The SNOT-22 factorial structure in European patients with chronic rhinosinusitis: new clinical insights.

PURPOSE: The sino-nasal outcomes test-22 (SNOT-22) represents the reference questionnaire to assess patients with chronic rhinosinusitis (CRS). As weak correlations between objective CRS parameters and SNOT-22 total score have been observed, factor analyses have aimed to identify underlying factorial structures. However, ambiguous factor loadings and problematic item-domain assignments have resulted. Moreover, such factor analyses have mainly been performed in non-European CRS patients, while European data remain sparse. This study thus sought to address these issues. METHODS: Principal component analysis and confirmatory factor analysis were performed from SNOT-22 questionnaires completed by European CRS patients. Goodness of fit, internal consistencies, and factor loadings were calculated. Item-domain assignment was based on statistical grounds and clinical meaningfulness. Additionally, this study investigated correlations between SNOT-22 domains and external reference criteria, including Lund-Mackay score, Lund-Naclerio score and the brief symptom inventory 18 (BSI-18). RESULTS: One hundred and thirty-four European CRS patients were included. Principal component analysis proposed four SNOT-22 domains ("nasal symptoms", "otologic symptoms", "sleep symptoms", "emotional symptoms"), which explained 63.6% of variance. Observed item-domain-assignment differed from previously proposed item-domain assignments. All factor loadings were > 0.5, except "cough" (0.42) and "facial pain or pressure" (0.49). For confirmatory factor analysis, satisfactory goodness of fit (RMSEA = 0.66; CFI = 0.92; TLI = 0.90) and internal consistencies (Cronbach-α: total score = 0.93; domains = 0.75-0.91) were observed. Significant positive correlations were found between the "nasal symptoms" domain and both the Lund-Mackay score (r = 0.48; p < 0.001) and the Lund-Naclerio score (r = 0.27, p < 0.01). Significant positive correlations were also identified between "emotional symptoms" and BSI-18 total score (r = 0.64, p < 0.001). CONCLUSIONS: Principal component analysis performed for SNOT-22 questionnaires completed by European CRS patients indicated a different item-domain-assignment than previously reported. Confirmatory factor analysis suggested acceptable and clinically plausible psychometric properties for the resulting factorial structure. Significant correlations between the "nasal symptoms" and the "emotional symptoms" domains were observed with objective CRS parameters. The resulting factorial structure with different item-domain assignments may thus be more suitable for European CRS patients.

Assessment of health-related quality-of-life in patients with chronic Rhinosinusitis - Validation of the German Sino-Nasal Outcome Test-22 (German-SNOT-22).

PURPOSE: The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS). The SNOT-22 has been validated for various languages, yet no validation is available for the German version. Thus, we provide a validation of the SNOT-22 for German. METHODS: In this prospective observational study 139 CRS-patients and 36 control-participants were included. CRS-patients completed the German-SNOT-22 before treatment (T0) and four (T1), twelve (T2) and 48 weeks after inclusion (T3). At T0, Mackay-Naclerio-, Lund-Mackay- and Brief-Symptom-Inventory-18 (BSI-18) scores were collected as external reference for the German-SNOT-22 and its subscales. At T1, T2, and T3 health-transition-items (HTIs) were raised to explore responsivity. Control-participants completed the German-SNOT-22 at T0. Reliability (internal consistency, item-total correlation), validity (concurrent validity, discriminatory validity) and responsiveness (distribution- and anchor-based) were explored for the German-SNOT-22. RESULTS: At T0, the mean German-SNOT-22 total-score for CRS patients was 38.0 (± 20.9) and responded to treatment (T1 = 26.3 ± 19.1; T2 = 25.8 ± 20.6; T3 = 20.5 ± 16.3). For control-participants, the mean total-score at T0 was 15.1 (±10.9). The German-SNOT-22 was reliable (excellent internal consistency α = 0.93; good overall item-total correlations r = 0.39-0.85), valid (significant correlations between Mackay-Naclerio-, Lund-Mackay- and BSI-18 scores, all r > 0.39, p < 0.01) and responsive (significant correlations between HTIs and mean change in German-SNOT-22 total-score F = 9.57, p < 0.001). CONCLUSION: The German-SNOT-22 validated here matches the original SNOT-22. It is a reliable, valid and responsive questionnaire to assess symptoms, HRQOL and treatment-response in CRS-patients. Good psychometric properties were observed.

GAGEC1, a cancer/testis associated antigen family member, is a target of TGF-beta1 in age-related prostatic disease.

Transforming growth factor beta (TGF-beta) is a multi-functional cytokine that plays a fundamental role during embryonic development and tissue homeostasis in metazoans. Changes in TGF-beta signalling are implicated in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), two of the most common diseases affecting ageing males. GAGEC1 belongs to the GAGE-related family of cancer/testis associated antigens and in males is expressed only in prostate and testis. Previous reports demonstrate that GAGEC1 is up-regulated in symptomatic BPH and PCa. We demonstrate GAGEC1 up-regulation by TGF-beta1 in primary prostatic stromal and epithelial cells. Our data suggest that disease-associated increases in TGF-beta1 may account for the increase in GAGEC1 expression in BPH and PCa. Given its restricted spatial expression in males, GAGEC1 represents a promising target for therapeutic intervention of BPH and PCa.

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial.

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m(2)) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P =.0075). It also offered higher progression-free survival (46% v 25% at 5 years; P =.0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P =.041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P =.0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.

Elective ipsilateral neck irradiation of patients with locally advanced maxillary sinus carcinoma.

BACKGROUND: The current study was conducted to investigate retrospectively whether elective ipsilateral neck irradiation (EINI) is effective in controlling subclinical neck disease in patients with locally advanced (T3 and T4) nonmetastatic (N0, M0) squamous cell carcinoma (SCC) of the maxilla. METHODS: Between 1987 and 1993 a total of 44 patients were treated with EINI. The primary tumor bed was treated with 60 grays (Gy) in patients undergoing radical maxillectomy or with 66 Gy in patients undergoing partial maxillectomy. The ipsilateral upper and lower neck (down to the clavicle) was treated with either opposing anteroposterior-posteroanterior fields or appositional electron fields. The dose of elective neck radiotherapy was 50 Gy in 25 daily fractions. RESULTS: The 5-year and 10-year survival rates (with standard error [SE]) were 66% (SE 7%) and 60% (SE 8%), respectively, whereas the 5-year and 10-year recurrence free survival rates both were 64% (SE 7%). The 10-year local recurrence free survival rate was 69% (SE 7%), whereas the 10-year regional recurrence free survival rate was 94% (SE 4%). Of the 2 patients who developed a recurrence in the neck, 1 was salvaged successfully by surgery, producing an ultimate 10-year regional recurrence free survival rate of 97%. The 10-year distant metastasis free survival rate was 91% (SE 4%). CONCLUSIONS: The findings of the current study appear to suggest the potential efficacy of EINI in patients with locally advanced, nonmetastatic SCC of the maxilla and that the high rate of control of cervical lymph nodes may lead to better overall survival than that reported in the majority of the recent series.