Broll R, Lembcke K, Stock C, Zingler M, Duchrow M, Schimmelpenning H, Strik M, Muller G, Kujath P, Bruch H P
Klinik fur Chirurgie, Chirurgische Forschung, Medizinische Universitat zu Lubeck.
Langenbecks Arch Chir. 1996;381(1):51-8. doi: 10.1007/BF00184256.
The tumor spread and the radicality of surgical resection are the most important facts in a patient's prognosis. In spite of curative tumor resection many patients die from metastases or local tumor recurrence. One possible reason is early dissemination of tumor cells which cannot be detected with clinical methods of examination. For this reason the aim of our study was to examine both bone marrow and peritoneal lavage for disseminated tumor cells with an immunocytochemical technique in patients with a gastrointestinal carcinoma. We also wanted to find out whether there was any correlation between the incidence of tumor cell detection and the TNM classification, staging and tumor grading and whether disseminated tumor cells have any prognostic significance. Our study included 54 patients who underwent surgery in our clinic for a carcinoma of the stomach (20 patients) or the colorectum (34 patients) from November 1993 to December 1994. At the beginning of the operation bone marrow had been taken from the iliac spine, and the abdomen was irrigated with 1000 ml saline solution immediately after laparotomy or laparoscopy. After cell separation with Ficoll density centrifugation 5 x 10(5) cells were applied per slide by a cytospin technique. For detection of the tumor cells we used the APAAP technique and the following monoclonal antibodies: KL1, CK2, anti-CEA, 17-1A (bone marrow) and Ber-EP4, B72.3, anti-CEA and 17-1A (peritoneal lavage). Altogether 77% of all patients had tumor cells in the bone marrow and 69% in peritoneal lavage fluid. It was possible to detect tumor cells in bone marrow (67%) and peritoneal lavage fluid (25%) even of patients with T1 tumors. The percentage increased with depth of wall infiltration. There was a marked difference in bone marrow aspirates between patients with lymph-node-negative tumors (N0) and those with lymph-node-positive tumors (N+): 65% had tumor cells in N0 and 85% in N+ stages. This trend was also seen in patients with (M1) and without (M0) metastases, in both bone marrow aspirates and peritoneal lavage fluid. In bone marrow there was a good correlation of tumor cells with staging, but in peritoneal lavage fluid this was not so. Finally, we detected tumor cells more often in bone marrow and peritoneal lavage fluid of patients with poorly differentiated tumors (G3) or diffuse Lauren type than in patients with moderately differentiated tumors (G2) or intestinal Lauren type. After a median follow-up period of 12.5 months patients with disseminated tumor cells had a lower survival rate than patients without tumor cells.
肿瘤扩散和手术切除的根治程度是影响患者预后的最重要因素。尽管进行了根治性肿瘤切除,许多患者仍死于转移或局部肿瘤复发。一个可能的原因是肿瘤细胞早期播散,而临床检查方法无法检测到。因此,我们研究的目的是采用免疫细胞化学技术检测胃肠道癌患者骨髓和腹腔灌洗液中的播散肿瘤细胞。我们还想了解肿瘤细胞检测的发生率与TNM分类、分期和肿瘤分级之间是否存在关联,以及播散肿瘤细胞是否具有任何预后意义。我们的研究纳入了1993年11月至1994年12月在我们诊所接受手术治疗的54例胃癌(20例)或结直肠癌(34例)患者。手术开始时,从髂嵴采集骨髓,剖腹术或腹腔镜检查后立即用1000ml生理盐水冲洗腹腔。通过Ficoll密度离心法进行细胞分离后,用细胞离心涂片技术每张载玻片接种5×10⁵个细胞。为了检测肿瘤细胞,我们使用了碱性磷酸酶抗碱性磷酸酶(APAAP)技术和以下单克隆抗体:KL1、CK2、抗癌胚抗原(CEA)、17-1A(骨髓)以及Ber-EP4、B72.3、抗CEA和17-1A(腹腔灌洗液)。所有患者中,共有77%的患者骨髓中发现肿瘤细胞,69%的患者腹腔灌洗液中发现肿瘤细胞。即使是T1期肿瘤患者,也有可能在骨髓(67%)和腹腔灌洗液(25%)中检测到肿瘤细胞。随着壁层浸润深度的增加,这一比例也随之升高。淋巴结阴性(N0)肿瘤患者和淋巴结阳性(N+)肿瘤患者的骨髓抽吸物存在显著差异:N0期患者中有65%发现肿瘤细胞,N+期患者中有85%发现肿瘤细胞。在有转移(M1)和无转移(M0)的患者中,骨髓抽吸物和腹腔灌洗液中均呈现出这一趋势。骨髓中肿瘤细胞与分期有良好的相关性,但腹腔灌洗液中并非如此。最后,与中分化肿瘤(G2)或肠型劳伦(Lauren)分型患者相比,在低分化肿瘤(G3)或弥漫型劳伦分型患者的骨髓和腹腔灌洗液中,我们更常检测到肿瘤细胞。在中位随访期12.5个月后,有播散肿瘤细胞的患者生存率低于无肿瘤细胞的患者。