Change in abdominal obesity after colon cancer surgery - effects of left-sided and right-sided colonic resection.

BACKGROUND: Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots. MATERIAL AND METHODS: Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately. RESULTS: A total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2-9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2-6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2-7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4-9%, p < 0.001) increase in SAT and a 4% (95% CI: 1-7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2-10%, p < 0.01) after 3 years. CONCLUSION: After 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT.

Exercise training to increase tumour natural killer-cell infiltration in men with localised prostate cancer: a randomised controlled trial.

OBJECTIVES: To explore the effects of preoperative high-intensity interval training (HIIT) compared to usual care on tumour natural killer (NK)-cell infiltration in men with localised prostate cancer (PCa), as NK-cell infiltration has been proposed as one of the key mechanisms whereby exercise can modulate human tumours. PATIENTS AND METHODS: A total of 30 patients with localised PCa undergoing radical prostatectomy (RP) were randomised (2:1) to either preoperative aerobic HIIT four-times weekly (EX; n = 20) or usual care (CON; n = 10) from time of inclusion until scheduled surgery. Tumour NK-cell infiltration was assessed by immunohistochemistry (CD56+ ) in diagnostic core needle biopsies and corresponding prostatic tissue from the RP. Changes in cardiorespiratory fitness, body composition, blood biochemistry, and health-related quality of life were also evaluated. RESULTS: The change in tumour NK-cell infiltration did not differ between the EX and CON groups (between-group difference: -0.09 cells/mm2 , 95% confidence interval [CI] -1.85 to 1.66; P = 0.913) in the intention-to-treat analysis. The total number of exercise sessions varied considerably from four to 30 sessions. The per-protocol analysis showed a significant increase in tumour NK-cell infiltration of 1.60 cells/mm2 (95% CI 0.59 to 2.62; P = 0.004) in the EX group. Further, the total number of training sessions was positively correlated with the change in NK-cell infiltration (r = 0.526, P = 0.021), peak oxygen uptake (r = 0.514, P = 0.035) and peak power output (r = 0.506, P = 0.038). CONCLUSION: Preoperative HIIT did not result in between-group differences in tumour NK-cell infiltration. Per-protocol and exploratory analyses demonstrate an enhanced NK-cell infiltration in PCa. Future studies are needed to test the capability of exercise to increase tumour immune cell infiltration.

Effects of a physical activity program from diagnosis on cardiorespiratory fitness in children with cancer: a national non-randomized controlled trial.

BACKGROUND: Children with cancer experience impaired cardiorespiratory fitness and physical function during and after treatment restricting their possibilities to engage in social activities including sport, leisure activities, and school. The objectives were to determine the effects of classmate-supported, controlled, supervised, in-hospital, physical activity program to preserve cardiorespiratory fitness and physical function from time of diagnosis in children with cancer. METHODS: National non-randomized controlled trial including schoolchildren aged 6-18 years at diagnosis treated with chemo-/radiotherapy. We included 120 of 128 eligible patients (94%) in the intervention group (62.5% boys, 11.2 ± 3.1 years) from East Denmark and 58 patients in the control group (57% boys, 11.0 ± 3.2 years) from West Denmark. Eight children from the control group withdrew from participation. The groups were comparable in anthropometrics and cancer diagnoses (p > 0.05). The intervention consisted of (i) supervised in-hospital physical activity from diagnosis and throughout intensive treatment, (ii) 90-min general educational session on cancer and therapy in the child's school class, and (iii) selection of two classmates as ambassadors who took turns to support the child's physical training during the daytime. The primary outcome was cardiorespiratory fitness (VO2peak, mL/min/kg) at 6 months after diagnosis (sex, age, diagnosis adjusted). Secondary outcomes were sit-to-stand, timed-up-and-go, handgrip strength, and balance test scores. RESULTS: Ambassadors were identified for all, and 2542 individual and 621 group training sessions were held. VO2peak deteriorated over time in the control group (- 0.17 [95% CI - 0.32 to - 0.02] per week, p = 0.02), but not in the intervention group (p = 0.14). At 6 months from diagnosis, VO2peak was higher in the intervention group (29.6 ± 5.6 mL/kg/min) than in the control group (22.1 ± 5.6 mL/kg/min) (p = 0.01), and the intervention group had a better physical function at 3 and 6 months (p < 0.0001). CONCLUSIONS: Peer-supported, supervised, in-hospital, physical activity is safe and feasible in children with cancer during treatment. Further, the results suggest that the intervention might mitigate impairments in cardiorespiratory fitness during treatment in children with cancer. TRIAL REGISTRATION: The study was prospectively registered on the 11 January 2013. Clinicaltrial.gov NCT01772849 and NCT01772862 .

Voluntary wheel running can lead to modulation of immune checkpoint molecule expression.

BACKGROUND: Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy. MATERIAL AND METHODS: The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors. RESULTS: Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels. CONCLUSION: B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.

Cancer Survivors' Receptiveness to Digital Technology-Supported Physical Rehabilitation and the Implications for Design: Qualitative Study.

BACKGROUND: Physical activity is associated with a positive prognosis in cancer survivors and may decrease the risk of adverse effects of treatment. Accordingly, physical activity programs are recommended as a part of cancer rehabilitation services. Digital technology may support cancer survivors in increasing their level of physical activity and increase the reach or efficiency of cancer rehabilitation services, yet it also comes with a range of challenges. OBJECTIVE: The aim of this qualitative study was to explore cancer survivors' receptiveness to using digital technology as a mode of support to increase their physical activity in a municipality-based cancer rehabilitation setting. METHODS: Semistructured interviews were conducted with 11 cancer survivors (3 males, 8 females, age range 32-82 years) who were referred for cancer rehabilitation and had participated in a questionnaire survey using the Readiness and Enablement Index for Health Technology (READHY) questionnaire. Data analysis was based on the content analysis method. RESULTS: Two themes were identified as important for the interviewees' receptiveness to using digital technology services in connection with their physical activity during rehabilitation: their attitude toward physical activity and their attitude toward digital technology-assisted physical activity. Our results indicated that it is important to address the cancer survivors' motivation for using technology for physical activity and their individual preferences in terms of the following: (1) incidental or structured (eg, cardiovascular and strength exercises or disease-specific rehabilitative exercises) physical activity; (2) social or individual context; and (3) instruction (know-how) or information (know-why). CONCLUSIONS: The identified preferences provide new insight that complements the cancer survivors' readiness level and can likely help designers, service providers, and caregivers provide solutions that increase patient receptiveness toward technology-assisted physical activity. Combining digital technology informed by cancer survivors' needs, preferences, and readiness with the capacity building of the workforce can aid in tailoring digital solutions to suit not only individuals who are receptive to using such technologies but also those reluctant to do so.

Technology in exercise-based cancer rehabilitation: a cross-sectional study of receptiveness and readiness for e-Health utilization in Danish cancer rehabilitation.

Background: During recent years, there has been an increased focus on technology within cancer survivorship and physical activity rehabilitation. Failure to acknowledge the individuals wishes and/or limitations in the use of technology introduces risk of neglecting or excluding low-resource individuals, thus adding to an already existing inequity within cancer management. It is important to identify vulnerable sub-populations with particular needs when introducing health technology to offer appropriate rehabilitation and support individuals in taking advantage of technology in their physical activity rehabilitation. We report how a population of cancer survivors referred to municipality-based rehabilitation can be segmented, according to their receptiveness and readiness for health technology utilization, to understand their potential barriers towards using technology. Methods: We used a cross-sectional design with convenience sampling among Danish cancer survivors (n = 305) referred to rehabilitation. Participants completed a questionnaire survey covering background information and a new tool to assess self-reported health technology readiness. Demographic, disease and behavioral factors were described in relation to the participants' receptiveness to use technology in physical activity rehabilitation. Participants were stratified according to their health technology readiness and the resulting groups described with regards to the above-mentioned factors. Results: Almost 30% of the participants were un-receptive to use technology in relation to physical activity rehabilitation and were characterized by being more vulnerable with regards to sociodemographic characteristics and scoring lower on dimensions related to eHealth literacy. Stratification of the participants according to their health technology readiness profile revealed four distinct profiles that were significantly different in sociodemographic, disease and behavioral factors. Conclusion: To reduce the risk of alienating low-resource individuals when introducing health technology, evaluation of the individuals' receptiveness to use technology in a rehabilitation context and their readiness for health technology may help tailor the extent to which technology should be offered to assist the cancer survivors.

Development of the Multidimensional Readiness and Enablement Index for Health Technology (READHY) Tool to Measure Individuals' Health Technology Readiness: Initial Testing in a Cancer Rehabilitation Setting.

BACKGROUND: The increasing digitization of health care services with enhanced access to fast internet connections, along with wide use of smartphones, offers the opportunity to get health advice or treatment remotely. For service providers, it is important to consider how consumers can take full advantage of available services and how this can create an enabling environment. However, it is important to consider the digital context and the attributes of current and future users, such as their readiness (ie, knowledge, skills, and attitudes, including trust and motivation). OBJECTIVE: The objective of this study was to evaluate how the eHealth Literacy Questionnaire (eHLQ) combined with selected dimensions from the Health Education Impact Questionnaire (heiQ) and the Health Literacy Questionnaire (HLQ) can be used together as an instrument to characterize an individual's level of health technology readiness and explore how the generated data can be used to create health technology readiness profiles of potential users of health technologies and digital health services. METHODS: We administered the instrument and sociodemographic questions to a population of 305 patients with a recent cancer diagnosis referred to rehabilitation in a setting that plans to introduce various technologies to assist the individuals. We evaluated properties of the Readiness and Enablement Index for Health Technology (READHY) instrument using confirmatory factor analysis, convergent and discriminant validity analysis, and exploratory factor analysis. To identify different health technology readiness profiles in the population, we further analyzed the data using hierarchical and k-means cluster analysis. RESULTS: The confirmatory factor analysis found a suitable fit for the 13 factors with only 1 cross-loading of 1 item between 2 dimensions. The convergent and discriminant validity analysis revealed many factor correlations, suggesting that, in this population, a more parsimonious model might be achieved. Exploratory factor analysis pointed to 5 to 6 constructs based on aggregates of the existing dimensions. The results were not satisfactory, so we performed an 8-factor confirmatory factor analysis, resulting in a good fit with only 1 item cross-loading between 2 dimensions. Cluster analysis showed that data from the READHY instrument can be clustered to create meaningful health technology readiness profiles of users. CONCLUSIONS: The 13 dimensions from heiQ, HLQ, and eHLQ can be used in combination to describe a user's health technology readiness level and degree of enablement. Further studies in other populations are needed to understand whether the associations between dimensions are consistent and the number of dimensions can be reduced.

Exercise regulates breast cancer cell viability: systemic training adaptations versus acute exercise responses.

PURPOSE: Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses, in breast cancer survivors could regulate breast cancer cell viability in vitro. METHODS: Blood samples were collected from breast cancer survivors, partaking in either a 6-month training intervention or across a 2 h acute exercise session. Changes in training parameters and systemic factors were evaluated and pre/post exercise-conditioned sera from both studies were used to stimulate breast cancer cell lines (MCF-7, MDA-MB-231) in vitro. RESULTS: Six months of training increased VO2peak (16.4 %, p < 0.001) and muscle strength, and reduced resting levels of plasma cholesterol (-18.2 %, p = 0.003) and cytokines. Yet, these systemic adaptations had no effect on breast cancer cell viability in vitro. During 2 h of acute exercise, increases in serum lactate (6-fold, p < 0.001), epinephrine (2.9-fold, p = 0.009), norepinephrine (2.2-fold, p < 0.001), and cytokines, including IL-6 (2.1-fold, p < 0.001) were detected. Incubation with serum obtained after exercise reduced viability by -9.2 % in MCF-7 (p = 0.04) and -9.4 % in MDA-MB-231 (p < 0.001) compared to resting serum. CONCLUSION: Systemic changes to a 2 h exercise session reduced breast cancer viability, while adaptations to 6 months of training had no impact. Our data question the prevailing dogma that training-dependent baseline reductions in risk factors mediate the protective effect of exercise on breast cancer. Instead, we propose that the cancer protection is driven by accumulative effects of repeated acute exercise responses.

Effect of intermittent aerobic exercise on sleep quality and sleep disturbances in patients with rheumatoid arthritis - design of a randomized controlled trial.

BACKGROUND: Poor sleep is prevalent in patients with systemic inflammatory disorders, including rheumatoid arthritis, and, in addition to fatigue, pain, depression and inflammation, is associated with an increased risk of co-morbidity and all-cause mortality. Whereas non-pharmacological interventions in patients with rheumatoid arthritis have been shown to reduce pain and fatigue, no randomized controlled trials have examined the effect of non-pharmacological interventions on improvement of sleep in patients with rheumatoid arthritis. The aim of this trial was to evaluate the efficacy of an intermittent aerobic exercise intervention on sleep, assessed both objectively and subjectively in patients with rheumatoid arthritis. METHODS/DESIGN: A randomized controlled trial including 44 patients with rheumatoid arthritis randomly assigned to an exercise training intervention or to a control group. The intervention consists of 18 session intermittent aerobic exercise training on a bicycle ergometer three times a week. Patients are evaluated according to objective changes in sleep as measured by polysomnography (primary outcome). Secondary outcomes include changes in subjective sleep quality and sleep disturbances, fatigue, pain, depressive symptoms, physical function, health-related quality of life and cardiorespiratory fitness. DISCUSSION: This trial will provide evidence of the effect of intermittent aerobic exercise on the improvement of sleep in patients with rheumatoid arthritis, which is considered important in promotion of health and well-being. As such, the trial meets a currently unmet need for the provision of non-pharmacological treatment initiatives of poor sleep in patients with rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01966835.

The impact of surgery and oncological treatment on risk of type 2 diabetes onset in patients with colorectal cancer: nationwide cohort study in Denmark.

Background: Comorbidity with type 2 diabetes (T2D) results in worsening of cancer-specific and overall prognosis in colorectal cancer (CRC) patients. The treatment of CRC per se may be diabetogenic. We assessed the impact of different types of surgical cancer resections and oncological treatment on risk of T2D development in CRC patients. Methods: We developed a population-based cohort study including all Danish CRC patients, who had undergone CRC surgery between 2001 and 2018. Using nationwide register data, we identified and followed patients from date of surgery and until new onset of T2D, death, or end of follow-up. Results: In total, 46,373 CRC patients were included and divided into six groups according to type of surgical resection: 10,566 Right-No-Chemo (23%), 4645 Right-Chemo (10%), 10,151 Left-No-Chemo (22%), 5257 Left-Chemo (11%), 9618 Rectal-No-Chemo (21%), and 6136 Rectal-Chemo (13%). During 245,466 person-years of follow-up, 2556 patients developed T2D. The incidence rate (IR) of T2D was highest in the Left-Chemo group 11.3 (95% CI: 10.4-12.2) per 1000 person-years and lowest in the Rectal-No-Chemo group 9.6 (95% CI: 8.8-10.4). Between-group unadjusted hazard ratio (HR) of developing T2D was similar and non-significant. In the adjusted analysis, Rectal-No-Chemo was associated with lower T2D risk (HR 0.86 [95% CI 0.75-0.98]) compared to Right-No-Chemo.For all six groups, an increased level of body mass index (BMI) resulted in a nearly twofold increased risk of developing T2D. Conclusions: This study suggests that postoperative T2D screening should be prioritised in CRC survivors with overweight/obesity regardless of type of CRC treatment applied. Funding: The Novo Nordisk Foundation (NNF17SA0031406); TrygFonden (101390; 20045; 125132).

Patient Activation through Counseling and Exercise--Acute Leukemia (PACE-AL)--a randomized controlled trial.

BACKGROUND: Patients with acute leukemia experience a substantial symptom burden and are at risk of developing infections throughout the course of repeated cycles of intensive chemotherapy. Physical activity in recent years has been a strategy for rehabilitation in cancer patients to remedy disease and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured and supervised counseling and exercise program. METHODS/DESIGN: This paper presents the study protocol: Patient Activation through Counseling and Exercise--Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours + 30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70-80%) on an ergometer cycle, strength exercises using hand weights and relaxation exercise. Individual health counseling sessions include a self directed home walk program with a step counter. The primary endpoint is functional performance/exercise capacity (6 minute walk distance). The secondary endpoints are submaximal VO2 max test, sit to stand and bicep curl test, physical activity levels, patient reported outcomes (quality of life, anxiety and depression, symptom prevalence, intensity and interference). Evaluation of clinical outcomes will be explored including incidence of infection, hospitalization days, body mass index, time to recurrence and survival. Qualitative exploration of patients' health behavior and experiences. DISCUSSION: PACE-AL will provide evidence of the effect of exercise and health promotion counseling on functional and physical capacity, the symptom burden and quality of life in patients with acute leukemia during out patient management. The results will inform clinical practice exercise guidelines and rehabilitation programs for patients undergoing treatment for acute leukemia. Optimizing the treatment and care pathway may ease the transition for patients from illness to the resumption of everyday activities. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01404520.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the 'FC Prostate' randomized controlled trial.

BACKGROUND: Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The 'Football Club (FC) Prostate' study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. METHODS/DESIGN: Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2-3 times/week for 45-60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. DISCUSSION: The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01711892.

Demonstration and manifestation of self-determination and illness resistance--a qualitative study of long-term maintenance of physical activity in posttreatment cancer survivors.

OBJECTIVE: The aim of this study was to describe posttreatment cancer survivors' lived experience of long-term maintenance of physical activity (PA). METHODS: A qualitative, salutogenetic-oriented study was conducted based on four audiotaped, semistructured focus group interviews. Interviewee selection was carried out through purposeful sampling. Twenty-three cancer survivors (17 women and 6 men; median age 50 years, range 29-70) who were physically inactive prior to their diagnosis but who had been exercising regularly for a minimum of 18 months posttreatment participated in the study. The participants were recruited from The Copenhagen PACT Study that evaluated the effect of a one-year rehabilitation program (supervised exercise [weekly], expert lectures [trimonthly], in-group coaching [bimonthly] and individual coaching [3 × 1 h]). Data were analyzed by use of systematic condensation analysis inspired by Giorgi's descriptive phenomenological methodology (see Sketch of a psychological phenomenological method, in: Giorgi A (ed.), Phenomenology and Psychological Research, Duquesne University Press, Pittsburgh, 1985). RESULTS: The analysis revealed five categories, which were summarized into an overall sentence describing the essence of long-term PA maintenance in cancer survivors: demonstration and manifestation of self-determination and illness resistance. In sum, the participants described regular PA as a prerequisite for feeling and staying well and preserving and pursuing own potentials whereby PA maintenance becomes a goal in itself. CONCLUSIONS: This study indicates that cancer survivors' continued motivation for PA may be dependent on the fulfillment of a personal and conscious experience of being in the process of creating and living a comprehensible and meaningful life. Future theory-based interventions to encourage PA maintenance in cancer survivors could potentially benefit by integration of humanistic and existential psychology in addition to social cognitive theory and theory of planned behavior.

Exercise training as prophylactic strategy in the management of neutropenia during chemotherapy.

Chemotherapy-induced immune-suppression is a common, but potential detrimental, adverse reaction in patients undergoing treatment for cancer and strategies with capacity to boost the immune cell populations are needed. Physical exercise training is a potent regulator of immune cell viability and function and may serve as a viable, non-pharmacological prophylactic strategy in addition to the current pharmacological management by, for example, granulocyte-colony stimulating factor (G-CSF). Here, we review the mechanistic evidence linking exercise training to haematopoietic function and subsequent possible amelioration of chemotherapy-related neutropenia. First, we briefly describe neutrophil regulation and management of neutropenia in cancer patients. Second, we summarize the effect of acute and chronic exercise training on neutrophils and their progenitors, and finally, we outline the current clinical evidence of exercise interventions in ongoing anti-cancer treatment in regard to neutropenia incidence, treatment tolerance and related outcomes. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc.

The effects of acute exercise and inflammation on immune function in early-stage prostate cancer.

Background: The immune system plays a vital role in cancer development and progression. Strategies mobilizing cytotoxic cells of the immune system to combat immunosuppression in cancer may help to improve the treatment response of patients. To this end, we aimed to characterize the anti-cancer effect of acute exercise, including the involvement of inflammatory signals. Patients and methods: Twenty patients with early-stage prostate cancer (PCa) scheduled to undergo prostatectomy performed one bout of acute exercise consisting of a watt-max test and four high-intensity intervals. Natural Killer (NK), NKT-like and T cell phenotype, NK cell cytotoxic activity (NKCA), and NKCA per-cell against cell lines of leukemia (K562) and prostate cancer origin (LNCaP and PC-3) were assessed. Inflammatory markers (TNF-α, IL-6, and CRP) were measured in plasma. Results: Exercise increased NK, NKT-like, and CD8 T cell concentration in the circulation. Furthermore, exercise shifted immune cells towards a mature and cytotoxic phenotype e.g., NK cells exhibited higher CD57 as well as lower NKG2A expression. NKT-like and CD8 cells exhibited elevated CD57, TIGIT and Granzyme-B expression. Exercise significantly improved NKCA against K562 (+16% [5%; 27%]; p = 0.002) and LNCaP (+24% [14%; 34%]; p < 0.001) but not PC-3. NKCA per NK cell decreased during exercise and increased 1-h post exercise compared to baseline in K562, LNCap, and PC-3 cell lines. Baseline IL-6 correlated with lymphocyte, monocyte and T cell concentration pre-exercise and inversely correlated with the fold-change of mobilized lymphocytes and CD8 T cells during exercise. Furthermore, baseline IL-6 and TNF-α inversely correlated with NKCA against PC-3 cells during exercise. Conclusions: Acute exercise mobilized cytotoxic immune cells and improved NKCA in patients with PCa whereas low-grade inflammation might impair the response. Whether the observed improvements impact long-term outcomes warrant further investigation. Clinical trial number: NCT03675529.

Efficacy and Acceptability of Intermittent Aerobic Exercise on Polysomnography-Measured Sleep in People With Rheumatoid Arthritis With Self-Reported Sleep Disturbance: A Randomized Controlled Trial.

OBJECTIVE: This study's objective was to investigate the efficacy and acceptability of intermittent aerobic exercise training on sleep parameters, fatigue, pain, depressive symptoms, physical function, and cardiorespiratory fitness in people with rheumatoid arthritis (RA). METHODS: Thirty-eight people with RA were assigned to intermittent aerobic exercise training (three sessions/week for 6 weeks; intervention group, n = 17) or usual care (control group, n = 21). The primary outcome was a change in polysomnography-assessed sleep efficiency from baseline to the end of the intervention. Secondary outcomes were sleep quality (Pittsburgh Sleep Quality Index), fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire), depression (Center for Epidemiological Studies-Depression), and cardiorespiratory fitness (watt max test). RESULTS: No between-group differences were found in changes in polysomnography-assessed sleep efficiency (0.04; 95% confidence interval [CI]: -0.02 to 0.09, P = 0.17). In the intervention group, sleep efficiency was improved significantly from baseline (0.84; 95% CI: 0.80-0.88) compared with the end of the intervention (6 weeks) (0.88; 95% CI: 0.85-0.92); however, there was no significant difference in the control group. Fatigue and depression measures were significantly lower in the intervention group than in the control group. Between-group differences were overall fatigue (-16.1; 95% CI: -25.1 to -7.0, P = 0.001), physical fatigue (-5.0; 95% CI: -7.3 to -2.7, P = 0.0001), cognitive fatigue (-2.4; 95% CI: -4.2 to 0.6, P = 0.009), living with fatigue (-2.5; 95% CI: -4.5 to -0.5, P = 0.01), and depressive symptoms (-6.8; 95% CI: -12.4 to -1.1, P = 0.02). CONCLUSION: The intervention yielded no significantly better sleep efficiency compared with usual care. However, aspects of fatigue, including physical and cognitive fatigue, and depressive symptoms were significantly improved in the intervention group.

A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

INTRODUCTION: Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors. PATIENTS AND METHODS: This was a single-center, double-blind, randomized, controlled trial. The main eligibility criterion was LH above the age-adjusted upper limit of normal in combination with free testosterone in the lower half of the age-adjusted normal range (mild Leydig cell insufficiency) >1 year after TC treatment. Eligible patients were randomly assigned (1:1) to 12 months transdermal TRT (Tostran, gel, 2%) or placebo with a maximum daily dose of 40 mg. The primary outcome was difference in Δ2 hour glucose measured with oral glucose tolerance test between groups assessed at 12 months. Outcomes were assessed after 6-, 12- and 3 months post-treatment. The study was registered at www. CLINICALTRIAL: gov (NCT02991209) and ended June 2019. RESULTS: Between October 2016 and February 2018, 140 patients were screened for eligibility and 69 were randomized to testosterone (n = 35, 51%) or placebo (n = 34, 49%). TRT was not associated with a statistically significant difference in Δ2 hour glucose compared to placebo after 12 months of treatment (0.04 mmol/L (95% CI: -0.53, 0.60)). There was no statistically significant difference in Δ2 hour insulin between the groups after 12 months of treatment (28.23 pmol/L (95% CI: -34.40, 90.86)). Similarly, TRT was not associated with significant improvement in components of metabolic syndrome. TRT was associated with a decrease in fat mass after 12 months compared to placebo (-1.35 kg, (95% CI: -2.53, -0.18)). CONCLUSION: In TC survivors with mild Leydig cell insufficiency, TRT was not associated with improvement of metabolic health. These findings do no not support routine use of TRT in these patients.

Effects of acute exercise training on tumor outcomes in men with localized prostate cancer: A randomized controlled trial.

Postdiagnosis physical activity is associated with improved cancer outcomes, but biological mechanisms mediating anticancer effects remain unclear. Recent findings suggest that physiological adaptations to acute exercise comprise potential anticancer effects, but these remain poorly explored in clinical settings. The objective of this study was to explore the effects of a single exercise bout on tumor oxygenation and immune cell infiltration in patients with prostate cancer. Thirty patients with localized prostate cancer were randomized (2:1) to either one high-intensity interval training bout or no exercise on the day before radical prostatectomy. Immunohistochemical analyses were performed on prostatic tissue from surgery and assessed for tumor hypoxia, natural killer (NK) cell infiltration, and microvessel density (MVD). Acute systemic response in blood lymphocytes, epinephrine, norepinephrine, IL-6, tumor necrosis factor, cortisol, lactate, and glucose was also evaluated. We did not find between-group differences in tumor hypoxia (Mann-Whitney U test, U = 83.5, p = 0.604) or NK cell infiltration (U = 77.0, p = 0.328). Also, no significant correlation was found between MVD and tumor hypoxia or NK cell infiltration. One exercise bout is likely insufficient to modulate tumor hypoxia or NK cell infiltration. Future studies may elucidate if an accumulation of several exercise bouts can impact these outcomes (NCT03675529, www.clinicaltrials.gov).

Perioperative exercise training for patients with gastrointestinal cancer undergoing surgery: A systematic review and meta-analysis.

Exercise training is emerging as a supportive treatment strategy in surgical oncology, but its effects remain uncertain in patients with gastrointestinal cancer. The primary objective of this systematic review and meta-analysis was to evaluate the effects of perioperative exercise training on gastrointestinal cancer-specific mortality, recurrence, and surgical outcomes (postoperative complications, hospitalization, surgical stress) in patients with gastrointestinal cancer. Randomized or quasi-randomized controlled trials evaluating the effects of perioperative exercise training versus control in patients with GI cancer were eligible. MEDLINE, EMBASE, CENTRAL, CINAHL, PEDro, and SPORTDiscus were systematically searched on June 20, 2020. Data were synthesized using random-effects meta-analyses. Risk of bias was assessed using the Cochrane risk of bias tool 2, and the certainty of evidence was assessed using GRADE. Study selection, data extraction, risk of bias, and GRADE assessments were performed independently by two authors. Ten randomized controlled trials comprising 448 participants with gastrointestinal cancer were eligible. Meta-analyses indicated no statistical effects of exercise on postoperative complications (risk ratio: 1.11, 95% CI: 0.84; 1.47), readmissions (risk ratio: 2.76; 95% CI: 0.00, 9394.76), or postoperative length of stay (difference in means: -0.47, 95% CI: -17.2; 16.2 days). None of the eligible studies assessed gastrointestinal cancer-specific mortality or recurrence. Overall risk of bias was high or of some concerns in all studies, and the certainty of evidence was very low. The effects of perioperative exercise on cancer-specific and surgical outcomes are unknown in patients with gastrointestinal cancer due to lack of studies and very low certainty of evidence.