Propranolol and infantile hemangiomas: Outcome from a tricentric study.

INTRODUCTION: The introduction of propranolol as systemic therapy for infantile hemangiomas (IH) has changed the natural history of these tumors. Cases presenting with ulceration, functional limitation, and visceral or life-threatening localization are excellent indications to medical therapy. The aim was to report the medium term follow-up after the introduction of propranolol in 3 referral centers with particular attention to outcome and surgical treatments. MATERIALS AND METHODS: In the period 2011-2018 348 patients underwent systemic therapy with propanolol at a mean age of 3.5 months (range 1-10). The indications to begin the treatment were: visceral localization (10,6%), ulceration (20%), risk of severe esthetic impairment (27%), and peri­orifices localization (42.4%). RESULTS: The minimum follow-up was 1 year. Propranolol was administered for a mean of 11 months (range: 6-19) and in 22 cases it was resumed for extra 4.5 months due to rebound. Overall, 97.4% responded to therapy without severe side effects. Seven patients underwent surgery and 9 laser therapy . Twenty-four cases are scheduled for surgery for evident inesthetisms and 4 will undergo laser therapy to complete the treatment. CONCLUSIONS: The use of propranolol has considerably decreased the surgical indications for IH, improved the esthetic and functional outcome, and simplified the definitive surgical treatment. The response rate to therapy is very high and in case of failure both laser and surgery are still very effective. The correct diagnosis, early starting, and adequate duration of therapy are key factors for the success of treatment.

The use of biological membranes for correction of congenital malformations.

Many congenital malformations often require a multidisciplinary and multistep surgical treatment, including the use of biological membranes. Aims of the study were to describe the use of these membranes for the correction of malformations, their clinical performance at follow-up, and patient's tolerance to them. The study included patients treated between 2009 and November 2020 in two referral centers. They were affected by abdominal wall defects (AWD), esophageal atresia/tracheo-esophageal fistula (EA/TEF), diaphragmatic hernia (CDH), spinal defects (SD), and anorectal malformations (ARM). The human origin membranes used during surgery were amniotic membrane, fascia lata, and pericardium provided by the local tissue bank and the porcine-derived membrane available on the market. Thirty-one patients were retrieved. The sample included 10 AWD, 7 EA/TEF, 5 CDH, 4 SD, 2 ARM, and 3 miscellaneous defects. The median age at repair was 139 days (range: 10,5-1494). The median follow-up was 1021 days (range: 485,5-1535). Two patients were lost at follow-up. The defects were successfully repaired and the membranes perfectly tolerated in 28/29 cases. In 1 case of CDH the fascia lata was replaced with a Goretex patch due to recurrence of the defect. This is the largest series on the use of biological membranes in congenital malformations. The variety of tissues allows to choose the best material for each malformation. The excellent tolerance and performance of this first series of patients encourage the use of these membranes to correct different type of malformations at any age.

Eosinophil fungal rhinosinusitis caused by Fusarium infection secondary to odontogenic maxillary sinus disease: when collaboration between otolaryngologist and allergologist leads to the correct diagnosis and therapy.

SUMMARY: Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now "rhinosinusitis". On the basis of numerous causative factors, often co-existing in the same patient, the diagnosis of rhinosinusitis is also made by a wide variety of practitioners (allergologists, otolaryngologists, pulmonologists, primary care physicians, paediatricians, and many others). Approximately 5-15% of the population suffers from chronic rhinosinusitis, and in 10-12% of them, it is of dental origin. The treatment of odontogenic maxillary sinus disease is directed to the management of the rhinosinusitis and of the odontogenic source. The widespread use of dental implants and reconstructive procedures for dental implant placement has led to new types of complication, as in this case report, due to chronic eosinophilic rhinosinusitis secondary to Fusarium infection in the maxillary sinus. The patient was initially evaluated by the allergologist, and subsequently successfully treated by the otolaryngologist with Functional Endoscopic Sinus Surgery. The advantages of endoscopic sinus surgery include more accurate visualization, no external incision, reduced soft tissue dissection, and reduced hospital stay. Chronic maxillary sinusitis of dental origin is a common disease that requires treatment of the sinusitis as well as of the odontogenic source.

Rectal adenocarcinoma in patients with anorectal malformations: report of two cases and a review of the literature.

AIM: Anorectal malformation (ARM) is a rare congenital disorder of the anus and rectum. In the last 30 years virtually all patients born with ARM have survived and surgeons from adult care may be called to deal with new and long-term sequelae, including tumors of the pulled-through anorectum. Two new cases of colorectal carcinoma in young adults born with ARM and a review of the literature is reported to emphasize the importance of a multidisciplinary follow-up. METHODS: A man and a woman, with previous history of ARM, presented at 34 years of age with symptoms of intestinal occlusion and a large pelvic mass. Both patients had no familial history of colorectal carcinoma. RESULTS: The patients underwent biopsies (mucinous rectal adenocarcinoma) and stadiation (T4N0M0). In one case the microsatellite instability showed a stable profile. Despite maximal treatments, including surgery, chemo- and radio-therapy, they both died a few years after diagnosis for progression of disease. CONCLUSION: Case studies are too limited to suggest guidelines for prevention and treatment of such complications, but the life-long follow-up is mandatory in the framework of a well-established network between pediatric and adult surgeons. The risk of tumor development in these patients should not be neglected and colleagues from adult care should be aware of the possibility this occurs in their practice.

White matter lesions and vascular vertigo: clinical correlation and findings on cranial magnetic resonance imaging.

OBJECTIVE: Vestibular disorders and anxiety are closely related, probably because they share some neuronal pathways. Ageing and patient comorbidities are important facilitating factors, and multiple vascular risk factors could contribute to the onset of a vestibular syndrome called vascular vertigo. White matter lesions (WMLs) are often seen on magnetic resonance imaging (MRI) scans of elderly people and are related to various geriatric disorders, including dizziness. The cause of this correlation could be the disruption of neuronal networks that mediate higher vestibular cortical function. Numerous neuronal pathways link the vestibular network with limbic structures and the prefrontal cortex modulates anxiety through its connections to the amygdala. These could also explain nausea and sickness. The aim of the present work was to investigate the correlation between WML, vascular vertigo and cognitive functions. PATIENTS AND METHODS: Our team at the Poliambulanza Foundation Hospital of Brescia studied 90 patients (mean age 75 years) suffering from vascular vertigo with positive WML on MRI, by mapping the lesions and by grading anxiety and sickness symptoms. Furthermore, the same patients were treated with sulodexide (a glycosaminoglycan with antithrombotic activity) for 90 days (500 LSU/day for the first 45 days and 250 LSU/day for the following 45 days) to evaluate the efficacy on the vestibular symptoms. RESULTS: The results showed that the most frequent WML sites were frontal (n=34) and capsule (n=30) areas. Patients had a significant improvement on anxiety and sickness scores (p=0.0001 and p=0.02 respectively) after sulodexide treatment. CONCLUSIONS: In patients with vascular vertigo we confirmed the correlation between dizziness and anxiety and showed preliminary data regarding the efficacy of sulodexide in relieving in these patients anxiety and sickness.

Peristeen(®) transanal irrigation in paediatric patients with anorectal malformations and spinal cord lesions: a multicentre Italian study.

AIM: In paediatric and adult patients with neurogenic bowel, transanal irrigation (TAI) of the colon has gained popularity due to the introduction of a specifically designed device. The aim of this pilot study was to present the results of TAI using the Peristeen(®) TAI system in a group of paediatric patients with anorectal malformation (ARM) and congenital or acquired spinal cord lesions (SCLs). METHOD: Eight Italian paediatric surgery and spina bifida centres participated in the study. The inclusion criteria were age between 6 and 17 years, weight above 20 kg and unsatisfactory bowel management. Patients with chronic inflammatory bowel disease, mental disability and surgery within the previous 3 months were excluded. At the beginning of treatment (T0) and after 3 months (T1) the Bristol scale, a questionnaire assessing bowel function, and two questionnaires on quality of life (QoL) for patients aged 6-11 years (CHQ-pf50) and 12-17 years (SF36) were administered. RESULTS: Eighty-three patients were enrolled, and seventy-eight completed the study (41 ARMs, 37 SCLs). At T1, constipation was reduced in ARMs from 69% to 25.6% and in SCLs from 92.7% to 41.5%, faecal incontinence in ARMs from 50% to 18.6% and in SCLs from 39% to 9.8% and flatus incontinence in ARMs from 20.9% to 9.8% and in SCLs from 31.7% to 10%. At T0, the Bristol Stool Scale types were 1-2 in 45% of ARMs and 77.5% of SCL patients, whereas at T1 types 1-2 were recorded in only 2.5% of SCL patients. QoL improved in both groups. In the younger group, a significant improvement in QoL was recorded in ARM patients for eight of nine variables and in SCL patients for seven of nine variables. CONCLUSION: This study showed that Peristeen TAI resulted in a significant time reduction in colonic cleansing, increased independence from the carer and improved QoL in paediatric patients with ARMs and SCLs.

Towards the perfect ARM center: the European Union's criteria for centers of expertise and their implementation in the member states. A report from the ARM-Net.

BACKGROUND: Pediatric surgeons and patient organisations agree that fewer centers for anorectal malformations with larger patient numbers are essential to reach better treatment. The European Union transacts a political process which aims to realize such centers of expertise for a multitude of rare diseases. All the centers on a specific rare disease should constitute an ERN on that disease. ARM-Net members in different countries report on first experiences with the implementation of national directives, identifying opportunities and risks of this process. METHODS: Relevant details from the official European legislation were analyzed. A survey among the pediatric surgeons of the multidisciplinary ARM-Net consortium about national implementation was conducted. RESULTS: European legislation calls for multidisciplinary centers treating children with rare diseases, and proposes a multitude of quality criteria. The member states are called to allocate sufficient funding and to execute robust governance and oversight, applying clear methods for evaluation. Participation of the patient organisations is mandatory. The national implementations all over Europe differ a lot in respect of extent and timeframe. CONCLUSIONS: Establishing Centers of Expertise and a ERN for anorectal malformations offers great opportunities for patient care and research. Pediatric surgeons should be actively engaged in this process.

Congenital diaphragmatic hernia: focus on abnormal muscle formation.

BACKGROUND: CDH is a major birth defect, characterized by high mortality. How the initial defective mesenchymal substructures affects muscle malformation is unclear. Defects of genes involved in diaphragmatic development, such as friend-of-GATA2 (Fog2), may play an important role in its pathogenesis. We investigated the expression of Fog2 and proteins of myogenesis in a series of CDH and in diaphragms at different fetal ages, in order to clarify the role of muscular components during diaphragmatic development in cases with CDH. MATERIAL AND METHODS: Specimen were obtained from seven diaphragms of CDH cases undergoing surgery, 3 entire diaphragms from non repaired CDH, 5 control diaphragms at different gestational ages (16, 17, 22, 32, and 40g.w.), and 3 biopsy samples of normal voluntary muscle. The thickness of diaphragms at the edge of the defect in CDH and in developing diaphragms was measured. All samples were processed for HE staining and immunohistochemistry. Immunohistochemical expression of MyoD, Myf4, Pax7, Mib1 and Fog2 was evaluated. RESULTS: Mean thickness at the edge of the defect was 4.14mm. Contralateral hemi-diaphragm in 3 autopsies and in controls at 32 and 40weeks measured 2.25mm; histology showed a higher density of desmin-positive muscular cells at the edge of defect. CDH displayed scattered Myf4-positive cells (range 0%-10%, mean 2.4%), numerous Pax7-positive cells (range 0%-24%, mean 12.1%) and less than 1% Mib1-positive cells. Controls showed a reduction of positive cell with the progression of gestational age for Myf4 (30% at 16 weeks, 20% at 17 weeks, 5% at 22 weeks, 1% at 32 and 40 weeks), Pax7 (85% at 16 weeks and 17 weeks, 35% at 22 weeks, 11% at 32 weeks) and Mib1 (20% at 16 weeks, 8% at 17 weeks, 7% at 22weeks, 2% at 32 weeks). Fog-2 was diffusely positive in mesenchymal, mesothelial and muscular cells, in diaphragms from 16 to 22 weeks, decreasing to 20% of positive muscular cells in 32-week diaphragm. In CDH only mesothelial and mesenchymal cells were positive. Stem cell markers were negative in cases and controls. COMMENT: CDH shows a thick muscular border, with high number of mature muscle cells and significant increase of quiescent satellite cells (PAX7+, Mib1-). Abnormal architecture may affect the normal process of myogenesis and thus signaling and cell-cell interactions of myocytes. The expression of Fog2 in mesothelial and mesenchymal cells in CDH demonstrates the absence of a genetic defect involving Fog2 in our cases. Being Fog2 expressed in muscle cells at early stage supports the hypothesis that the altered diaphragmatic genesis may undermine also the muscular component instead of the only mesenchymal one.

A cross-sectional nationwide survey on esophageal atresia and tracheoesophageal fistula.

BACKGROUND: Our study aims at disclosing epidemiology and most relevant clinical features of esophageal atresia (EA) pointing to a model of multicentre collaboration. METHODS: A detailed questionnaire was sent to all Italian Units of pediatric surgery in order to collect data of patients born with EA between January and December 2012. The results were crosschecked by matching date and place of birth of the patients with those of diagnosis-related group provided by the Italian Ministry of Health (MOH). RESULTS: A total of 146 questionnaires were returned plus a further 32 patients reported in the MOH database. Basing on a total of 178 patients with EA born in Italy in 2012, the incidence of EA was calculated in 3.33 per 10,000 live births. Antenatal diagnosis was suspected in 29.5% patients. 55.5% showed associated anomalies. The most common type of EA was Gross type C (89%). Postoperative complications occurred in 37% of type C EA and 100% of type A EA. A 9.5% mortality rate was reported. CONCLUSIONS: This is the first Italian cross-sectional nationwide survey on EA. We can now develop shared guidelines and provide more reliable prognostic expectations for our patients.

Autism and esophageal achalasia in childhood: a possible correlation? Report on three cases.

Chronic gastrointestinal symptoms are commonly reported in autistic patients. Dysphagia is often present, and it is generally related to behavioral eating disorders. The association between autism and esophageal achalasia has not been described in literature yet. We report our experience with three cases of autistic children we recently treated for esophageal achalasia. In the first case (a 14-year-old male), achalasia was diagnosed with barium swallow and esophageal manometry and was successfully treated with three pneumatic endoscopic dilatations (follow-up: 3 years). In the second case (a 12-year-old female), achalasia was diagnosed with barium swallow and esophageal manometry and was treated with Heller myotomy after two unsuccessful pneumatic endoscopic attempts (follow-up: 3 months). In the last case, a 15-year-old male underwent barium swallow and endoscopy that confirmed achalasia. He was treated with Heller myotomy, and he is asymptomatic at a 6-month follow-up. To our knowledge, this is the first report of a possible association between autism and esophageal achalasia. Because of the rarity of both diseases, their association in the same patient is unlikely to be casual even if speculation on their common etiology is impossible at present. This finding needs further confirmation, but it is sufficient, in our opinion, to indicate proper evaluation with barium swallow and/or manometry in any autistic children with eating difficulty.

Induction of meconium evacuation and stooling habit development in premature infants: role of gestational age.

AIM: Meconium obstruction has been viewed as a cause of bowel dysfunction and poorer outcome in preterm neonates. This study investigated whether the need of meconium induction over the 7th postnatal day would relate with later bowel habit development. The study was carried out at the Department of Pediatrics, University of Padua, Italy. METHODS: This was a prospective study, performed on 80 premature infants, separately analyzed in three subgroups according to the gestational ages (Subgroup A [16]: 23-26/6; Subgroup B [26]: 27/0-30/6; and Subgroup C [38]: 31/0-34/6 weeks), after the induction from 7th day of life of meconium evacuation by saline enema. To evaluate stooling habit development, data on constipation occurrence were obtained via a telephone interview with parents six months after neonatal care. RESULTS: At the 23-26/6 weeks subgroup A there was a significant increased risk (RR; 95%, CI) of saline enema to induce meconium passage as compared to subgroups B (2.27; 1.11-4.47) and subgroup C (2.28; 1.04-4.94), with a significant P per trend decrease (P<0.05) with increasing gestational age. Even, at six months of life, subgroup A showed a significant increased risk of constipation as compared to subgroups B (3.25; 1.04-9.75) and C (3.73; 1.19-11.63), respectively. CONCLUSION: The results of this study indicate that meconium retention over the first week of life is a relatively common features in premature subgroup infants of 23-26/6 weeks of gestation. These premature infants at 6 months of age show a stooling habit characterized by frequent constipation.

Increased adipogenic conversion of muscle satellite cells in obese Zucker rats.

AIMS/HYPOTHESIS: Visceral and intermuscular adipose tissue (IMAT) depots account for most obesity-related metabolic and cardiovascular complications. Muscle satellite cells (SCs) are mesenchymal stem cells giving rise to myotubes and also to adipocytes, suggesting their possible contribution to IMAT origin and expansion. We investigated the myogenic differentiation of SCs and the adipogenic potential of both preadipocytes and SCs from genetically obese Zucker rats (fa/fa), focusing on the role of Wnt signaling in these differentiation processes. METHODS: SCs were isolated by single-fiber technique from flexor digitorum brevis muscle and preadipocytes were extracted from subcutaneous adipose tissue (AT). Morphological features and gene expression profile were evaluated during in vitro myogenesis and adipogenesis. Wingless-type MMTV integration site family member 10b (Wnt10b) expression was quantified by quantitative PCR in skeletal muscle and AT. RESULTS: We did not observe any difference in the proliferation rate and in the myogenic differentiation of SCs from obese and lean rats. However, a decreased insulin-induced glucose uptake was present in myotubes originating from fa/fa rats. Under adipogenic conditions, preadipocytes and SCs of obese animals displayed an enhanced adipogenesis. Wnt10b expression was reduced in obese rats in both muscle and AT. CONCLUSIONS/INTERPRETATION: Our data suggest that the increase in different fat depots including IMAT and the reduced muscle insulin sensitivity, the major phenotypical alteration of obese Zucker rats, could be ascribed to an intrinsic defect, either genetically determined or acquired, still present in both muscle and fat precursors. The involvement of Wnt10b as a regulator of both adipogenesis and muscle-to-fat conversion is suggested.

Design and development of nanovehicle-based delivery systems for preventive or therapeutic supplementation with flavonoids.

To date more than 4000 compounds are recognized to belong to the class of flavonoids. These natural phenolic drugs are poorly soluble in water and are rapidly degraded and metabolized in the human body, but nevertheless are very promising for their potential contribution to the prevention and therapy of major chronic diseases, including cardiovascular and neurodegenerative diseases and cancer. In recent years a number of flavanols (e.g. catechins), flavonols (e.g. quercetin, myricetin) and isoflavones (e.g. genistein, daidzein) have been confirmed to possess strong antioxidant, anti-inflammatory, anti-proliferative and anti-aging activities. Incorporation into lipidic or polymer-based nanoparticles appears to markedly help the oral delivery of flavonoids, as these particles can protect the drug from degradation in the gastrointestinal tract and, by virtue of their unique absorption mechanism through the lymphatic system, also from first-pass metabolism in the liver. In addition, both oral and parenteral administration of flavonoids exploits a pharmacologic delivery route that guarantees sustained release of the active principle at the desired site of action. A comprehensive review of studies currently available on the in vitro and in vivo experimental administration of flavonoids by means of nanovectors may be of use as a foundation for the development of advanced delivery systems for these powerful compounds, in view of their adoption in primary and secondary disease prevention.

Bronchogenic cysts of the neck: a rare localization and review of the literature.

Personal experience in the diagnosis and management of two patients, one adult and one child, with pathologically proven bronchogenic cysts is described. Both patients presented with a solitary neck mass that proved to be bronchogenic cysts on histological examination. Aim of the review is to define the cytology, histopathological and clinical characteristics of bronchogenic cysts and discuss the features that distinguish them from other cervical cysts. Definitive treatment requires surgical excision.

Early prenatal diagnosis of cloacal exstrophy with fetal magnetic resonance imaging.

Prenatal diagnosis of cloacal exstrophy can be challenging during pregnancy and, subsequently, the counseling very difficult. Available ultrasonographic criteria may be inadequate, especially in early gestational ages. A case of early prenatal detection of cloacal exstrophy with fetal magnetic resonance imaging is reported herein for the first time.

Polypoid lesion of the gallbladder in childhood: case report and literature review.

Gallbladder polypoid lesions are rare in the pediatric patient and sometimes represent an incidental finding. A 13 year old male was referred to the Padua Hospital Pediatric Department for an obesity. A routine abdominal ultrasound (US) detected a gallbladder polypoid lesion 6 mm in diameter, initially considered a gallbladder adenoma. Investigation did not detect any other biliary tract abnormality. After seven months, the asymptomatic patient underwent a follow-up US which revealed the disappearance of the polypoid mass. The following concerns are raised: what is the size of the polypoid mass that should be considered for surgery? How does the presence of symptoms worsen the diagnosis and lead to preferring a surgical approach (cholecystectomy) over an echographic follow-up?

Procoagulant activity in children with community acquired pneumonia, pleural effusion and empyema.

UNLABELLED: In patients with community-acquired pneumonia (CAP), bacterial-cell-wall-derived fragments may induce the coagulation cascade. To contribute to the knowledge of underlying mechanisms, we have studied the fibrinolytic activity in children with CAP and parapneumonic effusions. PATIENTS AND METHODS: Twenty previously healthy children admitted to our Department with CAP were studied; with (n = 11) or without (n = 9) pleural effusion (PPE). We also investigated 10 children with empyema. In all children we analyzed coagulation and fibrinolytic parameters and compared the results to nine controls. RESULTS: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were not significantly modified in the three groups as compared to controls (P = 0.975, P = 0.535, respectively). The fibrinogen levels were significantly increased in respect to the control group (P < 0.0001). The median values of D-dimer showed an increasing trend that was statistically significant: children with pneumonia 244 microg/L, with pneumonia and PPE 751 microg/L and with empyema 2003 microg/L, in respect to values (48 microg/L) of our control group (P < 0.0001). CONCLUSION: The results suggest that plasma level of D-dimer can give an additional contribution for the evaluation of the severity of CAP and its complications in children.