Reddy et al. further demonstrated that preoperative bevacizumab treatment was associated with less blood loss (median, 425 vs 600 mL) and lower red blood cell transfusion rates (43.9% vs 23.1%) after hepatic resection and also that the addition of bevacizumab to preoperative L-OHP/Iri did not increase morbidity after hepatic resection, if bevacizumab administration was discontinued at least 8 weeks before hepatic resection.[52] In our experience of patients with L-OHP-based chemotherapy for unresectable
colorectal liver metastasis, the incidence and severity of SOS was significantly lower in patients with bevacizumab (n = 9) than in patients without bevacizumab (n = 7) (grade 2–3, 22.2% vs 71.4%; P < 0.05). Furthermore,
the change AZD2014 datasheet in spleen volume and serum hyaluronic acid, which was used to assess the damage of sinusoidal endothelial cells, were significantly lower in patients with bevacizumab compared with patients without bevacizumab (changes in spleen volume, 110.3 ± 27.5% vs 146.3 ± 34.2%, P < 0.05; serum hyaluronic acid levels, 33.6 ± 21.2 vs 124.5 ± 34.0 ng/mL, P < 0.05) (Fig. 3). Regarding the relationship between the cumulative dose of bevacizumab and postoperative complications, Anne et al. reported that the addition of bevacizumab with L-OHP-based chemotherapy may protect against sinusoidal injury selleck compound without increasing the risk of morbidity, and neither duration of chemotherapy (1–5 vs ≥6 cycles) nor the interval between cessation (5 weeks) of chemotherapy LY294002 molecular weight and hepatic resection were associated with postoperative complications despite the bevacizumab treatment.[56] Meanwhile, in the series published by Kishi et al. patients
with short (1–8 cycles) or long (≥9 cycles) preoperative chemotherapy with FOLFOX with or without bevacizumab were analyzed.[37] In this article, they revealed that nine cycles or more of FOLFOX was the only independent prognostic factor for postoperative liver insufficiency, and concluded that the addition of bevacizumab may significantly reduce the incidence of SOS, but did not impact on the rate of postoperative liver insufficiency in patients with extended duration of chemotherapy. In experimental studies for reduction of SOS, several investigators have tried some possible agents except bevacizumab for the monoclotarine-induced SOS model (Table 5).[58-62] Narita et al. demonstrated that preoperative upregulation of heme oxygenase-1 by a phosphodiesterase-III inhibitor was effective for maintenance of the sinusoidal lining in sinusoidal endothelial cells and blockage of monoclotarine-induced SOS, and resulted in a significant improvement in survival rate after 70% hepatectomy.