Does thyroglossal duct arborization play a role in the post-surgical outcome of Sistrunk procedure in children?

PURPOSE: The purpose of the present study is to analyze thyroglossal duct cyst (TGDC) histopathological features, with focus on "arborization", in a cohort of pediatric patients who underwent surgical removal, and evaluate a possible correlation with clinical recurrences. METHODS: A retrospective analysis of all patients who underwent surgical resection for TGDC at the division of Pediatric Surgery of the University of Pisa from 2015 to 2020 was performed; for each patient, the following data were recorded: age, sex, clinical presentation, localization, size of the lesion, diagnostic tools, histopathological features, perioperative complications, recurrence and follow-up. RESULTS: With respect to arborization, following histopathological analysis 25/30 patients (83.3%) presented thyroglossal duct branching. After a median follow-up of 3.5 years, only 2 out of 30 patients (6.7%), one male and one female, respectively aged 4 y.o. and 6 y.o., presented recurrence within one year from first surgery. CONCLUSION: Surgery for TGDC remains a challenge for pediatric surgeons, while arborization was present in most of our cases which underwent surgery. With respect to the role of arborization, our study did not highlight sufficient conclusive data regarding their role in recurrence: instead, it showed wide resection as satisfactory, being the arborization present in most of the cases at histopathology.

Laparoscopic appendectomy with single port vs conventional access: systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Conventional three-access laparoscopic appendectomy (CLA) is currently the gold standard treatment, however, Single-Port Laparoscopic Appendectomy (SILA) has been proposed as an alternative. The aim of this systematic review/meta-analysis was to evaluate safety and efficacy of SILA compared with conventional approach. METHODS: Per PRISMA guidelines, we systematically reviewed randomised controlled trials (RCTs) comparing CLA vs SILA for acute appendicitis. The randomised Mantel-Haenszel method was used for the meta-analysis. Statistical data analysis was performed with the Review Manager software and the risk of bias was assessed with the Cochrane "Risk of Bias" assessment tool. RESULTS: Twenty-one studies (RCTs) were selected (2646 patients). The operative time was significantly longer in the SILA group (MD = 7,32), confirmed in both paediatric (MD = 9,80), (Q = 1,47) and adult subgroups (MD = 5,92), (Q = 55,85). Overall postoperative morbidity was higher in patients who underwent SILA, but the result was not statistically significant. In SILA group were assessed shorter hospital stays, fewer wound infections and higher conversion rate, but the results were not statistically significant. Meta-analysis was not performed about cosmetics of skin scars and postoperative pain because different scales were used in each study. CONCLUSIONS: This analysis show that SILA, although associated with fewer postoperative wound infection, has a significantly longer operative time. Furthermore, the risk of postoperative general complications is still present. Further studies will be required to analyse outcomes related to postoperative pain and the cosmetics of the surgical scar.

Follow-up study of three cases of congenital microgastria.

Current knowledge on congenital microgastria is limited due to its extreme rarity, and the paucity of nutritional and quality of life follow-ups. Patients affected by congenital microgastria cases followed at out center were screened, and general and nutritional status were evaluated at follow-up visits through validated questionnaires. Three cases were included: one patient died because of a complex syndromic picture where microgastria was imperatively approached conservatively. The remaining cases underwent Hunt-Lawrence at 2 and 17 months. After 2 years and 27 years postoperatively, both patients are on full oral intake. The 28-yearold patient did not reach a BMI higher than 18. She rated her quality of life as unimpacted, with a Gastrointestinal Quality of Life Index of 111. In the other case, parents reported about their 2-yearold child an Infant Gastrointestinal Symptom Questionnaire of 13, corresponding to "no distress". Our findings confirm the literature trend supporting the role of early surgery in microgastria to improve outcomes. We presented the nutritional status and quality of life in two cases of congenital microgastria operated according to Hunt-Lawrence at a 2-year and 27-year distance, which is the longest follow-up reported to date.

Intradiaphragmatic pulmonary sequestrations: a surgical challenge. Case series.

Bronchopulmonary sequestrations (BPSs) are rare congenital anomalies characterized by non-functioning embryonic lung tissue receiving anomalous blood supply. They are most commonly located within the thorax (supradiaphragmatic) or into the abdominal cavity (infradiaphragmatic). Intradiaphragmatic extralobar BPs (IDEPS) are an exceptionally rare finding, representing a diagnostic and operative challenge. We report three cases of IDEPS and their surgical management, describing our experience and approach to such rare clinical entities. From 2016 to 2022, we treated 3 cases of IDEPS. Surgical techniques, histopathological findings and clinical outcomes were retrospectively evaluated for each case and compared. Three different surgical techniques were used to approach each lesion, from open thoracotomy to a combined laparoscopic and thoracoscopic approach. Histopathological analysis of the specimens revealed hybrid pathological features, proper of both congenital pulmonary airway malformation (CPAM) and extralobar pulmonary sequestration. IDEPS represent a surgical challenge for pediatric surgeons, given their complex surgical planning. In our experience, the thoracoscopic approach is safe and feasible when performed by trained surgeons, even though a combined thoracoscopic-laparoscopic approach allows for optimal vessels control. The presence of CPAM elements within the lesions supports their surgical removal. Additional studies are required to better characterize IDEPS and their management.

Intestinal Bowel Lengthening within the First 6 Months of Life: Institutional Experience and Review of the Literature.

Background: Management of short bowel syndrome in children has been surrounded by much debate with timing of the lengthening procedure still controversial. Early bowel lengthening procedure (EBLP) has been defined as any bowel lengthening procedure performed before 6 months of age. The purpose of this paper is to report the institutional experience in EBLP and to review the literature on this subject to identify common indications. Methods: An institutional retrospective analysis of all the intestinal lengthening procedures was performed. Furthermore, an Ovid/Embase search regarding children who underwent bowel lengthening in the past 38 years was conducted. Primary diagnosis, age at procedure, type of procedure, indication, and outcome were analyzed. Results: Ten EBLP were performed in Manchester from 2006 to 2017. Median age at surgery was 121 days (102-140), preoperative small bowel (SB) length was 30 cm (20-49) while postoperative SB length was 54 cm (40-70), with a median increased bowel length of 80%. Ninety-seven papers were reviewed, with more than 399 lengthening procedures performed. Twenty-nine papers matched criteria with more than 60 EBLP were observed of which 10 were performed in a single center from 2006 to 2017. EBLP was performed due to SB atresia, to excessive bowel dilatation or failure to enteral feeds, at a median age of 60 days (1-90). Serial transverse enteroplasty was the most frequent procedure used lengthening the bowel from 40 cm (29-62.5) to 63 cm (49-85), with a median increased bowel length of 57%. Conclusions: This study confirms that no clear consensus on indication or timing to perform early SB lengthening is reported. According to the gathered data, EBLP should be considered, only in cases of actual necessity after review of qualified intestinal failure center.

Next generation sequencing panel target genes: possible diagnostic tool for ectodermal dysplasia related diseases.

BACKGROUND: Ectodermal dysplasias (EDs) are a large and complex group of disorders affecting the ectoderm-derived organs; the clinical and genetic heterogeneity of these conditions renders an accurate diagnosis more challenging. The aim of this study is to demonstrate the clinical utility of a targeted resequencing panel through enhancing the molecular and clinical diagnosis of EDs. Given the recent developments in gene and protein-based therapies for X-linked hypohidrotic ectodermal dysplasia, there is a re-emerging interest in identifying the genetic basis of EDs and the respective phenotypic presentations, in an aim to facilitate potential treatments for affected families. METHODS: We assessed seventeen individuals, from three unrelated families, who presented with diverse phenotypes suggestive of ED. An extensive multidisciplinary clinical evaluation was performed followed by a targeted exome resequencing panel (including genes that are known to cause EDs). MiSeqTM data software was used, variants with Qscore >30 were accepted. RESULTS: Three different previously reported hemizygous EDA mutations were found in the families. However, a complete genotype-phenotype correlation could not be established, neither in our patients nor in the previously reported patients. CONCLUSIONS: Targeted exome resequencing can provide a rapid and accurate diagnosis of EDs, while further contributing to the existing ED genetic data. Moreover, the identification of the disease-causing mutation in an affected family is crucial for proper genetic counseling and the establishment of a genotype-phenotype correlation which will subsequently provide the affected individuals with a more suitable treatment plan.

Biomaterial Inks from Peptide-Functionalized Silk Fibers for 3D Printing of Futuristic Wound-Healing and Sensing Materials.

This study illustrates the sensing and wound healing properties of silk fibroin in combination with peptide patterns, with an emphasis on the printability of multilayered grids, and envisions possible applications of these next-generation silk-based materials. Functionalized silk fibers covalently linked to an arginine-glycine-aspartic acid (RGD) peptide create a platform for preparing a biomaterial ink for 3D printing of grid-like piezoresistors with wound-healing and sensing properties. The culture medium obtained from 3D-printed silk fibroin enriched with RGD peptide improves cell adhesion, accelerating skin repair. Specifically, RGD peptide-modified silk fibroin demonstrated biocompatibility, enhanced cell adhesion, and higher wound closure rates at lower concentration than the neat peptide. It was also shown that the printing of peptide-modified silk fibroin produces a piezoresistive transducer that is the active component of a sensor based on a Schottky diode harmonic transponder encoding information about pressure. We discovered that such biomaterial ink printed in a multilayered grid can be used as a humidity sensor. Furthermore, humidity activates a transition between low and high conductivity states in this medium that is retained unless a negative voltage is applied, paving the way for utilization in non-volatile organic memory devices. Globally, these results pave the way for promising applications, such as monitoring parameters such as human wound care and being integrated in bio-implantable processors.

Combined procedures for surgical short bowel syndrome: experience from two European centres.

BACKGROUND: Autologous gastrointestinal reconstructive surgery (AGIR) has become a key component of intestinal rehabilitation programs. However, the best surgical option for short bowel syndrome (SBS) remains unknown. This paper presents our experience using combined procedures as primary treatment. METHODS: We collected data on SBS patients who underwent surgery from 2008 to 2021 in two tertiary European Centres. Combined procedures were defined as more than one technique used on the same patient. Charts were reviewed for demographics, type of procedures, complications, and outcomes. Data are presented as median and IQR. Wilcoxon signed rank was used for all paired analyses. RESULTS: Twenty-one children (12 females) underwent combined procedures. Preoperative median small bowel length was 20 cm (IQR: 15-35 cm); after lengthening, it was 35.5 cm (IQR: 30.75-50.50 cm) (P < 0.001). Combined procedures were simultaneous in 15 patients and sequential in 6. At a median of 9.2 years (IQR: 7.55-9.78 years) follow-up, complications were three bowel obstructions after strictures of anastomosis and two wound infections. Two patients achieved enteral autonomy, and others followed a weaning home parenteral nutrition regimen with a median of 4 nights off (IQR: 3-4 nights) starting with a median of 7 nights (IQR: 7-7 nights). CONCLUSIONS: Combined AGIR techniques are practical and safe in SBS treatment when tailored to meet patients' needs, combining lengthening, tailoring, and reducing transit time procedures. Therefore, combined AGIR may be considered a resource in intestinal rehabilitation units' armamentarium.

The role of liver transplantation in the care of primary hepatic vascular tumours in children.

Liver transplantation (LT) is the standard of care for many liver conditions, such as end-stage liver diseases, inherited metabolic disorders, and primary liver malignancies. In the latter group, indications of LT for hepatoblastoma and hepatocellular carcinoma evolved and are currently available for many non-resectable cases. However, selection criteria apply, as the absence of active metastases. Evidence of good long-term outcomes has validated the LT approach for managing these malignancies in the context of specialist and multidisciplinary approach. Nevertheless, LT's role in treating primary vascular tumours of the liver in children, both benign and malignant, remains somewhat controversial. The rarity of the different diseases and the heterogeneity of pathological definitions contribute to the controversy and make evaluating the benefit/risk ratio and outcomes quite difficult. In this narrative review, we give an overview of primary vascular tumours of the liver in children, the possible indications and the outcomes of LT.

Biocompatible and Printable Ionotronic Sensing Materials Based on Silk Fibroin and Soluble Plant-Derived Polyphenols.

The emergence of ionotronic materials has been recently exploited for interfacing electronics and biological tissues, improving sensing with the surrounding environment. In this paper, we investigated the synergistic effect of regenerated silk fibroin (RS) with a plant-derived polyphenol (i.e., chestnut tannin) on ionic conductivity and how water molecules play critical roles in regulating ion mobility in these materials. In particular, we observed that adding tannin to RS increases the ionic conductivity, and this phenomenon is accentuated by increasing the hydration. We also demonstrated how silk-based hybrids could be used as building materials for scaffolds where human fibroblast and neural progenitor cells can highly proliferate. Finally, after proving their biocompatibility, RS hybrids demonstrate excellent three-dimensional (3D) printability via extrusion-based 3D printing to fabricate a soft sensor that can detect charged objects by sensing the electric fields that originate from them. These findings pave the way for a viable option for cell culture and novel sensors, with the potential base for tissue engineering and health monitoring.

Engineering Auxetic Cylinders and Intestine to Improve Longitudinal Intestinal Lengthening and Tailoring Procedure.

Auxetic materials can be exploited for coupling different types of tissues. Herein, we designed a material where the microorganism metabolic activity yields the formation of buckled/collapsed bubbles within gelling silicone cylinders thus providing auxetic properties. The finite element model of such hollow auxetic cylinders demonstrated the tubular structure to promote worm-like peristalsis. In this scenario, the described hybrid auxetic structures may be applied to the longitudinal intestinal lengthening and tailoring procedure to promote enteral autonomy in short bowel syndrome. The presented material and analytical design synergistic approach offer a pioneering step for the clinical translation of hybrid auxetic materials.

Treatment of Food Aversion and Eating Problems in Children with Short Bowel Syndrome: A Systematic Review.

Food Aversion (FA) is a strong refusing behaviour to the oral assumption of food that can affect children with Short Bowel Syndrome (SBS). Management includes behavioural and Messy Play treatments, with few reports on systematic strategies to return the patient to enjoyable eating. We conducted a systematic review to better understand this complex and vital issue. (1) Materials and Methods: We investigated publications using MEDLINE, Embase, and the Web of Science to include articles published up to July 2022. The inclusion criteria were original articles including paediatric patients (aged < 18 years old) affected by SBS and Intestinal Failure (IF) who underwent treatment for FA. (2) Results: A total of 24 patients received treatment­15 (62.5%) patients were male and 9 (37.5%) were female. The age range was from 1 month to 16 years. Treatment of FA was carried out by behavioural therapy in 2 patients and Messy Play Therapy in 12 patients already surgically and pharmacologically managed for SBS. The treatment results showed complete weaning from Parenteral Nutrition in 9/14 cases (64%) using the behavioural treatment and 7/12 cases using Messy Play Therapy. (3) Conclusions: FA is a rare but disabling condition that often affects SBS patients, worsening their overall health and quality of life. This condition should be addressed in an Intestinal Rehabilitation Centre context. Our review sheds light on the literature gap regarding FA, and further studies are required to understand better which treatment options best suit SBS paediatric patients.

Intestinal twin-to-twin transplant for short gut: Review of the literature and discussion of a complex case.

Paediatric Intestinal Transplantation (IT) presents the highest mortality on the waiting-list due to anatomical disproportion. Living-Donor IT (LDIT) offers the best advantages and when performed among identical monozygotic twins, it also benefits from unique immunology. According to MEDLINE/Pubmed, twin-to-twin LDIT has been performed in seven cases (6:7 males, median age of 32 years). None of the patients received immunosuppression postoperatively. Only one paediatric twinto- twin LDIT was carried out with a 160-cm mid-ileum tract: an interposed 4/5-cm arterial graft was required to ensure a tensionfree anastomosis to the anterior wall of the infra-renal abdominal aorta. In contrast, venous anastomosis was done directly to the inferior cava vein. We present a case for debate of a 13- month-old SBS patient where a twin-LDIT was discussed with parents, who decided to wait after careful analysis and ethical considerations.

Extended Overview of Ocular Phenotype with Recent Advances in Hypohidrotic Ectodermal Dysplasia.

The term ectodermal dysplasias (EDs) describes a heterogeneous group of inherited developmental disorders that affect several tissues of ectodermal origin. The most common form of EDs is hypohidrotic ectodermal dysplasia (HED), which is characterized by hypodontia, hypotrichosis, and partial or total eccrine sweat gland deficiency. HED is estimated to affect at least 1 in 17,000 people worldwide. Patients with HED have characteristic facies with periorbital hyperpigmentation, depressed nasal bridge, malar hypoplasia, and absent or sparse eyebrows and eyelashes. The common ocular features of HED include madarosis, trichiasis, and ocular chronic surface disease due to dry eye syndrome, which manifests clinically with discomfort, photophobia, and redness. Dry eye is common in HED and results from a combination of ocular surface defects: mucus abnormalities (abnormal conjunctival mucinous glands), aqueous tear deficiency (abnormalities in the lacrimal gland) and lipid deficiency (due to the partial or total absence of the meibomian glands; modified sebaceous glands with the tarsal plate). Sight-threatening complications result from ocular surface disease, including corneal ulceration and perforation with subsequent corneal scarring and neovascularization. Rare ocular features have been reported and include bilateral or unilateral congenital cataracts, bilateral glaucoma, chorioretinal atrophy and atresia of the nasolacrimal duct. Recognition of the ocular manifestations of HED is required to perform clinical surveillance, instigate supportive and preventative treatment, and manage ocular complications.

Increased trend of thyroid cancer in childhood over the last 30 years in EU countries: a call for the pediatric surgeon.

Given the increasing incidence of thyroid cancer cases affecting the pediatric population in Europe, an epidemiological analysis of the available data is essential in order to update standards of care and recommend diagnostic and therapeutic strategies coherent to the new epidemiological trend. An observational study was conducted, considering the time interval 1991-2012, acquiring data collected by the International Agency for Research on Cancer (IARC) through the "Cancer Incidence in 5 continents plus" (CI5 plus) project and dividing patients into four groups of age (0-4, 5-9, 10-14, 15-19 years old). Data retrieved were compared to the latest report from Global Cancer Observatory, collected through the GLOBOCAN 2020 project, dividing patients in two groups: age 10-14, 15-19. Our findings highlighted an increasing prevalence of thyroid cancer rates in patients aged from 10 to 15 years old and from 15 to 19 years old, mainly in the female population, in Belarus (from 1991 to 2007), Cyprus, and Italy (from 2008 to 2012). Moreover, a further increase in incidence was highlighted in Italy according to data from GLOBOCAN 2020, with respect to other European countries. CONCLUSION: An increasing prevalence of thyroid cancer is seen in age groups 10-19. Further research is required to understand the underlying cause and concomitantly identify the most proper screening and diagnostic techniques of thyroid nodules. Indeed, this is crucial to reach optimal surgical standards and better prognosis, possibly with more conservative approaches and maybe less postoperative complications. WHAT IS KNOWN: • Thyroid cancer is the 4th most common malignancy in children. WHAT IS NEW: • In the last decades, an increasing pattern has been recorded. • In the US, it has outlined breast cancers as the most common cancer in females.

Use of Teduglutide in Children With Intestinal Failure: A Systematic Review.

Background and Objectives: Short-bowel syndrome (SBS) results from the loss of a significant portion of the small intestine leading to a state of malabsorption. After an intestinal loss, there is a process of adaptation involving the Glucagon-Like Peptide-2 (GLP-2), an enteroendocrine peptide also involved in nutrient absorption. Teduglutide is a recombinant analog of GLP-2 approved in 2016 to treat selected SBS pediatric patients who are dependent on parenteral support. The present systematic review aims to evaluate the efficacy of Teduglutide in pediatric patients with SBS in reducing the need for parenteral nutrition (PN). Materials and Methods: We performed a literature search on MEDLINE and Embase to include articles up to November 2021. We included articles that involved using Teduglutide in the SBS pediatric population to define its efficacy in reducing the need for PN. The key words used were GLP-2, teduglutide, child. Results: Fourteen studies completely fulfilled the inclusion criteria. Two hundred 23 patients were treated with Teduglutide, and the median duration of treatment was 45 weeks (IQR: 36-52.5 weeks). One-hundred and fifty-two patients were treated with 0.05 mg/Kg/d of subcutaneous Teduglutide, 38 received 0.025 mg/Kg/d and 8 received either 0.125 mg/Kg/d or 0.20 mg/Kg/d. A total of 36 patients achieved enteral autonomy (EA) after a median of 24 weeks of treatment (IQR: 24-48 weeks) and 149 patients showed a reduction in PN needs in terms of volume, calories, or hours per day. Eleven studies reported complications: gastrointestinal were the most common, with 89 cases reported in treated patients and 11 in non-treated patients. Conclusion: Teduglutide appears safe and effective in reducing PN requirements and improving EA in the pediatric population. However, more studies are needed to understand its efficacy in the long term and after discontinuation and possible complications. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022301593].

Peptide-Functionalized Silk Fibers as a Platform to Stabilize Gelatin for Use in Ingestible Devices.

The combination of pharmacologic and endoscopic therapies is the gold standard for treating intestinal failures. The possibility of chemical solubility in water is mandatory for intelligent capsules. Functionalised silk fibroin with peptides and covalently linking different molecular entities to its structure make this protein a platform for preparing gels dissolving in the small and large intestine for drug delivery. In the present study, we linked a peptide containing the cell-adhesive motif Arginine-Glycine-Aspartic acid (RGD) to degummed silk fibres (DSF). Regenerated silk fibroin (RS) films obtained by dissolving functionalised DSF in formic acid were used to prepare composite gelatin. We show that such composite gelatin remains stable and elastic in the simulated gastric fluid (SGF) but can dissolve in the small and large intestines' neutral-pH simulated intestine fluid (SIF). These findings open up the possibility of designing microfabricated and physically programmable scaffolds that locally promote tissue regeneration, thanks to bio-enabled materials based on functionalised regenerated silk.