Richard Werkmeister

HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

BackgroundHypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker.Methods85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis.ResultsHIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1α expression specified a subgroup of high-risk patients (p < 0.05).ConclusionHIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy.

Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity

BackgroundIntermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCCs) of the oral cavity.Methods308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Cks), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis.ResultsThe expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCCs and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin.ConclusionThe expression of Ck 8/18 in SCCs of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCCs.

Clinical relevance of erbB-1 and -2 oncogenes in oral carcinomas

To gain a better understanding of molecular changes in oral squamous cell carcinomas, we tested fresh tumour specimens from 110 patients for erbB-1 and -2 oncogene aberrations using the competitive differential polymerase chain reaction. The significance of established tumour characteristics such as TNM stage, differentiation and oncogene aberrations for tumour progression were analyzed. ErbB-2 amplification with a gene copy number > 1.6 in tumour tissue and erbB-1 deletion with a gene copy number < 0.4 in tumour-surrounding mucosa are of clinical relevance and indicate an early tumour recurrence or metastasis (p < 0.05). In T1/T2 tumours an erbB-2 gene dosage study allows differentiation between tumours with high or low risk for early progression. In a multivariate statistical analysis T stage (p < 0.01) and erbB-2 amplification in tumour material (p < 0.05) were independent prognostic variables.

Rehabilitation with dental implants of oral cancer patients.

The aim of this study was to evaluate the risks and complications of rehabilitation with dental implants after tumour surgery and radiotherapy. After a disease-free survival of 18 months, 29 patients who had undergone oral cancer treatment were rehabilitated with dental implants. The complication rate of implants in irradiated, non-irradiated and grafted bone was analyzed at least 3 years after implant placement. In the healing period, 28.6% of the implants in irradiated bone and 8.4% in non-irradiated bone showed soft tissue complications. Of the implants, 26.7% in the irradiated and 14.7% in the non-irradiated mandibular bone were lost in the first 36 months after placement. Thirty-one point two percent of implants inserted in non-irradiated bone grafts were affected and did not osseointegrate. Of 109 inserted implants, 70 were suitable for prosthetic rehabilitation. There are high complication rates after implant placement in oral cancer patients. Irradiation adversely affects soft tissue healing. Osseointegration is frequently disturbed, especially when implants were placed in non-vascularized bone grafts.

The erbB oncogenes as prognostic markers in oral squamous cell carcinomas

BACKGROUND In clinical practice it became clear that conventional prognostic parameters of oral squamous cell carcinomas (OSCC) are of limited value for the prediction of a disease-free survival. The overexpression of erbB oncogenes is of importance for the clinical course of a variety of solid tumors. After discovering amplifications of erbB oncogenes even in OSCC, it was the aim of the present study to clarify the potential of oncogenes as additional prognostic markers. MATERIALS AND METHODS The amplification of the erbB oncogenes in tumorous tissue of 85 OSCC patients was determined using the double-differential polymerase chain reaction. Histologically healthy mucosa in these patients was also studied. In univariate analysis the amplification of erbB oncogenes with clinical and histopathological prognostic parameters was compared. RESULTS No significant correlation between common prognostic parameters and erbB-2 amplification was found. Patients whose OSCC tissue showed an average gene copy number for erbB-2 of greater than 1.2, for erbB-3 below 0.11, and a ratio of erbB-1 and erbB-2 below 0.31 had a statistically significant decrease in disease-free survival. Even in histologically healthy oral mucosa from tumor patients an amplification of erbB oncogenes was found. CONCLUSIONS ErbB oncogene amplifications in oral squamous cell carcinomas play a significant role as a prognostic factor and seem to be effective in predicting decrease in disease-free survival. Genetic abnormalities in tumor-surrounding tissue support the field cancerization hypothesis.

Operative Verfahren der Mund-, Kiefer- und Gesichtschirurgie an nach Thiel fixierten Körperspenden

Ergebnisse: Die Eignung von nach Thiel fixierten Körperspenden als Modelle für Forschung und Lehre in der Mund-Kiefer-Gesichts-Chirurgie wurde untersucht. An Thiel-fixierten Körperspenden wurden verschiedene operative Zugangswege durchgeführt und die Verwendbarkeit der Präparate von Anatomen und Operateuren beurteilt. Diskussion: Es zeigte sich eine hohe Realitätsnähe in Farbe, Struktur und Konsistenz. Das verwendete Konservierungsverfahren eignet sich in besonderer Weise als Voraussetzung für Forschung und die ärztliche Aus-, Fort- und Weiterbildung. Methods: This study investigates whether human cadavers embalmed according to Thiel can be used for research and education in oral-maxillo-facial surgery. Different surgical approaches were tested on such cadavers. The usability of the specimen was judged jointly by anatomists and surgeons. Color, structure, and consistency of the different tissues were comparable to vital conditions. Thiel’s embalming technique applied to human cadavers provides an optimal basis for research and for basic and postgraduate medical education.METHODS This study investigates whether human cadavers embalmed according to Thiel can be used for research and education in oral-maxillo-facial surgery. Different surgical approaches were tested on such cadavers. The usability of the specimen was judged jointly by anatomists and surgeons. Color, structure, and consistency of the different tissues were comparable to vital conditions. Thiels embalming technique applied to human cadavers provides an optimal basis for research and for basic and postgraduate medical education.

Perioperative complications in infant cleft repair

BackgroundCleft surgery in infants includes special risks due to the kind of the malformation. These risks can be attributed in part to the age and the weight of the patient. Whereas a lot of studies investigated the long-term facial outcome of cleft surgery depending on the age at operation, less is known about the complications arising during a cleft surgery in early infancy.MethodsWe investigated the incidence and severity of perioperative complications in 174 infants undergoing primary cleft surgery. The severity and the complications were recorded during the intraoperative and the early postoperative period according to the classification by Cohen.ResultsOur study revealed that minor complications occurred in 50 patients. Severe complications were observed during 13 operations. There was no fatal complication in the perioperative period. The risk of complications was found to be directly correlated to the body weight at the time of the surgery. Most of the problems appeared intraoperatively, but they were also followed by complications immediately after the extubation.ConclusionIn conclusion, cleft surgery in infancy is accompanied by frequent and sometimes severe perioperative complications that may be attributed to this special surgical field.

Regeneration der Mundschleimhaut im Planum buccale nach Entnahme zur Rekonstruktion von bulbären Urethrastenosen

Bei der operativen Behandlung der zumeist traumatisch bedingten bulbären Urethrastrikturen des Manns werden zunehmend Mundschleimhauttransplantate verwandt. In den Jahren 1996 und 1997 haben wir bei 12 Patienten mit langstreckigen Urethrastenosen Mundschleimhauttransplantate von bis zu 7 cm Länge und 4 cm Breite aus dem Planum buccale entnommen. Bei 2 Patienten wurde die Entnahmestelle primär verschlossen, bei jeweils 4 Patienten erfolgte die temporäre Defektdeckung mit Lyodura oder Syspurderm und bei 2 Patienten wurden die großen Schleimhautdefekte mit Ethisorp überbrückt. Die Schmerzhaftigkeit im Entnahmebezirk wurde während der ersten postoperativen Woche von den Patienten auf einer Analogskala von 1–10 beurteilt. 10 der 12 Patienten gaben geringe bis mittelgradige Schmerzen im Entnahmegebiet an. Bei den 2 Patienten, deren Entnahmestelle mit Ethisorp gedeckt wurde, lag eine stärkere Schmerzhaftigkeit vor, was in der Rigidität des Materials begründet liegen kann. Alle Patienten zeigten eine gute Schleimhautregeneration im Bereich der Entnahmestelle unabhängig vom verwendeten Material. Während der 4- bis 18monatigen Nachuntersuchungszeit wurde als einzige Komplikation eine Narbenstrangbildung zum Unterkiefervestibulum festgestellt. Mundöffnungsbehinderungen, Speichelabflußstörungen und persistierende Hypästhesien des N. mentalis und N. buccalis wurden nicht beobachtet. The use of free buccal mucosal grafts in the treatment of urethral strictures has become very popular. In 1996 and 1997 we harvested free buccal mucosal grafts up to 7 cm long and 4 cm wide from 12 patients who underwent urologic surgery for urethral strictures. In 2 patients the donor site was closed primarily by sutures. Four patients received Lyodura and another 4 patients received Syspurderm as temporary wound coverage. In 2 patients Ethisorp patches were used. Donor site pain was judged by the patients on a visual analogue scale during the first postoperative week. The 2 patients who received the Ethisorp patches complained of more intense pain, probably caused by the rigidity of the material. In all patients regeneration of the donor site mucosa was good. During the follow-up period of 4–18 months scar formation at the lower vestibulum was noticed as the only complication. Permanent limitation of mouth opening, stenosis of the parotid duct or hypesthesia did not occur.

Current concepts in cleft care: A multicenter analysis

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery.