BackgroundConfocal laser endomicroscopy (CLE) is an optical biopsy method allowing in vivo microscopic imaging at 1000-fold magnification. It was the aim to evaluate CLE in the human oral cavity for the differentiation of physiological/carcinomatous mucosa and to establish and validate, for the first time, a scoring system to facilitate CLE assessment.MethodsThe study consisted of 4 phases: (1) CLE-imaging (in vivo) was performed after the intravenous injection of fluorescein in patients with histologically confirmed carcinomatous oral mucosa; (2) CLE-experts (n = 3) verified the applicability of CLE in the oral cavity for the differentiation between physiological and cancerous tissue compared to the gold standard of histopathological assessment; (3) based on specific patterns of tissue changes, CLE-experts (n = 3) developed a classification and scoring system (DOC-Score) to simplify the diagnosis of oral squamous cell carcinomas; (4) validation of the newly developed DOC-Score by non-CLE-experts (n = 3); final statistical evaluation of their classification performance (comparison to the results of CLE-experts and the histopathological analyses).ResultsExperts acquired and edited 45 sequences (260 s) of physiological and 50 sequences (518 s) of carcinomatous mucosa (total: 95 sequences/778 s). All sequences were evaluated independently by experts and non-experts (based on the newly proposed classification system). Sensitivity (0.953) and specificity (0.889) of the diagnoses by experts as well as sensitivity (0.973) and specificity (0.881) of the non-expert ratings correlated well with the results of the present gold standard of tissue histopathology. Experts had a positive predictive value (PPV) of 0.905 and a negative predictive value (NPV) of 0.945. Non-experts reached a PPV of 0.901 and a NPV of 0.967 with the help of the DOC-Score. Inter-rater reliability (Fleiss` kappa) was 0.73 for experts and 0.814 for non-experts. The intra-rater reliability (Cronbach’s alpha) of the experts was 0.989 and 0.884 for non-experts.ConclusionsCLE is a suitable and valid method for experts to diagnose oral cancer. Using the DOC-Score system, an accurate chair-side diagnosis of oral cancer is feasible with comparable results to the gold standard of histopathology—even in daily clinical practice for non-experienced raters.

The aims of this investigation were to histologically evaluate in monkeys the effect of a repetitive mechanical trauma alone on the peri-implant tissues, and the effect of a repetitive mechanical trauma in combination with ligature-induced peri-implantitis on the peri-implant tissues. The study used 5 male cynomolgus monkeys. Prior to the start of the study, all premolars and the first and second molars in the mandible were extracted. After a healing period of 12 weeks, following tooth extraction, split/full thickness flaps were elevated on both sides of the mandible in order to expose the bony ridge. Four implants, of 3.75 mm in diameter and 7 mm in length, were then inserted on each side and the flaps were readapted and sutured in place. Following a healing period of 16 weeks, the second stage procedure was performed, impressions were taken, and custom-made crowns using a non-precious metal alloy were fabricated and inserted on all implants 4 weeks after abutment connection. At the same time peri-implantitis was induced on one side of the mandible by placing plaque-retentive ligatures around the implants. On the other side, an oral hygiene program consisting of thrice weekly brushing with a toothbrush and flour of pumice mixed with 2% chlorhexidine was initiated. Four months later, a repetitive mechanical trauma was initiated on implants 1 and 2 on both sides in the mandible. Consequently, a split mouth design was obtained: 1) test 1=ligature-induced peri-implantitis alone (LPNO); 2) test 2=ligature-induced peri-implantitits with a repetitive mechanical trauma (LPMT); 3) test 3=healthy peri-implant tissues with a repetitive mechanical trauma (MT); and 4) control (NO)=healthy peri-implant tissues with no repetitive mechanical trauma. Following 16 weeks of repetitive mechanical trauma the animals were sacrificed. Histologic observations and computed-assisted histometric and histomorphometric analyses were performed to determine the amount of peri-implant bone loss and the percentage of direct mineralized bone-to-implant contact around each endosseous oral implant. Histologically, all implants yielded osseointegration at the light microscopic level. There was a significant difference regarding the mean direct mineralized bone-to-implant contact length as a fraction of the total implant length between the healthy (i.e., MT and NO) and diseased sites (i.e., LPNO and LPMT) (P < 0.05). When comparing the percent of direct mineralized bone-to-implant contact for the 2 best threads of each implant and group, no significant difference (P=0.675) could be detected. Under the conditions of this study, the repetitive mechanical trauma showed no histologic effect on the peri-implant bone loss neither in healthy nor in diseased implant sites. The effects of excessive loading on osseointegration are presently not clearly understood. The key problem seems to be the determination when loading on implants exceeds the physiological range of bone adaptation which may then cause implant failure. Further research to elucidate this pro...

No abstract