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.

Skin microvascular reactivity in trained adolescents.

Whilst endothelial dysfunction is associated with a sedentary lifestyle, enhanced endothelial function has been documented in the skin of trained individuals. The purpose of this study was to investigate whether highly trained adolescent males possess enhanced skin microvascular endothelial function compared to their untrained peers. Seventeen highly and predominantly soccer trained boys (V(O)(2)(peak): 55 +/- 6 mL kg(-1) min(-1)) and nine age- and maturation-matched untrained controls (V(O)(2)(peak): 43 +/- 5 mL kg(-1) min(-1)) aged 13-15 years had skin microvascular endothelial function assessed using laser Doppler flowmetry. Baseline and maximal thermally stimulated skin blood flow (SkBF) responses were higher in forearms of trained subjects compared to untrained participants [baseline SkBF: 11 +/- 4 vs. 9 +/- 3 perfusion units (PU), p < 0.05; SkBF(max): 282 +/- 120 vs. 204 +/- 68 PU, p < 0.05]. Similarly, cutaneous vascular conductance (CVC) during local heating was superior in the forearm skin of trained versus untrained individuals (CVC(max): 3 +/- 1 vs. 2 +/- 1 PU mmHg(-1), p < 0.05). Peak hyperaemia following arterial occlusion and area under the reactive hyperaemia curve were also greater in forearm skin of the trained group (peak hyperaemia: 51 +/- 21 vs. 35 +/- 15 PU, p < 0.05; area under curve: 1596 +/- 739 vs. 962 +/- 796 PUs, p < 0.05). These results suggest that chronic exercise training in adolescents is associated with enhanced microvascular endothelial vasodilation in non-glabrous skin.

Unreported symptomatic and asymptomatic ischaemic heart disease in patients presenting with TIA or minor stroke detected by the London School of Hygiene Cardiovascular Questionnaire and Minnesota coding of a routine ECG.

In a prospective study of 87 patients with TIA or minor stroke (48 men and 39 women, average age 65 years) a history of ischaemic heart disease (IHD) was present in 30 (angina in 25 and myocardial infarction (MI) in 19, 14 having both). The London School of Hygiene Questionnaire did not confirm the diagnosis of IHD in 7 patients, but did detect a further 5 patients with angina and/or MI. The Minnesota coding of the ECG revealed 5 patients with asymptomatic suspect IHD and 15 with probable IHD (a total of 23%). Cardiomegaly (cardiothoracic ratio greater than 0.5) was present in 28 patients, 9 with a history of MI and 8 with a history of angina. These findings indicate that IHD is common in patients with cerebral vascular disease. As both probable IHD on Minnesota coding of the ECG and the presence of cardiomegaly are highly predictive of a poorer outcome, the findings add further weight to the argument that, amongst patients with minor cerebral ischaemia, a sub-group at high risk of death due to IHD can be detected by using simple methods rather than by performing routine coronary angiography on all patients as has been suggested in recent times.