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Recent discussions have suggested expanding the inclusion criteria for active prostate cancer surveillance to include cases with a Gleason score (GS) of 3+4=7. In this study, we examined this proposed use of a limited percent Gleason pattern 4 (%GP4) to identify candidates of active surveillance among 315 patients who underwent radical prostatectomy for prostate cancer with a GS of 6 or 3+4=7 via needle biopsy. The latter cases were divided into 4 groups using highest or overall %GP4 cut-off values of 5% and 10% as determined from prostate needle biopsies. The frequency of adverse pathology and risk of biochemical recurrence were compared between the GS 6 and both GS 3+4=7 groups. Adverse pathology was defined as a GS 4+3=7 or higher, pT3b staging or positive lymph node metastasis. Notably, the Gleason pattern 4 <5% and GS 6 groups did not differ significantly in terms of the frequency of adverse pathology and risk of biochemical recurrence by the highest method. However, other highest Gleason pattern 4 categories had significantly higher frequencies and risks. Using the overall method, even the Gleason pattern 4 <5% group had a significantly higher frequency of adverse pathology and risk of biochemical recurrence relative to the GS 6 group. In conclusion, our findings suggest that patients with a GS 3+4=7 on biopsy with a highest %GP4 <5% are similar candidates for active surveillance to men with GS 6 cancers.

Over 90% of positive sentinel lymph nodes were identified at two predominant sites. Priority should be given to the removal of these sentinel lymph nodes, which are located closer to the prostate, in pelvic lymph node dissection. Particular attention should be paid to identifying these nodes to reduce the possibility of overlooking lymph node metastasis.

Metabolic derangements are a clinically significant complication of major trauma (e.g., burn injury) and include various aspects of metabolism, such as insulin resistance, muscle wasting, mitochondrial dysfunction and hyperlactatemia. Nonetheless, the molecular pathogenesis and the relation between these diverse metabolic alterations are poorly understood. We have previously shown that burn increases farnesyltransferase (FTase) expression and protein farnesylation and that FTase inhibitor (FTI) prevents burn-induced hyperlactatemia, insulin resistance, and increased proteolysis in mouse skeletal muscle. In this study, we found that burn injury activated mTORC1 and hypoxia-inducible factor (HIF)-1α, which paralleled dysfunction, morphological alterations (i.e., enlargement, partial loss of cristae structure) and impairment of respiratory supercomplex assembly of the mitochondria, and ER stress. FTI reversed or ameliorated all of these alterations in burned mice. These findings indicate that these burn-induced changes, which encompass various aspects of metabolism, may be linked to one another and require protein farnesylation. Our results provide evidence of involvement of the mTORC1-HIF-1α pathway in burn-induced metabolic derangements. Our study identifies protein farnesylation as a potential hub of the signaling network affecting multiple aspects of metabolic alterations after burn injury and as a novel potential molecular target to improve the clinical outcome of severely burned patients.

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