Proliferative activity and loss of function of tumour suppressor genes as 'biomarkers' in diagnosis and prognosis of benign and preneoplastic oral lesions and oral squamous cell carcinoma.

Oral cancer is a disease of the elderly and is closely connected with cigarette smoking and alcohol consumption. Since the successful introduction of multidisciplinary treatment, the survival rate has not changed. Because of the high mortality and potentially disfiguring treatment, today's efforts are aimed at eliminating risk factors, chemoprophylaxis, improvement in diagnostic procedures, and understanding of the genetic mechanisms of oral carcinogenesis. Immunohistochemical and molecular biology analysis of biopsy tissue and cell lines of preneoplastic and neoplastic lesions that originate from the oral mucosa have shown that alterations in tumour suppressor genes such as p53 and Rb gene may have an important role in oral carcinogenesis and may be potentially useful prognostic 'biomarkers' in oral carcinogenesis. Statistical analysis of immunohistochemical data from 216 patients did not identify significant or consistent differences of p53, MDM2, or RB expression with respect to stage of disease, malignant transformation, metastatic node involvement, recurrence, or survival. Nevertheless, p53 overexpression seems to correlate strongly with histological progression of the disease, which confirms the importance of p53 alterations in oral carcinogenesis. Overexpression of p53 is usually found in the less differentiated proliferating cells in benign and malignant oral lesions. Assessment of the proliferating activity is possible by immunohistochemical staining with monoclonal antibodies against proliferating nuclear antigen and Ki-67. Statistical analysis shows that overexpression of p53 combined with high proliferative activity predicts a less favourable course of disease in oral squamous cell carcinoma.

[p53 as a biomarker in radiotherapy of carcinoma of the mouth cavity]. / p53 als Biomarker in der Radiotherapie der Mundhöhlenkarzinome.

Multimodal therapy of oral squamous cell carcinomas today is based on surgery, radiotherapy and chemotherapy. Despite the combination of all three therapeutic options, there is still a large number of treatment failures and therefore major questions remain. Recent investigations suggest that mutations of the p53 tumor suppressor gene may account for some of the therapeutic failures. Inactivation of the gene may be an important determinant of the efficacy of today's multimodal therapy protocols. In 90 patients with squamous cell carcinomas of the oral cavity biopsy specimens were taken before and after preoperative radiochemotherapy. From all patients, biopsy and resection material was available for immunohistochemical analysis of p53. After radiation treatment, 51 patients (57%) showed a complete response; 39 patients (43%) only showed a partial response or did not respond at all. Among the responders, 82% of the pretherapeutic tumors were p53 positive, whereas among the nonresponders only 56% of the pretherapeutic tumors were p53 positive. The majority of the residual tumors were also p53 negative according to immunohistology after radiation treatment. In our study, detection of p53 protein by immunohistochemistry seemed to be connected with a more radiosensitive reaction of the tumors. Nevertheless, successful strategies for radiation therapy may need to take into account the tissue of origin and the status of p53 in the tumor.

[Use of condyle positioning plate in sagittal split ramus osteotomy of mandible].

17 patients underwent an orthognathic operation. The condyle positioning plate was used in each sagittal split ramus osteotomy of mandible in order to maintain the condyle position. The results of postoperative X-ray examination showed that no obvious displacement of condyle in posterioranterior, and vertical dimension was detected in all joints and obvious horizontal condyle displacement were only found in two joints. Based on this work the author believe that condyle positioning plate is useful to position condyle during operation.

[Functional stability of Champy miniplate osteosynthesis in mandibular angle fractures]. / Die Funktionsstabilität der Miniplattenosteosynthese nach Champy bei Kieferwinkelfrakturen.

This paper presents the results of the treatment of fractures of the mandibular angle using miniplate osteosynthesis. From 1984 to 1993 347 patients with 358 fractures were operated in the department of Maxillofacial Surgery at the University of Cologne. In all cases total bone healing could be observed while complications were rare.

[Miniplate osteosynthesis of mandibular fracture in local anesthesia--indications and outcome in 316 patients]. / Miniplattenosteosynthese der Unterkieferfraktur in Lokalanästhesie--Indikation und Ergebnisse bei 316 Patienten.

In an retrospective analysis of 316 patients with mandibular fractures treated between 1984 and 1993 at the maxillo-facial surgery of university of Cologne could be shown that the application of miniplate in local anesthesia causes no more complication than in general anesthesia. We would therefore recommend this technique for not to complicated cases of isolated or double fractures of the mandible. In cases of obstacles to general anesthesia it may be favoured even in severe cases.

[Lingual osteotomy--a little regarded technique for removal of the displaced mandibular wisdom tooth]. / Die linguale Osteotomie--eine wenig beachtete Technik zur Entfernung des verlagerten Unterkieferweisheitszahnes.

Between 1980 and 1982, 769 wisdom teeth of the lower jaw were removed from 410 patients. The lingual bone splitting technique was used 813 times and vestibular osteotomy 586 times. Statistics concerning intra- and postoperative complications using both methods were gathered and compared. Hypoeasthesia resulting to permanent damage was observed once in the area of the N. lingualis and three times in the area of the N. alveolaris inferior. These results were similar to those obtained by English-speaking authors and indicate the suitability of the lingual bone splitting technique as an alternative to the vestibular approach. The indication for lingual bone splitting osteotomy in our sample was above all the horizontal and vertical impacted wisdom tooth. The decision to use lingual osteotomy should follow radiographic and clinical assessment of the relation between crown and lingual corticalis. This technically and anatomically convincing approach can be unconditionally recommended to the experienced surgeon as a time-saving alternative.

[Dento-alveolar surgery of the irradiated jaw: is infected osteoradionecrosis a preventable complication?]. / Dentoalveoläre Chirurgie im bestrahlten Kiefer: ist die infizierte Radioosteonekrose eine vermeidbare Komplikation?

In spite of preventive procedures before, during and after radiotherapy, profound caries and periodontal breakdown of healthy teeth occur. In the course of dentoalveolar surgery in the region of irradiated bone, the risk of development of an infected osteoradionecrosis can be reduced by prophylactic antibodies, prevention of extensive detaching of the periosteum careful osteotomy or extraction, complete smoothing of sharp alveolar ridges and epiperiosteal plastic coverage. When extensive dentoalveolar surgery is necessary, the application of prophylactic pre- and postoperative hyperbaric oxygen may reduce the rate of complications even more.

Use of superoxide dismutase (SOD) in patients with temporomandibular joint dysfunction--a preliminary study.

The aim of this preliminary study was to investigate and assess the effect of intra-articular injection of superoxide dismutase (SOD) in patients with temporomandibular joint (TMJ) dysfunction who had not responded to conservative therapy in a first study. Thirty joints in 29 patients were studied. The results showed that intra-articular injection of superoxide dismutase was effective in 25 joints (83%). It was concluded that intra-articular injection of superoxide dismutase may be an alternative therapy for patients with TMJ dysfunction who fail to respond to conservative treatment.

p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa.

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. The purpose of this study was, therefore, to determine the role of alterations of the tumour suppressor gene p53, and the proliferation status of the lesions determined by PCNA expression. We investigated p53 and PCNA expression in 265 tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oral mucosa by immunohistology. Quantitative analysis showed a gradual increase in PCNA expression from normal mucosa to moderately differentiated SCC. p53 expression was detectable in benign premalignant lesions. The increase in the number of p53-positive biopsies was correlated with the dysplasia and loss of differentiation in the premalignant and malignant lesions.

p53 and Ki 67 expression in preneoplastic and neoplastic lesions of the oral mucosa.

Some lesions of the oral mucosa such as leukoplakia and erythroplakia may develop into squamous cell carcinoma (SCC). At present, however, there is no method available to predict malignant transformation. It is known that the grade of dysplasia is related to the potential malignant development, but this is unreliable as the only indicator. In 64 hyperplastic lesions and 85 SCC of the oral mucosa, a correlation between the expression of the mutated tumor-suppressor gene p53 and the dysplasia of the lesions was found. Ki 67 was used as a proliferation marker. The results imply that expression of mutated p53 is an indicator for potential malignant development in benign lesions of the oral mucosa.

Teeth in the fracture line.

The department of maxillo-facial surgery in Cologne University has, for some 15 years, routinely treated patients with mandibular fractures, in which a tooth lies in the fracture line, by means of Champy miniplates. A review of such cases was conducted to determine the viability of such teeth not electively extracted at the time of fracture reduction. It was found that only rarely did the "salvaged" tooth subsequently require extraction and we believe our results should encourage the clinician to attempt to retain "fracture line" teeth unless there is an absolute contraindication.

[Comparative experimental studies on reconstructive miniplates]. / Vergleichende experimentelle Untersuchungen von Minirekonstruktionsplatten.

In an experimental study reconstructive miniplates consisting of 1.0 mm thick stainless steel and 1.27 mm thick pure titanium were comparatively examined. Plate stress trials showed better results for stainless steel in tension, and at the same time better results for titanium plates in bending trials over the edge and the plane. In lever trials of second order titanium plates showed equal or better results when used for reconstructing lower jaw specimens and plastic models. Our experimental results lead to the conclusion, that the plates tested can guarantee exercise stability of lower jaw reconstructions during the primary healing phase. Considering their more favorable E-modulus and better biocompatibility the new titanium miniplates with the dimensions mentioned are superior the stainless steel miniplates in the fixation of lower jaw grafts.

[Densitometry of the bony structures of the human TMJ]. / Densitometrische Untersuchungen der knöchernen Strukturen des menschlichen Kiefergelenkes.

Four millimeter sagittal section of 65 formalin-fixed human TMJs were prepared. The X-rays of these specimen were evaluated numerically in a densitometer. The distribution of bone material and densities in condyle and fossa led to a classification of condylar and fossa types. In 48 specimen a combination of increased density of the condyle on the facial aspect with a thin bony lamella in the roof of the fossa, which either shows high density or very little material of low density, a so-called parchment fossa, was observed. The varying degrees of density as a function of mechanical stresses are discussed. The transfer of forces in the human TMJ during mastication exposes the superio-anterior or superio-facial segments of the condyle and the posterior slope of the articular tubercle to loading forces, while at the same time the roof of the fossa remains free of load.

[Is resection still a timely procedure in the treatment of keratocysts?]. / Ist die Kieferresektion bei der Behandlung der Keratozysten noch zeitgemäss?

Between 1977 and 1987 a total of 31 patients with keratocysts were treated at the maxillofacial surgery department of the University of Cologne. In two patient groups with 11 major mandibular cysts each, two different approaches were used: mandibular resection in one, and enucleation following previous fixation of the cyst epithelium with Carnoy's solution in the other group. The fact that only one recurrence was observed in the second group, gives us reason to recommend this safe and, for the patient, unstressful procedure.