Curigliano G, Petit J Y, Bertolini F, Colleoni M, Peruzzotti G, de Braud F, Gandini S, Giraldo A, Martella S, Orlando L, Munzone E, Pietri E, Luini A, Goldhirsch A
Department of Medicine, Division of Medical Oncology, Clinical Pharmacology and New Drugs Development Unit, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy.
Breast Cancer Res Treat. 2005 Sep;93(1):35-40. doi: 10.1007/s10549-005-3381-1.
To assess if feature, extent and duration of surgery could influence levels of systemic proangiogenic cytokines vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta).
We collected blood samples from 82 consecutive breast cancer patients who underwent various types of surgery, classified according to the magnitude of tissue injury in: minimal (quadrantectomy), moderate (mastectomy without reconstruction), and heavy [mastectomy followed by reconstruction with transversus recto-abdominal muscle cutaneous flap (TRAM)]. Samples were collected one day before surgery (D(-1)), at the end of surgical tumor removal (D0), and on 1st (D(+1)), 2nd (D(+2)) and 5th (D(+5)) day after surgery. Serum VEGF, bFGF and TGF-beta levels were measured by the enzyme immunoassay method.
On average a continuous decrease was observed for all growth factors from the day before operation to the 5th day after operation. On day (D(+5)) an increase was observed for patients who underwent extended respect to moderate surgery. These differences were found statistically significant for bFGF and VEGF (p = 0.05 and p = 0.025 respectively). A statistically different trend for type of operation was observed also for TGF-beta at 24-48 h: a minor reduction, compared to time of operation, was observed for minimal surgery, an intermediate reduction for moderate surgery and a higher decrease for extended surgery.
Angiogenic cytokines perioperative levels could be increased on 5th day (D(+5)) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.
评估手术的特征、范围和持续时间是否会影响全身促血管生成细胞因子血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和转化生长因子β(TGF-β)的水平。
我们收集了82例连续接受各种手术的乳腺癌患者的血样,根据组织损伤程度分为:轻微(象限切除术)、中度(未行重建的乳房切除术)和重度[乳房切除术后采用腹直肌肌皮瓣(TRAM)重建]。在手术前一天(D(-1))、手术切除肿瘤结束时(D0)以及手术后第1天(D(+1))、第2天(D(+2))和第5天(D(+5))采集样本。采用酶免疫测定法测量血清VEGF、bFGF和TGF-β水平。
从手术前一天到手术后第5天,所有生长因子平均持续下降。在第5天(D(+5)),接受扩大手术的患者与中度手术患者相比有所升高。这些差异在bFGF和VEGF方面具有统计学意义(分别为p = 0.05和p = 0.025)。在24 - 48小时时,TGF-β也观察到手术类型的统计学差异趋势:轻微手术与手术时相比下降较小,中度手术下降中等,扩大手术下降更大。
血管生成细胞因子的围手术期水平可能在第5天(D(+5))因手术范围而升高,并应诱导对残留癌细胞的围手术期刺激。更好地了解伤口愈合过程中事件后遗症发生的时间间隔可能是定义能够干扰肿瘤生长同时保留伤口愈合过程的新治疗策略的基础。