Genetic Risk For Depression and Quality of Life in Patients With Head and Neck Cancer.

Importance: Although patients with head and neck cancer (HNC) have been shown to experience high distress, few longitudinal studies include a comprehensive evaluation of biopsychosocial factors affecting quality of life (QoL), including genetic risk for depression. Objective: To identify factors at the time of cancer diagnosis associated with QoL scores at 3 months after treatment in patients newly diagnosed with a first occurrence of HNC. Design, Setting, and Participants: This prospective longitudinal study of 1464 participants with a 3-month follow-up, including structured clinical interviews and self-administered measures was carried out at the Department of Otolaryngology Head and Neck Surgery at 2 tertiary care McGill University Affiliated Hospitals, McGill University Health Centre, and Jewish General Hospital. Eligible patients were adults newly diagnosed within 2 weeks with a primary first occurrence of HNC, had a Karnofsky Performance Scale score higher than 60, and an expected survival of more than 6 months. Two hundred and twenty-three patients (72%) consented to participate and completed the baseline questionnaire, and 71% completed the 3-month follow-up measures. Exposures: An a priori conceptual model including sociodemographics, medical variables, psychosocial risk factors, and a polygenic risk score for depression (PRS-D) was tested. Main outcomes and measures: The Functional Assessment of Cancer Therapy-Head and Neck measured QoL at baseline and at 3 months. Results: Participants were mostly men (68.7%), with a mean (range) age of 62.9 (31-92) years, 36.6% having a university degree, 35.6% living alone, and 71.4% diagnosed with advanced HNC with mostly cancers being of the oropharynx (42.2%), oral cavity (17%), and larynx (16.3%). QoL at 3 months after HNC diagnosis was associated with higher PRS-D (B = -4.71; 95% CI, -9.18 to -0.23), and a diagnosis of major depressive disorder within 2 weeks of an HNC diagnosis (B = -32.24; 95% CI, -51.47 to 13.02), lifetime suicidal ideation (B = -22.39; 95% CI, -36.14 to -8.65), living with someone (B = 12.48; 95% CI, 3.43-21.52), having smoked cigarettes in the past 30 days pre-HNC diagnosis (B = -15.50; 95% CI, -26.07 to -4.93), chemotherapy type (B = -11.13; 95% CI, -21.23 to -1.02), and total radiotherapy dose (Gy) (B = -0.008; 95% CI, -0.01 to -0.002). Conclusions and relevance: This study identified the predictive value of a genetic predisposition to depression on QoL and function immediately after oncologic treatments. These findings highlight the potential importance of genetic profiling pretreatment to identify those most susceptible to experience QoL and functional compromise. Depression is a clear area of public health concern and should be a central focus in the treatment of patients with HNC.

Quality of Life After Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharynx Cancer.

Importance: Efforts are underway to deintensified treatment protocols for patients with human papillomavirus virus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) to achieve similar excellent oncologic outcomes while reducing treatment-related adverse effects. Transoral robotic surgery (TORS) as primary treatment often requires adjuvant therapy due to the high incidence of nodal metastasis. Treatment with neoadjuvant chemotherapy followed by TORS and neck dissection (NECTORS), reserving radiation therapy for salvage, yields excellent oncologic outcomes. Objective: To assess patient-reported quality of life (QOL) and functional outcomes among patients with HPV-OPSCC who undergo NECTORS. Design, Settings, and Participants: This was a multicenter prospective cohort study of patients with HPV-OPSCC treated with the NECTORS protocol in 2017 to 2022. Consecutive patients with stage III or IVa HPV-OPSCC treated with NECTORS in 2017 to 2022 who had completed the primary QOL questionnaire at baseline and at least once during the 24-month follow-up period were included. Ninety-four patients were eligible, and 67 were included in the analyses. Outcome Measures: QOL questionnaires at baseline, and at month 1, 3, 6, 12, 18, and 24 posttreatment. Global score on the 30-item European Organization for Research and Treatment of Cancer Core quality of life questionnaire (EORTC QLQ-C30) was the primary outcome; the head and neck extension module (EORTC QLQ-HN35); the MD Anderson Dysphagia Inventory for dysphagia-related QOL; and the Decision Regret Scale were also used. Paired t tests assessed change between the baseline and 12- or 24-month patient-reported outcomes. Results: Among the study population of 67 patients (median [range] age, 63 [58-67] years; 54 [80.6%] male) with HPV-OPSCC, the most frequent cancer subsites were palatine tonsil (41 [61%]) and base of tongue (26 [39%]); none required adjuvant RT. Global QOL at 24 months improved compared with baseline (mean difference, 9.49; 95% CI, 2.45 to 16.53). All EORTC QLQ-C30 functional scores returned to baseline or improved within 3 to 6 months posttreatment and remained stable at 24 months. EORTC QLQ-HN35 symptom scale scores improved or were stable at 24 months. The MD Anderson Dysphagia Inventory scores demonstrated no significant difference between baseline and month 12 for global scores (mean difference, 6.15; 95% CI, -4.18 to 16.49) and composite scores (mean difference, 2.73; 95% CI, -1.62 to 7.09). Median (range) score on the Decision Regret Scale was 5 of 100 (0-30), representing mild overall regret. Conclusion and Relevance: The findings of this multicenter cohort study indicate that use of the NECTORS protocol is associated with excellent QOL outcomes. QOL measures returned to baseline levels or were better than baseline, which represents positive outcomes for patients with HPV-OPSCC who undergo this treatment regimen.

Long-read sequencing of oropharyngeal squamous cell carcinoma tumors reveal diverse patterns of high-risk Human Papillomavirus integration.

Introduction: In North America and in most European countries, Human Papillomavirus (HPV) is responsible for over 70% of oropharyngeal squamous cell carcinomas. The burden of OPSCC, in high-income countries, has been steadily increasing over the past 20 years. As a result, in the USA and in the UK, the burden of HPV-related oropharyngeal squamous cell carcinoma in men has now surpassed that of cervical cancer in women. However, the oncogenic impact of high-risk HPV integration in oropharyngeal squamous cell carcinomas hasn't been extensively studied. The present study aimed to explore the patterns of HPV integration in oropharyngeal squamous cell carcinomas and to assess the feasibility and reliability of long-read sequencing technology in detecting viral integration events in oropharyngeal head and neck cancers. Methods: A cohort of eight HPV-positive OPSCC pre-treatment patient tumors (four males and four females), were selected. All patients received a p16INK4A positive OPSCC diagnosis and were treated at the McGill University Health Centre, a quaternary center in Montreal. A minimum of 20mg of tumor tissue was used for DNA extraction. Extracted DNA was subjected to Nanopore long-read sequencing to detect and analyze for the presence of high-risk HPV sequences. PCR and Sanger sequencing experiments were performed to confirm Nanopore long-read sequencing readings. Results: Nanopore long-read sequencing showed that seven out of eight patient samples displayed either integrated or episomal high-risk HPV sequences. Out of these seven samples, four displayed verifiable integration events upon bioinformatic analysis. Integration confirmation experiments were designed for all four samples using PCR-based methods. Sanger sequencing was also performed. Four distinct HPV integration patterns were identified: concatemer chromosomal integration in a single chromosome, bi-chromosomal concatemer integration, single chromosome complete integration and bi-chromosomal complete integration. HPV concatemer integration also proved more common than full HPV integration events. Conclusion and relevance: Long-read sequencing technologies can be effectively used to assess HPV integration patterns in OPSCC tumors. Clinically, more research should be conducted on the prognostication value of high-risk HPV integration in OPSCC tumors using long-read sequencing technology.

Blood and saliva-derived ctDNA is a marker of residual disease after treatment and correlates with recurrence in human papillomavirus-associated head and neck cancer.

BACKGROUND: There is an alarming increase in human papillomavirus-associated head and neck cancer (HNC), reaching epidemic levels. While patient prognosis is generally good, off-target treatment effects are associated with decreased quality of life. Thus, non-invasive strategies to predict treatment response and risk of recurrence could help de-escalate treatment. In this study, we tested circulating tumor (ct)DNA in liquid biopsies (blood/saliva) of HPV-positive HNC patients to assess treatment response and disease progression. METHODS: A total of 235 blood and saliva samples were collected from 60 HPV-positive and 17 HPV-negative HNC patients (control group) before and/or after treatment. Samples were analyzed using ddPCR for HPV16/18/31/33/35/45 and correlated with imaging and pathological examination. RESULTS: HPV-ctDNA detection was significantly higher prior to treatment (91%) than after treatment (8.0%) (χ2 p < 0.00001), with high concordance between saliva and blood (93%). In matched samples, all patients positive for ctDNA before treatment showed significant reductions in ctDNA levels post treatment (p < 0.0001). All but one patient with persistent ctDNA after treatment showed residual tumor and subsequent recurrence. Finally, fragmentomic analysis revealed shifts in cell-free DNA fragment size after treatment, suggesting a complementary biomarker for treatment response. CONCLUSIONS: Blood and saliva were found to be good sources of HPV-ctDNA. The presence of ctDNA strongly correlated with treatment response, demonstrating clinical utility as a non-invasive biomarker to monitor tumor progression in HPV-positive HNC. Liquid biopsy based ctDNA testing could be an effective approach to predict recurrence and stratify patients for de-escalation of treatment, thereby improving quality of life.

Genetic predisposition to depression and inflammation impacts symptom burden and survival in patients with head and neck cancer: A longitudinal study.

OBJECTIVE: The primary purpose of this study was to investigate the contribution of genetic predispositions to depression and inflammation, as measured through polygenic risk scores, on symptom burden (physical and psychological) in patients with head and neck cancer in the immediate post-treatment period (i.e., at three months post-diagnosis), as well as on 3-, 6-, 12-, 24- and 36-month survival. METHODS: Prospective longitudinal study of 223 adults (72 % participation) newly diagnosed with a first occurrence of primary head and neck cancer, paired with genetic data (Illumina PsychArray), validated psychometric measures, Structured Clinical Interviews for DSM Disorders (SCID-I), and medical chart reviews. RESULTS: Symptom burden at 3 months was predicted by (R2 adj. = 0.38, p < 0.001): a baseline SCID-I Anxiety Disorder (b = 1.69, B = 0.23, 95%CI = 0.43-2.94; p = 0.009), baseline levels of HADS anxiety (b = 0.20, B = 0.29, 95%CI = 0.07-0.34; p = 0.003), the polygenic risk score (PRS) for depression (b = 0.66, B = 0.18, 95%CI = 0.003-1.32; p = 0.049), and cumulated dose of radiotherapy (b = 0.002, B = 0.46, 95%CI = 0.001-0.003; p < 0.001). When controlling for factors known to be associated with cancer survival, patients with a higher PRS associated with depression and inflammation, respectively, presented higher risk of death within 36 months (b = 1.75, Exp(B) = 5.75, 95%CI = 1.55-21.27, p = 0.009 and b = 0.14, Exp(B) = 1.15, 95%CI = 1.01-1.30, p = 0.03). CONCLUSIONS: Our results outline three potential pathways of symptom burden in patients with head and neck cancer: a genetic predisposition towards depression; an initial anxiety disorder upon being diagnosed with cancer or high levels of anxiety upon diagnosis; and a dose-related response to radiotherapy. One may want to investigate early interventions in these areas to alleviate symptom burden in patients faced with a life-threatening disease, as well as consider targeting genetic predisposition towards depression and inflammation implicated in survival. The high prevalence of distress in patients with head and neck cancer is an opportunity to study genetic predispositions, which could potentially be broadly generalized to other cancers and diseases.

Biopsychosocial Markers of Body Image Concerns in Patients with Head and Neck Cancer: A Prospective Longitudinal Study.

(1) Background: Patients and survivors of head and neck cancer (HNC) are at a high risk of developing body image concerns. Despite the prevalence of body image concerns in patients with HNC, there is a lack of longitudinal research exploring the wide array of its associated determinants. The current longitudinal study examined the determinants and longitudinal course of body image dissatisfaction in patients with HNC. (2) Methods: Patients participated in Structured Clinical Interviews and self-administered questionnaires at four time-points: (T1) upon cancer diagnosis, (T2) at 3 months post-diagnosis, (T3) at 6 months post-diagnosis, and (T4) at 12 months post-diagnosis. They also underwent a disfigurement rating on an objective scale. (3) Results: Two hundred and twenty-four patients participated in our study. Fourteen percent to twenty-eight percent of patients reported at least moderate body image concerns across time points, with the lowest rates at baseline and the highest at 3 months (T1). It was found that patients more predisposed to developing higher levels of body image concerns presented physical markers (i.e., advanced cancer stage, lower physical functioning, higher disfigurement), psychosocial markers (i.e., higher depression, higher anxiety, and higher levels of coping with denial), and health disparities (i.e., younger age, female sex, French language, and marital status, with divorced and widowers most affected). (4) Conclusions: The findings of this study highlight the multifaceted nature of body image concerns in patients with HNC and its biopsychosocial determinants. Clinicians should pay specific attention to these biopsychosocial markers in their clinics to predict high levels of body image concerns and tailor communication/refer for support accordingly.

Body Image Concerns in Patients With Head and Neck Cancer: A Longitudinal Study.

Objective: Head and neck cancer (HNC) treatments are known to significantly affect functionality and appearance, leading to an increased risk for body image disturbances. Yet, few longitudinal studies exist to examine body image in these patients. Based on a conceptual model, the current study aimed to determine, in patients newly diagnosed with HNC: (1) the prevalence, level, and course of body image concerns; (2) correlates of upon cancer diagnosis (pre-treatment) body image concerns; (3) predictors of immediate post-treatment body image concerns; and (4) association between body image concerns and levels of anxiety, depression, suicidal ideation, support (i.e., satisfaction with support from physician, social/family wellbeing, and unmet support needs), and alcohol and drug misuse. Methods: Two hundred and twenty-three (participation rate = 72%), newly diagnosed with a primary HNC were assessed using structured clinical interviews and psychometric measures at three, and 6 months after diagnosis. Primary outcome was 3-month, as it was most salient to body image disturbance. Multiple linear regression analyses were conducted on the potential body image predictors, based on the model. Results: Sixty-eight percent of patients with HNC (n = 148 of 218) presented some level of body image concerns. Body image concerns at baseline (i.e., upon cancer diagnosis, pre-treatment) and post-treatment were significantly related and significantly increased from pre- to post-treatment. Immediately post-treatment (i.e., at 3 month follow-up), 89% (n = 132 of 148) presented some level of body image concerns. Correlates of body image concerns in patients with HNC at baseline included: physical symptom burden, difficulties with communication and eating, coping with the cancer diagnosis using denial, suicidal ideation, and having had a past anxiety diagnosis. When controlling for sociodemographic and medical variables, body image concerns in patients with HNC in the immediate post-treatment were predicted by: baseline body image, physical symptom burden, and neuroticism. Conclusion: This longitudinal study helps identify patients more susceptible to experience body image disturbance following head and neck cancer. Clinicians ought to pay special attention to body image concerns upon cancer diagnosis, physical symptom burden, and neuroticism, and may want to target these factors in future preventive interventions.

Visual cortex plasticity in cochlear implant users revealed in a visual motion detection task.

OBJECTIVE: The aim of this study was to investigate brain reorganization following cochlear implantation using electroencephalography, an implant-compatible technique to record electrical brain activity. METHODS: We investigated cortical plasticity in cochlear implant (CI) users using visual evoked potentials in response to visual motion changes. We estimated visual and auditory neural sources in CI users (n = 20) and normal hearing (NH) matched control participants (n = 22). RESULTS: Results showed intra-modal plasticity in the visual cortex of CI users, revealed by higher P1 and visual mismatch negativity amplitude, and greater contribution of the visual cortex during visual motion changes compared to NH controls. CONCLUSIONS: Our results suggest more efficient processing of visual information in CI users that may reflect enhanced multimodal compensatory strategies during speech processing. SIGNIFICANCE: This study showcases an objective, implant-compatible method that could be used in a clinical setting to measure and longitudinally track cortical plastic changes, enabling a better understanding of the link between individual patterns of cortical plasticity and CI outcomes.

Psychosocial outcomes of human papillomavirus (HPV)- and non-HPV-related head and neck cancers: A longitudinal study.

OBJECTIVES: Human papillomavirus (HPV) has prompted a need to further investigate how this new biomarker changes the head and neck cancer (HNC) psychosocial landscape. This study aimed to: (a) characterize the sociodemographic, psychological, and social profiles of patients with HPV-positive versus -negative squamous cell carcinoma of the head and neck; and (b) identify how HPV status contributes to anxiety and depression (primary outcome), quality of life (QoL), and sexuality needs. METHODS: We conducted a prospective longitudinal study of 146 patients newly diagnosed with oral, oropharyngeal, nasopharyngeal, and hypopharyngeal cancer. Seventy-nine patients were HPV-positive and 67 HPV-negative. Patients completed self-administered psychometric measures upon HNC and 3-month follow-up, and Structured Clinical Interviews for DSM Diagnoses. RESULTS: Patients with HPV-negative tumors generally presented with higher anxiety and depression and lower QoL immediately post-HNC diagnosis (<2 weeks) compared to HPV-positive cancers. A Major Depressive Disorder (MDD) immediately post-HNC diagnosis negatively affected patients' anxiety and depression and QoL levels upon diagnosis only when the cancer was HPV-positive. Immediately posttreatment, HPV status was not associated with outcomes. A previous history of suicidal ideation, and upon cancer diagnosis cigarette smoking, anxiety and depression, and feeling close to one's partner were instead explanatory. CONCLUSION: While patients with HPV-positive HNC generally present with initially lower psychological distress, their vulnerability immediately posttreatment indicates an equal need for support. Head and neck clinics may need to better address MDD, anxiety and depression, a prior history of suicidal ideation, health behavior change, and quality of relationships.

Longitudinal study indicating antecedent psychosocial vulnerability as predictor of anxiety disorders post-treatment in people with head and neck cancer.

OBJECTIVE: This study aimed to: (1) determine the contribution of pre-cancer psychosocial vulnerability as an independent predictor of anxiety disorder (AD) onset immediately post-treatment in patients diagnosed with a first occurrence of head and neck cancer (HNC), controlling for sociodemographics and medical variables; and (2) estimate prevalence of AD and identify trajectories from the moment of diagnosis to the immediate post-treatment (i.e., over a period of 3 months) in this population. METHODS: Two-hundred twenty-four consecutive patients (participation rate = 72%) newly diagnosed with a primary HNC were assessed with a structured clinical interview for a mental disorder, validated psychometric measures, and medical chart reviews. RESULTS: Twenty-five percent of patients presented a lifetime AD, 19.4% within 2 weeks of HNC diagnosis, and 16.6% immediately post-treatment; representing 26.7% of patients with AD at any timepoint from the moment of diagnosis to immediately post-treatment. Patients were more likely to present an AD immediately post-treatment when they: were diagnosed with advanced-stage cancer (OR = 3.40, p = 0.006), presented a upon cancer diagnosis AD (OR = 2.45, p = 0.008) and/or experienced childhood abuse (OR = 1.96, p = 0.03). CONCLUSIONS: Several AD trajectories may arise when patients are diagnosed with primary HNC. Health professionals should address AD and screen for risk factors (i.e., advanced stage cancer, AD upon cancer diagnosis, history of childhood abuse) as early as possible to assure optimal mental health care in this vulnerable population.

Epidemiology and Patient Distribution of Oral Cavity and Oropharyngeal SCC in Canada.

BACKGROUND: Oral cavity cancers (OCCs) and oropharyngeal cancers (OPCs) continue to be a major source of morbidity and mortality worldwide requiring the shared effort of numerous specialists. Tobacco and alcohol consumption have long been identified as risk factors for both OCC and OPC. In addition, human papilloma virus (HPV) is gaining its position as the main causal agent for OPC. OBJECTIVE: The objective of this study is to analyze the epidemiology of OCC and OPC in Canada. METHODS: Data pertaining to the year of diagnosis, the patient's sex, age at the time of diagnosis, province/territory, city and postal code of oral cavity, and oropharyngeal malignancies diagnosed during 1992-2010 were extracted from the Canadian Cancer Registry and Le Registre Québécois du Cancer. RESULTS: In total, 21 685 OCC cases and 15 965 OPC cases were identified from 1992 to 2010. Of those, 84.97% were oral cavity squamous cell carcinomas (SCCs), 88.10% were oropharyngeal SCCs, and both had a significant male predominance. While oral cavity SCC incidence stabilized over the study period, oropharyngeal SCC continued to increase. Oral cavity SCC incidence increased with age, while oropharyngeal SCC incidence peaked in the 50- to 59-year age group. Detailed geographic distribution analysis of patients at the provincial/territorial, city, and postal code levels identified several patient clusters. CONCLUSIONS: This work highlights important epidemiological differences in trends between oral and oropharyngeal cancers, identifies high-incidence postal codes for each malignancy, and correlates incidence/mortality with known risk factors including alcohol/tobacco use and HPV infections, therefore providing a comprehensive understanding of epidemiology for these cancers in Canada.

Immediate post-treatment supportive care needs of patients newly diagnosed with head and neck cancer.

OBJECTIVE: This study aimed at identifying supportive care needs of patients with head and neck cancer (HNC-P) immediately post-treatment, finding early predictors of unmet needs, and contrasting how immediate post-treatment needs differed from needs in longer-term survivorship. METHODS: Prospective longitudinal study of 223 consecutive adults (313 approached; 72% participation) newly diagnosed with a first occurrence of primary HNC. Patients completed the Supportive Care Needs Survey-Short Form (SCNS), the Structured Clinical Interview for DSM-IV, and other outcomes. Medical chart reviews were conducted. RESULTS: A total of 68% of patients (n = 145/223) completed the SCNS. The multiple linear regression indicated that when controlled for medical variables, patients presented higher levels of unmet needs when they presented with higher level of anxiety upon HNC diagnosis (p = 0.03), higher neuroticism (p = 0.03), and more stressful life events in the year pre-diagnosis (p = 0.01). Patients immediately post-treatment had a wider variety of unmet needs compared with those in extended survivorship, with psychological unmet needs most prevalent at both time points. Immediately post-treatment, patients needed more support regarding pain (p = 0.04) and worries about treatment results (p = 0.05), whereas patients in longer-term survivorship needed more support regarding anxiety (p = 0.02), changes in sexual relationships (p = 0.04), and fear of death and dying (p = 0.001). CONCLUSION: This study identifies areas needing further development to improve quality of care for HNC-P in the immediate post-treatment period, as well as early determinants of unmet needs. HNC clinics may want to routinely screen for anxiety, neuroticism, and burden from other life events, to pro-actively address needs upon treatment completion and alleviate disease burden.

Magnetic Resonance Imaging Texture Analysis Predicts Recurrence in Patients With Nasopharyngeal Carcinoma.

BACKGROUND: The personalization of oncologic treatment using radiomic signatures is mounting in nasopharyngeal carcinoma (NPC). We ascertain the predictive ability of 3D volumetric magnetic resonance imaging (MRI) texture features on NPC disease recurrence. METHODS: A retrospective study of 58 patients with NPC undergoing primary curative-intent treatment was performed. Forty-two image texture features were extracted from pre-treatment MRI in addition to clinical factors. A multivariate logistic regression was used to model the texture features. A receiver operating characteristic curve on 100 bootstrap samples was used to maximize generalizability to out-of-sample data. A Cox proportional model was used to predict disease recurrence in the final model. RESULTS: A total of 58 patients were included in the study. MRI texture features predicted disease recurrence with an area under the curve (AUC), sensitivity, and specificity of 0.79, 0.73, and 0.71, respectively. Loco-regional recurrence was predicted with AUC, sensitivity, and specificity of 0.82, 0.73 and 0.74 respectively while prediction for distant metastasis had an AUC, sensitivity, and specificity of 0.92, 0.79 and 0.84, respectively. Texture features on MRI had a hazard ratio of 4.37 (95% confidence interval 1.72-20.2) for disease recurrence when adjusting for age, sex, smoking, and TNM staging. CONCLUSION: Texture features on MRI are independent predictors of NPC recurrence in patients undergoing curative-intent treatment.

Cell culture of differentiated human salivary epithelial cells in a serum-free and scalable suspension system: The salivary functional units model.

Saliva aids in digestion, lubrication, and protection of the oral cavity against dental caries and oropharyngeal infections. Reduced salivary secretion, below an adequate level to sustain normal oral functions, is unfortunately experienced by head and neck cancer patients treated with radiotherapy and by patients with Sjögren's syndrome. No disease-modifying therapies exist to date to address salivary gland hypofunction (xerostomia, dry mouth) because pharmacotherapies are limited by the need for residual secretory acinar cells, which are lost at the time of diagnosis, whereas novel platforms such as cell therapies are yet immature for clinical applications. Autologous salivary gland primary cells have clinical utility as personalized cell therapies, if they could be cultured to a therapeutically useful mass while maintaining their in vivo phenotype. Here, we devised a serum-free scalable suspension culture system that grows partially digested human salivary tissue filtrates composing of acinar and ductal cells attached to their native extracellular matrix components while retaining their 3D in vivo spatial organization; we have coined these salivary spheroids as salivary functional units (SFU). The proposed SFU culture system was sub-optimal, but we have found that the cells could still survive and grow into larger salivary spheroids through cell proliferation and aggregation for 5 to 10 days within the oxygen diffusion rates in vitro. In summary, by using a less disruptive cell isolation procedure as the starting point for primary cell culture of human salivary epithelial cells, we demonstrated that aggregates of cells remained proliferative and continued to express acinar and ductal cell-specific markers.

Growth of Pituitary Macroadenomas Postpartial Resection: Implications for Adjuvant Radiotherapy.

Objective To determine the volumetric growth in macroadenomas (MAs) patients with residual postoperative disease and to identify subpopulations with rapid postoperative growth rate that may benefit from early salvage radiotherapy (RT). Methods Patients who had undergone a partial resection for MAs and did not receive immediate postoperative RT were eligible. Residual tissue was contoured on serial magnetic resonance imaging and planimetric and volumetric changes in size were measured. Growth rates were established by a single observer using serial volumetric measurements. Data were analyzed to find a relationship among growth rate, adjuvant treatment, and patient and tumor characteristics. Results Thirty-one patients met the eligibility criteria. Nine patients (29%) required adjuvant treatment because of tumor growth. Volumetric growth was identified 95% of the time compared with 64% planimetrically. Planimetric growth could not be established in 10% of patients showing volumetric changes. Median growth rate was 0.4464 mL/y. Growth rate positively correlated with size of residual postoperative volume ( p < 0.001). Receiving salvage treatment positively correlated with growth rate ( p = 0.001), particularly at a rate above 2.19 mL/y ( p = 0.0064). Five patients (16%) had a growth rate above this level, all of which required salvage treatment. Patients with postoperative residual volume > 3.95 mL were most likely to experience rapid growth rate and require salvage treatment ( p = 0.007). Conclusion Volumetric measurement was found to be superior to planimetric measurement in detecting changes in patients with residual tumors. Patients with postoperative residual volume > 3.95 mL should be considered for early treatment with RT.

Contextual and historical factors for increased levels of anxiety and depression in patients with head and neck cancer: A prospective longitudinal study.

BACKGROUND: This study aimed at examining predictors of clinical anxiety and depressive symptoms in patients with head and neck cancer (HNC) at 3, 6, and 12 months post-diagnosis, with a particular interest in contextual and historical factors. METHODS: Prospective longitudinal study of 219 consecutive patients newly diagnosed with a first occurrence of primary HNC, including psychometric measures, Structured Clinical Interview for DSM-IV Diagnoses (SCID), and medical chart reviews. RESULTS: Point prevalence of clinical anxiety symptoms (Hospital Anxiety and Depression Scale-Anxiety subscale) was 32.0%, 21.9%, 12.1%, and 12.6% at baseline, 3, 6, and 12 months; and clinical depressive symptoms on the Depression Subscale was 19.4%, 21.9%, 13.5%, and 9.2%, respectively. Predictors of anxiety and depressive symptoms included upon diagnosis SCID major depressive or anxiety disorder, stressful life events in previous year, neuroticism, and levels of anxiety and depressive symptoms upon cancer diagnosis. CONCLUSIONS: This study emphasizes the predictive contribution of broader personal contextual and historical factors that increase psychological vulnerability in HNC and merit consideration.

Neurophysiological Differences in Emotional Processing by Cochlear Implant Users, Extending Beyond the Realm of Speech.

OBJECTIVE: Cochlear implants (CIs) restore a sense of hearing in deaf individuals. However, they do not transmit the acoustic signal with sufficient fidelity, leading to difficulties in recognizing emotions in voice and in music. The study aimed to explore the neurophysiological bases of these limitations. DESIGN: Twenty-two adults (18 to 70 years old) with CIs and 22 age-matched controls with normal hearing participated. Event-related potentials (ERPs) were recorded in response to emotional bursts (happy, sad, or neutral) produced in each modality (voice or music) that were for the most part correctly identified behaviorally. RESULTS: Compared to controls, the N1 and P2 components were attenuated and prolonged in CI users. To a smaller degree, N1 and P2 were also attenuated and prolonged in music compared to voice, in both populations. The N1-P2 complex was emotion-dependent (e.g., reduced and prolonged response to sadness), but this was also true in both populations. In contrast, the later portion of the response, between 600 and 850 ms, differentiated happy and sad from neutral stimuli in normal hearing but not in CI listeners. CONCLUSIONS: The early portion of the ERP waveform reflected primarily the general reduction in sensory encoding by CI users (largely due to CI processing itself), whereas altered emotional processing (by CI users) could be found in the later portion of the ERP and extended beyond the realm of speech.

Reversible external auditory canal ligation (REACL): A novel surgical technique to induce transient and reversible hearing loss in developing rats.

BACKGROUND: Cases of sensory loss provide an excellent model to study the plastic nature of cortical sensory systems. Models of reversible sensory loss are particularly useful for establishing the timeline of various critical periods for cortical plasticity. However, there currently is an absence of adequate methods to produce reversible hearing loss in neonatal and developing rodents. NEW METHOD: We propose a novel and reversible adaptation of an existing surgical technique-external auditory canal ligation (EACL)-that produces a reliable and moderate hearing loss. RESULTS: Auditory brainstem responses (ABRs) were used to measure both the magnitude of the hearing loss induced by EACL and the auditory thresholds following hearing restoration. The EACL and reopening procedures, as assessed by visual inspection, had success rates of 81% and 78%, respectively. The average hearing thresholds, as assessed with ABRs, increased by nearly 40 decibels across all tested frequencies. Hearing thresholds returned to normal levels following the reopening procedure. COMPARISON WITH EXISTING METHODS: Our procedure yields similar benefits to other methods, such as producing a reliable and moderate hearing loss that is entirely reversible. Furthermore, to our knowledge, it is the first that can be performed in neonatal rodents, thus allowing researchers the opportunity to assess the effects of sensory loss on behavior and cortical neurophysiology during developmental critical periods. CONCLUSION: Our modified technique of reversible external auditory canal ligation offers an easy, and reliable method to induce a transient state of hearing loss that mimics naturally occurring congenital conductive hearing loss.

Development and validation of the McGill body image concerns scale for use in head and neck oncology (MBIS-HNC): A mixed-methods approach.

OBJECTIVE: The aim of this study was to develop and validate a patient-reported outcome measure to evaluate body image concerns in head and neck cancer (HNC) patients. METHODS: Items were created using a combination of deductive (eg, US Food and Drug Administration Qualification of Clinical Outcome Assessments, literature review) and inductive approaches (eg, subject matter experts, HNC patients). Items were translated for use in both Canadian English and Canadian French using back-translation. A two-step empirical validation process using the Classical Test Theory (CTT) and Rasch Measurement Theory (RMT) was conducted with 224 and 258 HNC patients, respectively, having undergone disfiguring surgery within the past 3 years. RESULTS: Analyses suggest two subscales for MBIS-HNC: social discomfort (10 items) and negative self-image (11 items). The McGill Body Image Concerns Scale-Head and Neck Cancer (MBIS-HNC) is reliable with high internal consistency (0.98), high test-retest reliability over a two-week period (ICC = 0.88), moderate to high convergent validity (range r = 0.43-0.81), and divergent validity (range r = 0.12-0.15). RMT was used in addition to CTT. Disordered thresholds led to the modification of the number of response options, and items were deleted based on differential item functioning and high local dependency. Unidimensionality of both subscales and supporting a total score was confirmed. The measure was however characterized by the presence of an important floor effect, confirmed with poor targeting as demonstrated by the person-item threshold distribution. CONCLUSION: Evidence gathered from our theory-driven validation study using CTT and RMT provides practitioners and researchers with a useful and easy to use self-report measure.