Samir S. Khariwala

The “New” Head and Neck Cancer Patient—Young, Nonsmoker, Nondrinker, and HPV Positive: Evaluation

Objective The near epidemic rise of the incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) presents the practitioner with a “new” head and neck cancer patient, vastly different from those with the traditional risk factors who formed the basis of most practitioners’ training experience. Accordingly, a thorough and disease-specific evaluation process is necessitated. This article will review the evaluation of the HPV-related cancer patient, including a review of the HPV-positive oropharyngeal cancer epidemic from the surgeon’s perspective, evaluation of the primary lesion, evaluation of the neck mass, and role of imaging, to provide a framework for addressing the challenging questions patients may ask. Data Sources Available peer-reviewed literature and practice guidelines. Review Methods Assessment of selected specific topics by authors solicited from the Head and Neck Surgery and Oncology Committee of the American Academy of Otolaryngology—Head and Neck Surgery Foundation and the American Head and Neck Society. Conclusions and Implications for Practice The dramatic rise in OPSSC related to HPV is characterized by a “new” cancer patient who is younger and lacks traditional risk factors. Today’s caregiver must be prepared to appropriately evaluate, counsel, and treat these patients with HPV-positive disease with the expectation that traditional treatment algorithms will evolve to maintain or improve current excellent cure rates while lessening treatment related side effects.

Everolimus (RAD) Inhibits In Vivo Growth of Murine Squamous Cell Carcinoma (SCC VII)

Objective: Everolimus (RAD) is an mTOR inhibitor closely related to rapamycin. A potent immunosuppressive agent, it has also shown evidence of antineoplastic properties. SCC VII is a spontaneously arising murine squamous cell carcinoma line. This study examines the effect of everolimus on SCC VII proliferation. The data may provide support for the use of everolimus in transplant recipients with a history of malignancy.

The Effect of Treating Institution on Outcomes in Head and Neck Cancer

Objective Factors leading patients with head and neck cancer (HNCA) to seek radiation or chemoradiation in an academic center versus the community are incompletely understood, as are the effects of site of treatment on treatment completion and survival. Study Design Historical cohort study. Setting Tertiary academic center, community practices. Methods A historical cohort study was completed of patients with mucosal HNCA identified by International Classification of Disease, Ninth Revision (ICD-9) codes receiving consultation at the authors’ institution from 2003 to 2008. Patients who received primary and adjuvant radiation at an academic center or in the community were included. The authors compared treatment completion rates and performed univariate and multivariate analyses of treatment outcomes. Results Of 388 patients, 210 completed treatment at an academic center and 145 at a community center (33 excluded, location unknown). Patients with HNCA undergoing radiation at an academic site had more advanced disease (P = .024) and were more likely to receive concurrent chemotherapy. Academic hospitals had a higher percentage of noncurrent smokers, higher median income, and higher percentage of oropharyngeal tumors. There was no significant difference in the rate of planned treatment completion between community and academic centers (93.7% vs 94.7%, P > .81) or rate of treatment breaks (22.4% vs 28.4%, P > .28). On Kaplan-Meier analysis, the 5-year survival rate was 53.2% (95% confidence interval [CI], 45.3%-61.1%) for academic centers and 32.8% (95% CI, 22.0%-43.6%) for community hospitals (P < .001). Conclusion In this cohort, although treatment completion and treatment breaks were similar between academic and community centers, survival rates were higher in patients treated in an academic setting.

Swallowing Outcomes After Microvascular Head and Neck Reconstruction: A Prospective Review of 191 Cases

Background: The use of microvascular free tissue flaps tailored specifically to the ablative surgical defects has allowed precise anatomic reconstructions to be performed and, in turn, has improved patient outcomes. We report here the postoperative swallowing outcomes of patients undergoing microvascular reconstructions for a range of head and neck defects at the Cleveland Clinic.

Thoracodorsal artery scapular tip autogenous transplant: vascularized bone with a long pedicle and flexible soft tissue.

OBJECTIVE To demonstrate that the 3 reconstructive advantages of the thoracodorsal artery scapular tip transplant (Tdast), a long pedicle, independently mobile tissue components, and the 3-dimensional nature of the scapular tip, will improve the quality and success of complex reconstructions by avoiding vein grafting, preventing the need for 2 separate transplants, and facilitating bony inset. DESIGN Prospective case series. SETTING Tertiary care academic medical center. PATIENTS Twenty-one patients (male to female ratio, 16:5; mean age, 52 years) underwent reconstruction of the upper, middle, and lower face from 2001 through 2006. Indications for reconstruction were tumor ablation in 11 patients, secondary reconstruction in 4 patients, osteoradionecrosis in 4, and posttraumatic reconstruction in 2. Seventeen patients underwent radiation. INTERVENTIONS All patients underwent harvest of an autogenous transplant of scapular tip bone and latissimus dorsi soft tissue based on the thoracodorsal artery. The mean bone length was 5.2 cm (range, 2.5-9.0 cm), and the mean cutaneous surface area was 68 cm² (range, 20-250 cm²). MAIN OUTCOME MEASURES Reduction of vein grafting, avoidance of 2 transplants, use of the triangular shape of the scapular tip in reconstruction, complications, and shoulder function. RESULTS The success rate of transplantation was 100%. The use of this transplant avoided vein grafting in 16 patients and the need for 2 separate transplants in 11 patients, and the 3-dimensional nature of the scapular tip facilitated inset in 13 patients. In 14 patients, more than 1 of these reconstructive advantages was achieved. In 6 patients, all 3 were accomplished. Eleven patients experienced a complication. The major complication rate was 33%, and the minor complication rate was 33%. The mean Constant-Murley test of shoulder function score was 87 of 100 (range, 74-100). CONCLUSIONS The Tdast is an excellent choice for reconstruction in the head and neck as an alternative to procedures requiring vein grafting and multiple free tissue transplants, or in which the 3-dimensional contour of the scapular tip aids in reconstruction. The complication rate should be assessed in the context of the risk factors of the patient population and the outcome with respect to stable employment, increasing body mass index, and maintenance of shoulder function.

Sensitivity, Specificity, and Posttest Probability of Parotid Fine-Needle Aspiration A Systematic Review and Meta-analysis

Objectives (1) To analyze the sensitivity and specificity of fine-needle aspiration (FNA) in distinguishing benign from malignant parotid disease. (2) To determine the anticipated posttest probability of malignancy and probability of nondiagnostic and indeterminate cytology with parotid FNA. Data Sources Independently corroborated computerized searches of PubMed, Embase, and Cochrane Central Register were performed. These were supplemented with manual searches and input from content experts. Review Methods Inclusion/exclusion criteria specified diagnosis of parotid mass, intervention with both FNA and surgical excision, and enumeration of both cytologic and surgical histopathologic results. The primary outcomes were sensitivity, specificity, and posttest probability of malignancy. Heterogeneity was evaluated with the I2 statistic. Meta-analysis was performed via a 2-level mixed logistic regression model. Bayesian nomograms were plotted via pooled likelihood ratios. Results The systematic review yielded 70 criterion-meeting studies, 63 of which contained data that allowed for computation of numerical outcomes (n = 5647 patients; level 2a) and consideration of meta-analysis. Subgroup analyses were performed in studies that were prospective, involved consecutive patients, described the FNA technique utilized, and used ultrasound guidance. The I2 point estimate was >70% for all analyses, except within prospectively obtained and ultrasound-guided results. Among the prospective subgroup, the pooled analysis demonstrated a sensitivity of 0.882 (95% confidence interval [95% CI], 0.509-0.982) and a specificity of 0.995 (95% CI, 0.960-0.999). The probabilities of nondiagnostic and indeterminate cytology were 0.053 (95% CI, 0.030-0.075) and 0.147 (95% CI, 0.106-0.188), respectively. Conclusion FNA has moderate sensitivity and high specificity in differentiating malignant from benign parotid lesions. Considerable heterogeneity is present among studies.

Carcinogenicity and DNA adduct formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in F-344 rats

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is metabolized to enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), found in the urine of virtually all people exposed to tobacco products. We assessed the carcinogenicity in male F-344 rats of (R)-NNAL (5 ppm in drinking water), (S)-NNAL (5 ppm), NNK (5 ppm) and racemic NNAL (10 ppm) and analyzed DNA adduct formation in lung and pancreas of these rats after 10, 30, 50 and 70 weeks of treatment. All test compounds induced a high incidence of lung tumors, both adenomas and carcinomas. NNK and racemic NNAL were most potent; (R)-NNAL and (S)-NNAL had equivalent activity. Metastasis was observed from primary pulmonary carcinomas to the pancreas, particularly in the racemic NNAL group. DNA adducts analyzed were O (2)-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O (2)-POB-dThd), 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine(7-POB-Gua),O (6)-[4-(3-pyridyl)-4-oxobut-1-yl]deoxyguanosine(O (6)-POB-dGuo),the 4-(3-pyridyl)-4-hydroxybut-1-yl(PHB)adductsO (2)-PHB-dThd and 7-PHB-Gua, O (6)-methylguanine (O (6)-Me-Gua) and 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing adducts. Adduct levels significantly decreased with time in the lungs of rats treated with NNK. Pulmonary POB-DNA adducts and O (6)-Me-Gua were similar in rats treated with NNK and (S)-NNAL; both were significantly greater than in the (R)-NNAL rats. In contrast, pulmonary PHB-DNA adduct levels were greatest in the rats treated with (R)-NNAL. Total pulmonary DNA adduct levels were similar in (S)-NNAL and (R)-NNAL rats. Similar trends were observed for DNA adducts in the pancreas, but adduct levels were significantly lower than in the lung. The results of this study clearly demonstrate the potent pulmonary carcinogenicity of both enantiomers of NNAL in rats and provide important new information regarding DNA damage by these compounds in lung and pancreas.

Transformation in mandibular imaging with sweep imaging with fourier transform magnetic resonance imaging

OBJECTIVE Current imaging techniques are often suboptimal for the detection of mandibular invasion by squamous cell carcinoma. The aim of this study was to determine the feasibility of a magnetic resonance imaging (MRI)-based technique known as sweep imaging with Fourier transform (SWIFT) to visualize the structural changes of intramandibular anatomy during invasion. DESIGN Descriptive case study. SETTING Tertiary academic institution. PATIENTS Patients with oral carcinoma who underwent segmental mandibulectomy. INTERVENTIONS Two specimens from each patient were imaged using a 9.4-T Varian MRI system. The SWIFT images were correlated with histologic sections. RESULTS The SWIFT technique with in vitro specimens produced images with sufficient resolution (156-273 μm) and contrast to allow accurate depiction of tumor invasion of cortical and medullary bone. Both specimens had histopathologic evidence of mandibular invasion with tumor. A high degree of correlation was found between magnetic resonance images and histopathologic findings. CONCLUSIONS The SWIFT MRI offers 3-dimensional assessment of cortical and medullary bone in fine detail and excellent qualitative agreement with histopathologic findings. Imaging with the SWIFT MRI technique demonstrates great potential to identify mandibular invasion by oral carcinoma.

Pulsed immunosuppression with everolimus and anti-αβ T-cell receptor : Laryngeal allograft preservation at six months

Objectives: Laryngeal transplantation can restore the voice in patients who have undergone laryngectomy. However, the prospect of lifelong immunosuppression is a drawback to this procedure. We present data from a study aimed at minimizing the need for immunosuppression while maintaining graft viability through a novel pulsed-dosing protocol. Methods: Larynges were transplanted from Lewis–brown Norway (RT11+n, F1) rats to Lewis (RT11) recipients. All recipients received 7 days of treatment with everolimus and mouse anti-rat αβ T-cell receptor (anti-TCR) monoclonal antibodies beginning the day before transplantation. At 90 days after transplantation, all recipients received a pulse of the same treatment combination for 5 days. From 90 to 180 days after transplantation, the rats received no treatment (group 1, n = 5), 2.5 mg/kg everolimus per day (group 2, n = 5), or 1.0 mg/kg everolimus per day (group 3, n = 5). Results: Histologic analysis of rats that received everolimus as pulse therapy evidenced no signs of rejection, whereas animals that were untreated after 90 days had normal to mild chronic rejection. T-cell reconstitution occurred 65 days after perioperative immunosuppressive treatment, but less rapidly after pulse therapy. Also, peripheral chimerism was generated in all 3 groups. Conclusions: In the rat laryngeal transplantation model, short-term perioperative therapy with everolimus and anti-TCR followed by pulsing is a viable alternative to the concerns associated with continuous, lifelong immunosuppression.

Tobacco carcinogen metabolites and DNA adducts as biomarkers in Head and Neck cancer: Potential screening tools and prognostic indicators

Head and neck squamous cell carcinoma (HNSCC) is one of many cancers that are strongly associated with tobacco use. Whereas HNSCC is often seen in tobacco users, many tobacco users do not develop carcinoma; and the differences between smokers with and without HNSCC are poorly studied to date. Some smokers may be inherently more susceptible to developing carcinoma due to patterns of tobacco use, innate metabolism of carcinogens, or altered excretion. Identifying those smokers at greatest risk for HNSCC would have great benefit through targeted smoking cessation efforts and enhanced surveillance. One approach to better understand the extent of exposure to, and metabolism of, tobacco carcinogens is through the use of tobacco‐specific metabolites. Tobacco‐specific metabolites can identify patterns of dose, exposure, and metabolism, and perhaps ultimately characterize the important differences between smokers who develop HNSCC and smokers who do not.