A Clinical Study to Assess Diffuse Reflectance Spectroscopy with an Auto-Calibrated, Pressure-Sensing Optical Probe in Head and Neck Cancer.

Diffuse reflectance spectroscopy (DRS) is a powerful tool for quantifying optical and physiological tissue properties such as hemoglobin oxygen saturation and vascularity. DRS is increasingly used clinically for distinguishing cancerous lesions from normal tissue. However, its widespread clinical acceptance is still limited due to uncontrolled probe-tissue interface pressure that influences reproducibility and introduces operator-dependent results. In this clinical study, we assessed and validated a pressure-sensing and automatic self-calibration DRS in patients with suspected head and neck squamous cell carcinoma (HNSCC). The clinical study enrolled nineteen patients undergoing HNSCC surgical biopsy procedures. Patients consented to evaluation of this improved DRS system during surgery. For each patient, we obtained 10 repeated measurements on one tumor site and one distant normal location. Using a Monte Carlo-based model, we extracted the hemoglobin saturation data along with total hemoglobin content and scattering properties. A total of twelve cancer tissue samples from HNSCC patients and fourteen normal tissues were analyzed. A linear mixed effects model tested for significance between repeated measurements and compared tumor versus normal tissue. These results demonstrate that cancerous tissues have a significantly lower hemoglobin saturation compared to normal controls (p < 0.001), which may be reflective of tumor hypoxia. In addition, there were minimal changes over time upon probe placement and repeated measurement, indicating that the pressure-induced changes were minimal and repeated measurements did not differ significantly from the initial value. This study demonstrates the feasibility of conducting optical spectroscopy measurements on intact lesions prior to removal during HNSCC procedures, and established that this probe provides diagnostically-relevant physiologic information that may impact further treatment.

A Retrospective Study of Lymph Node Yield in Lateral Neck Dissection for Papillary Thyroid Carcinoma.

OBJECTIVE: Lateral neck dissection (LND) is important in managing papillary thyroid carcinomas (PTCs). This study aimed to evaluate the relationship between lymph node yield (LNY) for LND and patient outcomes, specifically postoperative serum thyroglobulin levels (sTG) and radioiodine uptake on thyroid scan, and to estimate a threshold LNY to signify adequate LND. METHODS: Patients diagnosed with PTC who underwent LND from 2006 to 2015 at a single institution were included. Linear regression with restricted cubic splines was used to characterize the association of LNY with outcomes. Outcomes were log-transformed to achieve a more symmetric distribution prior to regression. For nonlinear associations, a Monte Carlo Markov Chain procedure was used to estimate a threshold LNY associated with postoperative outcome. This threshold was then used to define high LNY versus low LNY in the subsequent analyses. RESULTS: In total, 107 adult patients were included. There was a significant relationship between LNY and postoperative sTG level (P = .004), but not radioiodine uptake (P = .64). An LNY of 42.96 was identified, which was associated with the maximum change in sTG level. No association was found between LNY groups (LNY ≥ 43 vs < 43) and radioiodine uptake, risk of complication, or longer operative times (all P > .05). High LNY was associated with a decrease in log(sTG) (estimate = -1.855, P = .03), indicating that adequacy of LND is associated with an 84.4% decrease in sTG. CONCLUSION: These results suggest an association between LNY and postoperative sTG level, with an estimated threshold of 43 nodes. This has implications for adequate therapeutic LND; additional work is needed to validate thresholds for clinical practice.

Assessing effects of pressure on tumor and normal tissue physiology using an automated self-calibrated, pressure-sensing probe for diffuse reflectance spectroscopy.

Diffuse reflectance spectroscopy (DRS) represents a quantitative, noninvasive, nondestructive means of assessing vascular oxygenation, vascularity, and structural properties. However, it is known that such measurements can be influenced by the effects of pressure, which is a major concern for reproducible and operator-independent assessment of tissues. Second, regular calibration is a necessary component of quantitative DRS to account for factors such as lamp decay and fiber bending. Without a means of reliably controlling for these factors, the accuracy of any such assessments will be reduced, and potentially biased. To address these issues, a self-calibrating, pressure-controlled DRS system is described and applied to both a patient-derived xenograft glioma model, as well as a set of healthy volunteers for assessments of oral mucosal tissues. It was shown that pressure had a significant effect on the derived optical parameters, and that the effects on the optical parameters were magnified with increasing time and pressure levels. These findings indicate that not only is it critical to integrate a pressure sensor into a DRS device, but that it is also important to do so in an automated way to trigger a measurement as soon as possible after probe contact is made to minimize the perturbation to the tissue site.

Rare cases of large parapharyngeal lipomas.

Primary tumors of the parapharyngeal space are extremely rare, and lipomas are among the least common primary parapharyngeal space masses. Parapharyngeal lipomas typically present as a painless neck mass, and some may present with neurologic deficits or vascular compromise attributed to the lipomas' mass effect on nearby neurovascular structures. We report long term follow-up of two large parapharyngeal lipomas. One lesion was managed expectantly, and the other was managed with a partial transcervical excision. We demonstrate that conservative management and long term patient follow-up may be reasonable if the patient is asymptomatic and liposarcoma is ruled out. Considering the uncertainty in the need for removal, the management strategy for the individual patient is best to be tailored to their clinical presentation.

Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma.

OBJECTIVES: We propose the use of morphological optical biomarkers for rapid detection of human head and neck squamous cell carcinoma (HNSCC) by leveraging the underlying tissue characteristics in aerodigestive tracts. MATERIALS AND METHODS: Diffuse reflectance spectra were obtained from malignant and contra-lateral normal tissues of 57 patients undergoing panendoscopy and biopsy. Oxygen saturation, total hemoglobin concentration, and the reduced scattering coefficient were extracted. Differences in malignant and normal tissues were examined based on two different groupings: anatomical site and morphological tissue type. RESULTS AND CONCLUSIONS: Measurements were acquired from 252 sites, of which 51 were pathologically classified as SCC. Optical biomarkers exhibited statistical differences between malignant and normal samples. Contrast was enhanced when parsing tissues by morphological classification rather than anatomical subtype for unpaired comparisons. Corresponding linear discriminant models using multiple optical biomarkers showed improved predictive ability when accounting for morphological classification, particularly in node-positive lesions. The false-positive rate was retrospectively found to decrease by 34.2% in morphologically- vs. anatomically-derived predictive models. In glottic tissue, the surgeon exhibited a false-positive rate of 45.7% while the device showed a lower false-positive rate of 12.4%. Additionally, comparisons of optical parameters were made to further understand the physiology of tumor staging and potential causes of high surgeon false-positive rates. Optical spectroscopy is a user-friendly, non-invasive tool capable of providing quantitative information to discriminate malignant from normal head and neck tissues. Predictive models demonstrated promising results for real-time diagnostics. Furthermore, the strategy described appears to be well suited to reduce the clinical false-positive rate.

Applying the Society of Radiologists in Ultrasound recommendations for fine-needle aspiration of thyroid nodules: effect on workup and malignancy detection.

OBJECTIVE: The Society of Radiologists in Ultrasound (SRU) recommendations on thyroid nodules are intended to "diagnose thyroid cancers that have reached clinical significance, while avoiding unnecessary tests and surgery in patients with benign nodules." The aim of our study was to determine the proportion of thyroid nodules undergoing ultrasound-guided fine-needle aspiration (FNA) that do not meet SRU recommendations. MATERIALS AND METHODS: This study is a retrospective study of 400 consecutive ultrasound-guided thyroid FNA encounters from July 2010 through June 2011. An encounter was defined as presentation to the department of radiology on a given date for FNA of one or more thyroid nodules. The criteria for performing biopsy of a nodule were determined by the referring clinicians. Nodules were categorized on the basis of sonographic findings as meeting SRU recommendations for biopsy, which we refer to as "SRU-positive," or not, which we refer to as "SRU-negative." Patients without a definitive pathology diagnosis of Bethesda class benign or malignant nodules were excluded. The characteristics of malignancies were compared for SRU-positive and SRU-negative encounters. RESULTS: The final study group consisted of 360 biopsy encounters for 350 patients and 29 malignancies (8%). Of the 360 biopsy encounters, 86 (24%) were SRU-negative encounters. Malignancy rates in SRU-positive and SRU-negative encounters were 9% (24/274) and 6% (5/86), respectively, and were not significantly different (p=0.5). Eighteen malignancies (75%) in the SRU-positive group were localized, whereas the others had nodal metastases (4/24) or distant metastases (2/24). SRU-positive encounters included medullary carcinoma, anaplastic carcinoma, and melanoma metastasis in addition to papillary carcinoma. All SRU-negative malignancies were localized papillary carcinomas. CONCLUSION: One in four thyroid biopsy encounters at our institution did not meet SRU recommendations for biopsy. The application of SRU recommendations reduces the number of benign nodules that undergo workup. Potentially missed malignancies in SRU-negative nodules are less aggressive by histologic type and stage compared with SRU-positive malignancies.

Trends in incidentally identified thyroid cancers over a decade: a retrospective analysis of 2,090 surgical patients.

BACKGROUND: The aim of this study was to describe trends in the incidence of incidental thyroid cancers and compare their characteristics with clinically presenting cancers. METHODS: We performed a retrospective review of patients with thyroid cancer who underwent thyroid surgery from 2003 to 2012. Patients' initial presentation was categorized as incidental (on imaging or final surgical pathology) or clinical (palpable or symptomatic) cancer. Characteristics of incidental and clinical cancers were compared. RESULTS: Of the 2,090 patients who underwent thyroid surgery, 680 (33 %) were diagnosed with cancer. One hundred ninety (28 %) were incidental cancer, of which 101 were detected on imaging studies and 89 were detected on analysis of the surgical pathology specimens. The incidence of thyroid cancer increased by 7.6-fold from 2003 to 2012. The proportion of incidental cancers on imaging did not increase, but incidental cancers found on pathology steadily increased from 6 % in 2003 to 20 % in 2012. 84 % of the cancers were papillary cancer, and the proportion of papillary cancer was similar for both clinical and incidental cancers. Clinical cancers were larger than incidental cancers on imaging (2.2 vs. 1.8 cm, p = 0.02). Incidental cancers on imaging were less likely to have lateral compartment nodal metastases (7 vs. 13 %, p < 0.001). CONCLUSIONS: Thyroid cancer diagnoses have increased at our institution, but the proportion of incidental cancers identified on imaging relative to clinical cancers has been stable over a decade and is not the sole explanation for the observed increase in thyroid cancer diagnoses. Incidental cancers on imaging are smaller in size and less likely to have lateral compartment nodal metastases than clinical cancers.

Comparison of complications in free flap reconstruction for osteoradionecrosis in patients with or without hyperbaric oxygen therapy.

BACKGROUND: Hyperbaric oxygen (HBO) therapy induces native tissue oxygenation. The hypothesis was patients with mandibular osteoradionecrosis (ORN) and a history of HBO therapy would have less free flap reconstruction complications than patients without HBO therapy. METHODS: We conducted a multisite retrospective review involving radical debridement and free flap reconstruction for ORN between January 1, 1995 and June 30, 2011. Patients were stratified based on receiving prior HBO therapy or not. RESULTS: Thirty-nine of 89 patients (43.8%) had HBO therapy whereas 50 of 89 (56.2%) did not. The HBO therapy group had significantly less patients with diabetes. There was no statistical difference in overall complication in patients between groups (p = .5478). However, there was marginal significance of increased infections in the patients with a history of HBO therapy (p = .0545). CONCLUSION: Although no significant differences in free flap reconstruction complication rates were observed between these 2 patient cohorts, there was marginal significance of increased infections in the patients with a history of HBO therapy. A prospective multi-institutional randomized study examining issues of infection would address issues inherent in this retrospective study.

Journal Club: incidental thyroid nodules detected at imaging: can diagnostic workup be reduced by use of the Society of Radiologists in Ultrasound recommendations and the three-tiered system?

OBJECTIVE: The purpose of this study was to determine the number of thyroid nodule workups that could be eliminated and the number of malignant tumors that would be missed if the Society of Radiologists in Ultrasound (SRU) recommendations and the three-tiered system were applied to incidental thyroid nodules (ITN) detected at imaging. MATERIALS AND METHODS: This retrospective study included ITN in 390 consecutively registered patients who underwent ultrasound-guided fine-needle aspiration of one or more thyroid nodules from July 2010 to June 2011. Images were reviewed, and nodules were categorized according to two workup criteria: ITN seen on ultrasound images were categorized according to SRU recommendations, and those seen on CT, MR, or PET/CT images were classified according to the three-tiered risk-categorization system. RESULTS: In this study 114 of 390 (29%) patients had nodules first detected incidentally during imaging studies, and 107 patients met the inclusion criteria. These patients had 47 ITN seen at ultrasound and 60 ITN seen at either CT, MRI, or PET/CT. If the SRU recommendations had been applied, 14 of 47 (30%) patients with ITN on ultrasound images would not have received fine-needle aspiration and one of four cases of cancer would have been missed. The missed malignant tumor was a 14-mm localized papillary carcinoma. If the three-tiered system had been applied, 21 of 60 (35%) patients with ITN on CT, MR, or PET/CT images would not have received fine-needle aspiration, but none of the three malignancies would have been missed. Overall, 35 of 107 (33%) of patients with ITN did not meet the SRU recommendations or the three-tiered criteria. CONCLUSION: Use of the SRU recommendations and three-tiered system can reduce the workup of ITN by one third compared with current practice without specific guidelines. One case of localized papillary carcinoma was missed when the SRU recommendations were used.

Surgical Training and Education in Promoting Professionalism: a comparative assessment of virtue-based leadership development in otolaryngology-head and neck surgery residents.

INTRODUCTION: Surgical Training and Education in Promoting Professionalism (STEPP) was developed in 2011 to train tomorrow's leaders during residency. It is based on virtue ethics and takes an approach similar to West Point military academy. The purpose of this research was: (i) to compare the virtue profiles of our residents with that of the military cohort using a standardized virtue assessment tool; and (ii) to assess the value of virtue education on residents. METHODS: As part of STEPP, otolaryngology residents participated in a virtue-based validated assessment tool called Virtue in Action (VIA) Inventory. This was completed at the initiation of STEPP in July 2011 as well as 1 year later in June 2012. Comparison of the VIA to a military cohort was performed. Leadership 'Basic Training' is a series of forums focused on virtues of initiative, integrity, responsibility, self-discipline, and accountability. A pre- and post-test was administered assessing resident perceptions of the value of this 'Basic Training'. RESULTS: Virtues are shared between otolaryngology residents (n=9) and military personnel (n=2,433) as there were no significant differences in strength scores between two military comparison groups and otolaryngology-head and neck surgery (OHNS) residents. There was a significant improvement (p<0.001) in the understanding of components of the leadership vision and a significant improvement in the understanding of key leadership concepts based on 'Basic Training'. All residents responded in the post-test that the STEPP program was valuable, up from 56%. CONCLUSIONS: A virtue-based approach is valued by residents as a part of leadership training during residency.

Utility of Intraoperative Frozen Sections during Thyroid Surgery.

Objective. To describe the usefulness of intraoperative frozen section in the diagnosis and treatment of thyroid nodules where fine needle aspirate biopsies have evidence of follicular neoplasm. Study Design. Retrospective case series. Methods. All patients have a fine needle aspirate biopsy, an intraoperative frozen section, and final pathology performed on a thyroid nodule after initiation of the Bethesda System for Reporting Thyroid Cytopathology in 2009 at a single tertiary referral center. Sensitivity, specificity, positive predictive value, and negative predictive value are calculated in order to determine added benefit of frozen section to original fine needle aspirate data. Results. The sensitivity and specificity of the frozen section were 76.9% and 67.9%, respectively, while for the fine needle aspirate were 53.8% and 74.1%, respectively. The positive and negative predictive values for the fine needle aspirates were 25% and 90.9%, respectively, while for the frozen sections were 27.8% and 94.8%, respectively. There were no changes in the operative course as a consequence of the frozen sections. Conclusion. Our data does not support the clinical usefulness of intraoperative frozen section when the fine needle aspirate yields a Bethesda Criteria diagnosis of follicular neoplasm, suspicious for follicular neoplasm, or suspicious for malignancy at our institution.

Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer.

PURPOSE: We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC). EXPERIMENTAL DESIGN: Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT. RESULTS: Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%-100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median K(trans) values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median K(trans) values that decreased during therapy. CONCLUSIONS: Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure.

Treatment-induced changes in vocal cord mobility and subsequent local recurrence after organ preservation therapy for laryngeal carcinoma.

BACKGROUND: As multidisciplinary cancer treatment evolves, strategies to identify patients needing early resection/salvage are necessary. Some have suggested that vocal cord function after organ-preservation treatment may be an indicator. METHODS: A retrospective review was performed of patients presenting with fixed or impaired vocal cord function at a tertiary center. Local recurrence rates were examined in patients with and without improved/normal mobilization after treatment. RESULTS: Sixty-nine patients met the inclusion criteria, with 35 patients having vocal cord fixation and 34 patients with impaired mobility. After treatment, 44 patients had normalization of vocal cord function, while 25 patients did not, with 2-year local control rates of 70% and 77%, p = .23, respectively. No difference in local control was found between patients with normalized/improved cord function (n = 53) and those who remained the same/worsened (n = 16; p = .81). CONCLUSION: Therapy-induced changes in vocal cord mobility did not correlate with local recurrence. Other criteria are needed to identify patients most likely to benefit from early surgical resection/salvage after organ preservation.

Intended single-modality management of T1 and T2 tonsillar carcinomas: retrospective comparison of radical tonsillectomy vs radiation from a single institution.

BACKGROUND: T1 and T2 tonsillar squamous cell cancer with limited neck disease can be managed with single-modality radiation or surgery. Over 11 years, 17 patients underwent radical tonsillectomies; and 33 patients underwent radiation-based treatments for T1 and T2 and N0 to N2a tonsil cancer. Patients were intended to receive single-modality treatment based on presentation; however, some ultimately received adjuvant treatments. METHODS: A retrospective chart review to compare overall survival (OS), disease-specific survival (DSS), and locoregional control (LRC) between the groups was used. RESULTS: In surgical group, of 17 patients, 11 underwent surgery alone, 3 underwent surgery and radiation, and 3 underwent surgery with concurrent chemoradiation. Five-year OS for the surgical and radiation groups was 93% and 72%, respectively (no significance achieved). Five-year DSS rates (93% and 80%) and LRC (69% and 89%) similarly did not yield any significant difference. CONCLUSION: Surgery remains a viable option in the management of T1 and T2 tonsillar cancers with comparable LRC, OS, and DSS.

Extent of neck dissection required after concurrent chemoradiation for stage IV head and neck squamous cell carcinoma.

BACKGROUND: The management of initially bulky nodal disease after primary nonsurgical treatment for stage IV head and neck squamous cell carcinoma (HNSCC) continues to be a subject of debate. METHODS: A retrospective chart review of neck management in patients after chemoradiation was performed. RESULTS: Of the initially positive necks analyzed, 210/329 (65%) had a complete clinical response to treatment and 161 necks underwent neck surgery. Patients were pathologically positive 13.8% and 39.6% of the time after clinical complete or partial response, respectively. Regional recurrence was more frequent in necks with partial clinical (p = .04) or pathologic responses (p < .01) and with primary site recurrences (p < .01). CONCLUSIONS: It is still safest at our institution to perform selective neck dissection on patients with > or = N2 neck disease when initially observed to prevent unsalvageable regional recurrence until more accurate interval assessment tools are confirmed.

Impact of preepiglottic space tumor involvement on concurrent chemoradiation therapy.

PURPOSE: The aim of the study was to determine the prognostic impact of preepiglottic space (PES) involvement on local failure after concurrent chemoradiation therapy for squamous cell carcinoma. MATERIALS AND METHODS: Retrospective chart review of patients who underwent concurrent chemoradiation therapy for T3 or T4 laryngeal, T4 hypopharyngeal, and T3 or T4 oropharyngeal squamous cell carcinoma were eligible for inclusion. Patients were then stratified by the presence or absence of PES tumor involvement. A multivariate analysis was performed on the presence of recurrence using the following pretreatment variables: PES involvement, tumor extent, pathologic cell differentiation, lymph node involvement, age, and sex. RESULTS: A total of 102 patients were included in the study. Twenty-seven (28%) patients had documented PES involvement. Mean follow-up for all patients was 46 months. Involvement of the PES was not significantly associated with local tumor persistence or recurrence (P = .69). No other variables significantly impacted tumor recurrence. CONCLUSION: Preepiglottic space involvement does not negatively impact local tumor control after concurrent chemoradiation therapy.

Does vocal cord fixation preclude nonsurgical management of laryngeal cancer?

OBJECTIVES/HYPOTHESIS: To determine whether vocal cord fixation precludes nonsurgical management of T3/T4 laryngeal carcinoma. STUDY DESIGN: A retrospective chart review. METHODS: Between 1989 and 2005 patient records with T3/T4 squamous cell carcinoma of the larynx with vocal cord fixation at presentation were reviewed. All were treated with a concomitant cisplatin-based chemoradiotherapy protocol and were part of the institutional head and neck cancer chemoradiotherapy registry. Only patients with adequate pre- and post-treatment fiberoptic evaluations were included. Charts were reviewed for demographics and tumor characteristics; return of vocal cord function; local, regional, or distant recurrence after treatment; and need for salvage surgery. The Kaplan-Meier method was used to estimate outcomes, and the log-rank test was used to compare those patients whose vocal cords remained fixed to those with recovery of function. RESULTS: Twenty-three patients met the inclusion criteria, 19 males and 4 females. The median age was 59 years (range, 39-73). Fourteen patients had T3 and nine had T4 tumors. Twelve patients recovered full range of mobility, three had partial recovery, and eight did not recover motion. The median follow-up was 68 months (range, 34-191). Comparing patients with post-treatment partial or fully mobile cords to those with persistent fixation revealed the following: A projected five-year overall survival of 100% versus 25%, (P < .001), freedom from recurrence of 86.7 versus 25% (P < .001), local control without surgery of 86.7% versus 30% (P = .003), and survival with functional larynx of 86.7% versus 25% (P = .008), respectively. CONCLUSIONS: Nonsurgical therapy in patients with pretreatment vocal cord fixation is feasible. However, persistence of vocal cord fixation after definitive chemoradiotherapy is a poor prognostic sign and early surgical intervention should be considered. Laryngoscope, 2009.