Comparative retrospective study on the modalities of biopsying peripheral neuroblastic tumors: a report from the Italian Pediatric Surgical Oncology Group (GICOP)

Background: Peripheral neuroblastic tumors are the most common extracranial solid neoplasms in children. Early and adequate tissue sampling may speed up the diagnostic process and ensure a prompt start of optimal treatment whenever needed. Different biopsy techniques have been described. The purpose of this multi-center study is to evaluate the accuracy and safety of the various examined techniques and to determine whether a preferential procedure exists. Methods: All children who underwent a biopsy, from January 2010 to December 2014, as a result of being diagnosed with a peripheral neuroblastic tumor, were retrospectively reviewed. Data collected included patients’ demographics, clinical presentation, intraoperative technical details, postoperative parameters, complications, and histology reports. The Mann–Whitney U and Fisher's exact tests were used for statistical analysis. Results: The cohort included 100 patients, 32 of whom underwent an incisional biopsy (performed through open or minimally invasive access) (Group A), and the remaining 68 underwent multiple needle-core biopsies (either imaging-guided or laparoscopy/thoracoscopy-assisted) (Group B). Comparing the two groups revealed that Group A patients had a higher rate of complications, a greater need for postoperative analgesia, and required red blood cell transfusion more often. Overall adequacy rate was 94%, without significant differences between the two groups (100% vs. 91.2% for Group A and Group B, respectively, P = 0.0933). Conclusions: Both incision and needle-core biopsying methods provided sub-optimal to optimal sampling adequacy rates in children affected by peripheral neuroblastic tumors. However, the former method was associated with a higher risk of both intraoperative and postoperative complications compared with the latter

A metagenomics study on Hirschsprung's disease associated enterocolitis: Biodiversity and gut microbial homeostasis depend on resection length and patient's clinical history

Objectives: Since 2010, several researches demonstrated that microbiota dynamics correlate and can even predispose to Hirschsprung (HSCR) associated enterocolitis (HAEC). This study aims at assessing the structure of the microbiota of HSCR patients in relation to extent of aganglionosis and HAEC status. Methods: All consecutive HSCR patients admitted to Gaslini Institute (Genova, Italy) between May 2012 and November 2014 were enrolled. Institutional review board (IRB) approval was obtained. Stools were sampled and 16S rDNA V3-V4 regions were sequenced using the Illumina-MiSeq. Taxonomy assignments were performed using QIIME RDP. Alpha diversity indexes were analyzed by Shannon and Simpson Indexes, and Phylogenetic Diversity. Results: We enrolled 20 patients. Male to female ratio was 4:1. Six patients suffered from Total Colonic Aganglionosis (TCSA). Considering sample site (i.e., extent of aganglionosis), we confirmed the known relationship between sample site and both biodiversity and composition of intestinal microbiota. Patients with TCSA showed lower biodiversity and increased Proteobacteria/Bacteroidetes relative abundance ratio. When addressing biodiversity, composition and dynamics of TCSA patients we could not find any significant relationship with regard to HAEC occurrences. Conclusions: The composition of HAEC predisposing microbiota is specific to each patient. We could confirm that total colon resections can change the composition of intestinal microbiota and to dramatically reduce microbial diversity. The subsequent reduction of system robustness could expose TCSA patients to environmental microbes that might not be part of the normal microbiota. Future long-term studies should investigate both patients and their family environment, as well as their disease history

Non-standard approach to infants and children with megacolon: laparotomy and endorectal pull-through for diagnosis and treatment in difficult countries with low resources in a non-profit setting: return to the past Soave's ERPT

BACKGROUND: Hirschsprung's disease is an important cause of pediatric constipation with high risk of bacterial enterocolitis. Its diagnosis is histological and the suction biopsy is the gold standard. In resource-limited countries, the main diagnostic exam is the contrast enema and mini-invasive surgery lacks. We present the management of a cohort of patients with megacolon in Haiti, a low-resource country. METHODS: Children with megacolon and fecal impaction admitted at St Damien Children Hospital in Port-Au-Prince in June, August and December 2017 were included. We considered only patients with an evident transition zone on contrast enema who underwent endorectal pull-through (ERPT). Short term complications were recorded. RESULTS: Twenty children with clinical megacolon were admitted, eleven were included in the study. No suction rectal biopsy and intraoperative histological evaluation were performed. In ten children a Soave ERPTwith anastomosis at 5PODwas performed, in the other case a Boley primary anastomosis was preferred. One patient complicated with a peritonitis. No major complications were recorded. Colostomy was not considered a good option. CONCLUSIONS: In developing countries, Soave ERPT with definitive anastomosis after few days could be considered a valid option. Colostomy is suggested only in case of scant general conditions or bad colon appearance

Pathways and microbiome modifications related to surgery and enterocolitis in Hirschsprung disease

Background: Hirschsprung disease (HSCR) is a congenital anomaly of the enteric nervous system. Abnormal microbiome composition was reported in HSCR patients. In this study, we addressed and analyzed microbiome modifications with relation tosurgery and HSCR associated enterocolitis (HAEC). Methods: The faecal microbiome of 31 HSCR patients (overall 64 samples) was analyzed. HAEC was diagnosed and classified according to a combination of Pastor’s and Elhalabi’s criteria. Stool samples were analyzed by 16S sequencing (7 out of 9 polymorphic regions). Compositional and relative abundance profiles, as well as the functional potentials of the microbial community, were analyzed with the marker gene sequencing profiles using PICRUSt. Results: The relative abundance of Bacteroidetes showed a severe decrease with slow recovery after surgery. Conversely, Proteobacteria transiently increased their abundance. Noteworthy, a strong linkage has been found between Proteobacteria descendants and HAEC occurrences. The inferred functional analysis indicated that virulence factors and fimbriae or pili might be associated with HAEC. Conclusions: Our study, addressing microbiome dynamics, demonstrated relevant changes after surgical manipulation. Alpha-diversity analyses indicated that surgery deeply affects microbiome composition. Proteobacteria and Enterobacteriaceae seem to play a pivotal role in HAEC occurrences. Several virulence factors, such as fimbriae or pili, might explain the HAEC-predisposing potential of selected microbiomes. These results suggest some innovative therapeutic approaches that deserve to be tested in appropriate clinical trials

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

The intestine is essential for the modulation of nutrient absorption and the removal of waste. Gut pathologies, such as cancer, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and celiac disease, which extensively impact gut functions, are thus critical for human health. Targeted drug delivery is essential to tackle these diseases, improve therapy efficacy, and minimize side effects. Recent strategies have taken advantage of both active and passive nanocarriers, which are designed to protect the drug until it reaches the correct delivery site and to modulate drug release via the use of different physical-chemical strategies. In this systematic review, we present a literature overview of the different nanocarriers used for drug delivery in a set of chronic intestinal pathologies, highlighting the rationale behind the controlled release of intestinal therapies. The overall aim is to provide the reader with useful information on the current approaches for gut targeting in novel therapeutic strategies