Chemotherapy-induced Sinusoidal Injury (CSI) score: a novel histologic assessment of chemotherapy-related hepatic sinusoidal injury in patients with colorectal liver metastasis
Open accessAbstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Senescence is a possible cause of decreased liver function in the sinusoidal area.
“These findings align with the known liver injury and sinusoidal obstruction caused by oxaliplatin,85,86,87 suggesting senescence as a possible cause of decreased liver function in the sinusoidal area.”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [87]
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- Authors
- Stevenson, H. L., Prats, M. M., & Sasatomi, E.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Sasatomi, Eizaburo
- Venue
- BMC Cancer
- Published
- 2017-01-07
- Volume
- 17
- Issue
- 1
- Pages
- 35-35
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC5219653
- OpenAlex
- W2567870389
- Cited by
- 37
- References
- 36
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 5 · 2018: 3 · 2017: 1
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- veno-occlusive disease, colorectal liver metastases, neoadjuvant chemotherapy, CD34, smooth muscle actin, glutamine synthetase, hepatic stellate cells, sinusoidal endothelial cells, immunohistochemistry scoring, hepatectomy, liver insufficiency, histologic grading
- MeSH terms
- Oxaliplatin, Actins, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Female, Fluorouracil, Glutamate-Ammonia Ligase, Hepatectomy, Hepatic Veno-Occlusive Disease, Humans, Liver Neoplasms, Male, Middle Aged, Organoplatinum Compounds, Colorectal Neoplasms, Antigens, CD34, Neoadjuvant Therapy
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