Eisuke Kondo

Preoperative natural killer cell activity as a prognostic factor for distant metastasis following surgery for colon cancer.

Background/Aims: To determine whether preoperative natural killer (NK) cell activity has any prognostic significance in colon cancer patients. Methods: The study population consisted of 140 patients with colon cancer. NK cell activity was determined within 2 weeks before surgery in 128 patients and at the time of diagnosis in the remaining 12 patients who either did not undergo surgery or who underwent palliative surgery only. Disease progression and postoperative prognosis were examined in relation to NK cell activity. Results: Decreases in NK cell activity did not necessarily correspond to tumor stage. In curatively operated stage I–III diseases, preoperative NK cell activity of 20% or less correlated with poor survival. Lower activity was also associated with metachronous distant metastases but not with local recurrences. In particular, more than half the stage III patients with attenuated NK cell activity developed metastases. Multivariate analysis indicated that attenuated NK cell activity was a significant parameter for predicting distant metastasis following curative surgery for colon cancer. Conclusion: Preoperative NK cell activity has a significant prognostic value in curatively operated colon cancer, particularly for the development of metachronous distant metastasis in stage III patients.

Natural killer cell activity and distant metastasis in rectal cancers treated surgically with and without neoadjuvant chemoradiotherapy.

BACKGROUND We investigated whether impaired preoperative natural killer (NK) cell activity correlates with asynchronous distant metastasis after curative surgery for rectal cancers. In addition, we examined if preoperative chemoradiotherapy for rectal cancers impairs NK cell activity and contributes to the induction of distant metastasis. STUDY DESIGN Preoperative NK cell activity was examined in 174 rectal cancer patients. All patients were enrolled in this study and followed until asynchronous distant metastasis occurred. RESULTS The mean NK activity in patients with stage IV disease (n = 20) was significantly lower than seen in other stages. There were no differences among stage I to stage III patients. In stage III patients, the cumulative distant metastasis-free rate after curative surgery was significantly lower in cases with NK activity of 25% or less than those with more than 25%. Preoperative chemoradiotherapy for stage I to III patients significantly impaired NK cell activity (n = 39), and the metastasis-positive ratio significantly increased among patients with stage II or stage III diseases (n = 30). Multivariate analysis indicated that dichotomized NK cell activity was a significant risk factor that is associated with distant metastasis as well as nodal involvement. CONCLUSIONS In primary rectal cancers, NK cell activity is not necessarily impaired in accordance with the disease progression. It is considered an important background factor for developing asynchronous distant metastases in stage III rectal cancers. Neoadjuvant chemoradiotherapy impaired NK cell activity in selected patients, suggesting the necessity of concurrent immunotherapy for better outcomes.

Vα14+ NK T cells : A novel lymphoid cell lineage with regulatory function

Abstract A novel lymphoid lineage, NK T cells, was recently found. The NK T cells are the major population in the periphery comprising 5% of splenic T cells and 40% of bone marrow T cells. They express a unique TCR composed of invariant Vα14Jα281 and Vβ8.2 together with NK receptor (NKRPI). Surprisingly, the invariant Vα14+ TCR is exclusively expressed on NK T cells but not on conventional T cells. As the selective decrease in Vα14+ NK T cell population in the periphery is tightly correlated with autoimmune disease development, Vα14+ NK T cells control development of autoimmune diseases. We also found that Vα14 TCR gene rearrangement and transcripts were detected at an early embryogenesis (d9.5) before the thymus formation. Therefore NK T cells are in the distinct category from conventional T cells. The target of NK T cells is found to be CD1 (class 1b, monomorphic class I MHC-like molecule) present on bone marrow–derived cells and is killed by Fas-FasL interaction or perforin-mediated mechanisms. These results indicate that NK T cells consist of an immunoregulatory system different from defense system in terms of homogeneous repertoire, extrathymic development in early stage of gestation, and their regulatory functional role. (J Allergy Clin Immunol 1996;98:S263-9)

Relevance of Abdominal Gas Analysis and Transit Study after Colorectal Cancer Surgery

Background: Colon gas volume analysis using abdominal radiographs is an objective and reproducible method for evaluating functional bowel disorders. The aim of this study was to clarify the relevance of colon gas distribution and transit time in rectosigmoid cancer patients after surgery. Methods: Segmental colon gas volume score was calculated using plain abdominal radiography and evaluated in 40 patients who had undergone sphincter-saving resection. Segmental colonic transit time was analysed using radiopaque markers in the same patients. Results: Transit times in the right colon (RCT) were 15.3 ± 1.1 h and in the left colon (LCT) 11.2 ± 1.1 h. Gas volume scores in the RCS and LCS were 1.10 ± 0.13% and 1.06 ± 0.14%, respectively. Neither colonic transit time nor colon gas volume score correlated with the operation methods for rectosigmoid colon cancer. A positive correlation of RCS and a negative correlation of LCS/RCS with ageing were noted in male patients but not in female patients. There was no correlation between RCT and RCS (r = 0.028); however, LCT correlated with LCS (r = 0.318, P < 0.05). The ratio of colonic transit time (LCT/RCT) was 0.84 ± 0.10, while that of colon gas volume score (LCS/RCS) was 1.29 ± 0.21. There was a significant correlation between LCT/RCT and LCS/RCS (r = 0.541, P < 0.001). Conclusions: Analysis of colon gas volume is useful for evaluating colonic transit time in rectosigmoid cancer patients after sphincter-saving surgery.