Neighbourhood characteristics, lifestyle factors, and child development: Secondary analysis of the All our families cohort study.

Background: Neighbourhood characteristics have been found to influence child development, but little is known about lifestyle factors that may moderate this relationship, which can provide modifiable targets for policies and programing. This study investigated the association between neighbourhood characteristics (e.g., deprivation, disorder) during pregnancy and child development at age 5 in relation to various lifestyle factors (e.g., physical activity, parent-child reading, community resource use) during early childhood. Methods: A secondary analysis was conducted using multilevel modeling of data from the All Our Families cohort, recruited in Canada from 2008 to 2010. Participants self-reported on demographics during pregnancy, lifestyle factors at 3 years, and child development at 5 years using the Ages and Stages Questionnaire (ASQ-3). Neighbourhood deprivation was evaluated using the Vancouver Area Deprivation Index (VANDIX), while disorder was measured using police services' community crime reports. Results: Geocoded information was available for 2,444 participants. After adjusting for covariates, multilevel modeling indicated a significant negative association between neighbourhood deprivation and overall child development (b = -.726, 95% CI: -1.344, -.120). Parent-child reading was found to be a significant moderator of the effect of neighbourhood disorder (b = .005, 95% CI: .001, .009). There were no statistically significant moderation effects for physical activity or community resource use. Conclusion: Neighbourhood deprivation during pregnancy is associated with early child development. Parent-child reading may function as a protective factor in the presence of higher neighbourhood disorder. Overall, neighbourhood-level effects should be considered in policies and community programs that promote family and child well-being.

Compression therapy versus surgery in the treatment of patients with varicose veins: A RCT.

OBJECTIVE: Superficial venous reflux and varicose veins are common. The aim of this randomized controlled trial was to assess effectiveness of compression therapy compared with surgery for superficial venous reflux. METHODS: 153 patients with CEAP class C2-C3 and superficial venous reflux were randomized to receive either conservative treatment (compression stockings) (n = 77) or surgery (n = 76). Clinical examination including duplex ultrasound (DUS) was performed at entry and 1 and 2 years after randomization (compression group) or surgery (surgery group). Venous Clinical Severity Score without compression stockings (VCSS-S), Venous Segmental Disease Score (VSDS), Venous Disability Score (VDS), and health-related quality of life (HRQoL) were assessed at entry and at the follow-ups. Data were analysed on an intention-to-treat basis and according to the actual treatment performed. RESULTS: At 2 years, 70/76 patients in the surgery group and 11/77 patients in the compression group had been operated on. VCSS-S decreased from 4.6 to 3.5 in the compression group (p < .01) and from 4.8 to 0.6 in the surgery group (p < .001). VSDS decreased from 7.7 to 7.0 in the compression group and from 8.2 to 0.9 in the surgery group (p < .0001). HRQoL did not change in the compression group, but improved significantly in the surgery group. CONCLUSION: The surgical elimination of non-complicated superficial venous reflux is an effective treatment when compared with providing compression stockings only.

Adipose tissue-related proteins locally associated with resolution of inflammation in obese mice.

OBJECTIVE: Resolution of low-grade inflammation of white adipose tissue (WAT) is one of the keys for amelioration of obesity-associated metabolic dysfunctions. We focused on the identification of adipokines, which could be involved at the early stages of resolution of WAT inflammation. METHODS AND PROCEDURE: Male C57BL/6J mice with obesity induced in response to a 22-week feeding corn oil-based high-fat (cHF) diet were divided into four groups and were fed with, for 2 weeks, control cHF diet or cHF-based diets supplemented with: (i) concentrate of n-3 long-chain polyunsaturated fatty acids, mainly eicosapentaenoic and docosahexaenoic acids (cHF+F); (ii) thiazolidinedione drug rosiglitazone (cHF+TZD); and (iii) both compounds (cHF+F+TZD). RESULTS: The short-term combined intervention exerted additive effect in the amelioration of WAT inflammation in obese mice, namely in the epididymal fat, even in the absence of any changes in either adipocyte volume or fat mass. The combined intervention elicited hypolipidaemic effect and induced adiponectin, whereas the responses to single interventions (cHF+F, cHF+TZD) were less pronounced. In addition, analysis in WAT lysates using protein arrays revealed that the levels of a small set of adipose tissue-related proteins, namely macrophage inflammatory protein 1γ, endoglin, vascular cell adhesion molecule 1 and interleukin 1 receptor antagonist, changed in response to the anti-inflammatory interventions and were strongly reduced in the cHF+F+TZD mice. These results were verified using both the analysis of gene expression and enzyme-linked immunosorbent analysis in WAT lysates. In contrast with adiponectin, which showed changing plasma levels in response to dietary interventions, the levels of the above proteins were affected only in WAT. CONCLUSIONS: We identified several adipose tissue-related proteins, which are locally involved in resolution of low-grade inflammation and remodelling of WAT.

Prolonged fasting and the effects on biomarkers of inflammation and on adipokines in healthy lean men.

Obesity and insulin resistance are associated with low-grade systemic inflammation, which is related to increased concentrations of plasma FFAs, glucose, or insulin. Prolonged fasting induces insulin resistance due to elevated plasma FFAs, but is not accompanied by hyperinsulinemia or hyperglycemia. This makes it possible to study effects of physiologically increased FFA concentrations on inflammatory markers, when insulin and glucose concentrations are not increased. In random order, 10 healthy young lean men (mean BMI: 22.8 kg/m2) were fasted or fed in energy balance for 60 h with a 2-week wash-out period. Subjects stayed in a respiration chamber during the 60-h periods. Blood samples were taken after 12, 36, and 60 h. Then, a hyperinsulinemic-euglycemic clamp was performed.Fasting decreased insulin sensitivity by 45% and increased FFA concentrations 5-fold. Fasting did not change concentrations of the inflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-8, or of hs-CRP. Effects on vascular endothelial growth factor (VEGF)--which may positively relate to insulin resistance, and on chemerin and leptin--adipokines related to obesity, and obesity-related pathologies, were also studied. At t=60 h, VEGF concentrations were significantly increased during the fasted period (p<0.05). At the same time point, chemerin (p<0.01) and leptin (p<0.01) were significantly decreased after fasting. For leptin, this decrease was also significant after 36 h (p<0.01). Adiponectin levels remained unchanged. In healthy young lean men, fasting-induced increases in FFAs leading to insulin resistance do not cause changes in concentrations of the inflammatory cytokines. VEGF concentrations increased and those of chemerin decreased.

Hypoxia reduces the response of human adipocytes towards TNFα resulting in reduced NF-κB signaling and MCP-1 secretion.

OBJECTIVE: Obesity is associated with adipose tissue hypoxia, and is thought to be linked to the chronic low-grade inflammation of adipose tissue, although the precise mechanism has remained unclear. In this study, we investigated the effect of a prominent hypoxia on human primary adipocyte secretion and tumor necrosis factor alpha (TNFα)-induced nuclear factor-κB (NF-κB) signaling. RESULTS: Using cytokine array and ELISA analysis, we compared the secretion patterns of normoxic and hypoxic (1% O(2)) adipocytes and observed various alterations in adipokine release. We could reproduce known alterations like an induction of interleukin (IL)-6, vascular endothelial growth factor, leptin and a reduction in adiponectin release under hypoxia. Interestingly, we observed a significant reduction in the secretion of macrophage chemotactic protein (MCP)-1 and other NF-κB-related genes, such as growth-regulated oncogene-α, eotaxin and soluble TNF-Receptor1 (TNF-R1) under hypoxia. TNFα stimulation of hypoxic adipocytes resulted in a significantly reduced phosphorylation of NF-κB and its inhibitor IκBα compared with normoxic cells. Furthermore, chronic treatment of hypoxic adipocytes with TNFα resulted in an expected higher secretion of the chemokines MCP-1 and IL-8, but under hypoxia, the secretion level was substantially lower than that under normoxia. This reduction in protein release was accompanied by a reduced mRNA expression of MCP-1, whereas IL-8 mRNA expression was not altered. Additionally, we observed a significantly reduced expression of the TNF-receptor TNF-R1, possibly being one cause for the reduced responsiveness of hypoxic adipocytes towards TNFα stimulation. CONCLUSION: In conclusion, human primary adipocytes show a basal and TNFα-induced reduction of MCP-1 release under hypoxia. This effect may be due to a reduced expression of TNF-R1 and therefore attenuated TNFα-induced NF-κB signaling. These observations demonstrate a reduced responsiveness of hypoxic adipocytes towards inflammatory stimuli like TNFα, which may represent an adaptation process to maintain adipose tissue function under hypoxia and inflammatory conditions.

Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells.

OBJECTIVE: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with neurotrophic and anti-angiogenic properties. More recently it became evident that PEDF is upregulated in patients with type 2 diabetes and also contributes to insulin resistance in mice. During characterization of the secretome of in vitro differentiated human adipocytes by two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-MS, we found that PEDF is one of the most abundant proteins released by adipocytes. The aim of this study was to investigate the regulation and autocrine function of PEDF in human adipocytes and to determine its paracrine effects on human skeletal muscle cells (hSkMC) and human smooth muscle cells (hSMC). METHODS AND RESULTS: Human primary adipocytes secrete 130 ng ml(-1) PEDF over 24 h from 1 million cells, which is extremely high as compared with adiponectin, interleukin-6 (IL-6) or IL-8. This release of PEDF is significantly higher than from other primary cells, such as adipose-tissue located macrophages (50-times), hSkMC and hSMC (5-times). PEDF protein expression significantly increases during adipogenesis, which is paralleled by increased PEDF secretion. Furthermore, tumor necrosis factor-α and hypoxia significantly downregulate PEDF protein levels. PEDF secretion was significantly reduced by troglitazone and hypoxia and significantly increased by insulin. Treatment of adipocytes and hSkMC with PEDF induced insulin resistance in adipocytes, skeletal and smooth muscle cells at the level of insulin-stimulated Akt phosphorylation, which was dose dependent and more prominent in adipocytes. Furthermore, inflammatory nuclear factor-κB (NF-κB) signaling was induced by PEDF. In hSMC, PEDF induced proliferation (1.7-fold) and acutely activated proliferative and inflammatory signaling pathways (NF-κB, p38 mitogen-activated protein kinase and mammalian target of rapamycin). CONCLUSION: PEDF is one of the most abundant adipokines and its secretion is inversely regulated by insulin and hypoxia. PEDF induces insulin resistance in adipocytes and hSkMC and leads to inflammatory signaling in hSMC. Because of these diverse actions, PEDF is a key adipokine, which could have an important role in diabetes and obesity-related disorders.

Insulin resistance, leptin and monocyte chemotactic protein-1 levels in diabetic and non-diabetic Afro-Caribbean subjects.

AIM: To determine how the levels of leptin and monocyte chemotactic protein-1 (MCP-1) are associated with insulin resistance (IR) in obese, non-obese, diabetic and non-diabetic subjects. METHODS: 112 type 2 diabetics and 43 non-diabetics were studied fasting. Anthropometric indices were measured and glucose, insulin, leptin and MCP-1 were measured in blood. IR was calculated. RESULTS: MCP-1 level was significantly higher in diabetics than non-diabetics irrespective of gender (p < 0.05). Irrespective of diabetes status, the serum leptin concentration was significantly higher (p < 0.05) in obese and females subjects than in non-obese and male subjects respectively. There were no significant correlations between IR and MCP-1 or leptin in all subgroups of subjects studied. General linear modelling analysis showed that only diabetes state significantly predicted MCP-1 levels (p < 0.05) whereas non of the factors predicted leptin levels (p > 0.05). CONCLUSION: Routine measurement of leptin and MCP-1 would be potentially useful in assessment of patients for the metabolic syndrome or coronary heart disease especially in black population.

Prediction of 10-year coronary heart disease risk in Caribbean type 2 diabetic patients using the UKPDS risk engine

OBJECTIVE: Primary prevention of Coronary Heart Disease (CHD) in diabetic patients should be based on absolute CHD risk calculation. This study was aimed to determine the levels of 10-year CHD risk in Caribbean type 2 diabetic patients using the diabetes specific United Kingdom Prospective Diabetes Study (UKPDS) risk engine calculator. SUBJECTS AND METHODS: Three hundred and twenty-five (106 males, 219 females) type 2 diabetic patients resident in two Caribbean Islands of Tobago and Trinidad met the UKPDS risk engine inclusion criteria. Records of their sex, age, ethnicity, smoking habit, diabetes duration, systolic blood pressure, total cholesterol, HDL-cholesterol and glycated haemoglobin were entered into the UKPDS risk engine calculator programme and the absolute 10-year CHD and stroke risk levels were computed. The 10-year CHD and stroke risks were statistically stratified into <15%, 15-30% and >30% CHD risk levels and differences between patients of African and Asian-Indian origin were compared. RESULTS: In comparison with patients in Tobago, type 2 diabetic patients in Trinidad, irrespective of gender, had higher proportion of 10-year CHD risk (10.4 vs. 23.6%, P<0.001) whereas the overall 10-year stroke risk prediction was higher in patients resident in Tobago (16.9 vs. 11.4%, P<0.001). Ethnicity-based analysis revealed that irrespective of gender, higher proportion of patients of Indian origin scored >30% of absolute 10-year CHD risk compared with patients of African descent (3.2 vs. 28.2%, P<0.001). CONCLUSIONS: The results of the study identified diabetic patients resident in Trinidad and patients of Indian origin as the most vulnerable groups for CHD. These groups of diabetic patients should have priority in primary or secondary prevention of coronary heart disease.

Insulin resistance, leptin and monocyte chemotactic protein-1 levels in diabetic and non-diabetic Afro-Caribbean subjects

AIM: To determine how the levels of leptin and monocyte chemotactic protein-1 (MCP-1) are associated with insulin resistance (IR) in obese, non-obese, diabetic and non-diabetic subjects. METHODS: 112 type 2 diabetics and 43 non-diabetics were studied fasting. Anthropometric indices were measured and glucose, insulin, leptin and MCP-1 were measured in blood. IR was calculated. RESULTS: MCP-1 level was significantly higher in diabetics than non-diabetics irrespective of gender (p < 0.05). Irrespective of diabetes status, the serum leptin concentration was significantly higher (p < 0.05) in obese and females subjects than in non-obese and male subjects respectively. There were no significant correlations between IR and MCP-1 or leptin in all subgroups of subjects studied. General linear modelling analysis showed that only diabetes state significantly predicted MCP-1 levels (p < 0.05) whereas non of the factors predicted leptin levels (p > 0.05). CONCLUSION: Routine measurement of leptin and MCP-1 would be potentially useful in assessment of patients for the metabolic syndrome or coronary heart disease especially in black population.

Split-shot sinker facilitates seton treatment of anal fistulae.

OBJECTIVE: The cutting seton is an inexpensive and effective method of treating high complex perianal fistulae. Following placement of the seton, advancement through the external sphincter muscles requires progressive tightening of the seton. The requirement for maintaining the appropriate tension and onset of perianal pressure necrosis are problems frequently encountered using this technique. METHOD: Using a 3-0 polypropylene suture, a red-rubber catheter, and a nontoxic tin split-shot sinker, we minimized or eliminated these problems. RESULTS: We initially used this technique in one patient with satisfactory results. CONCLUSION: This technique is technically easy, safe, inexpensive, and efficient, and we are using it in all patients with high perianal fistulae who require a seton.

Prediction of 10-year coronary heart disease risk in Caribbean type 2 diabetic patients using the UKPDS risk engine.

OBJECTIVE: Primary prevention of Coronary Heart Disease (CHD) in diabetic patients should be based on absolute CHD risk calculation. This study was aimed to determine the levels of 10-year CHD risk in Caribbean type 2 diabetic patients using the diabetes specific United Kingdom Prospective Diabetes Study (UKPDS) risk engine calculator. SUBJECTS AND METHODS: Three hundred and twenty-five (106 males, 219 females) type 2 diabetic patients resident in two Caribbean Islands of Tobago and Trinidad met the UKPDS risk engine inclusion criteria. Records of their sex, age, ethnicity, smoking habit, diabetes duration, systolic blood pressure, total cholesterol, HDL-cholesterol and glycated haemoglobin were entered into the UKPDS risk engine calculator programme and the absolute 10-year CHD and stroke risk levels were computed. The 10-year CHD and stroke risks were statistically stratified into <15%, 15-30% and >30% CHD risk levels and differences between patients of African and Asian-Indian origin were compared. RESULTS: In comparison with patients in Tobago, type 2 diabetic patients in Trinidad, irrespective of gender, had higher proportion of 10-year CHD risk (10.4 vs. 23.6%, P<0.001) whereas the overall 10-year stroke risk prediction was higher in patients resident in Tobago (16.9 vs. 11.4%, P<0.001). Ethnicity-based analysis revealed that irrespective of gender, higher proportion of patients of Indian origin scored >30% of absolute 10-year CHD risk compared with patients of African descent (3.2 vs. 28.2%, P<0.001). CONCLUSIONS: The results of the study identified diabetic patients resident in Trinidad and patients of Indian origin as the most vulnerable groups for CHD. These groups of diabetic patients should have priority in primary or secondary prevention of coronary heart disease.

Cannabinoid type 1 receptors in human skeletal muscle cells participate in the negative crosstalk between fat and muscle.

AIMS/HYPOTHESIS: Cannabinoid type 1 receptor (CB1R) antagonists such as rimonabant (Rim) represent a novel approach to treat obesity and related metabolic disorders. Recent data suggest that endocannabinoids are also produced by human adipocytes. Here we studied the potential involvement of endocannabinoids in the negative crosstalk between fat and muscle. METHODS: The protein level of CB1R in human skeletal muscle cells (SkM) during differentiation was analysed using western blotting. SkM were treated with adipocyte-conditioned medium (CM) or anandamide (AEA) in combination with the CB1R antagonists Rim or AM251, and insulin-stimulated Akt phosphorylation and glucose uptake were determined. Furthermore, signalling pathways of CB1R were investigated. RESULTS: We revealed an increase of CB1R protein in SkM during differentiation. Twenty-four hour incubation of SkM with CM or AEA impaired insulin-stimulated Akt(Ser473) phosphorylation by 60% and up to 40%, respectively. Pretreatment of cells with Rim or AM251 reduced the effect of CM by about one-half, while the effect of AEA could be prevented completely. The reduction of insulin-stimulated glucose uptake by CM was completely prevented by Rim. Short-time incubation with AEA activated extracellular regulated kinase 1/2 and p38 mitogen-activated protein kinase, and impaired insulin-stimulated Akt(Ser473) phosphorylation, but had no effect on Akt(Thr308) and glycogen synthase kinase 3alpha/beta phosphorylation. In addition, enhanced IRS-1 (Ser307) phosphorylation was observed. CONCLUSIONS/INTERPRETATION: Our results show that the CB1R system may play a role in the development of insulin resistance in human SkM. The results obtained with CM support the notion that adipocytes may secrete factors which are able to activate the CB1R. Furthermore, we identified two stress kinases in the signalling pathway of AEA and enhanced IRS-1(Ser307) phosphorylation, potentially underlying the development of insulin resistance.

A comparative study of the prevalence of the metabolic syndrome and its components in type 2 diabetic patients in two Caribbean islands using the new International Diabetes Federation definition.

BACKGROUND AND AIM: Tobago and Trinidad are two Caribbean islands with distinct genetic background and lifestyles; while Tobago is serene and a tourist centre, Trinidad is characterized by a hustling and bustling lifestyle. The study was aimed at determining and comparing the prevalence of the metabolic syndrome (MetS) and its critical components in type 2 diabetic patients using the new International Diabetes Federation (IDF) definition. METHODS: Four hundred and thirteen (166 Tobago, 247 Trinidad) type 2 diabetic patients visiting 10 lifestyle disease clinics were studied. Blood pressure, anthropometric parameters (height, weight, body mass index and waist circumference) and overnight fasting blood samples were taken. Plasma glucose and serum triglycerides, total cholesterol, LDL- and HDL-cholesterol, insulin, and adiponectin were determined. Insulin resistance (IR) was determined using the HOMA method. RESULTS: The patients in Tobago were significantly older than patients in Trinidad (p < 0.001) but the duration of diabetes (9.4 +/- 0.5 vs. 11.1 +/- 0.7 yr), medications, generalized (31.7 vs. 38.8%) and central (78.5 vs. 83.7%) obesity were similar (p > 0.05). In comparison with patients in Tobago, diabetic patients in Trinidad, irrespective of gender, had significantly higher prevalence of IDF critical components such as raised BP, raised triglycerides and reduced HDL-cholesterol (all, p < 0.001). Thus, while more patients in Trinidad were diagnosed with MetS based on three or four components, more patients in Tobago were diagnosed based on two components (p < 0.001). CONCLUSIONS: There were high prevalence rates of the components of the MetS in both the islands of Tobago and Trinidad. Quantitatively, the aggregation of the components is higher in patients in Trinidad, which constitute greater risk for adverse cardiovascular outcome. Controlling central obesity should be the target in preventing MetS in the two islands.

Expression of chemokine receptors in insulin-resistant human skeletal muscle cells.

Adipokines including chemokines are able to induce insulin resistance in human skeletal muscle cells, which may also be relevant for the observed link between obesity and diabetes. This study is aimed to analyze the expression of chemokine CC motif receptors (CCRs) in the insulin-resistant state in human skeletal muscle cells. Differentiated skeletal muscle cells were incubated for 24-72 hours with high concentrations of glucose and insulin (GI) or TNFalpha. In addition, myocytes were co-stimulated with monocyte chemotactic protein (MCP)-1 or adipocyte-conditioned medium (CM) and TNFalpha for 24 and 48 hours. Treatment with GI rapidly induced insulin resistance whereas TNFalpha impaired insulin signaling in a more chronic fashion (48-72 h). CM and MCP-1 also induced insulin resistance that was, however, not increased by co-stimulation with TNFalpha. Expression of CCR2 was decreased during differentiation but up-regulated in insulin-resistant myocytes after treatment with GI (24-72 h) and TNFalpha (72 h). Expression of CCR4 and CCR10 was down-regulated after treatment with TNFalpha, MCP-1, and CM. Our data show that the expression of CCR2, CCR4, and CCR10 is differentially regulated by different insulin resistance-inducing treatments in myotubes. However, we could not find a clear correlation between the level of insulin resistance and CCR expression in myotubes. In conclusion, we propose that upregulation of CCR2 in skeletal muscle does not represent a major step leading to muscle insulin resistance.

Lower limb amputations in Southern Finland in 2000 and trends up to 2001.

OBJECTIVES: To assess the current incidence of major lower limb amputations in Southern Finland and epidemiological trends during the last 17 years. MATERIALS AND METHODS: In a retrospective survey for the year 2000 patient data was gathered from hospital records in the eight surgical hospitals in the area studied. Follow-up was 1 year. Amputation data for years 1984-1995 was gathered from reports done before at the same area and amputation figures for years 1990-2001 also from the National Research and Development Centre for Welfare and Health. RESULTS: In year 2000, the incidence of major amputations was 154/million inhabitants. The reason for major amputation was chronic critical lower limb ischaemia in 71.8% and acute ischaemia in 16.5% of the cases. The below-knee (BK)/above-knee (AK) ratio was 0.76. After 1 year only 48% of the patients were alive. From 1984 to 2000 amputation incidence showed a decrease of 41%. The decline in age-adjusted amputation incidence from 1990 to 2000 was 30% and by 2001 as much as 40%. There was a significant inverse correlation both between incidence of infrainguinal bypass and amputation (r=-0.682, p=0.021) and between infrapopliteal bypass and amputation (r=-0.682, p=0.021). CONCLUSIONS: There was a reduction in the number of amputations in Southern Finland during the past 17 years. This occurred synchronously with the increase in vascular reconstructions. Our data suggests that vascular surgery saves patients from BK-amputations and therefore relative amount of AK-amputations inevitably rises.

A new technique for esophagojejunostomy after total gastrectomy for gastric cancer.

BACKGROUND: The critical part of any operation involving a proximal gastric resection is the esophageal anastomosis. Leakage from this anastomosis is one of the main reasons for postoperative morbidity and death after gastrectomy. Application of the double-stapling technique affords many of the same advantages that it does for low rectal tumors, especially in obese patients with narrow costal margins. METHODS: A new technique for esophagojejunostomy after total gastrectomy for gastric cancer is described. RESULTS: This technique has been used in 3 patients. At a follow-up of 22 months, there have been no anastomotic leaks or evidence of clinical stenoses. CONCLUSIONS: This technique minimizes manipulation and dissection around the distal esophagus. Not only does this make the operation easier, but it also allows for a longer proximal resection margin. Possibly this will result in lower rates of esophageal breakdown.