Effect of actionable somatic mutations on racial/ethnic disparities in head and neck cancer prognosis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated. METHODS: In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%). RESULTS: Hispanic whites and African Americans had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage. CONCLUSION: We have provided the proof-of-principal data to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the way for precision medicine to overcome HNSCC survival disparities. © 2016 Wiley Periodicals, Inc. Head Neck 38:1234-1241, 2016.

The Effects of Preoperative Embolization on Carotid Body Paraganglioma Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: There is no definitive consensus on the impact of preoperative embolization on carotid body paraganglioma management. The purpose of this study was to assess the effects of preoperative embolization on carotid body paraganglioma excision. DATA SOURCES: A systematic search was conducted without limits, and it included studies published on or before July 2013 from PubMed, CINAHL, Web of Knowledge, and the Cochrane Library. Relevant synonyms for the search terms "paraganglioma,""carotid body tumor," and "embolization" were applied. REVIEW METHODS: Studies evaluating patients undergoing surgical intervention with embolization for carotid body tumors were included. Two reviewers independently assessed the titles and abstracts for inclusion and extracted the data. The guidelines set forth by the Cochrane Collaboration were followed in the process of data extraction. Data were pooled with a fixed effects model, and standardized mean difference (SMD) and 95% confidence intervals (95% CIs) are reported. RESULTS: A total of 22 studies (15 nonrandomized studies with a comparator, 7 single-arm studies) were included, enrolling 578 patients with 607 tumors. Patients undergoing preoperative embolization had significantly less estimated blood loss compared with those of surgical excision only (12 studies; 295 tumors; SMD: -0.52; 95% CI: -0.77, -0.28). Patients undergoing preoperative embolization had less operative time compared with that of surgical excision only (6 studies; 174 tumors; SMD: -0.46; 95% CI: -0.77, -0.14). CONCLUSION: Surgical excision with preoperative embolization appears to decrease estimated blood loss and operative time when compared with that without preoperative embolization for carotid body paragangliomas.

Intensity-modulated radiation therapy as primary treatment for oropharyngeal squamous cell carcinoma.

BACKGROUND: Over the past decade, intensity-modulated radiation therapy (IMRT) has gained widespread use in the treatment of head and neck cancer. METHODS: All patients with squamous cell carcinoma of the oropharynx treated with primary IMRT with or without chemotherapy over a 5-year period were reviewed. Outcomes and morbidity were analyzed and compared with previously published data. RESULTS: In all, 170 patients were included in the analysis. The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 92%, 91%, 80%, and 87%, respectively. Feeding tubes were present in 55% of patients during treatment, but remained in only 1% 2 years following treatment. CONCLUSIONS: This study confirms that IMRT yields excellent treatment outcomes for oropharyngeal carcinoma. Although acute toxicity remains a problem, late toxicity rates are low and long-term feeding tube dependence is rare compared with conventional radiation therapy.

Chondrosarcoma of the subglottic larynx: submucosal microdissection with the operating microscope.

OBJECTIVES/HYPOTHESIS: Chondrosarcoma is a rare malignancy of the head and neck with fewer than 600 cases described in the literature. Treatment typically consists of conservation surgery with preservation of airway and preoperative voice quality. We describe five patients treated with a conservative transcervical approach utilizing the operating microscope for submucosal microdissection. STUDY DESIGN: Retrospective case series at a National Cancer Institute-designated comprehensive cancer center. METHODS: A retrospective case series from February 2004 to February 2011 was performed for all consecutive patients with laryngeal chondrosarcoma treated by the senior author with transcervical submucosal microdissection utilizing the operating microscope. RESULTS: Five patients with laryngeal chondrosarcoma were treated between February 2004 and February 2011. There were three male and two female patients who ranged in age from 56 to 87 years (mean, 72 years) at presentation. All five tumors were located at the level of the cricoid cartilage. Hoarseness was the most common presenting symptom (60%). Eighty percent of patients had limited vocal cord mobility. No patients required neck dissection or received radiation or chemotherapy. None of the five patients had recurrence after this approach. CONCLUSIONS: Laryngeal chondrosarcoma is a rare tumor. Conservative surgical resection remains the mainstay of treatment. The use of an operating microscope can aid in successful resection of laryngeal chondrosarcoma while preserving laryngeal mucosa and function. LEVEL OF EVIDENCE: 4.

Endoscopic repair of Zenker's diverticulum by harmonic scalpel.

PURPOSE: Although endoscopic staple-assisted esophagodiverticulostomy (ESED) has become the initial treatment of choice for most patients with Zenker's diverticulum (ZD), anatomical restraints prevent its use in all cases. We describe an endoscopic approach for treating ZD using the harmonic scalpel, which can be used in certain cases where diverticulum anatomy precludes ESED. MATERIALS AND METHODS: Medical records of 7 consecutive patients who underwent endoscopic repair of ZD using the harmonic scalpel (Harmonic Ace, Ethicon Endo-Surgery, Inc, Cincinnati, OH) were reviewed. Data collected included demographics, symptoms, surgical details, complications, and postoperative outcomes. Main outcome measures were time to resumption of oral diet, symptom resolution, and complications. RESULTS: All patients (N = 7) who underwent endoscopic repair of ZD using the harmonic scalpel resumed an oral diet at initial follow-up visit after surgery (mean, 7 days; range, 4-9 days) and rated their symptoms as being completely resolved at subsequent follow-up (mean, 4 months; range, 1.5-8 months). There were no complications. CONCLUSIONS: Endoscopic repair of ZD using the ultrasonic cutting shears is a safe and efficacious procedure that allows for endoscopic treatment in certain cases that cannot be treated by ESED. Further study is warranted in larger series to determine efficacy and safety compared with established endoscopic techniques.

HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment.

Myeloid-derived suppressor cells (MDSCs) are a major component of the immune-suppressive network described in cancer and many other pathological conditions. We demonstrate that although MDSCs from peripheral lymphoid organs and the tumor site share similar phenotype and morphology, these cells display profound functional differences. MDSC from peripheral lymphoid organs suppressed antigen-specific CD8(+) T cells but failed to inhibit nonspecific T cell function. In sharp contrast, tumor MDSC suppressed both antigen-specific and nonspecific T cell activity. The tumor microenvironment caused rapid and dramatic up-regulation of arginase I and inducible nitric oxide synthase in MDSC, which was accompanied by down-regulation of nicotinamide adenine dinucleotide phosphate-oxidase and reactive oxygen species in these cells. In contrast to MDSC from the spleen, MDSC from the tumor site rapidly differentiated into macrophages. Exposure of spleen MDSC to hypoxia resulted in the conversion of these cells to nonspecific suppressors and their preferential differentiation to macrophages. Hypoxia-inducible factor (HIF) 1α was found to be primarily responsible for the observed effects of the tumor microenvironment on MDSC differentiation and function. Thus, hypoxia via HIF-1α dramatically alters the function of MDSC in the tumor microenvironment and redirects their differentiation toward tumor-associated macrophages, hence providing a mechanistic link between different myeloid suppressive cells in the tumor microenvironment.

Lipid accumulation and dendritic cell dysfunction in cancer.

Dendritic cells (DCs), a type of professional antigen-presenting cells, are responsible for initiation and maintenance of immune responses. Here we report that a substantial proportion of DCs in tumor-bearing mice and people with cancer have high amounts of triglycerides as compared with DCs from tumor-free mice and healthy individuals. In our studies, lipid accumulation in DCs was caused by increased uptake of extracellular lipids due to upregulation of scavenger receptor A. DCs with high lipid content were not able to effectively stimulate allogeneic T cells or present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of major histocompatibility complex and co-stimulatory molecules. However, lipid-laden DCs had a reduced capacity to process antigens. Pharmacological normalization of lipid abundance in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects of cancer vaccines. These findings suggest that immune responses in cancer can be improved by manipulating the lipid levels in DCs.

Otolaryngologic management of delayed pharyngoesophageal perforation following anterior cervical spine surgery.

Delayed pharyngoesophageal perforation is a rare complication following anterior cervical spine surgery. Patients usually present weeks to years after surgery with vague symptoms, such as dysphagia and neck pain. We report five cases of delayed pharyngoesophageal perforation following anterior cervical spine surgery with hardware fixation. Successful surgical management of these patients required removal of hardware and closure of the defect supported with a vascularized flap.

Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSC) are a major component of the immune suppressive network described in cancer and many other pathological conditions. Recent studies have demonstrated that one of the major mechanisms of MDSC-induced immune suppression is mediated by reactive oxygen species (ROS). However, the mechanism of this phenomenon remained unknown. In this study, we observed a substantial up-regulation of ROS by MDSC in all of seven different tumor models and in patients with head and neck cancer. The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). MDSC from tumor-bearing mice had significantly higher expression of NOX2 subunits, primarily p47(phox) and gp91(phox), compared with immature myeloid cells from tumor-free mice. Expression of NOX2 subunits in MDSC was controlled by the STAT3 transcription factor. In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. These findings expand our fundamental understanding of the biology of MDSC and may also open new opportunities for therapeutic regulation of these cells in cancer.

Using hand-held computing devices in the practice of otolaryngology-head and neck surgery.

Personal digital assistants (PDAs) have taken an increasing role in the practice of otolaryngology. PDAs provide an extension of the resources available on the user's PC. Handheld devices currently are being used for e-prescribing, charge capture, and accessing daily schedules and reference tools. Future applications may include education on medications, dictation, order entry, and test-results reporting. These applications of PDAs in the practice of otolaryngology will be reviewed.

Intraoperative radiotherapy for head and neck and skull base cancer.

BACKGROUND: The purpose of this study was to evaluate the use of intraoperative electron beam radiotherapy (IORT) as an adjuvant modality in the treatment of advanced head and neck and skull base cancer. METHODS: Between 1991 and 1996, 34 patients with squamous cell carcinoma (SCCA) and 10 patients with non-SCCA were enrolled in this prospective nonrandomized clinical trial. Most patients had been previously treated with combinations of surgery, external beam radiotherapy, and chemotherapy. The most frequent sites treated were the skull base (56%) and the neck (44%). IORT was delivered in a dedicated operating room suite with energies of 6 to 15 MeV (6 MeV most commonly used) at doses of 12.5 to 22.5 Gy. RESULTS: At 2 years overall and disease-free survival was 32% and 21%, respectively, for the SCCA patients and 50% and 40%, respectively, for the non-SCCA patients. Tumor control rates at 2 years in the IORT field were 46% for the SCCA patients and 52% for the non-SCCA patients. For squamous cell histology, survival in patients with microscopic residual tumor did not differ from those with no residual tumor, but they both had significantly longer disease-free survival than those patients with gross residual at the time of IORT (p =.03), with a trend toward longer overall survival (p =.09). The only complication directly attributable to IORT was a neuropathy in a patient who received an IORT dose of 22.5 Gy (cumulative dose 130.1 Gy). CONCLUSIONS: IORT at a dose of 12.5 Gy is safe and produces tumor control and survival for patients likely to have microscopic residual disease in sites difficult to resect such as the skull base.

Rhinomanometry

Apresenta-se uma atualizaçäo sobre a técnica e o valor clínico da rinomanometria