Mark D. DeLacure

Motility-related proteins as markers for head and neck squamous cell cancer

Hypothesis Increased cell motility is a hallmark of cancer cells. Proteins involved in cell motility may be used as molecular markers to characterize the malignant potential of tumors.

Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma

BackgroundHalf of the patients with head and neck squamous cell carcinoma (HNSCC) can be expected to fail therapy, indicating that more aggressive treatment is warranted for this group. We have developed a novel risk model that can become a basis for developing new treatment paradigms. Here we report on the performance of our model in a new multicenter cohort. DesignEligible patients from 3 institutions (Montefiore Medical Center, University of Manitoba, and New York University Medical Center) were identified and pathology slides from their resection specimens were reviewed by Margaret Brandwein-Gensler; risk category was assigned as previously published. Kaplan-Meier analysis was performed for disease progression and survival. Cox proportional hazards regression was performed, adjusted for potential confounders. A teaching module was also developed; attending pathologists were asked to score coded slides after a lecture and multiheaded microscope teaching session. Agreement was assessed by calculating Cohen unweighted κ coefficients. ResultThe validation cohort consisted of 305 patients, from the above institutions, with 311 primary HNSCC of the oral cavity, oropharynx, and larynx. The median follow-up period for all patients was 27 months. Risk category predicts time to disease progression (P=0.0005), locoregional recurrence (P=0.013), and overall survival (P=0.0000) by Kaplan-Meier analysis. High-risk status is significantly associated with decreased time to disease progression, adjusted for clinical confounders (P=0.015, hazard ratio 2.32, 95% confidence interval 1.18-4.58) compared with collapsed intermediate and low-risk groups. We also demonstrate substantial interrater agreement (κ=0.64), and very good rater agreement when compared with the standard (κ=0.87). ConclusionsWe demonstrate significant predictive performance of the risk model in a new cohort of patients with primary HNSCC, adjusted for confounders. Our training experience also supports the feasibility of adapting the risk model in clinical practice.

Changes in abundance of oral microbiota associated with oral cancer

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.

Comparison of quality of life outcomes in laryngeal cancer patients following chemoradiation vs. total laryngectomy

OBJECTIVE : To evaluate quality of life issues in patients with laryngeal cancer after treatment with either chemoradiation or total laryngectomy and radiation therapy. METHODS : Forty-nine patients with a history of stage II-IV laryngeal squamous cell carcinoma treated primarily with either chemoradiation or by total laryngectomy with postoperative radiation completed the University of Washington Quality of Life instrument, version 4. Patients were identified on a volunteer basis in an academic university head and neck clinic setting. Each patient completed the above instrument, and statistical analysis was performed by Wilcoxon and X 2 , tests. RESULTS : Instruments were completed by all 49 patients: 15 patients who underwent primary chemoradiation and 34 patients who underwent a total laryngectomy followed by radiation. Domains reported in both treatment groups without significant differences were appearance, activity, recreation, moods, taste, saliva, anxiety, and general questions. However, there were significant differences between the 2 groups in the domains of pain, swallowing, chewing, speech, and shoulder function. The laryngectomy patients reported greater impairment of speech (P = 0.001), and shoulder function (P = 0.018), whereas the chemoradiation patients suffered from greater pain, difficulty swallowing (P = 0.061), and problems chewing (P = 0.027). CONCLUSIONS : Most patients with laryngeal cancer, whether treated primarily with chemoradiation or total laryngectomy, reported excellent functional outcomes and health-related quality of life. Pain, swallowing, chewing, saliva, and shoulder function were recorded as significant factors affecting their daily quality of life.

Reconstruction of segmental mandibular defects by distraction osteogenesis for mandibular reconstruction

Distraction osteogenesis is an established technique for the lengthening of long bones and correction of selected craniofacial deformities. Regenerate osteoid bone matrix formed during the distraction phase is malleable and can recreate the three‐dimensional form of native bones. Animal experiments and early clinical experience have confirmed that distraction osteogenesis can be used for the reconstruction of segmental bony defects. Herein we discuss the principles of distraction osteogenesis in reference to reconstruction of segmental bony defects and report its clinical application of the mandible continuity defects.

Malignant Solitary Fibrous Tumor of the Tongue

Solitary fibrous tumor is a generally benign spindle-cell neoplasm that has been predominantly described in the visceral pleura and other serosal sites and is extremely rare in the head and neck area. We report the first known case of malignant solitary fibrous tumor of the tongue in a 57-year-old female patient who experienced rapid growth of a longstanding right anterior tongue mass, with associated dysphagia and dysarthria. Magnetic resonance imaging was suggestive of a low-flow vascular malformation not requiring preoperative embolization. The patient underwent partial peroral glossectomy for the excision of the tumor. Final pathology, however, was consistent with solitary fibrous tumor, characterized as malignant by histopathologic criteria, and the patient was returned for re-excision of the close surgical margins. The patient has experienced symptomatic improvement, and she remains free of recurrence 12 months later. All reports of solitary fibrous tumors of the oral cavity and 3 reports of the tongue tumors described in the literature to date represent benign lesions. To our knowledge, this is the first report of a malignant solitary fibrous tumor of the tongue. Presentation, differential diagnosis, criteria for malignancy, treatment, and possible prognostic implications of this rare entity are discussed.

Lymphoscintigraphy, Sentinel Lymph Node Biopsy, and Mohs Micrographic Surgery in the Treatment of Merkel Cell Carcinoma

Background. Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high incidence of occult nodal metastases. MCC is believed to be similar in natural history to thick or ulcerated melanomas in its propensity for locoregional recurrence and early lymph node metastasis. Studies have shown that nodal status is statistically correlated to survival in MCC. Radiolocalization and superselective lymph node biopsy is a recent technique that has been proven to be of great value in evaluating the status of occult lymph node disease in malignant melanoma and breast cancer patients. Objective. In previously untreated patients, an orderly progression of metastases is observed for both cutaneous carcinomas and malignant melanomas and is anticipated for MCC. Methods/results. We present two patients with MCC of the head and neck who underwent simultaneous Mohs micrographic surgery and sentinel lymph node biopsy with intraoperative radiolocalization. Conclusion. Sentinel lymph node biopsy and intraoperative lymphoscintigraphy may prove to be a useful technique in evaluating occult nodal involvement and in limiting the potentially unnecessary morbidity of more comprehensive lymph node dissections in MCC patients who do not yet have metastatic involvement.

The External Approach for Submucosal Lesions of the Larynx

OBJECTIVE: The surgical excision of benign submucosal lesions of the larynx can be performed using a variety of techniques including direct laryngoscopy and external approaches. We propose that small submucosal lesions of the larynx can be removed via the external approach without a tracheotomy. STUDY DESIGN: Retrospective chart review. SETTING: Six patients at The Long Island Jewish Medical Center and at the New York University School of Medicine underwent an external approach for the removal of benign submucosal laryngeal lesions without tracheotomies. Lesions included a mixed laryngopyocele, an internal laryngopyocele, a mixed laryngocele, a paraganglioma, a neurilemmoma and a lymphoma. Follow-up ranged from 1 to 9 years. RESULTS: All patients were female with an average age of 72. No patient required a tracheotomy. One patient remained intubated for 24 hours postoperatively to ensure an adequate airway. Mild dysphagia was noted in all patients, but it was short-lived and did not require alternate methods of alimentation. There have been no recurrences of disease. CONCLUSION: The external approach without tracheotomy allows for good exposure with minimal functional disability for the removal of benign sub-mucosal lesions of the larynx.

Acellular dermal composite allografts for reconstruction of the radial forearm donor site.

Purpose:Since its description in the 1970s, the radial forearm free flap has earned a clearly defined role in the armamentarium of reconstructive head and neck surgery. Three decades later, the donor site remains an intrinsic drawback primarily due to its esthetic impact, although functional morbidity is significant in a minority. These points do not outweigh significant advantages but are occasionally reasons for the choice of alternative flaps. Modifications evolved in an effort to improve these undesirable features include primary closure, rotation-advancement, proximal paddle placement, full-thickness skin graft (FTSG) and suprafascial dissection. We describe a novel technique of engineering a composite graft of cadaveric acellular dermal matrix and autologous split-thickness skin graft (STSG) for a better donor-site closure. Methods:From December 1995 to August 2003, 23 patients underwent radial forearm reconstruction of head and neck defects. Control patients (Group I; n = 5) had donor sites closed by conventional STSG technique (0.014–0.016 inch). In 18 patients (Group II), the donor site was closed with a composite technique (dermal allograft, 0.020–0.030 inch, and an ultrathin STSG, 0.0080 inch). Both groups of patients were retrospectively studied for comparative defects. Contralateral upper extremities also served as controls. All patients underwent a standardized functional examination of the donor and contralateral extremities, as well as an outcome questionnaire. All extremities were photographed for visual comparison by the author. Results:Three of the 5 group I patients were available for follow-up, which averaged 64 months (60–72 months). Thirty-three percent had a decrease in functional parameters and 67% complained of paresthesia. Patient satisfaction was 3.5/5. Six of the 18 patients were excluded from Group II due to insufficient follow-up or inability to follow. Follow-up averaged 8 months (1–24 months). Functional parameters in all patients were comparable to the contralateral extremity, except in 1 patient. In this case, a 0.030-inch allograft was used which never revascularized, inhibiting wrist motion. Other patients exhibited excellent range of motion of the wrist and fingers. This was the only patient in this group that exhibited paresthesia of the donor site. Patient satisfaction was 4.6/5. Esthetic results were extremely gratifying as judged by the author. Esthetic results were better than those observed in Group I. Conclusions/Significance:Composite grafting with acellular dermal matrix and STSG provides a comparable (trending to superior) result with traditional STSG for the treatment of radial forearm graft donor sites. Even if functionally equivalent, it is esthetically superior and therefore a technique warranting further investigation.

The changing demographics of head and neck squamous cell carcinoma in the United States.

Objectives/Hypothesis: Head and neck squamous cell carcinoma (HNSCCA) has declined in the United States since the late 1970s. During this time, substantial immigration from other countries has occurred, and the average lifespan has increased. We tested the hypothesis that these trends have altered the HNSCCA patient population.