Correlation of Ultrasound Scores with Endoscopic Activity in Crohn's Disease: A Prospective Exploratory Study.

BACKGROUND AND AIMS: Intestinal ultrasound [IUS] is widely accepted as a reliable tool to monitor Crohn's disease [CD]. Several IUS scores have been proposed, but none has been formally accepted by international organizations. Our aim here was to compare the available scores regarding their correlation with endoscopic activity. METHODS: Consenting CD patients undergoing ileocolonoscopy at our Unit between September 2021 and February 2023 were included. Endoscopic activity was defined as SES-CD ≥ 3 or Rutgeerts score ≥ i2b for operated patients. IUS was performed within 6 weeks of endoscopy and scored with IBUS-SAS, BUSS, Simple-US and SUS-CD scores. All correlations were performed using Spearman's rank coefficient [rho = ρ]. Receiver operating characteristic [ROC] curves were compared with the Hanley and McNeil method. RESULTS: Of 73 CD patients, 45 [61.6%] presented endoscopic activity, of whom 22 were severe [30.1%]. All IUS scores showed a significant positive correlation with endoscopy [p < 0.0001], with IBUS-SAS ranking the highest [ρ = 0.87]. Similarly, IBUS-SAS was the most highly correlated with clinical activity [ρ = 0.58]. ROC analysis of IBUS-SAS for any endoscopic activity showed the highest area under the curve (0.95 [95% confidence interval 0.87-0.99]), with sensitivity of 82.2% and specificity of 100% for a cut-off value of 25.2. IBUS-SAS was statistically superior to all the other scores in detecting severe endoscopic activity [SES-CD ≥ 9 or Rutgeerts i4]. CONCLUSIONS: All IUS scores provided solid correlation with endoscopy and clinical symptoms. IBUS-SAS outperformed the others due to a more granular description that might help in stratifying different levels of disease activity. Therefore, the use of IBUS-SAS in centres with well-founded expertise in IUS can be suggested.

Radiofrequency ablation for intraductal extension of ampullary adenomatous lesions: proposal for a standardized protocol.

Background and study aims Intraductal extension of ampullary adenoma represents a challenging endoscopic issue. Intraductal radiofrequency ablation (RFA) has been recently suggested, but evidence and standardization of this technique are still lacking. This study aimed to provide a long-term evaluation of clinical efficacy and safety of intraductal RFA ablation with a standardized algorithm of treatment. Patients and methods Data were prospectively collected from consecutive patients with intraductal extension of adenomatous ampullary lesions from January 2016 to November 2018. Endpoints of the study were clinical success evaluated on histology results at the last follow-up, technical success, and adverse events assessment. Results Nine patients with intraductal (biliary ± pancreatic) extension of ampullary adenomas were treated with RFA during the study period. Histology on the papillectomy specimen confirmed intraductal involvement with low-grade dysplasia (LGD) in five cases (56 %), high-grade dysplasia (HGD) in three (33 %), and HGD with intramucosal adenocarcinoma in one patient (11 %). Additional argon plasma coagulation to ablate the adenoma on the duodenal mucosa was applied in five patients (56 %). Technical success was 100 %. One patient (11 %) with failed pancreatic stenting, developing acute pancreatitis after RFA, recovered with medical therapy. After a median follow-up of 21 months (IQR 20-31), six patients (67 %) achieved clinical success being free of recurrence, whereas one was diagnosed with persistence of adenocarcinoma, one with recurrent HGD, and one with recurrent LGD. Conclusions In our experience, intraductal RFA achieved acceptable results after a 2-year follow-up. Further studies are required to confirm our results and to select those patients most likely to respond.

Motion training on a validated mechanical ERCP simulator improves novice endoscopist performance of selective cannulation: a multicenter trial.

Background and study aims Current data show that traditional training methods in endoscopic retrograde cholangiopancreatography (ERCP) fall short of producing competent trainees. We aimed to evaluate whether a novel approach to simulator-based training might improve the learning curve for novice endoscopists training in ERCP. Methods We conducted a multicenter, randomized controlled trial using a validated mechanical simulator (the Boskoski-Costamagna trainer). Trainees with no experience in ERCP received either standard cannulation training or motion training before undergoing standard cannulation training on the mechanical simulator. Trainees were timed and graded on their performance in selective cannulation of four different papilla configurations. Results Thirty-six trainees (16 in the motion training group, 20 in the standard group) performed 720 timed attempts at cannulating the bile duct on the simulator. Successful cannulation was achieved in 698 of 720 attempts (96.9 %), with no significant difference between the two study groups ( P  = 0.37). Trainees in the motion training group had significantly lower median cannulation times compared to the standard group (36 vs. 48 seconds, P  = 0.001) and better technical performance on the first papilla type ( P  = 0.013). Conclusions Our findings suggest that motion training could be an innovative method aimed at accelerating the learning curve of novice trainees in the early phase of their training. Future studies are needed to establish its role in ERCP training programs.

Erratum: Laparoscopic sleeve gastrectomy versus endoscopic sleeve gastroplasty: a systematic review and meta-analysis.

[This corrects the article DOI: 10.1055/a-1300-1085.].

Training in endoscopic retrograde cholangio-pancreatography: a critical assessment of the broad scenario of training programs and models.

Introduction: Endoscopic Retrograde Cholangio-Pancreatography (ERCP) applications are rapidly evolving toward increasingly complex therapeutic approaches alongside with technological innovations. There are no globally agreed indications on the ERCP training path, which often requires too much time and does not always guarantee adequate skills.Areas covered: Frequency and difficulty of execution are the main objective criteria on which to draw up a training program: novel trainees should approach ERCP first through the simplest and most frequent procedures. An extensive use of training models would reduce the patient's performer-related risks. Amongst a wide variety of models, mechanical simulators have received large approval. In fact, they can be best-suited to each trainee's learning curve thanks to their precision and safety and by virtue of the unlimited repeatability of their use. However, more solid evidences are still needed.Expert opinion: Hands-on ERCP training should systematically employ mechanical simulators at least in the early stages of the learning process. An implementation of these models through sensors that objectively detect abnormalities in the movements would provide detailed feedbacks and deeper awareness. Simulators might also be useful for expert endoscopists to refine their skills. Rapid prototyping and 3D printing might be the way to create customized training models for successful training programs.

Laparoscopic sleeve gastrectomy versus endoscopic sleeve gastroplasty: a systematic review and meta-analysis.

Background and study aims Laparoscopic sleeve gastrectomy (LSG) is the current standard for bariatric surgery, but it is affected by several postoperative complications. Endoscopic sleeve gastroplasty (ESG) was created as a less invasive alternative to LSG. However, its efficacy and safety compared with LSG is unclear. Materials and methods Relevant publications were identified in MEDLINE/Cochrane/EMBASE/OVID/ PROSPERO and NIH up to January 2020. Studies were selected that included obese patients with a baseline body mass index (BMI) between 30 and 40 kg/m² with a minimum of 12 months of follow-up and with reported incidence of complications. The mean difference in percentage of excess weight loss (%EWL) at 12 months between LSG and ESG represented the primary endpoint. We also assessed the difference in pooled rate of adverse events. The quality of the studies and heterogeneity among them was analyzed. Results Sixteen studies were selected for a total of 2188 patients (LSG: 1429; ESG: 759) with a mean BMI 34.34 and 34.72 kg/m² for LSG and ESG, respectively. Mean %EWL was 80.32 % (±â€Š12.20; 95 % CI; P  = 0.001; I²â€Š= 98.88) and 62.20 % (±â€Š4.38; 95 % CI; P  = 0.005; I²â€Š= 65.52) for the LSG and ESG groups, respectively, corresponding to an absolute difference of 18.12 % (±â€Š0.89; 95 % CI, P  = 0.0001). The difference in terms of mean rate of adverse events was 0.19 % (±â€Š0.37; 95 %CI; χ 2  = 1.602; P  = 0.2056). Conclusions Our analysis showed a moderate superiority of LSG versus ESG. No difference in terms of safety was shown between the two groups. ESG is a less-invasive, repeatable and reversable and acceptable option for mild-moderate obese patients.

Fibrin glue injection: Rescue treatment for refractory post-sphincterotomy and post-papillectomy bleedings.

OBJECTIVES: Endoscopic sphincterotomy (ES) and papillectomy (EP) are associated with a non-negligible risk of post-procedural bleeding. Despite first-line endoscopic hemostasis being achieved by several methods, patients may experience bleeding persistence or recurrence. In such cases, fibrin glue (FG) injection may be used as a rescue therapy before more invasive approaches. The aim of this study was to evaluate the efficacy and safety of endoscopic FG injection to treat refractory post-ES and post-EP bleeding. METHODS: Data were collected retrospectively from patients with refractory immediate or delayed bleeding following ES or EP, between October 2007 and November 2019, at a single institution. Clinical success was defined as bleeding control after FG injection. RESULTS: Overall, 70 patients were included. Clinical success was reached in 64 (91.4%) patients after one session of FG injection. Of six (8.6%) patients in whom the treatment failed, one required subsequent insertion of a fully covered self-expanding metal stent (FC-SEMS) due to immediate massive bleeding, while five experienced bleeding recurrence. Such events were managed with an additional session of FG injection that failed in two cases. Therefore, one patient underwent FC-SEMS plus selective embolization, whereas the other underwent diagnostic arteriography. No severe periprocedural complications occurred. Two cases of intrabiliary glue migration were treated by endoscopic removal with a retrieval basket. CONCLUSIONS: Rescue therapy with endoscopic FG injection appears to be effective and safe to treat refractory post-ES and post-EP bleeding. Further studies are required to confirm these preliminary data.

Bilio-pancreatic endoscopy during COVID-19 pandemic.

On 31 December 2019, the WHO China Country Office was informed of cases of pneumonia of unknown etiology detected in Wuhan (Hubei Province of China). In January 2020, a new coronavirus named SARS-CoV2 was isolated and, since that time, SARS-CoV2 related disease (COVID-19) rapidly spread all over the world becoming pandemic in March 2020. The COVID-19 outbreak dramatically affected the public-health and the health-care facilities organization. Bilio-pancreatic endoscopy is considered a high-risk procedure for cross-contamination and, even though it is not directly involved in COVID-19 diagnosis and management, its reorganization is crucial to guarantee high standards of care minimizing the risk of SARS-CoV2 transmission among patients and health-care providers. Bilio-pancreatic endoscopic procedures often require a short physical distance between the endoscopist and the patient for a long period of time, a frequent exchange of devices, the involvement of a large number of personnel, the use of complex endoscopes difficult to reprocess. On this basis, endoscopic units should take precautions with adjusted management of bilio-pancreatic endoscopy. The aim of this article is to discuss the approach to bilio-pancreatic endoscopy in the COVID-19 era with focus on diagnostic algorithms, indications, management of the endoscopic room, proper use of Personal Protective Equipment and correct reprocessing of instrumentation.

Procedures and devices for bariatric and metabolic endoscopy.

Obesity is a leading cause of preventable death in developed countries, with a rising incidence over time. Lifestyle modification, pharmacotherapy, and bariatric surgery are the mainstays of bariatric therapy, even though burdened by several limitations in terms of efficacy or safety. Bariatric endoscopy has been developed in the last decades as a minimally invasive alternative, aimed to bridge the gap between conservative and interventional conventional therapies. This review aims to provide an updated overview of the bariatric and metabolic available endoscopic procedures and to drive the choice of the right procedure for the right patient.

Metabolic endoscopy by duodenal mucosal resurfacing: expert review with critical appraisal of the current technique and results.

INTRODUCTION: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for type 2 diabetes (T2D) consisting of circumferential hydrothermal ablation of the duodenal mucosa. AREAS COVERED: A review was conducted on the reports available up to March-2020. On a total of 79 patients, DMR induced a significant mean HbA1c, FPG and HOMA-IR reduction at 6 months (0.9 ± 0.2%, 1.7 ± 0.5 mmol/L and 2.9 ± 1.1 mUI/L respectively - P < 0.001). DMR metabolic efficacy directly correlates with the length of the ablated mucosa (mean 3 months HbA1c reduction 1.2% vs 2.5% after short and long ablation respectively - P < 0.05), while it is independent of weight-loss. Severe AEs were registered in 3.7% of the cases. EXPERT OPINION: DMR plays a promising role in metabolic impairment improvement inducing a morpho-functional duodenal alteration not necessarily depending on weight-loss. Technical-functional improvements of the device and appropriate training aimed at its correct use are needed to lower the rate of severe AEs and technical failure. The current role of DMR needs to be clarified, but it might be proposed for poorly controlled T2D in accurately selected patients. Evidence on DMR is still scanty and further research is mandatory to standardize the endoscopic technique and its indications.

Technical and clinical outcomes of endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in patients with COVID-19.

BACKGROUND: The unprecedented situation caused by the coronavirus disease 2019 (COVID-19) pandemic has profoundly affected endoscopic practice in regard to access, volume, and workflow. We aimed to assess the potential changes in the technical outcomes of endoscopic retrograde cholangiopancreatography (ERCP) procedures carried out in patients with confirmed SARS-CoV-2 infection. METHODS: We conducted an international, multicenter, retrospective, matched case-control study of ERCP procedures carried out in patients with confirmed COVID-19. The main outcome was technical success of the procedure as assessed by the endoscopist, and the secondary outcome was the development of procedure-related adverse events. Each case was matched in a 1:4 ratio with controls extracted from each center's database in order to identify relevant changes in outcome measures compared with the pre-pandemic era. RESULTS: Eighteen procedures performed in 16 COVID-19 patients [14 men, 65 years (9-82)] and 67 controls were included in the final analysis. Technical success was achieved in 14/18 COVID-19 cases, which was significantly lower as compared with the control group (14/18 versus 64/67, p = 0.034), with an endoscopic reintervention required in 9/18 cases. However, the rate of procedure-related adverse events was low in both groups (1/18 versus 10/67, p = 0.44). On multivariable analysis, COVID-19 status remained the only risk factor for technical failure of the procedure [odds ratio of 19.9 (95% confidence interval 1.4-269.0)]. CONCLUSIONS: The COVID-19 pandemic has affected the volume and practice of ERCP, resulting in lower technical success rates without significantly impacting patient safety. Prioritizing cases and following recommendations on safety measures can ensure good outcome with minimal risk in dedicated centers.

Per-oral endoscopic myotomy for esophageal diverticula with or without esophageal motility disorders.

INTRODUCTION: Mid-esophageal and epiphrenic diverticula (MED) can be associated with esophageal motility disorders. Per-oral endoscopic myotomy (POEM) is an established treatment for esophageal motility disorders that has also been introduced for the treatment of MED. METHODS: Data were prospectively collected from patients with MED treated with POEM at our institution. When esophageal motility disorders were present, myotomy was performed extending the myotomy to the lower esophageal sphincter (LES) to treat the motility dysfunction associated with the diverticulum. In the absence of esophageal motility disorder, POEM was performed without including the LES in the myotomy to achieve diverticulotomy. RESULTS: Four patients were treated with POEM for MED between April 2017 and March 2018. The patients suffered from distal esophageal spasm, jackhammer esophagus or esophago-gastric junction outflow obstruction. One patient had no esophageal motility disorder. Diverticulum size was 3 cm in one case and 6 cm in the others. Preoperative Eckardt scores ranged from 6 to 8. No life-threatening complications were reported. Intraoperative pneumoperitoneum was described in two cases and one patient experienced aspiration pneumonia. The patients with motility disorders were asymptomatic at 6-8 months follow-up. The patient without documented underlying esophageal motility disorder had an Eckardt score of 3 at 9-months follow-up. Two cases of gastro-esophageal reflux were successfully managed with proton pump inhibitors. CONCLUSIONS: In the case of MED and esophageal motility disorder, POEM permitted treatment of the underlying cause of the diverticulum, achieving favorable early clinical outcomes. In the absence of motility disorder, POEM was feasible with promising early outcomes, and could be a valid alternative to surgical diverticulectomy in selected patients.

Golimumab in inflammatory bowel diseases: present and future scenarios.

Golimumab is the third anti-TNF agent approved for the treatment of ulcerative colitis. Despite initial success demonstrated by PURSUIT trials, only few real-life studies have been published evaluating its efficacy and safety in clinical practice. Its subcutaneous route and monthly administration represent an advantage in patient compliance, respectively, vs infliximab (intravenous) and adalimumab (two doses per month). The most important weakness of the molecule which often leads clinicians to choose another anti-TNF is the impossibility to dose escalate or reduce the frequency of administrations in case of secondary failure; ongoing studies are trying to solve this problem by monitoring drug levels and the eventual presence of neutralizing anti-drug antibodies. No advantage has still been demonstrated for combination therapy of golimumab with immunosuppressants and further studies are necessary to evaluate this aspect. Preliminary data also report golimumab efficacy in Crohn's disease with higher doses than in ulcerative colitis with an acceptable safety profile. Additional studies are needed in this field to confirm the initial findings.

Metabolic Signature of Primary Biliary Cholangitis and Its Comparison with Celiac Disease.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by ongoing inflammatory destruction of the interlobular bile ducts, eventually leading to chronic cholestasis and biliary cirrhosis. This study primarily aims to define the metabolomic signature of PBC after comparison with healthy controls (HC). Second, it aims to evaluate the possible metabolic association between PBC and celiac disease (CD), an immune-mediated disorder frequently associated with PBC. Serum and urine samples from 20 PBC, 21 CD, and 19 sex-matched HC subjects were collected. 1H nuclear magnetic resonance (NMR) spectra for all samples were acquired, and multivariate statistics were used to evaluate the differences among the three groups and to provide information about the involved metabolites. The classification accuracies to discriminate PBC and HC groups were 78.9-84.6% for serum and 76.9% for urine. In comparison to HC, PBC patient sera were characterized by altered levels ( p value <0.05) of pyruvate, citrate, glutamate, glutamine, serine, tyrosine, phenylalanine, and lactate. PBC patient urine showed lower levels ( p value <0.05) of trigonelline and hippurate with respect to HC. Furthermore, the NMR metabolomic fingerprint was able to cluster PBC with respect to CD patients, and the classification accuracies in the discriminations between these groups were 81.9-91.7% for serum and 77.7% for urine. Our results show that PBC displays a unique metabolomic fingerprint, which led to speculation about an impaired energy metabolism, probably associated with an altered gut microbiota. PBC and CD showed two distinct metabolic fingerprints. These data could provide clues for the comprehension of the PBC pathogenetic mechanisms and the detection of novel therapeutic targets.

Clinical efficacy and safety of golimumab in biologically experienced and naive patients with active ulcerative colitis: A real-life experience from two Italian IBD centers.

OBJECTIVE: To evaluate the efficacy and safety of golimumab in biological naive and experienced patients with moderately to severely active ulcerative colitis (UC) treated at two Italian IBD centers. METHODS: We retrospectively reviewed our prospectively maintained UC database from March 2015 to March 2017. Patients received golimumab 200 mg at week 0, 100 mg at week 2, then 50 mg or 100 mg every 4 weeks. Follow-up was recorded at 12 and 24 weeks and in March 2017, with a median follow-up of 64 weeks. The main outcomes evaluated were clinical remission (CR) and adverse event rates. RESULTS: Of the 59 patients (44% naive and 56% experienced), CR rate was 47% at 12-week follow-up, 55% (among the 49 patients on treatment) at 24-week follow-up and 49% (among 35 patients on treatment) at the last follow-up visit. Median treatment duration was 52 weeks (interquartile range 30-64 weeks) among patients treated for >6 months. Overall, 10 (17%) patients experienced adverse events, of whom 50% discontinued treatment. The most frequent adverse events were infections. Biological naive and experienced patients did not differ in terms of CR and adverse event rates. CONCLUSIONS: Our real-life experience showed that CR decreased over time and was achieved by almost one-third of the cohort at the last follow-up visit. Golimumab showed an overall favorable safety profile and the results were not different between biological naive and experienced patients. Future research is needed to confirm our results and to identify criteria to select patients most likely to respond.

Full-Thickness Resection Device for Complex Colorectal Lesions in High-Risk Patients as a Last-Resort Endoscopic Treatment: Initial Clinical Experience and Review of the Current Literature.

The full-thickness resection device (FTRD) is a novel endoscopic device approved for the resection of colorectal lesions. This case-series describes the device and its use in high-risk patients with colorectal lesions and provides an overview of the potential indications in recently published data. Between December 2014 and September 2015, 3 patients underwent endoscopic full thickness resection using the FTRD for colorectal lesions: 1 case for a T1 adenocarcinoma in the region of a surgical anastomosis after recto-sigmoidectomy, 1 case for a non-lifting colonic adenoma with low-grade dysplasia in an 89-year old patient and 1 for a recurrent adenoma with high-grade dysplasia in a young patient with ulcerative rectocolitis who was under immunosuppression after renal transplantation. Both technical and clinical success rates were achieved in all cases. The size of removed lesions ranged from 9 to 30 mm. Overall, the most frequent indication in the literature has been for lifting or non-lifting adenoma, submucosal tumors, neuroendocrin tumors, incomplete endoscopic resection (R1) or T1 carcinoma. Colorectal FTRD is a feasible technique for the treatment of colorectal lesions and represents a minimally invasive alternative for either surgical or conventional endoscopic resection strategies.

Ultrastructural changes in human gingival fibroblasts after exposure to 2-hydroxy-ethyl methacrylate.

Polymerized resin-based materials are successfully utilized in medical applications. One draw- back is the release of monomers from the matrix due to an incomplete polymerization or degradation processes. Released monomers can diffuse in the systemic circulation and induceadverse effects to biological tissues. Although there are many hypotheses about the induction of cell death by resin monomers, the underlying mechanisms are still under discussion. The aim of the study was to investigate the morphological modifications in human gingival fibroblasts exposed to 2-hydroxy-ethyl methacrylate (HEMA) to better elucidate the mechanism of cell death induced by resin monomers. Primary cultures of gingival fibroblasts were exposed to 3mM HEMA for 24 h, 72 h, 96 h. Morphological investigations were performed by scanning and transmission electron microscopy, while western blot for caspase-3 was carried out to ver- ify apoptosis. Electron microscopy images showed deep changes in the cell surface and cyto- plasm after 72 h and 96 h of HEMA treatment. Autophagic vesicles were easily observed just after 24 h. Cleaved caspase-3 was detected after 72 h of treatment. These findings suggest that resin based materials induced cell death by the cooperation of apoptosis and autophagy mecha- nisms. The understanding of these mechanisms will lead to the development of smart biomate- rials without or with low adverse effects.