Actinic cheilitis: epithelial expression of COX-2 and its association with mast cell tryptase and PAR-2

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including oral cancers. Recent studies have shown that mast cell-derived protease tryptase can induce COX-2 expression by the cleavage of proteinase-activated receptor-2 (PAR-2). Actinic cheilitis (AC) is a premalignant form of lip cancer characterized by an increased density of tryptase-positive mast cells. To investigate the possible contribution of tryptase to COX-2 overexpression during early lip carcinogenesis, normal lip (n=24) and AC (n=45) biopsies were processed for COX-2, PAR-2 and tryptase detection, using RT-PCR and immunohistochemistry. Expression scores were obtained for each marker and tested for statistical significance using Mann-Whitney and Spearmann's correlation tests as well as multivariate logistic regression analysis. Increased epithelial co-expression of COX-2 and PAR-2, as well as, elevated subepithelial density of tryptase-positive mast cells were found in AC as compared to normal lip (P<0.001). COX-2 overexpression was found to be a significant predictor of AC (P<0.034, forward stepwise, Wald), and to be correlated with both tryptase-positive mast cells and PAR-2 expression (P<0.01). The results suggest that epithelial COX-2 overexpression is a key event in AC, which is associated with increased tryptase-positive mast cells and PAR-2. Therefore, tryptase may contribute to COX-2 up-regulation by epithelial PAR-2 activation during early lip carcinogenesis.     

Radiation exposures of cancer patients from medical X-rays: how relevant are they for individual patients and population exposure?

X-ray procedures have a substantial impact not only on patient care but also on man-made radiation exposure. Since a reliable risk-benefit analysis of medical X-rays can only be performed for diagnosis-related groups of patients, we determined specific exposure data for patients with the ten most common types of cancer. For all patients with the considered cancers undergoing medical X-ray procedures in a maximum-care hospital between 2000 and 2005, patient- and examination-specific data were retrieved from the hospital/radiology information system. From this data, the cumulative 5-year effective dose was estimated for each patient as well as the mean annual effective dose per patient and the mean patient observation time for each cancer site. In total, 151,439 radiographic, fluoroscopic, and CT procedures, carried out in 15,866 cancer patients (age, 62 ± 13 years), were evaluated. The mean 5-year cumulative dose varied between 8.6 mSv (prostate cancer) and 68.8 mSv (pancreas cancer). Due to an increasing use of CT scans, the mean annual effective dose per patient increased from 13.6 to 18.2 mSv during the 6-year period. Combining the results obtained in this study for a particular hospital with cancer incidence data for Germany, we estimated that cancer patients having X-ray studies constitute at least 1% of the population but receive more than 10% of the total effective dose related to all medical X-ray procedures performed nationwide per year. A large fraction of this dose is radiobiologically ineffective due to the reduced life expectancy of cancer patients.     

Alterations of intraretinal layers in acute central serous chorioretinopathy

Purpose: Optical coherence tomography (OCT) is restricted by its low scanning speed and limited resolution. High‐definition raster‐scanning OCT (HD‐OCT) was used to evaluate changes in retinal microstructure in patients with acute central serous chorioretinopathy (CSCR) and to find new morphological features. Methods: Eighteen patients with subretinal fluid accumulation caused by acute CSCR were imaged in a cross‐sectional study design. High‐speed frequency‐domain HD‐OCT was used to image an area of 6 × 6 mm in the macular retina. Three‐dimensional analyses were performed using en‐face imaging and section analysis of single HD‐OCT scans. Results: Detailed information about fluid accumulation can be obtained in all compartments. Discrete changes in reflectivity are visualized within the outer nuclear or plexiform layers in > 90% of patients. Subretinal fluid appears as a dome‐shaped pool of fluid and is not associated with a loss of photoreceptor layer integrity. Deposits are demarcated beneath the outer cone segments. Multiple small pigment epithelial detachments are present in > 60% of patients. Conclusions: High‐definition OCT provides extensive information regarding precise topographic and layer‐specific localization of discrete morphological changes. Along with well‐known changes in the retinal microstructure, hyper‐reflectivity can be imaged in the outer nuclear or plexiform layers and may represent intraretinal changes indicating the presence of subretinal pathologies or retinal maladjustment caused by the underlying pathology.     

Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view

Introduction

Mammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies.

Methods

Our aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years.

Results

Where only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67).

Conclusion

This indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals.     

Variable size computer-aided detection prompts and mammography film reader decisions

Introduction

The purpose of the present study was to investigate the effect of computer-aided detection (CAD) prompts on reader behaviour in a large sample of breast screening mammograms by analysing the relationship of the presence and size of prompts to the recall decision.

Methods

Local research ethics committee approval was obtained; informed consent was not required. Mammograms were obtained from women attending routine mammography at two breast screening centres in 1996. Films, previously double read, were re-read by a different reader using CAD. The study material included 315 cancer cases comprising all screen-detected cancer cases, all subsequent interval cancers and 861 normal cases randomly selected from 10,267 cases. Ground truth data were used to assess the efficacy of CAD prompting. Associations between prompt attributes and tumour features or reader recall decisions were assessed by chi-squared tests.

Results

There was a highly significant relationship between prompting and a decision to recall for cancer cases and for a random sample of normal cases (P < 0.001). Sixty-four per cent of all cases contained at least one CAD prompt. In cancer cases, larger prompts were more likely to be recalled (P = 0.02) for masses but there was no such association for calcifications (P = 0.9). In a random sample of 861 normal cases, larger prompts were more likely to be recalled (P = 0.02) for both mass and calcification prompts. Significant associations were observed with prompting and breast density (p = 0.009) for cancer cases but not for normal cases (P = 0.05).

Conclusions

For both normal cases and cancer cases, prompted mammograms were more likely to be recalled and the prompt size was also associated with a recall decision.     

Significance of age in acute myeloid leukemia patients younger than 30 years: a common analysis of the pediatric trials AML-BFM 93/98 and the adult trials AMLCG 92/99 and AMLSG HD93/98A

BACKGROUND: Data on the impact of age in acute myeloid leukemia (AML) patients <30 years treated in pediatric and adult trials are scarce. METHODS: In all, 891 patients <18 years were treated in the pediatric trials AML-BFM 93/98 and 290 adolescents and young adults (>16 to <30 years) in the AMLCG 92/99 and AMLSG HD93/98A trials. Treatment schedules and dose intensities were comparable. RESULTS: Initial features and risk factors differed considerably between infants (<2 years) and older age groups and only slightly between children (2 to <13), adolescents (13 to <21) and young adults (21 to <30). Treatment results were most favorable in children (5-year event free survival [EFS]: 54% +/- 3%), slightly inferior in adolescents (46% +/- 4%, P = .03), and unfavorable in young adults (28% +/- 5%, P = .0001). Excluding patients with favorable karyotypes, the results were similar in infants and children (EFS: 44% +/- 4% and 46% +/- 3%, respectively) and inferior in adolescents (35% +/- 4%) and young adults (23% +/- 4%). There was an increased, age-related percentage and inferior outcome in patients with >5% bone marrow blasts after induction. EFS was especially poor in young adults, with blasts >5%. The blast count after induction was of no prognostic value in patients with favorable karyotypes, but a significant risk factor in patients with other cytogenetics. CONCLUSIONS: Biologic data differed mainly between infants and older age groups. When comparing the same age groups, outcome was similar between the trial groups, which differed from reports concerning acute lymphoblastic leukemia. However, the prognosis decreased after childhood independent of other risk factors. This indicates that even in the younger cohorts increasing age may be an additional unfavorable factor.     

Parotid cancer: Impact of changes from the 1997 to the 2002 American Joint Committee on Cancer classification on outcome prediction

BACKGROUND: The TNM classification [American Joint Committee on Cancer (AJCC)] of salivary gland cancer was revised again in 2002. In the present study, the outcome prediction of the new TNM system was compared with the old 1997 TNM system in 202 patients with primary parotid cancer. METHODS: All patients treated from 1986 to 2006 were reclassified in both TNM systems. Disease-free survival (DFS) rates were calculated. The prognostic validity of both the TNM system and other factors were analyzed univariately (log-rank test) and multivariately (Cox regression). RESULTS: AJCC TNM stage changes from 1997 to 2002 altered the disease staging in 35% of the patients. Concerning DFS, the new TNM 2002 staging allowed significantly better separation of stage III, but not of stage I versus stage II. The TNM 2002 staging was the most powerful predictor for DFS according to multivariate analysis. The 1997 system showed no independent significance. The subclassification of the new stage IV was not satisfactory; no clear distinction of IVA versus III, and IVA versus IVB was possible. CONCLUSIONS: The TNM 2002 staging is more valid than the 1997 system, but a significant problem was observed in separating stage I from stage II, and within the stage IV subgroups.     

Fluid-debris level in follicular cysts: a pathognomonic sign of ovarian torsion

Background Early diagnosis of ovarian torsion is mandatory to avoid common complications. Sonography is the imaging modality of choice, but diagnosis is still a challenge. Objective To report an additional sonographic feature of ovarian torsion in order to improve diagnostic accuracy. Materials and methods Grey-scale and colour Doppler pelvic sonography was performed in 12 patients with acute onset of intermittent lower abdominal pain and in 1 asymptomatic patient with a palpable mass in the labium majus. Patient ages ranged from 4 months to 17 years. Results In all patients an enlarged ovary with peripheral cysts was demonstrated. High-resolution sonography detected fluid-debris levels within these cystic structures in 11 of the 13 patients (sensitivity 85%) and provided an additional diagnostic sign. Six patients had cystic teratoma. Conclusions We confirm the fluid-debris level as a pathognomonic sonographic sign of ovarian torsion with or without associated teratoma.