Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Surgery, Gil Medical Center, Gachon University, Incheon, Republic of Korea.
Ann Surg Oncol. 2022 Mar;29(3):2077-2086. doi: 10.1245/s10434-021-10924-z. Epub 2021 Oct 19.
Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS). However, MMC has a side effect of myelosuppression. This study aimed to evaluate the clinical manifestations and impact of MMC-induced neutropenia after CRS and HIPEC in colorectal cancer patients.
A total of 124 colorectal cancer patients who underwent CRS with HIPEC between March 2015 and January 2019 were evaluated. Patients with malignancies of non-colorectal origin, hospital stay longer than 60 days, peritoneal cancer index > 30, and complete cytoreduction score > 2 were excluded. MMC 35 mg/m was administered for 90 min at 41-43 °C. The patients were divided into three groups: no neutropenia, mild neutropenia (grade 1-2), and severe neutropenia (grade 3-4).
In total, mild and severe neutropenia occurred in 30 (24.2%) and 48 (38.7%) patients, respectively. Age and body surface area were significantly different among the neutropenia groups. Severe neutropenia developed significantly earlier than mild neutropenia (6.9 days vs. 10.4 days, p < 0.001) and also lasted significantly longer (4.6 days vs. 2.5 days, p = 0.005). The rate of major postoperative complications was significantly higher in the severe neutropenia group than in the no and mild neutropenia groups (8.3% vs. 6.7% vs. 6.5%, p = 0.015) CONCLUSIONS: Severe neutropenia starts earlier and lasts longer than mild neutropenia after CRS and HIPEC using an MMC triple method. The higher rate of major postoperative complications in patients with severe neutropenia highlights the importance of postoperative management during the neutropenia period.
丝裂霉素 C(MMC)是细胞减灭术后腹腔热灌注化疗(HIPEC)中最常用的化疗药物。然而,MMC 有骨髓抑制的副作用。本研究旨在评估 MMC 诱导的结直肠癌患者细胞减灭术后 HIPEC 中性粒细胞减少的临床表现和影响。
共评估了 124 例 2015 年 3 月至 2019 年 1 月期间接受 CRS 联合 HIPEC 的结直肠癌患者。排除非结直肠癌来源的恶性肿瘤、住院时间超过 60 天、腹膜癌指数>30、完全减瘤评分>2 的患者。MMC 以 35mg/m 的剂量在 41-43°C 下输注 90 分钟。患者分为三组:无中性粒细胞减少症、轻度中性粒细胞减少症(1-2 级)和重度中性粒细胞减少症(3-4 级)。
共有 30 例(24.2%)和 48 例(38.7%)患者发生轻度和重度中性粒细胞减少症。中性粒细胞减少症组之间的年龄和体表面积有显著差异。重度中性粒细胞减少症的发生明显早于轻度中性粒细胞减少症(6.9 天 vs. 10.4 天,p<0.001),持续时间也明显更长(4.6 天 vs. 2.5 天,p=0.005)。重度中性粒细胞减少症组的主要术后并发症发生率明显高于无中性粒细胞减少症组和轻度中性粒细胞减少症组(8.3% vs. 6.7% vs. 6.5%,p=0.015)。
采用 MMC 三联法行 CRS 和 HIPEC 后,重度中性粒细胞减少症的起始时间早于轻度中性粒细胞减少症,持续时间也更长。重度中性粒细胞减少症患者主要术后并发症发生率较高,提示在中性粒细胞减少期间术后管理的重要性。