Jan D. Raguse

Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence

BACKGROUND Increases in incidence of oropharyngeal squamous cell carcinoma (OPSCC) in countries with falling tobacco use have been attributed to a growing role of human papilloma virus (HPV) in the carcinogenesis. Trends of HPV prevalence in populations with persistently high portions of smokers are poorly characterised. PATIENTS AND METHODS Registry data from East Germany were used to determine incidence trends between 1998 and 2011. Data from patients treated at the Charité University Medicine Berlin between 2004 and 2013 (cohort 1, N=436) were used for estimation of trends in HPV prevalence, smoking and survival. HPV prevalence was prospectively confirmed in cohort 2 (N=213) comprising all primary HNSCC cases at the Charité in 2013. RESULTS Between 1998 and 2011 incidence of both OPSCC and non-OPSCC increased. An increase in HPV prevalence (% of HPV+ cases in 2004-2006 versus 2012-2013: 27% versus 59%, P=0.0004) accompanied by a moderate decrease in the portion of current smokers was observed in OPSCC but not in non-OPSCC. The change in disease epidemiology in OPSCC was associated with significant improvement in overall survival. Increased HPV prevalence in OPSCC (48%) compared to non-OPSCC (11%) was confirmed in cohort 2. CONCLUSIONS Despite clear differences to the United States in terms of tobacco use, the increase in OPSCC incidence in a European population was also mainly attributed to HPV, and the HPV status significantly affected prognosis. For clinical trial design it is important to consider the large group of smokers within HPV-induced OPSCC.

The human vomeronasal type-1 receptor family— detection of volatiles and cAMP signaling in HeLa/Olf cells

The human genome harbors 5 remnant genes coding for vomeronasal type‐1 receptors, com pared with 187 of such receptors in mice. In rodents, vomeronasal type‐1 receptors are typically expressed in the vomeronasal organ. They are believed to be highly selective and sensitive pheromone detectors, as may be inferred from one receptor, V1rb2, responding to picomolar concentrations of the mouse pheromone 2‐heptanone. Expression patterns, ligands, and signal transduction of human vomeronasal type‐1 receptors have, however, remained largely obscure. Our aim was to deorphan and functionally characterize these 5 pu tative human pheromone receptors. Here, we report functional expression for all 5 receptors in HeLa/Olf cells. The recombinant, N‐terminally tagged receptors expressed at the plasma membrane of HeLa/Olf cells and responded differentially to 19 of 140 odorants in a combinatorial way. C9–C10 aliphatic alcohols or alde hydes emerged as the best agonists at submicromolar concentrations above human odorant thresholds. Sur prisingly, and in contrast to mouse V1rb2, all human vomeronasal type‐1 receptors activated cAMP signaling via G protein αolf, when expressed in HeLa/Olf cells. While a biological function of human vomeronasal type‐1 receptors is still elusive, our data show that their major functional characteristics are similar to those of odorant receptors.—Shirokova, E., Raguse, J. D., Meyerhof, W., Krautwurst, D. The human vomeronasal type‐1 receptor family‐detection of volatiles and cAMP signaling in HeLa/Olf cells. FASEB J. 22, 1416–1425 (2008)

Regeneration of intraoral defects after tumor resection with a bioengineered human dermal replacement (Dermagraft).

&NA; The experiences of seven patients with squamous cell carcinomas of the oral cavity who underwent reconstruction with a bioengineered human dermal replacement (Dermagraft) are examined. The human dermal replacement consists of fibroblasts seeded onto a three‐dimensional polymer scaffold to create a living dermal structure. In this setting, the fibroblasts secrete a mixture of growth factors and matrix proteins in physiological concentration that is essential for wound healing and epithelization. The fibroblast tissue remains metabolically active after cryopreservation and can be used as an off‐the‐shelf tissue to cover medium‐sized defects and avoid donor‐site morbidity. In the first series of patients treated with this tissue, defect closure was achieved without functional problems, allowing optimal postoperative monitoring for tumor recurrence. (Plast. Reconstr. Surg. 109: 889, 2002.)

Drill‐related root injury caused by intraoperative intermaxillary fixation: an analysis of 1067 screw applications

BACKGROUND/AIMS Intermaxillary fixation is a standard procedure for the treatment of mandibular fractures or in orthognathic surgery. Predrilling for screws poses the risk of accidental tooth root injury, potentially leading to further pathological processes. Limited evidence about accidental tooth injury during intermaxillary fixation is available due to heterogenous study designs. The aim of this study was to evaluate the risk of root trauma using predrilled transgingival fixation screws and the clinical consequences for the affected teeth. MATERIALS AND METHODS In this retrospective study, the data of open reduction and internal fixation surgery files with intraoperative application of predrilled intermaxillary fixation screws were analysed. The postoperative radiographic images were evaluated for the occurrence of tooth root injury. Patients diagnosed with root injury were clinically followed up with respect to the dental health for the affected teeth. RESULTS A total of 133 radiologically diagnosed tooth root injuries were recorded (12.5% of screws). The median follow-up interval was 16 months (range: 3-77 months). The return rate was 49.5% for all patients. Of these, four of the injured teeth (3%) needed endodontic treatment. No toothache was reported, no tooth was lost, and no negative impact on periodontal health was clinically evident. CONCLUSION Intermaxillary fixation with predrilled transgingival screws is a safe way to manage mandibular fractures. The incidence of tooth root injury is not uncommon, but the adverse side effects are rare and the health of the affected teeth is mostly not compromised.

Expression patterns of CD168 correlate with the stage and grade of squamous cell carcinoma of head and neck

The receptor for hyaluronan-mediated motility CD168 is associated with the processes of oncogenesis and metastasis. The objective of the present study was to determine the possible association between the expression and distribution of CD168 and the tumor stage of head-and-neck squamous cell carcinoma (SCC). Formalin-fixed and paraffin-embedded tumor samples obtained from 100 patients during primary resection of SCC from the oral cavity, oropharynx, hypopharynx or larynx were included in the present study. The patients were divided into two risk groups: Low risk, representing the early stage of completely resected SCCs with good-to-moderate differentiation, and the high-risk group, representing the advanced stage SCCs with positive resection margins, vascular invasion or locoregional metastasis. All specimens were stained with a monoclonal antibody against CD168. Percentage and staining intensity of CD168-positive cells were scored, and their spatial distribution within the tumor nests was noted. The results obtained were correlated with the tumor stage. The quantification of CD168 expression revealed significant differences between the two risk groups (t-test, P=0.002), with higher scores in tumors resected from the high-risk SSC group compared with those from the low-risk group. In addition, in the high-risk group, the CD168-positive cells were present predominantly in the periphery (70.4%) of tumor nests, whereas in the low-risk group, only 56.6% were located there; however, this trend did not reach the level of statistical significance. Taken together, the results from the present study suggested that CD168 expression patterns could potentially be used as a predictor of tumor aggressiveness, and therefore they may be a prognostic factor in head-and-neck SCC.

Retrospective long-term analysis of bone level changes after horizontal alveolar crest reconstruction with autologous bone grafts harvested from the posterior region of the mandible.

Purpose The goal of this study was to evaluate the long-term success of horizontal alveolar crest augmentation of the retromolar region of the mandible with particulated bone, as well as factors affecting subsequent peri-implant bone loss. Methods A total of 109 patients (68 female, 41 male) suffering from alveolar ridge deficiencies of the maxilla and mandible were included in this study. All patients were treated with particulated retromolar bone grafts from the mandible prior to the insertion of endosseous dental implants. Mesial and distal peri-implant crestal bone changes were assessed at six time points. Several parameters, including implant survival and the influence of age, gender, localisation of the implant, diameter, covering procedures, and time points of implant placement, were analysed to identify associations with bone level changes using the Mann-Whitney U-test, the Kruskal-Wallis test, and Spearmans rank-order correlation coefficient. Results A total of 164 dental implants were placed in the maxilla (n=97) and in the mandible (n=67). The mean observation period was 105.26±21.58 months after implantation. The overall survival rate was 97.6% after 10 years. Overall, peri-implant bone loss was highest during the first year, but decreased over time. The mean amount of bone loss after 10 years was 2.47 mm mesially and 2.50 mm distally. Bone loss was significantly influenced by implant type and primary stability. Conclusions The use of particulated autologous retromolar bone grafts is a reliable technique for the horizontal reconstruction of local alveolar ridge deficiencies. Our results demonstrate that implants placed in augmented bone demonstrated similar bone level changes compared to implants inserted in non-augmented regions.

Severe tooth loss after root damage caused by predrilled intermaxillary fixation screw: a case report

Intermaxillary fixation (IMF) with screws is routinely used as a conservative therapy or to obtain normal occlusion during the surgical procedure of open reduction and internal fixation for treating mandibular fractures. The risk of iatrogenic dental damage caused by interdental drilling is widely known. Several side effects are described, including loss of response to pulp sensibility testing, root fracture, and, loss of the tooth. This is a case report about a young man who had undergone temporary IMF treatment with a single proven root damage. The patient did not appear for follow-up but he presented 5 years afterward with local purulent osteomyelitis concerning the affected and the adjacent teeth. Osteotomy and extraction of two premolars and one molar were necessary for rehabilitation. This case report illustrates the importance of careful use of predrilled IMF screws and the necessity of frequent follow-ups in cases of proven tooth root damage due to IMF treatment.

Volatile Organic Compounds in the Breath of Oral Squamous Cell Carcinoma Patients: A Pilot Study

Objective To assess the feasibility of detecting signature volatile organic compounds in the breath of patients with oral squamous cell carcinoma. Study Design Prospective cohort pilot study. Setting University hospital. Subjects and Methods Using gas chromatography and mass spectrometry, emitted volatile organic compounds in the breath of patients before and after curative surgery (n = 10) were compared with those of healthy subjects (n = 4). It was hypothesized that certain volatile organic compounds disappear after surgical therapy. A characteristic signature of these compounds for diseased patients was compiled and validated. Results Breath analyses revealed 125 volatile organic compounds in patients with oral cancer. A signature of 8 compounds that were characteristic for patients with oral cancer could be detected: 3 from this group presented were absent after surgery. Conclusion The presented results confirmed the hypothesis of an absence of cancer-associated volatile organic compounds in the breath after therapy. In this pilot study, we proved the feasibility of this test approach. Further studies should be initiated to establish protocols for usage in a clinical setting.

Possible Estrogen Dependency in the Pathogenesis of Branchial Cleft Cysts

Background Even though branchial cleft cysts are currently accepted as a congenital anomaly, there is often a long delay until clinical presentation; branchial cleft cysts classically appear in the second to fourth decade of life. Our observation of their occurrence in three pregnant women encouraged us to contemplate a possible hormonal influence. Methods Immunohistological analysis was performed for the evaluation of the estrogen receptor alpha (ERα) in paraffin-embedded tissue specimens of 16 patients with a diagnosis of branchial cleft cyst, with three of them being pregnant. Results Expression of ERα was detected within epithelial cells only in branchial cleft cysts in pregnant females; moreover, higher growth fractions (Ki-67/Mib1) were found. Conclusion The fact that the estrogen receptor was expressed only in pregnant women, in contrast to 13 investigated cases, may suggest that the high level of estrogen in pregnancy is a possible explanation for the spontaneous growth of branchial cleft cysts.

The lower trapezius island myocutaneous flap in tunnelled technique to cover complicated tissue defects located between the craniocervical and cervicothoracic junction following spinal surgery

PURPOSE Stable coverage of complicated defects located between the craniocervical and cervicothoracic junction following wound healing disturbance after spinal surgery can be challenging. Especially in cases where devices are exposed, well-vascularized coverage is required to achieve stable wound conditions. Therefore, the aim of the present study was to evaluate the clinical outcome of the lower trapezius island myocutaneous flap (LTIMF) as a possible treatment option. MATERIALS AND METHODS Four patients with a mean age of 68.8 years (ranging from 50 to 93 years) with wound healing disturbance following spinal surgery leading to defects of the dorsal neck/upper back refractory to conservative treatment and surgical debridement were included. All defects were reconstructed with a LTIMF based on the transverse cervical artery. RESULTS Mean follow-up was 16.5 months (ranging from 5 to 30 months). No major flap failure occurred; minor complications in three patients including lateral superficial skin necrosis were easily handled. In all patients, excellent functional and aesthetic results were achieved. CONCLUSION The lower trapezius island myocutaneous flap represents a reliable treatment option to cover complicated defects located between the craniocervical and cervicothoracic junction following wound disturbance after spinal surgery.