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1.
Dis Colon Rectum ; 55(2): 140-6, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22228156

RESUMEN

BACKGROUND: Single-incision laparoscopic surgery is a development in the field of minimally invasive surgery that is being increasingly used for colorectal procedures. OBJECTIVE: We report on the short-term results of single-port laparoscopic ileocolic resection in patients with ileocecal Crohn's disease. DESIGN: This investigation is a retrospective matched-pair control study. Data were obtained from a prospectively maintained single-institution inflammatory bowel disease database. SETTINGS: This study was conducted at a tertiary care university hospital. PATIENTS: Twenty consecutive patients receiving elective single-port ileocolic resection between April 2010 and May 2011 were included (6 male, 14 female; age, 31.6 ± 10.8 years; BMI, 21.5 ± 2.6 kg/m). Their data were compared with the data of 20 individually matched patients who had undergone standard 3-trocar laparoscopic-assisted ileocolic resection between 2007 and 2010 (6 male, 14 female; age, 31.7 ± 10.7 years; BMI, 21.2 ± 2.5 kg/m). All patients had medically refractory stenosis of the terminal ileum in histologically confirmed Crohn's disease. INTERVENTIONS: Single-port laparoscopic-assisted or standard laparoscopic-assisted ileocolic resection was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the surgical details and early outcome. RESULTS: : The mean length of the paraumbilical single-port incision was 3.8 cm (range, 2.5-5.0 cm). Conversion rates were similar in both groups (1/20 vs 2/20, p = 0.55). Additional strictureplasties or short-segment small-bowel resections were performed in both groups. The overall complication rate was 20% (4/20) in both groups. There were no observed differences in postoperative pain scores and hospital stay duration. LIMITATIONS: The limitations of this study were as follows: this study was a comparison of 2 different time points with possible selection bias, there was no prestudy power calculation, and the study might be underpowered. CONCLUSIONS: Single-port ileocolic resection is a safe procedure for the surgical treatment of stenotizing Crohn's disease of the terminal ileum. Avoidance of additional trocars was the only identified benefit.


Asunto(s)
Colectomía/métodos , Enfermedad de Crohn/cirugía , Íleon/cirugía , Laparoscopía/métodos , Adulto , Anastomosis Quirúrgica , Colitis/cirugía , Estudios de Factibilidad , Femenino , Humanos , Ileítis/cirugía , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
2.
Dis Colon Rectum ; 55(7): 756-61, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22706127

RESUMEN

BACKGROUND: Development of biologic agents has led to new therapeutic options for patients with refractory ulcerative colitis, and intensive medical therapy allows delay of restorative colectomy. However, the overall rate of colectomies has not changed. The decision as to timing of the operation is difficult. OBJECTIVE: Our aim was to elucidate the patients' views about the timing of their own proctocolectomy. DESIGN: This was a retrospective review of a prospectively designed database combined with a follow-up survey questionnaire. SETTINGS AND PARTICIPANTS: We included patients who underwent proctocolectomy and ileal pouch-anal anastomosis for refractory ulcerative colitis from 1999 through 2009 at our university hospital. MAIN OUTCOME MEASURES: A questionnaire was sent to patients asking whether they would have preferred to have had the operation performed earlier, later, or at the same time as it was actually done and to give the number of years or months earlier or later that they would have preferred. They were also asked to give reasons for their preference. Patients who preferred an earlier operation were compared with those satisfied with the timing regarding measures of postoperative quality of life and pouch function collected from the institution's prospective database. RESULTS: Of 84 eligible patients, 70 (83%) responded. Of these, 37 (53%) would have preferred an earlier operation; 33 patients (47%) were satisfied with the timing. No patient would have chosen a later operation. Patients who preferred an earlier operation wished it to have been a median of 2 years earlier (range, 2-120 months). The main reasons for a preferred earlier time point were postoperative improvement of stool regulation in 89% (33/37), reduction of bleedings in 84% (31/37), and relief of pain in 68% (25/37). No significant differences were observed between groups regarding postoperative quality of life or pouch function. LIMITATIONS: Limitations of the study included lack of validation and a nonsymmetrical structure of the questionnaire. CONCLUSIONS: About half of the patients of our study would have preferred to have had proctocolectomy earlier than it had been performed, mainly because of the relief of symptoms that they experienced after the operation. For patients with an emerging refractory course of ulcerative colitis, earlier restorative proctocolectomy should be considered as an alternative to further intensified medical treatment.


Asunto(s)
Anastomosis Quirúrgica , Colitis Ulcerosa/cirugía , Satisfacción del Paciente/estadística & datos numéricos , Proctocolectomía Restauradora , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Encuestas y Cuestionarios , Factores de Tiempo , Adulto Joven
3.
Langenbecks Arch Surg ; 397(1): 37-44, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21594657

RESUMEN

PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis is associated with pouch-related septic complications (PRSC) in 10% of patients. This study questioned if PRSC have a negative impact on pouch function and quality of life. PATIENTS AND METHODS: One hundred thirty consecutive patients undergoing IPAA for ulcerative colitis between 1997 and 2009 were reviewed. At 1-year follow-up, patients were asked to complete questionnaires including a pouch function score (Oresland score, 0-16 points, 0 optimum) and two quality of life scores [Short Inflammatory Bowel Disease Questionnaire (SIBDQ), 1-7 points, 7 optimum; Gastrointestinal Quality of Life Index (GIQLI), 0-144 points, 144 optimum]. RESULTS: Twelve out of 130 patients (9.2%) undergoing IPAA developed PRSC. These included anastomotic dehiscence (five), pouch leakage (three, one patient had a combined leak), peripouchal abscess (three), pouch-anal fistula (one), and pouch-vaginal fistula (one). Omission of diverting ileostomy was a risk factor for PRSC (OR 4.62, CI 1.17-18.4). PRSC led to four pouch failures (33%), whereas no failure occurred in the control group (p < 0.001). Median 3 (range, 1-10) further operations were necessary until the pouch was salvaged or definitively lost. If the pouch was salvaged, functional Oresland score (8.2 ± 1.3 vs. 6.6 ± 0.5; p = 0.127), SIBDQ (5.0 ± 0.5 vs. 5.5 ± 0.1; p = 0.203), and GIQLI (95.8 ± 8.4 vs. 107.3 ± 2.6; p = 0.119) were not significantly inferior to uncomplicated controls. CONCLUSIONS: In case of PRSC, even multiple surgical approaches are worthwhile as the outcome of salvaged pouches in terms of function and quality of life is not substantially inferior to patients without septic complications.


Asunto(s)
Colitis Ulcerosa/cirugía , Reservorios Cólicos/efectos adversos , Calidad de Vida , Sepsis/etiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proctocolectomía Restauradora , Reoperación , Terapia Recuperativa , Sepsis/terapia , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/terapia , Adulto Joven
4.
Langenbecks Arch Surg ; 397(8): 1359-66, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22875224

RESUMEN

PURPOSE: We present our current clinical approach for the treatment of postoperatively infected wounds of the abdominal wall healing by secondary intention that may help in the design of a randomized controlled trial to develop a standardized wound treatment pathway. METHODS: Patients with postoperatively infected abdominal wounds treated with either Advanced Wound Care (AWC) dressings or vacuum-assisted closure (VAC) therapy were enrolled in the study. Follow-up was carried out prospectively for wound healing and incidence of incisional hernia at the earliest 3 years after surgery. RESULTS: Sixty-two patients were included and wounds were initially treated antiseptically for 5.19 ± 2.91 days. Prior to VAC therapy, AWC dressings were applied for 8.75 ± 2.93 days to reduce reinfection. Greater wound size (>12 × 6 × 6cm) and extensive secretion (>200 ml/day) argued for the VAC system. Overall incidence of incisional hernia was 20.4%, with 18.4% occurring in AWC-treated patients and 27.3% in VAC-treated patients. Based on these results, a wound treatment pathway was established in our department. CONCLUSION: The established wound treatment pathway has helped to increase both workflow efficacy and outcome in the treatment of abdominal wounds. Wound size, amount of secretion, and status of infection were the parameters we used for the determination of appropriate treatment. The observational data gathered during the initiation of our pathway lay the basis for future randomized controlled trials that will determine the most appropriate treatment options in the setting of a standardized wound treatment pathway.


Asunto(s)
Pared Abdominal/cirugía , Terapia de Presión Negativa para Heridas , Infección de la Herida Quirúrgica/terapia , Cicatrización de Heridas , Vendajes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infección de la Herida Quirúrgica/patología
5.
Ann Surg Oncol ; 18(1): 253-60, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20628822

RESUMEN

BACKGROUND: Prognostic and staging information for esophageal cancer impacts clinical decision making. miRNAs, a newly discovered class of biomarkers and their expression might add additional information relevant to this. In this study we evaluated the expression of selected miRNAs and their relationship to tumor stage and survival in patients with locally advanced tumors following esophagectomy. MATERIALS AND METHODS: A total of 43 individuals undergoing esophagectomy (without neoadjuvant therapy) for locally advanced but not metastatic (pT2/3; pN0/1) disease (22 adenocarcinoma [EAC], 21 squamous cell carcinoma [SCC]) were included in this study. Perioperative clinical and survival data were collected and managed on a database. The expression of miR-21, miR-106a, miR-148a, miR-205 in formalin-fixed paraffin-embedded specimens was evaluated by TaqMan qPCR assays. Expression was compared with clinicopathological features of the cancers and outcome. RESULTS: In EAC, miR-148a expression levels were inversely associated with cancer differentiation. miR-21 expression levels were higher in SCC if distant lymph node metastases were present. miR-148a levels were lower when EAC was more proximally located, and miR-21 levels were lower when SCC was more proximal. miR-106a and miR-148a were lower in patients with SCC who developed recurrent disease or had a tumor-related death. CONCLUSIONS: In patients with locally advanced esophageal squamous cell carcinoma, but not adenocarcinoma, alterations in the expression of miR-21 correlate with tumor location and lymph node status. Furthermore, miR-106a and miR-148a expression correlates with disease recurrence and tumor-related mortality. miRNA markers might inform the initial assessment of these patients, and predict those at higher risk of postsurgical recurrence.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Esofagectomía , MicroARNs/genética , Recurrencia Local de Neoplasia/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia
6.
World J Surg ; 35(3): 608-16, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21221582

RESUMEN

BACKGROUND: The predictive value of positron emission tomography-computed tomography (PET-CT) in primary staging and response control in patients with esophageal carcinoma (EC) is under discussion. In the present study initial staging and metabolic response of PET-CT was correlated with tumor regression and survival in patients with multimodal treatment of EC. METHODS: The authors conducted a retrospective analysis on a prospective database for 83 patients with EC (42 squamous cell, 39 adenocarcinoma, 2 anaplastic carcinoma) undergoing PET-CT for primary staging. Twenty-four of the patients underwent primary esophagectomy, 9 had palliative treatment, and 50 neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil; 50.4 Gy). The PET-CT study was repeated 6 weeks after induction of chemotherapy and compared with endoscopic ultrasound (EUS). For response control, the metabolic response (tumor standardized uptake value [SUV] reduction) was correlated with histopathologic (ypT0-4) and histomorphologic response (tumor regression) and survival. RESULTS: At primary staging 81 of 83 EC (97.5%) showed an increased SUV uptake correlating with the EUS tumor stage. Suspicious lymph nodes were detected in 51 (61.4%) patients by PET-CT and 66 (79.5%) were detected by EUS. Fifteen patients had additional findings on PET-CT examination leading to a change in therapy in 9 patients (10.3%). Of 50 patients receiving a second PET-CT study, a SUV reduction >50% correlated with major histomorphologic response (tumor regression grade 4, <10% vital tumor cells) and histopathologic response (ypT0 ypN0). Furthermore, these patients showed a significantly increased survival (33.1 ± 3.5 months) compared to non-responders (21.7 ± 3.3 months; p = 0.02) and patients after primary surgery (29 ± 3.2 months; p = 0.05). CONCLUSIONS: The present study shows that PET-CT is a valuable tool for primary staging and response control in multimodal treatment of patients with EC.


Asunto(s)
Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias/métodos , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Esofagectomía/métodos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Cuidados Paliativos/métodos , Radioterapia Adyuvante , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Análisis de Supervivencia , Resultado del Tratamiento
7.
J Biomed Biotechnol ; 2010: 484987, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20011071

RESUMEN

A critical function of the epithelial lining is to form a barrier that separates luminal contents from the underlying interstitium. This barrier function is primarily regulated by the apical junctional complex (AJC) consisting of tight junctions (TJs) and adherens junctions (AJs) and is compromised under inflammatory conditions. In intestinal epithelial cells, proinflammatory cytokines, for example, interferon-gamma (IFN-gamma), induce internalization of TJ proteins by endocytosis. Endocytosed TJ proteins are passed into early and recycling endosomes, suggesting the involvement of recycling of internalized TJ proteins. This review summarizes mechanisms by which TJ proteins under inflammatory conditions are internalized in intestinal epithelial cells and point out comparable mechanism in nonintestinal epithelial cells.


Asunto(s)
Endocitosis/fisiología , Inflamación/metabolismo , Proteínas de la Membrana/metabolismo , Uniones Estrechas/metabolismo , Animales , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo
8.
Langenbecks Arch Surg ; 394(4): 623-9, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18594855

RESUMEN

INTRODUCTION: Big masses of the mediastinum causing dysphagia are both a diagnostic and a therapeutic challenge for gastroenterologists and surgeons. Besides of hernia and cysts, lymphomas, neurogenic as well as benign or malignant mesenchymal tumors are potential diagnoses. Since biopsies are often not conclusive, mostly the diagnosis can only be secured postoperatively. CASE REPORTS: In this article, we report on two cases of giant esophageal leiomyoma, in which radical surgical resection was performed for the relief of symptoms and to secure diagnosis accurately. The specimen revealed tumors of 750 and 550 g, respectively. Only histological and immunohistochemical examination could rule out malignant low grade leiomyosarcoma. CONCLUSION: Esophageal leiomyomas are approximately 50 times less common than carcinoma, but they are the most common benign tumors of the esophagus. Whereas removal of the tumor by enucleation by conventional thoracotomy or thoracoscopy can be performed in most cases, esophagectomy is required for giant tumors of the esophagus.


Asunto(s)
Neoplasias Esofágicas/cirugía , Esofagectomía , Leiomioma/cirugía , Adulto , Anciano , Endoscopía del Sistema Digestivo , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Humanos , Inmunohistoquímica , Leiomioma/diagnóstico , Leiomioma/metabolismo , Leiomioma/patología , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/patología , Masculino , Tomografía Computarizada por Rayos X
9.
Mucosal Immunol ; 12(4): 909-918, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30971752

RESUMEN

Pathobiology of several chronic inflammatory disorders, including ulcerative colitis and Crohn's disease is related to intermittent, spontaneous injury/ulceration of mucosal surfaces. Disease morbidity has been associated with pathologic release of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). In this report, we show that TNFα promotes intestinal mucosal repair through upregulation of the GPCR platelet activating factor receptor (PAFR) in the intestinal epithelium. Platelet activating factor (PAF) was increased in healing mucosal wounds and its engagement with epithelial PAFR leads to activation of epidermal growth factor receptor, Src and Rac1 signaling to promote wound closure. Consistent with these findings, delayed colonic mucosal repair was observed after administration of a neutralizing TNFα antibody and in mice lacking PAFR. These findings suggest that in the injured mucosa, the pro-inflammatory milieu containing TNFα and PAF sets the stage for reparative events mediated by PAFR signaling.


Asunto(s)
Epitelio/metabolismo , Membrana Mucosa/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Cicatrización de Heridas , Proteína ADAM10/metabolismo , Animales , Biomarcadores , Epitelio/patología , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Ratones , Membrana Mucosa/patología , FN-kappa B/metabolismo , Glicoproteínas de Membrana Plaquetaria/genética , Especies Reactivas de Oxígeno/metabolismo , Receptores Acoplados a Proteínas G/genética , Proteína de Unión al GTP rac1/metabolismo
10.
Am J Gastroenterol ; 103(4): 894-900, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18371136

RESUMEN

OBJECTIVES: Diagnostic and therapeutic interventions in the biliary and pancreatic system in the previously operated patient by conventional endoscopic retrograde cholangiopancreaticography (ERCP) are difficult and, depending on the surgical procedure, in many cases unsuccessful. We describe our experience of ERCP performed with a double balloon enteroscope (DBE) as an alternative examination technique for these patients. METHODS: In a retrospective analysis of all DBE procedures at our department between November 2004 and June 2007, 11 patients were identified with various anatomic variations in whom ERCP was performed using a DBE. RESULTS: In 72% of the patients, previous conventional ERCP examinations failed (8/11). In these patients, DBE-ERCP was successful in 63%. The overall success rate of DBE-ERCP in all patients was 64% (7/11 patients). In those patients, interventions such as papillotomy, calculus extractions, as well as stent placement could be performed even though tools for DBE-ERCP are still very limited. Despite most of the DBE-ERCPs having included therapeutic interventions, no major complications occurred in our case series and minor side effects were restricted to meteorism and mild to moderate abdominal pain. CONCLUSIONS: DBE-ERCP is an alternative method for diagnostic as well as therapeutic interventions in the biliary as well pancreatic system in the operated patient. However, it should be limited to selected patients, e.g., with contraindications for PTC, as it is a time-consuming as well as a cost-intensive procedure.


Asunto(s)
Enfermedades de las Vías Biliares/diagnóstico , Enfermedades de las Vías Biliares/terapia , Cateterismo/instrumentación , Colangiopancreatografia Retrógrada Endoscópica , Endoscopios Gastrointestinales , Enfermedades Pancreáticas/diagnóstico , Enfermedades Pancreáticas/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Resultado del Tratamiento
11.
J Gastrointest Surg ; 12(2): 256-62, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17823841

RESUMEN

BACKGROUND: Using an endoscopic ultrasound (EUS) miniprobe, even highly stenotic esophageal cancers precluding the passage of a conventional probe can be examined without prior dilatation. OBJECTIVE: To assess: (1) staging accuracy of conventional EUS probe and miniprobe, (2) variables influencing staging accuracy, (3) endoscopic features predicting tumor stage. METHODS: Ninety-seven consecutive patients with esophageal cancer undergoing complete surgical resection were included. Preoperative EUS was performed using a conventional probe in nonstenotic tumors and a miniprobe in stenotic tumors. Accuracy of EUS for T and N stages was compared to pathohistological staging. RESULTS: Overall EUS staging accuracy was 73.2% for T stage and 74.2% for N stage. It was similar for the miniprobe used in stenotic tumors vs the conventional probe used in nonstenotic tumors. Based on EUS, 84.5% of the patients would have been assigned to the appropriate therapy protocol (primary surgery vs neoadjuvant therapy). Endoscopic tumor features had no influence on staging accuracy. Tumor length >5 cm predicted advanced T and nodal positive stages. CONCLUSIONS: The miniprobe allows adequate EUS staging of stenotic esophageal tumors precluding the passage of a conventional probe. Therefore, dilatation therapy of stenotic cancers to conduct conventional EUS should be avoided.


Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Endosonografía/métodos , Neoplasias Esofágicas/patología , Unión Esofagogástrica , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/cirugía , Constricción Patológica , Endosonografía/instrumentación , Neoplasias Esofágicas/cirugía , Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Mol Biol Cell ; 16(10): 5040-52, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16055505

RESUMEN

Disruption of epithelial barrier by proinflammatory cytokines such as IFN-gamma represents a major pathophysiological consequence of intestinal inflammation. We have previously shown that IFN-gamma increases paracellular permeability in model T84 epithelial cells by inducing endocytosis of tight junction (TJ) proteins occludin, JAM-A, and claudin-1. The present study was designed to dissect mechanisms of IFN-gamma-induced endocytosis of epithelial TJ proteins. IFN-gamma treatment of T84 cells resulted in internalization of TJ proteins into large actin-coated vacuoles that originated from the apical plasma membrane and resembled the vacuolar apical compartment (VAC) previously observed in epithelial cells that lose cell polarity. The IFN-gamma dependent formation of VACs required ATPase activity of a myosin II motor but was not dependent on rapid turnover of F-actin. In addition, activated myosin II was observed to colocalize with VACs after IFN-gamma exposure. Pharmacological analyses revealed that formation of VACs and endocytosis of TJ proteins was mediated by Rho-associated kinase (ROCK) but not myosin light chain kinase (MLCK). Furthermore, IFN-gamma treatment resulted in activation of Rho GTPase and induced expressional up-regulation of ROCK. These results, for the first time, suggest that IFN-gamma induces endocytosis of epithelial TJ proteins via RhoA/ROCK-mediated, myosin II-dependent formation of VACs.


Asunto(s)
Membrana Celular/fisiología , Endocitosis , Interferón gamma/fisiología , Proteínas de la Membrana/metabolismo , Miosina Tipo II/fisiología , Uniones Estrechas/fisiología , Vacuolas/fisiología , Actinas/metabolismo , Adenosina Trifosfato/metabolismo , Línea Celular , Membrana Celular/ultraestructura , Polaridad Celular , Claudina-1 , Células Epiteliales/fisiología , Células Epiteliales/ultraestructura , Interferón gamma/farmacología , Péptidos y Proteínas de Señalización Intracelular , Quinasa de Cadena Ligera de Miosina/metabolismo , Ocludina , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Recombinantes , Regulación hacia Arriba , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rho
13.
Ann N Y Acad Sci ; 1072: 242-52, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17057204

RESUMEN

A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the underlying interstitium. This intestinal barrier is primarily regulated by the apical junctional complex (AJC) consisting of tight junctions (TJs) and adherens junctions (AJs) and is compromised in a number of intestinal diseases, including inflammatory bowel disease (IBD). In vitro studies have demonstrated that proinflammatory cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), that are increased in the intestinal mucosa of patients with IBD can induce a leaky mucosal barrier. There is a growing evidence that the increased permeability and altered AJC structure observed in IBD are mediated by internalization of junctional proteins. This review summarizes barrier defects observed in IBD and addresses mechanisms by which proinflammatory cytokines, such as IFN-gamma and TNF-alpha, modulate AJC structure and epithelial barrier function.


Asunto(s)
Enfermedades Inflamatorias del Intestino/fisiopatología , Uniones Estrechas/fisiología , Uniones Adherentes/inmunología , Uniones Adherentes/patología , Uniones Adherentes/fisiología , Citocinas/inmunología , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/patología , Interferón gamma/inmunología , Modelos Biológicos , Modelos Inmunológicos , Uniones Estrechas/inmunología , Uniones Estrechas/patología
14.
FASEB J ; 19(8): 923-33, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15923402

RESUMEN

Increased epithelial permeability is observed in inflammatory states. However, the mechanism by which inflammatory mediators such as IFN-gamma increase epithelial permeability is unknown. We recently observed that IFN-gamma induces disassembly of tight junctions (TJ); in this study we asked whether such TJ disassembly is mediated by endocytosis of junctional proteins. The role of three major internalization pathways in disruption of TJ in IFN-gamma-treated intestinal epithelial cells was analyzed using selective inhibitors and markers of the pathways. No role for the clathrin- and caveolar-mediated endocytosis in the IFN-gamma-induced internalization of TJ proteins was observed. However, inhibitors of macropinocytosis blocked internalization of TJ proteins and junctional proteins colocalized with macropinocytosis markers, dextran and phosphatidylinositol-3,4,5-trisphosphate. Internalized TJ proteins were identified in early and recycling endosomes but not in late endosomes/lysosomes. These results for the first time suggest that IFN-gamma produces a leaky epithelial barrier by inducing macropinoytosis of TJ proteins.


Asunto(s)
Endocitosis/efectos de los fármacos , Interferón gamma/farmacología , Proteínas/metabolismo , Uniones Estrechas/química , Uniones Estrechas/metabolismo , Caveolas/efectos de los fármacos , Caveolas/metabolismo , Línea Celular , Vesículas Cubiertas por Clatrina/efectos de los fármacos , Vesículas Cubiertas por Clatrina/metabolismo , Dextranos/metabolismo , Endosomas/química , Endosomas/metabolismo , Epitelio/ultraestructura , Técnica del Anticuerpo Fluorescente , Intestinos/ultraestructura , Lisosomas/química , Microscopía Inmunoelectrónica , Fosfatos de Fosfatidilinositol/metabolismo , Pinocitosis/efectos de los fármacos , Proteínas/análisis
15.
Anticancer Res ; 23(2C): 1875-81, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12820472

RESUMEN

BACKGROUND: Primary locally advanced and recurrent colorectal cancer still present a significant clinical challenge. Local failure rates are high in both situations. Promising results have been reported by combined radiochemotherapy, extensive surgery and intraoperative radiation therapy (IORT). Our aim was to perform IORT at a "non-dedicated" facility to improve the local tumour control rate without increasing the complication rate. MATERIALS AND METHODS: From February 1997 to April 2001, 19 patients with recurrent and 4 patients with primary locally advanced colorectal cancer underwent surgery and IORT. The histology was adenocarcinoma in all cases. A complete removal of the tumour was possible in 11 patients, while an incomplete resection was achieved in 12 cases. IORT doses ranged from 10-20 Gy and electron energies from 6-14 MeV were used. Fourteen patients had pre- or postoperative external beam radiochemotherapy. RESULTS: After a median follow-up of 27 months, 18 patients (78%) are alive. Five of these patients have a progressive disease. Five patients (22%) died in progressive disease. The amount of residual cancer remaining after surgery is an important factor regarding treatment outcome. Complications were observed in 8 patients (35%). These complications were severe only in 4 patients (17%). Fifteen patients (65%) have had no complications at all. No perioperative or postoperative deaths were seen. CONCLUSION: IORT combined with radical surgery, external beam radiotherapy and systemic chemotherapy is feasible at a "non-dedicated" facility without increasing the postoperative complications. A complete resection is the most important factor for a favourable outcome.


Asunto(s)
Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Cuidados Intraoperatorios/métodos , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Adenocarcinoma/tratamiento farmacológico , Adulto , Anciano , Terapia Combinada , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico
16.
Int J Surg ; 12(12): 1428-33, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25448666

RESUMEN

BACKGROUND: Laparoscopic splenectomy has been proposed to be the standard therapy for adult patients with medically refractory immune thrombocytopenia (ITP). However, due to inconsistent definitions of response, variable rates of long term response have been reported. Furthermore, new medical treatment options are currently challenging the role of splenectomy. The aims of this study were to (1) analyze long term response after splenectomy according to recently defined consensus criteria, (2) identify possible predictive response factors. METHODS: A case series of 72 consecutive patients with ITP undergoing laparoscopic splenectomy was retrospectively studied using univariate and multivariate analysis as well as logrank tests. RESULTS: Median follow-up was 32 (2-110) months. Mortality was 0% and morbidity was 8.2%. Response to splenectomy was achieved in of 63/72 patients (87.5%). Loss of response occurred in 19/63 (30.2%) in median after 3 (range 2-42) months. Preoperative platelet counts after boosting with steroids and immunoglobulins as well as the postoperative rise in platelet counts were statistically significant factors for response upon both univariate and multivariate analysis, whereas age, gender, body mass index, ASA classification, disease duration, accessory spleens, splenic weight, conversion to open surgery, or perioperative complications were not. Patients with a postoperative rise in platelet counts >150,000/µL had a significant better chance on stable long term response than those with a smaller increment (P < 0.001). CONCLUSIONS: Laparoscopic splenectomy is an effective and safe treatment option in order to obtain stable long term response in patients with ITP. Perioperative platelet counts are predictive factors of long term response.


Asunto(s)
Consenso , Laparoscopía , Púrpura Trombocitopénica Idiopática/cirugía , Esplenectomía/métodos , Análisis de Varianza , Estudios de Cohortes , Femenino , Humanos , Laparoscopía/efectos adversos , Modelos Lineales , Masculino , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/sangre , Estudios Retrospectivos , Bazo/cirugía , Esplenectomía/efectos adversos , Resultado del Tratamiento
17.
Thorac Cancer ; 3(2): 117-124, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-28920288

RESUMEN

Esophagectomy is a high-risk procedure that, despite advances over past years, is still associated with high morbidity and mortality. Anastomotic insufficiency is a devastating surgical complication as it is linked to postoperative morbidity and is the main cause for postoperative mortality. It can lead to sepsis and necessitate re-operation, further increasing morbidity and mortality through additional complications brought on by the repeated invasive procedures. However, not all anastomotic leakages entail such a critical course of events and can be sufficiently dealt with by less invasive measures. As a consequence, the approach to anastomotic leakage must be carefully selected in order to minimize additional procedure-related risks while ensuring adequate therapy. In this setting, less invasive treatments such as esophageal stents and clips, application of vicryl plugs in combination with fibrin glue, and endoscopic insertion of vacuum sponges, have emerged in recent years and become a viable alternative in the management of certain leakages. This review presents current algorithms for detection, classification and treatment of leakages after esophagectomy.

18.
Minim Invasive Surg ; 2012: 106878, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22619710

RESUMEN

Background. Single Port Laparoscopic Surgery (SPLS) is being increasingly employed in colorectal surgery for benign and malignant diseases. The particular role for SPLS in inflammatory bowel disease (IBD) has not been determined yet. In this review article we summarize technical aspects and short term results of SPLS resections in patients with Crohn's disease or ulcerative colitis. Methods. A systematic review of the literature until January 2012 was performed. Publications were assessed for operative techniques, equipment, surgical results, hospital stay, and readmissions. Results. 34 articles, published between 2010 and 2012, were identified reporting on 301 patients with IBD that underwent surgical treatment in SPLS technique. Surgical procedures included ileocolic resections, sigmoid resections, colectomies with end ileostomy or ileorectal anastomosis, and restorative proctocolectomies with ileum-pouch reconstruction. There was a wide variety in the surgical technique and the employed equipment. The overall complication profile was similar to reports on standard laparoscopic surgery in IBD. Conclusions. In experienced hands, single port laparoscopic surgery appears to be feasible and safe for the surgical treatment of selected patients with IBD. However, evidence from prospective randomized trials is required in order to clarify whether there is a further benefit apart from the avoidance of additional trocar incisions.

19.
J Gastrointest Surg ; 15(4): 576-83, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21152994

RESUMEN

AIM OF THE STUDY: To clarify the intestinal cancer risk in Crohn's disease (CD). METHODS: 20 clinical studies (1965-2008) with a total of 40,547 patients with Crohn's disease-associated cancer (CDAC) were included in the meta-analysis ("inverse variance weighted" method). RESULTS: The incidence of CDAC in any CD patient was 0.8/1,000 person years duration (pyd) (CI, 0.6-1.0). The incidences of different carcinomas were: colorectal cancer 0.5/1,000 pyd (CI, 0.3-0.6), small bowel carcinoma 0.3/1,000 pyd (CI, 0.1-0.5), and cancers arising from CD-associated fistulae 0.2/1,000 pyd (CI, 0.0-0.4). Compared to the incidence in an age-matched standard population, the risk of colorectal cancer was increased by factor 2-3 and of small bowel cancer by factor 18.75, respectively. Mean patient age at diagnosis of CD-associated colorectal cancer was 51.5 years, thus 20 years earlier than in a standard population. The mean duration of CD until diagnosis of CDAC was 18.3 years. Duration of CD, age at diagnosis of CD, and anatomical area of CD involvement had no significant influence on cancer incidence. CONCLUSIONS: CD is a risk factor for colorectal cancer, small bowel cancer, and fistula cancer; however, compared to ulcerative colitis, cancer risk is moderate.


Asunto(s)
Enfermedad de Crohn/complicaciones , Neoplasias Intestinales/etiología , Adulto , Humanos , Incidencia , Neoplasias Intestinales/diagnóstico , Neoplasias Intestinales/epidemiología , Persona de Mediana Edad , Prevalencia , Reino Unido/epidemiología , Estados Unidos/epidemiología
20.
Ann N Y Acad Sci ; 1165: 183-9, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19538305

RESUMEN

Impairment of the intestinal barrier is a key event in various gastrointestinal diseases, including inflammatory bowel diseases, celiac disease, gastrointestinal infections, diarrhea, and critical illness. Recent studies demonstrated that probiotic bacteria have beneficial effects in these diseases by effectively improving intestinal barrier function. This article reviews available data on the effect of probiotics on intestinal barrier function in vitro, in animal models, and in clinical studies.


Asunto(s)
Enfermedades Inflamatorias del Intestino/terapia , Mucosa Intestinal/metabolismo , Intestinos/microbiología , Probióticos/uso terapéutico , Animales , Escherichia coli Enteropatógena/patogenicidad , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Intestinos/citología , Intestinos/inmunología
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