RESUMEN
PURPOSE: Total parenteral nutrition causes liver damage in patients with short bowel syndrome (SBS), in whom intestinal failure-associated liver disease (IFALD) is the strongest risk factor for mortality. We previously demonstrated the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4-Is) for nutritional absorption and intestinal barrier function enhancement. Herein, we investigated the efficacy of DPP4-Is in preventing liver damage in SBS rat models. METHODS: Rats were allocated to one of five groups: normal saline (NS) + sham, DPP4-I + sham, NS + SBS, DPP4-I + SBS, and GLP-2 + SBS. DPP4-I or NS was administered orally once daily. Serum aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and total bile acid levels were measured to assess liver function. Moreover, we evaluated liver damage using the SAF (steatosis activity fibrosis) score, which is also used to assess nonalcoholic steatohepatitis. RESULTS: ALT levels and SAF scores were significantly lower in the DPP4-I + SBS group than in the NS + SBS group. Jejunal and ileal villus heights were significantly higher in the DPP4-I + SBS group than in the GLP-2 + SBS group. CONCLUSIONS: The downregulation of ALT levels and SAF scores triggered by DPP4-I use may be correlated with DPP4-I-induced adiposis inhibition in SBS and NASH models. Therefore, DPP4-I may be used to reduce IFALD in patients with SBS.
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Inhibidores de la Dipeptidil-Peptidasa IV , Fallo Hepático , Enfermedad del Hígado Graso no Alcohólico , Síndrome del Intestino Corto , Ratas , Animales , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/tratamiento farmacológico , Dipeptidil Peptidasa 4 , Péptido 2 Similar al Glucagón , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéuticoRESUMEN
PURPOSE: Bacterial overgrowth commonly occurs and favors bacterial translocation in short bowel syndrome (SBS). Glucagon-like peptide-2 (GLP-2) is effective for treating SBS, but is rapidly inactivated by dipeptidyl peptidase IV (DPP4). DPP4 inhibitor (DPP4I) is known to be effective for treating SBS. Here, we investigated cell junction protein function following DPP4I administration in a mouse model of SBS. METHODS: Mice were divided into four groups: naïve (n = 5), naïve + DPP4I (n = 6), control (n = 6), and DPP4I (n = 5). All control and DPP4I mice had 50% of their proximal small bowel resected. DPP4I or normal saline was administered orally twice daily from days 1-7 postoperatively. The functions of cell junction proteins were assessed by RT-PCR and immunohistochemistry. Body weights and blood glucose levels were recorded. RESULTS: E-Cadherin was significantly higher in the DPP4I group than in the control group. E-Cadherin, occludin, and claudin-4 were significantly higher in the naïve group than in the control group. Positive staining for E-cadherin and occludin varied widely between the control and DPP4I groups. CONCLUSION: Up-regulation of E-cadherin and occludin by DPP4I may be correlated with the anti-inflammatory action of DPP4I. Therefore, DPP4I may reduce bacterial translocation in SBS.
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Cadherinas/metabolismo , Claudina-4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Ocludina/metabolismo , Síndrome del Intestino Corto/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Regulación hacia ArribaRESUMEN
BACKGROUND: Interactions between enteric neural crest-derived cells (ENCC) and the surrounding intestinal microenvironment, such as the extracellular matrix (ECM), are critical for regulating enteric nervous system (ENS) development. Integrins are the major receptors for ECM molecules, such as laminin, which have been reported to be involved in the pathogenesis of Hirschsprung's disease. In this study, we examined the expression of ß1 integrin in the endothelin receptor B (Ednrb) knock out (KO) mouse gut, which presents with an aganglionic colon. METHODS: A Sox10-Venus-positive Ednrb KO mouse, where ENCC is labeled with fluorescent protein, 'Venus', was created. Sox10-Venus-positive Ednrb wild type (WT) were used as controls. Small intestine, proximal colon and distal colon were dissected on E13.5 and E15.5 and ß1 integrin expression of the gut tissue was examined by immunohistochemistry and real time RT-PCR. The cells of the gut dissected on E11.5 were isolated and cultured for 2 days. Venus-positive ENCC were immunostained with ß1 integrin and Tuj-1, which is a marker for neurons. RESULTS: The expression of ß1 integrin was not significantly different between KO and WT in all parts of the gut examined. However, the ß1 integrin expression in the isolated ENCC was significantly decreased in KO compared to WT. The average threshold area was 42.98 ± 17.47% in KO and 73.53 ± 13.77 in WT (p < 0.001). CONCLUSIONS: We demonstrated that ß1 integrin expression was specifically decreased in ENCC in Ednrb KO mice. Our results suggest that impaired interaction between integrin and its ligands may disturb normal ENS development, resulting in an aganglionic colon.
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Integrina beta1/metabolismo , Mucosa Intestinal/metabolismo , Cresta Neural/metabolismo , Animales , Enfermedad de Hirschsprung/etiología , Ratones Noqueados , Modelos Animales , Receptor de Endotelina B/genéticaRESUMEN
PURPOSE: The incidence of perforation during antibiotic therapy (AT) of children triaged as non-complicated acute appendicitis (NC-Ap) was investigated. METHODS: Abdominal ultrasonography (US) and/or computed tomography (CT) scans from cases of perforation identified at appendectomy for failed AT were reassessed blindly by a panel of board-certified specialists for any evidence of pre-AT morbidity suggestive of perforation. RESULTS: Of 521 cases triaged as NC-Ap, symptoms resolved with AT in 452 cases (86.8%). All 69/521 (13.2%) cases with persistent symptoms had urgent appendectomy, and 12/521 (2.3%) were found to have perforated. Blind reassessment of US and/or CT scans from these cases identified seven with evidence of perforation when they were triaged as NC-Ap. Thus, the actual incidence of perforation during AT for NC-Ap was actually 12-7 = 5/521 (0.95%). CONCLUSIONS: Perforation is generally believed to be a complication of AT, but inappropriate triaging of cases for AT can bias results by artificially inflating the number of perforations, in this study, by more than double. We are the first to assess the unbiased incidence of perforation during AT for NC-Ap, by reassessing pre-AT US and/or CT scans. The incidence of perforation during AT is actually negligible.
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Antibacterianos/uso terapéutico , Apendicitis/diagnóstico por imagen , Apendicitis/tratamiento farmacológico , Adolescente , Apendicectomía , Apendicitis/cirugía , Niño , Preescolar , Urgencias Médicas , Femenino , Humanos , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Triaje , UltrasonografíaRESUMEN
BACKGROUND: Combination therapy with two different traditional medicine formulations called hainosankyuto and juzentaihoto (TJ-122 and TJ-48; Tsumura & Co, Tokyo, Japan) may be effective for perianal abscess (PA), but their effectiveness has not been established. The present study investigated the effectiveness of combination therapy with TJ-122 and TJ-48 as the most effective conservative treatment for PA. METHODS: We identified 69 patients with PA under 2 years of age and divided them into four groups according to the formulations used: group 1, TJ-122 (n = 17); group 2, TJ-48 (n = 14); group 3, TJ-122 and TJ-48 (n = 19); and group 4, no traditional medicines (n = 19). Treatment was continued for 3-6 months after resolution of the PA in groups 1 and 2, and for 1 year in group 3. Age at presentation, duration of purulent discharge (PD), frequency of surgical intervention (incision and drainage [ID]; fistulotomy/fistulectomy), and recurrence rates were statistically analyzed. RESULTS: Mean age (months) was 8.6 ± 9.2, 6.9 ± 7.3, 5.2 ± 4.7, and 3.8 ± 3.1 in groups 1, 2, 3, and 4, respectively (P = n.s.). Mean PD (weeks) was 2.5 ± 2.2, 7.1 ± 10.8, 2.0 ± 0.0, and 2.7 ± 1.0, respectively. Duration of PD was significantly longer in group 2 than in groups 1 and 3 (P < 0.05). Mean number of ID procedures was 1.0 ± 0.2, 2.3 ± 0.5, 0, and 1.6 ± 0.2, respectively. Group 1 had significantly less ID than group 2 (P < 0.01). Recurrence rates were 6%, 36%, 0%, and 32%, respectively. Groups 1 and 3 had significantly less recurrence than group 2 (P < 0.05), and group 3 had significantly less recurrence than group 4 (P < 0.01). CONCLUSIONS: Combination therapy with TJ-122 and TJ-48 decreased recurrence and surgical intervention to zero in this study, demonstrating high effectiveness for treating PA in children.
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Absceso/tratamiento farmacológico , Enfermedades del Ano/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Medicina Tradicional China/métodos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Impaired function of the internal anal sphincter (IAS) may be implicated in postoperative obstructed defecation (POD) that may complicate Hirschsprung's disease (HD) patients. While innervation of part of the IAS in HD has been reported, accurate details based on anatomic landmarks that can explain the clinical morbidity seen in POD are lacking, and there appear to be no studies that specifically document the innervation of the "entire" IAS in HD. We used endothelin receptor-B knockout mice to represent HD (HD-mice) and C57B6 wild mice as controls (C-mice) to investigate the innervation of the entire IAS to assess the pathophysiology of POD experimentally. METHODS: The end-point of the longitudinal muscle layer was used to define the border between the IAS and the circular muscle layer (CML). Specimens of anorectum from HD- and C-mice were immunostained with PGP 9.5 and S100 as general nerve markers, nNOS and VIP as parasympathetic nerve markers, TH as a sympathetic nerve marker, and calretinin as a reliable diagnostic marker for HD. Immunostained cells/fibers were quantified using ImageJ. RESULTS: On fluorescence microscopy, PGP 9.5, nNOS, and calretinin were significantly lower in the IAS of HD-mice than in C-mice (p < 0.05, respectively), while there were no significant differences between HD-mice and C-mice for S100, VIP, or TH. CONCLUSION: We are the first to confirm that the expression of histochemical markers of innervation is abnormal throughout the "entire" IAS in HD-mice. Application of this finding may be beneficial for preventing POD and requires further research.
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Canal Anal/inervación , Canal Anal/metabolismo , Enfermedad de Hirschsprung/metabolismo , Músculo Liso/metabolismo , Animales , Biomarcadores/metabolismo , Calbindina 2/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Fluorescente , Óxido Nítrico Sintasa de Tipo I/metabolismo , Proteínas S100/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
INTRODUCTION: To review the surgical treatment of hypospadias (HP) associated with disorders of sex development (DSD). PATIENTS AND METHODS: HP cases were assessed for DSD by gross examination for atypical external genitalia, and assessment of hormone levels and karyotype. There were 58 HP cases with concomitant DSD treated between 1999 and 2017. DSD classification, type of HP, sex assignment, hormonal abnormality, surgical strategy, and post-urethroplasty complications (post-UPC) were reviewed. RESULTS: DSD were sex chromosome abnormalities (n = 4), 46,XY (n = 51), 46,XX (n = 1), and 47,XY + 21 (n = 2). HP was perineal: (n = 26), scrotal: (n = 16), penoscrotal: (n = 15), and midshaft: (n = 1); repair was primary (n = 6) or staged (n = 52). Mean age at final urethroplasty (UP) was 4.12 ± 0.21 years; all cases had soft tissue interposition at UP. At mean follow-up 5.16 ± 0.56 years after final UP, observed post-UPC (n = 8; 13.8%) were urethral stenosis (n = 3), urethral diverticulum (n = 2), urethrocutaneous fistula (n = 2), and curvature (n = 1). Mean onset of post-UPC was 1.24 ± 0.77 years (range 0.1-6.3). The second half of our cases (n = 29; treated 2015 ~) had significantly less post-UPC (0/29; 0%) than the first half (8/29; 27.6%) (p = 0.0075). CONCLUSIONS: Although UP for HP + DSD was formidably challenging, we achieved a significant decrease in post-UPC through a combination of surgical techniques and experience.
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Trastornos del Desarrollo Sexual/complicaciones , Trastornos del Desarrollo Sexual/cirugía , Hipospadias/complicaciones , Hipospadias/cirugía , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Perineo/cirugía , Estudios Retrospectivos , Escroto/cirugía , Resultado del Tratamiento , Uretra/cirugíaRESUMEN
PURPOSE: There are surprisingly few reports about reconstructive surgery for severe recurrent/persistent penile curvature (redo-PC). We present our experience. METHODS: We reviewed 9 redo-PC cases we treated between 1998 and 2016. RESULTS: Cases 1-3 and 5 were identified from 111 consecutive hypospadias patients we treated between 1998 and 2016 (4/111; 3.6%). Cases 4 and 6-9 had initial surgery elsewhere. Initial PC was severe (> 45°; n = 5), moderate (30°-45°; n = 1), or unknown (n = 3), treated by dorsal plication (DP) in 4/9 (cases 1-4), chordectomy in 2/9 (cases 5, 6), and unknown in 3/9 (cases 7-9); no case had tunica albuginea incision (TAI). Straightening after initial surgery was confirmed by artificial erection (AE) in 4/9, not confirmed (2/9), and unknown (3/9). Cases 1, 2, 7 and 8 had had previous failed redos. Scarring of buccal mucosa used for urethroplasty caused worse PC in cases 7 and 9. After TAI (n = 6; cases 1, 3-6, and 8) or scar removal with DP (n = 3; cases 2, 7, and 9), AE confirmed successful straightening in all cases, without sequelae after a mean follow-up of 2.6 years. CONCLUSION: TAI was most effective for redo-PC surgery. Preoperative AE and examination under anesthesia should be used to customize treatment.
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Hipospadias/cirugía , Pene/cirugía , Procedimientos de Cirugía Plástica/métodos , Uretra/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Preescolar , Progresión de la Enfermedad , Humanos , Lactante , Masculino , Mucosa Bucal/trasplante , Estudios RetrospectivosRESUMEN
BACKGROUND: We assessed the quality of life (QOL) of postoperative esophageal atresia (EA) with tracheoesophageal fistula (TEF) cases, comparing open with thoracoscopic repair. METHODS: A retrospective review of consecutive EA/TEF repairs (2001-2014) was performed, excluding cases with birth weight less than 2000 g and severe cardiac/chromosomal anomalies. Of 37 cases, 13 had thoracoscopic repair (TR) and 24 had open repair (OR) according to the operating surgeon's preference. QOL was determined regularly by scoring responses to a standard questionnaire about oral intake, vomiting, bougienage, coughing, growth retardation, learning ability, and thoracic deformity. Lower scores reflected poorer outcome. QOL after TR and OR was compared 1 year postoperatively (POQ) and after starting school (ScQ). RESULTS: Subject demographics were similar. Apart from two anastomotic leaks that resolved spontaneously after TR, there were no intraoperative complications or recurrence of TEF. Laparoscopic fundoplication was required for gastroesophageal reflux in four cases (OR 1; TR 3) (p = ns). QOL scores went from 6.5 â 11.5 in OR and 4.6 â 11.3 in TR, respectively. Final ScQ scores were similar, but POQ was significantly higher after OR (p < 0.05). CONCLUSION: Initial QOL scores were significantly lower after TR, but by school age QOL scores were similar.
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Esofagostomía/métodos , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Toracoscopía/métodos , Toracotomía/métodos , Fístula Traqueoesofágica/cirugía , Niño , Preescolar , Esofagostomía/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Masculino , Estudios Retrospectivos , Encuestas y Cuestionarios , Toracoscopía/estadística & datos numéricos , Toracotomía/estadística & datos numéricos , Resultado del TratamientoRESUMEN
AIM: Thoracoscopic lobectomy (TL) and open lobectomy (OL) were compared for treating congenital pulmonary airway malformation (CPAM) with preoperative complications, specifically pneumonia/abscess formation (PA). METHODS: The medical records of 46 CPAM patients treated by lobectomy at our institution from 1990 to 2014 were reviewed retrospectively. Four groups, TL for patients without PA (n = 17; TL-), TL for patients with PA (n = 8; TL+), OL for patients without PA (n = 16; OL-), and OL for patients with PA (n = 5; OL+) were compared for operative time, intra/postoperative complications, blood loss, duration of chest tube insertion, postoperative analgesia, pre: postoperative white blood cell (WBC) ratio, and duration of hospitalization. RESULTS: Operative time for TL+ was longest, but not statistically significant. Incidences of intra/postoperative complications were similar in all groups. Blood loss was significantly less for TL+ versus OL+ (p < .05). WBC ratio was significantly lower in TL+ versus OL+ (p < .05), similar for TL+ and TL-, and significantly higher in OL+ versus OL- (p < .01). Chest tube insertion was significantly longer in OL- versus TL- (p < .01). CONCLUSION: PA would not appear to be a contraindication to perform TL in CPAM. TL is associated with less surgical stress than OL despite longer operative time.
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Malformación Adenomatoide Quística Congénita del Pulmón/cirugía , Absceso Pulmonar/cirugía , Neumonectomía/métodos , Neumonía/cirugía , Malformación Adenomatoide Quística Congénita del Pulmón/complicaciones , Humanos , Lactante , Recién Nacido , Absceso Pulmonar/etiología , Neumonía/etiología , Estudios Retrospectivos , Cirugía Torácica Asistida por Video , ToracotomíaRESUMEN
Bronchogenic cysts are congenital cystic lesions of foregut origin, usually intrapulmonary or mediastinal, while esophageal cysts generally originate within the esophagus. To the best of our knowledge, this is the first report of a case of a completely intramural bronchogenic cyst of the cervical esophagus in a neonate.
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Quiste Broncogénico/cirugía , Quiste Esofágico/cirugía , Quiste Broncogénico/diagnóstico , Quiste Esofágico/diagnóstico , Esófago/patología , Esófago/cirugía , Humanos , Recién Nacido , Imagen por Resonancia Magnética , MasculinoRESUMEN
Glucagon-like peptide-2 (GLP-2) has been shown to be effective in patients with short bowel syndrome (SBS), but it is rapidly inactivated by dipeptidyl peptidase IV (DPP4). We used an orally active DPP4 inhibitor (DPP4-I), MK-0626, to determine the efficacy of this approach to promote adaptation after SBS, determined optimal dosing, and identified further functional actions in a mouse model of SBS. Ten-week-old mice underwent a 50% proximal small bowel resection. Dose optimization was determined over a 3-day post-small bowel resection period. The established optimal dose was given for 7, 30, and 90 days and for 7 days followed by a 23-day washout period. Adaptive response was assessed by morphology, intestinal epithelial cell (IEC) proliferation (proliferating cell nuclear antigen), epithelial barrier function (transepithelial resistance), RT-PCR for intestinal transport proteins and GLP-2 receptor, IGF type 1 receptor, and GLP-2 plasma levels. Glucose-stimulated sodium transport was assessed for intestinal absorptive function. Seven days of DPP4-I treatment facilitated an increase in GLP-2 receptor levels, intestinal growth, and IEC proliferation. Treatment led to differential effects over time, with greater absorptive function at early time points and enhanced proliferation at later time points. Interestingly, adaptation continued in the group treated for 7 days followed by a 23-day washout. DPP4-I enhanced IEC proliferative action up to 90 days postresection, but this action seemed to peak by 30 days, as did GLP-2 plasma levels. Thus DPP4-I treatment may prove to be a viable option for accelerating intestinal adaptation with SBS.
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Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Síndrome del Intestino Corto/metabolismo , Adaptación Fisiológica , Amilasas/sangre , Animales , Glucemia/metabolismo , Proliferación Celular/efectos de los fármacos , Dipeptidil Peptidasa 4/metabolismo , Modelos Animales de Enfermedad , Péptido 2 Similar al Glucagón/metabolismo , Receptor del Péptido 2 Similar al Glucagón , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/citología , Yeyuno/efectos de los fármacos , Yeyuno/ultraestructura , Masculino , Ratones , Receptor IGF Tipo 1/biosíntesis , Receptores de Glucagón/biosíntesis , Transportador 1 de Sodio-Glucosa/biosíntesis , Triazoles/uso terapéutico , Regulación hacia ArribaRESUMEN
Ewing sarcoma (ES) of the bladder is extremely rare. Here we report the successful treatment of the youngest case of ES arising from bladder encountered to date and a literature review. A 10-year-old boy who presented with polyuria and lower abdominal swelling was found to have a 13 cm mass arising from the bladder localized to the center of the lower abdomen. Biopsy confirmed ES. Following chemotherapy, the mass shrank to 5 cm and was found to be localized to the right side of the bladder with invasion of the right vas deferens. One-third of the right side of the bladder and part of the right vas deferens were resected. No viable cancer cells were detected in the resected specimen, and the surgical margins were reported to be negative. The patient is currently well with no recurrence or metastases after 11 months. There are 12 cases of Ewings sarcoma arising from the bladder reported in the English literature; two cases in children. Our case will be the third pediatric case and the youngest.
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Sarcoma de Ewing/cirugía , Vejiga Urinaria/cirugía , Niño , Terapia Combinada , Estudios de Seguimiento , Humanos , Masculino , Sarcoma de Ewing/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Application of distractive forces to small bowel induces intestinal growth, or enterogenesis. This emerging area of research may provide treatment for short bowel syndrome. Glucagon-like peptide 2(GLP-2) has also been reported to induce small bowel growth after bowel resection. We hypothesized that exogenous GLP-2 will result in enhanced distraction-induced enterogenesis. METHODS: Distraction-induced model was performed in 10-wk-old C57BL/6 mice using osmotic forces with high molecular weight polyethylene glycol (PEG)-stretch. Four groups were studied: Control group (PEG-/GLP-2-); PEG-stretch (PEG+/GLP-2-); GLP-2 control (PEG-/GLP-2+); and GLP-2 stretch (PEG+/GLP-2+). GLP-2 was given via subcutaneous osmotic pump over the 5 d of experiment. Morphology was measured by histomicrography. Epithelial cell (EC) proliferation was measured with proliferating cell nuclear antigen immunofluorescent staining. Total intestinal growth and blood vessel volume was assessed with Micro computed tomography volumetry. Vascular endothelial growth factor, fibroblast growth factor 1 and 2, and platelet-derived growth factor were measured by reverse-transcriptase polymerase chain reaction. RESULTS: EC proliferation increased significantly in all groups compared with controls, but was greatest in the GLP-2 stretch group. Diameter and length significantly increased in the PEG-stretch and GLP-2 stretch groups. Moreover, there was statistically greater diameter, crypt depth and EC proliferation in the GLP-2 stretch versus PEG-stretch groups. GLP-2 stretch vessel volume was greater than all other groups and was significantly increased compared with controls. The relative expression of platelet-derived growth factor increased significantly in the PEG-stretch group versus the Control group. CONCLUSIONS: GLP-2 had an additive effect on EC proliferation, tissue growth, histomorphology, and vascularization. We also demonstrated a unique action of GLP-2, the enhancement of intestinal vascularization. The combination of enterogenesis and GLP-2 may yield an improved approach to treat short bowel syndrome.
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Péptido 2 Similar al Glucagón/farmacología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/crecimiento & desarrollo , Síndrome del Intestino Corto/tratamiento farmacológico , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Enterocitos/citología , Péptidos y Proteínas de Señalización Intercelular/genética , Intestino Delgado/irrigación sanguínea , Masculino , Ratones , Ratones Endogámicos C57BL , Neovascularización Fisiológica/efectos de los fármacos , Polietilenglicoles/farmacología , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: We previously demonstrated angiotensin converting enzymes (ACE) over-expression in a dextran-sodium sulfate colitis model; ACE inhibitor (ACE-I) treatment reduced colitis severity in this model. However, ACE-I has not been tested in more immunologically relevant colitis models. AIM: We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model. METHODS: Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.) for 14 days. The ACE-I enalaprilat was given transanally at a dose of 6.25 mg/kg for 21 days. Prednisolone (PSL) with or without enalaprilat were used as therapeutic, comparative groups. All groups were compared to a placebo treated group. Outcome measures were clinical course, histology, abundance of pro-inflammatory cytokines/chemokines, and epithelial barrier function. RESULTS: Enalaprilat exhibited better survival (91 %) versus other treatment groups (PSL: 85.7 %, PSL + ACE-I: 71.4 %, placebo: 66.6 %). The ACE-I and PSL + ACE-I groups showed significantly better histological scores versus placebo mice. ACE-I and the PSL groups significantly reduced several pro-inflammatory cytokines versus placebo mice. FITC-dextran permeability was reduced in the ACE-I and PSL + ACE-I groups. Blood pressure was not affected in ACE-I treated mice compared to placebo mice. CONCLUSIONS: ACE-I was effective in reducing severity of colitis in an IL-10-/- model. The addition of prednisolone minimally augmented this effect. The findings suggest that appropriately dosed ACE-I with or without steroids may be a new therapeutic agent for colitis.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Colitis/inducido químicamente , Enalaprilato/farmacología , Interleucina-10/metabolismo , Animales , Colitis/tratamiento farmacológico , Colitis/patología , Sulfato de Dextran/toxicidad , Interleucina-10/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Distraction-induced intestinal growth may be a novel treatment for short bowel syndrome. Longitudinal, distractive tension created by the application of force creates a significant challenge: to produce adequate force, yet not cause perforation at the fixation points. This paper describes our development of a coupling strategy to allow for successful bowel lengthening. METHODS: A curvilinear hydraulic device was implanted in an isolated Roux limb of small bowel in young Yorkshire pigs. Bowel was lengthened over a 2-week period. Study groups included: Group 1: Twelve silk transmural anchoring sutures into an engineered-coupling ring at the ends of each device. Group 2: Addition of felt pledgets to the coupling rings on the serosal surface of the small bowel. Group 3: Extraluminal use of either thin AlloDerm(®), thick AlloDerm(®), or Strattice™ mesh to anchor the device. RESULTS: Group 1 (suture-only) resulted in a gradual pulling through the suture with increasing tension and no lengthening. Felt pledgets eroded in a similar fashion, causing abdominal sepsis. Thin AlloDerm(®) failed to prevent erosion; however, it protected against gross contamination. Animals in which either thick AlloDerm(®) or Strattice™ mesh was used survived complication free to the study endpoint. Both thick AlloDerm(®) and Strattice™ prevented erosion and perforation allowing for an average of 10.85 cm expansion. CONCLUSION: This study demonstrates the use of either thick AlloDerm(®) or Strattice™ reconstructive tissue matrix which allows for safe and effective coupling. Further, we suggest this approach could be an adjunct to esophageal lengthening procedures.
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Colágeno , Intestino Delgado/cirugía , Procedimientos de Cirugía Plástica/métodos , Prótesis e Implantes , Mallas Quirúrgicas , Animales , PorcinosRESUMEN
BACKGROUND: Distraction-induced enterogenesis, whereby the intestine lengthens with application of linear forces, is an emerging area which may provide a unique treatment for short bowel syndrome. With an increase in overall tissue mass, there is an increase in oxygen and nutrient demand. We hypothesized that a neovascularization within the mesentery is necessary to support the growing small bowel. METHODS: A curvilinear hydraulic device was used to induce growth within the small bowel of Yorkshire pigs, and the intestine was harvested after 14 days. High-resolution gross pictures were recorded of the mesentery at implantation and at harvest, and CT imaging of the bowel and mesentery was performed at harvest after dye injection. RESULTS: After 2 weeks of distraction, an average of 72.5 % (8.7 cm) bowel lengthening was achieved. Gross images of the mesentery between major vessels showed a blossoming of the microvasculature and this was confirmed by CT imaging with 3D reconstruction. Mesenteric sample taken from the distracted segment had a fourfold increase in the volume of microvasculature versus controls. CONCLUSION: Enterogenesis results not only in increased bowel length, but also significant increase in the mesenteric microvascularity. Presumably, this sustains the lengthened segment after application of longitudinal forces.
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Intestinos/crecimiento & desarrollo , Mesenterio/irrigación sanguínea , Animales , Diseño de Equipo , Neovascularización Fisiológica , Investigación/instrumentación , PorcinosRESUMEN
We report on technical modifications we developed for thoracoscopic esophagoesophagostomy in patients with esophageal atresia. They are: (1) placing stay sutures along the edges of the atretic esophagi and exteriorizing them through the thoracic wall to expose the luminal surfaces of the esophagi nicely and relieve tension on the anastomosis; (2) leaving 1/5 of the length of the distal and proximal ends of the atretic esophagi intact before placing the stay sutures, to avoid retraction of the mucosa into the lumen; (3) making the diameter of the proximal esophagus 1.5-2 times larger than the diameter of the distal esophagus to make the shape of the anastomosis more streamlined without notching.
Asunto(s)
Atresia Esofágica/cirugía , Esofagostomía/métodos , Técnicas de Sutura , Toracoscopía/métodos , Esófago/cirugía , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
BACKGROUND: A Z-shaped colorectal side-to-side anastomosis was introduced to improve the Duhamel procedure by eliminating the rectal blind pouch. We retrospectively reviewed all total colonic aganglionosis patients treated by laparoscopy-assisted Duhamel-Z (LapDZ) between 2009 and 2014 focusing on annual fecal continence evaluation scores (CES) as an indicator of outcome. METHODS: LapDZ was performed conventionally. Postoperatively, defecation was regulated with medications and enemas according to our standard protocol. Stool frequency, stool consistency, fecal soiling/incontinence, growth, and severity of enterocolitis were each scored (0-2) to give a total CES (maximum: 10). RESULTS: Eleven subjects (6 males and 5 females) were reviewed. Mean age and mean weight at LapDZ were 10.2 months and 8.4 kg, respectively. Mean length of the aganglionic ileum resected was 19.5 cm. Mean operative time was 6.2 hours. Postoperative recommencement of oral intake took 5.7 days on average. There were no intraoperative complications, no anastomotic leaks or strictures, and no intestinal obstruction. Postoperative blood transfusion was required in 1 case complicated by chronic bleeding. No subject has been constipated postoperatively. Follow-up was for 5 years. The number of subjects who had CES assessments each year was: after 1 year (n = 11), after 2 years (n = 10), after 3 years (n = 10), after 4 years (n = 8), and after 5 years (n = 5). Average annual CES during follow-up were 4.5, 6.1, 7.7, 8.1, and 8.4, respectively. CONCLUSION: LapDZ and strict management of postoperative bowel function may have contributed to improving CES over time.
Asunto(s)
Colon/cirugía , Incontinencia Fecal/etiología , Enfermedad de Hirschsprung/cirugía , Laparoscopía/métodos , Complicaciones Posoperatorias , Recto/cirugía , Anastomosis Quirúrgica/métodos , Preescolar , Incontinencia Fecal/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: CHARGE is our technique for reinforcing the ventral penile shaft with pedicled pericordal/scrotal fat, pedicled perimeatal connective tissue, or a combination of these at the time of initial hypospadias surgery. Such pedicled grafts "charge" poorly developed urethral plates and thin ventral foreskin prior to urethroplasty to improve compromised vascular perfusion that could prevent post-urethroplasty complications (post-UPC). METHODS: We reviewed post-UPC in 179 staged hypospadias repair patients (1997-2015). CHARGE, adopted routinely in 2010 was used in 39 patients (C-group), not indicated in 7 because ventral connective tissue was thick, and not used in 133 (NC-group). Initial hypospadias surgery included foreskin degloving with or without chordectomy, dorsal plication, tunica albuginea incision, or a combination of these. RESULTS: Subject demographics were similar. NC had significantly more post-UPC than C (25 versus 0; p<.01) comprising stenosis (n=14), fistula (n=7), diverticulum (n=2), and wound infection (n=2) that developed after a mean of 0.7±0.2years (range: 1day-2.8years). Extra time taken for CHARGE was less than 15minutes in all cases. Mean follow-up after urethroplasty (years) was significantly shorter in C (1.5±1.0 versus 5.7±3.8) (p<.01), but almost double the time taken to develop post-UPC. CONCLUSION: CHARGE would appear to prevent post-UPC. LEVEL OF EVIDENCE: Retrospective Comparative Study - Level III.