Eric R. Carlson

The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws.

PURPOSE Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a poorly understood pathologic entity from the standpoints of its nomenclature, frequency, pathogenesis, and best method of treatment. In particular, numerous recommendations have been made for treatment involving nonsurgical therapy. It is the purpose of this article to specifically examine the success of resection of the necrotic bone in the mandible and maxilla in these patients. PATIENTS AND METHODS We identified 103 sites of BRONJ in 82 patients. Of these sites of osteonecrosis, 32 were in the maxilla and 71 were in the mandible. Of the patients, 30 were taking an oral bisphosphonate medication whereas 52 were taking a parenteral bisphosphonate medication. Resection was performed in 95 sites of osteonecrosis in 74 patients, whereas 8 sites diagnosed in 8 patients were not resected. A total of 27 sites of BRONJ were resected in patients treated with oral bisphosphonates, and 68 sites of BRONJ were resected in patients treated with parenteral bisphosphonates. RESULTS Of the 95 resected sites, 87 (91.6%) healed in an acceptable fashion with resolution of disease. Of 27 resected sites in patients taking an oral bisphosphonate medication, 26 (96.3%) healed satisfactorily, with refractory disease developing in 1 site. Of 68 resected sites in patients taking a parenteral bisphosphonate medication, 61 (89.7%) healed satisfactorily, with refractory disease developing in 7 sites. All 29 patients (100%) undergoing resection of the maxilla related to either an oral or parenteral bisphosphonate healed acceptably. The 8 patients who had the development of refractory disease did so with a range of 7 to 250 days postoperatively (mean, 73 days). Of the 8 sites of refractory disease, 6 developed after a marginal resection of the mandible for BRONJ. Three sites of new primary disease developed in 2 patients postoperatively. Both patients were taking a parenteral bisphosphonate medication. Histologic examination of the resected specimens identified malignant disease in 4 specimens in 3 patients. CONCLUSION Resection of BRONJ permits acceptable healing in patients taking an oral bisphosphonate medication. In addition, resection of BRONJ of the maxilla in patients taking an oral or parenteral bisphosphonate medication follows a predictable course with regard to healing. Resection of BRONJ of the mandible in patients taking a parenteral bisphosphonate medication follows a variable postoperative course, although a high degree of success is realized. Surgeons should consider resection of necrotic bone of the maxilla and mandible that develops in patients taking bisphosphonate medications. In addition, refractory disease can be successfully managed with a more aggressive resection, specifically, a segmental resection of the mandible after a marginal resection of the mandible where refractory disease developed.

Isolation of Actinomyces species and Eikenella corrodens from patients with chronic diffuse sclerosing osteomyelitis.

Cultures from 26 patients with chronic diffuse sclerosing osteomyelitis of the mandible were studied. In most cases there was a mutualistic infection involving any one of the known human Actinomyces species together with Eikenella corrodens. In a few cases, Arachnia species were substituted for Actinomyces and gram-negative anaerobes for E corrodens. The specific culture protocol used to identify these organisms from clinical specimens is described. Taxonomic and experimental evidence that supports an infectious etiology are presented.

Nutritional Considerations for Head and Neck Cancer Patients: A Review of the Literature

PURPOSE Approximately 35% to 60% of all patients with head and neck cancer are malnourished at the time of their diagnosis because of tumor burden and obstruction of intake or the anorexia and cachexia associated with their cancer. The purpose of this article is to provide a contemporary review of the nutritional aspects of care for patients with head and neck cancer. MATERIALS AND METHODS A literature search was performed in Medline, Cochrane, and other available databases from 1990 through 2012 for the clinical effectiveness of nutritional support, treatment modalities, and methods of delivery in relation to patients with head and neck malignancies. Human studies published in English and having nutritional status and head and neck cancer as a predictor variable were included. Randomized controlled trials, meta-analyses, prospective clinical studies, and systemic reviews were selected based on their relevance to the abovementioned subtitles. The resultant articles were analyzed and summarized into the definition, impact, assessment, treatment, and modes of administration of nutrition on the outcome of patients with head and neck cancer. RESULTS Articles were reviewed that focused on the etiology and assessment of malnutrition and current nutritional treatments for cancer-induced anorexia and cachexia. Two hundred forty-eight articles were found: 2 clinical trials, 10 meta-analyses, 210 review studies, and 26 systematic reviews. Because of the lack of prospective data, a summative review of the conclusions of the studies is presented. CONCLUSION Nutritional interventions should be initiated before cancer treatment begins and these interventions need to be ongoing after completion of treatment to ensure optimal outcomes for patients. A nutritional assessment must be part of all comprehensive treatment plans for patients with head and neck cancer. Alternative medical interventions, such as immune-enhancing nutrients or anticytokine pharmaceutical agents, also may be effective as adjuvant therapies, but more research is needed to quantify their clinical effect.

The potential for HIV transmission through allogeneic bone a review of risks and safety

Over the past two decades, oral and maxillofacial surgeons have gained a greater appreciation for the biology of allogeneic bone healing, resulting in a dramatic increase in its indications and use. Unfortunately, this time period has also ushered in near epidemic proportions of HIV-infected persons, some of whom might be considered as potential donors of allogeneic bone. As this article will discuss, surgeons and tissue bank teams alike must be aware of the clinical and serologic criteria associated with an acceptable donor. Only in this way can contamination-free specimens be obtained and surgically implanted.

Does reducing CT artifacts from dental implants influence the PET interpretation in PET/CT studies of oral cancer and head and neck cancer?

In patients with oral head and neck cancer, the presence of metallic dental implants produces streak artifacts in the CT images. These artifacts negate the utility of CT for the spatial localization of PET findings and may propagate through the CT-based attenuation correction into the PET images. In this study, we evaluated the efficacy of an algorithm that reduces metallic artifacts in CT images and the impact of this approach on the quantification of PET images. Methods: Fifty-one patients with and 9 without dental implants underwent a PET/CT study. CT images through the patients dental implants were reconstructed using both standard CT reconstruction and an algorithm that reduces metallic artifacts. Attenuation correction factors were calculated from both sets of CT images and applied to the PET data. The CT images were evaluated for any reduction of the artifacts. The PET images were assessed for any quantitative change introduced by metallic artifact reduction. Results: For each reconstruction, 2 regions of interest were defined in areas where the standard CT reconstruction overestimated the Hounsfield units (HU), 2 were defined in underestimated areas, and 1 was defined in a region unaffected by the artifacts. The 5 regions of interest were transferred to the other 3 reconstructions. Mean HU or mean Bq/cm3 were obtained for all regions. In the CT reconstructions, metallic artifact reduction decreased the overestimated HUs by approximately 60% and increased the underestimated HUs by approximately 90%. There was no change in quantification in the PET images between the 2 algorithms (Spearman coefficient of rank correlation, 0.99). Although the distribution of attenuation (HU) changed considerably in the CT images, the distribution of activity did not change in the PET images. Conclusion: Our study demonstrated that the algorithm can enhance the structural and spatial content of CT images in the presence of metallic artifacts. The CT artifacts do not propagate through the CT-based attenuation correction into the PET images, confirming the robustness of CT-based attenuation correction in the presence of metallic artifacts. The study also demonstrated that considerable changes in CT images do not change the PET images.

Oral maxillary squamous carcinoma: An indication for neck dissection in the clinically negative neck

This multicenter study was undertaken to characterize the metastatic behavior of oral maxillary squamous carcinoma and to determine the role of selective neck dissection.

Odontogenic ameloblast-associated protein nature of the amyloid found in calcifying epithelial odontogenic tumors and unerupted tooth follicles.

We have previously reported that the amyloid found in three patients with calcifying epithelial odontogenic tumors (CEOT) was composed of N-terminal fragments of a putative 153-residue protein specified by a gene designated FLJ20513 now known to represent exons 5 through 10 of the odontogenic ameloblast-associated protein (ODAM) locus that encodes a 279-residue polypeptide. Confirmation of the amyloidogenic potential of ODAM has resulted from analyses of four other cases where we found, in addition, a 74-residue segment specified by exon 4. Through preparation of ODAM-related synthetic peptides, it was possible to localize the fibril-forming region of this molecule, as well as generate a monoclonal antibody that reacted specifically with the amyloid associated with CEOT. Notably, we also detected green birefringent congophilic material in unerupted tooth follicles – a precursor of CEOT – and demonstrated through immunologic and chemical analyses the ODAM nature of the deposits. Our studies have provided further evidence for this unique form of odontogenic amyloid that we provisionally designate “AODAM”.

p16 Immunohistochemistry Can Be Used to Detect Human Papillomavirus in Oral Cavity Squamous Cell Carcinoma

PURPOSE Human papillomavirus (HPV) is of etiologic significance in the development of oral squamous carcinoma and is noted to result in p16 overexpression. Identification of HPV is clinically important because the presence of HPV has prognostic and epidemiologic associations. Detection of HPV by polymerase chain reaction (PCR) is expensive and not widely accessible. The authors examined p16 immunohistochemistry (IHC) as a surrogate marker for high-risk HPV and its use as an alternative test to PCR. PATIENTS AND METHODS A retrospective cohort of patients with oral squamous cell carcinoma underwent surgery and then analysis with p16 IHC and HPV PCR. The p16 IHC staining intensity was graded from 0 to 3+, and these results were compared with PCR. Descriptive and frequency statistics were performed by comparing HPV PCR results with p16 IHC, patient age, gender, and outcome. RESULTS Eighty-one cases were included in the study. Forty-four study patients were men and 37 were women (mean age, 63.9 yr). Forty-five cases (55.6%) had 0 staining, 22 cases (27.2%) had 1+ staining, and 7 cases (8.6%) had 2+ staining. Seven cases (8.6%) had 3+ staining, all of which were positive for HPV serotype 16 by PCR. Three of 7 HPV PCR-positive cases had keratinization typical of an oral cavity location and not the basaloid growth of HPV oropharyngeal tumors. There was a statistical correlation (P < .001) among HPV PCR positivity, 3+ staining, and younger age. CONCLUSION p16 3+ staining correlates with HPV PCR positivity. p16 IHC is a technically simple and widely available test, and this study establishes the use of p16 IHC as an alternative test to HPV PCR. Given the clinical significance of HPV in oral squamous carcinoma, p16 IHC should be performed in all cases and included in the pathology report.

Management of antiresorptive osteonecrosis of the jaws with primary surgical resection.

In 2003, medical and dental professionals began to encounter an increasing number of patients exhibiting exposed necrotic bone of the jawswith underlying diagnoses of metastatic cancer and osteoporosis that were classified as bisphosphonate-related osteonecrosis of the jaws (BRONJ). The authors of anecdotal reports and peer-reviewed publications around that time concluded that the management of patients with BRONJwas extremely difficult because their surgical debridements were not completely effective in eradicating the necrotic bone. Therefore, it was recommended that surgical treatment be performed only in those patients who were symptomatic, such as those with a pathologic fracture associated with their osteonecrosis, in which case a segmental resection was indicated. As such, conservative therapy became the accepted method of management of this disease process based primarily on the experience and opinions of 2 reputable and highly respected members of the specialty of oral and maxillofacial surgery. In fact, these recommendations set the stage for the recapitulation of non–evidencebased conservative treatment recommendations in subsequently published peer-reviewed articles on this subject. BRONJ has since been classified under the umbrella of antiresorptive osteonecrosis of the jaws (ARONJ) owing to the fact that osteonecrosis of the jaws also has been observed in patients exposed to human receptor activator for nuclear factor-kB ligand inhibitor medications. It is the purpose of this Perspective to proclaim resection as the optimum and definitive management of stage I, II,

Comprehensive Review of Bisphosphonate Therapy: Implications for the Oral and Maxillofacial Surgery Patient

J a m r o i T u b o p Bisphosphonate medications have a broad array of ndications including the use of intravenous bisphoshonate medications in the management of hypercalemia of malignancy, skeletal-related events associted with bone metastases from solid tumors, and in he management of bone lesions in the setting of ultiple myeloma. Newer indications for intravenous isphosphonate medications include their use in steoporosis as alternatives to oral bisphosphonates. ral bisphosphonates are approved to treat osteopoosis. They prevent from 40% to 70% of fractures of he hip, spine, and other osteoporotic fractures. While steoporosis is the most common reason for the adinistration of oral bisphosphonates, their use in the reatment of Paget’s disease and osteogenesis imperecta has been described, and the use of bisphosphoate medications in the management of giant cell esions of the jaws has also been recommended. No oubt, the quality, and often the length of life of atients with many types of bone disease, is enhanced n patients treated with bisphosphonate medications. Until approximately 2003, cases of osteonecrosis of he jaws were primarily noted in patients with osteoyelitis and osteoradionecrosis, and associated with rominent bony protuberances, such as exostoses, ori, and mylohyoid ridges that underwent traumatic r spontaneous exposure to the oral cavity. Osteonerosis of the jaws has also been noted in patients with ome rare infections, diabetes and other endocrinopahies, as well as in some patients with cancer being reated with chemotherapy. In 2003 and 2004, oral and axillofacial surgeons were the first to recognize the resence of exposed and necrotic bone of the jaws in atients who underwent extraction of a tooth or placeent of an endosseous implant and who were taking isphosphonate medications. The identification of steonecrosis of the jaws in patients taking bisphospho© d