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Objective This study aimed to assess the cost-effectiveness of magnetic resonance imaging (MRI) with combinations of targeted biopsy (TBx) and systematic biopsy (SBx) for early prostate cancer detection in Sweden. Methods A cost-utility analysis was conducted from a lifetime societal perspective using a microsimulation model. Five strategies included no screening and quadrennial screening for men aged 55 to 69 years using SBx alone, TBx on positive MRI (MRI + TBx), combined TBx/SBx on positive MRI (MRI + TBx/SBx), and SBx on negative MRI with TBx/SBx on positive MRI (MRI − SBx, MRI + TBx/SBx). Test characteristics were based on a recent Cochrane review. We predicted the number of biopsies, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. Results The screening strategies were classified in Sweden as high costs per QALY gained compared with no screening. Using MRI + TBx and MRI + TBx/SBx reduced the number of biopsy episodes across a lifetime by approximately 40% compared with SBx alone. Both strategies showed strong dominance over SBx alone and MRI − SBx, MRI + TBx. Compared with MRI + TBx, the MRI + TBx/SBx strategy had an incremental cost-effectiveness ratio of more than €200 000 per QALY gained, which was classified in Sweden as a very high cost. These predictions were robust in the probabilistic sensitivity analysis. Limitations included generalizability of the model assumptions and uncertainty regarding the health-state values and study heterogeneity from the Cochrane review. Conclusions MRI + TBx and MRI + TBx/SBx showed strong dominance over alternative screening strategies. MRI + TBx resulted in similar or marginally lower gains in QALYs and lower costs than MRI + TBx/SBx. MRI + TBx was considered the optimal choice among the screening strategies.

Screening for prostate cancer using prostate-specific antigen (PSA) reduces prostate cancer mortality but can lead to adverse outcomes. We aimed to compare a traditional screening approach with a diagnostic strategy of blood-based risk prediction combined with MRI-targeted biopsies.We did a prospective, population-based, randomised, open-label, non-inferiority trial (STHLM3-MRI) in Stockholm county, Sweden. Men aged 50-74 years were randomly selected by Statistics Sweden and invited by mail to participate in screening; those with an elevated risk of prostate cancer, defined as either a PSA of 3 ng/mL or higher or a Stockholm3 score of 0·11 or higher were eligible for randomisation. Men with a previous prostate cancer diagnosis, who had undergone a prostate biopsy within 60 days before the invitation to participate, with a contraindication for MRI, or with severe illness were excluded. Eligible participants were randomly assigned (2:3) using computer-generated blocks of five, stratified by clinically significant prostate cancer risk, to receive either systematic prostate biopsies (standard group) or biparametric MRI followed by MRI-targeted and systematic biopsy in MRI-positive participants (experimental group). The primary outcome was the detection of clinically significant prostate cancer at prostate biopsy, defined as a Gleason score of 3 + 4 or higher. We used a margin of 0·78 to assess non-inferiority for the primary outcome. Key secondary outcome measures included the proportion of men with clinically insignificant prostate cancer (defined as a Gleason score of 3 + 3), and the number of any prostate MRI and biopsy procedures done. We did two comparisons: Stockholm3 (using scores of 0·11 and 0·15 as cutoffs) versus PSA in the experimental group (paired analyses) and PSA plus standard biopsy versus Stockholm3 plus MRI-targeted and systematic biopsy (unpaired, randomised analyses). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT03377881.Between Feb 5, 2018, and March 4, 2020, 49 118 men were invited to participate, of whom 12 750 were enrolled and provided blood specimens, and 2293 with elevated risk were randomly assigned to the experimental group (n=1372) or the standard group (n=921). The area under the receiver-operating characteristic curve for detection of clinically significant prostate cancer was 0·76 (95% CI 0·72-0·80) for Stockholm3 and 0·60 (0·54-0·65) for PSA. In the experimental group, a Stockholm3 of 0·11 or higher was non-inferior to a PSA of 3 ng/mL or higher for detection of clinically significant prostate cancer (227 vs 192; relative proportion [RP] 1·18 [95% CI 1·09-1·28], p0·0001 for non-inferiority), and also detected a similar number of low-grade prostate cancers (50 vs 41; 1·22 [0·96-1·55], p=0·053 for superiority) and was associated with more MRIs and biopsies. Compared with PSA of 3 ng/mL or higher, a Stockholm3 of 0·15 or higher provided identical sensitivity to detect clinically significant cancer, and led to fewer MRI procedures (545 vs 846; 0·64 [0·55-0·82]) and fewer biopsy procedures (311 vs 338; 0·92 (0·86-1·03). Compared with screening using PSA and systematic biopsies, a Stockholm3 of 0·11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers (227 [3·0%] men tested vs 106 [2·1%] men tested; RP 1·44 [95% CI 1·15-1·81]), lower detection of low-grade cancers (50 [0·7%] vs 73 [1·4%]; 0·46 [0·32-0·66]), and led to fewer biopsy procedures. Patients randomly assigned to the experimental group had a lower incidence of prescription of antibiotics for infection (25 [1·8%] of 1372 vs 41 [4·4%] of 921; p=0·0002) and a lower incidence of admission to hospital (16 [1·2%] vs 31 [3·4%]; p=0·0003) than those in the standard group.The Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening. Combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer.The Swedish Cancer Society, the Swedish Research Council, and Stockholm City Council.

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohns disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (>= 3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI = 1 and 58 (51%) >= 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option. Funding Agencies|Janssen Cilag AB, Sweden

Background Although prostate-specific antigen (PSA) testing is common, little is known about the pattern of retesting by either PSA values or subsequent prostate biopsies. Poor follow-up of high PSA values may lead to delayed diagnosis. Objective To estimate the probabilities of follow-up (including retesting, prostate biopsies, diagnosis, and cause-specific death) for men undergoing prostate cancer testing at a population level. Design, setting, and participants Cohort study design for men living in Stockholm with no previous diagnosis of prostate cancer between 2003 and 2015. Men were linked to the national health and population registries in Sweden. We report follow-up for men aged 50–79 yr at 2003 or at their index PSA test. Outcome measurements and statistical analysis State probabilities with 95% confidence intervals (CIs) were calculated using multistate Markov models. Results and limitations Among men not previously diagnosed with prostate cancer with an initial PSA value of ≥10ng/ml, the proportions at 1 yr with no subsequent testing or only elevated PSA test values >3ng/ml were 21.7% (95% CI: 19.5, 23.9), 25.2% (95% CI: 23.9, 26.6), and 47.7% (95% CI: 46.2, 49.1) for those aged 50–59, 60–69, and 70–79 yr, respectively. No significant changes were noticed when stratifying by comorbidities. Limitations include the lack of detail from patient medical charts. This detail would have allowed for more accurate assessment of appropriate clinical follow-up. Conclusions Regardless of medical history, a large proportion of men with PSA≥10ng/ml were not followed appropriately at 1 yr after the index PSA test. This may partially explain why opportunistic testing is not as effective as screening within trials to reduce prostate cancer mortality. Patient summary For men aged 50–69 yr, who undertake a prostate-specific antigen (PSA) test, a PSA level of >10ng/ml should prompt further investigation. However, we found that one out of 10 of these men did not receive repeat testing within 1 yr of the initial test. This may partially explain why opportunistic prostate cancer testing is less effective than screening trials.

ObjectiveAssess the cost-effectiveness of no screening and quadrennial magnetic resonance imaging (MRI)-based screening for prostate cancer using either Stockholm3 or prostate-specific antigen (PSA) test as a reflex test.MethodsTest characteristics were estimated from the STHLM3-MR study (NCT03377881). A cost-utility analysis was conducted from a lifetime societal perspective using a microsimulation model for men aged 55-69 in Sweden for no screening and three quadrennial screening strategies, including: PSA≥3ng/mL; and Stockholm3 with reflex test thresholds of PSA≥1.5 and 2ng/mL. Men with a positive test had an MRI, and those MRI positive had combined targeted and systematic biopsies. Predictions included the number of tests, cancer incidence and mortality, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Uncertainties in key parameters were assessed using sensitivity analyses.ResultsCompared with no screening, the screening strategies were predicted to reduce prostate cancer deaths by 7-9% across a lifetime and were considered to be moderate costs per QALY gained in Sweden. Using Stockholm3 with a reflex threshold of PSA≥2ng/mL resulted in a 60% reduction in MRI compared with screening using PSA. This Stockholm3 strategy was cost-effective with a probability of 70% at a cost-effectiveness threshold of €47,218 (500,000 SEK).ConclusionsAll screening strategies were considered to be moderate costs per QALY gained compared with no screening. Screening with Stockholm3 test at a reflex threshold of PSA≥2ng/mL and MRI was predicted to be cost-effective in Sweden. Use of the Stockholm3 test may reduce screening-related harms and costs while maintaining the health benefits from early detection.

The International Society of Urological Pathology (ISUP) hosts a reference image database supervised by experts with the purpose of establishing an international standard in prostate cancer grading. Here, we aimed to identify areas of grading difficulties and compare the results with those obtained from an artificial intelligence system trained in grading. In a series of 87 needle biopsies of cancers selected to include problematic cases, experts failed to reach a 2/3 consensus in 41.4% (36/87). Among consensus and non-consensus cases, the weighted kappa was 0.77 (range 0.68–0.84) and 0.50 (range 0.40–0.57), respectively. Among the non-consensus cases, four main causes of disagreement were identified: the distinction between Gleason score 3 + 3 with tangential cutting artifacts vs. Gleason score 3 + 4 with poorly formed or fused glands (13 cases), Gleason score 3 + 4 vs. 4 + 3 (7 cases), Gleason score 4 + 3 vs. 4 + 4 (8 cases) and the identification of a small component of Gleason pattern 5 (6 cases). The AI system obtained a weighted kappa value of 0.53 among the non-consensus cases, placing it as the observer with the sixth best reproducibility out of a total of 24. AI may serve as a decision support and decrease inter-observer variability by its ability to make consistent decisions. The grading of these cancer patterns that best predicts outcome and guides treatment warrants further clinical and genetic studies. Results of such investigations should be used to improve calibration of AI systems.

Vitamin D may reduce mortality from prostate cancer (PC). We examined the associations of post-treatment plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations with PC mortality. Participants were PC cases from the New South Wales Prostate Cancer Care. All contactable and consenting participants, at 4.9 to 8.6 years after diagnosis, were interviewed and had plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) measured in blood specimens. Cox regression allowing for left-truncation was used to calculate adjusted mortality hazards ratios (HR) and 95% confidence intervals (95% CI) for all-cause and PC-specific mortality in relation to vitamin D levels and other potentially-predictive variables. Of the participants (n = 111; 75·9% response rate), there were 198 deaths from any cause and 41 from PC in the study period. Plasma 25(OH)D was not associated with all-cause or PC-specific mortality (p-values > 0·10). Plasma 1,25(OH)2D was inversely associated with all-cause mortality (HR for highest relative to lowest quartile = 0·45; 95% CI: 0·29–0·69), and PC-specific mortality (HR = 0·40; 95% CI: 0·14–1·19). These associations were apparent only in men with aggressive PC: all-cause mortality HR = 0·28 (95% CI·0·15–0·52; p-interaction = 0·07) and PC-specific mortality HR = 0·26 (95% CI: 0·07–1.00). Time spent outdoors was also associated with lower all-cause (HR for 4th relative to 1st exposure quartile = 0·42; 95% CI: 0·24–0·75) and PC-specific (HR = 0·48; 95% CI: 0·14–1·64) mortality, although the 95% CI for the latter was wide. The inverse association between post-treatment plasma 1,25(OH)2D levels and all-cause and PC-specific mortality in men with aggressive PC, suggest a possible beneficial effect of vitamin D supplementation in these men.

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012–2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41–65%), avoid 76% (95% CI: 67–81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6–40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. Patient summary We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer.

Objective: Research suggests some men on active surveillance for low risk, localised prostate cancer, will opt for treatment before evidence of disease progression due to anxiety or uncertainty. This study aims to explore the experiences of men (and their partners) on active surveillance, to further understand the perceived benefits, challenges, and facilitators for adherence, in order to inform person‐centred support. Methods: Semi‐structured, qualitative interviews were conducted with participants (13 males currently or previously on active surveillance, 5 female partners) via telephone or face‐to‐face. Interviews were audiotaped, transcribed verbatim, and thematically analysed. Results: The majority of participants described active surveillance in a positive, nonchalant manner. However, some participants described feeling concerned, anxious, or worried before follow‐up appointments, often due to a fear of cancer progression. Despite this, most participants did not desire additional psychological support, as it had already been accessed or was considered unnecessary. Several factors appeared to facilitate their adherence and influence their experience, including their perception of cancer, the doctor‐patient relationship, and the coping strategies they used (e.g., seeking information online and preparing for the future). Conclusions: This study provides an insight into the facilitators, coping strategies, and views of men and partners who adhered to active surveillance (at least until disease progression). Most participants had adequate access to support and experienced few concerns, although fears were often heightened before appointments. The experiences, needs, and attitudes illustrated in this study may be used to develop effective person‐centred support for men on active surveillance at risk to leaving prematurely.

This study aimed to investigate the expression of programmed death receptor ligand 1 (PD-L1) and deficient mismatch repair (dMMR) in ductal adenocarcinoma of the prostate. A tissue microarray of 32 ductal and 42 grade-matched acinar adenocarcinomas was used. Slides were stained for PD-L1, PD-L2, MMR proteins, CD4 and CD8. PD-L1 expression in tumor cells was only seen in 3% (1/34) of ductal and 5% (2/42) of acinar adenocarcinomas (p = 1.0), while PD-L1 expression in tumor-infiltrating immune cells was seen in 29% (10/34) of ductal and 14% (6/42) of acinar adenocarcinomas (p = 0.16). dMMR, as defined by loss of one or more of the MMR proteins, was identified in 5% (4/73) of cases, including 1 ductal and 3 acinar adenocarcinomas. There was a suggested association between infiltration of CD8+ lymphocytes and ductal subtype (p = 0.04) but not between CD4+ lymphocytes and tumor type (p = 0.28). The study shows that both dMMR and PD-L1 expression is uncommon in tumor cells of both ductal and acinar adenocarcinoma of the prostate, while PD-L1 expression in tumor-infiltrating immune cells is a more common finding.

Background Active surveillance (AS) is increasingly utilized for low-risk prostate cancers, to delay or avoid treatment. Objective To (1) describe uptake and surveillance intensity of real-world use of AS and compare with national guidelines, and (2) describe transitions from conservative to curative treatment by different indications of disease progression. Design, setting, and participants A population-based cohort study of men diagnosed with low-risk prostate cancer, in Stockholm County, Sweden, during 2008–2017. Follow-up was up to 10 yr, with a median of 3.5 yr. Outcome measurements and statistical analysis Poisson regression was used to estimate incidence rate ratios of prostate-specific antigen (PSA) testing and biopsies. Cox regression was used to estimate hazard ratios of starting curative treatment. Results and limitations A total of 6021 men with low-risk prostate cancer were included in the analysis; 3116 (52%) had AS recorded as the intended primary management (AS cohort). During 1, 2, and 3 yr after diagnosis, the frequencies of at least one PSA test were 90%, 92%, and 88%, respectively, and those of postdiagnostic surveillance biopsies were 42%, 19% and 18%, respectively. During surveillance, 13% of men in the AS cohort were upgraded on rebiopsy, with Gleason upgrading being the strongest factor for starting curative treatment. One limitation is the generalizability to other populations because of differences between surveillance protocols and clinical settings. Conclusions Our results show that AS is underutilized and that monitoring differs from current guidelines. Optimization of AS protocols is important in order to increase adherence and avoid overtreatment. Patient summary Active surveillance has the potential to reduce overtreatment and avoid treatment-related side effects. Our results show that few men receive the recommended monitoring.

ObjectiveGiven a man’s current prostate- specific antigen (PSA) level, age and family history of prostate cancer, what are the benefits (decreased risk of higher Gleason score [GS] cancer at diagnosis) and harms (increased risk of false-positive biopsy recommendation) of waiting 1, 2, 3, 4 or 5–8 years until the next PSA test?DesignProspective cohort.SettingAll PSA tested men in Stockholm, Sweden, between 2003 and 2015.ParticipantsMen aged 50–74 years with at least two PSA tests between 2003 and 2015 (n=174 636).Main outcome measuresLog-binomial regression to calculate the risk ratio (RR) of GS ≥7 and GS 6 versus benign outcome at prostate biopsy and 12-year cumulative probability of experiencing a false-positive biopsy by testing interval, age, PSA level and first-degree family history.ResultsMen with PSA ≤1 ng/mL had low risk of GS ≥7 prostate cancer irrespective of testing interval; 3 at the next testing occasion, and of the 663 men biopsied after the next PSA test only 32 (5%) had GS ≥7 cancer. Men with PSA >1 ng/mL had increased risk of being diagnosed with GS ≥7 prostate cancer when screened with longer than annual intervals (RRs ranged from 1.4 to 3.2 depending on PSA level and testing interval). The results were consistent across age groups and family history status. This benefit needs to be balanced against the increased risk for false-positive biopsy recommendation with shorter testing intervals (twofold for annual vs biennial and threefold for annual vs triennial).ConclusionsMen aged 50–74 years with PSA ≤1 ng/mL can wait 3–4 years before having a new PSA test. For men with PSA >1 ng/mL, we observed an increased risk of being diagnosed with GS ≥7 prostate cancer with longer than annual testing intervals. This benefit needs to be balanced against the markedly increased risks for false-positive biopsy recommendations with shorter testing intervals recommendations.

Background: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. Methods: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. Results: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23–1.28) and 1.18 (95% CI: 1.14–1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index ⩾1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98–2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50–2.22) compared with those without bone fracture. Conclusions: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.

Summary Objectives Infections are a common cause of hospitalization in breast cancer patients. We studied the risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. Methods A Swedish registry-based study including 8338 breast cancer patients diagnosed between 2001 and 2008, followed prospectively for infection-related hospitalizations until 2010. Standardized incidence ratios (SIRs) were calculated using background rates from the general female population. Associations with clinical characteristics and mortality were analyzed using flexible parametric survival models. Results In total, 720 patients experienced an infection-related hospitalization during a median follow-up of 4.9 years. Infection rates were highest within the first year of diagnosis (SIR = 5.61, 95% CI; 4.98–6.32), and site-specific risks were most pronounced for sepsis (SIR = 3.14, 95% CI; 2.66–3.71) and skin infections (SIR = 2.80, 95% CI; 2.24–3.50). Older age at diagnosis, comorbidities, markers of tumor aggressiveness, chemotherapy and axillary node dissection were independent predictors of infectious disease risk. Infection-related hospitalizations were also independently associated with overall and breast cancer-specific death. Conclusions A significant number of breast cancer patients are hospitalized with an infection following diagnosis, which in turn predicts poor prognosis. The risk profile of infection-related hospitalizations is multifactorial, including patient, tumor and treatment-related factors.

Background: Infection-related hospitalizations are a serious complication in breast cancer patients, resulting in treatment delay, prolonged hospitalization and future morbidity and mortality. Little, however, is known about the actual risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. Methods: We conducted a prospective population-based study including 7071 women diagnosed with primary invasive non-metastatic breast cancer between 2001 and 2008 in the Stockholm-Gotland region (Sweden), with complete follow-up until 2010. Standardized incidence ratios (SIRs) for infection-related hospitalizations (overall and by site) were estimated using background rates from the general female population, matched on age and calendar period. Associations with clinical characteristics and breast cancer outcomes (breast cancer death, distant metastasis and locoregional recurrence) were analysed using flexible parametric survival models. Results: During a medium follow-up of 5.3 years, 657 hospital admissions with infections were observed and 1,2 and 5-year cumulative risks were 3.4, 4.7 and 8.1% respectively. Rates of infection-related hospitalizations were increased compared to the general female population (SIR = 2.12; 95% CI = 1.96-2.29) and site-specific SIRs were most pronounced for sepsis (SIR = 3.65; 95% CI = 3.13-4.26) and skin infections (SIR = 2.93; 95% CI = 2.35-3.64). The overall risk of infections was highest during the first year (SIR = 5.06; 95% CI, 4.46-5.74), and recurrent disease contributed to the long-term risk observed. Older age at diagnosis, chemotherapy, axillary radiotherapy, comorbidities and markers of tumor aggressiveness (large tumors, estrogen receptor negative tumors and lymph node positive tumors) were independent predictors of infectious disease risk. Analyses evaluating the prognostic impact of infections revealed an independent effect on breast cancer death and distant metastasis, associations that were mainly driven by sepsis (HR = 4.53; 95% CI, 3.25-6.33 and 1.69; 95% CI, 1.04-2.79 respectively). No association was found with future risk of locoregional recurrence. Conclusions: Physicians and patients should be aware of the risk of serious infections which persists beyond the initial treatment period. Infection-related hospitalizations are an independent marker of poor prognosis. Further research is needed to elucidate the role of sepsis in breast cancer progression. Citation Format: Brand JS, Colzani E, Johansson A, Giesecke J, Clements M, Bergh J, Hall P, Czene K. Infectious disease hospitalization in breast cancer patients: Risk and impact on prognosis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-22.

Background Risk prediction models and magnetic resonance imaging (MRI) of the prostate can reduce unnecessary biopsies and overdiagnosis of low-risk prostate cancer. However, it is unclear how these tools should be used in concert. Objective To develop a unified risk prediction model (S3M-MRI) that combines the Stockholm3 score (based on protein and genetic markers and clinical variables) and Prostate Imaging-Reporting and Data System v.2 scores modified for MRI without contrast (modPI-RADS). Design, setting, and participants We used data for 532 men from the prospective multicentre STHLM3-MRI diagnostic study to construct S3M-MRI. We compared S3M-MRI to Stockholm3 and modPI-RADS alone with respect to model discrimination, calibration, and net benefit. We also compared clinical outcomes for five diagnostic strategies according to the use of combinations of the three models. Results and limitations The area under the receiver operating characteristic curve (AUC) was 0.88 (95% confidence interval [CI] 0.85–0.91) for S3M-MRI, which was significantly higher (p = 0.04) than for Stockholm3 (0.86, 95% CI 0.83–0.89) and modPI-RADS (0.83, 95% CI 0.79–0.87). S3M-MRI had a higher net benefit on decision curve analysis for clinically relevant probability thresholds for biopsy recommendation in comparison to Stockholm3 and modPI-RADS. However, for different diagnostic strategies, sequential use of Stockholm3 followed by MRI only for Stockholm3-positive men resulted in a similar number of unnecessary biopsies (64 vs 69) and diagnosed International Society of Urological Pathology (ISUP) grade group 1 cancers (56 vs 51) at similar sensitivity for ISUP grade group ≥2 cancers, while avoiding 38% of MRI scans. Limitations include the ethnically homogeneous study population. Conclusions The unified S3M-MRI model was superior to the Stockholm3 model and modPI-RADS alone. However, the S3M-MRI improvement was marginal compared to sequential use of Stockholm3 followed by MRI, and resulted in 60% more MRI scans. Patient summary A new risk prediction model combining clinical variables, genetic and protein biomarkers, and results from prostate magnetic resonance imaging improved the clinical outcome performance of prostate cancer diagnostics.

Continuous glucose monitoring (CGM) has been demonstrated in randomized trials to improve glucose control in patients with type 1 diabetes (1), but until recently only a minority of participants in the German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registry and the U.S.-based T1D Exchange (T1DX) registry were using CGM (2,3). Over the past decade, both the accuracy and usability of CGM devices have improved considerably with expanded cost coverage of CGM by government statutory and private insurance. Some CGM devices are regulatory body approved for determining insulin dose in most circumstances, thereby reducing the number of fingersticks needed to monitor blood glucose. To assess change in CGM use over time across the age spectrum, we analyzed data from the T1DX and DPV registries for the years 2011, 2013, 2015, and 2017. CGM use (including both real-time and intermittent scanning CGM) at each data collection time point were obtained from clinic medical records. The number of participants with available data on CGM usage varied slightly depending on the calendar year for both registries. In DPV, the cohort size ranged from 17,632 to 21,707 for youth (aged 2 to

Ductal adenocarcinoma of the prostate (DAC) has morphological similarities to adenocarcinomas of other organs. DAC behaves in an aggressive manner and may present with metastases. These metastases may occur at unusual sites, which itself may cause diagnostic difficulties. It is important for therapeutic decisions that a prostatic origin of these metastases be established. Our aim was to compare the protein expression of DAC and adenocarcinomas of colon, endometrium, lung, pancreas, stomach and urinary bladder. A tissue microarray was constructed using 60 DAC, 6 colonic, 7 endometrial, 7 lung, 5 pancreatic, 5 gastric, and 9 urinary bladder adenocarcinomas. Slides were stained for estrogen, progesterone and androgen receptor, prolactin, PSA, prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK, p63, p504s, c-Myc, EGFR, Ki-67, p16, p21, p27, p53, PTEN, ERG, and PAX-8. Androgen receptor, prostein, PSA, and PSAP were almost invariably expressed in DAC. Ki-67-labeling index was lower in DAC than in other adenocarcinomas. The expression patterns of intestinal markers and cytokeratins in DAC were less specific and may lead to diagnostic errors if not combined with prostate-specific markers.

Background A decreased risk of prostate cancer (PCa) has been suggested in men taking aspirin, statins and metformin, although the evidence has been conflicting. We estimated the association between prescribed medications, prostate specific antigen (PSA) levels and the risk of either any PCa or high-grade PCa. Methods This population-based cohort study included 185,667 men having a first recorded PSA test and 18,574 men having a first prostate biopsy in Stockholm County, Sweden for the period 2007–2012. Detailed clinical information including PSA levels, biopsy results, comorbidities and educational level were obtained from population-based registers. High-grade prostate cancer was defined as a Gleason score of seven or higher. Differences in PSA levels by medication status were estimated using linear regression on log PSA values. PCa risk was estimated using multivariate logistic regression. Results Compared with men who were not on medication, the PSA level at the first PSA test was lower among men using 75 mg/dose aspirin (−3.9% change in PSA concentration; 95% confidence interval (CI): −5.8 to −2.1), statin (−4.6%; 95% CI: −6.2 to −2.9), metformin (−14%; 95% CI: −17 to −12) and insulin (−16%; 95% CI: −18 to −14). Men using any statins had an increased risk of both high-grade PCa (odds ratio (OR) 1.25; 95% CI: 1.10–1.42) and PCa of any grade (OR 1.16; 95% CI 1.04–1.29). There were no significant associations between aspirin or any antidiabetic medication and the risk of PCa. Conclusion We found no protective effect of aspirin, statins or antidiabetics in terms of risk for any PCa or high-grade PCa. Use of any statins was associated with an elevated risk of being diagnosed with high-grade prostate cancer.

New technologies such as human papillomavirus (HPV) testing and vaccination necessitate comprehensive policy analyses to optimize cervical cancer prevention. To inform future Scandinavian-specific policy analyses, we aimed to provide an overview of cervical cancer epidemiology and existing prevention efforts in Denmark, Norway and Sweden. We compiled and summarized data on current prevention strategies, population demography and epidemiology (for example, age-specific HPV prevalence and cervical cancer incidence over time) for each Scandinavian country by reviewing published literature and official guidelines, performing registry-based analyses using primary data and having discussions with experts in each country. In Scandinavia, opportunistic screening occurred as early as the 1950s and by 1996, all countries had implemented nationwide organized cytology-based screening. Prior to implementation of widespread screening and during 1960-66, cervical cancer incidence was considerably higher in Denmark than in Norway and Sweden. Decades of cytology-based screening later (i.e. 2010-2014), cervical cancer incidence has been considerably reduced and has converged across the countries since the 1960s, although it still remains lowest in Sweden. Generally, Scandinavian countries face similar cervical cancer burdens and utilize similar prevention approaches; however, important differences remain. Future policy analyses will need to evaluate whether these differences warrant differential prevention policies or whether efforts can be streamlined across Scandinavia.

Aims: Despite efforts to standardise grading of prostate cancer, even among experts there is still a considerable variation in grading practices. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading. Methods and results: The International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology reviewed independently microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval = 0.62-0.72) and consensus was reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed considerable disagreement. Once a two-thirds majority was reached, images were moved automatically into a public database available for all ISUP members at www.isupweb.org. Non-members are able to access a limited number of cases. Conclusions: It is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease interobserver variability. It will also help to identify instances where definitions of grades need to be clarified.

BackgroundKnowledge about the relationship between PSA, age and ISUP grade group (ISUP) 1 prostate cancer can improve clinical and biological understanding of prostate cancer. We aimed to investigate the associations between PSA and age and the risk of ISUP 1 and ISUP ≥ 2 prostate cancer, respectively.MethodsWe included 6 083 men aged 50-69 biopsied with a total of 72 996 individual biopsy cores from the prospective and population based Stockholm3 diagnostic study. We computed the risk of ISUP 1 and ISUP ≥ 2 prostate cancer and their respective associations with PSA and age. Since lower Gleason grades often are masked by higher grades in the overall Gleason score, we compared associations both for overall Gleason score and for Gleason on individual biopsy cores.ResultsISUP 1 prostate cancer was not significantly associated with PSA at diagnosis: odds ratios ranged from 0.82 (95%CI: 0.68-1.00) for PSA 3-4 ng/mL, 0.96 (95%CI: 0.79-1.16) for PSA 4-6 ng/mL, 0.95 (95%CI: 0.75-1.21) for PSA 6-10 ng/mL, and 0.92 (95%CI: 0.58-1.45) for PSA 10-15 ng/mL compared with PSA 2-3 ng/mL. Age was not significantly associated with risk of ISUP 1 cancer. This contrasts to the strong relationship between ISUP ≥ 2 prostate cancer and its respective associations with PSA and age.ConclusionsWe find no significant association between the risk of ISUP 1 prostate cancer and PSA and age at diagnosis indicating that PSA contribution from ISUP 1 prostate cancer is closer to that of benign prostate tissue than to that of ISUP ≥ 2 prostate cancer.

BACKGROUND: Metastatic breast cancer is a severe condition without curative treatment. How relative and absolute risk of distant metastasis varies over time since diagnosis, as a function of treatment, age and tumour characteristics, has not been studied in detail. METHODS: A total of 9514 women under the age of 75 when diagnosed with breast cancer in Stockholm and Gotland regions during 1990-2006 were followed up for metastasis (mean follow-up=5.7 years). Time-dependent development of distant metastasis was analysed using flexible parametric survival models and presented as hazard ratio (HR) and cumulative risk. RESULTS: A total of 995 (10.4%) patients developed distant metastasis; the most common sites were skeleton (32.5%) and multiple sites (28.3%). Women younger than 50 years at diagnosis, with lymph node-positive, oestrogen receptor (ER)-negative, >20 mm tumours and treated only locally, had the highest risk of distant metastasis (0-5 years' cumulative risk =0.55; 95% confidence interval (CI): 0.47-0.64). Women older than 50 years at diagnosis, with ER-positive, lymph node-negative and ≤20-mm tumours, had the same and lowest cumulative risk of developing metastasis 0-5 and 5-10 years (cumulative risk=0.03; 95% CI: 0.02-0.04). In the period of 5-10 years after diagnosis, women with ER-positive, lymph node-positive and >20-mm tumours were at highest risk of distant recurrence. Women with ER-negative tumours showed a decline in risk during this period. CONCLUSION: Our data show no support for discontinuation at 5 years of clinical follow-up in breast cancer patients and suggest further investigation on differential clinical follow-up for different subgroups of patients.

Background Because of the long latent period of asbestos-related mesothelioma, investigators suggest that the high incidence of this disease will continue in the coming decades. Objectives We describe the time trends of mesothelioma incidence and its relationship to historical consumption of asbestos in Hong Kong and project future trends of mesothelioma incidence. Methods We obtained local annual consumption of total asbestos for 1960–2006 (converted to kilograms per person per year). Age-standardized incidence rates (ASIRs) of mesothelioma were computed and depicted on graphs using the centered moving average method. Indirectly standardized rates were regressed on a transformation of consumption data that assumed that the latency between asbestos exposure and mesothelioma diagnosis followed a normal distribution with a mean ± SD of 42 ± 10.5 years. Results ASIRs for males started to increase substantially in 1994 and were highest in 2004; for females, ASIRs climbed in the 1980s and in the early 1990s but have fluctuated without obvious trends in recent years. The highest asbestos consumption level in Hong Kong was in 1960–1963 and then decreased sharply afterward. Using past asbestos consumption patterns, we predict that the mesothelioma incidence rate for males will peak in 2009, with the number of cases peaking in 2014, and then slowly decline in the coming decades. Conclusions Hong Kong experienced an epidemic of mesothelioma from 2000 to 2006 that corresponded with the peak of local asbestos consumption in the early 1960s assuming an average latent period of 42 years. The incidence is anticipated to decline in the coming decades but may not decrease back to the background risk level (the risk unrelated to asbestos exposure).

To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D).International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-18 years and ≥ 1 year duration of T1D) enrolled in the T1D Exchange (n = 11,435) and the Diabetes Prospective Follow-up (n = 21,501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed.Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P.001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P.001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant.Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D.

We aim to determine the relationship between season, personal solar UV exposure, serum 25(OH)D and 1,25(OH)2D and serum prostate-specific antigen (PSA) levels. Questionnaire data and blood samples were collected at baseline from participants of the Concord Health and Ageing in Men Project (n = 1,705), aged 70 and above. They were grouped as men ‘free of prostate disease’ for those with no record of having prostate cancer, benign prostatic hyperplasia, or prostatitis and with serum PSA levels below 20 ng/mL, and ‘with prostate disease’ for those with a record of either of these diseases or with serum PSA levels 20 ng/mL or above. Personal solar UV exposure (sUV) was estimated from recalled hours of outdoor exposure and weighted against ambient solar UV radiation. Sera were analysed to determine levels of PSA, 25(OH)D and 1,25(OH)2D, and analysed using multiple regression, adjusting for age, BMI and region of birth. The association between sUV and serum PSA levels was conditional upon season (p interaction = 0.04). There was no direct association between serum PSA and 25(OH)D in both groups of men. There was a positive association between serum PSA and 1,25(OH)2D in men with prostate disease (mean = 110.6 pmol/L; p heterogeneity = 0.03), but there was no such association in men free of prostate disease (mean = 109.3 pmol/L; p heterogeneity = 0.8). The association between PSA and sUV may only be evident at low solar UV irradiance, and this effect may be independent of serum vitamin D levels.

BACKGROUND: Cancer is a serious health issue in China, but accurate national counts for cancer incidence are not currently available. Knowledge of the cancer burden is necessary for national cancer control planning. In this study, national death survey data and cancer registration data were used to calculate the cancer burden in China using a Bayesian approach. METHODS: Cancer mortality and incidence rates for 2004-2005 were obtained from the National Cancer Registration database. The third National Death Survey (NDS), 2004-2005 database provided nationally representative cancer mortality rates. Bayesian modeling methods were used to estimate mortality to incidence (MI) ratios from the registry data and national incidence from the NDS for specific cancer types by age, sex and urban or rural location. RESULTS: The total estimated incident cancer cases in 2005 were 2,956,300 (1,762,000 males, 1,194,300 females). World age standardized incidence rates were 236.2 per 100,000 in males and 168.9 per 100,000 in females in urban areas and 203.7 per 100,000 and 121.8 per 100,000 in rural areas. CONCLUSIONS: MI ratios are useful for estimating national cancer incidence in the absence of representative incidence or survival data. Bayesian methods provide a flexible framework for smoothing rates and representing statistical uncertainty in the MI ratios. Expansion of China's cancer registration network to be more representative of the country would improve the accuracy of cancer burden estimates

The objective of this study is to describe a method for estimating the number of cancer survivors requiring different types of cancer care in the future. Methods Colon cancer data (1972–2007) from the New South Wales (NSW) Central Cancer Registry were used to estimate prevalence in 2008–2017, which was then divided into five phases of care (initial, post-treatment monitoring, treatment for recurrence and second colon cancer, long-term survivors and last year of life). Patterns of care study data were used to calculate the type and number of treatments required by patients in initial care. Results There were 17,375 patients living in NSW who had a past diagnosis of first primary colon cancer in 2007. Our statistical model suggests that by 2017, this number will have increased to 22,671. At least 2,430 patients are expected to require initial surgery for colon cancer in 2017, and of these, 753 will also require adjuvant chemotherapy. Furthermore, an additional 538 cases will require therapy due to cancer recurrence (307) or a second primary colon cancer (231). Conclusion Our proposed method provides more complete estimates of future cancer care needs. With some modifications, this method can be used to estimate the future prevalence of many major cancer types in many other jurisdictions. Implications for Cancer Survivors Our proposed method can be a useful tool for planning future cancer care with the goal of improving the cancer survivorship experience for survivors, their caregivers and their families.

PURPOSE: Lower urinary tract symptoms (LUTS) are very common among older men globally, but evidence regarding the relationship between LUTS and country of origin is limited. This study aimed to investigate the relationship between the prevalence of LUTS and region of birth in a large, ethnically diverse population of older men resident in New South Wales, Australia. METHODS: Data on LUTS, demographic and behavioural factors were collected by postal questionnaire from 2006 to 2009 and analysed for 95,393 men aged 45 and over from the 45 and Up Study, who had not had previous prostate surgery. Logistic regression was used to investigate the association between region of birth and moderate/severe LUTS, ascertained using a modified International Prostate Symptom Score, adjusting for age, income, education, alcohol consumption and smoking. RESULTS: Overall, 18,530 (19.4 %) men had moderate or severe LUTS. Compared to Australian-born men, prevalence of moderate/severe LUTS was significantly higher in men born in the Middle East & North Africa, Southeast Asia and North America regions (adjusted odds ratios (OR) = 1.43; 95 % CI = 1.23-1.66, OR = 1.25; 1.10-1.42, OR = 1.26; 1.05-1.52, respectively), whereas men from the UK & Ireland had significantly lower prevalence (OR = 0.85; 0.80-0.90). Patterns of association were generally similar for storage- and voiding-related types of LUTS. However, participants born in Sub-Saharan Africa showed a significantly elevated prevalence of moderate/severe voiding symptoms (1.22; 1.03-1.45) but not storage symptoms, compared to Australian-born respondents. CONCLUSION: The prevalence of LUTS and of specific subtypes of LUTS varies according to region of birth

5050The Stockholm-3 (STHLM3) Model can improve prostate cancer testing in men 50-69 years compared to current clinical practiceBackground: The Stockholm-3 model (STHLM3) is a combination of 6 plasm...

Ecological studies in predominantly European populations have reported higher cancer survival in areas of higher solar ultraviolet (UV) B irradiation, perhaps due to a cancer protective effect of vitamin D synthesized photochemically in the skin. Such studies have not been done in developing countries, perhaps because of lack of cancer registries that can do outcome follow-up. One minus the mortality-to-incidence ratio (1-MIR), however, can be used as a measure of survival, and MIR as a measure of fatality, in developing country cancer registries. We analyzed the association between ambient solar UVB and MIR in China.National cancer registration data in 32 counties of China in 2004-2005 were used to estimate MIR by age, sex, and area. The accuracy of 1-MIR as a measure of survival was assessed in the Cixian County cancer registry. Contemporary satellite measurements of cloud-adjusted ambient UVB intensity at 305 nm were taken from an NASA database and spatial Kriging methods used to estimate the average daily irradiance in each county. We estimated mortality hazard ratios (HRs) per 10 mW/m(2) of UVB for all cancers together, and the ten commonest cancer types by fitting a generalized linear model assuming mortality had a binomial distribution conditional on the sum of mortality and incidence, adjusted for sex, age, and location.The 5-year survival proportions for the main cancer types were in good agreement with 1-MIR in Cixian County. MIR ratios for all cancers combined were inversely associated with ambient UVB in men (HR = 0.96, 95% CI 0.93-0.99) and women (HR = 0.91, 95% CI 0.88-0.94) and in urban (HR = 0.95, 95% CI 0.94-0.96) and rural areas (HR = 0.90, 95% CI 0.87-0.93). Similar inverse associations were present for cancers of esophagus, stomach, and bladder in both sexes together and breast cancer in women. They were present in urban residents for all major cancers except liver cancer, bladder cancer, and breast cancer in women. For rural residents, most HRs were1.0 but, with the exception of breast cancer, their upper 95% confidence bounds were1.0.Ambient UVB was significantly inversely associated with MIR for all cancers together and four of ten cancer types. Solar UVB may increase survival from some cancers in China.

Background The National Cervical Screening Program in Australia currently recommends that women aged 18–69 years are screened with conventional cytology every 2 years. Publicly funded HPV vaccination was introduced in 2007, and partly as a consequence, a renewal of the screening program that includes a review of screening recommendations has recently been announced. This study aimed to provide a baseline for such a review by quantifying screening program resource utilisation and costs in 2010. Methods A detailed model of current cervical screening practice in Australia was constructed and we used data from the Victorian Cervical Cytology Registry to model age-specific compliance with screening and follow-up. We applied model-derived rate estimates to the 2010 Australian female population to calculate costs and numbers of colposcopies, biopsies, treatments for precancer and cervical cancers in that year, assuming that the numbers of these procedures were not yet substantially impacted by vaccination. Results The total cost of the screening program in 2010 (excluding administrative program overheads) was estimated to be A$194.8M. We estimated that a total of 1.7 million primary screening smears costing $96.7M were conducted, a further 188,900 smears costing $10.9M were conducted to follow-up low grade abnormalities, 70,900 colposcopy and 34,100 histological evaluations together costing $21.2M were conducted, and about 18,900 treatments for precancerous lesions were performed (including retreatments), associated with a cost of $45.5M for treatment and post-treatment follow-up. We also estimated that $20.5M was spent on work-up and treatment for approximately 761 women diagnosed with invasive cervical cancer. Overall, an estimated $23 was spent in 2010 for each adult woman in Australia on cervical screening program-related activities. Conclusions Approximately half of the total cost of the screening program is spent on delivery of primary screening tests; but the introduction of HPV vaccination, new technologies, increasing the interval and changing the age range of screening is expected to have a substantial impact on this expenditure, as well as having some impact on follow-up and management costs. These estimates provide a benchmark for future assessment of the impact of changes to screening program recommendations to the costs of cervical screening in Australia.

36 Background: Prostate-specific antigen (PSA) is used to screen for prostate cancer but suffers from a high false-positive rate that translates into unnecessary prostate biopsies and over-diagnosis of low-risk prostate cancers. We aimed to develop a model for prostate cancer screening with better test characteristics than PSA. Methods: STHLM3 is a prospective, population-based, paired screen-positive diagnostic study. It investigates whether the predefined STHLM3 model, a combination of 6 plasma protein biomarkers (PSA, free-PSA, intact-PSA, HK2, MIC-1, and MSMB), genetic polymorphisms (232 SNPs), and clinical variables (age, family history, previous biopsies, DRE, and prostate volume) can substantially reduce the proportion of men biopsied while maintaining the same sensitivity to diagnose Gleason score ≥ 7 prostate cancer as PSA ≥3 ng/ml. In addition, a health economic evaluation was performed comparing the STHLM3 model with current clinical practice in Stockholm. Results: 58,818 men without prostate cancer aged 50-69, participated in the STHLM3 study, with 6,700 undergoing subsequent prostate biopsy. The STHLM3 model performed significantly better (p

Background/Aims: Hepatocyte progenitors have frequently been cultured from rodents but reports from human liver are rare. Methods: Non-parenchymal cell fraction isolated from 19 explant livers (removed at orthotopic liver transplantation for acute or chronic liver disease) and histologically normal human liver was cultured. Results: Proliferating epithelioid colonies were identifiable after 2–3 weeks culture as a very rare event (Conclusion: Although there is clear histological evidence of hepatocyte precursors in human explant livers, predictable culture of such cells with differentiation toward mature hepatocyte phenotype remains elusive.

who reported that risk of prostate cancer follow-ing diagnosis of nonmelanoma skin cancers was reduced to agreater extent in those living in sunny countries (specificallyAustralia, Singapore and Spain) than in those living in lesssunny countries. The report of Tuohimaa et al.isproblematic.Australia, represented in this analysis only by the New SouthWales Central Cancer Registry (NSWCCR), cannot have beenincluded in the results Grant and Garland cite. The NSWCCRdoes not and has never registered basal and squamous cell car-cinomas of the skin. Moreover, the results of Tuohimaa et al.cannot be used to make valid inferences about associationsbetween sun exposure and cancer. The reasons are well sum-marized in an IARC Working Group report:‘‘The incidence of second cancers in individuals is elevatedby several known and unknown mechanisms, includingcommon aetiological factors and predispositions, andinfluenced by possible biases in the ascertainment of sec-ond cancers in the cancer registries. The net direction ofthese influences will mostly be in the direction of elevatedoccurrence of second cancers, against which a possibleeffect of sunlight and vitamin D (manifest through theoccurrence of NMSC [non-melanoma skin cancer]) couldbe difficult to detect with the type of cohort design thathas been used in these studies and the lack of informationon known risk factors in many of the studies.’’

Introduction Obesity and overweight have a range of health effects, yet little evidence is available on their effect on hospitalisation. This study quantifies the risk of hospitalisation relating to overweight and obesity. Methods 241 949 45 and Up Study participants with linked hospital admissions and death data were followed from recruitment (February 2006 onwards) through to June 2009. Self-reported height and weight were used to classify patients into BMI categories, using cut-points of 15, 18.5, 20, 22.5, 25, 27.5, 30 and 35 kg/m 2 . Rates of incident hospitalisation by BMI were compared using Cox regression, adjusting for a range of confounders. Results Preliminary results on the first 103 040 participants show incident hospitalisation rates to be 299 (95% CI 294 to 304) per 1000 person years for males and 248 (95% CI 243 to 252) for females. Compared with those of healthy-weight (BMI 20–22.5 kg/m 2 ), rates in those with severe obesity (BMI 35–50 kg/m 2 ) were higher among males (HR: 1.36, 95% CI 1.21 to 1.54) and females (HR: 1.52; 95% CI 1.38 to 1.67). There were clear gradients as weight increased from healthy to higher BMI, more so among females than males, and in people aged 45–64 compared to those aged 65–84, with no evidence of increasing risk of hospitalisation with increasing BMI in those aged over 85. Conclusions Given the excess risk of hospitalisation among overweight and obese individuals, the burden to the health system attributable to overweight and obesity is likely to be substantial, particularly among middle-age adults. High BMI was not significantly related to hospitalisation in the elderly.

A positive association between solar UV exposure and micronuclei (MN) frequency (biomarker of chromosome breakage or loss) was previously reported with the effect of solar UV exposure on DNA damage greater when serum vitamin D (25(OH)D) levels were insufficient ( Citation Format: Visalini Nair-Shalliker, Varinderpal Dhillon, Mark Clements, Bruce K. Armstrong, Michael Fenech. The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes, in a population of healthy adults in South Australia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2514. doi:10.1158/1538-7445.AM2013-2514