Development and validation of a faecal immunochemical test-based model in the work-up of patients with iron deficiency anaemia.

Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

New horizons in the endoscopic ultrasonography-based diagnosis of pancreatic cystic lesions.

Pancreatic cystic lesions (PCLs) are increasingly being identified because of the widespread use of high-resolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and therefore, accurate diagnosis is crucial to determine the best management strategy, either surgical resection or surveillance. However, the current standard of diagnosis is not accurate enough due to limitations of imaging and tissue sampling techniques, which entail the risk of unnecessary burdensome surgery for benign lesions or missed opportunities of prophylactic surgery for potentially malignant PCLs. In the last decade, endoscopic innovations based on endoscopic ultrasonography (EUS) imaging have emerged, aiming to overcome the present limitations. These new EUS-based technologies are contrast harmonic EUS, needle-based confocal endomicroscopy, through-the-needle cystoscopy and through-the needle intracystic biopsy. Here, we present a comprehensive and critical review of these emerging endoscopic tools for the diagnosis of PCLs, with a special emphasis on feasibility, safety and diagnostic performance.

Feasibility and Safety of Endoscopic Ultrasound-Guided Biliary Drainage (EUS-BD) for Malignant Biliary Obstruction Associated with Ascites: Results of a Pilot Study.

BACKGROUND: It has been suggested that EUS-BD may be a feasible and safer alternative to percutaneous transhepatic biliary drainage (PTBD) after failed ERCP in patients with ascites. To date, no study has specifically evaluated the performance of EUS-BD in this context. METHODS: Retrospective analysis was done for patients with and without ascites who underwent EUS-BD for malignant biliary obstruction after failed ERCP between July 2010 and September 2014. Complications and technical and clinical successes between the two groups were compared. RESULTS: A total of 31 patients were included: 20 patients without ascites (group 1) and 11 with ascites (group 2). Nineteen patients underwent EUS-hepaticogastrostomy (six in group 2), and 12 underwent EUS-choledochoduodenostomy (five in group 2). Technical success was achieved in all patients. Clinical success was observed in 95% (n = 19) in group 1 and 64% (n = 7) in group 2 (p = 0.042). In three out of four patients without clinical success in group 2, the follow-up period was not long enough to observe the clinical response because of early death within the 2 weeks after EUS-BD secondary to disease progression or preprocedural unresponsive sepsis. No significant differences were observed between groups 1 and 2 either in the overall rates of procedural-related complications (20 and 9%, respectively, p = 0.63) or in the rates of major complications (15 vs 9%, respectively, p = 0.639). Stent migration occurred in one patient in each group, intra- or post-procedural bleeding occurred in two patients in group 1, which was conservatively managed, and one patient in group 1 presented biliary leakage. Stent patency and the number of re-interventions were not significantly different. CONCLUSIONS: EUS-BD is technically feasible in patients with ascites. Our results suggest that EUS-BD may be a clinically effective and safe alternative after failed ERCP in patients with ascites.

Endoluminal solutions to bariatric surgery complications: A review with a focus on technical aspects and results.

Obesity is a growing problem in developed countries, and surgery is the most effective treatment in terms of weight loss and improving medical comorbidity in a high proportion of obese patients. Despite the advances in surgical techniques, some patients still develop acute and late postoperative complications, and an endoscopic evaluation is often required for diagnosis. Moreover, the high morbidity related to surgical reintervention, the important enhancement of endoscopic procedures and technological innovations introduced in endoscopic equipment have made the endoscopic approach a minimally-invasive alternative to surgery, and, in many cases, a suitable first-line treatment of bariatric surgery complications. There is now evidence in the literature supporting endoscopic management for some of these complications, such as gastrointestinal bleeding, stomal and marginal ulcers, stomal stenosis, leaks and fistulas or pancreatobiliary disorders. However, endoscopic treatment in this setting is not standardized, and there is no consensus on its optimal timing. In this article, we aim to analyze the secondary complications of the most expanded techniques of bariatric surgery with special emphasis on those where more solid evidence exists in favor of the endoscopic treatment. Based on a thorough review of the literature, we evaluated the performance and safety of different endoscopic options for every type of complication, highlighting the most recent innovations and including comparative data with surgical alternatives whenever feasible.

Can endoscopic papillectomy be curative for early ampullary adenocarcinoma of the ampulla of Vater?

BACKGROUND: The therapeutic role of endoscopic papillectomy (EP) for early ampullary cancer (AC) is still controversial. The aim of the present study was to evaluate the curative potential of EP for early AC and to identify predictors of lymph node metastases (LNMs). METHODS: We retrospectively reviewed 173 patients who were prospectively included in a database and who underwent EP between 1999 and 2013. Adenocarcinoma was present in 28 resected specimens. An additional surgery was proposed in cases of duodenal submucosal infiltration, duct ingrowth, R1 resection or lymphovascular invasion. Clinicopathological information and outcomes were collected, and predictors of LNMs were evaluated. RESULTS: Duodenal submucosal invasion was present in 16/28 cases and LNMs, in 9/28 cases. ACs of the biliopancreatic subtype were smaller (NS); 100 % had submucosal invasion, and 71 % had LNMs. Smaller tumour size, biliopancreatic subtype and submucosal invasion were significantly correlated with LNMs (p < 0.028, p < 0.028 and p < 0.014). Predictive factors of LNMs in the multivariate analysis were submucosal invasion and tumour size (OR 0.032, p < 0.023 and OR 0.711, p < 0.035). EP was curative in 100 % of cancers with R0 resection and no evidence of submucosal or lymphovascular invasion. CONCLUSION: EP may be curative for patients with AC limited to the duodenal mucosa or the sphincter of Oddi without lymphovascular invasion. Due to the presence of more invasive stages at diagnosis, EP may not be curative for ACs of the biliopancreatic subtype. The significance of tumour size is limited by other confounders, such as the histological subtype.

Role of contrast-enhanced harmonic endoscopic ultrasound in submucosal tumors.

With the widespread use of endoscopy, gastrointestinal submucosal lesions are now more commonly discovered. Although endoscopic ultrasound (EUS) is superior to all other imaging techniques for the diagnosis of submucosal tumors (SMTs), it is still suboptimal for differentiating hypoechoic lesions arising from the fourth sonographic gastrointestinal wall layer, which encompass tumors with very different prognosis. EUS tissue acquisition has provided with the unique opportunity to obtain histological confirmation, but it is not accurate enough to evaluate the malignant potential of gastrointestinal stromal tumors (GISTs). In the last years, contrast-enhanced harmonic EUS (CH-EUS) emerged as a powerful imaging modality to assess the microperfusion patterns of pancreatic tumors. Based on the distinct microvascularity of malignant SMTs, it was hypothesized that CH-EUS might also assist in the differential diagnosis of SMTs. Preliminary experience in this field is now available and suggests CH-EUS as a performant modality to distinguish between benign SMTs and GISTs and to evaluate the malignant potential of GISTs. High expectations are also relied on CH-EUS for the monitoring of antiangiogenic treatments of GISTs and the evaluation of gastrointestinal neuroendocrine tumors (NETs).

Review of endoscopic radiofrequency in biliopancreatic tumours with emphasis on clinical benefits, controversies and safety.

Most pancreatic cancers and extrahepatic cholangiocarcinomas are unresectable at the time of diagnosis, and even in case of a resectable cancer, for elderly or patients with coexistent comorbidities, surgery is not an option. Current treatment alternatives in these scenarios are very limited. Biliary stenting with self-expanding metal stents (SEMS) is the mainstay palliative treatment of biliary obstruction due to unresectable pancreatic cancer or cholangiocarcinoma. Nevertheless, more than 50% of SEMS become occluded after 6 mo due to tumour over- and ingrowth, leading to hospital readmissions and reinterventions that significantly impair quality of life. Regimes of chemotherapy or chemoradiotherapy also provide minimal survival benefits. Therefore, novel therapies are eagerly awaited. Radiofrequency (RF) energy causes coagulative necrosis leading to local destruction of the accessed malignant tissue and has an established role in the treatment of malignancies in several solid organs, especially liver cancers. However, pancreatic and extrahepatic biliary cancers are not easily accessed by a percutaneous route, making the procedure dangerous. Over the past five years, the development of dedicated devices compatible with endoscopic instruments has offered a minimally invasive option for RF energy delivery in biliopancreatic cancers. Emerging experience with endoscopic RF ablation (RFA) in this setting has been reported in the literature, but little is known about its feasibility, efficacy and safety. A literature review makes it clear that RFA in biliopancreatic tumours is feasible with high rates of technical success and acceptable safety profile. Although available data suggest a benefit of survival with RFA, there is not enough evidence to draw a firm conclusion about its efficacy. For this reason, prospective randomized trials comparing RFA with standard palliative treatments with quality-of-life and survival endpoints are required. Anecdotal reports have also highlighted a potential curative role of RFA in small pancreatic tumours and benign conditions, such as ductal extension of ampullomas, intrahepatic adenomas or non-tumoural biliary strictures. These newest indications also deserve further examination in larger series of studies.

Contrast-enhanced harmonic endoscopic ultrasound imaging: basic principles, present situation and future perspectives.

Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound (EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS (CH-EUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration (EUS-FNA) can not only render EUS more accurate but may also assist physicians in making decisions when EUS-FNA is inconclusive, increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity. The development of CH-EUS has also opened up exciting possibilities in other research areas, including monitoring responses to anticancer chemotherapy or to ethanol-induced pancreatic tissue ablation, anticancer therapies based on ultrasound-triggered drug and gene delivery, and therapeutic adjuvants by contrast ultrasound-induced apoptosis. Contrast harmonic imaging is gaining popularity because of its efficacy, simplicity and non-invasive nature, and many expectations are currently resting on this technique. If its potential is confirmed in the near future, contrast harmonic imaging will become a standard practice in EUS.

Interventional endoscopic ultrasonography: an overview of safety and complications.

BACKGROUND: In recent years, endoscopic ultrasonography (EUS)-guided techniques have been developed as alternatives to surgical, radiologic, or conventional endoscopic approaches for the treatment or palliation of several digestive diseases. The use of EUS guidance allows the therapeutic area to be targeting more precisely, with a possible clinical benefit and less morbidity. Nevertheless, the risks persist and must be taken into consideration. This review gives an overview of the complications observed with the most established procedures of therapeutic EUS. METHODS: The PubMed and Embase databases were used to search English language articles on interventional EUS. The studies considered for inclusion were those reporting on complications of EUS-guided celiac plexus block (EUS-CPB), EUS-guided celiac plexus neurolysis (EUS-CPN), drainage of fluid pancreatic and pelvic collections, and EUS-guided biliary and pancreatic drainage (EUS-BD and EUS-PD). Variations in methodology and design in most studies made a thorough statistical analysis difficult. Instead, a frequency analysis of complications and a critical discussion were performed. RESULTS: Although EUS-guided celiac plexus injection causes mainly mild and transient complications, growing experience shows that EUS-CPN is not as benign a procedure as previously thought. Most of the major complications have been observed in patients with chronic pancreatitis. The findings show that EUS-guided drainage of fluid collections is a safe procedure. Complications occur more often after the drainage of pancreatic abscesses and necrosis. Although the heterogeneity of studies dealing with pancreatobiliary drainage makes the evaluation of risks after these procedures difficult, complications after EUS-BD and EUS-PD are relatively frequent and can be severe. The technical complexity and the lack of specifically designed devices may account for their complication rates. CONCLUSIONS: Clinicians can consider EUS-guided celiac injection and EUS-guided drainage of fluid collections to be safe alternatives to surgical and radiologic interventions. Well-designed prospective trials are needed to assess the risks of EUS-BD and EUS-PD accurately before they are broadly advocated after a failed endoscopic retrograde cholangiopancreatography (ERCP).

Diagnostic endoscopic ultrasonography: assessment of safety and prevention of complications.

Endoscopic ultrasonography (EUS) has gained wide acceptance as an important, minimally invasive diagnostic tool in gastroenterology, pulmonology, visceral surgery and oncology. This review focuses on data regarding risks and complications of non-interventional diagnostic EUS and EUS-guided fine-needle biopsy (EUS-FNB). Measures to improve the safety of EUS und EUS-FNB will be discussed. Due to the specific mechanical properties of echoendoscopes in EUS, there is a low but noteworthy risk of perforation. To minimize this risk, endoscopists should be familiar with the specific features of their equipment and their patients' specific anatomical situations (e.g., tumor stenosis, diverticula). Most diagnostic EUS complications occur during EUS-FNB. Pain, acute pancreatitis, infection and bleeding are the primary adverse effects, occurring in 1% to 2% of patients. Only a few cases of needle tract seeding and peritoneal dissemination have been reported. The mortality associated with EUS and EUS-FNB is 0.02%. The risks associated with EUS-FNB are affected by endoscopist experience and target lesion. EUS-FNB of cystic lesions is associated with an increased risk of infection and hemorrhage. Peri-interventional antibiotics are recommended to prevent cyst infection. Adequate education and training, as well consideration of contraindications, are essential to minimize the risks of EUS and EUS-FNB. Restricting EUS-FNB only to patients in whom the cytopathological results may be expected to change the course of management is the best way of reducing the number of complications.

Evaluation of the bilio-pancreatic region using endoscopic ultrasonography in patients referred with and without abdominal pain and CA 19-9 serum level elevation.

CONTEXT: When assessing the bilio-pancreatic region, collating the findings of serum CA 19-9 values together with findings from various imaging tests--especially endoscopic ultrasonography--is not a simple issue in daily clinical practice. AIM: To assess the usefulness of endoscopic ultrasonography in an Endoscopic Ultrasonography Unit in two situations: patients with asymptomatic elevation of serum CA 19-9 and patients who presented with abdominal pain plus elevation of CA 19-9. METHODS: A retrospective study of those patients who underwent radial endoscopic ultrasonography between October 2004 and September 2005 in our institution, considering an elevation of CA 19-9 (equal to or greater than 37 U/mL) with or without symptoms. In each case, the parameters recorded were: levels of CA 19-9 one week before EUS, results from other imaging techniques (US, helical CT), and final diagnosis according to pathological and/or clinical evolution criteria. Patients with previous attacks of acute pancreatitis and also those who presented with bile duct dilation or space-occupying lesions in image studies (US and CT) were excluded. Twenty-two patients met the inclusion criteria. RESULTS: Asymptomatic elevation of CA 19-9 was found in 15 patients while 7 patients had elevated CA 19-9 levels as well as pain of uncertain origin. The results of EUS in the asymptomatic patients were: chronic pancreatitis in 7 patients, no pancreatic alterations in 3 patients, and renal cysts, choledocholithiasis, microlithiasis and liver cirrhosis in one patient, respectively. In patients with abdominal pain, EUS showed chronic pancreatitis in 6 cases and adenocarcinoma of the tail of the pancreas in the remaining patient. CONCLUSIONS: When EUS was indicated for the asymptomatic elevation of CA 19-9, the main findings were benign diseases. EUS was useful in studying patients with idiopathic abdominal pain and a slight elevation of CA 19-9 since it allowed us to detect chronic pancreatitis and even early adenocarcinoma of the pancreatic tail.