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背景和目的结直肠癌为世界最常见恶性肿瘤之一。全球每年约有120万新发病例,60万人死于本病。手术切除是患者长期无病生存的关键手段,但术后并发症却可对手术结局产生重要影响。吻合口瘘(anastomotic leak,AL)是结直肠癌根治手术的严重并发症类型,直接增加术后短期死亡率。根据不同手术类型,AL发生率约在3%至12%之间。目前仅有为数不多结果却彼此矛盾的研究关注结肠癌术后吻合口瘘对于肿瘤结局及长期生存的影响。而对于直肠癌患者的研究结果则一致显示AL与局部复发率及长期死亡率增加相关,而不影响远处转移发生率。与之相反,尚未有研究证实结肠癌术后AL与局部复发或远处转移相关。已有研究证实,AL可降低结肠癌患者的无病生存期及总生存期。本项针对结肠癌的丹麦全国性研究主要终点为确定AL对结肠癌术后存活超过120天以上患者局部复发及远处转移率的影响;次要终点为确定AL对患者长远期死亡率的影响。此外,通过一项亚组分析,评价AL对III期结肠癌患者实施辅助化疗(AC)的影响。方法本研究为一项丹麦全国范围的队列研究,所有9333例患者均来自丹麦结直肠癌研究组数据库,并结合丹麦病理登记系统与国家患者登记系统的相关数据。通过多变量Cox回归分析对混杂因素进行校正。结果研究结果表明,患者AL发生率为6.4%,术后120天内死亡744例。其余的8589例患者中,局部复发861例(10.0%),但与AL无关(校正风险比HR=0.78;95%CI:0.55~1.12;P=0.184)。远处转移1281例(14.9%),且AL患者远处转移发生率更高(校正HR=1.42,95%CI:1.13~1.178;P=0.003)。AL也与患者长期死亡率呈正相关(校正HR=1.20,95%CI:1.01~1.44;P=0.042)。在2841例III期患者中,AL与施行辅助化疗的可能性降低(校正HR=0.58,95%CI:0.45~0.74;P<0.001)以及初始治疗延迟显著相关(校16天,95%CI:12~20天;P<0.001)。结论结肠癌术后吻合口瘘显著增加远处转移发生率及长期全因死亡率。该结果或在部分程度上与取消或延迟辅助化疗相关。
Background and purpose Colorectal cancer is one of the most common malignancies in the world. About 1.2 million new cases occur globally each year, and 600,000 die from this disease. Surgical resection is the key to long-term disease-free survival of patients, but postoperative complications may have a significant impact on the surgical outcome. Anastomotic leak (AL) is a serious complication of radical surgery for colorectal cancer, which directly increases the postoperative short-term mortality. Depending on the type of surgery, the incidence of AL is between 3% and 12%. Only a few but conflicting studies have focused on the effect of postoperative anastomotic fistula on tumor outcome and long-term survival. However, the findings for patients with rectal cancer consistently show that AL is associated with increased local recurrence and increased long-term mortality without affecting the incidence of distant metastases. In contrast, no studies have demonstrated that AL is associated with local recurrence or distant metastasis after colon cancer surgery. It has been confirmed that AL can reduce the disease-free survival and overall survival of patients with colon cancer. The primary end point of this Danish national study on colon cancer was to determine the effect of AL on the local recurrence and distant metastasis in patients with colon cancer over 120 days after surgery; the secondary endpoint was to determine the effect of AL on long-term and long-term mortality in patients . In addition, the impact of adjuvant chemotherapy (AC) on AL in patients with stage III colon cancer was evaluated by a subgroup analysis. Methods This study was a Danish cohort study. All 9333 patients were from the Danish Colorectal Cancer Research Group database and combined data from the Danish Pathology Registry with the National Patient Registration System. Confounding factors were corrected by multivariate Cox regression analysis. Results The results of the study showed that the incidence of AL in patients was 6.4% and 744 cases died within 120 days after operation. Of the remaining 8589 patients, 861 (10.0%) had local recurrence but had no association with AL (adjusted hazard ratio HR = 0.78; 95% CI: 0.55-1.12; P = 0.184). Of 1281 patients (14.9%) distantly metastasized, AL patients had a higher incidence of distant metastases (adjusted HR = 1.42; 95% CI: 1.13 to 1.178; P = 0.003). AL also had a positive correlation with long-term patient mortality (adjusted HR = 1.20, 95% CI: 1.01 to 1.44; P = 0.042). In 2841 patients with stage III disease, AL was significantly associated with reduced likelihood of adjuvant chemotherapy (adjusted HR = 0.58, 95% CI: 0.45 to 0.74; P <0.001) and initial treatment delay (16 days, 95% CI: 12 to 20 days; P <0.001). Conclusions Postoperative anastomotic leakage of colon cancer significantly increases the incidence of distant metastasis and long-term all-cause mortality. This result is partly related to the abolition or delay of adjuvant chemotherapy.