Alex M. Mlynarek

Serum Proteomic Approach for the Identification of Serum Biomarkers Contributed by Oral Squamous Cell Carcinoma and Host Tissue Microenvironment

The lack of serum biomarkers for head and neck carcinoma limits early diagnosis, monitoring of advanced disease, and prediction of relapses in patients. We conducted a comprehensive proteomics study on serum from mice bearing orthotopic human oral squamous cell carcinomas (OSCC) with distinct invasive phenotypes. Matched established cell lines were transplanted orthotopically into tongues of RAG-2/gamma(c) mice and mouse serum was analyzed by 2-dimensional-differential gel electrophoresis(2D-DIGE)/liquid chromatography (LC)-MS/MS and by online 2D-LC-MS/MS of iTRAQ labeled samples. We identified several serum proteins as being differentially expressed between control and cancer-bearing mice and between noninvasive and invasive cancer (p<0.05). Differentially expressed proteins of human origin included the epidermal growth factor receptor (EGFR), cytokeratins, G-protein coupled receptor 87, Rab11 GTPase, PDZ-domain containing proteins, and PEST-containing nuclear proteins. Identified proteins of mouse origin included clusterin, titin, vitronectin, vitamin D-binding protein, hemopexin, and kininogen I. The levels of serum and cell secreted EGFR were further validated to match proteomic data regarding the inverse correlation with the invasive phenotype. In summary, we report a comprehensive patient-based proteomics approach for the identification of potential serum biomarkers for OSCC using an orthotopic xenograft mouse model.

Lateral neck radiography versus direct video rhinoscopy in assessing adenoid size.

OBJECTIVE To evaluate the usefulness of adynamic lateral neck radiographs and dynamic video rhinoscopy in assessing adenoid size and the relationship of these methods to associated symptoms and thus the severity of the disease. METHODS Children with suspected adenoid hypertrophy underwent standard lateral neck soft tissue radiographs: the percentage of airway occlusion, adenoid to nasopharynx (AN) ratio, airway to soft palate ratio, and adenoid thickness were assessed by a radiologist. The percentage of airway closure was assessed by direct fibre-optic rhinoscopy in an ear, nose, and throat clinic. Associated clinical symptoms were assessed by parents using a standardized questionnaire, evaluating the severity of symptoms (snoring, sleep apnea, mouth breathing, and otitis media) to give a total symptom score out of 16. RESULTS Nonparametric statistical analysis using Spearmans correlation coefficients was performed on 32 patients. There was a weak correlation, which approaches significance, between the percentage of airway occlusion assessed by fibre-optic rhinoscopy and the total symptom score (r = .344, p = .054). However, this correlation becomes significant when the frequency of otitis media is omitted (r = .367, p = .039). There was also a significant correlation between airway occlusion assessed by rhinoscopy and the percentage of airway occlusion as determined by lateral neck radiography (r = .431, p = .014). There was no correlation between any of the measurements taken by lateral soft tissue neck radiography and total symptom score. CONCLUSION Dynamic video rhinoscopy is more accurate at assessing adenoid hypertrophy, and the percentage of airway occlusion, as estimated by video rhinoscopy, is better correlated to the severity of symptoms than are values obtained by lateral neck radiography.

Recurrent Oral Cancer: Current and Emerging Therapeutic Approaches

Oral cavity cancer (OCC) is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.

Radiotherapy versus surgery for early T1-T2 glottic carcinoma.

OBJECTIVES To compare surgery and radiotherapy as treatments for early T1-T2 glottic cancer in terms of local and regional control, complications, cost, and voice outcome. METHODS Retrospective comparative review of 36 patients with T1 or T2 glottic carcinoma diagnosed between 1992 and 2003 at the McGill University Health Centre. Twelve patients postsurgery (group 1) and 26 patients postradiotherapy (group 2) were compared in terms of local and regional control and complications related to treatment. The costs of surgery and radiotherapy, including all personnel and equipment, were estimated. A cross-sectional study was undertaken of 11 patients with a history of T1 or T2 glottic carcinoma: 5 patients postsurgery, 4 patients postradiotherapy, and 2 patients postradiotherapy and surgery. Vocal fold function and voice quality were assessed by an otolaryngologist using videostroboscopy and a standardized questionnaire (Voice Handicap Index) and by an experienced speech-language pathologist using the Visipitch II computer program (Kay Elemetrics Corp., Lincoln Park, NJ). RESULTS Retrospective study: The recurrence rate following primary treatment was 37.5% for group 1 and 22% for group 2. Group 1 patients presented with 25% of local complications (vocal fold scars) and no systemic complications. Patients in group 2 presented with local and systemic complications: 35% for local and 27% for systemic. One patient had mild carotid stenosis, and one patient had mild esophageal stenosis. The cost of treatment with radiotherapy was five times higher than the cost of surgery. Cross-sectional study: Vocal fold function assessed by videostroboscopy was superior in group 2. However, patients in group 1 scored higher on the subjective (Voice Handicap Index questionnaire) and objective (Visipitch parameters) voice assessments. CONCLUSION Surgery and radiotherapy are both very effective in terms of local and regional control for early glottic carcinoma. However, surgery tends to be more cost-effective, with less complications and possibly a better voice outcome.

Reconstruction of cheek defects: a review of current techniques.

Purpose of reviewThe article discusses the fundamental principles of cheek reconstruction and summarizes recently published techniques and reviews in the field. Recent findingsReconstruction of the cheek is a complex endeavour. Patient, defect, and potential donor site factors must be carefully considered in the restoration of cheek form and function. Fortunately the surgeon, each with his or her own personal preferences and experience, has a wealth of techniques available from which to choose. New flaps and techniques are described including recent reviews of traditional techniques. Examples include a modification to the Mustardé flap, an axial pedicled flap from the radix nasi region, a technique of superficial musculoaponeurotic system plication to achieve primary closure of large defects, and reviews of the submental island flap, the subcutaneous cervicofacial flap, the medial sural artery perforator flap, and the anterolateral thigh flap. SummarySurgical innovation and conscientious assessments of traditional techniques continue to advance the field of cheek reconstruction towards improved aesthetic and functional outcomes.

Congenital mid-line cervical cleft: case report and review of literature

Congenital Mid-line Cervical Cleft (CMCC) is a rare but interesting congenital anomaly of the neck that is frequently misdiagnosed. Much controversy exist regarding its aetiology. Embryologically, the occurrence of CMCC is thought to be due to many hypotheses that include impaired mid-line fusion of the first or second branchial arches, exteriorisation of a thyroglossal duct remnant, and or increased pressure in the cervical area from the pericardial roof in the developing embryo. Histologically, the cleft usually consists of a stratified keratinized squamous epithelium with hyperkeratosis, dermal fibrosis and little or no skin appendages. Associated clinical features could include thyroglossal duct cysts, cleft lip/mandible/sternum, cervical contractures, mandibular spurs, microgenia and or bronchogenic cysts. In this article we present a patient with CMCC. An extensive review of the literature is also included.

Angiotensin-converting enzyme inhibitor-induced unilateral tongue angioedema

Angioedema, also known as angioneurotic edema or Quincke’s disease, is a localized transient swelling of sudden onset that can occur in the face, lips, tongue, hands, feet, and gastrointestinal system. Angiotensin-converting enzyme (ACE) inhibitors have been implicated in multiple cases of angioedema, with the oral region being the most common site of presentation. 1,2 Tongue edema has been reported to be one of the risk factors leading to airway compromise. 3 In this article we present a case of unilateral tongue angioedema induced by Vasotec (enalapril) and review the literature pertaining to this disease. To our knowledge, there are no reported cases in the English literature describing this unilateral form of tongue edema. CASE REPORT

Comparison of the Incidence of Postoperative Hypocalcemia following Total Thyroidectomy vs Completion Thyroidectomy

Objective To study the rate of postoperative hypocalcemia following completion thyroidectomy (CT), in comparison with the hypocalcemia rate following total thyroidectomy (TT). Study Design and Setting A retrospective study, performed at the McGill University Thyroid Cancer Center, Montreal, Quebec, Canada, from 2007 to 2012. Subjects and Methods Medical records of adult patients undergoing CT and TT operated by a single surgeon were reviewed. Data were extracted for demographics, postoperative calcium levels, surgical logs, and final surgical pathology. Hypocalcemia was defined as corrected serum calcium level ≤1.90 mmol/L, with concurrent serum parathyroid hormone <8 ng/L, and/or any signs or symptoms of hypocalcemia. Results There were 68 CTs and 146 TTs. Transient hypocalcemia occurred in 1 of 68 (1.5%) and 18 of 146 (12.5%) patients in the CT and TT groups, respectively. The rate of hypocalcemia was significantly lower in the CT compared with the TT group (P = .02). In both groups, there were no cases of permanent hypocalcemia. Conclusion The risk of transient of hypocalcemia in patients undergoing CT is significantly lower than the rate of hypocalcemia in patients undergoing TT.

Heat Generation During Ablation of Porcine Skin With Erbium:YAG Laser vs a Novel Picosecond Infrared Laser

IMPORTANCE Despite significant advances in surgery, most surgical tools remain basic. Lasers provide a means of precise surgical ablation, but their clinical use has remained limited because of undesired thermal, ionizing, or acoustic stress effects leading to tissue injury. A novel ultrafast, nonionizing, picosecond infrared laser (PIRL) system has recently been developed and is capable, in theory, of ablation with negligible thermal or acoustic stress effects. OBJECTIVE To measure and compare heat generation by means of thermography during ablation of ex vivo porcine skin by conventional microsecond-pulsed erbium:YAG (Er:YAG) laser and picosecond infrared laser (PIRL). DESIGN AND SETTING This study was conducted in an optics laboratory and used a pretest-posttest experimental design comparing 2 methods of laser ablation of tissue with each sample acting as its own control. INTERVENTION Ex vivo porcine skin was ablated in a 5-mm line pattern with both Er:YAG laser and PIRL at fluence levels marginally above ablation threshold (2 J/cm² and 0.6 J/cm², respectively). MAIN OUTCOMES AND MEASURES Peaks and maxima of skin temperature rises were determined using a thermography camera. Means of peak temperature rises were compared using the paired sample t test. Ablation craters were assessed by means of digital microscopy. RESULTS Mean peak rise in skin surface temperature for the Er:YAG laser and PIRL was 15.0°C and 1.68°C, respectively (P < .001). Maximum peak rise in skin surface temperature was 18.85°C for the Er:YAG laser and 2.05°C for the PIRL. Ablation craters were confirmed on digital microscopy. CONCLUSIONS AND RELEVANCE Picosecond infrared laser ablation results in negligible heat generation, considerably less than Er:YAG laser ablation, which confirms the potential of this novel technology in minimizing undesirable thermal injury associated with lasers currently in clinical use.

Dual-Energy CT Characteristics of Parathyroid Adenomas on 25-and 55-Second 4D-CT Acquisitions: Preliminary Experience.

Objective The objective of this study was to compare the dual-energy computed tomography (CT) characteristics of parathyroid adenomas (PAs), thyroid tissue, and lymph nodes (LNs) and assess whether the spectral information can improve distinction of these tissues. Methods Dual-energy CT scans from 20 patients with pathologically proven PAs were retrospectively evaluated, identifying 19 eligible PAs and region of interest analysis used for spectral characterization. Results There was a significant difference in multiple spectral parameters between PAs, LNs, and the thyroid gland (P < 0.05–0.0001). The greatest difference in spectral characteristics of PAs compared with that of LNs was on the 25-second acquisition, whereas the 55-second acquisition was better for distinguishing PAs from the thyroid gland. Conclusions Four-dimensional CT acquired in dual-energy CT mode has the potential to further enhance diagnostic accuracy for PA identification on individual phases of the perfusion study.