Technical failure during Colorectal Endoscopic Full Thickness Resection: The "through thick and thin" Study.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is an effective and safe technique for non-lifting colorectal lesions. Technical issues or failures with full-thickness resection device (FTRD) system are reported but there are no data about their details. The aim of our study was to quantify and classify FTRD technical failures. PATIENTS AND METHODS: We performed a retrospective study involving 17 Italian centres with experience in advanced resection techniques and OVESCO devices. Each centre shared and classified all the consecutive failures prospectively collected during colorectal EFTR by using FTRD from 2018 to 2022. Primary outcome was technical failure rate and classification; secondary outcomes included management, clinical success, and complications' assessment in this population. RESULTS: Included lesions were mainly recurrent (52%), with mean dimension of 18.4 (± 7.5) mm. Among 750 EFTRs, failures occurred in 77 patients (35 F, mean age 68.9 ±8.9 years). A classification was proposed in type I snare uncutting (53.2%), type II clip misdeployment (31.2%) and type III cap misplacement (15.6%). Among endoscopic treatment completed, rescue EMR was performed in 57 patients (79%), allowing en-bloc and R0 resection in 71% and 64% cases, respectively. Overall adverse events rate was 27.3%. Pooled estimates for the rate of failure, complications and rescue endoscopic therapy were similar between low- and high-volume centres (p=0.08, p = 0.702 and p= 0.713). CONCLUSIONS: Colorectal EFTR with FTRD is a challenging technique with a not negligible rate of technical failure and complications. Experience in rescue resection techniques and multidisciplinary management are mandatory in this setting.

Endoscopic submucosal dissection in colorectal neoplasia performed with a waterjet system-assisted knife: higher en-bloc resection rate than conventional technique.

BACKGROUND/AIMS: Colorectal endoscopic submucosal dissection (ESD) is burdened by its associated high risk of adverse events and long procedure time. Recently, a waterjet-assisted knife was introduced to simplify and speed up the procedure. The aim of this study was to evaluate the efficacy and safety of waterjet-assisted ESD (WESD) compared to that of the conventional ESD (CESD) technique. METHODS: The charts of 254 consecutive patients who underwent colorectal ESD between January 2014 and February 2021 for colorectal neoplasms were analyzed. The primary outcome was the en-bloc resection rate. Secondary outcomes were complete and curative resection rates, the need to switch to a hybrid ESD, procedure speed, the adverse event rates, and the recurrence rates. RESULTS: Approximately 174 neoplasias were considered, of which, 123 were removed by WESD and 51 by CESD. The en-bloc resection rate was higher in the WESD group (94.3% vs. 84.3%). Complete resection rates and curative resection rates were similar. The need to switch to a hybrid ESD was greater during CESD (39.2% vs. 13.8%). Procedure speed and adverse event rates were similar. During follow-up, one recurrence occurred after a WESD. CONCLUSION: WESD allows a high rate of en-bloc resections and less frequently requires a rescue switch to the hybrid ESD compared to CESD.

Endoscopic submucosal dissection: Italian national survey on current practices, training and outcomes.

BACKGROUND AND AIMS: Most of the evidence supporting endoscopic submucosal dissection (ESD) comes from Asia. European data are primarily reported by specialized referral centers and thus may not be representative of common European ESD practice. The aim of this study is to understand the current state of ESD practice across Italian endoscopy centers. METHODS: All Italian endoscopists who were known to perform ESD were invited to complete a structured questionnaire including: operator features and competencies, ESD training details and clinical outcomes over a 2-year period. RESULTS: Twenty-nine operators from 23 centers (69% response rate) completed the questionnaire: 18 (62%) were <50 years old; 7 (24%) were female; 16 (70%) were located in Northern Italy. Overall ESD volume was <40 cases in 9 (31%) operators, 40-80 in 8 (27.5%), 80-150 in 4 (13.8%) and >150 in 8 (27.5%). Colorectal ESD was predominant for operators with an experience >80 cases. En-bloc resection rates ranged from 77.2 to 97.2% depending on the anatomic location with an R0 resection rate range of 75.3-93.6%. ESD perforation rates in the colon and rectum were significantly lower when experience was >150 compared to 80-150 cases (p < 0.0001 and p = 0.006 for colon and rectum, respectively). CONCLUSION: ESD in Italy is performed by a significant number of operators. Overall, Italian endoscopists performing ESD have achieved a good competence level. However, there is much variability in training protocols, initial supervision of procedures, practice settings, case mix and procedural volume/year that are likely responsible for some of the suboptimal resectional outcomes and increased perforation risk, mainly in the colon. Standardized training programs, practice parameters and auditing of outcomes are required.

Endoscopic submucosal dissection of gastric superficial neoplastic lesions: a single Western center experience.

BACKGROUND: Endoscopic submucosal dissection (ESD) allows "en bloc" resection of superficial gastric lesions. OBJECTIVE: The aim of this study is to report "en bloc" resection rate, procedure results, post resection features, analysis of complications, and relapses at mid-long term follow-up on an Italian center case series of patients with superficial gastric neoplastic lesions treated with ESD. METHODS: This is a retrospective evaluation of a prospectively collected series of patients diagnosed with gastric superficial lesions who underwent ESD between November 2007 and May 2015. The analysis included demographic, clinical, endoscopic, and histological data. In detail, the following features were analyzed: (1) "en bloc" resection rate; (2) R0, R1, and RX rate; (3) complication rate; and (4) neoplastic recurrence during follow-up. A comparison was performed between lesions treated according to standard and to extended criteria. RESULTS: In the analysis, therefore, 70 superficial lesions and 70 endoscopic procedures were considered.Overall, 53 (76%) procedures were performed according to the extended-ESD criteria. The remaining 17 (24%) cases were performed according to standard criteria. In 68/70 (97%) procedures "en bloc" resection was successful. Forty-four (65.6%) patients had a R0 resection, while 15 (22%) patients had a R1 and the remaining 8 (12.4%) patients were RX. Two patients (2.8%) experienced a major complication. Overall, 7 patients (10.4%) required surgery: in two cases because of local recurrence, in one case for an intraprocedural complication not amenable to endoscopic treatment, in three patients with R1 vertical margins, and in the last patient because of an aggressive pathology (i.e. signet ring cell adenocarcinoma). The mean follow-up of patients with neoplastic lesions was 36.6 ± 13.1 months. CONCLUSION: ESD for early gastric cancer is a safe and effective technique when performed by experienced Endoscopists also in Western setting. When comparing the outcomes of the ESD in patients with standard and extended indication there is no significant difference in terms of complete resection, complications and local recurrence rates. Larger Western studies are needed to clearly define the role and the outcomes of ESD in regions at low incidence for gastric neoplasia.

Evaluation of Clensia®, a new low-volume PEG bowel preparation in colonoscopy: Multicentre randomized controlled trial versus 4L PEG.

BACKGROUND: Success of colonoscopy is linked to the adequacy of bowel cleansing. Polyethylene glycol 4L (PEG 4L) solutions are widely used for colonic cleansing but with limitations concerning tolerability and acceptability. AIM: To demonstrate the equivalence of a new low-volume PEG containing citrates and simeticone (Clensia) versus a standard PEG 4L. METHODS: In this, multicentre, randomised, observer-blind trial, patients received either Clensia 2L or PEG 4L solution. Primary endpoint was the proportion of patients with colon cleansing evaluated as excellent or good. RESULTS: 422 patients received Clensia (n=213) or PEG 4L (n=209). Rate of excellent/good bowel cleansing was 73.6% and 72.3% in Clensia and PEG 4L group respectively. Clensia was demonstrated to be equivalent to PEG 4L. No SAEs were observed. Clensia showed better gastrointestinal tolerability (37.0% vs 25.4%). The acceptability was significantly better with Clensia in terms of proportion of subjects who felt no distress (Clensia 72.8% vs PEG 4L 63%, P=0.0314) and willingness-to-repeat (93.9% vs 82.2%, P=0.0002). The rate of optimal compliance was similar with both formulations (91.1% for Clensia vs 90.9% for PEG 4L, P=0.9388). CONCLUSIONS: The low-volume Clensia is equally effective and safe in bowel cleansing compared to the standard PEG 4L, with better gastrointestinal tolerability and acceptability.

Usefulness of virtual chromoendoscopy in the evaluation of subtle small bowel ulcerative lesions by endoscopists with no experience in videocapsule.

BACKGROUND AND STUDY AIMS: In videocapsule endoscopy examination (VCE), subtle variations in mucosal hue or pattern such as those seen in ulcerations can be difficult to detect, depending on the experience of the reader. Our aim was to test whether virtual chromoendoscopy (VC) techniques, designed to enhance the contrast between the lesion and the normal mucosa, could improve the characterization of ulcerative mucosal lesions. PATIENTS AND METHODS: Fifteen trainees or young gastroenterologists with no experience in VCE were randomly assigned to evaluate 250 true ulcerative and 100 false ulcerative, difficult-to-interpret small bowel lesions, initially as white light images (WLI) and then, in a second round, with the addition of one VC setting or again as WLI, labeling them as real lesions or artifacts. RESULTS: On the overall image evaluation, an improvement in lesion characterization was observed by adding any chromoendoscopy setting, especially Blue mode and FICE 1, with increases in accuracy of 13 % [95 %CI 0.8, 25.3] and 7.1 % [95 %CI - 17.0, 31.3], respectively. However, when only false ulcerative images were considered, with the same presets (Blue mode and FICE 1), there was a loss in accuracy of 10.7 % [95 %CI - 10.9, 32.3] and 7.3 % [95 %CI - 1.3, 16.0], respectively. The interobserver agreement was poor for both readings. CONCLUSIONS: VC helps beginner VCE readers correctly categorize difficult-to-interpret small bowel mucosal ulcerative lesions. However, false lesions tend to be misinterpreted as true ulcerative with the same presets. Therefore care is advised in using VC especially under poor bowel preparation.

Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach.

Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response.

Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease.

BACKGROUND: The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD. METHODS: Thirty-one CD patients and 7 controls were enrolled. Circulating CD133(+) and CD34(+) HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3(+) lymphoid cells) and the putative ISC compartment (CD133(+) and Lgr5(+) epithelial cells). RESULTS: At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal. CONCLUSIONS: In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission.

Rifaximin for the treatment of diarrhoea-predominant irritable bowel syndrome.

INTRODUCTION: Rifaximin is a non-absorbable, semisynthetic antibiotic that acts as an inhibitor of bacterial RNA synthesis, with a broad spectrum of antibacterial activity. Due to its poor absorption, rifaximin has an increased exposure to the intestine, thus it is suitable for the treatment of many gastrointestinal (GI) diseases. In irritable bowel syndrome (IBS) pathogenesis, gut microbiota impairment may play a major role. The possibility of modulating intestinal bacteria using antibiotics, in particular, rifaximin, has been demonstrated to improve IBS symptoms in non-constipation subtypes of IBS. AREAS COVERED: We reviewed the use of rifaximin in diarrhoea-predominant IBS, focusing on its pharmacokinetic characteristics, its absorption in GI disease, its lack of interaction with other drugs and its new extended release formulation. EXPERT OPINION: Rifaximin, with its low systemic absorption and no clinically significant interactions with other drugs, may represent a treatment of choice for IBS, mainly due to its ability to act on IBS pathogenesis, through the modulation of gut microbiota. Further studies to analyse the effect of rifaximin treatment on the composition of faecal microbiota are warranted. In particular, they need to evaluate whether resistant bacterial strains are selected and whether they are still present in the faecal sample even a long time after therapy.

Colon capsule endoscopy: What we know and what we would like to know.

Colonoscopy is usually perceived as an invasive and potentially painful procedure, being also affected by a small, but definite, risk of major complications (cardiopulmonary complications, perforation, hemorrhage) and even mortality. To improve both acceptability and safety, PillCam Colon Capsule Endoscopy (CCE) (Given Imaging Ltd, Yoqneam, Israel) has been developed. CCE represents a non-invasive technique that is able to explore the colon without sedation and air insufflation. The Second Generation of Colon Capsule Endoscopy (PillCam Colon 2) (CCE-2) was proven to be an accurate tool to detect colonic neoplastic lesions when used in average risk individuals. To date, the evidence supports the use of CCE-2 in case of colonoscopy failure, in patients unwilling to perform colonoscopy and when colonoscopy is contraindicated. Other potential applications, such as colorectal cancer screening or diagnostic surveillance of inflammatory bowel disease need to be clarified. In this paper, the current "state of the art", potential application of CCE and future needs are evaluated.

The role of small intestinal bacterial overgrowth in Parkinson's disease.

Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society.

Role of gut microbiota in food tolerance and allergies.

Alterations of commensal flora may cause various gastrointestinal and extraintestinal diseases, including food intolerances and food allergies. According to the 'microflora hypothesis', alterations in the composition of gut microbiota in industrialized countries have disturbed the mechanisms of mucosal immune tolerance. Over the past few years several studies have looked for a role for probiotics in the treatment of food allergies with promising results.

Stem cell-based therapies for liver diseases: state of the art and new perspectives.

Millions of patients worldwide suffer from end-stage liver pathologies, whose only curative therapy is liver transplantation (OLT). Given the donor organ shortage, alternatives to OLT have been evaluated, including cell therapies. Hepatocyte transplantation has been attempted to cure metabolic liver disorders and end-stage liver diseases. The evaluation of its efficacy is complicated by the shortage of human hepatocytes and their difficult expansion and cryopreservation. Recent advances in cell biology have led to the concept of "regenerative medicine", based on the therapeutic potential of stem cells (SCs). Different types of SCs are theoretically eligible for liver cell replacement. These include embryonic and fetal SCs, induced pluripotent cells, annex SCs, endogenous liver SCs, and extrahepatic adult SCs. Aim of this paper is to critically analyze the possible sources of SCs suitable for liver repopulation and the results of the clinical trials that have been published until now.

Gut microbiota and obesity.

Intestinal epithelium, mucosal immune system, and bacterial flora represent a morpho-functional system on dynamic balance responsible for the intestinal metabolic and trophic functions, and the regulation of mucosal and systemic host's immunity. Obesity is a pathological condition affecting a growing number of people especially in the Western countries resulting from the failure of the organism's energetic balance based on the perfect equality of income, waste, and storage. Recent evidences explain the mechanisms for the microbial regulation of the host's metabolism both in health and disease. In particular, animal studies have explained how quali-/quantitative changes in microflora composition are able to affect the absorption of the nutrients and the energy distribution. Antibiotics, prebiotics, probiotics, and symbiotics are the instruments utilized in the current clinical practice to modulate the intestinal bacterial flora in man both in health and pathologic conditions with promising preliminary results on prevention and therapy of obesity and related metabolic diseases.

Stem cell-based therapy in gastroenterology and hepatology.

Protagonists of a new scientific era, stem cells are promising tools on which regenerative medicine relies for the treatment of human pathologies. Stem cells can be obtained from various sources, including embryos, fetal tissues, umbilical cord blood, and also terminally differentiated organs. Once forced to expand and differentiate into functional progenies, stem cells may become suitable for cell replacement and tissue engineering. The manipulation and/or stimulation of adult stem cells seems to be particularly promising, as it could improve the endogenous regenerative potential without risks of rejection and overcome the ethical and political issues related to embryonic stem cell research. Stem cells are already leaving the bench and reaching the bedside, despite an incomplete knowledge of the genetic control program driving their fate and plasticity. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy and acute or chronic hepatopaties. Nonetheless, critical aspects need to be further addressed, including the long-term safety, tolerability and efficacy of cell-based treatments, as well as their carcinogenic potential. Aim of this review is to summarize the state-of-the-arts on gastrointestinal and hepatic stem cells and on stem cell-based therapies in gastroenterology and hepatology, highlighting both the benefits and the potential risks of these new tools for the treatment and prevention of human diseases.