Is bisphosphonate-related osteonecrosis of the jaw an infection? A histological and microbiological ten-year summary.

The role of infection in the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is poorly understood. Large-scale epidemiological descriptions of the histology and microbiology of BRONJ are not found in the literature. Herein, we present a systematic review of BRONJ histology and microbiology (including demographics, immunocompromised associations, clinical signs and symptoms, disease severity, antibiotic and surgical treatments, and recovery status) validating that infection should still be considered a prime component in the multifactorial disease.

A new assay to screen for head and neck squamous cell carcinoma using the tumor marker metallopanstimulin.

OBJECTIVE: To date, no serologic marker has proven effective as a diagnostic test for head and neck squamous cell carcinoma (HNSCC). Levels of metallopanstimulin (MPS), as measured by a difficult to reproduce radioimmunoassay, are significantly elevated in untreated HNSCC patients. Our objective was to develop a simpler MPS assay. METHODS: Serum was obtained from HNSCC patients through Institutional Review Board approved protocols at the Penn State University College of Medicine and healthy volunteers donating blood at the hospital blood bank from 2000 to present. Serum MPS was immunoprecipitated, slot blotted, and Western blotted. MPS levels were quantified by densitometry. RESULTS: Forty-eight blood donors and 45 known HNSCC patients were studied. The MPS level was 14 ng/mL +/- 1 (SEM) for blood donors and 36 ng/mL +/- 3 (SEM) for known HNSCC patients. The difference was statistically significant (P < 0.0001). CONCLUSION: Slot blot analysis of MPS is a safe, effective, and reproducible assay that may be used to screen for HNSCC in high-risk populations.

The cost-effectiveness of fluorodeoxyglucose 18-F positron emission tomography in the N0 neck.

BACKGROUND: Although surgery and radiation are effective treatments of regional lymphatics for classification N0 head and neck squamous cell carcinoma (HNSCC) patients, both have morbidities that could be avoided in approximately 70% of patients without lymph node disease with better diagnostic information. 18-F fluoro-2-deoxyglucose positron emission tomography (FDG-PET) has shown promise in detecting subclinical lymph node disease, but its cost and availability have limited its use. Here, we sought to determine whether the use of FDG-PET was cost-effective as part of a treatment strategy for classification N0 HNSCC patients. METHODS: The cost-effectiveness of proceeding from classification of N0 by computed tomography to a PET scan was estimated using standard methods of economic evaluation. Costs were for a large, Midwestern university medical center. Probabilities were computed from a review of the literature. Utilities were obtained by a time-tradeoff method, and life expectancy was estimated using the Surveillance, Epidemiology, and End Results database. Outcomes measures were cost per year of life saved and cost per quality-adjusted life-year. RESULTS: Modified radical neck dissection was associated with the lowest morbidity (utility [u] = 0.93), and radical neck dissection plus radiation was associated with the highest (u = 0.68). Life expectancy was estimated to be 5.9 and 11.5 years for patients with and without lymph node disease, respectively. The incremental cost-effectiveness ratio for the PET strategy was $8718 per year of life saved, or $2505 per quality-adjusted life-year. CONCLUSIONS: A diagnostic and treatment strategy that proceeds from classification of N0 to a PET scan is cost-effective. Prospective studies that evaluate this strategy are important to assure that these simulation results are realized in clinical practice.

The use of lymphoscintigraphy and PET in the management of head and neck melanoma.

OBJECTIVES: Lymphoscintigraphy with sentinel node dissection and 18 fluoro-2-deoxyglucose positron emission tomography (PET) are being used independently in the management of many intermediate and thick melanomas of the head and neck. We report a series of patients with melanoma of the head and neck with Breslow depths greater than 1.0 mm and clinically negative regional nodes that were evaluated prospectively with PET and lymphoscintigraphy. STUDY DESIGN AND SETTING: Between July 1, 1998 and December 30, 2000 PET scans were obtained preoperatively on 18 patients undergoing resection of head and neck melanoma. Lymphoscintigraphy and sentinel node dissection was performed. Resection of the primary lesion was then carried out with adequate margins and the defects were reconstructed. RESULTS: Sentinel node(s) were found in 17/18 patients (94.4%); 5/18 (27.8%) of cases had metastases. PET detected nodal metastasis preoperatively in 3 patients (16.7%), one of which had a positive sentinel node dissection. CONCLUSION: PET and lymphoscintigraphy offer complimentary ways of evaluation for metastatic melanoma.

Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999.

BACKGROUND: After standard therapy for advanced head and neck carcinoma, 5-year survival rate is less than 50%. Our purpose was to develop a new treatment for advanced head and neck carcinoma by using preoperative chemotherapy. Long term efficacy and toxicity of induction paclitaxel and carboplatin is reported here. METHODS: Between 1994 and 1999, 62 consecutive patients with newly diagnosed head and neck carcinoma were treated with paclitaxel and carboplatin induction chemotherapy. Chemotherapy was administered every 21 days with 3 courses of paclitaxel (150-265 mg/m(2)) and carboplatin at a dose calculated using the Calvert formula area under the curve of 7.5. Patients who achieved complete or partial response at the primary received definitive radiation to the primary tumor and those with lymph node disease received neck dissection followed by radiation to the regional lymph nodes. Nonresponders received standard resection of primary tumor and draining lymph node basin followed by radiation. RESULTS: Sixty-two consecutive patients were treated. Seventy-four percent had Stage IV (according to the 5th edition of American Joint Committee on Cancer Staging manual) disease. The median duration of follow-up from initiation of chemotherapy was 64 weeks (range, 1-272 weeks). Overall complete plus partial response rate was 41 of 62 (66%). Responses were observed at all anatomic sites: oropharynx 20 of 33 (61%); hypopharynx 8 of 12 (67%); and larynx 13 of 17 (76%). Kaplan-Meier estimates of overall survival (OS), at 230 weeks, were significantly better in Stage IV oropharynx/hypopharynx responders than nonresponders (55% vs. 27%; P = 0.04). Of the variables evaluated in multivariate models, response at the primary tumor and lymph nodes were associated with improved disease free survival and OS. Organ preservation was achieved in 28 of 62 (45%) of patients at all anatomic sites: oropharynx 39%, hypopharynx 42%, larynx 59%. Seventeen of 28 (61%) patients had their primary organ site preserved for a mean duration of 78 weeks (range, 13-238 weeks). CONCLUSIONS: Induction paclitaxel and carboplatin was well tolerated. The response rate was encouraging considering most patients were Stage IV. Chemotherapy response identified a group with improved prognosis. Organ preservation was possible at all anatomic sites.

Comparison of Scientific Calipers and Computer-Enabled CT Review for the Measurement of Skull Base and Craniomaxillofacial Dimensions.

Traditionally, cadaveric studies and plain-film cephalometrics provided information about craniomaxillofacial proportions and measurements; however, advances in computer technology now permit software-based review of computed tomography (CT)-based models. Distances between standardized anatomic points were measured on five dried human skulls with standard scientific calipers (Geneva Gauge, Albany, NY) and through computer workstation (StealthStation 2.6.4, Medtronic Surgical Navigation Technology, Louisville, CO) review of corresponding CT scans. Differences in measurements between the caliper and CT model were not statistically significant for each parameter. Measurements obtained by computer workstation CT review of the cranial skull base are an accurate representation of actual bony anatomy. Such information has important implications for surgical planning and clinical research.

Cost considerations of converting to digital photography.

OBJECTIVES: To provide the practicing surgeon with data to make an informed economic decision regarding conversion from analog to digital photography. METHODS: A cost analysis of photography based on 35-mm vs digital platforms (low-, medium-, and high-cost hardware). RESULTS: Break-even thresholds for the investment in a digital platform of low, medium, and high costs were 3674, 15,789, and 34,000 images, respectively. CONCLUSION: Given the current excellent image quality and ongoing refinements in digital photography, a digital photography platform may be cost-effective for a busy facial plastic surgery practice.

Radioguided surgical advancements for head and neck oncology.

Radioguided surgery is an innovative means by which a radionuclide is used to preoperatively image and intraoperatively visualize a structure of interest to the surgeon for excisional biopsy. This technology has allowed a cost-effective, highly specific means by which to locate a structure (usually a lymph node) and access it for pathologic analysis. The result of radioguided surgery is increased specificity in tissue obtained for biopsy, minimal access incisions, and the reduction of inpatient hospital utilization. Radioguided surgery should not be confused with radiosurgery, which is the stereotactic application of external beam radiation, usually for intracranial tumors.

Green light photoplethysmography monitoring of free flaps.

BACKGROUND: Monitoring strategies have been developed to address the issue of detecting postoperative free flap ischemia in an effort to permit intervention and flap salvage. No one existing noninvasive method has been widely accepted in a clinical setting. Green light photoplethysmography (GLP) uses a diode to transmit green light into a tissue. Reflected light from hemoglobin in dermal capillary red blood cells is analyzed as light intensity along a frequency spectrum. A pure peak signal (1-2 Hz) is identified and provides a way to distinguish between perfused and nonperfused tissue. DESIGN: Prospective, blinded comparison. SUBJECTS: Sixty of 72 consecutive patients considered for free flap reconstruction were enrolled in a protocol to evaluate the efficacy of GLP. INTERVENTION: After free flap elevation, but before pedicle ligation, 120-second baseline measurements were obtained; 120-second measurements then occurred 5 minutes after the onset or release of individual venous or arterial occlusion. Signals were processed by fast Fourier transfer; a mean alternating current-direct current (AC/ DC) ratio was cultivated for each signal. All data were analyzed in a blinded fashion. RESULTS: The AC/DC ratio of GLP was statistically significant across all flap perfusion states (P<.001). Each condition resulted in a unique GLP signal within 5 minutes of manipulation of each vessel. CONCLUSIONS: Green light photoplethysmography with AC/DC ratio analysis provides a rapid, precise method with which to determine flap ischemia and can differentiate venous compromised and arterial compromised flaps almost immediately after the onset of an ischemic insult. It may provide a clinically useful tool for postoperative free flap monitoring.

Surveillance for recurrent head and neck cancer using positron emission tomography.

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.

Ankle-arm index as a screening examination for fibula free tissue transfer.

The frequent use of the fibula free flap for mandibular reconstruction has served as an impetus to develop a screening test for this flap. This would detect lower leg vascular disease that could jeopardize the flap or donor extremity. Data would allow a decision whether to pursue further lower leg imaging versus consideration of an alternative donor site. The ankle-arm index (AAI) was determined on a prospective series of 62 patients being considered for fibula free flap transfer. An AAI of less than 1.0 was found to be predictive of a high rate of lower leg vascular disease (by color flow Doppler imaging) that would jeopardize the flap or donor extremity. The AAI did not detect anomalous vasculature of the lower leg (N = 2). If the AAI is less than 1, an alternative donor site to the fibula should be considered, and if it is greater than 1, a color flow Doppler examination of the donor extremity is recommended.

Digital vs 35-mm photography. To convert or not to convert?

OBJECTIVES: To compare the quality of images generated from a conventional 35-mm camera with those generated from various digital cameras; and to note the costs of the cameras and ease of use. DESIGN: A prospective, randomised, independent analysis of specific facial images taken with a 35-mm camera and 3 digital cameras by 3 facial plastic surgeons who were blinded to camera type. SETTING: An academic medical center. SUBJECTS: Thirteen volunteer subjects ranging from age 27 to 58 years. MAIN OUTCOME MEASURES: The overall quality, focus, distortion, trueness of color, resolution, contrast, and presence of shadows were evaluated for each image. Attributes were scored on an ordinal scale of 1 to 5. A 1-way analysis of variance was used to test whether the average scores across cameras were significantly different. Results using analysis of variance did not differ from the results using a nonparametric Kruskal-Wallis test. When significant differences were found, the Duncan multiple range test was used to group significantly different scores. RESULTS: The null hypothesis that there is no difference between photographs taken with the various cameras was rejected (P < .001) for each of the image attributes. The images produced by the 35-mm camera (Nikon 6006) had the best overall quality, followed by the Olympus D600L, Kodak DCS 315, and Olympus D320L digital cameras. Differences in individual attributes between several of the cameras in each category were statistically significant (P < .05). CONCLUSIONS: The 35-mm camera produced the best overall image quality and ranked first for each of the individual attributes analyzed in this study. The Olympus D600L digital camera placed second in overall quality, but there was no statistically significant difference in focus, distortion, and resolution compared with the images generated by the 35-mm camera. The Olympus D600L digital camera also ranked second in color, contrast, and shadow. The Kodak DCS 315 and D320L digital cameras finished well behind the 35-mm camera in most categories. Although the 35-mm photographs were superior to the digital images, the surgeon should also consider other factors before selecting a system for photodocumentation of surgical results.

Overexpression of MPS antigens by squamous cell carcinomas of the head and neck: immunohistochemical and serological correlation with FDG positron emission tomography.

Survival from advanced primary or recurrent Squamous Cell Carcinoma (SCC) of the head and neck (H&N) is poor. More accurate detection of primary tumors and recurrence may provide ways to improve survival. No standard serum tumor marker is routinely used for surveillance of SCC-H&N. In this paper, we evaluated the performance characteristics of the MPS-H tumor marker test for the quantitative measurement of "MPS-H" heat-generated immunoreactive proteins and assessed the clinical utility of this marker in the detection and monitoring of SCC-H&N. In approximately 92% of the subjects having no evidence of SCC-H&N, the MPS-H levels were lower than 15 ng/mL. In 76% of patients having SCC-H&N at various stages (T1-T4), the MPS-H level was > 15 ng/mL (range: 20-200 ng/mL). In addition, we found a statistically significant correlation between PET positive cases and high MPS-H serum levels in SCC-H&N patients with recurrent disease. These results suggest that MPS-H may provide an initial screening test that would allow for selective PET imaging in these patients. Furthermore, we found that there was greater expression of MPS-1 in tumors of higher histological grades. Thus, in tumors with more histological aggressiveness there is more MPS-1, indicating the potential usefulness of this marker in prognosis for SSC-H&N. Considering the immunohistochemical, serological, and FDG-PET data presented here, and the compelling need to expedite the early diagnosis of primary and recurrent epithelial malignancies of the head and neck, we are further evaluating the system of MPS antigens in a large patient population as a tool for the early serologic and histologic diagnosis of SCC-H&N.

Preoperative color flow Doppler imaging for fibula free tissue transfers.

Fibula osteocutaneous free tissue transfer to reconstruct the oromandibular complex is a widely recommended technique following oncologic resection. Preoperative determination of adequate perfusion to the donor extremity is necessary to assure lower extremity viability after flap harvest. Vascular variations and/or peripheral arterial occlusive disease (PAOD) may exist whereby sacrifice of peroneal vessels can cause ischemia to the lower leg and foot. Additionally, variability of cutaneous perforators can make the fibula skin paddle viability unpredictable. Color flow Doppler (CFD) is a reliable modality to preoperatively assess the lower extremity in fibula osteocutaneous free tissue transfer patients. Prospective CFD examination of 38 consecutive patients (76 legs) considered for fibula free flap reconstruction was performed. A standard protocol was designed to evaluate the lower extremity vasculature and identify cutaneous perforators with CFD. Findings were studied with respect to flap choice, operative findings, and reconstruction outcomes. Number of cutaneous perforators and their impact on skin paddle design were also recorded. Color flow Doppler's ability to image peroneal vessels as well as determine collateral and distal perfusion were effective. CFD accurately identified bilateral vascular anomalies in one patient (2.6%), and significant arterial disease in three patients (7.9%). Cutaneous perforators were also accurately mapped and confirmed intraoperatively in 31 patients. In several instances, the information provided by the CFD examination altered flap selection, 4/38 patients (10.5%), or skin paddle design, 5/32 patients (15.6%). Color flow Doppler allowed successful fibula transfer in all the free flap candidates with normal exams. It has the advantages of low cost and no morbidity. CFD allows for accurate mapping of fibula cutaneous perforators which facilitates skin paddle design. We recommended the use of preoperative CFD in all patients being considered for fibular free flap surgery.

Spectral analysis of photoplethysmograms from radial forearm free flaps.

OBJECTIVE: Photoplethysmography utilizes a green-light-emitting diode to transmit light into a tissue. Reflected light from hemoglobin in dermal capillary red blood cells is received by a photo detector and is analyzed as light intensity along a frequency spectrum. This method of analysis allows for the removal of "noise" above (stray light and alternating current [AC]) and below (room vibrations and respiratory motion) the peak signal (1 to 2 Hz) and results in a means to distinguish between perfused and nonperfused tissues. METHODS: Twenty-two of 30 consecutive radial forearm free flap (RFFF) patients were enrolled in an approved human studies protocol to collect descriptive data for RFFFs that were perfused, arterial occluded, and venous occluded. The protocol was performed following completion of flap elevation and prior to pedicle ligation, flap inset, and microvascular anastomoses. Six 90-second measurements per flap were obtained (n = 132), processed by fast Fourier transform (FFT), and analyzed by blinded reviewers to determine their state of perfusion. Signal was collected 5 minutes after the onset or release of individual vessel occlusion. RESULTS: The reviewers' interpretations were compared with the status of the pedicle and analyzed for sensitivity (0.96), specificity (0.95), and positive predictive value (0.98). CONCLUSIONS: FFT analysis of photoplethysmograms from RFFF patients provides an accurate and rapid means for determining RFFF pedicle vessel patency. Photoplethysmography may provide a clinically useful tool for postoperative perfusion monitoring of free flaps in the future.

Comparison of cost and function in reconstruction of the posterior oral cavity and oropharynx. Free vs pedicled soft tissue transfer.

OBJECTIVE: To compare the cost and functional results of free and pedicled soft tissue reconstruction after posterior oral cavity and oropharyngeal extirpation. DESIGN: Retrospective study of 53 consecutive patients undergoing extirpation with primary soft tissue reconstruction from January 1, 1991, to December 31, 1995. Median follow-up was 298 days. SETTING: Academic tertiary care medical center. INTERVENTION: Twenty-four patients underwent reconstruction with a pedicled pectoralis major myocutaneous flap (PMMF); 29 patients, with a fasciocutaneous free flap (FF) (27 radial forearm, 1 lateral arm, and 1 scapular). MAIN OUTCOME MEASURES: Direct (inpatient hospital resources used and monetary costs) and intangible (post-operative complications and function) costs. RESULTS: Operative time was longer for FF reconstructions (P = .003), but both patient groups had similar intensive care unit and hospital stays. Treatment cost for FF reconstructions was $41,122, compared with $37,160 for PMMF reconstructions (P = .003). This difference was due to increased professional fees for FF reconstruction (P < .001) which was offset by intangible cost differences. The PMMF group tended toward an increased rate of flap-related complications, compared with the FF group. At last follow-up, 4 patients in the FF group (15%) and 3 in the PMMF group (15%) had their tracheotomy. In contrast, 17 (85%) patients in the PMMF group and 11 (39%) patients in the FF group required enteral tube feedings (P = .002). Also, 18 (64%) patients in the FF group were eating at least a soft diet compared with 6 (30%) patients in the PMMF group (P = .02). CONCLUSIONS: Comparison of direct costs reveals only a modest difference in reconstruction costs that is outweighed by the intangible costs of PMMF reconstruction. The functional benefits of FF reconstruction appear to justify its slight increased expense and its use rather than PMMF reconstruction after extirpation in the posterior oral cavity and oropharynx.