Background: Major surgery suppresses natural killer (NK) cell cytotoxic activity which is potentially harmful for cancer patients by favouring haematogenic tumour cell dissemination. The influence of a perioperative infusion of a standardized mistletoe extract (Iscador ®) on immune functions was tested in a prospective, sequential, randomized clinical trial. Patients and Methods: Colorectal cancer patients undergoing open tumour resection were randomly assigned to either mistletoe infusion or no additional therapy. We hypothesized that mistletoe infusion improves NK cell activity and increases expression of MHC class II antigen HLA-DR on monocytes 24 h and 7 days after surgery, respectively. For statistical analysis we used a sequential study design. The decision boundaries for the two triangular tests were calculated for altogether 62 patients. Results: The sequential study design allowed stopping the recruitment prematurely. NK cell activity differed significantly between the therapy groups 24 h after surgery (p = 0.027). The absolute number of HLA-DR molecules on monocytes did not differ 7 days after surgery. NK cell activity of patients treated with mistletoe extract did not change significantly during the course of the study (-7.9% 24 h after surgery), whereas HLA-DR expression changed significantly (-38.5% at day 7 after surgery). For control patients both parameters decreased significantly after surgery (NK cell activity: -44.4% at 24 h; HLA-DR expression: -32.9% at day 7 after surgery). Conclusion: Perioperative infusion of mistletoe extracts can prevent a suppression of NK cell activity in cancer patients. The impact of this therapy on relapse and survival should be tested in further studies.
Background & Aim: Extracts of Viscum album (European mistletoe) have immune-stimulatory and cytotoxic effects, with trials showing a well-established effect on the quality of life and prolonged survival in patients with advanced pancreatic cancer. Regression of tumours following intratumoural injection with Viscum album extract has been documented in individual cases. However, its influence on colon polyps has not been investigated.Case presentation: We present the case of a 78-year-old Caucasian male who had undergone hemi-colectomy for a stage IIIC colon cancer but who refused adjuvant chemotherapy. Five years later a newly detected highgrade dysplasia colon adenoma was discovered; however, the adenoma could not be resected endoscopically and the patient did not consent to surgery. Intratumoural injections with Viscum album L extract (Quercus; Iscador®Qu) were administered twice in an attempt to limit tumour growth. Eight months after the second intratumoural injection the adenoma had disappeared and biopsy revealed no intraepithelial dysplasia or adenoma.Conclusions: This is the first report showing complete regression of a colon adenoma after intratumoural injection with Viscum album extract. Prospective studies should evaluate if the treatment effect is reproducible and if this approach could be a useful pre-operative measure for colon adenomas too large for endoscopic resection.
Suppression of NK cell activity is considered to be an unfavourable prognostic factor for tumour progression. There is proof that mistletoe extracts may increase NK cell activity. However, the inverse relation between an increase of NK cell activity and clinical progress of cancer has not been investigated. Aim and Design: The relation of NK cell activity and progress of cancer in patients under therapy with mistletoe extracts was examined in a prospective, monocentric, cohort study. At the same time the in vitro killing of K562 cells and autologous tumour cells was compared. Patients and Methods: 40 patients with operable cancer of the breast or colon were included. The patients did not receive any immunologically relevant therapies except for mistletoe extracts. The absolute NK cell count in peripheral blood as well as the in vitro NK cell activity were monitored for up to 2 years and compared with clinical outcome as well as quality of life. Results: The absolute NK cell count in peripheral blood increased within the observation period. Patients without progression had a significantly higher mean activity of NK cells against K562 cells than patients with progression. In the latter group, only stage IV patients showed reduced NK cell activity. The killing activity against autologous tumour cells was <5% in about 77.5% of the patients and could not be evaluated further. The NK cell activity against K562 cells was not related to the number of NK cells. Conclusions: We found a relation between NK cell activity and the progression of malignant disease. In further studies the causality of this relation has to be clarified. The establishment of NK cell activity against autologous tumour cells as a suitable parameter during follow-up was not successful.
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