Safety and effectiveness of the radium-223-taxane treatment sequence in patients with metastatic castration-resistant prostate cancer in a global observational study (REASSURE).

BACKGROUND: Radium-223 and taxane chemotherapy each improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). Whether the radium-223-taxane sequence could extend survival without cumulative toxicity was explored. METHODS: The global, prospective, observational REASSURE study (NCT02141438) assessed real-world safety and effectiveness of radium-223 in patients with mCRPC. Using data from the prespecified second interim analysis (data cutoff, March 20, 2019), hematologic events and overall survival (OS) were evaluated in patients who were chemotherapy-naive at radium-223 initiation and subsequently received taxane chemotherapy starting ≤90 days ("immediate") or >90 days ("delayed") after the last radium-223 dose. RESULTS: Following radium-223 therapy, 182 patients received docetaxel (172 [95%]) and/or cabazitaxel (44 [24%]); 34 patients (19%) received both. Seventy-three patients (40%) received immediate chemotherapy and 109 patients (60%) received delayed chemotherapy. Median time from last radium-223 dose to first taxane cycle was 3.6 months (range, 0.3-28.4). Median duration of first taxane was 3.7 months (range, 0-22.0). Fourteen patients (10 in the immediate and four in the delayed subgroup) had grade 3/4 hematologic events during taxane chemotherapy, including neutropenia in two patients in the delayed subgroup and thrombocytopenia in one patient in each subgroup. Median OS was 24.3 months from radium-223 initiation and 11.8 months from start of taxane therapy. CONCLUSIONS: In real-world clinical practice settings, a heterogeneous population of patients who received sequential radium-223-taxane therapy had a low incidence of hematologic events, with a median survival of 1 year from taxane initiation. Thus, taxane chemotherapy is a feasible option for those who progress after radium-223. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02141438. PLAIN LANGUAGE SUMMARY: Radium-223 and chemotherapy are treatment options for metastatic prostate cancer, which increase survival but may affect production of blood cells as a side effect. We wanted to know what would happen if patients received chemotherapy after radium-223. Among the 182 men treated with radium-223 who went on to receive chemotherapy, only two men had severe side effects affecting white blood cell production (neutropenia) during chemotherapy. On average, the 182 men lived for 2 years after starting radium-223 and 1 year after starting chemotherapy. In conclusion, patients may benefit from chemotherapy after radium-223 treatment without increasing the risk of side effects.

Implementation of remote general movement assessment using the in-motion instructions in a high-risk norwegian cohort.

BACKGROUND: General Movement Assessment (GMA) is recommended for early detection of risk for cerebral palsy but requires trained clinical experts. We aimed to implement home- and hospital-based filming for remote GMA in a Norwegian high-risk infant cohort, as well as evaluating parents' experiences in filming their infant at home. METHODS: This knowledge translational study used a prospective cohort design including participants referred to neurodevelopmental follow-up across three sites in the Central Norway Regional Health Authority. Two home films of the fidgety type of general movements were collected between 12+1-14+6 and 15+1-17+6 weeks after term by parents. An additional film was collected at the hospital between 12+1 and 17+6 weeks after term. The instructional guide for all filming was the In-Motion App standards. Videos were transferred to a remote GMA team and classified as either "GMA scorable" or "GMA not scorable" based on Prechtl's GMA standards. Parents responded to an online survey using a 5-point Likert scale to collect information about their perspectives, experiences, and possible worries by filming their infant at home. RESULTS: One-hundred-and-two infants from 95 families participated. Ninety-two (96.8%) families transferred 177 home-based videos. Eighty-four (92%) of these had 95 videos taken in their local hospital. All 177 home-videos were "GMA scorable" and three (3,1%) out of 95 hospital-based videos were classified as "GMA not scorable". Eight families did not respond to the survey and two families did not receive the survey due to a technical error. Seventy-eight (91.7%) respondents agreed or strongly agreed that it was easy to perform home filming and five (5.9%) agreed that they were more worried about their child`s development after filming at home. Almost 80% of respondents agreed that a video for GMA can be taken at home instead of in hospital. CONCLUSIONS: This study strengthens the clinical implementation of home filming by parents and remote GMA for early detection of CP in high-risk follow-up programs. The implementation of remote GMA has the potential to facilitate early intervention to improve function in children with CP in line with international recommendations. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04287166 Date of registration: 27/02/2020.

Assessment by a multidisciplinary team conference affects treatment strategy and overall survival in patients with synchronous colorectal liver metastases.

BACKGROUND: The aim of this retrospective observational study was to investigate the geographical or sex differences in patients with synchronous colorectal liver metastases (sCRLM) in terms of assessment by a multidisciplinary team conference (MDT), curative treatment, and overall survival. METHOD: All sCRLM patients in the South-East Health Care Region of Sweden from 2009 to 2015 were included (n = 615). Data were derived from the Swedish Colorectal Cancer Registry, Swedish Registry of Liver and Bile Surgery and medical records. RESULTS: Patients who had a hepatobiliary unit (HBU) at the nearest hospital were more likely to undergo liver surgery (HBU+, 37% (n = 106), compared to HBU-, 22% (n = 60); p = 0.001) and had a better median survival (p < 0.001). No sex differences were observed. In multivariate Cox regression analyses of overall survival, assessment by an MDT that included a liver surgeon was independently linked to better survival (HR 0.574, 0.433-0.760). CONCLUSION: There were no sex differences in access to liver surgery or overall survival, however, there were geographical inequalities, where residency near a hospital with HBU was associated with increased overall survival and the possibility to receive liver surgery. Assessment at MDT with liver surgeon present was associated with greater survival, indicating its important role for treatment.

The Swedish childhood tumor biobank: systematic collection and molecular characterization of all pediatric CNS and other solid tumors in Sweden.

The Swedish Childhood Tumor Biobank (BTB) is a nonprofit national infrastructure for collecting tissue samples and genomic data from pediatric patients diagnosed with central nervous system (CNS) and other solid tumors. The BTB is built on a multidisciplinary network established to provide the scientific community with standardized biospecimens and genomic data, thereby improving knowledge of the biology, treatment and outcome of childhood tumors. As of 2022, over 1100 fresh-frozen tumor samples are available for researchers. We present the workflow of the BTB from sample collection and processing to the generation of genomic data and services offered. To determine the research and clinical utility of the data, we performed bioinformatics analyses on next-generation sequencing (NGS) data obtained from a subset of 82 brain tumors and patient blood-derived DNA combined with methylation profiling to enhance the diagnostic accuracy and identified germline and somatic alterations with potential biological or clinical significance. The BTB procedures for collection, processing, sequencing, and bioinformatics deliver high-quality data. We observed that the findings could impact patient management by confirming or clarifying the diagnosis in 79 of the 82 tumors and detecting known or likely driver mutations in 68 of 79 patients. In addition to revealing known mutations in a broad spectrum of genes implicated in pediatric cancer, we discovered numerous alterations that may represent novel driver events and specific tumor entities. In summary, these examples reveal the power of NGS to identify a wide number of actionable gene alterations. Making the power of NGS available in healthcare is a challenging task requiring the integration of the work of clinical specialists and cancer biologists; this approach requires a dedicated infrastructure, as exemplified here by the BTB.

Symptoms and life changes after total pancreatectomy: a qualitative study.

BACKGROUND: Total pancreatectomy (TP) is a major surgical procedure that involves lifelong exocrine and endocrine pancreatic insufficiency. Qualitative evidence is sparse regarding patients' experiences after the operation. The aim of this study was to explore patients' experiences of symptoms that occur after TP and how these symptoms affect their health and life situations. METHODS: A qualitative design with prospective consecutive sampling and an inductive thematic analysis was used. Semistructured interviews were postoperatively performed at 6-9 months with 20 patients undergoing TP in two university hospitals in Sweden. RESULTS: Two main themes emerged from the analysis: "Changes in everyday life" and "Psychological journey". Patients experienced symptoms related to diabetes as the major life change after the operation, and they were also limited by symptoms of exocrine insufficiency, difficulties with food intake and physical weakness. In the psychological journey that patients underwent, the support received from family, friends and the health care system was important. Moreover, patients experienced a general need for more extensive information, especially regarding diabetes. CONCLUSION: Patients experience a lack of sufficient support and education after TP, particularly concerning their diabetes. Further efforts should be undertaken to improve information and the organization of diabetes care for this patient group.

Laparoscopic distal pancreatectomy is more cost-effective than open resection: results from a Swedish randomized controlled trial.

BACKGROUND: Laparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective. METHODS: This cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping. RESULTS: Fifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: -0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection. CONCLUSION: Laparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.

DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study.

AIMS: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. METHODS: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. RESULTS: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients. CONCLUSIONS: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.

Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry.

BACKGROUND: The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features. METHODS: Data prospectively accumulated over a 4-year period in the Swedish Childhood Cancer Registry from patients aged 0-18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%). RESULTS: The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4-year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis. CONCLUSION: This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement.

Real-world outcomes of second novel hormonal therapy or radium-223 following first novel hormonal therapy for mCRPC.

Aim: To evaluate real-world clinical outcomes of radium-223 or alternative novel hormonal therapy (NHT) following first-line NHT for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: Retrospective analysis of the US Flatiron database (ClinicalTrials.gov identifier: NCT03896984). Results: In the radium-223 cohort (n = 120) versus the alternative NHT cohort (n = 226), proportionally more patients had prior symptomatic skeletal events and bone-only metastases, and first-line NHT duration was shorter. Following second-line therapy, 49 versus 39% of patients received subsequent life-prolonging therapy; of these, 47 versus 76% received taxane. Median overall survival was 10.8 versus 11.2 months. Conclusion: Real-world patients with mCRPC had similar median overall survival following second-line radium-223 or alternative NHT after first-line NHT. Many patients received subsequent therapy, with less taxane use after radium-223.

Lay abstract Patients with metastatic castration-resistant prostate cancer are often first treated with novel hormonal therapy (NHT) using abiraterone or enzalutamide. To aid decisions about what treatment to use next, we reviewed information about patients who were treated with an alternative NHT (226 patients) or the nuclear medicine radium-223 (120 patients) after the first NHT. Most patients given radium-223 had cancer that had spread to their bones only, whereas many patients given an alternative NHT had cancer in their bones and other parts of their body. Around one in four patients given radium-223 and one in five given an alternative NHT had symptoms related to their bone metastases after starting treatment. Five in every ten patients given radium-223 received further therapy, including chemotherapy in 50% of these patients, while four in every ten patients given an alternative NHT received further therapy, including chemotherapy in 75%. On average, patients lived for almost a year after starting radium-223 or an alternative NHT.

Patient-reported participation in hepatopancreatobiliary surgery cancer care: A pilot intervention study with patient-owned fast-track protocols.

OBJECTIVE: Fast-track concepts have been implemented in hepatopancreatobiliary surgery cancer care to improve postoperative recovery. For optimal postoperative care, patient participation is also required. The aim was to investigate and analyse whether an intervention with patient-owned fast-track protocols (PFTPs) may lead to increased patient participation and improve information for patients who underwent surgery for hepatopancreatobiliary cancer. METHODS: A quantitative comparative design with a control and intervention group was used. The participants in the intervention group followed a PFTP during their admission. After discharge, the patients answered a questionnaire regarding patient participation. Data analyses were performed with descriptive statistics and ANCOVA. RESULTS: The results are based on a total of 222 completed questionnaires: 116 in the control group and 106 in the intervention group. It is uncertain whether the PFTP increased patient participation and information, but its use may indicate an improvement for the patient group. CONCLUSION: A successful implementation strategy for the use of PFTP, with daily reconciliations, could be part of the work required to improve overall satisfaction with patient participation. CLINICALTRIALS: gov ID: NCT04061902.

Complications and chemotherapy have little impact on postoperative quality of life after pancreaticoduodenectomy - a cohort study.

BACKGROUND: With the poor prognosis of pancreatic cancer and the high rate of postoperative complications after pancreaticoduodenectomy, it is important to evaluate how the operation affects patients' quality of life. METHODS: This single-centre study included all patients undergoing pancreaticoduodenectomy from 2006 to 2016. Quality of life was measured with two questionnaires preoperatively, and at 6 and 12 months postoperatively. Comparisons between groups were made using a linear mixed models analysis. RESULTS: Of 279 patients planned for pancreaticoduodenectomy, 245 underwent the operation. The postoperative response rates were all 80% or more. Differences were found in one domain between the early and late time periods and three domains between patients receiving and not receiving adjuvant chemotherapy. No significant differences were found between patients with and without severe postoperative complications. However, the demographic variables of age group, sex, preoperative diabetes and smoking all exerted a significant impact on postoperative quality of life. CONCLUSION: While little or no impact was shown for the factors of postoperative complications, time period and adjuvant chemotherapy, demographic data, such as age, sex, preoperative diabetes and smoking, had considerable impacts on postoperative quality of life after pancreaticoduodenectomy.

Simultaneous or staged resection of synchronous colorectal cancer liver metastases: a 13-year institutional follow-up.

BACKGROUND: This study compared postoperative outcomes and survival rates of patients who underwent simultaneous or staged resection for synchronous colorectal cancer liver metastases. METHODS: Between 2005 and 2018, 126 patients were registered prospectively at a university hospital in Sweden, 63 patients who underwent simultaneous resection were matched against 63 patients who underwent staged resection. RESULTS: The length of hospital stay was shorter for the simultaneous resection group, at 11 vs 16 days, p = <0.001. Fewer patients experienced recurrence in the simultaneous resection group 39 vs 50 patients, p = 0.012. There were no significant differences in disease-free survival and overall survival between the groups. Age (hazard ratio [HR] 1.72; 95% CI 1.01-2.94; p = 0.049) and Clavien-Dindo score (HR 2.22; 95% CI 1.06-4.67; p = 0.035) had impact on survival. CONCLUSION: Colorectal cancer with synchronous liver metastases can be resected simultaneously, and enables a shorter treatment time without jeopardizing oncological outcomes.

Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection - A DRAGON collaborative analysis of 306 patients.

BACKGROUND: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. METHODS: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. RESULTS: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p < 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR ≥2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. CONCLUSION: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.

Patient preferences and experiences of participation in surgical cancer care.

BACKGROUND: Quality cancer care necessitates opportunities for patient participation, supposedly recognizing the individual's preferences and experiences for being involved in their health and healthcare issues. Previous research shows that surgical cancer patients wish to be more involved, requiring professionals to be sensitive of patients' needs. AIMS: To explore preference-based patient participation in surgical cancer care. METHODS: A cross-sectional study was conducted. The Patient Preferences for Patient Participation tool (4Ps) was used, which includes 12 attributes of preferences for and experiences of patient participation. Data were analyzed with descriptive and comparative statistical methods. RESULTS: The results are based on a total of 101 questionnaires. Having reciprocal communication and being listened to by healthcare staff were commonly deemed crucial for patient participation. While 60% of the patients suggested that taking part in planning was crucial for their participation, they had experienced this only to some extent. Learning to manage symptoms and phrasing personal goals were items most often representing insufficient conditions for preference-based patient participation. LINKING EVIDENCE TO ACTION: To support person-centered surgical care, further efforts to suffice preference-based participation are needed, including opportunities for patients to share their experiences and engage in the planning of healthcare activities.

ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO.

OBJECTIVE: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). BACKGROUND: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. METHODS: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. RESULTS: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). CONCLUSIONS: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.

Portal vein embolization with N-butyl cyanoacrylate glue is superior to other materials: a systematic review and meta-analysis.

OBJECTIVES: It remains uncertain which embolization material is best for portal vein embolization (PVE). We investigated the various materials for effectiveness in inducing future liver remnant (FLR) hypertrophy, technical and growth success rates, and complication and resection rates. METHODS: A systematic review from 1998 to 2019 on embolization materials for PVE was performed on Pubmed, Embase, and Cochrane. FLR growth between the two most commonly used materials was compared in a random effects meta-analysis. In a separate analysis using local data (n = 52), n-butyl cyanoacrylate (NBCA) was compared with microparticles regarding costs, radiation dose, and procedure time. RESULTS: In total, 2896 patients, 61.0 ± 4.0 years of age and 65% male, from 51 papers were included in the analysis. In 61% of the patients, either NBCA or microparticles were used for embolization. The remaining were treated with ethanol, gelfoam, or sclerosing agents. The FLR growth with NBCA was 49.1% ± 29.7 compared to 42.2% ± 40 with microparticles (p = 0.037). The growth success rate with NBCA vs microparticles was 95.3% vs 90.7% respectively (p < 0.001). There were no differences in major complications between NBCA and microparticles. In the local analysis, NBCA (n = 41) entailed shorter procedure time and reduced fluoroscopy time (p < 0.001), lower radiation exposure (p < 0.01), and lower material costs (p < 0.0001) than microparticles (n = 11). CONCLUSION: PVE with NBCA seems to be the best choice when combining growth of the FLR, procedure time, radiation exposure, and costs. KEY POINTS: • The meta-analysis shows that n-butyl cyanoacrylate (NBCA) is superior to microparticles regarding hypertrophy of the future liver remnant, 49.1% ± 29.7 vs 42.2% ± 40.0 (p = 0.037). • There is no significant difference in major complication rates for portal vein embolization using NBCA, 4% (24/681), compared with microparticles, 5% (25/494) (p > 0.05). • Local data shows a shorter procedure time, 215 vs 348 mins from arrival to departure at the interventional radiology unit, and fluoroscopy time, 43 vs 96 mins (p < 0.001), lower radiation dosage, 573 vs 1287 Gycm2 (p < 0.01), and costs, €816 vs €4233 (p < 0.0001) for NBCA compared to microparticles.

Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma.

Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10-15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Tumour exosome integrins determine organotropic metastasis.

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6ß4 and α6ß1 were associated with lung metastasis, while exosomal integrin αvß5 was linked to liver metastasis. Targeting the integrins α6ß4 and αvß5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Disease prevalence and number of health care visits among members of a nationwide sports organization compared to matched controls.

BACKGROUND: Physical activity has positive effects on several diseases and may reduce the risk of morbidity and the mortality rate. Whether the prevalence of disease and health care consumption differ between the members of sports organizations and the general population has not been established. Hence, this pilot study aimed to compare the prevalence of diseases known to be associated with physical inactivity and health care consumption in members of a large non-profit sports organization and an age-, sex- and geographically matched random sample from the general population. METHODS: Subjects in two Swedish cities who exercised at least once a week and had been members for at least two years in the non-profit sports organization Friskis&Svettis were invited. A randomized age-, sex- and geographically matched sample was drawn from the general population. Data on disease prevalence (by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes) and health care consumption were retrieved using the members' personal identification numbers through a regional health care database. Between-group differences in the prevalence of disease were compared using chi2-tests and logistic regression between members and controls. Health care consumption was defined as the number of visits, stratified by primary and hospital care, and was compared using chi2-tests and Mann-Whitney U-tests. RESULTS: In total, 3015 subjects were included in each group (response rate 11%). Controls had higher prevalence rates of musculoskeletal diseases (13.3% vs. 11.6%, p = 0.047), metabolic disease (10.4% vs. 5.4%, p < 0.001), hypertension (16.6% vs. 11.7%, p < 0.001), psychiatric diseases (8.9% vs. 7.1%, p = 0.012) and lung cancer (0.4% vs. 0%, p = 0.001) than the members. The total number of health care contacts was 22% higher in the controls than in the members, whereas the proportion of subjects with at least one health care visit was larger in the members (89% vs. 79%, p < 0.001). CONCLUSIONS: The prevalence rates of lifestyle diseases related to musculoskeletal, metabolic and psychiatric diseases, hypertension and lung cancer, and the overall health care consumption, were lower among members of a sports organization than among controls. However, longitudinal studies are needed to establish a cause-effect relationship between membership and disease development.

Patient involvement in surgical care-Healthcare personnel views and behaviour regarding patient involvement.

BACKGROUND: All professions in surgical care have a responsibility to include patients in their health care. By Swedish law, all care should be done in dialogue with the patient. The essential part of health care is the meeting between patient and healthcare professional. In the interaction, a decision can be made, and needs can be identified to a safer care. Previous studies on patient participation have focussed on patients' perspectives in surgical care, but there is a paucity of studies about the personnel's perspective of estimated patient involvement in surgical care. AIM: The aim of this study was to identify and describe healthcare personnel's view and behaviour regarding patient involvement in surgical care. METHOD: A quantitative study with various professions was conducted. A validated questionnaire was used, remaining questions grouped under following areas: patient involvement, acute phase, hospital time, discharge phase and questions on employment and workplace. RESULTS: A total of 140 questionnaires were sent out to a surgical clinic in Sweden, and 102 questionnaires were answered. All professionals stated that clear information is an important part of patient involvement in surgical care. Statistically significant differences existed between the professions in the subscale information. Physicians rated their information higher than the Registered Nurses (p = 0.005) and the practical nurses did (p = 0.001). Hindrances to involving patients were lack of time and other priority tasks. CONCLUSIONS: Professionals in surgical care graded information to be the most important thing for patient involvement. Participation in important decisions, including the possibility to express personal views and ask questions, is important factors for patient involvement. Barriers against patient involvement are lack of time and prioritisation of other work activities.