学报

Cryptogenic cirrhosis (CC), cirrhosis of unknown cause, is common in clinic. With the improvement of the level of diagnosis and the diversification of the diagnosis and treatment, the incidence of CC is gradually declining. In the process of diagnosis and treatment, perfect clinical thinking can help clinicians to analyze and evaluate the existing clinical data, and it is expected to further improve the diagnostic rate of CC. In this paper, the clinical thinking of CC diagnosis and treatment is expounded from the aspects of disease spectrum thinking, anatomy thinking and macroscopic micro thinking.

Methods for quantitative measurement in the computed tomography images of Tusanqi related hepatic sinusoidal obstruction syndrome / 中华消化杂志

Objective To explore the feasibility of applying threshold and region-growing based algorithm in computed tomography (CT) images for the estimation of hepatic lesion volumes in patients with Tusanqi related hepatic sinusoidal obstruction syndrome (SOS).Methods From July 2012 to January 2015,at the First Affiliated Hospital of Anhui Medical University,20 patients who were diagnosed with SOS and had complete CT images were enrolled.Stereology and threshold and regiongrowing based algorithm were performed to estimate volumes of the low-density region in the liver,respectively,and then the measured volumes of hepatic lesion and operation time were compared.Paired samples t test and the Bland-Altman statistical test were performed for statistical analysis.Results The hepatic lesion volumes measured by stereology and threshold and region-growing based algorithm were (1.001±0.327) dm3 and (1.045±0.363) dm3,respectively,and the difference was not statistically significant (P＞0.05).The consistency between the two methods was good.The operation time of threshold and region-growing based algorithm was (597.55±52.86) s (minimum 500 s),which was less than that of stereology (1 251.60 ± 105.88) s (minimum 1 075 s),and the difference was statistically significant (t =32.808,P＜ 0.01).Conclusion There is no statistically significant difference in the measured hepatic lesion volume of patients with SOS between stereology and the threshold and regiongrowing based algorithm,but the operation time of threshold and region-growing based algorithm is shorter.

Clinical characteristics of 115 cases of gynura segetum induced hepatic sinusoidal obstruction syndrome / 中华消化杂志

Objective To study the clinical characteristics of gynura segetum induced hepatic sinusoidal obstruction syndrome (HSOS).Methods From July 2008 to October 2016,a total of 115 cases of gynura segetum caused HSOS were retrospectively analyzed.The history of taking gynura segetum before disease onset was recorded and epidemiologic data of main clinical symptoms,clinical manifestations,laboratory examinations,imaging and pathological features were observed.Results Among the 115 cases of HSOS,there were 113 patients with abdominal pain,106 with anorexia and 42 with jaundice sclera.A total of 108 patients displayed increased serum total bilirubin,41 of them only with mildly increased total bilirubin.There were 29 patients with albumin lower than 30 g/L,64 patients with prolonged prothrombin time (PT) and PT of 11 patients was prolonged for more than three seconds.Meanwhile,31 patients were with prolonged activated partial prothrombin time (APTT).A total of 60 patients had low platelet count.And 92 patients underwent ultrasound examination,among them,71 patients had enlarged liver size,79 patients with uneven internal echo of liver,70 patients with ascites,14 patients with patchy low echo tissue around hepatic venous.A total of 60 patient accepted computed tomography (CT) examination,and all of them had ascites,14 patients with mildly enlarged spleen and eight patients with gastro-esophageal varices.The results of CT plain scan indicated hepatomegaly,decreased liver density,map-like changes of patchy low density in delayed phase,heterogeneous enhancement of liver parenchyma in arterial phase,compression and deformation of liver segment of inferior vena cava and halo sign around venous portal vein.The results of pathological examination demonstrated the widening of hepatic sinusoid with hemorrhage and congestion,destruction of liver plate in zone Ⅲ area.There were seven patients who received hepatic venous pressure gradient (HVPG) measurement which were all significantly increased.Conclusions The characteristics of patients with gynura segetum caused HSOS are abdominal pain,anorexia and jaundice;mildly increased serum total bilirubin and albumim liver enlargement,slow blood velocity of portal vein and splenic veim increased HVPG,hepatic sinus congestion and cell coagulation necrosis in zone Ⅲ area.

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.

Hepatic Sinusoidal Obstruction Syndrome Caused by Herbal Medicine: CT and MRI Features

OBJECTIVE: To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum. MATERIALS AND METHODS: The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images. RESULTS: Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565). CONCLUSION: Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.

Sinusoidal obstruction syndrome after oxaliplatin-based chemotherapy

No abstract available.

6-Thioguanine-Induced Hepatic Sinusoidal Obstruction Syndrome in a Leukemic Child with TPMT Heterozygote / 임상소아혈액종양

Hepatic sinusoidal obstruction syndrome (hSOS) can be developed as a common complication after hematopoietic stem cell transplantation (HSCT), and rarely after 6-thioguanine-based chemotherapy without HSCT. A four-year-old boy with heterozygotic polymorphism for thiopurine methyltransferase (TPMT) developed hSOS after he received chemotherapy with cytarabine, cyclophosphamide, intrathecal methotrexate and 6-thioguanine (6-TG) as reconsolidation chemotherapy of acute lymphoblastic leukemia (ALL). He was treated with defibrotide, N-acetylcysteine, urusodeoxycholic acid, glutathione, and supportive care. He recovered completely in nine days without long-term complication, and completed chemotherapy with 6-mercaptopurine without severe complication. We report a case of hSOS developed in an ALL patient with TPMT heterozygote after 6-TG based reconsolidation chemotherapy.

6-Thioguanine-Induced Hepatic Sinusoidal Obstruction Syndrome in a Leukemic Child with TPMT Heterozygote / 임상소아혈액종양

Hepatic sinusoidal obstruction syndrome (hSOS) can be developed as a common complication after hematopoietic stem cell transplantation (HSCT), and rarely after 6-thioguanine-based chemotherapy without HSCT. A four-year-old boy with heterozygotic polymorphism for thiopurine methyltransferase (TPMT) developed hSOS after he received chemotherapy with cytarabine, cyclophosphamide, intrathecal methotrexate and 6-thioguanine (6-TG) as reconsolidation chemotherapy of acute lymphoblastic leukemia (ALL). He was treated with defibrotide, N-acetylcysteine, urusodeoxycholic acid, glutathione, and supportive care. He recovered completely in nine days without long-term complication, and completed chemotherapy with 6-mercaptopurine without severe complication. We report a case of hSOS developed in an ALL patient with TPMT heterozygote after 6-TG based reconsolidation chemotherapy.

Advances in hepatic sinusoidal obstruction syndrome after liver transplantation / 中华肝胆外科杂志

In liver transplantation,hepatic sinusoidal obstruction syndrome (HSOS) is rare,which results in misdiagnosis and mistreatment.The prognosis of HSOS after liver transplantation is related to the implementation of early specific treatment.No systematic review has been reported on HSOS after liver transplantation.To raise awareness of HSOS after liver transplantation,this review summarizes the aetiology,pathology,clinical manifestations,laboratory findings,imaging features,diagnosis,differential diagnosis,treatment and prognosis of the condition.

Transplante hepático para síndromes hepatopulmonar e de obstrução sinusoidal / Liver transplantation for hepatopulmonary and sinusoidal obstruction syndrome

INTRODUÇÃO: A síndrome hepatopulmonar é complicação das doenças hepáticas que afeta a vascularização pulmonar, causando comprometimento do sistema respiratório e acompanha-se de elevada morbidade. O transplante hepático é o tratamento ideal para esses casos. O objetivo desse relato é descrever o caso de um paciente que apresentava síndrome hepatopulmonar avançada, devida à síndrome da obstrução sinusoidal.RELATO DO CASO: Homem de 23 anos foi encaminhado com o diagnóstico de síndrome hepatopulmonar avançada e cirrose hepática sem etiologia idefinida. Exames de imagem foram compatíveis com shunt intrapulmonar, porém sem alterações da vascularização pulmonar factíveis de serem embolizadas. A endoscopia digestiva alta demonstrou varizes esofágicas de pequeno calibre. Exames laboratoriais para função hepática estavam alterados. O paciente foi submetido a transplante hepático falecendo 14 dias após o procedimento devido a complicações relacionadas à sepse e insuficiência ventilatória refratária.CONCLUSÃO: Na vigência de síndrome hepatopulmonar o único tratamento efetivo é o transplante hepático, para os casos em que não houver área de shunt factível de ser realizada a embolização seletiva.

INTRODUCTION: The hepatopulmonary syndrome is a complication of liver diseases that affects the pulmonary vascular system compromising respiratory function. High morbidity rates are associated with this syndrome. Liver transplantation is the treatment of choice. The aim of this report is to present the case of a patient who sustained advanced hepatopulmonary syndrome resulting from the sinusoidal obstruction syndrome.CASE REPORT: A 23-year-old male was referred with the diagnosis of advanced hepatopulmonary syndrome and liver cirrhosis of undefined etiology. Imaging studies were consistent with intrapulmonary shunt yet without alterations in pulmonary vascularization amenable to embolization. Upper digestive endoscopy demonstrated small-caliber esophagian varices. Laboratory tests for liver function showed alterations. The patient underwent liver transplantation and died 14 days after, due to sepsis-related complications and refractory ventilatory failure.CONCLUSION: In cases when it is not feasible to perform selective embolization in the shunt area, the only effective treatment for hepatopulmonary syndrome is liver transplantation.