[show abstract][hide abstract] ABSTRACT: Previous studies tried to assess the association between socioeconomic status and laryngeal cancer. Alcohol and tobacco consumption explain already a large part of the social inequalities. Occupational exposures might explain a part of the remaining but the components and pathways of the socioeconomic contribution have yet to be fully disentangled. The aim of this study was to evaluate the role of occupation using different occupational indices, differentiating between physical, psycho-social and toxic exposures and trying to summarize the occupational burden into one variable.
A population-based case--control study conducted in Germany in 1998--2000 included 208 male cases and 702 controls. Information on occupational history, smoking, alcohol consumption and education was collected with face-to-face interviews. A recently developed job-classification index was used to account for the occupational burden. A sub-index focussed on jobs involving potentially carcinogenic agents (CAI) for the upper aero digestive tract.
When adjusted for smoking and alcohol consumption, higher odds ratios (ORs) were found for lower education. This OR decreased after further adjustment using the physical and psycho-social job indices (OR = 3.2, 95%-CI: 1.5-6.8), similar to the OR using the sub-index CAI (OR = 3.0, 95%-CI: 1.4-6.5).
The use of an easily applicable control variable, simply constructed on standard occupational job classifications, provides the possibility to differentiate between educational and occupational contributions. Such an index might indirectly reflect the effect of carcinogenic agents, which are not collected in many studies.
BMC Public Health 11/2013; 13(1):1080. · 2.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to measure the extent to which the association between socioeconomic status and laryngeal cancer among males is mediated by smoking, alcohol consumption, and occupational exposure.
We used Karlson et al's decomposition method for logit models, which returns the percentage of change in odds ratios (OR) due to confounding. This population-based, case-control study on laryngeal cancer was conducted in Germany in 1998-2000 and included 208 male cases and 702 controls. Information on occupational history, smoking, alcohol consumption, and education was collected through face-to-face interviews. Jobs coded according to ISCO-68 were linked to a recently developed job-classification index covering physical and psychosocial dimensions. A sub-index focused on jobs involving potentially carcinogenic agents (CAI) for the upper-aero digestive tract.
When adjusted for smoking and alcohol consumption, higher OR were found for lower education. This OR decreased after further adjustment using the overall job index [2.9, 95% confidence interval (95% CI) 1.4-6.2], similar to the OR using the sub-index CAI (OR 2.7, 95% CI 1.3-5.8). Applying the Karlson et al method, 25.4% (95% CI 22.6-28.2%) of the reduction in these OR was due to occupational exposure (CAI), while smoking and alcohol consumption contributed to around 26.1% (95% CI 23.2-28.9%) and 2.7% (95% CI 1.7-3.8%), respectively.
Occupational aspects, in particular the exposure to carcinogenic agents, explain a large portion of the association between low educational level and laryngeal cancer risk among males. Occupational effects are now easier to quantify using this recently developed and easily applicable index.
Scandinavian journal of work, environment & health 11/2013; · 3.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dacryocystorhinostomy (DCR) is performed in patients with saccal or postsaccal lacrimal duct obstruction. Focusing on the endonasal approach, we compared success rates, clinical outcome, complications and patient satisfaction of endoscopic vs. non-endoscopic techniques in endonasal DCR. We analyzed the results of 173 patients who underwent an endonasal DCR either utilizing a non-endoscopic (Group I) or an endoscopic technique (Group II) between 2006 and 2011. Irrigation tests followed the first day and at least 3 months after surgery. Postoperative patients' satisfaction and the occurrence of symptoms were documented and evaluated in a follow-up questionnaire. The minor complication rates of both endonasal DCR techniques were similarly low (10 %) without severe adverse events. The use of the endoscope prolonged the operating time significantly (28 ± 9 min Group I vs. 34 ± 14 min Group II, p = 0.003). The success rate was 90.2 % in Group II compared to only 57.9 % in Group I (p < 0.000). Further, we determined the absence of reflux during the irrigation test 1 day after surgery as a significant predictor for the later outcome (R = 1.598, p = 0.005). The follow-up questionnaire revealed a significant improvement in subjectively perceived symptoms by the surgical intervention for both endonasal techniques (p < 0.000). The endoscopically assisted DCR is a safe and successful endonasal technique for patients with saccal or postsaccal lacrimal duct obstructions. The use of the endoscope led to significant higher success rates compared to non-endoscopic techniques in our collective.
Archives of Oto-Rhino-Laryngology 11/2013; · 1.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ziel
Ziel dieser Studie war es, Daten zur psychoonkologischen Versorgungssituation von Krebspatienten im ambulanten und im stationären Bereich unter Routinebedingungen zu gewinnen. Dabei interessierten vorrangig die Versorgungsdichte sowie der Bedarf an und der Wunsch nach psychosozialer Versorgung.
Die Versorgungsdichte wurde anhand des Vergleichs von Inzidenzzahlen des Tumorregisters Leipzig, der Zahl der durch den psychoonkologischen Konsil-/Liaisondienst des Universitätsklinikums Leipzig betreuten Patienten und der Zahl der Ratsuchenden in der an der Universität angesiedelten ambulanten Krebsberatungsstelle im Jahr 2008 ermittelt. Bedarf an und Wunsch nach psychosozialer Hilfe wurden anhand von Daten einer Patientenbefragung am gleichen Klinikum untersucht.
Im stationären und im ambulanten Bereich wurden jeweils 11% der Krebspatienten psychoonkologisch betreut. Demgegenüber stehen ein sozialer Hilfebedarf bei 37% und ein psychologischer Hilfebedarf bei 52% der Patienten während des Krankenhausaufenthalts (1/2 Jahr später: je 42%). Insgesamt 41% der Befragten wünschten sich zu Beginn des Krankenhausaufenthalts Hilfe von einem Sozialarbeiter und 29% von einem Psychologen. Zwischen Patienten verschiedener Tumorentitäten bestanden große Unterschiede hinsichtlich der Versorgungssituation.
Im Vergleich zum Hilfebedarf und ihren Versorgungswünschen waren die Krebspatienten unter Routinebedingungen in einem Krankenhauses der Maximalversorgung als psychoonkologisch deutlich unterversorgt einzuschätzen.
[show abstract][hide abstract] ABSTRACT: Background: CCPA was proven to be a protective factor in ischemic reperfusion injury. The purpose was to determine how CCPA would affect the single tissue layers of the adipocutaneous flap. Methods: Seventy male WISTAR rats were divided into five experimental groups. Samples were taken of the area of flap necrosis and the wound margin after classical or pharmacological preconditioning on the fifth postoperative day. All samples were fixed in formaldehyde, embedded in paraplast and analyzed in 3-4 µm sections (haemalaun and eosin stain, light microscopy). Results: In general wound healing was alike and remained unaffected by the experimental design. Most sensitive part of the flap during preconditioning is the subcutis. Number of neutrophils and of plasma cells is reduced significantly (p<0.05). Conclusion: CCPA has an effect on each tissue layer of the flap. Subcutis became apparent as the most sensitive layer. CCPA influences complement pathway and neutrophils directly and indirectly. Head Neck, 2013.
[show abstract][hide abstract] ABSTRACT: High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients with HPV-positive OPSCC are highly curable with ionizing radiation and have better survival compared with HPV-negative patients, but the underlying molecular mechanisms remain poorly understood. We applied an array-based approach to monitor global changes in CpG island hypermethylation between HPV-negative and HPV-positive OPSCCs and identified a specific pattern of differentially methylated regions that critically depends on the presence of viral transcripts. HPV-related alterations were confirmed for the majority of candidate gene promoters by mass spectrometric, quantitative methylation analysis. There was a significant inverse correlation between promoter hypermethylation of ALDH1A2, OSR2, GATA4, GRIA4, and IRX4 and transcript levels. Interestingly, Kaplan-Meier analysis revealed that a combined promoter methylation pattern of low methylation levels in ALDH1A2 and OSR2 promoters and high methylation levels in GATA4, GRIA4, and IRX4 promoters was significantly correlated with improved survival in 3 independent patient cohorts. ALDH1A2 protein levels, determined by immunohistochemistry on tissue microarrays, confirmed the association with clinical outcome. In summary, our study highlights specific alterations in global gene promoter methylation in HPV-driven OPSCCs and identifies a signature that predicts the clinical outcome in OPSCCs.
Journal of Clinical Investigation 06/2013; 123(6):2488-501. · 12.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: The hedgehog signaling pathway (HH) is involved in tumorigenesis in a variety of human malignancies. In head and neck squamous cell carcinomas (HNSCC), Hh overexpression was associated with poor prognosis. Therefore, we analyzed the effect of Hh signaling blockade with cyclopamine on colony formation of cells from HNSCC samples.
HNSCC biopsies were cultured alone for reference or with serial dilutions of cyclopamine (5-5,000 nM), docetaxel (137.5-550 nM), or cisplatin (1,667-6,667 nM) and their binary combinations. Cytokeratin-positive colonies were counted after fluorescent staining.
Cyclopamine concentration-dependently inhibited HNSCC ex vivo [(IC50) at about 500 nM]. In binary combinations, cyclopamine additively enhanced the suppressive effects of cisplatin and docetaxel on HNSCC colony formation.
Our findings define SMO - a Hh component- as a potential target in HNSCC and suggest the utility of Hh targeting in future multimodal treatment regimens for HNSCC.
Anticancer research 06/2013; 33(6):2415-24. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intralesional use of cidofovir (Vistide(®)) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2-6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.
Archives of Oto-Rhino-Laryngology 02/2013; · 1.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Overexpression of the Hedgehog (HH) signalling pathway has been described in several malignancies and is associated with a poor prognosis. HH signalling blockade reduces tumour growth in vitro and in vivo. We aimed to determine whether head and neck squamous cell carcinomas (HNSCCs) express HH proteins in comparison to healthy mucosa. Patients and Methods: Formalin-fixed and paraffin-embedded tissue sections of 10 patients with HNSCC were stained with fluorescence-labelled antibodies for cytokeratin and HH proteins (SHH, PTCH1/2, SMO, Gli1-3) and photographs were taken with a laser scanning microscope. The pixel count and colour intensity were analysed in RGB (red/green/blue) colour mode, and expression levels were compared to healthy mucosa. Results: Image analysis in RGB mode provided objective evidence for the over-expression of HH signalling components in HNSCC, particularly with regard to the transcription factors Gli1 (10-fold) and SHH (5-fold) in comparison with healthy mucosa. The lowest levels were found for Gli3 in HNSCC. Conclusions: We postulate pivotal roles of Gli1 and SHH expression in the carcinogenesis of HNSCC. HH pathway overexpression appears to be involved in the initiation of tumour growth and spread due to its stem cell-modulating properties. Detection of HH pathway components, and especially Gli1 and SHH, in HNSCC might offer a promising target for further anticancer research in HNSCC.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Gaining a new voice is one of the major aims after total laryngectomy. The objective of this study was to describe the process and results of speech rehabilitation during the first year after surgery. METHODS: Speech intelligibility was measured 6 months (n = 273) and 1 year (n = 225) after total laryngectomy. RESULTS: Objective (23.4 to 47.5 points, p < .0001) and subjective (51.6 to 64.7 points, p < .0001) speech intelligibility improved between 6 months and 1 year after total laryngectomy. Patients who used tracheoesophageal puncture (TEP) had the best results in speech intelligibility 6 months and 1 year after total laryngectomy. In all, 12% of the patients who used TEP initially no longer used it 1 year later. Patients who had received rehabilitation had better objective speech intelligibility than those who did not. CONCLUSIONS: Speech improves considerably between 6 months and 1 year after total laryngectomy. Nonattendance of rehabilitation is associated with a worse functional outcome in speech rehabilitation. Head Neck, 2012.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer. METHODS: Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0) and 30 mg/m2 (DL -1), plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm. RESULTS: Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50%) showed complete pathologic regression. CONCLUSIONS: A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week. Trial registration number NCT01108042 (ClinicalTrials.gov Identifier).
BMC Cancer 10/2012; 12(1):483. · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Volume assessment in head and neck squamous cell carcinoma (HNSCC) is becoming a more and more clinical important parameter, especially in treatment planning and response control. Various authors showed a significant impact of tumour volume on treatment outcome and local control. Regarding the increasing impact of induction chemotherapy and primary chemoradiation on HNSCC, the need for an adequate measuring tool to judge treatment response becomes obvious. This study was performed to compare the momentary 'gold standard', the diameter-based approach, and tumour volume assessment in HNSCC with approaches based on segmentation algorithms in computer tomography (CT) scans.
CT scans were taken as part of the standardized staging investigations. Using these image data, 30 lymph nodes were defined and segmented. The segmentations were carried out with the newly developed software called 'NeckSegmenter'. After obtaining informed consent from the patient, neck dissection was performed and the excised lymph nodes underwent analysis of their true volume. The datasets were compared with each other and put in correlation with the segmented volumes.
Pearson's correlation index showed a higher correlation of the segmented volumes (r = 0.7979) with the true volumes than the results generated via diameter-based equation (r = 0.7974). Furthermore, the diameter-generated volumes show clearly too high volumes at 130% (confidence interval: 107.7-156.7%). The volumes generated with the segmentation are at 89.18% (confidence interval: 73.52-108.16%).
The data show a higher reliability for volumes estimated by the segmentation-based approach than the widely used diameter-based approach.
ANZ Journal of Surgery 09/2012; 82(10):737-41. · 1.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this article, a new surgical model for evaluating telemanipulators used in middle ear surgery is presented. The purpose of this work was to develop an evaluation and training system which imitates a typical surgical task of middle ear surgery and which can easily be repeated in order to get significant result. The abstract task can be performed manually or by means of a microsurgical telemanipulator and guaranties stable experimental conditions between different subjects at any time. As a task the stapedotomy was chosen, due to the high demands in positioning and in applying forces to the delicate structures in the middle ear. The manual and telemanipulated performance of 15 ENT surgeons and 17 medical students was compared using this evaluation and training system.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2012; 2012:932-5.
[show abstract][hide abstract] ABSTRACT: Immune and inflammatory responses and the regulation of cellular events seem to be major factors in ischemia-reperfusion (I/R) injury. The inhibition of nuclear transcription factor κB (NF-κB) by pyrrolidine dithiocarbamate (PDTC) shows beneficial effects in animal models in various diseases and tissues with respect to I/R injury. If these results from other tissues could be transferred to adipocutaneous flaps in rats, a new approach to pharmacologic preconditioning could be defined for tissue transfer, and PDTC could be a solution as a trigger and effector to ameliorate the aftermath of the I/R injury.
Fifty-six male WISTAR rats were divided into four experimental groups. An epigastric adipocutaneous flap was raised, and the average flap necrosis was assessed for all groups on the fifth postoperative day using planimetric software.
The control group had a significantly lower flap necrosis than the ischemic control group (p < .05). The PDTC nonischemic group had a significantly lower flap necrosis than the ischemic control group (p = .005). The ischemic PDTC group had a 10% reduction in flap necrosis that was not significant.
Our data show that a significant reduction in flap necrosis can be achieved by intravenous application of PDTC.
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale 06/2012; 41(3):176-82. · 0.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Die Entstehung einer Otomykose, insbesondere nach lokaler antibiotischer Therapie, ist nicht selten. Eine Verschleppung von
Pilzen in das Mittelohr kann jedoch schwerwiegende Komplikationen nach sich ziehen. Insbesondere präoperativ ist daher eine
Sanierung des äußeren Gehörgangs unbedingt erforderlich. Neben der gründlichen mechanischen Reinigung werden antimykotische
Ohrentropfen empfohlen. Alle derzeit auf dem Markt erhältlichen antimykotischen Ohrentropfen enthalten aber ototoxische Substanzen.
Bei Trommelfelldefekten besteht daher die Gefahr einer Innenohrschädigung. Als Alternative empfehlen wir eine 0,5%ige wässrige
Especially after prolonged antibiotic ototopic therapy otomycosis is not rare. An inoculation of fungi into the tympanic cavity
however may have serious sequelae. Therefore an eradication of fungi from the external auditory canal is imperative before
surgery. In addition to thorough cleaning of the outer ear canal antimycotic preparations are recommended in treating otomycosis.
However, all of the commercially available ear drops contain ototoxic agents. In the case of defects of the tympanic membrane
a damage of the inner ear may result. Alternatively, we suggest an aqueous solution of Miconazol 0,5%.