Ryan Paul, McCarthy Seán, Kelly Jacquie, Collins J Kevin, Dunne Colum, Grogan Liam, Breathnach Oscar, Shanahan Fergus, Carey P Declan, Walsh Thomas N, O'Sullivan Gerald C
Cork Cancer Research Centre, National University of Ireland, Cork, Dublin, Ireland.
J Surg Res. 2004 Mar;117(1):121-6. doi: 10.1016/j.jss.2003.12.008.
Bone marrow micrometastases are present in a high proportion of patients undergoing curative resection for esophagogastric cancer. The incorporation of preoperative systemic therapies into these patients' treatment is widely practiced. This study investigates the effect of neoadjuvant chemoradiotherapy (CRT) on the incidence of micrometastases and the viability of detected tumor cells.
Rib bone marrow was obtained from patients (n = 106) in three centers, who were selected for potentially curative resection. Patients received neoadjuvant CRT plus surgery (n = 55), or surgery alone (n = 51). To detect micrometastases, mononuclear cells were isolated from fresh marrow and immediately stained immunohistochemically with an anti-cytokeratin-18 antibody using the APAAP technique. Tumor cell viability was assessed by immunohistochemical staining of marrow cell cultures for cytokeratin-positive cells.
Micrometastases were detected in fresh marrow in 42% (23/55) of patients who received neoadjuvant CRT plus surgery, and in 67% (34/51) of patients treated with surgery alone. Viable tumor cells were demonstrated in 10 of 18 marrow cultures from CRT plus surgery cases. In this patient subset, combination of results of staining fresh and cultured marrow significantly increased micromet detection to 78%.
A significant proportion of patients with esophagogastric cancer have disseminated viable tumor cells at time of surgery, irrespective of pre-operative treatment. The use of marrow culture in parallel with fresh marrow staining may increase the detection of micrometastases. The persistence of tumor cells resistant to systemic therapy may explain why these regimens fail in a majority of patients.
在接受食管癌和胃癌根治性切除术的患者中,骨髓微转移的发生率很高。术前全身治疗已广泛应用于这些患者的治疗中。本研究调查了新辅助放化疗(CRT)对微转移发生率和检测到的肿瘤细胞活力的影响。
从三个中心的患者(n = 106)中获取肋骨骨髓,这些患者被选定进行潜在的根治性切除术。患者接受新辅助CRT联合手术(n = 55)或单纯手术(n = 51)。为了检测微转移,从新鲜骨髓中分离出单核细胞,并立即使用抗细胞角蛋白-18抗体通过碱性磷酸酶抗碱性磷酸酶(APAAP)技术进行免疫组织化学染色。通过对骨髓细胞培养物进行细胞角蛋白阳性细胞的免疫组织化学染色来评估肿瘤细胞的活力。
在接受新辅助CRT联合手术的患者中,42%(23/55)的新鲜骨髓中检测到微转移,而在单纯手术治疗的患者中这一比例为67%(34/51)。在18例CRT联合手术病例的骨髓培养物中,有10例显示存在存活的肿瘤细胞。在该患者亚组中,新鲜骨髓和培养骨髓染色结果相结合,显著提高了微转移的检测率至78%。
相当一部分食管癌和胃癌患者在手术时已存在播散的存活肿瘤细胞,无论术前治疗如何。同时使用骨髓培养和新鲜骨髓染色可能会增加微转移的检测率。对全身治疗耐药的肿瘤细胞持续存在,可能解释了为什么这些治疗方案在大多数患者中失败。