Splanchnic vein thrombosis in necrotizing pancreatitis:a post-hoc analysis of a nationwide prospective cohort

Background: Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum. Methods: We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT. Results: SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11–40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89–8.51), and younger age (OR 0.94; 95% CI 0.90–0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27–8.23 and OR 7.29; 95% CI 1.31–40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37–4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants. Discussion: SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes.</p

Splanchnic vein thrombosis in necrotizing pancreatitis:a post-hoc analysis of a nationwide prospective cohort

Background: Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum. Methods: We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT. Results: SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11–40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89–8.51), and younger age (OR 0.94; 95% CI 0.90–0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27–8.23 and OR 7.29; 95% CI 1.31–40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37–4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants. Discussion: SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes.</p

Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy:dysphagia is uncommon

BACKGROUND: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. METHODS: Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer ('SANO') trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0-100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. RESULTS: In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3-4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0-0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. CONCLUSION: Dysphagia and clinically relevant stenosis are uncommon during active surveillance.</p

Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy:dysphagia is uncommon

BACKGROUND: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. METHODS: Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer ('SANO') trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0-100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. RESULTS: In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3-4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0-0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. CONCLUSION: Dysphagia and clinically relevant stenosis are uncommon during active surveillance.</p

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS):study protocol for a nationwide prospective cohort study

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.Peer reviewe

Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial

BACKGROUND: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. METHODS: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. DISCUSSION: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. TRIAL REGISTRATION: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022)

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial

Background: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. Methods: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. Discussion: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. Trial registration: ClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021