Complications of the "Nuss Procedure" In Pectus Excavatum.

During the pediatric age range, one the most frequent deformities of the chest wall are Pectus Excavatum (PE). Currently the treatment of choice for PE is surgical intervention following the Nuss procedure. In this study, we present a description of the complications associated with surgical treatment of PE with the Nuss technique, in patients with symmetrical or asymmetrical deformity, in different stages of disease severity. The study was conducted in collaboration with the Pediatric Hospital "Istituto G. Gaslini" of Genoa. We analyzed a cohort of 402 patients (334 males and 68 females), who underwent corrective surgery between 2005 and 2018. Within this group of patients, we observed 82 cases with complications (20.39%), 20 of which were intraoperative (4.98%) and 62 post-operative (15.42%). For the evaluation of complications, this group was arbitrarily divided into patients with symmetric and asymmetric Pectus and in patients with mild, moderate and severe Pectus using Haller's index. Although a small group of patients presented complications, overall results from data analysis show that the Nuss technique represents the preferred surgical procedure for the treatment of PE, in agreement with literature. Furthermore, in our results show no correlation between asymmetry or severity of PE with complication related to the surgery.

Papillary Thyroid Carcinoma in Paediatric Age.

In children, differentiated thyroid carcinoma is a rare condition. Early diagnosis is not always easy, because of the lack of clinical symptoms, but it has a pivotal role in performing a correct therapeutic process. The study describes three cases of papillary thyroid carcinoma. None of the three patients had a positive familiarity or exposure to risk factors. In two cases, the tumor occurred as a non-injurious swelling in the anterior cervical region, in the other case it occurred with a latero-cervical lymphadenopathy that had been persistent for a year. In the first two patients we made a certain diagnosis by the needle aspiration of the thyroid nodule; in the other case the diagnosis was made by surgical exeresis and histological analysis of the lymph nodes. We also performed blood chemistry and hormonal tests, neck ultrasound, chest x-ray. The three children underwent total thyroidectomy and two of them also underwent right-sided cervical lymph node exeresis because there was the presence of metastasis. In our experience, the best therapeutic strategy for children with differentiated thyroid carcinoma is the total thyroidectomy, followed or not by latero-cervical lymph node exeresis and radioiodiotherapy. The removal of the whole gland reduces the risk of relapse.

Laparoscopic Repair of Paediatric Indirect Inguinal Hernia: Modified Flip Flap Technique.

In paediatric age, indirect inguinal hernia represents more than 95% of the hernial disease. It is a congenital type, in contrast with adulthood in which acquired forms are more frequently found (1). The laparoscopic correction of indirect inguinal hernia is one of the most common surgeries performed in paediatric age. In recent years, various techniques have been introduced for the videolaparoscopic correction of this disease. The aim of this study is to provide an assessment of the efficacy and safety of the execution of a modified Flip-Flap technique, using tissue glue for filling of Peritoneal-vaginal duct (DPV), performed in order to ensure greater suture tightness and reduce the incidence of postoperative hydrocele. author1, author2, author 2, author1, author1, author 2 The Authors present a retrospective review of their record of cases, considering a total of 187 patients aged between 18 months and 14 years. For the correction of the hernial defect, the modified VLS Flip-Flap technique was carried out. The evaluation of safety, efficacy, operating time, relapse rate and development of short-term complications (such as postoperative hydrocele, scrotal hematoma or ecchymosis, atrophy or iatrogenic testicle ascension) was considered in a mean follow-up of 6 months. The Authors suggest that this variant of the peritoneal Flip-Flap technique is simple to perform; its safety, reproducibility and effectiveness is proven and has a percentage of relapses and complications overlapping with the "open" approach and superior to other laparoscopic techniques.

Surgical VLS Therapy of Oesophageal Achalasia in Pediatric Age: Four Case Reports.

The Authors present a retrospective review of their record of cases, characterized by 4 cases of achalasia in which it was performed a Heller myotomy with front fundoplication (Thall) in laparoscopic approach in the period from 2012 to 2019. In paediatric achalasia, the laparoscopic Heller myotomy seems to be the best treatment because of its multiple advantages offered by the minimally invasive technique. First of all, thanks to the video-technique, which allows a complete and extended myotomy, the accuracy of this operation is maximized; moreover, the post-operative pain is widely reduced, thanks to the minimal dissection and traction of the tissues; finally, but not negligible, this approach ensures a better aesthetic result than the classic open technique. With regard to the front fundoplication, the Authors suggest that it is mandatory because, even if it extends the operating time, it ensures a natural protection to the myotomy herniated mucosa and avoids gastro-oesophageal reflux, which often occurs after the surgical correction, thus obliging to perform a reoperation.

Minimally Invasive Treatment of Urolithiasis in Children: Evaluation of the Use of Flexible Ureterorenoscopy and Laser Lithotripsy.

Urolithiasis is a multifactorial disease; in recent years, its incidence has gradually increased in pediatric age. Among the factors involved in urolithiasis pathophysiology, urinary tract anomalies and metabolic diseases are the most relevant, although ethnicity and environmental factors may have an important role. The advances in technology and miniaturization of endoscopic devices have permitted the use of Retrograde Intrarenal Surgery (RIRS) to treat kidney and ureteral stones. Nowadays, flexible ureterorenoscopy and laser lithotripsy, which are techniques that have been applied in the management of adult upper urinary tract disorders, are also used in children as a minimally invasive treatment of urolithiasis with encouraging, effective and safe results. The Authors report a retrospective review of their record of cases considering 21 pediatric urolithiasis treatment procedures performed between October 2017 and April 2019 in a total of 17 patients (10 males and 7 females). Six procedures involved the use of the flexible ureterorenoscope (FURS) while in 15 procedures the application of the laser fiber was used (FURSL). A case of laser lithotripsy for bladder stone was included. The average age of patients was 10.5 years (2-18 years). The renal pelvis dilatation pretreatment was evaluated in post-operative follow-up. From the evaluation of the sample in analysis, the use of RIRS has good results in the treatment of paediatric urolithiasis, emerging as a valid option in the management of the paediatric population in terms of efficacy and safety, with an improvement in patient outcomes.

Laparoscopic Splenectomy: Postero-Lateral Approach.

In paediatric population, the laparoscopic splenectomy has been preferred to the open surgery during the last years. Due to the improvement of the technique and the devices, the indications to the laparoscopic splenectomy have been increased, even though there is still a variety of conditions in which the execution of this technique is arduous. During the preoperative consult there is the need to carefully evaluate the existence of cholecystic lithiasis, the haemoglobin level in patients with SCA, platelet count in children with ITP and the vaccination status. An anterior and a lateral or hanging spleen approach are primarily used for laparoscopic splenectomy. In the last four years, near the Section of Pediatric Surgery of the Department of Pediatrics, Obstetrics and Medicine of the Reproduction of Siena University, 8 cases of splenomegaly have been treated, 7 by lateral videolaparoscopic splenectomy (5 males and 2 females, with medium age of 10,5 years) and 1 by anterior approach (10 years). The advantages shown by these techniques allow the laparoscopic splenectomy to be considered as a valid alternative to the open surgery. In children's laparoscopic splenectomy, the rate of complications is considerably low and the the major problem is the intraoperative hemorrhage. With increasing surgical experience, the minimally invasive approach appears to be superior in terms of faster postoperative recovery, shorter hospital stay, perioperative and postoperative advantages. Therefore, the laparoscopic technique may soon be accepted as the standard method in patients requiring splenectomy.

Pre and Post-Operative Ph-Metry in Videolaparoscopic Surgery for Gastro Oesophageal Reflux Disease.

Gastro-oesophageal reflux is common in children, especially in the first year of life, and it may be regarded as physiological. Good functioning of the lower oesophageal sphincter depends largely on the anatomical relationships between oesophagus, stomach and diaphragm hiatus. Relative immaturity of these structures in newborn babies and young children is a risk factor in reflux disease, which may result in a wide variety of typical and/or atypical symptoms and, sometimes, serious complications such as oesophagitis and stenosis. Reflux disease may be diagnosed and studied, basing on morphological and functional aspects and, since the advent of pH-metry, it is possible to personalise the therapeutic approach to children with reflux. Surgical treatment of reflux disease in children has recently been improved due to a mini-invasive surgical approach. Absolute indications are recurrent pneumonia, intractable pain due to oesophagitis and retarded growth, often in association with neurological impairment. In the last three years, 18 children with reflux disease underwent videolaparoscopic surgery in our department, 14 by the Nissen and 4 by the Toupet technique. Post-operative pH-metry always showed a reduction in exposure of the distal oesophagus to acid (integral of H+) and an improvement in oesophageal clearance (short refluxes percentage) indicative of good functioning of the gastro-oesophageal junction. PH-metry proved to be an invaluable technique for planning therapeutic strategy. In follow-up evaluations, it enabled us to monitor functioning of the gastro-oesophageal junction and to avoid other more difficult and invasive tests in patients with severe neurological impairment.

Congenital Cystic Adenomatoid Malformation of the Lung Tipe II: Three Cases Report.

Congenital cystic adenomatoid malformation (CCAM) is a rare congenital lung lesion. It may appear since birth (30-35%) with difficulty breathing or may have a late onset (60-65%) with recurring pulmonary infections or growth failure; in a small percentage of cases, the lesion can be completely asymptomatic. Fetal or post-natal surgery can be used as surgical treatment of these lesions. Postnatal surgery consists of a lobectomy, bilobectomy or pneumonectomy, based on the size of the lesion. The best age to undergo this surgery is around 2 years, but only if the injury is stable and the child has no complications. The study describes three cases of CCAM, observed at the Pediatric Surgery Section of the University of Siena. We analyzed those 3 cases whose approach was defined by the onset of symptoms, age and clinical condition of patients. In the first case the surgery was performed a few hours after birth due to the worsening of the clinical conditions; in the other two cases it was delayed because the patients were asymptomatic. The purpose of this study is to review the management of patients with CCAM in relation to clinical onset and the type of injury.

The conversion of eIF-2.GDP to eIF-2.GTP by eIF-2B requires Met-tRNA(fMet).

We have investigated why the recycling of eIF-2.GDP to eIF-2.GTP, mediated by the guanine nucleotide exchange factor eIF-2B, is rapid in rabbit reticulocyte lysate, reconstituted for optimal protein synthesis, but slow in an isolated reaction with purified eIF-2B. We have found that purified eIF-2B dissociates eIF-2.[3H]GDP as efficiently in the presence of GTP as it does in the presence of GDP provided Met-tRNA(fMet) is added. tRNA(fMet) is ineffective, and there is no Met-tRNA(fMet) requirement for exchange with GDP. Exchange of eIF-2 bound GDP for GTP is completely dependent upon Met-tRNA(fMet) in the presence of ATP, suggesting that under physiological conditions efficient recycling of eIF-2.GDP to eIF-2.GTP requires conversion of the latter, a relatively unstable complex, to a more stable Met-tRNA(fMet).eIF-2.GTP complex.

Regulation of eukaryotic initiation factor-2B activity by polyamines and amino acid starvation in rabbit reticulocyte lysate.

We recently reported that the translational control of protein synthesis by glucose 6-phosphate in gel-filtered, rabbit reticulocyte lysate is exerted on the activity of eukaryotic initiation factor (eIF)-2B, the factor that catalyzes the exchange of GTP for GDP bound to eIF-2, by a mechanism that is independent of the phosphorylation of eIF-2 (alpha subunit). We now demonstrate that two other conditions regulate the activity of eIF-2B in rabbit reticulocyte lysate: polyamines (spermidine and spermine) and amino acid deficiency. In the absence of added polyamines, protein synthesis in gel-filtered lysate is reduced to about 70% and eIF-2B activity to about 35% of optimal. The former is likely a result of the latter, since we find that reticulocyte lysate has about twice the eIF-2B necessary to recycle the eIF-2.GDP generated under conditions of optimal protein synthesis. In contrast, the reduction in eIF-2B activity (to about 50% of optimal) occurring in the absence of added amino acids in unfractionated or gel-filtered lysate is insufficient, by itself, to slow the rate of protein synthesis, and the inhibition of protein synthesis that does occur with amino acid deficiency is exerted on polypeptide chain elongation, not initiation. The reduction in eIF-2B activity occurring with amino acid deficiency cannot be reversed by adding more glucose 6-phosphate or polyamines nor can the reduced eIF-2B activity seen with polyamine deficiency be overcome by increasing the glucose 6-phosphate, suggesting that these three components regulate eIF-2B activity by different mechanisms.

Regulation of protein synthesis in rabbit reticulocyte lysate. Glucose 6-phosphate is required to maintain the activity of eukaryotic initiation factor (eIF)-2B by a mechanism that is independent of the phosphorylation of eIF-2 alpha.

Previous studies from other laboratories, using rabbit reticulocyte lysate filtered through Sephadex G-25 or G-50, have demonstrated that glucose 6-phosphate is required to maintain active rates of translation, but its mechanism of action is currently unsettled. We have tested whether glucose 6-phosphate is required to prevent activation of the hemin-controlled translational repressor and the phosphorylation of the smallest or alpha subunit of eukaryotic initiation factor 2 (eIF-2). We have found that antibody to the hemin-controlled translational repressor can completely restore protein synthesis in reticulocyte lysate, filtered through Sephadex G-25, that is incubated in the absence of hemin and presence of glucose 6-phosphate, but cannot restore protein synthesis in such lysate incubated in the presence of hemin and absence of glucose 6-phosphate. We have also found, using a modification of the method of Matts and London [1984) J. Biol. Chem. 259, 6708-6711) to measure the ability of gel-filtered lysate to dissociate and exchange GDP from eIF-2.GDP, that this endogenous eIF-2B activity is reduced to the same low level in the presence of hemin and absence of glucose 6-phosphate as it is in the absence of hemin and presence of glucose 6-phosphate. Although there is a low level of phosphorylation of eIF-2 alpha in gel-filtered lysate given hemin but no glucose 6-phosphate, it cannot account for the loss of eIF-2B activity, since this phosphorylation is removed by antibody to the hemin-controlled translational repressor or isocitrate, which do not restore protein synthesis or eIF-2B activity, and not by fructose 1,6-diphosphate, which does partially restore protein synthesis and eIF-2B activity. These findings suggest that sugar phosphates may exert a direct effect on eIF-2B and may be required for its proper function. Additional support for this conclusion is our finding that protein synthesis and eIF-2B activity in partially hemin-deficient lysate can be restored by high levels of glucose 6-phosphate or fructose 1,6-diphosphate without a reduction in the level of phosphorylated eIF-2 alpha, suggesting that such levels of sugar phosphate may permit restoration of normal function with a limiting amount of eIF-2B.

Evidence that phosphorylation of eIF-2(alpha) prevents the eIF-2B-mediated dissociation of eIF-2 X GDP from the 60 S subunit of complete initiation complexes.

Recent observations have indicated that eukaryotic initiation factor (eIF)-2 and GTP or GDP normally bind to 60 S ribosomal subunits in rabbit reticulocyte lysate and that when eIF-2 alpha is phosphorylated and polypeptide chain initiation is inhibited, eIF-2 X GDP accumulates on 60 S subunits due to impaired dissociation that is normally mediated by the reversing factor (eIF-2B). Current findings now indicate that inhibition due to phosphorylation of eIF-2 alpha is mediated, at least in part, by the inability to dissociate eIF-2 X GDP from the 60 S subunit of complete initiation complexes. At the onset of inhibition, there is an accumulation of Met-tRNA(f) and eIF-2 on the polysomes, despite a marked reduction in Met-tRNA(f) bound to 40 S subunits and Met-peptidyl-tRNA bound to the polysomes. This initial effect is not associated with the formation of "half-mers" (polysomes containing an extra unpaired 40 S subunit), and the 40 S X Met-tRNA(f) complexes, though reduced, still sediment at 43 S. When inhibition is maximal and the polysomes are largely disaggregated, there is an accumulation of 48 S complexes consisting of a 40 S subunit and Met-tRNA(f) bound to globin mRNA as well as small polysomal half-mers, such that residual protein synthesis occurs to about the same degree on "1 1/2"s and "2 1/2"s as on mono-, di-, and triribosomes. Exogenous eIF-2B increases protein synthesis on mono-, di-, and triribosomes and decreases that on half-mers. This is associated with reduced binding of Met-tRNA(f) and eIF-2 to ribosomal particles sedimenting at 80 S and greater and a shift from 48 S to 43 S complexes. These results suggest that eIF-2B must normally promote dissociation of eIF-2 X GDP from the 60 S subunit of complete initiation complexes before they can elongate but cannot when eIF-2 alpha is phosphorylated, resulting in the accumulation of these complexes, some of which dissociate into Met-tRNA(f) X 40 S X mRNA and 60 S X eIF-2 X GDP.