PURPOSE The aim of this study was to examine the external validity of the randomized TIME trial, when minimally invasive esophagectomy (MIE) was implemented nationally in the Netherlands, using data from the Dutch Upper GI Cancer Audit (DUCA) for transthoracic esophagectomy. METHODS Original patient data from the TIME trial were extracted along with data from the DUCA dataset (2011-2017). Multivariate analysis, with adjustment for patient factors, tumor factors, and year of surgery, was performed for the effect of MIE versus open esophagectomy on clinical outcomes. RESULTS One hundred fifteen patients from the TIME trial (59 MIE v 56 open) and 4,605 patients from the DUCA dataset (2,652 MIE v 1,953 open) were included. In the TIME trial, univariate analysis showed that MIE reduced pulmonary complications and length of hospital stay. On the contrary, in the DUCA dataset, MIE was associated with increased total and pulmonary complications and reoperations; however, benefits included increased proportion of R0 margin and lymph nodes harvested, and reduced 30-day mortality. Multivariate analysis from the TIME trial showed that MIE reduced pulmonary complications (odds ratio [OR], 0.19; 95% CI, 0.06 to 0.61). In the DUCA dataset, MIE was associated with increased total complications (OR, 1.36; 95% CI, 1.19 to 1.57), pulmonary complications (OR, 1.50; 95% CI, 1.29 to 1.74), reoperations (OR, 1.74; 95% CI, 1.42 to 2.14), and length of hospital stay. Multivariate analysis of the combined and MIE datasets showed that inclusion in the TIME trial was associated with a reduction in reoperations, Clavien-Dindo grade > 1 complications, and length of hospital stay. CONCLUSION When adopted nationally outside the TIME trial, MIE was associated with an increase in total and pulmonary complications and reoperation rate. This may reflect nonexpert surgeons outside of high-volume centers performing this minimally invasive technique in a nonstandardized fashion outside of a controlled environment.

Purified mackerel-oil extract or lard fat (9.1% wt/wt) was added to a basal diet of young pigs for 8 wk. Effects on plasma lipids, glucose and insulin, cardiac membrane phospholipids, cardiovascular performance, and morphology were studied. A time-dependent reduction of plasma triglyceride (62%), total cholesterol (41%), and HDL cholesterol (47%) was found in the mackerel-oil-fed pigs. The postprandial glucose and insulin response may indicate a mackerel-oil-induced resistance of insulin receptors. Although the polyunsaturated fatty acid composition of cardiac sarcolemma widely differed between the two groups, all determined indices of heart function were equal. It is concluded that consumption of a fish-oil diet with a low content of monoenes and supplemented with antioxidants reduces plasma lipid levels without producing pathological side effects.

The effect of chronic norepinephrine (NE) administration with increasing dosage from 1-4 mg/kg over a period of 2 weeks was studied on cardiac phospholipids and their fatty acid distribution in rats. Animals were fed a control diet or a 10% cod liver oil (CLO)-enriched diet. The relative distribution of various polyunsaturated fatty acids esterified to the 1- and 2-position of the phosphatidylethanolamine fraction was estimated. NE stress during control feeding significantly reduced the total phospholipid content in rat heart. No differences in the phospholipid class distribution were found. However, CLO feeding as well as chronic NE administration resulted in a decrease of omega 6 fatty acids, mainly C 18:2 omega 6 and C 20:4 omega 6, which was compensated with an increase in omega 3 fatty acids, mainly C 20:5 omega 3 and C 22:6 omega 3. The changes in fatty acid composition qualitatively agree with those reported by Gudbjarnason et al. (23), except that the mortality in our NE-treated control or CLO-fed groups was considerably lower. It can probably be attributed to a different mode of NE administration. On the other hand, at the end of the CLO feeding period in rats treated with NE or not, comparing with control fed rats without NE treatment, the incidence rate of ST segment elevation in electrocardiogram (ECG) recorded under light diethylether-induced anesthesia was higher. Independent of whether the fatty acid composition of myocardial phospholipids was dietary or pharmacologically manipulated, most of the polyunsaturated fatty acids were found at the 2-position of the phosphatidylethanolamine molecules. The polyunsaturated fatty acids account for 45-50% of the fatty acyl residues and preferentially occupy the 2-position, where they can exchange for each other.

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