[DOES CHOOSING BETWEEN DUSTING OR FRAGMENTATION DURING LASER LITHOTRIPSY OF URINARY STONES CHANGE THE LONG TERM RESULTS?]

INTRODUCTION: Variations in laser pulse energy and it's frequency during lithotripsy, affect the rate and the method of stone breaking. The main modes of lithotripsy are dusting and fragmentation. AIMS: Comparison between long term results of dusting versus fragmentation, by defining the stone free rate (SFR) for each method and the time period until re-treatment need. METHODS: Clinical and radiological follow-up of 43 patients who underwent laser intervention using dusting or fragmentation. Both groups shared similar demographic features, stone sizes and locations. For each group, the percentage of patients without stones requiring intervention during the follow-up period of 36 months was defined as a success parameter. The incidence of emergency department (ED) admissions and auxiliary interventions were assessed. RESULTS: Thirty-eight patients were included in the study. No difference in the median period of time to clinically significant stone was seen (p=0.213). No difference was found in SFR between the dusting (83.3%) and the fragmentation (84.6%) groups respectively (p=1.000). No statistically significant difference was shown in ED admissions due to renal colic occurring in 31.6% and 10.5% within dusting and fragmentation groups respectively (p=0.116). CONCLUSIONS: No difference in time period until clinically significant stone appearance was seen. No significant difference in SFR was found between the groups at the long term follow-up. DISCUSSION: It seems that within the dusting group, the ED admission rate could be somewhat higher. However, this impression lacks statistical significance. A long term prospective study with a larger population is needed to confirm these results.

Coupling presentation of MHC class I peptides to constitutive activation of antigen-presenting cells through the product of a single gene.

Priming of naive CD8 T cells by dendritic cells (DCs) entails both effective antigen presentation on MHC class I products and co-stimulatory signaling. Their optimal coupling is a major goal in the development of CTL-inducing vaccines. We recently reported that a membranal derivative of the invariant MHC-I light chain, ß(2)-microglobulin (ß(2)m), markedly stabilizes MHC-I molecules and can serve as a universal platform for exceptional presentation of genetically linked peptides. To test whether it is possible to equip the resulting MHC-I complexes with an inherent ability to activate antigen-presenting cells, we engrafted the intracellular Toll/IL-1 receptor domain of mouse Toll-like receptor (TLR) 4 or TLR2 onto the peptide-ß(2)m scaffold. We evaluated the level of peptide presentation and status of cell activation conferred by such constructs in stably transfected mouse RAW264.7 macrophages and mRNA-transfected mouse DC2.4 DCs. We show that the encoded peptide-ß(2)m-TLR polypeptides are expressed at the cell surface, pair with endogenous heavy chains, stabilize MHC-I products, prompt efficient peptide-specific T-cell recognition and confer a constitutively activated phenotype on the transfected cells, as judged by the up-regulation of pro-inflammatory genes and surface co-stimulatory molecules. Our results provide evidence that the product of a single recombinant gene can couple MHC peptide presentation to TLR-mediated signaling and offer a safe, economical and highly versatile modality for a novel category of genetic CTL-inducing vaccines.

Microenvironment-derived IL-1 and IL-17 interact in the control of lung metastasis.

Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression/metastasis. In this study, we have assessed the role of IL-1 and IL-17 in the control of antitumor immunity versus progression in a model of experimental lung metastasis, using 3LL and B16 epithelial tumor cells. The absence of IL-1 signaling or its excess in the lung microenvironment (in IL-1ß and IL-1R antagonist knockout [KO] mice, respectively) resulted in a poor prognosis and reduced T cell activity, compared with WT mice. In IL-1ß KO mice, enhanced T regulatory cell development/function, due to a favorable in situ cytokine network and impairment in APC maturation, resulted in suppressed antitumor immunity, whereas in IL-1R antagonist KO mice, enhanced accumulation and activity of myeloid-derived suppressor cells were found. Reduced tumor progression along with improved T cell function was found in IL-17 KO mice, compared with WT mice. In the microenvironment of lung tumors, IL-1 induces IL-17 through recruitment of γ/δ T cells and their activation for IL-17 production, with no involvement of Th17 cells. These interactions were specific to the microenvironment of lung tumors, as in intrafootpad tumors in IL-1/IL-17 KO mice, different patterns of invasiveness were observed and no IL-17 could be locally detected. The results highlight the critical and unique role of IL-1, and cytokines induced by it such as IL-17, in determining the balance between inflammation and antitumor immunity in specific tumor microenvironments. Also, we suggest that intervention in IL-1/IL-17 production could be therapeutically used to tilt this balance toward enhanced antitumor immunity.