Romano F, Caprotti R, Bravo A Ferrari, Conti M, Colombo G, Piacentini G, Uggeri F, Uggeri F
Dept. of Surgery (Chirurgia I), II University of Milan, Bicocca, Italy.
J Exp Clin Cancer Res. 2003 Jun;22(2):179-83.
Cell-mediated immunodeficiency is known to occur in advanced cancer patients, but it is less characterized in earlier stages. Pre-existing immunodeficiency may impair the recovery of postoperative lymphocytopenia, occurring generally within 8-14 days after surgical stress. This study was aimed to verify whether immunodeficiency exists in patients with operable gastric adenocarcinoma and whether radical surgery may restore a count of peripheral blood T helper cells (CD4) and CD4/CD8 ratio within physiological normal values in the late postoperative period. Thirty-five consecutive patients (M/F 18/17; mean age 67 years, range 42-82) with histologically proven gastric adenocarcinoma, undergoing surgery with radical intent, were studied. Assessment of total lymphocyte count and lymphocyte subsets was performed by FAC scan at baseline, then postoperatively 14 and 50 days after surgery. Normal reference values were according to CDC criteria for HIV immunodeficiency (total lymphocyte > 1500/mmc; CD4 cells > 500/mmc; CD4/CD8 > 1.2). Surgical interventions, including D2 locoregional lymphadenectomy, were as follows: 19 Roux Y total gastrectomies; 3 Roux Y subtotal gastrectomies and 13 Billroth II subtotal gastrectomies. Pathological nodal staging was pN0 in 18 and pN+ in 17 cases. Hystotype was intestinal in 14 patients, diffuse in 14 and unclassifiable in 7. Grading was G1 n = 7; G2 n = 7; G3 n = 21. Lymphocyte immunodeficiency was found at baseline in 41% of patients and at 14 days after surgery in 67% of patients. Recovery of postoperative surgery-induced lymphocytopenia occurred on the 50th day only in those patients with normal values at baseline (59%). CD4 deficiency was significantly more frequent in pN+ vs. pN0 patients, either at baseline (p < 0.001 ), on the 14th day (p < 0.02) and on the 50th day (p < 0.007) postoperatively. Cancer-related CD4 deficiency was a frequent finding in our consecutive series of gastric cancer patients; this systemic immune impairment was not restored after complete tumor removal, even in late postoperative period (50th day ). Further studies on a larger number of cases may confirm the prognostic value of lymphocyte count in early gastric cancer stages, and to verify whether early and late postoperative immunodeficiency may be prevented by IL-2 administration.
细胞介导的免疫缺陷在晚期癌症患者中较为常见,但在早期阶段特征尚不明确。术前存在的免疫缺陷可能会影响术后淋巴细胞减少症的恢复,这种情况通常在手术应激后8 - 14天内出现。本研究旨在验证可手术切除的胃腺癌患者是否存在免疫缺陷,以及根治性手术是否能使外周血T辅助细胞(CD4)计数和CD4/CD8比值在术后晚期恢复到生理正常范围内。对35例经组织学证实为胃腺癌且接受根治性手术的连续患者(男18例/女17例;平均年龄67岁,范围42 - 82岁)进行了研究。在基线、术后14天和术后50天通过流式细胞仪扫描评估总淋巴细胞计数和淋巴细胞亚群。正常参考值依据美国疾病控制与预防中心(CDC)关于HIV免疫缺陷的标准(总淋巴细胞> 1500/mm³;CD4细胞> 500/mm³;CD4/CD8 > 1.2)。手术干预包括D2区域淋巴结清扫,具体如下:19例行Roux Y全胃切除术;3例行Roux Y次全胃切除术;13例行毕罗Ⅱ式次全胃切除术。病理淋巴结分期为pN0的有18例,pN +的有17例。组织学类型为肠型的有14例,弥漫型的有14例,无法分类的有7例。分级为G1的n = 7;G2的n = 7;G3的n = 21。41%的患者在基线时发现淋巴细胞免疫缺陷,67%的患者在术后14天发现。仅基线值正常的患者(59%)在术后第50天出现术后手术诱导的淋巴细胞减少症恢复。术后,无论在基线时(p < 0.001)、第14天(p < 0.02)还是第50天(p < 0.007),pN +患者的CD4缺乏均显著多于pN0患者。在我们连续的胃癌患者系列中,与癌症相关的CD4缺乏是常见现象;即使在术后晚期(第50天),完全切除肿瘤后这种全身免疫损伤仍未恢复。对更多病例的进一步研究可能会证实淋巴细胞计数在早期胃癌阶段的预后价值,并验证是否可以通过给予白细胞介素 - 2预防术后早期和晚期免疫缺陷。