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NVP-AUY922, a potent heat shock protein (HSP) 90 inhibitor, downregulates the expression of many oncogenic proteins, including the human epidermal growth factor receptor-2 (HER2). Because HER2 downregulation is a potential biomarker for early response to HSP90-targeted therapies, we used the (89)Zr-labelled HER2 antibody trastuzumab to quantify the alterations in HER2 expression after NVP-AUY922 treatment with HER2 positron emission tomography (PET) imaging. The HER2 overexpressing human SKOV-3 ovarian tumour cell line was used for in vitro experiments and as xenograft model in nude athymic mice. In vitro HER2 membrane expression was assessed by flow cytometry and a radio-immuno assay with (89)Zr-trastuzumab. For in vivo evaluation, mice received 50mg/kg NVP-AUY922 intraperitoneally every other day. (89)Zr-trastuzumab was injected intravenously 6d before NVP-AUY922 treatment and after 3 NVP-AUY922 doses. MicroPET imaging was performed at 24, 72 and 144h post tracer injection followed by ex-vivo biodistribution and immunohistochemical staining. After 24h NVP-AUY922 treatment HER2 membrane expression showed profound reduction with flow cytometry (80%) and radio-immuno assay (75%). PET tumour quantification, showed a mean reduction of 41% (p=0.0001) in (89)Zr-trastuzumab uptake at 144h post tracer injection after NVP-AUY922 treatment. PET results were confirmed by ex-vivo (89)Zr-trastuzumab biodistribution and HER2 immunohistochemical staining. NVP-AUY922 effectively downregulates HER2, which can be monitored and quantified in vivo non-invasively with (89)Zr-trastuzumab PET. This technique is currently under clinical evaluation and might serve as an early biomarker for HSP90 inhibition in HER2 positive metastatic breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A)., Methods: In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed., Results: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression., Conclusion: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group., Trial Registration: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov., Competing Interests: Declarations. Ethics approval-: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Groningen (Date 2020/07/27 /METc 2019/713). Consent to participate-: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Author S Kruijff is an editor in the European Journal of Nuclear Medicine and Molecular Imaging., (© 2024. The Author(s).)

BACKGROUND. CT is the standard-of-care test for preoperative locoregional staging of colon cancer (CC) but has limited diagnostic performance. More accurate preoperative staging would guide selection among expanding patient-tailored treatment options. OBJECTIVE. The purpose of this study was to evaluate through systematic review the diagnostic performance of MRI for T and N staging and that of FDG PET/CT for N staging in the locoregional staging of CC. EVIDENCE ACQUISITION. PubMed, Embase, and the Cochrane Library were searched through December 31, 2023, for studies reporting the diagnostic performance of MRI or FDG PET/CT for primary (nonrectal) CC before resection without neoadjuvant therapy, with histopathology used as the reference standard. Study quality was assessed using the QUADAS-2 tool. Publication bias was assessed using the Deeks funnel plot asymmetry test. Primary outcomes were estimated pooled predictive values, which were stratified by T and N categories for MRI and by N categories for PET/CT. Secondary outcomes were pooled sensitivity and specificity. EVIDENCE SYNTHESIS. The systematic review included 11 MRI studies (686 patients) and five PET/CT studies (408 patients). Thirteen studies had at least one risk of bias or concern of applicability. The Deek funnel plot asymmetry test indicated possible publication bias in MRI studies for differentiation of T3cd-T4 disease from T1-T3ab disease and differentiation of node-negative disease from node-positive disease. For MRI, for discriminating T1-T2 from T3-T4 disease, PPV was 64.8% (95% CI, 52.9-75.5%) and NPV was 88.9% (95% CI, 82.7-93.7%); for discriminating T1-T3ab from T3cd-T4 disease, PPV was 83.4% (95% CI, 75.0-90.3%) and NPV was 74.6% (95% CI, 58.2-86.7%); for discriminating T1-T3 from T4 disease, PPV was 94.0% (95% CI, 89.4-97.3%) and NPV was 39.9% (95% CI, 24.9-56.6%); for discriminating node-negative from node-positive disease, PPV was 74.9% (95% CI, 69.3-80.0%) and NPV was 53.9% (95% CI, 45.3-62.0%). For PET/CT, for discriminating node-negative from node-positive disease, PPV was 76.4% (95% CI, 67.9-85.1%) and NPV was 68.2% (95% CI, 56.8-78.6%). Across outcomes, MRI and PET/CT showed pooled sensitivity of 55.1-81.4% and pooled specificity of 70.3-88.1%. CONCLUSION. MRI had the strongest predictive performance for T1-T2 and T4 disease. MRI and PET/CT otherwise had limited predictive values, sensitivity, and specificity for evaluated outcomes related to T and N staging. CLINICAL IMPACT. MRI and FDG PET/CT had overall limited utility for preoperative locoregional staging of colon cancer. TRIAL REGISTRATION. PROSPERO (International Prospective Register of Systematic Reviews) CRD42022326887.

Fluorescence molecular endoscopy (FME) is emerging as a "red-flag" technique with potential to deliver earlier, faster, and more personalized detection of disease in the gastrointestinal tract, including cancer, and to gain insights into novel drug distribution, dose finding, and response prediction. However, to date, the performance of FME systems is assessed mainly by endoscopists during a procedure, leading to arbitrary, potentially biased, and heavily subjective assessment. This approach significantly affects the repeatability of the procedures and the interpretation or comparison of the acquired data, representing a major bottleneck towards the clinical translation of the technology. Herein, we propose a robust methodology for FME performance assessment and quality control that is based on a novel multi-parametric rigid standard. This standard enables the characterization of an FME system's sensitivity through a single acquisition, performance comparison of multiple systems, and, for the first time, quality control of a system as a function of time and number of usages. We show the photostability of the standard experimentally and demonstrate how it can be used to characterize the performance of an FME system. Moreover, we showcase how the standard can be employed for quality control of a system. In this study, we find that the use of composite fluorescence standards before endoscopic procedures can ensure that an FME system meets the performance criteria and that components prone to performance degradation are replaced in time, avoiding disruption of clinical endoscopy logistics. This will help overcome a major barrier for the translation of FME into the clinics.

Background and Aims: Characterization of visible abnormalities in patients with Barrett's esophagus (BE) can be challenging, especially for inexperienced endoscopists. This results in suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CADx) systems may assist endoscopists. We aimed to develop, validate, and benchmark a CADx system for BE neoplasia., Methods: The CADx system received pretraining with ImageNet and then consecutive domain-specific pretraining with GastroNet, which includes 5 million endoscopic images. It was subsequently trained and internally validated using 1758 narrow-band imaging (NBI) images of early BE neoplasia (352 patients) and 1838 NBI images of nondysplastic BE (173 patients) from 8 international centers. CADx was tested prospectively on corresponding image and video test sets with 30 cases (20 patients) of BE neoplasia and 60 cases (31 patients) of nondysplastic BE. The test set was benchmarked by 44 general endoscopists in 2 phases (phase 1, no CADx assistance; phase 2, with CADx assistance). Ten international BE experts provided additional benchmark performance., Results: Stand-alone sensitivity and specificity of the CADx system were 100% and 98% for images and 93% and 96% for videos, respectively. CADx outperformed general endoscopists without CADx assistance in terms of sensitivity (P = .04). Sensitivity and specificity of general endoscopists increased from 84% to 96% and 90% to 98% with CAD assistance (P < .001). CADx assistance increased endoscopists' confidence in characterization (P < .001). CADx performance was similar to that of the BE experts., Conclusions: CADx assistance significantly increased characterization performance of BE neoplasia by general endoscopists to the level of expert endoscopists. The use of this CADx system may thereby improve daily Barrett surveillance., Competing Interests: Disclosure The following authors disclosed financial relationships: M. Barret: research funding from Pentax Medical; consulting fees from Medtronic; medical training honorarium from Olympus; and board membership with Norgine and Ambu. J. J. Bergman: research support from Olympus Tokyo; and support for institutional review board (IRB)-approved research from Medtronic. T. Beyna: paid consultancy and lecture fees from Olympus and MicroTech; paid consultancy from Boston Scientific; and lecture fees from Fujifilm, Pentax, and Erbe. A. J. de Groof: research support from Olympus Tokyo. R. Mallant-Hent: consulting fees from Janssen. O. Pech: speaker honorarium from Boston Scientific, Medtronic, Fujifilm, Olympus, Aohua, Falk, and BMS. R. Pouw: consulting fees from Medtronic and MicroTech; and speaker fees from Pentax Medical. K. Ragunath: consulting fees from Olympus and Boston Scientific; research support from Olympus. F. van der Sommen: research support from Olympus Tokyo. P. de With: research support from Olympus Tokyo. B. Weusten: financial support for IRB-approved studies, speaker fees, and consulting fees from Pentax Medical; research support from Aqua Medical; financial support for IRB-approved studies from the St. Antonius research fund; and chair of the European Society of Gastrointestinal Endoscopy working group for the revision of the BE guideline. All other authors disclosed no financial relationships. This study received financial and logistical support from Olympus (Tokyo, Japan). Olympus did not have an active role in the design of the study, analysis of the results, or the writing of the manuscript., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Early detection of (pre)malignant esophageal lesions is critical to improve esophageal cancer morbidity and mortality rates. In patients with advanced esophageal adenocarcinoma (EAC) who undergo neoadjuvant chemoradiation therapy, the efficacy of therapy could be optimized and unnecessary surgery prevented by the reliable assessment of residual tumors after therapy. Optical coherence tomography (OCT) provides structural images at a (sub)-cellular level and has the potential to visualize morphological changes in tissue. However, OCT lacks molecular imaging contrast, a feature that enables the study of biological processes at a cellular level and can enhance esophageal cancer diagnostic accuracy. We combined OCT with near-infrared fluorescence molecular imaging using fluorescently labelled antibodies (immuno-OCT). The main goal of this proof of principle study is to investigate the feasibility of immuno-OCT for esophageal cancer imaging. We aim to assess whether the sensitivity of our immuno-OCT device is sufficient to detect the tracer uptake using an imaging dose (∼100 times smaller than a dose with therapeutic effects) of a targeted fluorescent agent. The feasibility of immuno-OCT was demonstrated ex-vivo on dysplastic lesions resected from Barrett's patients and on esophageal specimens resected from patients with advanced EAC, who were respectively topically and intravenously administrated with the tracer bevacizumab-800CW. The detection sensitivity of our system (0.3 nM) is sufficient to detect increased tracer uptake with micrometer resolution using an imaging dose of labelled antibodies. Moreover, the absence of layered structures that are typical of normal esophageal tissue observed in OCT images of dysplastic/malignant esophageal lesions may further aid their detection. Based on our preliminary results, immuno-OCT could improve the detection of dysplastic esophageal lesions., Competing Interests: JFdB has IP licensed to Terumo, Heidelberg Engineering and ASML and receives royalties through his employer. The other authors declare that they have no conflict of interest., (© 2024 The Author(s).)

Objective: Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI)., Design: Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo-800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo-800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab., Results: FMI quantification showed a dose-dependent increase in vedo-800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3-163.7)) as the most suitable tracer dose compared with 4.5 mg (55.3 au (33.6-78.2)) (p=0.0002). Moreover, the fluorescence signal decreased by 61% when vedo-800CW was administered after a therapeutic dose of unlabelled vedolizumab, suggesting target saturation in the inflamed tissue. Fluorescence microscopy and immunostaining showed that vedolizumab penetrated the inflamed mucosa and was associated with several immune cell types, most prominently with plasma cells., Conclusion: These results indicate the potential of FMI to determine the local distribution of drugs in the inflamed target tissue and identify drug target cells, providing new insights into targeted agents for their use in IBD., Trial Registration Number: NCT04112212., Competing Interests: Competing interests: GD received research grants from Royal DSM, Takeda and Janssen Pharmaceuticals and speaker fees from AbbVie, Pfizer, Takeda and Janssen Pharmaceuticals. EAMF is supported by a ZonMW Clinical Fellowship grant (project number 90719075) and has received an unrestricted research grant from Takeda. MD and SJ are employees and shareholders of Regeneron Pharmaceuticals., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background:  This study evaluated the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v)., Methods:  This retrospective cohort study included patients undergoing ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. We defined R1v as cancer cells touching vertical resection margins and Rx as nonassessable margins. Reassessment of R1v specimens was performed by experienced pathologists until consensus was reached regarding vertical margins., Results:  101/110 included patients had macroscopically complete resections (17 T1a, 84 T1b), and 99/101 (98%) ER specimens were histologically reassessed, with R1v confirmed in 74 patients (75%), Rx in 16%, and R0 in 9%. Presence/absence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (52) and/or in the surgical resection specimen (14), and 33/66 (50%) had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal-appearing ER scar did not detect additional neoplasia. Of 25 patients who underwent endoscopic follow-up (median 37 months [interquartile range 12-50]), 4 developed local recurrence (16.0%), all detected as visible abnormalities., Conclusions:  After ER with R1v, 50% of patients had no residual neoplasia. Histological evaluation of ER margins appears challenging, as in this study 75% of documented R1v cases were confirmed during reassessment. Endoscopic reassessment 8-12 weeks after ER seems to accurately detect residual neoplasia and can help to determine the most appropriate strategy for patients with R1v., Competing Interests: B.L.A.M. Weusten has received financial research support from Pentax Medical and Aqua Medical, and has received lecture fees from and is a consultant for Pentax Medical. J.J.G.H.M. Bergman has received financial support for institutional review board-approved research from C2Therapeutics/Pentax Medical, Medtronic, and Aqua Medical. R.E Pouw is a consultant for Medtronic BV and MicroTech Europe, and has received speaker fees from Pentax. L. van Tilburg, E.P.D. Verheij, S.E.M. van de Ven, S.N. van Munster, L. Alvarez Herrero, W.B. Nagengast, E.J. Schoon, A. Alkhalaf, L. Oudijk, S.L. Meijer, M. Jansen, M. Doukas, and A.D. Koch declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Purpose: The ability to identify residual tumor tissues in patients with locally advanced esophageal cancer following neoadjuvant chemoradiotherapy (nCRT) is essential for monitoring the treatment response. Using the fluorescent tracer bevacizumab-800CW, we evaluated whether ultrasound-guided quantitative fluorescent molecular endoscopy (US-qFME), which combines quantitative fluorescence molecular endoscopy (qFME) with ultrasound-guided needle biopsy/single-fiber fluorescence (USNB/SFF), can be used to identify residual tumor tissues in patients following nCRT., Experimental Design: Twenty patients received an additional endoscopy procedure the day before surgery. qFME was performed at the primary tumor site (PTS) and in healthy tissue to first establish the optimal tracer dose. USNB/SFF was then used to measure intrinsic fluorescence in the deeper PTS layers and lymph nodes (LN) suspected for metastasis. Finally, the intrinsic fluorescence and the tissue optical properties-specifically, the absorption and reduced scattering coefficients-were combined into a new parameter called omega., Results: First, a 25-mg bevacizumab-800CW dose allowed for clear differentiation between the PTS and healthy tissue, with a target-to-background ratio (TBR) of 2.98 (IQR, 1.86-3.03). Moreover, we found a clear difference between the deeper esophageal PTS layers and suspected LN compared to healthy tissues, with TBR values of 2.18 and 2.17, respectively. Finally, our new parameter, omega, further improved the ability to differentiate between the PTS and healthy tissue., Conclusions: Combining bevacizumab-800CW with US-qFME may serve as a viable strategy for monitoring the response to nCRT in esophageal cancer and may help stratify patients regarding active surveillance versus surgery., (©2024 American Association for Cancer Research.)

Objective: Meningiomas are one of the most frequently occurring brain tumors and can be curatively treated with gross-total resection. A subtotal resection increases the chances of recurrence. The intraoperative identification of invisible tumor remnants by using a fluorescent tracer targeting an upregulated biomarker could help to optimize meningioma resection. This is called molecular fluorescence-guided surgery (MFGS). Vascular endothelial growth factor α (VEGFα) has been identified as a suitable meningioma biomarker and can be targeted with bevacizumab-IRDye800CW., Methods: The aim of this prospective phase I trial was to determine the safety and feasibility of bevacizumab-IRDye800CW for MFGS for intracranial meningiomas by administering 4.5, 10, or 25 mg of the tracer 2-4 days prior to surgery. Fluorescence was verified during the operation with the standard neurosurgical microscope, and tissue specimens were postoperatively analyzed with fluorescence imaging systems (Pearl and Odyssey CLx) and spectroscopy to determine the optimal dose. Uptake was compared in several tissue types and correlated with VEGFα expression., Results: No adverse events related to the use of bevacizumab-IRDye800CW occurred. After two interim analyses, 10 mg was the optimal dose based on ex vivo tumor-to-background ratio. Although the standard intraoperative imaging revealed no fluorescence, postoperative analyses with tailored imaging systems showed high fluorescence uptake in tumor compared with unaffected dura mater and brain. Additionally, tumor invasion of the dura mater (dural tail) and invasion of bone could be distinguished using fluorescence imaging. Fluorescence intensity showed a good correlation with VEGFα expression., Conclusions: Bevacizumab-IRDye800CW can be safely used in patients with meningioma; 10 mg bevacizumab-IRDye800CW provided an adequate tumor-to-background ratio. Adjustments of the currently available neurosurgical microscopes are needed to achieve visualization of targeted IRDye800CW intraoperatively. A phase II/III trial is needed to methodically investigate the benefit of MFGS with bevacizumab-IRDye800CW for meningioma surgery in a larger cohort of patients.

Background & Aims: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality., Methods: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration., Results: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration., Conclusion: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting., Methods: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up., Results: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5)., Conclusions: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia., Clinicaltrials: gov, NCT02384122., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Contamination of duodenoscopes is a significant concern due to the transmission of multidrug-resistant organisms (MDROs) among patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), resulting in outbreaks worldwide. In July 2020, it was determined that three different patients, all had undergone ERCP with the same duodenoscope, were infected. Two patients were infected with bla CTX-M-15 encoding Citrobacter freundii, one experiencing a bloodstream infection and the other a urinary tract infection, while another patient had a bloodstream infection caused by bla SHV-12 encoding Klebsiella pneumoniae. Molecular characterization of isolates was available as every ESBL-producing isolate undergoes Next-Generation Sequencing (NGS) for comprehensive genomic analysis in our center. After withdrawing the suspected duodenoscope, we initiated comprehensive epidemiological research, encompassing case investigations, along with a thorough duodenoscope investigation. Screening of patients who had undergone ERCP with the implicated duodenoscope, as well as a selection of hospitalized patients who had ERCP with a different duodenoscope during the outbreak period, led to the discovery of three additional cases of colonization in addition to the three infections initially detected. No microorganisms were detected in eight routine culture samples retrieved from the suspected duodenoscope. Only after destructive dismantling of the duodenoscope, the forceps elevator was found to be positive for bla SHV-12 encoding K. pneumoniae which was identical to the isolates detected in three patients. This study highlights the importance of using NGS to monitor the transmission of MDROs and demonstrates that standard cultures may fail to detect contaminated medical equipment such as duodenoscopes., (© 2024. The Author(s).)

Background: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus., Methods: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs)., Findings: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p<0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p<0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p<0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video)., Interpretation: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases., Funding: Olympus., Competing Interests: Declaration of interests MB is a consultant for Medtronic and a board member for Norgine and Ambu, and reports funding from Pentax Medical and medical training from Olympus. JJB reports financial support for institutional review board-approved research from C2Therapeutics and Pentax Medical, Medtronic, and Aqua Medical. TB reports consulting fees from Olympus, Boston Scientific, and Microtech; lecture fees from Olympus, Fujifilm, Pentax, Microtech, ERBE, and Medtronic; payment for expert testimony from Olympus; and participation on a data safety monitoring board or advisory board at Olympus. RCM-H reports consultant fees from Janssen. OP reports speaker honorarium from Boston Scientific, Medtronic, Fujifilm, Olympus, Aohua, Falk, and BMS. REP reports consulting fees from Medtronic and Microtech and speaker fees from Pentax. KR reports consulting fees from Olympus and lecture fees from Olympus. BLAMW reports financial support from Pentax Medical and St Antonius Research Fund; research support from Aqua Medical; consulting fees from Pentax Medical; and speaker fees from Pentax Medical and is chair of the European Society of Gastrointestinal Endoscopy guideline working group for the revision of the Barrett's oesophagus guideline. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with cT1-2 colon cancer (CC) have a 10-20% risk of lymph node metastases. Sentinel lymph node identification (SLNi) could improve staging and reduce morbidity in future organ-preserving CC surgery. This pilot study aimed to assess safety and feasibility of robot-assisted fluorescence-guided SLNi using submucosally injected indocyanine green (ICG) in patients with cT1-2N0M0 CC., Methods: Ten consecutive patients with cT1-2N0M0 CC were included in this prospective feasibility study. Intraoperative submucosal, peritumoral injection of ICG was performed during a colonoscopy. Subsequently, the near-infrared fluorescence 'Firefly' mode of the da Vinci Xi robotic surgical system was used for SLNi. SLNs were marked with a suture, after which a segmental colectomy was performed. The SLN was postoperatively ultrastaged using serial slicing and immunohistochemistry, in addition to the standard pathological examination of the specimen. Colonoscopy time, detection time (time from ICG injection to first SLNi), and total SLNi time were measured (time from the start of colonoscopy to start of segmental resection). Intraoperative, postoperative, and pathological outcomes were registered., Results: In all patients, at least one SLN was identified (mean 2.3 SLNs, SLN diameter range 1-13 mm). No tracer-related adverse events were noted. Median colonoscopy time was 12 min, detection time was 6 min, and total SLNi time was 30.5 min. Two patients had lymph node metastases present in the SLN, and there were no patients with false negative SLNs. No patient was upstaged due to ultrastaging of the SLN after an initial negative standard pathological examination. Half of the patients unexpectedly had pT3 tumours., Conclusions: Robot-assisted fluorescence-guided SLNi using submucosally injected ICG in ten patients with cT1-2N0M0 CC was safe and feasible. SLNi was performed in an acceptable timespan and SLNs down to 1 mm were detected. All lymph node metastases would have been detected if SLN biopsy had been performed., (© 2023. The Author(s).)

Introduction: In an era of exploring patient-tailored treatment options for colon cancer, preoperative staging is increasingly important. This study aimed to evaluate completeness and reliability of CT-based preoperative locoregional colon cancer staging in Dutch hospitals., Materials and Methods: Patients who underwent elective oncological resection of colon cancer without neoadjuvant treatment in 77 Dutch hospitals were evaluated between 2011 and 2021. Completeness of T-stage was calculated for individual hospitals and stratified based on a 60% cut-off. Concordance between routine CT-based preoperative locoregional staging (cTN) and definitive pathological staging (pTN) was examined., Results: A total of 59,558 patients were included with an average completeness of 43.4% and 53.4% for T and N-stage, respectively. Completeness of T-stage improved from 4.9% in 2011-2014 to 74.4% in 2019-2021. Median completeness for individual hospitals was 53.9% (IQR 27.3-80.5%) and were not significantly different between low and high-volume hospitals. Sensitivity and specificity for T3-4 tumours were relatively low: 75.1% and 76.0%, respectively. cT1-2 tumours were frequently understaged based on a low negative predictive value of 56.8%. Distinction of cT4 and cN2 disease had a high specificity (>95%), but a very low sensitivity (<50%). Positive predictive values of <60% indicated that cT4 and cN1-2 were often overstaged. Completeness and time period did not influence reliability of staging., Conclusion: Completeness of locoregional staging of colon cancer improved during recent years and varied between hospitals independently from case volume. Discriminating cT1-2 from cT3-4 tumours resulted in substantial understaging and overstaging, additionally cT4 and cN1-2 were overstaged in >40% of cases., (Copyright © 2023. Published by Elsevier Ltd.)

Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins., (© 2023. Springer Nature Limited.)

Background & Aims: Although random histological sampling from the esophagogastric junction (EGJ) after complete eradication of Barrett's esophagus (BE) is recommended, its clinical relevance is questionable. This study aimed to assess the incidence and long-term outcomes of findings from random EGJ biopsies in a nationwide cohort with long-term follow-up., Methods: We included all patients with successful endoscopic eradication therapy (EET), defined as complete endoscopic eradication of all visible BE (CE-BE), for early BE neoplasia from the Dutch registry. Patients were treated and followed-up in 9 expert centers according to a joint protocol. Outcomes included the incidence of intestinal metaplasia (IM) at the EGJ (EGJ-IM) and the association between IM and visible (dysplastic) BE recurrence., Results: A total of 1154 patients were included with a median follow-up of 43 months (interquartile range, 22-69 months). At the time of CE-BE, persisting EGJ-IM was found in 7% of patients (78/1154), which was reproduced during further follow-up in 46% of patients (42/78). No significant association existed between persisting EGJ-IM at CE-BE and recurrent non-dysplastic or dysplastic BE (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.63-2.13 and HR, 0.73; 95% CI, 0.17-3.06, respectively). Among patients with no EGJ-IM at the time of CE-BE (1043/1154; 90%), EGJ-IM recurred in 7% (72/1043) after a median of 21 months (interquartile range, 15-36 months), and was reproduced during further follow-up in 26% of patients (19/72). No association was found between recurrent EGJ-IM and non-dysplastic or dysplastic recurrence (HR, 1.18; 95% CI, 0.67-2.06 and HR, 0.27; 95% CI, 0.04-1.96, respectively)., Conclusion: Because EGJ-IM was not associated with a higher risk for recurrent disease, we recommend to consider abandoning random EGJ sampling after successful EET, under the condition that care is provided in expert centers, and the esophagus, including the EGJ, is carefully inspected (Netherlands Trial Register, NL7309)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Endoscopic detection of early neoplasia in Barrett's esophagus is difficult. Computer Aided Detection (CADe) systems may assist in neoplasia detection. The aim of this study was to report the first steps in the development of a CADe system for Barrett's neoplasia and to evaluate its performance when compared with endoscopists., Methods: This CADe system was developed by a consortium, consisting of the Amsterdam University Medical Center, Eindhoven University of Technology, and 15 international hospitals. After pretraining, the system was trained and validated using 1.713 neoplastic (564 patients) and 2.707 non-dysplastic Barrett's esophagus (NDBE; 665 patients) images. Neoplastic lesions were delineated by 14 experts. The performance of the CADe system was tested on three independent test sets. Test set 1 (50 neoplastic and 150 NDBE images) contained subtle neoplastic lesions representing challenging cases and was benchmarked by 52 general endoscopists. Test set 2 (50 neoplastic and 50 NDBE images) contained a heterogeneous case-mix of neoplastic lesions, representing distribution in clinical practice. Test set 3 (50 neoplastic and 150 NDBE images) contained prospectively collected imagery. The main outcome was correct classification of the images in terms of sensitivity., Results: The sensitivity of the CADe system on test set 1 was 84%. For general endoscopists, sensitivity was 63%, corresponding to a neoplasia miss-rate of one-third of neoplastic lesions and a potential relative increase in neoplasia detection of 33% for CADe-assisted detection. The sensitivity of the CADe system on test sets 2 and 3 was 100% and 88%, respectively. The specificity of the CADe system varied for the three test sets between 64% and 66%., Conclusion: This study describes the first steps towards the establishment of an unprecedented data infrastructure for using machine learning to improve the endoscopic detection of Barrett's neoplasia. The CADe system detected neoplasia reliably and outperformed a large group of endoscopists in terms of sensitivity., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Esophageal adenocarcinoma causes 6% of cancer-related deaths worldwide. Near-infrared fluorescence molecular endoscopy (NIR-FME) uses a tracer that targets overexpressed proteins. In this study, we aimed to investigate the feasibility of an epidermal growth factor receptor (EGFR)-targeted tracer, cetuximab-800CW, to improve detection of early-stage esophageal adenocarcinoma. Methods: We validated EGFR expression in 73 esophageal tissue sections. Subsequently, we topically administered cetuximab-800CW and performed high-definition white-light endoscopy (HD-WLE), narrow-band imaging, and NIR-FME in 15 patients with Barrett esophagus (BE). Intrinsic fluorescence values were quantified using multidiameter single-fiber reflectance and single-fiber fluorescence spectroscopy. Back-table imaging, histopathologic examination, and EGFR immunohistochemistry on biopsy samples collected during NIR-FME procedures were performed and compared with in vivo imaging results. Results: Immunohistochemical preanalysis showed high EGFR expression in 67% of dysplastic tissue sections. NIR-FME visualized all 12 HD-WLE-visible lesions and 5 HD-WLE-invisible dysplastic lesions, with increased fluorescence signal in visible dysplastic BE lesions compared with nondysplastic BE as shown by multidiameter single-fiber reflectance/single-fiber fluorescence, reflecting a target-to-background ratio of 1.5. Invisible dysplastic lesions also showed increased fluorescence, with a target-to-background ratio of 1.67. Immunohistochemistry analysis showed EGFR overexpression in 16 of 17 (94%) dysplastic BE lesions, which all showed fluorescence signal. Conclusion: This study has shown that NIR-FME using cetuximab-800CW can improve detection of dysplastic lesions missed by HD-WLE and narrow-band imaging., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

(1) Introduction: Near-infrared fluorescence (NIRF) combined with tumour-targeted tracers, such as bevacizumab-800CW, could aid surgical decision-making. This study explored the use of IRDye800CW, conjugated to bevacizumab, with four commercially available NIRF laparoscopes optimised for indocyanine green (ICG). (2) Methods: A (lymph node) phantom was made from a calibration device for NIRF and tissue-mimicking material. Serial dilutions of bevacizumab-800CW were made and ICG functioned as a reference. System settings, working distance, and thickness of tissue-mimicking material were varied to assess visibility of the fluorescence signal and tissue penetration. Tests were performed with four laparoscopes: VISERA ELITE II, Olympus; IMAGE1 S™ 4U Rubina, KARL STORZ; ENDOCAM Logic 4K platform, Richard Wolf; da Vinci Xi, Intuitive Surgical. (3) Results: The lowest visible bevacizumab-800CW concentration ranged between 13-850 nM (8-512 times diluted stock solution) for all laparoscopes, but the tracer was not visible through 0.8 cm of tissue in all systems. In contrast, ICG was still visible at a concentration of 0.4 nM (16,384 times diluted) and through 1.6-2.4 cm of tissue. Visibility and tissue penetration generally improved with a reduced working distance and manually adjusted system settings. (4) Conclusion: Depending on the application, bevacizumab-800CW might be sufficiently visible with current laparoscopes, but optimisation would widen applicability of tumour-targeted IRDye800CW tracers.

Optical biopsy in Barrett's oesophagus (BE) using endocytoscopy (EC) could optimize endoscopic screening. However, the identification of dysplasia is challenging due to the complex interpretation of the highly detailed images. Therefore, we assessed whether using artificial intelligence (AI) as second assessor could help gastroenterologists in interpreting endocytoscopic BE images. First, we prospectively videotaped 52 BE patients with EC. Then we trained and tested the AI pm distinct datasets drawn from 83,277 frames, developed an endocytoscopic BE classification system, and designed online training and testing modules. We invited two successive cohorts for these online modules: 10 endoscopists to validate the classification system and 12 gastroenterologists to evaluate AI as second assessor by providing six of them with the option to request AI assistance. Training the endoscopists in the classification system established an improved sensitivity of 90.0% (+32.67%, p < 0.001) and an accuracy of 77.67% (+13.0%, p = 0.020) compared with the baseline. However, these values deteriorated at follow-up (-16.67%, p < 0.001 and -8.0%, p = 0.009). Contrastingly, AI-assisted gastroenterologists maintained high sensitivity and accuracy at follow-up, subsequently outperforming the unassisted gastroenterologists (+20.0%, p = 0.025 and +12.22%, p = 0.05). Thus, best diagnostic scores for the identification of dysplasia emerged through human-machine collaboration between trained gastroenterologists with AI as the second assessor. Therefore, AI could support clinical implementation of optical biopsies through EC.

Flexible high-definition white-light endoscopy is the current gold standard in screening for cancer and its precursor lesions in the gastrointestinal tract. However, miss rates are high, especially in populations at high risk for developing gastrointestinal cancer (e.g., inflammatory bowel disease, Lynch syndrome, or Barrett's esophagus) where lesions tend to be flat and subtle. Fluorescence molecular endoscopy (FME) enables intraluminal visualization of (pre)malignant lesions based on specific biomolecular features rather than morphology by using fluorescently labeled molecular probes that bind to specific molecular targets. This strategy has the potential to serve as a valuable tool for the clinician to improve endoscopic lesion detection and real-time clinical decision-making. This narrative review presents an overview of recent advances in FME, focusing on probe development, techniques, and clinical evidence. Future perspectives will also be addressed, such as the use of FME in patient stratification for targeted therapies and potential alliances with artificial intelligence. KEY MESSAGES: • Fluorescence molecular endoscopy is a relatively new technology that enables safe and real-time endoscopic lesion visualization based on specific molecular features rather than on morphology, thereby adding a layer of information to endoscopy, like in PET-CT imaging. • Recently the transition from preclinical to clinical studies has been made, with promising results regarding enhancing detection of flat and subtle lesions in the colon and esophagus. However, clinical evidence needs to be strengthened by larger patient studies with stratified study designs. • In the future fluorescence molecular endoscopy could serve as a valuable tool in clinical workflows to improve detection in high-risk populations like patients with Barrett's esophagus, Lynch syndrome, and inflammatory bowel syndrome, where flat and subtle lesions tend to be malignant up to five times more often. • Fluorescence molecular endoscopy has the potential to assess therapy responsiveness in vivo for targeted therapies, thereby playing a role in personalizing medicine. • To further reduce high miss rates due to human and technical factors, joint application of artificial intelligence and fluorescence molecular endoscopy are likely to generate added value., (© 2022. The Author(s).)

Introduction: Despite evidence-based guidelines, variation in esophageal cancer care exists in daily practice. Many oncology networks deployed regional agreements to standardize the patient care pathway and reduce unwarranted clinical variation. The aim of this study was to explore the trends in variation of esophageal cancer care between participating hospitals of the Managed Clinical Network (MCN) in the Netherlands., Materials and Methods: Patients with esophageal cancer diagnosed from 2012 to 2016 were selected from the Netherlands Cancer Registry. Variation on treatment strategies, lead time to start of treatment, and 2-year survival, were calculated and compared between five clusters of hospitals within the network., Results: A total of 1763 patients, diagnosed in 17 hospitals, were included. 71% of all patients received treatment with a curative intent, which ranged from 69% to 77% between the clusters of hospitals in 2015-2016. Although variation in treatment modalities between the clusters was observed in 2012-2014, no significant variation existed in 2015-2016, except for patients receiving no treatment at all. The 2-year overall survival of patients receiving treatment with a curative intent did not vary significantly between the clusters of hospitals (range: 56%-63%). Nevertheless, the median lead time before patients started treatment with a curative intent varied between clusters of hospitals in 2015-2016 (range: 34-47 days; p < 0.001)., Conclusion: Limited variation in esophageal cancer treatment between clusters of hospitals in the MCN existed. This study shows that oncology networks can promote standardization of cancer care and reduce variation between hospitals through insight into variation., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization., Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate., Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 )., (© 2022. The Author(s).)

Background & Aims: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is safe and leads to complete eradication in the majority of patients. However, a subgroup will experience a more complex treatment course with a risk for failure or disease progression. Early identification of these patients may improve patient counseling and treatment outcomes. We aimed to develop a prognostic model for a complex treatment course., Methods: We collected data from a nationwide registry that captures outcomes for all patients undergoing endoscopic eradication therapy for early BE neoplasia. A complex treatment course was defined as neoplastic progression, treatment failure, or the need for endoscopic resection during the radiofrequency ablation treatment phase. We developed a prognostic model using logistic regression. We externally validated our model in an independent registry., Results: A total of 1386 patients were included, of whom 78 (6%) had a complex treatment course. Our model identified patients with a BE length of 9 cm or longer with a visible lesion containing high-grade dysplasia/cancer, and patients with less than 50% squamous conversion after radiofrequency ablation were identified as high risk for a complex treatment. This applied to 8% of the study population and included 93% of all treatment failures and 76% of all patients with advanced neoplastic progression. The model appeared robust in multiple sensitivity analyses and performed well in external validation (area under the curve, 0.84)., Conclusions: We developed a prognostic model that identified patients with a BE length of 9 cm or longer and high-grade dysplasia/esophageal adenocarcinoma and those with poor squamous regeneration as high risk for a complex treatment course. The good performance in external validation suggests that it may be used in clinical management (Netherlands Trial Register: NL7039)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

BACKGROUND : The optimal management for patients with low grade dysplasia (LGD) in Barrett's esophagus (BE) is unclear. According to the Dutch national guideline, all patients with LGD with histological confirmation of the diagnosis by an expert pathologist (i. e. "confirmed LGD"), are referred for a dedicated re-staging endoscopy at an expert center. We aimed to assess the diagnostic value of re-staging endoscopy by an expert endoscopist for patients with confirmed LGD. METHODS : This retrospective cohort study included all patients with flat BE diagnosed in a community hospital who had confirmed LGD and were referred to one of the nine Barrett Expert Centers (BECs) in the Netherlands. The primary outcome was the proportion of patients with prevalent high grade dysplasia (HGD) or cancer during re-staging in a BEC. RESULTS : Of the 248 patients with confirmed LGD, re-staging in the BEC revealed HGD or cancer in 23 % (57/248). In 79 % (45/57), HGD or cancer in a newly detected visible lesion was diagnosed. Of the remaining patients, re-staging in the BEC showed a second diagnosis of confirmed LGD in 68 % (168/248), while the remaining 9 % (23/248) had nondysplastic BE. CONCLUSION : One quarter of patients with apparent flat BE with confirmed LGD diagnosed in a community hospital had prevalent HGD or cancer after re-staging at an expert center. This endorses the advice to refer patients with confirmed LGD, including in the absence of visible lesions, to an expert center for re-staging endoscopy., Competing Interests: Dr. Weusten has received financial support for IRB-approved research from C2Therapeutics/Pentax Medical, and Aqua Medical. Dr. Bergman has received financial support for IRB-approved research from C2Therapeutics/Pentax Medical, Medtronic, and Aqua Medical. The remaining authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/).)

The optimal surgical treatment strategy for gastric cancer in older patients needs to be carefully evaluated due to increased vulnerability of older patients. We performed a database search for randomized controlled trials (RCTs) and cohort studies that included patients ≥70 years with potentially resectable stage I-III gastric cancer. Postoperative and survival outcomes were compared between groups undergoing 1) gastrectomy vs conservative treatment (best supportive care or non-operative treatment), 2) minimally invasive (MIG) vs open gastrectomy (OG), or 3) extended vs limited lymphadenectomy. When possible, results were pooled using risk ratios (RR). Thirty-one studies were included. Six retrospective studies compared overall survival (OS) between gastrectomy (N = 2332) and conservative treatment (N = 246). Longer OS was reported in the gastrectomy group in all studies, but study quality was low and meta-analysis was not feasible. Eighteen cohort studies compared MIG (N = 3626) and OG (N = 5193). MIG was associated with fewer complications (pooled RR 0.68, 95% confidence interval 0.54-0.84). OS was not different between the groups. Two RCTs and five cohort studies compared outcomes between extended (N = 709) and limited lymphadenectomy (N = 1323). Complication rates were comparable between the groups. Two cohort studies found longer OS or cancer-specific survival after extended lymphadenectomy. No quality of life (QoL) or functional outcomes were reported. In older patients with gastric cancer, there is low-quality evidence for better OS after gastrectomy vs conservative treatment. Compared to OG, MIG was associated with less postoperative morbidity. The evidence to support extended lymphadenectomy is limited. QoL and functional outcomes should be addressed in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)