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热化疗与手术治疗直肠癌间隔时间对细胞凋亡、增殖和肿瘤反应的影响。

Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.

机构信息

Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan Department of Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

出版信息

Anticancer Res. 2014 Jun;34(6):3141-6.

PMID:24922685
Abstract

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.

摘要

新辅助放化疗常用于提高局部晚期直肠癌的局部控制率和可切除性,在数周的间隔后进行手术。我们一直在进行术前放化疗联合局部高温(热化疗;HCRT)治疗局部晚期直肠癌的临床试验。在目前的研究中,我们评估了新辅助 HCRT 后较长(>10 周)间隔对病理反应、肿瘤学结果,特别是对直肠癌患者凋亡、增殖和 p53 表达的影响。我们确定了 48 例接受 HCRT 后手术的直肠腺癌患者纳入本研究。根据 HCRT 与手术之间的间隔,将患者分为两组,≤10 周(短间隔组)和>10 周(长间隔组)。长间隔组的病理完全缓解率(pCR)(43.5% vs. 16.0%)明显高于短间隔组。长间隔组 T 分期降期率(78.3% vs. 36.0%)和 N 分期降期率(52.2% vs. 36.0%)相对较高,短间隔组患者。此外,长间隔组的凋亡率相对较高,而短间隔组的 Ki-67 增殖指数和原发性肿瘤中 p53 的表达无明显差异。总之,我们表明 HCRT 后较长的间隔(>10 周)似乎有更好的 pCR 机会,这一结果得到了肿瘤反应标志物包括凋亡、增殖和 p53 表达的趋势的证实。

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