[Osteonecrosis of the jaws by using bisphosphonates]. / Biszfoszfonátok alkalmazása következtében kialakuló osteonecrosis az allcsontokban.

The new generation of bisphosphonates are often used in the treatment of osteoporosis or for certain tumors with bone defects. Between the period of September 2005 and May 2006 we have treated 8 patients at our clinic with a bisphosphonate-induced osteonecrosis in the maxillofacial region. All of these patients went through intravenous bisphosphonate treatment earlier. We have chosen two cases, where the appearance of side effects can be named as typical. Based upon the increasing number of international articles reporting and our own experiences in this matter, we would like to draw attention to the importance of prevention in treating these patients. In case of symptoms, if temporary suspension of the bisphosphonate therapy does not have severe consequences, combination of surgical and long-term antibiotic therapy could be the solution.

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-mum 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.

[A cross sectional study of titanium plates surface-treated with anodic oxidation]. / Anódos oxidációval felületkezelt titánlemezek keresztmetszeti vizsgálata.

It is an important modern trend to try to modify the surface properties of titanium implants with titanium oxide produced in various ways. One possibility of surface modification is the formation of an oxide layer by heat and electric treatment. The authors examined three osteosynthesis plates treated with anodic oxidation of Hungarian development. 5-10 microm thick slides were made of the plates in several cross sectional planes with a special cutting-grinding technique and were examined under a microscope with various magnifications. In the study it was seen that the surface of the basic metal was covered with a continuous oxide layer in all the cross sectional planes. No material faults were discovered on the surface. The thickness of the surface layer in various regions was found to be changing in the nm range, which coincides with the results of other studies. It was proven in the study by using the surface modification technique in part developed by the authors a passivating layer was formed on the surface of titanium, which separates it from the human organism.

[Survival prospects of mesopharyngeal carcinoma patients treated primarily with intraarterial chemotherapy. A retrospective study]. / Elsodlegesen intraarteriális kemoterápiával kezelt mesopharynx-carcinomás betegek túlélési kilátásai. Retrospektív vizsgálat.

BACKGROUND: The radical removal of mesopharyngeal tumors necessitates very extensive, aggressive surgery. In certain cases, therefore, they strive to ensure the quality of life of these patients by means of two other possibilities in the complex treatment: chemotherapy and irradiation; in this way, over radicality can be avoided. AIM: One of the elements of the complex therapy may be intraarterial chemotherapy. The present work relates to a study of the effects and side-effects of primary intraarterial chemotherapy administrated in the period 1995-2000, and the overall survival of the patients. PATIENTS AND METHOD: Remission was attained in a total of 30 patients who participated in primary intraarterial chemotherapy. The degree of severity of any complications that occurred was studied, as was the duration of survival. Treatment was performed by retrograde cannulation of the external carotid artery and the administration of a relatively low dose of drug for a relatively long time (5-14 days). The intra-arterial chemotherapy was supplemented with other modes of treatment. RESULTS: A clinically observable degree of tumor regression was detected in 83.3% of the cases after the intraarterial treatment. The 5-year survival rate was approximately 30%. CONCLUSIONS: The overall survival rate for oropharyngeal carcinoma patients treated with combined procedures is reported to range between 32% and 83%. Since our patients (with 2 exceptions) were in stage III or IV, and in many cases were inoperable, our 5-year survival rate of approximately 30% may be stated to be acceptable, while the quality of life of the patients was much more favourable than following the primary radical operation.

[Total upper lip necrosis and loxoscelism caused by violin spider bite]. / Pókcsípés okozta loxoscelizmus nagykiterjedésu felso ajak nekrózissal.

Arthropods and in particular spiders are a common embodiment of our fears, despite the fact that only a few species are dangerous to man. The authors present a case involving severe local and general reactions to a loxosceles (brown recluse spider) bite. They give an overview of the occurrence of loxosceles spiders, the signs and symptoms of envenomation and the therapeutic possibilities. The severe symptoms presenting following loxosceles envenomation is termed loxoscelism. Loxoscelism is characterised by local soft tissue necrosis of varying degree at the site of the sting, and rarely, life-threatening general reactions, such as haemolysis with ensuing anaemia, and renal failure. Therapeutic interventions following loxosceles bites range from dapsone treatment to hyperbaric oxygen therapy, but the most promising therapy is the use of the antiserum, commercially available in certain South-American countries where loxosceles bites are common. Treatment of soft tissue necrosis consists of necrectomy and surgical reconstruction following the resolution of the inflammatory symptoms.

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.

[Corrosion study of anodically and thermically surface-treated osteosynthesis plates]. / Anódosan és termikusan felületkezelt osteosynthesis lemezek korróziós vizsgálata.

For the fixation of mandibular fractures, at the Department of Oral Surgery and Dentistry at Semmelweis University, anodically and thermically treated TiO2/Ti osteosynthesis plates are used. The corrosion studies were performed in a generally-applied 3-electrode electrochemical measurement cell, with a calomel electrode as reference electrode, and a Pt net as conducting electrode. The cyclic voltammetric measurements demonstrated that the pore-free surface TiO2 layer forms a highly protective barrier on the surface of Ti. The electrochemical impedance spectrum reflected a decrease in inhomogeneity of the sample because of a decrease in the number of pinholes. Such a change is indicative of passivation. The reported techniques appear to comprise a reliable method of study for an evaluation of the long-term corrosion behaviour of implants.

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.

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 one's 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.

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 beta-tricalcium phosphate, and on the quality of the new bone formed. Defects formed in the mandibles of 10 Beagle dogs were filled with beta-tricalcium phosphate or with a mixture of beta-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 beta-tricalcium phosphate and leads to the formation of hard tissue with a quality similar to that of the autogenous bone.

[Surface analysis of interaction between titan implants treated with anod oxidation and the human organism]. / Anódos oxidációval felületkezelt titánimplantátumok es az emberi szervezet közötti kölcsönhatás vizsgálata felületanalitikai módszerekkel.

UNLABELLED: The examination of interaction between the titan implants treated with anod oxidation and the human organism carried out with surface analytical methods. The favourable properties of metallic titanium have led to its widespread use as an implant material. These properties can be further improved by surface treatment. We have been using anodically oxidized titanium plates for purposes of osteosynthesis for more than 15 years. A specially produced surface oxide layer (TiO2) improves the properties of the metal considerably, increasing the physical and chemical resistance of the plates to the aggressive effects of the organism. Thanks to this, it is now very rare for the plates to have to be removed after the bone healing. The present aim was to use XPS, SIMS and AES surface analytical methods to study the extent to which the positive charactheristics of the TiO2 coating are altered by the aggressive action of the organism during the years following implantation. In practice, we sought to establish the length of time during which the good properties of the plates do not change, and to determine when, it at all, the plates need to removed. MATERIAL AND METHODS: In our present work we studied titanium (ostheosynthesis) plates, removed from 3 patients, with XPS, AES and SIMS method. RESULTS: It was observed that the basic metal remained covered by a TiO2 layer. In consequence of the osseintegration, the Ca and P contents of this layer had increased, which may be explained by incorporation from the organism. CONCLUSION: The Ti implant with is modified surface was covered by a TiO2 layer 120-150 nm thick, which exhibited a homogeneous oxygen distribution. During many years, this had provided protection against the chemical and physical effects of the organism.

[Alveolar bone regeneration stimulated by a combination of platelet-rich plasma and Cerasorb graft in Beagle dogs. Histological and histomorphometric studies]. / Alveolaris csontregeneráció serkentése thrombocyta-dús plasma és Cerasorb-graft kombinációjával Beagle kutyákban (Szövettani és hisztomorfometriai vizsgálatok).

Healing of extraction wounds was examined in an animal experiment model on Beagle dogs. After bilateral extraction of the premolars of 12 dogs the alveoli were filled up with a combination of beta-tricalcium phosphate (Cerasorb) graft and platelet rich plasma (PRP) on the experimental side, and with Cerasorb alone on the control side. Biopsy specimens were taken from the regenerating bone at 6, 12 and 24 weeks after surgery for histological study. Results of the histologic and histomorphometric examinations revealed that after 6 weeks the newly formed bone was significantly denser on the experimental side. After 12 weeks this difference became moderate, and after 24 weeks the bone forming activity was nearly equal on the two sides. These results suggest that local administration of Cerasorb and PRP results in more intense bone regeneration, especially in the early phase.

[Significance of prognostic factors in oral squamous carcinoma]. / Prognosztikai faktorok jelentósége szájüregi laphámrákok esetében.

Despite the considerable advances in the diagnostic and therapeutic possibilities, the prognosis of epithelial tumors in the oral cavity is very poor. A knowledge of the prognostic factors at the beginning of treatment is therefore indispensable for determination of the appropriate therapy for the given patient. These factors may be linked to the patient (e.g. age, sex, general condition and immunological parameters) or to the tumor (localization, TNM stage, histological features, DNA content, or immunohistochemical and other parameters). A survey of the literature reveals that the TNM stage, the grade, the mode of invasion and the depth of the tumor are generally the most important factors influencing the fate of the patient. The prognosis primarily depends on the clinicopathological parameters, though even if they are known, it is not possible to screen out those patients who are at particular risk of a relapse. During the past 10 years, study of the DNA content, the proliferation markers and certain oncogenes has came into the focus of attention; great interest is also shown in the matrix metalloproteinases, which play key roles in the invasion and metastasis formation.

[Modern methods for studying the surface of titanium implants (literature review)]. / Titánimplantátumok felületének modern vizsgálati lehetóségei (Osszefoglaló referátum).

Studies of the coatings found on the surface of titanium implants employed in oral surgery are indispensable for understanding the interactions between the organism and the implant. This paper surveys the theory and practical applicability of the methods most frequently applied to study the surface structure and composition of the material. Detailed accounts are given of various structure investigation methods: scanning electron microscopy, stereo scanning electron microscopy, X-ray diffraction, atomic force microscopy and interference microscopy; and of various composition investigation methods: secondary ion mass spectroscopy, X-ray photoelectron spectroscopy, Auger electron spectroscopy; and also of the corrosion procedures for the study of electrochemical behaviour.

[The effect of platelet-rich plasma on new bone formation by augmentation with osseoconductive bone substitute material in beagle dogs]. / Platelet-rich plasma (thrombocyta-koncentrátum) hatása a csontképzõdésre oszteokonduktív csontpótlóval (beta-trikalcium-foszfát) történõ együttes alkalmazáskor Beagle kutyákon.

Animal experiments were carried out with osseoconductive bone substitute beta-tricalcium phosphate (beta-TCP), with the aim of assessing the effect of the growth factors synthesized by platelets on the speed of beta-TCP incorporation and on the quality of newly formed bone. The question arises whether the results attained with this synthetic material approach are comparable to those attained with autologous bone. Defects in the mandibles of beagle dogs were filled with beta-TCP or with the mixture of beta-TCP and platelet rich plasma (PRP) obtained from autologous blood. The quality of the newly formed bone and the effect of PRP were studied by histologic and histomorphometric methods. On the 6th week, bone formation seemed to be more effective when PRP was applied in comparison with beta-TCP alone, but the difference was not significant. On the 12th week bone formation was significantly greater. The results demonstrate that the use of PRP accelerates the remodelling of the synthetic bone-substitute material beta-TCP.

Repair of bony defect with combination biomaterials.

BACKGROUND: Numerous 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. AIM: A 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 METHODS: In one case, augmentation was carried out with beta-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 beta-tricalcium phosphate, with a mixture of beta-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. RESULTS: At 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. DISCUSSION: The 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 beta-tricalcium phosphate and platelet concentrate was used.

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 beta-tricalcium phosphate alone, autogenous bone mixed with these bone substitutes, or a combination of beta-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.

[SIMS (secondary ion mass spectroscopy) and XPS (x-ray photoelectron spectroscopy) study of titanium implant surfaces coated with anodic titanium-oxide layer]. / Anodikus titánoxid-réteggel bevont titán implantátumok felületének vizsgálata SIMS és XPS módszerrel.

The demands that must be satisfied by titanium implants applied in medical practice include chemical and physical durability. An anodic oxide protective layer formed on the surface of titanium implants serves for the better attainment of this aim. The composition of the passivizing layer and the changes in its thickness and binding state can be studied by method of material science, e.g. by secondary ion mass spectroscopy (SIMS) and X-ray photoelectron spectroscopy (XPS). In this way a possibility arises for the material technological classification of the Ti-TiO2 layer structure and for the observation of the physical and chemical reactions that occur between the implants and the tissues in the organism. The present XPS examinations revealed that the binding state of the titanium forming the surface of the plates involve neither significant quantities of titanium oxide nor impurities. In the SIMS investigation the thickness of the titanium oxide layer was found to be 120-150 nm. Determination of the thickness of the surface, the binding state of the titanium and the exact proportions of the impurities and additives furnishes a possibility for a subsequent comparison with the surface structure of plates removed from the organism. It is important for the assessment of the practical value of the protective layer.

[Bone substitution and remodeling of the jaw bones. A review]. / Csontpótlás és remodelling az állcsontokon (Osszefoglaló referátum).

Replacement of defects of the jawbones is one of the rapidly developing fields of maxillofacial surgery. The main criterion for the success of bone replacement is effective remodelling, i.e. the quantitative transformation of the inserted bone-substitute material into bone of the same quality and the same structure as the original. The aim of this report is to survey the literature background of our knowledge relating to remodelling. An account is given of the mechanism of transformation of the bone-substitute material into bone, and of clinical, radiological and histologic methods with which the transformation can be appropriately followed. Remodelling is a protracted process, and conclusions relating to it can be drawn only from examinations performed at isolated points of time, which are often difficult to objectify. We may speak of complete remodelling if the inserted material can no longer be recognized, and only bone with a structure agreeing with that of its environment is to be seen in the augmented area.