title: Liver injury due to chemotherapy-induced sinusoidal obstruction syndrome is associated with sinusoidal capillarization.
abstract: BACKGROUND
  Indocyanine green (ICG) retention is a validated test of hepatic function in patients with chronic liver disease. The underlying mechanism for the impairment of ICG retention in patients undergoing chemotherapy for colorectal liver metastases (CLM) remains unclear. We sought to elucidate the mechanism for impairment of ICG retention in patients with CLM.
  
  
  METHODS
  Clinicopathologic data of 98 patients with CLM undergoing hepatectomy were analyzed. The archived nontumoral liver parenchyma bearing no CLM were immunostained with CD34 antibody to determine the sinusoidal capillarization.
  
  
  RESULTS
  Of 98 patients, 80 received preoperative chemotherapy. Sinusoidal obstruction syndrome (SOS) occurred in 39 patients (39.8%). The development of SOS in patients receiving oxaliplatin-based chemotherapy was significantly higher compared to those receiving non-oxaliplatin-based chemotherapy (P=0.003). SOS was independently associated with abnormal ICG retention rate at 15 minutes (ICG-R15) (odds ratio 3.45, 95% confidence interval 1.31-9.04, P=0.012) and CD 34 overexpression (odds ratio 18.76, 95% confidence interval 4.58-76.81, P<0.001). ICG-R15 correlated with CD34 expression within the nontumoral liver parenchyma (r=0.707, P<0.001) and severity of SOS (r=0.423, P<0.001). CD34 positive areas were likely situated at the peripheral area of SOS, and both SOS score and number of cycles of oxaliplatin-based chemotherapy significantly correlated with CD34 expression (r=0.629, P<0.001 and r=0.522, P<0.001, respectively).
  
  
  CONCLUSIONS
  These results suggest that the deterioration of hepatic functional reserve due to SOS is associated with sinusoidal capillarization, indicated by CD34 overexpression within nontumoral liver parenchyma adjacent to SOS.
authors.affiliation: Centre de Chirurgie Viscérale et de Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Masato
authors.initials: M
authors.lastname: Narita
authors.forename: Elie
authors.initials: E
authors.lastname: Oussoultzoglou
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chenard
authors.forename: Pascal
authors.initials: P
authors.lastname: Fuchshuber
authors.forename: Muddasar
authors.initials: M
authors.lastname: Rather
authors.forename: Edoardo
authors.initials: E
authors.lastname: Rosso
authors.forename: Pietro
authors.initials: P
authors.lastname: Addeo
authors.forename: Daniel
authors.initials: D
authors.lastname: Jaeck
authors.forename: Philippe
authors.initials: P
authors.lastname: Bachellier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D007208:Indocyanine Green; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000209:etiology*; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D007208:Indocyanine Green; D002166:Camptothecin