RESUMEN
Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.
Asunto(s)
Glucuronidasa , Pancreatitis , Animales , Pancreatitis/tratamiento farmacológico , Pancreatitis/patología , Ratones , Glucuronidasa/metabolismo , Glucuronidasa/antagonistas & inhibidores , Trehalosa/farmacología , Trehalosa/uso terapéutico , Ceruletida , Aspirina/farmacología , Aspirina/uso terapéutico , Modelos Animales de Enfermedad , Enfermedad Aguda , Autofagia/efectos de los fármacos , Páncreas/efectos de los fármacos , Páncreas/patología , Páncreas/enzimología , Masculino , Ratones Transgénicos , Lipasa/metabolismo , Lipasa/antagonistas & inhibidores , Amilasas/sangre , Ratones Endogámicos C57BL , SaponinasRESUMEN
BACKGROUND: Post-cholecystectomy bile leak is relatively a well-known surgical complication. Several potential treatment modalities for such leaks are used. The early use of ERCP to exclude significant bile duct injury and to treat the leak by various endoscopic means is supported by a large bulk of data. However, there is no consensus as to the optimal endoscopic intervention. METHODS: A retrospective review of ERCP database was done to identify all cases of bile leak related to cholecystectomy. Patient records including surgical and endoscopic reports were reviewed, and telephone interviews were conducted to collect data. RESULTS: During the period 2004-2016, 100 patients (53 men, 47 women; mean age, 55 years) with post-cholecystectomy bile leak were referred for ERCP. Cholecystectomy was done laparoscopically in 82 patients (with an open conversion rate of 13%). In the majority of cases (77%), the leak was diagnosed by ongoing bile flow from the drains. The most common symptoms were pain (17%) and fever (4%). The most common site of the leak was the cystic duct stump (79%) followed by subvesical ducts (7%). Low grade leaks were seen in 84% of cases. Treatment included stent insertion alone (9%), sphincterotomy alone (11%), combination stent/sphincterotomy (76%) and others (1%). Failed ERCP was encountered in 3%. Endoscopic therapy was successful in 90 patients (90%). In subgroup analysis, success rate of procedures with stent insertion (with or without sphincterotomy) is significantly higher compared to procedures without stent insertion (95.3% vs 72.7%, p < 0.05). The failure rate of sphincterotomy alone procedures (3/11, 27%) is much higher compared to procedures with stent insertion (4/85, 5%) with p < 0.05. Four patients (4%) developed post-ERCP pancreatitis (mild to moderate) and one patient (1%) suffered from retroperitoneal perforation. CONCLUSION: The optimal endoscopic intervention for post-cholecystectomy bile leak should include temporary insertion of a biliary stent.
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Bilis/química , Colecistectomía/efectos adversos , Endoscopía , Centros de Atención Terciaria , Adolescente , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Femenino , Humanos , Laparoscopía/efectos adversos , Masculino , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Stents/efectos adversos , Resultado del TratamientoRESUMEN
Acute pancreatitis (AP) is one of the most common diseases in gastroenterology, affecting 2% of all hospitalized patients. Nevertheless, neither the etiology nor the pathophysiology of the disease is fully characterized, and no specific or effective treatment has been developed. Heparanase (Hpa) is an endoglycosidase that cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans (HSPGs) into shorter oligosaccharides, activity that is highly implicated in cell invasion associated with cancer metastasis and inflammation. Given that AP is a typical inflammatory disease, we investigated whether Hpa plays a role in AP. Our results provide keen evidence that Hpa expression and activity are significantly increased following cerulein-induced AP in wild type mice. In parallel to the classic manifestations of AP, namely elevation of amylase and lipase levels, pancreas edema and inflammation as well as induction of cytokines and signaling molecules, have been detected in this experimental model of the disease. Noteworthy, these features were far more profound in transgenic mice overexpressing heparanase (Hpa-Tg), suggesting that these mice can be utilized as a model system to reveal the molecular mechanism by which Hpa functions in AP. Further support for the involvement of Hpa in the pathogenesis of AP emerged from our observation that treatment of experimental AP with PG545 or SST0001(= Ronepastat), two potent Hpa inhibitors, markedly attenuated the biochemical, histological and immunological manifestations of the disease. Hpa, therefore, emerges as a potential new target in AP, and Hpa inhibitors are hoped to prove beneficial in AP along with their promising efficacy as anti-cancer compounds.
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Glucuronidasa/metabolismo , Pancreatitis/enzimología , Enfermedad Aguda , Animales , Ceruletida , Modelos Animales de Enfermedad , Glucuronidasa/antagonistas & inhibidores , Humanos , Pancreatitis/tratamiento farmacológicoAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , COVID-19 , Endoscopía Gastrointestinal , Humanos , SARS-CoV-2 , StentsAsunto(s)
Árabes/educación , Emigración e Inmigración , Endoscopía Gastrointestinal/tendencias , Árabes/estadística & datos numéricos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/estadística & datos numéricos , Femenino , Derechos Humanos/estadística & datos numéricos , Humanos , Colaboración Intersectorial , Israel/epidemiología , Masculino , Medio Oriente/epidemiologíaRESUMEN
Brush cytology is a sampling technique extensively used for mucosal surfaces, particularly to identify malignancies. A sample is obtained by rubbing the brush bristles over the stricture or lesion several times until cells are trapped. Brush cytology detection rate varies, with malignancy confirmed in 15-65% of cases of adenocarcinoma-associated biliary strictures and 44-80% of cases of cholangiocarcinoma. Despite the widespread use of brush cytology, there is no consensus to date defining the optimal biliary brushing parameters for the collection of suspicious lesions, such as the number of passes, brushing rate, and force applied. The aim of this work is to increase the brush cytology diagnostic yield by elucidating the underlying mechanical phenomena. First, the mechanical interactions between the brush bristles and sampled tissue are analyzed. During brushing, mucus and detached cells are transferred to the space between the bristles through the capillary rise and flow eddies. These mass transfer mechanisms and their dependence on mucus rheology as a function of pH, brush displacement rate, and bristle geometry and configuration are examined. Lastly, results from ex vivo brushing experiments performed on porcine stomachs are presented. Clinical practitioners from a variety of disciplines can apply the findings of this study to outline clear procedures for cytological brushing to increase the sensitivity and specificity of the brushings.
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Colangiopancreatografia Retrógrada Endoscópica , Colestasis , Humanos , Citología , Citodiagnóstico/métodos , Colestasis/patología , Sensibilidad y EspecificidadRESUMEN
Background and study aims Rising prevalence of pancreatic cysts and inconsistent management guidelines necessitate innovative approaches. New features of large language models (LLMs), namely custom GPT creation, provided by ChatGPT can be utilized to integrate multiple guidelines and settle inconsistencies. Methods A custom GPT was developed to provide guideline-based management advice for pancreatic cysts. Sixty clinical scenarios were evaluated by both the custom GPT and gastroenterology experts. A consensus was reached between experts and review of guidelines and the accuracy of recommendations provided by the custom GPT was evaluated and compared with experts. Results The custom GPT aligned with expert recommendations in 87% of scenarios. Initial expert recommendations were correct in 97% and 87% of cases, respectively. No significant difference was observed between the accuracy of custom GPT and the experts. Agreement analysis using Cohen's and Fleiss' Kappa coefficients indicated consistency among experts and the custom GPT. Conclusions This proof-of-concept study shows the custom GPT's potential to provide accurate, guideline-based recommendations for pancreatic cyst management, comparable to expert opinions. The study highlights the role of advanced features of LLMs in enhancing clinical decision-making in fields with significant practice variability.
RESUMEN
BACKGROUND: Obstructive jaundice and cirrhosis are associated with impaired renal function. Previously we demonstrated that increased intra-abdominal pressure (IAP, pneumoperitoneum) in normal rats induced renal dysfunction. This study investigated the renal effects of pneumoperitoneum in rats with acute jaundice and cirrhotic rats. METHODS: Following a baseline period, rats with obstructive jaundice or cirrhosis induced by acute or chronic bile duct ligation (BDL), respectively, and their sham-controls were subjected to consecutive IAPs of 10 and 14 mmHg for 45 min each. Urine flow (V), Na(+) excretion (UNaV), glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary NO metabolites ([Formula: see text]) and cGMP (UcGMP) were determined. RESULTS: Elevating IAP from 0 to 10 and 14 mmHg in normal rats caused IAP-dependent reductions in V, UNaV, GFR, RPF, [Formula: see text] and UcGMP. Basal renal function and hemodynamics were lower in rats with obstructive jaundice. In contrast to normal rats, application of elevated IAP of 10 and 14 mmHg significantly improved V, UNaV, GFR, RPF, and MAP along with increased [Formula: see text] and preserved UcGMP. Similarly, when identical IAP conditions were applied to cirrhotic rats, no deleterious changes in V, UNaV, GFR or RPF were observed. CONCLUSIONS: Application of pneumoperitoneum to rats with acute BDL improves kidney function and renal hemodynamics. Likewise, increased IAP does not exert adverse renal effects in cirrhotic rats. These effects are distinct from the deleterious renal consequences of increased IAP in normal rats. Perturbations in the generation of NO/cGMP during IAP in normal rats but not in rats with BDL or cirrhosis may contribute to these differences.
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Ictericia Obstructiva , Cirrosis Hepática , Neumoperitoneo Artificial/efectos adversos , Enfermedad Aguda , Animales , GMP Cíclico/orina , Tasa de Filtración Glomerular , Masculino , Nitratos/orina , Nitritos/orina , Ratas , Ratas Sprague-Dawley , Flujo Plasmático Renal , Sodio/orina , MicciónRESUMEN
We report 2 outbreaks of genetically unrelated carbapenem-resistant New Delhi metallo-ß-lactamase-producing Escherichia coli caused by contaminated duodenoscopes. Using endoscopes with disposable end caps, adherence to the manufacturer's reprocessing instructions, routine audits, and manufacturer evaluation are critical in preventing such outbreaks.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Escherichia coli , Humanos , beta-Lactamasas , Duodenoscopios , Brotes de Enfermedades/prevención & control , Carbapenémicos/farmacología , Pruebas de Sensibilidad Microbiana , AntibacterianosAsunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Hemobilia/diagnóstico por imagen , Hemobilia/etiología , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnóstico por imagen , Anciano , Angiografía por Tomografía Computarizada , Femenino , Humanos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND & AIMS: The risk of exacerbating sub-clinical hepatic encephalopathy (HE) by propofol has not been established. The aim of this study is to determine whether the use of propofol, for upper endoscopy in patients with cirrhosis, precipitates sub-clinical HE. METHODS: Sixty-one patients with compensated HCV and HBV cirrhosis (CP score 5-6) were randomly selected and divided into two groups (intent-to-treat population) matched for age, gender, and BMI. The first group received a single propofol sedation (N = 31, age 57 ± 12, dose range 70-100 mg/procedure) and the second group (N = 30, age 56 ± 12, dose 3-6 mg/procedure) received a single midazolam sedation, all done by an anesthesiologist. All patients completed number connection test (NCT), cognitive function score, time to recovery, time to discharge sheets, and hemodynamic parameters before sedation, and at discharge from the endoscopy unit, 1h post-procedure. Thirty control subjects without cirrhosis were matched to the cirrhotic patients who received sedation with regard to age, gender, BMI, and education level. RESULTS: A total of 58/61 cirrhotic patients (95%) had sub-clinical encephalopathy before the endoscopy (mean NCT 84.7 ± 77 s, normal < 30 s). No patient developed overt HE after sedation. There were no differences between groups in the incidence of adverse effects, cognitive function, MELD score, CP score, oxygen saturation, or respiratory and heart rates before and after sedation. Propofol did not exacerbate minimal HE when compared to midazolam (NCT changed from 87.5 ± 62 s prior to sedation to 74.2 ± 58 s after sedation in the propofol group versus 72.8 ± 62 s before to 85.6 ± 72 s after sedation in the midazolam group; p < 0.01). Time to recovery (4.1 ± 1.9 min vs. 11.5 ± 5.0 min, p < 0.001), and time to discharge (38.0 ± 9 min vs. 110 ± 42 min, p < 0.001) were significantly shorter with propofol than midazolam. Pre- and post-procedure NCT (from 25 ± 20 s to 24 ± 20 s), cognitive function score (from 25 to 26), time to recovery (3.5 ± 1.0 min), and time to discharge (35 ± 10 min) did not change in the healthy controls. CONCLUSIONS: Sedation with propofol has a shorter time recovery and a shorter time to discharge than midazolam and does not exacerbate sub-clinical hepatic encephalopathy in patients with compensated liver cirrhosis.
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Encefalopatía Hepática/etiología , Hipnóticos y Sedantes/efectos adversos , Cirrosis Hepática/diagnóstico , Midazolam/efectos adversos , Propofol/efectos adversos , Adulto , Anciano , Periodo de Recuperación de la Anestesia , Cognición , Sedación Consciente/efectos adversos , Endoscopía Gastrointestinal/efectos adversos , Femenino , Hemodinámica , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/psicología , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Método Simple CiegoRESUMEN
PURPOSE: Congestive heart failure is associated with impaired renal function. Previously we noted that increased intra-abdominal pressure (pneumoperitoneum) in normal rats induced renal dysfunction. In this study we investigated the renal effects of pneumoperitoneum in rats with compensated (urinary Na(+) excretion greater than 1,200 µEq per 24 hours) and decompensated (urinary Na(+) excretion less than 200 µEq per 24 hours) congestive heart failure, and the possible involvement of nitric oxide in these effects. MATERIALS AND METHODS: After a baseline period rats with congestive heart failure induced by aorto-caval fistula and sham operated controls underwent consecutive intra-abdominal pressures of 7, 10 or 14 mm Hg for 45 minutes each. Urinary flow, urinary Na(+) excretion, glomerular filtration rate, renal plasma flow and urinary nitric oxide metabolites were determined. RESULTS: There were no changes in urinary flow, urinary Na(+) excretion, glomerular filtration rate or renal plasma flow during 7 mm Hg insufflation in controls. However, significant decreases in these parameters were observed during 10 and 14 mm Hg in correlation with intra-abdominal pressure. Baseline renal function and hemodynamics were lower in rats with congestive heart failure in correlation with disease severity. Rats with decompensated congestive heart failure that underwent 10 and 14 mm Hg showed aggravated decreases in urinary flow, urinary Na(+) excretion, glomerular filtration rate and renal plasma flow. In contrast, no adverse renal effects were observed in rats with compensated congestive heart failure under identical intra-abdominal pressure conditions. Despite unaltered baseline urinary nitric oxide metabolites in the 2 congestive heart failure subgroups, the decompensated group showed decreased urinary nitric oxide metabolites after 14 mm Hg. Finally, rats with compensated congestive heart failure pretreated with the nitric oxide synthase inhibitor L-NAME showed worse renal function in response to pneumoperitoneum. CONCLUSIONS: Decompensated congestive heart failure renders rats susceptible to the adverse renal effects of pneumoperitoneum, a phenomenon that may involve alterations in the renal nitric oxide system.
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Insuficiencia Cardíaca/fisiopatología , Riñón/fisiopatología , Óxido Nítrico/fisiología , Neumoperitoneo Artificial/efectos adversos , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la EnfermedadRESUMEN
Physical analysis of the pancreatic cystic lesions (PCLs) fluid as expressed by the rheological behavior ("string sign") can improve the diagnostic yield and should be integrated in every multimodal PCLs workup.
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Quiste Pancreático , Neoplasias Pancreáticas , Biomarcadores , Líquido Quístico , Humanos , Páncreas/diagnóstico por imagen , Quiste Pancreático/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagenRESUMEN
Primary synovial sarcoma is exceedingly rare in the mediastinum. The differential diagnosis of this rare tumor is complex as a wide array of primary and metastatic tumors occur in this site.A definite diagnosis might be challenging even after tissue sampling. Immunohistochemistry can be very helpful and supportive for the diagnosis, but still inadequate in some cases as these tumors can mimic histopathologically other soft tissue tumors. Hence, in some case, an advanced pathological molecular analysis is needed.Endoscopic ultrasound (EUS) is an important diagnostic tool for mediastinal tumors. While EUS-fine needle aspiration (EUS-FNA) samples are usually inadequate for advanced pathological analysis, tissue acquisition by the newer generation of EUS-fine needle biopsy (EUS-FNB) needles might be sufficient.Here, we present the first report on primary mediastinal synovial sarcoma diagnosed by an immunohistochemical and FISH analysis performed on EUS-FNB tissue sample.
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Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Sarcoma Sinovial , Endosonografía , Humanos , Mediastino/diagnóstico por imagen , Sarcoma Sinovial/diagnóstico por imagenRESUMEN
Both fully (FCSEMS) and partially (PCSEMS) covered self-expandable metal stents are used for the endoscopic management of leaks, perforations, and fistulas. PCSEMS have lower migration rates as their uncovered flanges allow for anchorage into the surrounding tissue, but this consequently makes them difficult to be removed, with reported cases of esophageal perforation during the removal of the embedded PCSEMS. Stent-in-stent technique is mostly used, where a FCSEMS is placed co-axially into an existing PCSEMS causing pressure necrosis and facilitating subsequent removal of both stents. This technique, although effective, is expensive, requiring the use of a second stent. In this report, we describe a series of 3 patients with embedded PCSEMS removed by a new endoscopic technique, i.e., endoscopic sub-stent space dissection, without using a second stent.