Eureka: objective assessment of the empty pelvis syndrome to measure volumetric changes in pelvic dead space following pelvic exenteration.

BACKGROUND: Large tissue defects following pelvic exenteration (PE) fill with fluid and small bowel, leading to the empty pelvis syndrome (EPS). EPS causes a constellation of complications including pelvic sepsis and reduced quality of life. EPS remains poorly defined and cannot be objectively measured. Pathophysiology of EPS is multifactorial, with increased pelvic dead space potentially important. This study aims to describe methodology to objectively measure volumetric changes relating to EPS. METHODS: The true pelvis is defined by the pelvic inlet and outlet. Within the true pelvis there is physiological pelvic dead space (PDS) between the peritoneal reflection and the inlet. This dead space is increased following PE and is defined as the exenteration pelvic dead space (EPD). EPD may be reduced with pelvic filling and the volume of filling is defined as the pelvic filling volume (PFV). PDS, EPD, and PFV were measured intraoperatively using a bladder syringe, and Archimedes' water displacement principle. RESULTS: A patient undergoing total infralevator PE had a PDS of 50 ml. A rectus flap rendered the pelvic outlet watertight. EPD was then measured as 540 ml. Therefore there was a 10.8-fold increase in true pelvis dead space. An omentoplasty was placed into the EPD, displacing 130 ml; therefore, PFV as a percentage of EPD was 24.1%. CONCLUSIONS: This is the first reported quantitative assessment of pathophysiological volumetric changes of pelvic dead space; these measurements may correlate to severity of EPS. PDS, EPD, and PFV should be amendable to assessment based on perioperative cross-sectional imaging, allowing for potential prediction of EPS-related outcomes.

Oesophageal cancer: The effect of early nutrition support on clinical outcomes.

BACKGROUND AND AIMS: Malnutrition is prevalent in oesophageal cancer. Evidence for the use of nutrition support and prehabilitation in this cohort is variable. The aim of this study was to examine the effect of early nutrition support and functional measures of nutritional status on post-operative outcomes in adult patients with oesophageal cancer. METHODS: Retrospective review of adults with oesophageal cancer undergoing oesophagectomy (n = 151). Early nutrition support was defined as: oral or enteral nutrition supplementation during neoadjuvant treatment. Late nutrition support defined as: oral or enteral nutrition supplementation prescribed post-operatively. Nutrition outcome measures were; percentage weight loss from 3 to 6 months prior to diagnosis, peri- and post-operatively, and pre-operative assessment of handgrip-strength (HGS). RESULTS: Pre-operative weight loss ≥10% was a significant predictor of mortality at 1 year (OR 2.84, 95%CI 1.03-7.83, p = 0.04) independent of tumour stage, adjuvant treatment, age and gender. Adults prescribed early nutrition support during neoadjuvant treatment experienced less weight loss at 12-months post-oesophagectomy compared to adults prescribed late oral nutrition support (p=<0.05). Pre-operative HGS measurements were not a useful predictor of postoperative complications (p = 0.2), length of stay (p = 0.9) or 90-day mortality (p = 0.6). CONCLUSIONS: Pre-operative weight loss ≥10% was associated with mortality. Early nutrition support was associated with less weight loss at 12-months post-operatively. Pre-operative HGS measures did not have prognostic value as a stand-alone measure. Future work should investigate the efficacy of early nutrition support in reducing both pre- and post-operative weight loss to improve nutritional status and surgical outcomes as part of a multimodal prehabilitation programme in adults with oesophageal cancer.

Why women are not small men: sex-related differences in perioperative cardiopulmonary exercise testing.

BACKGROUND: The use of preoperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative outcomes is increasingly prevalent. CPET-derived information enables personalised perioperative care and enhances shared decision-making. Sex-related differences in physical fitness are reported in non-perioperative literature. However, little attention has been paid to sex-related differences in the context of perioperative CPET. AIM: We explored differences in the physical fitness variables reported in a recently published multi-centre study investigating CPET before colorectal surgery. We also report the inclusion rate of females in published perioperative CPET cohorts that are shaping guidelines and clinical practice. METHODS: We performed a post hoc analysis of the trial data of 703 patients who underwent CPET prior to major elective colorectal surgery. We also summarised the female inclusion rate in peer-reviewed published reports of perioperative CPET. RESULTS: Fitness assessed using commonly used perioperative CPET variables-oxygen consumption at anaerobic threshold (AT) and peak exercise-was significantly higher in males than in females both before and after correction for body weight. In studies contributing to the development of perioperative CPET, 68.5% of the participants were male. CONCLUSION: To our knowledge, this is the first study to describe differences between males and females in CPET variables used in a perioperative setting. Furthermore, there is a substantial difference between the inclusion rates of males and females in this field. These findings require validation in larger cohorts and may have significant implications for both sexes in the application of CPET in the perioperative setting.

Exercise prehabilitation may lead to augmented tumor regression following neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

  Purpose: We evaluate the effect of an exercised prehabilitation programme on tumour response in rectal cancer patients following neoadjuvant chemoradiotherapy (NACRT). Patients and Methods: Rectal cancer patients with (MRI-defined) threatened resection margins who completed standardized NACRT were prospectively studied in a post hoc, explorative analysis of two previously reported clinical trials. MRI was performed at Weeks 9 and 14 post-NACRT, with surgery at Week 15. Patients undertook a 6-week preoperative exercise-training programme. Oxygen uptake (VO2) at anaerobic threshold (AT) wasmeasured at baseline (pre-NACRT), after completion of NACRT and at week 6 (post-NACRT). Tumour related outcome variables: MRI tumour regression grading (ymrTRG) at Week 9 and 14; histopathological T-stage (ypT); and tumour regression grading (ypTRG)) were compared. Results: 35 patients (26 males) were recruited. 26 patients undertook tailored exercise-training with 9 unmatched controls. NACRT resulted in a fall in VO2 at AT -2.0 ml/kg-1/min-1(-1.3,-2.6), p < 0.001. Exercise was shown to reverse this effect. VO2 at AT increased between groups, (post-NACRT vs. week 6) by +1.9 ml/kg-1/min-1(0.6, 3.2), p = 0.007. A significantly greater ypTRG in the exercise group at the time of surgery was found (p = 0.02). Conclusion: Following completion of NACRT, exercise resulted in significant improvements in fitness and augmented pathological tumour regression.

Time from colorectal cancer diagnosis to laparoscopic curative surgery-is there a safe window for prehabilitation?

BACKGROUND: There is a growing interest in the adoption of formal prehabilitation programmes prior to elective surgery but regulatory targets mandate prompt treatment following cancer diagnosis. We aimed to investigate if time from diagnosis to surgery is linked to short- and long-term outcomes. METHODS: An exploratory analysis was performed utilising a dedicated, prospectively populated database. Inclusion criteria were biopsy-proven colorectal adenocarcinoma undergoing elective laparoscopic surgery with curative intent. Demographics, date of diagnosis and surgery was captured with patients dichotomised using 4-, 8- and 12-week time points. All patients were followed in a standardised pathway for 5 years. Overall survival was assessed with the Kaplan-Meier log-rank method. RESULTS: Six hundred sixty-eight consecutive patients met inclusion criteria. Mean time from diagnosis to surgery was 53 days (95% CI 48.3-57.8). Identified risk factors for longer time to surgery were males (OR 1.92 [1.2-3.1], p = 0.008), age ≤ 65 (OR 1.9 [1.2-3], p = 0.01), higher ASA scores (p = 0.01) stoma formation (OR 6.9 [4.1-11], p < 0.001) and neoadjuvant treatment (OR 5.06 [3.1-8.3], p < 0.001). There was no association between time to surgery and BMI (p = 0.36), conversion (16.3%, p = 0.5), length of stay (p = 0.33) and readmission or reoperation (p = 0.3). No differences in five-year survival were seen in those operated within 4, 8 and 12 weeks (p = 0.397, p = 0.962 and p = 0.611, respectively). Multivariate analysis showed time from diagnosis to surgery was not associated with five-year overall survival (HR 0.99, p = 0.52). CONCLUSION: Time from colorectal cancer diagnosis to curative laparoscopic surgery did not impact on overall survival. This finding may allow preoperative pathway alteration without compromising safety.

Systematic review: the impact of exercise on mesenteric blood flow and its implication for preoperative rehabilitation.

BACKGROUND: Exercise in the preoperative period, or prehabilitation, continues to evolve as an important tool in optimising patients awaiting major intra-abdominal surgery. It has been shown to reduce rates of post-operative morbidity and length of hospital stay. The mechanism by which this is achieved remains poorly understood. Adaptations in mesenteric flow in response to exercise may play a role in improving post-operative recovery by reducing rates of ileus and anastomotic leak. AIMS: To systematically review the existing literature to clarify the impact of exercise on mesenteric arterial blood flow using Doppler ultrasound. METHODS: PubMed, EMBASE and the Cochrane library were systematically searched to identify clinical trials using Doppler ultrasound to investigate the effect of exercise on flow through the superior mesenteric artery (SMA). Data were extracted including participant characteristics, frequency, intensity, timing and type of exercise and the effect on SMA flow. The quality of each study was assessed using the Downs and Black checklist. RESULTS: Sixteen studies, comprising 305 participants in total, were included. Methodological quality was generally poor. Healthy volunteers were used in twelve studies. SMA flow was found to be reduced in response to exercise in twelve studies, increased in one and unchanged in two studies. Clinical heterogeneity precluded a meta-analysis. CONCLUSION: The weight of evidence suggests that superior mesenteric arterial flow is reduced immediately following exercise. Differences in frequency, intensity, timing and type of exercise make a consensus difficult. Further studies are warranted to provide a definitive understanding of the impact of exercise on mesenteric flow.

A minimum core outcome dataset for the reporting of preclinical chemotherapeutic drug studies: Lessons learned from multiple discordant methodologies in the setting of colorectal cancer.

In vivo studies in animal models are critical tools necessary to study the fundamental complexity of carcinogenesis. A constant strive to improve animal models in cancer exists, especially those investigating the use of chemotherapeutic effectiveness. In the present systematic review, colorectal cancer (CRC) is used as an example to highlight and critically evaluate the range of reporting strategies used when investigating chemotherapeutic agents in the preclinical setting. A systematic review examining the methodology and reporting of preclinical chemotherapeutic drug studies using CRC murine models was conducted. A total of 45 studies were included in this systematic review. The literature was found to be highly heterogeneous with various cell lines, animal strains, animal ages and chemotherapeutic compounds/regimens tested, proving difficult to compare outcomes between similar studies or indeed gain any significant insight into which chemotherapeutic regimen caused adverse events. From this analysis we propose a minimum core outcome dataset that could be regarded as a standardised way of reporting results from in vivo experimentation.

The effect of neoadjuvant chemotherapy and chemoradiotherapy on exercise capacity and outcome following upper gastrointestinal cancer surgery: an observational cohort study.

BACKGROUND: In 2014 approximately 21,200 patients were diagnosed with oesophageal and gastric cancer in England and Wales, of whom 37 % underwent planned curative treatments. Potentially curative surgical resection is associated with significant morbidity and mortality. For operable locally advanced disease, neoadjuvant chemotherapy (NAC) improves survival over surgery alone. However, NAC carries the risk of toxicity and is associated with a decrease in physical fitness, which may in turn influence subsequent clinical outcome. Lower levels of physical fitness are associated with worse outcome following major surgery in general and Upper Gastrointestinal Surgery (UGI) surgery in particular. Cardiopulmonary exercise testing (CPET) provides an objective assessment of physical fitness. The aim of this study is to test the hypothesis that NAC prior to upper gastrointestinal cancer surgery is associated with a decrease in physical fitness and that the magnitude of the change in physical fitness will predict mortality 1 year following surgery. METHODS: This study is a multi-centre, prospective, blinded, observational cohort study of participants with oesophageal and gastric cancer scheduled for neoadjuvant cancer treatment (chemo- and chemoradiotherapy) and surgery. The primary endpoints are physical fitness (oxygen uptake at lactate threshold measured using CPET) and 1-year mortality following surgery; secondary endpoints include post-operative morbidity (Post-Operative Morbidity Survey (POMS)) 5 days after surgery and patient related quality of life (EQ-5D-5 L). DISCUSSION: The principal benefits of this study, if the underlying hypothesis is correct, will be to facilitate better selection of treatments (e.g. NAC, Surgery) in patients with oesophageal or gastric cancer. It may also be possible to develop new treatments to reduce the effects of neoadjuvant cancer treatment on physical fitness. These results will contribute to the design of a large, multi-centre trial to determine whether an in-hospital exercise-training programme that increases physical fitness leads to improved overall survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325883 - 29(th) March 2011.

Timing of surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer - A comparison of magnetic resonance imaging at two time points and histopathological responses.

PURPOSE: There is wide inter-institutional variation in the interval between neoadjuvant chemoradiotherapy (NACRT) and surgery for locally advanced rectal cancer. We aimed to assess the association of magnetic resonance imaging (MRI) at 9 and 14 weeks post-NACRT; T-staging (ymrT) and post-NACRT tumour regression grading (ymrTRG) with histopathological outcomes; histopathological T-stage (ypT) and histopathological tumour regression grading (ypTRG) in order to inform decision-making about timing of surgery. PATIENTS AND METHODS: We prospectively studied 35 consecutive patients (26 males) with MRI-defined resection margin threatened rectal cancer who had completed standardized NACRT. Patients underwent a MRI at Weeks 9 and 14 post-NACRT, and surgery at Week 15. Two readers independently assessed MRIs for ymrT, ymrTRG and volume change. ymrT and ymrTRG were analysed against histopathological ypT and ypTRG as predictors by logistic regression modelling and receiver operating characteristic (ROC) curve analyses. RESULTS: Thirty-five patients were recruited. Inter-observer agreement was good for all MR variables (Kappa > 0.61). Considering ypT as an outcome variable, a stronger association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.064 vs. p = 0.010; Volume change - p = 0.062 vs. p = 0.007). Similarly, considering ypTRG as an outcome variable, a greater association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.005 vs. p = 0.042; Volume change - p = 0.004 vs. 0.055). CONCLUSION: Following NACRT, greater tumour down-staging and volume reduction was observed at Week 14. Timing of surgery, in relation to NACRT, merits further investigation. TRIAL REGISTRATION NUMBER: NCT01325909.

Validation of preoperative cardiopulmonary exercise testing-derived variables to predict in-hospital morbidity after major colorectal surgery.

BACKGROUND: In single-centre studies, postoperative complications are associated with reduced fitness. This study explored the relationship between cardiorespiratory fitness variables derived by cardiopulmonary exercise testing (CPET) and in-hospital morbidity after major elective colorectal surgery. METHODS: Patients underwent preoperative CPET with recording of in-hospital morbidity. Receiver operating characteristic (ROC) curves and logistic regression were used to assess the relationship between CPET variables and postoperative morbidity. RESULTS: Seven hundred and three patients from six centres in the UK were available for analysis (428 men, 275 women). ROC curve analysis of oxygen uptake at estimated lactate threshold (V˙o2 at θ^L ) and at peak exercise (V˙o2peak ) gave an area under the ROC curve (AUROC) of 0·79 (95 per cent c.i. 0·76 to 0·83; P < 0·001; cut-off 11·1 ml per kg per min) and 0·77 (0·72 to 0·82; P < 0·001; cut-off 18·2 ml per kg per min) respectively, indicating that they can identify patients at risk of postoperative morbidity. In a multivariable logistic regression model, selected CPET variables and body mass index (BMI) were associated significantly with increased odds of in-hospital morbidity (V˙o2 at θ^L 11·1 ml per kg per min or less: odds ratio (OR) 7·56, 95 per cent c.i. 4·44 to 12·86, P < 0·001; V˙o2peak 18·2 ml per kg per min or less: OR 2·15, 1·01 to 4·57, P = 0·047; ventilatory equivalents for carbon dioxide at estimated lactate threshold (V˙E /V˙co2 at θ^L ) more than 30·9: OR 1·38, 1·00 to 1·89, P = 0·047); BMI exceeding 27 kg/m2 : OR 1·05, 1·03 to 1·08, P < 0·001). A laparoscopic procedure was associated with a decreased odds of complications (OR 0·30, 0·02 to 0·44; P = 0·033). This model was able to discriminate between patients with, and without in-hospital morbidity (AUROC 0·83, 95 per cent c.i. 0·79 to 0·87). No adverse clinical events occurred during CPET across the six centres. CONCLUSION: These data provide further evidence that variables derived from preoperative CPET can be used to assess risk before elective colorectal surgery.

Exercise intervention in people with cancer undergoing neoadjuvant cancer treatment and surgery: A systematic review.

BACKGROUND: Neoadjuvant cancer treatment decreases physical fitness. Low levels of physical fitness are associated with poor surgical outcome. Exercise training can stimulate skeletal muscle adaptations, such as increased mitochondrial content and improved oxygen uptake capacity that may contribute to improving physical fitness. This systematic review evaluates the evidence in support of exercise training in people with cancer undergoing the "dual hit" of neoadjuvant cancer treatment and surgery. METHODS: We conducted a systematic database search of Embase Ovid, Ovid Medline without Revisions, SPORTDiscus, Web of Science, Cochrane Central Register of Controlled Trials Library and ClinicalTrials.gov to identify trials addressing the effect of exercise training in people scheduled for neoadjuvant cancer treatment and surgery. Data extraction and analysis were based on a pre-defined plan. RESULTS: The database search yielded 6489 candidate abstracts. Ninety-four references included the required terms. Four studies were eligible for inclusion (breast cancer, locally advanced rectal cancer). All studies reported that exercise training was safe and feasible and that adherence rates were acceptable (66-96%). In-hospital exercise training improves physical fitness however the impact on HRQoL and other clinical important outcomes was uncertain. CONCLUSION: This is the first systematic review of the effects of exercise training in people scheduled for "dual-hit" treatment. This evidence synthesis indicates that this approach is safe and feasible but that there are insufficient controlled trials in this area to draw reliable conclusions about the efficacy of such an intervention, the optimal characteristics of the intervention, or the impact on clinical or patient reported outcomes.

Exercise intervention in people with cancer undergoing adjuvant cancer treatment following surgery: A systematic review.

BACKGROUND: Remaining physically active during and after cancer treatment is known to improve associated adverse effects, improve overall survival and reduce the probability of relapse. This systematic review addresses the question: is an exercise training programme beneficial in people with cancer undergoing adjuvant cancer treatment following surgery. METHODS: A systematic database search of Embase, Ovid, Medline without Revisions, SPORTDiscus, Web of Science, Cochrane Library and ClinicalTrials.gov for any randomised controlled trials (RCT) or non-RCT addressing the effect of an exercise training programme in those having adjuvant cancer treatment following surgery was conducted. RESULTS: The database search yielded 6489 candidate abstracts of which 94 references included the required terms. A total of 17 articles were included in this review. Exercise training is safe and feasible in the adjuvant setting and furthermore may improve measures of physical fitness and health related quality of life (HRQoL). CONCLUSION: This is the first systematic review on exercise training interventions in people with cancer undergoing adjuvant cancer treatment following surgery. Due to the lack of adequately powered RCTs in this area, it remains unclear whether exercise training in this context improves clinical outcomes other physical fitness and HRQoL. It remains unclear what is the optimal timing of initiation of an exercise programme and what are the best combinations of elements within an exercise training programme to optimise training efficacy. Furthermore, it is unclear if initiating such exercise programmes at cancer diagnosis may have a long-lasting effect on physically activity throughout the subsequent life course.

The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms--A blinded interventional study.

BACKGROUND: Perioperative beta-blockade is widely used, especially before vascular surgery; however, its impact on exercise performance assessed using cardiopulmonary exercise testing (CPET) in this group is unknown. We hypothesized that beta-blocker therapy would significantly improve CPET-derived physical fitness in this group. METHODS: We recruited patients with abdominal aortic aneurysms (AAA) of <5.5 cm under surveillance. All patients underwent CPET on and off beta-blockers. Patients routinely prescribed beta-blockers underwent a first CPET on medication. Beta-blockers were stopped for one week before a second CPET. Patients not routinely taking beta-blockers underwent the first CPET off treatment, then performed a second CPET after commencement of bisoprolol for at least 48 h. Oxygen uptake (.VO2) at estimated lactate threshold and .VO2 at peak were primary outcome variables. A linear mixed-effects model was fitted to investigate any difference in adjusted CPET variables on and off beta-blockers. RESULTS: Forty-eight patients completed the study. No difference was observed in .VO2 at estimated lactate threshold and .VO2 at peak; however, a significant decrease in .VE/.VCO2 at estimated lactate threshold and peak, an increase in workload at estimated lactate threshold., O2 pulse and heart rate both at estimated lactate threshold and peak was found with beta-blockers. Patients taking beta-blockers routinely (chronic group) had worse exercise performance (lower .VO2 ). CONCLUSIONS: Beta blockade has a significant impact on CPET-derived exercise performance, albeit without changing .VO2 at estimated lactate threshold and.VO2 at peak. This supports performance of preoperative CPET on or off beta-blockers depending on local perioperative practice. CLINICAL TRIAL REGISTRATION: NCT 02106286.

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 testing for the prediction of morbidity risk after rectal cancer surgery.

BACKGROUND: 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. METHODS: Patients scheduled for rectal cancer surgery underwent preoperative CPET (reported blind to patient characteristics) with recording of morbidity (recorded blind to CPET variables). Non-parametric receiver operating characteristic (ROC) curves and logistic regression were used to assess the relationship between CPET variables and postoperative morbidity. RESULTS: Of 105 patients assessed, 95 (72 men) were included; ten patients had no surgery and were excluded (3 by choice, 7 owing to unresectable metastasis). Sixty-eight patients had received neoadjuvant treatment. ROC curve analysis of oxygen uptake (V˙o2 ) at estimated lactate threshold (θ^L ) and peak V˙o2 gave an area under the ROC curve of 0·87 (95 per cent confidence interval 0·78 to 0·95; P < 0·001) and 0·85 (0·77 to 0·93; P < 0·001) respectively, indicating that they can help discriminate patients at risk of postoperative morbidity. The optimal cut-off points identified were 10·6 and 18·6 ml per kg per min for V˙o2 at θ^L and peak respectively. CONCLUSION: CPET can help predict morbidity after rectal cancer surgery.

The effects of neoadjuvant chemoradiotherapy on physical fitness and morbidity in rectal cancer surgery patients.

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable locally advanced rectal cancer improves outcome compared with surgery alone. Our primary hypothesis was that NACRT impairs objectively-measured physical fitness. We also wished to explore the relationship between fitness and postoperative outcome. METHOD: In an observational study, we prospectively studied 27 consecutive patients, of whom 25 undertook cardiopulmonary exercise testing (CPET) 2 weeks before and 7 weeks after standardized NACRT, then underwent surgery. In-hospital post-operative morbidity and mortality were recorded. Patients were followed up to 1 year for mortality. Data was analysed blind to clinical details. Receiver-operating characteristic (ROC) analysis defined the predictive value of CPET for in-hospital morbidity at day 5. RESULTS: Oxygen uptake ( [Formula: see text] in ml kg(-1) min(-1)) at estimated lactate threshold (θˆL) and at peak exercise ( [Formula: see text] at peak in ml kg(-1) min(-1)) both significantly decreased post-NACRT: [Formula: see text] at θˆL 12.1 (pre-NACRT) vs. 10.6 (post-NACRT), p < 0.001 (95%CI -1.7, -1.2); [Formula: see text] at peak 18.1 vs. 16.7, p < 0.001 (95%CI -3.1, -1.0). Optimal [Formula: see text] at θˆL and peak pre-NACRT for predicting postoperative morbidity were 12.0 and 18.1 ( [Formula: see text] at θˆL - AUC = 0.71, 77% sensitive and 75% specific; [Formula: see text] at peak - AUC = 0.75, 78% sensitive and 76% specific). Optimal [Formula: see text] at θˆL and peak post-NACRT for predicting postoperative morbidity were 10.7 and 16.7 ( [Formula: see text] at θˆL - AUC = 0.72, 77% sensitive and 83% specific; [Formula: see text] at peak - AUC = 0.80, 85% sensitive and 83% specific). CONCLUSION: NACRT before major rectal cancer surgery significantly decreased physical fitness as assessed by CPET. TRIALS REGISTRY NUMBER: NCT01334593.

The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone. However NAC has adverse effects. We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery. METHODS: We prospectively studied 116 patients with oesophageal or gastric cancer to assess the effect of NAC on physical fitness, of whom 89 underwent cardiopulmonary exercise testing (CPET) before NAC and proceeded to surgery. 39 patients were tested after all cycles of NAC but prior to surgery. Physical fitness was assessed by measuring oxygen uptake (VO2 in ml kg(-1) min(-1)) at the estimated lactate threshold (θL) and at peak exercise (VO2 peak in ml kg(-1) min(-1)). RESULTS: VO2 at θL and at peak were significantly lower after NAC compared to pre-NAC values: VO2 at θL 14.5 ± 3.8 (baseline) vs. 12.3 ± 3.0 (post-NAC) ml kg(-1) min(-1); p ≤ 0.001; VO2 peak 20.8 ± 6.0 vs. 18.3 ± 5.1 ml kg(-1) min(-1); p ≤ 0.001; absolute VO2 (ml min(-1)) at θL and peak were also lower post-NAC; p ≤ 0.001. Decreased baseline VO2 at θL and peak were associated with increased one year mortality in patients who completed a full course of NAC and had surgery; p = 0.014. CONCLUSION: NAC before cancer surgery significantly reduced physical fitness in the overall cohort. Lower baseline fitness was associated with reduced one-year-survival in patients completing NAC and surgery, but not in patients who did not complete NAC. It is possible that in some patients the harms of NAC may outweigh the benefits. Trials Registry Number: NCT01335555.