Department of Surgery, Eiju General Hospital, Tokyo, Japan.
Dis Esophagus. 2012 Feb;25(2):137-45. doi: 10.1111/j.1442-2050.2011.01221.x. Epub 2011 Jul 15.
Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY-adsorbent test values were significantly higher in group 2 patients. Oxidative index was significantly suppressed in group 1 compared to group 3. No significant intergroup differences were observed with regard to morbidity after surgery. Although the baseline levels of immunological function might have been different because of less-advanced cancer stages in group 3, neoadjuvant therapy significantly affected several immunological parameters. Preoperative administration of an immuno-enhanced diet did not significantly prevent neoadjuvant therapy-induced immunological deterioration prior to esophageal cancer surgery. Patients with esophageal cancer had elevated levels of oxidant and antioxidant activities before surgery, which were transiently decreased early after surgery. Although the underlying mechanisms for these perioperative changes are unclear, this study showed that an immuno-enhanced diet containing several antioxidants may reduce oxidative stress following esophageal cancer surgery. After these mechanisms are studied further, oxidative stress control may become another tool for perioperative management to reduce morbidity after esophageal cancer surgery.
新辅助治疗引起的免疫恶化可能是食管癌患者术后发病率高的一个关键因素。本研究旨在确定围手术期给予免疫增强饮食对接受新辅助治疗后行手术的患者免疫功能的影响。由于使用了含有多种抗氧化剂的免疫增强饮食,因此还研究了围手术期氧化应激以及免疫增强饮食对这种应激的影响。39 例接受类似手术的食管癌患者中,26 例术前接受化疗或放化疗的患者被随机分为两组:组 1(n=14)术前给予免疫增强饮食 5 天,组 2(n=12)术前不给任何肠内喂养产品。组 3(n=13)由未接受新辅助治疗且术前未给予任何肠内喂养产品的患者组成。对每位患者进行了几项凝血和纤溶标志物的测定和免疫评估。为了测量活性氧代谢物和总抗氧化能力,使用自由基选择性评估器进行了二氯代反应性氧代谢物(d-ROMs)和 OXY-吸附试验。与组 3 相比,组 1 和组 2 患者术前和术后早期淋巴细胞数量明显减少。组 1 和组 2 患者术后第 1 天的 B 细胞数量、CD4/CD8 比值和植物血凝素诱导的淋巴细胞转化试验也明显降低。与组 1 相比,组 2 的纤维蛋白和纤维蛋白原降解产物明显升高。d-ROMs 和 OXY-吸附试验值术前升高,术后早期短暂下降。与组 2 和组 3 相比,组 1 患者整个术后期间的 d-ROMs 值明显较低,而组 2 患者的 OXY-吸附试验值明显较高。与组 3 相比,组 1 的氧化指数明显受到抑制。各组间术后发病率无显著差异。尽管由于组 3 癌症分期较晚,免疫功能的基线水平可能不同,但新辅助治疗显著影响了几个免疫学参数。术前给予免疫增强饮食并不能显著预防食管癌术前新辅助治疗引起的免疫恶化。术前食管癌患者的氧化剂和抗氧化剂活性升高,术后早期短暂下降。尽管这些围手术期变化的潜在机制尚不清楚,但本研究表明,含有多种抗氧化剂的免疫增强饮食可能会降低食管癌手术后的氧化应激。在进一步研究这些机制后,氧化应激控制可能成为减少食管癌手术后发病率的另一种围手术期管理工具。