Introduction Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre‐operative conditioning of patients to improve post‐operative outcomes. The beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post‐operative outcome after major abdominal surgery. Methods EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six‐minute walking test (6MWT) distance were obtained. The primary outcome was post‐operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference. Results Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46–0.87 I2 34%, p = 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23–0.68, I2 = 0%, p = 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD −2.39 95% CI −4.86 to 0.08 I2 = 0%, p = 0.06) or change in 6MWT distance (WMD 9.06 95% CI −35.68, 53.81 I2 = 88%, p = 0.69) was observed. Conclusions Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.

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Purpose: The mechanisms underlying muscle wasting in patients with cancer remain poorly understood, and consequently there remains an unmet clinical need for new biomarkers and treatment strategies.Experimental Design: Microarrays were used to examine the transcriptome in single biopsies from healthy controls (n ¼ 6) and in paired biopsies [pre-resection baseline (weight-loss 7%) and 8 month postresection follow-up (disease-free/weight-stable for previous 2 months)] from quadriceps muscle of patients with upper gastrointestinal cancer (UGIC; n ¼ 12).Results: Before surgery, 1,868 genes were regulated compared with follow-up (false discovery rate, 6%). Ontology analysis showed that regulated genes belonged to both anabolic and catabolic biologic processes with overwhelming downregulation in baseline samples. No literature-derived genes from preclinical cancer cachexia models showed higher expression in baseline muscle. Comparison with healthy control muscle (n ¼ 6) revealed that despite differences in the transcriptome at baseline (941 genes regulated), the muscle of patients at follow-up was similar to control muscle (2 genes regulated). Physical activity (step count per day) did not differ between the baseline and follow-up periods (P ¼ 0.9), indicating that gene expression differences reflected the removal of the cancer rather than altered physical activity levels. Comparative gene expression analysis using exercise training signatures supported this interpretation.Conclusions: Metabolic and protein turnover-related pathways are suppressed in weight-losing patients with UGIC whereas removal of the cancer appears to facilitate a return to a healthy state, independent of changes in the level of physical activity.

BackgroundIntramyocellular lipids are an important source of fuel for mitochondrial fat oxidation and play an important role in intramuscular lipid homeostasis. We hypothesised that due to the phenotype associated with cancer cachexia, there would exist an association between increasing weight loss and the number/size of intramyocellular lipid droplets.MethodsNineteen cancer patients and 6 controls undergoing surgery were recruited. A rectus abdominis biopsy was performed and processed for transmission electron microscopy (TEM). The number of intramyocellular lipid droplets and lipid droplet diameter were calculated from the TEM images. CT scans, performed as part of patients' routine care, were analysed to determine amount of adipose (intermuscular, visceral and subcutaneous) and muscle tissue.ResultsCompared with controls, cancer patients had increased numbers of lipid droplets (mean (SD) 1.8 (1.9) vs. 6.4 (9.1) per ×2,650 field, respectively, p = 0.036). Mean (SD) lipid droplet diameter was also higher in cancer patients compared with controls (0.42 (0.13) vs. 0.24 (0.21) μm, p = 0.015). Mean lipid droplet count correlated positively with the severity of weight loss (R = 0.51, p = 0.025) and negatively with CT-derived measures of intermuscular fat (R = −0.53, p = 0.022) and visceral fat (R = −0.51, p = 0.029).ConclusionsThis study suggests that the number and size of intramyocellular lipid droplets is increased in the presence of cancer and increases further with weight loss/loss of adipose mass in other body compartments.

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Background There is great overlap between the presentation of cachexia, sarcopenia, and malnutrition. Distinguishing between these conditions would allow for better targeted treatment for patients. Objectives The aim was to systematically review validated screening tools for cachexia, sarcopenia, and malnutrition in adults and, if a combined tool is absent, make suggestions for the generation of a novel screening tool. Design A systematic search was performed in Ovid Medline, EMBASE, CINAHL, and Web of Science. Two reviewers performed data extraction independently. Each tool was judged for validity against a reference method. Psychometric evaluation was performed as was appraisal of the tools’ ability to assess the patient against consensus definitions. Results Thirty-eight studies described 22 validated screening tools. The Cachexia score (CASCO) was the only validated screening tool for cachexia and performed well against the consensus definition. Two tools assessed sarcopenia [the Short Portable Sarcopenia Measure (SPSM) and the SARC-F (Strength, Assistance with walking, Rise from a chair, Climb stairs, and Falls)] and scored well against the 1998 Baumgartner definition. The SPSM required large amounts of equipment, and the SARC-F had a low sensitivity. Nineteen tools screened for malnutrition. The 3-Minute Nutrition Score performed best, meeting consensus definition criteria (European Society for Clinical Nutrition and Metabolism) and having a sensitivity and specificity of >80%. No tool contained all of the currently accepted components to screen for all 3 conditions. Only 3 tools were validated against cross-sectional imaging, a clinical tool that is gaining wider interest in body-composition analysis. Conclusions No single validated screening tool can be implemented for the simultaneous assessment of cachexia, sarcopenia, and malnutrition. The development of a tool that encompasses consensus definition criteria and directs clinicians toward the underlying diagnosis would be optimal to target treatment and improve outcomes. We propose that tool should incorporate a stepwise assessment of nutritional status, oral intake, disease status, age, muscle mass and function, and metabolic derangement.

BackgroundIn order to grow the potential therapeutic armamentarium in the cachexia domain of supportive oncology, there is a pressing need to develop suitable biomarkers and potential drug targets. This pilot study evaluated several potential candidate biomarkers in skeletal muscle biopsies from a cohort of upper gastrointestinal cancer (UGIC) patients.MethodsOne hundred seven patients (15 weight-stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight-loss of UGIC patients was 8.1 (9.3%). Cachexia was defined as weight-loss ≥5%. Rectus abdominis muscle was obtained at surgery and was analysed by western blotting or quantitative real-time–polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt, n = 52), forkhead box O transcription factors (n = 59), ubiquitin E3 ligases (n = 59, control of muscle anabolism/catabolism), BNIP3 and GABARAPL1 (n = 59, as markers of autophagy), myosin heavy-chain (MyHC, n = 54), dystrophin (n = 39), β-dystroglycan (n = 52), and β-sarcoglycan (n = 52, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255 days (range 581–1955 days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non-cachectic cancer patients; and (iii) cancer patients surviving ≤1 vs. >1 year post operatively.ResultsCancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17), P = 0.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P = 0.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57), P = 0.024]. β-Dystroglycan levels were higher in cachectic compared with non-cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20), P = 0.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326 days, P = 0.023) and dystrophin levels (median 341 vs. 660 days, P = 0.008).ConclusionsThe present study has identified intramuscular protein level of β-dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers.

Cachexia is an important clinical problem affecting up to two thirds of cancer patients. It results from anorexia and metabolic change and leads to loss of both adipose tissue and lean body mass, particularly in the skeletal muscle compartment. An APR is seen in half of cancer patients at presentation, and is most often determined clinically by raised plasma C-reactive protein concentrations. Adverse outcome and shortened survival have been linked to the presence of an APR. This article explores the cause and consequences of the APR in cancer cachexia.