Bojan Pavlović

Oncological and Functional Outcome after Surgical Treatment of Early Glottic Carcinoma without Anterior Commissure Involvement

Introduction. Glottic carcinoma can be successfully diagnosed in its early stages and treated with high percentage of success. Organ preservation and optimal functional outcomes could be achieved with wide array of surgical techniques for early glottic cancer, including endoscopic approaches or open laryngeal preserving procedures, making surgery the preferred method of treatment of early glottic carcinoma in the last few years. Material and Methods. Prospective study was done on 59 patients treated for Tis and T1a glottic carcinoma over a one-year time period in a tertiary medical center. Patients were treated with endoscopic laser cordectomy (types II–IV cordectomies according to European Laryngological Society classification of endoscopic cordectomies) and open cordectomy through laryngofissure. Follow-up period was 60 months. Clinical and oncological results were followed postoperatively. Voice quality after the treatment was assessed using multidimensional voice analysis 12 months after the treatment. Results. There were no significant differences between oncological and functional results among two groups of patients, though complications were more frequent in patients treated with open cordectomy. Conclusion. Endoscopic laser surgery should be the first treatment of choice in treatment of early glottic carcinomas, though open approach through laryngofissure should be available for selected cases where anatomical factors present limiting adequate tumor removal.

Antibiofilm effects of topical corticosteroids and intranasal saline in patients with chronic rhinosinusitis with nasal polyps depend on bacterial species and their biofilm-forming capacity

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids and saline is a reliable option for their management. The aim of our study was to evaluate in vitro antibiofilm effects of corticosteroids and isotonic and hypertonic nasal saline in CRSwNP patients. The sinus mucosal specimens were harvested from the ethmoid cavity of 48 patients with CRSwNP and further subjected to hematoxylin–eosin staining and microbiology analysis. The biofilm-forming capacity of isolated bacterial strains was detected by microtiter-plate method and the effects of therapeutic doses of mometasone, fluticasone, isotonic and hypertonic saline on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one organism in 34 (80.9%) and two organisms in 8 (19.1%). Staphylococcus epidermidis (34%) and Staphylococcus aureus (28%) were the most prevalent bacteria in biofilms of CRSwNP patients. Corticosteroids and saline solutions significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively) with better efficacy of fluticasone and isotonic nasal saline. Treatment with fluticasone, mometasone, isotonic and hypertonic nasal saline completely prevented biofilm production in 66, 50, 84 and 38% of bacterial strains, respectively. The most significant density reduction was observed in biofilm formed by Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae compared to other bacterial species (p < 0.01, p < 0.05, p < 0.05, respectively). The antibiofilm effects of corticosteroids and saline solutions also greatly depended on bacterial biomass (p < 0.05), with the most significant effect on high compared to small amount of formed biofilm. The topical steroids and nasal saline are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and volume of formed biofilm.

Tumor necrosis factor–α promotes survival and phenotypic maturation of poly(I:C)-treated dendritic cells but impairs their Th1 and Th17 polarizing capability

BACKGROUND AIMS Toll-like receptor (TLR)-3 synthetic agonist polyinosinic-polycytidylic acid (poly(I:C)) is a promising agent for dendritic cell (DC)-based anti-tumor vaccines because of its ability to induce a strong maturation of DCs, but such an effect is followed by stimulation of DC apoptosis. Tumor necrosis factor (TNF)-α may promote the survival of poly(I:C)-stimulated DCs, but it is not known in detail how this combination affects the maturation and polarization capacity of monocyte-derived (Mo)DCs. METHODS Immature MoDCs, generated from human monocytes, were treated with different concentrations of poly(I:C) combined with TNF-α, and the effect on survival, phenotype, production of cytokines, allostimulatory and Th polarization capacity was assessed after 24 and 48 h. RESULTS We showed that TNF-α inhibited the dose-dependent pro-apoptotic effect of poly(I:C). However, TNF-α also decreased poly(I:C)-induced production of interleukin (IL)-12 and IL-23 by MoDCs, which correlated with their diminished capacity to stimulate cellular proliferation, interferon-γ and IL-17 production by allogeneic CD4(+)T cells in co-culture. Such an effect was more pronounced after 24 h and could not be restored by CD40 ligation. In the presence of CD40L, TNF-α even stimulated IL-10 production and immunoglobulin-like transcript 3 expression by poly(I:C)-matured DCs, which correlated with their increased capacity to induce IL-10 production by CD4(+)T cells. CONCLUSION Even though TNF-α could promote the survival of poly(I:C)-matured MoDCs, it also suppresses key anti-tumor functions of these cells, which could have important implications when considering this, already suggested, protocol for the DC-based anti-tumor therapy.

Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties

BACKGROUND AIMS Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited. METHODS We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise. RESULTS Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD14, low expression of CD1a and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1β and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-β production by fDC-primed CD3(+)T cells and their stronger anti-proliferative capacity. CONCLUSIONS We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.

Quantification of biofilm formation on silicone intranasal splints: An in vitro study

OBJECTIVES Biofilms are associated with persistent infections and resistant to conventional therapeutic strategies. The aim of this study was to investigate the quantity of biofilm produced on silicone intranasal splints. METHODS Quantity of biofilm formation on silicone splints (SS) was tested on 15 strains of Staphylococcus aureus and Moraxella catarrhalis, respectively. Antimicrobial susceptibility testing was performed in accordance with European Committee on Antimicrobial Susceptibility Testing recommendations. RESULTS All tested strains formed different amounts of biofilm on SS: 66.7% S. aureus and 93.3% M. catarrhalis were weak biofilm producers and 33.3% S. aureus and 6.7% M. catarrhalis were moderate biofilm producers. S. aureus formed significantly higher quantity of biofilm compared with M. catarrhalis (p < 0.05). Multidrug resistant S. aureus produced significantly higher amount of biofilm compared with non-multidrug resistant strains (p < 0.05). CONCLUSION Quantity of biofilm on SS is highly dependent on bacterial species and their resistance patterns. Future studies are needed to ascertain another therapeutic option for prophylaxis prior to SS placement.

Laryngeal Granuloma – Benefit in Treatment with Zinc Supplementation? / Larinksni Granulom - Korist Od Terapije Preparatima Cinka

Summary Laryngeal granulomas present as contact and postintubation ulcers and granulomas. Essentially, a contact granuloma is a pseudotumor of the lateral wall of the posterior glottis. The most common etiological factor is voice abuse, with predisponing factors such as reflux disease. Postintubation ulcers and granulomas, although of different etiology, according to all the other traits belong to this clinical entity. The therapy of choice is conservative treatment. Surgical laser excision is indicated for resistant cases and those whose size is causing respiratory distress. Treatment of laryngeal granulomas with zinc supplementation is reported in the literature as one of the forms of conservative treatment, and we wanted to consider it in this review. Zinc is an essential mineral that plays a vital role in many biochemical reactions and is considered very important for wound healing. Kratak sadržaj Larinksni granulom se predstavlja kon- taktnim i postintubacionim ulkusom i granulomom. U suštini, kontaktni granulom je pseudotumorski izraštaj late- ralnog zida zadnjeg dela glotisa. Najčešći etiološki faktor je neodgovarajuća upotreba glasa, uz predisponirajuće faktore kao što je refluksna bolest. Postintubacioni ulkus i granulom, iako drugačije etiologije, po svim ostalim osobinama pri- padaju ovom kliničkom entitetu. Preporučena terapija je konzervativno lečenje, a hirurška laserska ekscizija indiko- vana je za rezistentne slučajeve i one koji svojom veličinom izazivaju respiratorne smetnje. U literaturi se pominje per- oralna primena preparata cinka u terapiji larinksnog granulo- ma kao jedan od vidova konzervativnog lečenja, što smo i mi u ovom kratkom pregledu želeli da razmotrimo. Cink je esen- cijalni mineral koji igra ključnu ulogu u mnogim biohemij- skim reakcijama i smatra se da je veoma važan za zarastanje rana.

An anti-DEC-205 monoclonal antibody stimulates binding of thymocytes to rat thymic dendritic cells and promotes apoptosis of thymocytes

DEC-205, a transmembrane receptor responsible for cross-presentation of apoptotic cell-derived antigens, is expressed by cortical thymic epithelial cells (TEC) and thymic dendritic cells (TDC) in humans and mice, but its function in T-cell development is still unclear. In this work we have studied for the first time the expression of DEC-205 in the rat thymus by HD83 monoclonal antibody (mAb) and immunohistochemistry, as well as the ability of this mAb to modulate thymocyte – TDC interactions in vitro. We showed the positivity of cortical TEC in situ, including thymic nurse cells (TNC) in suspension, and TDC, whereas subcapsular, perivascular and medullary TEC were negative. All examined DEC-205 positive and DEC-205 negative structures were MHC class II positive. HD83 mAb increased apoptosis of thymocytes in co-culture with TDC in vitro and the process was associated with increased binding of thymocytes to TDC in a rosette form. Since negative selection of thymocytes by clonal deletion (apoptosis) was mediated predominantly by TDC, our results suggest the possible indirect effect of the DEC-205 molecule in these mechanisms.