Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study.

BACKGROUND AND AIM: Digital single-operator cholangioscopy (D-SOC) is an endoscopic procedure that is increasingly used for the management of bilio-pancreatic diseases. We aimed to investigate the efficacy and safety of D-SOC for diagnostic and therapeutic indications. METHODS: This is a multicenter, prospective study(January 2016-June 2019) across eighteen tertiary centers. The primary outcome was procedural success of D-SOC. Secondary outcomes were: D-SOC visual assessment and diagnostic yield of SpyBite biopsy in cases of biliary strictures, stone clearance rate in cases of difficult biliary stones, rate of adverse events(AEs) for all indications. RESULTS: D-SOC was performed in 369 patients (201(54,5%) diagnostic and 168(45,5%)therapeutic). Overall, procedural success rate was achieved in 360(97,6%) patients. The sensitivity, specificity, PPV, NPV and accuracy in biliary strictures were: 88,5%, 77,3%, 83,3%, 84,1% and 83,6% for D-SOC visual impression; 80,2%, 92,6%, 95,1%, 72,5% and 84,7% for the SpyBite biopsy, respectively. For difficult biliary stones, complete duct clearance was obtained in 92,1% patients (82,1% in a single session). Overall, AEs occurred in 37(10%) cases.The grade of AEs was mild or moderate for all cases, except one which was fatal. CONCLUSION: D-SOC is effective for diagnostic and therapeutic indications.Most of the AEs were minor and managed conservatively, even though a fatal event has happened that is not negligible and should be considered before using D-SOC.

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.

Antroduodenojejunal motor activity in untreated and treated celiac disease patients.

BACKGROUND AND AIM: Patients with celiac disease may present with abnormal upper gut motor activity. However, it is not known if these abnormalities persist after the introduction of a gluten-free diet. The present study aimed to compare antroduodenojejunal motor variables recorded in untreated celiac patients with those of celiac patients given a gluten-free diet and healthy volunteers. METHODS: Eleven untreated celiac disease patients, 12 age- and sex-matched celiac patients on a gluten-free diet (at least 12 months), and 33 controls entered the study. Antroduodenojejunal motility was recorded for 6 h during fasting and for 3 h after a standard meal by means of a perfused, multiple lumen catheter. RESULTS: More than 80% of untreated celiac patients had discrete motor abnormalities of the upper gut, in both fasting and fed recordings, compared to the other subjects. Patients on a gluten-free diet also showed motor abnormalities, albeit to a lesser extent. In these patients histological evaluation showed the persistence of mild mucosal abnormalities. CONCLUSIONS: Upper gut motor abnormalities are frequent in patients with celiac disease, even in those on a gluten-free diet. In the latter group, these abnormalities may suggest an incomplete adherence to the dietary regimen.

CD1-restricted recognition of exogenous and self-lipid antigens by duodenal gammadelta+ T lymphocytes.

Gammadelta T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal gammadelta T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCRalphabeta+, and either CD4+ or CD8+, whereas 20% were CD4-CD8- (6 clones) or TCRgammadelta+ (12 clones). A relevant percentage (up to 66%) of TCRgammadelta+ but few (<5%) TCRalphabeta+ T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [(3)H]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific gammadelta T cell clones. Thus, a substantial percentage of TCRgammadelta+ but few TCRalphabeta+ from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases.

Audit of constipation in a gastroenterology referral center.

This study was designed to assess the various subtypes of functional constipation in a referral gastrointestinal center of a Latino-American country. All patients referred for evaluation of constipation during a 10-year period were audited, and those with functional constipation according to Rome I criteria classified by physiologic tests of colonic transit, as well as tests of anorectal and pelvic floor function. More than 70% of patients with functional constipation had evidence of pelvic floor dysfunction, whereas those with slow transit and constipation-predominant irritable bowel syndrome subtypes were less frequently represented. Even in a setting different from those most frequently reported in the literature, pelvic floor dysfunction represents the most common cause of functional constipation. Simple, physiologic testing is needed and useful for the diagnosis. This fact has therapeutic implications, especially because many such patients may benefit from biofeedback.

Colonic propulsive and postprandial motor activity in patients with ulcerative colitis in remission.

BACKGROUND: Although it is known that colon motility is abnormal in ulcerative colitis, data are still scarce with regard to the underlying mechanisms. Recent evidence suggests that the propulsive activity is highly increased during the active phase of the disease, probably contributing to the diarrhoea. However, data are even scarcer in the quiescent phase of the disease. AIMS: To assess the colonic high-amplitude and low-amplitude propulsive activity and the colonic motor response to eating in patients with ulcerative colitis in remission. PATIENTS AND METHODS: Fourteen patients were recruited, all with the disease in remission as documented by clinical and endoscopic criteria. Twenty-four hour manometric recordings were obtained in these patients, and compared to those of 16 healthy controls. RESULTS: The high-amplitude propagated contractions were similar in both groups (5.8+/-2.6 events in ulcerative colitis patients and 5.5+/-0.8 in controls (P=0.13)), whereas patients tended to display a higher number of low-amplitude propagated events (134.4+/-34 vs. 60.9+/-16 in controls (P=0.058)). No differences were found in the colonic motor response to eating between patients and controls. CONCLUSIONS: Colonic propulsive activity in ulcerative colitis in remission is almost normal, even though the low-amplitude propagated activity tends to be similar to that observed in patients with the irritable bowel syndrome, thus possibly contributing to the persistence of abdominal symptoms in a subgroup of patients.

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17alpha-ethynyl-estradiol-induced cholestasis in rats.

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), the 7alpha-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17alpha-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 micromol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO(3)(-)), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO(3)(-) output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na(+) taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease.

Manometric assessment of idiopathic megarectum in constipated children.

AIM: Chronic constipation is a frequent finding in children. In this age range, the concomitant occurrence of megarectum is not uncommon. However, the definition of megarectum is variable, and a few data exist for Italy. We studied anorectal manometric variables and sensation in a group of constipated children with megarectum defined by radiologic criteria. Data from this group were compared with those obtained in a similar group of children with recurrent abdominal pain. METHODS: Anorectal testing was carried out in both groups by standard manometric technique and rectal balloon expulsion test. RESULTS: Megarectum patients displayed discrete abnormalities of anorectal variables and sensation with respect to controls. In particular, the pelvic floor function appeared to be impaired in most patients. CONCLUSION: Constipated children with megarectum have abnormal anorectal function and sensation. These findings may be helpful for a better understanding of the pathophysiological basis of this condition.