• anticoagulant therapy
• gynura segetum
• hepatic sinusoidal obstruction syndrome
• hepatic veno-occlusive disease
• pyrrolizidine alkaloids

• Male
• Child
• Humans
• Child, Preschool
• Hepatic Veno-Occlusive Disease/chemically induced
• Hepatic Veno-Occlusive Disease/diagnosis
• Hepatic Veno-Occlusive Disease/therapy
• Drugs, Chinese Herbal/adverse effects
• Pyrrolizidine Alkaloids/adverse effects
• Hypertension, Portal

• Artery resection
• Conversion surgery
• FOLFIRINOX
• Locally advanced
• Pancreatic cancer

• Humans
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Gastroenterology
• Japan
• Neoadjuvant Therapy/methods
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/surgery

• colon cancer
• colorectal live metastasis
• neoadjuvant chemotherapy
• propensity score
• resection

• liver surgery
• non-alcoholic fatty liver disease
• nutrition
• protein
• protein diet

• Humans
• Non-alcoholic Fatty Liver Disease/pathology
• Liver/surgery
• Liver/pathology
• Risk Factors
• Hepatectomy/adverse effects
• Colorectal Neoplasms/surgery
• Colorectal Neoplasms/pathology

Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early.

In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT.

Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase  ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32–0.41). The change in rate of LSM by SWE was correlated with an SV increase  ≥ 30% (r = 0.40).

The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.

The online version contains supplementary material available at 10.1007/s10147-022-02235-4.

• Liver stiffness measurement
• Oxaliplatin
• Shear-wave elastography
• Sinusoidal obstruction syndrome
• Ultrasonography

• extravasated platelet aggregation
• hepatocytes
• sinusoidal capillarization
• sinusoidal obstruction syndrome
• thrombopoietin

Platelet index was reported to be used as a potential prognostic marker in patients with liver fibrosis. We aimed to explore the association between plateletcrit (PCT) and severity of hepatic sinusoidal obstruction syndrome (HSOS).

Seventy consecutive patients who diagnosed as HSOS by CT and medical history during January 2017‐November 2021 were included. All patients were divided into two groups which confirmed as favorable prognosis and poor prognosis on the basis of Child‐Turcotte‐Pugh score system. The clinical manifestation and laboratory parameters of two groups were retrospectively selected. PCT was evaluated within two groups, and the diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve.

The significant difference between the two groups not only in diarrhea, abdominal pain, abdominal distention, urine volume, and skin ecchymosis (p < 0.005), but also in WBC count, NE count, PLT count, TBIL, and D‐Dimer (p < 0.005) were found. The PCT level was significantly higher in HSOS patients with poor prognosis (0.169 ± 0.060) than favorable prognosis patients (0.110 ± 0.047). The area under the receiver operating characteristic curve of RDW in predicting poor prognosis was 0.781, with 67.70% sensitivity and 79.5%specificity.

The PCT level was correlated positively with the poor prognosis in HSOS patients. PCT can be a promising indicator for predicting prognosis in HSOS

• hepatic function evaluation
• hepatic sinusoidal obstruction Syndrome
• inflammation
• plateletcrit

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). The disease has a high mortality rate, a poor prognosis and limited treatment options. Managing pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) is a significant challenge for hepatologists. This case report describes five patients with PA-HSOS that were treated with low molecular weight heparin (LMWH) between 2014 and 2019. All five patients had a history of taking PA-containing herbal preparations before the onset of the disease. They all met the Nanjing diagnostic criteria and were diagnosed with PA-HSOS. Symptomatic treatment was administered to all five patients. In addition to symptomatic treatment, all five patients were treated with LMWH for approximately 8–21 days. After treatment, their ascites disappeared, symptoms improved and the hepatic venous blood flow had improved compared with before treatment. There was no obvious discomfort during the 6 months of follow-up. LMWH may play a useful role in the early treatment of PA-HSOS. Therefore, for patients in the early stages of PA-HSOS, in addition to symptomatic treatment, early anticoagulant intervention can be attempted to improve patient prognosis under close monitoring of coagulation.

• Low molecular weight heparin
• early anticoagulant intervention
• hepatic sinusoidal obstruction syndrome

• Gd-EOB-DTPA
• diagnostic imaging
• drug-induced liver injury
• magnetic resonance imaging
• oxaliplatin

• chemotherapy
• chemotherapy-associated liver injury
• colorectal cancer
• hepatotoxicity
• liver metastases
• sinusoidal obstruction syndrome

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.

• Hepatic sinusoidal obstruction syndrome
• Pyrrolizidine alkaloids
• Hepatic sinusoidal endothelial cells
• Pyrrole-protein adducts
• Diagnostic criteria
• Symptomatic treatment
• Anticoagulant therapy

• Anticoagulants/therapeutic use
• Biopsy
• China
• Endothelial Cells/pathology
• Endothelium, Vascular/cytology
• Endothelium, Vascular/pathology
• Fluid Therapy/methods
• Glucocorticoids
• Hepatic Veins/cytology
• Hepatic Veins/diagnostic imaging
• Hepatic Veins/pathology
• Hepatic Veno-Occlusive Disease/chemically induced
• Hepatic Veno-Occlusive Disease/diagnosis
• Hepatic Veno-Occlusive Disease/therapy
• Humans
• Liver/blood supply
• Liver/diagnostic imaging
• Liver/pathology
• Liver Function Tests
• Liver Transplantation
• Magnetic Resonance Imaging
• Plants, Edible/chemistry
• Plants, Edible/toxicity
• Portasystemic Shunt, Transjugular Intrahepatic
• Pyrrolizidine Alkaloids/toxicity
• Tomography, X-Ray Computed
• Treatment Outcome

Hepatic sinusoidal obstruction syndrome (HSOS), previously known as hepatic veno-occlusive disease, is a kind of vascular disorder of the liver. HSOS is caused by toxic destruction of hepatic sinusoidal endothelial cells. Major etiologies of HSOS include hematopoietic stem cell transplantation, oxaliplatin-containing chemotherapy, intake of pyrrolizidine alkaloid-containing herbal remedies, etc. There have been many studies on the imaging manifestations of HSOS in recent years. This paper summarizes the imaging manifestations of HSOS by reviewing the latest literature and our work.

• Hepatic sinusoidal obstruction syndrome
• Pyrrolizidine alkaloid
• Hematopoietic stem cell transplantation
• Imaging

• Colorectal cancer
• FNH-like lesion
• Gd-EOB-DTPA
• Hepatobiliary phase
• Liver MRI
• Oxaliplatin
• Sinusoidal obstruction syndrome

• Esophagogastric varices
• Hepatotoxicity
• Non-cirrhosis
• Oxaliplatin
• Sinusoidal obstruction syndrome (SOS)

The FOLFIRINOX regimen is the standard first-line treatment for advanced pancreatic adenocarcinoma (aPDAC). However, because of its potential toxicity, predictive biomarkers could help clinical decision-making.

A cohort of 97 aPDAC patients treated with first-line FOLFIRINOX were studied. The association between splenic volume and progression-free survival (PFS) and overall survival (OS) was evaluated using univariate and multivariable Cox analyses. The external validation cohort was composed of 117 patients treated with Gemcitabine and 52 patients treated with FOLFIRINOX.

In the training cohort, the splenic volume of 97 patients was measured at baseline and at the end of therapy. The spleen size increased in 81% of patients, with at least a 50% increase in 27% of patients. Baseline splenomegaly predicted PFS (HR 1.812, 95% CI = [1.036–3.169]; p = 0.03) and OS (HR 1.983, 95% CI = [1.085–3.624]; p = 0.02) in the training cohort. These results were then validated in an external cohort of patients who were treated with FOLFIRINOX excluding those in the control cohort who were treated with gemcitabine. In a multivariate model based on the CoxBoost method, the following were selected as predictive markers of FOLFIRINOX efficacy (AUC = 0.81): performance status, liver metastasis, baseline Ca199 and CEA levels and baseline splenomegaly. The predictive ability of the model was validated in the external cohort that was also treated with FOLFIRINOX.

Baseline splenomegaly is a predictive marker of a poor response to FOLFIRINOX in aPDAC and remained predictive when associated with other clinical variables.

• FOLFIRINOX
• advanced pancreatic carcinoma
• biomarker
• splenic volume

Preoperative neoadjuvant therapy for colorectal liver metastases (CRLM) is increasing in use and can lead to chemotherapy-induced damage to sinusoidal integrity, namely sinusoidal obstruction syndrome (SOS). SOS has been associated with an increased need for intraoperative blood transfusions, increased length of hospitalization post-surgery, decreased tumor response, and a shorter overall survival after resection due to liver insufficiency. It is critical for clinicians and pathologists to be aware of this type of liver injury, and for pathologists to include the status of the background, non-neoplastic liver parenchyma in their pathology reports. In this study, expression of CD34 by sinusoidal endothelial cells (SECs), increased expression of smooth muscle actin (SMA) by hepatic stellate cells (HSCs), and aberrant expression of glutamine synthetase (GS) by noncentrizonal hepatocytes were semiquantitatively evaluated in liver resection or biopsy specimens from patients with CRLM to determine their diagnostic value for assessing chemotherapy-induced sinusoidal injury (CSI).

The expression of each marker was compared among 22 patients with CRLM with histologically evident SOS (SOS+) and 8 patients with CRLM who had not undergone chemotherapy. Each case was given a histologic grade using the sinusoidal obstruction syndrome index score (SOS-I) to assess the likelihood of SOS. Cases were also given an immunohistochemical grade using the total CSI score calculated as the sum of CD34, SMA, and GS scores.

Abnormal staining patterns for CD34 and SMA were significantly more frequent and extensive in SOS+ cases than in the controls (81.8% vs. 25%, P < 0.01; 72.7% vs. 25%, P = 0.03). Aberrant GS expression in midzonal and periportal hepatocytes was only observed in SOS+ cases (31.8% vs. 0%), but this difference did not reach statistical significance. The CSI score was significantly higher in the SOS+ cases when compared to controls (P < 0.01), and was associated with a higher SOS histologic grade (P = 0.02).

The CSI score, calculated using an immunohistochemical panel consisting of CD34, SMA, and GS, may serve as an objective marker of chemotherapy-induced sinusoidal injury and could help diagnose this peculiar form of liver injury.

• Colorectal liver metastasis
• FOLFOX
• Impaired liver function
• Oxaliplatin
• Sinusoidal obstruction syndrome

• Chronic hepatitis C infection
• Cost–utility analysis
• Daclatasvir
• Japan
• Ledipasvir/sofosbuvir
• Simeprevir
• Telaprevir

• Antiviral Agents/administration & dosage
• Benzimidazoles/administration & dosage
• Cost-Benefit Analysis
• Drug Therapy, Combination
• Fluorenes/administration & dosage
• Genotype
• Hepacivirus/genetics
• Hepatitis C, Chronic/drug therapy
• Humans
• Sofosbuvir/administration & dosage

• Biomarker
• DNA adducts
• Kinetics
• Pyrrolizidine alkaloid

• colon cancer
• oxaliplatin
• sinusoidal obstruction syndrome

• Aged
• Analysis of Variance
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Biomarkers/blood
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Female
• Hepatic Veno-Occlusive Disease/chemically induced
• Hepatic Veno-Occlusive Disease/pathology
• Humans
• Liver Cirrhosis/etiology
• Liver Cirrhosis/pathology
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Organoplatinum Compounds/administration & dosage
• Organoplatinum Compounds/adverse effects
• Oxaliplatin
• Pilot Projects
• Prognosis
• Retrospective Studies
• Risk Assessment
• Spleen/drug effects
• Splenomegaly/chemically induced
• Splenomegaly/pathology
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Survival Rate

• HCC
• REILD
• colorectal adenocarcinoma
• hepatocellular carcinoma
• liver metastases
• radioembolization-induced liver disease

Oxaliplatin based chemotherapy is often used as adjuvant therapy in colon and rectal cancer. A reported side effect is Sinusoidal Obstruction Syndrome which is characterized by a spectrum of pathologic changes, from sinusoidal dilation, peri-sinusoidal haemorrhage, peliosis and nodular regenerative hyperplasia. Very rarely it can cause the development of liver nodules mimicking liver metastases. Herein, we report a case of Sinusoidal Obstruction Syndrome causing a liver nodule suspicious of liver metastasis on imaging. This is the third reported case of this complication of oxaliplatin toxicity, in which resection was performed and pathological diagnosis confirmed.

We report the case of a 59 year old man with stage III colon cancer who underwent sigmoidectomy followed by adjuvant chemotherapy with oxaliplatin. One year after surgery a liver nodule was detected and the patient underwent right hepatectomy. Pathology showed no liver nodule and diagnosed sinusoidal obstruction syndrome.

We describe the third reported case of a liver lesion mimicking a liver metastasis after oxaliplatin-based chemotherapy for colon cancer. We suggest that in patients heavily treated with oxaliplatin with de novo liver nodules, this differential diagnosis should be considered. In particular, in this population of patients an intense imagiologic evaluation and even a preoperative biopsy should be pursued to confirm the diagnosis of malignancy and avoid overtreatment.

• colorectal liver metastasis
• extravasated platelet aggregation
• oxaliplatin
• sinusoidal obstruction syndrome