Clinical procedures used to diagnose inflammatory bowel disease: real-world evidence from a Danish nationwide population-based study.

OBJECTIVE: Although clinical guidelines exist, the diagnostic work-up for diagnosing inflammatory bowel disease (IBD) is complex and varies in clinical practice. This study used real-life data to characterise the current diagnostic procedures used to establish IBD diagnoses in a Danish nationwide setting. DESIGN: Person-level data on patients diagnosed with IBD between 1 January 2014 and 30 June 2018 were linked between Danish health registers. Information on age, sex, registration of other gastrointestinal diseases, and diagnostic procedures (endoscopies, biopsies, and imaging) performed in relation to the first IBD hospital admission was analysed for the total study population and was stratified by IBD type, sex, and age. RESULTS: The majority of the 12 871 patients with IBD included underwent endoscopy (84%), had a biopsy taken (84%), and/or underwent imaging procedures (44%). In total, 7.5% of the population (6% for Crohn's disease and 8% for ulcerative colitis) were diagnosed with IBD despite not undergoing any of these diagnostic procedures. Patients with Crohn's disease underwent more procedures than patients with ulcerative colitis (94% vs 92%, p<0.001). Children underwent slightly fewer diagnostic procedures than adults (92% vs 93%, p=0.004). Slightly more men underwent at least one procedure than women (92% vs 94%, p<0.001). CONCLUSION: For 7.5% of patients with IBD, this study did not detect any registrations of the recommended diagnostic procedures for establishing an IBD diagnosis. Further research is needed to examine whether these findings are mainly explained by limitations of the register data or also indicate shortcomings of the general approach to IBD.

Forecasting lung cancer incidence, mortality, and prevalence to year 2030.

BACKGROUND: Lung cancer incidence and prevalence is increasing worldwide and there is a focus on prevention, early detection, and development of new treatments which will impact the epidemiological patterns of lung cancer. The clinical characteristics and the trends in incidence, mortality, and prevalence of lung cancer in Denmark from 2006 through 2015 are described and a model for predicting the future epidemiological profile of lung cancer through 2030 is introduced. METHODS: The study population comprised all cases of lung cancer, registered in the Danish Cancer Registry, who were alive on January 1, 2006 or had a first-time ever diagnosis of lung cancer during 2006 through 2015. Information on morphology, stage of the disease, comorbidity and survival was obtained from other Danish health registers. Based on NORDCAN data and estimated patient mortality rates as well as prevalence proportions for the period 2006 through 2015, future case numbers of annual incidence, deaths, and resulting prevalence were projected. RESULTS: A total of 44.291 patients were included in the study. A shift towards more patients diagnosed with lower stages and with adenocarcinoma was observed. The incidence increased and the patient mortality rate decreased significantly, with a doubling of the prevalence during the observation period. We project that the numbers of prevalent cases of lung cancer in Denmark most likely will increase from about 10,000 at the end of 2015 to about 23,000 at the end of 2030. CONCLUSIONS: Our findings support that lung cancer is being diagnosed at an earlier stage, that incidence will stop increasing, that mortality will decrease further, and that the prevalence will continue to increase substantially. Projections of cancer incidence, mortality, and prevalence are important for planning health services and should be updated at regular intervals.

End-of-life anticancer treatment - a nationwide registry-based study of trends in the use of chemo-, endocrine, immune-, and targeted therapies.

BACKGROUND: Anticancer treatments near the end of a patient's life should generally be avoided, as it leaves the patient with no significant anticancer effect but increases the risk of severe side effects. We described the pattern of all end-of-life anticancer treatment in a population of Danish cancer patients. METHODS: Using the Danish national health registries, we identified all patients deceased due to cancer 2010-2015. Anticancer treatment registered in the last 30 days of life was categorized as end-of-life treatment. Predictors of such treatment were investigated using logistic regression models. RESULTS: We identified 42,277 patients (median age 70 years) of whom 16% received end-of-life anticancer treatment. This proportion did not change during the study period (p = .09). Chemotherapy alone was the most frequent treatment, accounting for 78% of all end-of-life treatment in 2010, decreasing to 71% in 2015. In contrast, end-of-life use of immunotherapy, targeted therapy and endocrine therapy increased during the study period. Breast cancer as index cancer was associated with the highest frequency of end-of-life treatment (23%), followed by malignant melanoma (21%), and prostate cancer (18%). Factors associated with lower odds for end-of-life treatment were female sex, older age, high burden of comorbidity, and being diagnosed >6 months prior to death. CONCLUSIONS: We found a stable overall rate at 16% of patients receiving anticancer treatment within one month prior to death in this nationwide sample of cancer deaths. Further research is needed to assess whether this level of end-of-life treatment is justified or reflects inappropriate use.

Characteristics of finasteride users in comparison with nonusers: A Nordic nationwide study based on individual-level data from Denmark, Finland, and Sweden.

PURPOSE: Published epidemiological studies on the association between finasteride use and the risk of male breast cancer have been inconclusive due to methodological limitations including a few male breast cancer cases included. Determinants of male breast cancer have been studied, but it remains unexplored whether these are also related to finasteride use and thereby constitute potential confounders. This study aimed to assess whether there are differences between finasteride users and nonusers with regard to numerous potential confounders. METHODS: In total, 246 508 finasteride users (≥35 years) were identified in the prescription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). An equal number of nonusers were sampled. The directed acyclic graph (DAG) methodology was used to identify potential confounders for the association between finasteride and male breast cancer. A logistic regression model compared finasteride users and nonusers with regard to potential confounders that were measurable in registries and population surveys. RESULTS: Finasteride users had higher odds of testicular abnormalities (odds ratio [OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exogenous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabetes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry or in high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), living in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70; 0.50-0.99) compared to nonusers. CONCLUSIONS: Systematic differences between finasteride users and nonusers were found emphasizing the importance of confounder adjustment of associations between finasteride and male breast cancer.

Long-Term Outcome of Patients Operated with Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment.

PURPOSE: To determine the long-term outcome of patients operated with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD) and to identify potential predictors for poor visual outcome. METHODS: Prospective, observational 30-month study of patients operated for primary RRD with PPV. Examinations were performed preoperatively and after months 2, 6, and 30. RESULTS: Eighty-four patients (84 eyes) were included and 73 (86.9%) participated at month 30. The macula was attached in 30 (35.7%) patients at primary operation. The majority of patients (n = 59, 80.8%) achieved a good final best corrected visual acuity (BCVA ≤0.3 logMAR, ≥0.5 Snellen) with a better outcome in patients with the macula attached than detached (0.02 vs. 0.17 logMAR, p = 0.007). Variables associated with poor visual outcome were baseline BCVA >0.3 logMAR (p = 0.03), female gender (p = 0.02), silicone oil (p = 0.03), and larger areas of retinal detachment (p = 0.01). In multivariable regression analysis, female gender (OR = 8.5 [95% CI 1.8-39.8]) was the strongest risk factor for poor visual outcome. CONCLUSION: The majority of patients operated for primary RRD achieved a reasonable long-term visual outcome. Notably, female gender was associated with poor visual outcome, indicating a need for closer follow-up.

Patient reported outcome data as performance indicators in surgically treated lung cancer patients.

OBJECTIVE: Quality in lung cancer care is in Denmark routinely evaluated using quality indicators. The indicators are reported from national registries and are based on data from health care professionals. However, data based on the patients' perspective are rarely reported. The aim of this study was to propose a model for the use of patient reported outcomes (PROs) as quality indicators, enabling us to compare PROs across the surgical departments in Denmark. METHODS: All patients registered in the Danish Lung Cancer Registry (DLCR) from 1 October 2013 until 30 September 2015 who received surgical treatment were eligible (N = 1718). They were asked to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire six months after surgery. From QLQ-C30 we chose global health status (GHS) and role function (RF) as indicators to be tested. An indicator threshold for good performance was set to ≥ 65 points (on a scale 0-100 where 100 was the best). Results were compared between the four thoracic surgical departments in Denmark. RESULTS: Of 1615 patients alive six months after surgery, questionnaires were completed by 1002 patients (62.0%). The patients from the four departments differed significantly in clinical variables at diagnosis, and the departments differed significantly in the surgical procedures performed. After adjustment for case-mix, the patients in Department 2 had a better RF than patients from the other departments. CONCLUSION: Significant differences in RF and in the fulfilment of the indicator requirement for RF were observed. Since these findings might indicate differences in the quality of performance between participating departments, subsequent audit is recommended. The analyses and results indicate that it is feasible to use PROs as supplementary outcome indicators in the evaluation of the quality of surgical treatment for lung cancer. Our model could serve as a useful foundation for further research.

Finasteride Use and Risk of Male Breast Cancer: A Case-Control Study Using Individual-Level Registry Data from Denmark, Finland, and Sweden.

BACKGROUND: In case reports, concerns have been raised as to whether finasteride use increases the risk of male breast cancer. Previous epidemiologic evidence on the potential link is conflicting. This study aimed to assess whether an association between finasteride use and male breast cancer exists after accounting for potential confounders. METHODS: The source population consisted of all men (≥35 years) from Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). Cases with incident male breast cancer were identified in the cancer registries and matched with 50 density-sampled, age, and country-matched male population controls per case. Exposure information on finasteride use was derived from the prescription registries. Potential confounders were identified using the directed acyclic graph methodology and measured by use of information from nation-wide registries. RESULTS: The study population comprised 1,005 male breast cancer cases and 43,058 controls. Confounder-adjusted odds of finasteride exposure were not statistically significantly increased [OR, 1.09; 95% confidence interval (CI), 0.77-1.54] in breast cancer cases relative to controls. There was no evidence of a dose-response relationship, as the group with greatest exposure to finasteride was associated with lowest OR of male breast cancer [OR, 0.72 (95% CI, 0.40-1.30)]. Sensitivity analyses did not reveal marked changes in results with different exposure definitions or for specific subgroups. CONCLUSIONS: Results from this study provided no evidence that finasteride use was associated with male breast cancer. IMPACT: This large confounder-adjusted study supports the view that exposure to finasteride is not associated materially with male breast cancer risk.

Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease.

BACKGROUND: Anti-tumor necrosis factor-α (TNF-α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti-TNF therapy among patients with CD or UC. AIM: A new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti-TNF response. METHODS: Fifty-three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender). RESULTS: Ten SNPs were associated with anti-TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02-3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00-1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02-1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33-0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24-4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27-0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06-2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44-0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01-2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65-0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01-1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57-0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66-1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04)). CONCLUSIONS: The results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF-α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti-TNF therapy. Our multi-SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.

Patient-reported outcomes (PROs) in lung cancer: Experiences from a nationwide feasibility study.

OBJECTIVES: Our objectives were to examine the feasibility of a nationwide collection of patient-reported outcomes (PROs) in a lung cancer population as well as in various sub-populations, and to describe the characteristics of responders compared to non-responders. MATERIALS AND METHODS: All patients diagnosed with lung cancer in Denmark are registered in the Danish Lung Cancer Registry (DLCR). The 7,295 patients registered in DLCR from 1 October 2013 until 30 September 2015 who had received treatment were eligible. Using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 questionnaires, we employed two different methods of delivery, resulting in two different project parts. In project part 1, the baseline questionnaire was handed out at the hospital departments before treatment. The following questionnaires were sent out as paper versions three times within one year. In project part 2, all questionnaires were electronic versions delivered in association with planned hospital visits. RESULTS: Of the 7,295 lung cancer patients 4,229 (58%) completed at least one questionnaire, and 2,459 completed two or more. Only 562 baseline questionnaires were returned before treatment (7.7%), whereas 43.4%-57.4% of the potential responders completed the following questionnaires. The best response rates were achieved among patients treated with surgery and among patients who discussed their questionnaires with health care personnel. When comparing patient characteristics, responders had a significantly better health and a higher socioeconomic position than non-responders. CONCLUSION: A decentralised model used for delivering the initial questionnaire to the patients was insufficient. It is our estimation that sending out electronic versions of the baseline questionnaires, as was done with the following questionnaires, would result in a significantly better patient coverage. Despite the severe morbidity and high mortality rate in lung cancer, reasonable response rates were achieved at follow-ups to this method, and PRO collection in this population was feasible.

The Influence of Antidepressants on the Disease Course Among Patients With Crohn's Disease and Ulcerative Colitis-A Danish Nationwide Register-Based Cohort Study.

BACKGROUND: Psychiatric comorbidity might modify the disease course adversely in patients with inflammatory bowel disease (IBD). Treatment options include antidepressants, which, apart from improving mood, have anti-inflammatory properties that might modify the disease course. This nationwide study aimed to examine the influence of antidepressants on the disease course among patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Patients registered with an incident diagnosis of CD or UC in the Danish National Patient Register (2000-2017) were included. Information on antidepressant use and proxy measures of disease activity (health care and drug utilization) was extracted from national population registers. Poisson regression was performed to estimate disease activity rates by antidepressant use adjusted for confounders. Furthermore, the analyses were performed stratified by IBD subtype and type of antidepressants. RESULTS: A total of 42,890 patients were included (UC: 69.5%; CD: 30.5%). When adjusted for confounders, a lower incidence rate of disease activity was found among antidepressant users compared with nonusers in both CD (incidence rate ratio [IRR], 0.75; 95% confidence interval [CI], 0.68-0.82) and UC (IRR, 0.90; 95% CI, 0.84-0.95) patients. Further, markedly lower rates of disease activity were found among CD (IRR, 0.51; 95% CI, 0.43-0.62) and UC (IRR, 0.67; 95% CI, 0.59-0.75) patients with no use of antidepressants before IBD onset. CONCLUSIONS: In this nationwide study, antidepressant use was found to be beneficial on the disease course among patients with UC and CD, particularly in patients with no use of antidepressants before IBD onset. Randomized controlled trials are warranted to investigate the potential of antidepressants being an adjunct treatment to conventional IBD therapy.

Excess medical comorbidity and mortality across the lifespan in schizophrenia.: A nationwide Danish register study.

INTRODUCTION: People with severe mental illness have greater risk of un-detected and inadequately treated medical disorders, adding up to the risk of premature death. This study investigated how chronic medical comorbidity evolved across the lifespan in schizophrenia and the associated impact on mortality. METHOD: A register-based retrospective nested case-control study was conducted, identifying incident cases of cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), cancer and diabetes, as well as mortality due to these diseases, across the lifespan in schizophrenia. SAMPLE: A schizophrenia cohort consisting of 4924 individuals aged 18-40 years registered with a diagnosis of schizophrenia (ICD-8: 295.0-3 + 295.9) during admission to a psychiatric hospital unit in 1970-79. Schizophrenia cases were age and gender matched with 22,597 controls in the general population. RESULTS: Rate ratio (RR) of CVD and cancer were similar to controls. The RR of COPD and diabetes were increased across the lifespan. The probability of having been diagnosed prior to dying from CVD, cancer, pulmonary diseases or diabetes was markedly reduced in schizophrenia cases compared to controls. The RR of all-cause mortality and mortality from CVD, COPD and diabetes remained elevated in all age groups in schizophrenia. Registration of medical comorbidity was associated with increased survival. CONCLUSION: Excess medical comorbidity persists across the lifespan and into older age. No age-related decrease in incidence of major chronic medical comorbidities in schizophrenia was found except for diabetes.

Topographical distribution of sentinel nodes and metastases from T1-T2 oral squamous cell carcinomas.

OBJECTIVE: The objective is to investigate the topographical distribution of sentinel nodes (SNs) and lymph node metastases in T1-2cN0 oral squamous cell carcinomas (OSCCs). METHODS: The study entailed a prospective enrolment of 220 patients with clinical T1-2N0 OSCCs who underwent preoperative lymphoscintigraphy (LSG) followed by gamma probe-guided sentinel lymph node biopsy (SLNB). Patients with positive SNs were treated with completion neck dissection. Excised lymph nodes were grouped into the neck level according to the international guidelines. RESULTS: The SN detection rate by LSG was 99.1%. Patients with midline tumours had bilateral lymphatic drainage on LSG in 15/21 (71.5%). There were 45/199 (22.6%) patients with lateralised tumours that had unexpected bilateral or contralateral drainage patterns on LSG. Fifty-five patients (25.0%) were SLNB positive, and metastases were found in 72/781 (9.2%) of the excised SNs. Metastatic involvement of neck level IV was rare and only observed in patients with anterior tongue cancer. No patients had level V involvement. Eleven patients developed isolated cervical recurrences, with no new primary tumour as origin. The SLNB procedure ensured an overall sensitivity of 83.3% and a negative predictive value of 93.3%. CONCLUSION: Completion neck dissection of level I-III in SLNB-positive patients might be sufficient in most patients with OSCC except patients with anterior tongue cancer, but further studies are needed to support this potential therapeutic algorithm. Our study showed that SLNB was helpful in clarifying unexpected bilateral or contralateral metastatic drainage patterns. In our cohort, 8/55 patients with occult metastasis would have been missed by elective neck dissection of the ipsilateral neck.

Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries.

A potential link has been suggested between dispensed finasteride and increased risk of male breast cancer (MBC). Due to the rare occurrence of MBC, it remains to be established if such a relationship exists. The purpose of this study was to combine nationwide registers in four countries to assess the potential association between dispensed finasteride and MBC. A cohort of all males with dispensed finasteride in Denmark, Finland, Norway, and Sweden (1,365,088 person years) was followed up for up to 15 years for breast cancer, and compared to a cohort of males unexposed to finasteride. Individual-level register data included country, dates of dispensed finasteride, MBC diagnosis, and death. Incidence rate ratios (IRRs) were estimated using a generalized linear model with a Poisson distribution. An increased risk of MBC was found among finasteride users (IRR = 1.44, 95% confidence interval [95% CI] = 1.11-1.88) compared to nonusers. The IRR increased to 1.60 (95% CI = 1.20-2.13) when users in Norway and Sweden with short follow-up time were excluded. The highest IRR was seen among men with medium duration of dispensed finasteride, medium accumulated consumption of finasteride, and among men with first dispensed finasteride prescription 1-3 years prior to diagnosis. The analyses suggested possible ascertainment bias and did not support a clear relationship between dispensed finasteride and MBC. In conclusion, a significant association between dispensed finasteride and MBC was identified. However, due to limited data for adjustment of potential confounding and surveillance bias in the present study, further research is needed to confirm these results.

Magnetic Resonance Signal Intensity Ratio Measurement Before Uterine Artery Embolization: Ability to Predict Fibroid Size Reduction.

PURPOSE: To evaluate whether the magnetic resonance imaging (MRI) signal intensity (SI) ratio between the dominant fibroid and the periphery striated muscle can predict fibroid volume reduction >50% after uterine fibroid embolization (UFE). MATERIALS AND METHODS: From October 2013 until May 2016, 52 patients were included in this prospective study. The SI ratio before UFE was calculated using circular region of interests placed on the dominant fibroid and the iliac muscle. The SI fibroid-to-iliac muscle ratio was calculated as SI of the dominant fibroid/SI of the iliac muscle on T1-, T2-, and T1 post-contrast-weighted sequences. The dominant fibroid volume was measured and analyzed before and after UFE. RESULTS: In all, 46 patients who completed the three-month follow-up MRI were available for analysis. The correlation between SI fibroid-to-muscle ratio at the T2-weighted sequence and imaging volume reduction outcome was statistically significant (p < 0.002). All other parameters showed no statistically significant reduction in fibroid volume: (p < 0.68) for SI ratio at T1-weighted, (p < 0.13) for SI ratio at T1 post-contrast, and (p < 0.58) for fibroid volume. Spearman's rank showed positive correlation (r = 0.439, p < 0.003) between the fibroid-to-muscle SI ratio on T2-weighted sequence. The area under curve (AUC) for SI fibroid-to-muscle ratio on T2-weighted sequence was 0.776. For the other parameters, the AUC values were 0.512, 0.671, and 0.578, respectively. CONCLUSION: SI dominant fibroid-to-muscle ratio at T2-weighted sequence before UFE was significantly related to dominant fibroid volume reduction after UFE and may be used for better patient selection.

Transfer between hospitals as a predictor of delay in diagnosis and treatment of patients with Non-Small Cell Lung Cancer - a register based cohort-study.

BACKGROUND: Lung cancer is the second most frequent cancer diagnosis in Denmark. Although improved during the last decade, the prognosis of lung cancer is still poor with an overall 5-year survival rate of approximately 12%. Delay in diagnosis and treatment of lung cancer has been suggested as a potential cause of the poor prognosis and as consequence, fast track cancer care pathways were implemented describing maximum acceptable time thresholds from referral to treatment. In Denmark, patients with lung cancer are often transferred between hospitals with diagnostic facilities to hospitals with treatment facilities during the care pathway. We wanted to investigate whether this organizational set-up influenced the time that patients wait for the diagnosis and treatment. Therefore, the objective of this study was to uncover the impact of transfer between hospitals on the delay in the diagnosis and treatment of Non-Small Cell Lung Cancer (NSCLC). METHODS: We performed a historical prospective cohort study using data from the Danish Lung Cancer Registry (DLCR). All patients diagnosed with primary NSCLC from January 1st 2008 to December 31st 2012 were included. Patients with unresolved pathology and incomplete data on the dates of referral, diagnosis and treatment were excluded. RESULTS: A total of 11 273 patients were included for further analyses. Transfer patients waited longer for treatment after the diagnosis, (Hazard ratio (HR) 0.81 (0.68-0.96)) and in total time from referral to treatment (HR 0.84 (0.77-0.92)), than no-transfer patients. Transfer patients had lower odds of being diagnosed (Odds Ratio (OR) 0.82 (0.74-0.94) and treated (OR 0.66 (0.61-0.72) within the acceptable time thresholds described in the care pathway. CONCLUSION: Fast track cancer care pathways were implemented to unify and accelerate the diagnosis and treatment of cancer. We found that the transfer between hospitals during the care pathway might cause delay from diagnosis to treatment as well as in the total time from referral to treatment in patients with Non Small-Cell Lung Cancer. The difference between no-transfer and transfer patients persists after adjusting for known predictors of delay.

Cancer of unknown primary: Registered procedures compared with national integrated cancer pathway for illuminating external validity.

Cancer of unknown primary (CUP) ranges within top 10 cancers in both incidence and mortality. As primary identification is crucial to choosing treatment, guidelines on CUP emphasize the diagnostic strategy. Whether guidelines are complied with, or if they are indeed helpful, is however unclear. We compared procedures performed in suspected CUP patients with recommendations of national guidelines to assess external validity of guidelines.The Danish National Patient Registry (NPR) comprising population data was utilized to identify the suspected CUP patients during 2009 to 2010 and explore exposure to procedures and patient survival. The cohort was investigated in terms of validity of diagnosis through cross-referencing with the Cancer Registry (CR), which served as gold standard for cancer diagnoses and patients' cancer histories.The NPR cohort consisted of 542 patients (275 males, 264 females) of whom 210 (38.7%) had a CUP diagnosis confirmed. Within the cohort, 347 patients (64.0%) had a registration in CR matching with the NPR registration. Exposure to diagnostic procedures included biopsy (n = 439, 81.0%) and image modalities (n = 532, 98.2%). Survival was poor with 67 (12.4%) individuals alive after 4 years.The validity of a CUP diagnosis in NPR was low when using data from CR as reference. More than half the suspected CUP patients had a previous cancer diagnosis with CUP being the most frequent. Patients were diagnosed in compliance with guidelines indicating high external validity, but less than 1 quarter had their primary identified and the 1-year survival was approximately 20%. Research is needed to develop efficacious methods for primary detection.

Uterine fibroid embolization with acrylamido polyvinyl microspheres: prospective 12-month clinical and MRI follow-up study.

Background Uterine fibroid embolization (UFE) is an effective minimally invasive treatment aimed to obtain complete fibroid infarction. Purpose To evaluate the degree of fibroid infarction after embolization with acrylamido polyvinyl alcohol microspheres (Bead Block). Material and Methods This prospective study included 26 pre-menopausal women in the period October 2013 to January 2015. UFE with the use of Bead Block microspheres 700-900 µm was obtained until flow stasis was achieved. Contrast-enhanced magnetic resonance imaging (MRI) was used to define residual contrast enhancement in the total fibroid burden and enhancement >10% was defined as insufficient embolization. The dominant fibroid volume and total uterine volume changes were assessed. Clinical outcome was analyzed using the quality of life questionnaire (UFS-QOL). Results Twenty-four of the 26 patients (92%) had a technically successful UFE with complete flow-stop in both uterine arteries. Twenty-two of the 26 patients (85%) completed 3 months of MRI control and 20 patients (77%) completed 12 months of MRI control. There were 16 of 22 patients (73%) with complete fibroid burden infarction and/or without residual contrast enhancement of the fibroids of more than 10% at 3 months of control. Six of 22 patients (27%) had insufficient fibroid burden infarction with residual contrast enhancement of more than 10%. Twenty-two and 18 of 26 patients completed the 3-month and 12-month questionnaire, respectively. UFS-QOL analyses showed that 91% of the patients had significant clinical improvement. Conclusion Sixteen of the 22 patients had complete fibroid burden infarction using Bead Block microspheres (700-900 µm); however, unacceptably high insufficient fibroid burden infarction in almost one-fourth of the patients were recorded.

20-year follow-up study of Danish HHT patients-survival and causes of death.

BACKGROUND: Hereditary Haemorrhagic Telangiectasia (HHT) is a dominantly inheritable disorder, with a wide variety of clinical manifestations due to presence of multiple arteriovenous manifestations. The most common mutations are found in HHT1 (ENG) and HHT2 (ACVRL1) patients, causing alterations in the TGF-ß pathway which is responsible for angiogenesis. Modulations of angiogenesis may influence cancer rates. The objective of the study was to evaluate 20-year survival according to HHT subtype, as well as to evaluate differences in causes of death comparing HHT patients and controls. We also wanted to investigate whether cancer morbidity among HHT patients differs from that among controls. RESULTS: We included all HHT patients in the County of Fyn, Denmark, prevalent as of January 1st 1995 in total 73 HHT patients. In addition three age- and sex- matched controls per HHT patient were evaluated, in total 218 controls (one was lost due to registration failure). The controls were defined at start of follow-up in 1995. Information on lifestyle factors was not available. A total of 32 (44%) HHT patients and 97 (44%) controls passed away during follow-up. The survival curves were evenly distributed showing similar survival rates in the two groups. Cancer diagnoses had been registered in the follow-up period in 4 (5%) HHT patients and in 38 (17%) controls. CONCLUSION: The mortality was not increased among Danish HHT patients compared to controls. This study is based on a clinical unselected series of HHT patients with the whole spectrum of severity, independent of need for medical care. Our data also suggest that HHT patients to a lesser degree than the background population are affected by cancer.

Site-specific identification of heparan and chondroitin sulfate glycosaminoglycans in hybrid proteoglycans.

Heparan sulfate (HS) and chondroitin sulfate (CS) are complex polysaccharides that regulate important biological pathways in virtually all metazoan organisms. The polysaccharides often display opposite effects on cell functions with HS and CS structural motifs presenting unique binding sites for specific ligands. Still, the mechanisms by which glycan biosynthesis generates complex HS and CS polysaccharides required for the regulation of mammalian physiology remain elusive. Here we present a glycoproteomic approach that identifies and differentiates between HS and CS attachment sites and provides identity to the core proteins. Glycopeptides were prepared from perlecan, a complex proteoglycan known to be substituted with both HS and CS chains, further digested with heparinase or chondroitinase ABC to reduce the HS and CS chain lengths respectively, and thereafter analyzed by nLC-MS/MS. This protocol enabled the identification of three consensus HS sites and one hybrid site, carrying either a HS or a CS chain. Inspection of the amino acid sequence at the hybrid attachment locus indicates that certain peptide motifs may encode for the chain type selection process. This analytical approach will become useful when addressing fundamental questions in basic biology specifically in elucidating the functional roles of site-specific glycosylations of proteoglycans.

Cancer risk and mortality after kidney transplantation: a population-based study on differences between Danish centres using standard immunosuppression with and without glucocorticoids.

BACKGROUND: Kidney recipients receive immunosuppression to prevent graft rejection, and long-term outcomes such as post-transplant cancer and mortality may vary according to the different protocols of immunosuppression. METHODS: A national register-based historical cohort study was conducted to examine whether post-transplant cancer and all-cause mortality differed between Danish renal transplantation centres using standard immunosuppressive protocols including steroids (Centres 2, 3, 4) or a steroid-free protocol (Centre 1). The Danish Nephrology Registry, the Danish Civil Registration System, the Danish National Cancer Registry and the Danish National Patient Register were used. A historical cohort of 1450 kidney recipients transplanted in 1995-2005 was followed up with respect to post-transplant cancer and death until 31 December 2011. RESULTS: Compared with Center 1 the adjusted post-transplant cancer risk was 6-39% lower in Centre 3 [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.67-1.32], in Centre 2 (HR 0.72, 95% CI 0.52-0.98) and in Centre 4 (HR 0.61, 95% CI 0.44-0.83). Compared with Center 1, the adjusted post-transplant mortality was 21-55% higher in Centre 4 (HR 1.21, 95% CI 0.91-1.61), in Centre 3 (HR 1.35, 95% CI 0.98-1.86) and in Centre 2 (HR 1.55, 95% CI 1.17-2.05). On average, post-transplant cancer was associated with a 4-fold increase in the risk of death (HR 4.25, 95% CI 3.36-5.38). CONCLUSIONS: There was a tendency of a higher post-transplant cancer occurrence, but lower all-cause mortality, in the Danish transplantation centre that adhered to a standard steroid-free immunosuppressive protocol.