Departments of *HPB and Digestive Surgery and †Pathology, Ospedale Mauriziano Umberto I, Torino, Italy; and Departments of ‡Visceral and Transplantation Surgery and §Clinical Pathology, University Hospitals, Geneva, Switzerland.
Ann Surg. 2013 Nov;258(5):731-40; discussion 741-2. doi: 10.1097/SLA.0b013e3182a6183e.
We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy.
CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear.
Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases.
A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively).
TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment.
我们分析了化疗相关肝损伤（CALI）、肿瘤病理缓解分级（TRG）和微转移对接受术前化疗的结直肠癌肝转移患者行肝切除术后长期预后的影响。
CALI 会加重肝切除术的短期预后，但对长期预后的影响尚不清楚。最近，TRG 的预后作用已被提出。微转移（微小血管或胆管侵犯）在术前化疗中减少，但对生存的影响尚不清楚。
1998 年至 2011 年间接受奥沙利铂和/或伊立替康为基础的术前化疗的结直肠癌肝转移患者符合研究条件。排除手术死亡率或不完全切除（R2）的患者。所有标本均进行了评估以确定 CALI、TRG 和微转移情况。
共纳入 323 例患者。124 例（38.4%）患者存在 2-3 级窦状隙阻塞综合征（SOS），73 例（22.6%）存在 2-3 级脂肪变性，30 例（9.3%）存在脂肪性肝炎。所有患者中，22.9%为 TRG 1-2（主要缓解），55.7%为 TRG 4-5（无缓解）。37.8%的患者检测到微血管侵犯，5.6%的患者检测到微小胆管浸润。SOS 分级越高，病理缓解率越低：2-3 级 SOS 患者的 TRG 1-2 发生率为 16.9%，0-1 级 SOS 患者为 26.6%（P = 0.032）。中位随访 36.9 个月后，5 年生存率为 38.6%。CALI 未对生存产生负面影响。多因素分析显示，2-3 级脂肪变性的生存优于 0-1 级脂肪变性（5 年生存率为 52.5%比 35.2%，P = 0.002）。TRG 比活细胞百分比更能分层患者的预后：TRG 1-2 组 5 年生存率为 60.4%，TRG 3 组为 40.2%，TRG 4-5 组为 29.8%（P = 0.0001）。微血管和胆管侵犯对预后有负面影响（无侵犯者的 5 年生存率为 23.3%，有侵犯者为 45.7%，P = 0.017；无侵犯者为 0%，有侵犯者为 42.3%，P = 0.032）。
TRG 被证实是一个关键的预后决定因素。CALI 不会对长期预后产生负面影响，但 2-3 级 SOS 患者的肿瘤反应会降低。脂肪变性对生存有保护作用。微转移对预后评估有显著影响。
