[High-risk prostate cancer surgical margins during robot-assisted radical prostatectomy]. / Marges chirurgicales des cancers de prostate à haut risque en prostatectomie totale robot-assistée.

OBJECTIVE: To evaluate the feasibility of robot-assisted radical prostatectomy (RARP) in high risk prostate cancer (HR). The rate of positive surgical margins (PSM) was compared between anticipated HR cancer according to D'Amico risk classification and discovered postoperative HR cancer. MATERIALS AND METHODS: A retrospective study was conducted between 2006 and 2013 on patients who underwent RARP. Before surgery, patients were divided according to the D'Amico risk classification. After surgery, HR was defined as pT3a or pT3b, or Gleason score≥8 or positive lymph nodes. The rate of PSM was compared according to the D'Amico risk classification and postoperative HR. RESULTS: During the study, 485 patients were reviewed. Before surgery, 10 % of cancers were classified as D'Amico 3 (49/485). After surgery, 27.6 % (134/485) were classified as HR. There was a significant difference between the rate of PSM in HR/D'Amico 3 and HR/non D'Amico 3 cancer, respectively 22.9 % and 34.3 % (P<0.001). CONCLUSION: The RARP is feasible in HR with an average of 30 % of PSM as in open surgery. However, the accurate assessment of preoperative HR will allow a more adapted dissection and a decrease of rate of PSM. So it is necessary to improve the detection of HR and so to select the most suitable cancer for surgery. LEVEL OF EVIDENCE: Level 5.

Inhibition of lung tumorigenesis by NSAIDS: a working hypothesis.

A 7-week treatment with the tobacco carcinogen NNK induced 8-10 lung adenomas per A/J mouse. NNK suppressed humoral and cellular immune responses and increased plasma PGE2 and LTB4 levels. This protocol is particularly suitable for testing NSAIDs and lipoxygenase inhibitors as cancer preventive agents. Sulindac and ASA inhibited lung tumorigenesis by 52 and 60%, respectively, attenuated the suppressive effect of NNK, and lowered the plasma PGE2 to basal levels. In contrast, naproxen neither inhibited lung tumorigenesis nor increased NNK-suppressed NK cell cytotoxicity. NSAIDs and lipoxygenase inhibitors had additive preventive efficacies against NNK-induced lung tumorigenesis. However, sulindac was not effective in preventing lung tumorigenesis induced by B[a]P, which lacks immunosuppressive activity. These results and those published by other investigators lead to the following hypothesis: Reactive intermediates derived from NNK interfere with the stimulation of the complex NF-kappa B/I kappa B. NF-kappa B is involved in the regulation of immune and inflammatory responses. The authors propose that NNK-derived intermediates induce the expression of COX-2 and lipoxygenase involved in NNK activation. This hypothesis provides a rationale for the lack of efficacy of naproxen to prevent tumorigenesis, to attenuate NNK-induced synthesis of PGE2, and to increase NK cell cytotoxicity. According to this hypothesis, PGE2 synthesis and induction of apoptosis contribute to varying degrees to the mechanism of cancer prevention.

Chemopreventive efficacies of aspirin and sulindac against lung tumorigenesis in A/J mice.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs. In this study, we demonstrated the efficacy of aspirin to inhibit lung tumorigenesis in A/J mice. Lung tumors (9.9 tumors/mouse) were induced by the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), administered in drinking water between week 0 and week +7. Groups of mice were fed sulindac (123 mg/kg diet), acetylsalicylic acid (ASA; 294 mg/kg), non-buffered Aspirin (294 mg/kg) or buffered Aspirin (294 mg/kg) in AIN-76A diet from week -2 to the end of the bioassay (week +23). These doses are comparable to the maximal doses recommended for humans. ASA and non-buffered Aspirin were the most effective inhibitors and reduced lung multiplicities by 60 and 62%, respectively. Sulindac inhibited lung tumor multiplicity by 52%. Inhibition by buffered Aspirin was not statistically significant. We evaluated the efficacies of NSAIDs to inhibit NNK activation by h1A2 v2 cells expressing human P-450 1A2. Salicylates, at doses of 500 microM and 1 mM, had no effect on NNK activation. Sulindac and its sulfide and sulfone metabolites (1 mM) inhibited NNK metabolism by 90, 92 and 65%, respectively. We observed a 76% inhibition with SKF 525A, a P-450 inhibitor. Taken together, these results indicate that salicylates and sulindac could be equally effective as chemopreventive agents, but they could differ in their mode of action.