Zusammenfassung
Um den Einfluß des chirurgischen Traumas beim Ösophaguskarzinom auf das zelluläre Immunsystem zu erfassen, wurden perioperativ in einer prospektiven Studie die Aktivität der natürlichen Killerzellen sowie die Serumkonzentrationen von Interleukin-2, Interleukin-6 un TNF-α bei transmediastinaler Dissektion (n=12) vs. transthorakaler En-bloc-Resektion (n=10) der Speiserörhre im Vergleich zu einer Kontrollgruppe mit thorakoabdominalen chirurgischen Eingriffen bei nicht maligner Grunderkrankung erfaßt. Die Bestimmung der NK-Zell-Aktivität erfolgte präoperativ sowie am 4. und 10. Tag postoperativ durch einen standardisierten Europiumchlorid-release-Assay unter Verwendung von K-562-Targetzellen, die Lymphokine Interleukin-2, Interleukin-6 und TNF-α wurden zusätzlich am 1. und 7. Tag postoperativ mit stadardisierten ELISA-Assays bestimmt.
In unserem Patientengut sank die NK-Zellaktivität am 4. postoperrativen Tag sowohl in der Kontrollgrupe al auch bei beiden Operations verfahren zur Speiseröhrenresektion signifikant (p<0,05) zum Ausgangswert: in der Kontrollgruppe durchschnittlich um 45%, nach transmediastinaler Speriseröhrendissektion (1-Höhlen-Eingriff) durchschnittlich um 34%, nauch transthorakaler En-bloc-Resektion (2-Höhlen-Eingriff) im Mittel um 63% zum präoperativen Wert. Die transthorakale En-bloc-Resektion der Speiseröhre führte durch das größere chirurgische Trauma zu einer stäkeren Abnahme der zytotoxischen Aktivität der natürlichen Killerzellen. Eine Suppression der immunologischen Tumorabwehr insbesondere in der vulnerablen perioperativen Phase kann damit indirekt das Risiko der Manifestation von hämatogene Metastasen auf dem Boden einer intraoperativen Tumorzelldissemination u. a. bedingt durch Tumormanipulation begünstigen und damit prognostisch relevant werden.
Abstract
In order to assess the impact of surgical trauma involved in the therapy of esophageal carcinoma on the cellular immune system, a perspective study was performed involving perioperative hematological parameters. The activity of natural killer cells and the serum concentrations of interleuin-2, interleukin-6 and TNF-α were measured in 12 cases of transmediastinal dissection and 10 cases of transthioracic en bloc esophageal resection and compared to values of a control group of thoracic and abdominal surgical patients with non-malignant maladies. Natural killer cells assume a central role in the non-specific immunological response in tumor patients. Their main function is the destruction of tumor cells via cytotoxic activities amplified by the release of interleukin-2 and TNF-α. Natural killer cell activity was measured prior to surgery and on postoperative days 4 and 10 using a standardized europium chloride release assay, utilizing K 562 target cells. Lymphokines interleukin-2, interleukin-6, and THF-α were also measured on postoperative days 1 and 7 using standardized ELISA assays. The activity of natural killer cells in our patient group sank significantly (P<0.05) on postoperative day 4 and likewise in the control group and both study groups, activity sank to the original values. In the control groups, natural killer cell activity averaged 45% of preoperative values, in comparison with an average of 63% following transmediastinal esophageal carcinoma resection (one cavity procedure), and transthoracic en bloc resection patients only reached 61% of preoperative values, transmediastinal dissection patients assumed 75%, and 77% was achieved by control group members. Transthoracic en bloc resection of the esophagus led to a more extreme reduction in cytotoxic cellular activity owing to the greater surgical trauma. Suppression of the immunological tumor resistance, especially in the vulnerable perisurgical pahse, can have an indirect negative effect on the manifestation risk of hematogenic metastases owing to intraoperative tumor cell dissemination resulting from tumor manipulation and may thus be prognostically relevant.
Key words: Esophageal carcinoma, Surgical stress, Natural killer cell activity, Cytokines
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