Long-Term Survival Associated with Direct Oral Feeding Following Minimally Invasive Esophagectomy: Results from a Randomized Controlled Trial (NUTRIENT II).

Advancements in perioperative care have improved postoperative morbidity and recovery after esophagectomy. The direct start of oral intake can also enhance short-term outcomes following minimally invasive Ivor Lewis esophagectomy (MIE-IL). Subsequently, short-term outcomes may affect long-term survival. This planned sub-study of the NUTRIENT II trial, a multicenter randomized controlled trial, investigated the long-term survival of direct versus delayed oral feeding following MIE-IL. The outcomes included 3- and 5-year overall survival (OS) and disease-free survival (DFS), and the influence of complications and caloric intake on OS. After excluding cases of 90-day mortality, 145 participants were analyzed. Of these, 63 patients (43.4%) received direct oral feeding. At 3 years, OS was significantly better in the direct oral feeding group (p = 0.027), but not at 5 years (p = 0.115). Moreover, 5-year DFS was significantly better in the direct oral feeding group (p = 0.047) and a trend towards improved DFS was shown at 3 years (p = 0.079). Postoperative complications and caloric intake on day 5 did not impact OS. The results of this study show a tendency of improved 3-year OS and 5-year DFS, suggesting a potential long-term survival benefit in patients receiving direct oral feeding after esophagectomy. However, the findings should be further explored in larger future trials.

Population median imputation was noninferior to complex approaches for imputing missing values in cardiovascular prediction models in clinical practice.

OBJECTIVES: To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical setting. STUDY DESIGN AND SETTING: The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information - diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naïve approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics. RESULTS: C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82-0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74-0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age). CONCLUSION: Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing.

Is the SMART risk prediction model ready for real-world implementation? A validation study in a routine care setting of approximately 380 000 individuals.

AIMS: Reliably quantifying event rates in secondary prevention could aid clinical decision-making, including quantifying potential risk reductions of novel, and sometimes expensive, add-on therapies. We aimed to assess whether the SMART risk prediction model performs well in a real-world setting. METHODS AND RESULTS: We conducted a historical open cohort study using UK primary care data from the Clinical Practice Research Datalink (2000-2017) diagnosed with coronary, cerebrovascular, peripheral, and/or aortic atherosclerotic cardiovascular disease (ASCVD). Analyses were undertaken separately for cohorts with established (≥6 months) vs. newly diagnosed ASCVD. The outcome was first post-cohort entry occurrence of myocardial infarction, stroke, or cardiovascular death. Among the cohort with established ASCVD [n = 244 578, 62.1% male, median age 67.3 years, interquartile range (IQR) 59.2-74.0], the calibration and discrimination achieved by the SMART model was not dissimilar to performance at internal validation [Harrell's c-statistic = 0.639, 95% confidence interval (CI) 0.636-0.642, compared with 0.675, 0.642-0.708]. Decision curve analysis indicated that the model outperformed treat all and treat none strategies in the clinically relevant 20-60% predicted risk range. Consistent findings were observed in sensitivity analyses, including complete case analysis (n = 182 482; c = 0.624, 95% CI 0.620-0.627). Among the cohort with newly diagnosed ASCVD (n = 136 445; 61.0% male; median age 66.0 years, IQR 57.7-73.2), model performance was weaker with more exaggerated risk under-prediction and a c-statistic of 0.559, 95% CI 0.556-0.562. CONCLUSIONS: The performance of the SMART model in this validation cohort demonstrates its potential utility in routine healthcare settings in guiding both population and individual-level decision-making for secondary prevention patients.

The Effect of Postoperative Complications After Minimally Invasive Esophagectomy on Long-term Survival: An International Multicenter Cohort Study.

BACKGROUND: Esophagectomy is a technically challenging procedure, associated with significant morbidity. The introduction of minimally invasive esophagectomy (MIE) has reduced postoperative morbidity. OBJECTIVE: Although the short-term effect on complications is increasingly being recognized, the impact on long-term survival remains unclear. This study aims to investigate the association between postoperative complications following MIE and long-term survival. METHODS: Data were collected from the EsoBenchmark Collaborative composed by 13 high-volume, expert centers routinely performing MIE. Patients operated between June 1, 2011 and May 31, 2016 were included. Complications were graded using the Clavien-Dindo (CD) classification. To correct for short-term effects of postoperative complications on mortality, patients who died within 90 days postoperative were excluded. Primary endpoint was 5-year overall survival. RESULTS: A total of 915 patients were included with a mean follow-up time of 30.8 months (standard deviation 17.9). Complications occurred in 542 patients (59.2%) of which 50.2% had a CD grade ≥III complication [ie, (re)intervention, organ dysfunction, or death]. The incidence of anastomotic leakage (AL) was 135 of 915 patients (14.8%) of which 84 patients were classified as a CD grade ≥III. Multivariable analysis showed a significantly deteriorated long-term survival in all patients with AL [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.25-2.24]. This inverse relation was most distinct when AL was scored as a CD grade ≥III (HR 1.83, 95% CI 1.30-2.58). For all other complications, no significant association with long-term survival was found. CONCLUSION: The occurrence and severity of AL, but not overall complications, after MIE negatively affect long-term survival of esophageal cancer patients.

Would treatment decisions about secondary prevention of CVD based on estimated lifetime benefit rather than 10-year risk reduction be cost-effective?

OBJECTIVE: To test the hypothesis that treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years. METHODS: A microsimulation model was constructed for 10,000 patients with stable cardiovascular disease (CVD). Costs and quality-adjusted life years (QALYs) due to recurrent cardiovascular events and (non)vascular death were estimated for lifetime benefit-based compared to 10-year risk-based treatment, with PCSK9 inhibition as an illustration example. Lifetime benefit in months gained and 10-year absolute risk reduction were estimated using the SMART-REACH model, including an individualized treatment effect of PCSK9 inhibitors based on baseline low-density lipoprotein cholesterol. For the different numbers of patients treated (i.e. the 5%, 10%, and 20% of patients with the highest estimated benefit of both strategies), cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER), indicating additional costs per QALY gain. RESULTS: Lifetime benefit-based treatment of 5%, 10%, and 20% of patients with the highest estimated benefit resulted in an ICER of €36,440/QALY, €39,650/QALY, or €41,426/QALY. Ten-year risk-based treatment decisions of 5%, 10%, and 20% of patients with the highest estimated risk reduction resulted in an ICER of €48,187/QALY, €53,368/QALY, or €52,390/QALY. CONCLUSION: Treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years.

Direct Oral Feeding Following Minimally Invasive Esophagectomy (NUTRIENT II trial): An International, Multicenter, Open-label Randomized Controlled Trial.

OBJECTIVE: Patients undergoing an esophagectomy are often kept nil-by-mouth postoperatively out of fear for increasing anastomotic leakage and pulmonary complications. This study investigates the effect of direct start of oral feeding following minimally invasive esophagectomy (MIE) compared with standard of care. BACKGROUND: Elements of enhanced recovery after surgery (ERAS) protocols have been successfully introduced in patients undergoing an esophagectomy. However, start of oral intake, which is an essential part of the ERAS protocols, remains a matter of debate. METHODS: Patients in this multicenter, international randomized controlled trial were randomized to directly start oral feeding (intervention) after a MIE with intrathoracic anastomosis or to receive nil-by-mouth and tube feeding for 5 days postoperative (control group). Primary outcome was time to functional recovery. Secondary outcome parameters included anastomotic leakage, pneumonia rate, and other surgical complications scored by predefined definitions. RESULTS: Baseline characteristics were similar in the intervention (n = 65) and control (n = 67) group. Functional recovery was 7 days for patients receiving direct oral feeding compared with 8 days in the control group (P = 0.436). Anastomotic leakage rate did not differ in the intervention (18.5%) and control group (16.4%, P = 0.757). Pneumonia rates were comparable between the intervention (24.6%) and control group (34.3%, P = 0.221). Other morbidity rates were similar, except for chyle leakage, which was more prevalent in the standard of care group (P = 0.032). CONCLUSION: Direct oral feeding after an esophagectomy does not affect functional recovery and did not increase incidence or severity of postoperative complications.

Feeding protocol deviation after esophagectomy: A retrospective multicenter study.

BACKGROUND: Esophagectomy is associated with high postoperative morbidity rates, which can result in decreased quality of life and impaired recovery. Implementation of enhanced recovery after surgery (ERAS) protocols have made a great impact in optimizing postoperative recovery. However, the best timing to start oral intake is still unclear. Conservative feeding protocols have been developed with a nil-by-mouth period in the first postoperative days to reduce postoperative complication rates (e.g. anastomotic leakage and pneumonia). This study aimed to evaluate adherence to the feeding protocol following minimal invasive esophagectomy and identify reasons for protocol deviation. METHODS: All consecutive patients who underwent an esophagectomy with gastric tube reconstruction between 2014 and 2016 in two high-volume hospitals in the Netherlands were retrospectively analyzed. All patients were planned to receive enteral tube feeding via jejunostomy directly after surgery. Data regarding postoperative feeding related symptoms (e.g. nausea, vomiting, regurgitation) and adherence to the postoperative feeding protocol were gathered. RESULTS: A total of 186 patients were included. Feeding protocol deviation was observed in 109 patients (59%) and was significantly more common in patients with anastomotic leakage, chyle leakage, and acute respiratory distress. Postoperative feeding related symptoms were present in 107 patients (58%) and were significantly more common in female patients and patients with a cervical anastomosis. CONCLUSION: In this study, more than half of the patients deviated from the intended feeding protocol after esophagectomy. Postoperative complications appeared to be the main reason for feeding protocol deviation. This study shows that a predefined feeding protocol including an oral fasting period is often violated because of complications.

Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all-cause mortality: Findings from the SMART cohort.

AIM: To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all-cause mortality caused by type 2 diabetes (T2D). METHODS: Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL-cholesterol, triglycerides and micro-albuminuria), and what proportion of the effect of T2D on cardiovascular events and all-cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2D patients. RESULTS: Only 35% (95% CI 15-71%) of the excess cardiovascular risk caused by T2D is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance [proportion of mediated effect (PME) 18%, 95% CI 3-37%], followed by elevated triglycerides (PME 8%, 95% CI 4-14%) and micro-albuminuria (PME 7%, 95% CI 3-17%). Only 42% (95% CI 18-73%) of the excess mortality risk was mediated by the classical risk factors considered. The largest mediated effect was by micro-albuminuria (PME 18%, 95% CI 10-29%) followed by insulin resistance (PME 15%, 95% CI 1-33%). CONCLUSION: A substantial amount of the increased cardiovascular risk and all-cause mortality caused by T2D cannot be explained by traditional vascular risk factors. Future research should focus on identifying non-classical pathways that might further explain the increased cardiovascular and mortality risk caused by T2D.

Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitus.

AIMS: Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke. METHODS AND RESULTS: We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83-0.84) and 0.64-0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment. CONCLUSION: Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predictions of individual-level treatment effects facilitate translation of trial results to individual patients.

Learning Curve and Associated Morbidity of Minimally Invasive Esophagectomy: A Retrospective Multicenter Study.

OBJECTIVE: To investigate the morbidity that is associated with the learning curve of minimally invasive esophagectomy. BACKGROUND: Although learning curves have been described, it is currently unknown how much extra morbidity is associated with the learning curve of technically challenging surgical procedures. METHODS: Prospectively collected data were retrospectively analyzed of all consecutive patients undergoing minimally invasive Ivor Lewis esophagectomy in 4 European expert centers. The primary outcome parameter was anastomotic leakage. Secondary outcome parameters were operative time and textbook outcome ("optimal outcome"). Learning curves were plotted using weighted moving average and CUSUM analysis was used to determine after how many cases the plateau was reached. Learning associated morbidity was calculated with area under the curve analysis. RESULTS: This study included 646 patients. Three of the 4 hospitals reached the plateau of 8% anastomotic leakage. The length of the learning curve was 119 cases. The mean incidence of anastomotic leakage decreased from 18.8% during the learning phase to 4.5% after the plateau had been reached (P < 0.001). Thirty-six extra patients (10.1% of all patients operated on during the learning curve) experienced learning associated anastomotic leakage, that could have been avoided if patients were operated by surgeons who had completed the learning curve. The incidence of textbook outcome increased from 28% to 53% and the mean operative time decreased from 344 minutes to 270 minutes. CONCLUSIONS: A considerable number of 36 extra patients (10.1%) experienced learning associated anastomotic leakage. More research is urgently needed to investigate how learning associated morbidity can be reduced to increase patient safety during learning curves.

FA01.02: THE EFFECT OF POSTOPERATIVE COMPLICATIONS AFTER MIE ON LONG-TERM SURVIVAL: A RETROSPECTIVE, MULTI-CENTER COHORT STUDY.

BACKGROUND: Esophagectomy has a high incidence of postoperative morbidity. Complications lead to a decreased short-term survival, however the influence of those complications on long-term survival is still unclear. Most of the performed studies are small, single center cohort series with inconclusive or conflicting results. Minimally invasive esophagectomy (MIE) has been shown to be associated with a reduced postoperative morbidity. In this study, the influence of complications on long-term survival for patients with esophageal cancer undergoing a MIE were investigated. METHODS: Data was collected from the EsoBenchmark database, a collaboration of 13 high-volume centers routinely performing MIE. Patients were included in this database from June 1, 2011 until May 31, 2016. Complications were scored according to the Clavien-Dindo (CD) classification for surgical complications. Major complications were defined as a CD grade ≥ 3. The data were corrected for 90-day mortality to correct for the short-term effect of postoperative complications on mortality. Overall survival was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox-regression analyses. RESULTS: A total of 926 patients were eligible for analysis. Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543 patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD grade ≥ 3). A significant worse long-term survival was observed in patients with any AL (HR 1.73, 95% CI 1.29-2.32, P < 0.001) and for patients with AL CD grade ≥3 (HR 1.86, 95% CI 1.32-2.63, P < 0.001). Major cardiac complications occurred in 18 patients (1.9%) and were related to a decreased long-term survival (HR 2.72, 95% CI 1.38-5.35, p 0.004). For all other complications, no significant influence on long-term survival was found. CONCLUSION: The occurrence and severity of anastomotic leakage and cardiac complications after MIE negatively affect long-term survival of esophageal cancer patients. DISCLOSURE: All authors have declared no conflicts of interest.

Routinely measured hematological parameters and prediction of recurrent vascular events in patients with clinically manifest vascular disease.

BACKGROUND AND AIMS: The predictive value of traditional risk factors for vascular events in patients with manifest vascular disease is limited, underscoring the need for novel biomarkers to improve risk stratification. Since hematological parameters are routinely assessed in clinical practice, they are readily available candidates. METHODS: We used data from 3,922 vascular patients, who participated in the Second Manifestations of ARTerial Disease (SMART) study. We first investigated associations between recurrent vascular events and 22 hematological parameters, obtained from the Utrecht Patient Oriented Database (UPOD), and then assessed whether parameters associated with outcome improved risk prediction. RESULTS: After adjustment for all SMART risk score (SRS) variables, lymphocyte %, neutrophil count, neutrophil % and red cell distribution width (RDW) were significantly associated with vascular events. When individually added to the SRS, lymphocyte % improved prediction of recurrent vascular events with a continuous net reclassification improvement (cNRI) of 17.4% [95% CI: 2.1, 32.1%] and an increase in c-statistic of 0.011 [0.000, 0.022]. The combination of lymphocyte % and neutrophil count resulted in a cNRI of 22.2% [3.2, 33.4%] and improved c-statistic by 0.011 [95% CI: 0.000, 0.022]. Lymphocyte % and RDW yielded a cNRI of 18.7% [3.3, 31.9%] and improved c-statistic by 0.016 [0.004, 0.028]. However, the addition of hematological parameters only modestly increased risk estimates for patients with an event during follow-up. CONCLUSIONS: Several hematological parameters were independently associated with recurrent vascular events. Lymphocyte % alone and in combination with other parameters enhanced discrimination and reclassification. However, the incremental value for patients with a recurrent event was limited.

Accuracy of oscillometric blood pressure measurement in atrial fibrillation.

OBJECTIVE: The primary aim of this study was to assess the accuracy of automated oscillometry (AO) in outpatients with atrial fibrillation (AF). The secondary aim was to explore whether AO accuracy is influenced by beat-to-beat blood pressure (BP) variability or heart frequency (HF). METHODS: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by AO and beat-to-beat BP using a validated Volume Clamp Method (VCM) technique. AO accuracy was analyzed separately in tertiles of beat-to-beat BP variability and HF. RESULTS: The main study included 58 AF and 38 sinus rhythm (SR) patients in whom the Welch Allyn Spot Vital Signs (WASVS) was used. An auxiliary study in 23 AF patients used the Philips M3002A IntelliVue ×2. For AF and SR patients, respectively, SBP by WASVS deviated by +0.1 (±14.8) mmHg and -7.9 (±15.7) mmHg from VCM. WASVS-DBP was higher than VCM in AF and SR by 6.3 (±9.2) mmHg and 5.0 (±7.7) mmHg, respectively. High beat-to-beat BP variability and high HF decreased WASVS accuracy for both SBP and DBP. SBP and DBP measurements by Philips M3002A IntelliVue ×2 deviated by -6.8 (±13.2) mmHg and 9.4 (±8.1) mmHg, respectively. CONCLUSION: Overall, AO accuracy in AF is limited; in individual patients, AO inaccuracy may be considerable. AO accuracy is especially reduced in patients showing large beat-to-beat BP variability or high HF.

Decline in risk of recurrent cardiovascular events in the period 1996 to 2014 partly explained by better treatment of risk factors and less subclinical atherosclerosis.

BACKGROUND: To quantify the decline in recurrent major cardiovascular events (MCVE) risk in patients with clinically manifest vascular disease between 1996 and 2014 and to assess whether the improvements in recurrent MCVE-risk can be explained by reduced prevalence of risk factors, more medication use and less subclinical atherosclerosis. METHODS AND RESULTS: The study was conducted in the Second Manifestations of ARTerial disease (SMART) cohort in patients entering the cohort in the period 1996-2014. The prevalence of risk factors and subclinical atherosclerosis was measured at baseline. Incidence rates per 100person-years for recurrent MCVE (including stroke, myocardial infarction, retinal bleeding, retinal infarction, terminal heart failure, sudden death, fatal rupture of abdominal aneurysm) were calculated, stratified by the year of study enrolment. For the attributable risk of changes in risk factors, risk factor treatment, and subclinical atherosclerosis on the incidence rates of recurrent MCVE, adjusted rate ratios were estimated with Poisson regression. 7216 patients had a median follow-up of 6.5years (IQR 3.4-9.9). The crude incidence of recurrent MCVE declined by 53% between 1996 and 2014 (from 3.68 to 1.73 events per 100person-years) and by 75% adjusted for age and sex. This improvement in vascular prognosis was 36% explained by changes in risk factors, medication use and subclinical atherosclerosis. CONCLUSION: The risk of recurrent MCVE in patients with clinically manifest vascular disease has strongly declined in the period between 1996 and 2014. This is only partly attributable to lower prevalence of risk factors, improved medication use and less subclinical atherosclerosis.

The feeding route after esophagectomy: a review of literature.

Enhanced recovery programs effectively optimize perioperative care and reduce postoperative morbidity. In esophagectomy, several components of the ERAS program are successfully introduced. However, timing and type of postoperative feeding remain a matter of debate. Adequate nutritional support is essential in patients undergoing an esophagectomy. These patients often present with weight loss and their eating pattern is strongly altered by the procedure and reconstruction. Total parenteral nutrition (TPN) is associated with severe septic complications and enteral nutrition (EN) does not increase major complications. Therefore, early EN after esophagectomy is favored over TPN. However, with enteral feeding tubes minor complications occur frequently (13-38%) and in some cases this can hamper recovery. Based on experience in other types of upper gastro-intestinal surgery, early start of oral feeding could improve time to functional recovery after surgery. The total length of stay was significantly shorter in four prospective studies (6-12 vs. 8-13 days). However, large randomized controlled trials are lacking and the potential benefit of early oral feeding after esophageal surgery remains elusive. EN is nowadays the optimal feeding route after esophagectomy. TPN should only be used in specific cases in which EN is contraindicated. Early initiation of oral intake is promising and could improve postoperative recovery. However, further research is needed to substantiate these results.

McKeown or Ivor Lewis totally minimally invasive esophagectomy for cancer of the esophagus and gastroesophageal junction: systematic review and meta-analysis.

BACKGROUND: Minimally invasive esophagectomy (MIE) has consistently been associated with improved perioperative outcome and similar oncological safety compared to open esophagectomy. However, it is currently unclear what type of MIE is preferred for patients with resectable esophageal cancer. METHODS: Literature was searched in Medline, Embase and the Cochrane library combining relevant search terms. Articles that included patients undergoing totally minimally invasive esophagectomy (TMIE) or hybrid minimally invasive esophagectomy (HMIE) and compared McKeown with Ivor Lewis procedures were included. Studies were excluded if they included >10% of patients undergoing a procedure other than MIE McKeown or MIE Ivor Lewis (i.e., transhiatal resections). The primary outcome parameter was anastomotic leakage. Secondary outcome parameters were: other complications, reinterventions, reoperations, hospital length of stay, ICU length of stay, postoperative mortality, operative time, blood loss, R0 resection rate, lymph nodes examined, quality of life and costs. RESULTS: Five studies with a total of 1,681 patients undergoing TMIE were included. There were no studies comparing HMIE McKeown versus HMIE Ivor Lewis. There were no randomized controlled trials and all included studies were cohort studies with a moderate risk of bias. No meta-analysis could be performed for R0 resection rate, survival, quality of life and costs because there was insufficient data available for these parameters. The incidence of anastomotic leakage did not differ between the groups [relative risk (RR) =1.39, 95% confidence interval (CI) =0.90-10.38, P=0.14]. TMIE Ivor Lewis was associated with a lower incidence of recurrent laryngeal nerve (RLN) trauma (RR =6.70, 95% CI =3.09-14.55, P<0.001), a shorter hospital length of stay [standardized mean difference (SMD) =0.17, 95% CI =0.06-0.28, P=0.002] and less blood loss (SMD =0.69, 95% CI =0.25-1.12, P=0.002). CONCLUSIONS: TMIE Ivor Lewis is associated with improved outcome regarding RLN trauma, hospital length of stay and blood loss as compared to TMIE-McKeown, but the incidence of anastomotic leakage is not different. The evidence is limited, of low quality and at risk for bias. A randomized controlled trial is currently being performed in order to demonstrate whether a McKeown or Ivor Lewis procedure should be preferred in patients undergoing MIE.

SPRINT trial: It's not just the blood pressure!

Background The SPRINT trial showed a beneficial effect of systolic blood pressure treatment targets of 120 mmHg on cardiovascular risk compared to targets of 140 mmHg. However, differences in medication use, most importantly diuretics, are suggested as an alternative explanation. This post-hoc analysis aimed to determine whether the reduced event rate can be attributed to changes in systolic blood pressure (ΔSBP) . Methods Analyses were based on all 9361 participants of the SPRINT trial. ΔSBP was defined as the change between baseline and 6-month follow-up systolic blood pressure. Major cardiovascular events were myocardial infarction, other acute coronary syndromes, stroke, heart failure, or cardiovascular death. Cox regression was used to describe the relation between ΔSBP and major cardiovascular events. Analyses were performed separately for patients in the lowest tertile of baseline systolic blood pressure, as the SPRINT trial reported the highest treatment effect in this subgroup. Results The relation between ΔSBP and major cardiovascular events was a hazard ratio per 10 mmHg decrease of 0.93 (95% confidence interval 0.89-0.98). Similar results were found within the lowest tertile of baseline systolic blood pressure: hazard ratio per 10 mmHg decrease 0.91 (95% confidence interval 0.82-1.01). Conclusion Our results show that lowering blood pressure prevents cardiovascular disease. However, not all the positive effects in the SPRINT trial could be explained by ΔSBP. Alternative explanations, such as differences in medication use, should be considered for the positive findings of the SPRINT trial.

Nasogastric decompression following esophagectomy: a systematic literature review and meta-analysis.

Routine use of nasogastric tubes for gastric decompression has been abolished in nearly all types of gastro-intestinal surgery after introduction of enhanced recovery after surgery programs. However, in esophagectomy the routine use of nasogastric decompression is still a matter of debate. To determine the effects of routine nasogastric decompression following esophagectomy compared with early or peroperative removal of the nasogastric tube on pulmonary complications, anastomotic leakage, mortality, and postoperative recovery. A systematic literature review and meta-analysis of studies comparing early or peroperative versus late removal of nasogastric tubes. A total of seven comparative studies were included (n = 608). In two randomized trials, and one retrospective cohort study, peroperative removal of the nasogastric tube was compared with routine nasogastric decompression. In one randomized trial early removal of the nasogastric tube (on postoperative day 2) was compared with removal of the nasogastric tube on the 6th-10th postoperative day. In the remaining three trials a fast-track protocol without a nasogastric tube was compared with conventional care with a nasogastric tube during the first postoperative days. Peroperative or early removal of the nasogastric tube did not result in a significantly different rate of anastomotic leakage, pulmonary complications or mortality in individual studies, nor in the meta-analysis. In the meta-analysis, hospital stay was significantly shorter with peroperative or early removal of the nasogastric tube when all studies were included, but not when the meta-analysis was limited to randomized trials. This systematic review did not find a difference in adverse outcomes between nasogastric decompression or no nasogastric decompression following esophagectomy.

Nutritional route in oesophageal resection trial II (NUTRIENT II): study protocol for a multicentre open-label randomised controlled trial.

INTRODUCTION: Early start of an oral diet is safe and beneficial in most types of gastrointestinal surgery and is a crucial part of fast track or enhanced recovery protocols. However, the feasibility and safety of oral intake directly following oesophagectomy remain unclear. The aim of this study is to investigate the effects of early versus delayed start of oral intake on postoperative recovery following oesophagectomy. METHODS AND ANALYSIS: This is an open-label multicentre randomised controlled trial. Patients undergoing elective minimally invasive or hybrid oesophagectomy for cancer are eligible. Further inclusion criteria are intrathoracic anastomosis, written informed consent and age 18 years or older. Inability for oral intake, inability to place a feeding jejunostomy, inability to provide written consent, swallowing disorder, achalasia, Karnofsky Performance Status <80 and malnutrition are exclusion criteria. Patients will be randomised using online randomisation software. The intervention group (direct oral feeding) will receive a liquid oral diet for 2 weeks with gradually expanding daily maximums. The control group (delayed oral feeding) will receive enteral feeding via a jejunostomy during 5 days and then start the same liquid oral diet. The primary outcome measure is functional recovery. Secondary outcome measures are 30-day surgical complications; nutritional status; need for artificial nutrition; need for additional interventions; health-related quality of life. We aim to recruit 148 patients. Statistical analysis will be performed according to an intention to treat principle. Results are presented as risk ratios with corresponding 95% CIs. A two-tailed p<0.05 is considered statistically significant. ETHICS AND DISSEMINATION: Our study protocol has received ethical approval from the Medical research Ethics Committees United (MEC-U). This study is conducted according to the principles of Good Clinical Practice. Verbal and written informed consent is required before randomisation. All data will be collected using an online database with adequate security measures. TRIAL REGISTRATION NUMBERS: NCT02378948 and Dutch trial registry: NTR4972; Pre-results.