PURPOSE

Osteonecrosis of the jaw (ONJ) has been observed recently in patients with cancer who are receiving intravenous bisphosphonate (BP) therapy. The incidence of BP-associated ONJ has not been well established. The purpose of this study was to determine the incidence of ONJ in a cohort of patients with multiple myeloma (MM), breast cancer (BC), or prostate cancer (PC) who were receiving BP therapy.

PATIENTS AND METHODS

A retrospective chart review was performed. Medical record numbers were identified by ICD-9 codes: 203.0, 203.01, 174.9, and 185.0 for active MM, MM in remission, BC, and PC, respectively. Patients were included if they were evaluated and/or treated between January 1, 2000, and December 31, 2005, and had received zoledronic acid and/or pamidronate. Patients were excluded if they had a history of radiation therapy to the jaws or of tumors or cysts. ONJ was defined as clinical evidence of "exposed necrotic bone" in the mouth.

RESULTS

Through evaluation of 1,086 patient medical records, it was determined that 447 subjects met the inclusion criteria: 11 of 292 patients with MM (3.8%; 95% confidence interval [CI], 1.6%, 6.0%) had ONJ, as did 2.5% of 81 patients with BC (0%, 6.9%) and 2.9% of 69 patients with PC (0%, 5.9%).

CONCLUSION

The incidence of ONJ associated with intravenous BPs was at least 3.8 per 100 patients with MM, 2.5 per 100 patients with BC, and 2.9 per 100 patients with PC during the 5-year study period. The next phase of this study involves assessment of risk factors that differentiate these patients from those treated with BPs who do not develop ONJ.

The alveolar surface comprises >99% of the internal surface area of the lungs. At birth, the fetal lung rapidly converts from a state of net fluid secretion, which is necessary for normal fetal lung development, to a state in which there is a minimal amount of alveolar liquid. The alveolar surface epithelium facing the air compartment is composed of TI and TII cells. The morphometric characteristics of both cell types are fairly constant over a range of mammalian species varying in body weight by a factor of approximately 50,000. From the conservation of size and shape across species, one may infer that both TI and TII cells also have important conserved functions. The regulation of alveolar ion and liquid transport has been extensively investigated using a variety of experimental models, including whole animal, isolated lung, isolated cell, and cultured cell model systems, each with their inherent strengths and weaknesses. The results obtained with different model systems and a variety of different species point to both interesting parallels and some surprising differences. Sometimes it has been difficult to reconcile results obtained with different model systems. In this section, the primary focus will be on aspects of alveolar ion and liquid transport under normal physiologic conditions, emphasizing newer data and describing evolving paradigms of lung ion and fluid transport. We will highlight some of the unanswered questions, outline the similarities and differences in results obtained with different model systems, and describe some of the complex and interweaving regulatory networks.

Current methods including the use of various biological and synthetic sealants are ineffective in the closure of intraoperative air leaks that often occur during cardiothoracic surgeries, resulting in a decreased quality of life for patients. We present the development of a novel lung air leak sealant using tissue engineered cell sheets. In contrast to previous materials such as fibrin glue, these bioengineered cell sheets immediately and permanently seal air leaks in a dynamic fashion that allows for the extensive tissue contraction and expansion involved in respiration, without any postoperative recurrences. Additionally, we demonstrate that mesothelial cells migrate to cover the transplanted cells sheets, thereby confirming excellent biocompatibility and integration with the host tissues. Finally, we present the use of skin fibroblasts as an effective and readily available autologous cell source that can be easily applied. This study shows for the first time, the development of an immediate and permanent lung air leak sealant, suitable for future clinical applications.

Clinical trials are often stopped prematurely by Data and Safety Monitoring Boards, sponsors, or the investigators for reasons such as unexpected harmful effects of the intervention, clear lack of benefit, or futility due to sluggish recruitment or an unexpectedly low outcome rate in the placebo group. Planning for closeout, however, usually does not begin until after the trial is well underway. This article describes the experience of the Heart and Estrogen/progestin Replacement Study (HERS) investigators when data from the first year of follow-up revealed a clear but non-significant divergence in outcome rates between the treatment groups, and planning for early closure was initiated. Three advantages of beginning early to plan for closeout are described and approaches to planning closeout are suggested.