Dan Lythgoe

Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study

BACKGROUND Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which the effects on physical fitness are unknown. The aim of this feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme (SRETP) on oxygen uptake [Formula: see text] at lactate threshold ([Formula: see text]) in such patients. METHODS We prospectively studied 39 consecutive subjects (27 males) with T3-4/N+ resection margin threatened rectal cancer who completed standardized NACRT. Subjects underwent cardiopulmonary exercise testing at baseline (pre-NACRT), at week 0 (post-NACRT), and week 6 (post-SRETP). Twenty-two subjects undertook a 6 week SRETP on a training bike (three sessions per week) between week 0 and week 6 (exercise group). These were compared with 17 contemporaneous non-randomized subjects (control group). Changes in [Formula: see text] at [Formula: see text] over time and between the groups were compared using a compound symmetry covariance linear mixed model. RESULTS Of 39 recruited subjects, 22 out of 22 (exercise) and 13 out of 17 (control) completed the study. There were differences between the exercise and control groups at baseline [age, ASA score physical status, World Health Organisation performance status, and Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) predicted mortality]. In all subjects, [Formula: see text] at [Formula: see text] significantly reduced between baseline and week 0 [-1.9 ml kg(-1) min(-1); 95% confidence interval (CI) -1.3, -2.6; P<0.0001]. In the exercise group, [Formula: see text] at [Formula: see text] significantly improved between week 0 and week 6 (+2.1 ml kg(-1) min(-1); 95% CI +1.3, +2.9; P<0.0001), whereas the control group values were unchanged (-0.7 ml kg(-1) min(-1); 95% CI -1.66, +0.37; P=0.204). CONCLUSIONS NACRT before rectal cancer surgery reduces physical fitness. A structured exercise intervention is feasible post-NACRT and returns fitness to baseline levels within 6 weeks. CLINICAL TRIAL REGISTRATION NCT 01325909.

Cardiopulmonary exercise variables are associated with postoperative morbidity after major colonic surgery: a prospective blinded observational study

BACKGROUND Postoperative complications are associated with reduced fitness. Cardiopulmonary exercise testing (CPET) has been used in risk stratification. We investigated the relationship between preoperative CPET and in-hospital morbidity in major colonic surgery. METHODS We prospectively studied 198 patients undergoing major colonic surgery (excluding neoadjuvant cancer therapy), performing preoperative CPET (reported blind to clinical state), and recording morbidity (assessed blind to CPET), postoperative outcome, and length of stay. RESULTS Of 198 patients, 62 were excluded: 11 had emergency surgery, 25 had no surgery, 23 had incomplete data, and three were unable to perform CPET. One hundred and thirty-six (89 males, 47 females) were available for analysis. The median age was 71 [inter-quartile range (IQR) 62-77] yr. Sixty-five patients (48%) had a complication at day 5 after operation. Measurements significantly lower in patients with complications than those without were O2 uptake (VO₂) at estimated lactate threshold (θ(L)) [median 9.9 (IQR 8.3-12.7) vs 11.2 (9.5-14.2) ml kg(-1) min(-1), P<0.01], VO₂ at peak [15.2 (12.6-18.1) vs 17.2 (13.7-22.5) ml kg(-1) min(-1), P=0.01], and ventilatory equivalent for CO2 (V(E)/VCO₂) at θ(L) [31.3 (28.0-34.8) vs 33.9 (30.0-39.1), P<0.01]. A final multivariable logistic regression model contained VO₂ at θ(L) {one-point change odds ratio (OR) 0.77 [95% confidence interval (CI) 0.66-0.89], P<0.0005; two-point change OR 0.61 (0.46-0.81) and gender [OR 4.42 (1.78-9.88), P=0.001]}, and was reasonably able to discriminate those with and without complications (AUC 0.71, CI 0.62-0.80, 68% sensitivity, 65% specificity). CONCLUSIONS CPET variables are associated with postoperative morbidity. A multivariable model with VO₂ at θ(L) and gender discriminates those with complications after colonic surgery.

Cardiopulmonary exercise testing for the prediction of morbidity risk after rectal cancer surgery

This study investigated the relationship between objectively measured physical fitness variables derived by cardiopulmonary exercise testing (CPET) and in‐hospital morbidity after rectal cancer surgery.

Randomized clinical trial of prehabilitation before planned liver resection

Patients with low fitness as assessed by cardiopulmonary exercise testing (CPET) have higher mortality and morbidity after surgery. Preoperative exercise intervention, or prehabilitation, has been suggested as a method to improve CPET values and outcomes. This trial sought to assess the capacity of a 4‐week supervised exercise programme to improve fitness before liver resection for colorectal liver metastasis.

Enhanced recovery in the resection of colorectal liver metastases.

There is limited evidence for the use of enhanced recovery after surgery (ERAS) in patients undergoing hepatectomy, and the impact of the evolution of ERAS over time has not been examined. This study sought to evaluate the effect of an evolving ERAS program in patients undergoing hepatectomy for colorectal liver metastases (CRLM).

Cardiopulmonary exercise testing before liver surgery

Cardiopulmonary exercise testing (CPET) assessed “poorer” fitness correlates with poorer outcomes in blinded studies. Whether this correlation will persist when CPET is utilized to stratify care as part of a multi‐modal enhanced recovery after surgery (ERAS) program is unclear. This study examined whether CPET variables were associated with postoperative morbidity in patients undergoing hepatectomy within an ERAS program.

The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.

Background In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness. Methods We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg−1.min−1), and the post-exercise phosphocreatine recovery rate constant (min−1), a measure of muscle mitochondrial capacity in vivo. Results Median age was 67 years (IQR 64–75). Differences (95%CI) in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold −2.4 ml.kg−1.min−1 (−3.8, −0.9), p = 0.004; Oxygen uptake at Peak −4.0 ml.kg−1.min−1 (−6.8, −1.1), p = 0.011; and post-exercise phosphocreatine recovery rate constant −0.34 min−1 (−0.51, −0.17), p<0.001. Conclusion The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery. Trial Registration Clinicaltrials.gov registration NCT01859442

Comparison of oxygen uptake during arm or leg cardiopulmonary exercise testing in vascular surgery patients and control subjects

BACKGROUND Cardiopulmonary exercise testing by cycle ergometry (CPET(leg)) is an established assessment tool of perioperative physical fitness. CPET utilizing arm ergometry (CPET(arm)) is an attractive alternative in patients with lower limb dysfunction. We aimed to determine whether oxygen uptake obtained by CPET(leg) could be predicted by using CPET(arm) alone and whether CPET(arm) could be used in perioperative risk stratification. METHODS Subjects underwent CPET(arm) and CPET(leg). To evaluate the ability of VO₂ obtained from CPET(arm) to predict VO₂ from CPET(leg), we calculated prediction intervals (PIs) at lactate threshold θ(L) and peak exercise in both groups. Receiver operating characteristic (ROC) curves were used to risk stratify patients into high and low categories based on published criteria. RESULTS We recruited 20 vascular surgery patients (17 males and three females) and 20 healthy volunteers (10 males and 10 females). In both groups, PIs for at and peak were wider than clinically acceptable (patient group - VO₂ at θ(L) CPET(arm) ranged from 55% to 108% of CPET(leg) and from 54% to 105% at peak; healthy volunteers - 37-77% and 41-79%, respectively). The area under the ROC for CPET(arm) VO₂ in patients was 0.84 [95% confidence interval (CI): 0.66, 1.0] at θ(L), and 0.76 (95% CI: 0.54, 0.99) at peak. CONCLUSIONS Although a relationship exists between VO₂ values for CPET(arm) and CPET(leg), this is insufficient for accurate prediction using CPET(arm) alone. This however does not necessarily preclude the use of CPET(arm) in perioperative risk stratification.

Garment fit and protection from sustained +Gz acceleration with 'full-coverage' anti-G trousers.

INTRODUCTION Garment fit may influence the effectiveness with which Full-Coverage Anti-G Trousers (FCAGT) transmit pressure to the skin surface, and hence provide protection from sustained +Gz acceleration. A search of the available literature, however, did not reveal any prior work quantifying this effect. METHODS Three related studies were performed. In Study I, using a mannequin, garment-to-surface pressure transmission ratios were measured at various locations under normally fitted (NF) and loosely fitted (LF) FCAGT. In Study II, garment pressure-volume ratios and lung volumes were measured at +1 Gz in six men wearing FCAGT in three conditions: NF, LF, or NF with inflatable socks at 13 kPa differential pressure (NF+SOCKS). In Study III, relaxed +Gz tolerance (RGT) and ratings of perceived exertion (RPE) at +7, +8, and +9 Gz were measured in eight men wearing FCAGT in four experimental conditions: NF; LF; abdomen LF, legs NF; or abdomen NF, legs LF. RESULTS LF did not affect pressure transmission over the lower limbs or lower abdomen, but transmission over the upper abdomen was significantly compromised. Lung volumes were reduced with FCAGT inflation, but LF was associated with greater expiratory reserve volumes and increased FCAGT volume. Under +Gz acceleration, LF over the abdomen (with or without lower limb LF) decreased RGT and increased RPE, but not with lower limb LF when abdominal fit was normal. DISCUSSION Care should be taken to achieve and maintain a snug FCAGT fit, especially of the abdominal portion of the FCAGT, to ensure optimal anti-G protection during sustained acceleration.

Latent Class Modeling with A Time-To-Event Distal Outcome: A Comparison of One, Two and Three-Step Approaches

Latent class methods can be used to identify unobserved subgroups which differ in their observed data. Researchers are often interested in outcomes for the identified subgroups and in some disciplines time-to-event outcome measures are common, e.g., overall survival in oncology. In this study Monte Carlo simulation is used to evaluate the empirical properties of latent class effect estimates on a time-to-event distal outcome using one, two and three-step approaches. Both standard and inclusive bias-corrected three-step approaches are considered. One-step latent class effect estimates are shown to be superior to the evaluated alternatives. Both the two-step approach and a standard three-step approach, where subjects are partially assigned to latent classes, produced unbiased estimates with nominal confidence interval coverage when latent classes were well separated, but not otherwise. Keywords: latent class analysis, time-to-event, two-step, joint modeling