Martin Kunkel

Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma.

The overexpression of glucose transporters, especially of Glut‐1, is a common characteristic of human malignancies, including head and neck carcinoma. Recently, the assessment of glucose metabolism in the tumor with [18F]‐2‐fluoro‐2 deoxy‐D‐glucose (FDG) and positron emission tomography (FDG‐PET) has been used to identify particularly aggressive tumors. The authors tested the hypothesis that both glucose transport and its metabolism play a key role in the progression of oral squamous cell carcinoma (OSCC).

Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome

Purpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells. Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-γ inducible proteasome subunits and of the peptide transporter TAP with that of HLA class I antigens in biopsies and cell lines from primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA class I antigen expression in surgically removed lesions were correlated with the course of the disease in order to assess the clinical significance of deficient expression of these molecules. Results: A high frequency of LMP2, LMP7, and TAP1 down-regulation or loss was found in tumor lesions and cell lines obtained from HNSCC cancer patients. These defects could be corrected by incubating cells with IFN-γ. Furthermore, LMP2, LMP7, TAP1, TAP2, and HLA class I antigen expression rates in primary HNSCC lesions were found to predict overall survival. Lastly, the level of LMP7 expression was significantly associated with disease recurrence at 2 years. Conclusions: Our results suggest that the analysis of APM component expression in HNSCC lesions can provide useful prognostic information in patients with HNSCC.

Actinomycosis of the jaws—histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis

Actinomycosis of the jaws is a rare disease, which has been recently described in patients with infected osteoradionecrosis (IORN) and bisphosphonate-associated osteonecrosis (BON). We investigated our archive material for Actinomycosis of the jaws with special regard to underlying disease. Out of a total number of 45 patients with Actinomycosis, 43 (93.5%) suffered from BON (58.7%) or IORN (35.6%), while there were only 3 patients (6.7%) without anti-tumor treatment. In all cases, we found direct association of Actinomyces colonies with bone; in the surrounding medullary space, mixed inflammatory infiltrates with variable amounts of osteoclasts were a typical finding. Pseudoepitheliomatous hyperplasia occurred in 60.9% of patients. Cell-rich vessel obliteration was seen in less than 25.9% of BON patients, while hyalinized vessel obliteration was obtained in 37.5% of IORN patients. Additionally performed polymerase chain reaction (PCR) on paraffin-embedded and ethylene diamine tetracetic acid (EDTA)-decalcified tissue specimens confirmed the presence of Actinomyces israelii in seven of seven cases analyzed. We conclude that Actinomycosis of the jaws is a particular complication in patients with BON and/or IORN. Patients with Actinomycosis of the jaws during or after these forms of anti-cancer therapy are suggested to represent a distinct patient cohort with a relevant impairment of their general condition.

Detection of recurrent oral squamous cell carcinoma by [18F]-2-fluorodeoxyglucose-positron emission tomography: Implications for prognosis and patient management

Patients with recurrent oral squamous cell carcinoma (OSCC) have a dismal prognosis and represent a therapeutic challenge. A positron emission tomography (PET) scan with [18F]‐2‐fluorodeoxyglucose ([18F]FDG) can improve early cancer detection. The current study evaluates the prognostic value of [18F]FDG‐PET scan in patients with recurrent OSCC.

Surgically assisted rapid palatal expansion. An acoustic rhinometric, morphometric and sonographic investigation.

This study aimed to evaluate the effect of surgically assisted rapid palatal expansion on the skeletal structures of the midface.Ten patients (mean age 28.5 years) were investigated by means of acoustic rhinometry, study model analysis and sonography before and after the procedure of surgically assisted rapid palatal expansion.The measurements revealed that surgically assisted rapid palatal expansion not only resulted in transverse expansion of the maxilla, providing dental arch space for lining up the teeth; the procedure also caused a substantial enlargement of the maxillary apical base and of the palatal vault, providing space for the tongue for correct swallowing and thus preventing relaps. There was a distinct subjective improvement in nasal breathing associated with enlargement of the nasal valve towards normal values and with an increase of nasal volume in all compartments.The measurements showed a marked influence of surgically assisted rapid palatal expansion on the skeletal structures of the midface. The significant widening can be demonstrated by non-invasive examination. Success of the osteotomy procedure can be readily monitored by sonographic examination of the expansion and the subsequent ossification, which allows individually adjusted retention periods and avoids frequent radiation exposure.ZusammenfassungIn der vorliegenden Untersuchung sollten die Auswirkungen der chirurgisch unterstützten Gaumennahterweiterung auf dentoalveoläre, maxillär-basale und nasale Strukturen des Gesichtsschädels mit nicht invasiven Untersuchungstechniken evaluiert werden.Dazu wurden zehn erwachsene Patienten vor und nach chirurgisch unterstützter Gaumennahterweiterung mittels reflexionsakustischer Rhinometrie, Modellanalyse und Sonographie untersucht.Es zeigte sich, dass die chirurgisch unterstützte Gaumennahterweiterung auch beim erwachsenen Patienten nicht nur zu einer transversalen dentoalveolären Dehnung des Oberkiefers (Platz im Zahnbogen zur Ausrichtung der Zähne) führt, sondern auch die apikale Oberkieferbasis und das Gaumenvolumen (Platz für die Zunge beim regelrechten Schlucken und damit Rezidivprophylaxe) werden entscheidend vergrößert. Die chirurgische Gaumennahterweiterung führt darüber hinaus zu einer deutlichen Vergrößerung von Nasenvolumen und Nasenklappe mit auch subjektiver Verbesserung der Nasenatmung. Sonographisch waren die Segmentbewegung im Laufe der Dehnung ebenso nachweisbar wie die spätere Reossifizierung und vollständige Rekortikalisierung.Die Messungen belegen einen ausgeprägten Einfluss der chirurgisch unterstützten Gaumennahterweiterung auf die skelettalen Strukturen des Mittelgesichtes, deren deutliche Weitung durch nicht invasive Untersuchungsverfahren nachweisbar ist. Die sonographische Untersuchung kann den Fortschritt der transversalen Dehnung objektivieren und erlaubt eine individuelle Anpassung der Retentionszeit ohne zusätzliche Strahlenexposition.

Diagnosis of oral squamous cell carcinoma and its precursor lesions

Improvement of survival rate and quality of life after treatment of oral squamous cell carcinoma as well as cost reduction requires reliable early diagnosis of the tumor and its precursor lesions. Four different screening methods are primarily employed: toluidine blue staining (visually detected lesions: sensitivity 70–100%, specificity 25–67%), photodynamic diagnosis (sensitivity 94–99%, specificity 60–89%), autofluorescence (no data published so far) and modern oral cytology (sensitivity 80%,specificity 95–100%).Additional analytic procedures such automated image analysis, DNA image cytometry and immunocytochemistry can be used to enhance the low sensitivity of conventional oral cytology.While these methods have achieved sensitivity and specificity approaching 100%, the studies involved clearly‐defined entities such as large oral squamous cell carcinomas and aphthae. The modern and methodenhanced oral cytology is a simple, value‐based and inexpensive tool for early diagnosis of oral squamous cell carcinoma and its precursor lesions. Surgical biopsy and histopathological examination remains the gold standard for definitive diagnosis.

Quantifying Radioxerostomia: Salivary Flow Rate, Examiner’s Score, and Quality of Life Questionnaire

Background and Purpose:Salivary flow rates alone are not sufficient to quantify all aspects of radioxerostomia. This is a problem in studies aiming to reduce radioxerostomia. The aim of this study was to evaluate the association between objectively measured salivary flow rate and subjective xerostomia ratings by the physician (RTOG scale) or the patients (quality of life [QoL] questionnaire).Patients and Methods:In a case-control study patients who underwent recall for oral cancer were screened. Inclusion criteria for this diagnostic, noninterventional study were: history of oral carcinoma, surgical and radiation therapy, time interval from start of radiation therapy > 90 days, salivary glands within the radiation field. The control group consisted of patients, who had not received radiotherapy. RTOG salivary gland score, quality of life (EORTC QLQ-C30 and H&N35), and sialometry were recorded.Results:Patients with RTOG score 0 had mean salivary flow rates of 0.3 ml/min, those with RTOG 1 0.12 ml/min, RTOG 2 0.02 ml/min, and RTOG 3 < 0.01 ml/min. RTOG score 4 (total fibrosis) did not occur. Based on salivary flow rates, all patients were grouped into xerostomia < 0.2 ml/min (30 patients) and nonxerostomia (twelve patients). QoL results revealed significant differences between patients with xerostomia and nonxerostomia for physical function, dyspnea, swallowing, social eating, dry mouth, nutritional support, and a tendency to higher values for appetite loss.Conclusion:The correlation between “subjective” QoL parameters and salivary flow was confirmed. The different subjective aspects of radioxerostomia seem to be better differentiated by the EORTC QoL questionnaire.Hintergrund und Ziel:Die Speichelfließrate allein reicht nicht aus, um alle Aspekte der Radioxerostomie zu erfassen. Dies stellt ein Problem für Studien dar, die auf die Reduktion der Radioxerostomie abzielen. Ziel dieser Studie war die Evaluation der Zusammenhänge zwischen objektiv gemessener Speichelfließrate und subjektiven Xerostomiebewertungen durch den Untersucher (RTOG-Score) oder den Patienten (Lebensqualitätsfragebogen).Patienten und Methodik:In einer Fall-Kontroll-Studie wurden Patienten im Rahmen des onkologischen Recalls untersucht. Einschlusskriterien für diese nichtinterventionelle, diagnostische Studie waren: chirurgische und Strahlentherapie nach Oropharynxkarzinom, Zeit nach Beginn der Strahlentherapie > 90 Tage, Speicheldrüsen im Strahlenfeld. Die Kontrollgruppe bestand aus Patienten ohne Strahlentherapie. Der RTOG-Speicheldrüsenscore, Lebensqualität (EORTC QLQ-C30 und H&N35) und Sialometrie wurden erfasst.Ergebnisse:Patienten mit RTOG 0 wiesen eine mediane Speichelfließrate von 0,3 ml/min auf, mit RTOG 1 0,12 ml/min, RTOG 2 0,02 ml/min und RTOG 3 < 0,01 ml/min. RTOG 4 (vollständige Fibrose) kam nicht vor. Basierend auf der Speichelfließrate wurden alle Patienten in die Gruppen „Xerostomie“ < 0,2 ml/min (30 Patienten) und „Nichtxerostomie“ (zwölf Patienten) eingeteilt. Die Ergebnisse der Lebensqualität erbrachten signifikante Unterschiede für diese beiden Gruppen für folgende Dimensionen: „physische Funktion“, Dyspnoe, Schlucken, Essen in Gesellschaft, trockener Mund, Zusatznahrung und eine Tendenz für höhere Werte bei Appetitverlust.Schlussfolgerung:Die Korrelation zwischen „subjektiven“ Lebensqualitätsparametern und der Speichelfließrate konnte bestätigt werden. Die verschiedenen subjektiven Aspekte der Xerostomie scheinen mit dem EORTC-Fragebogen deutlicher differenzier- und quantifizierbar.

Success rate of second-generation palatal implants.

OBJECTIVE To analyze the clinical outcome of a prospective two-center study of second-generation palatal implants 6 months after functional loading. MATERIAL AND METHODS From 2005 to 2006, 30 patients aged 12 to 41 years were included in the study. In all patients, orthodontic treatment required stationary anchorage. The palatal implants (Straumann, Basel, Switzerland) were placed in the median region of the anterior palate. RESULTS All implants were initially stable at the time of placement. However, two (6.7%) were lost during the unloaded healing period. The remaining 28 (93.3%) were subjected to functional loading after a mean healing period of 12 weeks. Typical signs of slight superficial inflammation were observed in the peri-implant mucosa (n = 28). During the orthodontic loading phase, the implants were equipped with either a modified pendulum appliance for distalization or a transpalatal arch for stationary anchorage to the posterior teeth. No implant loosening or loss was registered during the active treatment period. CONCLUSIONS The failure rate of palatal implants of the second generation was low (6.7%). Slight inflammatory reactions of peri-implant tissue caused neither implant loss nor pain.

Maintenance of marginal bone support and soft tissue esthetics at immediately provisionalized OsseoSpeed™ implants placed into extraction sites: 2‐year results

BACKGROUND Placement of implants into extraction sockets targets the maintenance of peri-implant hard and soft tissue structures and the support of a natural and esthetic contour. The main advantages of immediate implant insertion in comparison with delayed implant placement protocols are as follows: a reduced treatment time, less number of sessions, and, thus, the less invasive procedure. This study examines the clinical performance (survival rate, marginal bone levels and Pink Esthetic Score [PES]) of OsseoSpeed implants placed into extraction sockets with immediate provisionalization in the anterior maxilla after a follow-up of at least 12 months. METHODS Twenty patients received a total number of 37 OsseoSpeed implants which were immediately inserted into extraction sockets with or without facial bone deficiencies of various dimensions. A flapless procedure was applied, and the implants were immediately provisionalized with temporary crowns without occlusal contacts. Facial gaps between implant surface and facial bone or the previous contour of the alveolar process were grafted with autogenous bone chips. Implants in diameters 3.5, 4.0, 4.5, and 5.0 with lengths of 11-17 mm were used in the study. During the course of the study, interproximal marginal bone levels, the thickness of the facial bony wall, implant success rate according to the criteria established by Buser, and the PES were assessed per implant. RESULTS One patient with three implants did not continue the study after prosthesis delivery, the remaining 34 implants were still in function at the final follow-up (survival rate: 100%). The mean follow-up period was 27 months (range, 12-40 months). Marginal bone height at the level of the implant shoulder averaged -0.1 ± 0.55 mm (range, -1.25 to 1.47 mm) at the final follow-up. The mean PES ratings were 11.3 ± 1.8 (range, 6-14) at the final follow-up. In 78% of the patients, the PES was preserved or even improved. CONCLUSIONS Success rates, marginal bone levels, and esthetic results suggest proof of principle for the preservation of marginal bone height at immediately placed and provisionalized OsseoSpeed implants after a follow-up of at least 12 months. Even implant sites with facial bony deficiencies can be successfully treated with a favorable esthetic outcome using the immediate implant insertion, immediate reconstruction, and immediate provisionalization technique.

Metabolic and proteomic differentials in head and neck squamous cell carcinomas and normal gingival tissue

PurposeA high lactate content in malignant head and neck cancer (Head and neck squamous cell carcinomas, HNSCC) is associated with a higher risk of metastatic spread and lower overall patient survival. However, until present, the underlying mechanisms are not clearly understood. Here, a systematic comparison of glucose metabolism in HNSCC and homologous normal tissue is presented for the first time.MethodsThe concentrations of glucose, lactate and ATP were measured in cryobiopsies of 29 human HNSCC and of 9 normal mucosa using bioluminescence imaging. The protein expression of lactate dehydrogenase (LDH) was analyzed by Western blotting.ResultsTumors own a higher content of lactate and LDH in comparison with normal tissues. However, within the tumor group, the grade of LDH expression shows substantially strong variation and overlap with normal values. Furthermore, LDH expression was not correlated with tumor lactate content. Investigating a small subpopulation, patients with a short-term survival had significantly higher tumor lactate levels compared to patients with long-term survival.ConclusionsThe data provide clear evidence of an enhanced glycolysis in tumors compared to normal tissue. This may partially but not completely attributable to an elevated expression of LDH. High tumor lactate levels may be predictive for restricted patient survival. In conclusion, lactate measurements, for example non-invasively with MRT, should be advanced for use in clinical routine as a supportive tool for tumor diagnosis and prognosis.