Commentary: importance of considering sex and gender when designing cancer care programs.

Due to perceived methodological complications, scientific studies have often excluded females. As a result, male-based findings have been generalized to females, despite physiological and biological differences between sexes. Gender has been even less considered in the literature, with little exploration specifically beyond traditional man/woman representation. This practice is compounded by a lack of what sex and gender encompass, including their erroneous use as synonyms. Sex- and gender-based differences, which are not clearly defined and recognized in scientific literature, are disregarded in health care delivery and, specifically relevant to the focus of this commentary, the development of cancer care programs. Conversely, accounting for sex- and gender in anti-cancer treatments and pathways can help create effective and personalized programming which could lead to an increased likelihood of adoption and adherence to treatment protocols. Although sex- and gender-specific programming may not be necessary in all situations, awareness of the concepts and possible impact on cancer care programs is paramount as more inclusive and personalized methodologies take shape. The goals of this commentary are to (a) clarify the terms sex and gender and (b) raise awareness of their applications and considerations for cancer care program design.

Outcomes reported in randomised trials of surgical prehabilitation: a scoping review.

BACKGROUND: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation. METHODS: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework. RESULTS: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein. CONCLUSIONS: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses.

Reporting quality of randomized controlled trials in prehabilitation: a scoping review.

BACKGROUND: Inadequate study reporting precludes interpretation of findings, pooling of results in meta-analyses, and delays knowledge translation. While prehabilitation interventions aim to enhance candidacy for surgery, to our knowledge, a review of the quality of reporting in prehabilitation has yet to be conducted. Our objective was to determine the extent to which randomized controlled trials (RCTs) of prehabilitation are reported according to methodological and intervention reporting checklists. METHODS: Eligibility criteria: RCTs of unimodal or multimodal prehabilitation interventions. SOURCES OF EVIDENCE: search was conducted in March 2022 using MEDLINE, Embase, PsychINFO, Web of Science, CINAHL, and Cochrane. CHARTING METHODS: identified studies were compared to CONSORT, CERT & Modified CERT, TIDieR, PRESENT, and CONSORT-SPI. An agreement ratio (AR) was defined to evaluate if applicable guideline items were correctly reported. Data were analyzed as frequency (n, %) and mean with standard deviation (SD). RESULTS: We identified 935 unique articles and included 70 trials published from 1994 to 2022. Most prehabilitation programs comprised exercise-only interventions (n = 40, 57%) and were applied before oncologic surgery (n = 32, 46%). The overall mean AR was 57% (SD: 20.9%). The specific mean ARs were as follows: CONSORT: 71% (SD: 16.3%); TIDieR: 62% (SD:17.7%); CERT: 54% (SD: 16.6%); Modified-CERT: 40% (SD:17.8%); PRESENT: 78% (SD: 8.9); and CONSORT-SPI: 47% (SD: 22.1). CONCLUSION: Altogether, existing prehabilitation trials report approximately half of the checklist items recommended by methodological and intervention reporting guidelines. Reporting practices may improve with the development of a reporting checklist specific to prehabilitation interventions.

Barriers and facilitators to participation in exercise prehabilitation before cancer surgery for older adults with frailty: a qualitative study.

BACKGROUND: Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. METHODS: This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. RESULTS: Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. CONCLUSIONS: Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions.

Home-based prehabilitation with exercise to improve postoperative recovery for older adults with frailty having cancer surgery: the PREHAB randomised clinical trial.

BACKGROUND: Frailty is a state of vulnerability as a result of decreased reserves. Prehabilitation may increase reserve and improve postoperative outcomes. Our objective was to determine if home-based prehabilitation improves postoperative functional recovery in older adults with frailty having cancer surgery. METHODS: This double blind randomised trial enrolled people ≥60 yr having elective cancer surgery and ≥3 weeks from enrolment to surgery as eligible. Participation in a remotely supported, home-based exercise prehabilitation program plus nutritional guidance was compared with standard care plus written advice on age-appropriate activity and nutrition. The primary outcome was 6-min walk test (6MWT) distance at the first postoperative clinic visit. Secondary outcomes included physical performance, quality of life, disability, length of stay, non-home discharge, and 30-day readmission. RESULTS: Of 543 patients assessed, 254 were eligible and 204 (80%) were randomised (102 per arm); 182 (94 intervention and 88 control) had surgery and were analysed. Mean age was 74 yr and 57% were female. Mean duration of participation was 5 weeks, mean adherence was 61% (range 0%-100%). We found no significant difference in 6MWT at follow-up (+14 m, 95% confidence interval -26-55 m, P=0.486), or for secondary outcomes. Analyses using a prespecified adherence definition of ≥80% supported improvements in 6MWT distance, complication count, and disability. CONCLUSIONS: A home-based prehabilitation program did not significantly improve postoperative recovery or other outcomes in older adults with frailty having cancer surgery. Program adherence may be a key mediator of prehabilitation efficacy. CLINICAL TRIAL REGISTRATION: NCT02934230.

Feasibility of a novel mixed-nutrient supplement in a multimodal prehabilitation intervention for lung cancer patients awaiting surgery: A randomized controlled pilot trial.

OBJECTIVE: To investigate, in lung cancer patients awaiting elective surgery, the feasibility of delivering a novel four-week multimodal prehabilitation intervention and its effects on preoperative functional capacity and health-related quality of life (HRQoL), compared to standard hospital care. METHODS: Adult patients awaiting elective thoracotomy for lung cancer stages I, II or IIIa, were approached to participate in an open-label, randomized controlled trial of two parallel arms: multimodal prehabilitation combining a mixed-nutrient supplement with structured supervised and home-based exercise training, and relaxation-strategies (Prehab) or standard hospital care (Control). Feasibility was assessed based on recruitment and adherence rates to the intervention and study outcome assessment. Functional capacity, measured by the 6-min walk test (6MWT), and HRQoL were measured at baseline and after four weeks (preoperative). RESULTS: Within 5 months, 34 patients were enrolled and randomized (2:1) to Prehab (n = 24; median age = 67 years) or Control (n = 10; median age = 69 years); recruitment rate of 58.6%. The study was interrupted by the COVID-19 pandemic. Adherence to the prescribed intensity of the supervised exercise program was 84.1% (SD 23.1). Self-reported adherence to the home-based exercise program was 88.2% (SD 21) and to the nutritional supplement, 93.2% (SD 14.2). Adherence to patients' preoperative assessment was 82% and 88% in Prehab and Control, respectively. The mean adjusted difference in 4-week preoperative 6MWT between groups was 37.7 m (95% CI, -6.1 to 81.4), p = 0.089. There were no differences in HRQoL between groups. CONCLUSION: Within a preoperative timeframe, it was feasible to deliver this novel multimodal prehabilitation intervention in lung cancer patients awaiting surgery.

Effects of preoperative nutrition and multimodal prehabilitation on functional capacity and postoperative complications in surgical lung cancer patients: a systematic review.

OBJECTIVE: To determine the effect of preoperative nutrition and multimodal prehabilitation on clinical and functional outcomes in surgical lung cancer patients. METHODS: We searched MEDLINE, Cochrane Library and CENTRAL, EMBASE, Scopus, and clinical trial registries ( clinicaltrials.gov , International Clinical Trials Registry Platform and Google Scholar) to identify studies involving a preoperative nutrition-based intervention or multimodal prehabilitation (nutrition with exercise) of at least 7 days, in lung cancer patients awaiting surgery. Studies must have reported results on at least one of the following outcomes: functional capacity, pulmonary function, postoperative complications, and length of hospital stay. The quality of included studies was assessed using the Cochrane risk of bias assessment tool for randomized trials and the modified Newcastle-Ottawa scale for non-controlled trials. RESULTS: Five studies were included (1 nutrition-only and 4 multimodal prehabilitation studies). Due to substantial heterogeneity in the interventions across studies, a meta-analysis was not conducted. Findings suggest that multimodal prehabilitation, compared with standard hospital care, is associated with improvements in both functional walking capacity and pulmonary function during the preoperative period; however it does not appear to have an effect on postoperative outcomes. Rather, the finding of significantly lower rates of postoperative complications in the intervention group was unique to the nutrition-only study. CONCLUSION: Multimodal prehabilitation programs that combine nutrition and exercise may have beneficial effects on various physical function outcomes in patients with lung cancer awaiting surgery. Optimizing preoperative nutrition may have postoperative benefits which remain to be confirmed.

Malnourished lung cancer patients have poor baseline functional capacity but show greatest improvements with multimodal prehabilitation.

OBJECTIVE: The objective is to characterize the presence of malnutrition, examine the association between malnutrition and baseline functional capacity (FC), and the extent to which patients benefit from preoperative multimodal prehabilitation in patients undergoing lung resection for cancer. METHODS: Data from 162 participants enrolled in multimodal prehabilitation or control before lung cancer surgery were analyzed. Malnutrition was measured using the Patient-Generated Subjective Global Assessment (PG-SGA) according to triage levels: low-nutrition-risk (PG-SGA 0-3), moderate-nutrition-risk (4-8) and high-nutrition-risk (≥9). Baseline differences in FC, measured by the 6-minute walk test (6MWT), were compared. Factorial analysis of covariance (ANCOVA) was conducted to examine the effect of nutrition status and intervention on mean change in 6MWT preoperatively. RESULTS: 51.2% patients were considered low-nutrition-risk, 37.7% moderate-nutrition-risk, and 11.1% high-nutrition-risk. Low-nutrition-risk patients had significantly higher 6MWT at baseline (mean of 484 m [standard deviation (SD) = 88]) compared with moderate-nutrition-risk (432 m [SD = 107], P = .005) and high-nutrition-risk groups (416 m [SD = 90], P = .022). The adjusted mean change in 6MWT between prehabilitation vs control was 18.1 (95% confidence interval, 3.8 to 32.3) vs 5.6 m (-14.1 to 25.4) in low-nutrition-risk (P = .309), 28.5 (11 to 46) vs -4 m (-31.3 to 23.4) in moderate-nutrition-risk (P = .053), and 58.9 (16.7 to 101.2) vs -39.7 m (-80.2 to 0.826) in high-nutrition-risk group (P = .001). CONCLUSIONS: Lung cancer patients at high-nutrition-risk awaiting surgery had significantly lower baseline FC compared with low-nutrition-risk patients but experienced significant improvements in preoperative FC upon receiving multimodal prehabilitation.

The Potential of Prehabilitation in Radical Cystectomy Pathways: Where Are We Now?

OBJECTIVE: The growing recognition of prehabilitation has caused an emerging paradigm shift in surgical cancer care and an integrated component of the cancer care continuum. This narrative review aims to update and inform the urological community of the potential of prehabilitation before radical cystectomy. DATA SOURCES: A nonsystematic narrative review was performed through a database search in PubMed, and CINAHL using the following search terms: enhanced recovery after surgery (ERAS); Frailty; Prehabilitation and/or Rehabilitation; Physical Activity and/or exercises; Nutrition; Nutritional Care; Smoking cessation; Alcohol cessation; Prevention; Supportive Care; and combined with Radical Cystectomy. CONCLUSION: A multimodal and multi-professional approach during the preoperative period may offer an opportunity to preserve or enhance physiological integrity and optimize surgical recovery. Studies indicate a positive effect of prehabilitation on postoperative functional capacity and earlier return to daily activities and health related quality of life. Meaningful outcomes that reflect recovery from a patient's perspective and clinical outcome measures, as well as validating metrics, are necessary to establish whether prehabilitation diminish the risk of developing long-term disability in high-risk patients. IMPLICATIONS FOR NURSING PRACTICE: Uro-oncology nurses are at the forefront in every ERAS program and vital in screening patients ahead of surgery for common risk factors, current impairments, and limitations that can compromise baseline functional capacity. The growing movement to standardize clinical implementation of prehabilitation, indicate there is a clear need for further investigation, optimization of a multimodal approach and an open discussion between health care providers from different areas of expertise who might best support and promote these initiatives.

Effect of two different pre-operative exercise training regimens before colorectal surgery on functional capacity: A randomised controlled trial.

BACKGROUND: Multimodal prehabilitation, including exercise training, nutritional therapy and anxiety reduction, has been shown to attenuate functional decline associated with surgery. Due to the growing interest in functional status as a targeted surgical outcome, a better understanding of the optimal prescription of exercise is critical. OBJECTIVE: The objective is to compare peri-operative functional trajectory in response to two different exercise training protocols within a 4-week, supervised, multimodal prehabilitation programme. DESIGN: This was a single blinded, single centre, randomised controlled study. Participants performed four assessments: at baseline, after prehabilitation (just before surgery), and at 1 and 2 months after surgery. PATIENTS: Adult patients scheduled for elective resection of nonmetastatic colorectal cancer were included provided there were no absolute contraindications to exercise nor poor language comprehension. INTERVENTION: Patients followed either high-intensity interval training (HIIT), or moderate intensity continuous training (MICT), as part of a 4-week multimodal prehabilitation programme. Both groups followed the same supervised resistance training, nutritional therapy and anxiety reduction interventions. All patients followed standardised peri-operative management. MAIN OUTCOME MEASURE: Changes in oxygen consumption at anaerobic threshold, measured with sequential cardio-pulmonary exercise testing, were assessed and compared between groups. RESULTS: Forty two patients were included in the primary analysis (HIIT n = 21 vs. MICT n = 21), with mean ±â€ŠSD age 64.5 ±â€Š11.2 years and 62% were men. At 2 months after surgery, 13/21 (62%) in HIIT and 11/21 (52%) in MICT attended the study visits. Both protocols significantly enhanced pre-operative functional capacity, with no difference between groups: mean (95% confidence interval) oxygen consumption at anaerobic threshold 1.97 (0.75 to 3.19) ml kg min in HIIT vs. 1.71 (0.56 to 2.85) in MICT, P = 0.753. At 2 months after surgery, the HIIT group showed a higher improvement in physical fitness: 2.36 (0.378 to 4.34) ml kg min, P = 0.021. No adverse events occurred during the intervention. CONCLUSION: Both MICT and HIIT enhanced pre-operative functional capacity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03361150.

Effect of Multimodal Prehabilitation vs Postoperative Rehabilitation on 30-Day Postoperative Complications for Frail Patients Undergoing Resection of Colorectal Cancer: A Randomized Clinical Trial.

Importance: Research supports use of prehabilitation to optimize physical status before and after colorectal cancer resection, but its effect on postoperative complications remains unclear. Frail patients are a target for prehabilitation interventions owing to increased risk for poor postoperative outcomes. Objective: To assess the extent to which a prehabilitation program affects 30-day postoperative complications in frail patients undergoing colorectal cancer resection compared with postoperative rehabilitation. Design, Setting, and Participants: This single-blind, parallel-arm, superiority randomized clinical trial recruited patients undergoing colorectal cancer resection from September 7, 2015, through June 19, 2019. Patients were followed up for 4 weeks before surgery and 4 weeks after surgery at 2 university-affiliated tertiary hospitals. A total of 418 patients 65 years or older were assessed for eligibility. Of these, 298 patients were excluded (not frail [n = 290], unable to exercise [n = 3], and planned neoadjuvant treatment [n = 5]), and 120 frail patients (Fried Frailty Index,≥2) were randomized. Ten patients were excluded after randomization because they refused surgery (n = 3), died before surgery (n = 3), had no cancer (n = 1), had surgery without bowel resection (n = 1), or were switched to palliative care (n = 2). Hence, 110 patients were included in the intention-to-treat analysis (55 in the prehabilitation [Prehab] and 55 in the rehabilitation [Rehab] groups). Data were analyzed from July 25 through August 21, 2019. Interventions: Multimodal program involving exercise, nutritional, and psychological interventions initiated before (Prehab group) or after (Rehab group) surgery. All patients were treated within a standardized enhanced recovery pathway. Main Outcomes and Measures: The primary outcome included the Comprehensive Complications Index measured at 30 days after surgery. Secondary outcomes were 30-day overall and severe complications, primary and total length of hospital stay, 30-day emergency department visits and hospital readmissions, recovery of walking capacity, and patient-reported outcome measures. Results: Of 110 patients randomized, mean (SD) age was 78 (7) years; 52 (47.3%) were men and 58 (52.7%) were women; 31 (28.2%) had rectal cancer; and 87 (79.1%) underwent minimally invasive surgery. There was no between-group difference in the primary outcome measure, 30-day Comprehensive Complications Index (adjusted mean difference, -3.2; 95% CI, -11.8 to 5.3; P = .45). Secondary outcome measures were also not different between groups. Conclusions and Relevance: In frail patients undergoing colorectal cancer resection (predominantly minimally invasive) within an enhanced recovery pathway, a multimodal prehabilitation program did not affect postoperative outcomes. Alternative strategies should be considered to optimize treatment of frail patients preoperatively. Trial Registration: ClinicalTrials.gov identifier: NCT02502760.

Depression and functional status in colorectal cancer patients awaiting surgery: Impact of a multimodal prehabilitation program.

OBJECTIVE: Depression and poor functional status (FS) frequently co-occur. Though both predict adverse surgical outcomes, research examining preoperative functional performance (FP; self-reported) and functional capacity (FC; performance-based) measures in depressed cancer patients is lacking. Prehabilitation, a preoperative intervention including exercise, nutrition, and stress-reduction, may improve FC; however, whether depressed patients benefit from this intervention remains unknown. The primary objectives were to (a) assess differences in FP and FC and (b) explore the impact of prehabilitation on FC in individuals with depressive symptoms versus those without. METHOD: A secondary analysis was conducted on 172 colorectal cancer patients enrolled in three studies comparing prehabilitation with a control group (rehabilitation). Measures were collected at 4 weeks pre- and 8 weeks postoperatively. FP, FC, and psychological symptoms were assessed using the 36-Item Short Form Health Survey, Six-Minute Walk Distance (6MWD), and Hospital Anxiety and Depression Scale (HADS), respectively. Subjects were divided into three groups according to baseline psychological symptoms: no psychological-symptoms (HADS-N), anxiety-symptoms (HADS-A), or depressive-symptoms (HADS-D). Main objectives were tested using analyses of variance, chi-square tests, and multivariate logistic regression. RESULTS: At baseline, HADS-D reported lower FP, had shorter 6MWD, and a greater proportion walked ≤ 400 m. Prehabilitation was associated with significant improvements in 6MWD in HADS-D group but not in HADS-N or HADS-A groups. CONCLUSION: Poorer FS was observed in subjects with depressive symptoms, and these subjects benefited most from prehabilitation intervention. Future research could examine whether severity of depression and co-occurrence of anxiety differentially impact FS and whether prehabilitation can improve psychological symptoms and quality of life. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

In-hospital resistance training to encourage early mobilization for enhanced recovery programs after colorectal cancer surgery: A feasibility study.

BACKGROUND: The enhancement of post-operative care is under constant evolution and, with the addition of enhanced recovery programs, is changing the traditional in-hospital paradigm. Despite these advances, there is a clear lack of focus regarding early post-surgical mobilization, which has been identified as an important aspect of recovery. This pilot study investigates the feasibility of initiating resistance exercise to promote early mobilization in colorectal cancer patients during the in-hospital period. METHOD: Patients participated in a supervised progressive resistance exercise program, adapted to their physical ability (either in bed, seated or standing), within the first 24 h following surgery. They were seen each day during the hospital stay and encouraged to continue exercising upon discharge. All patients were asked to return to the lab at four weeks after surgery for re-evaluation to establish recovery. RESULTS: Patient compliance to the in-hospital program was high, with 90% of patients engaging in exercise on the first post-operative day (POD 1) and no adverse effects reported during study. By POD 2, over 70% of patients met enhanced recovery after surgery (ERAS) recommendations. CONCLUSION: It is feasible to initiate a progressive post-operative resistance exercise program in patients undergoing colorectal resection. The results suggest the positive aspects of incorporating resistance exercise into post-operative care. This may facilitate a clear and easy to implement exercise intervention that can take into consideration patient physical status and limited facility space in the hospital environment.

The impact of improved functional capacity before surgery on postoperative complications: a study in colorectal cancer.

Background: Poor functional capacity (FC) is an independent predictor of postoperative morbidity. However, there is still a lack of evidence as to whether enhancing FC before surgery has a protective effect on postoperative complications. The purpose of this study was to determine whether an improvement in preoperative FC impacted positively on surgical morbidity. Methods: This was a secondary analysis of a cohort of patients who underwent colorectal resection for cancer under Enhanced Recovery After Surgery care. FC was assessed with the 6-min walk test, which measures the distance walked in 6 min (6MWD), at 4 weeks before surgery and again the day before. The study population was classified into two groups depending on whether participants achieved a significant improvement in FC preoperatively (defined as a preoperative 6MWD change ≥19 meters) or not (6MWD change <19 meters). The primary outcome measure was 30-d postoperative complications, assessed with the Comprehensive Complication Index (CCI). The association between improved preoperative FC and severe postoperative complication was evaluated using multivariable logistic regression. Results: A total of 179 eligible adults were studied: 80 (44.7%) improved in 6MWD by ≥19 m preoperatively, and 99 (55.3%) did not. Subjects whose FC increased had lower CCI (0 [0-8.7] versus 8.7 [0-22.6], p = .022). Furthermore, they were less likely to have a severe complication (adjusted OR 0.28 (95% CI 0.11-0.74), p = .010), and to have an ED visit. Conclusion: Improved preoperative FC was independently associated with a lower risk of severe postoperative complications. Further investigation is required to establish a causative relationship conclusively.

Multimodal prehabilitation in colorectal cancer patients to improve functional capacity and reduce postoperative complications: the first international randomized controlled trial for multimodal prehabilitation.

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients' functional capacity and postoperative complications. METHODS/DESIGN: This international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis. DISCUSSION: Multimodal prehabilitation is expected to enhance patients' functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer. TRIAL REGISTRATION: Trial Registry: NTR5947 - date of registration: 1 August 2016.

Supervised exercise training with multimodal pre-habilitation leads to earlier functional recovery following colorectal cancer resection.

BACKGROUND: Exercise training is a component of the pre-habilitation program. While in one previous study the training was home-based, in a subsequent investigation it was supervised in hospital. The hypothesis of this secondary analysis of the two studies was to determine whether supervised exercise further accelerates the return to baseline walking ability. METHODS: Data from two consecutive randomized control trials (RCT) comparing pre-habilitation to the rehabilitation of cancer patients scheduled for colorectal surgery were pooled for analysis. The interventions were similar and included home-based exercise training, nutritional counseling and protein supplementation, and relaxation techniques administered either before surgery (pre-habilitation) or after surgery (rehabilitation). Patients in the second RCT received additional supervised exercise sessions. Functional capacity was assessed with the 6-minute walk test (6 MWT) at baseline, before surgery, and at 4 and 8 weeks after surgery. Adjusted logistic regression was used to determine the improvement of the 6-minute walk distance (6MWD). RESULTS: Baseline mean 6MWD of 63 patients in the supervised group was 465.1 m (SD, 115), and that of 77 patients in the nonsupervised group was 407.8 m (SD, 109) (P < 0.01). Perioperative supervised exercise training enhanced further functional capacity and muscle strength when compared with the nonsupervised group (P < 0.01). Those receiving exercise supervision had over two times higher chances to return to baseline after surgery. Supervised pre-habilitation was the best combination (4 weeks OR = 7.71, and at 8 weeks OR = 8.62). CONCLUSION: Supervised exercise training leads to meaningful changes in functional capacity thus accelerating the postoperative return to baseline activities.

PREHAB study: a protocol for a prospective randomised clinical trial of exercise therapy for people living with frailty having cancer surgery.

INTRODUCTION: Exercise prehabilitation may improve outcomes after surgery. Frailty is a key predictor of adverse postoperative outcomes in older people; the multidimensional nature of frailty makes this a population who may derive substantial benefit from exercise prehabilitation. The objective of this trial is to test the efficacy of exercise prehabilitation to improve postoperative functional outcomes for people living with frailty having cancer surgery with curative intent. METHODS AND ANALYSIS: We will conduct a single-centre, parallel-arm randomised controlled trial of home-based exercise prehabilitation versus standard care among consenting patients >60 years having elective cancer surgery (intra-abdominal and intrathoracic) and who are frail (Clinical Frailty Scale >4). The intervention consists of > 3 weeks of exercise prehabilitation (strength, aerobic and stretching). The primary outcome is the 6 min walk test at the first postoperative clinic visit. Secondary outcomes include the short physical performance battery, health-related quality of life, disability-free survival, complications and health resource utilisation. The primary outcome will be analysed by intention to treat using analysis of covariance. Outcomes up to 1 year after surgery will be ascertained through linkage to administrative data. ETHICS AND DISSEMINATION: Ethical approval has been granted by our ethics review board (Protocol Approval #2016009-01H). Results will be disseminated through presentation at scientific conferences, through peer-reviewed publication, stakeholder organisations and engagement of social and traditional media. TRIAL REGISTRATION NUMBER: NCT02934230; Pre-results.

Maximizing patient adherence to prehabilitation: what do the patients say?

PURPOSE: Multimodal prehabilitation programs (exercise, nutrition, and anxiety reduction) have been shown to be successful for enhancing patients' physical function prior to surgery, although adherence remains a challenge. Given the short pre-operative period, maintaining adherence is critical to maximize program effectiveness. This study was designed to better understand patients' perspectives of prehabilitation and to identify factors related to program adherence. METHODS: A qualitative descriptive study was conducted based on 52 cancer patients enrolled in a prehabilitation program at the Montreal General Hospital, Montreal, Canada. Data was collected with a structured questionnaire designed to evaluate the program. RESULTS: Patients enjoyed their experience in prehabilitation, especially the exercise program and training sessions. The primary motivating factor for participation was to be physically prepared for the surgery. The most challenging exercise component was resistance training, while the most enjoyed was the aerobic training. Approximately 50% of patients were interested in group fitness classes as opposed to supervised individual training sessions for reasons related to social support. The preferred methods for exercise program delivery were home-based and one supervised exercise session per week. The biggest barrier to participation was related to transportation. CONCLUSIONS: These findings highlight the need to make prehabilitation programs more patient-centered. This is critical when designing more effective therapeutic strategies tailored to meet patients' specific needs while overcoming program non-adherence.

Evaluation of supervised multimodal prehabilitation programme in cancer patients undergoing colorectal resection: a randomized control trial.

BACKGROUND: Prehabilitation has been previously shown to be more effective in enhancing postoperative functional capacity than rehabilitation alone. The purpose of this study was to determine whether a weekly supervised exercise session could provide further benefit to our current prehabilition program, when comparing to standard post-surgical rehabilitation. METHODS: A parallel-arm single-blind randomized control trial was conducted in patients scheduled for non-metastatic colorectal cancer resection. Patients were assigned to either a once weekly supervised prehabilitation (PREHAB+, n = 41) or standard rehabilitation (REHAB, n = 39) program. Both multimodal programs were home-based program and consisted of moderate intensity aerobic and resistance exercise, nutrition counseling with daily whey protein supplementation and anxiety-reduction strategies. Perioperative care was standardized for both groups as per enhanced recovery after surgery (ERAS®) guidelines. Functional exercise capacity, as determined by the 6-minute walk test distance (6MWD), was the primary outcome. Exercise quantity, intensity and energy expenditure was determined by the CHAMPS questionnaire. RESULTS: Both groups were comparable for baseline walking capacity (PREHAB+: 448 m [IQR 375-525] vs. REHAB: 461 m [419-556], p=.775) and included a similar proportion of patients who improved walking capacity (>20 m) during the preoperative period (PREHAB+: 54% vs. REHAB: 38%, p = .222). After surgery, changes in 6MWD were also similar in both groups. In PREHAB+, however, there was a significant association between physical activity energy expenditure and 6MWD (p < .01). Previously inactive patients were more likely to improve functional capacity due to PREHAB+ (OR 7.07 [95% CI 1.10-45.51]). CONCLUSIONS: The addition of a weekly supervised exercise session to our current prehabilitation program did not further enhance postoperative walking capacity when compared to standard REHAB care. Sedentary patients, however, seemed more likely to benefit from PREHAB+. An association was found between energy spent in physical activity and 6MWD. This information is important to consider when designing cost-effective prehabilitation programs.

Adaptation of mitochondrial expression and ATP production in dedifferentiating vascular smooth muscle cells.

Atherosclerosis is one of the leading causes of morbidity and mortality in the Western world. Although the clinical manifestations of this disease are well documented, the etiology and progression remain to be fully understood. Recently, the mitochondria have been implicated in important cellular processes involved in development of atherosclerosis. Despite the link between mitochondria and atherosclerosis, early-phase mechanisms of the disease have yet to be elucidated. The aim of this project was to explore the role of mitochondria in vascular smooth muscle (VSMC) dedifferentiation. A murine in vitro model, involving organ culture of aortic tissue in serum-free media, was used. Mitochondrial function was measured by high-resolution respirometry. Proteins associated with the VSMC phenotype switch, as well as mitochondrial density, were assessed by immunoblotting. The findings show that intrinsic mitochondrial Complex I activity is significantly upregulated during VSMC dedifferentiation. Diminished coupling between phosphorylation and oxidation was also found, indicating a greater ADP:ATP ratio. This data suggests increased leak in the electron transport chain and altered mitochondrial function specifically at Complex I. This project provides important information regarding the role of mitochondria in the early atherosclerotic process and that detectable changes in mitochondrial function and expression are related to VSMC dedifferentiation.