Focal Active Colitis: What Are Its Clinical Implications? A Narrative Review.

Focal active colitis (FAC) is described as a histolopathological term indicating the isolated finding of focal neutrophil infiltration in the colonic crypts. Currently, there exist numerous debates regarding the clinical significance of diagnosing FAC, which may or may not have clinical relevance as it is frequently detected in colorectal biopsies without any other microscopic abnormalities. The objective of this narrative review is to provide an overview of the available evidence concerning the clinical implications of FAC, both in the adult population (among five studies available in the scientific literature) and in the pediatric context (based on two available studies).

Gastroparesis: The Complex Interplay with Microbiota and the Role of Exogenous Infections in the Pathogenesis of the Disease.

Gastroparesis (GP) is a disorder of gastric functions that is defined by objective delayed gastric emptying in the absence of mechanical obstruction. This disease is characterized by symptoms such as nausea, post-prandial fullness, and early satiety. GP significantly impacts patients' quality of life and contributes to substantial healthcare expenses for families and society. However, the epidemiological burden of GP is difficult to evaluate, mainly due its significant overlap with functional dyspepsia (FD). GP and FD represent two similar diseases. The pathophysiology of both disorders involves abnormal gastric motility, visceral hypersensitivity, and mucosal inflammation. Moreover, both conditions share similar symptoms, such as epigastric pain, bloating, and early satiety. The latest evidence reveals that dysbiosis is directly or indirectly connected to gut-brain axis alterations, which are the basis of pathogenesis in both FD and GP. Furthermore, the role of microbiota in the development of gastroparesis was demonstrated by some clinical studies, which found that the use of probiotics is correlated with improvements in the gastric emptying time (GET). Infections (with viruses, bacteria, and protozoa) represent a proven etiology for GP but have not been sufficiently considered in current clinical practice. Previous viral infections can be found in about 20% of idiopathic GP cases. Moreover, delayed gastric emptying during systemic protozoal infections represents a huge concern for compromised patients, and few data exist on the topic. This comprehensive narrative review analyzes the relationship between microorganisms and GP. We explore, on the one hand, the correlation between gut microbiota dysbiosis and GP pathogenesis, including treatment implications, and, on the other hand, the association between exogenous infections and the etiology of the disease.

The Role of Microbiota in Upper and Lower Gastrointestinal Functional Disorders.

Functional gastrointestinal disorders (FGIDs), also known as disorders of gut-brain interaction, are a group of disorders characterized by chronic gastrointestinal symptoms in the absence of demonstrable pathology on conventional testing [...].

Digital single-operator cholangioscopy in treating difficult biliary stones: results from a multicenter experience.

BACKGROUND: In clinical practice, standard endoscopic treatment of biliary stones fails in up to 10% of patients, and more invasive procedures such as percutaneous trans-hepatic interventions or surgery might become necessary. The aim of this multicenter retrospective study, based on prospectively-collected data, was to evaluate both the efficacy and the safety of digital-single operator cholangioscopy (D-SOC) to treat difficult biliary stones in cases with a previous failure of conventional endoscopic methods. METHODS: Only patients with a previous failure of endoscopic standard treatment and a D-SOC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone clearance rate per procedure and per patient. RESULTS: Out of 1258 ERCP performed at our centers, 31 cholangioscopes in 21 patients were solely performed for the treatment of difficult biliary stones using EHL or LL. A complete biliary stone removal was achieved in 67.7% (21/31) of all procedures including initial and repeated examinations, while in 35.4% (11/31) of all procedures an incomplete removal was accomplished of which 36.3% had a partial stone removal. In 22 procedures EHL was adopted as techniques to fragment and remove biliary stones, while in 9 procedures LL was used. In both the techniques, the complete stone removal rate and the incomplete stone removal rate were similar (75% vs. 77.7%, P>0.05). Furthermore, the success rate of digital D-SOC to treat difficult biliary stones was assessed per patient: overall, 100% of patients with difficult biliary stones were successfully treated using D-SOC. Only one patient experienced mild cholangitis classified ad mild adverse event following ASGE (American Society of Gastrointestinal Endoscopy) lexicon. CONCLUSIONS: Our data indicate that digital D-SOC assisted biliary stone treatment is highly efficient for the treatment of difficult biliary stones even in such patients in whom previous conventional endoscopic methods to treat biliary stones have failed. Therefore, D-SOC might be considered the new standard of care for these patients, being both, effective and safe.

Use of catheter-based cholangioscopy in the diagnosis of indeterminate stenosis: a multi-centre experience.

BACKGROUND: Direct bile ducts visualization through cholangioscopy has gained popularity due to its better diagnostic accuracy than a standard ERCP in indeterminate biliary stricture. AIM: We aimed to review our catheter-based cholangioscopy interventions in patients with indeterminate biliary stenosis, using the SpyGlass Direct Visualization System (SDVS) and summarize our experience in terms of procedures and results. RESULTS: we collected 25 consecutive patients with indeterminate biliary stricture over 3 years. The overall procedural success in our cohort amounted to 96% (24/25). If we focus on the diagnostic procedures, the ability to merely visualize the region of interest/lesion and perform biopsy of the lesion was possible in 96 % (24/25) In our cohort localization in the common bile duct (P = 0.03; 95 % CI 0.27-0.96) was found as positive determining factor for diagnosis. Sensitivity, specificity and accuracy for visual diagnosis by SDVS in our cohort were 100, 83.3 and 96 %, respectively. The use of biopsy or obtaining a histological diagnosis to assist in identifying patients with malignant stenosis, to exclude malignancy and to correctly classify diagnosed patients resulted in a sensitivity of 100 %, a specificity of 73% % with an overall accuracy of 94.4 %. Only a mild adverse event (cholangitis, treated conservatively) occurred. CONCLUSIONS: Today, the SDVS should be considered essential in diagnosing indeterminate biliary strictures, since the procedure is associated with high procedural success in terms of diagnostic accuracy, alters clinical outcome in over 80 % of considered insolvable cases, with an acceptable safety profile.

An Unusual Presentation of Crohn's Disease Diagnosed Following Accidental Ingestion of Fruit Pits: Report of Two Cases and Review of the Literature.

The clinical course of Crohn's disease (CD) is often complicated by intestinal strictures, which can be fibrotic, inflammatory, or mixed, therefore leading to stenosis and eventually symptomatic obstruction. We report two cases of subclinical CD diagnosed after fruit pit ingestion, causing bowel obstruction; additionally, we conducted a narrative review of the scientific literature on cases of intestinal obstruction secondary to impacted bezoars due to fruit pits. Symptoms of gastrointestinal bezoars in CD patients are not diagnostic; and the diagnosis should be based on a combined assessment of history, clinical presentation, imaging examination and endoscopy findings. This report corroborates the concept that CD patients are at a greater risk of bowel obstruction with bezoars generally and shows that accidental ingestion of fruit pits may lead to an unusual presentation of the disease. Therapeutic options in this group of patients differ from the usual approaches implemented in other patients with strictures secondary to CD.

Microbiota Gut-Brain Axis in Ischemic Stroke: A Narrative Review with a Focus about the Relationship with Inflammatory Bowel Disease.

The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer's disease, and Parkinson's disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only the focus of neuroscience, but also the starting point for research regarding many diseases such as inflammatory bowel diseases (IBD). The bi-directional interaction between gut microbiota and the brain is not completely understood. The aim of this review is to sum up the evidencesconcerningthe role of the gut-brain microbiota axis in ischemic stroke and to highlight the more recent evidences about the potential role of the gut-brain microbiota axis in the interaction between inflammatory bowel disease and ischemic stroke.

Could Chronic Idiopatic Intestinal Pseudo-Obstruction Be Related to Viral Infections?

Chronic idiopathic intestinal pseudo-obstruction (CIIPO) is a disease characterized by symptoms and signs of small bowel obstruction in the absence of displayable mechanical obstruction. Due to the known neuropathic capacity of several viruses, and their localization in the intestine, it has been hypothesized that such viruses could be involved in the pathogenesis of CIIPO. The most frequently involved viruses are John Cunningham virus, Herpesviridae, Flaviviruses, Epstein-Barr virus and Citomegalovirus. Therefore, the present narrative review aims to sum up some new perspectives in the etiology and pathophysiology of CIIPO.

Effectiveness and Tolerability of Very-low Volume Preparation for Colonoscopy: A Narrative Review.

An adequate bowel preparation is essential for a successful colonoscopy, in particular, in the setting of colorectal cancer screening. However, up to one-quarter of colonoscopies are associated with inadequate bowel preparation, which may result in reduced polyp and adenoma detection rates, prolonged procedural time, and an increased likelihood of repeat the procedure. The ideal intestinal preparation should provide an optimal observation of the mucosa (at least > 90% of the visible surface), with adequate acceptability and safety for the patient. With this premise, a very low-volume 1 L PEG-ASC solution (Plenvu; Norgine, Harefield, United Kingdom) has been recently introduced to improve patients' experience in colonoscopy by reducing the total intake of liquids to be consumed. This could represent a valid option for bowel cleansing, considering CRC screening and surveillance programs, improving both the quality of the examination and the patients' compliance. Nevertheless, it must be emphasized that a "one size fits all" preparation strategy is not feasible and that a bowel preparation regime must always be selected and tailored by the clinician for each patient, evaluating the best options on a case by case basis. This narrative review aims to sum up the evidence regarding new bowel preparation regimens in order to help clinicians to tailor the best choice for patients undergoing colonoscopy.

Use of artificial intelligence in improving adenoma detection rate during colonoscopy: Might both endoscopists and pathologists be further helped.

Colonoscopy remains the standard strategy for screening for colorectal cancer around the world due to its efficacy in both detecting adenomatous or pre-cancerous lesions and the capacity to remove them intra-procedurally. Computer-aided detection and diagnosis (CAD), thanks to the brand new developed innovations of artificial intelligence, and especially deep-learning techniques, leads to a promising solution to human biases in performance by guarantying decision support during colonoscopy. The application of CAD on real-time colonoscopy helps increasing the adenoma detection rate, and therefore contributes to reduce the incidence of interval cancers improving the effectiveness of colonoscopy screening on critical outcome such as colorectal cancer related mortality. Furthermore, a significant reduction in costs is also expected. In addition, the assistance of the machine will lead to a reduction of the examination time and therefore an optimization of the endoscopic schedule. The aim of this opinion review is to analyze the clinical applications of CAD and artificial intelligence in colonoscopy, as it is reported in literature, addressing evidence, limitations, and future prospects.

Tenapanor for the treatment of irritable bowel syndrome with constipation.

INTRODUCTION: Irritable bowel syndrome with constipation is associated with higher rates of functional impairment, as compared to other subtypes of the syndrome. Conventional laxative-based pharmacologic therapy of IBS-C, which is mostly symptom-based, is often unsatisfactory. Tenapanor represents a first-in-class orally available inhibitor of NHE3, which is minimally absorbed in the GI tract, what constitutes a significant therapeutic benefit, as it may act on the drug target. AREAS COVERED: Aim of this article is to sum up the evidences about pharmacodynamics and pharmacokinetics of tenapanor, focusing on animal models and in vitro studies, but also discuss clinical trials on tenapanor's safety and efficacy in view of its important potential role in IBS-C treatment. EXPERT OPINION: In the challenging setting of irritable bowel syndrome with constipation, tenapanor represents a novel strategy in the pipeline of the therapies of IBS-C. Its pharmacokinetic and pharmacodynamic profile provides that it is minimally absorbed from the intestinal lumen and that its action is local, but not systemic action, therefore guaranteeing the reduction of drug-drug interactions, toxicity and severe adverse effects. Phase 2b and 3 trials showed an optimal satisfaction of primary and secondary endpoints.

Could JC virus be linked to chronic idiopathic intestinal pseudo-obstruction?

JC virus is a member of the Polyomavirus family, infects humans worldwide, and 90% of the population carry antibodies to the virus by adult life. The initial infection is asymptomatic, but it may become persistent. JC virus DNA is frequently present in the upper and lower gastrointestinal tracts of healthy adults. Chronic idiopathic intestinal pseudo-obstruction, one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Because of the known neuropathic capability of this virus, and its frequent presence in the gut, it has been proposed that JCV might be detectable in tissues of patients with chronic idiopathic intestinal pseudo-obstruction, and possibly be involved in the pathogenesis of this disease, because the virus may actively infect the enteroglial cells of the myenteric plexuses of the patients with chronic idiopathic intestinal pseudo-obstruction. We report two cases of upper idiopathic intestinal pseudo-obstruction associated with JCV infection.

Potential clinical value of quantitative fluorine-18-fluorodeoxyglucose-PET/computed tomography using a graph-based method analysis in evaluation of incidental lesions of gastrointestinal tract: correlation with endoscopic and histopathological findings.

OBJECTIVES: To identify the clinical relevance of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with 18F-FDG PET/CT and to assess the potential benefit of using semiquantitative PET measures to discern malignant from benign lesions. METHODS: Forty-one patients who underwent F-FDG PET/CT scans during the oncologic follow-up, revealing abnormal incidental 18F-FDG accumulations in the GIT were included in this retrospective analysis. Incidental PET/CT findings were correlated with endoscopic and histological findings. Semiquantitative PET values (SUVmax, SUVmean, SULpeak, and TLG) were evaluated by using a new graph-based method. Two sample t-test analysis has been performed to evaluate the differences of PET parameters between precancerous or cancerous lesions and inflammatory disease. RESULTS: Nine of the 41 patients had an IDL of the GIT on F-FDG PET/CT (detection rate 22%). Endoscopic examination and biopsy have confirmed the presence of precancerous or cancerous lesions as follow: colonic adenoma with high-grade dysplasia (N = 2), colonic adenoma with low-grade dysplasia (N =3), colonic metastatic lesion from primary breast cancer (N =1), gastric carcinoma (N=3). Precancerous or cancerous lesions showed a higher SUVmax, SUVmean, SULpeak, and TLG with a mean value of 10.6 (range, 5.3- 16.7), 6.2 (range, 2.1-10.6), 5.2 (2.7-11), and 66.6 (range, 7.4-164), than patients with inflammatory and endoscopically negative lesions. Two sample t-test analysis showed that SUVmean (P = 0.03), SULpeak (P = 0.05) were statistically different between the two subgroups. CONCLUSION: The use of new semiquantitative PET parameters may increase the diagnostic yield of FDG PET in the case of abnormal incidental F-FDG accumulations.

Superior Mesenteric Artery Syndrome: Clinical, Endoscopic, and Radiological Findings.

BACKGROUND: The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss. Studies to determine the optimal methods of diagnosis and treatment are required. AIMS AND METHODS: This study aims at analyzing the clinical presentation, diagnosis, and management of SMA syndrome. Ten cases of SMA syndrome out of 2074 esophagogastroduodenoscopies were suspected. A contrast-enhanced computed tomography (CECT) scan was performed to confirm the diagnosis. After, a gastroenterologist and a nutritionist personalized the therapy. Furthermore, we compared the demographical, clinical, endoscopic, and radiological parameters of these cases with a control group consisting of 10 cases out of 2380 EGDS of initially suspected (but not radiologically confirmed) SMA over a follow-up 2-year period (2015-2016). RESULTS: The prevalence of SMA syndrome was 0.005%. Median age and body mass index were 23.5 years and 21.5 kg/m2, respectively. Symptoms developed between 6 and 24 months. Median aortomesenteric angle and aorta-SMA distance were 22 and 6 mm, respectively. All patients improved on conservative treatment. In our series, a marked (>5 kg) weight loss (p = 0.006) and a long-standing presentation (more than six months in 80% of patients) (p = 0.002) are significantly related to a diagnosis of confirmed SMA syndrome at CECT after an endoscopic suspicion. A "resembling postprandial distress syndrome dyspepsia" presentation may be helpful to the endoscopist in suspecting a latent SMA syndrome (p = 0.02). The narrowing of both the aortomesenteric angle (p = 0.001) and the aortomesenteric distance (p < 0.001) was significantly associated with the diagnosis of SMA after an endoscopic suspicion; however, the narrowing of the aortomesenteric distance seemed to be more accurate, rather than the narrowing of the aortomesenteric angle. CONCLUSION: SMA syndrome represents a diagnostic and therapeutic challenge. Our results show the following findings: the importance of the endoscopic suspicion of SMA syndrome; the preponderance of a long-standing and chronic onset; a female preponderance; the importance of the nutritional counseling for the treatment; no need of surgical intervention; and better diagnostic accuracy of the narrowing of the aorta-SMA distance. Larger prospective studies are needed to clarify the best diagnosis and management of the SMA syndrome.

Minimally invasive surgical approach for radicalization of incidental post-cholecystectomy gallbladder carcinoma: safety, feasibility and outcomes.

BACKGROUND AND AIMS: Gallbladder carcinoma is a rare but aggressive malignant neoplasm. The incidence of intra- or post-operative incidental gallbladder carcinoma diagnosis following laparoscopic cholecystectomy is estimated to be 1-2%. Aggressive re-resection is warranted as the majority of patients have residual disease either in the liver or the lymph nodes. However the use of a minimally invasive surgical approach (MISA) to perform a radicalization in these patients has not been investigated yet. We retrospectively analyzed surgical and oncologic outcome of a small selected cohort of patients with incidental gallbladder carcinoma whom underwent redo radicalization surgery by MISA. MATERIAL AND METHODS: From April 2012 to June 2014 at our department six patients (three females and three males) with incidental findings of gallbladder carcinoma pT1b (stage I) following laparoscopic cholecystectomy, and referred to our center from other secondary-level referral hospitals, underwent a redo surgery for radicalization by means of laparoscopic (n. 3) or robotic approach (n. 3). A retrospective analysis of prospective collected data was performed. RESULTS: The redo procedure consisted of a liver resection (segments IVb + V) and lymph nodes clearance of hepatoduodenal hilum and common hepatic artery. Conversion rate was zero. Median operative time was 290 (250-310) min. Estimate blood loss was 175 (100-350) ml. Total hospital stay was 6 (5-10) days. All liver resections were performed without inflow vascular clamping. One patient was re-operated for hemoperitoneum while peri-operative mortality was zero. Oncologically, an R0 resection was always achieved with a mean number of lymph nodes retrieved of 17,5 (14-22). The stage of the neoplasm was confirmed in all cases but one, who was found to have a pN1 status (stage IIIb). At 21 (6-32) months follow-up all patients are alive and no recurrence has been observed. CONCLUSIONS: Our data suggest that radicalization of patients with stage I incidental postoperative gallbladder carcinoma can be done by a MISA without compromising the oncologic outcome. Larger studies are needed to validate these results.

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond.

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.

JC Virus and Lung Adenocarcinoma: Fact or Myth?

BACKGROUND/AIM: An association has been reported between lung cancer and John Cunningham (JC) virus infection. The aim of this study was to evaluate the prevalence of JC virus in a small cohort of patients with lung adenocarcinoma and assess its presence in nodal metastasis. MATERIALS AND METHODS: Consecutive samples of 13 surgically-removed lung tumors and 13 surrounding normal cancer-free tissues were selected. Five cases included metastatic lymph nodes. JC virus infection was assessed through nested PCR. RESULTS: Seven out of thirteen patients with lung adenocarcinoma had a positive PCR test for JC virus. One of the five patients with nodal metastasis had a positive PCR test for JC virus. None of the thirteen specimens from the control group presented with JC virus infection. The difference between the two groups regarding JC virus infection was statistically significant (p=0.008). CONCLUSION: Our study suggests that JC virus might be involved in lung carcinogenesis.

Inflammation in irritable bowel syndrome: Myth or new treatment target?

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.