Endoscopic Submucosal Dissection of Gastric Neoplastic Lesions. An Italian, Multicenter Study

Endoscopic submucosal dissection (ESD) allows removing neoplastic lesions on gastric mucosa, including early gastric cancer (EGC) and dysplasia. Data on ESD from Western countries are still scanty. We report results of ESD procedures performed in Italy. Data of consecutive patients who underwent ESD for gastric neoplastic removal were analyzed. The en bloc resection rate and the R0 resection rates for all neoplastic lesions were calculated, as well as the curative rate (i.e., no need for surgical treatment) for EGC. The incidence of complications, the one‐month mortality, and the recurrence rate at one‐year follow‐up were computed. A total of 296 patients with 299 gastric lesions (80 EGC) were treated. The en bloc resection was successful for 292 (97.6%) and the R0 was achieved in 266 (89%) out of all lesions. In the EGC group, the ESD was eventually curative in 72.5% (58/80) following procedure. A complication occurred in 30 (10.1%) patients. Endoscopic treatment was successful in all 3 perforations, whereas it failed in 2 out of 27 bleeding patients who were treated with radiological embolization (1 case) or surgery (1 case). No procedure‐related deaths at one‐month follow‐up were observed. Lesion recurrence occurred in 16 (6.2%) patients (6 EGC and 10 dysplasia). In conclusion, the rate of both en bloc and R0 gastric lesions removal was very high in Italy. However, the curative rate for EGC needs to be improved. Complications were acceptably low and amenable at endoscopy

Bismuth-based quadruple therapy following H. Pylori eradication failures: A multicenter study in clinical practice

Background & Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice. Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated. Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported. Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practic

Endoscopic repair of post-surgical gastrointestinal complications

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Endoscopic management of patients with post-surgical leaks involving the gastrointestinal tract: a large case series

Background: Post-surgical anastomotic leaks often require a re-intervention, are associated with a definite morbidity and mortality, and with relevant costs. We described a large series of patients with different post-surgical leaks involving the gastrointestinal tract managed with endoscopy as initial approach. Methods: This was a retrospective analysis of prospectively collected cases with anastomotic leaks managed with different endoscopic approaches (with surgical or radiological drainage when needed) in two endoscopic centres during 5 years. Interventions included: (1) over-the-scope clip (OTSC) positioning; (2) placement of a covered self-expanding metal stent (SEMS); (3) fibrin glue injection (Tissucol); and (4) endo-sponge application, according to both the endoscopic feature and patient’s status. Results: A total of 76 patients underwent endoscopic treatment for a leak either in the upper (47 cases) or lower (29 cases) gastrointestinal tract, and the approach was successful in 39 (83%) and 22 (75.9%) patients, respectively, accounting for an overall 80.3% success rate. Leak closure was achieved in 84.9% and 78.3% of patients managed by using a single or a combination of endoscopic devices. Overall, leak closure failed in 15 (19.7%) patients, and the surgical approach was successful in all 14 patients who underwent re-intervention, whilst one patient died due to sepsis at 7 days. Conclusions: Our data suggest that an endoscopic approach, with surgical or radiological drainage when needed, is successful and safe in the majority of patients with anastomotic gastrointestinal leaks. Therefore, an endoscopic treatment could be attempted before resorting to more invasive, costly and risky re-intervention

Bismuth-based quadruple therapy following H. Pylori eradication failures: A multicenter study in clinical practice

Background & Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice. Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated. Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported. Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practic

Endoscopic management of patients with post-surgical leaks involving the gastrointestinal tract: a large case series

Background: Post-surgical anastomotic leaks often require a re-intervention, are associated with a definite morbidity and mortality, and with relevant costs. We described a large series of patients with different post-surgical leaks involving the gastrointestinal tract managed with endoscopy as initial approach. Methods: This was a retrospective analysis of prospectively collected cases with anastomotic leaks managed with different endoscopic approaches (with surgical or radiological drainage when needed) in two endoscopic centres during 5 years. Interventions included: (1) over-the-scope clip (OTSC) positioning; (2) placement of a covered self-expanding metal stent (SEMS); (3) fibrin glue injection (Tissucol); and (4) endo-sponge application, according to both the endoscopic feature and patient’s status. Results: A total of 76 patients underwent endoscopic treatment for a leak either in the upper (47 cases) or lower (29 cases) gastrointestinal tract, and the approach was successful in 39 (83%) and 22 (75.9%) patients, respectively, accounting for an overall 80.3% success rate. Leak closure was achieved in 84.9% and 78.3% of patients managed by using a single or a combination of endoscopic devices. Overall, leak closure failed in 15 (19.7%) patients, and the surgical approach was successful in all 14 patients who underwent re-intervention, whilst one patient died due to sepsis at 7 days. Conclusions: Our data suggest that an endoscopic approach, with surgical or radiological drainage when needed, is successful and safe in the majority of patients with anastomotic gastrointestinal leaks. Therefore, an endoscopic treatment could be attempted before resorting to more invasive, costly and risky re-intervention

Endoscopic submucosal dissection of gastric neoplastic lesions: An Italian, multicenter study

Endoscopic submucosal dissection (ESD) allows removing neoplastic lesions on gastric mucosa, including early gastric cancer (EGC) and dysplasia. Data on ESD from Western countries are still scanty. We report results of ESD procedures performed in Italy. Data of consecutive patients who underwent ESD for gastric neoplastic removal were analyzed. The en bloc resection rate and the R0 resection rates for all neoplastic lesions were calculated, as well as the curative rate (i.e., no need for surgical treatment) for EGC. The incidence of complications, the one-month mortality, and the recurrence rate at one-year follow-up were computed. A total of 296 patients with 299 gastric lesions (80 EGC) were treated. The en bloc resection was successful for 292 (97.6%) and the R0 was achieved in 266 (89%) out of all lesions. In the EGC group, the ESD was eventually curative in 72.5% (58/80) following procedure. A complication occurred in 30 (10.1%) patients. Endoscopic treatment was successful in all 3 perforations, whereas it failed in 2 out of 27 bleeding patients who were treated with radiological embolization (1 case) or surgery (1 case). No procedure-related deaths at one-month follow-up were observed. Lesion recurrence occurred in 16 (6.2%) patients (6 EGC and 10 dysplasia). In conclusion, the rate of both en bloc and R0 gastric lesions removal was very high in Italy. However, the curative rate for EGC needs to be improved. Complications were acceptably low and amenable at endoscopy

Over-the-scope clips in the treatment of gastrointestinal tract iatrogenic perforation: a multicenter retrospective study and a classification of gastrointestinal tract perforations

AIM: To determine the outcome of the management of iatrogenic gastrointestinal tract perforations treated by over-the-scope clip (OTSC) placement. METHODS: We retrospectively enrolled 20 patients (13 female and 7 male; mean age: 70.6 ± 9.8 years) in eight high-volume tertiary referral centers with upper or lower iatrogenic gastrointestinal tract perforation treated by OTSC placement. Gastrointestinal tract perforation could be with oval-shape or with round-shape. Oval- shape perforations were closed by OTSC only by suction and the round-shape by the “twin-grasper” plus suction. RESULTS: Main perforation diameter was 10.1 ± 4.3 mm (range 3-18 mm). The technical success rate was 100% (20/20 patients) and the clinical success rate was 90% (18/20 patients). Two patients (10%) who did not have complete sealing of the defect underwent surgery. Based upon our observations we propose two types of perforation: Round-shape “type-1 perforation” and oval-shape “type-2 perforation”. Eight (40%) out of the 20 patients had a type-1 perforation and 12 patients a type-2 (60%). CONCLUSION: OTSC placement should be attempted after perforation occurring during diagnostic or thera- peutic endoscopy. A failed closure attempt does not impair subsequent surgical treatment

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle