György Szabó

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.

European expert consensus on rotational atherectomy.

The interest in rotational atherectomy (RA) has increased over the past decade as a consequence of more complex and calcified coronary stenoses being attempted with percutaneous coronary interventions. Yet adoption of RA is hampered by several factors: amongst others, by the lack of a standardised protocol. This European expert consensus document stems from the awareness of the large heterogeneity in the protocols adopted to perform rotational atherectomy. The objective of the present document is to provide some points of consensus among highly experienced operators on the most controversial steps of RA in an attempt to build the basis of a standardised and universally accepted protocol.

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.

Possibilities of preventing osteoradionecrosis during complex therapy of Tumors of the oral cavity

In recent years, there has been a dramatic increase in the number of tumors of the head and neck. Their successful treatment is one of the greatest challenges for physicians dealing with oncotherapy. An organic part of the complex therapy is preoperative or post-operative irradiation. Application of this is accompanied by a lower risk of recurrences, and by a higher proportion of cured patients. Unfortunately, irradiation also has a disadvantage: the development of osteoradionecrosis, a special form of osteomyelitis, in some patients (mainly in those cases where irradiation occurs after bone resection or after partial removal of the periosteum). Once the clinical picture of this irradiation complication has developed, its treatment is very difficult. A significant result or complete freedom from complaints can be attained only rarely. Attention must therefore be focussed primarily on prevention, and the oral surgeon, the oncoradiologist and the patient too can all do much to help prevent the occurrence of osteoradionecrosis. Through coupling of an up-to-date, functional surgical attitude with knowledge relating to modern radiology and radiation physics, the way may be opened to forestall this complication that is so difficult to cure.

A randomised comparison of transradial and transfemoral approach for carotid artery stenting: RADCAR (RADial access for CARotid artery stenting) study

AIMS Limited data exist on radial access in carotid artery stenting. This multicentre prospective randomised study was performed to compare the outcome and complication rates of transradial and transfemoral carotid artery stenting. METHODS AND RESULTS The clinical and angiographic data of 260 consecutive patients with high risk for carotid endarterectomy, treated between 2010 and 2012 by carotid stenting with cerebral protection, were evaluated. Patients were randomised to transradial (n=130) or transfemoral (n=130) groups and several parameters were evaluated. Primary combined endpoint: major adverse cardiac and cerebral events, rate of access-site complications. Secondary endpoints: angiographic outcome of the procedure, fluoroscopy time and X-ray dose, procedural time, crossover rate to another puncture site and hospitalisation in days. Procedural success was achieved in all 260 patients (100%), the crossover rate was 10% in the TR and 1.5% in the TF group (p<0.05). A major access-site complication was encountered in one patient (0.9%) in the TR group and in one patient (0.8%) in the TF group (p=ns). The incidence of major adverse cardiac and cerebral events was 0.9% in the TR and 0.8% in the TF group (p=ns). Procedure time (1,620 [1,230-2,100] vs. 1,500 [1,080-2,100] sec, p=ns) and fluoroscopy time (540 [411-735] vs. 501 [378-702] sec, p=ns) were not significantly different, but the radiation dose was significantly higher in the TR group (195 [129-274] vs. 148 [102-237] Gy*cm2, p<0.05) by per-protocol analysis. Hospitalisation days were significantly lower in the TR group (1.17±0.40 vs. 1.25±0.45, p<0.05). By intention-to-treat analysis there was a significantly higher radiation dose in the TR group (195 [130-288] vs. 150 [104-241], p<0.05), but no difference in major events (0.9 vs. 0.8, p=ns) and length of hospitalisation in days (1.4±2.6 vs. 1.25±0.45, p=ns). CONCLUSIONS The transradial approach for carotid artery stenting is safe and efficacious; however, the crossover rate is higher with transradial access. There are no differences in the total procedure duration and fluoroscopy time between the two approaches but the radiation dose is significantly higher in the radial group, and the hospitalisation is shorter with the use of transradial access by per-protocol analysis. By evaluating the patient data according to intention-to-treat analysis we found no difference in major adverse events and hospitalisation. In both groups, vascular complications rarely occurred.

Hit-to-lead optimization of pyrrolo[1,2-a]quinoxalines as novel cannabinoid type 1 receptor antagonists.

Hit-to-lead optimization of a novel series of N-alkyl-N-[2-oxo-2-(4-aryl-4H-pyrrolo[1,2-a]quinoxaline-5-yl)-ethyl]-carboxylic acid amides, derived from a high throughput screening (HTS) hit, are described. Subsequent optimization led to identification of in vitro potent cannabinoid 1 receptor (CB1R) antagonists representing a new class of compounds in this area.

Chemical and Biological Investigation of Cyclopropyl Containing Diaryl-pyrazole-3-carboxamides as Novel and Potent Cannabinoid Type 1 Receptor Antagonists

Obesity is a major clinical problem in the western world, and many molecular targets have been explored in the search for effective therapeutic agents. One of these, antagonism of the cannabinoid 1 (CB1) receptor, rose to prominence following reports demonstrating the positive modulation of food intake by the CB1 antagonist, rimonabant (3) (SR141716A). In the present study, various diaryl-pyrazole derivatives containing cycloalkyl building blocks were synthesized and tested for CB1 receptor binding affinities. Thorough structure-activity relationship (SAR) studies to optimize the pyrazole substituents led to several novel CB1 antagonists with K(i) <or= 5 nM and with acceptable metabolic stability with human liver microsomes. Among these analogues, we identified 5-(4-cyclopropylphenyl)-1-(2,4-dichlorophenyl)-4-ethyl-N-pyrrolidin-1-yl-1H-pyrazole-3-carboxamide (11r), which exhibited a favorable pharmacological profile with outstanding efficacy in reducing serum lipid parameters of metabolic syndrome compared to clinical references.

Atypical courses of the mandibular canal: Comparative examination of dry mandibles and x-rays

Knowledge of the course of the mandibular canal and its anatomic variations is of great importance in oral surgery, especially in preprosthetic operations and the insertion of endosteal implants and during the planning of removable dentures prepared in cases involving extensively atrophied mandibles. We review the literature on duplicated mandibular canals, which is based exclusively on radiologic findings. Then, we compare this with an examination of dry mandibles and further radiologic studies. The incidence of duplicated mandibular canals observed in macroscopic examinations of mandibles was substantially higher than that revealed by radiographs. One case involving a novel variation, a triple mandibular canal, is reported.

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.