tbuckley/cabot-search huggingface dataset:
ENDOSCOPY TO ENDOSURGERY: ENDOSCOPIC ENUCLEATION OF GASTRIC GIST
Authors: P Soriani, VG Mirante, C Barbera, T Gabbani, L Miglioli, M Manno
Journal: Endoscopy (2018)

According to recent National Comprehensive Cancer Network guidelines, gastrointestinal (GI) stromal tumors (GISTs) bigger than 2 cm should be removed, while smaller incidental GISTs with no signs of malignancy can be removed or active surveilled. However, a small tumor size does not exclude the potential for malignancy in GIST. So, Japanese guidelines recommends resection even if the tumor is small. Here the case of a 72-year-old man, with an history of coronary artery disease, recent pulmonary embolism requiring long-term anticoagulant therapy, who underwent upper GI endoscopy for anemia. A 10 mm sub-epithelial mass was found in posterior wall of gastric antrum. The patient underwent endoscopic ultrasonography (GF-UCT180; Olympus), that showed a hypoechoic homogeneous intramural mass arising from the muscularis propria, with mild hypervascular pattern after contrast-enhanced study, suspected for GIST. In order to achieve a definitive diagnosis, fine needle aspiration was performed using a 22-gauge needle (Expect-SlimLine; Boston Scientific). Histology and immunehistochemical staining revealed a low-risk GIST (low mitotic index, positive reactions for CD117, CD34, DOG-1). CT scan excluded metastatic disease. Because patient's anxiety about possible disease progression and the high anesthesiological risk, after multidisciplinary evaluation, an endoscopic enucleation was performed, using CO2 and under deep sedation. Marking dots around the lesion and submucosal dissection were performed using T-type Hybrid-Knife (ERBE Elektromedizin GmbH). After submucosal dissection, the lesion was enucleated. However, due to the deeper location of the tumor into the muscular layer, 3 iatrogenic perforations occurred. Owing to the thinness of the remnants tissues surrounding the leakages, the deployment of through-the-scope clips wasn't enough to achieve complete closure. So, double over-the-scope clips were placed, gaining technical and clinical success, as demonstrated by contrast medium injection. The procedure took about 60 min, resulting in an en-bloc resection. Low molecular weight heparin was reintroduced 24 hours after the procedure. Upper GI endoscopy with contrast medium injection after 5 days excluded perforations and the patient was discharged. The latest endoscopic control 3 months later revealed regular scar. Even challenging, this case illustrates the feasibility and safety of endoscopic enucleation of gastric GIST, in a high-risk patient who was receiving anticoagulant therapy.
Functional Rescue of Dystrophin Deficiency in Mice Caused by Frameshift Mutations Using Campylobacter jejuni Cas9
Authors: Taeyoung Koo, Ngoc B. Lu-Nguyen, Alberto Malerba, Eunji Kim, Daesik Kim, Ornella Cappellari, Hee-Yeon Cho, George Dickson, Linda Popplewell, Jin-Soo Kim
Journal: Molecular Therapy (2018)

Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle-wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as a gene-editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the EGFP gene in the tibialis anterior muscle of the Dmd knockout mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the disrupted Dmd reading frame from out of frame to in frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9, has great potential for the treatment of DMD and other neuromuscular diseases. Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle-wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as a gene-editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the EGFP gene in the tibialis anterior muscle of the Dmd knockout mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the disrupted Dmd reading frame from out of frame to in frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9, has great potential for the treatment of DMD and other neuromuscular diseases.
PREDICTIVE FACTORS OF ESOPHAGEAL VARICES RECURRENCE AFTER PROPHYLACTIC ENDOSCOPIC BAND LIGATION
Authors: J Pereira Rodrigues, S Fernandes, L Proença, M Sousa, JC Silva, S Leite, AP Silva, T Freitas, J Carvalho
Journal: Endoscopy (2018)

Eradication of esophageal varices (EV) by endoscopic band ligation (EBL) is an effective variceal bleeding prophylactic therapy. However variceal recurrence following EBL is common. We aimed to determine the outcome of prophylactic EBL and understand factors related to EV recurrence.
Receipt of a pediatric liver offer as the first offer reduces waitlist mortality for adult women
Authors: Jin Ge, Richard Gilroy, Jennifer C. Lai
Journal: Hepatology (2018)

In liver transplantation, adults with small stature have a greater susceptibility to waitlist mortality. This may explain the persistent waitlist mortality disparity that exists for women. We hypothesized that women who receive early offers of pediatric donor livers have improved waitlist survival, and that preferentially offering these organs to women mitigates this sex‐based disparity. We analyzed donor liver offers from 2010 to 2014. Adult candidates who received a first offer that ranked within the first three match run positions from the donors' perspective were classified based on gender and whether they received a pediatric versus adult offer. We used competing risks regression to associate first offer type and waitlist mortality. A total of 8,101 waitlist candidates received a first offer that was ranked within the first three match run positions: 5.6% (293/5,202) men and 6.2% (179/2,899) women received a pediatric donor liver as their first offer. In multivariable analyses, compared with adult‐first men, adult‐first women (subhazard ratio [sHR] 1.33, 95% confidence interval 1.17‐1.51, P &lt; 0.01) had an increased pretransplant mortality risk while pediatric‐first men and pediatric‐first women had noninferior risks of morality. Pediatric‐to‐adult and adult‐to‐adult recipients had similar risks of graft failure and posttransplant mortality. Conclusion : Our study examines allograft selection by donor age, recipient sex, and in effect size as a means to address disparities in waitlist mortality. We found that women who received a pediatric donor liver as the first offer had a lower risk of waitlist mortality compared with those who receive adult offers. Our data provides a simple approach to mitigating the increased waitlist mortality experienced by women by incorporating donor and recipient size as variables into organ allocation. (H epatology 2018).
Non-Barrett's esophageal and gastric tumors: diagnosis and treatment
Authors: M. Ciocirlan, R. Gincul, V. Lepilliez, M. Pioche, M. Ionescu, M. Diculescu
Journal: Endoscopy (2012)

The 2012 Digestive Disease Week (DDW; 19 – 22 May, San Diego, California, USA) presented small-step advances in the field of non-Barrett’s esophageal and gastric tumors. In patients with ear – nose – throat (ENT) cancer, narrow-band imaging (NBI) might be useful in endoscopic screening for early esophageal squamous neoplasia, but confirmation of its role has yet to be reported. The yield and intervals of endoscopic screening for gastric neoplasia are better understood, and so are the results and complications of gastroesophageal endoscopic submucosal dissection (ESD) together with their predictive factors. Endoscopic therapy of advanced tumors was another important theme at DDW, with ESD after radiotherapy for advanced esophageal cancer and gastrojejunostomy for neoplastic gastric outlet obstruction being reported. Relevant abstracts are discussed below.
Metronomic therapy with 5-FU, weekly nab-paclitaxel, leucovorin, and oxaliplatin, plus bevacizumab for advanced pancreatic cancer: A phase II study.
Authors: William H. Isacoff, Howard A. Reber, Oscar J Hines, Timothy R. Donahue, Fay M. Purcell, Barbara M. Clerkin, Kara M. Clerkin
Journal: Journal of Clinical Oncology (2012)

e14582 Background: The objective of this open label phase 2 study was to evaluate low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy for patients with advanced pancreatic cancer. Continuous infusion of 5FU, calcium leucovorin plus paclitaxel and oxaliplatin has been shown to be active in patients with pancreatic cancer. As a protracted low dose infusion, 5FU is anti-angiogenic and has been demonstrated to be synergistic with bevacizumab. Bevacizumab and nab-paclitaxel are synergistic as seen in the treatment of breast cancer. Methods: Since July 2008, we treated 40 patients with 5FU (180mg/m 2 /day x 14 days) via an ambulatory pump. Calcium leucovorin (20mg/m 2 ) IVP, nab-paclitaxel (100mg/m 2 ) IV as a 30 minute infusion and oxaliplatin (75mg/m 2 ) IV as a 60 minute infusion were given on days 1, 8, and 15. Bevacizumab (5mg/kg) IV over 30 minutes was given on days 1 and 15. Cycles were repeated every 35 days. There were 24 females and 16 males. The median age was 58. 34 patients had stage IV disease. Results: The median overall survival is greater than 17 months. A partial response was observed in 50% of the patients. There were 22 patients with prior treatment, 11 of whom responded to the protocol. 34 patients began treatment with an elevation of their CA19-9 greater than 40. Of these, 26 patients were subsequently noted to have greater than 50% reduction in their CA 19-9; 17 of whom had an objective CT scan response to therapy. Toxicity (grade 3 and 4) included stomatitis, diarrhea, fatigue, nausea, neuropathy, hypertension and renal failure. Hematologic toxicity included anemia, neutropenia and thrombocytopenia. 19 patients stopped treatment due to disease progression, 18 patients stopped due totoxicity. There were no chemotherapy related deaths. Conclusions: This non-gemcitabine based regimen resulted in response rates and survival benefits greater than that which is ususally observed with gemcitabine based therapy. Low dose continuous (metronomic therapy) cytotoxic chemotherapy when combined with anti-angiogenic therapy is safe and effective for patients with advanced pancreatic cancer.
Ryanodine Receptor Calcium Leak in Circulating B-Lymphocytes as a Biomarker in Heart Failure
Authors: Alexander Kushnir, Gaetano Santulli, Steven R. Reiken, Ellie Coromilas, Sarah J. Godfrey, Danielle L. Brunjes, Paolo C. Colombo, Melana Yuzefpolskaya, Seth I. Sokol, Richard N. Kitsis, Andrew R. Marks
Journal: Circulation (2018)

Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2+ is released from the sarcoplasmic reticulum into the cytoplasm through type-2 ryanodine receptor/Ca2+ release channels. In CHF, chronically elevated circulating catecholamine levels cause pathological remodeling of type-2 ryanodine receptor/Ca2+ release channels resulting in diastolic sarcoplasmic reticulum Ca2+ leak and decreased myocardial contractility. Similarly, skeletal muscle contraction requires sarcoplasmic reticulum Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1-mediated sarcoplasmic reticulum Ca2+ leak, contributing to myopathy and weakness. Circulating B-lymphocytes express RyR1 and catecholamine-responsive signaling cascades, making them a potential surrogate for defects in intracellular Ca2+ handling because of leaky RyR channels in CHF.Whole blood was collected from patients with CHF, CHF following left-ventricular assist device implant, and controls. Blood was also collected from mice with ischemic CHF, ischemic CHF+S107 (a drug that specifically reduces RyR channel Ca2+ leak), and wild-type controls. Channel macromolecular complex was assessed by immunostaining RyR1 immunoprecipitated from lymphocyte-enriched preparations. RyR1 Ca2+ leak was assessed using flow cytometry to measure Ca2+ fluorescence in B-lymphocytes in the absence and presence of RyR1 agonists that empty RyR1 Ca2+ stores within the endoplasmic reticulum.Circulating B-lymphocytes from humans and mice with CHF exhibited remodeled RyR1 and decreased endoplasmic reticulum Ca2+ stores, consistent with chronic intracellular Ca2+ leak. This Ca2+ leak correlated with circulating catecholamine levels. The intracellular Ca2+ leak was significantly reduced in mice treated with the Rycal S107. Patients with CHF treated with left-ventricular assist devices exhibited a heterogeneous response.In CHF, B-lymphocytes exhibit remodeled leaky RyR1 channels and decreased endoplasmic reticulum Ca2+ stores consistent with chronic intracellular Ca2+ leak. RyR1-mediated Ca2+ leak in B-lymphocytes assessed using flow cytometry provides a surrogate measure of intracellular Ca2+ handling and systemic sympathetic burden, presenting a novel biomarker for monitoring response to pharmacological and mechanical CHF therapy.
CRYOBALLOON ABLATION OF DYSPLASTIC BARRETT'S ESOPHAGUS CAUSES SHORTER DURATION AND LESS SEVERE POST-PROCEDURAL PAIN AS COMPARED TO RADIOFREQUENCY ABLATION
Authors: S van Munster, A Overwater, J Bergman, B Weusten
Journal: Endoscopy (2018)

Radiofrequency ablation (RFA) is safe and effective for eradication of Barrett's Esophagus (BE), but associated with significant post-procedural pain. Cryoballoon ablation (CRYO) is an alternative method which preserves the extracellular matrix and might therefore result in less pain. Early uncontrolled studies suggest comparable safety and efficacy. Therefore, secondary features like pain might become decisive for treatment selection. We compare post-procedural pain between focal CRYO and RFA.
HIGH RISK OF ESOPHAGEAL VARICES IN PATIENTS WITH FONTAN SURGERY: A PROSPECTIVE MULTICENTER PILOT STUDY
Authors: E Rodríguez de Santiago, L Téllez Villajos, E Garrido-Lestache, E Garrido Gómez, L Aguilera Castro, V La Mura, R Romera, A Olavarría, M Álvarez, E Llop, JC García-Pagán, E Vázquez Sequeiros, I Sánchez, F Gea, MJ Del Cerro, A Albillos
Journal: Endoscopy (2018)

Fontan surgery (FS) allows the venous return to reach the pulmonary circulation bypassing the ventricle in patients with single ventricle. This results in sustained systemic venous hypertension and liver damage in long-term. Nevertheless, natural history of liver disease in these patients has been poorly studied; prevalence and features of esophageal varices (EV) are unknown. The AIM of this study is to estimate the prevalence and characterize EV in this special population.
ENDOSCOPIC MUCOSAL RESECTION OF SPORADIC NON-AMPULLARY DUODENAL ADENOMA: A DECADE OF EXPERIENCE FROM A TERTIARY REFERRAL CENTRE
Authors: K van Boxtel, M San Juan Acosta, S Beg, J Ortiz Fernández-Sordo, A Parra-Blanco, K Ragunath
Journal: Endoscopy (2018)

Endoscopic Mucosal Resection (EMR) offers a minimally invasive approach to the management of sporadic non-ampullary duodenal adenomas. However, there is limited data in Europe on the safety and efficacy. We aimed to describe the largest European experience from a tertiary referral centre.
Dosimetric analysis for thyroid disorders after radiotherapy to the neck
Authors: Z. Akgun, B. Atasoy, Z. Ozen, B. Gulluoglu, M. U. Abacioglu
Journal: Journal of Clinical Oncology (2009)

e17025 Background: In our study, we aimed to evaluate the possible predictors of thyroid disorders after radiotherapy to the neck, focusing on radiation dose-volume factors. Methods: Thyroid function was measured in 65 patients treated with radiation ports including the thyroid, between 2005 and 2008. All of the radiation-induced thyroid dysfunction was determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4), thyroglobulin antibodies (ATG), thyroid peroxidase antibodies (TPA), thyroid binding globulin (TBG) levels. In 65 patients, radiation dose-volume parameters were calculated; e.g. total volume of the thyroid, mean radiation dose to the thyroid, and percentage of the thyroid volume which received radiation doses of no less than 10–50 Gy (V10-V50). The evaluated risk factors for thyroid dysfunction included these dose-volume parameters, sex, age, treatment modality and primary disease. Results: Most patients (72.3%) had a normal thyroid function, 17 (26.2%) hypothyroidism, 1 (1.5%) hyperthyroidism, and 12 (18.4%) thyroiditis with normal thyroid function. Four of 17 patients with hypothyroidism had overt hypothyroidism. In our analysis, DVHs (dose volume histograms) were calculated and no associations were found between the V10, V20, V40, and V50 percentages and thyroid disorders. V30 and minimum absorbed thyroid dose (Dmin) more than 25 Gy appeared to be correlated with high TSH values (p = 0.01 and p = 0.04, respectively). The patients with hypothyroidism were between 40–60 years. Female gender was associated with a higher incidence of TBG abnormality. Baseline TSH values were available in 16 patients, and hypothyroidism was diagnosed in 4 (25%) of them. No correlation was found between tumor-related variables and incidence of thyroid disorders. Conclusions: Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. Further prospective well designed studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are therefore needed, and thyroid should be considered as an organ at risk in all patients treated for head and neck tumors. No significant financial relationships to disclose.
Kaposiform haemangioendothelioma: clinical features, complications and risk factors for Kasabach-Merritt phenomenon
Authors: Y. Ji, K. Yang, S. Peng, S. Chen, B. Xiang, Z. Xu, Y. Li, Q. Wang, C. Wang, C. Xia, L. Li, X. Liu, G. Lu, G. Yang, H. Wu
Journal: British Journal of Dermatology (2018)

Few studies have reported the clinical features, complications and predictors of Kasabach–Merritt phenomenon (KMP) associated with Kaposiform haemangioendothelioma (KHE). To determine the clinical characteristics present at diagnosis and to identify features that may aid clinicians in managing KHE. We conducted a cohort study of 146 patients diagnosed with KHE. KHE precursors or lesions were present at birth in 52·1% of patients. In 91·8% of patients, lesions developed within the first year of life. The median age at diagnosis of KHE was 2·3 months (interquartile range 1·0–6·0). The extremities were the dominant location, representing 50·7% of all KHEs. Among KHEs in the cohort, 63·0% were mixed lesions (cutaneous lesions with deep infiltration). Approximately 70% of patients showed KMP. A KHE diagnosis was delayed by ≥ 1 month in 65·7% of patients with KMP. Patients with KMP were more likely to have major complications than patients without KMP (P = 0·023). Young age (< 6 months), trunk location, large lesion size (> 5·0 cm) and mixed lesion type were associated with KMP in a univariate analysis. In the multivariate analysis, only age [odds ratio (OR) 11·9, 95% confidence interval (CI) 4·07–34·8; P < 0·001], large lesion size (OR 5·08, 95% CI 2·24–11·5; P < 0·001) and mixed lesion type (OR 2·96, 95% CI 1·23–7·13; P = 0·016) were associated with KMP. Most KHEs appeared before 12 months of age. KHEs are associated with various major complications, which can occur in combination and develop early in the disease process. Young age, large lesion size and mixed lesion type are important predictors of KMP.
Intérêt de la biopsie sous échoendoscopie couplée à la recherche de la mutation du gène KRAS pour le diagnostic différentiel entre cancer du pancréas et pancréatite chronique: résultats finaux d'une étude prospective multicentrique française
Authors: B Bournet, A Souque, P Senesse, E Assenat, M Barthet, N Lesavre Rosenzweig, A Aubert, D O'Toole, P Hammel, P Lévy, P Ruszniewski, M Bouisson, J Escourrou, P Cordelier, L Buscail
Journal: Endoscopy (2009)

Introduction: Le diagnostic différentiel entre cancer du pancréas (CP) et pancréatite chronique (PC) est très difficile. Le but était d'évaluer de façon prospective et multicentrique si en associant cytopathologie à partir de ponction-biopsie sous EE (PB-EE) et recherche de la mutation de KRAS il était possible d'améliorer le diagnostic différentiel entre CP et PC dans sa forme pseudo-tumorale.
Endoscopic Ultrasound (EUS), Chronic Pancreatitis, and Pancreatic Cancer (PC) Precursors in High Risk Individuals
Authors: MI Canto, K Brune, M Goggins, C Yeo, S Jagannath, S Kantsevoy, A Kalloo, R Hruban
Journal: Endoscopy (2006)

EUS and ERCP in high risk individuals (HRI) with an inherited predisposition for PC have shown chronic pancreatitis (CP)-like abnormalities but the significance of these changes has not been understood. AIM: To determine the prevalence of pancreatic EUS abnormalities in asymptomatic HRI and correlate these with ERCP, pancreatic function, and pathology. Methods: In 2 prospective cohort studies (1998–2004), 112 HRI (105 HRI with ≥2 affected first degree relatives with PC, 7 had Peutz-Jeghers syndrome) had screening EUS. ERCP was performed by another endoscopist without knowledge of EUS findings. Serum trypsin and secretin stimulated-peak bicarbonate concentration was measured in HRI and normal controls. Surgery was performed for suspected neoplasms or dysplastic tissue in EUS-FNA. Pancreata were examined by an experienced pathologist. Results: The prevalence of EUS changes of CP (≥4 of 9 features) in HRI was 72.3%. Mild ERCP abnormalities were present in 85.6%. Serum trypsin was lower in HRI than in controls (mean=66.4 vs. 169.1, p=.0001). But, mean peak bicarbonate concentration was similar in HRI and controls (106.8 meq/L vs. 105.4 meq/L, respectively, p=0.83). Subtotal pancreatectomy was performed on 15 HRI: pancreatic neoplasms were found in 11 and pancreatic intraepithelial neoplasia (PanIN) 1–3 were present in 13. The mean PanIN density in HRI pancreata was 12.2% (range 1–27.3%). Both IPMNs and PanIN were associated with parenchymal lobulocentric atrophy and CP. PanIN density was positively and linearly correlated with the number of EUS features of CP (Spearman's R=0.87, p=.005) but not ERCP grade of CP (Spearman's R=0.41, p=.31). Conclusions: EUS features of CP are highly prevalent in HRI with an inherited predisposition to PC and are associated with both IPMN and PanI. EUS features of CP correlate with PanIN density and PanIN-associated lobulocentric atrophy.