Juvenile recurrent parotitis: Review and proposed management algorithm.

INTRODUCTION: Despite being the second most common salivary disease in childhood, the aetiology and appropriate management of juvenile recurrent parotitis (JRP) remains uncertain. Consequently patients may be misdiagnosed, or even undergo indeterminate or potentially invasive procedures without benefit. This article reviews the current understanding of the epidemiology and pathophysiology of JRP, and to appraise the management options available. METHODS AND RESULTS: Medline and Google Scholar databases were searched and peer reviewed journal articles assessed. The epidemiology of JRP remains uncertain, and the clinical presentation of JRP can vary widely in frequency and severity. Diagnosis is still largely based on clinical signs and symptoms including parotid swelling, pain and fever. Investigation typically focuses on the exclusion of other diseases and immunodeficiencies, however there are noted typical radiological findings on both ultrasound and magnetic resonance imaging. The ideal management of this condition still remains unclear, however symptoms typically resolve by puberty. Treatment focuses on minimally invasive procedures such as sialography and sialendoscopy to reduce the frequency and severity of acute episodes. CONCLUSIONS: Acute episodes of JRP can occur up to 30 times per year and have a significant impact on the quality of life of an affected child. Consequently a management algorithm is proposed based on the exclusion of other pathology. There is increasing evidence for non-ablative, minimally invasive approaches such as sialography and sialendoscopy to reduce the impact of this disease.

Future directions in soft tissue sarcoma treatment.

Sarcoma is a broad term for mesenchymal malignancies that arise from soft tissue or bone. Despite classification by histologic subtype, clinical behavior and response to therapy have great variability. Modern genetic sequencing techniques have been able to identify additional genetic variability and subsequently new targeted therapies. In this review, we discuss the current state of STS diagnostics and treatment and explore some of the more promising areas in which progress is being made. We discuss therapies targeting PDGFRα/KIT, ß-Catenin/APC/NOTCH, IDH-1/2 mutations, MDM2 amplifications, EZH2/INI1 expression loss, ALK fusion, and ASPSCR1-TFE3 fusion. We also discuss the progress that has been made within immunotherapies. While soft tissue sarcomas still portend a poor prognosis, these targeted therapies and immunotherapies provide treatment with less toxic side effects.

Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma.

Background: To identify aberrant promoter methylation of genomic loci encoding microRNA (mgmiR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate a biomarker panel of mgmiRs to improve the diagnostic accuracy of HNSCC in tissues and saliva. Methods: Methylation of promoter regions of mgmiR candidates was initially screened using HNSCC and control cell lines and further selected using HNSCC and control tissues by quantitative methylation-specific PCR (qMS-PCR). We then examined a panel of seven mgmiRs for validation in an expanded cohort including 189 HNSCC and 92 non-HNSCC controls. Saliva from 86 pre-treatment HNSCC patients and 108 non-HNSCC controls was also examined using this panel of seven mgmiRs to assess the potentials of clinical utilization. Results: Among the 315 screened mgmiRs, 12 mgmiRs were significantly increased in HNSCC cell lines compared to control cell lines. Seven out of the 12 mgmiRs, i.e., mgmiR9-1, mgmiR124-1, mgmiR124-2, mgmiR124-3, mgmiR129-2, mgmiR137, and mgmiR148a, were further found to significantly increase in HNSCC tumor tissues compared to control tissues. Using multivariable logistic regression with dichotomized variables, a combination of the seven mgmiRs had sensitivity and specificity of 92.6 and 92.4% in tissues and 76.7 and 86.1% in saliva, respectively. Area under the receiver operating curve for this panel was 0.97 in tissue and 0.93 in saliva. This model was validated by independent bootstrap validation and random forest analysis. Conclusions: mgmiR biomarkers represent a novel and promising screening tool, and the seven-mgmiR panel is able to robustly detect HNSCC in both patient tissue and saliva.

Long-Term Follow-Up of Desmoid Fibromatosis Treated with PF-03084014, an Oral Gamma Secretase Inhibitor.

BACKGROUND: Desmoid fibromatosis is a fibroblastic neoplasm driven by aberrations within the WNT pathway, exhibiting mutations in ß-catenin or APC. We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014. METHODS: PF-03084014 was administered orally at doses ranging from 20 to 330 mg twice daily. Tumor assessments were performed using computed tomography/magnetic resonance imaging (CT/MRI) within 4 weeks of study entry, and every other cycle through cycle 9. After cycle 9, patients were evaluated as clinically indicated. RESULTS: Seven patients with desmoid fibromatosis were treated between December 2009 and December 2016 at the University of Colorado. Five patients (71.4%, 95% confidence interval [CI] 29.0-96.3%) achieved a partial response (PR), with a mean time to achieving response of 11.9 months (95% CI 2.5-21.4 months). All patients who achieved a PR continue to maintain responses between 47.9 and 73+ months. Four patients stopped treatment yet remain free of progression between 11 and 53+ months. One patient had PFS of 42+ months, with a 17% decrease in the target lesion. A biopsy performed at the end of the study showed decreased tumoral cellularity compared with previous biopsies. Effective treatment doses ranged from 80 to 330 mg administered orally twice daily. CONCLUSIONS: PF-03084014 was effective in treating desmoid tumors, with an objective response rate of 71.4% (95% CI 29.0-96.3%) in this small cohort of patients. PF-03084014 exhibits promising activity, even at relatively low doses (80 mg twice daily), with high tolerability leading to prolonged disease control even after therapy discontinuation.

Chronic otitis media with effusion following radiation therapy.

The incidence of chronic otitis media with effusion (COME) after radiotherapy for nasopharyngeal or sinonasal tumors is relatively high. It is often a difficult-to-treat problem in these patients. In this retrospective study, we sought to describe the clinical course of COME in 51 patients-33 men and 18 women, aged 39 to 90 years (mean: 58.9 ± 15)-who had been referred to the Henry Ford Health System in Detroit between 2001 and 2011 for management of a tumor that had involved either the nasopharyngeal area or the sinonasal area. The median length of follow-up from the time of cancer diagnosis was 32 months. Of the 51 patients, 23 (45.1%) developed COME before, during, or after radiation therapy. Of these 23 patients, 13 (56.5%) did not experience any improvement after treatment with various combinations of therapies, including myringotomy, tympanostomy tube placement, otic drops, oral antibiotics, and corticosteroid nasal sprays. No patient- or tumor-specific factors were found to be significantly associated with the incidence of COME after irradiation to the sinonasal area. Older age and squamous cell tumor pathology were found to be significant factors for the resolution of COME after it had developed, whereas treatments with tympanostomy tubes and ear drops were not. Because of the high incidence of COME after radiotherapy and the high rate of COME's failure to resolve after tympanostomy tube insertion, we suggest that these patients require an alternative treatment.

Review of perforator flaps in head and neck cancer surgery.

PURPOSE OF REVIEW: Perforator flaps are increasingly being used to reconstruct head and neck defects. They offer several advantages over nonperforator-based flaps with lower donor site morbidity and a versatile range of reconstructive options. The anterolateral thigh flap is well established in the head and neck and is a good example of a reliable perforator free flap. With the increasing use of both free and regional perforator-based flaps, it is timely to review their anatomy, clinical applications, and role in head and neck reconstruction. We also discuss increasingly popular perforator flaps such as the submental flap for the head and neck. RECENT FINDINGS: The anterolateral thigh flap is now commonly used to reconstruct a wide variety of head and neck defects. The submental flap fills a niche role for reconstruction of intraoral defects. SUMMARY: Perforator flaps are now mainstream reconstructive options in the head and neck surgeon's armamentarium.

Head and neck cancer screenings and human papillomavirus knowledge across diverse suburban and urban populations.

BACKGROUND: Minimal research has explored community dwelling adults' knowledge of the human papillomavirus (HPV) in relation to head and neck cancer (HNC). The purpose of this study was to report on community dwelling adults' knowledge of HPV in relation to infection, symptoms, and the development of HNC. METHODS: Cross-sectional assessment of community-dwelling adults on history of behavioral risk factors for HNC, health literacy, and knowledge regarding HPV in relation to HNC. RESULTS: Of those who completed the measure of health literacy, 17.1% read at or below an 8th grade level. Participants reported a range of history of behaviors putting them at increased risk for HPV and HNC. Respondents answered an average of 67.2% of HPV questions correctly, only one person answered all 15 questions correctly. There were no differences in knowledge of HPV in relation to HNC based upon demographics, suburban versus urban location, health literacy, or cancer history. CONCLUSIONS: Adults reported a range of behaviors associated with an increased risk of HPV transmission but also displayed large gaps in knowledge regarding HPV in relation to HNC.

Oropharyngeal carcinoma in young adults: an alarming national trend.

OBJECTIVES: To assess the incidence, treatment methods, and outcomes of oropharyngeal squamous cell carcinoma (OPSCC) in patients younger than 45 years. STUDY DESIGN: Retrospective population based. SETTING: Surveillance Epidemiology End Results (SEER) 9 database. SUBJECTS AND METHODS: The SEER 9 database was queried from 1973 to 2009 for OPSCC patients <45 years of age. RESULTS: There were 1603 patients with OPSCC younger than 45 years. The incidence in patients between 36 and 44 years increased from 0.79 to 1.39 (per 100,000). In the same time period, there was an increase in the rate from 0.20 to 0.42 in whites and a decrease in the rate in African American (AA) patients from 0.67 to 0.32. The proportion of grade III/IV tumors also steadily increased from 28% in 1973 to 1979 to 43% in 2000 to 2009 (P < .0001). Surgery alone was performed in 220 patients (13.72%) and in combination with radiation therapy in 734 patients (45.79%). Five-year survival for the study cohort is 54%. Compared with white patients, AA patients had worse survival (P < .0001). Patients who had surgery, either alone (localized stage patients) or in combination with radiation, had the highest 5-year survival followed by those who had radiation. CONCLUSIONS: There was an increase in OPSCC in the study patients within the past 4 decades, particularly in those aged 36 to 44 years. Interestingly, the incidence in whites increased and in AA patients it decreased. It is important to note that most of these patients were treated with surgery, either alone or with radiation therapy. The rising incidence within recent decades is thought to be related to human papillomavirus transmission and changes in sexual practices.

Gastrostomy tube use after transoral robotic surgery for oropharyngeal cancer.

Objective. To evaluate factors that influence gastrostomy tube (g-tube) use after transoral robotic surgery (TORS) for oropharyngeal (OP) cancer. Study Design/Methods. Retrospective review of TORS patients with OP cancer. G-tube presence was recorded before and after surgery at followup. Kaplan-Meier and Cox hazards model evaluated effects of early (T1 and T2) and advanced (T3, T4) disease, adjuvant therapy, and free flap reconstruction on g-tube use. Results. Sixteen patients had tonsillar cancer and 13 tongue base cancer. Of 22 patients who underwent TORS as primary therapy, 17 had T1 T2 stage and five T3 T4 stage. Seven underwent salvage therapy (four T1 T2 and three T3 T4). Nine underwent robotic-assisted inset free flap reconstruction. Seventeen received adjuvant therapy. Four groups were compared: primary early disease (PED) T1 and T2 tumors, primary early disease with adjunctive therapy (PEDAT), primary advanced disease (PAD) T3 and T4 tumors, and salvage therapy. Within the first year of treatment, 0% PED, 44% PEDAT, 40% PAD, and 57% salvage patients required a g-tube. Fourteen patients had a temporary nasoenteric tube (48.3%) postoperatively, and 10 required a g-tube (34.5%) within the first year. Four of 22 (18.2%) with TORS as primary treatment were g-tube dependent at one year and had received adjuvant therapy. Conclusion. PED can be managed without a g-tube after TORS. Similar feeding tube rates were found for PEDAT and PAD patients. Salvage patients have a high rate of g-tube need after TORS.

Frailty as a predictor of morbidity and mortality in inpatient head and neck surgery.

IMPORTANCE: The increasing number of elderly and comorbid patients undergoing surgical procedures raises interest in better identifying patients at increased risk of morbidity and mortality, independent of age. Frailty has been identified as a predictor of surgical complications. OBJECTIVE: To establish the implications of frailty as a predictor of morbidity and mortality in inpatient otolaryngologic operations. DESIGN: Retrospective review of medical records. SETTING: National Surgical Quality Improvement Program (NSQIP) participating hospitals. PATIENTS: NSQIP participant use files were used to identify 6727 inpatients who underwent operations performed by surgeons specializing in otolaryngology between 2005 and 2010. The study sample was 50.3% male and 10.2% African American, with a mean (range) age of 54.7 (16-90) years. MAIN OUTCOMES AND MEASURES: A previously described modified frailty index (mFI) was calculated on the basis of NSQIP variables. The effect of increasing frailty on morbidity and mortality was evaluated using univariate analysis. Multivariate logistic regression was used to compare mFI with age, ASA, and wound classification. RESULTS The mean (range) mFI was 0.07 (0-0.73). As the mFI increased from 0 (no frailty-associated variables) to 0.45 (5 of 11) or higher, mortality risk increased from 0.2% to 11.9%. The risk of Clavien-Dindo grade IV complications increased from 1.2% to 26.2%. The risk of all complications increased from 9.5% to 40.5%. All results were significant at P < .001. In a multivariate logistic regression model to predict mortality or serious complication, mFI became the dominant significant predictor. CONCLUSIONS AND RELEVANCE: The mFI is significantly associated with morbidity and mortality in this retrospective survey. Additional study with prospective analysis and external validation is needed. The mFI may provide an improved understanding of preoperative risk, which would facilitate perioperative optimization, risk stratification, and counseling related to outcomes.

Human papilloma virus prevalence in a multiethnic screening population.

OBJECTIVE: The goal was to determine the prevalence of high-risk HPV16 using saliva in a screening population in Detroit, Michigan. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction was applied to detect HPV16 in saliva DNA from 349 screening subjects without head and neck cancer (HNC), 156 with HNC, and 19 controls. Cut points for human papilloma virus (HPV) positivity were >0 and >0.001 copy/cell. Proportions were compared between groups using exact χ(2) or Fisher exact tests (P < .05). RESULTS: At a cut point >0, each group had an overall HPV prevalence of more than 5%, with a higher prevalence of 30.8% in the HNC patient group. At a cut point >0.001, the prevalence was lower: 0% in the control, 1.2% in the screening, and 16.7% in the HNC group. In the latter, for both cut points, HPV prevalence was different across sites (<0.001) and significantly higher in the oropharynx than larynx or site as other after Hochberg's adjustment. At >0, women in the screening group had a higher prevalence of HPV than did men (P = .010), and at >0.001, the prevalence was higher for men in the HNC group than for women (P = .035). In the screening group, at >0, only African Americans had a higher prevalence than Caucasian Americans (P = .025). CONCLUSIONS: In the screening group, a 6.9% and 1.2% screening rate was noted at cut points >0 and >0.001, respectively. The results provide data to inform public health considerations of the feasibility of saliva as a screening tool in at-risk populations with the long-term goal of prophylactic vaccination against oral HPV.

Head and neck cancer in transplant recipients.

OBJECTIVES/HYPOTHESIS: The development of malignancy in organ transplant patients is a well-known complication of long-term immunosuppressive therapy. We sought to characterize our institution's 20-year experience with head and neck cancer after solid organ transplantation. STUDY DESIGN: Retrospective review. METHODS: Patients who underwent a solid organ transplant with subsequent development of a head and neck malignancy, including cutaneous and noncutaneous (upper aerodigestive tract and salivary gland) cancers, from January 1990 through December 2011 were identified. Patients were stratified according to cancer type, location, stage, and survival and compared to a nontransplant cohort in our institution's tumor registry. RESULTS: Of 95 patients identified, 17 had noncutaneous and 78 had cutaneous head and neck malignancies post-transplant. Among the noncutaneous group, no statistically significant differences occurred in age, gender, stage, or 5-year survival status when compared to the nontransplant tumor registry cohort. However, significantly fewer transplant patients were alive at 1 year. Among the cutaneous group, >50% had multiple malignancies. The total incidence of head and neck cancer following organ transplantation was 2.6%. CONCLUSIONS: Although the development of head and neck cancer is a rare side effect of immunosuppression, it still warrants attention. These patients have been found to be less likely to survive >1 year when compared to their nontransplant counterparts. Patients who develop head and neck malignancies following organ transplantation require aggressive screening, treatment, and follow-up, as this diagnosis may portend a poor prognosis.

Risk factors for well-differentiated thyroid carcinoma in patients with thyroid nodular disease.

OBJECTIVES: Evaluate current accepted risk factors for well-differentiated thyroid carcinoma, and develop a predictive model to determine one's risk of malignancy given a thyroid nodule. STUDY DESIGN: Retrospective analysis of 600 patients. SUBJECTS AND METHODS: Patients with benign thyroid nodular disease and with well-differentiated thyroid cancer were randomly selected. Patient, clinical, and investigational data were compared by means of univariate and multivariate regression analyses. RESULTS: Age, regional lymphadenopathy, ipsilateral vocal cord palsy, solid and/or calcified nodules, and an aspiration biopsy being malignant or suspicious predicted for cancer (P < 0.05). Regional lymphadenopathy and vocal cord palsy are perfect predictors of malignancy. Multivariate analysis indicated age, solid and/or calcified nodules, and all fine-needle aspiration biopsy results to be significant in assessing risk (P < 0.05). CONCLUSION: Taking individual risk factors in isolation is not always reliable. Using a predictive model, one can anticipate a patient's risk of malignancy when the diagnosis is unclear.

Predictors of morbidity following free flap reconstruction for cancer of the head and neck.

BACKGROUND: Free flap reconstruction of head and neck cancer defects is complex with many factors that influence perioperative complications. The aim was to determine if there was an association between perioperative variables and postoperative outcome. METHODS: We evaluated 185 patients undergoing free flap reconstruction following ablation of head and neck cancer between 1999 and 2001. Demographic, laboratory, surgical and anesthetic variables were analyzed using univariate and multivariable techniques. RESULTS: Ninety-eight patients (53%) developed complications, of which 74 were considered major, giving a major morbidity rate of 40%. Predictors of major complications were increasing patient age, ASA class, and smoking. Predictors of medical complications were ASA class, smoking, age and crystalloid replacement. Predictors of surgical complications were tracheostomy, preoperative hemoglobin, and preoperative radiotherapy. CONCLUSION: Patient age, comorbidity, smoking, preoperative hemoglobin, and perioperative fluid management are potential predictors of postoperative complications following free flap reconstruction for cancer of the head and neck.

Prediction of pharyngocutaneous fistulas after laryngectomy.

OBJECTIVE: To assess the predictive value of wound amylase as an indicator for pharyngocutaneous fistula development following laryngectomy for cancer. DESIGN AND SETTING: We conducted a prospective observational study at a tertiary referral center of 102 consecutive laryngeal or hypopharyngeal cancer patients undergoing laryngectomy with or without pharyngectomy. INTERVENTION: Data were collated on potential predictors of fistula formation compared with rate of development of clinical fistulas, all confirmed radiologically. MAIN OUTCOME MEASURES: Rate of fistula formation was determined for the following potential predictors: extent of resection (extended laryngectomy), postoperative wound (drain) amylase, previous radiotherapy, neck dissection, preoperative and postoperative hemoglobin and albumin levels, and postoperative transfusion. Sensitivity, specificity, and positive and negative predictive values of significant predictors were ascertained. RESULTS: The only significant predictors of fistula formation were extent of resection (extended laryngectomy) and drain amylase >4000 IU/L. If both factors are combined, the sensitivity, specificity, and positive and negative predictive values for fistula development are 83, 94, 63, and 98 percent, respectively. CONCLUSION: We advocate that patients be managed postoperatively according to the presence or absence of these given predictors to reduce occurrence of fistula formation in the high-risk group.

Lead in a Baltimore shipyard.

OBJECTIVE: The goal was to monitor the effectiveness of the Coast Guard Yard's lead program by comparing a shipyard period in 1991 to one in 2002-2003. METHODS: Comparisons of airborne lead levels by paint removal techniques, airborne lead levels by welding techniques, and blood lead levels of workers were evaluated by chi2 analysis. RESULTS: Airborne lead levels in paint removal techniques decreased over time for all methods used. Airborne lead levels in welding techniques decreased over time for all methods used. Blood lead levels of the high-risk group revealed a 2-fold reduction (prevalence rate ratio = 8.3; 95% confidence interval, 3.7-18.6) and in the low-risk group revealed a 1.6-fold reduction (prevalence rate ratio = 6.2; 95% confidence interval, 0.86-44.7). CONCLUSION: The Coast Guard Yard runs an effective lead program that exceeds the national Healthy People 2010 goal for lead. The results validate the Coast Guard Yard's use of air-line respirators and lead-free paint on all vessels.

Variables predicting distant metastases in thyroid cancer.

OBJECTIVES: Distant metastases from thyroid cancer are uncommon and have a variable prognosis. We present a series of patients with distant metastases to determine which patients are at risk of developing distant disease and to examine the significant prognostic variables. STUDY DESIGN: Retrospective chart review of 30 patients with distant metastases compared with 633 controls from the Mount Sinai Thyroid Cancer Database and literature review. METHODS: The prevalence of distant metastases was 4.5%, and median follow-up of survivors was 12.7 years. Histologic type was Hurthle cell carcinoma in 3, follicular in 3, papillary in 19, and 5 patients had focal anaplasia either in the primary site or regional metastases. Predictors for distant metastases, locoregional control, and survival were analyzed. RESULTS: Cumulative survival for patients with distant metastases was 49.5% at 10 years and 12.9% at 20 years. Site of metastases was lung in 26, bone in 11 and brain in 1 patient, with 8 patients having multiple sites. The median time to diagnosis of distant metastases was 3 months. Variables that predicted for development of distant disease were male sex, age, size, extrathyroidal extension, regional metastases, and elevated thyroglobulin. Survival in patients without distant disease was significantly better than those with distant metastases (P < .001). Variables that predicted poor outcome in patients with distant metastases on analysis were age greater than 45 years (P = .003) and histologic type of thyroid cancer (P = .009). CONCLUSION: Although patients with thyroid cancer and distant metastases may live prolonged periods with disease, it does significantly impact on patient survival. Age remains an important variable in both predicting for development of distant metastases and also influences long-term survival in patients with existing distant metastases.