RESUMEN
The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia.
Asunto(s)
Neoplasias del Colon/microbiología , Neoplasias Colorrectales Hereditarias sin Poliposis/microbiología , Microbioma Gastrointestinal/genética , Adenoma/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Colectomía/efectos adversos , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Heces/microbiología , Femenino , Humanos , Masculino , Metagenómica , Persona de Mediana Edad , Estudios Prospectivos , ARN Ribosómico 16S/genética , Transcriptoma , Microambiente TumoralRESUMEN
Background and study aim: Obstruction of biliary self-expandable metal stents (SEMSs) is seen frequently. Radiofrequency ablation (RFA) causes tissue necrosis. This study aimed to assess the efficacy of RFA for management of occluded SEMS. Patients and methods: Patients with biliary malignancy and treated for an occluded SEMS were retrospectively reviewed. The study group comprised patients treated with RFA using an Habib endoprobe inside the SEMS.âThe control group comprised patients treated only with insertion of a plastic stent into an occluded SEMS.âThe end points were; 90-day stent patency rate, time to stent reocclusion, 30-day mortality, and 3â-âand 6-month survival rates. Results: During the 5-year study period 25 patients with an occluded SEMS underwent RFA and 25 patients underwent a plastic stent placement only. Both groups were matched for age and diagnosis. Immediate biliary drainage was restored in all patients. In the RFA group, the stenosis was ablated successfully in 14 patients (56â%); ablation failed in 11 and a plastic stent was then inserted into the SEMS for these. The control group had only placement of a plastic stent across the stenosis. Stent patency rate at 90 days was 56â% and 24â% in the RFA and control groups, respectively (Pâ=â0.04). The mean stent patency time was significantly longer in the RFA group compared to the control group (119.5 vs. 65.3 days, Pâ=â0.03). Conclusion: The application of RFA for occluded SEMS improves stent patency. RFA is an alternative treatment of tissue ingrowth in malignant biliary obstruction.
Asunto(s)
Neoplasias del Sistema Biliar/complicaciones , Ablación por Catéter , Colestasis/cirugía , Falla de Prótesis , Stents Metálicos Autoexpandibles/efectos adversos , Anciano , Colestasis/etiología , Endoscopía del Sistema Digestivo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Gastrointestinal endoscopy is a remarkably safe set of diagnostic and therapeutic techniques, and yet a small number of significant complications and adverse events are expected. Serious complications may have a material effect on the patient's health and well-being. They need to be anticipated and prevented if possible and managed effectively when identified. When complications occur they need to be discussed frankly with patients and their families. Informed consent, prevention, early detection, reporting, and systems improvement are critical aspects of effective complication management. Optimal complication management may improve patient satisfaction and outcome, as well as preserving the reputation and confidence of the endoscopist, and may minimize litigation.
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Enfermedades del Sistema Digestivo/diagnóstico , Endoscopía Gastrointestinal/efectos adversos , Complicaciones Posoperatorias , Intervención Médica Temprana , Endoscopía Gastrointestinal/métodos , Humanos , Consentimiento Informado , Manejo de Atención al Paciente/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control , Mejoramiento de la CalidadRESUMEN
BACKGROUND: Endoscopic ampullectomy is increasingly performed in patients with familial adenomatous polyposis (FAP)-associated ampullary adenomas. We sought to define the procedure-associated morbidities and long-term outcomes. METHODS: We performed a retrospective chart review of patients with FAP who underwent endoscopic ampullectomy at two tertiary institutions between 1999 and 2010. The severity of duodenal polyposis was classified according to Spigelman's classification. RESULTS: Of 26 FAP patients who underwent endoscopic ampullectomy, 21 arose in the setting of Spigelman's stage II duodenal polyposis. Adverse events associated with endoscopic ampullectomy included acute pancreatitis (19.2%), abdominal pain (7.6%), and bleeding (3.8%). The mean resected adenoma size was 0.99 ± 0.34 cm. Three adenomas (12.0%) contained foci of high-grade dysplasia. Follow-up data were available for 24 patients. The mean follow-up duration was 84.5 ± 36.2 months. Adenoma recurrence was observed in 14 patients (58.3%; 14/24) at a mean of 38.3 months after initial ampullectomy. Adenomas ≥10 mm recurred more frequently than smaller adenomas (76.9 vs. 36.4%; p = 0.002). Positive margins were not associated with higher recurrence rates. No cancers were observed during long-term follow-up. Three patients underwent a Whipple procedure, but none was performed for a recurrent ampullary adenoma. CONCLUSIONS: Endoscopic ampullectomy in FAP can be performed safely. Because ampullary adenomas frequently recur after endoscopic ampullectomy, close surveillance is essential. Smaller tumors are less likely to recur, suggesting a benefit for early recognition of these lesions.
Asunto(s)
Adenoma/cirugía , Poliposis Adenomatosa del Colon/cirugía , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/cirugía , Endoscopía del Sistema Digestivo , Recurrencia Local de Neoplasia/patología , Adenoma/patología , Poliposis Adenomatosa del Colon/patología , Adolescente , Adulto , Anciano , Colectomía/estadística & datos numéricos , Neoplasias del Conducto Colédoco/patología , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto JovenRESUMEN
Toxic liver injury is a leading cause of liver failure and death because of the organ's inability to regenerate amidst massive cell death, and few therapeutic options exist. The mechanisms coordinating damage protection and repair are poorly understood. Here, we show that S-nitrosothiols regulate liver growth during development and after injury in vivo; in zebrafish, nitric-oxide (NO) enhanced liver formation independently of cGMP-mediated vasoactive effects. After acetaminophen (APAP) exposure, inhibition of the enzymatic regulator S-nitrosoglutathione reductase (GSNOR) minimized toxic liver damage, increased cell proliferation, and improved survival through sustained activation of the cytoprotective Nrf2 pathway. Preclinical studies of APAP injury in GSNOR-deficient mice confirmed conservation of hepatoprotective properties of S-nitrosothiol signaling across vertebrates; a GSNOR-specific inhibitor improved liver histology and acted with the approved therapy N-acetylcysteine to expand the therapeutic time window and improve outcome. These studies demonstrate that GSNOR inhibitors will be beneficial therapeutic candidates for treating liver injury.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Hígado/efectos de los fármacos , Donantes de Óxido Nítrico/farmacología , S-Nitrosotioles/farmacología , Acetaminofén/toxicidad , Aldehído Oxidorreductasas/metabolismo , Animales , Hígado/crecimiento & desarrollo , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/uso terapéutico , S-Nitrosotioles/uso terapéutico , Pez Cebra , Proteínas de Pez Cebra/metabolismoAsunto(s)
Colon , Enfermedad de Crohn , Mucosa Intestinal , Obstrucción Intestinal , Complicaciones Posoperatorias , Adolescente , Colon/patología , Colon/cirugía , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Humanos , Mucosa Intestinal/patología , Mucosa Intestinal/cirugía , Obstrucción Intestinal/etiología , Obstrucción Intestinal/patología , Obstrucción Intestinal/cirugía , Masculino , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/cirugíaRESUMEN
Developmental signals determine organ morphology and position during embryogenesis. To discover novel modifiers of liver development, we performed a chemical genetic screen in zebrafish and identified retinoic acid as a positive regulator of hepatogenesis. Knockdown of the four RA receptors revealed that all receptors affect liver formation, however specific receptors exert differential effects. Rargb knockdown results in bilateral livers but does not impact organ size, revealing a unique role for Rargb in conferring left-right positional information. Bilateral populations of hepatoblasts are detectable in rargb morphants, indicating Rargb acts during hepatic specification to position the liver, and primitive endoderm is competent to form liver on both sides. Hearts remain at the midline and gut looping is perturbed in rargb morphants, suggesting Rargb affects lateral plate mesoderm migration. Overexpression of Bmp during somitogenesis similarly results in bilateral livers and midline hearts, and inhibition of Bmp signaling rescues the rargb morphant phenotype, indicating Rargb functions upstream of Bmp to regulate organ sidedness. Loss of rargb causes biliary and organ laterality defects as well as asplenia, paralleling symptoms of the human condition right atrial isomerism. Our findings uncover a novel role for RA in regulating organ laterality and provide an animal model of one form of human heterotaxia.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Mesodermo/metabolismo , Receptores de Ácido Retinoico/metabolismo , Proteínas de Pez Cebra/metabolismo , Pez Cebra/embriología , Pez Cebra/metabolismo , Animales , Animales Modificados Genéticamente , Tipificación del Cuerpo , Embrión no Mamífero/metabolismo , Hígado/embriología , Hígado/metabolismo , Modelos Animales , Proteína Nodal/metabolismo , Fenotipo , Receptores de Ácido Retinoico/genética , Transducción de Señal , Tretinoina/metabolismo , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Receptor de Ácido Retinoico gammaAsunto(s)
Conductos Biliares/fisiopatología , Constricción Patológica/terapia , Hipercolesterolemia/etiología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Fosfatasa Alcalina/metabolismo , Enfermedades de las Vías Biliares/etiología , Enfermedades de las Vías Biliares/terapia , Bilirrubina/metabolismo , Constricción Patológica/etiología , Femenino , Hepatitis Autoinmune/terapia , Humanos , Hipercolesterolemia/diagnóstico , Pruebas de Función Hepática , Donadores Vivos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE: To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN: Multicenter randomized trial. SETTING: Four teaching hospitals. PATIENTS: Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS: Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES: Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS: From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS: Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS: There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration.
Asunto(s)
Neoplasias del Sistema Biliar/patología , Colangiopancreatografia Retrógrada Endoscópica , Colestasis/terapia , Cuidados Paliativos , Stents , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/complicaciones , Neoplasias del Sistema Biliar/terapia , Colestasis/etiología , Colestasis/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Diseño de Equipo , Femenino , Humanos , Masculino , Metales , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoRESUMEN
Lower gastrointestinal (GI) hemorrhage is a significant cause of morbidity and mortality, particularly in elderly patients. Lower endoscopic evaluation is established as the diagnostic procedure of choice in the setting of acute lower GI hemorrhage.
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Endoscopía Gastrointestinal/métodos , Hemorragia Gastrointestinal/terapia , Hemostasis Endoscópica/métodos , Tracto Gastrointestinal Inferior , Angiodisplasia/complicaciones , Colitis/complicaciones , Divertículo/complicaciones , Urgencias Médicas , Hemorragia Gastrointestinal/etiología , Hemorroides/complicaciones , HumanosAsunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/efectos adversos , Vasculitis Retiniana/diagnóstico , Vasculitis/patología , Adulto , Biopsia , Colitis Ulcerosa/complicaciones , Colon/patología , Diagnóstico Diferencial , Fiebre/etiología , Humanos , Masculino , Seno Pilonidal/cirugía , Complicaciones Posoperatorias , Púrpura/etiología , Piel/patología , Tromboflebitis/etiología , Vasculitis/diagnóstico , Trastornos de la Visión/etiologíaAsunto(s)
Resinas de Intercambio de Catión/efectos adversos , Colon/patología , Perforación Intestinal/patología , Poliestirenos/efectos adversos , Sorbitol/efectos adversos , Dolor Abdominal/etiología , Anciano , Aortografía , Colon/irrigación sanguínea , Colon/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/complicaciones , Diagnóstico Diferencial , Humanos , Ileus/diagnóstico , Arteria Ilíaca/diagnóstico por imagen , Claudicación Intermitente/complicaciones , Perforación Intestinal/inducido químicamente , Perforación Intestinal/complicaciones , Isquemia/diagnóstico , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Necrosis , Tromboembolia/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Duodenoscope assisted cholangiopancreatoscopy allows direct visualization of the pancreatic duct and bile duct. There are several circumstances where direct ductal visualization might be helpful in clarifying a diagnosis or providing targeted treatment. Duodenoscope assisted cholangiopancreatoscopy is currently employed for a variety of indications including: indeterminate ductal strictures and filling defects, marginal chronic pancreatitis, treatment of large intraductal stones, localization of intraductal papillary mucinous tumors, and localization and treatment of hemobilia. There have however been no randomized controlled trials evaluating the diagnostic or therapeutic functions of duodenoscope assisted cholangiopancreatoscopy. This article reviews recent descriptive studies that attempt to clarify the clinical role of this technology.
RESUMEN
BACKGROUND: The aim of this study was to identify predictors of outcome after pancreatic duct stent placement for duct disruption. METHODS: Patients were identified from endoscopy databases. Disruption was defined by extravasation of contrast from the pancreatic duct during endoscopic retrograde pancreatography. Data collected included demographic information, imaging studies, management before and outcome after stent placement. Success was defined as resolution of the disruption clinically, on radiologic imaging, and/or at endoscopic retrograde pancreatography. RESULTS: Forty-three patients (23 women, 20 men; mean age 57 years, [SD] 15.2 years) were studied. The etiology of pancreatic duct disruption was acute pancreatitis in 24, chronic pancreatitis in 9, operative injury in 7, and trauma in 3 patients. In 25 patients there was resolution of the disruption, whereas stent therapy was unsuccessful in 16 and the outcome was indeterminate in 2 patients. On univariate analysis, stent positioned to bridge the disruption (p = 0.04) and longer duration of stent therapy (p = 0.002) were associated with a successful outcome. Female gender (p = 0.05) and acute pancreatitis (p = 0.05) were associated with a lack of success. On multivariate analysis, only the bridging stent position remained correlated to outcome. Complications occurred in 4 patients. CONCLUSIONS: A bridging stent is associated with a successful outcome after pancreatic duct stent placement for duct disruption.
Asunto(s)
Conductos Pancreáticos , Stents , Enfermedad Aguda , Adulto , Anciano , Colangiopancreatografia Retrógrada Endoscópica , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conductos Pancreáticos/lesiones , Pancreatitis/complicaciones , Stents/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Optical coherence tomography (OCT) is a high-resolution imaging technique that produces cross-sectional images in vivo. This is a report of the first use of OCT to acquire images of the biliary tree during ERCP. METHODS: A 2.6-mm diameter OCT catheter delivered through the accessory channel of a duodenoscope was used to acquire images of the intrahepatic and extrahepatic bile ducts in 5 patients. Histology-correlated OCT images of 5 cadaveric livers, each imaged at 3 sites, were used to guide interpretation of the in vivo images. RESULTS: Biliary ductal epithelium and subepithelial structures, including peribiliary glands, vasculature, and hepatic parenchyma, were visualized in vivo. The papillary architecture of cholangiocarcinoma was identified by OCT. There were no OCT-related complications. CONCLUSIONS: High-resolution OCT imaging of the biliary tree is feasible and may provide useful diagnostic information during ERCP.