title: Chemotherapy-induced Sinusoidal Injury (CSI) score: a novel histologic assessment of chemotherapy-related hepatic sinusoidal injury in patients with colorectal liver metastasis.
abstract: 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.
authors.affiliation: Department of Pathology, The University of Texas Medical Branch, John Sealy Annex Building - Room 2.148, 301 University Blvd., Galveston, TX, 77555-0588, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Stevenson
authors.affiliation: Department of Pathology, The University of Texas Medical Branch, John Sealy Annex Building, 301 University Blvd., Galveston, TX, 77555-0588, USA.
authors.forename: Mariana M
authors.initials: MM
authors.lastname: Prats
authors.affiliation: Department of Pathology, The University of Texas Medical Branch, John Sealy Annex Building - Room 2.148, 301 University Blvd., Galveston, TX, 77555-0588, USA. sasatomi@med.unc.edu.|Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill Women's & Children's Hospitals, Room 30212, 101 Manning Drive, Chapel Hill, NC, 27514, USA. sasatomi@med.unc.edu.
authors.forename: Eizaburo
authors.identifier: 0000-0002-5925-422X
authors.initials: E
authors.lastname: Sasatomi
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006498:Hepatectomy; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin
chemical_list: D000199:Actins; D018952:Antigens, CD34; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005974:Glutamate-Ammonia Ligase; D002955:Leucovorin; D005472:Fluorouracil
keywords: Colorectal liver metastasis; FOLFOX; Impaired liver function; Oxaliplatin; Sinusoidal obstruction syndrome