Definitive radio(chemo)therapy versus upfront surgery in the treatment of HPV-related localized or locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: The treatment of stage I-III HPV+ oropharyngeal squamous cell carcinoma (HPV-OPSCC) is based on either surgery ± adjuvant therapy or exclusive radio±chemotherapy. We sought to compare these two therapeutic strategies in terms of efficacy, tolerance and quality of life (QoL). METHODS: Patients treated for stage I-III HPV-OPSCC from 2010 to 2021 in 3 academic centers were included and sorted according to the treatment strategy: surgery or exclusive radio±chemotherapy. Efficacy and tolerance were retrospectively assessed, and a transversal exploratory QoL assessment was performed using QoL instruments. RESULTS: A total of 83 patients were included, with 21 undergoing non-minimally invasive surgery and 62 receiving definitive radio-±chemotherapy. 2-year progression-free survival (PFS) and overall survival (OS) were respectively 80% and 86% in the surgical group and 92% and 95% in the non-surgical group, with no significant difference. At the end of treatment, 64.5% of patients presented with a grade III toxicity, without significant difference between the two groups. No patient had late grade III toxicity at 24 months. Forty-five patients (11 in the surgical group, 34 in the non-surgical group) participated in an exploratory quality-of-life analysis. Patients reported significantly more fatigue and loss of appetite after surgery, whereas patients in the radio±chemotherapy group described significantly more salivary and oral problems and difficulty swallowing, but the median time between treatment completion and the response to the questionnaires. CONCLUSION: There was no significant difference in efficacy, physician-reported toxicity and overall patient-reported quality of life was found between non-minimally invasive surgery and radio±chemotherapy in the treatment of stage I-III HPV-OPSCC.

The French way of voice rehabilitation post total laryngectomy: current clinical practices and tendencies.

BACKGROUND: Vocal rehabilitation post total laryngectomy (TL) lacks clinical guidelines, especially with the presence of multiple modalities. OBJECTIVES: To describe the tendencies of vocal rehabilitation post TL in France and compare it with other countries. We try to identify the most practiced modalities and recognize statistically significant influencing factors. MATERIALS AND METHODS: An electronic anonymous survey was answered by 75 ENT surgeons from France. The survey outlined the common practiced vocal rehabilitation modalities and had two versions depending on if the participant practices the tracheoesophageal speech (TES) or not. RESULTS: 96% use TES in their practice. Single modality TES and double modality TES with esophageal speech (ES) are the two most practiced modalities. 99% agreed that there is no age limit for the TES. Single modality ES was offered 92% more when more than 10 TL were performed per year (p < .05). No influencing factors found for single modality TES or double modality TES with ES (p > .05).Conclusion: In line with tendencies from other countries, the TES is the most practiced modality of vocal rehabilitation coupled or not with the ES. TES has no age limit as per our participants. The least practiced modality is the singe modality ALS.

Characterization of human oxidoreductases involved in aldehyde odorant metabolism.

Oxidoreductases are major enzymes of xenobiotic metabolism. Consequently, they are essential in the chemoprotection of the human body. Many xenobiotic metabolism enzymes have been shown to be involved in chemosensory tissue protection. Among them, some were additionally shown to be involved in chemosensory perception, acting in signal termination as well as in the generation of metabolites that change the activation pattern of chemosensory receptors. Oxidoreductases, especially aldehyde dehydrogenases and aldo-keto reductases, are the first barrier against aldehyde compounds, which include numerous odorants. Using a mass spectrometry approach, we characterized the most highly expressed members of these families in the human nasal mucus sampled in the olfactory vicinity. Their expression was also demonstrated using immunohistochemistry in human epitheliums sampled in the olfactory vicinity. Recombinant enzymes corresponding to three highly expressed human oxidoreductases (ALDH1A1, ALDH3A1, AKR1B10) were used to demonstrate the high enzymatic activity of these enzymes toward aldehyde odorants. The structure‒function relationship set based on the enzymatic parameters characterization of a series of aldehyde odorant compounds was supported by the X-ray structure resolution of human ALDH3A1 in complex with octanal.

Nasal Odorant Competitive Metabolism Is Involved in the Human Olfactory Process.

Within the peripheral olfactory process, odorant metabolizing enzymes are involved in the active biotransformation of odorants, thus influencing the intensity and quality of the signal, but little evidence exists in humans. Here, we characterized the fast nasal metabolism of the food aroma pentane-2,3-dione in vivo and identified two resulting metabolites in the nasal-exhaled air, supporting the metabolizing role of the dicarbonyl/l-xylulose reductase. We showed in vitro, using the recombinant enzyme, that pentane-2,3-dione metabolism was inhibited by a second odorant (e.g., butanoic acid) according to an odorant-odorant competitive metabolic mechanism. Hypothesizing that such mechanism exists in vivo, pentane-2,3-dione, presented with a competitive odorant, both at subthreshold concentrations, was actually significantly perceived, suggesting an increase in its nasal availability. Our results, suggesting that odorant metabolizing enzymes can balance the relative detection of odorants in a mixture, in turn influencing the intensity of the signal, should be considered to better manage flavor perception in food.

Salvage total glossectomy and total glosso-laryngectomy: Are they worth it? A GETTEC French multicenter study.

BACKGROUND: Salvage total glossectomy (TG) or total glosso-laryngectomy (TGL) remain controversial, as highly morbid procedures. The objective was to describe oncological and functional outcomes after salvage TG or TGL. METHODS: We performed a multicenter retrospective study, including patients with previous neck irradiation undergoing TG or TGL for squamous cell carcinoma involving the base of tongue. RESULTS: We included 42 patients: 27 in the TG group and 15 in the TGL group. For the entire cohort, median OS and DFS were estimated at 19 months (95% IC [14-44]) and 10 months (95% IC [7-13]) respectively, with no difference between the two groups. After a median follow-up of 90 months, 10 patients (24%) were alive and free of disease. Att he end of follow-up, we noted a gastrostomy dependency of 89% and 87 %respectively in the TG and TGL group, and 48% of patients in the TG group had a tracheotomy. CONCLUSION: Although local control is difficult to achieve after salvage TG or TGL, these procedures are associated with acceptable survival and chance of cure for a last-resort situation. TG and TGL can be proposed in selected motivated patients after careful shared decision-making.

Oral tongue squamous cell carcinomas in young patients according to their smoking status: a GETTEC study.

BACKGROUND: Incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing, especially in young adults, despite decreasing tobacco and alcohol consumption. METHODS: This multicentric retrospective study of 185 young adults with OTSCC (median follow-up 43 months), investigated risk factors, tumour characteristics and oncological outcomes according to the smoking status. RESULTS: Overall, 38% of patients were smokers (S). Non-smokers (NS) were significantly younger than S. Sex ratios were 1.1 for N and 1.8 for S. NS patients were less frequently cannabis or alcohol users than S, but were more likely to have a history of leukoplakia. Second primaries were observed in NS (4.4%) and in S (12.7%). Despite more frequent local relapse in NS (p = 0.018), there was no difference in diagnostic stage and overall survival between groups. CONCLUSION: OTSCC affects differently young S and NS patients suggesting the existence of a specific clinical entity of OTSCC in non-smoking young adults.

Evaluation of the quality of the information received during head and neck cancer announcement: Prospective two-center study.

BACKGROUND: Providing patient with cancer with appropriate information following the disclosure of a cancer diagnosis has multiple benefits. The objective was to evaluate the quality of the information received during an announcement for head and neck cancer and to determine predictive factors. METHODS: We conducted a prospective two-center study using self-questionnaires to assess the patient's perception of the quality of the announcement. RESULTS: Satisfaction scores on the information provided about the overall disease were 7.7/10. The main positive predictors of quality were a satisfactory consultation setting (P = .004), assessment of pain by a physician (P = .04), physician availability (P = .003), accurate information about tumor stage, quality of information regarding the type (P < .0001) and purpose (P = .001) of treatment and its side effects (P = .006), and the interview with the oncology nurse coordinator (P < .05). CONCLUSIONS: Patients who received the announcement of head and neck cancer perceived the information received during the pretherapeutic period as satisfactory.

Impact of waiting time on nodal staging in head and neck squamous-cell carcinoma treated with radical intensity modulated radiotherapy.

BACKGROUND AND PURPOSE: To evaluate the influence of delays for radiotherapy on survival, recurrence and upstaging for head and neck squamous-cell carcinoma (HNSCC) with no nodal involvement treated with intensity modulated radiotherapy (IMRT). MATERIAL AND METHODS: This retrospective study included 63 consecutive patients with HNSCC located in the pharynx and larynx and treated with exclusive IMRT with or without chemotherapy. Survival, loco-regional or distant failure and upstaging were analyzed according to the waiting time. RESULTS: Mean waiting time for treatment was 62.5 days for the hypopharynx subgroup (range = 37-102), 63 days for the larynx subgroup (range = 19-128) and 58.5 days for the oropharynx subgroup (range = 29-99) (p = 0.725). Nine patients (14%) experienced upstaging. Loco-regional or distant failure occurred in 18 patients. Beyond a delay of 50 days, 19% of patients had local failure, 17% nodal recurrence and 11% distant failure. Within a delay of 50 days, no nodal or distant failure was observed and only 1 patient experienced local recurrence. Upstaging and overall survival were not significantly affected by an increased waiting time. CONCLUSION: For N0 patients treated with IMRT for HNSCC, waiting time around 50 days after the diagnosis was not significantly associated with an excessive risk of upstaging or recurrence.

A multi-generational study on low-dose BPA exposure in Wistar rats: effects on maternal behavior, flavor intake and development.

Bisphenol A (BPA) is a common endocrine disruptor found as an environmental and food contaminant. It exerts both developmental and behavioral effects, mainly when exposure occurs in early life. The aim of this study was to determine the multi-generational effects of chronic, human-relevant low-dose exposure to BPA on development, maternal behavior and flavor preference in Wistar rats. BPA was orally administered at a daily dose of 5 µg/kg body weight to F0 pregnant dams from the first day of gestation (GD 1) until the last day of lactation (LD 21), and then to F1 offspring from weaning (PND 21) to adulthood (PND 100). F2 offspring were not exposed. Development and clinical signs of toxicity were assessed daily. Maternal behavior was evaluated by observing nursing and pup-caring actions, as well as "non-maternal" behaviors in F0 and F1 dams from parturition until LD 8. The flavor preferences of F1 and F2 offspring were evaluated based on the intake of sweet, salt and fat solutions using the two-bottle choice test on PND 21-34 and PND 86-99. BPA exposure: 1) decreased maternal behavior in F1 dams, 2) caused developmental defects in both F1 and F2 offspring, with a noticeable decrease in anogenital distance in male rats, and 3) did not affect flavored solution intake in F1, but induced changes in sweet preference in F2 juveniles and in salt and fat solution intakes in F2 adults, and 4) induced a body weight increase in the F2 generation only, whereas food intake and water consumption did not change. Taken as a whole, our findings showed that both gestational (F0) and lifelong (F1) exposures to a human-relevant dose of BPA could induce multi-generational effects on both development and behavior. These results suggest possible selective neuroendocrine defects and/or epigenetic changes caused by BPA exposure.

Oral homeostasis disruption by medical plasticizer component bisphenol A in adult male rats.

OBJECTIVES/HYPOTHESIS: Bisphenol A (BPA) is a synthetic estrogen-like chemical mimetic widely used in the manufacture of polycarbonate plastics and epoxy resins found in numerous consumer products including food packaging, medical devices, and dental sealants. Because it is recovered in fluids and it can reach high levels in saliva, this study aimed to evaluate its safety on oral homeostasis by examining its effects on salivary glands, mouth epithelium, water consumption, and salt preference, each parameter being estrogen sensitive. STUDY DESIGN: Randomized controlled trial involving rats. METHODS: A dose-response study was conducted in adult Wistar rats randomized into five groups (n = 12). BPA was administered over 6 weeks via drinking water to obtain daily dose exposures of 0 µg/kg, 5 µg/kg, 50 µg/kg, 5 mg/kg, and 12.5 mg/kg of body weight. To evaluate salt preference, 1% NaCl solution and pure water intakes were measured for 3 days by offering two-bottle choices. The rats were then killed; oral biopsies were done and submandibular glands were removed for histologic and morphometric analysis. RESULTS: According to the dose-response curve, BPA decreased total drinking but increased salt preference, which was inversely proportional to water consumption (Kruskal-Wallis, P < .01). It also causes oral dryness and histologic changes in the acinar structures of the submandibular glands at the lowest doses (Kruskal-Wallis, P < .01). CONCLUSIONS: This study shows that oral exposure to BPA in the rat disrupts thirst and buccal homeostasis and raises questions about the salivary gland secretions.

Management of postcricoid and upper esophageal hemangioma.

To discuss management of postcricoid and upper esophageal hemangiomas in infants. Four children presenting with progressive feeding and/or respiratory disturbance underwent endoscopy including systematic esophagoscopy revealing the hemangioma of the postcricoid area and extending to the lumen of the upper esophagus. In the three children with severe disturbance, systemic steroids were insufficient and open surgical excision brought the hemangioma under control. No significant stenosis occurred despite prolonged progressive oral feeding up to 1 month after surgery. The fourth child whose disturbance was moderate, was managed by intralesional steroids. Various solutions have been proposed for the treatment, i.e. conservative approach or partial or complete destruction or excision, management of postcricoid hemangioma by intralesional steroids or by open surgical excision. Indications will require greater series.