Joseph M. Huryn

Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bisphosphonate therapy

Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past 5 years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate (IVBP) therapy, but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. To further categorize risk factors associated with ONJ and potential clinical outcomes of this condition, we performed a retrospective study of patients with metastatic bone disease treated with intravenous bisphosphonates who have been evaluated by the Memorial Sloan-Kettering Cancer Center Dental Service between January 1, 1996 and January 31, 2006. We identified 310 patients who met these criteria. Twenty-eight patients were identified as having ONJ at presentation to the Dental Service and an additional 7 patients were subsequently diagnosed with ONJ. Statistically significant factors associated with increased likelihood of ONJ included type of cancer, duration of bisphosphonate therapy, sequential IVBP treatment with pamidronate followed by zoledronic acid, comorbid osteoarthritis or rheumatoid arthritis, and benign hematologic conditions. Our data do not support corticosteroid use or oral health as a predictor of risk for ONJ. Clinical outcomes of patients with ONJ were variable with 11 patients demonstrating improvement or healing with conservative management. Our ONJ experience is presented here.

Dental extractions in the irradiated head and neck patient: a retrospective analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria, and end results.

Abstract Background This study was designed to use our institutional experience with irradiated head and neck patients to evaluate 1) dental extraction incidence and sequelae; 2) those patients who developed osteoradionecrosis via extraction and the efficacy of hyperbaric oxygen therapy; and 3) guidelines for extraction protocols in this population. Materials and methods A group of 1,194 patients with a history of radiation to the head and neck, who were evaluated and treated in the Dental Service at Memorial Sloan-Kettering Cancer Center, were reviewed. The 187 who required dental extractions were analyzed using patient demographics, tumor location, staging, histopathology, radiation dosage, field, and timing, dental extraction indications, location, surgical methods, and sequelae. Results Almost 85% of the patients reviewed did not require extraction. Only 4 of those who underwent extractions at Memorial Sloan-Kettering Cancer Center developed osteoradionecrosis. Conclusions The use of multidisciplinary team communications and careful extraction selection by prognosis and symptomatology regardless of preexisting dental pathologies, atraumatic extraction procedures, and meticulous follow-up can lower both extraction and osteoradionecrosis rates.

Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis

BackgroundThe present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling.MethodsThe gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR.ResultsHierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only GLUT3 showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). PACE4mRNA expression failed to show correlation with any of the relevant parameters.ConclusionThe characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.

Osseointegrated implants and functional prosthetic rehabilitation in microvascular fibula free flap reconstructed mandibles

The mandibulectomy deformity can be alleviated by immediate mandibular reconstruction using the microvascular fibula free flap. Before the advent of microvascular reconstruction, conventional and maxillofacial prosthetic rehabilitation offered limited success after surgery due to the failure to reestablish the bony foundation and soft tissues (tongue, floor of mouth, vestibule) anatomically and physiologically. With proper multidisciplinary pretreatment planning and postoperative treatment, osseointegrated implants can be strategically placed in patients with these reconstructed mandibles to restore occlusal and masticatory function. The records of seven patients who underwent reconstructive surgery and osseointegrated implants were reviewed, with an emphasis on the variety of prosthetic designs and principles used to maximize long-term efficiency and preservation of tissues.

Resection and immediate microvascular reconstruction in the management of osteoradionecrosis of the mandible

Management of osteoradionecrosis (ORN) remains a difficult and challenging problem. The traditional approach using debridement, antibiotics, and occasionally hyperbaric oxygen is usually successful in treating minimal ORN. However, when bone and soft‐tissue necrosis is extensive, the conservative approach usually requires intensive care over a long period of time and often yields unsatisfactory functional and cosmetic results.

Effects of therapy on dentofacial development in long-term survivors of head and neck rhabdomyosarcoma: The memorial sloan-kettering cancer center experience

Purpose To describe potential effects of multimodality therapy on dental and facial development in long-term survivors of head and neck rhabdomyosarcoma. Patients and Methods The medical records of all patients aged 20 years or less presenting between 1985 and 1996 with a diagnosis of rhabdomyosarcoma and treated by protocol were reviewed. Head and neck rhabdomyosarcoma patients who were followed in the Dental Service and were alive and free of disease with at least a 5-year follow-up were included in the review. Ten patients satisfied the inclusion criteria and form the basis of this report. The median age at diagnosis of the 10 patients was 4.3 years (range 10 months to 19.5 years). All patients were treated with chemotherapy, two patients underwent surgery, and all but one patient received external beam radiation therapy. Results Clinical or radiographic dentofacial abnormalities were observed in 8 of the 10 (80%) patients. Abnormalities included enamel defects, bony hypoplasia/facial asymmetry, trismus, velopharyngeal incompetency, tooth/root agenesis, and disturbance in root development. Bony hypoplasia and disturbance in root formation were the most common findings. Conclusions Multimodality therapy for head and neck rhabdomyosarcoma can result in dentofacial abnormalities that affect the patients quality of life. The care of the long-term survivor requires a multidisciplinary approach, including early involvement of the dental team.

Intravenous bisphosphonate–related osteonecrosis of the jaw: Long-term follow-up of 109 patients

OBJECTIVE We report long-term follow-up of patients with intravenous bisphosphonate-related osteonecrosis of the jaw (BRONJ). STUDY DESIGN Medical and dental histories, including type and duration of bisphosphonate treatment and comorbidities, were analyzed and compared with clinical course of 109 patients with BRONJ at Memorial Sloan-Kettering Cancer Center Dental Service. RESULTS Median onset of BRONJ in months was 21 (zoledronic acid), 30 (pamidronate), and 36 (pamidronate plus zoledronic acid), with a significant difference between the pamidronate plus zoledronic acid and zoledronic acid groups (P = .01; Kruskal-Wallis). The median number of doses for BRONJ onset was significantly less with zoledronic acid (n = 18) than pamidronte plus zoledronic acid (n = 36; P = .001), but not pamidronate alone (n = 29). An association between diabetes (P = .05), decayed-missing-filled teeth (P = .02), and smoking (P = .03) and progression of BRONJ was identified through χ(2) test. CONCLUSIONS This long-term follow-up of BRONJ cases enhances the literature and contributes to the knowledge of BRONJ clinical course.

Efficacy of speech aid prostheses for acquired defects of the soft palate and velopharyngeal inadequacy—clinical assessments and cephalometric analysis: A Memorial Sloan-Kettering Study

Restoration of speech after surgical resection for oropharyngeal cancer traditionally includes maxillofacial prosthetic intervention. Relatively few publications with objective speech outcomes exist. The purpose of this study was to evaluate speech outcome relative to the size of the surgical defect, the type of speech prosthesis, and the height and position of the speech bulb in relation to the posterior pharyngeal wall in the nasopharynx.

Molecular profiling of oral microbiota in jawbone samples of bisphosphonate-related osteonecrosis of the jaw

Oral Diseases (2012) 18, 602–612 Objective:  Infection has been hypothesized as a contributing factor to bisphosphonate (BP)‐related osteonecrosis of the jaw (BRONJ). The objective of this study was to determine the bacterial colonization of jawbone and identify the bacterial phylotypes associated with BRONJ. Materials and methods:  Culture‐independent 16S rRNA gene‐based molecular techniques were used to determine and compare the total bacterial diversity in bone samples collected from 12 patients with cancer (six, BRONJ with history of BP; six, controls without BRONJ, no history of BP but have infection). Results:  Denaturing gradient gel electrophoresis profile and Dice coefficient displayed a statistically significant clustering of profiles, indicating different bacterial population in BRONJ subjects and control. The top three genera ranked among the BRONJ group were Streptococcus (29%), Eubacterium (9%), and Pseudoramibacter (8%), while in the control group were Parvimonas (17%), Streptococcus (15%), and Fusobacterium (15%). H&E sections of BRONJ bone revealed layers of bacteria along the surfaces and often are packed into the scalloped edges of the bone. Conclusion:  This study using limited sample size indicated that the jawbone associated with BRONJ was heavily colonized by specific oral bacteria and there were apparent differences between the microbiota of BRONJ and controls.

Sarcomas With Cic-rearrangements are a Distinct Pathologic Entity With Aggressive Outcome: A Clinicopathologic and Molecular Study of 115 Cases.

CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available. However, most studies reported so far include small series with limited follow-up information, which preclude a more definitive assessment. The present work investigates the clinicopathologic features of a large cohort of sarcomas with CIC gene rearrangement, to define their clinical presentation, morphologic spectrum, and outcome. Our study further examines the overall survival of the CIC-positive cohort compared with a control group of EWSR1-rearranged Ewing sarcoma matched for age and stage. The study cohort included 115 patients, with a mean age of 32 years and a slight male predominance. Most tumors occurred in the soft tissue (86%), predominantly deep-seated and equally divided among trunk and extremity, followed by visceral locations (12%) and rarely in the bone (3%). Microscopically, most tumors showed round to ovoid cytomorphology but half of the cases showed also focal areas of spindling and epithelioid/rhabdoid phenotype, with frequent myxoid stromal changes. Variable CD99 reactivity was seen in 84% cases, with a diffuse pattern only in 23% of cases, whereas nuclear WT1 was seen in 92%. A CIC-DUX4 fusion was detected in 57% of cases, with either DUX4 on 4q35 (35%) or on 10q26 in 25 (22%) cases. No FOXO4 gene rearrangements were present in 39 cases tested. Clinical follow-up was available in 57 patients, with a 5-year survival of 43%, which was significantly lower than the 77% 5-year survival in the control Ewing sarcoma group (P=0.002). Our findings show that CIC-DUX4 sarcomas occur most commonly in young adults within the somatic soft tissues, having a wide spectrum of morphology including round, epithelioid and spindle cells, and associated with an aggressive clinical course, with an inferior overall survival compared with Ewing sarcoma. The results support the classification of CIC-rearranged tumors as an independent molecular and clinical subset of small blue round cell tumors distinct from Ewing sarcoma.