Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVES: The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. MATERIALS AND METHODS: A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. RESULTS: Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. CONCLUSION: Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.

Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration - a pilot study in vitro.

BACKGROUND: The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field. METHODS: In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds' morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 µm, 300 µm, 375 µm, 450 µm and 500 µm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63. RESULTS: All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 µm and 500 µm, a preferred box size for initial osteoblast attachment could not be found. CONCLUSIONS: These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas.

OBJECTIVES: Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors. MATERIALS AND METHODS: This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS. RESULTS: In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient's age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13. CONCLUSION: Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs. CLINICAL RELEVANCE: The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.

Correlation of MAGE-A tumor antigens and the efficacy of various chemotherapeutic agents in head and neck carcinoma cells.

OBJECTIVES: The present study examined the relationship between MAGE-A tumor antigens and the efficacy of diamindichloridoplatin (DDP), 5-fluorouracil (5-FU), docetaxel, and paclitaxel for in vitro treatment of head and neck cancer. METHODS: In the present study, five cell lines of human squamous cell carcinomas were treated with DDP (25-400 µM), 5-FU (0.75-12 mM), docetaxel (1.56-25 nM), and paclitaxel (1.56-25 nM) for a period of 24 or 48 h. The efficacy of the agents was observed dynamically using real-time cell analysis. Subsequently, the expression levels of MAGE-A1, MAGE-A5, MAGE-A8, MAGE-A9, MAGE-A11, and MAGE-A12 were determined by quantitative real-time polymerase chain reaction. Chemosensitivity and MAGE-A-expression were correlated by linear regression. RESULTS: The tumor cell lines showed a highly differentiated response to the chemotherapeutic agents. Expression of MAGE-A11 was significantly associated with a poorer response to treatment with DDP, 5-FU, docetaxel, and paclitaxel. Two cell lines, one of which was MAGE-A11-positive, showed a significant and concentration-dependent cisplatin-induced growth spurt during the first 24 h after treatment. MAGE-A5 was connected to a positive effect on treatment with paclitaxel within the first 24 h after application. In association with docetaxel treatment, MAGE-A8 was connected to a poorer susceptibility. CONCLUSIONS: The results describe, for the first time, a correlation between these MAGE-A tumor antigens and the susceptibility of head and neck cancer cells to DDP, 5-FU, docetaxel, and paclitaxel. CLINICAL RELEVANCE: These findings could affect the antineoplastic treatment of patients with MAGE-A11-positive tumors.

The value of Allen's test in harvesting a radial forearm flap: correlation of ex-vivo angiography and histopathological findings.

The radial forearm flap is one of the most commonly raised free flaps. In most cases an Allen's test is sufficient for preoperative assessment of the palmar arch, but an intact palmar arch does not imply that the radial artery is suitable for microvascular anastomosis. For a patient operated for oral squamous cell carcinoma, reconstruction was planned with a radial forearm flap. The flap had to be discarded because of advanced atherosclerosis in the presence of a negative Allen's test. The correlation of an ex-vivo angiography and the histopathologic findings was assessed. In cases of expected vascular disease, further examinations like color flow Doppler ultrasound are recommended to ensure sufficient perfusion of the radial artery.

[Re-re-relapse of a MALT lymphoma of the conjunctiva]. / Re-Re-Rezidiv eines MALT-Lymphoms der Bindehaut.

BACKGROUND: The MALT lymphoma (mucosa-associated lymphoid-like tissue lymphomas) is a rare entity and belongs to the low-grade non-Hodgkin (NHL) lymphomas. In 8 % of cases it arises in the conjunctiva. In some cases a MALT lymphoma of the conjunctiva is misdiagnosed as chronic conjunctivitis. Mostly a MALT lymphoma of the conjunctiva can be cured by radiation and has a good prognosis. CASE REPORT: A 61-year-old female presented to our hospital because of alteration of the conjunctiva and worsening of her general condition. Symptoms were fatigue, lassitude, night sweat, loss of appetite and gastrointestinal problems. The medical history revealed treatment for a MALT lymphoma 4 years previously and a relapse 3 years previously. Both were resected totally. Staging at those times gave no hint for metastases. The ophthalmological examination showed an adherent prominence with conjunctival injection of the right eye at 10 - 11 o'clock. It corresponded to the localisation of the primary tumour in 2002 and the relapse in 2003. Slit lamp and fundoscopic examinations only revealed a cataracta incipiens. CLINICAL COURSE: To confirm the diagnosis a biopsy was done. The histological examination demonstrated a relapse of the MALT lymphoma. Staging gave no hint for metastases. The patient was referred to the oncological unit for chemotherapy (R-CHOP regime). CONCLUSION: This case shows that a relapse of the MALT lymphoma may arise although the previous tumour and its relapse were resected totally. In patients with tumours in their medical history suffering from unspecific discomfort, a biopsy should may be be considered despite the lack of apparent macroscopic findings.

[Performance of conventional oral brush biopsies]. / Wertigkeit der konventionellen oralen Bürstenbiopsie.

BACKGROUND: This study evaluated the performance of oral brush biopsies using standard morphological analysis and haematoxylin and eosin (HE) staining for detecting oral squamous cell carcinomas and their respective precursor lesions PATIENTS AND METHODS: Brush biopsies were obtained in 169 consecutive patients who underwent routine biopsies and histological examination for clinically suspicious oral lesions. Air-dried smears were processed by acetone fixation and HE staining. Cytological assessment used well-established criteria of atypia to classify the specimen as either "tumor negative" (no signs of atypia, no malignant cells) or "tumor positive" (malignant cells, any sign of atypia or doubtful cells). RESULTS: Despite a sufficient number of cells, a definite cytological diagnosis could not be established in six cases. According to the criteria specified above, these specimens were classified as "tumor positive." The cytological analysis identified 49 out of 62 oral malignancies (sensitivity 79%). Seven out of 107 benign lesions were classified as false positive (specificity 93%). The positive and negative predictive values were each 88%. CONCLUSION: Oral brush biopsies will identify only about 80% of oral malignancies when the smears are processed by routine HE stains and are analysed via standard morphological criteria. Thus, this technique should not be used for diagnostic proof or to exclude malignant cells in a lesion suspicious for cancer. However, oral brush biopsy provides a versatile back-up strategy to uncover the true nature of the disease if a lesion is clinically considered benign by mistake.

Traumatic dislocation of the globe into the maxillary sinus.

The complete traumatic dislocation of the globe into the maxillary sinus is a very rare event. Due to the intense force affecting the orbit, the impact on the globe and its accompanying structures is normally very severe. A case is reported of complete dislocation of the globe into the maxillary sinus with nearly complete recovery of vision and motility.

Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC).

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common malignancy worldwide. The past decades have not led to substantial improvement in diagnosis and therapy. Analysis of miRNA-expression may help to determine the progression profiles and outcomes of many different diseases, including HNSCC. Therefore, in this investigation, 43 formalin-fixed, paraffin-embedded (FFPE) samples of oral squamous cell carcinoma were micro-dissected, analysed for expression of 30 miRNAs and were compared with non-tumorous tissue. Furthermore, correlation analysis was performed, investigating possible correlations of miRNA-expression and patient or tumour-linked data, such as age, sex, tumour stage and size. miRNA extraction from FFPE samples functioned well for OSCC, and several miRNAs were differently expressed in tumours compared with non-tumorous tissue (i.e., miR-99*; miR-224; miR-205*), indicating their possible utility as biomarkers. Moreover, some miRNAs showed significant correlations with clinical and pathological data (e.g. tumour size: miR-3156, P = 0.033; T-stage: miR-212, P = 0.0009).

Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma.

MAGE-A proteins are highly expressed in oral squamous cell carcinoma (OSCC) and are promising targets for cancer immunotherapy. This study examined the presence of MAGE-A expression within the tumor center (TC) and tumor invasive front (TIF) and evaluated its relationship to poor prognosis. The expression rate of each MAGE-A subtype, A1-A12, was examined in 68 OSCCs at the TIF and TC. Slides (1-µm) of tissue microarrays (diameter =0.6 mm) were immunohistochemically stained, and the findings were correlated to clinical data. Approximately 95% of the tumors had MAGE-A expression. Higher expression in the TC was shown significantly for MAGE-A1, -A5, -A6, -A9 and -A12 (P<0.05). MAGE-A2 and -A3 exhibited the opposite behavior (not significant, P>0.05). Age, tumor size, grade and survival time were not associated with the expression of certain MAGE-A subgroups. When expression in the whole tumor tissue was considered, only MAGE-A1 was expressed at a significantly higher rate in male patients (P=0.034). At the TIF, MAGE-A9 and the UICC disease stage were significantly correlated (P=0.0263), and MAGE-A6 and the UICC disease stage exhibited a strong trend (P=0.0596). The expression of MAGE-A3, -A4, -A5, -A9 and -A11 was significantly associated with lymph node metastasis, while MAGE-A4 was expressed in all regions of the tumors (TIF and TC). This study showed that higher expression of most MAGE-A antigens occurred at the TC rather than at the TIF. MAGE­A1, -A3, -A4, -A5, -A9 and -A11 were significantly associated with clinically advanced stages of disease and seem to be of particular interest.

Performance of cone beam computed tomography in comparison to conventional imaging techniques for the detection of bone invasion in oral cancer.

Detecting bone invasion in oral cancer is crucial for therapy planning and the prognosis. The present study evaluated cone beam computed tomography (CBCT) for detecting bone invasion in comparison to standard imaging techniques. A total of 197 patients with diagnoses of oral cancer underwent CBCT as part of preoperative staging between January 2007 and April 2013. The sensitivity, specificity, and accuracy of CBCT were compared with panoramic radiography (PR), multi-slice computed tomography (CT) or magnetic resonance imaging (MRI), and bone scintigraphy (BS) using McNemar's test. Histopathology and clinical follow-up served as references for the presence of bone invasion. CBCT and BS (84.8% and 89.3%, respectively), as well as CBCT and CT/MRI (83.2%), showed comparable accuracy (P = 0.188 and P = 0.771). CBCT was significantly superior to PR, which was reconstructed based on a CBCT dataset (74.1%, P = 0.002). In detecting bone invasion, CBCT was significantly more accurate than PR and was comparable to BS and CT/MRI. However, each method has certain advantages, and the best combination of imaging methods must be evaluated in prospective clinic trials.

[Better evaluation of HRT (Heidelberg Retina Tomography) images by 3-dimensional display]. / Bessere Auswertung von HRT-Aufnahmen durch dreidimensionale Darstellung.

BACKGROUND: The Heidelberg retina tomograph (HRT) is routinely used for the analysis of the structures of the eye ground (glaucoma diagnosis). The Dresden 3D-display, developed by the Technical University Dresden, is an autostereoscopic display which facilitates the three-dimensional presentation of geometrical data. The aim of this study was to test whether the spatial presentation improves the precision of measurements. METHODS: Out of the patients who attended our hospital for glaucoma treatment within the past 3 years, 17 (9 women and 8 men) were chosen on grounds of a long follow-up time. In addition the patients had to have had at least 4 HRT examinations (mean: 5.29). The patients data was explored in three ways: 1. regular HRT examination, 2. manual follow-up HRT examination and 3. examination with the Dresden 3D-display. RESULTS AND CONCLUSIONS: The measurements performed with the Dresden 3D-display showed a significantly higher precision compared to traditional HRT measurements. With spatial presentation a better assessment of the measured HRT data is possible.

SAPHO syndrome with ankylosis of the temporomandibular joint.

SAPHO syndrome is a rare combination of different symptoms with unknown aetiology. A complete ankylosis of the temporomandibular joint (TMJ) in a patient with SAPHO syndrome has not been described previously. The goal of this case report is to present the disease, give an overview about the frequency of mandibular involvement and describe different therapeutic strategies. The complication of an ankylosis of the TMJ is noted and the literature is reviewed. The authors report a 42-year-old patient with SAPHO syndrome and recurrent swelling of the right mandible and the soft tissue. The persisting involvement of the mandible resulted in a complete osseous ankylosis of the right TMJ and required resection with alloplastic replacement of the right condyle. SAPHO syndrome should be suspected in some cases of 'therapy resistant osteomyelitis' of the mandible. Smaller joints, such as the TMJ may also be affected. Treatment of SAPHO syndrome should include antibiotics and NSAIDs; corticosteroids may be helpful. Surgery is the ultimate treatment.

Historical development of alloplastic temporomandibular joint replacement after 1945 and state of the art.

The variety of temporomandibular joint (TMJ) prostheses and condylar reconstruction plates available is in contradiction to their rare application. This emphasizes that alloplastic TMJ reconstruction is still evolving. This article reviews the history of TMJ reconstruction. Medline as well as public and private libraries have been searched. Current systems are reviewed. Prosthetic devices can be differentiated into fossa-eminence prostheses, ramus prostheses and condylar reconstruction plates, and total joint prostheses. Fossa and total joint prostheses are recommended when the glenoid fossa is exposed due to excessive stress (degenerative disorders, arthritis, ankylosis, multiply operated pain patients). Singular replacement of the condyle is preferred as a temporary solution in ablative surgery. The use of prosthetic devices for long-term replacement should be restricted to selected cases, taking care to retain the disk, in order to prevent penetration into the middle cranial fossa. The term 'condylar reconstruction plate' reflects this more clearly than 'ramus prosthesis' which suggests permanent reconstruction. Long-term studies comparing the functional and aesthetic results of the various prostheses and condylar reconstruction plates are not available, which leaves the choice to personal experience.

[Traumatic dislocation of the globe into the maxillary sinus--is a rehabilitation possible?]. / Ist eine Rehabilitation nach einer kompletten Bulbusluxation in die Kieferhöhle bei Orbitabodenfraktur möglich?

BACKGROUND: The complete traumatic dislocation of the globe into the maxillary sinus after orbital floor fractures is a very rare event. It results from direct transmission of a traumatic force which impinges the orbital frame or may result from an increasing pressure to the orbital contents. Diplopia or evidence of a displaced globe necessitates an exploration and reconstruction of the orbital floor. CASE REPORT: A 62-year-old male was admitted to our hospital because of a blunt injury to the orbital region caused by a machine for planing timber. On examination the patient had a massive right periorbital haematoma and no globe was visibly found. The CT scan revealed a blow-out fracture of the orbital floor with a complete dislocation of the right globe into the right maxillary sinus. Using a bright flashlight on the right maxillary region the patient reported light perception. The operative exploration showed no impaired integrity of the globe, no apparent laceration of the orbital muscles and a preserved continuity of the optic nerve. The dislocated globe was repositioned manually into the orbit and secured by an antral balloon catheter. CLINICAL COURSE: Postoperative magnetic resonance imaging showed a correct anatomic status. The muscles did not seem to be lacerated and the continuity of the optic nerve was demonstrated. Incarcerations were not existent. 9 months postoperatively the vision recovered to 1.0 p. The motility was slightly diminished (elevation and abduction 20 degrees, adduction 25 degrees and downwards 20 degrees over midline). The patient suffered from diplopia when looking 25 degrees to the right and 20 degrees upwards. The anisocoria with a slight dilation of the pupil had declined in the right eye but was still present. CONCLUSION: This case of complete dislocation of the globe into the maxillary sinus demonstrates that only few injuries may result and that after operative reconstruction of the orbital floor a good functional result can achieved.

[Congenital mature teratoma of the right orbit]. / Kongenitales reifes Teratom der rechten Orbita.

BACKGROUND: Teratomas are congenital embryonic tumours composed of a wide diversity of tissues derived from the three germinal layers (ectoderm, mesoderm, endoderm). Located in the orbit they endanger the eye and the bony structures. The main goal of treatment is preservation of the eye. In most cases this will not be feasible. CASE REPORT: A newborn boy was admitted to our hospital because of a prenatally known protrusion of the right globe. On examination the baby had a large retrobulbar orbital tumour, which displaced the globe ventrally. On MRI the tumour had an extent of 5 cm. It compromised the frontal bone and reached intracranially. No other malformations were found. The tumour was transorbitally resected and the eye exenterated. A congenital mature teratoma was diagnosed. To preserve orbital volume an implant was inserted (Hema globe, 18 mm). FOLLOW-UP: The healing course was uneventful. Illig implants were changed without difficulties. After 10 months an individual prosthesis was inserted. Control CT scans showed no signs of tumour. CONCLUSIONS: The case presented underlines the possible extent and impact of congenital mature teratomas. Despite the extent of the tumour and the very young age of the patient a satisfactory treatment result was achieved.

[Pleomorphic malignant fibrous histiocytoma of the periorbital region]. / Pleomorphes malignes fibröses Histiozytom der Periorbitalregion.

BACKGROUND: Pleomorphic malignant fibrous histiocytomas (undifferentiated pleomorphic sarcomas) belong to the soft tissue tumours and are more likely in elder patients. About 3 % percent of all pleomorphic malignant fibrous histiocytomas arise in the head and neck region. 30 % of these histiocytomas develop in the paranasal sinuses. Occurrence in the periorbital region is a very rare event. In spite of their pleomorphic pattern the treatment is solely surgical excision. Haematogenic or loco-regional lymphogenic metastases are very rare. PATIENT: A 91 year old female patient presented because of a prominent tumour in the upper right periorbital region. As stated in the case history, the tumour had developed within the previous 6 months. The tumour measured about 3 x 4 cm. It was tight to resiliant and seemed to not be adherent to the underlying structures. Pain or hypesthaesia were not existent. Due to the mass of the tumour a ptosis was present. Additionally, there was a mechanical lack in the movement of the eyeball in the upper direction. The papilla was vital and differentiated. Visual acuity was decreased due to a mature cataract. CLINIC: Neither CT nor MRI could give a clue to the tumour entity. Infiltration of the periorbital structures or the eyeball could not be ruled out. A biopsy was classified as a malignant fibrous tumour with the subclassification of an atypical fibroxanthoma. The final histopathological classification after total excision of the tumour showed perineural growth and angioinvasion. Therefore the tumour classification was changed to pleomorphic malignant fibrous histiocytoma (undifferentiated pleomorphic sarcoma). The defect was closed with a full skin graft on the basis of a galea periosteal flap. CONCLUSION: The histopathological examination could not provide the correct diagnosis initially. Immunohistochemical stainings (Vimentin) were carried out to characterise the tumour. This underlines that even with state of the art procedures the classification of neoplasias can be very difficult. In the process of finding the right diagnosis sometimes a change from benign to malignant occurs and alters the treatment regime.