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Standardized assessment of the gastroesophageal valve during endoscopy, attainable via the Hill classification, is important for clinical assessment and therapeutic decision making. The Hill classification is associated with the presence of hiatal hernia (HH), a common endoscopic finding connected to gastro-esophageal reflux disease. A novel efficient medical artificial intelligence (AI) training pipeline using active learning (AL) is designed. We identified 21,970 gastroscopic images as training data and used our AL to train a model for predicting the Hill classification and detecting HH. Performance of the AL and traditionally trained models were evaluated on an external expert-annotated image collection. The AL model achieved accuracy of 76%. A traditionally trained model with 125% more training data achieved 77% accuracy. Furthermore, the AL model achieved higher precision than the traditional one for rare classes, with 0.54 versus 0.39 (p < 0.05) for grade 3 and 0.72 versus 0.61 (p < 0.05) for grade 4. In detecting HH, the AL model achieved 94% accuracy, 0.72 precision and 0.74 recall. Our AL pipeline is more efficient than traditional methods in training AI for endoscopy.
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Inteligencia Artificial , Humanos , Reflujo Gastroesofágico/diagnóstico , Hernia Hiatal/diagnóstico , Hernia Hiatal/diagnóstico por imagen , Gastroscopía/métodos , Unión Esofagogástrica/patología , Unión Esofagogástrica/diagnóstico por imagen , Aprendizaje Basado en Problemas/métodosRESUMEN
BACKGROUND AND AIMS: Endoscopy simulators are primarily designed to provide training in interventions performed during procedures. Peri-interventional tasks such as checking patient data, filling out forms for team time-out, patient monitoring, and performing sedation are often not covered. This study assesses the face, content, and construct validity of the ViGaTu (Virtual Gastro Tutor) immersive virtual reality (VR) simulator in teaching these skills. METHODS: 71 nurses and physicians were invited to take part in VR training. The participants experienced an immersive VR simulation of an endoscopy procedure, including setting up the endoscopic devices, checking sign-in and team time-out forms, placing monitoring devices, and performing sedation. The actions performed by the participants and their timing were continuously recorded. Face and content validity, as well as the System Usability Scale (SUS), were then assessed. RESULTS: 43 physicians and 28 nurses from 43 centers took a mean of 27.8 min (standard deviation ± 14.42 min) to complete the simulation. Seventy-five percent of the items for assessing face validity were rated as realistic, and 60% of items assessing content validity and usefulness of the simulation for different learning goals were rated as useful by the participants (four out of five on a Likert scale). The SUS score was 70, demonstrating a high degree of usability. With regard to construct validity, experienced endoscopy staff were significantly faster in setting up the endoscope tower and instruments than beginners. CONCLUSIONS: This multicenter study presents a new type of interdisciplinary endoscopy training system featuring peri-interventional tasks and sedation in an immersive VR environment.
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Competencia Clínica , Entrenamiento Simulado , Realidad Virtual , Humanos , Entrenamiento Simulado/métodos , Reproducibilidad de los Resultados , Femenino , Adulto , Masculino , Endoscopía Gastrointestinal/educación , Enfermeras y Enfermeros , Persona de Mediana Edad , MédicosRESUMEN
Postoperative disease recurrence in Crohn's disease represents a relevant issue despite recent advancements in surgical and medical therapies. Additional criteria are necessary to improve the identification of patients at risk and to enable selective therapeutic approaches. The role of resection margins on disease recurrence remains unclear and general recommendations are lacking. A single-center retrospective analysis was performed including all patients who received ileocecal resection due to Crohn's disease. Resection margins were analyzed by two independent pathologists and defined by histopathological criteria based on previous consensus reports. 158 patients were included for analysis with a median follow up of 35 months. While postoperative morbidity was not affected, positive resection margins resulted in significantly increased rates of severe endoscopic recurrence at 6 months (2.0% versus 15.6%, p = 0.02) and overall (4.2% versus 19.6%, p = 0.001), which resulted in significantly increased numbers of surgical recurrence (0% versus 4.5%, p = 0.04). Additionally, positive margins were identified as independent risk factor for severe endoscopic disease recurrence in a multivariate analysis. Based on that, positive margins represent an independent risk factor for postoperative endoscopic and surgical disease recurrence. Prospective studies are required to determine whether extended resection or postoperative medical prophylaxis is beneficial for patients with positive resection margins.
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Enfermedad de Crohn , Márgenes de Escisión , Recurrencia , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/patología , Masculino , Femenino , Adulto , Factores de Riesgo , Estudios Retrospectivos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Adulto Joven , Anciano , Periodo PosoperatorioRESUMEN
BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) is standard therapy for nonpedunculated colorectal polyps ≥20 mm. It has been suggested recently that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AEs), but evidence from a randomized trial is missing. METHODS: In this randomized controlled multicentric trial involving 19 centers, nonpedunculated colorectal polyps ≥20 mm were randomly assigned to cold or hot EMR. The primary outcome was major AE (eg, perforation or postendoscopic bleeding). Among secondary outcomes, major AE subcategories, postpolypectomy syndrome, and residual adenoma were most relevant. RESULTS: Between 2021 and 2023, there were 396 polyps in 363 patients (48.2% were female) enrolled for the intention-to-treat analysis. Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001; odds ratio [OR], 0.12; 95% CI, 0.03-0.54). Rates for perforation and postendoscopic bleeding were significantly lower in the cold group, with 0% vs 3.9% (P = .007) and 1.0% vs 4.4% (P = .040). Postpolypectomy syndrome occurred with similar frequency (3.1% vs 4.4%; P = .490). After cold resection, residual adenoma was found more frequently, with 23.7% vs 13.8% (P = .020; OR, 1.94; 95% CI, 1.12-3.38). In multivariable analysis, lesion diameter of ≥4 cm was an independent predictor both for major AEs (OR, 3.37) and residual adenoma (OR, 2.47) and high-grade dysplasia/cancer for residual adenoma (OR, 2.92). CONCLUSIONS: Cold resection of large, nonpedunculated colorectal polyps appears to be considerably safer than hot EMR; however, at the cost of a higher residual adenoma rate. Further studies have to confirm to what extent polyp size and histology can determine an individualized approach. German Clinical Trials Registry (Deutsches Register Klinischer Studien), Number DRKS00025170.
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Pólipos del Colon , Colonoscopía , Resección Endoscópica de la Mucosa , Hemorragia Posoperatoria , Humanos , Femenino , Masculino , Pólipos del Colon/cirugía , Pólipos del Colon/patología , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Persona de Mediana Edad , Anciano , Colonoscopía/métodos , Colonoscopía/efectos adversos , Alemania , Resultado del Tratamiento , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/epidemiología , Adenoma/cirugía , Adenoma/patología , Perforación Intestinal/etiología , Perforación Intestinal/epidemiología , Perforación Intestinal/cirugía , Neoplasia Residual , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Carga Tumoral , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Criocirugía/efectos adversos , Criocirugía/métodosRESUMEN
INTRODUCTION: Comprehensive and standardized colonoscopy reports are crucial in colorectal cancer prevention, monitoring, and research. This study investigates adherence to national and international guidelines by analyzing reporting practices among 21 endoscopists in 7 German centers, with a focus on polyp reporting. METHODS: We identified and assessed German, European, American, and World Health Organization-provided statements to identify key elements in colonoscopy reporting. Board-certified gastroenterologists rated the relevance of each element and estimated their reporting frequency. Adherence to the identified report elements was evaluated for 874 polyps from 351 colonoscopy reports ranging from March 2021 to March 2022. RESULTS: We identified numerous recommendations for colonoscopy reporting. We categorized the reasoning behind those recommendations into clinical relevance, justification, and quality control and research. Although all elements were considered relevant by the surveyed gastroenterologists, discrepancies were observed in the evaluated reports. Particularly diminutive polyps or attributes which are rarely abnormal (e.g., surface integrity) respectively rarely performed (e.g., injection) were sparsely documented. Furthermore, the white light morphology of polyps was inconsistently documented using either the Paris classification or free text. In summary, the analysis of 874 reported polyps revealed heterogeneous adherence to the recommendations, with reporting frequencies ranging from 3% to 89%. CONCLUSION: The inhomogeneous report practices may result from implicit reporting practices and recommendations with varying clinical relevance. Future recommendations should clearly differentiate between clinical relevance and research and quality control or explanatory purposes. Additionally, the role of computer-assisted documentation should be further evaluated to increase report frequencies of non-pathological findings and diminutive polyps.
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Pólipos del Colon , Colonoscopía , Neoplasias Colorrectales , Adhesión a Directriz , Humanos , Colonoscopía/normas , Colonoscopía/estadística & datos numéricos , Colonoscopía/métodos , Adhesión a Directriz/estadística & datos numéricos , Pólipos del Colon/patología , Pólipos del Colon/diagnóstico , Alemania , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/normas , Mejoramiento de la Calidad , Gastroenterólogos/estadística & datos numéricos , Gastroenterólogos/normas , Documentación/normas , Documentación/estadística & datos numéricos , Documentación/métodosRESUMEN
OBJECTIVE: Carbon emissions generated by gastrointestinal endoscopy have been recognised as a critical issue. Scope 3 emissions are mainly caused by the manufacturing, packaging and transportation of purchased goods. However, to our knowledge, there are no prospective data on the efficacy of measurements aimed to reduce scope 3 emissions. DESIGN: The study was performed in a medium-sized academic endoscopy unit. Manufacturers of endoscopic consumables were requested to answer a questionnaire on fabrication, origin, packaging and transport. Based on these data, alternative products were purchased whenever possible. In addition, staff was instructed on how to avoid waste. Thereafter, the carbon footprint of each item purchased was calculated from February to May 2023 (intervention period), and scope 3 emissions were compared with the same period of the previous year (control period). RESULTS: 26 of 40 companies answered the questionnaire. 229 of 322 products were classified as unfavourable. A switch to alternative items was possible for 47/229 items (20.5%). 1666 endoscopies were performed during the intervention period compared with 1751 examinations during the control period (-4.1%). The number of instruments used decreased by 10.0% (3111 vs 3457). Using fewer and alternative products resulted in 11.5% less carbon emissions (7.09 vs 8.01 tons of carbon equivalent=tCO2 e). Separation of waste led to a reduction of 20.1% (26.55 vs 33.24 tCO2e). In total, carbon emissions could be reduced by 18.4%. CONCLUSION: Use of fewer instruments per procedure, recycling packaging material and switching to alternative products can reduce carbon emissions without impairing the endoscopic workflow.
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Huella de Carbono , Carbono , Humanos , Estudios Prospectivos , Endoscopía Gastrointestinal , Examen FísicoRESUMEN
BACKGROUND AND STUDY AIMS: Artificial intelligence (AI)-based systems for computer-aided detection (CADe) of polyps receive regular updates and occasionally offer customizable detection thresholds, both of which impact their performance, but little is known about these effects. This study aimed to compare the performance of different CADe systems on the same benchmark dataset. METHODS: 101 colonoscopy videos were used as benchmark. Each video frame with a visible polyp was manually annotated with bounding boxes, resulting in 129â705 polyp images. The videos were then analyzed by three different CADe systems, representing five conditions: two versions of GI Genius, Endo-AID with detection Types A and B, and EndoMind, a freely available system. Evaluation included an analysis of sensitivity and false-positive rate, among other metrics. RESULTS: Endo-AID detection Type A, the earlier version of GI Genius, and EndoMind detected all 93 polyps. Both the later version of GI Genius and Endo-AID Type B missed 1 polyp. The mean per-frame sensitivities were 50.63â% and 67.85â%, respectively, for the earlier and later versions of GI Genius, 65.60â% and 52.95â%, respectively, for Endo-AID Types A and B, and 60.22â% for EndoMind. CONCLUSIONS: This study compares the performance of different CADe systems, different updates, and different configuration modes. This might help clinicians to select the most appropriate system for their specific needs.
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Pólipos del Colon , Neoplasias Colorrectales , Humanos , Pólipos del Colon/diagnóstico por imagen , Inteligencia Artificial , Colonoscopía/métodos , Neoplasias Colorrectales/diagnósticoRESUMEN
INTRODUCTION: Advanced endoscopic therapy techniques have been developed and have created alternative treatment options to surgical therapy for several gastrointestinal diseases. This work will focus on new endoscopic tools for special indications of advanced endoscopic resections (ER), especially endoscopic submucosal dissection (ESD), which were developed in our institution. This paper aims to analyze these specialized instruments and identify their status. METHODS: Initially, the technical process of ESD was analyzed, and the following limitations of the different endoscopic steps and the necessary manipulations were determined: the problem of traction-countertraction, the grasping force needed to pull on tissue, the instrument tip maneuverability, the limited angulation/triangulation, and the mobility of the scope and instruments. Five instruments developed by our team were used: the Endo-dissector, additional working channel system, external independent next-to-the-scope grasper, 3D overtube working station, and over-the-scope grasper. The instruments were used and applied according to their special functions in dry lab, experimental in vivo, and clinical conditions by the members of our team. RESULTS: The Endo-dissector has a two-fold function: (1) grasping submucosal tissue with enough precision and strength to pull it off the surrounding mucosa and muscle, avoiding damage during energy application and (2) effectively dividing tissue using monopolar energy. The AWC system quickly fulfills the lack of a second working channel as needed to complete the endoscopic task on demand. The EINTS grasper can deliver a serious grasping force, which may be necessary for a traction-countertraction situation during endoscopic resection for lifting a larger specimen. The 3D overtube multifunctional platform provides surgical-like work with bimanual-operated instruments at the tip of the scope, which allows for a coordinated approach during lesion treatment. The OTSG is a grasping tool with very special features for cleaning cavities with debris. CONCLUSIONS: The research and development of instruments with special features can solve unmet needs in advanced endoscopic procedures. The latter may help to increase indications for the endoscopic resections of gut lesions in the future.
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BACKGROUND : Reliable documentation is essential for maintaining quality standards in endoscopy; however, in clinical practice, report quality varies. We developed an artificial intelligence (AI)-based prototype for the measurement of withdrawal and intervention times, and automatic photodocumentation. METHOD: A multiclass deep learning algorithm distinguishing different endoscopic image content was trained with 10â557 images (1300 examinations, nine centers, four processors). Consecutively, the algorithm was used to calculate withdrawal time (AI prediction) and extract relevant images. Validation was performed on 100 colonoscopy videos (five centers). The reported and AI-predicted withdrawal times were compared with video-based measurement; photodocumentation was compared for documented polypectomies. RESULTS: Video-based measurement in 100 colonoscopies revealed a median absolute difference of 2.0 minutes between the measured and reported withdrawal times, compared with 0.4 minutes for AI predictions. The original photodocumentation represented the cecum in 88 examinations compared with 98/100 examinations for the AI-generated documentation. For 39/104 polypectomies, the examiners' photographs included the instrument, compared with 68 for the AI images. Lastly, we demonstrated real-time capability (10 colonoscopies). CONCLUSION : Our AI system calculates withdrawal time, provides an image report, and is real-time ready. After further validation, the system may improve standardized reporting, while decreasing the workload created by routine documentation.
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Inteligencia Artificial , Endoscopía Gastrointestinal , Humanos , Colonoscopía , Algoritmos , DocumentaciónRESUMEN
BACKGROUND AND PURPOSE: The Gastrointestinal Quality of Life Index (GIQLI) is an instrument for the assessment of quality of life (QOL) in diseases of the upper and lower GI tract, which is validated in several languages around the world. The purpose of this literature review is the assessment of the GIQLI in patients with benign colorectal diseases. Reports on GIQLI data are collected from several institutions, countries, and different cultures which allows for comparisons, which are lacking in literature. METHODS: The GIQL Index uses 36 items around 5 dimensions (gastrointestinal symptoms (19 items), emotional dimension (5 items), physical dimension (7 items), social dimension (4 items), and therapeutic influences (1 item). The literature search was performed on the GIQLI and colorectal disease, using reports in PubMed. Data are presented descriptively as GIQL Index points as well as a reduction from 100% maximum possible index points (max 144 index points = highest quality of life). RESULTS: The GIQLI was found in 122 reports concerning benign colorectal diseases, of which 27 were finally selected for detailed analysis. From these 27 studies, information on 5664 patients (4046 female versus 1178 male) was recorded and summarized. The median age was 52 years (range 29-74.7). The median GIQLI of all studies concerning benign colorectal disease was 88 index points (range 56.2-113). Benign colorectal disease causes a severe reduction in QOL for patients down to 61% of the maximum. CONCLUSIONS: Benign colorectal diseases cause substantial reductions in the patient's QOL, well documented by GIQLI, which allows a comparison QOL with other published cohorts.
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Enfermedades del Colon , Neoplasias Colorrectales , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Calidad de VidaRESUMEN
BACKGROUND AND AIMS: Colonoscopy is currently the most effective way of detecting colorectal cancer and removing polyps, but it has some drawbacks and can miss up to 22% of polyps. Microwave imaging has the potential to provide a 360° view of the colon and addresses some of the limitations of conventional colonoscopy. This study evaluates the feasibility of a microwave-based colonoscopy in an in vivo porcine model. METHODS: A prototype device with microwave antennas attached to a conventional endoscope was tested on four healthy pigs and three gene-targeted pigs with mutations in the adenomatous polyposis coli gene. The first four animals were used to evaluate safety and maneuverability and compatibility with endoscopic tools. The ability to detect polyps was tested in a series of three gene-targeted pigs. RESULTS: the microwave-based device did not affect endoscopic vision or cause any adverse events such as deep mural injuries. The microwave system was stable during the procedures, and the detection algorithm showed a maximum detection signal for adenomas compared with healthy mucosa. CONCLUSIONS: Microwave-based colonoscopy is feasible and safe in a preclinical model, and it has the potential to improve polyp detection. Further investigations are required to assess the device's efficacy in humans.
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Background: Interventional endoscopic procedures require complex manipulations and precise maneuvering of end-effectors. One focus in research on improved endoscopic instrument function was based on surgical experience to gain additional traction. The idea has emerged using assisting instruments by applying external tools next-to-the endoscope to follow surgical concepts. The aim of this study is the assessment of flexible endoscopic grasping instruments regarding their function and working-radius introducing the concept of an intraluminal "next-to the-scope" endoscopic grasper. Methods: In this study endoscopic graspers are evaluated (1:through-the-scope-grasper, TTSG; 2:additional-working-channel-system AWC-S;3:external-independent-next-to-the-scope-grasper EINTS-G) regarding their working-radius, grasping abilities, maneuverability and the ability to expose tissue with varying angulation. Results: The working radius of the tools attached or within the endoscope (TTS-G and AWC-S) benefit from the steering abilities of the scope reaching 180-210 degrees in retroflexion; EINTS-G is limited to 110-degrees. The robust EINTS-grasper has the advantage of stronger grip for grasping and pulling force, which enables manipulation of larger objects. The independent maneuverability during ESD-dissection provides better tissue-exposure by changing the traction-angulation. Conclusion: The working radius of tools attached to the endoscope benefit from scope- steering. The EINTS-grasper has the advantage of stronger grasping force and pulling within the GI-tract and independent maneuverability enables improved tissue-exposure. WC200.
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Disección , Humanos , Resultado del Tratamiento , Disección/métodos , Diseño de EquipoRESUMEN
[This corrects the article DOI: 10.3389/fnut.2022.1033265.].
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BACKGROUND: Measurement of colorectal polyp size during endoscopy is mainly performed visually. In this work, we propose a novel polyp size measurement system (Poseidon) based on artificial intelligence (AI) using the auxiliary waterjet as a measurement reference. METHODS: Visual estimation, biopsy forceps-based estimation, and Poseidon were compared using a computed tomography colonography-based silicone model with 28 polyps of defined sizes. Four experienced gastroenterologists estimated polyp sizes visually and with biopsy forceps. Furthermore, the gastroenterologists recorded images of each polyp with the waterjet in proximity for the application of Poseidon. Additionally, Poseidon's measurements of 29 colorectal polyps during routine clinical practice were compared with visual estimates. RESULTS: In the silicone model, visual estimation had the largest median percentage error of 25.1â% (95â%CI 19.1â%-30.4â%), followed by biopsy forceps-based estimation: median 20.0â% (95â%CI 14.4â%-25.6â%). Poseidon gave a significantly lower median percentage error of 7.4â% (95â%CI 5.0â%-9.4â%) compared with other methods. During routine colonoscopies, Poseidon presented a significantly lower median percentage error (7.7â%, 95â%CI 6.1â%-9.3â%) than visual estimation (22.1â%, 95â%CI 15.1â%-26.9â%). CONCLUSION: In this work, we present a novel AI-based method for measuring colorectal polyp size with significantly higher accuracy than other common sizing methods.
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Pólipos del Colon , Colonografía Tomográfica Computarizada , Neoplasias Colorrectales , Humanos , Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/patología , Inteligencia Artificial , Colonoscopía/métodos , Colonografía Tomográfica Computarizada/métodos , Instrumentos Quirúrgicos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patologíaRESUMEN
BACKGROUND: Gastric (anastomotic or staple-line) leaks after bariatric surgery are rare but potentially life-threatening complications. Endoscopic vacuum therapy (EVT) has evolved as the most promising treatment strategy for leaks associated with upper gastrointestinal surgery. OBJECTIVE: The aim of this study was to evaluate the efficiency of our gastric leak management protocol in all bariatric patients over a 10-year period. Special emphasis was placed on EVT treatment and its outcome as a primary treatment or as a secondary treatment when other approaches failed. SETTING: This study was performed at a tertiary clinic and certified center of reference for bariatric surgery. METHODS: In this retrospective single-center cohort study, clinical outcomes of all consecutive patients after bariatric surgery from 2012 to 2021 are reported, with special emphasis placed on gastric leak treatment. The primary endpoint was successful leak closure. Secondary endpoints were overall complications (Clavien-Dindo classification) and length of stay. RESULTS: A total of 1046 patients underwent primary or revisional bariatric surgery, of whom 10 (1.0%) developed a postoperative gastric leak. Additionally, 7 patients were transferred for leak management after external bariatric surgery. Of these, 9 patients underwent primary and 8 patients underwent secondary EVT after futile surgical or endoscopic leak management. The efficacy of EVT was 100%, and there were no deaths. Complications did not differ between primary EVT and secondary treatment of leaks. Length of treatment was 17 days for primary EVT versus 61 days for secondary EVT (P = .015). CONCLUSIONS: EVT for gastric leaks after bariatric surgery led to rapid source control with a 100% success rate both as primary and secondary treatment. Early detection and primary EVT shortened treatment time and length of stay. This study underlines the potential of EVT as a first-line treatment strategy for gastric leaks after bariatric surgery.
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Cirugía Bariátrica , Terapia de Presión Negativa para Heridas , Humanos , Terapia de Presión Negativa para Heridas/efectos adversos , Terapia de Presión Negativa para Heridas/métodos , Estudios Retrospectivos , Estudios de Cohortes , Gastrectomía/métodos , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Cirugía Bariátrica/efectos adversosRESUMEN
BACKGROUND: Differentiated neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs), targets for therapy with either unlabeled or radioactively labeled somatostatin analogs (SSA). Associated with worse prognosis, dedifferentiated NET loose SSTR expression, which may be linked to deregulation of Wnt/ß-catenin signaling on an intracellular level. The aim of the present study was to investigate the effect of Wnt/ß-catenin signaling pathway alterations on SSTR expression and its function in NET. METHODS: The NET cell lines BON-1 and QGP-1 were incubated with the Wnt-inhibitors 5-aza-2'-deoxycytidine (5-aza-CdR), Quercetin, or Niclosamide, or the Wnt activator lithium chloride (LiCl). Expression of SSTR1, SSTR2, and SSTR5 was determined by quantitative RT-PCR (qRT-PCR), immunocytomicroscopy and western blot. Changes in the Wnt pathway were analyzed by qRT-PCR of selected target genes and the TaqMan Array Human WNT Pathway. Receptor-associated function was determined by measuring the cellular uptake of [125I-Tyr3] octreotide. RESULTS: The mRNAs of SSTRs 1-5 were expressed in both cell lines. Wnt inhibitors caused downregulation of Wnt target genes, while 5-aza-CdR had the highest inhibitory effect. LiCl lead to an upregulation of Wnt genes, which was more marked in QGP-1 cells. SSTR expression increased in both cell lines upon Wnt inhibition. All three Wnt inhibitors lead to a marked increase in the specific uptake of [125I-Tyr3]octreotide, with 5-aza-CdR showing the greatest effect (increase by more than 50% in BON-1 cells), while a decreased uptake of [125I-Tyr3]octreotide was seen upon activation of Wnt signaling by LiCl. CONCLUSIONS: We demonstrate here that Wnt signaling orchestrates SSTR expression and function in a preclinical NET model. Wnt inhibition increases [125I-Tyr3]octreotide uptake offering an opportunity to enhance the efficacy of SSTR-targeted theranostic approaches.
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Tumores Neuroendocrinos , Octreótido , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Radioisótopos de Yodo , Tumores Neuroendocrinos/patología , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Somatostatina , Proteínas Wnt/metabolismoRESUMEN
Carbon monoxide (CO) is a therapeutic gas with therapeutic potential in intestinal bowel disease. Therapeutic efficacy in the gastrointestinal tract (GIT) must be paired with safe and convenient use. Therefore, we designed an oral CO releasing system (OCORS) pairing tunable CO release into the GIT while preventing the release of any other molecule from within the device, causing safety concerns. The dimensions of the device, which is manufactured from 3D printed components, are within compendial limits. This is achieved by controlling CO decarbonylation from a molybdenum complex with a FeCl3 solution. OCORS' surrounding silicon membranes control release rates, as does the loading with carbonylated molybdenum complex and FeCl3 solution. Herein we describe the development of the system, the characterization of the CO releasing molecule (CORM), and the CO release kinetics of the overall system. Neither the CORM nor isocyanoacetate as a potential reaction byproduct were cytotoxic. Finally, we demonstrated by design validation in an in vivo porcine model that, except for the release of the therapeutic CO, OCORS isolates all components during transit through the stomach. We could show that OCORS generated and released CO locally into the stomach of the animals without systemic exposure, measured as the carboxyhemoglobin content in the blood of the pigs. In conclusion, OCORS derisks oral development by limiting patient exposure to (desirable) CO while preventing contact with any further (undesirable) chemical, by-, or degradation products. CO generating devices come in reach, which now can be used by anyone, anywhere, and anytime.
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Monóxido de Carbono , Molibdeno , Animales , Porcinos , Monóxido de Carbono/uso terapéutico , Monóxido de Carbono/metabolismoRESUMEN
Diverticulosis and diverticular disease are ranked among the most common gastroenterological diseases and conditions. While for many years diverticulitis was found to be mainly an event occurring in the elder population, more recent work in epidemiology demonstrates increasing frequency in younger subjects. In addition, there is a noticeable trend towards more complicated disease. This may explain the significant increase in hospitalisations observed in recent years. It is not a surprise that the number of scientific studies addressing the clinical and socioeconomic consequences in the field is increasing. As a result, diagnosis and conservative as well as surgical management have changed in recent years. Diverticulosis, diverticular disease and diverticulitis are a complex entity and apparently an interdisciplinary challenge. To meet theses considerations the German Societies for Gastroenterology and Visceral Surgery decided to create joint guidelines addressing all aspects in a truely interdisciplinary fashion. The aim of the guideline is to summarise and to evaluate the current state of knowledge on diverticulosis and diverticular disease and to develop statements as well as recommendations to all physicians involved in the management of patients with diverticular disease.