Perioperative Management in Patients With Undergoing Direct Oral Anticoagulant Therapy in Oral Surgery - A Multicentric Questionnaire Survey.

AIM: The purpose of this study was to survey the current opinions of hospitals and medical practices concerning the perioperative management of patients undergoing direct oral anticoagulant therapy (DOAC) and discuss recommendations for the clinical practice. MATERIALS AND METHODS: A questionnaire with 13 topics and multiple ordinal-polytomous subitems was designed and sent to 120 Departments of Oral and Maxillofacial Surgery in Austria, Switzerland and Germany, as well as to 85 oral and maxillofacial/oral surgeons in medical offices in Hamburg, Germany. The data were statistically evaluated by Chi-square, Fisher's exact and Jonckheere-Terpstra tests. RESULTS: The rate of response was 42%. Thirty-seven percent of respondents reported treating over 50 patients per year with undergoing DOAC therapy and only 18% assess a high bleeding risk [33% for vitamin K antagonists (VKA)]. In contrast to that, 62% of respondents would interrupt the DOAC therapy for extraction of one tooth, while 94% would continue VKA therapy. Significantly more clinicians apply suture than those in a medical office. The use of additional hemostatic measures varied between clinic and medical practice. There was a clear request for more detailed guidelines. CONCLUSION: The study shows the current opinion for perioperative management of patients undergoing DOAC therapy. Multi-centric studies under controlled conditions are needed for a safer treatment of anticoagulated patients as therapy strategies differ greatly between institutions and therefore a complication analysis is hardly possible.

Repair of Occipital Bone Defects in Neurofibromatosis Type 1 by Means of CAD/CAM Prefabricated Titanium Plates.

Certain skeletal defects may develop in neurofibromatosis type 1 (NF1), a common tumor-suppressor syndrome, such as cranial lesions confined to the lambdoid suture region. Here, we report on the repair of osseous defects of occipital bone in a NF1 patient with history of skull trauma and tumorous hemorrhage. Computer-aided design and computer-aided manufacturing (CAD/CAM)-assisted devices were applied to safely close the bone defects. The variable phenotype of NF1 in the occipital skull region is discussed and a brief review is presented on NF1-related therapies for tumors and malformations of the occipitoparietal skull region.

Evaluation of Periodontal Space Widening in Patients with Antiresorptive Drug-related Osteonecrosis of the Jaws (ARONJ) on Panoramic Radiographs.

BACKGROUND/AIM: The purpose of this study was to evaluate a potential widening of the periodontal space as an initial measurable imaging criterium on panoramic radiographs in patients with the diagnosis of antiresorptive drug related osteonecrosis of the jaw (ARONJ). PATIENTS AND METHODS: A retrospective analysis of panoramic radiographs of 16 patients (12 females and 4 males; mean age is 70.5 years, standard deviation is 14 years) was performed, over a period of 12 months with the diagnosis of ARONJ. Panoramic radiographs of 16 healthy patients (12 females and 4 males; mean age was 70.6 years, standard deviation was 13.8 years) without diagnosis of ARONJ served as controls. All images were taken with the same device and were evaluated by two experienced maxillofacial surgeons and one dentist. RESULTS: Compared to the control group, a mean widening of the periodontal space of 0.06 mm (confidence interval (CI)=0.05-0.17 mm) was found in the study group. However, this difference was not statistically significant. CONCLUSION: Although a very extensive and sophisticated interindividual comparison was performed to evaluate for slight changes of the periodontal space in patients with antiresorptive drug therapy, our results demonstrate that PDS widening is not a predictive parameter for ARONJ. Therefore, our results indicate that panoramic radiographs are not sufficient enough to allow assessment of stages and disease progress in ARONJ patients regarding to periodontal space widening.

Sensitivity and specificity of sentinel lymph node biopsy in patients with oral squamous cell carcinomas using indocyanine green fluorescence imaging.

PURPOSE: The purpose of this clinical study was to evaluate the sensitivity and specificity of cervical sentinel lymph node biopsy after mapping with indocyanine green fluorescence (ICG) for imaging early-stage oral cancer. PATIENTS AND METHODS: A sentinel lymph node biopsy (SLNB) was performed during a selective neck dissection (SND) in 20 patients with oral squamous cell carcinoma (OSCC, cT1 or cT2, N0 status). The sentinel lymph nodes (SLN) were identified using an infrared video camera after ICG injection. Lymph nodes were examined histologically. The endpoint of this study was to investigate the rate of false-negative results in SLNB. RESULTS: Sentinel lymph nodes could be detected after 8.1 min (range 1-22 min). In eight out of 20 cases, lymph node metastases were found during histopathological evaluation of the neck dissection specimen. In four cases a metastasis could be found in the detected SLN (sensitivity 50%). In the other four cases metastases were found in different lymph nodes. Specificity was 100%, positive predictive value 100%, and negative predictive value 75%. CONCLUSION: In this study, reliability of sentinel lymph node biopsy after ICG imaging could not be verified, as there were false-negative results in 50% of the cases. Therefore, SND can still be recommended as for patients with cT1 or cT2 OSCC, and a N0 neck status.

Functional donor site morbidity longer than one year after fibula free flap: A prospective biomechanical analysis.

OBJECTIVES: The fibula free flap is the workhorse procedure for osseous reconstruction. The objective of this study was to investigate long-term functional outcomes of the harvesting site. PATIENTS AND METHODS: About 19 patients (10 male, 9 female, mean age 58.1 years) were available for the long-term analysis 13-51 months after surgery. Jumping mechanography and balance testing on a ground force reaction plate (Leonardo Mechanograph GFRP) were performed before and surgery. The Esslinger Fitness Index (EFI, maximum peak power in W/kg normalized for age and gender) was considered as primary endpoint. Secondary outcomes were maximum force, range of motion in the ankle joint, sensory limitations, the American Orthopedic Foot and Ankle Society Score (AOFAS-Score), and subjective perceptions. RESULTS: We found no significant difference between pre- and postoperative EFI (70.4% versus 66.0%, P = 0.07) and body sway (1.72 cm2 versus 2.60 cm2 , P = 0.093). The AOFAS-Score was reduced by 8.8 points (99.1 points versus 90.3 points, P < 0.001). Dorsal extenstion (31.6° versus 24.1°, P < 0.001) and flexion (32.3 versus 25.6° flexion, P = 0.011) were significantly reduced and 6 patients had chronic pain. CONCLUSIONS: Reduced peak power and balance ability seem to be reversible short-term effects after fibula harvesting. We recommend preoperative patient education and standardized protocols for physiotherapy.

Obstacles in spatial evaluation of CBCT-reformatted panoramic imaging.

OBJECTIVES: Conventional panoramic radiography (cPR) underlines procedure-related limitations in the display of objects. CBCT is presumed to overcome these constraints. To virtualize a cPR view, reformatted panoramic images (rPIs) can be generated. This study evaluated the rPI with regard to its susceptibility to sterical object deposition in comparison with cPR. METHODS: A specially developed implant model with dental implants each of 4.0-mm diameter and 11.0-mm length was depositioned by shift, rotation and tilt of 5.00 mm (±0.01 mm) of horizontal shift and 5.0° (±0.167°), respectively, on a highly precise goniometer rotation table, and cPRs and rPIs were generated. Automated evaluation of the cPRs was carried out using a specially developed software. rPIs were processed and analyzed by a semi-automated image analysis. RESULTS: Object deposition lead to distortive effects in the rPI analogue to cPR, but they appear in display only. Objects illustrated in the rPI were dimensionally correct, but sterical relations are elusive. Results are obtained for the horizontal shift, declination and reclination, lateral tilt and rotation. CONCLUSIONS: Distortions within the rPI represent the illustration of the hyperbolic-shaped layer out of the three-dimensional data set. With this study, we demonstrated these procedure-related inherent but practically underestimated consequences. Effects of sterical object malpositioning must be compensated by the observer by adequate virtual adjustment of the processed layer. Accurate virtual adjustment leads to vertical dimensions. Sterical relations, e.g. angulation of two objects, are irretraceable unless precisely referenced.

Postoperative bleeding risk for oral surgery under continued rivaroxaban anticoagulant therapy.

OBJECTIVES: The purpose of this study was to assess the risk of postoperative bleeding complications after oral procedures performed under continued mono or dual anticoagulation therapy with rivaroxaban (and aspirin). METHODS: This retrospective single-center observational study included 52 oral procedures performed under continued oral anticoagulant therapy with rivaroxaban (20 mg/day). Among them, two procedures were performed under continued dual therapy with aspirin (100 mg/day) added to the regimen. Postoperative bleeding events were compared with 285 oral procedures in patients without any anticoagulation/antiplatelet therapy. RESULTS: Postoperative bleeding complications after oral surgery occurred significantly more often in patients under continued rivaroxaban therapy (11.5 %) than in the control cases without anticoagulation/antiplatelet medication (0.7 %). All of the bleeding events were manageable: Two of them were treated with local compression, three by applying new fibrin glue with (one case) or without (two cases) secondary sutures, one occurred during a weekend and was therefore treated under inpatient conditions with suture replacement. All postoperative bleeding episodes occurred during the first postoperative week. CONCLUSIONS: According to our data, continued anticoagulation therapy with rivaroxaban significantly increases postoperative bleeding risk for oral surgical procedures, although the bleeding events were manageable. CLINICAL RELEVANCE: Oral surgeons, cardiologists, general physicians, and patients should be aware of the increased bleeding risk after oral surgical procedures. Close observation up to 1 week postoperatively is advisable to prevent excessive bleeding.

Prospective biomechanical evaluation of donor site morbidity after radial forearm free flap.

Although the radial forearm free flap (RFF) is a commonly-used microvascular flap for orofacial reconstruction, we are aware of few prospective biomechanical studies of the donor site. We have therefore evaluated the donor site morbidity biomechanically of 30 consecutive RFF for orofacial reconstruction preoperatively and three months postoperatively. This included the Mayo wrist score, the Disabilities of the Arm, Shoulder and Hand (DASH) score, grip strength, followed by tip pinch, key pinch, palmar pinch, and range of movement of the wrist. Primary defects were all closed with local full-thickness skin grafts from the donor site forearm, thereby circumventing the need for a second defect. Postoperative functional results showed that there was a reduction in hand strength measured by (grip strength: -24.1%, in tip pinch: -23.3%, in key pinch: -16.5, and in palmar pinch: -19.3%); and wrist movement measured by extension (active=14.3% / passive= -11.5%) and flexion = -14.8% / -8.9%), and radial (-9.8% / -9.8%) and ulnar (-11.0% / -9.3%) abduction. The Mayo wrist score was reduced by 9.4 points (-12.9%) and the DASH score increased by 16.1 points (+35.5%) compared with the same forearm preoperatively. The local skin graft resulted in a robust wound cover with a good functional result. Our results show that the reduction in hand strength and wrist movement after harvest of a RFF is objectively evaluable, and did not reflect the subjectively noticed extent and restrictions in activities of daily living. Use of a local skin graft avoids a second donor site and the disadvantages of a split-thickness skin graft.

Linear accuracy and reliability of volume data sets acquired by two CBCT-devices and an MSCT using virtual models: a comparative in-vitro study.

OBJECTIVE: To discriminate clinically relevant aberrance, the accuracy of linear measurements in three-dimensional (3D) reconstructed datasets was investigated. MATERIALS AND METHODS: Three partly edentulous human skulls were examined. Landmarks were defined prior to acquisition. Two CBCT-scanners and a Quad-slice CT-scanner were used. Actual distances were physically measured with calipers and defined as a reference. Subsequently, from digital DICOM datasets, 3D virtual models were generated using maximum intensity projections (MIPs). Linear measurements were performed by semi-automated image analysis. Virtual and analogue linear measurements were compared using repeated measurements in a mixed model (p ≤ 0.05). RESULTS: No significant difference was found among all of the digital measurements when compared to one another, whereas a significant difference was found in matched-pairs analysis between CBCT and calipers (p = 0.032). All digitally acquired data resulted in lower mean values compared to the measurements via calipers. A high level of inter-observer reliability was obtained in the digital measurements (inter-rater correlation = 0.988-0.993). CONCLUSIONS: The reconstructed datasets led to highly consistent values among linear measurements. Yielding sub-millimeter precision, these modalities are assumed to reflect reality in a clinically irrelevant altered manner. During data acquisition and evaluation, a maximum of precision must be achieved.

Long-term biomechanical analysis of donor site morbidity after radial forearm free flap.

BACKGROUND: Although the radial forearm free flap (RFF) is a commonly used microvascular graft for head and neck reconstruction, long-term biomechanical results regarding donor site morbidity are rare. PATIENTS AND METHODS: In a prospective panel study, 32 patients were included. Biomechanical assessment was performed preoperatively, three months postoperatively and two years postoperatively. The primary endpoint of the study was grip strength. In addition, the Mayo wrist score, DASH score (disabilities of the arm, shoulder and hand score), fine motor skill strengths (tip pinch, key pinch, palmar pinch) and the range of motion were analysed. Primary defects were closed with local full-thickness skin grafts (FTSG) from the donor site forearm avoiding a secondary defect site. RESULTS: In the long-term analysis, grip strength was reduced in both arms. A significant improvement over time was found only for the donor arm. A persistent deficit of tip pinch strength and dorsal extension was recorded. Persistent sensory limitations occurred in four cases. Patient contentment after two years of follow-up was high and daily life routine was not restricted. CONCLUSION: Gross and fine motor skill limitations are reversible short-term effects after RFF harvesting and do not restrict daily routine in the long term. These findings substantiate the value of the RFF as a workhorse in reconstructive surgery.

Thromboelastometry: A contribution to perioperative free-flap management.

BACKGROUND: Microvascular tissue transfer is a fundamental part of reconstructive surgery. Different perioperative anticoagulation regimens exist, influencing hemostatic parameters. Since bleeding and thrombosis are major reasons for revision procedures and flap loss, current practice regarding anticoagulative treatment needs further refinement. Thromboelastometry has been demonstrated as worthwhile in the determination of alterations of the anticoagulation cascade. We evaluated this aspect of thromboelastometry for free flap surgery. METHODS: Thirty-five patients undergoing free-flap surgery were enrolled in this study. Blood samples were obtained at three time points: at the beginning of surgery, at time of anastomosis and after 24 h. At each time point, thromboelastometry with special regard to clotting times for the intrinsic and extrinsic paths of coagulation was immediately performed. Global coagulation markers and clinical parameters were collected simultaneously. RESULTS: Hemostatic changes were deducible using thromboelastometry perioperatively. Measured parameters differed significantly over time (p < 0.05). Heparin therapy showed a significant effect on the measured slope of INTEM-clotting times (p < 0.001). Altered values of thromboelastometry suggested non-inferiority to standard testing. Neither standard testing nor thromboelastometry were capable of predicting adverse events such as thrombosis, bleeding or flap loss (p > 0.05). CONCLUSIONS: Thromboelastometry monitors hemostatic effects almost in real-time and could serve as a supplementary tool in microvascular tissue transfer once its use has been standardized. The utilization of thromboelastometry allows for assessment of the anticoagulation needs of individual patients undergoing free flap surgery, which is frequently accompanied by hemostatic changes in the perioperative setting. Our findings implicate further validation of thromboelastometry in free-flap surgery.

Intraosseous heat generation during sonic, ultrasonic and conventional osteotomy.

OBJECTIVES: To assess heat generation in osteotomies during application of sonic and ultrasonic saws compared to conventional bur. METHODS: Two glass-fiber isolated nickel-chromium thermocouples, connected to a recording device, were inserted into fresh bovine rib bone blocks and kept in 20 ± 0.5 °C water at determined depths of 1.5 mm (cortical layer) and 7 mm (cancellous layer) and 1.0 mm away from the planned osteotomy site. Handpieces, angulated 24-32°, were mounted in a vertical drill stand, and standardized weights were attached to their tops to exert loads of 5, 8, 15 and 20 N. Irrigation volumes of 20, 50 and 80 ml/min were used for each load. Ten repetitions were conducted using new tips each time for each test condition. The Mann-Whitney-U test was used for statistical analysis (p < 0.05). RESULTS: Both ultrasonic and sonic osteotomies were associated with significantly lower heat generation than conventional osteotomy (p < 0.01). Sonic osteotomy showed non-significantly lower heat generation than ultrasonic osteotomy. Generated heat never exceeded the critical limit of 47 °C in any system. Variation of load had no effect on heat generation in both bone layers for all tested systems. An increased irrigation volume resulted in lower temperatures in both cortical and cancellous bone layers during all tested osteotomies. CONCLUSION: Although none of the systems under the conditions of the present study resulted in critical heat generation, the application of ultrasonic and sonic osteotomy systems was associated with lower heat generation compared to the conventional saw osteotomy. Copious irrigation seems to play a critical role in preventing heat generation in the osteotomy site.

Postoperative bleeding risk for oral surgery under continued clopidogrel antiplatelet therapy.

OBJECT: To determine the incidence of postoperative bleeding for oral osteotomy carried out under continued monoantiplatelet therapy with clopidogrel and dual therapy with clopidogrel/aspirin. Design. Retrospective single center observatory study of two study groups and a control group. METHODS: A total of 64 and 60 oral osteotomy procedures carried out under continued monoclopidogrel therapy and dual clopidogrel/aspirin therapy, respectively, were followed for two weeks for postoperative bleeding. Another 281 similar procedures were also followed as a control group. All oral osteotomy procedures were carried out on an outpatient basis. RESULTS: We observed postoperative bleeding in 2/281 (0.7%) cases in the control group, in 1/64 (1.6%) cases in the clopidogrel group, and in 2/60 (3.3%) cases in the dual clopidogrel/aspirin group. The corresponding 95% confidence intervals are 0-1.7%, 0-4.7%, and 0-7.8%, respectively, and the incidences did not differ significantly among the three groups (P > 0.09). Postoperative hemorrhage was treated successfully in all cases with local measures. No changes of antiplatelet medication, transfusion, nor hospitalisation were necessary. No major cardiovascular events were recorded. CONCLUSIONS: Our results indicate that minor oral surgery can be performed safely under continued monoantiplatelet medication with clopidogrel or dual antiplatelet medication with clopidogrel/aspirin.

Impact of malpositioning on panoramic radiography in implant dentistry.

OBJECTIVES: The widely used panoramic radiography as a special kind of tomography underlies intrinsic procedural restrictions such as poor definition, inconsistent magnification, geometric distortion and spatial depositioning of objects situated outside the focal trough. This results in a non-anatomic display of the radiographed anatomic structures. Individual mandibular angle and width of the jaws, adjustment of the focal trough, jaw incongruence as well as patient positioning increase the inconsistency in display of the radiographed objects. This study precisely evaluated the quantitative impact of object malpositioning on the display in panoramic radiography. MATERIALS AND METHODS: A special dental implant model was highly accurate three dimensionally malpositioned and panoramic radiographs were taken. Automated image analysis was performed to exclude subjective assessment error. RESULTS: Precise and retraceable object deposition of up to 5 mm or 5° resulted in relevant deposition of objects and significant changes in object size and inter-object distances in the panoramic image. Unidirectional malpositioning lead to multiple errors in display. CONCLUSIONS: The extent of malpositioning-related display errors additionally to the known physicotechnical insufficiencies of the panoramic radiography demonstrates its limitations in precisely interpreting spatial relationships. CLINICAL RELEVANCE: Measurements within the panoramic radiography must not claim reliability. For a single object securely positioned in the focal trough and perpendicular to the central X-ray beam, measurements may be trustworthy on clinical scale. Once sterical relationships to other structures are evaluated, reliability must be questioned.

Imaging of the midfacial and orbital trauma.

The severity of midfacial and orbital injuries depends on the one hand on cause, force vector, load point, or area and on the other hand on the bony and soft tissue resistance as well as individual anatomy. These variables result in a variety of possible injuries of the midfacial and orbital complex. The time critical choice of an adequate imaging modality of these injuries is influenced by the possible severity of concomitant injuries. Besides the confirmation of a clinical diagnosis, the need for high-resolution three-dimensional imaging for preoperative planning of facial reconstruction using intraoperative navigation has become more and more important in the past years. To achieve optimal functional and esthetic outcomes, the anatomical complexity of the midface has to be addressed and the adequate imaging modality has to be chosen keeping the upcoming surgical treatment in mind. The current imaging modalities for midfacial and orbital trauma are presented and critically evaluated depending on the indications. Furthermore, new strategies to support surgeons in achieving best possible midfacial reconstructions are discussed. An algorithm to choose the adequate imaging modality in midfacial and orbital traumatology is provided.

Squamous cell carcinoma of the oral cavity and circulating tumour cells.

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma (OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells (CTCs) and disseminated tumour cells (DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool to determine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.

Prognostic relevance of circulating tumor cells in blood and disseminated tumor cells in bone marrow of patients with squamous cell carcinoma of the oral cavity.

PURPOSE: Current staging methods for squamous cell carcinomas (SCC) of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Because hematogenous tumor cell dissemination is a key event in tumor progression, we assessed the prognostic significance of disseminated tumor cells (DTC) in bone marrow and circulating tumor cells (CTC) in peripheral blood from patients with OSCC. EXPERIMENTAL DESIGN: From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest, and mononuclear cells (MNC) were enriched by Ficoll density gradient centrifugation. To detect DTCs, MNCs were immunostained with the pan-keratin antibody A45-B/B3. Results were correlated with clinicopathologic parameters and clinical outcome such as recurrence and death during follow-up time (mean 916 days). RESULTS: Ten of 80 patients (12.5%) harbored CTCs in peripheral blood, whereas in 18 of 90 patients (20.0%) DTCs in bone marrow could be detected. Surprisingly, in only 2 patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found for CTCs and tumor size (P = 0.04), nodal status and DTCs (P = 0.02), and distant metastasis with CTCs (P = 0.004) and DTCs (P = 0.005). Univariate and multivariate analyses revealed that CTCs and DTCs were significant and independent predictors of recurrence-free survival (P < 0.001). CONCLUSIONS: Both DTCs and CTCs are independent prognostic markers in patients with OSCC, predicting relapse with higher sensitivity at various disease stages than routine staging procedures. Bone marrow might be an interesting target organ for future therapeutic interventions.

Intraoperative efficiency of fluorescence imaging by Visually Enhanced Lesion Scope (VELscope) in patients with bisphosphonate related osteonecrosis of the jaw (BRONJ).

OBJECTIVES: The purpose of this study was to determine the potential of tissue fluorescence imaging by using Visually Enhanced Lesion Scope (VELscope) for the detection of osteonecrosis of the jaw induced by bisphosphonates (BRONJ). METHODS: We investigated 20 patients (11 females and 9 males; mean age 74 years, standard deviation ± 6.4 years), over a period of 18 month with the diagnosis of BRONJ in this prospective cohort study. All patients received doxycycline as a fluorescending marker for osseous structures. VELscope has been used intraoperatively using the loss of fluorescence to detect presence of osteonecrosis. Osseous biopsies were taken to confirm definite histopathological diagnosis of BRONJ in each case. RESULTS: Diagnosis of BRONJ was confirmed for every patient. In all patients except one, VELscope was sufficient to differentiate between healthy and necrotic bone by visual fluorescence retention (VFR) and visual fluorescence loss (VFL). 19 cases out of a total of 20 showed no signs of recurrence of BRONJ during follow-up (mean 12 months, range 4-18 months). CONCLUSION: VELscope examination is a suitable tool to visualize necrotic areas of the bone in patients with bisphosphonate related osteonecrosis of the jaw. Loss of fluorescence in necrotic bone areas is useful intraoperatively as a tool for fluorescence-guided bone resection with relevant clinical interpretation.

Immunohistochemical and FISH analysis of EGFR and its prognostic value in patients with oral squamous cell carcinoma.

OBJECTIVES: To study immunohistochemical expression of the epithelial growth factor receptor (EGFR) in oral carcinomas and the head and neck region to examine possible associations with various features of the tumors and survival of the patients. MATERIALS AND METHODS: Sections were made from two tissue arrays composed of 206 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, and examined for EGFR expression and Ki-67 labeling index by means of immunohistochemistry, and for EGFR gene amplification by means of fluorescence in situ hybridization. Correlation between resulting parameters and with clinical features was evaluated using chi-square test and Kaplan-Meyer analysis. RESULTS: A statistically significant association was observed for strong EGFR immunohistochemical (IHC) expression with advanced lymph node involvement (P = 0.02). EGFR immunohistochemical expression did not significantly correlate with patient disease specific (DS) or overall survival (OS). EGFR gene amplification was not correlated with any of the tumor features nor to survival of the patients (DS and OS). DISCUSSION: Epithelial growth factor receptor IHC expression and gene amplification might be suitable to predict locoregional control in oral squamous cell carcinoma patients but an inappropriate predictor for patients survival.

Incidence of bisphosphonate-related osteonecrosis of the jaw in consideration of primary diseases and concomitant therapies.

BACKGROUND: Since its first description by Marx in 2003, the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the subject of numerous scientific discussions for oral and maxillofacial surgeons. Many retrospective studies on its etiology and pathogenesis have been carried out to explain pathological mechanisms; most of them just take a close look at the issue of dosage and application. Recently, attempts have been made, to identify co-factors which might promote the development of BRONJ. PATIENTS AND METHODS: The present study is based on data of 169 patients with osseous metastatic malignancies. All patients received intravenous bisphosphonate therapy. On the basis of medical history, malignancy, and primary treatment, the modality of bisphosphonate therapy, and existing comorbidities and medication were analyzed. The role of immunosuppressive drugs, influence of underlying diseases, and general factors such as age and gender were examined. The predictability of necrotic involvement, influenced by the underlying malignancy and its specific therapy, e.g. radiation and cytostatic therapy were analyzed and statistically evaluated. RESULTS: A total of 8.9% (n=15) of patients developed BRONJ. The average time between diagnosis of malignancy and BRONJ was 80 months. Nine patients suffered from breast cancer, five had prostate cancer and one renal cancer. Separation into stage and histological subtype did not show any significant correlation, nor did age or gender, to the occurrence of BRONJ. However statistical analysis did show a significant correlation concerning monocytostatic (p=0.0215) and triple-cytostatic therapy (p=0.0137). The majority of patients with BRONJ (60%) received a bisphosphonate therapy including zoledronate. Single application with one bisphosphonate was administered in 28 cases; 44 patients had a medical history of different use of bisphosphonate. Concomitant medication did not suggest possible correlation, nor did accompanying diseases, arterial hypertension (33.33%) or arterial microcirculatory disturbances (20%). CONCLUSION: The evaluation of our results is pioneering. The influence of cytostatics and combined therapy of cytotoxic drugs on the pathogenesis of BRONJ is demonstrated here statistically. We confirmed a drug- and dose-dependent occurrence of BRONJ. Further prospective studies should be performed to elucidate the role of tissue perfusion and oxygen saturation, and the influence of immunosuppressive drugs in relation to the occurrence of BRONJ, as well as on wound healing of initial lesions.