Mucosal adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG in the human colonic mucosa. A proof-of-concept study

AIM To investigate the adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG (LGG) in the colonic mucosa of healthy and ulcerative colitis (UC) patients, both in vivo and ex vivo in an organ culture model. METHODS For the ex vivo experiment, a total of 98 patients (68 UC patients and 30 normal subjects) were included. Endoscopic biopsies were collected and incubated with and without LGG or LGG-conditioned media to evaluate the mucosal adhesion and anti-inflammatory effects [reduction of tumor necrosis factor alpha (TNFa) and interleukin (IL)-17 expression] of the bacteria, and extraction of DNA and RNA for quantification by real-time (RT)-PCR occurred after the incubation. A dose-response study was performed by incubating biopsies at "regular", double and 5 times higher doses of LGG. For the in vivo experiment, a total of 42 patients (20 UC patients and 22 normal controls) were included. Biopsies were taken from the colons of normal subjects who consumed a commercial formulation of LGG for 7 d prior to the colonoscopy, and the adhesion of the bacteria to the colonic mucosa was evaluated by RT-PCR and compared with that of control biopsies from patients who did not consume the formulation. LGG adhesion and TNFa and IL-17 expression were compared between UC patients who consumed a regular or double dose of LGG supplementation prior to colonoscopy. RESULTS In the ex vivo experiment, LGG showed consistent adhesion to the distal and proximal colon in normal subjects and UC patients, with a trend towards higher concentrations in the distal colon, and in UC patients, adhesion was similar in biopsies with active and quiescent inflammation. In addition, bioptic samples from UC patients incubated with LGG conditioned media (CM) showed reduced expression of TNFa and IL-17 compared with the corresponding expression in controls (P < 0.05). Incubation with a double dose of LGG increased mucosal adhesion and the anti-inflammatory effects (P < 0.05). In the in vivo experiment, LGG was detectable only in the colon of patients who consumed the LGG formulation, and bowel cleansing did not affect LGG adhesion. UC patients who consumed the double LGG dose had increased mucosal concentrations of the bacteria and reduced TNFa and IL-17 expression compared with patients who consumed the regular dose (48% and 40% reduction, respectively, P < 0.05). CONCLUSION In an ex vivo organ culture model, LGG showed consistent adhesion and anti-inflammatory effects. Colonization by LGG after consumption for a week was demonstrated in vivo in the human colon. Increasing the administered dose increased the adhesion and effectiveness of the bacteria. For the first time, we demonstrated that LGG effectively adheres to the colonic mucosa and exerts antiinflammatory effects, both ex vivo and in vivo

Application of clinical indexes in ulcerative colitis patients in regular follow-up visit. correlation with endoscopic 'mucosal healing' and implication for management

OBJECTIVE: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. Several clinical indexes have been proposed for UC disease activity evaluation, but none have been properly validated. Moreover, the reference parameter for the scores and their prognostic value is not clear. Mucosal healing has been recently proposed as an important end-point. Aim of the present study was to evaluate the correlation of four clinical indexes with objective diagnostic tools for UC evaluation, the discriminative ability in identifying patients with endoscopic mucosal healing, and to analyze the possible prognostic indication for disease course in 1 year of follow-up. PATIENTS AND METHODS: We analyzed data of 75 patients recorded in regular follow-up visit in IBD clinic at S. Andrea Hospital, Rome, between 2007-2011. We recorded clinical data and lab tests at the time of the visit, and endoscopic/ histological repor ts performed within 1 month. Clinical indexes (Seo' activity index, Simple Clinical Colitis Activity Index, partial Mayo score and Endoscopic-Clinical Correlation Index) were calculated and correlation to endoscopic and histologic activity, and to C-reactive protein increment, was assessed by mean of Spearman's rank correlation. Discriminative ability of the indexes for patients with and without endoscopic mucosal healing was tested by calculation of area under ROC curve (AUC). Patients with low and high clinical scores were compared for number of flares and increment of therapy during 1 year of follow-up. RESULTS: Clinical indexes had a good correlation with endoscopic activity (mean r = 0.73 ± 0.06), a fair correlation with CRP-increment (mean r = 0.55 ± 0.01) and a poor one with histologic activity (mean r = 0.35 ± 0.01). The discriminatory ability of the indexes for endoscopic mucosal healing was good for all the indexes (mean AUC = 0.87 ± 0.05). Patients with high clinical score had more flares and required more frequently increase of therapy at 1 year of follow up compared with patients with low score. CONCLUSIONS: Clinical indexes have a good correlation with endoscopic activity and can discriminate patients with and without mucosal healing. Patients with low and high score have different risk of disease flare and of need to increase therapy at 1 year. Clinical indexes may represent a useful tool for disease assessment in clinical practice in UC outpatients with mildmoderate disease

Clinical management of endoscopically resected pT1 colorectal cancer

Background Implementation of colorectal cancer (CRC) screening programs increases endoscopic resection of polyps with early invasive CRC (pT1). Risk of lymph node metastasis often leads to additional surgery, but despite guidelines, correct management remains unclear. Our aim that are diagnosed and treated endoscopically and this number is expected to increase [1,2].Methods We retrospectively reviewed patients undergoing endoscopic resection of pT1 CRC from 2006 to 2016. Clinical, endoscopic, surgical treatment, and follow-up data were collected and analyzed. Lesions were categorized according to endoscopic/histological risk-factors into low and high risk groups. Comorbidities were classified according to the Charlson comorbidity index (CCI). Surgical referral for each group was computed, and dissociation from current European CRC screening guidelines recorded. Multivariate analysis for factors affecting the post-endoscopic surgery referral was performed.Results Seventy-two patients with endoscopically resected pT1-CRC were included. Overall, 20 (27.7%) and 52 (72.3%) were classified as low and high risk, respectively. In the low risk group, 11 (55%) were referred to surgery, representing over-treatment compared with current guidelines. In the high risk group, nonsurgical endoscopic surveillance was performed in 20 (38.5%) cases, representing potential under-treatment. After a median follow-up of 30 (6-130) months, no patients developed tumor recurrence. At multivariate analysis, age (OR 1.21, 95 %CI 1.02 -1.42; P = 0.02) and CCI (OR 1.67, 95 %CI 1.12 -3.14; P= 0.04) were independent predictors for subsequent surgery.Conclusions A substantial rate of inappropriate post-endoscopic treatment of pT1-CRC was observed when compared with current guidelines. This was apparently related to an overestimation of patient-related factors rather than endoscopically or histologically related factors

Improving assessment and management of large non-pedunculated colorectal lesions in a Western center over 10 years. lessons learned and clinical impact

Background and study aims Outcomes of endoscopic assessment and management of large colorectal (CR) non-pedunculated lesions (LNPLs) are still under evaluation, especially in Western settings. We analyzed the clinical impact of changes in LNPL management over the last decade in a European center.Patients and methods All consecutive LNPLs &gt;= 20mm endoscopically assessed (2008-2019) were retrospectively included. Lesion, patient, and resection characteristics were compared among clinically relevant subgroups. Multivariate logistic regression (for predictors of submucosal invasion [SMI] and recurrence), Kaplan-Meier curves and ROC curves (for temporal cut-offs in trends analyses) were used.Results A total of 395 LNPLs were included (30mm [range 20-40]; SMI=9.6%; primary endoscopic resection [ER]=88.4%). Pseudo-depression and JNET classification independently predicted SMI beyond single morphologies/location. After complete ER, involvement of ileocecal valve/dentate line, piece-meal resection and high-grade dysplasia independently predicted recurrence. Rates of 5-year recurrence-free, surgery-free and cancer-free survival were 77.5%, 98.6% and 100%, respectively, with 93.8% recurrences endoscopically managed and no death attributable to ER or CR cancer (versus 3.4% primary surgery mortality). ROC curves identified the period &gt;= 2015 (following Endoscopic Submucosal Dissection [ESD] introduction and education on pre-resective lesion assessment) as associated with improved lesions' characterization, increased en-bloc resection of SMI lesions (87.5% vs 37.5%; p=0.0455), reduced primary surgery (7.5% vs 16.7%; p=0.0072), surgical referral of benign lesions (5.1% vs 14.8%; p=0.0019), and recurrences.Conclusions ESD introduction and educational interventions allowed ER of more complex lesions, offset by increased complementary surgery for complications or intrinsic histological risk. Nevertheless, overall, they have reduced surgery demand and increased appropriateness and safety of LNPL management in our center

Unusual findings in Peutz-Jeghers syndrome: endoscopic and histologic appearance of gastric hamartomatous polyposis with foveolar dysplasia

No abstract availabl

Gastric xanthomatosis in a patient with severe lipid metabolic disorder

Gastric xanthomas are rare in routine endoscopy, generally ranging from to 2 to 5 mm in diameter, mostly isolated, but in some cases multiple. Their nature has not yet been cleared. In fact, even if they have histochemical characteristics similar to cutaneous xanthelasmas, they are not generally considered closely related to lipid metabolism disorders. The Authors report a case with some peculiarities regarding number, location and dimension of the gastric xanthomas, and point out the possibility of a metabolic disorder in their aetiopathogenesis