ACR Appropriateness Criteria® Staging and Post-Therapy Assessment of Head and Neck Cancer.

Imaging of head and neck cancer at initial staging and as part of post-treatment surveillance is a key component of patient care as it guides treatment strategy and aids determination of prognosis. Head and neck cancer includes a heterogenous group of malignancies encompassing several anatomic sites and histologies, with squamous cell carcinoma the most common. Together this comprises the seventh most common cancer worldwide. At initial staging comprehensive imaging delineating the anatomic extent of the primary site, while also assessing the nodal involvement of the neck is necessary. The treatment of head and neck cancer often includes a combination of surgery, radiation, and chemotherapy. Post-treatment imaging is tailored for the evaluation of treatment response and early detection of local, locoregional, and distant recurrent tumor. Cross-sectional imaging with CT or MRI is recommended for the detailed anatomic delineation of the primary site. PET/CT provides complementary metabolic information and can map systemic involvement. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

BACKGROUND: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. METHODS: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses. RESULTS: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). CONCLUSIONS: With careful selection, surgery alone for AJCC 7th pT0-T2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.

Impact of PET/CT on Staging and Treatment of Advanced Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: To understand the effects of positron emission tomography/computed tomography (PET/CT) evaluation on patients with previously untreated head and neck squamous cell carcinoma (HNSCC) with clinical evidence of regional lymph node involvement. STUDY DESIGN: Prospective blinded study. SETTING: Tertiary care cancer center. SUBJECTS AND METHODS: Informed consent was obtained and data collected from 52 consecutive previously untreated patients with HNSCC and clinical evidence of cervical metastasis. All patients underwent conventional evaluation for HNSCC and whole body PET/CT. Data were evaluated by 5 independent reviewers, who performed TNM staging per the American Joint Committee on Cancer (seventh edition) manual and proposed a treatment plan prior to viewing, and after reviewing, PET/CT. Cases where at least 3 of 5 reviewers agreed were considered significant. RESULTS: There were 0 patients for whom review of the PET/CT altered the T-class assessment (95% CI, 0-6.8), 12 (23.1%) for whom PET/CT altered N classification (95% CI, 12.5-34.5), and 2 (3.8%) for whom PET/CT altered the M classification (95% CI, 0.5-13.2). For 5 patients (9.6%), overall stage was altered per PET/CT review (95% CI, 3.2-21). For 3 patients (5.8%), PET/CT findings prompted reviewers to alter treatment recommendations (95% CI, 1.2-15.9). CONCLUSION: When added to more conventional patient evaluation, PET/CT results in changes to the TNM categories, but overall staging and treatment were less frequently affected. Whether PET/CT should be used routinely for patients with stage III and IV HNSCC is still subjective and merits further study.

Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells.

The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication.

S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC.

Thyroidectomy Hemostasis.

Total thyroidectomy has significantly changed over the years from a morbid procedure to one that is performed routinely on an outpatient basis. This article reviews the history of thyroid surgery with regard to hemostasis, discusses surgical vascular anatomy, and describes the methods of hemostasis. It compares traditional hemostatic surgical techniques with newer techniques such as the Harmonic Scalpel and LigaSure hand pieces. The use of adjunctive hemostatic agents and indications for a drain in thyroid are discussed.

Thyroid Cancer and Tumor Collaborative Registry (TCCR).

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC.

Biomechanical assessment of fixation methods for segmental mandible reconstruction with fibula in the polyurethane model.

BACKGROUND: A variety of plating techniques are employed by microsurgeons to provide rigid fixation for vascularized bone constructs of the mandible. The aim of this study was to biomechanically compare three commonly utilized plating techniques for rigid fixation of fibula bone flaps in reconstructing lateral segmental mandibular defects. MATERIALS AND METHODS: Polyurethane mandibles with 3-cm segmental defects were reconstructed using polyurethane fibula models. Three fixation techniques were compared (n = 5 models per group): Group 1 used two 2.0-mm miniplates at each osteotomy site, Group 2 used a single 2.3-mm plate, and Group 3 used a single 2.7-mm plate. Biomechanical testing of maximum force and displacement at failure for each plating technique was assessed and statistical comparison performed. RESULTS: The average displacement for Group 1 was 14.08 ± 1.42 mm, Group 2 was 5.79 ± 0.89 mm, and Group 3 was 6.03 ± 1.59 mm. Group 1 had significantly greater (P < 0.05) displacement when compared with Group 2 and 3. Analysis of variance demonstrated the three groups varied significantly in mean displacement (0 < 0.01). The average force before failure for Group 1 was 616.4 ± 33.83N, Group 2 was 737.8 ± 72.57N, and Group 3 was 681.0 ± 67.98N. Group 2 withstood significantly greater force than Group 1 (P < 0.05), and withstood greater force than Group 3, although the difference was not significant. Analysis of variance showed the three groups varied significantly in mean force at failure (P < 0.05). CONCLUSION: Reconstruction using a single 2.3-mm plate provided the best rigid fixation for lateral segmental defects of the mandible. © 2016 Wiley Periodicals, Inc. Microsurgery 36:330-333, 2016.

[(99m)Tc]Tilmanocept Accurately Detects Sentinel Lymph Nodes and Predicts Node Pathology Status in Patients with Oral Squamous Cell Carcinoma of the Head and Neck: Results of a Phase III Multi-institutional Trial.

BACKGROUND: [(99m)Tc]Tilmanocept, a novel CD206 receptor-targeted radiopharmaceutical, was evaluated in an open-label, phase III trial to determine the false negative rate (FNR) of sentinel lymph node biopsy (SLNB) relative to the pathologic nodal status in patients with intraoral or cutaneous head and neck squamous cell carcinoma (HNSCC) undergoing tumor resection, SLNB, and planned elective neck dissection (END). Negative predictive value (NPV), overall accuracy of SLNB, and the impact of radiopharmaceutical injection timing relative to surgery were assessed. METHODS AND FINDINGS: This multicenter, non-randomized, single-arm trial (ClinicalTrials.gov identifier NCT00911326) enrolled 101 patients with T1-T4, N0, and M0 HNSCC. Patients received 50 µg [(99m)Tc]tilmanocept radiolabeled with either 0.5 mCi (same day) or 2.0 mCi (next day), followed by lymphoscintigraphy, SLNB, and END. All excised tissues were evaluated for tissue type and tumor presence. [(99m)Tc]Tilmanocept identified one or more SLNs in 81 of 83 patients (97.6 %). Of 39 patients identified with any tumor-positive nodes (SLN or non-SLN), one patient had a single tumor-positive non-SLN in whom all SLNs were tumor-negative, yielding an FNR of 2.56 %; NPV was 97.8 % and overall accuracy was 98.8 %. No significant differences were observed between same-day and next-day procedures. CONCLUSIONS: Use of receptor-targeted [(99m)Tc]tilmanocept for lymphatic mapping allows for a high rate of SLN identification in patients with intraoral and cutaneous HNSCC. SLNB employing [(99m)Tc]tilmanocept accurately predicts the pathologic nodal status of intraoral HNSCC patients with low FNR, high NPV, and high overall accuracy. The use of [(99m)Tc]tilmanocept for SLNB in select patients may be appropriate and may obviate the need to perform more extensive procedures such as END.

Modifiable risk factors and thyroid cancer.

OBJECTIVE: To evaluate the association between modifiable patient risk factors including tobacco use, alcohol consumption, body mass index (BMI), and thyroid cancer. STUDY DESIGN: Retrospective study with chart review. SETTING: Midwest university hospital. SUBJECTS AND METHODS: Retrospective study comparing Midwest patients with thyroid cancer from our Thyroid Tumor and Cancer Registry with Midwest controls without a personal history of cancer. Descriptive statistics were created from patient questionnaires and chart reviews. Odds ratios (ORs) were reported for significant associations. RESULTS: There were 467 patients with cancer and 255 controls. The thyroid cancer group included 404 papillary, 47 follicular, 13 medullary, and 3 anaplastic cancers. When comparing all patients with cancer with controls, smoking more than 100 lifetime cigarettes was associated with a reduced cancer risk (OR, 0.68; 95% confidence interval [CI], 0.50-0.94). Secondhand smoke exposure did not show a statistically significant relationship to thyroid cancer. Compared with never drinking, current drinking was associated with a reduced cancer risk (OR, 0.46; 95% CI, 0.29-0.73) as was consuming 1 to 2 drinks daily compared to drinking <1 drink daily (OR, 0.58; 95% CI, 0.34-0.89). There was no difference between median BMI at age 20 years, lifetime maximum BMI, or current BMI between patients with cancer and controls. CONCLUSION: Our data showed no positive correlation between tobacco use, alcohol consumption, or obesity and thyroid cancer risk. Our data suggest that tobacco use and mild alcohol consumption may be associated with a slightly reduced risk of thyroid cancer. There was no association between BMI and thyroid cancer in our study population.

Implications of carotid sinus hypersensitivity following preoperative embolization of a carotid body tumor. An indication for prophylactic intraoperative cardiac pacing.

IMPORTANCE Carotid body tumors are rare neoplasms of neural crest origin that are both highly vascularized and locally invasive. Treatment options for these tumors often include surgery with preoperative embolization, which can pose major cardiovascular risk to patients. As demonstrated by this case report, hemodynamic instability following preoperative embolization of a carotid body tumor may indicate severe carotid sinus hypersensitivity and the need for temporary cardiac pacing. OBSERVATIONS This case report describes a man in his early 30s who presented for staged surgical resection of bilateral carotid body tumors with preoperative embolization. After embolization of the second tumor, the patient displayed transient episodes of bradycardia and hypotension, which resolved with medical management. Surgery commenced, and with minimal manipulation intraoperatively, the patient became asystolic and required resuscitation. Following a negative cardiac workup, a temporary pacemaker was implanted, and surgical resection of the tumor was successfully completed. CONCLUSIONS AND RELEVANCE Carotid sinus hypersensitivity is a rare but serious risk of preoperative embolization of carotid body tumors. Postembolization bradycardia or hypotension should be assessed as potential harbingers of carotid sinus hypersensitivity, and the need for temporary intraoperative cardiac pacing should be strongly considered.

No benefit in staging fluorodeoxyglucose-positron emission tomography in clinically node-negative head and neck cutaneous melanoma.

BACKGROUND: Fluorodeoxyglucose-positron emission tomography (FDG-PET) has a high sensitivity for detecting metastasis from melanoma, but its application in early-stage melanomas is questionable. The purpose of this study was to determine if positron emission tomography (PET) is beneficial in staging of clinically node negative (cN0) head and neck melanoma. METHODS: After institutional review board approval, patients with head and neck melanoma treated at 2 cancer centers (between 2000 and 2010) were identified using International Classification of Disease (ICD)-9 codes. A retrospective medical chart review of cN0 patients was performed for the treatment course and outcomes. RESULTS: A total of 165 patients were treated; of these, 106 were node negative. FDG-PET was included in initial staging of 47 cN0 patients. None had true distant metastasis detected on PET. The imaging also failed to detect nodal metastasis in 2 patients who had disease on lymphatic sampling. CONCLUSION: FDG-PET did not alter the initial staging or treatment in patients with cN0 head and neck melanoma. Therefore, its routine use for staging is not warranted.

Ultrasound for localization in primary hyperparathyroidism.

OBJECTIVE: To evaluate the capability of ultrasound for preoperative localization in primary hyperparathyroidism. STUDY DESIGN: Prospective study. SETTING: Multi-institutional Midwest Head and Neck Cancer Consortium. SUBJECTS AND METHODS: Two hundred twenty patients who underwent preoperative localization and had parathyroid surgery were evaluated. The findings of preoperative localization studies were correlated with surgical findings. RESULTS: Preoperative ultrasonography, sestamibi scintigraphy, or both were obtained in 77%, 93%, and 69% of the patients, respectively. Preoperative ultrasonography and sestamibi scintigraphy localized an abnormality in 71% and 79% of patients, respectively. At the time of surgery, the localization by ultrasound was accurate in 82%. The accuracy of localization was similar for sestamibi scintigraphy (85%). In patients with inaccurate ultrasound localization, the sestamibi scintigraphy correctly identified the site of disease in only 45%. In patients with a nonlocalizing ultrasound, sestamibi scintigraphy was able to localize disease in only 47%, with 2 being in the mediastinum. CONCLUSIONS: Ultrasonography is an acceptable initial localization study for patients with primary hyperparathyroidism. In patients with nonlocalizing ultrasound, sestamibi scintigraphy should be obtained, but can be expected to detect an abnormality in less than 50% of patients.

Immunoglobulin G4-related sclerosing disease of the paranasal sinus.

BACKGROUND: Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. We present a case of a 69-year-old man with maxillary sinus IgG4 sclerosing disease, with orbital invasion treated with rituximab and dexamethasone pulse therapy. Surgery was used as well to debulk the disease and to obtain tissue for diagnosis. METHODS: A PubMed search using the key phrase "IgG4-related Sclerosing Disease" was performed. There were 304 different articles regarding the disease for a multitude of different organ sites. Of the 304 articles, there were 3 articles that reported this disease in the paranasal sinuses. CONCLUSIONS: IgG4-related sclerosing disease is a rare entity in the head and neck. There are documented reports of steroid therapy for this disease, but the patient presented here demonstrated clinical progression of disease with steroids alone. The use of combination therapy of surgery, dexamethasone, and rituximab provided clinical improvement and stable disease determined by radiographic means.

Postoperative respiratory failure after thyroid and parathyroid surgery: analysis of national surgical quality improvement program.

BACKGROUND: The risk-benefit analysis of any operation is influenced by its perioperative complications. Our objective was to examine the relationship between preoperative clinical characteristics and postoperative respiratory failure (PRF: mechanical ventilation for >48 hours after surgery or reintubation) within 30 days of thyroid and parathyroid surgeries. METHODS: American College of Surgeons' multicenter, prospective, National Surgical Quality Improvement Program (NSQIP) datasets (2007/2008) were used. Multivariable logistic regression was performed. RESULTS: Eighty-three of 20,778 (0.4%) patients developed PRF. Comparing patients who developed PRF to those who did not, 30-day mortality was seen in 13 of 83 versus 11 of 20,695 patients (p < .0001); and mean length of stay (LOS) was 9.1 (±9.5) days versus 1.1 (±1.6) days (p < .0001). Multivariable analysis demonstrated preoperative pneumonia, dependent functional status, dyspnea, dialysis dependence, hypertension, advanced age, and combined thyroid and parathyroid surgery as risk factors for PRF. CONCLUSION: PRF after thyroid and parathyroid surgeries is uncommon, but associated with significantly increased 30-day morbidity and mortality.

Outcomes after thyroidectomy and parathyroidectomy.

BACKGROUND: Previous reports on postoperative outcomes following thyroid and parathyroid surgery are limited by relatively small sample size. We report 30-day outcomes following thyroid and parathyroid surgery and analyze factors affecting length of stay (LOS) and postoperative adverse events (AEs). METHODS: The multicenter, prospective, National Surgical Quality Improvement Program (NSQIP) datasets (2007/2008) were used. Multivariable logistic regression and analysis of covariance (ANCOVA) were performed. RESULTS: Patients undergoing thyroidectomy, parathyroidectomy, or both were identified (n = 13,380, 6154, 1535, respectively). Thirty-day mortality was 0.08%, 0.16%, and 0.2%, respectively; 30-day morbidity was 3.50%, 3.02%, and 4.04%, respectively. Mean LOS values were 1.1 ± 1.4, 1.1 ± 2.1, and 1.4 ± 3.1 days, respectively. Congestive heart failure, dependent functional status, dialysis dependence, and chronic corticosteroid use were significantly associated with increased LOS and postoperative AE. CONCLUSIONS: Morbidity and mortality rates following thyroid and parathyroid surgery are low. These data could be used by third-party interests, and surgeons should be aware of them to ensure their outcomes are in the national norm.

Ultrasound-guided procedures for the office.

Ultrasonography has an ever increasing role in the management of a wide variety of diseases affecting the head and neck. While ultrasonography is most commonly used for imaging of thyroid pathology, it also can be utilized in a host of diagnostic and therapeutic procedures. This article reviews the office-based ultrasound-guided procedures in the head and neck and discusses technical considerations for performing these interventions.

The small round blue cell tumors of the sinonasal area.

The diagnostic classification of small round blue cell tumors of the sinonasal area to include diverse malignancies of epithelial, hematolymphoid, neuroectodermal, and mesenchymal origin is challenging to the surgical pathologist using conventional histopathologic approaches because the cytomorphologic features are often overlapping or indistinctive. Rare or occasional clinical presentations in atypical age groups or unusual locations, as well as small biopsy samples may further complicate the differential diagnosis. Immunohistochemistry represents an extensively investigated ancillary technique that may aid in the provision of a definitive diagnosis. In recent years, certain small round blue cell tumors have been shown by cytogenetic analysis to have specific and primary chromosomal alterations, providing clinicians with a valuable tool to enhance their diagnostic armamentarium. The addition of molecular cytogenetic [fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH)] and molecular pathologic [polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR] approaches has further enhanced the sensitivity and accuracy of detecting these genetic alterations including assessment in formalin-fixed, paraffin-embedded tissues. Establishing an accurate diagnosis of a small round blue cell tumor of the sinonasal tract frequently requires adjunctive studies including immunohistochemical and molecular analyses.