Trends in incidence and predictions of cutaneous melanoma across Europe up to 2015.

BACKGROUND: Melanoma is a significant health problem in Caucasian populations. The most recently available data from cancer registries often have a delay of several months up to a few years and they are generally not easily accessible. OBJECTIVES: To assess recent age- and sex-specific trends in melanoma incidence and make predictions for 2010 and 2015. METHODS: A retrospective registry-based analysis was performed with data from 29 European cancer registries. Most of them had data available from 1990 up to 2006/7. World-standardized incidence rates (WSR) and the estimated annual percentage change (EAPC) were computed. Predictions were based on linear projection models. RESULTS: Overall the incidence of melanoma is rapidly rising and will continue to do so. The incidence among women in Europe was generally higher than in men. The highest incidence rates were seen for Northern and north-western countries like the UK, Ireland and the Netherlands. The lowest incidence rates were observed in Portugal and Spain. The incidence overall remained stable in Norway, where, amongst young (25-49 years) Norwegian males rates significantly decreased (EAPC -2.8, 95% CI -3.6; -2.0). Despite a low melanoma incidence among persons above the age of 70, this age group experienced the greatest increase in risk during the study period. CONCLUSIONS: Incidence rates of melanoma are expected to continue rising. These trends are worrying in terms of disease burden, particularly in eastern European countries.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes.

OBJECTIVE: To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. METHODS: A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). RESULTS: The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. CONCLUSION: The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Mammographic screening programmes in Europe: organization, coverage and participation.

OBJECTIVES: To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. METHODS: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. RESULTS: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. CONCLUSIONS: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

Prediagnosis lifestyle exposures and survival of gastric cancer patients: a cohort study from Portugal.

BACKGROUND: Dietary habits and smoking are recognised as important gastric cancer determinants. However, their impact on prognosis remains poorly understood. We aimed to quantify the association between lifestyles and survival of gastric cancer patients. METHODS: In 2001-2006, 568 patients were recruited in the two major public hospitals in the north of Portugal. Participants were inquired about smoking and dietary habits regarding the year preceding the diagnosis. The vital status of all participants, up to 2011 (maximum follow-up: 10 years), was assessed through the North Region Cancer Registry. Cox proportional hazards regression models were used to estimate adjusted (at least for age, sex and education) hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: No significant differences in gastric cancer survival were observed according to smoking status (current vs never smokers, HR=1.00, 95% CI: 0.72-1.38) or alcohol intake (current vs never consumers, HR=0.87, 95% CI: 0.61-1.25). Only a dietary pattern (high consumptions of most food groups and low vegetable soup intake) was significantly associated with a better prognosis among patients with the extent of disease classified as regional spread (HR=0.45, 95% CI: 0.22-0.93). CONCLUSION: This study shows that prediagnosis lifestyles have a small impact in the survival of gastric cancer patients.

DNA content in malignant salivary gland tumours.

OBJECTIVE: Our aim was to evaluate the DNA content in malignant salivary gland tumours using image cytometry and its possible relationships with clinical and morphologic findings, disease course and prognosis. PATIENTS AND METHODS: The study sample comprised 31 patients diagnosed and treated for primary malignant salivary gland tumours. Formalin-fixed, paraffin-embedded surgical specimens of all patients were Feulgen-stained for DNA content analysis by image cytometry. Statistical analysis was used to investigate possible relationships between DNA content variables and clinical and histological findings, disease course and patient survival. RESULTS: Seventeen (55%) cases of our sample were graded as DNA diploid, four (13%) as DNA aneuploid and 10 (32%) as DNA multiploid. In 15 (48%) cases, the 5c exceeding rate (5cER) was higher than 1.7%. DNA ploidy correlated with N stage and tumour size. DNA ploidy and 5cER had a statistically significant prognostic influence on overall and disease-free survival in univariate analysis. However, in multivariate analysis, stage classification was the only parameter with an independent prognosis value. CONCLUSION: Abnormal DNA content is a common finding in salivary gland cancers. Our results suggest an important role of DNA content analysis in the evaluation of these tumours.

Epidermal growth factor receptor immunoexpression evaluation in malignant salivary gland tumours.

OBJECTIVE: The aim of this study was to determine epidermal growth factor receptor (EGFR) expression in malignant salivary gland tumours and its possible relationships with clinical and morphological findings, disease course and prognosis. PATIENTS AND METHODS: The study sample comprised 88 patients diagnosed and treated for primary malignant salivary gland tumours between January 1992 and December 2002. We analysed EGFR expression using immunohistochemistry on formalin-fixed, paraffin embedded surgical specimens of all patients. Statistical analysis was used to investigate possible relationships between EGFR expression and clinical findings, histological findings, disease course and patients survival. RESULTS: Of all cases, 32 (36.4%) were EGFR positive. There was a statistically significant correlation between EGFR expression and histological grade. No other variable was correlated with EGFR expression including the overall and disease-free survival. Stage classification was the only parameter in multivariate analysis that was an independent predictor of low overall and disease-free survival. CONCLUSION: EGFR is not a useful indicator of prognosis in malignant salivary gland tumours. However, the EGFR expression in salivary gland cancers like adenocarcinomas, undifferentiated carcinomas, mucoepidermoid carcinomas or salivary duct carcinomas suggests that these tumours may be a candidate for therapy investigation directed at EGFR.

Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients.

The clinical significance of ERBB2 amplification/overexpression in gastric cancer remains unclear. In this study, we evaluated the ERBB2 status in 463 gastric carcinomas using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), and compared the findings with histopathological characteristics and with disease-specific survival. ERBB2 overexpression (2+ and 3+) and amplification (ratio ERBB2/CEP17 >or= 2) were found in 43 (9.3%) and 38 (8.2%) gastric carcinomas, respectively. Perfect IHC/FISH correlation was found for the 19 cases scored as 0 (all negative by FISH), and also for the 25 cases scored as 3+ (all positive by FISH). One out of six carcinomas scored as 1+ and 12 out of 18 carcinomas scored as 2+ were positive by FISH. ERBB2 amplification was associated with gastric carcinomas of intestinal type (P=0.007) and with an expansive growth pattern (P=0.021). ERBB2 amplification was detected in both histological components of two mixed carcinomas, indicating a common clonal origin. A statistically significant association was found between ERBB2 amplification and worse survival in patients with expansive gastric carcinomas (P=0.011). We conclude that ERBB2 status may have clinical significance in subsets of gastric cancer patients, and that further studies are warranted to evaluate whether patients whose gastric carcinomas present ERBB2 amplification/overexpression may benefit from therapy targeting this surface receptor.

Validation of a consciousness level scale for palliative care.

The main objective of this study is to validate a Consciousness Scale for palliative care. The scale was named Consciousness Scale for palliative care (CSPC). The validation had two phases: 1) face validity--the scale was assessed by seven healthcare professionals, both doctors and nurses, experienced in palliative care; 2) reliability and construct validity--performed by four investigators, two nurses and two doctors. The construct validation was performed by comparing the CSPC with a Visual Analogue Scale (VAS) of 100 mm, anchored in the terms 'awake' and 'unarousable', and then with the Glasgow Coma Scale (GCS). In this study, all four observers completed 44 periods of observation relative to 38 patients resulting in a total of 176 observations. In the phase of face validation, there were no discrepancies in relation to the issue: the scale provides measures for measurement; the scale can be useful to clinical practice; the scale can improve communication among professionals and the scale is easy to use. As a measure of internal consistency, Cronbach's alpha was found to be very high (0.99). The inter-rater reliability was also very high with an intraclass correlation coefficient of 0.99 (P < 0.001). The correlation of the CSPC to the VAS was 0.94 (P < 0.001) and the CSPC to the GCS was -0.82 (P < 0.001). The CSPC can be a very useful tool for assessing consciousness in palliative care patients. It is very ease to use, not time consuming and can be used with minimal training. Communication between professionals can be improved in the clinical setting and in the research environment.

Neovascularisation is a prognostic factor of early recurrence in T1/G2 urothelial bladder tumours.

BACKGROUND: Of patients with superficial bladder cancer, a group are still at risk of disease recurrence, progression and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial cell carcinoma (UCC), and is a potential therapeutic target. However, the selection of the appropriate patients remains a dilemma. PATIENTS AND METHODS: Vascular endothelial growth factor (VEGF) expression and the presence of angiogenesis and occurrence of CD31, CD34, endoglin and factor VIII immunoexpression, were evaluated in 66 superficial papillary UCCs of the bladder and were correlated with classical histopathological factors and disease outcome. RESULTS: VEGF immunoreactivity was observed in 100% of cases, and more intensely in the luminal surface. The presence of microvessel clusters independently of a fibrovascular core was observed in 22.7% of cases. Of these, the T1/G2 subgroup had an independent and significantly lower recurrence-free survival (P = 0.0002). CONCLUSIONS: These results indicate that the presence of angiogenesis in tumour urothelium is a potential prognostic factor in superficial UCC, particularly in T1/G2 tumours, and may be used to select patients for anti-angiogenic treatments.

Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder.

AIMS: Cell-cycle regulatory proteins are important indicators in determining progression trough the cell-cycle and progression to invasive cancer in patients presenting with superficial bladder cancer. We performed an immunohistochemical study in order to evaluate the prognostic value of the expression of p16, p27, pRb, p53 and Ki-67 in superficial grade I and II papillary urothelial cell carcinoma of the bladder. METHODS: p16, p27, p53, pRb and Ki-67 immunoexpression was studied in 14 pTa, 35 pT1a and 7 pT1b bladder tumours at presentation and at recurrence of their tumours. The recurrence-free survival and the progression-free survival were analysed according to these regulatory cell-cycle proteins expression. RESULTS: For survival in univariate analysis a high Ki-67 labelling index was a poor prognostic factor for recurrence-free and progression-free survival (P=0.0014 and P=0.012, respectively). Ki-67 labelling index was also an independent recurrence-free survival prognostic factor (P=0.0005). The p16, p27, p53 and pRb immunoreactivity was not significantly associated with recurrence or progression rate in this group of bladder carcinomas. CONCLUSIONS: These data suggest that the Ki-67 labelling index can be a reliable marker in predicting recurrence and/or progression in superficial low-grade bladder carcinomas and may be relevant in planning adjuvant therapy.

Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers.

Apocrine ductal carcinoma in situ (ADCIS) has been called a special type of ductal carcinoma in situ (DCIS) because the histologic grading is considered difficult using the classification schemes that have been proposed for common DCIS. However, ADCIS encompasses a spectrum of lesions with different morphologic aspects ranging from minimally atypical to overtly malignant. To define a classification scheme for ADCIS, 35 cases (22 pure and 13 associated with invasive carcinoma) were selected on the basis of conventional morphology on hematoxylin and eosin (H&E)-stained sections. Each case was assigned to 1 of 3 histologic grades (low, intermediate, and high) based on nuclear morphology and the presence of necrosis. In addition, the expression of hormone receptors p53, bcl-2, c-erbB-2, and Ki-67 was evaluated by immunohistochemistry, and the DNA ploidy was determined by image cytometry. Fifteen cases were classified as high histologic grade, 10 as low histologic grade, and the other 10 as intermediate grade. All but 4 cases, irrespective of grade, had the same hormonal immunophenotype: androgen receptor positivity (97.1%) and estrogen receptor and progesterone receptor negativity (94.3% and 97.1% respectively). Twenty-one cases (61.8%) showed p53 expression, and 47.1% of the cases were positive for c-erbB-2. The median positivity for Ki-67 was 5.2%. ADCIS has a unique morphologic and hormonal profile, distinct from common DCIS, deserving a specific classification. The proposed classification scheme allows for categorization of ADCIS according to the most important morphologic features already seen in common DCIS, ie, nuclear grade and necrosis. The expression of biologic markers other than hormonal receptors and bcl2 in ADCIS seems in general to be similar to that in common DCIS. Ki-67 and c-erbB-2 are expressed more frequently in intermediate and high histologic grade ADCIS.

Prognostic value of Ki-67 expression in localized cutaneous malignant melanoma.

BACKGROUND: The proliferative activity of some tumors is related to the development of metastatic disease and survival. Thus it could be used as a potential prognostic variable. OBJECTIVE: The purpose of this study was to determine the prognostic value of the Ki-67 index and of a "proliferation-based prognostic index" (PBPI, derived as tumor thickness x Ki-67 index/100) in localized cutaneous malignant melanoma (CMM). METHODS: The Ki-67 index (percent of total tumor nuclei) was determined in a series of 84 localized CMMs, with the use of the alkaline phosphatase-antialkaline phosphatase labeling method in formalin-fixed, paraffin-embedded material, and was correlated with other prognostic variables. Survival analysis was performed to determine whether the Ki-67 index and the PBPI could be predictive of metastatic spread or recurrent disease. A stratified analysis of these two parameters according to the tumor thickness was done. RESULTS: An association among the Ki-67 index and location, Clark level, tumor thickness and stage, and prognostic index was detected. Increased Ki-67 index and PBPI were associated with poorer overall survival (P =.03 and P <.0001, respectively) and disease-free survival (P =.01 and P <.0001, respectively). However, after stratification for thickness, only the PBPI showed independent prognostic significance, restricted to tumors thicker than 4 mm (P =. 03). CONCLUSION: The determination of the PBPI in CMM conveys prognostic information for localized thick (>4 mm) CMM, identifying two groups of patients with distinct outcome.

[Diagnosis of paradoxal and concomitant pulmonary thromboembolism with transesophageal echocardiography: a clinical case]. / Diagnóstico de tromboembolismo paradoxal e pulmonar concomitante por ecocardiografia transesofágica: um caso clínico.

There is some controversy regarding the indications for transesophageal echocardiography in patients with suspected systemic embolism. The present case report refers to a 65 year old male admitted to the hospital for ischemic acute cerebrovascular accident, which was confirmed by cerebral computerized tomography. A transthoracic echocardiogram was performed showing right atrial and ventricular dilatation. A transesophageal echocardiogram was also performed to exclude thromboembolism and clarify dilatation of the right cavities. Mild spontaneous echocontrast was present in the left atrium without images of thrombus; an interatrial septal aneurysm with patent foramen ovale was found with right to left flow; an image compatible with a very mobile, large, proximal thrombus in the main pulmonary artery was observed. A venous duplex scan was performed, demonstrating venous thrombosis in the right popliteal and femoral veins. Pulmonary arteriography showed a large thrombus in the right pulmonary branch extending to the median lobe and a smaller thrombus in the left pulmonary branch. Apparently, the patient had no predisposing factors for thromboembolism. Full-dose heparin was started followed by oral anticoagulation. An inferior vena cava filter was implanted. At hospital discharge the pulmonary thrombus had disappeared and the right cardiac cavities had returned to normal size. The interatrial aneurysm had disappeared and foramen ovale was no longer patent. After 36 months of clinical follow up on oral anticoagulation, the patient remains asymptomatic without neurological sequelae nor respiratory distress.

Ontogeny of 3beta-hydroxysteroid dehydrogenase expression in the rat adrenal gland as studied by immunohistochemistry.

The enzyme 3beta-hydroxysteroid dehydrogenase plays a crucial role in the steroidogenic process in the adrenal gland. In the present study we tried to characterize its localization and developmental changes in the rat adrenal cortex during the postnatal period, using immunohistochemical methods. The development of the different zones evidenced specific particularities: the zona glomerulosa almost lacked 3beta-HSD in the first days after birth; then, 3beta-HSD increased, attaining a maximum around day 20 and afterwards it decreased again and remained less intense than the neighbouring zona fasciculata up until adulthood (65 days of age). The zona fasciculata was already intensely stained at birth and the expression of 3beta-HSD increased rapidly reaching a maximum after 2 weeks of life and that level was maintained from then on. The inner part of the zona fasciculata and the zona reticularis both of which develop postnatally were faintly immunostained before day 20. The expression of 3beta-HSD increased after that age to become approximately as intense as in the outer zona fasciculata and so remaining until day 90. The development of the zona glomerulosa was parallel to the secretion of aldosterone. The same did not occur with the zona fasciculata as the intensity of staining during the first 14 postnatal days was accompanied by very low levels of corticosterone.

Intracystic (encysted) papillary carcinoma of the breast: a clinical, pathological, and immunohistochemical study.

Intracystic papillary carcinoma (IPC) of the breast is a rare tumor with predilection for elderly women and distinctive pathological features that must be distinguished from ductal carcinoma in situ (DCIS) of papillary type and from invasive papillary carcinoma. The clinical, radiological, and pathological features of 29 cases of IPC are reported. The cases were divided into three groups (IPC alone, associated with DCIS, or associated with invasive carcinoma) and studied in terms of their size, predominant architectural pattern, nuclear grade, and presence of necrosis. Immunohistochemical studies were performed to evaluate the c-erbB2 oncoprotein, estrogen receptors, and ki-67 antigen expression. The median age of the patients was 75 years. Microscopically, nine tumors (31.0%) were IPC alone, nine (31.0%) had IPC associated with DCIS, and 11 (38.0%) were IPC associated with invasive carcinoma. Most of the IPC cases had low or intermediate nuclear grade, no necrosis, strongly expressed estrogen receptor, and was negative for c-erbB-2. Nuclear grade 3 and necrosis were found only in cases of IPC associated with invasive carcinoma. The median Ki-67 antigen expression was 10.6%. One patient with IPC alone had a recurrence 5 years later. Lymph node metastases were found in one patient who had the tumor with the biggest invasive area. IPC is a low-grade carcinoma with overall good prognosis. However, there is a high frequency of DCIS or invasive carcinoma associated with it, and the prognosis of these cases is related to the type, grade, and size of the associated lesions.

[Life style and occupational risk factors in bladder carcinoma]. / Estilo de vida e factores de risco ocupacionais no carcinoma da bexiga.

Bladder cancer is a useful model for the study of the relationship between lifestyle, occupation and cancer. In the present hospital based case-control study, performed in the north of Portugal, we evaluated the role of occupational exposure and the effect of different lifestyles as risk factors for bladder cancer. We inquired 98 incident cases of bladder cancer (70 men, 28 women) and 202 hospital controls (100 men, 102 women), selected based on the absence of cancer, urinary or lung diseases, and admitted for orthopedic or acute abdominal surgery. Demographic, and socio-economical variables were recorded. A detailed job history was obtained, and exposure to smoking, alcohol and coffee were assessed. Never married subjects and those with higher school degrees presented lower risk of bladder cancer. Smoking was significantly associated with cancer both in men (OR=2.7) and women (OR=5.7). Alcohol, in contrast, had a protective effect, even after adjusting for different confounders. In women, coffee and alcohol had a significant multiplicative effect. No particular industrial sector was associated with an increased risk of bladder cancer. However, those exposed to any of the substances usually considered as risk factors for bladder cancer presented higher risks (OR=1.7, 95% confidence intervals: 0.9-3.0). This study showed that lifestyles have an important role in the causality of bladder cancer, and that occupational exposure probably has less impact in the occurrence of the disease in the general population.

[Familial cancer of the breast]. / Cancro da mama familiar.

Genetic, cultural and environmental factors are influences shared in familial breast cancer. The objective of this study was to evaluate the prevalence of familial breast cancer and its association with social and clinical characteristics of women. A hospital-based descriptive study was made, and 300 patients with the diagnosis of breast cancer, made in 1992, were investigated. 17,4% of the women had a history of familial breast cancer. The presence of a positive history for familial breast cancer was associated with high social level for post-menopausal women. Age at diagnosis was older for women whose affected relative was their sister, not their mother. The need for the continuing efforts of epidemiologists, pathologists and geneticists to recognize the explanatory model of the disease is emphasized.