Geografiske Forskjeller i Behandling og Prognose ved Akutt Hjerneinfarkt i Troms Fylke

Hjerneslag rammer om lag 12 000 mennesker i Norge hvert år, og er en av de hyppigste dødsårsakene globalt. Prognosen korrelerer sterkt med tid fra symptomdebut til behandling. Trombolysebehandling bør gis så fort som mulig innen 4,5 timer. I Nord-Norge er det store avstander, og det kan være lang transporttid fra distrikt til sykehus. Målet med denne oppgaven er å se om det er like muligheter for slagbehandling for de som får hjerneinfarkt i distrikt sammenlignet med de som får hjerneinfarkt i by, og om det er forskjell i prognose etter hjerneinfarkt i disse to pasientgruppene. Dette er en prospektiv kvalitetsstudie med utgangspunkt i en studiepopulasjon på 231 pasienter delt inn i to grupper; symptomdebut i eller utenfor «Tromsø by». Datamaterialet er innhentet fra UNNs egne registreringer i Norsk Hjerneslagregister og journaler i DIPS og AMIS for året 2019. Inklusjonskriterier er pasienter som ble utskrevet fra UNN Tromsø dette året med «hjerneinfarkt» som utskrivelsesdiagnose. Overflytningspasienter fra andre lokalsykehus, intrahospitale hjerneslag, samt pasienter som fikk hjerneinfarkt utenom kommunene som tilhører UNN Tromsøs nedslagsfelt ble ekskludert fra studien. Pasientene som fikk hjerneinfarkt i byen hadde høyere sannsynlighet for å få trombolysebehandling sammenlignet med pasienter som fikk hjerneinfarkt i distriktet (justert OR 2,19, 95% KI 1,17-4,09, p=0,014). Trombolysepasientene i distriktet fikk behandlingen gjennomsnittlig 1 time og 15 minutter senere enn trombolysepasientene i by (β=1,25, 95% KI 0,48-2,02, p=0,002). Til tross for dette fant vi ingen signifikant sammenheng mellom sted (by eller distrikt) for symptomdebut og sannsynlighet for et «godt utfall» i etterkant av hjerneinfarktet (justert OR 1,52, 95% KI 0,81 – 2,85, p=0,196). Funnene i denne studien indikerer at det foreligger en kvalitativ forskjell i slagbehandling for pasienter med symptomdebut i by og distrikt, som ikke er i tråd med pasientrettighetsloven som har som formål å sikre Norges befolkning lik tilgang på helsehjelp av god kvalitet. En mulig løsning på problemet er å ta i bruk desentralisert diagnostikk og trombolysebehandling ved akutt hjerneslag. Det vil kunne gi flere pasienter i distriktet mulighet til behandling innenfor tidsvinduet for trombolyse. På sikt vil dette trolig kunne bedre utfallet for disse pasientene, selv om vår studie ikke fant en sammenheng mellom sted for symptomdebut og prognose

Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer

<p>Abstract</p> <p>Background</p> <p>The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.</p> <p>Methods</p> <p>On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.</p> <p>Results</p> <p>The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both <it>P </it>< 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (<it>P </it>= 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both <it>P </it>< 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (<it>P </it>< 0.001), whereas in the metastases the expression was highest in tumor cell areas (<it>P </it>< 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (<it>P </it>< 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.</p> <p>Conclusions</p> <p>Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer.</p

A four-surface schematic eye of macaque monkey obtained by an optical method

AbstractSchematic eyes for four Macaca fascicularis monkeys were constructed from measurements of the positions and curvatures of the anterior and posterior surfaces of the cornea and lens. All of these measurements were obtained from Scheimpflug photography through the use of a ray-tracing analysis. Some of these measurements were also checked (and confirmed) by keratometry and ultrasound. Gaussian lens equations were applied to the measured dimensions of each individual eye in order to construct schematic eyes. The mean total power predicted by the schematic eyes agreed closely with independent measurements based on retinoscopy and ultrasound results, 74.2 ± 1.3 (SEM) vs 74.7 ± 0.3 (SEM) diopters. The predicted magnification of 202 μm/deg in one eye was confirmed by direct measurement of 205 μm/deg for a foveal laser lesion. The mean foveal retinal magnification calculated for our eight schematic eyes was 211 ± (SEM) μm/deg, slightly less than the value obtained by application of the method of Rolls and Cowey [Experimental Brain Research, 10, 298–310 (1970)] to our eight eyes but just 4% more than the value obtained by application of the method of Perry and Cowey [Vision Research, 12, 1795–1810 (1985)]

Trajectories of body mass index in adulthood and risk of subtypes of postmenopausal breast cancer

Background - Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes. Methods - Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group-based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women. Results - A total of 7223 incident invasive postmenopausal breast cancer cases occurred during follow-up. Increased overweight duration and age at the onset of overweight or obesity were associated with luminal A-like breast cancer. Significant heterogeneity was observed in the association between age at overweight and overweight duration and the intrinsic-like subtypes (pheterogeneity 0.03). Compared with women who remained at normal weight throughout adulthood, women with a descending BMI trajectory had a reduced risk of luminal A-like breast cancer (HR 0.54, 95% CI 0.33–0.90), whereas women with ascending BMI trajectories were at increased risk (HR 1.09; 95% CI 1.01–1.17 for “Normal-overweight”; HR 1.20; 95% CI 1.07–1.33 for “Normal-obesity”). Overweight duration and weighted cumulative years of overweight and obesity were inversely associated with luminal B-like breast cancer. Conclusions - In this exploratory analysis, decreasing body fatness from obesity in adulthood was inversely associated with overall, hormone receptor-positive and luminal A-like breast cancer in postmenopausal women. This study highlights the potential health benefits of reducing weight in adulthood and the health risks associated with increasing weight throughout adult life. Moreover, our data provide evidence of intrinsic-like tumor heterogeneity with regard to age at onset and duration of overweight

Nyksund - en reise

Nyksund - en reis

Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study

publishedVersio

Analysis of the immune microenvironment in resected non-small cell lung cancer: the prognostic value of different T lymphocyte markers

[EN] The prognosis of non-small cell lung cancer (NSCLC) remains poor and heterogeneous and new biomarkers are needed. As the immune system plays a pivotal role in cancer, the study of immune-related markers may provide valuable prognostic information of NSCLC. In 122 formalin-fixed, paraffin-embedded tumor tissue samples from early-stage NSCLC, tumor and tumor-near stromal areas were microdissected and gene expression levels of conventional and regulatory T cell markers were assessed by quantitative polymerase chain reaction. Also, the presence of infiltrating CD4+, CD8+, and FOXP3+ cells in tumor samples was assessed by immunohistochemistry. The relative proportion of conventional and regulatory T cells present in the tumor environment was assessed and found to be key to understand the importance that the immune system analysis has in the prognostics of NSCLC patients. The presence of CD8+ cells in the tumor compartment was associated with better outcome, whereas the presence of FOXP3+ cells was associated with worse overall survival. The negative prognostic value of combined biomarkers, indicating high levels of FOXP3 in the stroma and low levels of CD4 or CD8 in tumors, was observed at mRNA level and was validated by immunohistochemistry. In conclusion, the proportion of T helper and cytotoxic cells vs. regulatory T cells in different locations of the tumor microenvironment have opposite prognostic impacts in resected NSCLC.This work was supported by the Red Temática de Investigación Cooperativa en Cáncer (RD12/0036/0025) and the Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional (PI09/01147, PI09/01149 and PI12/02838).Usó-Marco, M.; Jantus-Lewintre, E.; Bremnes, RM.; Calabuig-Fariñas, S.; Blasco-Cordellat, A.; Pastor, E.; Borreda, I.... (2016). Analysis of the immune microenvironment in resected non-small cell lung cancer: the prognostic value of different T lymphocyte markers. Oncotarget. 7(33):52849-52861. https://doi.org/10.18632/oncotarget.10811S528495286173

High Expression of IRS-1, RUNX3 and SMAD4 Are Positive Prognostic Factors in Stage I–III Colon Cancer

Colon cancer is a common malignancy and a major contributor to human morbidity and mortality. In this study, we explore the expression and prognostic impact of IRS-1, IRS-2, RUNx3, and SMAD4 in colon cancer. Furthermore, we elucidate their correlations with miRs 126, 17-5p, and 20a-5p, which are identified as potential regulators of these proteins. Tumor tissue from 452 patients operated for stage I–III colon cancer was retrospectively collected and assembled into tissue microarrays. Biomarkers’ expressions were examined by immunohistochemistry and analyzed using digital pathology. In univariate analyses, high expression levels of IRS1 in stromal cytoplasm, RUNX3 in tumor (nucleus and cytoplasm) and stroma (nucleus and cytoplasm), and SMAD4 in tumor (nucleus and cytoplasm) and stromal cytoplasm were related to increased disease-specific survival (DSS). In multivariate analyses, high expression of IRS1 in stromal cytoplasm, RUNX3 in tumor nucleus and stromal cytoplasm, and high expression of SMAD4 in tumor and stromal cytoplasm remained independent predictors of improved DSS. Surprisingly, with the exception of weak correlations (0.2 < r < 0.25) between miR-126 and SMAD4, the investigated markers were mostly uncorrelated with the miRs. However, weak to moderate/strong correlations (0.3 < r < 0.6) were observed between CD3 and CD8 positive lymphocyte density and stromal RUNX3 expression. High expression levels of IRS1, RUNX3, and SMAD4 are positive prognostic factors in stage I–III colon cancer. Furthermore, stromal expression of RUNX3 is associated with increased lymphocyte density, suggesting that RUNX3 is an important mediator during recruitment and activation of immune cells in colon cancer

Profiling of VEGFs and VEGFRs as Prognostic Factors in Soft Tissue Sarcoma: VEGFR-3 Is an Independent Predictor of Poor Prognosis

BACKGROUND: In non-gastrointestinal stromal tumor soft tissue sarcoma (non-GIST STS) optimal treatment is surgery with wide resection margins. Vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are known to be key players in the initiation of angiogenesis and lymphangiogenesis. This study investigates the prognostic impact of VEGFs and VEGFRs in non-GIST STS with wide and non-wide resection margins. METHODS: Tumor samples from 249 patients with non-GIST STS were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of VEGF-A, -C and -D and VEGFR-1, -2 and -3. RESULTS: In the univariate analyses, VEGF-A (P=0.040) in the total material, and VEGF-A (P=0.018), VEGF-C (P=0.025) and VEGFR-3 (P=0.027) in the subgroup with wide resection margins, were significant negative prognostic indicators of disease-specific survival (DSS). In the multivariate analysis, high expression of VEGFR-3 (P=0.042, HR=1.907, 95% CI 1.024-3.549) was an independent significant negative prognostic marker for DSS among patients with wide resection margins. CONCLUSION: VEGFR-3 is a strong and independent negative prognostic marker for non-GIST STSs with wide resection margins

Reproductive factors and risk of melanoma : a population-based cohort study

Background The association between reproductive factors and risk of cutaneous melanoma (CM) is unclear. We investigated this issue in the Norwegian Women and Cancer cohort study. Objectives To examine the association between the reproductive factors age at menarche, menstrual cycle length, parity, age at first and last birth, menopausal status, breastfeeding duration and length of ovulatory life, and CM risk, overall and by histological subtypes and anatomical site. Methods We followed 165 712 women aged 30-75 years at inclusion from 1991-2007 to the end of 2015. Multivariable Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results The mean age at cohort enrolment was 49 years. During a median follow-up of 18 years, 1347 cases of CM were identified. No reproductive factors were clearly associated with CM risk. When stratifying by histological subtype we observed significant heterogeneity (P = 0 center dot 01) in the effect of length of ovulatory life on the risk of superficial spreading melanoma (HR 1 center dot 02, 95% CI 1 center dot 01-1 center dot 04 per year increase) and nodular melanoma (HR 0 center dot 97, 95% CI 0 center dot 94-1 center dot 01 per year increase). When stratifying by anatomical site, menopausal status (HR 0 center dot 54, 95% CI 0 center dot 31-0 center dot 92, postmenopausal vs. premenopausal) and menstrual cycle length (HR 1 center dot 07, 95% CI 1 center dot 01-1 center dot 13, per day increase) were associated with CM of the trunk, and significant heterogeneity between anatomical sites was observed for menopausal status (P = 0 center dot 04). Conclusions In this large population-based Norwegian cohort study, we did not find convincing evidence of an association between reproductive factors and risk of CM.Peer reviewe