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.

Efficacy and safety of cold snare resection in preventive screening colonoscopy.

BACKGROUND AND AIM: Removal of polyps during colonoscopy effectively prevents the development of colorectal cancer. So far, snare resection with high frequency current with or without prior submucosal saline injection is the method of choice. The aim of this study was to evaluate the feasibility, safety, and outcome of cold snare resection during routine endoscopy. METHODS: In this prospective study, 522 patients undergoing outpatient colonoscopy were included. Cold snare resection for diminutive (< 6 mm), small (6 - 9 mm), and larger polyps (> 9 - 15 mm) was performed using a dedicated cold snare device (Exacto ® ) without prior submucosal injection. Outcome parameters included bleeding rate, perforation rate, procedure time, histologic evaluation of polyp margins, and success rates. The data were compared to a group of patients undergoing hot snare resection. RESULTS: Overall, 1233 polyps were removed using cold snare resection with an overall success rate of 99.4 %. All failures of cold snare resection occurred in the cecum (8/82, failure rate 9.8 %). In the remaining colon, the success rate was 100 %. Immediate post-polypectomy bleeding occurred in 0.49 % of all patients and was most frequently seen in polyps larger than 9 mm. The procedure time was significantly shorter using cold snare resection compared with hot snare resection (27.6 min vs. 35.7 min, P  < 0.01). CONCLUSION: Cold snare resection can be performed safely in outpatients for removal of small polyps in screening colonoscopy. It does not require prior saline injection and reduces procedure time without an increased risk of bleeding.

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.

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.

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.

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.

As compared to allopurinol, urate-lowering therapy with febuxostat has superior effects on oxidative stress and pulse wave velocity in patients with severe chronic tophaceous gout.

We prospectively evaluated whether an effective 12-month uric acid-lowering therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and/or vascular function. Patients with chronic tophaceous gout who did not receive active ULT were included. After clinical evaluation, serum uric acid levels (SUA) and markers of oxidative stress were measured, and carotid-femoral pulse wave velocity (cfPWV) was assessed. Patients were then treated with allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level ≤ 360 µmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and the cfPWV were measured again. Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function (estimated glomerular filtration rate <60 ml/min) in the febuxostat group. Uric acid lowering with either inhibitors of XO resulted in almost equally effective reduction in SUA levels. The both treatment groups did not differ in their baseline cfPWV (allopurinol group: 14.1 ± 3.4 m/s, febuxostat group: 13.7 ± 2.7 m/s, p = 0.80). However, after 1 year of therapy, we observed a significant cfPWV increase in the allopurinol group (16.8 ± 4.3 m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3 ± 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout. However, we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening. Since cardiovascular events are an important issue in treating patients with gout, this unexpected finding may have important implications and should be further investigated in randomized controlled trials.

Reaction of facial soft tissues to treatment with a Herbst appliance.

OBJECTIVE: The objective of this prospective longitudinal study was to investigate the reaction of facial soft tissues to treatment with a Herbst appliance. We aimed to quantify three-dimensionally (3D) the isolated effect of the Herbst appliance and volume changes in the lip profile. PATIENTS AND METHODS: The 3D data of the facial soft tissues of 34 patients with skeletal Class II (17 female and 17 male, mean age 13.5 ± 1.8 years) were prepared in a standardized manner immediately before (T1) and after (T2) treatment with a Herbst appliance. Anthropometric evaluation was carried out in sagittal and vertical dimensions. To quantify volume changes, pretherapeutic and posttherapeutic images were superimposed three-dimensionally and the difference volumes calculated. Following testing for normal distribution, a statistical analysis was carried out using the paired t test. RESULTS: We observed ventral development of the soft tissues of the lower jaw with flattening of the profile curvature and anterior displacement of the sublabial region in a total of 27 patients. Anterior facial height was lengthened and the facial depth at the lower jaw increased. The largest percentage changes were noted in the lip profile, with a reduction in the red margin of the upper lip and an increase in lower lip height. We also observed a reduction of the sublabial fold in conjunction with a simultaneous increase in volume. CONCLUSION: The influence of the Herbst appliance on the facial soft tissues is expected to result in a positive treatment outcome, particularly in patients with a convex profile, a retrusive lower lip, and a marked sublabial fold. We observed a broad clinical spectrum of individual reactions in the facial soft tissues. It is, thus, not possible to detect a linear relationship between the Herbst treatment and soft tissue changes, making soft tissue changes difficult to predict.

[Secondary synovial chondromatosis of the ankle joint]. / Sekundäre synoviale Chondromatose des oberen Sprunggelenks.

Synovial chondromatosis of the ankle is a rare condition, particularly secondary chondromatosis. In view of a possible traumatic pathogenesis, chondromatosis should be kept in mind in daily trauma and orthopedics practice. Diagnostic imaging gives a first indication. The key to differentiating between the primary and secondary forms is histological identification. This case shows the necessity of exact differentiation, even in cases of a causal link with a specific injury.

E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung.

BACKGROUND: Interactions of endothelial selectins with tumour cell glycoconjugates have been shown to have a major role in tumour cell dissemination in previous experiments. However, experiments validating this observation were limited in value, as 'metastases' in these experiments were artificially induced by i.v. injection rather than developed spontaneously as in true metastases. METHODS: Endothelial (E) and platelet (P)-selectin-deficient severe combined immunodeficient (scid) mice were generated and human HT 29 colon cancer cells were subcutaneously inoculated in these mice and in wild-type scid mice. Tumour growth, spontaneous metastasis formation in the lung and adherence of HT29 cells to E- and P-selectin under flow were determined. RESULTS: The number of metastases decreased by 84% in E- and P-selectin-deficient scid mice, compared with wild-type scid mice. The remaining 16% metastases in the E- and P-selectin-deficient scid mice grew within the pulmonary artery and not in the alveolar septae as they did in wild-type scid mice. Flow experiments indicate that tumour cells roll and tether on an E- and P-selectin matrix similar to leukocytes; however, firm adhesion is mainly mediated in E-selectin. CONCLUSION: Our results indicate that E- and P-selectins have a crucial role in spontaneous metastasis formation. As the human HT 29 colon cancer cells are positive for the lectin Helix pomatia agglutinin (HPA), which identified the metastatic phenotype in earlier clinical studies, these results are of particular clinical relevance.

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.

[Development of a specialised paediatric palliative home care service]. / Die Entwicklung einer spezialisierten ambulanten pädiatrischen Palliativversorgung.

In Germany annually 1,500-3,000 children die from life-limiting diseases. Symptoms and course of disease differ considerably depending on the character of the underlying disease. Due to the desire of the children and their families to spend the end of life at home a paediatric palliative home care service was founded at the university children's hospital of Duesseldorf. In the last 20 years a specialised paediatric palliative team evolved from an unstructured voluntary activity. Prospective aims are an area-wide professional supply of all paediatric palliative patients and the improvement of the cooperation with the resident paediatrician and paediatric palliative nursing services. Furthermore the establishment of networks as well as a proper communication among the professionals is inalienable.

[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.