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PURPOSE: Patients suffering from Ménière's disease (MD) experience vertigo, and impairments in hearing and quality of life (QoL). This study aims to investigate the impact of cochlear implantation (CI) on various aspects affecting patients with MD. METHODS: A single tertiary centre's CI database for CI recipients with MD between 2014 and 2022 was screened retrospectively. Hearing, vertigo, tinnitus symptoms, and hearing-related QoL were assessed. Pre- and postoperative hearing tests in conjunction with subjective outcome measures by visual analogue scale (VAS) and validated tools such as the Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI) and Nijmegen Cochlear Implant Questionnaire (NCIQ), as well as the assessment of the pre- and postoperative Functional Level Scale (FLS) were examined. RESULTS: Eleven ears were included (median age: 59 years at implantation). Following implantation, there was a significant enhancement in Word Recognition Scores at sound levels of 65 dB and 80 dB compared to before treatment (preop vs. 12 months postop: p = 0.012). However, no significant enhancement was observed for 50 dB. MD-related impairments improved significantly postoperatively, as measured by the VAS (vertigo: p = 0.017; tinnitus: p = 0.042), DHI (p = 0.043), THI (p = 0.043) and NCIQ (p < 0.001). The FLS improved significantly (p = 0.020). CONCLUSION: CI has positive effects on all areas examined in our cohort. However, discrimination of speech at low sound pressure levels remained problematic postoperatively. In patients suffering from MD, the prioritized treatment goals include not only improved hearing but also the rehabilitation of vertigo and tinnitus, as well as the enhancement of QoL. Validated instruments are useful screening tools.
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Psychological assessment plays a crucial role in the preoperative phase of septorhinoplasty (SRPL), exerting potential influence on both pre- and postoperative aspects of quality of life (QoL). In this prospective study, SRPL patients were systematically screened using two validated questionnaires for body dysmorphic disorder (BDD) and one each for anxiety, depression, and somatic symptom disorder (SSD). Nasal perception was evaluated utilizing two disease-specific, self-report instruments: The Rhinoplasty Outcomes Evaluation (ROE) and the Functional Rhinoplasty Outcome Inventory-17 (FROI-17). A total of 95 patients were enrolled. Positive screening rates were 40.4 and 28.3% for BDD, 37.3% for elevated anxiety, 16.4% for depression, and 22.4% for SSD. Mean scores on the ROE and FROI indicated lower QoL in all positive screening groups. Statistically significant differences were observed for anxiety (FROI total score: 47.1 ± 14.6 to 37.8 ± 16.2; p = 0.021) and BDD (ROE: 43.7 ± 15.7 to 32.5 ± 15.5; p = 0.003 and FROI total score: 47.4 ± 15.3 to 37.8 ± 17.1; p = 0.014). The Hospital Anxiety and Depression Scale exhibited a significant correlation with the preoperative FROI score (r = 0.34, p = 0.005). Patients with positive screenings for depression, anxiety, BDD, and SSD demonstrated compromised QoL during preoperative assessments compared with their negative counterparts, reflecting diminished nasal perception in both esthetic and functional dimensions. Surgeons must be cognizant of these psychological aspects during preoperative evaluations.
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BACKGROUND: Various surgical techniques using transpalatinal, transseptal, and transnasal approaches for surgical repair of choanal atresia have been developed over the past 200 years. Endoscopic endonasal surgery with resection of dorsal septal parts and without the use of stents is the current scientific trend, as high success rates with low complication rates can be achieved. This study examined whether this technique has actually become standard in Germany, and also investigates the role played by stents. METHODS: A total of 52 ear, nose, and throat (ENT) hospitals in Germany, including all 39 university ENT hospitals and 13 non-university maximum-care ENT hospitals, were asked which surgical technique they use for choanal atresia repair and whether stents are used. RESULTS: For dorsal septal resection, 39 of 44 responding hospitals (89%) indicated that they resect dorsal septal parts, 85% of the university hospitals and 100% of the non-university hospitals. For use of stents, 20 of 48 responding hospitals (42%) reported not using stents, whereas 39% of the university hospitals and 50% of the non-university hospitals do use them. CONCLUSION: Endoscopic endonasal choanal atresia repair with resection of dorsal septal parts is, in most instances, used as the standard technique in large ENT hospitals in Germany. Routine use of stents is still widespread. The future aim should be to reduce the use of stents in the treatment of choanal atresia and to use this method only in difficult, individual cases.
Subject(s)
Choanal Atresia , Humans , Choanal Atresia/surgery , Postoperative Complications , Endoscopy/methods , Nose , StentsABSTRACT
BACKGROUND: Chronic rhinosinusitis (CRS) has a negative impact on health-related quality of life (HRQoL). Functional endoscopic sinus surgery (FESS) is the treatment of choice for those not responding to medical treatments. To date, the short-term effects of FESS on HRQoL are still unclear. OBJECTIVE: Evaluation of the short-term effects of FESS on HRQoL in CRS patients using the SNOT-22 questionnaire. METHODS: The results of the validated German version of the Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire were analysed from 89 patients with CRS before surgery and 10-14 days (n = 77), four (n = 77), six weeks (n = 76) and 6 months (n = 71) after FESS, and compared with those of 1,000 healthy controls selected using a non-probability quota sample in accordance to the distribution of the German Microcensus. RESULTS: Compared to the preoperative mean SNOT-22 score (47.35), CRS patients significantly improved in HRQoL 10-14 days (31.75, p < 0.01), 4 weeks (25.84, p < 0.01), 6 weeks (24.16, p < 0.01) and 6 months after FESS (27.16, p < 0.01). Pre- and 6 months postoperatively, the five most important SNOT-22 items were nasal obstruction, smell and taste reduction, thick, mucous nasal secretions, need to blow the nose and postnasal drip. At the 2, 4 and 6-week follow-up, the reduction in smell and taste was most frequently perceived as limiting the HRQoL. CONCLUSIONS: This follow-up study shows for the first time that the reduction in smell and taste should be treated and controlled concervatively in the short term after FESS.
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BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease at the clinical phenotype level (without nasal polyp [CRSsNP] vs with nasal polyp [CRSwNP]) and at the underlying inflammatory endotype level (type 2 vs non-type 2). Whether the endotype is associated with clinical presentation in patients with CRSsNP has yet to be explored in detail. OBJECTIVE: To identify associations between endotypes and their clinical significance in patients with CRSsNP based on tissue interleukin-5 levels. METHODS: A total of 104 patients with CRSsNP who underwent functional endoscopic sinus surgery between 2013 and 2017 were endotyped. We collected immunologic and clinical parameters and evaluated whether there were associations between the endotype and clinical features using Visual Analog Scale (VAS), Sino-Nasal Outcome Test-22 (SNOT-22), Sniffin' Sticks test, Lund-Mackay CT score, and nasal endoscopy. RESULTS: Mean tissue interleukin-5 levels were used to identify type 2 inflammation (non-type 2: 3.37 vs type 2: 191.98 pg/g tissue; P < .001). There were no significant clinical differences measured by patient-reported outcome measures between patients with type 2 CRSsNP and those with non-type 2 CRSsNP preoperatively. Type 2 and non-type 2 CRSsNP did not differentiate in CT score, Sniffin' Sticks test, and nasal endoscopy. Postoperative SNOT-22 and VAS scores correlated well with each other (r = 0.75; P < .01). Postoperative VAS scores were in both groups significantly lower than before the operation (type 2: 5.07 vs 2.99; P < .01; non-type 2: 5.74 vs 3.22; P < .01), but not associated to the inflammatory subtype. CONCLUSION: The type of inflammation does not affect the symptoms, the computed tomography scan, or the postoperative results in CRSsNP in contrast to former findings in CRSwNP. TRIAL REGISTRATION: Belgian registration number (B.U.N.) No. B6702020000097.
Subject(s)
Nasal Polyps , Rhinitis , Sinusitis , Humans , Interleukin-5 , Rhinitis/diagnosis , Chronic Disease , Sinusitis/complications , Inflammation , Patient Reported Outcome MeasuresABSTRACT
BACKGROUND AND PURPOSES: How closed reduction (CR) to repair a nasal fracture affects the patient's quality of life (QoL) has not been investigated. Here, we assessed QoL before and after CR using disease-specific questionnaires and compared the QoL scores of patients with nasal fractures with normative scores from a reference cohort. METHODS: This was a prospective study of 96 patients with nasal fractures undergoing CR. Patients were interviewed about aesthetic, functional, and QoL issues before and after surgery using the Functional Rhinoplasty Outcome Inventory (FROI-17) and the Rhinoplasty Outcome Evaluation (ROE). Photographs of the nasal area were taken before and after surgery and reviewed. Data were compared with those from a reference cohort (n = 1000). RESULTS: Most fractures were type I (80.6%) and most were caused by sport-related accidents (36.5%). The ROE scores increased from 67.3 preoperatively to 73.4 postoperatively (p = 0.001). The FROI-17 also improved, indicating the overall effect of the nose on QoL (p = 0.002). Compared with the reference cohort, patients felt more affected by nasal symptoms before surgery (- 9.37, p = 0.02) than by more general aspects. ROE scores returned to normative values after surgery (p < 0.001). The postoperative cohort had lower scores for the FROI-17 item overall effects of the nose on QoL than the reference cohort did, although the nasal symptom score remained higher in patients than in reference controls. CONCLUSIONS: This study showed that CR can improve the aesthetical but not the functional outcome of the nose.
Subject(s)
Nasal Obstruction , Rhinoplasty , Skull Fractures , Humans , Quality of Life , Prospective Studies , Nose/surgery , Esthetics , Treatment Outcome , Nasal Obstruction/surgery , Nasal Septum/surgery , Patient SatisfactionABSTRACT
Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can arise in cases of definitive nonsurgical treatment. To address this medical need, we established a random forest prediction model for the risk assessment of perineural invasion, including occult perineural invasion, and characterized distinct cellular and molecular features based on our new and extended classification. RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas were used as a training cohort to identify differentially expressed genes that are associated with perineural invasion. A random forest classification model was established based on these differentially expressed genes and was validated by inspection of H&E-stained whole image slides. Differences in epigenetic regulation and the mutational landscape were detected by an integrative analysis of multiomics data and single-cell RNA-sequencing data were analyzed. We identified a 44-gene expression signature related to perineural invasion and enriched for genes mainly expressed in cancer cells according to single-cell RNA-sequencing data. A machine learning model was trained based on the expression pattern of the 44-gene set with the unique feature to predict occult perineural invasion. This extended classification model enabled a more accurate analysis of alterations in the mutational landscape and epigenetic regulation by DNA methylation as well as quantitative and qualitative differences in the cellular composition in the tumor microenvironment between head and neck squamous cell carcinoma with or without perineural invasion. In conclusion, the newly established model could not only complement histopathologic examination as an additional diagnostic tool but also guide the identification of new drug targets for therapeutic intervention in future clinical trials with head and neck squamous cell carcinoma patients at a higher risk for treatment failure due to perineural invasion.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/genetics , Epigenesis, Genetic , Risk Assessment , RNA , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Tumor MicroenvironmentABSTRACT
PURPOSE: Assessing cochlear implant (CI)-associated patient outcomes is a focus of implant research. Most studies have analyzed outcomes retrospectively with low patient numbers and few measurement time points. In addition, standardized CI-specific health-related quality of life (HRQoL) instruments have not been used. To address this, we prospectively assessed HRQoL in patients before and after implantation. METHODS: We assessed HRQoL using the Nijmegen Cochlear Implant Questionnaire (NCIQ), Abbreviated Profile of Hearing Aid Benefit (APHAB), Hearing Participation Scale (HPS), and the Visual Analogue Scale (VAS) in 100 deaf or severely hearing-impaired patients (57 unilaterally deaf and 43 bilaterally deaf) before and 3, 6, and 12 months after cochlear implantation. We compared the results of unilaterally and bilaterally hearing-impaired patients and patients with or without a hearing aid. Principal component (PCA) and exploratory factor analyses (EFA) were also conducted. RESULTS: The NCIQ measured improvements in all 6 domains after CI and correlated well with other QoL instruments. The PCA revealed that the NCIQ can be better explained by physical, physical advanced, and socio-psychological components. The APHAB score ameliorated over time, except for the background noise domain. The overall HPS score improved over time, but the hearing handicap subscore significantly decreased. Sociodemographic influences on the questionnaire scores were relatively weak. CONCLUSION: Assessing HRQoL is essential for quantifying the patient outcome after CI. NCIQ scores in our patient cohort showed improved HRQoL in all domains and we recommend that the NCIQ be used as a first-line questionnaire for assessing QoL in hearing-impaired patients after CI.
Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Humans , Prospective Studies , Quality of Life , Retrospective Studies , Surveys and Questionnaires , Treatment OutcomeABSTRACT
Could primary chemoradiotherapy (pCRT) possibly be viewed as an alternative standard therapy to upfront total laryngectomy (TL)? According to the new German S3 guideline, despite higher rates of local recurrence, there would be no survival disadvantage and salvage surgery would be a curative option. In several large database studies and case series, statistically significant survival disadvantages of more than 30% between pCRT and TL have been reported for T4 laryngeal cancer. According to the literature, the success rate of salvage TL for T4 laryngeal cancer is only about 25-50%. Larynx preservation (LP) studies which could qualify the recommendation of pCRT as an alternative standard therapy to TL in T4 carcinomas should 1) evaluate T4a cancers within the T4 category; 2) perform subgroup analysis of laryngeal and hypopharyngeal cancers; 3) be sufficiently highly powered; 4) provide long-term outcomes of at least 5 years; 5) with oncological and 6) functional outcomes (duration of the need for tracheostomy and/or feeding tube dependency; necessity and success of salvage laryngectomies). 7) Specification of the criteria of the respective T4 classification (invasion through the outer cortex of the cartilage, or infiltration of which extralaryngeal structures) and 8) evaluation of pretreatment laryngeal function (at least: tracheostomy, feeding tube dependency). Collection of all the aforementioned data of T4 patients treated with pCRT in a large prospective observational cohort study in German-speaking countries is suggested. In case of rejection of TL by T4 laryngeal cancer patients, differentiation between primary spontaneous reluctance and a definitive, carefully considered decision is important. This distinction should be achieved by sensitive discussions. Not only oncological but also functional outcome probabilities should be included in the overall decision-making process.
Subject(s)
Carcinoma, Squamous Cell , Laryngeal Neoplasms , Larynx , Carcinoma, Squamous Cell/surgery , Humans , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/surgery , Laryngectomy , Larynx/surgery , Neoplasm Staging , Prospective Studies , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: By today's standard, the optimal treatment of every individual tumor patient is discussed and determined in an interdisciplinary tumor board. According to the new S3 guidelines, larger volume T3 laryngeal cancers which are no longer safely resectable with larynx-sparing surgery are ideal candidates for a larynx preservation approach using primary chemoradiation (pCRT). So far, no clear criteria have been defined under what circumstances primary radiotherapy alone (pRT) might be acceptable in case chemotherapy (CT) is prohibited or in what cases, even in T3, upfront total laryngectomy with risk-adapted adjuvant treatment (TL±a[C]RT) should be recommended. METHOD: The literature was searched for parameters chosen as criteria for an inclusion in the surgical rather than the conservative arm in non-randomized LP studies or which proved to be significant prognostic markers after conservative treatment. Development of a counselling tool for therapeutic decision making. RESULTS: Significant prognostic markers were tumor volume (<â¯3.5 ccm/<â¯6â¯ccm vs. 6-12â¯ccm vs. >â¯12â¯ccm), presence and kind of vocal cord fixation (none vs. Succo I/II vs. Succo III/IV), extent of cartilage infiltration (none vs. minimal vs. multiple/gross), nodal status (N01 vs. N2-3), and laryngeal dysfunction (pretreatment necessity of feeding tube or tracheostomy). CONCLUSION: For T3 laryngeal cancers, pRT could be acceptable when the tumor volume is <â¯3.5â¯ccm for glottic and <â¯6â¯ccm for supraglottic tumors and there are no further risk factors. pCRT can be regarded as the standard for LP for tumors between 6â¯ccm and 12â¯ccm, vocal cord fixation Succo pattern I/II, only minimal cartilage infiltration and a high nodal burden. For tumor >â¯12 ccm, vocal cord fixation Succo pattern III/IV, gross or multiple cartilage infiltration or clinically relevant laryngeal dysfunction, upfront TL±a[C]RT should be considered.
Subject(s)
Laryngeal Neoplasms , Larynx , Glottis/pathology , Humans , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/surgery , Laryngectomy , Larynx/surgery , Neoplasm Staging , Retrospective StudiesABSTRACT
BACKGROUND: The Nijmegen Cochlear Implant Questionnaire (NCIQ) is a disease-specific questionnaire to determine the health-related quality of life (HRQoL) of patients before and after cochlear implantation. OBJECTIVE: This study aimed to assess the validity and reliability of the German translation of the NCIQ. MATERIALS AND METHODS: A prospective study was performed in 100 postlingually deaf or severely hearing-impaired patients. HRQoL was assessed using the NCIQ, the Abbreviated Profile of Hearing Aid Benefit (APHAB), and the Hearing Participation Scale (HPS) before as well as 3 and 6 months after cochlear implantation. An untreated group of postlingually deaf or severely hearing-impaired patients (nâ¯= 54) served as a control. Cronbach's α and test-retest reliability were measured. The content, discrimination, and agreement validity were tested. The evaluation of construct validity was based on recently published data. Sensitivity and receiver operating curve (ROC) analysis, including consideration of the area under the curve (AUC), were used as quality criteria. RESULTS: The test-retest analysis showed stable NCIQ values 3 and 6 months postoperatively. The Cronbach's α values indicated good internal consistency. The NCIQ validly discriminated between treated and untreated patient groups. There were statistically significant albeit weak correlations between the NCIQ and the APHAB (râ¯= -0.22; pâ¯= 0.04) and the HPS (râ¯= 0.30; pâ¯= 0.01). Sensitivity and ROC analyses showed good measurement quality of the German-speaking NCIQ. CONCLUSION: The German translation of the NCIQ reliably and validly measures HRQoL before and after cochlear implantation and can be used for clinical monitoring after treatment with cochlear implants.
Subject(s)
Cochlear Implantation , Cochlear Implants , Hearing Loss , Speech Perception , Hearing Loss/diagnosis , Humans , Prospective Studies , Quality of Life , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
PURPOSE: The study aimed to determine normative values for the Tonsillectomy Outcome Inventory 14 (TOI-14) in a healthy middle-European cohort. We also compared these generated values with TOI-14 scores from a patient population with recurrent tonsillitis (RT) and explored the factorial structure of the TOI-14. METHODS: We systematically studied the responses of healthy individuals (reference cohort) and patients with RT (clinical cohort) to the TOI-14 survey. The reference cohort contained 1000 participants, who were recruited using the Respondi panel for market and social science research. This subsample was quoted to the population distribution of the German Microcensus and selected from a non-probability panel. Tonsillitis patients were assessed before and 6 and 12 months after tonsillectomy. Data were analysed using principal component and exploratory factor analyses. RESULTS: The PCA revealed three TOI-14 domains (physiological, psychological and socio-economic), which explained 73% of the total variance. The reference cohort perceived a good quality of life (QOL) with a TOI-14 total score of 11.8 (physiological: 8.0, psychological: 5.8, and socio-economic subscale score: 13.9). TOI-14 scores were higher in the patient cohort, indicating that the TOI-14 discriminates between patients with RT and healthy individuals with no RT. Age and female gender significantly influenced the total TOI-14 score, especially in the psychological (age) and socio-economic (gender) subscales. CONCLUSION: We have developed a set of normative values that, together with the TOI-14, can determine the disease burden indicating tonsillectomy.
Subject(s)
Tonsillectomy , Tonsillitis , Female , Health Status , Humans , Quality of Life , Recurrence , Surveys and Questionnaires , Tonsillitis/surgeryABSTRACT
OBJECTIVES: To evaluate the rate of surgical site infection (SSI) and associated risk factors after parotid gland surgery including the impact of antibiotic prophylaxis. DESIGN: Retrospective single-centre clinical study. SETTING: Tertiary referral centre for head and neck surgery. PARTICIPANTS: Seven hundred and fifty four patients who underwent parotid gland surgery at the University Hospital Heidelberg, Germany, between 2007 and 2014 were enrolled in this study. Data on patient age, American Society of Anesthesiologists (ASA) classification system, smoking status, diabetes mellitus, operation time, and antibiotic prophylaxis were collected. Additionally, the National Healthcare Safety Network (NHSN) risk index was calculated. Association of these factors with SSI was evaluated in univariate analyses and a multivariate logistic regression model. MAIN OUTCOME MEASURES: Rate of SSI. RESULTS: Twenty four patients (3.2%) had an SSI according to the NHSN definition. In univariate analyses, only smokers (P = .048) and male patients (P = .01) had a significantly higher rate of SSI. Since the majority of smokers were men (62.3%), the effect of male gender, smoking, together with the NHSN risk index was further investigated as predictors of SSI within a logistic regression model. All three predictors showed a significant effect on SSI. CONCLUSIONS: Parotid gland surgery has a low rate of SSI. In our cohort, male gender, smoking and high NHSN risk index scores were significantly associated with SSI, whereas antibiotic prophylaxis had no protective effect.
Subject(s)
Antibiotic Prophylaxis , Parotid Diseases/surgery , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Female , Germany/epidemiology , Humans , Male , Middle Aged , Operative Time , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Lip, oral cavity, and pharynx cancers (ICD-10: C00-C14) describe a heterogeneous group of tumors with strong variations in incidence, mortality, and survival by entity. OBJECTIVES: This work provides a detailed overview of epidemiologic measures for these tumor entities, taking into account heterogeneity in age, sex, location, and stage. MATERIAL AND METHODS: Incidence and mortality data for Germany for the years 1999-2016 were extracted from the interactive database of the Center for Cancer Registry Data (ZfKD). Age and stage distributions and five-year relative survival were calculated on the pooled ZfKD data set (diagnosis years 1999-2017). RESULTS: In 2016, overall incidence and mortality for all entities were 17.6 and 7.0 per 100,000 men and 6.5 and 1.8 per 100,000 women, respectively. The five-year relative survival in 2015-2017 was 53 and 63%, respectively. There were marked differences in survival as well as age and stage distributions between entities. Trend analyses showed an increase in age at diagnosis, particularly in male patients, and no change in stage distributions. However, five-year relative survival increased from 45% (men) and 59% (women) in 1999-2002 to 52% and 63% in 2013-2017. CONCLUSION: The marked heterogeneity of the studied tumors highlights the need to differentiate the analysis by sex and entity for meaningful interpretation of epidemiologic metrics. With the expansion of clinical cancer registration in Germany, additional analyses including other important clinical factors will be possible in the future.
Subject(s)
Mouth Neoplasms , Pharyngeal Neoplasms , Female , Germany/epidemiology , Humans , Incidence , Male , Mouth Neoplasms/epidemiology , Pharyngeal Neoplasms/epidemiology , RegistriesABSTRACT
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) patients frequently develop treatment resistance to cetuximab, a monoclonal antibody against EGFR, as well as radiotherapy. Here we addressed extracellular signal-regulated kinase 1/2 (ERK1/2) regulation by cetuximab or fractionated irradiation (IR) and conducted in silico prognostic evaluation of the EGFR-MAPK axis in HNSCC. METHODS: Expression of ERK1/2 phosphorylation (pERK1/2) was determined in HNSCC cell lines, which were treated with cetuximab or fractionated-IR. Furthermore, the effect of fractionated IR on pERK1/2 was confirmed in an ex vivo HNSCC tissue culture model. Expression and prognostic significance of EGFR-ERK axis was evaluated in a cohort of radiotherapy plus cetuximab-treated HNSCC. Correlations among EGFR-MAPK signalling components and association between transcript and protein expression profiles and patient survival in HNSCC were analysed using publicly available databases. RESULTS: ERK1/2 phosphorylation was rebounded by prolonged cetuximab administration and was induced by fractionated IR, which could be suppressed by a MEK inhibitor as a radiosensitiser. In silico assessments suggested that EGFR-MAPK cascade genes and proteins could predict HNSCC patients' survival as a prognostic signature. CONCLUSIONS: Activation of ERK1/2 signalling contributes to the cellular defence of HNSCC against cetuximab and fractionated IR treatment. EGFR-MAPK axis has a prognostic significance in HNSCC.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Mitogen-Activated Protein Kinase 1/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Animals , Cell Line, Tumor , Cetuximab/pharmacology , Drug Resistance, Neoplasm/drug effects , ErbB Receptors/genetics , Humans , Insect Proteins , MAP Kinase Signaling System/drug effects , Mice , Mitogen-Activated Protein Kinase Kinases/genetics , Prognosis , Protein Kinase Inhibitors/pharmacology , Squamous Cell Carcinoma of Head and Neck/pathology , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE: The main side effect of prostate-specific membrane antigen targeting alpha therapy (PSMA TAT) is dry mouth syndrome. Inflammation of the salivary glands and consequent reduced salivary function have been reported in patients after radioiodine therapy. The beneficial effects of sialendoscopy on radiation-induced inflammation in tissue are well known. Thus sialendoscopy with dilatation, saline irrigation and steroid injections (prednisolone) was performed before and after 225Ac-PSMA-617 TAT to reduce inflammatory effects in the salivary glands and to improve or prevent xerostomia. METHODS: Eleven men with metastatic castration-resistant prostate cancer (mean age 68.5 years, range 58-80 years) underwent sialendoscopy, dilatation, saline irrigation and steroid injection of both submandibular and both parotid glands before or after every cycle of 225Ac-PSMA-617 TAT. Sialendoscopy and steroid injection were performed by a senior ENT physician. Quality of life was evaluated using two health-related quality of life (HRQOL) questionnaires, the Xerostomia Questionnaire (XQ) and the Xerostomia Inventory (XI) before and 3 months after the intervention. RESULTS: In all 11 patients both parotid and both submandibular glands were affected by radiation sialadenitis and sialendoscopy was performed. The patients experienced no complications after sialendoscopy, and showed a significant improvement in HRQOL as measured using the XQ and XI. After sialendoscopy the XQ score decreased significantly from 77.7 ± 13.6 to 42.7 ± 14.8 (p = 0.003) and the XI score decreased from 44.5 ± 6.9 to 25.8 ± 12.8 (p = 0.003). Due to the limited number of patients we only report tendencies. CONCLUSION: Sialendoscopy with dilatation, saline irrigation and steroid injection had beneficial effects on salivary gland function and HRQOL in patients undergoing 225Ac-PSMA-617 RLT. However, even with sialadenoscopic support after multiple cycles of TAT, salivary gland function was reduced and xerostomia was present. Therefore, not only inflammation but also the direct effect of radiation is a putative cause of dry mouth. Further research is necessary to determine the main side effects of PSMA TAT.
Subject(s)
Actinium/adverse effects , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Radiopharmaceuticals/adverse effects , Salivary Glands/surgery , Surgery, Computer-Assisted/methods , Xerostomia/surgery , Actinium/therapeutic use , Aged , Aged, 80 and over , Dipeptides/adverse effects , Dipeptides/therapeutic use , Heterocyclic Compounds, 1-Ring/adverse effects , Heterocyclic Compounds, 1-Ring/therapeutic use , Humans , Male , Middle Aged , Prednisolone/therapeutic use , Prostate-Specific Antigen , Radiopharmaceuticals/therapeutic use , Salivary Glands/diagnostic imaging , Surgery, Computer-Assisted/adverse effects , Therapeutic Irrigation/adverse effects , Therapeutic Irrigation/methods , Xerostomia/etiologyABSTRACT
OBJECTIVES: Though xerostomia is a frequent oral symptom, there is no validated disease-specific questionnaire in German. The purpose of this study was to translate and validate versions of the Xerostomia Inventory and the Summated Xerostomia Inventory in a German-speaking population. PARTICIPANTS AND METHODS: Thirty-nine patients including 18 patients suffering from radiation-induced xerostomia enrolled in this study. Both questionnaires were translated into German language according to international accepted guidelines. For validation, we evaluated reliability, validity, and responsiveness using the COSMIN manual for cross-cultural adaptation. RESULTS: Cronbach's α was 0.92 for XI and 0.91 for SXI, showing both high internal consistency. Patients suffering from xerostomia showed significantly higher average scores demonstrating its discriminant validity. Confirmatory factor analysis showed excellent "goodness-of-fit" values for SXI and good to moderate values for XI, confirming the assumed factor structures. The Xerostomia Inventory and its summated version both showed excellent test-retest reliability in the non-xerostomia group (ICC = 0.85 and 0.84). CONCLUSIONS: The XI and SXI in their cross-cultural adapted versions are the first validated self-report assessments for xerostomia in German language. They are characterized by practical design and can be easily interpreted by the treating physician.
Subject(s)
Oral Health , Psychometrics/methods , Quality of Life , Radiation Injuries/diagnosis , Surveys and Questionnaires/standards , Translations , Xerostomia/diagnosis , Endoscopy , Female , Humans , Language , Male , Psychometrics/statistics & numerical data , Radiation Injuries/etiology , Reproducibility of Results , Xerostomia/etiology , Xerostomia/psychologyABSTRACT
OBJECTIVES: This study aimed to evaluate sensory dysfunction resulting from great auricular nerve (GAN) sacrifice versus preservation in parotid surgery for benign lesions and its imact on long-term health-related quality of life (QOL). DESIGN: Retrospective. SETTING/MAIN OUTCOME MEASURES: Participants were divided into two groups (GAN and non-GAN), and both short-term (two postoperative weeks) and long-term (at least 5 years) QOL were assessed. The second item of the Parotidectomy Outcome Inventory-8 (POI-8) was used to analyse postoperative sensory loss. All items of the POI-8 questionnaire were used to determine health-related QOL.We used t test for dependent samples and Mann-Whitney U-test to compare patient groups PARTICIPANTS: A total of 137 patients (65 male and 72 female) enrolled in this study. Average age at the time of surgery was 53 years (±12.8). RESULTS: The GAN preservation group had significantly better sensation than the GAN sacrifice in short term (2.8 vs 2.1; P = 0.017). Both groups experienced improved sensation in the long term, and there was a trend towards better QOL in the GAN-preservation group. However, the difference in sensation was not statistically significant (1.7 vs 1.3; P = 0.145). Health-related QOL also increased in the long term (compared to short term) for both groups (7.6 ± 6.2 to 12 ± 7.6; P < 0.0001) postoperatively. GAN preservation did not significantly improve sensation in long term, nor did it increase health-related QOL postoperatively. CONCLUSION: Although GAN preservation was easily feasible, it only improved sensation in short term. We report a negative result: GAN preservation did not significantly improve sensation in long-term, nor did it increase health-related QOL postoperatively when compared to GAN sacrifice.
Subject(s)
Ear Auricle/innervation , Hearing Loss, Sensorineural/prevention & control , Otorhinolaryngologic Surgical Procedures/methods , Parotid Diseases/surgery , Parotid Gland/surgery , Quality of Life , Sensation/physiology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hearing Loss, Sensorineural/physiopathology , Humans , Male , Middle Aged , Parotid Diseases/physiopathology , Parotid Gland/innervation , Postoperative Complications , Retrospective Studies , Surveys and Questionnaires , Time Factors , Young AdultABSTRACT
PURPOSE: Health-related quality of life measurements are gaining in importance in clinical medicine. Little is known about the long-term quality of life changes after septorhinoplasty. This study was designed to analyse the long-term quality of life impacts of septorhinoplasty, using disease-specific instruments-rhinoplasty outcome evaluation (ROE) and Functional Rhinoplasty Outcome Inventory-17 (FROI-17); as well as a generic instrument-Short-Form 36 Health Survey (SF-36). METHODS: Patients completed the FROI-17, the ROE and the SF-36 preoperatively and at 12 and 60 months postoperatively. General demographic and clinical information (age, gender, allergies, medication, medical and surgical history) were collected from all patients. RESULTS: We report a significant increase in disease-specific QOL after primary septorhinoplasty (as measured with the ROE & FROI-17) and in two scales of the SF-36 generic instrument (role-functioning physical and mental health) 1 year after surgery. Our patients showed further significant increase in disease-specific QOL (FROI-17) after their primary septorhinoplasty (1 year vs. 5 years postoperatively). SF-36 results showed significant improvements 5 years postoperatively (compared to preoperative scores) in six out of eight scales (physical functioning, role-functioning physical, bodily pain, vitality, social functioning and mental health). CONCLUSION: Septorhinoplasty can improve disease-specific and non-disease-specific QOL in the short- and long-term postoperative period. These improvements remain measurable 5 years after surgery.