Gastrointestinal Motility and Response to Levodopa in Parkinson's Disease: A Proof-of-Concept Study.

BACKGROUND: Simultaneous measurement of gastrointestinal transit time (GITT) and plasma levodopa concentration (PLC) is crucial to understanding the effect of dysfunctional motility on levodopa response in patients with Parkinson's disease (PwPD). OBJECTIVE: The aim is to determine if altered segmental GITT correlates with clinical response and PLC variability in PwPD. METHODS: Ten typical and 10 erratic responders ingested the SmartPill (SP) wireless motility capsule. Serial PLC and finger tapping, obtained every 30 minutes for 3 hours after SP/levodopa ingestion, evaluated the correlation between GITT, clinical response, and PLC. Glucose breath testing assessed small intestinal bacterial overgrowth (SIBO). RESULTS: GITT was not significantly different in "typical" and "erratic" responders. SIBO was positive in half of the erratic and negative in most typical responders. CONCLUSION: SP is a feasible technology for assessing GITT in PwPD. A larger study may be able to significantly differentiate/correlate GITT in different segments of the GI tract with response to levodopa. © 2022 International Parkinson and Movement Disorder Society.

Plasma miRNA-based signatures in CRC screening programs.

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607-0.682), 0.670 (0.626-0.714) and 0.682 (0.580-0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.

Upper gastrointestinal active bleeding ulcers: review of literature on the results of endoscopic techniques and our experience with Hemospray.

INTRODUCTION AND OBJECTIVES: Acute gastrointestinal (GI) bleeding can lead from mild to immediately life-threatening clinical conditions. Upper GI bleeding (UGIB) is associated with a mortality of 6-10%. Spurting and oozing bleeding are associated with major risk of failure. Hemospray™ (TC-325), a new hemostatic powder, may be useful in these cases. Aim of this study is to review the efficacy of traditional endoscopic treatment in Forrest 1a-1b ulcers and to investigate the usefulness of Hemospray in these patients. PATIENTS AND METHODS: A MEDLINE search was performed and articles that evaluated hemostatic efficacy and rebleeding rate with traditional endoscopic techniques related to Forrest classification were reviewed. Patients with Forrest 1a-1b ulcers were treated with Hemospray, either as monotherapy or in association with other endoscopic techniques. Primary outcome was immediate hemostasis, secondary outcomes were recurrent bleeding and adverse events related to Hemospray use. RESULTS: Analysis of literature showed that mean initial hemostasis success rate in Forrest 1a-1b ulcers was of 92.8%, and mean rebleeding rate was of 13.3%. We enrolled 13 patients treated with Hemospray. Initial hemostasis was achieved in 100% and we reported three cases of rebleeding. No adverse events occurred. CONCLUSION: Forrest 1a-1b bleeding ulcer is very difficult to treat. Hemospray appears to be an effective hemostatic therapy for these ulcers. However, additional prospective studies are needed to validate these findings.

Brunner's glands hyperplasia: diagnosis with EUS-FNA for suspected pancreatic tumor involving the duodenum.

CONTEXT: Brunner's gland hyperplasia is a rare, benign, proliferative disorder of the duodenum. Large masses may cause obstructive and compressive symptoms which may depend upon the location of the tumour. Owing to its rarity, these lesions can be mistaken for malignancy on radiological and endoscopic examinations. Symptomatic Brunner's gland hyperplasia associated with pancreatitis is very rare and the literature is limited to a few case reports endoscopic ultrasound may be useful to obtain a correct diagnosis. CASE REPORT: We describe an unusual case of diffuse Brunner's gland hyperplasia of duodenum mimicking a malignancy involving the pancreas, in which EUS-FNA avoided a possible major surgery. CONCLUSION: Brunner's gland hyperplasia imaging is very similar to malignant pancreatic mass; EUS with FNA is mandatory to reach a correct diagnosis, avoiding surgery.

Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors derived from the neuroendocrine cell system, which that have increased in incidence and prevalence in recent years. Despite improvements in radiological and metabolic imaging, endoscopy still plays a pivotal role in the number of GEP-NENs. Tumor detection, characterization, and staging are essential in management and treatment planning. Upper and lower gastrointestinal (GI) endoscopy is essential for correct localization of the primary tumor site of GI NENs. Endoscopic ultrasonography (EUS) has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors. Correct staging and histological diagnosis have important prognostic implications. Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall. Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.

Serologic diagnosis of celiac disease: May it be suitable for adults?

The diagnosis of coeliac disease (CD) in adult patients requires the simultaneous assessment of clinical presentation, serology, and typical histological picture of villous atrophy. However, several years ago, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines approved new criteria for the diagnosis in children: Biopsy could be avoided when anti-transglutaminase antibody (TGA) values exceed the cut-off of × 10 upper limit of normal (ULN) and anti-endomysium antibodies are positive, independently from value. This "no biopsy" approach is a decisive need for pediatric population, allowing to avoid stressful endoscopic procedures in children, if unnecessary. This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh's classification. Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels. Therefore, we aim to perform a narrative review on the topic in adults. Despite that some studies confirmed that the × 10 ULN threshold value has a very good diagnostic performance, several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture. In conclusion, the heterogeneity of study reports as well as some conditions, which may hamper the serological diagnosis of CD (such as seronegative CD and non-celiac villous atrophy) and are much more common in adults than in children, could represent a limitation for the "no biopsy" approach to CD diagnosis in patients outside the pediatric age.

Novel frontiers of agents for bowel cleansing for colonoscopy.

The incidence of colorectal cancer (CRC) is characterized by rapid declines in the wake of widespread screening. Colonoscopy is the gold standard for CRC screening, but its accuracy is related to high quality of bowel preparation (BP). In this review, we aimed to summarized the current strategy to increase bowel cleansing before colonoscopy. Newly bowel cleansing agents were developed with the same efficacy of previous agent but requiring less amount of liquid to improve patients' acceptability. The role of the diet before colonoscopy was also changed, as well the contribution of educational intervention and the use of adjunctive drugs to improve patients' tolerance and/or quality of BP. The review also described BP in special situations, as lower gastrointestinal bleeding, elderly people, patients with chronic kidney disease, patients with inflammatory bowel disease, patients with congestive heart failure, inpatient, patient with previous bowel resection, pregnant/lactating patients. The review underlined the quality of BP should be described using a validate scale in colonoscopy report and it explored the available scales. Finally, the review explored the possible contribution of bowel cleansing in post-colonoscopy syndrome that can be related by a transient alteration of gut microbiota. Moreover, the study underlined several points needed to further investigations.

Complications and early mortality in percutaneous endoscopic gastrostomy placement in lombardy: A multicenter prospective cohort study.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the most common endoscopic procedure used to provide nutritional support. AIM: To prospectively evaluate the mortality and complication incidences after PEG insertion or replacement. METHODS: All patients who underwent PEG insertion or replacement were included. Details on patient characteristics, ongoing therapies, comorbidities, and indication for PEG placement/replacement were collected, along with informed consent form signatures. Early and late (30-day) complications and mortality were assessed. RESULTS: 950 patients (47.1% male) were enrolled in 25 centers in Lombardy, a region of Northern Italy. Patient mean age was 73 years. 69.5% of patients had ASA status 3 or 4. First PEG placement was performed in 594 patients. Complication and mortality incidences were 4.8% and 5.2%, respectively. The most frequent complication was infection (50%), followed by bleeding (32.1%), tube dislodgment (14.3%), and buried bumper syndrome (3.6%). At multivariable analysis, age (OR 1.08 per 1-year increase, 95% CI, 1.0-1.16, p = 0.010) and BMI (OR 0.86 per 1-point increase, 95% CI, 0.77-0.96, p = 0.014) were factors associated with mortality. PEG replacement was carried out in 356 patients. Thirty-day mortality was 1.8%, while complications occurred in 1.7% of patients. CONCLUSIONS: Our data confirm that PEG placement is a safe procedure. Mortality was not related to the procedure itself, confirming that careful patient selection is warranted.

Performance of the over-the-scope clip system in the endoscopic closure of iatrogenic gastrointestinal perforations and post-surgical leaks and fistulas.

The increased invasiveness of endoscopic procedures and complex surgical interventions has resulted in an increased number of gastrointestinal iatrogenic defects, such as perforations, leak and fistulas. The conventional treatment for these gastrointestinal defects is surgery, with considerable risks especially in emergency situations and in patients with comorbidities. The Ovesco over-the-scope clip (OTSC) system (Ovesco Endoscopy AG, Tübingen, Germany) and more recently, the Padlock Clip™ (Aponos Medical, Kingston, NH, USA) have shown promising results in the treatment of gastrointestinal defects. Several case reports and case series have demonstrated the efficacy of the OTSC system for the closure of full-thickness defects. Clinical success is best achieved in patients undergoing closure of a perforation or a leak. Closure of fistulas remains a clinical challenge since fibrosis or necrotic and inflamed tissue surrounding lesions may cause clip failure. Over-the-scope clips are a less invasive endoscopic option for managing patients with gastrointestinal defects before a more invasive surgical approach is attempted. Moreover, a failed attempt of OTSC deployment does not preclude subsequent surgical treatment.

Endoscopic ultrasound core needle for diagnosing of solid pancreatic lesions: is rapid on-site evaluation really necessary?

INTRODUCTION: Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) has a crucial role in the diagnosis of solid pancreatic lesions and rapid on-site evaluation (ROSE) can increase its diagnostic yield. Rapid on-site evaluation is not always available and after EUS-FNA provides a cytology specimen with scant cellularity. Fine needle biopsy (FNB) specimens containing core tissue may theoretically overcome the limitations of EUS-FNA sampling. It could be hypothesized that EUS-FNB without ROSE could achieve the same adequacy and accuracy of EUS-FNB with ROSE. The aim of this review is to evaluate the evidence on the role of ROSE in the setting of EUS-guided tissue acquisition with core needles in patients with solid pancreatic lesions. EVIDENCE ACQUISITION: All relevant articles were extracted up to February 2017 based on the results of searches in PubMed, Scopus and Google Scholar. EVIDENCE SYNTHESIS: A total of 21 pertinent articles were finally included. Among the included studies, 11 were performed without ROSE, 8 with ROSE, and 2 were performed both with and without ROSE. In the ROSE group we found a sensitivity, specificity, overall diagnostic adequacy and overall diagnostic accuracy of 96%, 100%, 86.5%, 85.5%, respectively, while in the no-ROSE group 86.6%, 100%, 89.5%, 86.1% were found, respectively. Mild pancreatitis (mean rates, 3.43%) and abdominal pain (mean rates, 3.6%) were reported as most frequent adverse events. CONCLUSIONS: Endoscopic ultrasound guided-FNB without ROSE offers similar results in terms of adequacy and accuracy as in the presence of an on-site cytopathologist.

Hemospray for treatment of acute bleeding due to upper gastrointestinal tumours.

BACKGROUND: Hemospray is a new endoscopic haemostatic powder that can be used in the management of upper gastrointestinal bleedings. AIMS: To assess the efficacy and safety of Hemospray as monotherapy for the treatment of acute upper gastrointestinal bleeding due to cancer. METHODS: The endoscopy databases of 3 Italian Endoscopic Units were reviewed retrospectively and 15 patients (8 males; mean age 74 years) were included in this study. RESULTS: Immediate haemostasis was achieved in 93% of cases. Among the successful cases, 3 re-bled, one case treated with Hemospray and injection had a good outcome, while 2 cases died both re-treated with Hemospray, injection and thermal therapy. No complications related to Hemospray occurred. Finally, 80% of patients had a good clinical outcome at 30days and 50% at six months. CONCLUSION: Hemospray may be considered an effective and safe method for the endoscopic management of acute neoplastic upper gastrointestinal bleedings.

Single versus two-operator endoscopic biliary cannulation technique: a multicenter matched-case analysis.

BACKGROUND: The aim of this study was to compare the outcomes of physician-controlled, using both long and short endoscopic-retrograde-cholangiopancreatography wire systems, and assistant-controlled guide-wire biliary cannulation techniques, and to perform a literature review on this topic. METHODS: The endoscopic databases of three Endoscopic Centers were reviewed to identify all consecutive patients with an intact papilla who, between July 2013 and December 2014, underwent an endoscopic-retrograde-cholangiopancreatography. A total of 240 patients (80 for each group) were matched 1:1, by gender, age and indications for procedure and were included in the analysis. All articles of physician-controlled vs. assistant-controlled guide-wire biliary cannulation techniques, were extracted up to December 2016, and included in the review. RESULTS: There were no statistically significant differences in primary and final (using rescue technique) cannulation rate between the three groups. The mean primary cannulation time and overall cannulation time were shorter in the two groups of physician-controlled guide-wire compared to the assistant-controlled guide-wire group, but the difference was not statistically significant. The total procedure time did not differ significantly between the three groups, but the physician-controlled guide-wire using short wire system was associated with a trend toward a shorter time compared to the other two techniques. There were no statistically significant differences in complication rates between the three groups. Three pertinent articles were included in the review. The mean procedure success and complication rates were 92% and 7%, respectively. CONCLUSIONS: The literature review and our results show that all these techniques have equally efficacy and safety for guide-wire cannulation.

Outcomes of Radiofrequency Ablation for Dysplastic Barrett's Esophagus: A Comprehensive Review.

Barrett's esophagus is a condition in which the normal squamous lining of the esophagus has been replaced by columnar epithelium containing intestinal metaplasia induced by recurrent mucosal injury related to gastroesophageal reflux disease. Barrett's esophagus is a premalignant condition that can progress through a dysplasia-carcinoma sequence to esophageal adenocarcinoma. Multiple endoscopic ablative techniques have been developed with the goal of eradicating Barrett's esophagus and preventing neoplastic progression to esophageal adenocarcinoma. For patients with high-grade dysplasia or intramucosal neoplasia, radiofrequency ablation with or without endoscopic resection for visible lesions is currently the most effective and safe treatment available. Recent data demonstrate that, in patients with Barrett's esophagus and low-grade dysplasia confirmed by a second pathologist, ablative therapy results in a statistically significant reduction in progression to high-grade dysplasia and esophageal adenocarcinoma. Treatment of dysplastic Barrett's esophagus with radiofrequency ablation results in complete eradication of both dysplasia and of intestinal metaplasia in a high proportion of patients with a low incidence of adverse events. A high proportion of treated patients maintain the neosquamous epithelium after successful treatment without recurrence of intestinal metaplasia. Following successful endoscopic treatment, endoscopic surveillance should be continued to detect any recurrent intestinal metaplasia and/or dysplasia. This paper reviews all relevant publications on the endoscopic management of Barrett's esophagus using radiofrequency ablation.

Biliary and pancreatic stenting: Devices and insertion techniques in therapeutic endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography.

Stents are tubular devices made of plastic or metal. Endoscopic stenting is the most common treatment for obstruction of the common bile duct or of the main pancreatic duct, but also employed for the treatment of bilio-pancreatic leakages, for preventing post- endoscopic retrograde cholangiopancreatography pancreatitis and to drain the gallbladder and pancreatic fluid collections. Recent progresses in techniques of stent insertion and metal stent design are represented by new, fully-covered lumen apposing metal stents. These stents are specifically designed for transmural drainage, with a saddle-shape design and bilateral flanges, to provide lumen-to-lumen anchoring, reducing the risk of migration and leakage. This review is an update of the technique of stent insertion and metal stent deployment, of the most recent data available on stent types and characteristics and the new applications for biliopancreatic stents.

Pancreatic necrosectomy: an evidence-based systematic review of the levels of evidence and a comparison of endoscopic versus non-endoscopic techniques.

INTRODUCTION: Endoscopic necrosectomy is now becoming common worldwide as a minimally-invasive treatment alternative to surgical necrosectomy. The aims of this systematic review are to record the entire body of the literature accumulated over the past 15 years on endoscopic necrosectomy techniques and to compare the outcomes of endoscopic versus non-endoscopic techniques. EVIDENCE ACQUISITION: All relevant articles were extracted up to December 2015 based on the results of searches in PubMed, Scopus and Google Scholar. EVIDENCE SYNTHESIS: A total of 46 pertinent articles were finally included for the purpose of this systematic review. Most of the studies in our review included small numbers of patients, were retrospective and had low/moderate overall levels of evidence. The mean technical and clinical success rates reported were 99% and 89%, respectively, the mean overall complication rate was 22% and the mean overall mortality rate was 5%. The most common complications were bleeding, which occurred in 11% of patients, perforations/pneumoperitoneum which occurred in 3%, and air embolism in 0.4% of patients. The access to the cavity was created by direct endoscopic puncture in 205 patients, while endoscopic ultrasound guidance was used in 733, with no difference in technical success (99% vs. 99%), clinical success (87% vs. 89%), complications (32% vs. 21%) and mortality (7% vs. 5%) rates. Compared to the percutaneous and surgical therapies, the endoscopic techniques exhibited higher success rates and lower morbidity and mortality rates. CONCLUSIONS: Endoscopic necrosectomy is becoming the standard of care for the treatment of pancreatic necrotic collections.

Endoscopic management of bile duct injury after hepatobiliary tract surgery: a comprehensive review.

Bile duct injuries (BDIs) are the most serious complications after hepatobiliary surgery and are associated with high morbidity and mortality. The incidence of iatrogenic injuries of bile ducts has increased after the advent of laparoscopic cholecystectomy. BDIs present with biliary leak or biliary obstruction or a combination of both. Successful treatment of these complications requires a multidisciplinary team that includes biliary endoscopists, interventional radiologists and hepatobiliary surgeons. Endoscopic treatment is the main option for biliary leak. Depending on colangiographic appearance of the biliary damage, several endoscopic techniques (naso-biliary drainage, biliary sphincterotomy, placement of prosthesis) are used, allowing to achieve the leak sealing in most cases. In complex biliary fistulas the use of covered self-expandable metal stents is another therapeutic option with high success rates. The most common endoscopic therapy for biliary strictures involves balloon dilation and placement of multiple plastic stents followed by the periodic exchange of the stents. This is usually performed every three months by placing an increasing number of stents each time, until complete resolution of the stricture. Self-expandable metal stents have a larger diameter compared to plastic stents and therefore, higher patency rate. Covered self-expandable stents are an alternative option with the advantage of providing better permeability, preventing occlusion, and reducing the number of the required procedures. The aim of this paper was to review the endoscopic management of patients with bile duct injuries after hepatobiliary surgery.