Effectiveness of Prehabilitation Modalities on Postoperative Outcomes Following Colorectal Cancer Surgery: A Systematic Review of Randomised Controlled Trials.

BACKGROUND: Postoperative morbidity in patients undergoing curative colorectal cancer surgery is high. Prehabilitation has been suggested to reduce postoperative morbidity, however its effectiveness is still lacking. OBJECTIVE: The aim of this study was to investigate the effectiveness of prehabilitation in reducing postoperative morbidity and length of hospital stay in patients undergoing colorectal cancer surgery. METHODS: A comprehensive electronic search was conducted in the CINAHL, Cochrane Library, Medline, PsychINFO, AMED, and Embase databases from inception to April 2023. Randomised controlled trials testing the effectiveness of prehabilitation, including exercise, nutrition, and/or psychological interventions, compared with usual care in patients undergoing colorectal cancer surgery were included. Two independent review authors extracted relevant information and assessed the risk of bias. Random-effect meta-analyses were used to pool outcomes, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. RESULTS: A total of 23 trials were identified (N = 2475 patients), including multimodal (3 trials), exercise (3 trials), nutrition (16 trials), and psychological (1 trial) prehabilitation. There was moderate-quality evidence that preoperative nutrition significantly reduced postoperative infectious complications (relative risk 0.65, 95% confidence interval [CI] 0.45-0.94) and low-quality evidence on reducing the length of hospital stay (mean difference 0.87, 95% CI 0.17-1.58) compared with control. A single trial demonstrated an effect of multimodal prehabilitation on postoperative complication. CONCLUSION: Nutrition prehabilitation was effective in reducing infectious complications and length of hospital stay. Whether other multimodal, exercise, and psychological prehabilitation modalities improve postoperative outcomes after colorectal cancer surgery is uncertain as the current quality of evidence is low. PROTOCOL REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/VW72N ).

International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults.

BACKGROUND: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery. METHODS: Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology. RESULT: Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery. CONCLUSIONS: MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Sarcopenia and Myosteatosis Predict Adverse Outcomes After Emergency Laparotomy: A Multi-center Observational Cohort Study.

OBJECTIVE: To determine the relationship between BC, specifically low skeletal muscle mass (sarcopenia) and poor muscle quality (myosteatosis) and outcomes in emergency laparotomy patients. BACKGROUND: Emergency laparotomy has one of the highest morbidity and mortality rates of all surgical interventions. BC objectively identifies patients at risk of adverse outcomes in elective cancer cohorts, however, evidence is lacking in emergency surgery. METHODS: An observational cohort study of patients undergoing emergency laparotomy at ten English hospitals was performed. BC analyses were performed at the third lumbar vertebrae level using preoperative computed tomography images to quantify skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SM-RA). Sex-specific SMI and SM-RA were determined, with the lower tertile splits defining sarcopenia (low SMI) and myosteatosis (low SM-RA). Accuracy of mortality risk prediction, incorporating SMI and SM-RA variables into risk models was assessed with regression modeling. RESULTS: Six hundred ten patients were included. Sarcopenia and myosteatosis were both associated with increased risk of morbidity (52.1% vs 45.1%, P = 0.028; 57.5% vs 42.6%, P = 0.014), 30-day (9.5% vs 3.6%, P = 0.010; 14.9% vs 3.4%, P < 0.001), and 1-year mortality (27.4% vs 11.5%, P < 0.001; 29.7% vs 12.5%, P < 0.001). Risk-adjusted 30-day mortality was significantly increased by sarcopenia [OR 2.56 (95% CI 1.12-5.84), P = 0.026] and myosteatosis [OR 4.26 (2.01-9.06), P < 0.001], similarly at 1-year [OR 2.66 (95% CI 1.57-4.52), P < 0.001; OR2.08 (95%CI 1.26-3.41), P = 0.004]. BC data increased discrimination of an existing mortality risk-prediction model (AUC 0.838, 95% CI 0.835-0.84). CONCLUSION: Sarcopenia and myosteatosis are associated with increased adverse outcomes in emergency laparotomy patients.

Empty pelvis syndrome: a systematic review of reconstruction techniques and their associated complications.

AIM: Empty pelvis syndrome is a major contributor to morbidity following pelvic exenteration. Several techniques for filling the pelvis have been proposed; however, there is no consensus on the best approach. We evaluated and compared the complications associated with each reconstruction technique with the aim of determining which is associated with the lowest incidence of complications related to the empty pelvis. METHOD: The systematic review protocol was prospectively registered with PROSPERO (CRD42021239307). PRISMA-P guidelines were used to present the literature. PubMed and MEDLINE were systematically searched up to 1 February 2021. A dataset containing predetermined primary and secondary outcomes was extracted. RESULTS: Eighteen studies fulfilled our criteria; these included 375 patients with mainly rectal and gynaecological cancer. Only three studies had a follow-up greater than 2 years. Six surgical interventions were identified. Mesh reconstruction and breast prosthesis were associated with low rates of small bowel obstruction (SBO), entero-cutaneous fistulas and perineal hernia. Findings for myocutaneous flaps were similar; however, they were associated with high rates of perineal wound complications. Omentoplasty was found to have a high perineal wound infection rate (40%). Obstetric balloons were found to have the highest rates of perineal wound dehiscence and SBO. Silicone expanders effectively kept small bowel out of the pelvis, although rates of pelvic collections remained high (20%). CONCLUSION: The morbidity associated with an empty pelvis remains considerable. Given the low quality of the evidence with small patient numbers, strong conclusions in favour of a certain technique and comparison of these interventions remains challenging.

Cardiopulmonary exercise testing has greater prognostic value than sarcopenia in oesophago-gastric cancer patients undergoing neoadjuvant therapy and surgical resection.

BACKGROUND: Sarcopenia (low skeletal muscle mass), myosteatosis (low skeletal muscle radiation-attenuation) and fitness are independently associated with postoperative outcomes in oesophago-gastric cancer. This study aimed to investigate (1) the effect of neoadjuvant therapy (NAT) on sarcopenia, myosteatosis and cardiopulmonary exercise testing (CPET), (2) the relationship between these parameters, and (3) their association with postoperative morbidity and survival. METHODS: Body composition analysis used single slice computed tomography (CT) images from chest (superior to aortic arch) and abdominal CT scans (third lumbar vertebrae). Oxygen uptake at anaerobic threshold (VO2 at AT) and at peak exercise (VO2 Peak) were measured using CPET. Measurements were performed before and after NAT and an adjusted regression model assessed their association. RESULTS: Of the 184 patients recruited, 100 underwent surgical resection. Following NAT skeletal muscle mass, radiation-attenuation and fitness reduced significantly (p < 0.001). When adjusted for age, sex, and body mass index, only pectoralis muscle mass was associated with VO2 Peak (p = 0.001). VO2 at AT and Peak were associated with 1-year survival, while neither sarcopenia nor myosteatosis were associated with morbidity or survival. CONCLUSION: Skeletal muscle and CPET variables reduced following NAT and were positively associated with each other. Cardiorespiratory function significantly contributes to short-term survival after oesophago-gastric cancer surgery.

Exercise interventions for people undergoing multimodal cancer treatment that includes surgery.

BACKGROUND: People undergoing multimodal cancer treatment are at an increased risk of adverse events. Physical fitness significantly reduces following cancer treatment, which is related to poor postoperative outcome. Exercise training can stimulate skeletal muscle adaptations, such as increased mitochondrial content and improved oxygen uptake capacity may contribute to improved physical fitness. OBJECTIVES: To determine the effects of exercise interventions for people undergoing multimodal treatment for cancer, including surgery, on physical fitness, safety, health-related quality of life (HRQoL), fatigue, and postoperative outcomes. SEARCH METHODS: We searched electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, SPORTDiscus, and trial registries up to October 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared the effects of exercise training with usual care, on physical fitness, safety, HRQoL, fatigue, and postoperative outcomes in people undergoing multimodal cancer treatment, including surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, performed the data extraction, assessed the risk of bias, and rated the quality of the studies using Grading of Recommendation Assessment, Development, and Evaluation (GRADE) criteria. We pooled data for meta-analyses, where possible, and reported these as mean differences using the random-effects model. MAIN RESULTS: Eleven RCTs were identified involving 1067 participants; 568 were randomly allocated to an exercise intervention and 499 to a usual care control group. The majority of participants received treatment for breast cancer (73%). Due to the nature of the intervention, it was not possible to blind the participants or personnel delivering the intervention. The risk of detection bias was either high or unclear in some cases, whilst most other domains were rated as low risk. The included studies were of moderate to very low-certainty evidence. Pooled data demonstrated that exercise training may have little or no difference on physical fitness (VO2 max) compared to usual care (mean difference (MD) 0.05 L/min-1, 95% confidence interval (CI) -0.03 to 0.13; I2 = 0%; 2 studies, 381 participants; low-certainty evidence). Included studies also showed in terms of adverse effects (safety), that it may be of benefit to exercise (8 studies, 507 participants; low-certainty evidence). Furthermore, exercise training probably made little or no difference on HRQoL (EORTC global health status subscale) compared to usual care (MD 2.29, 95% CI -1.06 to 5.65; I2 = 0%; 3 studies, 472 participants; moderate-certainty evidence). However, exercise training probably reduces fatigue (multidimensional fatigue inventory) compared to usual care (MD -1.05, 95% CI -1.83 to -0.28; I2 = 0%; 3 studies, 449 participants moderate-certainty evidence). No studies reported postoperative outcomes. AUTHORS' CONCLUSIONS: The findings should be interpreted with caution in view of the low number of studies, the overall low-certainty of the combined evidence, and the variation in included cancer types (mainly people with breast cancer), treatments, exercise interventions, and outcomes. Exercise training may, or may not, confer modest benefit on physical fitness and HRQoL. Limited evidence suggests that exercise training is probably not harmful and probably reduces fatigue. These findings highlight the need for more RCTs, particularly in the neoadjuvant setting.

The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial.

BACKGROUND: Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. METHODS: In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; M age = 64 years; 64% male) and in the control group (CG; M age = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; n EC = 24; n CG = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; n EC = 23; n CG = 10), and post-exercise intervention (Time 3; n EC = 22; n CG = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 min. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed-rank tests. RESULTS: No significant between-group differences in changes were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. CONCLUSIONS: The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. TRIAL REGISTRATION: This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011).

Preparing for and Not Waiting for Surgery.

Cancer surgery is an essential treatment strategy but can disrupt patients' physical and psychological health. With worldwide demand for surgery expected to increase, this review aims to raise awareness of this global public health concern, present a stepwise framework for preoperative risk evaluation, and propose the adoption of personalised prehabilitation to mitigate risk. Perioperative medicine is a growing speciality that aims to improve clinical outcome by preparing patients for the stress associated with surgery. Preparation should begin at contemplation of surgery, with universal screening for established risk factors, physical fitness, nutritional status, psychological health, and, where applicable, frailty and cognitive function. Patients at risk should undergo a formal assessment with a qualified healthcare professional which informs meaningful shared decision-making discussion and personalised prehabilitation prescription incorporating, where indicated, exercise, nutrition, psychological support, 'surgery schools', and referral to existing local services. The foundational principles of prehabilitation can be adapted to local context, culture, and population. Clinical services should be co-designed with all stakeholders, including patient representatives, and require careful mapping of patient pathways and use of multi-disciplinary professional input. Future research should optimise prehabilitation interventions, adopting standardised outcome measures and robust health economic evaluation.

External validation of a deep learning model for automatic segmentation of skeletal muscle and adipose tissue on abdominal computed tomography images.

BACKGROUND: Body composition assessment using computed tomography (CT) images at the L3-level is increasingly applied in cancer research. Robust high-throughput automated segmentation is key to assess large patient cohorts and to support implementation of body composition analysis into routine clinical practice. We trained and externally validated a deep learning neural network (DLNN) to automatically segment L3-CT images. METHODS: Expert-drawn segmentations of visceral and subcutaneous adipose tissue (VAT/SAT) and skeletal muscle (SM) of L3-CT-images of 3,187 patients undergoing abdominal surgery were used to train a DLNN. The external validation cohort was comprised of 2,535 patients with abdominal cancer. DLNN performance was evaluated with (geometric) Dice Similarity (DS) and Lin's Concordance Correlation Coefficient. RESULTS: There was a strong concordance between automatic and manual segmentations with median DS for SM, VAT, and SAT of 0.97 (interquartile range, IQR: 0.95-0.98), 0.98 (IQR: 0.95-0.98), and 0.95 (IQR: 0.92-0.97), respectively. Concordance correlations were excellent: SM 0.964 (0.959-0.968), VAT 0.998 (0.998-0.998), and SAT 0.992 (0.991-0.993). Bland-Altman metrics indicated only small and clinically insignificant systematic offsets; SM radiodensity: 0.23 hounsfield units (0.5%), SM: 1.26 cm2.m-2 (2.8%), VAT: -1.02 cm2.m-2 (1.7%), and SAT: 3.24 cm2.m-2 (4.6%). CONCLUSION: A robustly-performing and independently externally validated DLNN for automated body composition analysis was developed. ADVANCES IN KNOWLEDGE: CT-based body composition analysis is highly prognostic for long-term overall survival in oncology. This DLNN was succesfully trained and externally validated on several large patient cohorts and will therefore enable large scale population studies and implementation of body composition analysis into clinical practice.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Patients' perceptions of quality of life during active treatment for locally advanced rectal cancer: the importance of preoperative exercise.

PURPOSE: The purpose of this longitudinal study was to explore advanced rectal cancer patients' perceptions of quality of life (QoL) during participation in a pre-surgery structured exercise program. METHODS: Patients (n = 10) participated in repeated semi-structured in-depth interviews which covered four broad QoL domains (i.e., physical, psychological, social, and spiritual well-being). Patients' personal accounts of QoL were explored prior to (0 weeks), midway (3 weeks), and at completion (6 weeks) of the program. Data were analyzed using strategies grounded in a phenomenological approach. RESULTS: Participation in the program facilitated positive changes in QoL over time by (1) fostering a greater sense of vitality, (2) cultivating a positive attitude, (3) enhancing social connections, and (4) fostering a strong sense of purpose in life for these patients. CONCLUSIONS: Based on these data, preoperative exercise programs can be effective in promoting QoL among patients diagnosed and treated for locally advanced rectal cancer during a particularly difficult time in the cancer trajectory. Additional research is needed to develop and evaluate implementation strategies to facilitate the delivery of preoperative exercise programs as part of routine care in this population.

Potential mechanisms of multimodal prehabilitation effects on surgical complications: a narrative review.

Continuous advances in prehabilitation research over the past several decades have clarified its role in improving preoperative risk factors, yet the evidence demonstrating reduced surgical complications remains uncertain. Describing the potential mechanisms underlying prehabilitation and surgical complications represents an important opportunity to establish biological plausibility, develop targeted therapies, generate hypotheses for future research, and contribute to the rationale for implementation into the standard of care. In this narrative review, we discuss and synthesize the current evidence base for the biological plausibility of multimodal prehabilitation to reduce surgical complications. The goal of this review is to improve prehabilitation interventions and measurement by outlining biologically plausible mechanisms of benefit and generating hypotheses for future research. This is accomplished by synthesizing the available evidence for the mechanistic benefit of exercise, nutrition, and psychological interventions for reducing the incidence and severity of surgical complications reported by the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). This review was conducted and reported in accordance with a quality assessment scale for narrative reviews. Findings indicate that prehabilitation has biological plausibility to reduce all complications outlined by NSQIP. Mechanisms for prehabilitation to reduce surgical complications include anti-inflammation, enhanced innate immunity, and attenuation of sympathovagal imbalance. Mechanisms vary depending on the intervention protocol and baseline characteristics of the sample. This review highlights the need for more research in this space while proposing potential mechanisms to be included in future investigations.