Treatment of supraglottic squamous cell carcinoma with advanced technologies: observational prospective evaluation of oncological outcomes, functional outcomes, quality of life and cost-effectiveness (SUPRA-QoL).

BACKGROUND: Over the past decade, therapeutic options in head and neck supraglottic squamous cell carcinoma have constantly evolved. The classical total laryngectomy has been partially replaced by alternative organ- and function-sparing techniques with the same prognosis but less morbidity, such as Radiotherapy, Transoral Laser Microsurgery (TLM) and Trans-Oral Robotic Surgery (TORS). Up to now, a prospective comparison of these innovant techniques has not been conducted. METHODS/DESIGN: We will conduct an original international multicentric prospective nonrandomized clinical trial to compare the efficacy between these treatments (Arm 1: Radiotherapy ± chemotherapy; Arm 2: TLM and Arm 3: TORS) with 4 classes of outcomes: quality of life (QoL), oncological outcomes, functional outcomes and economic resources. The population will include cT1-T2 /cN0-N1/M0 supraglottic squamous cell carcinoma. The primary outcome is a Clinical Dysphagia QoL evaluation assessed by the MD Anderson Dysphagia questionnaire. Secondary outcomes include others QoL evaluation, oncological and functional measures and cost parameters. The sample size needs to reach 36 patients per arm (total 108). DISCUSSION: In the current literature, no prospective head-to-head trials are available to compare objectively these different treatments. With the increase of highly efficient treatments and the increase of oncological survival, it is imperative also to develop management strategies that optimize QoL and functional results. We will conduct this innovate prospective trial in order to obtain objective data in these two main issues. TRIAL REGISTRATION: NCT05611515 posted on 10/11/2022 (clinicaltrial.fgov).

Transoral radiofrequency of the terminal branches of the recurrent nerve in the treatment of adductor spasmodic dysphonia: our experience over 11 patients.

PURPOSE: Spasmodic dysphonia (SD) or laryngeal dystonia is as a rare vocal disorder characterized by involuntary action-induced endolaryngeal contraction. In the last decade, botulin toxin injection has become the standard treatment in adductor spasmodic dysphonia necessitating repetitive injections. The purpose of this study is to analyze retrospectively data from patients treated with the minimal-invasive transoral radiofrequency-induced thermotherapy (RFITT) of the terminal branches of the recurrent nerve. METHODS: Between 2009 and 2015, 11 patients (six females and five males aged from 32 to 91 years) with adductor SD were treated with RFITT. Pre-operative and post-operative vocal assessments (VHI-30, GRBASI, and acoustic-aerodynamics measurements), number of surgical revisions, delay between procedures, and post-operative complications were recorded. Statistical analyses were carried out on the first vocal assessment performed 2-8 weeks after the first procedure. RESULTS: Based on available data from ten patients, voice handicap index (VHI) showed improvement with a mean value of -17.7 points (p-value (pval) = 0.014, adjusted p-value (adj pval) = 0.21); instability has also revealed improvement in six patients (pval = 0.05, adj pval = 0.31). Four patients underwent only one procedure including one patient showing still long-term beneficial results after 5 years of follow-up. Other patients required one to three new procedures with an average time between procedures of 15.3 months. Over 24 surgeries performed on a total of 11 patients, one definitive treatment-related severe adverse event was reported. CONCLUSION: Thanks to long-lasting effect, repetitive treatments are less frequent compared to botulin toxin therapy. In our opinion, RFITT is a promising alternative to botulin toxin as a second-step procedure in case of toxin resistance or patient's lack of compliance.

Mercury and metal(loid) deposition to remote Nova Scotia lakes from both local and distant sources.

Kejimkujik National Park, in Nova Scotia, Canada, is a sensitive region for metal(loid) contamination, such as mercury, in part due to long-range atmospheric deposition from global and regional industrial centers. The region is remote from industrial centres, but is downwind of major pollution sources in the Eastern United States and Canada, and historically had numerous gold mining sites. Due to a paucity of long-term atmospheric deposition monitoring in this region, little is known about the response of Kejimkujik lakes to multiple changing global, regional and local atmospheric Hg and metal(loid) sources. Here, we used multiple lake sediment cores to reconstruct anthropogenic depositional fluxes of metal(loid)s of concern for the last ~210years. Results showed that Kejimkujik lake sediments are highly enriched in lead (Pb), antimony (Sb) and tin (Sn), with post-industrial metal(loid) concentrations being >4-fold greater than natural baseline levels (prior to ~1800) and moderately enriched in silver (Ag), bismuth (Bi), cadmium (Cd), copper (Cu), mercury (Hg), rubidium (Rb), tellurium (Te), thallium (Tl), vanadium (V), tungsten (W) and zinc (Zn), with post-industrial metal(loid) concentrations being between 1.5 and 4-fold greater than natural baseline levels (prior to ~1800). Lake sediment core reconstructions of total atmospheric Hg deposition matched well with Hg wet deposition monitoring data from the overlapped period (1997-2010) being 9.1±2.7µg/m2/yr and 7.0±0.7µg/m2/yr respectively. Lakes closest to historic gold mining sites show spikes in Ag, Cd, Sb, Tl, Zn and W during mining periods (~1880 and 1950). Most of the enriched metal(loid)s (EF >1.5) (Ag, Bi, Cu, Hg, Pb, Sb, Sn, V and W) do not appear affected by redox and remobilisation issues. For the other enriched metal(loid)s (EF >1.5) (Cd, Tl, and Zn), remobilisation from upper sediments appears to be occurring within these acidic and DOC rich Kejimkujik lakes.

Patellofemoral arthroplasty versus total knee arthroplasty for patients with patellofemoral osteoarthritis: equal function and satisfaction but higher revision rate for partial arthroplasty at a minimum eight years' follow-up.

AIMS: The primary aim of this study was to compare the knee-specific functional outcome of patellofemoral arthroplasty with total knee arthroplasty (TKA) in the management of patients with patellofemoral osteoarthritis. PATIENTS AND METHODS: A total of 54 consecutive Avon patellofemoral arthroplasties were identified and propensity-score-matched to a group of 54 patients undergoing a TKA with patellar resurfacing for patellofemoral osteoarthritis. The Oxford Knee Score (OKS), the 12-Item Short-Form Health Survey (SF-12), and patient satisfaction were collected at a mean follow up of 9.2 years (8 to 15). Survival was defined by revision or intention to revise. RESULTS: There was no significant difference in the mean OKS (p > 0.60) or SF-12 scores (p > 0.28) between the groups. There was a lower rate of satisfaction at the final follow-up for the TKA group (78% vs 87%) but this was not statistically significant (odds ratio 0.56, p = 0.21). Length of stay was significantly shorter (p = 0.008) for the Avon group (difference 1.8 days, 95% confidence interval (CI) 0.4 to 3.2). The ten-year survival for the Avon group was 92.3% (95% CI 87.1 to 97.5) and for the TKA group was 100% (95% CI 93.8 to 100). This difference was not statistically significant (log-rank test, p = 0.10). CONCLUSION: Patients undergoing an Avon patellofemoral arthroplasty have a shorter length of stay, and a functional outcome and rate of satisfaction that is equal to that of TKA. The benefits of the Avon arthroplasty need to be balanced against the increased rate of revision when compared with TKA.

Birinapant sensitizes platinum-resistant carcinomas with high levels of cIAP to carboplatin therapy.

Platinum drugs are the frontline therapy in many carcinomas, including high-grade serous ovarian cancers. Clinically, high-grade serous carcinomas have an apparent complete response to carboplatin, but tumors invariably recur and response to platinum drugs diminishes over time. Standard of care prohibits re-administration of platinum drugs to these patients who are labeled as having platinum-resistant disease. In this stage patients are treated with non-platinum agents and outcomes are often poor. In vivo and in vitro data presented here demonstrate that this clinical dogma should be challenged. Platinum drugs can be an effective therapy even for platinum-resistant carcinomas as long as they are combined with an agent that specifically targets mechanisms of platinum resistance exploited by the therapy-resistant tumor subpopulations. High levels of cellular inhibitor of apoptosis proteins cIAP1 and 2 (cIAP) were detected in up to 50% of high-grade serous and non-high-grade serous platinum-resistant carcinomas. cIAP proteins can induce platinum resistance and they are effectively degraded with the drug birinapant. In platinum-resistant tumors with ≥22.4 ng of cIAP per 20 µg of tumor lysate, the combination of birinapant with carboplatin was effective in eliminating the cancer. Our findings provide a new personalized therapeutic option for patients with platinum-resistant carcinomas. The efficacy of birinapant in combination with carboplatin should be tested in high-grade serous carcinoma patients in a clinical trial.

Consistency of effects of tropical-forest disturbance on species composition and richness relative to use of indicator taxa.

Lawton et al. (1998) found, in a highly cited study, that the species richness of 8 taxa each responds differently to anthropogenic disturbance in Cameroon forests. Recent developments in conservation science suggest that net number of species is an insensitive measure of change and that understanding which species are affected by disturbance is more important. It is also recognized that all disturbance types are not equal in their effect on species and that grouping species according to function rather than taxonomy is more informative of responses of biodiversity to change. In a reanalysis of most of the original Cameroon data set (canopy and ground ants, termites, canopy beetles, nematodes, and butterflies), we focused on changes in species and functional composition rather than richness and used a more inclusive measure of forest disturbance based on 4 component drivers of change: years since disturbance, tree cover, soil compaction, and degree of tree removal. Effects of disturbance on compositional change were largely concordant between taxa. Contrary to Lawton et al.'s findings, species richness for most groups did not decline with disturbance level, providing support for the view that trends in species richness at local scales do not reflect the resilience of ecosystems to disturbance. Disturbance affected species composition more strongly than species richness for butterflies, canopy beetles, and litter ants. For these groups, disturbance caused species replacements rather than just species loss. Only termites showed effects of disturbance on species richness but not composition, indicating species loss without replacement. Although disturbance generally caused changes in composition, the strength of this relationship depended on the disturbance driver. Butterflies, litter ants, and nematodes were correlated with amount of tree cover, canopy beetles were most strongly correlated with time since disturbance, and termites were most strongly correlated with degree of soil disturbance. There were moderately divergent responses to disturbance between functional feeding groups. Disturbance was most strongly correlated with compositional differences of herbivores within beetles and nematodes and humus feeders within termites. Our results suggest that consideration of the impact of different forms of disturbance on species and functional composition, rather than on net numbers of species, is important when assessing the impacts of disturbance on biodiversity.

Long-term complications after facial, pharyngeal, laryngeal and tracheal traumas.

Long-term complications after facial, pharyngeal, laryngeal and tracheal traumas. OBJECTIVE: To review and summarize the existing evidence for long-term anatomical and functional complications after pharyngeal, laryngeal and tracheal traumas. DATA SOURCES: The MEDLINE database and the bibliographies of relevant studies were selected, analysed and appraised prior to December 2015. METHODS: With regard to the search strategy, the selected items were: ((long-term complications) AND pharyngeal) AND laryngeal) AND tracheal) AND traumas. Abstracts and titles were screened for relevance, while full articles of the se- lected records were evaluated and critically appraised after inclusion. Data concerning life-threatening situations, as well as long-term severe adverse effects were collected.

Transoral robotic surgery (TORS) with the Medrobotics Flex™ System: first surgical application on humans.

Head and neck surgery can be fraught with difficulties in accessing the pharynx and larynx. Minimally invasive surgery has developed with the recent advances in technology. Currently, we have a variety of high-definition multichannel videoendoscopes and robots in our armamentarium. We present our experience in a new robotic surgical system-'The Medrobotics Flex™ System' at our tertiary referral unit. We aimed to assess the safety, functionality and ease of use of this new device in this prospective study. Thus far, this is the first study in live human subjects who have undergone surgery for the following conditions: (1) obstructive sleep apnoea involving the base of tongue, the tonsil and the velum; (2) vocal fold polyp; (3) carcinoma of the lateral edge of the tongue. There were no complications in our series and the system provided good visualisation and access to these subsites without compromising safety or success. In summary, we found the Medrobotics Flex™ System to have certain other advantages including ease of set up and use besides being reliable and safe.

The da Vinci robotic system in head and neck surgery.

Intuitive Surgical Inc. (Sunnyvale, Ca, USA) extended the use of the da Vinci robot to head and neck surgery in 2005 following the previous use in urological, gynecological and cardiothoracic surgery. It then gained wide popularity throughout the globe. Our aim is to describe the da Vinci Robot System and discuss its applications in head and neck surgery. Continued refinements and applications in robotic surgery for otolaryngology will in time be possible as new robotic procedures are developed for endolaryngeal work.

Functional outcomes after transoral robotic surgery for squamous cell carcinoma of the oropharynx.

Over the past decade, the development of transoral robotic surgery (TORS) brought a new opportunity in the treatment of early T-stage oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study is to review the functional outcomes after TORS. Indeed, dysphagia is among the most commonly cited functional impairments in OPSCC survivors treated by surgeries with an open approach or conventional radiotherapy. We performed a review of the literature and analysed functional outcomes after TORS. Althought the technique is very recent, early functional and oncologic outcome data are promising and the major studies analysing these parameters support that TORS is feasible and safe as well as oncologically and functionally efficacious.

Transoral robotic tongue base reduction in surgical management of obstructive sleep apnea syndrome.

Management of base of tongue (BOT) is a challenging topic in surgical management of obstructive sleep apnea syndrome. After the introduction of transoral robotic surgery technology (TORS) into the otolaryngology practice, surgery on the BOT was performed more effectively. Base of tongue reduction can be performed alone or as a part of a multilevel surgery. Patient selection is important and will be discussed further in this study. Available studies show promising and encouraging results for TORS future use in BOT.

Transoral robotic surgery for base of tongue neoplasms.

Surgery to the base of tongue (BOT) in the presence of neoplasm is a challenging topic for head and neck surgeons. This area is difficult to access and includes important neurovascular structures such as the hypoglossal nerve and lingual artery. The pivotal role of the tongue base in swallowing makes planning the surgical approach more challenging. The surgical approaches vary from open neck/mandibulotomy to transoral laser surgery (TLS) which have significant disadvantages. After introduction of transoral robotic surgery (TORS) to otolaryngology practice with the da Vinci Surgical system, we have in our armamentarium a new approach to the BOT. The improved exposure with new retractors, 3-dimensional (3-D) visualization and magnification and advanced motion capacity allow for increased ease to perform surgery in this difficult area. In recent years, several articles published the data about safety and feasibility of TORS for various conditions. This article presents our approach to the BOT for neoplasms including malignant and benign lesions.

Is bone tenderness, as measured by manual algometry, associated with vitamin D deficiency?

OBJECTIVE: To explore the relationship between serum 25-hydroxycholecalciferol (25[OH]D3) and pressure-pain thresholds, as measured by algometer, in advance of a main study to determine whether PPT is a potentially cost-effective proxy measure of 25[OH]D3 status in the general population. METHODS: The cross-sectional pilot study involved a convenience sample of twenty-two subjects (10 males, 12 females), aged 18 to 67 years. All subjects consented to three trials of pressure-pain threshold readings on both tibiae and the manubrium. Serum 25[OH]D3 levels were determined from blood samples drawn post-algometry. RESULTS: The average pressure pain thresholds were 14.92 (±6.03), 15.07(±6.07), 11.10 (±6.68) for the left and right tibia and sternum, respectively. The stability between the measurements was very high with the interclass correlation coefficient (95% CI) calculated as 0.94 (0.62-1.00), 0.9 (0.81-1.00), 0.96(0.93-1.00). The Pearson correlation coefficients were 0.03 for the left tibia, 0.17 for the right tibia and 0.20 for the sternum, J Dresser, M MacIntyre, B Chisholm, GE Lawson showing a negligible correlation for the left and right tibia, but a low positive correlation for the sternum. CONCLUSION: We did not find preliminary evidence of a strong or otherwise clinically meaningful correlation between bone tenderness and manual algometry in this pilot study. Only a weak linear relationship between PPT in the sternum and serum 25[OH]D3 concentrations was found. Replication of this study is warranted in larger and more representative study populations of interest. Discussion on a number of feasibility issues is provided to inform those future studies.

OBJECTIF: Étudier la relation entre le taux sérique de 25-hydroxycholécalciférol (25 [OH] D3) et les seuils de tolérance à la pression, tels que mesurés par un algésimètre, en préparatif d'une étude principale pour déterminer si le STP pourrait être une mesure de remplacement économique de l'état de 25[OH]D3 dans la population générale. MÉTHODOLOGIE: L'étude pilote transversale a porté sur un échantillon pratique de vingt-deux sujets (10 hommes, 12 femmes), âgés de 18 à 67 ans. Tous les sujets ont consenti à trois essais lecture des seuils de tolérance à la pression sur le tibia et le manubrium. Les taux sériques de 25[OH]D3 ont été déterminés à partir d'échantillons de sang prélevés après la mesure par l'algésimètre. RÉSULTATS: Les seuils moyens de tolérance à la pression étaient 14,92 (±6,03), 15,07(±6,07), 11,10 (±6,68) pour respectivement les tibias gauche, droit et le sternum. La stabilité entre les mesures était très élevée avec le coefficient de corrélation interclasse (IC à 95 %) calculée comme 0,94 (0,62 à 1,00), 0,9 (0,81 à 1,00), 0,96 (0,93 à 1,00). Les coefficients de corrélation de Pearson ont été de 0,03 pour le tibia gauche, 0,17 pour le tibia droit et 0,20 pour le sternum, montrant une corrélation négligeable pour les tibias gauche et droit, mais une faible corrélation positive pour le sternum. CONCLUSION: Nous n'avons pas relevé dans cette étude pilote des preuves préliminaires d'une corrélation forte ou cliniquement significative entre la sensibilité des os et l'algométrie manuelle. Seule une faible relation linéaire entre le SPT dans le sternum et les taux sériques de 25[OH]D3 a été constatée. Une reproduction de cette étude est recommandée dans de plus grandes populations cibles qui seraient plus représentatives. Une discussion portant sur plusieurs questions de faisabilité est offerte pour renseigner ces futures études.

Use of cidofovir in HPV patients with recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis is a viral-induced disease, associated with exophytic epithelial lesions affecting the upper airways. Problem of treatment is the high recurrence of papilloma growth after surgical removal; therefore, adjuvant therapy schemes have been established. We used cidofovir, 7.5 mg/ml, in adjuvant therapy in the past years. Out of 31 adult patients treated with the drug, 26 (83.9 %) are at the moment in complete response. 19 (73 % of pts with CR) of those 26 patients were cured with a number of injections between 1 and 4 (mean 2.5). We did not see any clinical manifestation of renal toxicity or neutropenia (superinfection) necessitating a blood test. Six patients presented dysplasia during the treatment with the drug, while six patients had dysplasia prior to cidofovir injection. Due to recurrent nature of the disease and the high number of mechanical and laser surgeries required we treated one tracheal stenosis, two scarred larynx, and two glottic synechiaes. There is still an ongoing discussion within the European Laryngological Society about the effectiveness and possible side effects of this drug. Results show promising long-term effects of adjuvant use of cidofovir, without any relevant side effects.

Total knee replacement in patients with haemophilia: the Scottish experience.

INTRODUCTION: Patients with haemophilia commonly develop arthropathy secondary to recurrent haemarthroses. Although modern treatment with replacement coagulation factors has reduced the prevalence of end-stage arthropathy, total joint replacement is still required in a small group of patients. These patients may be at higher risk of complications and the outcome of surgery may not be comparable to reports of outcomes of total joint replacement in the general population. The purpose of this study was to describe the change in function in patients undergoing total knee replacement for haemophilic arthropathy. PATIENTS AND METHODS: Patients undergoing total knee arthroplasty in a tertiary centre had prospective evaluations of patient reported outcome measures and range of movement. Their post-operative function was evaluated in a combined orthopaedic-haematology clinic. Eight male patients underwent 13 total knee replacements from 1999 to 2007 and were followed up for a median of 78 months (range 17-116). RESULTS: The median Oxford knee score improved from 45.5 pre-operatively to 28 (p = 0.049). There was a similar improvement in SF-12 physical (p = 0.017) and Knee Society scores (objective p = 0.001; function p = 0.002). Four total knee replacements were performed in patients with inhibitor antibodies and were treated with recombinant activated factor VIIa. These patients had reduced range of movement (p = 0.047). No patients suffered deep infection. CONCLUSIONS: Total knee replacement in patients with haemophiliac arthropathy resulted in improvement in range of movement and function. The presence of factor VIII inhibitors resulted in reduced range of movement, but similar patient reported outcome measures.

Abdominal pain and a raised amylase? It's not always pancreatitis. . .

We report the case of a 72 year old man with a history of COPD and heavy alcohol consumption who was initially diagnosed with acute pancreatitis based on a presentation with epigastric pain and elevated serum amylase. Review of his notes revealed several previous similar admissions and extensive normal investigations apart from persistently elevated amylase. Further analysis showed evidence of macroamylasaemia which accounted for the apparently high serum amylase level.