Growth differentiating Factor 15 (GDF15) is linked to several cancers, but its effect on chemoresistance in colorectal cancer (CRC) remains unclear. Here, we investigated the role of GDF15 in the chemotherapeutic response of CRC patients to oxaliplatin (L-OHP). GDF15 levels in serum and tumour tissues were detected in CRC patients have received L-OHP-based neoadjuvant chemotherapy. The effects of GDF15 neutralization or GDF15 knockdown on cell proliferation, apoptosis and intracellular reactive oxygen species (ROS) levels were analysed in vitro and in vivo. Co-immunoprecipitation (Co-IP), Chromatin Immunoprecipitation (ChIP) and luciferase reporter assays were used to explore the interaction between GDF15 and Nrf2. In this study, we found that GDF15 alleviates oxidative stress to induce chemoresistance of L-OHP in CRC. Mechanically, GDF15 posttranscriptionally regulates protein stability of Nrf2 through the canonical PI3K/AKT/GSK3β signaling pathway, and in turn, Nrf2 acts as a transcription factor to regulate GDF15 expression to form a positive feedback loop, resulting in the maintenance of redox homeostasis balance in CRC. Furthermore, a positive correlation between GDF15 and Nrf2 was observed in clinical CRC samples, and simultaneous overexpression of both GDF15 and Nrf2 was associated with poor prognosis in CRC patients treated with L-OHP. Simultaneous inhibition of both GDF15 and Nrf2 significantly increases the response to L-OHP in an L-OHP-resistant colorectal cancer cells-derived mouse xenograft model. This study identified a novel GDF15-Nrf2 positive feedback loop that drives L-OHP resistance and suggested that the GDF15-Nrf2 axis is a potential therapeutic target for the treatment of L-OHP-resistant CRC.

目的 分析腹腔镜低位直肠癌前切除术肠系膜下动脉高位结扎和低位结扎对低位前切除综合征(LARS)的影响.方法 采用回顾性队列研究方法,收集2019年1月至2020年8月期间在上海交通大学医学院附属仁济医院胃肠外科腹腔镜低位直肠癌前切除术的282例病人的临床资料.根据术中是否保留左结肠动脉(LCA),分为低位结扎组(n=126)和高位结扎组(n=156),比较两组术后LARS发生率和严重程度,并通过单因素和多因素分析LARS的危险因素.结果 对126例低位结扎病人术后3个月,6个月和12个月的影像学随访发现,117例(92.86％)病人术后左结肠动脉通畅,仅9例(7.14％)病人术后左结肠动脉闭塞.282例病人术后3个月,6个月,12个月 LARS 总发生率为:57.44％(162/282),42.91％(121/282),34.04％(96/282);术后3个月后无新发LARS病例.低位结扎组的术后3个月、6个月LARS的发生率明显低于高位结扎组(46.83％vs.66.03％,P=0.00;35.71％vs.48.72％,P=0.03).而术后12个月低位结扎组和高位结扎组LARS发生率差异无统计学意义(25.40％vs.34.62％,P--0.09).通过单因素分析,发现肿瘤大小＞3.5 cm(P=0.01)、非专业化水平(P=0.01)、高位结扎(P=0.03)、吻合口距齿状线距离≤2 cm(P=0.01)是LARS的危险因素;进一步通过多因素分析,发现高位结扎(P=0.02)、非专业化水平(P=0.01)、吻合口距齿状线距离≤2cm(P=0.01)是LARS的独立危险因素.结论 腹腔镜低位直肠癌前切除术中保留左结肠动脉可以降低术后LARS的发生率,尤其是轻度LARS病人,其近期疗效较满意,有临床推广价值.

Background Anastomotic leakage (AL) is one of most severe postoperative complications following low anterior resection (LAR) for rectal cancer, and has an adverse impact on postoperative recovery. The occurence of AL is associated with several factors, while few studies explored the role of intracorporeal barbed suture reinforcement in it. Methods Consecutive cases underwent laparoscopic LAR for rectal cancer from Mar. 2018 to Feb. 2021 in our center were retrospectively collected. Cases were classified into the intracorporeal barbed suture reinforcement group and the control group according to whether performing intracorporeal reinforcement with barbed suture, and AL incidences were compared between two groups. Propensity score matching (PSM) was then performed based on identified risk factors to reduce biases from covariates between two groups. AL incidences in the matched cohort were compared. Results A total of 292 cases entered into the study, and AL incidences were significantly lower in the intracorporeal barbed suture reinforcement group compared with the control group (10.00% vs 2.82%, P = 0.024). Sex, BMI, preoperative adjuvant chemoradiotherapy and anastomotic level were chose for PSM analyses based on previous studies. In the matched cohort, the AL incidences were still significantly lower in the intracorporeal barbed suture reinforcement group (10.57% vs 2.44%, SD = 0.334). Conclusions Intracorporeal barbed suture reinforcement is associated with low AL incidences after laparoscopic LAR for rectal cancer, which is a potential procedure for reducing AL and worthy of application clinically.

Adhesive intestinal obstruction is the most common type of ileus, and conserva-tive treatment serves as its preferred treatment option. In the course of conservative treatment, gastrointestinal decompression will relieve symptoms, prevent ileus progression and promote gas-trointestinal function recovery, which has significant clinical effects. Currently, decompression effects of nasointestinal tubes and nasogastric tubes are controversial. There is a previous Meta-analysis evaluating decompression effects of these two methods, but this analysis includes non-randomized controlled trial and lacks research about Chinese patients. Therefore, the authors con-duct a Meta-analysis to evaluate decompression effects of nasointestinal tubes versus nasogastric tubes for adhesive intestinal obstruction.

Surgery is recognized as the core treatment for colorectal liver metastasis (CRLM), while its recurrence rate remains relatively high, even for resectable CRLM. This hints that the efficacy of treatment involves not only technological factors of surgery, but also biological behavior of tumor. For resectable CRLM, neoadjuvant therapy is beneficial to eliminate the micro-metastasis, reduce postoperative recurrence rate, screen tumor biological behavior and improve prognosis. However, questions about which kind of CRLM patients fits for neoadjuvant therapy and what regimen should be used are still debatable. This paper reviews stratified management of resectable CRLM, choice of neoadjuvant regimen, especially the application value of targeted therapy, based on the latest guidelines and studies.