Department of Surgery, The University of Chicago Medicine, Chicago, IL.
Department of Pathology, The University of Chicago Medicine, Chicago, IL.
Ann Surg. 2023 Dec 1;278(6):954-960. doi: 10.1097/SLA.0000000000006052. Epub 2023 Jul 31.
To determine the timeframe and associated changes in the microenvironment that promote the development of a diet-induced local-regional recurrence in a mouse model of colorectal surgery.
Postoperative recurrence and metastasis occur in up to 30% of patients undergoing attempted resection for colorectal cancer (CRC). The underlying mechanisms that drive the development of postoperative recurrences are poorly understood. Preclinical studies have demonstrated a diet and microbial-driven pathogenesis of local-regional recurrence, yet the precise mechanisms remain undefined.
BALB/C mice were fed a western diet (WD) or standard diet (SD), underwent a colon resection and anastomosis, given an Enterococcus faecalis enema on postoperative day (POD) 1, and subjected to a CT26 cancer cell enema (mimicking shed cancer cells) on POD2. Mice were sacrificed between POD3 and POD7 and cancer cell migration was tracked. Dynamic changes in gene expression of anastomotic tissue that were associated with cancer cell migration was assessed.
Tumor cells were identified in mice fed either a SD or WD in both anastomotic and lymphatic tissue as early as on POD3. Histology demonstrated that these tumor cells were viable and replicating. In WD-fed mice, the number of tumor cells increased over the early perioperative period and was significantly higher than in mice fed a SD. Microarray analysis of anastomotic tissue found that WD-fed mice had 11 dysregulated genes associated with tumorigenesis.
A WD promotes cancer cells to permeate a healing anastomosis and migrate into anastomotic and lymphatic tissue forming viable tumor nodules. These data offer a novel recurrence pathogenesis by which the intestinal microenvironment promotes a CRC local-regional recurrence.
确定促进结直肠手术后饮食诱导局部区域性复发的微环境变化时间框架及其相关变化。
接受结直肠癌（CRC）切除术的患者中，多达 30%的患者会发生术后复发和转移。导致术后复发的潜在机制尚不清楚。临床前研究已经证明了饮食和微生物驱动的局部区域性复发发病机制，但确切的机制仍未定义。
BALB/C 小鼠分别喂食西式饮食（WD）或标准饮食（SD），进行结肠切除术和吻合术，术后第 1 天给予粪肠球菌灌肠，第 2 天给予 CT26 癌细胞灌肠（模拟脱落癌细胞）。在 POD3 和 POD7 之间处死小鼠并追踪癌细胞迁移。评估与癌细胞迁移相关的吻合组织的基因表达的动态变化。
在 POD3 时，在接受 SD 或 WD 喂养的小鼠的吻合组织和淋巴组织中均发现了肿瘤细胞。组织学表明这些肿瘤细胞是有活力和复制的。在 WD 喂养的小鼠中，肿瘤细胞数量在早期围手术期内增加，明显高于 SD 喂养的小鼠。对吻合组织的微阵列分析发现，WD 喂养的小鼠有 11 个与肿瘤发生相关的失调基因。
WD 促进癌细胞穿透愈合的吻合口并迁移到吻合口和淋巴组织中形成有活力的肿瘤结节。这些数据提供了一种新的复发发病机制，即肠道微环境促进 CRC 的局部区域性复发。
