Faculty Bibliography

BACKGROUND: : Tumors of the mandible are complex, often requiring replacement of bone, soft tissue, and teeth. The fibula flap has become a routine procedure in large tumors of the jaw, providing bone and soft tissue at the time of the resection. In current practice, dental reconstruction is delayed for 3 to 6 months, leaving the patient without teeth in the interim. This can be disfiguring and anxiety provoking for the patient. METHODS: : In this article, the authors present three patients with benign tumors of the mandible who underwent virtually guided resection, fibula reconstruction, and insertion of an implant-retained dental prosthesis in one operation. In addition, the authors report their early experience using this technique in the maxilla. RESULTS: : The authors present a case series of three patients with benign mandibular tumors and one patient with a benign maxillary tumor who underwent total reconstruction using computer-aided design and computer-aided manufacturing technology in a single stage. CONCLUSIONS: : In the right situation, total mandibular reconstruction is possible in a single stage. This is demonstrated by the successful outcomes of these patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: : Therapeutic, V.

Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering "Green" chemoprevention. Cancer Prev Res; 6(5); 410-8. (c)2013 AACR.

PURPOSE: Promoter hypermethylation has been recently proposed as mean for HNSCC detection in salivary rinses. In a prospective study of high-risk population, we showed that EDNRB promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. EXPERIMENTAL DESIGN: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was performed and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by Quantitative methylation-specific PCR. RESULTS: HOXA9, EDNRB and DCC methylation were associated (p=0.012; p<0.0001; p=0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (p=0.0003) or DCC (p=0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (p=0.008; p=0.026; p=0.046) and multivariate analysis (p=0.012; p=0.037; p=0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with similar AUC (0.61, 95%CI=0.60-0.81) when compared to EDNRB and DCC combined AUC (0.60, 95%CI=0.51-0.69), sensitivity of 46% and specificity of 72%. Combination of EDNRB, DCC and CRC was optimal AUC (0.67, 95%CI=0.58-0.76). CONCLUSION: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.

Oral medicine is a specialized area of study within the scope of dental medicine. This discipline is often viewed as the crossroads between medicine and dentistry and has become integral in both pre-and postdoctoral dental education. Oral medicine is recognized as a dental specialty throughout most of the world and currently represents an emerging specialty in the United States. Historically, oral medicine has been loosely defined in the United States without a clear consensus definition. Recent published studies regarding international oral medicine postdoctoral programs and clinical practice have helped to provide more specific information regarding oral medicine from many perspectives. This article will review the literature relevant to defining oral medicine in the United States and present a new definition of this important discipline based on recent studies.

The growing number of individuals with comorbidities experiencing care transitions represents a challenge to the current health care system. A qualitative study of empirical literature, using the Dimensional Analysis approach, was conducted to elucidate the theoretical underpinnings of the phenomenon of individuals with comorbidities undergoing care transitions. The findings were arranged in a novel schematic demonstrating that the relationship among individual attributes, comorbidities, and care processes informed the individual's risk for adverse outcomes. This schematic is useful for future nursing research studies evaluating innovative programs implemented to improve health outcomes among vulnerable populations undergoing care transitions.

Object Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). Results Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Conclusions Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

Objective This contemporary review aims to categorize the disease entities that cause bilateral parotid enlargement and to develop a question-based algorithm to improve diagnosis of bilateral parotid masses. Data Sources A PubMed search for bilateral and parotid showed 818 results. Of these, 68 relevant studies were reviewed to compile a list of disease processes that can cause bilateral parotid enlargement. Review Methods A total of 22 diseases entities were reviewed. The disease processes were initially grouped into 6 categories based on etiology: sialadenosis, infection, neoplasm, autoimmune, iatrogenic, and miscellaneous. For each lesion, the incidence, history, and physical examination were compiled in a matrix. Conclusion After reviewing the matrix, it was clear that grouping diseases based on specific history and physical findings limits the differential diagnosis. The most important factors included disease incidence, timing of onset, nodular or diffuse, pain, and overlying skin changes. With this algorithm, the differential diagnosis can be limited from 28 to 7 or fewer likely diagnoses for a given presentation. Implications for Practice Bilateral parotid disease has a wide differential diagnosis with an expanding number of available tests. An algorithm, based solely on data obtained from the history and physical examination in the first patient encounter, may reduce the differential and aid the clinician in deciding on further workup and treatment. Following the algorithm presented here should allow the clinician to arrive at a diagnosis rapidly without ordering unnecessary tests and wasting resources.

Background Whole brain radiation therapy (WBRT) reduces local recurrence in patients after surgical resection of brain metastases without improving overall survival. Involved field radiation therapy (IFRT) has been used at our center to avoid delayed neurotoxicity associated with WBRT in well-selected patients with surgically resected single brain metastases. The purpose of this study was to evaluate the long-term outcomes of these patients. Methods Thirty-three consecutive patients with single brain metastases from a known primary tumor were treated with gross total resection followed by IFRT between 2006 and 2011. The postoperative surgical bed was treated to 40.05 Gy in 15 fractions of 2.67 Gy with conformal radiation therapy. Patients received serial MRIs and neurological exams in follow-up. Surgery, WBRT, or stereotactic radiosurgery was performed as salvage treatment when necessary. Results The median follow-up was 16 months (range: 2-65 months). Local control, distant brain recurrence-free survival, and overall survival at 12 and 24 months were 90.3% and 85.8%, 60.7% and 51.4%, and 65.6% and 61.5%, respectively. Overall, 5 (15%) patients developed recurrence at the resection cavity, and 13 (39%) patients experienced recurrence at a new intracranial site. Two patients received WBRT, 8 stereotactic radiosurgery, 2 surgery, and 2 both chemotherapy and IFRT as salvage. Four patients died from CNS disease progression. Conclusion For patients with newly diagnosed single brain metastases treated with surgical resection, postoperative IFRT to the resection cavity achieves reasonable rates of local control and is an excellent alternative to WBRT.

The anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab has been shown to improve survival in patients with metastatic non-CNS melanoma. The purpose of this study was to investigate the efficacy of CTLA-4 inhibitors in the treatment of metastatic melanoma with limited brain metastases treated with stereotactic radiosurgery (SRS). Between January 2008 and June 2011, 58 patients with limited brain metastases from melanoma were treated with SRS with a median dose of 20 Gy delivered to the 50% isodose line (range, 15-20 Gy). In 25 patients, ipilimumab was administered intravenously at a dose of 3 mg/kg over 90 min every 3 weeks for a median of four doses (range, 1-8). Local control (LC), freedom from new brain metastases, and overall survival (OS) were assessed from the date of the SRS procedure. The median LC, freedom from new brain metastases, and OS for the entire group were 8.7, 4.3, and 5.9 months, respectively. The cause of death was CNS progression in all but eight patients. Six-month LC, freedom from new brain metastases, and OS were 65, 35, and 56%, respectively, for those who received ipilimumab and 63, 47, and 46% for those who did not (P=NS). Intracranial hemorrhage was noted in seven patients who received ipilimumab compared with 10 patients who received SRS alone (P=NS). In this retrospective study, administration of ipilimumab neither increased toxicity nor improved intracerebral disease control in patients with limited brain metastases who received SRS.