Does Prolonged Enteral Feeding With Supplemental Omega-3 Fatty Acids Impact on Recovery Post-esophagectomy: Results of a Randomized Double-Blind Trial.

OBJECTIVE: This randomized controlled trial (RCT) hypothesized that prolonged enteral nutrition (EN) with supplemental eicosapentanoic acid (EPA), an omega-3 fatty acid with immune and anabolic properties, may impact on clinical and nutritional outcomes. BACKGROUND: Esophagectomy is associated with significant weight loss and catabolism, and negatively impacts quality of life (QL). Strategies to counter sustained catabolism have therapeutic rationale. METHODS: This multicenter, double-blind, placebo-controlled RCT was powered on a 5% difference in lean body mass (LBM) at 1 month. Patients were randomly assigned to receive either EN-EPA (2.2 g EPA/day) (n = 97) or isocaloric isonitrogenous standard EN (EN-S) (n = 94), preoperatively (5 days orally), and postoperatively via a jejunostomy until 1 month postdischarge. Assessments perioperatively, and at 1, 3, and 6 months included weight, body mass index (BMI), body composition, muscle strength, cytokines, complications, and QL. RESULTS: The median (range) nutrition support was for 51 (36 to 78) days, and overall compliance was 96%. For the entire cohort, a significant (P < 0.005) decrease in weight (-7.4 ±â€Š6.6 kg), BMI (-2.6 ±â€Š2.2 kg/m), LBM (-2.5 ±â€Š8.7 kg), and fat mass (-3.4 ±â€Š5.8 kg) was evident from preoperatively to 6 months. The mean (±SD) loss of LBM (kg) at 1 month was -3.7 ±â€Š8.7 in the EN-S group, compared with -5.6 ±â€Š12.1 in the EN-EPA group (P = 0.355). Per-protocol analysis revealed no difference between the EN-EPA and EN-S in any clinical, nutritional, functional, QL or immune parameter at any time point. CONCLUSIONS: The thesis that EPA impacts on anabolism, immune function, and clinical outcomes post-esophagectomy was not supported. Compliance with home EN was excellent, but weight, muscle, and fat loss was significant in 30% of patients, highlighting the complexity of postoperative weight loss.

The development of the metabolic syndrome and insulin resistance after adjuvant treatment for breast cancer.

BACKGROUND: Adjuvant breast cancer treatment is associated with a number of adverse physical changes, including weight gain, and therefore may represent a critical period for the development of metabolic disturbance. OBJECTIVE: The aim of this study was to evaluate changes in the presentation of the metabolic syndrome (MetSyn) and insulin resistance from breast cancer surgery to postcompletion of adjuvant treatment. METHODS: Sixty-one participants who had completed metabolic screening, including fasting blood samples and anthropometric measurements, on the morning of breast cancer surgery were recruited. Measures were repeated after completion of adjuvant treatment. Change in the proportion of participants presenting with the MetSyn was evaluated using the related-samples McNemar test, and changes in measures of glucose metabolism (fasting insulin, insulin resistance [homeostatic model assessment index], and glycosylated hemoglobin [HbA1c]) were analyzed using paired t tests. The Kruskal-Wallis test was used to compare differences in changes in metabolic parameters across clinical and lifestyle characteristics. RESULTS: There was a significant (P < .001) increase in fasting insulin (mean [SE] change, 2.73 [0.57] mU/L), homeostatic model assessment index (0.58 [0.14]), and HbA1c level (4.49 [5.63] mmol/mol) from baseline to follow-up along with an increase in the proportion diagnosed with the MetSyn (P = .03). Those with the MetSyn at diagnosis experienced a greater increase in insulin resistance. Premenopausal women experienced greatest increases in HbA1c level. CONCLUSIONS: Results demonstrate the development of significant metabolic dysfunction, characterized by glucose dysmetabolism and MetSyn, after adjuvant treatment for breast cancer. IMPLICATIONS FOR PRACTICE: Interventions to improve the metabolic profile of breast cancer survivors are warranted.

A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers.

BACKGROUND: Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers. METHODS/DESIGN: Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. DISCUSSION: The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive of breast cancer occurrence.

Impact of obesity on surgical and oncological outcomes in the management of colorectal cancer.

INTRODUCTION: Obesity is an established risk factor for colorectal cancer, particularly in males, and may negatively impact on oncologic outcomes. The aim of this study was to examine the impact of body mass index (BMI) on mortality and morbidity, tumour pathology, and overall survival in a consecutive cohort of Irish colorectal cancer patients treated with curative intent. METHODS: A retrospective analysis of BMI data entered prospectively into a comprehensive electronic database of colorectal cancer patients was undertaken. Patients were excluded if they had emergency surgery, previous malignancy or the BMI was not recorded. Analysis was performed comparing genders, obese with non-obese and comparing BMI categories. RESULTS: Of the 414 patients, 10% were underweight (<20 kg/m(2)); 35% were normal weight (20-25 kg/m(2)); 37% were overweight (25-30 kg/m(2)), and 18% were obese (≥ 30.00 kg/m(2)). Obesity overall was not significantly associated with pathological stage (p=0.099) or positive lymph node status (p=0.109) or degree of nodal involvement (p=0.068). Obesity was significantly (p<0.05) associated with more advanced pathological stage, node positivity and degree of nodal involvement in male only and colon cancer only analysis. There was no difference in the overall incidence of major (p=0.244) and minor complications (p=0.078) when comparing obese with non-obese, but pelvic abscesses were more common in obese patients (p=0.037). The underweight cohort had a higher rate of major complications (p=0.041), sepsis (p=0.024) and post-operative death (p=0.006). Survival was equivalent between BMI categories and obese and non-obese groups (p=0.469). CONCLUSION: Obesity was associated with more advanced tumours in males and in colon cancer patients only and with a higher risk of post-operative pelvic abscesses but no significant differences with non-obese cohorts in the main outcome measures of in-hospital mortality, major morbidity and survival. Conversely, the adverse consequences of under-nutrition were highlighted in this study.

Barrett esophagus: prevalence of central adiposity, metabolic syndrome, and a proinflammatory state.

BACKGROUND: Obesity is a risk factor for esophageal adenocarcinoma, with a pathway through inflammation and metaplasia secondary to reflux the dominant hypothesis. The proinflammatory impact of adipocytokines associated with the metabolic syndrome of central adiposity may also be relevant. The objective of this study was to explore this profile in Barrett esophagus. METHODS: Patients with specialized intestinal metaplasia were invited to attend the metabolic syndrome screening where they underwent anthropometry, segmental bioelectrical impedance analysis, and blood pressure measurement, and had blood taken for quantification of fasting lipids, insulin, glucose, C-reactive protein, and adipocytokines. RESULTS: One hundred two patients were studied. Forty-six percent of Barrett patients had metabolic syndrome and 78% were centrally obese. Patients with metabolic syndrome were significantly more obese by body mass index, had a 9.4 cm greater waistline, were more hypertensive, and were insulin resistant with 25% having fasting hyperinsulinemia compared with Barrett patients without metabolic syndrome. Metabolic syndrome was associated with elevated C-reactive protein, leptin, and a trend toward decreased adiponectin levels. Sixty percent of patients with long-segment Barrett had metabolic syndrome, and 92% were centrally obese compared with 23.8% and 62%, respectively (P = 0.007 and 0.005) in short-segment Barrett. Long-segment Barrett was associated with hyperinsulinemia and significantly increased levels of interleukin-6 compared with short-segment Barrett. CONCLUSIONS: The prevalence of metabolic syndrome in Barrett far exceeds population norms, and the syndrome was significantly associated with the length of specialized intestinal metaplasia. The data do suggest that the metabolic syndrome may be relevant to the continuum of metaplasia within the Barrett cohort.

Impact of obesity on outcomes in the management of localized adenocarcinoma of the esophagus and esophagogastric junction.

OBJECTIVE: Obesity trends in the Western world parallel the increased incidence of adenocarcinoma of the esophagus and esophagogastric junction. The implications of obesity on standard outcomes in the management of localized adenocarcinoma, particularly operative risks, have not been systematically addressed. METHODS: This retrospective analysis of prospectively collected data included 150 consecutive patients (36 [24%] obese [body mass index > 30] and 114 nonobese), of whom 43 were normal weight (body mass index 20-25) and 71 were overweight (body mass index 25-30). Eighty-one patients underwent multimodal therapy. The primary end points were in-hospital mortality and morbidity, and median and overall survivals. RESULTS: Thirty of 36 obese patients (84%) had a body mass index from 30 to 35. Compared with those of the nonobese cohort, obese patients had significantly increased respiratory complications (P = .037), perioperative blood transfusions (P = .021), anastomotic leaks (P = .009), and length of stay (P = .001), but no difference in mortality (P = .582) or major respiratory complications (P = .171). Median and overall survivals were equivalent (P = .348) in both groups. CONCLUSIONS: Obesity was associated with increased respiratory complications and anastomotic leak rates but not with major respiratory complications, mortality, or survival. These outcomes suggest that the added risks of obesity on standard outcomes in esophageal cancer surgery are modest and should not independently have a significant impact on risk assessment in esophageal cancer management.

Short-term nutritional implications of total gastrectomy for malignancy, and the impact of parenteral nutritional support.

AIMS: To report on peri-operative nutritional status in gastric cancer patients undergoing total gastrectomy, and to examine the role of post-operative parenteral nutrition. METHODS: Retrospective study of prospectively collected data on 90 consecutive patients who underwent total gastrectomy for malignancy. RESULTS: At diagnosis 46% of patients reported clinically severe weight loss, and dietary intake was inadequate in 72% of patients. Post-operatively 42% were given total parenteral nutrition (TPN) and 53% were given intravenous fluids (IVF) alone. TPN patients spent a mean of 13.6 days on nutrition support versus IVF patients who spent a mean of 9.2 days without any form of nutrition. IVF patients lost significantly more weight in hospital than TPN patients (5.2 kg versus 3.1 kg, p=0.008). 69% of IVF patients lost severe amount of weight versus 34% in the TPN group (p=0.01). Post-discharge, IVF patients continued to lose significantly more weight than those given TPN post-operatively (7.5 kg versus 2.9 kg, p=0.01) corresponding to 10.5% of their body weight from discharge to follow up versus 4.9% for TPN group (p=0.014). From pre-illness to follow up, patients lost an average of 15.5 kg--IVF patients lost 17.8 kg versus 9.6 kg in TPN (p<0.01). There was no difference in post-operative complications between the groups; however, patients with >10% weight loss had a significantly higher rate of complications and a significantly higher mortality rate than patients who lost <10% body weight (26.2% versus 51.9%, p=0.036 and 11.1% versus 0%, p=0.027, respectively). On multivariate logistic regression analysis >10% weight loss at diagnosis was the only predictive factor of post-operative complications OR 3.1 (95% CI 1.0-9.6), p=0.04). CONCLUSIONS: There is a high prevalence of malnutrition in gastric cancer patients undergoing surgery. Total gastrectomy is associated with dramatic weight loss, which continues beyond the surgeon's view post-discharge, with patients losing an average of 15.5 kg by 3-month follow up. Provision of nutrition support in the form of TPN post-operatively significantly reduces in-hospital weight loss and also helps to attenuate further weight loss post-discharge.

Post-oesophagectomy early enteral nutrition via a needle catheter jejunostomy: 8-year experience at a specialist unit.

BACKGROUND AND AIMS: The purpose of this study was to prospectively evaluate post-operative jejunostomy feeding in terms of nutritional, biochemical, gastrointestinal and mechanical complications in patients undergoing upper gastrointestinal surgery for oesophageal malignancy. METHODS: The study included 205 consecutive patients who underwent oesophagectomy for malignancy. All patients had a needle catheter jejunostomy (NCJ) inserted at the conclusion of laparotomy. Patients were followed prospectively to record nutritional intake, type of feed administered, rate progression, tolerance, weight changes and complications either mechanical, biochemical or gastrointestinal. RESULTS: Ninety-two per cent of patients were successfully fed exclusively by NCJ post-oesophagectomy, and 94% of patients were tolerating a maintenance regimen of 2000 ml feed over 20 h by day 2 post-operatively. Patients spent a median of 15 days on jejunostomy feeding post-surgery (range 2-112 days); however, 26% required prolonged jejunostomy feeding (>20 days). Minor gastrointestinal complications were effectively managed by slowing the rate of infusion, or administering medication. Three (1.4%) serious complications of jejunostomy feeding occurred, all requiring re-laparotomy, one resulting in death. NCJ feeding was extremely effective in preventing severe post-operative weight loss in the majority of oesophagectomy patients post-op. However, oral intake was generally poor at discharge with only 65% of requirements being met orally. Sixteen patients (8%) patients required home jejunostomy feeding. By the first post-operative month, a further 6% (12) patients were recommenced on jejunostomy feeding. CONCLUSION: NCJ feeding is an effective method of providing nutritional support post-oesophagectomy, and allows home support for the subset that fail to thrive. Serious complications, most usually intestinal ischaemia or intractable diarrhoea, are rare.