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OBJECTIVES: Advanced ERCP techniques (AETs) for difficult biliary stones include peroral cholangioscopy (POC) with electrohydraulic/laser lithotripsy (EHL/LL), endoscopic papillary large balloon dilation (EPLBD) and mechanical lithotripsy (ML). We assess the efficacy of AETs. METHODS: A retrospective query for AETs. PRIMARY OUTCOME: Complete duct clearance. Secondary outcome: Complete duct clearance by technique. Statistical Analysis version 9.3 (SAS Inc., Cary, NC). RESULTS: From 1/00 to 10/12, 349 patients were identified of which 222 (80% had prior ERCPs) had AETs. 211 with sufficient follow-up underwent 295 ERCPs; 280 of which were AET's. Index AETs: POC with EHL/LL (n = 46/211, 22%), ML (n = 84/211, 40%), EPLBD with mean balloon size of 11.5 ± 1.7 mm (n = 39/211, 18%) and combination AETs (n = 42/211, 20%). Stone characteristics: 76% had ≥1 stone, 81% extrahepatic and 32% had strictures. Number of stones (mean 2.5 and range 1-20) did not differ among groups. EPLBD had higher percentage (95%) of extrahepatic stones (p = .0003). The 'Combination' and 'POC' groups had larger stones (mean 17.7 mm ±6.4 and 16.8 mm ±6.1, respectively; p < .001). Complete clearance: 209/211 (99%) at index AET 167/211 (79%) or after mean of 2.5 ± 0.7 AETs in 42/211 (20%). Partial clearance: 2/211 (1%). Clearance at index AETs was higher with EPLBD (90%, p = .014). Adverse Events: 7/280 (2.5%). CONCLUSIONS: AETs achieved clearance in 99%. EPLBD had higher clearance at index AET likely owing to higher extrahepatic stones. Larger stones, but not number, were associated with increased combination AETs and total ERCPs.
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Colangiopancreatografia Retrógrada Endoscópica/métodos , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/cirugía , Anciano , Anciano de 80 o más Años , Cateterismo , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colecistectomía Laparoscópica , Colorado , Bases de Datos Factuales , Dilatación , Femenino , Hospitales Universitarios , Humanos , Litotricia , Masculino , Persona de Mediana Edad , Pancreatitis/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Endoscopic ultrasound (EUS) plays an integral role in the evaluation of pancreatic cysts lesions (PCLs). The aim of the study was to determine predictors of surgical referral in patients with PCLs undergoing EUS. METHODS: We performed a multicenter retrospective study of patients undergoing EUS for evaluation of PCLs. Demographics, EUS characteristics, and fine-needle aspiration results were recorded. Patients were categorized into surgery or surveillance groups on the basis of post-EUS recommendations. Univariate and multivariate analyses were performed to identify predictors of surgical referral. RESULTS: 1804 patients were included. 1301 patients were recommended to undergo surveillance and 503 patients were referred for surgical evaluation, of which 360 patients underwent surgery. Multivariate analysis revealed the following 5 independent predictors of surgical referral: symptoms of weight loss on presentation (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.44-5.03), EUS findings of associated solid mass (OR, 7.34; 95% CI, 3.81-14.16), main duct communication (OR, 4.13; 95% CI, 1.71-9.98), multilocular macrocystic morphology (OR, 2.79; 95% CI, 1.78-4.38), and fine-needle aspiration findings of mucin on cytology (OR, 3.06; 95% CI, 1.94-4.82). CONCLUSIONS: This study identifies factors associated with surgical referral in patients with PCLs undergoing EUS. Future studies should focus on creation of risk stratification models to determine the need for surgery or enrollment in surveillance programs.
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Endosonografía , Neoplasias Quísticas, Mucinosas y Serosas/diagnóstico por imagen , Neoplasias Quísticas, Mucinosas y Serosas/cirugía , Pancreatectomía , Quiste Pancreático/diagnóstico por imagen , Quiste Pancreático/cirugía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Derivación y Consulta , Anciano , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Estados Unidos , Espera VigilanteRESUMEN
BACKGROUND AND AIMS: There are limited data on learning curves and competence in ERCP. By using a standardized data collection tool, we aimed to prospectively define learning curves and measure competence among advanced endoscopy trainees (AETs) by using cumulative sum (CUSUM) analysis. METHODS: AETs were evaluated by attending endoscopists starting with the 26th hands-on ERCP examination and then every ERCP examination during the 12-month training period. A standardized ERCP competency assessment tool (using a 4-point scoring system) was used to grade the examination. CUSUM analysis was applied to produce learning curves for individual technical and cognitive components of ERCP performance (success defined as a score of 1, acceptable and unacceptable failures [p1] of 10% and 20%, respectively). Sensitivity analyses varying p1 and by using a less-stringent definition of success were performed. RESULTS: Five AETs were included with a total of 1049 graded ERCPs (mean ± SD, 209.8 ± 91.6/AET). The majority of cases were performed for a biliary indication (80%). The overall and native papilla allowed cannulation times were 3.1 ± 3.6 and 5.7 ± 4, respectively. Overall learning curves demonstrated substantial variability for individual technical and cognitive endpoints. Although nearly all AETs achieved competence in overall cannulation, none achieved competence for cannulation in cases with a native papilla. Sensitivity analyses increased the proportion of AETs who achieved competence. CONCLUSION: This study demonstrates that there is substantial variability in ERCP learning curves among AETs. A specific case volume does not ensure competence, especially for native papilla cannulation.
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Colangiopancreatografia Retrógrada Endoscópica/normas , Competencia Clínica , Gastroenterología/educación , Curva de Aprendizaje , Cateterismo/normas , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/estadística & datos numéricos , Educación de Postgrado en Medicina , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND AND AIMS: The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS: Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS: A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipple's procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS: Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.
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Antígeno Carcinoembrionario/metabolismo , Cistadenocarcinoma Mucinoso/diagnóstico , Cistoadenoma Mucinoso/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Cistadenocarcinoma Mucinoso/metabolismo , Cistoadenoma Mucinoso/metabolismo , Diagnóstico Diferencial , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Pancreáticas/metabolismo , Curva ROC , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Long-term population-based data comparing endoscopic therapy (ET) and surgery for management of malignant colorectal polyps (MCPs) are limited. OBJECTIVE: To compare colorectal cancer (CRC)-specific survival with ET and surgery. DESIGN AND SETTING: Population-based study. PATIENTS: Patients with stage 0 and stage 1 MCPs were identified from the Surveillance Epidemiology and End Results (SEER) database (1998-2009). Demographic characteristics, tumor size, location, treatment modality, and survival were compared. Propensity-score matching and Cox proportional hazards regression models were used to evaluate the association between treatment and CRC-specific survival. INTERVENTIONS: ET and surgery. MAIN OUTCOME MEASUREMENTS: Mid-term (2.5 years) and long-term (5 years) CRC-free survival rates and independent predictors of CRC-specific mortality. RESULTS: Of 10,403 patients with MCPs, 2688 (26%) underwent ET and 7715 (74%) underwent surgery. Patients undergoing ET were more likely to be older white men with stage 0 disease. Surgical patients had more right-sided lesions, larger MCPs, and stage 1 disease. There was no difference in the 2.5-year and 5-year CRC-free survival rates between the 2 groups in stage 0 disease. Surgical resection led to higher 2.5-year (97.8% vs 93.2%; P < .001) and 5-year (96.6% vs 89.8%; P < .001) CRC-free survival in stage 1 disease. These results were confirmed by propensity-score matching. ET was a significant predictor for CRC-specific mortality in stage 1 disease (hazard ratio 2.40; 95% confidence interval, 1.75-3.29; P < .001). LIMITATIONS: Comorbidity index not available, selection bias. CONCLUSIONS: ET and surgery had comparable mid- and long-term CRC-free survival rates in stage 0 disease. Surgical resection is the recommended treatment modality for MCPs with submucosal invasion.
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Adenocarcinoma/terapia , Adenoma/terapia , Colectomía , Colonoscopía , Neoplasias Colorrectales/terapia , Pólipos Intestinales/terapia , Recto/cirugía , Adenocarcinoma/mortalidad , Adenoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Pólipos Intestinales/mortalidad , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Programa de VERF , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: Per oral pancreatoscopy (POP) with electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) permits stone fragmentation and removal during endoscopic retrograde cholangiopancreatography. Our study evaluates the safety and efficacy of POP in patients with main pancreatic duct (PD) stones. METHODS: This was a cohort study of patients undergoing POP with EHL/LL for PD stones between January 2000 and March 2011. Technical success was defined as complete or partial stone clearance, and clinical success as greater than 50% reduction in opiate use, pain, or hospitalizations. RESULTS: Forty-six patients underwent POP for PD stones using a 10F cholangioscope (POP-Endo) (n = 31) or catheter-based system (POP-Cath, n = 15). Electrohydraulic lithotripsy/LL was performed in 39 (85%) of 46 patients. Stone extraction without EHL or LL was performed in 7 (15%) of 46 patients. Technical success for POP-Endo versus POP-Cath was 27 (87%) of 31 versus 15 (100%) of 15 patients (P = 0.29). Complete clearance was achieved in 21 (68%) of 31 versus 11 (73%) of 15 patients, respectively (P = 0.519). Per oral pancreatoscopy-related complications were found in 10%. Follow-up in 43 (93%) of 46 patients was a median of 18 months (range, 1-60 months). Overall clinical success was 74%. CONCLUSIONS: Per oral pancreatoscopy-guided endotherapy leads to partial or complete stone clearance in most patients with PD stones. The technical success rates between POP-Endo versus POP-Cath systems appear similar and are associated with clinical improvement in most patients.
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Cálculos/terapia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Endoscopía del Sistema Digestivo/métodos , Pancreatitis Crónica/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cálculos/complicaciones , Cálculos/diagnóstico , Catéteres , Estudios de Cohortes , Endoscopía del Sistema Digestivo/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Litotricia/métodos , Litotripsia por Láser/métodos , Masculino , Persona de Mediana Edad , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND STUDY AIM: The incidence of cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) ranges between 7 and 14 %. Despite using multiple tissue sampling modalities, detection of CCA remains a challenge. Probe-based confocal laser endomicroscopy (pCLE) has been utilized to visualize subepithelial biliary mucosa in patients with indeterminate strictures. We assessed the technical feasibility and operating characteristics of pCLE in a cohort of PSC patients with dominant biliary strictures (DS). PATIENTS AND METHODS: This was a chart review of a prospectively maintained database at a single tertiary referral center of 15 PSC patients with 21 dominant stenoses undergoing pCLE. A data collection sheet included demographics, ERCP, cholangioscopy, pCLE (Miami criteria), tissue sampling results, and follow-up to 12 months or liver transplantation. Operating characteristics for pCLE and ERCP tissue sampling were calculated. RESULTS: Sufficient visualization of DS by pCLE was achieved in 20/21 (95 %). pCLE sensitivity, specificity, PPV, and NPV were 100 % (95 % CI 19.3-100 %), 61.1 % (95 % CI 35.8-82.6 %), 22.2 % (95 % CI 3.5-59.9 %), and 100 % (95 % CI 71.3-100 %), respectively, in detecting neoplasia. In comparison, concomitant tissue sampling yielded sensitivity, specificity, PPV, and NPV of 0 % (95 % CI 0-80.7 %), 94.4 % (95 % CI 72.6-99.1 %), 0 % (95 % CI 0-83.5 %), and 89.5 % (95 % CI 66.8-98.4 %), respectively. CONCLUSIONS: pCLE achieves a high technical success rate in patients with PSC and DS. This single center, small series, suggests that pCLE may have a high sensitivity and negative predictive value to exclude neoplasia. If verified in larger prospective studies, the technology may be utilized to risk stratify dominant strictures in patients with PSC.
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Neoplasias de los Conductos Biliares/diagnóstico , Conductos Biliares Intrahepáticos , Colangiocarcinoma/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Colangitis Esclerosante/complicaciones , Colestasis Intrahepática/etiología , Adulto , Anciano , Neoplasias de los Conductos Biliares/complicaciones , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/complicaciones , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Microscopía Confocal/instrumentación , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y EspecificidadAsunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Papilar/diagnóstico , Endoscopía del Sistema Digestivo/instrumentación , Aumento de la Imagen/instrumentación , Páncreas/anomalías , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma Mucinoso/patología , Anciano , Biopsia , Carcinoma Ductal Pancreático/patología , Carcinoma Papilar/patología , Colangiopancreatografia Retrógrada Endoscópica , Diabetes Mellitus Tipo 1/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Páncreas/patología , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Tomografía Computarizada por Rayos XRESUMEN
Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.
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Terapia Genética , Cirrosis Hepática/terapia , Animales , Apoptosis , Matriz Extracelular/fisiología , Humanos , Metaloproteinasa 8 de la Matriz/genética , Oligonucleótidos Antisentido/uso terapéutico , Proteínas Serina-Treonina Quinasas , Especies Reactivas de Oxígeno , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genética , Superóxido Dismutasa/genética , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Our previous study demonstrated that polycationic liposomes are highly stable in the bloodstream and represent an effective agent for liver gene delivery. We report here that liposome-mediated extracellular superoxide dismutase (EC-SOD) gene delivery successfully prevented acute liver injury in mice. The therapeutic efficacy of EC-SOD gene delivery by polycationic liposomes was determined against the toxicity of superoxide anions and hydroxyethyl radicals in HepG2 cells and in a mouse model of acute liver injury caused by D-galactosamine and lipopolysaccharide intoxication. Transfection of HepG2 cells with an EC-SOD plasmid led to a striking increase in superoxide dismutase activity in the medium. The transfected cells had much less cell death after reactive oxygen species exposure compared with untransfected or control plasmid-transfected cells. In a model of acute liver injury, serum alanine aminotransferase levels in mice receiving portal vein injections of EC-SOD lipoplexes were much lower than in those receiving normal saline, liposomes alone, or control lipoplexes. Liver histology confirmed that there was less cell death in the EC-SOD lipoplex-treated group. Quantitative reverse transcriptase polymerase chain reaction showed a 55-fold increase in human EC-SOD gene expression in the liver of mice injected with EC-SOD lipoplexes. Serum superoxide dismutase activity in EC-SOD lipoplex-treated mice was higher than in the control groups; this was associated with higher liver glutathione levels and reduced lipid peroxidation. In conclusion, polycationic liposome-mediated EC-SOD gene delivery protects against reactive oxygen species toxicity in vitro and against lipopolysaccharide-induced acute liver injury in D-galactosamine-sensitized mice.