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Click here to get back to where you came from The New York Philharmonic Orchestra will premiere the work by Portuguese composer Andreia Pinto Correia under the direction of conductor Gustavo Dudamel who will also direct Robert Schumann’s third and fourth symphonies According to the New York Philharmonic Orchestra’s website the piece was commissioned from the Portuguese composer as part of a performance series dedicated to Robert Schumann which will take place throughout March at the Rose Theater in New York will explore the relationship between German composers Robert and Clara Schumann featuring interpretations of the works by the tow Romantic period composers-pianists will concur with performances of other contemporary pieces by composers Nico Muhly and Gabriela Ortiz.  was inspired by a line on a letter penned by Robert Schumann to his friend Johann Verhulst “We are all pretty well; the melancholy birds of night still flit round me from time to time O endereço abaixo não existe na globo.com We analyzed the department and surgeon learning curves during implementation of the percutaneous internal ring suturing (PIRS) technique in our department. Children proposed for inguinal hernia or communicating hydrocele repair were included (n = 607). After mentorship, all surgeons were free to propose open or PIRS repair. From gathered data, we assessed department and surgeon learning curves through cumulative experience focusing in perioperative complications, conversion, ipsilateral recurrence, postoperative complications, and metachronous hernia, with benchmarks defined by open repair. Thirty-five laparoscopic cases per surgeon are required for perioperative complications, conversion, and ipsilateral recurrence reach the benchmark. The gap between the percentage of males, in those operated by PIRS and in those proposed for surgery, monitors the confidence of the team in the program. Volume 5 - 2017 | https://doi.org/10.3389/fped.2017.00207 Introduction: We analyzed the department and surgeon learning curves during implementation of the percutaneous internal ring suturing (PIRS) technique in our department Methods: Children proposed for inguinal hernia or communicating hydrocele repair were included (n = 607) all surgeons were free to propose open or PIRS repair we assessed department and surgeon learning curves through cumulative experience focusing in perioperative complications Results: Department-centered analysis revealed that perioperative complications and ipsilateral recurrence rates were higher in the beginning reaching the benchmarks when each surgeon performed Postoperative complications and metachronous hernia rates were independent from learning curves with the metachronous hernia rate being significantly lower in PIRS patients the percentage of males in those operated by PIRS progressively increased reaching the percentage of males Conclusion: Thirty-five laparoscopic cases per surgeon are required for perioperative complications and ipsilateral recurrence reach the benchmark in those operated by PIRS and in those proposed for surgery monitors the confidence of the team in the program we evaluate our department- and surgeon-centered learning curves trying to extract some lessons we can share with other centers implementing a similar program This study was approved by the scientific ethic committee from our institution with the reference: SECVS 133/2014 All staff members involved in the program were consultants with basic training as pediatric surgeons and different skill levels in laparoscopic surgery We included all children submitted to surgical repair of indirect inguinal hernia (at any age) or communicating hydrocele (older than 2 years old) since June 2011 until November 2016 in our department The patients were either operated by open approach (OA group) or by percutaneous internal ring suturing (PIRS group) The decision of proposing the minimally invasive approach was surgeon-dependent and determined by each surgeon’s experience Patients with hernias other than indirect inguinal hernia were excluded and the bleeding was controlled with external compression a postoperative complication emerging 4 weeks after surgery Both techniques were performed under general anesthesia (laryngeal mask) with the patient lying in a supine position we used a classic technique that divides the sac and closes the peritoneum at the level of the internal inguinal ring after opening the skin and the aponeurosis of the external oblique muscle The procedures were performed under general anesthesia (laryngeal mask) with the patient lying in a supine position. The surgeon stood at the right side of the patient regardless of the affected side, and the monitor was placed at the bottom of the table. Our minimally invasive approach included the ligation of the processus vaginalis based on PIRS technique as described by Patkowsky et al. (11) (see Video S1 in Supplementary Material) it included a single transumbilical incision for a 5-mm trocar (30° optics) we introduced a 3-mm dissection grasper above the trocar for the optics through a stab incision across the linea alba to help in mobilization of the peritoneum Insufflation pressure was between 6 and 10 mmHg depending on the age of the patient The peritoneal cavity was inspected to confirm the diagnosis If there was a contralateral patent processus vaginalis or a different type of hernia Either a 16G Abbocath or a 18-G hypodermic needle (depending on surgeon preference) armed with a loop of Prolene® 2-0 thread was introduced through the skin at the level of the deep inguinal ring the needle was passed extraperitoneally between the peritoneum and the vas deferens and testicular vessels Then the needle punched the peritoneum and entered the peritoneal cavity to push the thread through the barrel of the needle into the peritoneal cavity The needle was pulled out of the abdominal cavity leaving the Prolene® loop inside this time armed with an Ethibond® 2-0 thread which dissected the peritoneum of the other half of the ring and passed through the peritoneal opening created before The Ethibond® was pushed inside the Prolene® loop and the needle was taken off the Prolene® loop was pulled out of the patient’s body taking the Ethibond® end with it Both Ethibond® ends were exiting the skin through the same puncture point and a perfect Ethibond® cerclage was created around the internal inguinal ring leaving no peritoneal gaps extreme care was taken not to damage the vas deferens the round ligament was included into the cerclage The knot was tied extracorporeally and buried under the skin Steri-strip® were used over the skin puncture point at a cartoon fashion The umbilical access was closed with absorbable suture and covered with a waterproof dressing All patients were discharged home at the same day of surgery unless they had clinical contraindication Global data regarding both OA and PIRS groups were analyzed and compared when appropriate To assess the success of implementation of the minimally invasive program for repairing inguinal hernia and communicating hydrocele the learning curves were studied in two different ways: through a department- and a surgeon-centered analysis The intervention on each patient was always considered a single procedure independently of being unilateral and bilateral repairs the OA group was used to set the benchmarks of the department PIRS group was divided in chronological sequential tertiles (PIRS 1st–114th; PIRS 115th–228th; PIRS 229th–341st) The following rates were calculated for each tertile: i The first three rates aimed to assess either the efficacy of the technique and the expertise of the surgical team The other two rates mainly assessed the belief of the surgical team on the benefits of the procedure and their own self-confidence in performing the technique The tertiles were compared with each others and with the benchmark (when appropriate) the staff surgeons who adopted PIRS as the technique of choice were selected in order to achieve individual sequential case series we calculated the rate of perioperative complications The results were displayed in a surgeon’s cumulative experience chart A visual analysis was performed based on the events decline to determine the serial number of cases required to complete the learning curve Data analysis was performed using SPSS software version 24.0 (SPSS Chi-square test was used to compare the distribution of categorical variables between groups Statistical significance was defined as a two-sided p-value < 0.05 Six hundred seven cases matched the inclusion criteria and were included in this study (Table 1) Even though the mean ages had been similar in both groups the rate of male gender was lower in PIRS group whereas a higher percentage of hydrocele cases fell in OA group This clearly suggest a case-selection bias introduced by the surgical team during their learning curve based on beliefs and confidence in the PIRS technique In cases of unilateral hernia (or hydrocele) treated by PIRS we could identify a contralateral silent patent processus vaginalis (patent processus vaginalis without previous diagnosis) in around one-fifth of the cases we identified a mismatch with preoperative laterality (when laterality was not confirmed or no patency was identified preoperatively) in 4.4% of children Three cases of PIRS group were converted to open surgery due to technical difficulty Reported perioperative complications (puncture of femoral vessels) were not statistically different between OA (n = 1; 0.4%) and PIRS groups (n = 8; 2.3%) yet we identified a slight tendency for higher rate in PIRS group but regarding postoperative complications (hematoma and foreign-body reactions) the rates were clearly similar in both groups (n = 6; 2.3% and n = 9; 2.6%) Metachronous contralateral recurrence was significantly lower in the PIRS group (n = 1; 0.3% vs whereas PIRS ipsilateral recurrences were not different from the OA group (n = 5; 1.5% and n = 1; 0.4%) Demographic characteristics and clinical outcomes of the open approach (OA) and percutaneous internal ring suturing (PIRS) groups Department-centered analysis of the learning curve of percutaneous internal ring suturing (PIRS) technique considering (A) perioperative and (B) postoperative complications rates and (C) ipsilateral recurrence rate p < 0.05 indicated significance: * vs Confidence of the surgical team on the technique reflected by (A) conversion to open surgery rate and (B) rate of male gender proposed for percutaneous internal ring suturing (PIRS) the full horizontal line represents the overall rate of males among our population Surgeon-centered analysis of the learning curve of percutaneous internal ring suturing (PIRS) technique The graph reflects the cumulative experience of five staff surgeons throughout their first 50 surgeries by PIRS The performance was evaluated by the (A) rate of perioperative complications and (C) rate of conversion to open surgery The dotted lines represent the tendency lines The dashed vertical line crossing the x-axis at point 35 marks the end of the learning curve as no events occur after the 35th case of each surgeon tends to decrease along cumulative experience and was not the focus of this study In the department-centered learning curve analysis five of the six staff members adhered to the program there was a disparity on the implementation cadence by each of them we also performed a surgeon-centered learning curve analysis The cosmesis was excellent with our strategy to insert the optics and dissecting 3-mm instrument through the umbilicus there were no visible scars at the end of the procedure perioperative complications and ipsilateral recurrence rates showed some undulant pattern despite the downward trend along the tertiles The underlying explanation might be the surgeons’ cadence disparity when starting their learning process as each surgeon’s accumulated experience contributing to each tertile was not the same When analyzing the surgeon-centered learning curves we perceived a more consistent decline in perioperative complications and ipsilateral recurrence with experience In contrast to perioperative complications the postoperative complications rate was consistently similar along all tertiles (PIRS group) and the benchmark (OA group) We concluded that postoperative complications are not dependent on the learning curve and most likely occur due to the type of thread The most common postoperative complications were incisional infections and foreign-body reactions most inguinal foreign-body reactions in PIRS group occurred around 2 months after the procedure and the only measure that could resolve it was the removal of the stitch which did not determine recurrence in the majority of cases Likely the associated inflammation promoted effective and definitive closure of the defect this was the outcome that mostly demanded experience once at least 35 procedures by surgeon were necessary to minimize it some staff members used a blunt needle (hypodermic needle) which carries less risk of laceration although it has the risk to drag or/and entrap the vas deferens we emphasize that ligation of the peritoneum at the level of the internal inguinal ring with no peritoneal gaps might be a determinant factor for the low ipsilateral recurrence rate and absence of residual hydrocele observed in the last tertile of patients we had a successful experience fixing communicating hydroceles with this technique It was interesting to testify that large defects in small infants where we just ligated the peritoneum without reducing the internal ring muscular defect This raises the necessity to ascertain unknown mechanisms led by the peritoneum in the process of anatomic–physiologic closure of the patent processus vaginalis we had no complications related with the closure of the contralateral patent processus vaginalis the closure of an asymptomatic patent processus vaginalis was technically less demanding as the patency tends to be smaller we identified a prevalence of 17% asymptomatic patent processus vaginalis that were fixed within the same surgical intervention metachronous hernia occurred in 5.3% of the patients We speculate that almost a third of the metachronous hernias are avoidable if a laparoscopic approach with identification and closure of an asymptomatic patent processus vaginalis is adopted in procedures performed by less experienced surgeons because in many of them there is a fold of peritoneum under the round ligament that might easily be missed during cerclage that intends to leave no peritoneal gaps we realized we could use the gap between the percentage of males in our population and the percentage of males in those proposed for laparoscopic repair as an index to monitor the confidence of the surgical teams that decide to adopt a minimally invasive repair program our study demonstrates that independently of previous surgical experience in minimally invasive surgery pediatric surgeons easily adhere to the implementation of a minimally invasive program to repair inguinal hernia and communicating hydrocele In contrast to postoperative complications which were technique and experience independent there was a learning curve for perioperative complications and conversion rates that reached the nadir after each surgeon performed at least 35 cases the laparoscopic repair is a safe and effective approach whereas the cosmesis and the virtual extinction of metachronous contralateral hernia were the major advantages The gap between the percentage of males in those proposed for surgical repair and the percentage of males in patients operated by PIRS can be used as an index to monitor the confidence of the surgical teams that decide to adopt a similar program to repair inguinal hernia and communicating hydrocele by minimally invasive surgery This study was carried out in accordance with the recommendations of the Declaration of Helsinki with written informed consent from all subjects The protocol was approved by the scientific ethic committee from our institution The manuscript was written by CB and JC-P and revised by JC The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest This work was supported by the Fundação para a Ciência e Tecnologia (FCT) co-funded by Programa Operacional Regional do Norte (ON.2—O Novo 267 Norte); from the Quadro de Referência Estratégico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and from the Projeto Estratégico—LA 26—2013–2014 (PEst-C/SAU/LA0026/2013) The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fped.2017.00207/full#supplementary-material Percutaneous 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hernia repairs with minimum 2-year follow-up Is contralateral exploration necessary in preterm infants with unilateral inguinal hernia J Pediatr Surg (2006) 41(12):2004–7 Lamas-Pinheiro R and Correia-Pinto J (2017) Learning Curves for Laparoscopic Repair of Inguinal Hernia and Communicating Hydrocele in Children Received: 20 July 2017; Accepted: 11 September 2017; Published: 27 September 2017 Copyright: © 2017 Barroso, Etlinger, Alves, Osório, Carvalho, Lamas-Pinheiro and Correia-Pinto. 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Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH) the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups could not be amplified from human or rat fetal lungs by RT-PCR the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia most likely through a GHSR1a-independent pathway The aforementioned reports led to the hypothesis that ghrelin may be an important factor modulating lung development in CDH ghrelin expression in human and rat normal and hypoplastic fetal lungs was characterized the effect of exogenous administration of ghrelin in a nitrofen-induced CDH rat model was tested Our findings show that ghrelin expression is augmented in CDH and that exogenous administration of ghrelin is able to partially attenuate pulmonary hypoplasia in CDH they were considered very severe cases of pulmonary hypoplasia 10 normal lungs between 13.5 and 39 wk of gestation None of these patients received supplemental oxygen or mechanical ventilation All autopsies were performed within 24 h of death according to the standard protocol designed by the Dutch Pediatric Pathology Society The specimens were fixed by immersion in 4% buffered formalin embedded in paraffin and processed for immunohistochemistry Immunostainings were performed on formalin-fixed and paraffin-embedded human tissues Lung sections (5 μm) were placed on SuperFrost®Plus slides (Menzel-Glaser The primary antibodies were polyclonal rabbit antihuman ghrelin (H-031-30 CA) and polyclonal rabbit antihuman GHSR1a (Cys° amino acids 330–366 After dewaxing in xylene and rehydration in ethanol the samples were incubated in 3% hydrogen peroxide in methanol to quench the endogenous peroxidase Antigen retrieval was achieved by boiling in 10 mM citrate buffer followed by cooling down to room temperature Incubation with primary antibody occurred at 4°C overnight: anti-ghrelin (1:3000) and anti-GHSR1a (1:500) Negative control reactions consisted in omission of the primary antibody Positive control reactions for ghrelin in human stomach tissue and GHSR1a in human pituitary tissue were performed goat anti-rabbit horseradish peroxidase conjugated serum (1:100) (P 0448 was carried out at room temperature for 2 h To visualize the peroxidase activities in sections diaminobenzidine tetrahydrochloride (Sigma–Aldrich Co.) was used Sections were counterstained with hematoxyline Computer-assisted morphometric analysis was performed using a StereoInvestigator program (MicroBrigthField On each slide immunoreactive bronchi were identified and traced using 20× objective to calculate the epithelial bronchial area the number of immunopositive cells on each bronchus was counted Using these data the proportion of ghrelin-expressing cells per epithelial bronchial area was calculated Animal experiments were performed accordingly to the Portuguese law for animal welfare Animals were housed in an accredited mouse house and treated as specified in the ‘Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health' (National Institutes of Health Publication No.85-23 Barcelona) were maintained in appropriate cages under controlled conditions fed with commercial solid food and after mating they were checked for introital plugging Forty pregnant rats at day 9.5 of gestation randomly received by gavage either a single-dose of 100 mg of 2,4-dichorophenyl-p-nitrophenylether (nitrofen) dissolved in 1 mL of olive oil (n = 28) or an equal volume of vehicle (n = 12) rats were then randomly assigned to two different protocols fetuses were removed by caesarian section at 12.5 whereas nitrofen-exposed fetuses were removed at 17.5 19.5 and 21.5 dpc since only after that gestational age we could clearly distinguish the fetuses with or without CDH Fetuses with 12.5 and 15.5 dpc were processed in toto for hybridization studies the lungs were excised and the wet weights of each lung were measured Random left lung samples were collected and processed for in situ hybridization Samples used for the quantification of ghrelin's expression by real time-PCR were immersed in RNAlater (Qiagen This protocol resulted in three experimental groups: 1) control group not exposed to nitrofen nor ghrelin; 2) nitrofen group nitrofen-exposed fetus without diaphragmatic defect; 3) CDH group nitrofen-exposed fetus with left diaphragmatic defect This protocol resulted in six experimental groups: 1) control + saline group exposed neither to nitrofen nor ghrelin treated with saline; 2) nitrofen + saline group nitrofen-exposed fetus without diaphragmatic defect treated with saline; 3) CDH + saline group nitrofen-exposed fetus with left diaphragmatic defect treated with saline; 4) control + ghrelin group not exposed to nitrofen and treated with ghrelin; 5) nitrofen + ghrelin group nitrofen-exposed fetus without diaphragmatic defect treated with ghrelin; 6) CDH + ghrelin group nitrofen-exposed fetus with left diaphragmatic defect treated with ghrelin Total mRNA from each sample was extracted using the RNeasy Mini Kit Protect (Qiagen Quantification of total mRNA was done by spectrophotometry (BioPhotometer The reverse transcription was carried out on a T-gradient thermocycler (Biometra Germany) using the kit Superscript II (Invitrogen Total cDNA was used for the relative quantification by real time-PCR of ghrelin and of the reference gene β-actin using the LightCycler (Roche, Germany). All primers used were intron-spanning (Table 2) and primer design was based on the available sequences in GenBank (NCBI-NLM-PubMed-Gene) Real time-PCR reactions consisted in SYBR Green PCR master mix (QuantiTech SYBRgreen PCR 100 ng of cDNA and 10 pmol of each primer (Thermo Electron Ghrelin amplification consisted of 15 min hot-start 72°C 20 s) and acquisition mode at 80°C for 5 s β-actin amplification was performed with 15 min hot-start Ghrelin and β-actin standard amplification curves (ST curves) were made with randomly selected cDNA samples setting at r = 0.99 100 ng of the RT reaction was used for PCR amplification Standard amplification conditions were used and the PCR reactions performed in an automatic thermal cycler (MyCycler All quantitative data are presented as mean ± SE whereas for the evaluation of the effect on pulmonary hypoplasia of ghrelin's administration in control Upon statistically significant differences a test of Student-Newman-Keuls was selected to perform a pair–wise multiple comparisons Statistical significance was set at p < 0.05 Developmental production of ghrelin in normal and hypoplastic (CDH) human lungs. A) Immunohistochemistry in normal human fetal lungs. B) Immunohistochemistry in CDH human fetal lungs. Scale bar = 50 μm. Results of morphometric analysis from Control (▪) and CDH (⋄) human lungs Ghrelin expression pattern during the development of normal and CDH rat lung A) In situ hybridization in normal fetal lung B) In situ hybridization in hypoplastic CDH lung Since no significant differences were observed between nitrofen and CDH groups pictures depicting ISH of lungs of CDH fetuses are the only ones presented Ghrelin mRNA expression levels during normal fetal rat lung development, expressed in arbitrary units normalized for β-actin, obtained by real time-PCR (n = 7 for all studied developmental ages). p < 0.05:* versus 15.5dpc. Ghrelin expression levels obtained by real time-PCR in nitrofen-induced CDH rat model Ghrelin mRNA levels expressed in arbitrary units normalized for β-actin at day 17.5 in control group fetuses (black bars n = 8) and CDH group fetuses (dark grey bars p < 0.05: * verus Control group; § versus Nitrofen group Ghrelin was used for checking RT-PCR for fetal lung sample B) RT-PCR for GHSR in adult rat material (Pituitary Stomach and Heart) and in fetal rat lung (Control Nitrofen and CDH from gestational age 17.5 The reference gene used for checking RT-PCR was β-actin Effect of ghrelin administration to nitrofen-treated dams between 13.5 and 17.5dpc Organ-to-body weight ratio for all experimental groups was determined Control + saline (n = 27); Control + ghrelin (n = 13); Nitrofen + saline (n = 20); Nitrofen + ghrelin (n = 24); CDH + saline (n = 23); CDH + ghrelin (n = 34) p < 0.05: * versus Nitrofen + saline group; § versus CDH + saline group The present study revealed that in normal fetal lungs ghrelin was expressed in primitive epithelial cells as early as the pseudoglandular stage of development with decreasing levels of expression throughout gestation Although a similar expression pattern was observed in hypoplastic lungs ghrelin was overexpressed in the CDH lungs from human and rat Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of the CDH-related pulmonary hypoplasia This effect is mediated most likely through a GHSR1a-independent pathway since GHSR1a was not detected in human and rat fetal lungs the early presence of ghrelin expressing cells as well as their prominent number in the fetal lung may indicate a developmental role for ghrelin In human or rat CDH-associated hypoplastic fetal lungs ghrelin expression remained restricted to the epithelium The number of ghrelin-positive cells per epithelial bronchial area in human lung was increased mainly in early stages of lung development suggesting overexpression of ghrelin in CDH lungs In experimental CDH rat lungs ghrelin mRNA levels were significantly higher than in lungs of age-matched controls age-matched statistical comparisons could not be performed due to the reduced number of available samples representative of each fetal lung gestational stage Ghrelin produced in the lung may represent one of the major factors responsible for the mid-gestational peak of GH ghrelin levels were always higher in the CDH groups than in age-matched controls in all studied gestational ages ghrelin overexpression in hypoplastic lungs does not seem to relate with lung immaturity interpreting these findings as a compensatory mechanism related to impaired lung development prompt us to hypothesize that NEB could act as sensors of lung growth ghrelin should be considered as a growth factor released in response to the pulmonary hypoplasia associated with CDH Experimental observations indicated that in nitrofen-exposed pups ghrelin administration could normalize lung growth in the nitrofen group and increase lung-to-body weight ratio in the CDH group by 18% The potential clinical relevance of this effect should be emphasized since such an increase in lung parenchyma can be determinant in providing a better adaptation of CDH fetus to extra-uterine life since heart-to-body weight ratio of the newborn pups was not altered lung-to-body weight ratio in normal fetus was not significantly changed by ghrelin either ghrelin overexpression in CDH should not be interpreted as a causative factor of lung underdevelopment but rather a consequence of lung hypoplasia a countermeasure that elicits attenuation of lung underdevelopment in CDH fetuses a peak of ghrelin expression during the pseudoglandular stage of normal lung development was reported Ghrelin overexpression in hypoplastic lungs and the effect of ghrelin exogenous administration to nitrofen-treated dams suggests a role for ghrelin in the mechanisms involved in attenuating CDH-associated lung hypoplasia Jaffray B 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death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT Ghigo E 2004 Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor Wollmann HA 2000 Growth hormone and growth factors during perinatal life Harvey S 2005 Growth hormone expression in the perinatal and postnatal rat lung Beck F 1995 Localization of growth hormone receptor/binding protein messenger ribonucleic acid (mRNA) during rat fetal development: relationship to insulin-like growth factor-I mRNA Waters MJ 1992 Prenatal expression of the growth hormone (GH) receptor/binding protein in the rat: a role for GH in embryonic and fetal development? Skinner SJ 1998 Fetal rat lung epithelium has a functional growth hormone receptor coupled to tyrosine kinase activity and insulin-like growth factor binding protein-2 production Puri P 2004 Upregulated expression of EGF and TGF-alpha in the proximal respiratory epithelium in the human hypoplastic lung in congenital diaphragmatic hernia Puri P 1998 Upregulated tumor necrosis factor-alpha gene expression in the hypoplastic lung in patients with congenital diaphragmatic hernia Puri P 2003 Increased expression of ICAM-1 and VCAM-1 in the lung of nitrofen-induced congenital diaphragmatic hernia in rats Timmermans JP 2003 Functional morphology of pulmonary neuroepithelial bodies: extremely complex airway receptors Anat Rec A Discov Mol Cell Evol Biol 270: 25–40 Perrin DG 1995 Pulmonary neuroendocrine cell system: an overview of cell biology and pathology with emphasis on pediatric lung disease and Berstein J (eds) Perspectives in Pediatric Pathology Cutz E 1997 Abnormal expression of pulmonary bombesin-like peptide immunostaining cells in infants with congenital diaphragmatic hernia Spindel ER 1988 Gastrin-releasing peptide (mammalian bombesin) gene expression in health and disease Van Lommel A 2001 Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development Cutz E 1993 Oxygen sensing in airway chemoreceptors Sunday ME 1995 Bombesin and [Leu8]phyllolitorin promote fetal mouse lung branching morphogenesis via a receptor-mediated mechanism Tibboel D 1995 Pulmonary neuroendocrine cells in neonatal rats with congenital diaphragmatic hernia Download references Tena-Sempere for providing the plasmid with ghrelin for the riboprobe synthesis Note added in proof: After this manuscript had been accepted a paper describing abnormalities in norepinephrine and respiratory systems in Mecp2-/y mice was published: Viemari JC Hilaire G 2006 Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice Life and Health Sciences Research Institute (ICVS) Gustavo Melo-Rocha & Jorge Correia-Pinto Tiago Henriques-Coelho & Jorge Correia-Pinto This project was funded by Fundação para a Ciência e a Tecnologia (POCI/SAU-OBS/56428/2004) was supported by the Fundação para a Ciência e a Tecnologia (SFRH/BD/9631/2002) through the G.A.B.B.A was funded by Fundação para a Ciência e a Tecnologia (SFR/BI/9763/2003) Download citation DOI: https://doi.org/10.1203/01.pdr.0000202748.66359.a9 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Metrics details Upper urinary tract urothelial carcinomas are usually managed by radical nephroureterectomy (RNU) often followed by intravesical chemotherapy to minimize recurrence Open surgery is the gold standard procedure for RNU and it has been increasingly replaced by minimally invasive strategies endoscopic ureteral excision leaves the bladder unsutured and precluding the immediate administration of intravesical chemotherapy Here we describe a new method to close the bladder wall after ureteral excision using barbed sutures via the endoscopic access Our results in 8 female pigs demonstrate that this method is effective to close the bladder wall The procedure was completed in a median time of 24 min and no adverse events were registered in the follow-up or at the three-week necropsy This technique improves a previous approach described by our group because the device is more flexible and allows to tie the knots inside the bladder Barbed sutures have been used in the clinical practice for other types of surgeries and therefore this method can further be adapted to human patients with no safety concerns Its use may allow to administer intravesical chemotherapy which reduces tumor recurrence and improves patient outcomes chemotherapy administration also requires an adequately closed bladder wall since chemotherapy leakage might cause potentially lethal effects the large diameter and rigid structure of the device forced to enlarge the urethral access and pull out the strings to tie the knots this technique had limited human applications we aim to develop an endoscopic method to close the bladder wall that can be applied to human patients submitted to open or laparoscopic RNU We present a new technique using barbed sutures and discuss its advantages for human application This study describes feasibility of an endoscopic procedure in an animal model The study followed the internal protocol for animal experiments and was approved by the ethics subcommittee for Life and Health Sciences of University of Minho (017/2019) Proof-of concept experiment and training for the procedure was first done in a female pig which had been used for previous studies and was about to be sacrificed The endoscopic procedure was controlled by open surgery to verify bladder closure the bladder was filled with a saline solution of 3% methylene blue until fully distended The same surgeon with experience in endoscopic surgery completed the procedure in all animals A 0.035-inch flexible tip guidewire was inserted through the urethra with the help of a rigid ureteroscope (Karl Storz,Tuttlingen An urethral dilator was inserted to allow introducing a 21-F rigid cystoscope A full-thickness circular incision was done around the ureteral bladder orifice, with endoscopic scissors (26168A; Karl Storz, Tuttlingen, Germany) introduced through the working channel of the cystoscope (Figs. 1, 1–3). Surgical steps: 1. Access with flexible guidewire; 2. Scissor Incision; 3. View of the bladder defect; 4. Suture with needle holder; 5. Passing the tip of the needle through the end loop; 6. Final result. V-locTM90 suture: 1- needle, 2- Ampliation to show the anchoring projections on the surface of the suture, 3- blind loop at the distal part of the suture. Illustration of the steps (1–5) to close bladder incision using barbed sutures Illustration kindly provided by Ana Goios The bladder incision was closed using the V-LocTM90 Absorbable Suture, currently used in the clinical practice to close other types of wounds. This barbed suture device has a semi-circumferential needle, small projections along the wire that help anchoring the knots, and a blind loop in the distal part (Fig. 2) The kidney and detached ureter were excised by standard laparoscopic RNU and controlled by cystoscopy one week after the procedure they were sacrificed and necropsied to assess healing quality and inspect for bowel adherences we reported: (a) time to perform the procedure from end of bladder incision to end of bladder closure; (b) postoperative events; (c) 1-week cystoscopy findings; (d) necropsy findings Time summary statistics is presented by median and range The first proof-of-concept experiment was completed successfully. The bladder was adequately closed and no leakage was detected in the methylene blue test. Kidney and distal ureter with bladder cuff were removed en bloc (Supplementary Fig. 1) We completed the procedure in all 8 animals with precisely placed sutures and no complications in a median time of 24 min (range: 17 min 45 sec – 30 min and 10 sec) A surgeon with experience in endoscopic surgery completed the procedure easily Here we describe a new endoscopic technique to close the bladder wall after detaching the ureter The technique here described uses barbed sutures to close the bladder wall through the endoscopic access The sutures were effective in holding the suture as verified through follow-up cystoscopy and necropsy Since the bladder was adequately closed in all animals it is safe to conclude that the risk of tumor spillage into the urinary tract is reduced and that chemotherapy can be administered in the immediate post-operative period with no risk of leakage to the peritoneal cavity because it uses a more flexible and smaller diameter device and can thus be applied it to female or male humans patients the present strategy allows tying the knots inside the bladder which simplifies the procedure and reduces infection risks Surgeons experienced in endoscopy can easily learn this technique which only requires specific training in tying the knots internally The new procedure is derived from devices already in use in the clinical practice therefore it raises no ethical concerns or specific clinical trials for validation This technique may be further explored for other applications such as for trans-cytoscopic excision of bladder tumors followed by primary repair Despite the advantages of the pig as an animal model for surgical procedures its urinary system differs from the human in several aspects and particularly in size the pig bladder is more mobile and difficult to pierce we anticipate that the technique will be easier in human patients than in pigs The procedure also presented some limitations Since the needle holder was manipulated through the working channel of the nephroscope the range of movements of the needle holder was limited to the width of the working channel and the camera and needle holder had to be manipulated in block We also recognize some limitations on this study The procedure was tested in a convenience sample of 8 animals the study did not require statistical inferences and this number resulted from a compromise with the ethical concerns of animal testing We trust that this should not preclude from applying the technique to human patients because: (a) this can be considered an adaptation of previously existing methodologies and (b) in all animals the bladder was adequately closed with no adverse events only one surgeon did the experiment in all animals and therefore we cannot infer how other professionals will adapt to the technique gives confidence that other surgeons with experience in endoscopy will easily learn it We present a technique to close the bladder wall in laparoscopic RNU since it maintains a minimally invasive procedure but allows to administer chemotherapy in the hours following the surgery It can be applied to human patients because it is based on devices already in use in the clinical practice If human experiments confirm its feasibility this could contribute to improve the outcomes of oncologic patients subject to RNU European Association of Urology Guidelines on Upper Urinary Tract Urothelial Cell Carcinoma: 2015 Update Influence of positive surgical margin status after radical nephroureterectomy on upper urinary tract urothelial carcinoma survival Does the surgical technique for management of the distal ureter influence the outcome after nephroureterectomy EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016 The oncological results of laparoscopic nephroureterectomy for upper urinary tract transitional cell cancer are equal to those of open nephroureterectomy Oncological Outcomes of Laparoscopic Nephroureterectomy Versus Open Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An European Association of Urology Guidelines Systematic Review Impact of Distal Ureter Management on Oncologic Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma Oncologic outcomes following three different approaches to the distal ureter and bladder cuff in nephroureterectomy for primary upper urinary tract urothelial carcinoma Prophylactic Intravesical Chemotherapy to Prevent Bladder Tumors after Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinomas: A Systematic Review and Meta-Analysis Prevention of Bladder Tumours after Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinoma: A Prospective Randomised Clinical Trial of a Single Postoperative Intravesical Dose of Mitomycin C (the ODMIT-C Trial) Prospective Randomized Phase II Trial of a Single Early Intravesical Instillation of Pirarubicin (THP) in the Prevention of Bladder Recurrence After Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: The THP Monotherapy Study Group Trial A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials Novel method of full-thickness bladder closure with an endoscopic suturing machine: a survival study in a porcine model Endoscopic Closure of Transmural Bladder Wall Perforations Download references The authors acknowledge Ana Goios for support in manuscript writing and technical editing and for producing original illustrations for Figure 3 Life and Health Sciences Research Institute Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine performed the experiments and drafted the manuscript The authors declare no competing interests Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-019-54304-w Sorry, a shareable link is not currently available for this article. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Background: Sacrococcygeal Pilonidal Disease (PD) is commonly treated with excision and primary closure techniques (EPC). Minimally invasive techniques (MIT), such as EPSiT and Pit-picking, had been recently advocated promising better outcomes. We analyzed mid-term results from our center after introduction of MIT to treat PD. Methods: Patients submitted to MIT (n = 44) with a median follow-up of 37 months were analyzed and compared with patients submitted to EPC (n = 70) with a median follow-up of 5 years. Both groups included patients operated in our department between 2011 and 2016 and have similar demographic and clinical characteristics. We compared operative time and post-operative parameters such as time with pain, dressing time and time to relapse. Conclusions: MIT has the advantage of having a shorter time with pain in the postoperative period, while EPC benefits from a shorter dressing time. In general, the relapse of the disease tends to manifest more precociously in MIT patients. Moreover, in the subgroup of patients with previous surgery, MIT seems to have significantly better results when compared to EPC. Volume 7 - 2019 | https://doi.org/10.3389/fped.2019.00215 Background: Sacrococcygeal Pilonidal Disease (PD) is commonly treated with excision and primary closure techniques (EPC) had been recently advocated promising better outcomes We analyzed mid-term results from our center after introduction of MIT to treat PD Methods: Patients submitted to MIT (n = 44) with a median follow-up of 37 months were analyzed and compared with patients submitted to EPC (n = 70) with a median follow-up of 5 years Both groups included patients operated in our department between 2011 and 2016 and have similar demographic and clinical characteristics We compared operative time and post-operative parameters such as time with pain Results: The post-operative time with pain was significantly lower whereas the dressing time was significantly longer The relapse rate was similar in both groups but the follow-up is shorter in the MIT group the analysis of patients free of disease using Kaplan-Meier curves revealed that relapse tends to occur more precociously in MIT than in EPC patients (p = 0.014) in the subgroup of patients with previous surgery MIT's relapse rate was significantly lower than in the EPC group (30 vs Conclusions: MIT has the advantage of having a shorter time with pain in the postoperative period while EPC benefits from a shorter dressing time the relapse of the disease tends to manifest more precociously in MIT patients MIT seems to have significantly better results when compared to EPC There is still no consensus regarding the best treatment and various surgical techniques have been described (1–4). In cases where the abscess is the initial presentation, acute-phase drainage can be the definite treatment (1, 5) For the remaining, the ideal method would be the one with the lowest morbidity, shorter healing time and lower relapse rate (1–3) surgeons propose different techniques from lay open excision with primary closure to minimally invasive techniques (MIT) pediatric surgeons commonly use EPC with suture in the midline because it seems to have better cosmetic results During the last years, MIT had been advocated promising better outcomes (7, 9, 17–19) This led us to introduce MIT in our department since the last 3 years we analyzed mid-term results from our center after introduction of MIT to treat PD descriptive and retrospective analytical study was performed One hundred and fourteen patients were submitted to surgical treatment of Sacrococcygeal Pilonidal Disease (PD) in our department between 2011 and 2016 We gathered data through consultation of the clinical registry and telephone interviews with the patients Patients that were already discharged from outpatient visits were interviewed by phone and re-evaluated by a surgeon whenever a relapse was suspected Patients were divided into two groups according to the surgical technique used: (i) MIT group where patients were operated by EPSiT or Pit-Picking techniques; (ii) EPC group where patients were submitted to EPC in the midline Inclusion criteria were as follows: Patients with the diagnosis of PD submitted to surgery in our Pediatric Surgery Department with a follow-up time of at least 2 years Patients with more than one surgery during the study period were only included once with data corresponding to the last surgery Six patients were excluded once they could not respond to the telephone interview Relapse was determined: (i) by the need for a new surgery; or (ii) if diagnosed by a pediatric surgeon and registered in the clinical chart the study compared MIT and EPC in smaller groups according to the evolution and presentation of the disease (previous surgeries: yes or no; fistulas: none single or multiple; disease onset time: less than 6 months we analyzed possible factors that could contribute to relapse: Age; Gender; BMI; Presence of fistulas; Disease onset time (months); Previous surgery; Family History; Intra-operative Antibiotherapy; Dressing time (days); Post-operative complications (i.e. In the EPC, an elliptical cutaneous incision was performed, including the openings of the fistulas; the sinus was excised in depth, followed by approximation of the tissues and cutaneous suturing in the midline (1, 3) EPSiT included a small circular incision of 0.5 cm around the fistula opening to insert the fistuloscope as developed by Meinero in 2011. Hair removal, cleaning of the infected area and cauterization of the sinus granulation tissue and fistulas were performed (7) Pit-Picking consisted on the excision of the fistulas and curettage as described by Bascom in 1980 (10) This study was approved by the Ethical Committee of our Hospital (Reference 103/2017) and approved by the Ethical Subcommittee of Life and Health Sciences of University of Minho Normality was tested by graphical methods (histograms Q-Q plots) numerical methods (skewness and kurtosis indices) and the Shapiro-Wilk test In cases where the sample was significantly different from a normal distribution (age dressing time and follow-up time) a non-parametric test The chi-square test was also used to compare the categorical variables A survival analysis was performed to show the time to relapse on a Kaplan-Meier curve The Log Rank test was used to compare the time to relapse between the two groups a Logistic Regression was used to analyze possible factors that could contribute to relapse The statistical analysis was done using the IBM SPSS Statistics for Windows Significant results were considered for p < 0.05 A total of 114 surgeries were performed, 44 by MIT and 70 by EPC. The characteristics of the groups are shown in Table 1 There were no significant differences between the two groups regarding gender existence of previous surgery (relapsed disease) and family history but a significantly higher number of MIT patients presented multiple fistulas the duration of the operation for MIT was significantly shorter as well as the duration of post-operative pain EPC had significantly shorter dressing time the time with analgesics (median = 1 day) and the necessary time to return to daily life activity (median = 3 days) walk without pain (median = 1 day) and sit without pain (median = 1 day) were consistently shorter on MIT than in EPC (p < 0.001) It is important to highlight that we did not find differences between both groups regarding the use of intra-operatory antibiotherapy post-operative complications and depilation of the sacrococcygeal zone Comparative analysis of the intra- and post-operative parameters The 5-year relapse rate from our department using EPC was 41.4%, whereas the mid-term relapse rate of MIT was 40.9%. However, it should be emphasized that the follow-up time was shorter in MIT than in EPC (37 vs. 55 months, p < 0.001). In fact, the analysis of patients free of disease using Kaplan-Meier curves (Figure 1) revealed that relapse tends to occur more precociously in MIT than in EPC patients (14.5 months vs in the subgroup of PD patients with previous surgery (n = 10 in each group) MIT relapse rate was significantly lower than in the EPC group (30 vs Other subgroups' analysis (number of fistulas and time of disease) did not introduce differences between MIT and EPC (p > 0.05) Kaplan Meier's curve of time to relapse Regarding the factors that contribute to relapse the logistic regression identified only the variable “post-operative complications” with a significant result (p = 0.037; r2 = 0.052) This study confirms that MIT as treatment of PD in adolescents significantly attenuate post-operative discomfort, which would already be expected according to the literature (7, 8) the mid-term analysis suggests that they do not offer a lower relapse rate when compared to the classic excision and primary closure technique MIT seem to overcome all results obtained with the excision and primary closure technique Overall, this study compared two groups with similar pre-operative characteristics except for age and number of fistulas but these had low effect size (20). In addition, this may reflect a preference of the surgeon for MIT when there are multiple fistulas (avoiding a wider excision). That difference can also explain, at least in part, the longer dressing and healing time in the MIT group, as more fistulas are associated with a longer dressing time (7) because of that we compared our MIT group with our benchmark represented by the EPC group with a median follow-up of 5 years Our study even suggests that the relapse might be more precocious in MIT raising the possibility of a higher relapse rate as time goes onward According to the literature, MIT can be used for both first surgery or relapsed PD, being equally effective (7) as in relapsed cases MIT presented better results This was not mentioned by any other study up to now Although our series with previous surgery is small these results are worth further investigation Possible causes to relapse include tracts not completely excised associated with newly perforating hairs into the healing pilonidal skin scar (3). However, many factors are still not understood. Many studies tried to identify risk factors like prolonged sitting job, familiar and personal history, longer cavity diameter, young age and high BMI but none of them studied a pediatric population (26–28) we did not find a definitive risk factor as post-operative complications only predicted 5% of the relapses Limited by being a retrospective, single-center study, our work has the advantages of using a population instead of a sample (thus avoiding a selection bias); including more than 100 patients which allows to draw safer conclusions; having homogeneous groups; the groups' characteristics being accordingly to what is described in the literature i.e., mostly males, overweight/obese, and young people with familiar background (1, 2, 4) our study provides the longest follow-up of MIT in children Knowing that the PD relapse is essentially a time-dependent phenomenon it is imperative to increase the follow-up time we can verify our premise that MIT patients relapse more precociously and if the relapse rate is equal or lower whilst with a different relapse pattern MIT might have an important role in relapsed cases if the results observed in this study are confirmed MIT has the advantage of having a shorter time with pain in the postoperative period This study was carried out in accordance with the recommendations of the Ethical Committee of Hospital of Braga with written informed consent from all subjects All subjects gave written informed consent in accordance with the Declaration of Helsinki The protocol was approved by the Ethical Committee of our Hospital (Reference 103/2017) and and JC-P were involved in interpretation and analysis of data The manuscript was written by AIO and revised by CB CrossRef Full Text Timeline of recurrence after primary and secondary pilonidal sinus surgery Patient characteristics and symptoms in chronic pilonidal sinus disease Prognosis after simple incision and drainage for a first-episode acute pilonidal abscess PubMed Abstract | Google Scholar Treatment of adolescent pilonidal disease with a new modification to the Limberg flap: symmetrically rotated rhomboid excision and lateralization of the Limberg flap technique Endoscopic pilonidal sinus treatment: a prospective multicentre trial Endoscopic pilonidal sinus treatment (E.P.Si.T.) Endoscopic pilonidal sinus treatment: a systematic review and meta-analysis Pit-picking-operation bei patienten mit sinus pilonidalis CrossRef Full Text | Google Scholar Long-term follow-up for pilonidal sinus surgery: a review of literature with metanalysis Laser epilation is a safe and effective therapy for teenagers with pilonidal disease Successful treatment of recurrent pilonidal sinus with laser epilation Control of hair growth using long-pulsed alexandrite laser is an efficient and cost effective therapy for patients suffering from recurrent pilonidal disease Laser hair depilation in the treatment of pilonidal disease: a systematic review Laser depilation and hygiene: preventing recurrent pilonidal sinus disease Preliminary report on endoscopic pilonidal sinus treatment in children: results of a multicentric series Endoscopic pilonidal sinus treatment versus total excision with primary closure for sacrococcygeal pilonidal sinus disease in the pediatric population Endoscopic pilonidal sinus treatment: long-term results of a prospective series 20. Cohen J. Statistical Power Analysis for the Behavioral Sciences, 2nd ed. Available online at: http://www.utstat.toronto.edu/~brunner/oldclass/378f16/readings/CohenPower.pdf (accessed November 12 Google Scholar Safety and efficacy of minimally invasive video-assisted ablation of pilonidal sinus Outcomes of endoscopic pilonidal sinus treatment (EPSiT): a systematic review Google Scholar Pediatric endoscopic pilonidal sinus treatment a revolutionary technique to adopt in children with pilonidal sinus fistulas: our preliminary experience Does full wound rupture following median pilonidal closure alter long-term recurrence rate Risk factors for complications and recurrence after the Karydakis flap The risk of recurrence of Pilonidal disease after surgical management Pilonidal sinus disease: risk factors for postoperative complications and recurrence Keywords: Sacrococcygeal Pilonidal Disease Osório A and Correia-Pinto J (2019) Minimally Invasive Surgical Treatment of Pilonidal Disease: Mid-Term Retrospective Analysis of a Single Center Received: 16 November 2018; Accepted: 14 May 2019; Published: 04 June 2019 Copyright © 2019 Oliveira, Barroso, Osório and Correia-Pinto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited *Correspondence: Ana Isabel Oliveira, YW5haXNhYmVsb2xpdmVpcmE5NUBnbWFpbC5jb20= Get our news on your inbox! Suscribe x MercoPress, en Español Montevideo, May 5th 2025 - 12:05 UTC Foreign travelers brought in US$7.341 billion in revenue to Brazil last year the South American country's Central Bank (BCB) announced on Friday citing a report from the Ministry of Tourism These figures represented the best results in 15 years and an increase of 6.28% compared to the US$6.907 billion in 2023  The activity thus surpassed the returns on foreign trade of strategic export products such as cotton or copper ore “This is the highest value recorded in the last 15 years surpassing even the period of the 2014 FIFA World Cup when foreign tourists spent 6.914 billion dollars,” the Ministry of Tourism said “The arrival of foreign visitors to Brazil not only boosts the economy but also reaffirms Brazil's strength and beauty as a desired destination on the world stage,” Tourism Minister Celso Sabino argued Nearly a week after leading Brazilian airlines Azul and Gol announced their intentions to merge into a large-scale carrier the former announced Friday the suspension of services to smaller destinations effective March The company will no longer operate in Campos and Barreirinha (MA) due to various factors “ranging from the increase in aviation operating costs impacted by the global crisis in the supply chain and the rise in the dollar added to issues of fleet availability and supply and demand adjustments,” according to a statement Fernando de Noronha will only be served from Recife flights from Juazeiro do Norte will be handled at the company's main hub operations at Caruaru Airport will be performed by single-engined 9-passenger-seat Cessna Grand Caravan aircraft “The customers affected are being notified in advance,” Azul explained signed a memorandum of understanding to begin negotiations for a merger that would create an airline holding 60% of the country's passenger aviation share Turkish Airlines and LATAM Brasil announced an extension of their codeshare operations adding five new domestic routes from São Paulo's Guarulhos Airport to Aracaju Passengers may now book flights with either carrier and enjoy reciprocal benefits such as earning and redeeming miles on these codeshare routes Commenting for this story is now closed.If you have a Facebook account, become a fan and comment on our Facebook Page This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page https://doi.org/10.1136/archdischild-2018-315910 If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service You will be able to get a quick price and instant permission to reuse the content in many different ways A 14-year-old girl with no psychiatric background presented with painful epigastric mass and vomiting Physical examination showed emaciated appearance Abdominal ultrasound identified a hyperechoic curvilinear mass with acoustic shadowing Abdominal CT revealed a heterogeneous image in the gastric lumen An upper gastrointestinal endoscopy identified a ‘comet tail’ extension to duodenum suggestive of Rapunzel syndrome Abdominal tomography with a heterogeneous image in … Funding The authors have not declared a specific grant for this research from any funding agency in the public Patient consent Parental/guardian consent obtained Ethics approval Comissão de Ética para a Saúde do Hospital de Braga (CESHB) Provenance and peer review Not commissioned; internally peer reviewed.