Covered versus bare-metal stenting of the mesenteric arteries in patients with chronic mesenteric ischaemia (CoBaGI): a multicentre, patient-blinded and investigator-blinded, randomised controlled trial.

BACKGROUND: Mesenteric artery stenting with a bare-metal stent is the current treatment for atherosclerotic chronic mesenteric ischaemia. Long-term patency of bare-metal stents is unsatisfactory due to in-stent intimal hyperplasia. Use of covered stents might improve long-term patency. We aimed to compare the patency of covered stents and bare-metal stents in patients with chronic mesenteric ischaemia. METHODS: We conducted a multicentre, patient-blinded and investigator-blinded, randomised controlled trial including patients with chronic mesenteric ischaemia undergoing mesenteric artery stenting. Six centres in the Netherlands participated in this study, including two national chronic mesenteric ischaemia expert centres. Patients aged 18 years or older were eligible for inclusion when an endovascular mesenteric artery revascularisation was scheduled and a consensus diagnosis of chronic mesenteric ischaemia was made by a multidisciplinary team of gastroenterologists, interventional radiologists, and vascular surgeons. Exclusion criteria were stenosis length of 25 mm or greater, stenosis caused by median arcuate ligament syndrome or vasculitis, contraindication for CT angiography, or previous target vessel revascularisation. Digital 1:1 block randomisation with block sizes of four or six and stratification by inclusion centre was used to allocate patients to undergo stenting with bare-metal stents or covered stents at the start of the procedure. Patients, physicians performing follow-up, investigators, and radiologists were masked to treatment allocation. Interventionalists performing the procedure were not masked. The primary study outcome was the primary patency of covered stents and bare-metal stents at 24 months of follow-up, evaluated in the modified intention-to-treat population, in which stents with missing data for the outcome were excluded. Loss of primary patency was defined as the performance of a re-intervention to preserve patency, or 75% or greater luminal surface area reduction of the target vessel. CT angiography was performed at 6 months, 12 months, and 24 months post intervention to assess patency. The study is registered with ClinicalTrials.gov (NCT02428582) and is complete. FINDINGS: Between April 6, 2015, and March 11, 2019, 158 eligible patients underwent mesenteric artery stenting procedures, of whom 94 patients (with 128 stents) provided consent and were included in the study. 47 patients (62 stents) were assigned to the covered stents group (median age 69·0 years [IQR 63·0-76·5], 28 [60%] female) and 47 patients (66 stents) were assigned to the bare-metal stents group (median age 70·0 years [63·5-76·5], 33 [70%] female). At 24 months, the primary patency of covered stents (42 [81%] of 52 stents) was superior to that of bare-metal stents (26 [49%] of 53; odds ratio [OR] 4·4 [95% CI 1·8-10·5]; p<0·0001). A procedure-related adverse event occurred in 17 (36%) of 47 patients in the covered stents group versus nine (19%) of 47 in the bare-metal stent group (OR 2·4 [95% CI 0·9-6·3]; p=0·065). Most adverse events were related to the access site, including haematoma (five [11%] in the covered stents group vs six [13%] in the bare-metal stents group), pseudoaneurysm (five [11%] vs two [4%]), radial artery thrombosis (one [2%] vs none), and intravascular closure device (none vs one [2%]). Six (13%) patients in the covered stent group versus one (2%) in the bare-metal stent group had procedure-related adverse events not related to the access site, including stent luxation (three [6%] vs none), major bleeding (two (4%) vs none), mesenteric artery perforation (one [2%] vs one [2%]), mesenteric artery dissection (one [2%] vs one [2%]), and death (one [2%] vs none). INTERPRETATION: The findings of this trial support the use of covered stents for mesenteric artery stenting in patients with chronic mesenteric ischaemia. FUNDING: Atrium Maquet Getinge Group.

Endoscopic screening of the upper gastrointestinal tract for second primary tumors in patients with head and neck cancer in a Western country.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival. METHODS: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma. RESULTS: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening. CONCLUSION: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities.

Bite-on-bite biopsies for the detection of residual esophageal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: Active surveillance after neoadjuvant treatment is increasingly implemented. The success of this strategy relies on the accurate detection of residual cancer. This study aimed to assess the diagnostic value of a second (bite-on-bite) biopsy for the detection of residual esophageal cancer and to correlate outcomes to the distribution of residual cancer found in the resection specimen. METHODS: A multicenter prospective study of esophageal cancer patients undergoing active surveillance after neoadjuvant chemoradiotherapy was performed. At clinical response evaluations, an upper gastrointestinal (GI) endoscopy was performed with at least four bite-on-bite biopsies of the primary tumor site. First and second biopsies were analyzed separately. Patients with histopathological evidence of residual cancer were included in the primary analysis. Two pathologists blinded for biopsy outcome examined all resection specimens. RESULTS: Between October 2017 and July 2020, 626 upper GI endoscopies were performed in 367 patients. Of 138 patients with residual cancer, 112 patients (81 %) had at least one positive biopsy. In 14 patients (10 %) only the first biopsy was positive and in 25 patients (18 %) only the second biopsy (P = 0.11). Remarkably, the rates of patients with tumor-free mucosa and deeper located tumors were higher in patients detected by the first biopsy. The second biopsy increased the false-positive rate by 3 percentage points. No adverse events occurred. CONCLUSIONS: A second (bite-on-bite) biopsy improves the detection of residual esophageal cancer by almost 20 percentage points, at the expense of increasing the false-positive rate by 3 percentage points. The higher detection rate is explained by the higher number of biopsies obtained rather than by the penetration depth.

MRI-based pre- and postprandial flow in the mesenteric vasculature of patients with suspected chronic mesenteric ischemia.

PURPOSE: The physiological increase of mesenteric blood flow after a meal is impaired in patients with occlusive chronic mesenteric ischemia (CMI). This principle could be used to develop a highly desired diagnostic test assessing the sufficiency of the collateral mesenteric circulation. This study assesses the potential to identify CMI patients using two-dimensional time-resolved phase-contrast magnetic resonance imaging (2D PC-MRI) flow measurements. METHOD: This prospective cohort study included patients with suspected CMI, based on: typical history, imaging, and functional testing. Cardiac gated 2D PC-MRI flow measurements (expressed as ml/min/kg) were performed in mesenteric arteries and veins during inspiration and expiration, after six hours of fasting and 20, 30, and 40 min after a meal challenge with a high caloric drink. RESULTS: Flow measurements were obtained in 19 patients: 8 CMI and 11 non-CMI. CMI patients showed a significantly smaller increase in postprandial blood flow in the superior mesenteric artery (SMA) at 30 and 40 min (30 min CMI 1.27(0.12-2.44) vs. non-CMI 7.82(6.28-10.90); 40 min CMI 0.30(-0.26-3.16) vs. non-CMI 7.94(6.32-10.90)) and a lower total arterial flow at 40 min (CMI 3.21(-0.72-5.05) vs. non-CMI 9.31(5.58-13.83)). Repeated flow measurements showed normalization of impaired postprandial venous flow after mesenteric artery stenting in one patient. CONCLUSIONS: The significantly lower increase in postprandial mesenteric blood flow in CMI patients confirms the promise of mesenteric blood flow measurements, before and 30-40 min after a meal, as a future diagnostic test to identify CMI patients among patients with a high clinical suspicion of CMI and mesenteric artery stenosis.

Recommendations for endoscopic surveillance after esophageal atresia repair in adults.

BACKGROUND: Endoscopic surveillance of adults with esophageal atresia is advocated, but the optimal surveillance strategy remains uncertain. This study aimed to provide recommendations on appropriate starting age and intervals of endoscopic surveillance in adults with esophageal atresia. METHODS: Participants underwent standardized upper endoscopies with biopsies. Surveillance intervals of 3-5 years were applied, depending on age and histopathological results. Patient's age and time to development of (pre)malignant lesions were calculated. RESULTS: A total of 271 patients with esophageal atresia (55% male; median age at baseline endoscopy 26.7 (range 15.6-68.5) years; colon interposition n = 17) were included. Barrett's esophagus was found in 19 (7%) patients (median age 32.3 (17.8-56.0) years at diagnosis). Youngest patient with a clinically relevant Barrett's esophagus was 20.9 years. Follow-up endoscopies were performed in 108 patients (40%; median follow-up time 4.6 years). During surveillance, four patients developed Barrett's esophagus but no dysplasia or cancer was found. One 45-year-old woman with a colon interposition developed an adenoma with high-grade dysplasia which was radically removed. Two new cases of esophageal carcinoma were diagnosed in patients (55 and 66 years old) who were not under surveillance. One of them had been curatively treated for esophageal carcinoma 13 years ago. CONCLUSIONS: This study shows that endoscopic screening of patients with esophageal atresia, including those with a colon interposition, can be started at 20 years of age. Up to the age of 40 years a surveillance interval of 10 years appeared to be safe. Endoscopic surveillance may also be warranted for patients after curative esophageal cancer treatment.

Tissue Type Differences in ABCB1 Expression and Paclitaxel Tissue Pharmacokinetics in Patients With Esophageal Cancer.

Background: Data from previous work suggests that there is no correlation between systemic (plasma) paclitaxel exposure and efficacy in patients treated for esophageal cancer. In this trial, we investigated ATP-binding cassette efflux transporter expression and intratumoral pharmacokinetics of paclitaxel to identify changes which could be a first sign of chemoresistance. Methods: Patients with esophageal cancer treated with paclitaxel and carboplatin (± concomitant radiotherapy) were included. During the first and last cycle of weekly paclitaxel, blood samples and biopsies of esophageal mucosa and tumor tissue were taken. Changes in paclitaxel exposure and expression of ABCB1 (P-glycoprotein) over time were studied in both tumor tissue and normal appearing esophageal mucosa. Results: ABCB1 was significantly higher expressed in tumor tissue compared to esophageal tissue, during both the first and last cycle of paclitaxel (cycle 1: p < 0.01; cycle 5/6: p = 0.01). Interestingly, ABCB1 expression was significantly higher in adenocarcinoma than in squamous cell carcinoma (p < 0.01). During the first cycle, a trend towards a higher intratumoral paclitaxel concentration was observed compared to the esophageal mucosa concentration (RD:43%; 95%CI: -3% to 111% p = 0.07). Intratumoral and plasma paclitaxel concentrations were significantly correlated during the first cycle (AUC0-48 h: r = 0.72; p < 0.01). Conclusion: Higher ABCB1 expression in tumor tissue, and differences between histological tumor types might partly explain why tumors respond differently to systemic treatment. Resistance by altered intratumoral paclitaxel concentrations could not be demonstrated because the majority of the biopsies taken at the last cycle of paclitaxel did contain a low amount of tumor cells or no tumor.

Screening for synchronous esophageal second primary tumors in patients with head and neck cancer.

Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC.

Predictive value of endoscopic esophageal findings for residual esophageal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: Endoscopic evaluation of the esophageal mucosa may play a role in an active surveillance strategy after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study investigated the yield of endoscopic findings for detection of residual disease. METHODS: Patients from the multicenter preSANO cohort, who underwent nCRT followed by surgery for esophageal or junctional cancer, were included. Upper endoscopy was performed 6 and 12 weeks after nCRT. Patients with residual disease at 6 weeks underwent immediate surgery. Endoscopic records were reviewed for presence of stenosis, suspicion of residual tumor, scar tissue, and ulceration. Presence and type of endoscopic findings were compared with outcome of the resection specimen. RESULTS: 118 of 156 patients (76 %) had residual disease in the resection specimen. Endoscopic suspicion of residual tumor was significantly associated with presence of residual disease. At 6 weeks, 40/112 patients with residual disease and 4/33 patients with complete response had endoscopic suspicion of residual tumor (36 % vs. 12 %; P = 0.01), while this was reported in 16/73 and 0/28 patients, respectively, at 12 weeks (22 % vs. 0 %; P < 0.01). Positive predictive value of endoscopic suspicion of residual tumor was 91 % at 6 weeks and 100 % at 12 weeks. Endoscopic findings of non-passable stenosis, passable stenosis, scar tissue, or ulceration were not associated with residual disease. CONCLUSIONS: Endoscopic suspicion of residual tumor was the only endoscopic finding associated with residual disease. Based on its positive predictive value, this endoscopic finding may contribute to the diagnostic strategy used in active surveillance.

Active Surveillance Versus Immediate Surgery in Clinically Complete Responders After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Multicenter Propensity Matched Study.

OBJECTIVE: This study compared outcomes of patients with esophageal cancer and clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) undergoing active surveillance or immediate surgery. BACKGROUND: Since nearly one-third of patients with esophageal cancer show pathologically complete response after nCRT according to CROSS regimen, the oncological benefit of immediate surgery in cCR is topic of debate. METHODS: Patients with cCR based on endoscopic biopsies and endoscopic ultrasonography with fine-needle aspiration initially declining or accepting immediate surgery after nCRT were identified between 2011 and 2018. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), rate and timing of distant dissemination, and postoperative outcomes. RESULTS: Some 98 patients with cCR were identified: 31 in the active surveillance- and 67 in the immediate surgery group with median followup of survivors of 27.7 and 34.8 months, respectively. Propensity score matching resulted in 2 comparable groups (n = 29 in both groups). Patients undergoing active surveillance or immediate surgery had a 3-year OS of 77% and 55% (HR 0.41; 95% CI 0.14-1.20, P = 0.104), respectively. The 3-year PFS was 60% and 54% (HR 1.08; 95% CI 0.44-2.67, P = 0.871), respectively. Patients undergoing active surveillance or immediate surgery had a comparable distant dissemination rate (both groups 28%), radical resection rate (both groups 100%), and severity of postoperative complications (Clav- ien-Dindo grade ≥ 3: 43% vs 45%, respectively). CONCLUSION: In this retrospective study, OS and PFS in patients with cCR undergoing active surveillance or immediate surgery were not significantly different. Active surveillance with postponed surgery for recurrent disease was not associated with a higher distant dissemination rate or more severe adverse postoperative outcomes.

[The buried bumper syndrome]. / Het 'buried bumper'-syndroom.

The buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy (PEG). Hereby the internal PEG bumper is overgrown by hypertrophic gastric mucosa and embedded into the gastric wall. Most often an endoscopic approach to remove the bumper is successful. If not, an operative removal of the plate is necessary. In this paper, we present a case of a patient in whom a BBS was diagnosed. Besides the therapeutic options to treat a BBS, in this paper we want to focus on the prevention of this complication. Consideration needs to be given as to how long after the procedure should it be loosened to prevent BBS. The distance a PEG tube is advanced and whether it should be rotated is crucial in order to prevent BBS.

Critical appraisal of 13C breath tests for microsomal liver function: aminopyrine revisited.

As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the (13) C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the (13) C(2) -aminopyrine and the (13) C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the (13) C(2) -aminopyrine breath test in clinical practice.