RESUMO
PURPOSE: Fecal incontinence is a problem for many patients born with an anorectal malformation (ARM) that can impact quality of life. It is unknown if racial, ethnic, and socioeconomic disparities relate to fecal continence in these children. We sought to examine outcomes and potential disparities in care. METHODS: We performed a multicenter retrospective study of children > 3y with ARM evaluated at sites participating in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC). The primary outcome was fecal continence. We evaluated for associations between fecal continence and race, sex, age, and insurance status. RESULTS: 509 patients with ARM from 11 institutions were included. Overall, 24% reported complete fecal continence, and fecal continence was associated with older age (p < .001). For school-aged children, 27% reported complete continence, while 53% reported none. On univariate analysis, patients with combined private and public insurance showed lower rates of continence when compared to those with private insurance (23 vs. 12%; p = 0.02). Age was associated with continence on univariate and multivariable analyses. CONCLUSION: Rates of complete fecal continence in this population are low. Differences based on payor status may exist. There were no observed disparities related to sex and race. Further investigation is warranted to improve care for this patient population. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Multi-institutional retrospective comparative study.
Assuntos
Malformações Anorretais , Cirurgia Colorretal , Incontinência Fecal , Humanos , Criança , Malformações Anorretais/cirurgia , Malformações Anorretais/complicações , Estudos Retrospectivos , Reto/cirurgia , Qualidade de Vida , Canal Anal/anormalidades , Incontinência Fecal/epidemiologia , Incontinência Fecal/complicaçõesRESUMO
PURPOSE: Achieving effective anticoagulation during neonatal extracorporeal membrane oxygenation (ECMO) without increasing the risk of hemorrhage remains challenging. The use of antithrombin III (AT-III) for this purpose has been examined, but studies have been limited to intermittent bolus dosing. We aimed to evaluate the efficacy and safety of an institutionally developed AT-III continuous infusion protocol in neonates receiving ECMO for the treatment of congenital diaphragmatic hernia (CDH). METHODS: In this single center, retrospective study, all neonates with a CDH who received ECMO support during the study period were included. Data on anticoagulation labs and therapy, life-threatening bleeding, and circuit changes were analyzed. RESULTS: Eleven patients were divided into two groups: patients with AT-III continuous infusion (n = 5) and without (n = 6). There were no differences in the gestational age (p = 0.29), sex (p = 1.00), ECMO duration (p = 0.59), or initial AT-III levels (p = 0.76) between groups. Patients in the AT-III infusion group had on average 18.5% higher AT-III levels (p < 0.0001). Patients receiving continuous AT-III infusions spent a significantly higher percentage of ECMO time within the therapeutic range, measured using anti-Factor Xa levels (64.9±4.2% vs. 29.1±8.57%, p = 0.008), and required fewer changes to the heparin infusion rate (6.48±0.88 vs 2.38±0.36 changes/day changes/day, p = 0.005). Multivariate analysis revealed continuous infusion of AT-III did not increase the rate of intracranial or surgical bleeding (p = 0.27). CONCLUSION: AT-III as a continuous infusion in CDH neonates on ECMO provides a decreased need to modify heparin infusion and more consistent therapeutic anticoagulation without increasing the risk of life-threatening bleeding.
Assuntos
Oxigenação por Membrana Extracorpórea , Hérnias Diafragmáticas Congênitas , Recém-Nascido , Humanos , Antitrombina III , Oxigenação por Membrana Extracorpórea/métodos , Estudos Retrospectivos , Anticoagulantes/uso terapêutico , Hemorragia , Heparina/uso terapêuticoRESUMO
OBJECTIVE: When patients deteriorate after decannulation from extracorporeal membrane oxygenation (ECMO), a second run of extracorporeal support may be considered. However, repeat cannulation can be difficult and poor outcomes associated with multiple ECMO runs are a concern. The aim of this study was to evaluate outcomes and identify factors associated with survival and mortality in cases of multiple runs of extracorporeal membrane oxygenation. DESIGN: Retrospective cohort analysis of the Extracorporeal Life Support Organization Registry. SETTING: The Extracorporeal Life Support Organization's registry was queried for neonates, children, and adults receiving 2 or more runs of ECMO during the same hospitalization, for any indication, from 1998 to 2015. PATIENTS: 1,818 patients from the Extracorporeal Life Support Organization Registry. RESULTS: Of the 1,818 patients, 1,648 underwent 2 runs and 170 underwent 3 or more runs of ECMO. The survival to discharge rate was 36.7% for 2 runs and 29.4% for 3 or more runs. No significant differences in survival were detected in analysis by decade of ECMO run (p = 0.21). Pediatric patients had less mortality than adults (OR: 0.45, 95%CI: 0.24-0.82). Cardiac support on the first run portrayed worse mortality than pulmonary support regardless of final run indication (OR:1.38, 95%CI: 1.09-1.75). Across all age groups, patients receiving pulmonary support on the last run tended to have higher survival rates regardless of support type on the first run. The only first run complication independently predictive of mortality on the final run was renal complications (OR: 1.60, 95%CI: 1.28-1.99). CONCLUSIONS: Though the use of multiple runs of ECMO is growing, outcomes remain poor for most cohorts. Survival decreases with each additional run. Patients requiring additional runs for a pulmonary indication should be considered prime candidates. Renal complications on the first run significantly increases the risk of mortality on subsequent runs, and as such, careful consideration should be applied in these cases.
Assuntos
Oxigenação por Membrana Extracorpórea , Criança , Humanos , Recém-Nascido , Sistema de Registros , Estudos RetrospectivosRESUMO
Pediatric patients with either functional or organic bowel dysfunction may suffer from constipation and fecal incontinence and represent a complex group in whom management is often difficult. Many noninvasive and invasive treatments have been proposed, with variable efficacy and adverse effects. Transanal irrigation (TAI) is now an accepted alternative, in both children and adults, for bowel dysfunction that has not responded to conservative and medical therapies. There is, however, still some uncertainty about the use of TAI in pediatric populations. Hence, a group of specialists from different nations and pediatric disciplines, all with long-standing experience of bowel management in children, performed a literature search and had round table discussions to determine the best-practice use of TAI in the pediatric patient population. Based on these findings, this article provides best-practice recommendations on indications, patient selection, important considerations before treatment, patient and family training, treatment regimens, troubleshooting, and practical aspects of TAI. We conclude that careful patient selection, a tailored approach, directly supervised training, and sustained follow-up are key to optimize outcomes with TAI in children with functional or organic bowel dysfunction.
Assuntos
Constipação Intestinal/terapia , Incontinência Fecal/terapia , Irrigação Terapêutica/métodos , Adolescente , Canal Anal , Criança , Pré-Escolar , Humanos , Lactente , Seleção de Pacientes , Irrigação Terapêutica/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Angiogenesis, a known pathogenic component of neoplastic and nonneoplastic diseases, serves as a therapeutic target. Vascular endothelial growth factor (VEGF) and angiogenesis are clinically elevated in inflammatory bowel disease. By targeting vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) with receptor tyrosine kinase inhibitors in a murine model of colitis, we hypothesize that angiogenesis will be suppressed and disease severity improved. METHODS AND METHODS: Sorafenib, sunitinib, and axitinib were administered by oral gavage in a murine model of dextran sodium sulfate (DSS) colitis. Inflammation score, microvessel density (MVD), and gene expression of VEGF, VEGFR, platelet-derived growth factor, PDGFR, Ang-2, and epidermal growth factor receptor was assessed. RESULTS: Inflammation and MVD were elevated in groups receiving DSS, but were similar between DSS-only and treatment cohorts. Unexpected weight loss was present in the gavaged groups versus DSS only. In treated groups, VEGFR was significantly decreased (P = 0.002) and VEGF gene expression trended down (P = 0.213) versus DSS only. Neither the platelet-derived growth factor/PDGFR pathway nor the alternative pathways, Ang-2 and epidermal growth factor receptor, were significantly changed from DSS control in treatment cohorts. CONCLUSIONS: This study confirms the association between inflammation and MVD. Antiangiogenic receptor tyrosine kinase inhibitors suppressed the VEGF/VEGFR pathway but the expected decrease in colonic MVD did not follow, suggesting possible involvement of other angiogenic pathway(s). In the DSS model of colitis, vehicle selection and mouse strain can impact disease response.
Assuntos
Colite/tratamento farmacológico , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Indóis/uso terapêutico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirróis/uso terapêutico , Animais , Axitinibe , Colite/metabolismo , Colite/patologia , Colite/fisiopatologia , Imidazóis/farmacologia , Indazóis/farmacologia , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microvasos/efeitos dos fármacos , Microvasos/patologia , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirróis/farmacologia , Sorafenibe , Sunitinibe , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of the present study was to describe the quality of life and parenting stress associated with a child with fecal incontinence (FI). METHODS: Female caregivers (nâ=â170) of children of 3 to 12 years age with FI completed a broad and general measure of quality of life and a measure of parenting stress. Results were compared with proxy reports for a normative sample of healthy children. RESULTS: Caregivers of children with FI reported significantly impaired quality of life for their children and increased parenting stress in all of the respective domains relative to healthy controls. Impairments reported by caregivers were large in magnitude. Similarly, rates of parenting stress were at or greater than the 98th percentile for caregivers of children with FI. CONCLUSIONS: Children with fecal incontinence and their families are in need of interventions targeting their quality of life and the stress associated with caregiving. FI appears to be particularly stressful for caregivers who may be in need of support beyond medical management of their child's bowel. Moreover, additional refinements in disease-specific quality of life assessment are needed in this population. Such refinement would allow for more precise measurement of the quality of life processes that are unique to FI.
Assuntos
Incontinência Fecal/psicologia , Pais/psicologia , Qualidade de Vida , Estresse Psicológico/psicologia , Cuidadores/psicologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Extensive heterotopic gastric mucosa of the small intestine is a rare, but potentially life-threatening condition characterized by multifocal or long-segment heterotopic gastric mucosa within the bowel lumen that is often associated with other anomalies including malrotation and annular pancreas. Although the imaging findings are characteristic, this entity may be unrecognized due to its unusual imaging appearance and rarity. CT or MR enterography and 99mTc-sodium pertechnetate scintigraphy can provide complementary information that enables specific diagnosis and accurate assessment of disease extent. We present a case of extensive heterotopic gastric mucosa of the small intestine imaged by simultaneous, combined 99mTc-sodium pertechnetate single photon-emission computed tomography (SPECT)/CT enterography to both familiarize the reader with the condition and describe an imaging strategy that enables specific diagnosis and assists with treatment planning.
Assuntos
Coristoma/diagnóstico por imagem , Enteropatias/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Imagem Multimodal , Endoscopia por Cápsula , Criança , Coristoma/cirurgia , Diagnóstico Diferencial , Feminino , Mucosa Gástrica , Humanos , Enteropatias/cirurgia , Intestino Delgado/cirurgia , Compostos Radiofarmacêuticos , Pertecnetato Tc 99m de Sódio , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Angiogenesis is a known pathologic factor in chronic inflammatory diseases. Regarding the murine dextran sodium sulfate (DSS) colitis model, different mouse strains produce variable clinical and inflammatory responses. We hypothesize that DSS colitis applied to diverse mouse strains will similarly elevate colonic microvessel density in parallel with inflammation, but will do so with different angiogenic profiles. MATERIALS AND METHODS: We induced DSS colitis in 129S2/SvPas, BALB/c, and C57BL/6 mice, then performed histologic and molecular analysis at day 7 to evaluate colonic inflammation and angiogenesis. RESULTS: Inflammation and microvessel density were similarly increased in DSS groups. The C57BL/6 cohort mounted a more severe colitis with 25% weight loss and greater colonic ulceration. Gene expression of angiogenic factors at baseline and in colitis groups were widely variable among strains. BALB/c mice exhibited higher angiogenic gene expression in control and DSS groups compared with other strains, specifically platelet-derived growth factor, angiopoietin-1, angiopoietin-1 (Ang-2), vascular endothelial growth factor receptor, and PDGF receptor. When evaluating the effect of DSS relative to controls, BALB/c mice were not significantly affected. 129S2/SvPas mice exhibited broad suppression of growth factors, significantly platelet-derived growth factor, Ang-2, and PDGF receptor. In contrast, C57BL/6 mice displayed increased gene expression, especially for angiopoietin-1 and Ang-2. CONCLUSIONS: Genetic heterogeneity influences the angiogenic profile elicited by DSS colitis. We demonstrate that within a model of murine colitis, mouse strain significantly affects inflammation-associated angiogenesis. These results may impact strain selection when using a colitis model focusing on inflammation and angiogenesis. Future studies to further define the angiogenesis pathway and potentially alter the disease course with targeted antiangiogenics are warranted.
Assuntos
Colite/induzido quimicamente , Sulfato de Dextrana/farmacologia , Neovascularização Fisiológica/genética , Animais , Colite/fisiopatologia , Colo/irrigação sanguínea , Mucosa Intestinal/irrigação sanguínea , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Especificidade da Espécie , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Understanding the host response to oncolytic viruses is important to maximize their antitumor efficacy. Despite robust cytotoxicity and high virus production of an oncolytic herpes simplex virus (oHSV) in cultured human sarcoma cells, intratumoral (ITu) virus injection resulted in only mild antitumor effects in some xenograft models, prompting us to characterize the host inflammatory response. Virotherapy induced an acute neutrophilic infiltrate, a relative decrease of ITu macrophages, and a myeloid cell-dependent upregulation of host-derived vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, bevacizumab and r84, the latter of which binds VEGF and selectively inhibits binding to VEGF receptor-2 (VEGFR2) but not VEGFR1, enhanced the antitumor effects of virotherapy, in part due to decreased angiogenesis but not increased virus production. Neither antibody affected neutrophilic infiltration but both partially mitigated virus-induced depletion of macrophages. Enhancement of virotherapy-mediated antitumor effects by anti-VEGF antibodies could largely be recapitulated by systemic depletion of CD11b(+) cells. These data suggest the combined effect of oHSV virotherapy and anti-VEGF antibodies is in part due to modulation of a host inflammatory reaction to virus. Our data provide strong preclinical support for combined oHSV and anti-VEGF antibody therapy and suggest that understanding and counteracting the innate host response may help enable the full antitumor potential of oncolytic virotherapy.
Assuntos
Vetores Genéticos/imunologia , Células Mieloides/imunologia , Neoplasias/imunologia , Vírus Oncolíticos/imunologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Bevacizumab , Antígeno CD11b/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Vetores Genéticos/administração & dosagem , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Células Mieloides/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Neovascularização Patológica/terapia , Terapia Viral Oncolítica , Sarcoma/imunologia , Sarcoma/metabolismo , Sarcoma/terapia , Simplexvirus/imunologia , Células Estromais/metabolismo , Células Estromais/virologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/imunologia , Replicação Viral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Anorectal malformations (ARMs) without fistula occur in approximately 5 % of all cases of ARM. The high frequency of Trisomy 21 associated to this type of malformation has been previously described. A review of the literature revealed only one previous publication discussing ARM without fistula with or without Trisomy 21; all other publications focused their discussion in patients with Trisomy 21. We felt that ARM without fistula has very specific characteristics and therapeutic implications that deserved a special discussion, which prompted us to review our experience. METHODS: A retrospective review of the medical records of patients with ARM without fistula was performed between September 1980 and March 2014. From a series of 2,189 cases of ARMs, 92 had no fistula identified. Information related to demographic, anatomic, and prognostic factors, as well as outcome variables was obtained and compared to those results obtained from other types of ARMs. RESULTS: Seventy-six patients were males and 16 females. Thirty-seven patients (40 %) had Trisomy 21. Eighty-six patients were primarily operated on and six had a reoperation after a failed attempted repair at another institution. Of the six patients that were reoperated, five had an attempted repair in the newborn period without a colostomy and the operation was aborted after the rectum could not be found. The location of the blind rectum was at the level of the bulbar urethra in males or 1-2 cm from the perineal skin in females in 80 patients; and in 9 patients it was found at the level of the prostatic urethra. In five patients, during the repair, there was an incidental opening of the urethra, which was repaired with uneventful recovery. The sacrum was normal in 61 patients; 4 patients had a sacral ratio <0.4, which indicated poor prognosis for fecal continence. Sixty-four patients had normal urinary tract, four patients had an absent kidney, ten had bilateral hydronephrosis, and three unilateral. Long-term outcomes related to bowel control were available in 52 cases: 11 of 18 patients with Trisomy 21(61 %) had voluntary bowel movements and 29 of 34 (85 %) without Trisomy 21 had voluntary bowel movements. All patients without Trisomy 21 had urinary control. CONCLUSION: Anorectal malformation without fistula is a unique defect. In our series, it occurs in 4 % of all ARMs. Even when patients do not have a fistula, the operation is not technically easier due to the presence of an extensive common wall between the rectum and urethra in males or vagina in females. The ARM with no fistula has a good reasonable functional prognosis, even in patients with associated Trisomy 21 and conveys a low frequency of associated urologic defects.
Assuntos
Canal Anal/anormalidades , Anus Imperfurado/epidemiologia , Reto/anormalidades , Malformações Anorretais , Anus Imperfurado/diagnóstico , Feminino , Saúde Global , Humanos , Incidência , Masculino , Fístula RetalRESUMO
PURPOSE: The presence of esophageal atresia (EA) in patients with an anorectal malformation (ARM) is well known. The purpose of this work is to find out the most common type of ARM associated to EA and the functional prognostic implication of this association, which has not been described in previous publications. METHODS: We reviewed our database for demographic, functional, and associated anomalies data in our patients with EA and ARM, and then compared them with those of our general series of ARM without esophageal atresia. RESULTS: Out of 1,995 ARM patients, 167 had a concomitant EA (8.3 %). Prostatic fistula was the most common type of defect in the male EA patients (45.9 %) and cloacas were on the female group (57.9 %). EA patients had worse bowel (47 vs. 67 %) and urinary control (56.6 vs. 79.4 %) when compared to the general series (GS). Functional prognosis was significantly worse in cloacas and in patients subjected to re-operations (p < 0.001). EA patients had a 0.52 average sacral ratio and in the GS was 0.65 (p < 0.001). EA patients had a significantly higher incidence of tethered cord (32.3 vs. 17.6 %), cardiac anomalies (32.3 vs. 22.5 %) including VSD (12.5 vs. 4.5 %), hydronephrosis (36.5 vs. 15.4 %), absent kidney (26.3 vs. 10.5 %), duodenal atresia (7.7 vs. 1.7 %), vertebral anomalies (28.1 vs. 14 %), extremity defects (11.3 vs. 3.1 %), tracheal anomalies (6.5 vs. 0.4 %), and developmental delay (5.9 vs. 1.4 %). CONCLUSIONS: The presence of esophageal atresia in ARM patients has a significant, probably coincidental, impact on bowel and urinary control. This association is also related with worse types of ARM defects and with more severe associated anomalies. This association should increase the awareness on the provider in terms of what to expect on functional prognosis and a throughout search for associated anomalies.
Assuntos
Anormalidades Múltiplas , Canal Anal/anormalidades , Anus Imperfurado/epidemiologia , Atresia Esofágica/epidemiologia , Reto/anormalidades , Malformações Anorretais , Feminino , Saúde Global , Humanos , Incidência , Masculino , PrevalênciaRESUMO
Surgical management of pediatric Crohn's disease is fundamentally palliative, aiming to treat the sequalae of complicated disease while preserving intestinal length. Multidisciplinary discussion of risk factors and quality of life should take place prior to operative intervention. Though the surgical management of pediatric Crohn's disease is largely based on the adult literature, there are considerations specific to the pediatric population - notably disease and treatment effects on growth and development. Intrabdominal abscess is approached with percutaneous drainage when feasible, reserving surgical intervention for the patient who is unstable or failing medical therapy. Pediatric patients with fibrostenotic disease should be considered for strictureplasty when possible, for maximum preservation of bowel length. Patients with medically refractory Crohn's proctocolitis should be treated initially with fecal diversion without proctocolectomy.
Assuntos
Doença de Crohn , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/complicações , Criança , Abscesso Abdominal/cirurgia , Abscesso Abdominal/etiologia , Drenagem/métodosRESUMO
INTRODUCTION: A proximal resection margin greater than 5 cm from the intra-operative histologically determined transition zone has been deemed necessary to minimize the risk of transition zone pull-through. This extended resection may require the sacrifice of vascular supply and even further bowel resection. The impact of extended proximal resection margin on post-operative complications and functional outcomes is unclear. METHODS: A retrospective chart review of patients who underwent primary pull-through for Hirschsprung disease at a single institution between January 2008 and December 2022 was performed. An adequate proximal margin was defined by a circumferential normally ganglionated ring and absence of hypertrophic nerves. The extended margin was defined as the total length of proximal colon with normal ganglion cells and without hypertrophic nerves. Fecal incontinence severity was assessed with the Pediatric Fecal Incontinence Severity Score (PFISS). RESULTS: Eighty seven patients met criteria for inclusion. Median age at primary pull-through was 17 days (IQR 10-92 days), 55% (n = 48) of patients had an extended proximal margin (EPM) ≤ 5 cm, and 45% (n = 39) had an EPM > 5 cm. An EPM ≤5 cm was not associated with increased rates of Hirschsprung associated enterocolitis (≤5 cm 43%, >5 cm 39%, P = 0.701), diversion post pull-through (≤5 cm 10%, >5 cm 5%, P = 0.367) or reoperation for transition zone pull-through (≤5 cm 3%, >5 cm 0%, P = 0.112). EPM ≤5 cm had more frequent involuntary daytime bowel movements (P = 0.041) and more frequent voluntary bowel movements (P = 0.035). There were no differences in other measures of fecal incontinence severity. CONCLUSIONS: Shorter proximal extended margins beyond the adequate ganglionated margin do not significantly impact post-operative complication rates and have an unclear effect on fecal incontinence. TYPE OF STUDY: Case Control. LEVEL OF EVIDENCE: Level III.
Assuntos
Incontinência Fecal , Doença de Hirschsprung , Criança , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Incontinência Fecal/etiologia , Incontinência Fecal/complicações , Margens de Excisão , Doença de Hirschsprung/complicações , Hipertrofia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Total colonic aganglionosis (TCA) is a rare variant of Hirschsprung disease (HD) where the colon and portion of distal ileum lack ganglion cells. Most pediatric use either a straight ileoanal (Swenson or Yancey-Soave) or a short Duhamel pull-through for TCA. There are no large studies comparing these techniques. We aimed to compare short-and medium-term outcomes between these approaches. METHOD: A retrospective review was performed among children with TCA from 2001 to 2019 undergoing a primary Duhamel or Swenson pull-through across three large children's hospitals. Patients undergoing redo and patients with greater than 30 % small bowel aganglionosis were excluded. We gathered data on demographics, operative approach, and outcomes at one, two, and three years. Continuous variables were analyzed with t-tests and categorical variables with Chi square or Fisher's tests. RESULTS: There were 54 patients, with 26 (48 %) undergoing Duhamel and 28 (52 %) undergoing Swenson pull-through. There were no differences in sex, age, medical comorbidities, or operative details, including age at pull-through, laparoscopic vs open, length of involved small bowel, and operative time. Length of stay and post-operative complications were not different. Three years after pull-through, patients undergoing Duhamel had fewer stools per day (1-3 stools 69.6 % vs 14.3 %, p = 0.003) and were less likely to be prescribed fiber supplementation (4.2 % vs 43.8 %, p = 0.003). There were no differences in irrigations, botulinum toxin administration, loperamide, or HD admissions. CONCLUSION: Both Duhamel and straight pull-throughs are safe for treatment of TCA, with acceptable short- and medium-term outcomes. Further studies on patient-reported outcomes are necessary to examine long-term differences. LEVEL OF EVIDENCE: III.
Assuntos
Doença de Hirschsprung , Laparoscopia , Criança , Humanos , Doença de Hirschsprung/cirurgia , Doença de Hirschsprung/complicações , Hospitalização , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Masculino , FemininoRESUMO
BACKGROUND: Hirschsprung Disease (HD) is a rare cause of functional bowel obstruction in children. Patients are typically diagnosed in the neonatal period and undergo pull-through (PT) soon after diagnosis. The optimal management and post-operative outcomes of children who present in a delayed fashion are unknown. METHODS: A multi-center retrospective review of children with HD was performed at participating Pediatric Colorectal and Pelvic Learning Consortium sites. Children were stratified by age at diagnosis (neonates <29 days; infants 29 days-12 months; toddler 1 year-5 years and child >5 years). RESULTS: 679 patients with HD from 14 sites were included; Most (69%) were diagnosed in the neonatal period. Age at diagnosis was not associated with differences in 30-day complication rates or need for PT revision. Older age at diagnosis was associated with a greater likelihood of undergoing fecal diversion after PT (neonate 10%, infant 12%, toddler 26%, child 28%, P < 0.001) and a greater need for intervention for constipation or incontinence postoperatively (neonate 56%, infant 62%, toddler 78%, child 69%, P < 0.001). CONCLUSION: Delayed diagnosis of HD does not impact 30-day post-operative outcomes or need for revision surgery but, delayed diagnosis is associated with increased need for fecal diversion after pull-through. LEVEL OF EVIDENCE: III.
Assuntos
Diagnóstico Tardio , Doença de Hirschsprung , Complicações Pós-Operatórias , Humanos , Doença de Hirschsprung/cirurgia , Doença de Hirschsprung/diagnóstico , Estudos Retrospectivos , Lactente , Diagnóstico Tardio/estatística & dados numéricos , Pré-Escolar , Feminino , Masculino , Recém-Nascido , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Resultado do Tratamento , Criança , Reoperação/estatística & dados numéricosRESUMO
PURPOSE: Antegrade colonic enemas (ACE) can be an effective management option for defecation disorders and improve quality of life. Best practice regarding channel placement is unclear and variation may exist around preferred initial type of channel, age at placement, and underlying diagnoses. We aimed to describe practice patterns and patient characteristics around ACE channel placement. METHODS: We conducted a multicenter retrospective study of children with an ACE channel cared for at sites participating in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) from 2017 to 2022. Kruskal-Wallis test was utilized to test the age at surgery by site with significance level of 0.05. RESULTS: 500 patients with ACE channel were included. 293 (58.6%) patients had their ACE procedure at a PCPLC center. The median age at surgery was 7.6 [IQR 5.3-11.0] years for the overall cohort and 8.1 [IQR 5.3-11.5] years for placement at PCPLC centers. For PCPLC centers, median age at placement varied significantly across centers (p = 0.009). 371 (74.2%) patients received Malone appendicostomy, 116 (23.2%) received cecostomy, and 13 (2.6%) received Neo-Malone appendicostomy. Median age of patients by channel type was 7.7 [IQR 5.3-11.0], 7.5 [IQR 5.7-11.0], and 9.8 [IQR 4.2-11.6] years, respectively. The most common indication for cecostomy was idiopathic/refractory constipation (52.6%), whereas anorectal malformation was the most common indication for Malone (47.2%) and Neo-Malone (61.5%). Among ACE channels placed at PCPLC centers, there was variation across institutions in preferred initial channel type. The 4 highest volume centers favored Malone appendicostomy over cecostomy. CONCLUSION: There is variation in practice of ACE channel placement. At specialty pediatric colorectal centers, age at time of placement and type of channel placed varied across institutions. Further work is needed to better characterize diagnosis- and age-focused patient centered outcomes to clarify recommendations for our patients who benefit from these procedures. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.
Assuntos
Constipação Intestinal , Enema , Padrões de Prática Médica , Humanos , Estudos Retrospectivos , Enema/métodos , Criança , Feminino , Masculino , Pré-Escolar , Constipação Intestinal/terapia , Padrões de Prática Médica/estatística & dados numéricos , Cecostomia/métodosRESUMO
BACKGROUND: In the setting of inflammatory bowel disease, inflammation is associated with a simultaneous increase in angiogenesis; moreover, elevated vascular endothelial growth factor (VEGF) levels implicate angiogenesis as a pathologic contributor to disease severity. We hypothesize that selectively inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) in a model of murine colitis will reduce angiogenesis, resulting in decreased inflammation and disease severity, providing mechanistic insight into the role of pathologic angiogenesis in IBD. MATERIALS AND METHODS: In a dextran sodium sulfate model of murine colitis, anti-VEGFR2 monoclonal antibody (DC101) or placebo was administered. Clinical assessments followed by histologic and molecular tissue analysis were performed to quantify inflammation, microvessel density (MVD), VEGF and VEGFR2 gene expression, and phosphorylated mitogen-activated protein kinase protein expression. RESULTS: Weight loss began after d 6 with the treatment group demonstrating a more favorable percent weight change. Inflammation and MVD were similar between cohorts, both increasing in parallel toward a plateau. VEGF and VEGFR2 messenger RNA expression were not significantly different, but phosphorylated mitogen-activated protein kinase was elevated in the DC101 cohort (P = 0.03). CONCLUSIONS: Despite a more favorable weight change profile in the treated group, no difference was observed between cohorts regarding clinical disease severity. However, a parallel rise in inflammation and MVD was observed coinciding with weight loss, suggesting their relationship in IBD. VEGFR2 downstream signaling was significantly elevated in the treated cohort, possibly by VEGF-independent signal transduction. Early and effective inhibition of angiogenesis by limiting downstream VEGF signaling or targeting multiple angiogenic pathways may block angiogenesis, thereby reducing disease severity and provide evidence toward the mechanism and clinical benefit of antiangiogenics in the setting of IBD.
Assuntos
Anticorpos Monoclonais/farmacologia , Colite/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia , Doença Aguda , Animais , Peso Corporal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/imunologia , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/efeitos dos fármacos , Microcirculação/imunologia , Neovascularização Patológica/imunologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
The mucosa of alimentary tract heals more rapidly than cutaneous wounds. The underlying mechanisms of this enhanced healing have not been completely elucidated. Constant exposure to salivary growth factors has been shown to play a critical role in mucosal homeostasis and tissue repair. Angiogenesis also has an essential role in successful wound repair. One of the main angiogenic growth factors, vascular endothelial growth factor (VEGF), has a pleiotropic role in tissue repair via neovascularization, reepithelialization, and regulation of extracellular matrix. We have previously reported a critical role for salivary VEGF in bowel adaptation after small bowel resection. We hypothesize that salivary VEGF is an essential stimulus for oral mucosal tissue repair, and use the murine palatal wound model to test our hypothesis. In a loss-of-function experiment, we removed the primary source of VEGF production through selective submandibular gland (SMG) sialoadenectomy in a murine model and observed the effects on wound closure and neovascularization. We then performed a selective loss-of-function experiment using the protein VEGF-Trap to inhibit salivary VEGF. In a gain-of-function experiment, we supplemented oral VEGF following SMG sialoadenectomy. After SMG sialoadenectomy, there was significant reduction in salivary VEGF level, wound closure, and vessel density. Lower levels of salivary VEGF were correlated with impaired neovascularization and reepithelialization. The selective blockade of VEGF using VEGF-Trap resulted in a similar impairment in wound healing and neovascularization. The sole supplementation of oral VEGF after SMG sialoadenectomy rescued the impaired wound healing phenotype and restored neovascularization to normal levels. These data show a novel role for salivary-VEGF in mucosal wound healing, and provide a basis for the development of novel therapeutics aimed at augmenting wound repair of the oral mucosa, as well as wounds at other sites in the alimentary tract.
Assuntos
Mucosa Bucal/lesões , Neovascularização Fisiológica/fisiologia , Palato/lesões , Saliva/química , Fator A de Crescimento do Endotélio Vascular/fisiologia , Cicatrização/fisiologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Receptores de Fatores de Crescimento do Endotélio Vascular/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Saliva/fisiologia , Glândula Submandibular/cirurgia , Cicatrização/efeitos dos fármacosRESUMO
Pyloric atresia is an uncommon congenital gastric outlet obstruction, accounting for only 1% of gastrointestinal atresias. Up to 55% of cases have associated anomalies, the most common of which is epidermolysis bullosa. Fetal MRI findings of the epidermolysis bullosa-pyloric atresia association have not been previously reported. We present a case of this association diagnosed by prenatal MRI with corroborative postnatal imaging and surgical findings.
Assuntos
Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/embriologia , Obstrução da Saída Gástrica/diagnóstico , Obstrução da Saída Gástrica/embriologia , Imageamento por Ressonância Magnética/métodos , Diagnóstico Pré-Natal/métodos , Piloro/anormalidades , Humanos , Recém-Nascido , Piloro/embriologia , Estatística como AssuntoRESUMO
BACKGROUND: This study sought to characterize sexual function and fecal incontinence related quality of life (QOL) outcomes for adult males with anorectal malformation (ARM) or Hirschsprung's Disease (HD). METHODS: We conducted a cross-sectional survey study of male patients ≥18 years with ARM or HD. Patients were identified from our institutional database, contacted and consented by telephone, and sent a REDCap survey via email. The International Index of Erectile Function (IIEF-5) and Male Sexual Health Questionnaire (MSHQ) evaluated erectile dysfunction (ED) and ejaculatory dysfunction (EjD), respectively. The Cleveland Clinic Incontinence Score (CCIS) and the Fecal Incontinence Quality of Life Scale (FIQLS) assessed fecal incontinence-related outcomes. A linear regression analysis of IIEF-5 scores compared to CCIS scores was used to evaluate for an association between ED and incontinence. RESULTS: Of 63 patients contacted, 48 completed the survey. The median age for respondents was 22.5 years (IQR 20-25). There were 19 patients with HD and 29 patients with ARM. On the IIEF-5 survey, 35.3% report some level of ED. On the MSHQ-EjD survey, the median score was 14 out of 15 (IQR 10.75-15), indicating few EjD concerns. The median CCIS was 5 (IQR 2.25-7.75) and the median FIQL scores ranged from 2.7 to 3.5 depending on the domain assessed, demonstrating some QOL challenges secondary to fecal incontinence. On linear regression analysis, IIEF-5 and CCIS scores were weakly associated (B = -0.55, p = 0.045). CONCLUSIONS: Male adult patients with ARM or HD may have ongoing concerns with sexual function and fecal incontinence. LEVEL OF EVIDENCE: Level 4. TYPE OF STUDY: Cross-Sectional Survey Study.