Celena Scheede-Bergdahl

Prehabilitation to Enhance Perioperative Care

Patients who are elderly, malnourished, anxious, and have a low physical function before surgery are likely to have suboptimal recovery from cancer surgery. A multimodal prehabilitation program is proposed, consisting of exercise training and nutritional and psychological support, which increases physiologic reserve before the stress of surgery. This interventional approach seems to improve ability to undergo the stress of surgery and faster recovery. The integration of exercise, adequate nutrition, and psychosocial components, with medical and pharmacologic optimization in the presurgical period, deserves to receive more attention by clinicians to elucidate the most effective interventions.

Effect of gender on lipid-induced insulin resistance in obese subjects

OBJECTIVE In obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during a hyperinsulinemic-euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor the intramyocellular lipid deposition has been compared directly in obese females and males. DESIGN We studied eight obese females and eight obese males (body mass index (BMI): 32.6+/-1.4 and 32.8+/-0.8 respectively, non significant (NS)) matched for cardiorespiratory fitness relative to lean body mass (43.7+/-1.6 and 47.6+/-1.3 ml/kg min respectively, NS). METHODS Each subject underwent two hyperinsulinemic-euglycemic clamps with infusion of lipid or saline respectively. Furthermore, the subjects exercised during the last half an hour of each clamp. RESULTS The lipid-induced reduction in glucose disposal during the clamp was similar in females and males (46+/-10 and 60+/-4% respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (P<0.001 and P=0.01 respectively). Muscle ceramide, triacylglycerol (TAG), diacylglycerol (DAG), and glycogen content were similar between sexes and remained unchanged during the clamp and when exercise was superimposed. CONCLUSIONS The lipid-induced inhibition of glucose disposal is similar in obese females and males. However, obese females are more insulin sensitive compared with obese males (both during saline and lipid infusion), which is not due to differences in the concentration of the muscle lipid intermediates such as ceramide and DAG.

Muscle perfusion and metabolic heterogeneity: insights from noninvasive imaging techniques.

Recent developments in noninvasive imaging techniques have enabled the study of local changes in perfusion and metabolism in skeletal muscle as well as patterns of heterogeneity in these variables in humans. In this review, the principles of these techniques along with some recent findings on functional heterogeneity in human skeletal muscle will be presented.

Multimodal prehabilitation improves functional capacity before and after colorectal surgery for cancer: a five-year research experience

Abstract Background: Multimodal prehabilitation is a preoperative conditioning intervention in form of exercise, nutritional assessment, whey protein supplementation, and anxiety-coping technique. Despite recent evidence suggesting that prehabilitation could improve functional capacity in patients undergoing colorectal surgery for cancer, all studies were characterized by a relatively small sample size. The aim of this study was to confirm what was previously found in three small population trials. Material and methods: Data of 185 participants enrolled in a pilot single group study and two randomized control trials conducted at the McGill University Health Center from 2010 to 2015 were reanalyzed. Subjects performing trimodal prehabilitation (exercise, nutrition, and coping strategies for anxiety) were compared to the patients who underwent the trimodal program only after surgery (rehabilitation/control group). Functional capacity was assessed with the six-minute walk test (6MWT), a measure of the distance walked over six minutes (6MWD). A significant functional improvement was defined as an increase in 6MWD from baseline by at least 19 m. Changes in 6MWD before surgery, at four and eight weeks were compared between groups. Results: Of the total study population, 113 subjects (61%) underwent prehabilitation. Changes in 6MWD in the prehabilitation group were higher compared to the rehabilitation/control group during the preoperative period {30.0 [standard deviation (SD) 46.7] m vs. −5.8 (SD 40.1) m, p < 0.001}, at four weeks [−11.2 (SD 72) m vs. −72.5 (SD 129) m, p < 0.01], and at eight weeks [17.0 (SD 84.0) m vs. −8.8 (SD 74.0) m, p = 0.047]. The proportion of subjects experiencing a significant preoperative improvement in physical fitness was higher in those patients who underwent prehabilitation [68 (60%) vs. 15 (21%), p < 0.001]. Conclusion: In large secondary analysis, multimodal prehabilitation resulted in greater improvement in walking capacity throughout the whole perioperative period when compared to rehabilitation started after surgery.

Differential Glucose Uptake in Quadriceps and Other Leg Muscles During One-Legged Dynamic Submaximal Knee-Extension Exercise

One-legged dynamic knee-extension exercise (DKE) is a widely used model to study the local cardiovascular and metabolic responses to exercise of the quadriceps muscles. In this study, we explored the extent to which different muscles of the quadriceps are activated during exercise using positron emission tomography (PET) determined uptake of [18F]-fluoro-deoxy-glucose (GU) during DKE. Five healthy male subjects performed DKE at 25 W for 35 min and both the contracting and contralateral resting leg were scanned with PET from mid-thigh and distally. On average, exercise GU was the highest in the vastus intermedius (VI) and lowest in the vastus lateralis (VL; VI vs VL, p < 0.05), whereas the coefficient of variation was highest in VL (VL vs VI, p < 0.05). Coefficient of variation between the mean values of the four quadriceps femoris (QF) muscles in the exercising leg was 35 ± 9%. Compared to mean GU in QF (=100%), GU was on average 73% in VL, 84% in rectus femoris, 115% in vastus medialis, and 142% in VI. Variable activation of hamstring muscles and muscles of the lower leg was also observed. These results show that GU of different muscles of quadriceps muscle group as well as between individuals vary greatly during DKE, and suggests that muscle activity is not equal between quadriceps muscles in this exercise model. Furthermore, posterior thigh muscles and lower leg muscles are more active than hitherto thought even during this moderate exercise intensity.

Surgical Prehabilitation in Patients with Cancer: State-of-the-Science and Recommendations for Future Research from a Panel of Subject Matter Experts

This review by a 10-member panel of experts in surgical prehabilitation addresses processes that may improve oncologic care. Surgical prehabilitation is the process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of surgical treatment. The panel focused on the current state-of-the-science and recommended future research that would help to identify the elements that enhance preoperative physical, nutritional, and psychological health in anticipation of surgery, mitigate the burden of disease, facilitate the return of patient health status to baseline values, decrease postoperative morbidity, and reduce health care costs.

Promoting a culture of prehabilitation for the surgical cancer patient

Abstract Background: Traditional rehabilitative approaches to perioperative cancer care have focused on the postoperative period to facilitate the return to presurgical baseline conditions. However, there is some realization that the preoperative period can be a very effective time for intervention as the patients are more amenable to target their physiological condition to prepare to overcome the metabolic cost of the surgical stress. Methods: We undertook a narrative review of the current literature on surgical prehabilitation and discussed the current evidence of preoperative interventions before cancer surgery in order to increase physiological reserve before surgery and accelerate postoperative recovery. Results: Published data indicate the positive impact of prehabilitation on postoperative functional capacity and return to daily activities. However, the current evidence on the impact on short- and long-term clinical outcome is limited, and more research needs to be conducted. Conclusion: Preliminary findings indicate that a group of interventions such as exercise, nutrition and anxiety reduction in the preoperative period can complement the enhanced recovery program and facilitate the return to baseline activities of daily living. It is not clear at this stage whether the preoperative increase in functional capacity mitigates the burden of postoperative morbidities and subsequent cancer therapies. Therefore, more research is warranted.

Insulin and non-insulin mediated vasodilation and glucose uptake in patients with type 2 diabetes

AIMS The objective was to re-examine endothelial function, insulin mediated vasodilation and glucose extraction in the forearm of patients with type 2 diabetes (T2DM) and matched control subjects (CON) to investigate whether blood flow impairments result from diabetes per se or from concurrent disease. METHODS 18 subjects (10 with T2DM, 8 CON) had graded brachial artery infusions of endothelial dependent (acetylcholine: 15, 30, 60 microg/min), endothelial independent (sodium nitroprusside: 1, 3, 10 microg/min) and partially endothelial mediated (adenosine: 50, 150, 500 microg/min) vasodilators. The protocol was repeated during a hyperinsulinemic clamp. Forearm blood flow and glucose extraction were measured at each dose of vasodilator (with/without insulin). Measurements were also taken in the control arm, reflecting systemic insulin infusion only. RESULTS Non-insulin mediated increases in bulk forearm blood flow were similar in T2DM and CON. However, insulin mediated forearm blood flow responses and glucose extraction were lower in T2DM versus CON. CONCLUSION The vasodilatory effect of insulin is impaired in T2DM although bulk flow capacity is maintained. Insulin mediated glucose extraction is reduced during concomitant maximal stimulation of forearm blood flow with endothelial-dependent vasodilators, despite maintaining flow. This is consistent with previous work that associates T2DM with impaired insulin mediated capillary recruitment.

Exercise-induced regulation of matrix metalloproteinases in the skeletal muscle of subjects with type 2 diabetes.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) play a critical role during vascular remodelling, in both health and disease. Impaired MMP regulation is associated with many diabetes-related complications. This study examined whether exercise-induced regulation of MMPs is maintained in the skeletal muscle of patients with uncomplicated type 2 diabetes (T2DM). Subjects [12 T2DM, 9 healthy control subjects (CON)] underwent 8 weeks of physical training. Messenger RNA (mRNA) was measured at baseline, during and after 8 weeks of training. Protein was measured pre- and post-training. At baseline, there were no effects of diabetes on MMP or TIMP mRNA or protein. mRNA and protein response to training was similar in both groups, except active MMP-2 protein was elevated post training in T2DM only. Our results indicate that exercise-induced stimulation of MMPs is preserved in skeletal muscle of patients with T2DM. This early stage of diabetes may provide an opportunity for intervention and prevention of complications.

Systematic review of exercise training in colorectal cancer patients during treatment

Colorectal cancer surgery results in considerable postoperative morbidity, mortality and reduced quality of life. As many patients will undergo additional (neo)adjuvant therapy, it is imperative that each individual optimize their physical function. To elucidate the potential of exercise in patient optimization, we investigated the evidence for an exercise program before and after surgical treatment in colorectal cancer patients. A systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions, the guidelines of the Physical Therapy Journal and the PRISMA guidelines. No literature pertaining to exercise training during preoperative neoadjuvant treatment was found. Seven studies, investigating the effects of regular exercise during adjuvant chemotherapy for patients with colorectal cancer or a mixed population, were identified. A small effect (effect size (ES) 0.4) of endurance/interval training and strength training (ES 0.4) was found in two studies conducted in patients with colorectal and gastrointestinal cancer. In five studies that included a mixed population of cancer patients, interval training resulted in a large improvement (ES 1.5; P≤.05). Endurance training alone was found to increase both lower extremity strength and endurance capacity. The effects of strength training in the lower extremity are moderate, whereas, in the upper extremity, the increase is small. There is limited evidence available on exercise training during treatment in colorectal cancer patients. One study concluded exercise therapy may be beneficial for colorectal cancer patients during adjuvant treatment. The possible advantages of training during neoadjuvant treatment may be explored by prehabilitation trials.