Diverticular Inflammation and Complication Assessment classification, CODA score and fecal calprotectin in clinical assessment of patients with diverticular disease: A decision curve analysis.

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification. METHODS: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions. RESULTS: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other. CONCLUSIONS: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended.

PPIs and gastric cancer: any causal relationship?

Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into therapy, inducing acid. Lasting the years, several studies focused on the potential relationship between inducing hypo-achlorhydria and risk of developing gastric cancer. In 1988 omeprazole, the first proton pump inhibitor, entered therapy. In 1996, Kuipers underlined the danger of progression of chronic atrophic gastritis in subjects taking PPIs. In 2018, one paper from Korea and an another on from Sweden suggested a possible relationship between long-term PPI therapy and the development of gastric cancer. Over the years, several articles, meta-analyzes and population based  focused on relationship between long-term of PPI use and the onset of gastric cancer, with conflicting results. As reported, the presence of bias in the collection of cases, in particular concerning the evaluation of the H.p. status and presence of atrophic gastritis and intestinal metaplasia in subjects treated with PPI, can lead to noticeable errors in the results and conclusions, as demonstrated in the literature by exhaustive methodological studies of pharmacoepidemiology. A possible bias in the collection of case histories is due to the fact that PPIs are often administered to dyspeptic patients, among which there are patients already carriers of gastric neoplasia: the so-called inverse causality.  Literature data, amended by methodological bias (sampling errors, lack of comparative assessment of Hp status and atrophic gastritis) NOT support a causal relationship between long-term PPIs therapy and the onset of gastric cancer.

Improvement of Symptoms in Patients Affected by Chronic Atrophic Gastritis Using L-Cysteine (Acetium®).

BACKGROUND: Chronic atrophic gastritis (CAG) alone is a precancerous condition for gastric cancer. Achlorhydria plays an important role in the formation of a class I carcinogen, acetaldehyde. L-cysteine has been claimed to bind acetaldehyde covalently. Symptoms are present in 55% of CAG patients, of whom 70% have upper gastrointestinal complaints. The aim of this study was to investigate the properties of L-cysteine in the modification of symptom patterns in CAG patients. METHODS: Consecutive patients with histological diagnosis of CAG (OLGA ≥1 with gastric corpus involvement) were evaluated with serological determination of gastric function, clinical assessment of symptoms using the visual analog score (VAS) and the global symptomatic score (GSS), and considered for therapy with L-cysteine, 300 mg daily. Data regarding symptoms were collected at enrollment and after 3, 6, 12, 18, and 24 months, with an ultimate follow-up of 2 years. RESULTS: A total of 330 patients with CAG were divided in group 1 (77 patients treated with L-cysteine) and group 2 (50 patients who received no specific treatment - control group). A statistically significant improvement in the VAS score (7.8 at baseline vs. 4.5 after 24 months; p < 0.01) was observed in patients treated with L-cysteine, while no significant changes in symptom pattern/intensity were recorded in the 2-year follow-up of untreated patients with CAG. CONCLUSIONS: Long-term treatment with L-cysteine provides symptom improvement in CAG patients and might be proposed as maintenance therapy in such patients.

A non-invasive combined strategy to improve the appropriateness of upper gastrointestinal endoscopy.

Background and aim Increasing the appropriateness of upper gastrointestinal endoscopy (UGIE) improves the quality of care while containing costs. The aim of this study was to improve the appropriateness of UGIE through a process involving evaluation of prescriptions and the use of a non-invasive alternative. Materials and methods A senior endoscopist evaluated the appropriateness of all outpatient referrals for UGIE and established the proper timing. Referrals were either accepted and programmed, canceled, or substituted by a non-invasive evaluation of gastric function, determining serum levels of gastrin-17 (G17), Pepsinogen I (PGI) and II (PGII), and antibodies against Helicobacter pylori. Results A total of 5102 requests for UGIE examinations were evaluated; 540 (10.4%) were inappropriate and had been prescribed for: gastroesophageal reflux disease (n=307), surveillance with erroneous timing (n=113), dyspepsia (n=66), other indications (n=20), and absence of written indication (n=34). Gastric function was evaluated in 282/540 patients; findings included normal values in 94 patients without proton-pump inhibitor therapy (PPI) and in 48 on PPI, active H pylori infection in 56, previous H pylori infection in 30, GERD in n=50, and atrophic gastritis in n=4. UGIE was performed in the latter 4 cases.  Within 2 years (range 1-22 months) of the initial refusal, 105/504 patients underwent UGIE, with normal endoscopic findings in 71/105 (67.5%), and with no cases of cancer. Conclusions This strategy, based on a strict control of prescriptions, is effective to increase the appropriateness while containing public health costs. The use of gastric function testing improves patient selection for UGIE endoscopy.

Recovery of gastric function in patients affected by chronic atrophic gastritis using l-cysteine (Acetium®): one year survey in comparison with a control group.

BACKGROUND AND AIM: Chronic Atrophic Gastritis (CAG) is a precancerous condition for gastric cancer (GC) as single risk factor, being a consequence of a previous Helicobacter pylori (Hp) infection or based on autoimmune mechanisms. Achlorhydria plays an important role towards the formation of a class I carcinogen, acetaldehyde, after food intake. L-cysteine has been claimed to be able to bind in a covalent way acetaldehyde when administered at means. METHODS: In this study we enrolled two CAG groups of patients, one treated whit 300 mg/daily of L-cysteine for one year, the other one untreated. We assessed gastric function lasting the one year follow-up by using non invasive surrogates, i.e. Pepsinogen I (PGI) and gastrin 17 (G17). RESULTS: In the group of 77 CAG on therapy we found a statistically significative increase in PGI values and a decrease in G17 levels, in comparison with unchanged values in control group. CONCLUSIONS: L-cysteine seems able to provide a recovery in gastric function when administered in CAG patients and could be proposed as a possible therapy in such patients.

Management of Helicobacter pylori infection: Guidelines of the Italian Society of Gastroenterology (SIGE) and the Italian Society of Digestive Endoscopy (SIED).

Helicobacter pylori infection is very common and affects more than one-third of adults in Italy. Helicobacter pylori causes several gastro-duodenal diseases, such as gastritis, peptic ulcer and gastric malignancy, and extra-gastric diseases. The eradication of the bacteria is becoming complex to achieve due to increasing antimicrobial resistance. To address clinical questions related to the diagnosis and treatment of Helicobacter pylori infection, three working groups examined the following topics: (1) non-invasive and invasive diagnostic tests, (2) first-line treatment, and (3) rescue therapies for Helicobacter pylori infection. Recommendations are based on the best available evidence to help physicians manage Helicobacter pylori infection in Italy, and have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.

Barrett's esophagus: results from an Italian cohort with tight endoscopic surveillance.

BACKGROUND AND AIM: Barrett's Esophagus represents a condition that predisposes to the development of esophageal adenocarcinoma. The aim of the present study was to analyze the demographic and clinical characteristics of patients with BE, to establish the presence of risk factors for this condition, and to determine the frequency of dysplastic lesions as well as the evolution towards adenocarcinoma under tight endoscopic control. METHODS: In this study, we retrospectively collected and analyzed data from a cohort of patients with Barrett's Esophagus identified through endoscopic records of ULSS7 in Northern Italy, who underwent upper esophagogastroduodenoscopy over a 10-year period from July 2008 to December 2020. RESULTS: A total of 264 patients were identified as having BE and included in the study. Mean follow-up was 6.7 years (range: 3 months-13 years). Demographic characteristics of the study population included mean age of 62.7 years (range 33-90 years), with 62.5% of the study population being aged 60 or older, and a male predominance. Females were significantly older than males (65.7 years, range 37-90 vs 61.9 years, range 33-87, p=0.043, respectively). CONCLUSIONS: The present study confirms the importance of tight endoscopic control in the management of BE, favoring early detection of BE degeneration towards high-grade dysplasia or adenocarcinoma. In a subset of patients with high-risk factors including male sex, cigarette smoking and heavy alcohol intake, it may be worthwhile to consider endoscopic control over time in order to detect the development of BE.

Prognostic performance of the 'DICA' endoscopic classification and the 'CODA' score in predicting clinical outcomes of diverticular disease: an international, multicentre, prospective cohort study.

OBJECTIVE: To investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA). DESIGN: A multicentre, prospective, international cohort study. SETTING: 43 gastroenterology and endoscopy centres located in Europe and South America. PARTICIPANTS: 2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications. INTERVENTIONS: A 3-year follow-up was performed. MAIN OUTCOME MEASURES: To predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score). RESULTS: The 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p<0.001), and 0.15% (95% CI 0.04% to 0.59%) in DICA 1, 3.0% (95% CI 1.9% to 4.7%) in DICA 2 and 11.0% (95% CI 7.5% to 16.0%) in DICA 3 (p<0.001), respectively. The 3-year cumulative probability of diverticulitis and surgery was ≤4%, and ≤0.7% in CODA A; <10% and <2.5% in CODA B; >10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981). CONCLUSIONS: DICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score. TRIAL REGISTRATION NUMBER: NCT02758860.

The prevalence of symptomatic uncomplicated diverticular disease could be lower than expected: a single-center colonoscopy-based cohort study.

AIM: The real prevalence of symptomatic uncomplicated diverticular disease (SUDD) is still unknown. The aim of this study was to assess the prevalence of SUDD, post-diverticulitis SUDD (PD-SUDD) and irritable bowel syndrome (IBS)-like symptoms in a real-life population. METHODS: A cohort of patients, submitted to colonoscopy from 1st January 2012 to 30th April 2018 was revised. RESULTS: A cohort of 5451 patients with diverticulosis was identified during the study period. Abdominal pain was recorded in 1141 patients (20.93%), diarrhea in 288 (5.28%) and constipation in 536 (9.83%) patients. SUDD was recorded in 371 patients (6.81% of the patients having diverticulosis and 32.51% of the patients experiencing abdominal pain), PD-SUDD was recorded in 103 patients (1.89% of the patients having diverticulosis and 9.03% of the patients experiencing abdominal pain) and IBS-like was recorded in 348 patients (6.38% of the patients having diverticulosis and 30.5% of the patients experiencing abdominal pain). Three hundred and nineteen patients were not part of any of the previous categories (5.85% of the patients having diverticulosis and 27.96% of the patients experiencing abdominal pain). SUDD and PD-SUDD were more frequent in older ages (>60 years), while IBS-like symptoms were more frequent in younger. Nonspecific abdominal pain was equally distributed in through the ages. CONCLUSION: The prevalence of SUDD seems to be lower than expected, and most of patients with diverticulosis and abdominal symptoms may suffer from IBS-like or other causes.

Low Levels of Gastrin 17 are Related with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD.

BACKGROUND AND AIMS: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms. METHODS: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD. RESULTS: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett's esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p<0.0001). Similarly, in the primary care setting, 163 GERD patients had statistically significant low levels of G-17 as compared with 132 dyspeptic patients (0.5±0.2 pg/L vs. 4.0±2.6 pg/L, p<0.0001). Moreover, in the primary care setting, no statistically significant differences were found for G-17 levels between patients with erosive and non-erosive reflux pattern (0.4±0.2 vs 0.7±0.3; p=0.08). In primary care, the accuracy of G-17 less than 1 pg/L to diagnose non-invasively GERD was 94.3%. CONCLUSIONS: Low levels of G-17 were detected in patients with erosive esophagitis and Barrett's esophagus in a referral center and in patients with typical GERD symptoms in a sample of patients from a primary care setting.

Risk factors for endoscopic severity of diverticular disease of the colon and its outcome: a real-life case-control study.

BACKGROUND: Diverticular disease is an increasing global problem. AIMS: To assess the factors associated with the severity of diverticular disease and its outcome, analyzing a real-life population. METHODS: A cohort of patients, submitted to colonoscopy from 1 January 2012 to 30 April 2018 was revised. The endoscopic severity of diverticular disease was scored according to the Diverticular Inflammation and Complications Assessment (DICA) classification. RESULTS: A cohort of 11 086 patients was identified during the study period, 5635 with diverticulitis and 5451 without diverticulosis. Blood hypertension, diabetes and angiotensin receptor blocker users occurred more frequently in the study group, while the prevalence of colorectal cancer (CRC) was significantly lower. Age >70 years, BMI >30 and blood hypertension were factors independently related to the presence of diverticulosis, while diabetes and CRC were significantly associated with the absence of diverticulosis. Female sex, age, smoke, appendectomy, proton-pump inhibitors and acetyl-salicylic acid use were directly related to the severity of diverticular disease, while CRC and colonic polyp occurrence were inversely related to the severity of diverticular disease, significantly. Female sex, age >70 years and smoke were significantly related to the severity of diverticular disease. CRC and colonic polyps were significantly less in DICA 3 patients. DICA 3 patients were more often symptomatic, at higher risk of hospital admission, longer hospital stay and higher mean costs. CONCLUSIONS: Several factors are associated with the severity of diverticular disease according to the DICA classification. The DICA classification is also predictive of the outcome of the disease in terms of hospital admission, stay and costs.

The "DICA" endoscopic classification for diverticular disease of the colon shows a significant interobserver agreement among community endoscopists.

BACKGROUND AND AIM: An endoscopic classification of Diverticular Disease (DD), called DICA (Diverticular Inflammation and Complication Assessment) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement levels for this classification among an endoscopist community setting. METHODS: A total of 66 endoscopists independently scored a set of DD endoscopic videos. The percentages of overall agreement on the DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of the inter-rater agreement. RESULTS: The overall agreement levels were: 70.2% for DICA 1, 70.5% for DICA 2, 81.3% for DICA 3. The free marginal κ was: 0.553 for DICA 1, 0.558 for DICA 2, 0.719 for DICA 3. The agreement levels among the expert group were: 78.8% for DICA 1, 80.2% for DICA 2, 88.5% for DICA 3. The free marginal κ among the expert group were: 0.682 for DICA 1, 0.712 for DICA 2, 0.828 for DICA 3. The agreement of expert raters on the single item of the DICA classification was superior to the agreement of the overall group. CONCLUSIONS: The overall inter-rater agreement for DICA score in this study ranges from moderate to good, with a significant improvement in the expert subgroup of raters. Diverticular Inflammation and Complication Assessment is a simple and reproducible endoscopic scoring system.

Long-term efficacy of rifaximin to manage the symptomatic uncomplicated diverticular disease of the colon.

Although rifaximin is currently advised in managing symptomatic uncomplicated diverticular disease (SUDD) of the colon, no long-term data are available. This retrospective study assessed the outcome of a large cohort of patients with SUDD, treated with rifaximin, during an 8-year follow-up. The study group (group A) included 346 patients with SUDD (median age 64 years, IQR 58-69, 62.4% females), treated with rifaximin 800 mg/d for 7 days every month. The control group (group B) included 470 patients with SUDD (median age 65 years, IQR 59-74 years, 60.8% females), taking any other treatment on demand. Two symptoms (left lower abdominal pain and bloating) were assessed by a visual analog scale (VAS), graded from 0=no symptom to 10=the most severe symptom. Daily bowel movements were also reported. Median (IQR) VAS score for pain was 6 (5-7) in group A and 6 (6-7) in group B at baseline (p=0.109); at 8-year follow-up it was 3 (3-4) and 6 (5-7), respectively (p<0.000). Both bloating and daily bowel movements were significantly reduced in group A. Acute diverticulitis occurred in 9 (2.6%) patients in group A and in 21 (4.5%) patients in group B (p=0.155). Surgery occurred in 4 (1.2%) patients in group A and 9 (1.9%) in group B (p=0.432). Disease-related mortality occurred in no patient in group A and 2 (0.4%) patients in group B (p=0.239). No side effects were recorded during the entire study period. Rifaximin is effective to relieve symptoms and reduce the risk of disease-related complications in patients with SUDD.

The DICA Endoscopic Classification for Diverticular Disease of the Colon Shows a Significant Interobserver Agreement among Community Endoscopists: an International Study.

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. METHODS: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. RESULTS: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. CONCLUSIONS: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

What's New in Diagnosing Diverticular Disease.

In this session different issues for the diagnosis of diverticular disease (DD) were considered including "Biomarkers", "Computer tomography", "Ultrasonography in detecting acute diverticulitis", "Endoscopy" and "The DICA classification: a new predictive tool in managing diverticular disease". Most patients affected by DD suffer from recurrent attacks of abdominal pain without evidence of an active inflammatory process, causing a difficult differential diagnosis with other intestinal conditions. Several biomarkers, serological, fecal, urinary and genetic were considered, but recent studies confirmed that only CRP and fecal calprotectin are matching with the criteria for an ideal biomarker for DD. Colonoscopy still remains the gold standard for the diagnosis of DD, playing a key role in many clinical settings, such as colonic diverticular bleeding, or to differentiate inflammatory bowel disease (IBD) and segmental colitis associated with diverticulosis (SCAD); Moreover, in 2015 has been developed the DICA (Diverticular Inflammation and Complication Assessment) endoscopic classification that considers 10 different parameters, each one with a score, and the sum of items scores represents the severity of the disease; in this way the endoscopic exam would be able to predict the outcome of DD for each patient. On the other hand, computer tomography (CT) is the gold standard for acute diverticulitis (AD) with an excellent sensitivity and specificity; recently, metanalysis of prospective studies have shown that intestinal ultrasonography (IUS) and CT have the same sensitivity for the diagnosis of an AD and the advantage is that IUS is less expensive, non-invasive and easily accessible.

Endoscopic ultrasound in pediatric population: a comprehensive review of the literature.

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.

Applications of wireless capsule endoscopy in pediatric age: an update.

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.

Digestive disorders and Intestinal microbiota.

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.

Renal lithiasis and inflammatory bowel diseases, an update on pediatric population.

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.