Oropharyngeal tumor cells induce COX-2 expression in peripheral blood monocytes by secretion of IL-1α.

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.

A Mobile Patient-Facing App for Tracking Patient-Reported Outcomes in Head and Neck Cancer Survivors: Single-Arm Feasibility Study.

BACKGROUND: Patients with head and neck cancer (HNC) frequently experience disease-related symptoms and treatment adverse effects that impact their overall quality of life. Cancer-specific mobile health apps for patient-related outcomes allow patients to communicate with their clinicians and proactively track their symptoms, which have been shown to improve clinical management and disease outcomes. OBJECTIVE: The purpose of this study was to evaluate the feasibility of LogPAL, a novel iPhone-based mobile health app designed to help HNC survivors track and manage their posttreatment symptoms. METHODS: Patients who completed curative treatment for HNC in the preceding 24 months were recruited from 2 clinical sites within a single institution. Upon enrollment, participants completed a brief sociodemographic survey, downloaded the app onto their iPhone devices, and were asked to complete a series of biweekly questionnaires (based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) via the app for an 8-week study period. The primary feasibility endpoints included retention (retaining >80% of the enrolled participants for the duration of the study period), adherence (>50% of the participants completing 100% of the questionnaires over the study period), and usability (a mean system usability scale [SUS] score >68). Additional postintervention questions were collected to assess perceived usefulness, acceptance, and overall satisfaction. RESULTS: Between January and October 2019, 38 participants were enrolled in the study. Three participants dropped out, and 3 were classified as nonusers. The remaining 32 (87%) were eligible for analysis. Their mean age was 57.8 (SD 12.3) years (range 24-77 years, 81% [26/32] male). Overall, 375 of 512 (73.2%) questionnaires were completed, with 17 (53%) of the 32 participants adherent. Participant-reported usability was acceptable; the mean SUS score was 71.9 (95% CI 64.3-79.5) with high satisfaction of LogPAL usefulness and likelihood to recommend to other cancer survivors. CONCLUSIONS: This single-arm prospective pilot study showed that LogPAL is a feasible, regularly used, accepted app for HNC survivors, justifying a full-scale pilot. Based on the findings from this study, future iterations will aim to improve usability and test intervention efficacy.

Outcomes of nonsurgical management of locally advanced carcinomas of the sinonasal cavity.

OBJECTIVE: To determine the outcome of definitive concurrent chemoradiation with platinum for locally advanced sinonasal carcinomas. STUDY DESIGN: Retrospective cohort. METHODS: Twenty-three nonsurgically and definitively treated patients diagnosed between July 1998 and February 2009 were analyzed. Patients with adenoid cystic carcinoma or adenocarcinoma were treated with photons and neutrons; the other histologies received photons alone. The vast majority received chemotherapy. Descriptive statistics were utilized, and Kaplan-Meier estimates were computed. RESULTS: Female (57%) and Caucasian (74%) preponderance were observed. Eighty-seven percent were unresectable; the maxillary and nasoethmoid sites were equally prevalent. Intensity-modulated radiation therapy (IMRT) and photons alone were utilized in 74% and 70%, respectively. Platinum agents were given in 95% of chemotherapy patients. Complete response was observed in 64% of patients. Median progression-free survival (PFS) and overall survival (OS) were 28.8 and 65.3 months, respectively. Three-year PFS and OS rates were 44% and 72%, respectively; 5-year PFS and OS rates were 30% and 60%, respectively. Intensity-modulated radiation therapy and a maxillary site of origin showed a trend toward superior PFS; higher-dose regimens were associated with somewhat shorter PFS. Relapse was observed in 59% of patients, predominantly local. There were few unanticipated adverse effects, and no grade IV/V events were reported. CONCLUSION: Advanced sinonasal carcinomas are chemoradiosensitive tumors, albeit with a high propensity for local relapse. There is a definite indication for IMRT and a potential curative role of platinum-based chemoradiation regimens. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:855-861, 2017.

Surgeon performed ultrasound-guided fine-needle aspirates of the thyroid: 1067 biopsies and learning curve in a teaching center.

BACKGROUND: Surgeon performed ultrasound-guided fine-needle aspirates (UG-FNAs) reduce delay in diagnosis and allow for surgeon surveillance. We present the first report on a learning curve and impact of head and neck surgical trainees on adequacy rates. METHODS: Thyroid UG-FNA biopsies from 2009 to 2013 were reviewed retrospectively. Specimen adequacy, cytologic diagnosis, and surgical pathology were used to calculate adequacy and accuracy. RESULTS: One thousand sixty-seven biopsies were examined in 723 individuals. The adequacy rate from adoption into practice improved from 71% to 78% to 85% over 300 cases. When UG-FNA was subsequently taught to trainees, adequacy rates varied among trainees (p < .037), and there were higher nondiagnostic rates earlier in training (p = .04). Adequacy was not related to size or palpability, but cystic lesions yielded more inadequate specimens (p < .001). CONCLUSION: Surgeon performed UG-FNA biopsy can be performed adequately in an outpatient setting. Adequacy rates reach acceptable levels after 300 cases, whereas trainee involvement impacts adequacy rates. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1281-E1284, 2016.

Informed consent: do information pamphlets improve post-operative risk-recall in patients undergoing total thyroidectomy: prospective randomized control study.

BACKGROUND: Informed consent consists of basic five elements: voluntarism, capacity, disclosure, understanding, and ultimate decision-making. Physician disclosure, patient understanding, and information retention are all essential in the doctor-patient relationship. This is inclusive of helping patients make and manage their decisions and expectations better and also to deal with any consequences and/or complications that arise. This study investigates whether giving patients procedure-specific handouts pre-operatively as part of the established informed consent process significantly improves overall risk-recall following surgery. These handouts outline the anticipated peri-operative risks and complications associated with total thyroidectomy, as well as the corrective measures to address complications. In addition, the influence of potential confounders affecting risk-recall, such as anxiety and pre-existing memory disturbance, are also examined. METHODS: Consecutive adult (≥18 years old) patients undergoing total thyroidectomy at a single academic tertiary care referral centre are included. Participants are randomly assigned into either the experimental group (with pamphlets) or the control group by a computerized randomization system (Clinstat). All participants filled out a Hospital Anxiety and Depression Scale (HADS) and they are tested by the physician for short-term memory loss using the Memory Impairment Screen (MIS) exam. All patients are evaluated at one week post-operatively. The written recall questionnaire test is also administered during this clinical encounter. RESULTS: Forty-nine patients are included--25 of them receive verbal consent only, while another 24 patients received both verbal consent and patient education information pamphlets. The overall average of correct answers for each group was 83% and 80% in the control and intervention groups, respectively, with no statistically significant differences. There are also no statistically significant differences between the two groups, in both interview duration, in time between interviews, and in recall tests. No correlation is also apparent between the pre-op HADS score and the recall questionnaire overall score. CONCLUSIONS: A pre-operative thyroid surgical information pamphlet alone might not be sufficient to enhance patient test scores and optimally educate the patient on their expected care pathway in thyroid surgery. Supplementation with alternative means of patient education perhaps using emerging technologies needs to be further investigated.

Up-front neck dissection followed by concurrent chemoradiation in patients with regionally advanced head and neck cancer.

BACKGROUND: The appropriate management of the neck in patients with regionally advanced head and neck cancer remains controversial. The purpose of this study was to retrospectively analyze our institutional experience with up-front neck dissection followed by definitive chemoradiotherapy. METHODS: Fifty-five patients with radiographic evidence of large or necrotic lymph nodes underwent up-front neck dissection followed by definitive chemoradiation. RESULTS: The 5-year overall survival (OS) and progression-free survival (PFS) rates were estimated at 71.3% and 64.7%, respectively. There were 2 failures in the dissected neck, for a control rate of 96.7%. There were 7 locoregional failures and 12 distant failures, for locoregional and distant control rates of 87.3% and 78.2%, respectively. CONCLUSION: Up-front neck dissection followed by chemoradiotherapy resulted in excellent locoregional control, OS, and PFS. Utilization of this strategy should be considered in carefully selected patients with regionally advanced head and neck cancer. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.

Intrastriatal serotonin 5-HT2 receptors mediate dopamine D1-induced hyperlocomotion in 6-hydroxydopamine-lesioned rats.

Striatal dopamine (DA) and serotonin (5-HT) functions are altered following DA denervation. Previous research indicates that intrastriatal coadministration of D1 and 5-HT2 receptor agonists synergistically increase locomotor behavior in DA-depleted rats. In the present study, we examined whether striatal 5-HT2 mechanisms also account for supersensitive D1-mediated locomotor behavior following DA denervation. Adult male Sprague-Dawley rats were subjected to bilateral striatal cannulation and then received either intracerebroventricular (i.c.v.) or intrastriatal 6-hydroxydopamine (6-OHDA; 200 microg or 20 microg/side, respectively). After at least 3 weeks, i.c.v.-lesioned rats received intrastriatal infusions of the 5-HT2 receptor antagonist ritanserin (2.0 microg/side) or its vehicle (DMSO) followed by systemic SKF 82958, a D1 agonist (1.0 mg/kg, i.p.) and locomotor activity was monitored. In another experiment, intrastriatal sham and 6-OHDA-lesioned rats received bilateral intrastriatal infusions of ritanserin (2.0 microg/side) or its vehicle (DMSO) followed by intrastriatal infusions of SKF 82958 (5.0 microg/side) or vehicle (0.9% saline). Rats with DA loss demonstrated supersensitive locomotor responses to both systemic and intrastriatal SKF 82958. Ritanserin pretreatment blunted systemic SKF 82958-induced hyperlocomotion and returned intrastriatal D1-mediated hyperactivity to sham lesion levels. The results of this study suggest that striatal 5-HT2 receptors contribute to D1-mediated hyperkinesias resulting from DA loss and suggest a pharmacological target for the alleviation of dyskinesia that can develop with continued DA replacement therapy.