Laparo-Endoscopic Rendez-Vous in the Treatment of Cholecysto-Choledocolithiasis in the Pediatric Population.

OBJECTIVES: The incidence of choledocolithiasis is reported to be increasing in children. As for the adult population, several different therapeutic strategies have been described, however it is unclear which of those should be considered the gold standard. There is evidence-based literature in adults that supports a combined "rendez-vous" endoscopic retrograde cholangiopancreatography-laparoscopic cholecystectomy technique. This allows management of the choledocholithiasis during the same anesthetic episode as the cholecystectomy. By contrast, there are just two case reports in children reporting this approach. The aim of this study is to report our experience with this technique in a series of children with choledocholithiasis. METHODS: All patients who underwent the "rendez-vous technique" at our institution between 2009 and 2020 were reviewed and evaluated for outcomes and complications. RESULTS: Eleven children with cholecysto-choledocholithiasis were evaluated: the procedure was successful in 10 whereas in one patient it was aborted due to technical difficulties. All patients resolved their clinical condition without major complications. CONCLUSION: To our knowledge, this is the first consistent series of "rendez-vous technique" in the pediatric population, proving its feasibility and safety.

Management of Hepatitis-B Virus Infection in Immunocompromised Children: A Single Center Experience.

OBJECTIVES: The aims of the study was to expand the pediatric experience on hepatitis-B virus (HBV) reactivation, a known complication in patients with hematologic malignancies or on immunosuppression. METHODS: Retrospective appraisal of HBV therapy/prophylaxis in immunocompromised children, studied from April 2006 to March 2020. RESULTS: Eighteen HBV-positive patients, 5 girls, median age 11.1 (4.1--17.9) years were included. Seventeen of 18 were immunosuppressed at HBV-infection diagnosis. Seventeen were at high risk of reactivation, 1 at moderate risk. Five of 18 had acute hepatitis B as first infection or reactivation, 6 had HBeAg-positive infection, 1 an HBeAg-negative infection and 6 HBsAg-negative infection. Median follow-up was 2.7 (0.7--12.5) years. No HBV-related mortality was observed. Prophylaxis had to be repeated in 1. Lamivudine was used in 6/12 viremic patients and HBV-DNA negativization obtained in 2/6 (33%). Tenofovir-DF was used in 2/12 and entecavir in 4/12: 100% attained HBV-DNA negativization. Therapy had to be switched from tenofovir-DF to entecavir in 1 patient because of renal impairment. Virological breakthroughs were observed in 1 lamivudine-treated patient, leading to a hepatitis flare; 1 patient on entecavir had a hepatitis flare at immunoreconstitution. Mortality was 33% in the HBsAg-positive group. Seven prophylactic treatments were administered to 6 patients with HBsAg-negative infection: tenofovir-DF in 2 HBV-DNA-positive, lamivudine in 5 HBV-DNA-negative, without reverse HBsAg seroconversion, morbidity or mortality. CONCLUSIONS: There is a residual risk of acute hepatitis B in immunocompromised children, mortality rate was substantial, potentially related to the delays in commencing chemotherapy caused by liver dysfunction. Tenofovir-DF or entecavir are the drugs of choice for HBV treatment in immunocompromised children.

Overexpression of endogenous retroviruses in children with celiac disease.

Human endogenous retroviruses (HERVs) represent 8% of our genome. Although no longer infectious, they can regulate transcription of adjacent cellular genes, produce retroviral RNAs, and encode viral proteins that can modulate both innate and adaptive immune responses. Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders. Celiac disease (CD) is considered an autoimmune disease, but HERV expression has not been studied in celiac patients. The aim of this study is to assess the transcription levels of pol genes of HERV-H, -K, and -W and of their TRIM28 repressor in WBCs from celiac children and age-matched control subjects. A PCR real-time TaqMan amplification assay was used to evaluate HERV and TRIM28 transcripts with normalization of the results to glyceraldehyde-3-phosphate dehydrogenase. The RNA levels of pol genes of the three HERV families were significantly higher in WBCs from 38 celiac patients than from 51 control subjects. TRIM28 transcription was comparable between the two study populations.Conclusion: Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD. Given their proinflammatory and autoimmune properties, this suggests that HERVs may contribute to the development of CD in susceptible individuals. What is Known: • Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders. What is New: • Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD.

Fecal calprotectin in the pediatric population: a 2020 update.

Calprotectin is a calcium and zinc-binding protein, formed by a hetero complex of S100A8 and S100A9 proteins, which belong to the S-100 protein family consisting in more than 20 different proteins with a tissue-specific expression pattern. This protein is secreted extracellularly from stimulated neutrophils or released by cell disruption or death. The presence of calprotectin in feces quantitatively relates to neutrophil migration toward the gastrointestinal (GI) tract; thus, it represents a useful marker of intestinal inflammation. Fecal calprotectin (FC) has been proven largely useful for determining the inflammatory origin of GI symptoms differentiating between organic and non-organic diseases. Indeed, increased FC levels are also seen in gastroenteritis, microscopic colitis, polyps, malignancies and cystic fibrosis. To date, there are many evidences regarding usefulness in the detection of fecal calprotectin for the management of gastrointestinal disorders, both in children and adults but, especially in the pediatric population, still clear indications for its use are lacking. Its incorporation in primary care reduces the risk of missing an organic disease and facilitates the indication for expensive and invasive investigations as colonoscopy. We herein review and discuss the last evidence on the usefulness of FC in children, with its current indications and future prospective.

Transient elastography for non-invasive evaluation of post-transplant liver graft fibrosis in children.

As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.

Diagnosis and treatment of Helicobacter pylori in the pediatric population.

Although about 35 years have elapsed since the discovery of the Helicobacter pylori, its diagnosis and the choice of optimal eradication therapy are still to be defined. Over time, there has been an increase in interest, publications, recommendations and guidelines. Moreover, management of the disease in pediatric subjects differs somewhat to that of adults and requires a more delicate approach leading to alternative strategies for both diagnosis and treatment. Which patient should be investigated for H. pylori, when to perform noninvasive or invasive tests, what are the proper therapeutic options and best antibiotics regimen to eradicate the infection are practices changing with evidences through time. Therefore, an updated guideline was published by the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) in 2017. The aim of this review is to highlight what is new and what differs between adult and pediatric population regarding the management of H. pylori infection after the ESPGHAN/NASPGHAN guidelines, enriched with updates from literature reviews published over the last two years.

Bowel Preparation for Gastrointestinal Endoscopic Procedures With Sodium Picosulphate-Magnesium Citrate Is an Effective, Safe, and Well-Tolerated Option in Pediatric Patients: A Single-Center Experience.

To obtain optimal visualization of the colonic mucosa during gastrointestinal endoscopic procedures, an adequate bowel preparation is mandatory, but a standardized protocol is still lacking for pediatric patients. Polyethylene glycol (PEG) is currently the most used laxative, but the amount of liquid to be taken orally is a large volume for the pediatric population and it may not be well tolerated. The aim of our preliminary trial was to evaluate efficacy, tolerability, and safety of sodium picosulphate-magnesium citrate (SPMC) used as bowel preparation before colonoscopy in children. Fifty children who needed a colonoscopy were prospectively enrolled between April and December 2013 and SPMC was administered to them as bowel preparation. A questionnaire about the product tolerance was completed by the patients' parents. The grade of bowel preparation and any related side effect were evaluated. The mean value of the Boston Bowel Preparation Scale was 7, out of a maximum of 9. Only 5 patients had an inadequate bowel preparation. Seventy percent of the patients considered the taste of the preparation very palatable. The remaining 26% considered it not palatable or not palatable at all. During the preparation, 18% of children complained of nausea, 20% abdominal pain, 2% vomiting, and 2% manifested headache. Bowel preparation with SPMC offers an efficient alternative to PEG and allows, on equal terms of efficacy, tolerability and safety, a much lower amount of laxative to ingest, and remarkable quality, especially in infants and toddlers.

Foreign body ingestion in children: Definition of a nomogram to predict surgical or endoscopic intervention.

BACKGROUND AND AIMS: Foreign body ingestion (FBI) in children requires early identification to prevent adverse outcomes and may necessitate endoscopic or surgical intervention. This study aims to develop a nomogram that identifies children who require urgent surgical or endoscopic intervention by using the patient's medical history and clinical parameters collected at admission. METHODS: This study is a retrospective review (01/2015-12/2020) of a multicenter case series of children admitted for FBI. Data from 5864 records from 24 hospitals in Italy were analyzed. Logistic regression models were used to establish the probability of requiring surgical or endoscopic intervention based on patient history and clinical characteristics. The nomogram representing the results from the multivariable model was reported to examine the propensity for surgery/endoscopy. RESULTS: The study identified a significant association between intervention and various factors, including type of foreign body (blunt: reference category, disk battery (odds ratio OR:4.89), food bolus (OR:1.88), magnets (OR:2.61), sharp-pointed (OR:1.65), unknown (OR:1.02)), pre-existing diseases or conditions (OR 3.42), drooling (OR 10.91), dysphagia (OR 5.58), vomiting (OR 3.30), retrosternal pain (OR 5.59), abdominal pain (OR 1.58), hematemesis (OR 2.82), food refusal/poor feeding (OR 2.99), and unexplained crying (OR 2.01). The multivariable regression model showed good calibration and discrimination ability, with an area under the ROC curve of 0.77. CONCLUSIONS: This study developed the first nomogram to predict the probability of the need for surgical or endoscopic intervention in children with FBI, based on the information collected at admission. The nomogram will aid clinicians in identifying children who require early intervention to prevent adverse outcomes.

Accuracy of narrow-band imaging in predicting colonoscopy surveillance intervals and histology of distal diminutive polyps: results from a multicenter, prospective trial.

BACKGROUND: In vivo prediction of colorectal polyp histology by narrow-band imaging (NBI) could potentially avoid post-polypectomy histologic examination or resection of diminutive lesions, thereby reducing costs and risk. OBJECTIVE: To assess whether NBI is able to predict colonoscopy surveillance intervals and histology of distal diminutive polyps according to American Society for Gastrointestinal Endoscopy (ASGE) criteria. DESIGN: Prospective, multicenter study. SETTING: Five endoscopic centers. PATIENTS: Consecutive patients undergoing colonoscopy in 5 centers were included. INTERVENTION: Participating endoscopists were required to pass a before-study qualifying examination. Histology of polyps that were <10 mm was predicted at NBI and assigned a designation of high or low confidence. MAIN OUTCOME MEASUREMENTS: Accuracy of high-confidence NBI prediction for polyps ≤5 mm in predicting surveillance intervals and negative predictive value (NPV) for adenomatous histology in the rectosigmoid colon were compared with the ASGE thresholds (90% agreement, 90% NPV). RESULTS: A total of 278 patients (mean age, 63 years; 58% male) were enrolled. At colonoscopy, 574 (97.3%) polyps <10 mm (429 ≤5 mm, 60% adenomatous) were retrieved for histologic analysis. Sensitivity, specificity, positive and negative predictive values, and accuracy of high confidence-NBI predictions for adenomatous histology in lesions ≤5 mm were 90%, 88%, 89%, 89%, and 89%, respectively. High-confidence characterization of polyps ≤5 mm predicted the correct surveillance interval in 92% to 99% of cases, according to the American and European guidelines. NPV of high-confidence NBI for adenomatous histology for the rectosigmoid colon lesions ≤5 mm was 92%. LIMITATIONS: Only experienced endoscopists were included. CONCLUSION: High-confidence prediction of histology for polyps ≤5 mm appears to be sufficiently accurate to avoid post-polypectomy histologic examination of the resected lesions as well as to allow rectosigmoid hyperplastic polyps to be left in place without resection. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01675752.).

Handheld metal detector versus conventional chest and abdominal plain radiography in children with suspected metallic foreign body ingestion: can we safely abandon X-rays?

BACKGROUND: Ingestion of metallic foreign bodies (MFBs) is a frequent occurrence in children and is commonly diagnosed via X-rays. In recent years, the handheld metal detector (HMD) has been increasingly adopted by several pediatric hospitals as it is considered an effective and accurate diagnostic tool that avoids exposure to ionizing radiations. Sensitivity of HMD has been reported high (99.4%) in case of coin ingestion, but significantly lower (46%) when considering the ingestion of other types of MFBs. METHODS: We tested the effectiveness of the HMD in diagnosing ingested MFBs in children less than 14 years of age, in our Pediatric Emergency Department (PED). We prospectively evaluated all cases of MFBs ingestion that presented at the PED of our hospital from March 2015 to July 2017. RESULTS: Ninety-eight patients were included. The overall sensitivity was 63.2% (79.5% for coins, 25.5% for batteries and 56% for other objects) while the specificity was 95%. The HMD could have replaced the X-ray examination only if a MFB was detected below the xyphoid process. CONCLUSIONS: Based on our findings, a negative result of HMD is not sufficient to exclude an ingestion of MFBs. Therefore, in case of an evocative history and depending on type and size of the foreign body, a radiological investigation is still necessary.

Inflammatory Bowel Disease and Irritable Bowel Syndrome: What Differences in Mentalization Abilities? A Scoping Review.

Mentalization is a psychological process that enables individuals to understand the self and others in terms of intentional mental states. The aim of this scoping review was to provide an overview of the findings on mentalization in patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). A literature search, in line with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols extension for Scoping Review guidelines, was conducted in the following bibliographic databases: PubMed, PsycINFO, and Scopus. Databases were queried using the following strings (with Boolean operators): ("mentaliz*" OR "metacogniti*" OR "theory of mind" OR "ToM" OR "reflective function*") AND ("irritable bowel syndrome" OR "IBS" OR "inflammatory bowel disease" OR "IBD"). In line with the eligibility criteria, seven articles were included. Results showed that no significant differences in metacognitive ability were found between patients in the IBD and IBS groups. This review revealed the mentalizing difficulties for patients with IBD and IBS. These results should be interpreted with caution since they are based on a few studies that used different instruments to assess mentalizing processes. Future studies are needed to clarify the role of mentalization in patients with these gastrointestinal conditions.

A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life.

A dietary interview performed by expert personnel is the best method to check whether patients with coeliac disease follow a strict gluten-free diet (GFD). We previously developed a score based on four fast and simple questions that can be administered even by non-expert personnel. The aim of the present study is to verify the reliability of our questionnaire in a new cohort of patients. The questionnaire has a five-level score. From March 2008 to January 2011, the questionnaire was administered to 141 coeliac patients on a GFD, who were undergoing re-evaluation. The score obtained was compared with persistence of both villous atrophy and endomysial antibodies (EMA). The rate of lower scores was higher among the patients with persistence of either villous atrophy (Fisher's exact, P < 0·001; test for trend, P < 0·001) or positive EMA (Fisher's exact, P = 0·001; test for trend, P = 0·018). Given that the coeliac patients have been well instructed on what a GFD means and on how to follow it, our questionnaire is a reliable and simple method to verify compliance to a GFD.

Multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection and severe abdominal syndrome: the Lviv "OHMATDYT" (Western Ukraine) experience.

Multisystem inflammatory syndrome in children (MIS-C) associated with Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) usually develops 1-1.5 months after mild or asymptomatic COVID-19 in countries with high incidence. MIS-C has a polymorphism of clinical manifestations, which include prolonged fever, polymorphic rash, non-purulent conjunctivitis, pneumonia complicated by distress syndrome, myocarditis, coronary artery disease, toxic shock syndrome, limb edema, polyserositis, severe abdominal syndrome with diarrhea and others. Establishing this diagnosis requires significant efforts to rule out diseases of other etiology. The aim of our study was to analyze the clinical and laboratory features of children with MIS-C associated with SARS-CoV-2 and severe abdominal syndrome. Six children with MIS-C associated with SARS-CoV-2 and severe abdominal syndrome were hospitalized in Lviv Regional Children's Clinical Hospital "OHMATDYT", Ukraine, from April 2020 to September 2021. For differential diagnosis IgM, IgG to SARS-CoV-2 by ELISA, RNA to SARS-CoV-2 by PCR, bacteriological tests of blood, urine and feces were performed. Furthermore, the diagnostic work up included chest radiography, echocardiography, ultrasound of the lungs and abdominal organs. Laboratory findings revealed an increase in the normal value of inflammatory markers and high levels of IgG to SARS-CoV-2. Administration of intravenous immunoglobulin at a dose of 1 to 2 g/kg body weight per day prevented further coronary artery disease in patients and provided regression in already affected coronary arteries. At the same time, regression of abdominal syndrome was observed. Early diagnosis of MIS-C in patients with SARS-CoV-2 and severe abdominal syndrome allows to define the appropriate treatment strategy.

Impact of COVID-19 pandemic on pediatric endoscopy: A multicenter study on behalf of the SIGENP Endoscopy Working Group.

BACKGROUND: Aim of the present report was to investigate the repercussions of COVID-19 pandemic on the procedural volumes and on the main indications of pediatric digestive endoscopy in Italy. METHODS: An online survey was distributed at the beginning of December 2020 to Italian digestive endoscopy centers. Data were collected comparing two selected time intervals: the first from 1st of February 2019 to 30th June 2019 and the second from 1st February 2020 to 30th June 2020. RESULTS: Responses to the survey came from 24 pediatric endoscopy Units. Globally, a reduction of 37.2% was observed between 2019 and 2020 periods with a significant decrease in median number of procedures (111 vs 57, p < 0.001). Both the median number of procedures performed for new diagnoses and those for follow-up purposes significantly decreased in 2020 (63 vs 36, p < 0.001 and 42 vs 21, p< 0.001, respectively). We reported a drastic reduction of procedures performed for suspected Celiac Disease and Functional Gastrointestinal Disorders (55.1% and 58.0%, respectively). Diagnostic endoscopies for suspected IBD decreased of 15.5%, whereas procedures for Mucosal Healing (MH) assessment reduced of 48.3%. CONCLUSIONS: Our study provides real-world data outlining the meaningful impact of COVID-19 on pediatric endoscopy practice in Italy.

Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP).

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment. METHODS: Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP). RESULTS: A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians. CONCLUSION: In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice.

Intestinal ultrasonography in pediatric population.

Bowel ultrasound (US) is a low cost, non-invasive, bed side practice and a reproducible procedure that represents a high yield tool in clinical practice and in the diagnostic workup of a consistent group of acute and chronic gastrointestinal (GI) tract disease. Moreover, in case of GI diseases of neonatal and pediatric age, it allows an easier evaluation due to the small body size and scarce presence of fat tissue in the abdominal wall and peritoneal cavity and gas content. No particular preparation of the patient is needed, nevertheless a 3 to 5 hour fasting state improves the quality of the examination. The exam focuses on wall thickness and stratification, lumen content, distensibility and compressibility, presence of peristalsis of explorable segment of the GI tract and includes the investigation of mesentery, perivisceral tissues and nodes features. Color doppler flowmetry admits a qualitative evaluation of GI wall and mesentery vascularization. Healthy GI wall appears at a US evaluation as a multilayered structure in which hyperechoic and hypoechoic layers alternate sequentially. In this article we provide a quickly available overview on findings, signs and applications of US in major GI pediatric diseases.

Laparoscopic Repair of a Gastrocolocutaneous Fistula: Percutaneous Endoscopic Gastrostomy Placement Complications in Children.

Background: Gastrostomy tube placement (G-Tube) is a frequently offered procedure in children with feeding difficulties. Various procedures exist for G-Tube, with the pull technique more commonly used for a percutaneous endoscopic gastrostomy (PEG) in children, considered by many to be the safer approach. Major complications requiring reoperation range from 3% to 5%, depending on the study. In our center, PEG placement is performed by gastrointestinal endoscopists through the pull technique. In the last 5 years, there were 150 procedures, with 15 minor and 3 major complications. We will describe the last 3 cases, plus a fourth PEG placement at another center. Patients and Methods: Patients ranged from 2 to 10 years (median age: 4.5 years). Median weight was 10.7 kg (range: 7-18 kg). Patients were neurologically impaired children, except one with severe nephropathy. Results: Laparoscopic repair with a 3-trocar technique was effective, when the patient's general condition allowed for it. After fistula repair, a new gastrostomy was placed; this step can be performed endoscopically under laparoscopic control (or can be performed completely laparoscopically). Conclusions: In 4 patients, we faced unusual PEG placement complications, due to colon interposition during blind gastric puncture. In those with anatomical deformities or previous surgery, or dealing with toddlers (under 10 kg), we suggest laparoscopic-assisted PEG, or a full laparoscopic gastrostomy to avoid the risk of a major complication.