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Competing Interests: The authors declare that they have no conflict of interest.

Introduction: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab., Methods: Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor., Results: A positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823)., Discussion: These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Negri, Bottarelli, Pedrazzi, Maddalo, Leo, Milanese, Sala, Lecchini, Campanini, Bozzetti, Zavani, Di Rienzo, Azzoni, Silini, Sverzellati, Gaiani, de’ Angelis and Gnetti.)

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., Competing Interests: Conflict of interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Understanding molecular features of colon cancer has shed light on its pathogenesis and progression. Over time, some of these features acquired clinical dignity and were incorporated in decision making. Namely, microsatellite instability (MSI) due to mismatch repair of defects, which primarily was adopted for the diagnosis of Lynch syndrome, became recognized as the biomarker of a different disease type, showing a less aggressive behavior. MSI tumors harbor high amounts of tumor infiltrating lymphocytes (TILs) due to their peculiar load in neoantigens. However, microsatellite stable colon cancer may also show high amounts of TILs, and this feature is as well associated with better outcomes. High TIL loads are in general associated with a favorable prognosis, especially in stage II colon cancer, and therein identifies a patient subset with the lowest probability of relapse. With respect to post-surgical adjuvant treatment, particularly in stage III, TILs predictive ability seems to weaken along with the progression of the disease, being less evident in high risk patients. Moving from cohort studies to the analysis of a series from clinical trials contributed to increase the robustness of TILs as a biomarker. The employment of high TIL densities as an indicator of good prognosis in early-stage colon cancers is strongly advisable, while in late-stage colon cancers the employment as an indicator of good responsiveness to post-surgical therapy requires refinement. It remains to be clarified whether TILs could help in identifying those patients with node-positive cancers to whom adjuvant treatment could be spared, at least in low-risk groups as defined by the TNM staging system.

Foreign body and caustic ingestions in children are usually the most common clinical challenges for emergency physicians, general pediatricians and pediatric gastroenterologists. Management of these conditions often requires different levels of expertise and competence. Endoscopy is often necessary but there is a high risk of misusing this tool with incorrect timing and indications. The imprecise clinical history frequently leaves clinicians uncertain about timing and nature of the ingestion. Few clinical guidelines regarding management of these ingestions in children have been published, none of which from the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). An expert panel of Italian endoscopists was convened by the SIGENP Endoscopy Working Group to produce the present article that outlines practical clinical approaches to the pediatric patient with a variety of foreign body and caustic ingestions. The Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) has also endorsed the project since many adult endoscopists usually manage children with these conditions. Differently from the other published guidelines, the proposed one focuses on the role of the endoscopists (regardless of whether they are adult or pediatric gastroenterologists) in the diagnostic process of children with foreign body and caustic ingestions., Competing Interests: Conflict of Interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Knowledge of the real incidence of small intestinal bacterial overgrowth (SIBO) in obese children and its role in obesity development seems essential for a more effective approach to the treatment of this condition. In this prospective, single-blind study, presence of SIBO was evaluated in a group of children with overweight/obesity. A blood sample for evaluation of cytokine profile was collected to establish the potential relationship with inflammatory condition and lactulose breath test (LBT) to diagnose SIBO was performed. A total of 36 patients with excess of adipose tissue were recruited. Among them, 16 (44.4%) were overweight and 20 (45.6%) were obese. Overall, 26 (72.2%) children had a positive LBT and were considered suffering from SIBO, 12 (75.0%) among those overweight and 14 (70.0%) among those obese. Measurement of cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-17, IFN-α2, IFN-γ, TNF-α), cytokine antagonists (IL-1ra), chemokines (IP10, MCP-1, MIP1α, MIP1β), and growth factors (EGF, G-CSF, GM-CSF, and VEGF) secreted in culture supernatants by PHA activated-PBMCs revealed that in the study population proinflammatory cytokines IL-1, IL-6, IL-8, IL-12, IFN-γ, IL-18, and TNF-α were high, whereas anti-inflammatory mediators IL-4 and IL-10 were low. However, no significance difference between children with SIBO and those without were evidenced. Evaluation of relationship of severity of SIBO showed a significant positive relationship between EGF or IFN-α2 and H2 but not CH4 levels and an inverse significant relationship with CH4 but not H2. Despite its limitations and further studies are needed, this study seems to indicate that SIBO is extremely common in overweight and obese children and can be demonstrated not only in severely obese subjects but also in moderately overweight patients. The inflammatory state seems to precede obesity development and SIBO does not seem to have relevance in obesity development, with no relationship found between severity of SIBO and inflammatory state., (Copyright © 2020 Esposito, Biscarini, Federici, Cofini, Argentiero, Neglia, Lanciotti, de' Angelis and Principi.)

Acute colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of acute left-sided colonic diverticulitis (ALCD) according to the most recent available literature. The update includes recent changes introduced in the management of ALCD. The new update has been further integrated with advances in acute right-sided colonic diverticulitis (ARCD) that is more common than ALCD in select regions of the world.

Clostridioides difficile , formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of this article is to review diagnostic laboratory methods that are now available to detect C. difficile and to discuss the most recent recommendations on CDI treatment in children. Currently, there is no consensus on the best method for detecting C. difficile . Indeed, none of the available diagnostics possess at the same time high sensitivity and specificity, low cost and rapid turnaround times. Appropriate therapy is targeted according to age, severity and recurrence of the episode of infection, and the recent availability of new antibiotics opens new opportunities. De-escalation of antibiotics that are directly associated with CDI remains a priority and the cautious use of probiotics is recommended. Vancomycin represents the first-line therapy for CDI, although in children metronidazole can still be used as a first-line drug. Fidaxomicin is a new treatment option with equivalent initial response rates as vancomycin but lower relapse rates of CDI. Faecal microbiota transplantation should be considered for patients with multiple recurrences of CDI. Monoclonal antibodies and vaccines seem to represent a future perspective against CDI. However, only further studies will permit us to understand whether these new approaches could be effective in therapy and prevention of CDI in paediatric populations.

Background and Aims: Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy., Methods: This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients., Conclusions: The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.

Background: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies., Main Body: Conventional therapies have failed in treating some patients with EoE, which then requires aggressive procedures such as esophageal dilatation. The most effective available medical therapy for EoE is swallowed topic corticosteroids (fluticasone propionate and budesonide), which have two main drawbacks: they are related to well-known adverse effects (especially in the paediatric population), and there are not enough long-term data to confirm that they are able to reverse the remodelling process of the esophageal mucosa, which is the major cause of EoE symptoms (including dysphagia, abdominal pain, nausea, obstruction, perforation and vomiting). The monoclonal antibodies appear to be an interesting therapeutic approach. However, the studies conducted until now have shown substantial histological improvement not coupled with significant clinical improvements and no significant relationship between a decreasing number of eosinophils and clinical symptoms, highlighting the importance in the pathogenesis of EoE of cells such as T-helper cells, mast cells, B cells, epithelial cells and natural killer cells., Conclusions: Monoclonal antibodies targeting a signal involved in the pathogenesis of EoE may not break the complex self-propagating inflammatory activation responsible for perpetuation of the inflammatory response and the development of symptoms and complications. We speculate that combined biological therapies targeting more than one molecule or cell may provide better results, with conventional therapies potentially enhancing the effects of antibodies. However, further studies should aim to find the best therapeutic approach to target the cells involved in the remodelling process and to reverse the histological changes in this complex clinical condition.

Background: Celiac disease is an auto-immune disorder characterized by clinical manifestations that appear in genetically predisposed subjects after gluten ingestion. In the last years, there has been a progressive change in clinical manifestations. Our aim was to evaluate the nutritional status of children with celiac disease at diagnosis and how the gluten-free diet (GFD) influences their growth., Methods: A search on PubMed/Medline was performed using "celiac disease", "body mass index" and "children" as key words.  Medline, Scopus, PubMed publisher and Google Scholar were searched as well.  We selected clinical studies describing the nutritional status of patients before and after GFD using indicators like height, weight, BMI, skeletal age.  We excluded papers referred to adult population or in which other diseases were related to celiac disease. Also literature-reviews were excluded., Results: From 1999 to 2018, 10 studies were found. Overall, 1383 patients in pediatric age were evaluated for their nutritional status at diagnosis of celiac disease and after a variable period from 1 to 17 years of GFD. Indicators considered were height, weight, BMI and skeletal age., Conclusions: the nutritional status of celiac patients at diagnosis is variable including an increasing number of overweight and obese. GFD has a beneficial impact on growth changes determining a correction of BMI distribution towards a Gaussian shape.

Background and Aim: Endoscopic ultrasonography (EUS) with or without fine needle aspiration/biopsy (FNA/B) is a well-established diagnostic tool in adults for the evaluation and management of gastrointestinal (GI) tract disorders. Its use in children is still limited as well as literature in pediatric age is limited, although the application of EUS is now increasing. The present article aims to review the current literature about EUS indication, accuracy and safety in pediatric age., Methods: Electronic literature searches were conducted using Pubmed, Medline, Embase, and the Cochrane Central Register of Controlled Trials using the word pediatric endoscopic ultrasound, pediatric pancreaticobiliary AND/OR EUS, pediatric EUS technique. Main patients and procedures characteristics were analyzed. The primary endpoint was the indication of EUS. Secondary endpoints were the accuracy of the technique and the incidence of complications., Results: Data were extracted from 19 articles. A total of 571 patients were investigated, with a median age of 12,7 years. A total of 634 EUS procedures were performed. The majority of EUS procedures investigated the pancreaticobiliary tract (77,7%). Most studies showed a high positive impact on management with a median value of 81,7%. No major complications were reported. Five studies reported minor complications with a median value of 2%., Conclusions: EUS is safe and has a significant role in the diagnosis of pancreaticobiliary and GI diseases even in children, with a high therapeutic success. An increasing EUS utilization by pediatric gastroenterologists is expected and offering dedicated EUS training to some selected pediatric gastroenterologists might be indicated.

Gastroesophageal reflux disease (GERD) is due to the chronic exposure of the esophageal mucosa to acid secretion from the stomach. Helicobacter pylori (H.p.) infection, is a risk factor for the development of peptic ulcer, atrophic gastritis and gastric cancer, and causes various effects on gastric function. The relationship between GERD and H.pylori infection is still subject of debate. Background and aim: In literature no clear causal relationship has been established between GERD and H. pylori infection, although some papers support the onset of esophagitis in patients in whom the infection has been cured. Aim of this work is to review the most recent literature data about the relationship between reflux disease and H. pylori infection. Methods: Articles reviewed were found through literature searches on PubMed, Google Scholar using keywords such as gastroesophageal reflux disease, Helicobacter pylori, acid-related disorders, GERD and esophagitis.

Background and Aim of the Work: Although peripheral neuropathies in children are often of genetic origin, acquired causes should be carefully looked for and ruled out also in the pediatric age. Gastroenterological disorders can be complicated by peripheral neuropathy as a result of micronutrients deficiency, drug toxicity or because of shared pathophysiological mechanisms., Methods: In this descriptive review we sought to give an overview on the most relevant clinical conditions in which peripheral neuropathies are associated with gastro-intestinal disorders or symptoms., Results: We describe the clinical, demographic, and electrophysiological features of peripheral neuropathy in three main clinical scenarios: in the context of common gastroenterological disorders (inflammatory bowel and celiac disease), in the context of micronutrients deficiencies arising from malabsorption irrespective of etiology, and in a rare degenerative mitochondrial disorder, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) disorder., Conclusions: The association between gastrointestinal and peripheral nervous system symptoms is probably still underrecognized but has to be actively sought, in order to provide prompt diagnosis resulting in optimal care and long-term management with the aim to improve quality of life and, at least in some conditions, try to impact on prognosis.

Methods for the measure of gastric acid secretion include invasive and non-invasive tests. The gold-standard to measure the acid output is the collection of gastric after in basal condition (Basal Acid Output, B.A.O.) and after an i.m. injection of pentagastrin (Maximal Acid Output, M.A.O.). However, direct measurement of gastric acid production is out of order in clinical practice, but many GI symptoms are claimed to be related with acid disorders and empirically cured. Hypochlorhydria is associated with precancerous conditions such as chronic atrophic gastritis (CAG). Acid measurement with non-invasive methods (pepsinogens) is supported by international guidelines.

Autoimmune diseases, characterized by an alteration of the immune system which results in a loss of tolerance to self antigens often coexist in the same patient. Autoimmune atrophic gastritis, characterized by the development of antibodies agains parietal cells and against intrinsic factor, leads to mucosal destruction that affects primarily the corpus and fundus of the stomach. Autoimmune atrophic gastritis is frequently found in association with thyroid disease, including Hashimoto's thyroiditis, and with type 1 diabetes mellitus, Other autoimmune conditions that have been described in association with autoimmune atrophic gastritis are Addison's disease, chronic spontaneous urticaria, myasthenia gravis, vitiligo, and perioral cutaneous autoimmune conditions, especially erosive oral lichen planus. Interestingly, however, celiac disease, another frequent autoimmune condition, seems to play a protective role for autoimmune atrophic gastritis. The elevated prevalence of autoimmune disease clustering should prompt the clinicial to exclude concomitant autoimmune conditions upon diagnosis of any autoimmune disease.

Gastric cancer is, still nowadays, an important healthcare problem worldwide. In Italy, it represents the fifth tumour by frequency in both men and women over 70 years old. A crucial point is represented by the percentage of early gastric cancers usually found, which is actually very low, and it carries to a worse morbidity and mortality. The most important focus in this oncological disease, is to perform an effective detection of the most common precancerous lesion linked with this neoplasia, chronic atrophic gastritis, in order to avoid the future outcome of gastric cancer itself.

The most frequent pancreatic cancer is pancreatic adenocarcinoma. It has high and early locally and distant invasiveness; this is the reason why it often shows little sign or symptoms in early stage and poor prognosis after the diagnosis, frequently in advanced stage. Although it is possible to detect this tumor in early stage because of its neoplastic precursor (PanINs). Epidemiological data shows that pancreatic cancer is not very common but obvious it is one of the most neoplastic death-cause in the world. The trend of incidence is quite increasing through years, proportionally to the increase of risk factors. About risk factors, it is not easy to detect in all the cases but it is known the role of some of that: there are hereditary risk factors, such as genetic pattern like HBOC, HNPCC, FAP, PJS, FAMMM, HP and CF and environmental ones (modifiable) such as smoke, alcohol consumption, chronic pancreatitis, obesity and diabetes mellitus. This narrative review aims to analyze the epidemiological data of pancreatic cancer and associated risk factors.

Background: Shiga-toxin Escherichia coli productor (STEC) provokes frequently an important intestinal damage that may be considered in differential diagnosis with the onset of Inflammatory Bowel Disease (IBD). The aim of this work is to review in the current literature about Hemolytic Uremic Syndrome (HUS) and IBD symptoms at the onset, comparing the clinical presentation and symptoms, as the timing of diagnosis and of the correct treatment of both these conditions is a fundamental prognostic factor. A focus is made about the association between typical or atypical HUS and IBD and a possible renal involvement in patient with IBD (IgA-nephropathy)., Methods: A systematic review of scientific articles was performed consulting the databases PubMed, Medline, Google Scholar, and consulting most recent textbooks of Pediatric Nephrology., Results: In STEC-associated HUS, that accounts for 90% of cases of HUS in children, the microangiopathic manifestations are usually preceded by gastrointestinal symptoms. Initial presentation may be considered in differential diagnosis with IBD onset. The transverse and ascending colon are the segments most commonly affected, but any area from the esophagus to the perianal area can be involved. The more serious manifestations include severe hemorrhagic colitis, bowel necrosis and perforation, rectal prolapse, peritonitis and intussusception. Severe gastrointestinal involvement may result in life-threatening complications as toxic megacolon and transmural necrosis of the colon with perforation, as in Ulcerative Colitis (UC). Transmural necrosis of the colon may lead to subsequent colonic stricture, as in Crohn Disease (CD). Perianal lesions and strictures are described. In some studies, intestinal biopsies were performed to exclude IBD. Elevation of pancreatic enzymes is common. Liver damage and cholecystitis are other described complications. There is no specific form of therapy for STEC HUS, but appropriate fluid and electrolyte management (better hyperhydration when possible), avoiding antidiarrheal drugs, and possibly avoiding antibiotic therapy, are recommended as the best practice. In atypical HUS (aHUS) gastrointestinal manifestation are rare, but recently a study evidenced that gastrointestinal complications are common in aHUS in presence of factor-H autoantibodies. Some report of patients with IBD and contemporary atypical-HUS were found, both for CD and UC. The authors conclude that deregulation of the alternative complement pathway may manifest in other organs besides the kidney. Finally, searching for STEC-infection, or broadly for Escherichia coli (E. coli) infection, and IBD onset, some reviews suggest a possible role of adherent invasive E. coli (AIEC) on the pathogenesis of IBD., Conclusions: The current literature shows that gastrointestinal complications of HUS are quite exclusive of STEC-associated HUS, whereas aHUS have usually mild or absent intestinal involvement. Severe presentation as toxic megacolon, perforation, ulcerative colitis, peritonitis is similar to IBD at the onset. Moreover, some types of E. coli (AIEC) have been considered a risk factor for IBD. Recent literature on aHUS shows that intestinal complications are more common than described before, particularly for patients with anti-H factor antibodies. Moreover, we found some report of patient with both aHUS and IBD, who benefit from anti-C5 antibodies injection (Eculizumab).

Gastroenterological diseases are a source of morbidity, mortality and costs, and have a high frequency in general practice; for this reason, we have evaluated the current literature regarding the knowledge and management of these disorders by general practitioners, finding little knowledge and adherence to guidelines, highlighting the need for continuous updating in this regard, and greater collaboration between specialists and general practitioners.

Helicobacter pylori (H. pylori) infection is one of the most common infection in humans, affecting more than half of the population. The prevalence of the infection varies widely in rural developing areas (more than 80%) compared to urban developed ones (less than 40%), as a consequence of different socioeconomic and hygienic conditions. H. pylori infection is usually acquired during childhood; infected people usually remain asymptomatic, but about 30% of individuals may develop mild to severe upper gastrointestinal diseases such as gastritis, peptic ulcer, gastric cancer or MALT lymphoma. The transmission route is not clear yet; the person-to-person transmission, especially within the same family appears to be prevalent, but also environmental contamination is possible. The eradication without a specific therapeutic regimen is very unlikely and the reinfection rate after an effective eradication therapy is quite rare. The reinfection rate will increase if there are family members affected.

Background and Aim of the Work: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population. The aim of the review was to analyze literature data in order to identify the main risk conditions described in literature and the proposed treatment., Methods: A research on the databases PubMed, Medline, Embase and Google Scholar was performed by using the keywords "renal calculi/lithiasis/stones" and "inflammatory bowel diseases". A research on textbooks of reference for Pediatric Nephrology was also performed, with focus on secondary forms of nephrolithiasis., Results: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population, typically in patients who underwent extensive small bowel resection or in those with persistent severe small bowel inflammation. In IBD, kidney stones may arise from chronic inflammation, changes in intestinal absorption due to inflammation, surgery or intestinal malabsorption. Kidney stones are more closely associated with Crohn's Disease (CD) than Ulcerative Colitis (UC) in adult patients for multiple reasons: mainly for malabsorption, but in UC intestinal resection may be an additional risk. Nephrolithiasis is often under-diagnosed and might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Secondary enteric hyperoxaluria the main risk factor of UL in IBD, this has been mainly studied in CD, whether in UC has not been completely explained. In the long course of CD recurrent urolithiasis and calcium-oxalate deposition may cause severe chronic interstitial nephritis and, as a consequence, chronic kidney disease. ESRD and systemic oxalosis often develop early, especially in those patients with multiple bowel resections. Even if we consider that many additional factors are present in IBD as hypomagnesuria, acidosis, hypocitraturia, and others, the secondary hyperoxaluria seems to finally have a central role. Some medications as parenteral vitamin D, long-term and high dose steroid treatment, sulfasalazine are reported as additional risk factors. Hydration status may also play an important role in this process. Intestinal surgery is a widely described independent risk factor. Patients with ileostomy post bowel resection may have relative dehydration from liquid stool, which, added to the acidic pH from bicarbonate loss, is responsible for this process. In this acidic pH, the urinary citrate level excretion reduces. The stones most commonly seen in these patients contain uric acid or are mixed. In addition, the risk of calcium containing stones also increases with ileostomy. The treatment of UL in IBD involves correction of the basic gastrointestinal tract inflammation, restricted dietary oxalate intake, and, at times, increased calcium intake. Citrate therapy that increases both urine pH and urinary citrate could also provide an additional therapeutic benefit. Finally, patients with IBD in a pediatric study had less urologic intervention for their calculosis compared with pediatric patients without IBD.

Microsatellites are short tandem repeat DNA sequences of one to tetra base pairs distributed throughout the human genome, both in coding and non-coding regions. Owing to their repeated structure, microsatellites are particularly prone to replication errors that are normally repaired by the Mismatch Repair (MMR) system. MMR is a very highly conserved cellular process, involving many proteins, resulting in the identification, and subsequent repair of mismatched bases, likely to have arisen during DNA replication, genetic recombination or chemical or physical damage. Proteins within the MMR system include MLH1, PMS2, MSH2, MSH6, MLH3, MSH3, PMS1, and Exo1. Deficient MMR (dMMR) results in a strong mutator phenotype known as microsatellite instability (MSI), characterized by widespread length polymorphisms of microsatellite sequences due to DNA polymerase slippage. MSI is recognized as one of the major carcinogenetic pathways of colorectal cancer (CRC): it represents a molecular hallmark of hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome (LS); moreover it is detected in 15% of sporadic colorectal cancers, more often due to an epigenetic inactivation of MLH1. Identification of MSI CRC is important, as MSI may serve as a screening tool for detecting LS, a prognostic marker for patient outcome, and a predictive marker for response to chemotherapy and to immunotherapy.

Introduction: Intraoperative endoscopy is a procedure that supports open and laparoscopic surgery, helping the surgeon to identify the presence of endoluminal gastrointestinal lesions which need to be treated, with a correct diagnosis and an adequate therapy., Material and Methods: A search on PubMed was performed using "intraoperative esophagoscopy", "intraoperative duodenoscopy", and "intraoperative enteroscopy" as Mesh terms. The applied exclusion criteria were: papers written before 2000, not concerning pediatric or gastrointestinal pathology, literature-review articles, language different from English., Results: Sixteen studies from 2000 to 2018 were included. Overall, 1210 patients were treated. Different pathologies were considered. Complications were observed in a range of 0.3-14%. The most frequent complications were perforation, bleeding and mucosal tear. Mortality ranged between 0.7% and 1,2%., Conclusion: Intraoperative endoscopy is an indispensable tool for gastrointestinal surgery. In the hands of experienced endoscopists, intraoperative endoscopy can be performed safely, in time-efficient manner, facilitating diagnosis and treatment.

Although the actual prevalence of chronic atrophic gastritis is unknown and it is probable that this entity goes largely underdiagnosed, patients in whom diagnosis is established usually present advanced stages of disease. Destruction of parietal cells, either autoimmune-driven or as a consequence of Helicobacter pylori infection, determines reduction or abolition of acid secretion. Hypo/achloridia causes an increase in serum gastrin levels, with an increased risk of the development of neuroendocrine tumors. Microcytic, hypochromic anemia frequently precedes the development of megaloblastic, vitamin B12-associated anemia. Moreover, vitamin B12 deficiency,may cause elevation of homocysteine, with an increase in the cardiovascular risk, and may be associated with neurological manifestations, mainly characterized by spinal cord demyelination and atrophy, with ensuing sensory-motor abnormalities. Gastrointestinal manifestations seem to be associated with non-acid reflux and tend to be non-specific.

For thousands of years humans have lived in symbiosis with Helicobacter pylori. This infection is acquired mainly during childhood and, despite it represents one of the most common infections in humans, only a minority of infected people may develop health issues and life-threatening diseases. For diagnosing Helicobacter pylori infection in children we can use, at first, non-invasive diagnostic tests, if clinical pattern and/or history are of suspicion. Then, invasive tests i.e. gastroscopy are necessary to confirm the infection. As antibiotics are not widely available in children affected by Helicobacter pylori infection, they should be chosen based on individual antibiotic susceptibility testing obtained by gastric biopsy specimens or the local antibiotic resistance pattern, in empirical treatment is chosen. Test and treat strategy in children should be avoided. In this brief review we summarize how and in which children the infection should be investigate and which the most appropriate eradication treatment should be chosen.

In recent years the metagenomics techniques have allowed to study composition and function of the intestinal microbiota. The microbiota is a new frontier of biomedical research to be explored and there is growing evidence of its fundamental health-promoting activity. The present review gives a synthetic overview on the characteristics and the role of the microbiota in the adult with particular reference to physiology, pathophysiology and relationships with the host and the environment.

Celiac disease is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals. Many genes involved in the pathogenesis have been identified and a crucial role is known to be played by the Human Leukocyte Antigen (HLA) system. The main determinants for genetic susceptibility are HLA-DQA1 and HLA-DQB1 genes encoding for HLA-DQ2 and HLA-DQ8 molecules, carried by almost all patients affected. However, since HLA-DQ2 and HLA-DQ8 heterodimers explain almost 40% of the disease heritability, HLA typing should not be applied in diagnosis, but exclusively to clarify uncertain diagnoses, considering its negative predictive value.

In the last decade, a barge body of scientific literature has suggested that specific alterations of the gut microbiota may be associated with ther development and clinical course of several gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, gastrointestinal cancer and Clostridium difficile infection. These alterations are often referred to as "dysbiosis", a generic term designing reduction of gut microbiota biodiversity and alterations in its composition. Here, we provide a synthetic overview of the key concepts on the relationship between intestinal microbiota and gastrointestinal diseases, focusing on the translation of these concepts into clinical practice.

Usually, non-invasive tests are the first methods for diagnosing Helicobacter pylori (HP) infection. Among these, serological test, stool antigen research and urea breath test are the most used. Antibodies anti-HP are not recommended in low prevalence population, moreover they cannot reveal an ongoing infection, but they only prove a contact with the bacterium. Also, they can persist for a long time after the eradication of the infection, therefore, they should not be used to verify the success of eradication therapy. Stool antigen research and Urea Breath Test (UBT) are useful both in diagnosis and during follow-up after eradication treatment. The stool antigen test is cheaper than Urea breath test with similar sensitivity and specificity.  Non-invasive tests are not able to diagnose the associated complications to HP infection.

Gastric cancer is a common disease with high mortality. The definition of advanced gastric cancer is still debated. Radical surgery associated to appropriate systemic and intra-abdominal chemotherapy is the gold standard treatment. In presence of peritoneal carcinosis, reaching a complete cytoreduction is the key to achieve long-term survival. Adequate lymphadenectomy is also fundamental. Conversion therapy could be applied to selected IV stage patients. No definitive evidences exist regarding the oncological and surgical superiority of mini-invasive approaches over the classical open techniques.

Background: The small bowel has often been considered the mysterious "black hole" of the gastrointestinal tract. With regards to this, the development of the wireless capsule endoscopy (WCE) has represented a turning point. It is a non-invasive technique, enabling an excellent visualization of the small bowel (SB) mucosa without the use of radiation. The WCE was approved by the Food and Drug Administration (FDA) in 2001 for adults and in 2004 for children. The aim of the present review is to provide an update on indications, diagnostic yield, safety and limitations of WCE in children. Even though literature regarding the use of WCE in pediatric age is more limited than in adults, WCE is a useful and safe diagnostic tool for the exploration of the small bowel also in children. The indications for WCE are similar at any age, however the main indication in children is Crohn's disease (CD), while in the adults is the research of SB bleeding. The main limitation in pediatric age is the possibility for younger children to swallow the capsule. WCE in pediatric is a rapidly advancing technology and has the potential to further transform the evaluation and management of SB disease.

Background and Aim of the Work: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are cystic lesions with malignant potential. Given their increasing incidence in the latest years, a precise characterization and management of these lesions have become more and more crucial: even though the majority of IPMN has a benign and indolent course, it is fundamental to early recognize and stratify patients in order to accurately plan a tailored follow-up and to individuate those that would benefit of surgical treatment. The aim of this paper is to highlight the most recent evidence on IPMN available in the current literature., Methods: We performed a review of the recent literature and of the recent guidelines about pancreatic cystic lesions, especially IPMN., Results: The incidence of IPMN is now on the rise: an increasing number of patients, possibly because of the increasing diagnostic yield of imaging techniques, is being diagnosed with pancreatic cystic lesions, a great part of which are IPMN. The possibility of malignant transformation requires a careful approach to these patients, in the need of tailoring the follow-up and the therapy., Conclusion: A detailed diagnosis, the determination of risk factors for malignant transformation and a multisciplinary approach are of foremost importance for an effective management of IPMN.

Colonic Diverticulosis is one of the most common anatomical findings during colonoscopy. This condition has 60% incidence in the population over 60 years old. About 20% of patients will develop Diverticular Disease, and 5% of them will evolve into Diverticulitis. Until the last years there weren't any approaches for the endoscopic classification of this pathology. In 2013, in Florence, the first endoscopic classification was developed: DICA (Diverticular Inflammation and Complication Assessment). The aim of this article is to focus on the process of the development and the validation of the classification by the pool of gastroenterology experts, and, as well, its usefulness during the clinical practice.