Sinusoidal Injury Increases Morbidity After Major Hepatectomy in Patients With Colorectal Liver Metastases Receiving Preoperative Chemotherapy

Nakano, Hiroshi; Oussoultzoglou, Elíe; Rosso, Edoardo; Casnedi, Selenia; Chenard-Neu, Marie-Pierre; Dufour, Patrick; Bachellier, Philippe; Jaeck, Daniel

doi:10.1097/sla.0b013e31815774de

Cited by 415 publications

(368 citation statements)

References 25 publications

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“…74,75 Oxaliplatin is a key agent in such regimes, and may cause sinusoidal injury, onset of SOS, and increased morbidity before or after hepatectomy. [76][77][78] Histologic evidence of high-grade lesions of SOS has been reported to be present in 59% of patients receiving preoperative oxaliplatin treatment before hepatectomy, based on examination of the surrounding resected liver. 79 The presence of such sinusoidal injury had a detrimental effect both on the intra-and post-operative course of patients undergoing major liver resection.…”

Section: Cytoreductive Conditioning Prior To Hepatectomy For Metastatmentioning

confidence: 99%

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

Fan

Crawford

2014

Journal of Clinical and Experimental Hepatology

228

178

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Section: Cytoreductive Conditioning Prior To Hepatectomy For Metastatmentioning

confidence: 99%

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

Fan

Crawford

2014

Journal of Clinical and Experimental Hepatology

228

178

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“…In fact, since our initial report (1), several groups have confirmed the existence of oxaliplatin-related SOS in 25% to 36% of treated patients. This has led to concerns that oxaliplatin-associated hepatotoxicity may decrease the chances of curative liver surgery by increasing morbidity through preoperative hemorrhage, postoperative liver failure, delayed regeneration, and portal hypertension (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Rare fatal cases have been reported, inducing a group of experts to publish a cautionary note on the use of chemotherapy before surgical liver resection (14).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Rubbia‐Brandt

Tauzin

Brézault

et al. 2011

Molecular Cancer Therapeutics

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Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS.

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“…These histological changes have been observed in ≤40% of patients treated with oxaliplatin-based regimens undergoing liver resection (2)(3)(4)(5)(6). SOS is a cause for concern prior to major hepatectomy, as it is associated with increased perioperative morbidity and prolonged hospital stay (7). Clinically, the diagnostic factors associated with SOS include portal hypertension, splenomegaly, thrombocytopenia, abnormal indocyanine green (ICG) retention rate and elevations in the levels of liver enzymes, bilirubin and hyaluronic acid (8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Oxaliplatin-based chemotherapy induces extravasated platelet aggregation in the liver

Tajima

Ohta

Miyashita

et al. 2015

Molecular and Clinical Oncology

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Abstract.Oxaliplatin-based chemotherapy plays a central role in the treatment of patients with colorectal liver metastasis (CRLM). This treatment, however, has been associated with hepatic sinusoidal obstruction syndrome (SOS), a clinically important adverse effect characterized by a bluish hue of the liver, splenomegaly and thrombocytopenia, resulting in liver dysfunction. The significant association between the sinusoidal endothelium and platelets has suggested that oxaliplatin-based chemotherapy affects platelets in the liver. This study compared platelet counts in patients who did and did not receive oxaliplatin-based neoadjuvant chemotherapy (NAC). The peripheral blood platelet count was significantly lower in the NAC group (n=17) compared to that in the non-NAC, or control group (n=15) (P<0.05). The spleen index was also higher in the NAC group, although the difference was not significant. However, the spleens of the patients in the NAC group were significantly enlarged following treatment (P<0.01). Immunostaining for the platelet surface marker CD42b (glycoprotein Ib), revealed more platelets in the liver in the NAC compared to the control group, particularly in the centrilobular zone III, adjacent to the hepatic central vein and in contact with hepatocytes (P<0.01). The platelets present in the spaces of Disse, referred to as extravasated platelet aggregation (EPA), secrete a number of growth factors, including transforming growth factor-β, vascular endothelial growth factor-A, plasminogen activator inhibitor-1 and thromboxane A2. In conclusion, EPA may play an important role in the development of hepatic SOS. Moreover, antiplatelet drugs may prevent the onset of SOS and hepatic injury in patients treated with oxaliplatin-based chemotherapy for CRLM.

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Sinusoidal Injury Increases Morbidity After Major Hepatectomy in Patients With Colorectal Liver Metastases Receiving Preoperative Chemotherapy

Cited by 415 publications

References 25 publications

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Oxaliplatin-based chemotherapy induces extravasated platelet aggregation in the liver

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