Exercise in cancer care for people with lung cancer: A narrative synthesis.

OBJECTIVES: Lung cancer is the second most common cancer diagnosed worldwide, resulting in significant physical and psychological consequences. In this narrative review, we explore the role of exercise as an adjunct therapy to counteract health issues experienced by people before, during and after treatment for lung cancer, and offer recommendations for exercise prescription and future research. DESIGN: Narrative cornerstone review. METHODS: A narrative review was conducted to explore the role of exercise in cancer care for people diagnosed with lung cancer. RESULTS: Improvements in fitness, strength and quality of life have been demonstrated in people with lung cancer following participation in exercise programmes before, during and post treatment. Whilst combined aerobic (50-100 % heart rate maximum) and resistance (50-85 % of 1 repetition maximum) training, 2-5 times per week across the cancer continuum is typically prescribed, few people with lung cancer currently access exercise services. 'Optimal' exercise prescription is unclear, although is likely individual-specific. The immediate priority is to identify a tolerable starting exercise dosage, with the side effects of lung cancer and its treatment on the respiratory system, particularly shortness of breath (dyspnoea), likely driving the initial maximum threshold for session mode, duration and intensity. To date, exercise safety for people with lung cancer has been poorly evaluated and reported - few trials report it, but those that do report small numbers of serious adverse events. CONCLUSIONS: Recommendations for health professionals prescribing exercise therapy to people with lung cancer are provided, with consideration of the strengths and limitations of the current evidence base.

Validity of Patient-Reported Outcome Measures in Evaluating Nerve Damage Following Chemotherapy.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial adverse effect of anticancer treatments. As such, the assessment of CIPN remains critically important in both research and clinic settings. Objective: To compare the validity of various patient-reported outcome measures (PROMs) with neurophysiological and sensory functional measures as the optimal method of CIPN assessment. Design, Setting, and Participants: This cohort study evaluated participants treated with neurotoxic chemotherapy across 2 cohorts using a dual-study design. Participants commencing treatment were assessed prospectively at beginning of neurotoxic treatment, midtreatment, and at the end of treatment. Participants who completed treatment up to 5 years prior were assessed cross-sectionally and completed a single assessment time point. Participants were recruited from oncology centers in Australia from August 2015 to November 2022. Data analysis occurred from February to November 2023. Exposures: Neurotoxic cancer treatment including taxanes, platinums, vinca-alkaloids, proteasome inhibitors, and thalidomide. Main Outcomes and Measures: CIPN was assessed via PROMs (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-CIPN20], Functional Assessment of Cancer Therapy/Gynecological Cancer Group Neurotoxicity Questionnaire (FACT/GOG-Ntx), and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE]), neurological and neurophysiological assessment (Total Neuropathy Score and sural and tibial compound nerve amplitudes), and sensory measures (Grating orientation, Von Frey monofilament, and 2-point discrimination tasks). Core measurement properties of CIPN outcome measures were evaluated. Convergent and known-groups validity was assessed cross-sectionally following treatment completion, and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between those who reported high and low levels of CIPN symptoms using linear regressions. Results: A total of 1033 participants (median [IQR] age, 61 [50-59] years; 676 female [65.4%]) were recruited to this study, incorporating 1623 assessments. PROMs demonstrated best ability to accurately assess CIPN (convergent validity), especially the PRO-CTCAE composite score (r = 0.85; P < .001) and EORTC-CIPN20 (r = 0.79; P < .001). PROMS also demonstrated the best ability to discriminate between CIPN severity (known-groups validity) and to detect changes at onset of CIPN development (responsiveness), especially for EORTC-CIPN20 (d = 0.67; 95% CI, 0.52-0.83), FACT/GOG-Ntx (d = 0.65; 95% CI, 0.49-0.81) and the PRO-CTCAE (d = 0.83; 95% CI, 0.64-1.02). Other measures did not achieve threshold for convergent validity (α < 0.7). Neurophysiological and sensory measures did not demonstrate acceptable responsiveness. In regression models, neurological, neurophysiological, and sensory outcome measures were significantly impaired in participants who reported high levels of CIPN symptoms compared with those who reported low levels of CIPN symptoms. Conclusions and Relevance: In this cohort study of 1033 cancer patients, PROMs were the only measures to satisfy all 3 core measurement property criteria (convergent validity, known-groups validity, and responsiveness). These findings suggest that adoption of PROMs in clinical practice can equip clinicians with valuable information in assessing CIPN morbidity.

Newcastle disease virus vector-based SARS-CoV-2 vaccine candidate AVX/COVID-12 activates T cells and is recognized by antibodies from COVID-19 patients and vaccinated individuals.

Introduction: Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. Methods: This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Results: Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells. Discussion: The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

Exploring childhood cancer survivor, parent, healthcare and community professionals' experiences of, and priorities for, using digital health to engage in physical activity: a mixed methods study.

PURPOSE: Digital health interventions provide an innovative way to engage childhood cancer survivors in physical activity, yet few studies have explored the priorities of key stakeholders regarding using digital health. We aimed to investigate survivor, parent, and healthcare and community professional (HCP) experiences, priorities, and perceived importance of using digital health to promote physical activity behaviours for survivors. METHODS: Participants rated the importance of digital health features to promote physical activity in a survey. Guided by survey responses, we facilitated online focus groups or semi-structured interviews to discuss participants' experiences, priorities, and suggestions in-depth. We transcribed the data verbatim and conducted directed content analysis. RESULTS: Forty participants took part in focus groups or interviews (including 9 childhood cancer survivors aged 8-21 years, 13 parents, and 18 HCP). Four key priorities were identified: health behaviour education, peer and parent involvement, goalsetting, and support from an HCP. There was a strong preference for digital mediums to facilitate physical activity due to its accessibility and convenience. Common intervention suggestions included earlier intervention (before the survivorship period), tailored and age-appropriate programs, a combined diet and exercise approach, and concise education delivery. CONCLUSIONS: This study identified key priorities that may help to promote physical activity behaviours among childhood cancer survivors. Further research is needed to integrate these priorities into health behaviour interventions and evaluate their feasibility and efficacy. IMPLICATIONS FOR CANCER SURVIVORS: Incorporating these multi-perspective priorities into future interventions will help to ensure their sustainability, acceptability, and uptake. This will in turn support childhood cancer survivors to develop a healthy lifestyle into adulthood.

Physical activity and pain in people with cancer: a systematic review and meta-analysis.

PURPOSE: Physical activity can provide analgesic benefit but its effect on cancer-related pain is unclear. This review synthesised and appraised the evidence for the effect of physical activity on pain in people living with or beyond cancer. METHODS: A systematic search of Ovid Medline and Embase was performed to identify randomised controlled trials (RCTs), randomised cross-over studies (RXTs), and prospective observational studies that examined physical activity and pain outcomes in adults living with or beyond cancer. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to assess evidence quality. RESULTS: One hundred twenty-one studies (n = 13,806), including 102 RCTs, 6 RXTs, and 13 observational studies, met the criteria for inclusion. Meta-analyses of RCTs identified a decrease in pain intensity (n = 3734; standardised mean difference (SMD) - 0.30; 95% confidence interval (CI) - 0.45, - 0.15) and bodily pain (n = 1170; SMD 0.28; 95% CI 0.01, 0.56) but not pain interference (n = 207; SMD - 0.13, 95% CI - 0.42, 0.15) following physical activity interventions. Individual studies also identified a reduction in pain sensitivity but not analgesic use, although meta-analysis was not possible for these outcomes. High heterogeneity between studies, low certainty in some effect estimates, and possible publication bias meant that evidence quality was graded as very low to low. CONCLUSION: Physical activity may decrease pain in people living with and beyond cancer; however, high heterogeneity limits the ability to generalise this finding to all people with cancer or to specific types of cancer-related pain.

Effect of exercise interventions on hospital length of stay and admissions during cancer treatment: a systematic review and meta-analysis.

OBJECTIVE: To assess the effect of participating in an exercise intervention compared with no exercise during cancer treatment on the duration and frequency of hospital admissions. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, PEDro and Cochrane Central Registry of Randomized Controlled Trials. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised studies published until August 2023 evaluating exercise interventions during chemotherapy, radiotherapy or stem cell transplant regimens, compared with usual care, and which assessed hospital admissions (length of stay and/or frequency of admissions). STUDY APPRAISAL AND SYNTHESIS: Study quality was assessed using the Cochrane Risk-of-Bias tool and Grading of Recommendations Assessment, Development and Evaluation assessment. Meta-analyses were conducted by pooling the data using random-effects models. RESULTS: Of 3918 screened abstracts, 20 studies met inclusion criteria, including 2635 participants (1383 intervention and 1252 control). Twelve studies were conducted during haematopoietic stem cell transplantation regimens. There was a small effect size in a pooled analysis that found exercise during treatment reduced hospital length of stay by 1.40 days (95% CI: -2.26 to -0.54 days; low-quality evidence) and lowered the rate of hospital admission by 8% (difference in proportions=-0.08, 95% CI: -0.13 to -0.03, low-quality evidence) compared with usual care. CONCLUSION: Exercise during cancer treatment can decrease hospital length of stay and admissions, although a small effect size and high heterogeneity limits the certainty. While exercise is factored into some multidisciplinary care plans, it could be included as standard practice for patients as cancer care pathways evolve.

Patterns of physical activity and sedentary behavior in child and adolescent cancer survivors assessed using wrist accelerometry: A cluster analysis approach.

Physical activity levels among childhood cancer survivors are typically quantified as a total amount using time spent in various intensities. Yet, most analyses do not consider the transitory nature of children's behaviors and a more detailed approach could provide complimentary information. We aimed to explore various behavior profiles of survivors' daily and hourly physical activity patterns. We measured 8-18-year-old survivors' activity levels over 7 days using wrist accelerometry and cluster analysis. Of the 37 participant datasets, survivors engaged in mean (SD) 36.3 (19.0) min/day of MVPA and 4.1 (1.9) hrs/day of sedentary activity. The cluster analysis revealed five daily movement patterns: 'most active' (prevalence 11%), 'active' (22%), 'moderately active + moderately sedentary' (35%), 'moderately active + high sedentary' (5%) and 'least active' (27%). Younger survivors and those with less time since treatment completion were more likely to be in the active clusters. Hourly behaviors were characterized by short bursts of MVPA and moderate bouts of sedentary activity. Our approach provides an insightful analysis into the nature and timing of childhood cancer survivors' movement behaviours. Our findings may assist in the development of targeted interventions to improve physical activity levels.

Diverse strategies are needed to support physical activity engagement in women who have had breast cancer.

PURPOSE: Physical activity can improve health in people living with and beyond breast cancer; however, how to best support physical activity participation in this population is unclear. This qualitative study sought to identify important physical activity program components for breast cancer. METHODS: Women with previous breast cancer (n = 11) and allied health professionals (n = 7) participated in one-on-one semi-structured interviews (n = 15) or focus groups (n = 1). Qualitative data were analyzed using reflexive thematic analysis methods. RESULTS: Four main themes were generated including (1) the need for physical activity programs; (2) person-centered programs; (3) flexible physical activity programs; and (4) systems factors. These reflected the health and non-health benefits of physical activity, the need to facilitate agency, the diversity in individual characteristics, preferences, abilities, and commitments of people with lived experience of cancer, as well as the need for physical activity programs to be integrated within the broader health system. CONCLUSION: Strategies to support physical activity engagement for breast cancer should embrace the diversity of those who are diagnosed with cancer as well as the diversity in which physical activity can be achieved.

Physical activity and physical fitness assessments in adolescents and young adults diagnosed with cancer: a scoping review.

PURPOSE: This scoping review describes the assessment methodologies for physical activity (PA) and physical fitness assessments used in studies focusing on adolescents and young adults (AYAs) diagnosed with cancer. METHODS: A search of the literature was conducted in PubMed, CINAHL, Web of Science, and Cochrane Library following the PRISMA-ScR statement. A total of 34 studies were included in this review. RESULTS: PA was primarily assessed via self-reported questionnaires (30/34) either completed in-person (n = 17) or online (n = 13) at different time points and different stages along the cancer trajectory (i.e., from diagnosis onward). A total of 9 studies conducted a physical fitness assessment. CONCLUSIONS: PA and physical fitness measurements are key when trying to describe outcomes, assess for associations, track changes, measure intervention adherence, and test intervention efficacy and effectiveness. Considerable heterogeneity across studies was reported limiting the generation of formal recommendations or guidance for researchers, healthcare providers, and policy makers.

Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

Simultaneous pancreas-kidney transplantation: which graft warns the most?

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) is still characterized by high rates of postoperative complications. This study aims to offer an in-depth characterization of early, medium-term, and late complications following SPK to derive insights for postoperative management and follow-up. METHODS: Consecutive SPK transplantations were analysed. Pancreatic graft (P-graft)- and kidney graft (K-graft)-related complications were analysed separately. The global postoperative course was assessed in three timeframes (early, medium-term, and late) using the comprehensive complication index (CCI). Predictors of complications and early graft loss were explored. RESULTS: Complications occurred in 61.2% of patients, and the 90-day mortality was 3.9%. The overall burden of complications was significantly high during admission (CCI 22.4 ± 21.1) and decreased gradually afterwards. P-graft-related complications burdened the most in the early postoperative course (CCI 11.6 ± 13.8); postoperative ileus and perigraft fluid collection were the most frequent complications, and pseudoaneurysms, haemorrhages, and bowel leaks were the major concerns. K-related complications were milder but represented the largest proportion of the CCI in the late postoperative timeframe (CCI 7.6 ± 13.6). No predictors of P-graft- or K-graft-related complications were found. CONCLUSION: Pancreas graft-related complications represent the largest part of the clinical burden in the early postoperative timeframe but are negligible after 3 months. Kidney grafts have a relevant impact in the long term. The multidisciplinary approach to SPK recipients should be driven based on all graft-specific complications and tailored on a time-dependent basis.

Patient-Reported Outcome Measures in Chemotherapy-Induced Peripheral Neurotoxicity: Defining Minimal and Clinically Important Changes.

BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common complication of cancer treatment that produces functional disability. Increasingly, patient-reported outcome measures (PROMs) are used to assess CIPN, providing a broader symptom perspective than clinician-graded scales. Understanding when a reported change in CIPN symptoms meets the threshold for clinical significance is challenging. This study aimed to provide interpretation guidelines for validated CIPN PROMs, and thereby enable estimation of thresholds to identify clinically relevant symptoms. METHODS: Patients commencing neurotoxic cancer treatments were assessed at 3 timepoints: baseline, midtreatment, and end-of-treatment. Trajectory of CIPN development was assessed by means of CIPN PROMs, EORTC Quality of Life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity questionnaire (FACT/GOG-NTX). Thresholds were estimated for CIPN PROMs using the NCI CTCAE sensory neuropathy scale as the clinical anchor by midtreatment and end-of-treatment. Patients were assigned to a clinical change group according to CIPN development: either no development; grade 1 neuropathy (minimally important difference [MID]); or grade 2 neuropathy (clinically important difference). Distribution-based estimates (SD, 0.5) were also evaluated as supportive evidence. RESULTS: In total, 406 patients were recruited to the study, of whom 62% (n=199/320) developed CIPN by midtreatment and 80% (n=274/343) by end-of-treatment. Anchor-based MID estimates by midtreatment were 5.06 (95% CI, 4.26-5.86) for the QLQ-CIPN20 and 3.54 (95% CI, 2.87-4.20) for the FACT/GOG-NTX. End-of-treatment MIDs were estimated to be 7.32 (95% CI, 6.23-8.40) for the QLQ-CIPN20 and 4.84 (95% CI, 3.98-5.70) for the FACT/GOG-NTX. Distribution-based MID estimations yielded lower values than anchor-based methods, at 3.73 for the QLQ-CIPN20 and 2.64 for the FACT/GOG-NTX at midtreatment and 5.52 for the QLQ-CIPN20 and 3.64 for the FACT/GOG-NTX at end-of-treatment. CONCLUSIONS: Findings from the present series aid meaningful interpretation for commonly used validated CIPN PROMs and provide thresholds that serve as guidance on how to interpret score changes, which will be useful for design and evaluation of clinical trials and clinical practice.

The Relationship Between Psychological Distress and Physical Activity Is Non-linear and Differs by Domain: a Cross-Sectional Study.

BACKGROUND: There is increasing evidence for the relationship between physical activity (PA), sedentary behaviour and mental health. Limited data exists on sex-specific associations. We aimed to identify associations between PA dose and domain and television time with psychological distress, including sex-stratified models. METHODS: A total of 22,176 adults from the Melbourne Collaborative Cohort Study follow-up 2 cohort (2003-2007) participated in this cross-sectional study. Occupational, household, transport, leisure PA, hours watching television and psychological distress were assessed. Restricted cubic splines were used to examine the relationships between PA domains, television viewing time and psychological distress. RESULTS: The relationships between PA and psychological distress were non-linear (p < 0.05) and differed by PA domain. There were dose-dependent, inverse associations between distress with transport (B[95% CI] = -0.39[-0.49, -0.30]) and leisure PA (B[95% CI] = -0.35[-0.46, -0.25]). The effect estimates for transport and leisure PA with distress were larger for women. For household domain, a U-shaped curve with an elongated tail was seen. Median PA was associated with lower distress compared with lower quantities (B[95% CI] = -0.12[-0.22, -0.03]); however, this association was not evident with increasing household PA. There were no clear associations between occupational PA and distress. Higher television viewing was associated with higher distress (B[95% CI] = 0.16[0.02, 0.30]). CONCLUSIONS: Increasing PA and reducing television viewing may contribute to reduced psychological distress, particularly in women. Future interventions should incorporate leisure and transport PA and decrease television viewing to assess the impact on mental health.

Metabolic and lifestyle risk factors for chemotherapy-induced peripheral neuropathy in taxane and platinum-treated patients: a systematic review.

PURPOSE: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common dose-limiting toxicity of cancer treatment causing functional impairment and impacting quality of life. Effective prevention and treatment of CIPN are lacking, and CIPN risk factors remain ill-defined. Metabolic syndrome and associated conditions have emerged as potential risk factors, due to their high prevalence and independent association with nerve dysfunction. This systematic review aimed to investigate the association between these common metabolic-lifestyle factors and CIPN. METHODS: Searches were undertaken using Medline, Embase, CINAHL, Scopus, and Web of Science databases, with additional studies identified from bibliographic references cited by original and review articles. Articles that analyzed metabolic-lifestyle risk factors associated with CIPN for patients treated with platinum- or taxane-based chemotherapy were included. RESULTS: Searches identified 6897 titles; 44 articles had full text review, with 26 studies included. Overall incidence of neuropathy ranged from 16.9 to 89.4%. Obesity had the most consistent patient-oriented evidence as a risk factor for CIPN, with moderate evidence suggesting diabetes did not increase CIPN incidence or severity. A limited number of studies supported an association with low physical activity and greater CIPN risk. CONCLUSIONS: Comorbidities and lifestyle factors, particularly obesity and low physical activity, may contribute to the development of CIPN. The implementation of sensitive outcome measures in large-scale clinical trials is required to further elucidate CIPN risk factors and evaluate if changes in lifestyle would improve long-term CIPN outcomes for cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Better understanding of CIPN risk profiles may inform personalized medicine strategies and help elucidate pathophysiological mechanisms which could be targeted for neuroprotection.

Physical activity behaviors in cancer survivors treated with neurotoxic chemotherapy.

AIM: There are many barriers to physical activity among cancer survivors. Survivors treated with neurotoxic chemotherapy may develop chemotherapy-induced peripheral neuropathy (CIPN) and experience additional barriers related to sensorimotor and mobility deficits. This study examined physical activity behaviors, including physical activity predictors, among cancer survivors treated with neurotoxic chemotherapies. METHODS: A cross-sectional study of 252 participants, 3-24 months after neurotoxic chemotherapy, was undertaken. Physical activity was self-reported (IPAQ). CIPN was self-reported (FACT/GOG-Ntx-13), clinically graded (NCI-CTCAE), and objectively measured using neurological grading scales and neurophysiological techniques (tibial and sural nerve conduction studies). Balance (Swaymeter) and fine motor skills (grooved pegboard) were assessed. Regression models were used to identify clinical, demographic and CIPN predictors of walking and moderate-vigorous physical activity. RESULTS: Forty-four percent of participants did not meet recommended physical activity guidelines (≥150 min/week). Sixty-six percent presented with CIPN. Nineteen percent of participants with CIPN reported that symptoms interfered with their ability to be physically active. A lower proportion of survivors aged ≥60, with grade ≥1 CIPN or BMI ≥30, reported meeting physical activity guidelines (all p < .05). Regression models identified older age, higher BMI, and patient-reported CIPN associated with lower walking, while higher BMI and females were associated with lower moderate-vigorous physical activity. Neurologically assessed CIPN did not associate with walking or moderate-vigorous physical activity. CONCLUSION: Cancer survivors exposed to neurotoxic chemotherapy have low physical activity levels. Further work should examine the factors causing physical activity limitations in this cohort and designing interventions to improve physical function and quality of life in survivors.

Appraising pancreatic fistula in pancreas transplantation: A comprehensive complication index based analysis of postoperative outcomes and predictors of graft survival.

BACKGROUND: A definition of pancreatic fistula specifically addressing pancreas transplantation (PT) is lacking. This study sought to characterize pancreatic fistula in this setting and to define its clinical relevance on the postoperative course and long-term graft survival (GS). METHODS: Consecutive simultaneous pancreas and kidney transplantations were analysed. The global postoperative course was assessed through the comprehensive complication index (CCI). PF was defined according to the original International Study Group for Pancreatic Surgery (ISGPS) definition. Predictors of poor postoperative course and GS were explored. RESULTS: Seventy-eight patients were analysed. Surgical morbidity was 48.7%, with severe complications occurring in 39.7%. Ninety-day mortality was 2.6%. PF occurred in 56.6% of patients, although its average clinical burden was low and did not correlate with either early or long-term outcomes. Peri-graft fluid collections, postoperative day (POD) 1 drain fluid amylase (DFA) ≥ 2200 U/L, and POD 5 DFA/serum amylase ratio ≥7.0 independently correlated with poor postoperative course. Perigraft fluid collections were associated with reduced GS. CONCLUSION: Conventionally defined pancreatic fistula is frequent following PT, although its clinical impact is negligible. To define clinically relevant PF, novel cut-offs for DFA might be pondered in a future series, while perigraft fluid collections should be strongly considered.

An ecological study of obesity-related cancer incidence trends in Australia from 1983 to 2017.

Background: Overweight and obesity is a growing public health issue as it contributes to the future burden of obesity-related diseases, including cancer, especially in high-income countries. In Australia, 4.3% of all cancers diagnosed in 2013 were attributable to overweight and obesity. Our aim was to examine Australian age-specific incidence trends over the last 35 years for obesity-related cancers based on expert review (colorectal, liver, gallbladder, pancreas, breast in postmenopausal women, uterine, ovary, kidney, thyroid, and multiple myeloma) individually and pooled. Methods: Australian incidence data for 10 obesity-related cancers among people aged 25-84 years, diagnosed from 1983 to 2017, were obtained from the Australian Cancer Database. We used age-period-cohort modelling and joinpoint analysis to assess trends, estimating incidence rate ratios (IRR) by birth-cohort for each individual cancer and pooled, and the annual percentage change. The analyses were also conducted for non-obesity-related cancers over the same period. Findings: The total number of cancers where some proportion is obesity-related, diagnosed from 1983-2017, was 1,005,933. This grouping was 34.7% of cancers diagnosed. The IRR of obesity-related cancers increased from 0.77 (95% CI 0.73, 0.81) for the 1903 birth-cohort to 2.95 (95% CI 2.58, 3.38) for the recent 1988 cohort relative to the 1943 cohort. The IRRs of non-obesity related cancers were stable with non-significant decreases in younger cohorts. These trends were broadly similar across sex and age groups. Interpretation: The incidence of obesity-related cancers in Australia has increased by birth-cohort across all age-groups, which should be monitored. Obesity, a public health epidemic, needs to be addressed through increased awareness, policy support and evidence-based interventions. Funding: This research received no specific funding.