Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages.

INTRODUCTION: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. METHODS: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. RESULTS: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. DISCUSSION: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.

Sertoli - Leydig cell tumor with retiform areas and overgrowth of rhabdomyosarcomatous elements: case report and literature review.

BACKGROUND: Sertoli - Leydig cell tumors (SLCTs) are sex-cord stromal tumors that account less than 0.5 % of primary ovarian neoplasms. They are mostly benign and occur in reproductive age women. Variants with heterologous mesenchymal elements are exceptionaly rare. The usual presentation of SLCTs is with signs of androgen excess as majority of them produce androgens. CASE PRESENTATION: We present a case of a SLCT occurring in a 70 year old woman. Her presenting complaint was abdominal distension and pain. She had no signs of androgen or estrogen excess. Transvaginal ultrasound (TVUS) and CT scan showed a multilocular adnexal tumor and level of CA 125 was raised. A complete cytoreduction was achieved with surgical procedure. Histopathological examination revealed moderately differentiated SLCT with retiform areas and owergrowth of heterologous component in form of embrional rhabdomyosarcoma (RMS). She returned 7 months after the surgery with a large abdominal mass, ascites, right- sided hydronephrosis and massive pulmonary embolism. Due to the widespread disease and her poor general condition, she received only palliative care. She died 15 days after the admission. No autopsy was performed. CONCLUSIONS: Due to the rarity of SLCTs, especially those with retiform areas and heterologous elements, their management remains challenging. There is no firm evidence that adjuvant chemotherapy is effective in improving survival in SLCTs with malignant heterologous elements. Further studies with a higher number of cases and a longer follow-up are needed to better predicting the prognosis and determine the role of chemotherapy in such cases.

The significance of the pluripotency and cancer stem cell-related marker NANOG in diagnosis and treatment of ovarian carcinoma.

Ovarian cancer is among the most common gynecologic cancers and unfortunately the most common cause of death from gynecologic malignancies. Due to few early symptoms and insufficient screening programs, an early diagnosis of ovarian cancer is very difficult and new biomarkers related to early ovarian carcinogenesis are needed. In the last years a growing scientific knowledge about cancer stem cells and their markers opened a new perspective on screening and early diagnosis of ovarian cancer. The transcription factor NANOG is not only a pluripotency and cancer stem cell-related marker, but also promotes cancer stem cell-like characteristics of tumor, tumor growth, dissemination, immune evasion, and resistance to conventional therapy. The recent data showed that small stem cells resembling very small embryonic-like stem cells are present in the ovarian surface epithelium of adult human ovaries. These cells expressed several genes related to primordial germ cells, germinal lineage, and pluripotency, including NANOG, therefore their involvement in the manifestation of ovarian cancer are not excluded. As majority of cancer cells within a tumor are non tumorigenic, the therapies targeting these cells cause tumor regression, but the survived cancer stem cells regenerate the tumor, so tumor relapse or reoccur. The eradication of cancer actually requires the elimination of cancer stem cells, therefore new strategies in treatment that specifically target cancer stem cells are urgently needed. Although the therapeutic efficacy of targeting NANOG as a cancer treatment method is still in experimental phase, the gene therapy with small interfering RNA or short hairpin RNA have already shown some promising therapeutic potential. The authors can conclude that NANOG represents a promising diagnostic marker and agent for target therapy of ovarian cancer.

When elders choose: Which factors could influence the decision-making among elderly in the selection of health tourism services?

BACKGROUND: Elderly beneficiaries (age 65+) exhibit specific characteristics that influence the distribution of health tourism market. High incidence of multiple morbidities and functional disability are hallmarks in this age group. For these reasons, elderly population requires different elements and diverse spectrum of services within health tourism, in comparison to younger beneficiaries. Thus, differences would occur within heterogeneous elderly population itself. A preliminary study that we conducted showed that the level of functional independence was one of the significant factors that guided decision-making among elderly beneficiaries when it came to their health tourism-related choices. Results suggested that beneficiaries recognized and appreciated the effect of the natural remedies and attractions available at the given destination. HYPOTHESIS: Maritime and continental health tourism are two different entities commonly selected by elderly beneficiaries for therapeutic purposes. We propose that the climate conditions, geographical location and availability of regional natural remedies are the key factors to why different services were elected by different groups of elderly. The model of Croatia, an established country in the field of health tourism was utilized for this purpose. Differences in the diagnostic categories of beneficiaries are expected due to effects of marine (sea, Mediterranean climate) and continental (thermal water, healing mud) health tourism. In addition, multitudes of mutually intertwined factors affect decision-making process among elderly regarding their health tourism choices. Such factors include the scale of preferences (with special emphasis on well-being and health), leisure opportunities, marketing influences, cost (price) and the availability/diversity of health tourism services within the particular region. Moreover, individual psychosocial and physical characteristics, disabilities and other debilitating conditions, examined in our preliminary study, significantly contributed to the decision-making scheme. We shouldn't disregard sociodemographic and cultural preferences among elderly as potential factors. CONCLUSIONS: Confirmation of our hypothesis could change the usual approach towards the group of elderly beneficiaries (65+) in the health tourism domain. This approach is often largely based on chronological age criteria exclusively. The contents of this manuscript could serve as a blueprint for the development of comprehensive and sustainable health tourism strategies worldwide.

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

Risk factors for HR- and HER2-defined breast cancer in Slovenian postmenopausal women.

OBJECTIVE: The study aimed to investigate the influence of some generally recognized risk factors for hormone receptor (HR)- and human epidermal growth factor receptor 2 (HER2)-defined breast cancer among Slovenian postmenopausal women. METHOD: Eligible women diagnosed with breast cancer were compared with 709 controls of the same age and ethnicity. Immunohistochemistry and FISH analyses were used to classify cases into molecular subtypes: 454 HR(+), 106 HR(-), 81 HER2(+) and 603 HER2(-). Adjusted odds ratios and 95% confidence intervals were estimated using multivariate logistic regression analysis. RESULTS: Overweight and obese women were at increased risk of HR(+), HER2(-) and of HR(+), HR(-), HER2(-) tumors, respectively. Women who started menstruating at the age of 11 years or earlier were at decreased risk of ER(-)PR(-) tumors. Users of hormone replacement therapy (HRT) were negatively associated with HR(+) and HER2(-) tumors. The inverse effect was most pronounced with the use of estrogen-only HRT, and longer duration of HRT use did not result in a significant change in risk. In contrast, combined HRT decreased the risk of HER2(+) tumors. Having a first-degree relative with breast and/or ovarian cancer increased the risk of HR(+) and HER2(-) tumors. CONCLUSION: We conclude that certain breast cancer risk factors may vary by molecular subtypes. According to our results, HRT use may have a greater influence on HR (+) and HER2(-) breast cancers and the risk of HER2-defined breast cancer may differ with respect to the regimen of HRT.

Prognostic value of E-cadherin expression in thyroid follicular carcinoma.

AIMS: To evaluate the expression of E-cadherin, its association with various clinicopathological features and its possible relation with distant metastasis-free survival (DMFS) in follicular carcinoma of the thyroid. METHODS: E-cadherin expression was assessed immunohistochemically in sections from paraffin embedded tissues in a group of 54 patients with follicular carcinoma and its variants who were followed for a median of 7.25 years. RESULTS: Reduced E-cadherin expression, defined as <90% of cells showing membrane positivity, was found in 15 tumours and was significantly associated with widely invasive growth, insular morphology and lesser degree of differentiation, but was not related to patient sex and age or tumour size. In univariate analysis, DMFS was significantly worse in male patients (P<0.03), widely invasive tumours (P=0.0002), moderately/poorly differentiated tumours (P<0.05) and tumours showing reduced E-cadherin expression (P=0.0001). In multivariate analysis, the degree of invasiveness and E-cadherin expression were the only independent prognostic factors. Among widely invasive cases, those with reduced E-cadherin expression had significantly worse DMFS than those with preserved expression. CONCLUSIONS: Our findings suggest that E-cadherin expression could be used as a prognostic marker in widely invasive follicular carcinomas of the thyroid. Larger studies are needed to assess its prognostic value in the group of minimally invasive carcinomas.

Radioguided occult lesion localization (ROLL) of the nonpalpable breast lesions.

Standard localization techniques of the nonpalpable breast lesions (guide wire, carbon, skin marking) have several disadvantages. Radioguided occult lesion localization (ROLL) was recently proposed as a better alternative resulting in wider surgical margins and lower average specimen weight. The aim of our study was to compare ROLL to our previously published series of the standard guidewire localization, performed at the Institute of Oncology Ljubljana. ROLL was performed in 110 nonpalpable breast lesions. Human serum albumin macroaggregats, marked with 1.8-5.5 MBq 99mTc was injected in the nonpalpable lesion. During surgery the radioactive breast tissue was excised using hand held gamma probe. Nonpalpable breast lesions were excised in all 110 patients. The definitive histology revealed 32 invasive carcinomas, 19 DCIS, 5 LCIS in and 54 benign breast lesions. Mean specimen weight was 40 g which is less in comparison to 53 g of the guidewire series (p=0.002). Surgical margins were clear in 36/51 (70%) invasive breast cancer or DCIS patients and close or involved in 15/51 (30%) patients. Compared to the guidewire series, where 41/92 (44%) margins were clear and 51/92 (56%) were close or involved, the difference was statistically significant (p=0.005). ROLL proved to be superior to guidewire localization in our series, allowing excision of the nonpalpable breast lesion with wider surgical margins despite lower average specimen weight.

Breast biopsy with wire localization: factors influencing complete excision of nonpalpable carcinoma.

Our aim was to find out the factors influencing the complete excision of nonpalpable carcinoma. During a 2-year period, 215 patients (median age 55 years) underwent biopsy after wire localization of 222 nonpalpable breast lesions. Mammographic, surgical and pathological factors were correlated with the outcome of surgery using contingence tables in SPSS statistical software. A total of 96 carcinomas were diagnosed: 38 in situ and 58 invasive carcinomas. Surgical margins were clear in 43, close in 20 and involved in 33 cases. Factors correlated with clear surgical margins are mammographically spicular lesion, cytologically proven carcinoma, excision of more than 50 g of tissue, carcinoma smaller than 10 mm, invasive carcinoma without in situ component, and unicentric ductal carcinoma in situ ( p<0.05). Complete excision of multifocal in situ carcinoma or invasive carcinoma with extensive in situ component, which are diagnosed on mammogram as suspicious microcalcifications, remains a puzzling surgical task.

Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p<0.05) and this was independent of BMD. CONCLUSION: Past fracture as a risk indicator for future fracture is not strongly mediated through increased bone turnover.

The immunohistochemical and serological determination of p53 protein in patients with malignant lymphomas.

The product of mutated p53 gene is a protein with abnormal conformation, impaired DNA binding, and a prolonged half life, the latter of which results in immunohistochemically detectable levels within nuclei of malignant cells. The present study was aimed at the immunohistochemical determination of p53 overexpression in patients with various histological types of nonHodgkin's lymphomas (NHL), with a particular interest in gastric lymphomas. In these patients, as well as in controls, also serological determinations of p53 protein were performed using an ELISA method. Immunohistochemical overexpression of p53 protein was found in 21% of NHL patients, with the highest incidence of p53 immunoreactivity in cases of Burkitt's lymphoma, follicle center lymphoma grade III, and diffuse large B-cell lymphoma. In gastric lymphomas the overall incidence of p53 immunoreactivity was as high as 46%. Serological ELISA determinations of p53 protein in NHL patients and in controls remained below the lowest detection limit of the method in all 128 cases. Considering that p53 mutations are associated with poor response to therapy, and consequently with poor prognosis, it is of great importance to determine the subset of patients that are particularly at risk for an unfavorable outcome and should be treated more aggressively. Immunohistochemical determinations of p53 overexpression represent a rapid and simple, yet somewhat imperfect technique for an estimation of the frequency of mutational events. On the other hand, serological determinations of p53 protein are completely inadequate for the evaluation of p53 status.

Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study.

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX 'beta' versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)2) and age were considered alongside femoral neck BMD (FN-BMD, g/cm2) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p<0.001, deLong's test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more proactive approach to identifying women at high risk of hip fracture in the community.

Long term prognostic value of Nottingham histological grade and its components in early (pT1N0M0) breast carcinoma.

AIMS: To determine the prognostic usefulness of the Nottingham histological grade (NHG) and its components in a series of 270 patients with stage pT1N0M0 breast cancer with a median follow up of 12.5 years. METHODS: Microscopic slides were re-examined and the degree of tubule formation, nuclear pleomorphism, and mitotic counts were assessed and scored according to the suggested guidelines. The association with cancer specific survival (CSS) was evaluated by univariate and multivariate analyses. RESULTS: Whereas tumour size, patient age, menopausal status, type of surgery, or adjuvant treatment were not related to prognosis, histological type (p < 0.01) and NHG (p < 0.005) were associated with CSS. When evaluating the components of NHG separately, survival was not related to the score for pleomorphism, but was significantly better in tumours with score 1 or 2 for tubule formation (p < 0.007) and in those with score 1 for mitotic counts (p < 0.006). The two components retained independent significance in multivariate analysis. When the proposed cut off points for mitotic counts were replaced by lower ones based on tertile values, the mitotic index became the strongest prognostic factor (p = 0.0001) and histological type was the only additional factor of independent prognostic significance. CONCLUSIONS: These findings confirm the prognostic value of NHG in pT1N0M0 breast carcinoma, show that the evaluation of tubule formation and mitotic rate provides independent prognostic information, and suggest that the proposed cut off points for mitotic counts may be too high for this particular group of tumours.

Hyalinizing spindle cell tumor with giant rosettes of the broad ligament.

BACKGROUND: Hyalinizing spindle cell tumor with giant rosettes (HSTGR) is a rare, recently described tumor that most commonly occurs in the peripheral deep soft tissues. CASE: A 53-year-old woman was operated on because of a mass in the broad ligament which was first noted 17 years previously. The tumor showed typical features of HSTGR. Two years after surgery, the patient is alive with no evidence of disease. CONCLUSIONS: To our knowledge, the present case is the first description of HSTGR occurring in the broad ligament. Despite its bland morphology, HSTGR is a low-grade sarcoma, most probably a variant of low-grade fibromyxoid sarcoma. A wide resection of the tumor and prolonged follow-up are needed because patients may develop late metastases.

Effect of primary treatment on survival in anaplastic thyroid carcinoma.

AIMS: Anaplastic thyroid carcinoma (ATC) is a fatal disease despite combined treatment consisting of chemotherapy, radiotherapy and surgery. The optimal sequence of treatment modalities is not known. The purpose of our retrospective non-randomized study was to find out whether timing of the treatment modality had any influence on survival, and to find out if primary surgery prolongs survival in comparison to primary chemotherapy and/or radiotherapy. METHODS: From our database of 162 patients with ATC treated at the Institute of Oncology Ljubljana from 1972-98, 79 patients (26 men, 53 women; age: 40-86 years, mean age 65 years) were included in this retrospective study. The 83 patients with distant metastases on admission, with the survival shorter than one month or patients without any treatment were excluded. The 79 patients were classified into (1) primary surgery group (n=26) and (2) primary chemotherapy and/or radiotherapy group (n=53), including the 12 patients in whom surgery was performed after chemotherapy and/or radiotherapy. The survival of both groups was compared by log-rank test and group characteristics by ANOVA and(2 test using SPSS program. RESULTS: In comparison to the primary surgery group, the patients from the primary chemotherapy and/or radiotherapy group were older and had faster growing, and larger tumours, which were not confined to the thyroid, and more frequently had regional metastases. There was no difference in the survival of the two groups (P=0.17). Survival for longer than one year was observed in 25% of patients with primary surgery and in 21% of patients with primary chemotherapy and/or radiotherapy. The best results (50% survival at one year) were obtained in patients in whom the tumour was surgically removed after primary chemotherapy and radiotherapy. CONCLUSION: This study suggests that the timing of the treatment modalities has an impact on survival and that treatment should start with chemotherapy and/or radiotherapy, with surgery to follow if possible.)

Reactivation of primary hypertrophic osteoarthropathy by bronchogenic carcinoma.

This paper reports 2 cases of primary hypertrophic osteoarthopathy (PHO) which evolved into secondary hypertrophic osteoarthopathy (SHO) under the influence of bronchogenic carcinoma. The patients had a clinical picture of primary hypertrophic osteoarthropathy but without any signs of disease activity until in the last several months when a malignant bronchopulmonary condition developed. This activated all the symptoms: joint swelling; enlarged fingers and distal forearms and legs; moist palms and soles; unpleasant odour of perspiration; and deeper folds of the forehead and nasolabial furrow. A bone scan showed increased accumulation of the radioisotope in specific regions of the skeleton. To our knowledge, no similar cases have been described in the literature.

Radiological changes of the symphysis in ankylosing spondylitis.

PURPOSE: To evaluate the symphyseal changes in patients with ankylosing spondylitis. MATERIAL AND METHODS: Radiological-morphological changes of the symphysis were studied in 68 patients (66 men, 2 women) with ankylosing spondylitis whose age ranged from 21 to 75 years. The duration of the disease was from 2 to 50 years. RESULTS AND CONCLUSION: Changes in the symphysis were found in 16 patients (23.5%) and were less prominent than findings in the sacroiliac joints. We classified these changes into four stages: minimal changes, apparent destruction, reparation and ankylosis. The third and the fourth stages of the changes in the symphsis were found more frequently in patients who suffered from the disease for more than 15 years. Radiological evaluation of symphyseal changes can be helpful in the evaluation of disease progression as well as in establishing a differential diagnosis.

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.