Norbert Velich

Long-term results with different bone substitutes used for sinus floor elevation.

One of the surgical procedures preceding implantation is elevation of the base of the maxillary sinus. Numerous bone substituting materials (grafts) may be used for this purpose, including autogenous bone, heterografts, xenogenous bone, and synthetic materials alone or in combination or mixed with growth factors and bone morphogenetic protein (BMP) preparations. A study of the frequencies of the failures (graft material resorption or implant loss) after sinus elevations with various graft materials or their combinations was conducted. In the 5-year period from 1996 through 2001, a follow-up investigation of 810 maxillary sinus augmentations was performed, in which the sinus elevations involved the use of autogenous bone, a calcium carbonate-coated polymer, hydroxylapatite of algal origin, calcium carbonate gel produced from coral or &bgr;-tricalcium phosphate alone, autogenous bone mixed with these bone substitutes, or a combination of &bgr;-tricalcium phosphate and platelet-rich plasma. The incidences of graft resorption and implant loss after the augmentations with various bone substitutes were recorded. Total resorption (disappearance) of the bone substitute material was observed in 2.7% of the cases. An essential difference was not experienced between the various bone substitutes from this aspect, with the exception of the gel-state calcium carbonate, where 40% of the grafts were resorbed. In total, 5.46% of the implants were lost; the differences between the various materials were not significant.

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma Modulates Intratumoral CD4/CD8 Ratio and Tumor Microenvironment: A Multicenter Phase II Clinical Trial

PURPOSE To investigate the clinicopathologic effects of local neoadjuvant Leukocyte Interleukin Injection (LI) regimen in oral squamous cell carcinoma (OSCC) patients. Treatment regimen included LI 800 IU/d as interleukin-2 (IL-2), administered half peritumorally and half perilymphatically five times per week for 3 weeks; low-dose cyclophosphamide; indomethacin; zinc; and multivitamins. PATIENTS AND METHODS Thirty-nine patients diagnosed with T2-3N0-2M0 OSCC participated in the pathology portion of this phase II multicenter study (19 LI-treated patients and 20 historical controls). Clinical responses were determined by imaging. Paraffin-embedded tumor samples were obtained at surgery for all patients. Surgery for the LI-treated group was performed between days 14 and 54 after the end of treatment. Histologic evaluation, pathologic staging, necrosis, and American Joint Committee on Cancer grading were performed from hematoxylin and eosin sections. Immunohistochemistry and morphometry determined cellular infiltrate. RESULTS Two pathologically complete, two major (> 50%), and four minor responses (> 30% but < 50%) resulted from LI treatment (overall response rate, 42%). Histopathology showed that the intratumoral CD4+:CD8+ ratio was low (< 1) in patients not treated with LI (controls). An increase in tumor-infiltrating CD4+ and a decrease of CD8+ T cells was observed in LI-treated patients, leading to a significantly (P < .05) higher intratumoral CD4+:CD8+ ratio (> 2.5). This was paralleled by dendritic cell transition from tumor surface toward stromal interface (P < .05), with macrophage decrease and neutrophil accumulation, multifocal microscopic necrosis, and significant (P < .05) increase in tumor stroma of LI-treated patients compared with controls. CONCLUSION LI-treated OSCC patients were characterized by a markedly altered composition of tumor-infiltrating mononuclear cells, increased CD4+:CD8+ ratio, and increased tumor stroma to epithelial ratio, all of which were distinct from controls.

Repair of bony defect with combination biomaterials.

BackgroundNumerous possibilities are available for the reconstruction of facial bone defects. The materials used to fill such defects must satisfy various requirements. One of the most important is that they must undergo transformation into autologous bone tissue in the process of remodeling. AimA report is given of the long-term results of augmentations of large bone defects performed with different bone-substitute materials in two patients. Patients and methodsIn one case, augmentation was carried out with &bgr;-tricalcium phosphate after the removal of a fibromyxoma. In the second case, three large cystic lesions in the mandible of a patient with Gorlin-Goltz syndrome were filled with &bgr;-tricalcium phosphate, with a mixture of &bgr;-tricalcium phosphate and platelet concentrate, or with hydroxyapatite of algal origin. The process of ossification was checked at 6-month intervals by means of clinical, radiologic (orthopantomograms and two-dimensional and three-dimensional computer tomograms), and histologic methods. ResultsAt 1 year after the intervention, the site of the augmentation was in all cases occupied by hard tissue of good quality. With the given imaging procedures, it was difficult to distinguish between the original bone and the region filled with bone-substitute material. The three-dimensional computer tomogram images indicated that the contours and quality of the new bone corresponded with the physiologic and anatomical conditions. The histologic examinations show the remodeling of the bone-substitute materials. DiscussionThe bone-substitute materials applied in these cases fully satisfied the demands of transformation into bone (remodeling). The speed of remodeling seemed to be the fastest when the mixture of &bgr;-tricalcium phosphate and platelet concentrate was used.

Histomorphometric and densitometric evaluation of the effects of platelet-rich plasma on the remodeling of beta-tricalcium phosphate in beagle dogs.

Countless possibilities are available in maxillofacial surgery for the filling of bone defects. The best bone substitute known at present is osteogenic autogenous bone, but its use is accompanied by numerous disadvantages. The question has arisen of whether results attained with osteoconductive bone substitutes approach those achieved by the transplantation of autogenous bone. The aims of the investigation were to measure the effects in animal experiments of the growth factors to be found in the platelets on the rate of remodeling of β-tricalcium phosphate, and on the quality of the new bone formed. Defects formed in the mandibles of 10 Beagle dogs were filled with β-tricalcium phosphate or with a mixture of β-tricalcium phosphate and platelet-rich plasma obtained from autogenous blood. The quality of the hard tissue formed and the effect of the platelet-rich plasma were examined by statistical analysis of the densitometric results obtained after 6 weeks and the histological and histomorphometric results obtained after 12 weeks. The densitometric study revealed that the bone formation was significantly more effective when platelet-rich plasma was used; at this stage, histomorphometric evaluation did not indicate a significant difference. After 12 weeks, however, the histomorphometric study demonstrated a significant difference in favor of the bone substitute used together with platelet-rich plasma. The results strongly suggest that use of the platelet-rich plasma suspension accelerates the remodeling of β-tricalcium phosphate and leads to the formation of hard tissue with a quality similar to that of the autogenous bone.

Surface analysis methods of biomaterials used in oral surgery: literature review.

Titanium is the most frequently used biomaterial in oral surgery because of its positive physical and chemical properties. Clinical studies proved that the properties of titanium can be improved by surface modification techniques. To study the surface of biomaterials, the positive effects of the coatings, the response of the organism (corrosion resistance, physical and chemical stability, the thickness of various coatings, biocompatibility), one must choose and use the adequate analytical method for ones goal. In this article, the authors present the most frequently used analytical methods for the study of the surface morphology and composition of biomaterials. Also, they outline the advantages and disadvantages of specific analytical methods and the field where they are used.

Effect of induction chemotherapy on changes of laminin and syndecan expression in oral squamous cell carcinomas: a prospective, randomized, clinicopathologic and immunohistochemical study.

Sixty patients with tumors of the floor of the mouth or of the tongue (T2N0-1-2M0) were randomized into three treatment groups. The first two groups participated in low-dose inductive chemotherapy, surgery, and then radiotherapy, whereas the third control group underwent only surgery and radiotherapy. In all three groups, studies were made of the stage, grade, sex, localization, extents of expression of the pretreatment laminin and syndecan-1 and the cancer specific survival rate, and the correlations among these. The response to neoadjuvant chemotherapy was assessed by means of a method that we developed, involving measurement of the degree of histologic regression observed in response to chemotherapy. Immunohistochemical methods were applied to investigate the changes in degree of expression of laminin and syndecan-1 in response to the medication and their correlations with the survival. As concerns the overall tumorfree survival rate, a significant difference was not found between the two chemotherapeutic groups. However, there was a significant difference between the survival indices of those who participated in cytostatic treatment (70%) and the control group (40%). In the clinical and immunohistochemical examinations, the initial laminin and syndecan-1 levels obtained from biopsy samples could be used as prognostic factors. Our model measuring the extent of histologic regression clearly demonstrated that the survival indices of the patients who responded to the neoadjuvant cytostatic treatment with adequate tissue regression were better than those of the patients who responded to the treatment to only a decreased extent or not at all. The changes in the expressions of laminin and syndecan-1 in response to cystostatic treatment proved to be important predictive factors. The increase or stagnation of these clearly forecast a good prognosis, whereas their decrease was a definite indication of poor prognosis.

Overall survival of oropharyngeal cancer patients treated with different treatment modalities.

Therapeutic modalities of use in tumor therapy can be applied in various combinations to treat malignant lesions of the mesopharynx. A study was made of the overall survival of patients with mesopharyngeal carcinoma treated with different modalities in our institution in the period 1995-2000. In this retrospective study, a total of 66 patients were divided into 4 groups: Patients who took part in 1) intra-arterial chemotherapy and subsequent irradiation; 2) intra-arterial chemotherapy and surgical care; 3) only surgical care; or 4) only irradiation or palliative treatment. In each group, the five-year survival rate was examined, as a function of the age of the patient, the initial tumor size, the lymph node status and the clinical stage. The five-year overall survival rate in group 1 was 28.57%, in both group 2 and group 3 was 66.66%, and in group 4 was 20%. For all of the 66 patients, it was 43.93%. For groups 2 and 3, the Kendall rank correction test did not reveal a significant effect of the lymph node state or the clinical stage on the survival, whereas the effects of the age and the initial tumor size did prove to be significant. The Cox regression test showed the latter of these two effects to be the stronger. As 64 of the 66 patients examined were treated for tumors in clinical stages III or IV, the five-year survival rate of 43.93% may be said to be good. The comparison of groups 2 and 3 revealed that (in spite of the poorer initial prognosis in group 2) the survival rates were the same, i.e. the neoadjuvant intra-arterial chemotherapy improved the prognosis.

Effect of human organism on the oxide layer formed on titanium osteosynthesis plates: a surface analytical study.

The question of whether or not to remove the titanium osteosynthesis plates used in maxillofacial surgery is not yet answered. These plates can be left a long time in the organism if there is no harmful interaction between the plates and the organism. The authors examined the properties of the surface oxide layers formed on osteosynthesis titanium plates by subsequent thermal and anodic oxidation, together with the properties of plates removed from patients after three years. Surface analytical method Secondary Ion Mass Spectroscopy (SIMS) was chosen. It was found that inside of the about 200-&mgr;m thick oxide on the original plates the concentration of impurities is much lower than near the oxide/titanium interface. On the surface of plates removed from the human body, a C (carbon), Ca (calcium) and P (phosphorus) enrichment was detected, suggesting a biological interaction between the organism and the plate. The passivating layer formed with thermal and anodic oxidation has not changed significantly in three years; it resisted to the corrosive effect of the human organism.

Study of the interaction between Ti-based osteosynthesis plates and the human body by XPS, SIMS and AES

Ti implants with surfaces modified by anodic and thermal oxidation were used to promote osteosynthesis. X-ray photoelectron spectroscopy, secondary ion mass spectroscopy and Auger electron spectroscopy were used to study the surface composition and the depth homogeneity of the implant materials before implantation and after removal from the patient (3 years later). The surface of the Ti implants was modified through anodic and thermal oxidation. The surface of the Ti implant before use is covered by a 200?nm thick TiO2 layer, with homogeneously distributed O at depth. During the formation of this TiO2 layer, phosphate, Ca and a small amount of C are incorporated into the oxide. Similarly to the main impurities in the base Ti metal (Cr and Fe), the Ca and C accumulate at the oxide/metal interface. Three years after the implantation, the binding state of the Ti in the oxide layer was unchanged. The base metal remained covered by TiO2, the outer surface of which was partially covered by a mainly C-containing layer of varying thickness. The increases in the Ca and P contents of the TiO2 layer during the 3 years in the human body can be explained by incorporation from the body. Clinically, no metallosis or allergic reactions were observed.