Cerebral perfusion and metabolism with mild hypercapnia vs. normocapnia in a porcine post cardiac arrest model with and without targeted temperature management.

Aim: To determine whether targeting mild hypercapnia (PaCO2 7 kPa) would yield improved cerebral blood flow and metabolism compared to normocapnia (PaCO2 5 kPa) with and without targeted temperature management to 33 °C (TTM33) in a porcine post-cardiac arrest model. Methods: 39 pigs were resuscitated after 10 minutes of cardiac arrest using cardiopulmonary bypass and randomised to TTM33 or no-TTM, and hypercapnia or normocapnia. TTM33 was managed with intravasal cooling. Animals were stabilized for 30 minutes followed by a two-hour intervention period. Hemodynamic parameters were measured continuously, and neuromonitoring included intracranial pressure (ICP), pressure reactivity index, cerebral blood flow, brain-tissue pCO2 and microdialysis. Measurements are reported as proportion of baseline, and areas under the curve during the 120 min intervention period were compared. Results: Hypercapnia increased cerebral flow in both TTM33 and no-TTM groups, but also increased ICP (199% vs. 183% of baseline, p = 0.018) and reduced cerebral perfusion pressure (70% vs. 84% of baseline, p < 0.001) in no-TTM animals. Cerebral lactate (196% vs. 297% of baseline, p < 0.001), pyruvate (118% vs. 152% of baseline, p < 0.001), glycerol and lactate/pyruvate ratios were lower with hypercapnia in the TTM33 group, but only pyruvate (133% vs. 150% of baseline, p = 0.002) was lower with hypercapnia among no-TTM animals. Conclusion: In this porcine post-arrest model, hypercapnia led to increased cerebral flow both with and without hypothermia, but also increased ICP and reduced cerebral perfusion pressure in no-TTM animals. The effects of hypercapnia were different with and without TTM.(Institutional protocol number: FOTS, id 14931).

Lung tissue injury and hemodynamic effects of ventilations synchronized or unsynchronized to continuous chest compressions in a porcine cardiac arrest model.

Aim: Compare lung injury and hemodynamic effects in synchronized ventilations (between two chest compressions) vs. unsynchronized ventilations during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. Methods: Twenty pigs were randomized to either synchronized or unsynchronized group. Ventricular fibrillation was induced electrically and left for 1.5 minutes. Four minutes of basic chest compression:ventilation (30:2) CPR was followed by eight minutes of either synchronized or unsynchronized ventilations (10/min) during continuous compressions before defibrillation was attempted. Aortic, right atrial and intracerebral pressures, carotid and cerebral blood flow and cardiac output were measured. Airway monitoring included capnography and respiratory function monitor. Macro- and microscopic lung injuries were assessed post-mortem. Results: There were no significant differences between groups in any of the measured hemodynamic variables or inspiration time (0.4 vs. 1.0 s, p = 0.05). The synchronized ventilation group had lower median peak inspiratory airway pressure (57 vs. 94 cm H2O, p < 0.001), lower minute ventilation (3.7 vs. 9.4 l min-1, p < 0.001), lower pH (7.31 vs. 7.53, p < 0.001), higher pCO2 (5.2 vs. 2.5 kPa, p < 0.001) and lower pO2 (31.6 vs. 54.7 kPa, p < 0.001) compared to the unsynchronized group after 12 minutes of CPR. There was significant lung injury after CPR in both synchronized and unsynchronized groups. Conclusion: Synchronized and unsynchronized ventilations resulted in similar hemodynamics and lung injury during continuous mechanical compressions of pigs in cardiac arrest. Animals that received unsynchronized ventilations with one second inspiration time at a rate of ten ventilations per minute were hyperventilated and hyperoxygenated.Institutional protocol number: FOTS, id 6948.

Myocardial oxidative stress is increased in early reperfusion, but systemic antioxidative therapy does not prevent ischemia-reperfusion arrhythmias in pigs.

Background: Arrhythmias in the early phase of reperfusion after myocardial infarction (MI) are common, and can lead to hemodynamic instability or even cardiac arrest. Reactive oxygen species (ROS) are thought to play a key role in the underlying mechanisms, but evidence from large animal models is scarce, and effects of systemic antioxidative treatment remain contentious. Methods: MI was induced in 7 male and 7 female pigs (Norwegian landrace, 35-40 kg) by clamping of the left anterior descending artery (LAD) during open thorax surgery. Ischemia was maintained for 90 min, before observation for 1 h after reperfusion. Pigs were randomized 1:1 in an operator-blinded fashion to receive either i.v. N-acetylcysteine (NAC) from 70 min of ischemia and onwards, or 0.9% NaCl as a control. Blood samples and tissue biopsies were collected at baseline, 60 min of ischemia, and 5 and 60 min of reperfusion. ECG and invasive blood pressure were monitored throughout. Results: The protocol was completed in 11 pigs. Oxidative stress, as indicated by immunoblotting for Malondialdehyde in myocardial biopsies, was increased at 5 min of reperfusion compared to baseline, but not at 60 min of reperfusion, and not reduced with NAC. We found no significant differences in circulating biomarkers of myocardial necrosis, nor in the incidence of idioventricular rhythm (IVR), non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT) or ventricular fibrillation (VF) between NAC-treated and control pigs during reperfusion. Conclusion: Myocardial oxidation was increased early after reperfusion in a porcine model of MI, but systemic antioxidative treatment did not protect against reperfusion arrhythmias.

Compliance with recommended cancer patient pathway timeframes and choice of treatment differed by cancer type and place of residence among cancer patients in Norway in 2015-2016.

BACKGROUND: Cancer patient pathways (CPPs) were implemented in Norway to reduce unnecessary waiting times, regional variations, and to increase the predictability of cancer care for the patients. This study aimed to determine if 70% of cancer patients started treatment within the recommended time frames, and to identify potential delays. METHODS: Patients registered with a colorectal, lung, breast, or prostate cancer diagnosis at the Cancer Registry of Norway in 2015-2016 were linked with the Norwegian Patient Registry and Statistics Norway. Adjusting for sociodemographic variables, multivariable quantile (median) regressions were used to examine the association between place of residence and median time to start of examination, treatment decision, and start of treatment. RESULTS: The study included 20 668 patients. The proportions of patients who went through the CPP within the recommended time frames were highest among colon (84%) and breast (76%) cancer patients who underwent surgery and lung cancer patients who started systemic anticancer treatment (76%), and lowest for prostate cancer patients who underwent surgery (43%). The time from treatment decision to start of treatment was the main source of delay for all cancers. Travelling outside the resident health trust prolonged waiting time and was associated with a reduced odds of receiving surgery and radiotherapy for lung and rectal cancer patients, respectively. CONCLUSIONS: Achievement of national recommendations of the CCP times differed by cancer type and treatment. Identified bottlenecks in the pathway should be targeted to decrease waiting times. Further, CPP guidelines should be re-examined to determine their ongoing relevance.

Cerebral perfusion and metabolism with mean arterial pressure 90 vs. 60 mmHg in a porcine post cardiac arrest model with and without targeted temperature management.

AIM: To determine whether targeting a mean arterial pressure of 90 mmHg (MAP90) would yield improved cerebral blood flow and less ischaemia compared to MAP 60 mmHg (MAP60) with and without targeted temperature management at 33 °C (TTM33) in a porcine post-cardiac arrest model. METHODS: After 10 min of cardiac arrest, 41 swine of either sex were resuscitated until return of spontaneous circulation (ROSC). They were randomised to TTM33 or no-TTM, and MAP60 or MAP90; yielding four groups. Temperatures were managed with intravasal cooling and blood pressure targets with noradrenaline, vasopressin and nitroprusside, as appropriate. After 30 min of stabilisation, animals were observed for two hours. Cerebral perfusion pressure (CPP), cerebral blood flow (CBF), pressure reactivity index (PRx), brain tissue pCO2 (PbtCO2) and tissue intermediary metabolites were measured continuously and compared using mixed models. RESULTS: Animals randomised to MAP90 had higher CPP (p < 0.001 for both no-TTM and TTM33) and CBF (no-TTM, p < 0.03; TH, p < 0.001) compared to MAP60 during the 150 min observational period post-ROSC. We also observed higher lactate and pyruvate in MAP60 irrespective of temperature, but no significant differences in PbtCO2 and lactate/pyruvate-ratio. We found lower PRx (indicating more intact autoregulation) in MAP90 vs. MAP60 (no-TTM, p = 0.04; TTM33, p = 0.03). CONCLUSION: In this porcine cardiac arrest model, targeting MAP90 led to better cerebral perfusion and more intact autoregulation, but without clear differences in ischaemic markers, compared to MAP60. INSTITUTIONAL PROTOCOL NUMBER: FOTS, id 8442.

Factors associated with emergency-onset diagnosis, time to treatment and type of treatment in colorectal cancer patients in Norway.

BACKGROUND: International differences in survival among colorectal cancer (CRC) patients may partly be explained by differences in emergency presentations (EP), waiting times and access to treatment. METHODS: CRC patients registered in 2015-2016 at the Cancer Registry of Norway were linked with the Norwegian Patient Registry and Statistics Norway. Multivariable logistic regressions analysed the odds of an EP and access to surgery, radiotherapy and systemic anticancer treatment (SACT). Multivariable quantile regression analysed time from diagnosis to treatment. RESULTS: Of 8216 CRC patients 29.2% had an EP before diagnosis, of which 81.4% were admitted to hospital with a malignancy-related condition. Higher age, more advanced stage, more comorbidities and colon cancer were associated with increased odds of an EP (p < 0.001). One-year mortality was 87% higher among EP patients (HR=1.87, 95%CI:1.75-2.02). Being married or high income was associated with 30% reduced odds of an EP (p < 0.001). Older age was significantly associated with increased waiting time to treatment (p < 0.001). Region of residence was significantly associated with waiting time and access to treatment (p < 0.001). Male (OR = 1.30, 95%CI:1.03,1.64) or married (OR = 1.39, 95%CI:1.09,1.77) colon cancer patients had an increased odds of SACT. High income rectal cancer patients had an increased odds (OR = 1.48, 95%CI:1.03,2.13) of surgery. CONCLUSION: Patients who were older, with advanced disease or more comorbidities were more likely to have an emergency-onset diagnosis and less likely to receive treatment. Income was not associated with waiting time or access to treatment among CRC patients, but was associated with the likelihood of surgery among rectal cancer patients.

Live Tissue Training on Anesthetized Pigs for Air Ambulance Crews.

OBJECTIVE: Patients with life- or limb-threatening severe injuries pose a challenge to prehospital services. Time-critical decision making and treatment are challenging because of occasional incomplete information, limited resources, adverse environments, and a range of basic and advanced technical skills available. To prepare for these infrequent critical situations, medical personnel from the helicopter emergency medical service at Oslo University Hospital developed a 1-day advanced trauma training course focusing on individual skills and teamwork during resuscitative procedures. METHODS: Participants were trained under supervision in teams on an established live tissue model with anesthetized pigs. A questionnaire-based evaluation was conducted before and after training to measure the feasibility of covering the allocated learning objectives in the time allotted and participants' perception of any change in their skills as a result of the course. RESULTS: The self-reported skill level in all learning objectives improved significantly. Combining all learning objectives, the median self-reported skill level was significantly increased from 4 to 6 points (P < .001). CONCLUSION: Experienced prehospital physicians and other health staff reported an increased level of skill and competence in lifesaving and limb-saving procedures after completing a brief, intense 1-day course using living anesthetized pigs and cadaver models.

Measuring diaphragm movement and respiratory frequency using a novel ultrasound device in healthy volunteers.

PURPOSE: To evaluate the ability of a novel ultrasound (US) device, DiaMon, to monitor diaphragm movement via its proxy liver movement, and compare it with the respired flow measured with a flowmeter, in awake and healthy volunteers. We wanted to (1) establish the optimal anatomical position for attaching the DiaMon device to the abdominal wall, and (2) evaluate the accuracy of continuous monitoring of respiratory frequency. METHODS: Thirty healthy subjects were recruited. The DiaMon probe was applied subcostally in four different positions with the subjects in five different postures. The subjects breathed tidal volumes into a spirometer for 30-60 s with the DiaMon recording simultaneously. RESULTS: The device detected a readable signal in 83-100% of the position/posture-combinations. The technical correlation between the two signals was highest in the anterior axillary-supine position (mean ± SD: 0.95 ± 0.03), followed by paramidline-supine (0.90 ± 0.09) and midclavicular-supine (0.89 ± 0.12). The frequency measurements yielded a mean difference of 0.03 (95% limits of agreement - 0.11, 0.16) breaths per minute in the anterior axillary-supine position. CONCLUSION: The DiaMon device is able to detect liver movement in most subjects, and it measures breathing frequency accurately.

Patient and tumour characteristics associated with inclusion in Cancer patient pathways in Norway in 2015-2016.

BACKGROUND: Cancer patient pathways (CPPs) were implemented in 2015 to reduce waiting time, regional variation in waiting time, and to increase the predictability of cancer care for the patients. The aims of this study were to see if the national target of 70% of all cancer patients being included in a CPP was met, and to identify factors associated with CPP inclusion. METHODS: All patients registered with a colorectal, lung, breast or prostate cancer diagnosis at the Cancer Registry of Norway in the period 2015-2016 were linked with the Norwegian Patient Registry for CPP information and with Statistics Norway for sociodemographic variables. Multivariable logistic regression examined if the odds of not being included in a CPP were associated with year of diagnosis, age, sex, tumour stage, marital status, education, income, region of residence and comorbidity. RESULTS: From 2015 to 2016, 30,747 patients were diagnosed with colorectal, lung, breast or prostate cancer, of whom 24,429 (79.5%) were included in a CPP. Significant increases in the probability of being included in a CPP were observed for colorectal (79.1 to 86.2%), lung (79.0 to 87.3%), breast (91.5 to 97.2%) and prostate cancer (62.2 to 76.2%) patients (p < 0.001). Increasing age was associated with an increased odds of not being included in a CPP for lung (p < 0.001) and prostate cancer (p < 0.001) patients. Colorectal cancer patients < 50 years of age had a two-fold increase (OR = 2.23, 95% CI: 1.70-2.91) in the odds of not being included in a CPP. The odds of no CPP inclusion were significantly increased for low income colorectal (OR = 1.24, 95%CI: 1.00-1.54) and lung (OR = 1.52, 95%CI: 1.16-1.99) cancer patients. Region of residence was significantly associated with CPP inclusion (p < 0.001) and the probability, adjusted for case-mix ranged from 62.4% in region West among prostate cancer patients to 97.6% in region North among breast cancer patients. CONCLUSIONS: The national target of 70% was met within 1 year of CPP implementation in Norway. Although all patients should have equal access to CPPs, a prostate cancer diagnosis, older age, high level of comorbidity or low income were significantly associated with an increased odds of not being included in a CPP.

Mechanical Effects on Right Ventricular Function From Left Bundle Branch Block and Cardiac Resynchronization Therapy.

OBJECTIVES: The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction. BACKGROUND: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function. METHODS: In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers. RESULTS: Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure. CONCLUSIONS: LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185).

Decreasing waiting time for treatment before and during implementation of cancer patient pathways in Norway.

BACKGROUND: In 2015, Norway implemented cancer patient pathways to reduce waiting times for treatment. The aims of this paper were to describe patterns in waiting time and their association with patient characteristics for colorectal, lung, breast and prostate cancers. METHODS: National, population-based data from 2007 to 2016 were used. A multivariable quantile regression examined the association between treatment period, age, stage, sex, place of residence, and median waiting times. RESULTS: Reduction in median waiting times for radiotherapy among colorectal, lung and prostate cancer patients ranged from 14 to 50 days. Median waiting time for surgery remained approximately 21 days for both colorectal and breast cancers, while it decreased by 7 and 36 days for lung and prostate cancers, respectively. The proportion of lung and prostate cancer patients with metastatic disease at the time of diagnosis decreased, while the proportion of colorectal patients with localised disease and patients with stage I breast cancer increased (p < 0.001). After adjusting for case-mix, a patient's place of residence was significantly associated with waiting time for treatment (p < 0.001), however, differences in waiting time to treatment decreased over the study period. CONCLUSIONS: Between 2007 and 2016, Norway experienced improved stage distributions and consistently decreasing waiting times for treatment. While these improvements occurred gradually, no significant change was observed from the time of cancer patient pathway implementation.

Left ventricular end-systolic volume is a more sensitive marker of acute response to cardiac resynchronization therapy than contractility indices: insights from an experimental study.

AIMS: There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response. METHODS AND RESULTS: In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01). CONCLUSION: Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

Dysfunction of the systemic right ventricle after atrial switch: physiological implications of altered septal geometry and load.

Atrial switch operation in patients with transposition of the great arteries (TGA) leads to leftward shift and changes the geometry of the interventricular septum. By including the implications of regional work and septal curvature, this study investigates if changes in septal function and geometry contribute to reduced function of the systemic right ventricle (RV) in adult TGA patients. Regional myocardial work estimation has been possible by applying a recently developed method for noninvasive work calculation based on echocardiography. In 14 TGA patients (32 ± 6 yr, means ± SD) and 14 healthy controls, systemic ventricular systolic strains were measured by speckle tracking echocardiography and regional work was calculated by pressure-strain analysis. In TGA patients, septal longitudinal strain was reduced to -14 ± 2 vs. -20 ± 2% in controls ( P < 0.01) and septal work was reduced from 2,046 ± 318 to 1,146 ± 260 mmHg·% ( P < 0.01). Septal circumferential strain measured in a subgroup of patients was reduced to -11 ± 3 vs. -27 ± 3% in controls ( P < 0.01), and a reduction of septal work (540 ± 273 vs. 2,663 ± 459 mmHg·%) was seen ( P < 0.01). These reductions were in part attributed to elevated afterload due to increased radius of curvature of the leftward shifted septum. To conclude, in this mechanistic study we demonstrate that septal dysfunction contributes to failure of the systemic RV after atrial switch in TGA patients. This is potentially a long-term response to increased afterload due to a flatter septum and suggests that medical therapy that counteracts septal flattening may improve function of the systemic RV. NEW & NOTEWORTHY We have demonstrated that transposition of the great arteries patients with systemic right ventricles (RVs) have reduced function of the interventricular septum (IVS). Since the IVS is constructed to eject into the systemic circulation, it may seem unexpected that it does not maintain function when being part of the systemic RV. By applying the principles of regional work, wall tension, and geometry, we have identified unfavorable working conditions for the IVS when the RV adapts to systemic pressures.

Haemodynamic outcomes during piston-based mechanical CPR with or without active decompression in a porcine model of cardiac arrest.

BACKGROUND: Experimental active compression-decompression (ACD) CPR is associated with increased haemodynamic outcomes compared to standard mechanical chest compressions. Since no clinically available mechanical chest compression device is capable of ACD-CPR, we modified the LUCAS 2 (Physio-Control, Lund, Sweden) to deliver ACD-CPR, hypothesising it would improve haemodynamic outcomes compared with standard LUCAS CPR on pigs with cardiac arrest. METHODS: The modified LUCAS delivering 5 cm compressions with or without 2 cm active decompression above anatomical chest level was studied in a randomized crossover design on 19 Norwegian domestic pigs. VF was electrically induced and untreated for 2 min. Each pig received ACD-CPR and standard mechanical CPR in three 180-s. phases. We measured aortic, right atrial, coronary perfusion, intracranial and oesophageal pressure, cerebral and carotid blood flow and cardiac output. Two-sided paired samples t-test was used for continuous parametric data and Wilcoxon test for non-parametric data. P < 0.05 was considered significant. RESULTS: Due to injuries/device failure, the experimental protocol was completed in nine of 19 pigs. Cardiac output (l/min, median, (25, 75-percentiles): 1.5 (1.1, 1.7) vs. 1.1 (0.8, 1.5), p < 0.01), cerebral blood flow (AU, 297 vs. 253, mean difference: 44, 95% CI; 14-74, p = 0.01), and carotid blood flow (l/min, median, (25, 75-percentiles): 97 (70, 106) vs. 83 (57, 94), p < 0.01) were higher during ACD-CPR compared to standard mechanical CPR. Coronary perfusion pressure (CPP) trended towards higher in end decompression phase. CONCLUSION: Cardiac output and brain blood flow improved with mechanical ACD-CPR and CPP trended towards higher during end-diastole compared to standard LUCAS CPR.

Regional Dysfunction After Myocardial Infarction in Rats.

BACKGROUND: Detailed understanding of regional function after myocardial infarction (MI) is currently incomplete. We aimed at investigating regional myocardial strain and work in post-MI rats with and without heart failure. METHODS AND RESULTS: Six weeks after induction of MI, 62 male Wistar-Hannover rats with a range of infarct sizes, plus 14 sham-operated rats, were examined by cine and phase-contrast magnetic resonance imaging. After magnetic resonance imaging, the rats were catheterized, and left ventricular pressures were recorded. Regional strain and work were calculated from the magnetic resonance imaging and pressure data. On the basis of end-diastolic left ventricular pressure, 34 MI rats were classified as nonfailing (MINF) and 28 MI rats as failing (MICHF). In the region remote to the infarct, the MINF rats exhibited preserved strain and increased work compared with sham, whereas MICHF had reduced longitudinal strain and no increase in work in this region. In the noninfarcted region adjacent to the infarct, MICHF demonstrated substantially reduced work because of high levels of negative work. CONCLUSIONS: We have demonstrated a distinct difference in regional work between nonfailing and failing hearts after MI and offer novel insight into the relation between regional function and presence of congestion. Work analysis provided significant added value over strain analysis alone.

How Many Deaths from Colorectal Cancer Can Be Prevented by 2030? A Scenario-Based Quantification of Risk Factor Modification, Screening, and Treatment in Norway.

Background: Colorectal cancer mortality can be reduced through risk factor modification (adherence to lifestyle recommendations), screening, and improved treatment. This study estimated the potential of these three strategies to modify colorectal cancer mortality rates in Norway.Methods: The potential reduction in colorectal cancer mortality due to risk factor modification was estimated using the software Prevent, assuming that 50% of the population in Norway-who do not adhere to the various recommendations concerning prevention of smoking, physical activity, body weight, and intake of alcohol, red/processed meat, and fiber-started to follow the recommendations. The impact of screening was quantified assuming implementation of national flexible sigmoidoscopy screening with 50% attendance. The reduction in colorectal cancer mortality due to improved treatment was calculated assuming that 50% of the linear (positive) trend in colorectal cancer survival would continue to persist in future years.Results: Risk factor modification would decrease colorectal cancer mortality by 11% (corresponding to 227 prevented deaths: 142 men, 85 women) by 2030. Screening and improved treatment in Norway would reduce colorectal cancer mortality by 7% (149 prevented deaths) and 12% (268 prevented deaths), respectively, by 2030. Overall, the combined effect of all three strategies would reduce colorectal cancer mortality by 27% (604 prevented deaths) by 2030.Conclusions: Risk factor modification, screening, and treatment all have considerable potential to reduce colorectal cancer mortality by 2030, with the largest potential reduction observed for improved treatment and risk factor modification.Impact: The estimation of these health impact measures provides useful information that can be applied in public health decision-making. Cancer Epidemiol Biomarkers Prev; 26(9); 1420-6. ©2017 AACR.

Preoperative chemoradiotherapy for rectal cancer and impact on outcomes - A population-based study.

BACKGROUND AND PURPOSE: Preoperative (chemo)radiotherapy ((C)RT) for rectal cancer is, in Norway, restricted to patients with cT4-stage or threatened circumferential resection margin. This nationwide population-based study assessed the use of preoperative (C)RT in Norway and its impact on treatment outcomes. PATIENTS AND METHODS: Data from The Norwegian Colorectal Cancer Registry were used to identify all stage I-III rectal cancers treated with major resection (1997-2011: n=9193). Cumulative risk of local recurrence, distant metastasis, and relative survival was estimated for patients in 2007-2011 (n=3179). Multivariate regression-models were used to compare outcomes following preoperative (C)RT and surgery versus surgery alone. RESULTS: The proportion of patients given preoperative (C)RT increased from 5% to 49% during 1997-2011. Preoperative (C)RT was associated with reduced risk of local recurrence (hazard ratio (HR)=0.55; 95% CI=0.29-1.04) and a tendency of improved survival (excess HR=0.75; 95% CI=0.52-1.08) with significant effects in patients aged ≥70years (local recurrence: HR=0.35; 95% CI=0.13-0.91; survival: excess HR=0.58; 95% CI=0.35-0.95). CONCLUSIONS: This study indicates that when use of preoperative (C)RT is restricted to selected high-risk rectal cancers, preoperative (C)RT is associated with improved local recurrence, and possibly improved survival, when studied on a population-based level.

The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

BACKGROUND: Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. METHODS/DESIGN: This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. DISCUSSION: The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for colorectal cancer survivors is limited, the study may be of great importance for this cancer population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01570010 .

Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics.

Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-µm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 µm, with no bubbles >44 µm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.

Nationwide implementation of laparoscopic surgery for colon cancer: short-term outcomes and long-term survival in a population-based cohort.

BACKGROUND: Randomized trials show similar outcomes after open surgery and laparoscopy for colon cancer, and confirmation of outcomes after implementation in routine practice is important. While some studies have reported long-term outcomes after laparoscopic surgery from single institutions, data from large patient cohorts are sparse. We investigated short- and long-term outcomes of laparoscopic and open surgery for treating colon cancer in a large national cohort. METHODS: We retrieved data from the Norwegian Colorectal Cancer Registry for all colon cancer resections performed in 2007-2010. Five-year relative survival rates following laparoscopic and open surgeries were calculated, including excess mortality rates associated with potential predictors of death. RESULTS: Among 8707 patients with colon cancer that underwent major resections, 16 % and 36 % received laparoscopic procedures in 2007 and 2010, respectively. Laparoscopic procedures were most common in elective surgeries for treating stages I-III, right colon, or sigmoid tumours. The conversion rate of laparoscopic procedures was 14.5 %. Among all patients, laparoscopy provided higher 5-year relative survival rates (70 %) than open surgery (62 %) (P = 0.040), but among the largest group of patients electively treated for stages I-III disease, the approaches provided similar relative survival rates (78 vs. 81 %; P = 0.535). Excess mortality at 2 years post-surgery was lower after laparoscopy than after open surgery (excess hazard ratio, 0.7; P = 0.013), but similar between groups during the last 3 years of follow-up. Major predictors of death were stage IV disease, tumour class pN+, age > 80 years, and emergency procedures (excess hazard ratios were 5.3, 2.4, 2.1, and 2.0, respectively; P < 0.001). CONCLUSION: Nationwide implementation of laparoscopic colectomy for colon cancer was safe and achieved results comparable to those from previous randomized trials.