Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale.

PURPOSE: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. METHODS: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. RESULTS: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. CONCLUSIONS: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.

Course of social support and associations with distress after partial laryngectomy.

PURPOSE: Social support has been shown to be positively associated with quality of life and adjustment after a cancer diagnosis. The present study investigates the course of social support up to one year after partial laryngectomy and its association with distress. DESIGN: Longitudinal questionnaire study. SAMPLE: A total of 428 patients after partial laryngectomy (mean age: 64, SD = 11, 91% male). METHODS: Patients completed questionnaires before treatment (t1), one week after a partial laryngectomy (t2), 3 months (t3), and one year (t4) thereafter. Social support was evaluated at t2, t3, and t4 using a brief version of the Social Support Questionnaire. Distress was measured at t2, t3, and t4 using the HADS. Descriptive statistics for social support were computed across the three measurement points. Changes were analyzed by Wilcoxon signed-rank tests. Associations with distress were identified using linear regression analyses. FINDINGS: Social support increased between t2 and t3 and decreased to baseline level between t3 and t4. Distress at t2 was associated with social support at t2 (B = -0.15, p < 0.01) and distress at t3 with social support at t3 (B = -0.19, p < 0.01). Distress at t4 was related to social support at t2 (B = -0.10, p = 0.05). CONCLUSIONS: Although perceived social support increases after partial laryngectomy, it decreases again during the course of aftercare. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS OR POLICY: Social support resources should be assessed to identify patients at risk for worse psychological well-being.

Investigating the response scale of the EORTC QLQ-C30 in German cancer patients and a population survey.

BACKGROUND: The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions. METHODS: The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. The main analyses included compared the ziemlich and mäßig version of the questionnaire using analyses of covariance adjusted for sex, age, and health burden. RESULTS: In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: - 4.5 (95% CI - 7.8 to - 1.3), p = 0.006, Study 2: - 3.1 (95% CI - 4.6 to - 1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: - 6.8 (95% CI - 12.2 to - 1.4), p = 0.013; Study 2: - 4.5 (95% CI - 7.3 to - 1.7), p = 0.002. CONCLUSIONS: We found subtle but consistent differences between the two questionnaire versions. We recommend to use the optimized response option for the EORTC QLQ-C30 as well as for all other German modules. TRIAL REGISTRATION: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759 ).

[Smoking Behaviour after Partial Resection of the Larynx: The Role of Causal Attribution]. / Rauchverhalten von Krebspatienten nach Kehlkopfteilresektion: Welche Bedeutung hat die Kausalattribution?

OBJECTIVE: The aim of our study was to examine how different causal attributions in patients with laryngeal cancer are associated with smoking behaviours (smoking cessation rates and amount of cigarettes per day) after partial resection of the larynx. METHODS: Multicentre prospective cohort study including 4 interviews: between diagnosis and partial resection of larynx (t1), one week (t2), 3 months (t3) and 12 months (t4) after surgery. Presented in this study are t1 and t4. A total of 134 patients (mean age 62 years, 93% male) were interviewed at t1 and t4 between 2007 and 2013. Key items were causal attribution as well as previous and current smoking behaviour. Patients were grouped according to the subjectively stated causal attribution. Results were analysed descriptively and group as well as mean value comparisons were conducted. RESULTS: Smoking was the most commonly stated causal attribution (43.3%). The quantity of cigarettes decreased significantly by about 6 cigarettes from 17 (range 3-40) to 11 (range 2-30) cigarettes per day in this group (p=0.001). 25% of patients did not recognize a reason for their illness. In longitudinal analyses of all groups of different causal attributions, there was a non-significant decrease in the percentage of smokers. CONCLUSION: We show that causal attribution does not affect smoking cessation rate significantly in a positive way. But active smokers after PRL reduce their quantity of cigarettes per day significantly. This impact is more noticeable in patients who were able to define a causal attribution. Psycho-oncological care, information services and smoking cessation programs could contribute to this effect by making the causal attribution a subject of discussion.

[A group intervention to promote work ability in patients with head and neck cancer]. / Eine Gruppenintervention zur Förderung der Arbeitsfähigkeit für Patienten mit Kopf-Hals-Tumoren.

INTRODUCTION: Despite high distress the majority of head and neck cancer patients does not use any psycho-oncological counselling or psychotherapeutic support. Additionally, patients with head and neck cancer have an increased risk of not returning to work compared to other cancer patients. Therefore, we have developed a group intervention program which aims at improving work ability in patients with head and neck cancer as well as their quality of life, self-efficacy and psychological well-being. MATERIAL AND METHODS: In a randomized controlled trial head and neck cancer patients either receive a group intervention or socio-legal counselling. Male head and neck cancer patients with elevated levels of psychological and work-related distress are included. The group intervention consists of eight sessions. Groups are led by both a psychotherapist and a former head and neck cancer patient (peer). Feasibility and acceptability of the group intervention were tested by means of a pilot group. Each session was evaluated by pilot group participants. Semi-structured interviews were used to assess relevance of content and practicability. RESULTS: 113 patients were personally addressed, of which four patients participated in the pilot group. Patients reported that the intervention fit very well with their daily life and expressed satisfaction with it. Three patients emphasized the importance of the peer. DISCUSSION: The presence of the peer as identification figure seems to be of crucial importance. To increase recruitment numbers inclusion criteria will be modified and participation costs will be reduced.

Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma.

To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1∧ E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx.

Impact of socio-economic position on cancer stage at presentation: Findings from a large hospital-based study in Germany.

We explored the relationship between socio-economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance and postcode. Tumor stage was classified according to the Union International Contre le Cancer (UICC). To analyze disparities in the likelihood of late-stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used. Out of 1,012 patients, 572 (59%) had late-stage cancer. Separately tested, increased odds of advanced disease were associated with post-compulsory education compared to college degrees, with apprenticeship and no vocational training, with unemployment, disability pension, jobs with a low hierarchy level, blue collar jobs and with low income. Health insurance and community size were not related with late-stage cancer. Jointly modelled, there was evidence for an independent effect of unemployment (odds ratio (OR) 1.7, CI 1.0-2.8), disability pension (OR 1.8, CI 1.0-3.2) and very low income (OR 2.6, CI 1.1-6.1) on the likelihood of advanced disease stage. It is of great concern that these socio-economic gradients occur even in systems with equal access to health care.

The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer.

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.

Predicting treatment process steps from events.

MOTIVATION: The primary economy-driven documentation of patient-specific information in clinical information systems leads to drawbacks in the use of these systems in daily clinical routine. Missing meta-data regarding underlying clinical workflows within the stored information is crucial for intelligent support systems. Unfortunately, there is still a lack of primary clinical needs-driven electronic patient documentation. Hence, physicians and surgeons must search hundreds of documents to find necessary patient data rather than accessing relevant information directly from the current process step. In this work, a completely new approach has been developed to enrich the existing information in clinical information systems with additional meta-data, such as the actual treatment phase from which the information entity originates. METHODS: Stochastic models based on Hidden Markov Models (HMMs) are used to create a mathematical representation of the underlying clinical workflow. These models are created from real-world anonymized patient data and are tailored to therapy processes for patients with head and neck cancer. Additionally, two methodologies to extend the models to improve the workflow recognition rates are presented in this work. RESULTS: A leave-one-out cross validation study was performed and achieved promising recognition rates of up to 90% with a standard deviation of 6.4%. CONCLUSIONS: The method presented in this paper demonstrates the feasibility of predicting clinical workflow steps from patient-specific information as the basis for clinical workflow support, as well as for the analysis and improvement of clinical pathways.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on 24-hour blood and ocular perfusion pressures: the results of a randomized trial.

BACKGROUND: To compare the effect of bimatoprost and the fixed combination latanoprost-timolol (LTFC) on 24-hour systolic (SBP) and diastolic (DBP) blood pressure and on 24-hour ocular perfusion pressure (OPP). METHODS: 200 patients with glaucoma or ocular hypertension, controlled on the unfixed combination of latanoprost and timolol or eligible for dual therapy being not being fully controlled on monotherapy were enrolled in a randomized, double-masked, placebo-controlled, multicentre clinical trial. They were randomized to LTFC (8 a.m.) or bimatoprost (8 p.m.) and received 24-hour IOP curve at baseline, 6 and 12 weeks (supine and sitting position IOPs were recorded at 8 p.m., midnight, 5 a.m., 8a.m., noon and 4 p.m.). Holter 24-hour blood pressure curve was obtained between weeks 2 and 12. SBP, DBP, OPP were calculated and compared with ANOVA. Rates of diastolic OPP (DPP)≤50, ≤40, ≤30 mmHg in the 2 groups were calculated and compared using Fisher's test. RESULTS: Mean baseline SBP and DBP were 136.5±18.3 vs 134.2±20.1 mmHg (p=0.1) and 79.1±10.2 vs 78.2±10.1 mmHg (p=0.4) in the bimatoprost and LTFC groups respectively. Holter SBP was significantly higher for bimatoprost (135.1 mmHg vs 128.1 mmHg, p=0.04), while no statistically significant difference in DBP was found. DPP was similar in the 2 groups, and proportions of patients with at least one value of the 24-hour curve≤50, ≤40, ≤30 mmHg were 94%, 86%, 41% respectively. CONCLUSIONS: Bimatoprost and LTFC had similar DBPs and OPPs; SBP was significantly lower with LTFC. In this study, the percentage of "dippers" was considerably higher than the one described in previous studies on the role of perfusion pressure in glaucoma. TRIAL REGISTRATION: NCT02154217, May 21, 2014.

Patients' Reflections on Treatment Decision After Surgery for Laryngeal Cancer.

Importance: Clinicians should understand how patients who were treated with laryngeal cancer surgery think about this later on and what factors may be related with regretting surgery. Objective: To assess variables associated with a positive attitude toward laryngeal cancer surgery. Design, Setting, and Participants: This combination of 2 cohorts, based on patient interviews and questionnaires, was studied in 16 hospitals in Germany. Participants scheduled for laryngeal cancer surgery were enrolled before surgery and followed up until 1 year after surgery. Data collection began on November 28, 2001, and ended on March 15, 2015. Statistical analysis was performed from August 21, 2023, to January 19, 2024. Main Outcomes and Measures: The attitude toward surgery was measured with the Psychosocial Adjustment After Laryngectomy Questionnaire (scores range from 0 to 100, with high scores representing a positive attitude toward the surgery) at 1 year after surgery. In multivariate regression analysis, the following variables were investigated: type of surgery, number of surgeries to the larynx, receipt of radiotherapy and chemotherapy, quality of life, speech intelligibility (objectively measured), age, sex, educational level, employment status, having a partner or not, counseling by patient association, and shared decision-making. Results: Patients (n = 780; mean [SD] age, 60.6 [10.4] years; 701 [90%] male) who had received counseling from the patient association reported a more positive attitude toward surgery (adjusted B = 8.8; 95% CI, 1.0-16.6). Among patients after total laryngectomy, those with a university degree had a less positive attitude toward their surgery (adjusted B = -50.8; 95% CI, -84.0 to -17.6); this result was not observed in patients after partial laryngectomy (adjusted B = -4.8; 95% CI, -15.1 to 5.4). Among patients after partial laryngectomy, the attitude toward surgery was most positive in those who had experienced shared decision-making (mean [SD] questionnaire score, 84 [20] in those without a wish and 83 [20] in those with a wish for shared decision-making). Those who had wished they could decide together with the physician but where this eventually was not experienced expressed the most regret toward surgery (mean [SD] score, 71 [22]). There was no association between attitudes toward surgery and type of surgery (total vs partial laryngectomy) and all other variables tested. Conclusion and Relevance: In this cohort study, most patients with head and neck cancer reported a positive attitude toward surgery, suggesting low levels of decision regret. Counseling by members of patient associations as well as individualized shared decision-making prior to surgery may have a positive impact on decision regret and is advisable in daily practice.

High-Dose Glucocorticoids for the Treatment of Sudden Hearing Loss.

BACKGROUND: Systemic glucocorticoids are commonly used for primary therapy of idiopathic sudden sensorineural hearing loss (ISSNHL). However, the comparative effectiveness and risk profiles of high-dose over lower-dose regimens remain unknown. METHODS: We randomly assigned patients with sudden hearing loss of greater than or equal to 50 dB within 7 days from onset to receive either 5 days of high-dose intravenous prednisolone at 250 mg/d (HD-Pred), 5 days of high-dose oral dexamethasone at 40 mg/d (HD-Dex), or, as a control, 5 days of oral prednisolone (Pred-Control) at 60 mg/d followed by 5 days of tapering doses. The primary outcome was the change in hearing threshold (pure tone average) in the three most affected contiguous frequencies from baseline to day 30. Secondary outcomes included speech understanding, tinnitus, communication competence, quality of life, hypertension, and insulin resistance. RESULTS: A total of 325 patients were randomly assigned. Mean change in 3PTAmost affected hearing threshold from baseline to 30 days was 34.2 dB (95% CI, 28.4 to 40.0) in the HD-Pred group, 41.4 dB (95% CI, 35.6 to 47.2) in the HD-Dex group, and 41.0 dB (95% CI, 35.2 to 46.8) in the Pred-Control group (P=0.09 for analysis of variance). There were more adverse events related to trial medication in the HD-Pred (n=73) and HD-Dex (n=76) groups than in the Pred-Control group (n=46). CONCLUSIONS: Systemic high-dose glucocorticoid therapy was not superior to a lower-dose regimen in patients with ISSNHL, and it was associated with a higher risk of side effects. (Funded by the Federal Ministry of Education and Research [BMBF]; EudraCT number, 2015­002602­36.)

The effect of acetazolamide on different ocular vascular beds.

PURPOSE: To assess the effect of acetazolamide (AZ) on different ocular vascular beds. METHODS: In a prospective study, 32 healthy volunteers (16 male, 16 female) with a mean age of 23.9 ± 3.3 years (20-39 years) were included. Before and after intravenous administration of 1,000 mg AZ (single dose), ocular microcirculation parameters were measured every 20 min for 2 h. Retinal vessel diameters (VD) were measured by the retina vessel analyzer, blood flow (BF) in the neuroretinal rim by the laser doppler flowmeter according to Riva, and the parapapillary retinal BF by the scanning laser Doppler flowmeter. Additionally, the Langham ocular blood flow system was used to determine the ocular pulse amplitude (OPA) and the pulsatile ocular blood flow (pOBF). The measurements were correlated with systemic blood pressure (BP), ocular perfusion pressure (OPP), capillary base excess parameters and serum AZ levels. RESULTS: Arterial and venous VD were significantly increased by about 4-5% each. Papillary BF increased significantly about 40%. Parapapillary retinal flow dropped significantly about 19% (120 min). OPA and pOBF showed no statistically significant changes. BP showed no significant changes, and OPP was significantly increased. There were no correlations with pH or systemic perfusion parameters. CONCLUSIONS: AZ leads to a dilatation of retinal VD, to an increase of BF in the optic nerve head, and to a decrease of parapapillary retinal BF. The different BF changes in different vascular beds might be due to different regulatory mechanisms, steal effects, or different distributions of the carbonic anhydrase.

Serious Long-Term Effects of Head and Neck Cancer from the Survivors' Point of View.

The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were 'dry mouth' (DM) (n = 476; 46%), 'difficulty swallowing/eating' (DSE) (n = 408; 40%), 'hoarseness/difficulty speaking' (HDS) (n = 169; 16%), and 'pain in the head and neck' (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5-9.0; OR: 2.1, CI: 1.1-3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1-0.6; OR: 0.2, CI: 0.1-0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2-3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3-0.6) but increased odds of HDS (OR: 7.2, CI: 4.3-12.3). This study provides evidence of the serious long-term problems among HNCS.

iTRAQ analysis of a cell culture model for malignant transformation, including comparison with 2D-PAGE and SILAC.

To study human cancer development, cell culture models for malignant transformation can be used. In 1999 Hahn and Coworkers introduced such a model system and established herewith a basis for research on human tumorigenesis. Primary human fibroblasts are sequentially transduced with defined genetic elements (hTERT, SV40 ER, and H-RasV12), resulting in four defined cell lines, whereby the last has a fully transformed phenotype. In order to get a deeper insight into the molecular biology of human tumorigenesis, we compared the proteomes of these four cell lines following a multimethod concept. At the beginning we assumed SILAC and sample fractionation with COFRADIC is the method of choice to analyze the cell culture model for malignant transformation. Here, the compared samples are combined before sample preparation, thus avoiding differences in sample preparation, and using COFRADIC notably reduces sample complexity. Because 2D-PAGE is a standard method for the separation and visualization of closely related proteomes, we decided to analyze and compare the proteomes of these four cell lines in a first approach by differential 2D-PAGE. Surprisingly, we discovered much more unique results with iTRAQ and sample fractionation with SCX than with the combination of 2D-PAGE and SILAC-COFRADIC. Moreover, iTRAQ outperforms the other strategies not only in number of yielded results but also in analysis time. Here, we present the iTRAQ quantification results and compare them with the results of 2D-PAGE and SILAC-COFRADIC. We found changes in the protein level at each transition. Thereby, SV40 has the strongest impact on the proteome. In detail we identified 201 regulated proteins. Beside others, these proteins are involved in cytoskeleton, RNA processing, and cell cycle, such as CDC2, hnRNPs, snRNPs, collagens, and MCM proteins. For example, MCM proteins are up-regulated and collagens are down-regulated due to SV40 ER expression. Furthermore we made the observation that proteins containing the same domain have analogous regulation profiles during malignant transformation. For instance, several proteins containing a CH or LIM domain are down-regulated. Moreover, by this study and the defined cell culture model, changes could be clearly matched to specific steps during tumorigenesis.

The effect of education on the assessment of optic nerve head photographs for the glaucoma diagnosis.

BACKGROUND: To evaluate the effect of one lesson of continuing medical education (CME) of subjective assessment of optic nerve head appearance on sensitivity and specificity for the diagnosis of glaucoma. METHODS: Ophthalmologists and residents in ophthalmology attending an international glaucoma meeting arranged at Malmö University Hospital, Malmö, Sweden, were asked to grade optic nerve head (ONH) photographs of healthy and glaucomatous subjects at two sessions separated by a lecture on glaucoma diagnosis by ONH assessment. Each grader had access to an individual portfolio of 50 ONH photographs randomly selected from a web-based data bank including ONH photographs of 73 glaucoma patients and 123 healthy subjects. The individual portfolio of photographs was graded before and after the lecture, but in different randomized order. RESULTS: Ninety-six doctors, 91% of all attending the meeting, completed both assessment sessions. The number of correct classifications increased from 69 to 72% on the average. Diagnostic sensitivity increased significantly (p < 0.0001) from 70% to 80%, and the number of photographs classified as uncertain decreased significantly (p < 0.0001) from 22% to 13%. Specificity remained at 68%, and intra-grader agreement decreased. CONCLUSION: CME had only a small effect on the assessment of ONH for the glaucoma diagnosis. Sensitivity increased and the amount of uncertain classifications decreased, while specificity was unchanged.

Therapeutic options for treatment of Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin. Owing to the aggressiveness of this tumor and the bad overall survival, we reviewed the therapeutic strategies, including surgery, radiation, and chemotherapy to find out the potentially best treatment option for one patient treated at our hospital. In addition, we investigated MCC biopsies using the FLAVINO assay to find out if individual chemoresponse testing might be a useful supplement in decision-making for the optimal therapeutic option for our MCC patient. The different results achieved using cisplatin, docetaxel, and cetuximab led to the conclusion that an individual chemoresponse testing in a predictive short-time assay might potentially be a useful diagnostic tool in identifying potentially effective chemotherapy treatments.

jTraqX: a free, platform independent tool for isobaric tag quantitation at the protein level.

Many proteomic studies focus on quantitative aspects, using different stable isotope labeling techniques that require specialized software to analyze the generated data. Here we present jTraqX, an easy-to-use tool for processing and visualizing protein quantification data. jTraqX is platform independent and is compatible with all available 4-plex isobaric tags. jTraqX can be freely downloaded at http://sourceforge.net/projects/protms.

Assay-based response evaluation in head and neck oncology: requirements for better decision making.

This article gives an overview on different current strategies of assay-based response evaluation in head and neck squamous cell carcinomas (HNSCC) and critically summarizes their role and needs for future clinical evaluation. Due to a growing amount of data of phase III clinical trials of multimodality treatment options for HNSCC, treatment planning in regard to optimal outcome is becoming an interdisciplinary challenge. New concepts such as induction chemotherapy with bi- or ternary combinations of chemotherapeutics, integration of targeted therapies, concurrent and sequential chemoradiation concepts, and multimodality-based organ preservation strategies strongly compete with traditional definitive surgical procedures. Moreover, the outcome is difficult to predict due to heterogeneity of a tumor's response, impaired late functional outcome, and increased late toxicity if simultaneously applied to radiation. Retrospectively looking at non-responders with tumors classified as resectable, primary surgery is very likely to have achieved better results, since chemoradiation causes a high degree of early and late toxicities leading to extremely complicated terms and conditions in surgery following current multimodal therapeutic strategies. Unfortunately, predictive information on response characteristics of a given tumor before starting the therapy is not available in daily routine, although heterogeneity in response of a given tumor entity to treatments has been known for decades. Therefore, current therapy strategies for HNSCC still have to ignore this fact, creating an urgent need for the development of proper predictive assays. There are interesting clinical observations showing that response on induction chemotherapy may predict the outcome after radiotherapy. Some trials use this empiric phenomenon to pre-select non-responders for primary surgical treatment avoiding severe salvage complications after failure of complete chemoradiation treatment. Moving one step further, recent literature and our own investigations implicate that response evaluation of the individual patient's HNSCC in a suitable ex vivo assay just before starting the treatment is mature for clinical research. To this end, essential needs and hints are addressed and discussed.