Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases

Abstract

Background: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection.

Methods: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed.

Results: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration.

Conclusions: Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.

Keywords: Colorectal liver metastases; Conversion chemotherapy; Hepatectomy; Liver regeneration; Splenomegaly.

Fig 1

Changes in splenic volume during chemotherapy. a Splenic volume before and after preoperative chemotherapy (n = 51). b The relationship between SP index and chemotherapeutic regimen. IRI-based: FOLFIRI/IRIS with or without biologics (n = 20). OX-based: FOLFOX/CapeOX with or without anti-EGFR monoclonal antibodies (n = 18). OX + Bmab: FOLFOX/CapeOX with bevacizumab (n = 11). c SP index in patients who had 9 or more cycles of chemotherapy. d SP index in patients who had 8 or fewer cycles of chemotherapy. Data are mean ± standard error of the mean. A comparison was performed using the Mann-Whitney U test. A p value < 0.05 was considered to be significant

Fig 2

Representative case of splenomegaly induced by chemotherapy. a Abdominal dynamic multidetector-row computed tomography (MD-CT) findings before chemotherapy. b MD-CT findings after 20 cycles of oxaliplatin-based chemotherapy. The splenic volume increased during chemotherapy (SP index = 1.34). c Histological analysis (hematoxylin and eosin staining) of the liver after resection. The non-tumoral liver developed sinusoidal obstruction syndrome. Arrows indicate dilatation of sinusoids. Original magnification is × 200

Fig 3

Relationship between splenic enlargement and liver regeneration. a The relationship between splenic enlargement and liver regeneration. SP index ≥ 1.2: changes in splenic volume during chemotherapy were 1.2 or more (●, n = 16). SP index < 1.2: changes in splenic volume during chemotherapy were less than 1.2 (○, n = 27). No chemotherapy: patients received no preoperative chemotherapy before hepatectomy (▵, n = 67). There was statistical significance among these groups (SP index ≥ 1.2 vs SP index < 1.2 or no chemotherapy; p = 0.021, 0.033, respectively) defined by analyses of covariance. b The relationship between ICG-R15 and liver regeneration. ICG-R15 ≥ 10% (●, n = 40), ICG-R15 < 10% (○, n = 70). There was no significant difference in liver regeneration between the two groups (p = 0.40)