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2.
J Pediatr Gastroenterol Nutr ; 78(1): 68-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38291695

RESUMO

OBJECTIVES: Necrotizing enterocolitis (NEC) is a severe neonatal surgical condition, associated with a prolonged pro-inflammatory state, leading to high mortality and morbidity rates. Carbon dioxide (CO2 ) insufflation during laparoscopy may have an anti-inflammatory effect. We aimed to evaluate the effects of CO2 -insufflation on experimental colitis. METHODS: Acute colitis was induced in 6-week-old Balb/c mice by the administration of 2%-dextran sulfate-sodium (DSS) during 7 days (n = 45). On Day 4, two groups received intraperitoneal insufflation (duration: 30 mn, pressure: 5 mmHg) of CO2 ("DSS+CO2 ") or air ("DSS+air"). A group received no insufflation ("DSS"). Groups were compared for clinical severity using the disease activity index (DAI-body weight loss, stool consistency, and bleeding), histological severity (histopathological activity index, colon length, and ulcerations), colonic mucosecretion, and inflammation. RESULTS: DAI was significantly decreased in DSS+CO2 group, compared to DSS (p < 0.0001) or DSS+air (p < 0.0001) groups. Colon length was increased in DSS+CO2 treated mice compared to DSS (p = 0.0002). The histopathological activity index was lower in DSS+CO2 (vs. DSS, p = 0.0059/vs. DSS+air, p = 0.0389), with decreased ulcerations (3.77 vs. 10.7, p = 0.0306), and persistent mucosecretion with increased mucin-secreting cells. CONCLUSIONS: CO2 -insufflation attenuates DSS-induced colitis and improves both clinical and histological scores. Laparoscopy with CO2 insufflation represents a therapeutic anti-inflammatory strategy for NEC.


Assuntos
Colite , Insuflação , Animais , Camundongos , Dióxido de Carbono/efeitos adversos , Colo/patologia , Modelos Animais de Doenças , Colite/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Úlcera/patologia , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL
3.
J Pediatr Urol ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38281883

RESUMO

INTRODUCTION: Duplex renal collecting system or duplex kidney (DK) commonly is associated with uropathy, with upper pole obstruction or lower pole vesicoureteral reflux (VUR). Its management is variable, ranging from therapeutic abstention to total nephrectomy. In case of damage to a single renal pole, uretero-ureteral anastomosis (UUA) is one of the surgical techniques for preserving the pathological pole. It can be performed by laparotomy, laparoscopy, or both. The aims of this study are to report the results of UUA in pathological DK, and compare outcomes depending on the surgical approach. METHODS: This is a retrospective analysis study over 20 years, from April 2002 to July 2022, including all children from 0 to 15 years old who underwent UUA for a DK. Outcome measure included per- and post-operative complications, the occurrence of urinary tract infections and ultrasound measurements during follow-up. RESULTS: Thirty-three children underwent an UUA over 20 years. The median age at diagnosis was 25 days (range: 1 day-12 years). The median age at surgery was 13 months (range: 2 months - 13 years). The sex ratio was 0.22. Prenatal diagnosis was made in 87.9 % of cases (n = 29). The left kidney was affected in 72.7 % of cases. Twenty-seven children (81.8 %) had an ectopic ureteral opening of the upper pole ureter; four children (12.1 %) had ureterocele of the upper pole and 2 children (6.1 %) had vesicoureteral reflux of the inferior pole. UUA was performed by inguinal approach (laparotomy) in 17 children (51.5 %), by laparoscopy in 9 cases (27.3 %), and by laparoscopy combined with laparotomy in 7 cases (21.2 %). The complication rate was 12.1 % (n = 4), including recurrent pyelonephritis with superior polar hydronephrosis (n = 2); iatrogenic injury of the lower pole ureter (n = 1) and a urinoma (n = 1), that all required surgical management with a polar nephrectomy. Between each surgical approach, there were no significant differences in operative time, hospital stay, complications. CONCLUSION: UUA is an effective therapeutic option in duplex kidneys as it allows the preservation of the pathological pole with low complication rates, regardless of the surgical approach.

4.
Nat Rev Dis Primers ; 9(1): 54, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828049

RESUMO

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes in patients.


Assuntos
Síndrome de Down , Doença de Hirschsprung , Deficiência Intelectual , Síndrome de Waardenburg , Recém-Nascido , Humanos , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Doença de Hirschsprung/patologia , Síndrome de Down/complicações , Síndrome de Waardenburg/complicações , Canal Anal , Deficiência Intelectual/complicações
5.
Pediatr Res ; 94(5): 1779-1783, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37328687

RESUMO

BACKGROUND: Advances in surgical and neonatal care have led to improved survival of patients with œsophageal atresia (OA) over time. Morbidity remains significant, with one-third of patients being affected by a postoperative complication. Several aspects of management are not consensual, such as the use of œsophagogram before starting oral feeding. METHODS: We conducted a multicenter retrospective study, including all children with OA that underwent a primary anastomosis in the first days of life, between 2012 and 2018 in five French centers, to determine the usefulness of postoperative œsophagogram during the 10 days after early primary repair of OA to diagnose the anastomotic leak and congenital œsophageal stenosis. RESULTS: Among 225 included children, 90 (40%) had a routine œsophagogram and 25 (11%) had an anastomotic leak, clinically diagnosed before the scheduled œsophagogram in 24/25 (96%) children at median postoperative day 4. Ten patients had associated congenital œsophageal stenosis diagnosed on the œsophagogram in only 30% of cases. CONCLUSION: Early œsophagogram is rarely useful in the diagnosis of an anastomotic leak, which is clinically diagnosed before performing an œsophagogram in the majority of cases. The need for a postoperative œsophagogram should be evaluated on a case-by-case basis. IMPACT: Early œsophagogram is not helpful in the diagnosis of an anastomotic leak in the majority of cases. An anastomotic leak is most often diagnosed clinically before performing an œsophagogram. Early postoperative œsophagogram could be helpful for the diagnosis of congenital œsophageal stenosis. However, dysphagia occurs later and early diagnosis of congenital œsophageal stenosis has no impact on the management and outcome of asymptomatic children. Indication of postoperative œsophagogram has to be evaluated on a case-by-case basis.


Assuntos
Atresia Esofágica , Estenose Esofágica , Recém-Nascido , Criança , Humanos , Atresia Esofágica/diagnóstico por imagem , Atresia Esofágica/cirurgia , Atresia Esofágica/complicações , Estenose Esofágica/diagnóstico por imagem , Estenose Esofágica/cirurgia , Estenose Esofágica/complicações , Fístula Anastomótica/diagnóstico por imagem , Fístula Anastomótica/etiologia , Estudos Retrospectivos , Complicações Pós-Operatórias
6.
J Robot Surg ; 17(5): 2287-2295, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37336840

RESUMO

The aim of this study was to compare outcomes of laparoscopic and robotic-assisted colectomy in children. All children who underwent a colectomy with a laparoscopic (LapC) or robotic-assisted (RobC) approach in our institution (January 2010-March 2023) were included. Demographics, surgical data, and post-operative outcomes within 30 days were collected. Additional cost related to the robotic approach was calculated. Comparisons were performed using Fisher tests for categorical variables and Mann-Whitney tests for continuous variables. A total of 55 colectomies were performed: 31 LapC and 24 RobC (median age: 14.9 years). Main indications included: inflammatory bowel disease (n = 36, 65%), familial adenomatous polyposis (n = 6, 11%), sigmoid volvulus (n = 5, 9%), chronic intestinal pseudo-obstruction (n = 3, 5%). LapC included 22 right, 4 left, and 5 total colectomies. RobC included 15 right, 4 left, and 5 total colectomies. Robotic-assisted surgery was associated with increased operative time (3 h vs 2.5 h, p = 0.02), with a median increase in operative time of 36 min. There were no conversions. Post-operative complications occurred in 35% of LapC and 38% of RobC (p = 0.99). Complications requiring treatment under general anesthesia (Clavien-Dindo 3) occurred in similar rates (23% in LapC vs 13% in RobC, p = 0.49). Length of hospitalization was 10 days in LapC and 8.5 days in RobC (p = 0.39). The robotic approach was associated with a median additional cost of 2156€ per surgery. Robotic-assisted colectomy is as safe and feasible as laparoscopic colectomy in children, with similar complication rates but increased operative times and cost.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Criança , Adolescente , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Colectomia/efeitos adversos , Duração da Cirurgia , Resultado do Tratamento
7.
J Pediatr Surg ; 58(7): 1404-1405, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36931939
8.
J Robot Surg ; 17(1): 215-221, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35622191

RESUMO

Incisions in the supra-pubic region have been described robotic-assisted surgery to improve cosmetic results in adults, but seldom in children. We aimed to present an innovative trocar placement in the Pfannenstiel line, named Scarless Laparoscopic Incisions in Pfannenstiel (SLIP), and evaluate its feasibility for various intra-abdominal procedures and its cosmetic results in pediatric robotic surgery. We performed a monocentric prospective study, including children undergoing robotic-assisted surgeries using a SLIP approach (July 2019-September 2021). Data regarding demographics, surgery, and outcome were collected and reported as median (range), or number (percentage). Cosmetic results were evaluated with a questionnaire. A SLIP approach was performed in 50 children (24 cholecystectomies, 12 splenectomies, 2 cholecystectomies and splenectomies, 9 colonic resections, 2 choledochal cyst resections, and 1 pancreatic pseudocyst resection). Median age was 11 years (2-18) and median weight 35 kg (10.5-80). Conversion to laparoscopy occurred in two cases. Post-operative complications occurred in 5 patients (10%), after colectomies [intrabdominal abscess (n = 3), stoma dysfunction (n = 1), parietal abscess (n = 1)], of which 3 (6%) required reintervention (intrabdominal abscess n = 2, stoma dysfunction n = 1). Regarding scars, 68% (n = 28) of parents and patients reported the maximal score of 5/5 for global satisfaction and 63% (n = 26) had all scars hidden by underwear. SLIP approach is versatile and can be used in supra- and infra-mesocolic robotic-assisted procedures. The low complication rate shows its safety in both young children and teenagers and does not increase operative difficulties. It results in high patient satisfaction regarding scars, and a scarless abdomen.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Adulto , Adolescente , Humanos , Criança , Pré-Escolar , Procedimentos Cirúrgicos Robóticos/métodos , Cicatriz/etiologia , Estudos Prospectivos , Abscesso/etiologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Retrospectivos
9.
J Pediatr Surg ; 58(4): 708-714, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36585304

RESUMO

INTRODUCTION: In 2015, a protocol including early laparoscopy-assisted surgery in the treatment of necrotizing enterocolitis (NEC) was implemented at our institution. Carbon dioxide insufflation during laparoscopy may have an anti-inflammatory effect. We aimed to compare post-operative outcome after early laparoscopy-assisted surgery and classical laparotomy for NEC. MATERIAL AND METHODS: Charts of premature infants undergoing surgery for NEC (2012-2021) were reviewed. Cases operated by early laparoscopy-assisted surgery (2015-2021) were compared to infants operated for NEC between 2012 and 2015 (laparotomy-NEC). Outcomes were post-operative CRP, need for reintervention, mortality, and the occurrence of post-NEC intestinal strictures. CRP was measured on the day of surgery (POD-0), 2 days (POD-2), and 7 days after surgery (POD-7). Data were compared using contingency tables for categorical variables and Student t-test or Mann-Whitney test for continuous variables. RESULTS: Infants with NEC operated by early laparoscopy (n = 48) and laparotomy (n = 29) were similar in terms of perforation (60% vs 58%, p = 0.99) and POD-0 CRP (139 vs 124 mg/L, p = 0.94). Delay between first signs of NEC and surgery was shorter in the laparoscopy group (3 vs 6 days, p = 0.004). Early laparoscopy was associated with a lower CRP on POD-2 (108 vs 170, p = 0.005) and POD-7 (37 vs 68, p = 0.002), as well as a lower rate of post-operative intestinal stricture (34% vs 61%, p = 0.04). CONCLUSIONS: In addition to being safe and feasible in premature infants, early laparoscopic-assisted surgery was associated with decreased NEC-related post-operative inflammation and strictures. A prospective, randomized study is needed in order to evaluate short and long-term effects of laparoscopy in infants with NEC. LEVEL OF EVIDENCE: Level III.


Assuntos
Enterocolite Necrosante , Doenças do Recém-Nascido , Obstrução Intestinal , Perfuração Intestinal , Laparoscopia , Recém-Nascido , Humanos , Lactente , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Enterocolite Necrosante/complicações , Enterocolite Necrosante/cirurgia , Estudos Prospectivos , Doenças do Recém-Nascido/cirurgia , Inflamação/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/complicações , Perfuração Intestinal/cirurgia , Perfuração Intestinal/complicações
10.
Stem Cells Transl Med ; 11(10): 1089-1102, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36103370

RESUMO

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, ß-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV-treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV-based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.


Assuntos
Vesículas Extracelulares , Hérnias Diafragmáticas Congênitas , MicroRNAs , Ratos , Animais , Hérnias Diafragmáticas Congênitas/metabolismo , beta Catenina/metabolismo , Líquido Amniótico/metabolismo , Neuropilina-1/metabolismo , Ratos Sprague-Dawley , Pulmão/metabolismo , Células-Tronco/metabolismo , Diferenciação Celular , RNA Mensageiro/metabolismo , Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Efrinas/metabolismo , Modelos Animais de Doenças
11.
J Pediatr Surg ; 57(12): 826-833, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35618494

RESUMO

INTRODUCTION: Gastro-esophageal reflux disease (GERD) is the most frequent long-term morbidity of congenital diaphragmatic hernia (CDH) survivors. Performing a preventive fundoplication during CDH repair remains controversial. This study aimed to: (1) Analyze the variability in practices regarding preventive fundoplication; (2) Identify predictive factors for fundoplication. (3) Evaluate the impact of preventive fundoplication on gastro-intestinal outcomes in children with a CDH patch repair; METHODS: This prospective multi-institutional cohort study (French CDH Registry) included CDH neonates born in France between January 1st, 2010-December 31st, 2018. Patch CDH was defined as need for synthetic patch or muscle flap repair. Main outcome measures included need for curative fundoplication, tube feed supplementation, failure to thrive, and oral aversion. RESULTS: Of 762 CDH neonates included, 81 underwent fundoplication (10.6%), either preventive or curative. Median follow-up was 3.0 years (IQR: 1.0-5.0). (1) Preventive fundoplication is considered in only 31% of centers. The rates of both curative fundoplication (9% vs 3%, p = 0.01) and overall fundoplication (20% vs 3%, p < 0.0001) are higher in centers that perform preventive fundoplication compared to those that do not. (2) Predictive factors for preventive fundoplication were: prenatal diagnosis (p = 0.006), intra-thoracic liver (p = 0.005), fetal tracheal occlusion (p = 0.002), CDH-grade C-D (p < 0.0001), patch repair (p < 0.0001). After CDH repair, 8% (n = 51) required curative fundoplication (median age: 101 days), for which a patch repair was the only independent predictive factors identified upon multivariate analysis. (3) In neonates with patch CDH, preventive fundoplication did not decrease the need for curative fundoplication (15% vs 11%, p = 0.53), and was associated with higher rates of failure to thrive (discharge: 81% vs 51%, p = 0.03; 6-months: 81% vs 45%, p = 0.008), tube feeds (6-months: 50% vs 21%, p = 0.02; 2-years: 65% vs 26%, p = 0.004), and oral aversion (6-months: 67% vs 37%, p = 0.02; 1-year: 71% vs 40%, p = 0.03). CONCLUSIONS: Children undergoing a CDH patch repair are at high risk of requiring a curative fundoplication. However, preventive fundoplication during a patch repair does not decrease the need for curative fundoplication and is associated with worse gastro-intestinal outcomes in children. LEVEL OF EVIDENCE: II - Prospective Study.


Assuntos
Hérnias Diafragmáticas Congênitas , Humanos , Recém-Nascido , Criança , Lactente , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/cirurgia , Estudos Prospectivos , Estudos de Coortes , Insuficiência de Crescimento , Fundoplicatura
12.
Arch Dis Child ; 107(1): 52-58, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33863700

RESUMO

INTRODUCTION: With advances in surgical and neonatal care, the survival of patients with oesophageal atresia (OA) has improved over time. Whereas a number of OA-related conditions (delayed primary anastomosis, anastomotic stricture and oesophageal dysmotility) may have an impact on feeding development and although children with OA experience several oral aversive events, paediatric feeding disorders (PFD) remain poorly described in this population. The primary aim of our study was to describe PFD in children born with OA, using a standardised scale. The secondary aim was to determine conditions associated with PFD. METHODS: The Feeding Disorders in Children with Oesophageal Atresia Study is a national cohort study based on the OA registry from the French National Network. Parents of children born with OA between 2013 and 2016 in one of the 22 participating centres were asked to complete the French version of the Montreal Children's Hospital Feeding Scale. RESULTS: Of the 248 eligible children, 145 children, with a median age of 2.3 years (Q1-Q3 1.8-2.9, min-max 1.1-4.0 years), were included. Sixty-one children (42%) developed PFD; 13% were tube-fed (n=19). Almost 40% of children with PFD failed to thrive (n=23). The presence of chronic respiratory symptoms was associated with the development of PFD. Ten children with PFD (16%) had no other condition or OA-related complication. CONCLUSION: PFD are common in children with OA, and there is no typical profile of patients at risk of PFD. Therefore, all children with OA require a systematic screening for PFD that could improve the care and outcomes of patients, especially in terms of growth.


Assuntos
Atresia Esofágica/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Anastomose Cirúrgica/métodos , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Nutrição Enteral/métodos , Atresia Esofágica/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , França/epidemiologia , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/epidemiologia , Prevalência
13.
J Pediatr Surg ; 56(12): 2157-2164, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34030881

RESUMO

OBJECTIVE: Enhanced recovery after surgery (ERAS) has been widely implemented after minimally invasive surgeries (MIS) in adults. The aim of this study was to evaluate the current evidence available on ERAS after MIS in children. METHODS: Using a defined search strategy (PubMed, Cochrane, Scopus), we performed a systematic review of the literature, searching for studies reporting on ERAS after MIS (thoracoscopy, laparoscopy, retroperitoneoscopy) in children (1975-2019). This study was registered with PROSPERO-international prospective register of systematic reviews. A meta-analysis was conducted using comparative studies for length of stay (LOS), complication rates, and readmission rates. RESULTS: Of 180 abstracts screened, 20 full-text articles were analyzed, and 9 were included in our systematic review (1 randomized controlled trial, 3 prospective, and 5 retrospective studies), involving a total number of 531 patients. ERAS has been applied to laparoscopy for digestive (n = 7 studies) or urologic surgeries (n = 1), as well as thoracoscopy (n = 1). Mean LOS was decreased in ERAS children compared to controls (6 studies, -1.12 days, 95%IC: -1.5 to -0.82, p < 0.00001). There was no difference in complication rates between ERAS children and control children (5 studies, 13% vs 14%, OR = 0.84, 95%CI: 0.49-1.44, p = 0.52). The 30-day readmission rate was decreased in ERAS children compared to controls (6 studies, 4% vs 10%, OR = 0.34, 95%CI: 0.18-0.66, p = 0.001). CONCLUSIONS: Although the evidence regarding ERAS in MIS is scarce, these protocols seem safe and effective, by decreasing LOS and 30-day readmission rate, without increasing post-operative complication rates.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Adulto , Criança , Humanos , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
14.
Sci Transl Med ; 13(590)2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883273

RESUMO

Fetal lung underdevelopment, also known as pulmonary hypoplasia, is characterized by decreased lung growth and maturation. The most common birth defect found in babies with pulmonary hypoplasia is congenital diaphragmatic hernia (CDH). Despite research and clinical advances, babies with CDH still have high morbidity and mortality rates, which are directly related to the severity of lung underdevelopment. To date, there is no effective treatment that promotes fetal lung growth and maturation. Here, we describe a stem cell-based approach in rodents that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). Using fetal rodent models of pulmonary hypoplasia (primary epithelial cells, organoids, explants, and in vivo), we demonstrated that AFSC-EV administration promoted branching morphogenesis and alveolarization, rescued tissue homeostasis, and stimulated epithelial cell and fibroblast differentiation. We confirmed this regenerative ability in in vitro models of lung injury using human material, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. Investigating EV mechanism of action, we found that AFSC-EV beneficial effects were exerted via the release of RNA cargo. MicroRNAs regulating the expression of genes involved in lung development, such as the miR17-92 cluster and its paralogs, were highly enriched in AFSC-EVs and were increased in AFSC-EV-treated primary lung epithelial cells compared to untreated cells. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application in patients with pulmonary hypoplasia.


Assuntos
Líquido Amniótico , Vesículas Extracelulares , Pulmão/embriologia , Células-Tronco , Animais , Humanos , Roedores
15.
J Laparoendosc Adv Surg Tech A ; 31(3): 355-362, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33428520

RESUMO

Background: This study aimed to report a European multi-institutional experience about thoracoscopic management of children with congenital lung malformations. Methods: The records of 102 patients (49 girls and 53 boys) with median age at surgery of 1 year (range 6 months-1.5 years), who underwent thoracoscopic lobectomy in five European Pediatric Surgery units, were retrospectively collected. Indications for surgery included congenital pulmonary airway malformation (CPAM) (n = 47), intra- and extralobar pulmonary sequestration (n = 34), hybrid lesion (CPAM/intralobar sequestration) (n = 2), severe bronchiectasis (n = 9), congenital lobar emphysema (n = 8), and others (n = 2). The condition was asymptomatic in 77/102 (75.5%), whereas symptoms such as recurrent pneumonia and/or respiratory distress were present in 25/102 (24.5%). Results: Surgical procedures included 18 upper, 20 middle, and 64 lower lobe resections. No conversions to open were reported. A 3 mm sealing device and 5 mm stapler were adopted in the last 48/102 patients (47%). The median operative time was 92.2 minutes (range 74-141). The median operative time significantly decreased in patients in whom the vessel division and bronchial sealing were performed using sealing devices (75.5 minutes) compared with suture ligations (118.9 minutes) (P = .001). The median hospital stay was 3.7 days (range 2-6.2). Three/102 patients (2.9%) developed postoperative complications, including air leakage requiring pleural drainage (n = 1) (Clavien IIIb) and respiratory infection (n = 2) (Clavien II). A reoperation was required in one patient with residual pleuropulmonary blastoma (0.9%). All symptomatic patients reported resolution of symptoms postoperatively. Conclusions: Thoracoscopic lobectomy is a safe and effective procedure with excellent cosmetic outcome, in expert hands. Based upon our experience, we strongly recommend surgery in patients with congenital lung malformations by the first year of life, to reduce the risk of infection and make the procedure technically easier, despite the small patients' size. Surgeon's experience and use of miniaturized instruments and sealing devices remain key factors for successful outcome.


Assuntos
Bronquiectasia/cirurgia , Pneumopatias/cirurgia , Pneumonectomia/métodos , Toracoscopia , Sequestro Broncopulmonar/cirurgia , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Feminino , Humanos , Lactente , Tempo de Internação , Pneumopatias/congênito , Masculino , Duração da Cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Enfisema Pulmonar/congênito , Enfisema Pulmonar/cirurgia , Estudos Retrospectivos , Toracoscopia/efeitos adversos , Toracoscopia/instrumentação , Resultado do Tratamento
17.
Surg Endosc ; 35(8): 4251-4258, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32833100

RESUMO

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) and gastrostomy tube (GT) placement may be performed concomitantly in children with gastro-esophageal reflux disease (GERD) and failure to thrive. We aimed to evaluate the rate and risk factors for LNF failure in children undergoing concomitant LNF/GT. METHODS: A retrospective multi-institutional cohort study was conducted, reviewing patients that underwent LNF (2005-2014). Data collected included patient demographics, comorbidities, and type of GT (laparoscopy- or endoscopy-assisted). The primary outcome measure was LNF failure. Data was compared using contingency tables or Mann-Whitney tests, when appropriate. An exploratory analysis by Kaplan-Meier survival and Cox proportional hazards analysis was performed to determine predictors of time to LNF failure after LNF/GT. RESULTS: Of 189 children that underwent LNF, 99 (52%) had a concomitant GT (55% laparoscopy-, 45% endoscopy-assisted). LNF failed in 15% after LNF/GT and in 17% after LNF alone (p = 0.84), at a median age of 23 months (IQR 8-41). Using univariate analysis, we found that a younger age at the time of surgery (p = 0.05), prematurity (p = 0.0018), esophageal atresia (p = 0.01), and endoscopy-assisted GT (p = 0.02) were potential predictors of LNF failure after LNF/GT. After multivariate regression analysis, prematurity (p = 0.007) remained significantly associated with LNF failure after LNF/GT. No predictive factors for LNF failure after LNF alone were identified. CONCLUSIONS: Concomitant GT insertion and LNF is a common practice, as half of the children that undergo LNF also received GT insertion. Children born preterm or with esophageal atresia comprise a fragile population at high-risk of LNF failure after LNF/GT. Prospective, multicentric studies are needed to evaluate the best GT technique to use in children undergoing LNF.


Assuntos
Refluxo Gastroesofágico , Laparoscopia , Criança , Pré-Escolar , Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Gastrostomia , Humanos , Lactente , Recém-Nascido , Intubação Gastrointestinal , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
Pediatr Surg Int ; 36(12): 1397-1405, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070203

RESUMO

PURPOSE: To evaluate the impact of the COVID-19 pandemic-related lockdown on management and outcomes of children with acute appendicitis. METHODS: A retrospective cohort study was conducted, including children treated for acute appendicitis (January 20th-May 11th, 2020). The data regarding the severity of appendicitis and outcome were collected and compared for two time periods, before and after the nationwide lockdown (March 17th, 2020). RESULTS: The number of cases of acute appendicitis increased by 77% during the lockdown (n = 39 vs. n = 69, p = 0.03). During the lockdown, children treated for appendicitis were older (11.1 vs. 8.9 years, p = 0.003), and were more likely to live more than 5 km away from our institution (77% vs. 52%, p = 0.017). Less children had previously consulted a general practitioner (15% vs. 33%, p = 0.028), whereas more children were transferred from other hospitals (52% vs. 31%, p = 0.043). There was no difference in terms of length of hospital stay, rate of postoperative intra-abdominal abscess, ER visits, and readmissions between both periods. Three children (4%) were diagnosed with COVID-19 and appendicitis. CONCLUSIONS: Despite an increase in the number of children with appendicitis managed at our hospital during the COVID-19-related lockdown, management, and outcome remained similar. Although our pediatric center was strongly affected by this pandemic, maintaining our prior practice strategies for acute appendicitis avoided the occurrence of collateral damage for those children.


Assuntos
Apendicite/epidemiologia , Apendicite/cirurgia , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pediatria/métodos , Pneumonia Viral/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Centros de Atenção Terciária , Doença Aguda , Distribuição por Idade , COVID-19 , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento
20.
J Pediatr Surg ; 55(4): 625-634, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31227219

RESUMO

PURPOSE: To evaluate neurodevelopmental impairment (NDI) in children born with congenital diaphragmatic hernia (CDH). METHODS: Using a defined search strategy, a systematic review was conducted to define the incidence and types of NDI, to report abnormal neuroimaging findings and to evaluate possible NDI predictors. A meta-analysis was performed on comparative studies reporting risk factors for NDI, using RevMan 5.3. RESULTS: Of 3541 CDH children (33 studies), 829 (23%) had NDI, with a higher incidence in CDH survivors who received ECMO treatment (49%) vs. those who had no ECMO (22%; p<0.00001). NDI included neuromuscular hypotonia (42%), hearing (13%) and visual (8%) impairment, neurobehavioral issues (20%), and learning difficulties (31%). Of 288 survivors that had postnatal neuroimaging, 49% had abnormal findings. The main risk factors for NDI were severe pulmonary hypoplasia, large defect size, ECMO use. CONCLUSIONS: NDI is a relevant problem for CDH survivors, affecting 1 in 4. The spectrum of NDI covers all developmental domains and ranges from motor and sensory (hearing, visual) deficits to cognitive, language, and behavioral impairment. Further studies should be designed to better understand the pathophysiology of NDI in CDH children and to longitudinally monitor infants born with CDH to correct risk factors that can be modifiable. LEVEL OF EVIDENCE: Level III.


Assuntos
Hérnias Diafragmáticas Congênitas/complicações , Transtornos do Neurodesenvolvimento/etiologia , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea , Feminino , Seguimentos , Hérnias Diafragmáticas Congênitas/terapia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Neuroimagem , Fatores de Risco , Fatores Socioeconômicos , Sobreviventes
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