Paul A.J. Russo

Bis-phossy jaws - high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw.

INTRODUCTION Bisphosphonates (BPs) have transformed our ability to treat certain malignancies, osteoporosis and hypercalcaemia. This class of drug is assumed to be well tolerated by most. There are some important caveats to this assumption, however, one of the significances being the risk of osteonecrosis of the jaw (ONJ). MATERIAL AND METHODS This multi-centre retrospective study examined the role of different BPs on the development of ONJ, its clinical presentation and the efficacy of various treatment modalities, comparing these findings with the available literature. RESULTS A total of 78 patients from 17 centres were identified with ONJ. A majority of patients identified with ONJ had used Pamidronate or Zoledronate (93.6%) intravenously. 94.9% of patients had received BP in the course of treatment for malignancies and a majority had also received prior chemotherapy or exogenous steroids. 82.1% of patients had received BP for more than 1 year. The mean time from the introduction of BP to the development of ONJ in 24 patients from our department was 31.8 months. CONCLUSIONS The most common intraoral manifestation was exposed necrotic jawbone. Tooth extractions and oral surgical intervention appear to place patients on BP therapy at risk of ONJ, especially after intravenous BP treatments. ONJ proved in this study to be remarkably refractory to treatment, with radical resection being the only curative approach. We recommend that all patients receive necessary dental treatment prior to commencing BP therapy.

Diagnostic and therapeutic procedures for management of melanoma during pregnancy: risks for the fetus?

In the treatment of malignant melanoma, various stage‐dependent diagnostic and therapeutic procedures are widely accepted.The situation becomes more complicated in pregnant women due to potential hazardous side effects to the fetus. We report on a 36‐year‐old woman, who was admitted with a high‐risk malignant melanoma on the right cheek. Prior to surgery we performed computed tomography (CT)‐scans that were unremarkable with the exception of “two small cysts of the uterus” The primary melanoma was excised and a sentinel node biopsy was performed under general anesthesia using radioactive tracers. Afterwards, adjuvant therapy with interferon alpha 2b was initiated. Five weeks later our patient reported that she was pregnant with twins in their eleventh week of gestation, although she previously denied several questions regarding a potential pregnancy. She declined the offer of an abortion and elected to continue with the interferon treatment against our medical advice. In the 36th week of gestation, she developed regional lymph node metastases. Consequently, labor was induced, resulting in the delivery of healthy twins. Six months later our patient developed lung metastases. Despite several chemotherapy regimens, she died one year later. An interdisciplinary approach to obtaining informed consent and managing female high risk melanoma patients with potential or present pregnancy is presented.

Individualized therapy of disseminated cancer using malignant melanoma as a model.

Approximately 20 to 25% of patients with malignant melanoma will die of metastatic disease. The current standards of care for advanced metastatic melanoma (stage IV, AJCC classification) are poor. To date, randomized trials have failed to demonstrate that one regimen is better than another. It is therefore crucial that patients with disseminated malignant melanoma be recruited into clinical trials. In recent years, there have been impressive advances in our knowledge of the biology and nature of cancer development and the growth and progression to metastasis. The approach “from bench to bedside” is current reality in the treatment of several solid tumors and hematologic malignancies. The identification of new targets to facilitate individualized melanoma treatment is now an important issue. This article will give an overview of recent developments in clinical trials of targeted therapies in metastatic melanoma patients.

Antimicrobial Peptide Coating of Dental Implants: Biocompatibility Assessment of Recombinant Human Beta Defensin-2 for Human Cells

PURPOSE Artificial materials such as dental implants are at risk of bacterial contamination in the oral cavity. Human beta defensins (HBDs), small cationic antimicrobial peptides that exert a broad-spectrum antibacterial function at epithelial surfaces and within some mesenchymal tissues, could probably help to reduce such contamination. HBDs also have protective immunomodulatory effects and have been reported to promote bone remodeling. The aim of this study, therefore, was to investigate the influence of recombinant HBD-2 on the proliferation and survival of cells in culture. MATERIALS AND METHODS Human mesenchymal stem cells (hMSCs), human osteoblasts, human keratinocytes (control), and the HeLa cancer cell line (control) were incubated with recombinant HBD-2 (1, 5, 10, or 20 μg/mL). Cell proliferation and cytotoxicity were evaluated via a water-soluble tetrazolium salt (WST-1) and lactate dehydrogenase assays, respectively. RESULTS HBD-2 was not toxic in any tested concentration to hMSCs, osteoblasts, keratinocytes, or HeLa cells. Furthermore, proliferation of hMSCs and osteoblasts increased after treatment with HBD-2 at all tested concentrations, and keratinocyte proliferation increased when treated at 20 μg/mL. In contrast, HeLa cancer cells were not affected by HBD-2 as tested. CONCLUSIONS HBD-2 is not only biocompatible but also promotes proliferation of hMSCs, osteoblasts, and keratinocytes in culture. Further investigation of HBD-2 functional surface coating of artificial materials is recommended.