A conceptual framework for an oral cancer awareness campaign in Northern Germany - Challenges in campaign development and assessment.

Initial impetus for action: Oral cancer is still an underestimated disease in terms of incidence as well as mortality rates; it requires urgent prevention and early detection. At present, there is no best-practice systematic approach to raising awareness and informing the public about about this type of cancer in Germany. This article describes a framework that covers the significant stages of conceptual development and campaign design to promote oral cancer awareness in Germany. Solution: The challenges of the development, as well as evaluation of an oral cancer awareness campaign are shared in this article. Four key stages of the campaign are defined: (1) mass media, (2) target groups, (3) health care professionals, and (4) epidemiology. For each section, the following levels of assessment are proposed: (a) campaign development (formative assessment), (b) controlling and optimising campaign implementation (process assessment) and (c) measuring outcomes (summative assessment). Outcome: A process-oriented assessment concept for each of the four campaign sections was developed and merged to form a matrix, which includes each of the above sections regarding the prevention and early detection of oral cancer, as well as the three stages of campaign assessment. Future implications and learning points: The conceptual framework demonstrated that systematic planning and evaluation of different components helped to describe and evaluate an oral cancer campaign: For future campaigns, the use of a matrix covering different campaign targets as well as the entire campaign process, is recommended as a basis for campaign design and evaluation.

The pre-interventional psychiatric history - an underestimated confounder in benign intracranial lesions studies.

OBJECTIVES: The current study was designed to analyze the influence of a positive pre-interventional psychiatric history on the quality of life (QOL) after successful treatment of benign intracranial extra-cerebral lesions. METHODS: Patients treated due to meningioma WHO I or unruptured intracranial aneurysms in two German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm and neurological deficits among others. 131 patients who met the criteria of an objectively unaffected health status were included. The pre-interventional psychiatric histories and the rates of post-interventional headaches, sleeping disorders, symptoms of chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD) and QOL were determined by questionnaires which were mailed to the patients. RESULTS: 103 patients returned the questionnaires. Despite the objectively unaffected health status, the patients with a positive pre-interventional psychiatric history demonstrated a post-interventionally significantly lower QOL (p=0.002), a significantly higher Pittsburgh Sleep Quality Index sum score (p=0.009), as well as significantly higher rates of symptoms of a chronic fatigue syndrome (p=0.003) and PTSD (p=0.024), compared to the patient collective with a negative pre-interventional psychiatric status. CONCLUSION: The results of the current study demonstrate the importance of taking the pre-interventional psychiatric history as a significant and independent confounder into consideration when evaluating the outcome after treatment of benign intracranial extra-cerebral lesions. A pre-interventional psychiatric screening and an early psychological intervention might help to improve the overall outcome after successful treatment of such lesions.

Patient characteristics support unfavorable psychiatric outcome after treatment of unruptured intracranial aneurysms.

INTRODUCTION: Previous studies demonstrated an unfavorable psychological outcome after treatment of unruptured intracranial aneurysms despite an objectively favorable clinical and radiological outcome. The current study was therefore designed to analyze the psychiatric vulnerability of this specific patient collective. MATERIALS AND METHODS: Patients treated for a WHO grade I meningioma and incidental intracranial aneurysms in two German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm after more than 12 months and focal neurological deficits, among others. Seventy-five meningioma patients (M) and 56 incidental aneurysm patients (iA) met the inclusion criteria. The past medical psychiatric history, post-morbid personality characters and coping strategies were determined by questionnaires mailed to the patients in a printed version (Brief COPE, Big Five Personality Test). RESULTS: Fifty-eight M and 45 iA patients returned the questionnaires. Patients with iA demonstrated significantly higher pre-interventional rates of depressive episodes (p = 0.002) and psychological supervision (p = 0.038). These findings were especially aggravated in iA patients who received their cranial imaging for unspecific symptoms such as dizziness, headaches or tinnitus (n = 33, history of depressions: 39.4%; previous psychological supervision: 33.3%). Furthermore, the analysis of the Big Five personality traits revealed remarkably elevated neuroticism scores in the iA collective. CONCLUSION: The current study demonstrates an increased rate of positive pre-interventional psychiatric histories in the iA collective. Although those patients represent only a small subgroup, they still may play an important role concerning the overall outcome after iA treatment. Early detection and psychological support in this subgroup might help to improve the overall outcome. Further studies are needed to evaluate the influence of this new aspect on the multifactorial etiology of unfavorable psychiatric outcome after treatment of iA.

Dopamine treatment of brain-dead Fisher rats improves renal histology but not early renal function in Lewis recipients after prolonged static cold storage.

BACKGROUND: Brain death (BD) and cold preservation are major risk factors for an unfavorable transplantation outcome. Although donor dopamine treatment in brain-dead rats improves renal function and histology in allogeneic recipients, it remains to be assessed if this also holds true for the combinations of BD and prolonged static cold preservation. METHODS: BD was induced in F344 donor rats, which were subsequently treated with NaCl 1 mL/h (BD, n = 11), NaCl/hydroxy ethyl starch (BD-norm, n = 10), or 10 µg/min/kg dopamine (BD-dopa, n = 10). Renal grafts were harvested 4 h after BD and transplanted into bilateral nephrectomized Lewis recipients 6 h after cold preservation in University of Wisconsin solution. Renal function was evaluated by use of serum creatinine and urea concentrations at days 0, 1, 3, 5, and 10. Ten days after transplantation, recipients were killed and the renal allografts were processed for light microscopy and immune histology. RESULTS: Serum urea concentrations at days 5 and 10 were significantly lower in recipients that received a renal graft from dopamine-treated rats; for serum creatinine, only a trend was observed at day 10. Immune histology revealed a lower degree of ED1-positive cells in the donor dopamine-treated group. Under light microscopy, Banff classification revealed significantly less intimal arteritis in these grafts (P < .05). CONCLUSIONS: Although donor dopamine treatment clearly improves renal histology in this model, the beneficial effect on early renal function was marginal. It remains to be assessed if donor dopamine treatment has a beneficial effect on renal function in long-term follow-up.

[Dyspnea, fatigue and subpulmonary mass]. / Dyspnoe, Fatigue und subpulmonale Raumforderung.

A 52-year-old man was referred for progressive dyspnea and fatigue. The medical history was unremarkable and there were no signs of late infections or previous tumorous diseases. Physical examination revealed diminished breath sounds and a dull tone over the right lower side. Routine blood tests, arterial blood gas and body plethysmography were all within normal ranges. Chest X-ray and thorax computed tomography (CT) showed the presence of a homogeneous subpulmonary mass with a diameter of 10 cm which had a water-like density of approximately 1 Hounsfield unit (HU). The presence of an extraordinary large pericardial cyst compromising the right lower lobe and therefore causing dyspnea was confirmed by video-assisted thoracoscopic surgery (VATS). Pericardial cysts are rare congenital mediastinal masses. They are usually asymptomatic and are usually found incidentally during routine chest X-ray, CT, magnetic resonance imaging (MRI) or echocardiography. Most pericardial cysts are situated at the right cardiophrenic angle. When reaching a relevant size they can cause symptoms such as dyspnea, coughing, chest pain and fatigue. The imaging studies most useful for diagnosis are CT, MRI and echocardiography. Differential diagnoses are diaphragmatic hernia, trapped pleural effusion or other pleural or mediastinal tumors.

Recent trends in incidence and mortality of oral and pharyngeal cancer in Schleswig-Holstein in Northern Germany.

OBJECTIVE: Oral and pharyngeal cancer is still a serious public health problem with more than 10,000 new cases every year in Germany, more than 4,000 patients die of this tumour each year. Aim of the project was a detailed analysis on incidence and mortality rates by age, gender and tumour sites in Northern Germany. METHODS: The data on incidence and mortality rates from the population-based Cancer Registry of Schleswig-Holstein in Northern Germany were evaluated by age, gender and tumour sites from 2000 to 2006. RESULTS: Some 3,127 new cases of oral and pharyngeal cancer (72% men, 28% women) were registered. About half of all cases were aged 60-79 years. The incidence trends for 40-59 years described a slight decrease. Trends for pharyngeal cancer showed the highest incidence rates for both genders in those aged 60-79. This detailed analysis with subgroups showed interesting differences and revealed considerable variations, especially compared to the increasing trends in several European countries. CONCLUSIONS: These population-based data of Schleswig-Holstein showed interesting differences in the trends for incidence and mortality rates for age groups and tumour sites within the state and compared to the national German data and revealed noticeable different trends compared to several European countries. This population-based information informs effective cancer control.

[Diagnostic value of transthoracic ultrasound compared to chest radiography in the detection of a post-interventional pneumothorax]. / Diagnostische Wertigkeit der transthorakalen Sonografie vergleichend zur Thoraxübersicht beim Nachweis eines postinterventionellen Pneumothorax.

PURPOSE: Chest radiography is standard for the diagnosis of a pneumothorax. However, also ultrasound of the chest has considerable value in the detection of a pneumothorax. A typical sonographic feature is the lack of the lung gliding sign. Aim of our trial was to evaluate the significance of ultrasound of the chest in the diagnosis of a pneumothorax supplemented by using power colour Doppler imaging. PATIENTS AND METHODS: Following transbronchial biopsy, patients received transthoracic ultrasound of the chest for evaluation of a pneumothorax. Immediately afterwards, a chest radiograph was performed and results were compared. RESULTS: 1023 patients (321 female, 702 male, median age 47 years) were examined. In 30 patients (2.9%) chest radiograph revealed a pneumothorax, while in ultrasound of the chest a pneumothorax was diagnosed in 36 of the cases. Defining chest radiography as gold standard, ultrasound of the chest had a sensitivity of 100%, a specificity of 83% and an accuracy of 99%. CONCLUSION: Transthoracic ultrasound of the chest is a highly sensitive and specific diagnostic tool in the diagnosis of a pneumothorax. In comparison to chest radiography, it is better available and prevents administration of ionizing radiation. However, a disadvantage of ultrasound is the lack of quantification of a pneumothorax and the assessment of the indication for chest tube drainage.

[MRI in staging of lung cancer]. / MRT zum Staging des Lungenkarzinoms.

PURPOSE: Overview of magnetic resonance imaging (MRI) in staging of lung cancer. MATERIAL AND METHODS: Currently available methods of imaging lung cancer, lymph node and distant metastases by MRI are explained. At present, MRI is mainly used in the detection of cerebral metastases and assessment of infiltration of the thoracic wall and of the mediastinum. The capabilities of T2-weighted single-shot TSE (HASTE) and T1-weighted 3D gradient echo techniques (VIBE) are demonstrated. RESULTS: With the advent of new fast sequences like HASTE and VIBE the spatial resolution comes close to that of computed tomography but with an outstanding soft tissue contrast and without radiation exposure. The introduction of lymph node specific contrast media will improve sensitivity and specificity in N staging. Additionally, whole-body MRI is capable of detecting distant metastases, in particular in the organs at risk, i.e. brain, upper abdomen and musculoskeletal system. CONCLUSION: MRI is gaining importance as part of a multimodal imaging approach for staging of lung cancer.

Identification of known p53 point mutations by capillary electrophoresis using unique mobility profiles in a blinded study.

This study is part of an ongoing project at the National Institute of Standards and Technology (NIST) that generates a panel of DNA clones containing the most common mutations found in the human p53 tumor suppressor gene. This panel will be made available as a reference source for evaluation and testing for p53 mutations. Single strand conformation polymorphism (SSCP) analysis has found widespread acceptance as a tool for simply and rapidly screening for mutations, albeit with a detection rate that can be below 100%. We have begun to analyze mutations found in exon 7 of the p53 gene by SSCP using laser induced fluorescence capillary electrophoresis (LIF-CE). PCR fragments, containing single point mutations, were amplified from genomic DNA isolated from cell lines using primers labeled with two different fluorophores. This dual labeling approach allowed better traceability of mobility shifts as a function of the experimental conditions. While analyzing the clones H596, Colo320, Namalwa and wild type (reference samples) at different temperatures, ranging from 25 to 45 degrees C, it was observed that each mutation responded in a unique way to changes in temperature both in magnitude and direction of shifts relative to the wild type sample. In a blinded study, ten p53 exon 7 samples were matched automatically, using ABI PRISM Genotyper software, against the four reference samples. From these 10 samples, six were correctly identified as containing one of the reference mutations, two corresponded to wild type, and two were correctly identified as non-reference mutations. This approach should prove helpful in the rapid screening of target sequences that are known to bear a limited number of mutations.

Development of standard reference materials for diagnosis of p53 mutations: analysis by slab gel single strand conformation polymorphism.

We have amplified by polymerase chain reaction (PCR) a 2.0 kbp region of the p53 gene containing exons 5--9 from seven cell lines reported in the literature to contain the majority of mutations reported for this gene. Sequence analysis of these products show that all seven cell lines contain mutations within the mutational hot spots of the p53 gene. Six of the seven clones have single base substitutions and the seventh has a single base deletion. We have analyzed the seven p53 single point mutations by single strand conformation polymorphism (SSCP) analysis using fluorescence slab gel electrophoresis (SG-SSCP). Fluorescent-labeled PCR primers were used for amplification of specific exons for mutation detection. SG-SSCP was conducted using Model 373 and Model 377 DNA sequencers with GeneScan Software (Perkin Elmer, Applied Biosystem Division). Nine different gel systems were first tested for their ability to resolve the p53 mutations using the Model 373 instrument. Two gel systems were capable of resolving all of the mutations that were screened. Optimal results were obtained with 12% w/v acrylamide 50:1 plus 10% v/v glycerol. This gel system was used to evaluate the effect of temperature on the ability to resolve the mutations. The separation with respect to wild type varied for each mutation examined. Subambient temperature (20 degrees C) was preferable overall for discrimination of these mutations as a group. We intend to use this system to examine a much larger panel of p53 mutation standards that are now under development.

Detection of p53 point mutations by single strand conformation polymorphism: analysis by capillary electrophoresis.

We have analyzed five p53 single point mutations by single strand conformation polymorphism using capillary electrophoresis (CE-SSCP) and have compared these measurements to measurements obtained by slab gel electrophoresis (SG-SSCP). PCR primers were used for amplification of specific exons for mutation detection. 5' Primers were labeled with FAM (5-carboxyfluorescein) and 3' primers were labeled with JOE (2',7'-dimethoxy-4',5'-dichloro-6-carboxyfluorescein). CE-SSCP was performed using the Perkin Elmer ABI PRISM 310 Genetic Analyzer with GeneScan Software and the Beckman P/ACE 5510 CE equipped for laser-induced fluorescence detection. Although the shifts in migration times for the p53 mutations relative to the corresponding wild-type strands could be successfully detected by either SG or CE analysis, the individual electrophoresis run times were about tenfold faster and more automated with capillary electrophoresis. The CE-SSCP measurements were performed at temperatures ranging from 10 to 60 degrees C on a prototype instrument. For mutations measured at ambient temperature (25 degrees C), characteristic shifts in direction and magnitude were observed in the migration times of both strands of all mutations relative to the wild type. This demonstrated the ability of CE at ambient temperature to resolve these mutations. However, the magnitude and direction of shifts in migration time varied with temperature in a discrete pattern for each mutation and resulted in a temperature-specific profile for each mutation. This demonstrated that extended temperature control will be an important advantage in resolving single point mutations by CE-SSCP. In addition, by using CE, discrete intra-strand isoforms could be easily observed at different temperatures. The combination of mutation-specific temperature profiling and analysis of isoforms by CE-SSCP should be of help to the diagnostic community in the detection of genetic mutations.

A streamlined mutation detection system: multicolor post-PCR fluorescence labeling and single-strand conformational polymorphism analysis by capillary electrophoresis.

Effective use of knowledge of human genome sequences in studies of hereditary diseases or cancer heavily depends on efficient methods for detection of mutations in individual samples. We describe here a simple and efficient mutation scanning system in which PCR products are post-labeled with two different fluorescent dyes in one tube, and analyzed by an automated capillary electrophoresis system using single-strand conformation polymorphism (SSCP) conditions (PLACE-SSCP). With the appropriate use of an internal control DNA, differences in electrophoretic mobilities between a reference and samples are precisely evaluated, then the presence of mutations is statistically judged. Thirty-three of 34 known mutations in fragments of three unrelated sequence contexts up to 741 bp were detected using one electrophoresis condition at the confidence level of <0.3% false positive. All the mutations were detected by analyzing at two temperatures. The described system has the advantage of little human intervention, short analysis time, high sensitivity, and objectivity of data interpretation.