Tumorzelldissemination in das Knochenmark und in die Peritonealhohle eine immunzytochemische Untersuchung an Patienten mit einem Magen- oder kolorektalen Karzinom

Abstract

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 × 10⁵ 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 Laurén type than in patients with moderately differentiated tumors (G2) or intestinal Laurén 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.

Zusammenfassung

Die Tumorausdehnung und die Radikalität des chirurgischen Eingriffs sind für die Prognose eines Patienten von großer Bedeutung. Trotz kurativer Resektion des Tumors versterben jedoch viele Patienten an den Folgen der Fernmetastasierung oder einem lokalen Rezidiv. Die Ursache dafür könnte eine frühe Dissemination von Tumorzellen sein, welche derzeit mit den herkömmlichen klinischen Untersuchungsmethoden noch nicht erfaßt werden kann. Aus diesem Grunde war es das Ziel unserer Studie, das Knochenmark und die Peritonealspülflüssigkeit von Patienten mit einem gastrointestinalen Karzinom auf Tumorzellen mit immunzytochemischer Technik zu untersuchen. Außerdem wollten wir wissen, ob eine Korrelation zur TNM-Klassifikation, zum Tumorstadium und zum Tumordifferenzierungsgrad vorliegt und ob dem Tumorzellnachweis prognostische Relevanz zukommt. Wir