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Abstract: Background: Rates of distal and junctional adenocarcinomas are increasing in Western countries. Methods: Systematic review of epidemiological evidence linking obesity to esophageal adenocarcinoma (EA) was performed for studies published from 2005 to 2010. The current understanding of obesity''s role in the etiology and potential dysplastic progression of Barrett''s esophagus (BE) to EA is reviewed. Results: Accumulating epidemiological studies provide evidence of obesity''s role as a driving force behind the increasing rates of EA. The simplest construct is that obesity promotes reflux, causing chronic inflammation and BE, predisposing to adenocarcinoma. However, as obesity is positively associated with the prevalence of many cancers, other mechanisms are important. A link may exist between fat distribution patterns and the risk of BE and EA. Altered metabolic profiles in the metabolic syndrome (MetS) may be a key factor in cell cycle/genetic abnormalities that mark the progression of BE towards cancer. Research highlighting a unique role of MetS in the length of BE, and its association with systemic inflammation and insulin resistance is discussed, as well as adipokine receptor expression in both BE and esophageal epithelium, and how MetS and the systemic response impacts on key regulators of inflammation and tumorigenesis. Conclusions/impact: Obesity is positively associated with EA. The systemic inflammatory state consequent on the altered metabolism of obese patients, and the associated impact of adipocytokines and pro-coagulant factors released by adipocytes in central fat, may underlie obesity''s relationship to this cancer. Novel therapeutic agents that may antagonize adipo-cytokines and potentially offer a promising role in cancer therapy are discussed. [Copyright &y& Elsevier]

Summary: 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 (5.2kg versus 3.1kg, 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 (7.5kg versus 2.9kg, 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 15.5kg—IVF patients lost 17.8kg versus 9.6kg 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 15.5kg 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. [Copyright &y& Elsevier]

Objective: Changes in serum albumin may reflect systemic immunoinflammation and hypermetabolism in response to insults such as trauma and sepsis. Esophagectomy is associated with a major metabolic stress, and the aim of this study was to determine if the absolute albumin level on the first postoperative day was of value in predicting in-hospital complications.Methods: A retrospective study of 200 patients undergoing esophagectomy for malignant disease at St. James Hospital between 1999 and 2005 was performed. Patients who had pre and postoperative (days 1, 3, and 7) serum albumin levels measured were included in the study. Patients were subdivided into three postoperative albumin categories <20 g/l, 20-25 g/l, >25 g/l. Logistic regression analysis was performed to calculate the odds of morbidity and mortality according to the day 1 albumin level.Results: Patients with an albumin of less than 20 g/l on the first postoperative day were twice as likely to develop postoperative complications than those with an albumin of greater than 20 g/l (54 vs 28% respectively, p < 0.011). Correspondingly, these patients also had a significantly higher rate of Adult Respiratory Distress Syndrome (22 vs 5%, p < 0.001), respiratory failure (27 vs 8%, p < 0.01) and in-hospital mortality (27 vs 6% (p < 0.001). On multivariate logistic regression analysis, day 1 albumin level was independently related to postoperative complications (odds ratios, 0.89: 95%; confidence intervals, 0.83-0.96; p < 0.005). In addition, albumin <20 g/l on the first postoperative day was associated with the need for further surgery and a return to ICU.Conclusion: Serum albumin concentration on the first postoperative day is a better predictor of surgical outcome than many other preoperative risk factors. It is a low cost test that may be used as a prognostic tool to detect the risk of adverse surgical outcomes. [ABSTRACT FROM AUTHOR]

Summary: Background & 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 2000ml feed over 20h 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. [Copyright &y& Elsevier]

Abstract: Recent evidence links obesity with the rising incidence of oesophageal adenocarcinoma. In Ireland between 1995 and 2004 the incidence of oesophageal adenocarcinoma increased by 38%, and this coincided with a 67% increase in the prevalence of obesity. In this study, a prospective case-control study was undertaken in 760 patients presenting to a tertiary centre between 1994 and 2004 diagnosed with cancer of the oesophagus, gastric cardia or stomach. Data were compared with 893 healthy controls. Multivariate logistic regression models were used to calculate the odds ratio (OR) of developing either cancer type according to quartiles of body mass index (BMI). Based on pre-illness BMI, 82% of patients who developed adenocarcinoma of the oesophagus were either overweight or obese compared with 59% of the healthy control population (P <0.001). A dose-dependent relationship existed between BMI and oesophageal adenocarcinoma in males. The adjusted odds ratio was 4.3 (95% CI: 2.3–7.9) among males in the highest BMI quartile compared with males in the lowest quartile (P <0.001 for trend). Using common cut-off points for BMI, the OR of adenocarcinoma of the lower oesophagus was 11.3 times higher (95% CI: 3.5–36.4) for individuals with a BMI >30kg/m2 versus individuals with a BMI <22kg/m2 (P <0.001 for trend). For adenocarcinoma of the gastric cardia, males in the top quartile of BMI had an OR of 3.5 (95% CI: 1.3–9.4) compared with the lowest quartile (P =0.03 for trend). A significant (P <0.001) inverse relationship between BMI and oesophageal SCC was observed. The odds ratio for adenocarcinoma of the oesophagus, the oesophago-gastric junction and gastric cardia rose significantly with increasing BMI. For tumours of the lower oesophagus, obesity increased the risk 10.9-fold. The increased risk is significant in males only. [Copyright &y& Elsevier]

There is an impetus to provide appropriate sustained release oral delivery vehicles to protect biofunctional peptide loads from gastric degradation in vivo. This study describes the generation of a high load capacity pellet formulation for sustained release of a freely water-soluble dairy-derived hydrolysate, FHI-2571. The activity of this novel peptidic ghrelin receptor agonist is reported using in vitro calcium mobilization assays. Conventional extrusion spheronization was then used to prepare peptide-loaded pellets which were subsequently coated with ethylcellulose (EC) film coats using a fluid bed coating system in bottom spray (Wurster) mode. Aqueous-based EC coating dispersions produced mechanically brittle coats which fractured due to osmotic pressure build-up within pellets in simulated media. In contrast, an ethanolic-based EC coating solution provided robust, near zero-order release in both USP Type 1 and Type 4 dissolution studies. Interestingly, the functionality of aqueous-based EC film coats was restored by first layering pellets with a methacrylic acid copolymer (MA) subcoat, thereby hindering pellet core swelling in acidic media. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) was utilised as a complementary technique to confirm the results seen in USP dissolution studies. Retention of activity of the ghrelinergic peptide hydrolysate in the final encapsulated product was confirmed as being greater than 80%. The described pellet formulation is amenable to oral dosing in small animal studies in order to assess in vivo efficacy of the whey-derived ghrelinergic hydrolysate. In more general terms, it is also suitable as a delivery vehicle for peptide-based bioactives to special population groups e.g paediatric and geriatric. [ABSTRACT FROM AUTHOR]