Direct Single-Operator Cholangioscopy and Intraductal Ultrasonography in Patients with Indeterminate Biliary Strictures: A Single Center Experience.

The evaluation of biliary strictures poses a challenge due to the low sensitivity of standard diagnostic approaches, but the advent of direct single-operator cholangioscopy (DSOC) has revolutionized this paradigm. Our study aimed to assess the diagnostic performance of DSOC and DSOC-targeted biopsies, intraductal ultrasound (IDUS), and standard brush cytology in patients with indeterminate biliary strictures (IBS). We reviewed patients who underwent advanced diagnostic evaluation for IBS at our endoscopy unit from January 2018 to December 2022, all of whom had previously undergone at least one endoscopic attempt to characterize the biliary stricture. Final diagnoses were established based on surgical pathology and/or clinical and radiological follow-up spanning at least 12 months. A total of 57 patients, with a mean age of 67.2 ± 10.0 years, were included, with a mean follow-up of 18.2 ± 18.1 months. The majority of IBS were located in the distal common bile duct (45.6%), with malignancy confirmed in 35 patients (61.4%). DSOC and IDUS demonstrated significantly higher accuracies (89.5% and 82.7%, respectively) compared to standard cytology (61.5%, p < 0.05). Both DSOC visualization and IDUS exhibited optimal diagnostic yields in differentiating IBS with an acceptable safety profile.

The Endoscopic Retrograde Cholangiopancreatography and Endoscopic Ultrasound Connection: Unity Is Strength, or the Endoscopic Ultrasonography Retrograde Cholangiopancreatography Concept.

Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are both crucial for the endoscopic management of biliopancreatic diseases: the combination of their diagnostic and therapeutic potential is useful in many clinical scenarios, such as indeterminate biliary stenosis, biliary stones, chronic pancreatitis and biliary and pancreatic malignancies. This natural and evident convergence between EUS and ERCP, which by 2006 we were calling the "Endoscopic ultrasonography retrograde colangiopancreatography (EURCP) concept", has become a hot topic in the last years, together with the implementation of the therapeutic possibilities of EUS (from EUS-guided necrosectomy to gastro-entero anastomoses) and with the return of ERCP to its original diagnostic purpose thanks to ancillary techniques (extraductal ultrasound (EDUS), intraductal ultrasound (IDUS), cholangiopancreatoscopy with biopsies and probe-based confocal laser endomicroscopy (pCLE)). In this literary review, we retraced the recent history of EUS and ERCP, reported examples of the clinical applicability of the EURCP concept and explored the option of performing the two procedures in only one endoscopic session, with its positive implications for the patient, the endoscopist and the health care system. In the last few years, we also evaluated the possibility of combining EUS and ERCP into a single endoscopic instrument in a single step, but certain obstacles surrounding this approach remain.

Impact of Macroscopic On-Site Evaluation (MOSE) on Accuracy of Endoscopic Ultrasound-Guided Fine-Needle Biopsy (EUS-FNB) of Pancreatic and Extrapancreatic Solid Lesions: A Prospective Study.

This is a prospective and comparative study including 76 consecutive patients performing EUS-FNB for pancreatic and extrapancreatic solid lesions, randomized by alternate allocation to macroscopic on-site evaluation (MOSE) (40 patients) or to a conventional technique (40 patients), with three passes each. MOSE samples were differentiated into score 0: no visible material, score 1: only necrotic or haematic material, score 2: white core tissue ≤ 2 mm, or score 3: white core tissue > 2 mm. The conventional technique consisted in pushing all the needle content into a test tube for evaluation by the pathologist. In both groups, a 22-25 Gauge Franseen-tip needle (Acquire, Boston Scientific Co., Natick, MA, USA) was used. The study evaluated the diagnostic accuracy and adequacy of MOSE compared to the conventional technique and whether MOSE could optimize the number of passes during EUS-FNB. Results: The analysis was performed on 76 patients (38 MOSE, 38 conventional). The overall diagnostic adequacy was 94.7% (72/76) and accuracy was 84.2% (64/76). The diagnostic accuracy was similar in the two groups: MOSE 86.8% (33/38 lesions), vs. conventional 81.6%, 31/38 lesions, p = 0.76). Regarding diagnostic adequacy, the MOSE technique was 97.4% (111/114 passes) compared to 92.1% (105/114 passes) with the conventional technique, p = 0.06. The accuracy increased according to the MOSE score evaluation: it was 43.5%, 65.5% and 78.3% in patients with score 1, score 2, and score 3, respectively. Moreover, if in the first two passes the MOSE score was 2 or 3, the accuracy was 82.6% (20/23), and upon adding a third pass, the accuracy increased to 87% (20/23), which was not significantly different from the general accuracy of the MOSE samples (86.8%) (p = 0.86). Conclusions: The MOSE score showed a comparable diagnostic accuracy to the conventional technique. However, MOSE allows endoscopists to perform an inspective evaluation of the material, tends to perform better than the conventional technique in terms of diagnostic adequacy, and may potentially reduce the number of passes.

Screening and surveillance of oesophageal varices in patients with HCV-positive liver cirrhosis successfully treated by direct-acting antiviral agents.

BACKGROUND & AIMS: limited evidence is available to guide hepatologists regarding endoscopic surveillance of oesophageal varices (EV) in Hepatitis C Virus (HCV)-positive cirrhotic patients achieving a sustained virologic response. To address these issues, we conducted a long-term prospective study on 427 HCV-positive cirrhotic patients successfully treated by Direct Antiviral Agents (DAAs). METHODS: Patients were divided into two groups according to their baseline Baveno VI status: Group 1 (92, 21.5%, favourable Baveno VI status) and Group 2 (335, 78.5%, unfavourable Baveno VI status). Each patient underwent baseline endoscopy and was endoscopically monitored for a median follow-up of 65.2 months according to Baveno VI recommendations. RESULTS: About 4.3% of Group 1 patients showed baseline EV compared with 30.1% of Group 2 patients (p < .0001). No patients belonging to Group 1 without baseline EV developed EV at follow-up endoscopy compared with 6.5% in Group 2 patients (p = .02); 69/107 (64.5%) patients with baseline EV showed small varices. During the endoscopic follow-up, EV disappeared/improved in 36 (33.6%), were stable in 39 (36.4%) and worsened in 32 (29.9%) patients, all belonging to Group 2 (p = .001). Improvement in Baveno VI status was observed in 118/335 (35.2%, p < .0001) of Group 2 patients and among those without pre-therapy EV, none developed EV throughout the follow-up. CONCLUSIONS: HCV-positive cirrhotic patients cured by DAAs showing baseline favourable Baveno VI status and no worsening during follow-up can safely avoid endoscopic screening and surveillance. Patients having unfavourable Baveno VI status without baseline EV who improve their status may suspend further endoscopic surveillance.

Training in advanced bilio-pancreatic endoscopy.

As the clinical applications of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) take more and more root in everyday practice and these endoscopic procedures become increasingly more complex and interventional with a higher chance for complications, the demand for expert biliopancreatic endoscopists continues to increase. In response to this growing need, specific postgraduate fellowships have been developed, however the standardization of training programs and the assessment of the achieved competence still remains an open debate. ERCP and EUS competency often requires training beyond the scope of a standard GI fellowship program, which lasts at least 1-2 years, and there are some differences in the way to face the issues of advanced biliopancreatic endoscopy training between Europe, America and the Asian regions. Today there is no role for the self-teaching of ERCP and EUS through trial and error without supervision and, in the near future, it is necessary to critically revise current training guidelines, to establish a standardized curriculum for advanced biliopancreatic endoscopists and to implement universally validated skill assessment tools, able to ensure constant and targeted feedback to trainees.

Needle-based confocal endomicroscopy in the discrimination of mucinous from non-mucinous pancreatic cystic lesions.

BACKGROUND: Pancreatic cystic lesions (PCLs) are considered a precursor of pancreatic cancer. Needle-based confocal endomicroscopy (nCLE) is an imaging technique that enables visualization of the mucosal layer to a micron resolution. Its application has demonstrated promising results in the distinction of PCLs. This study evaluated the utility of nCLE in patients with indeterminate PCLs undergoing endoscopic ultrasound fine-needle aspiration (EUS-FNA) to distinguish mucinous from non-mucinous lesions. AIM: To evaluate the accuracy of nCLE in indeterminate PCLs undergoing EUS-FNA to distinguish mucinous from non-mucinous lesions. METHODS: Patients who required EUS-FNA between 2015 and 2017 were enrolled prospectively. During EUS-FNA, confocal imaging, analyses of the tumor markers carcinoembryonic antigen and amylase, and cytologic examination were conducted. All patients were followed for at least 12 mo and underwent laboratory testing and computed tomography scanning or magnetic resonance imaging. nCLE videos were independently reviewed by 6 observers to reach a final diagnosis (mucinous vs non-mucinous) based on criteria derived from previous studies; if there was disagreement > 20%, a final diagnosis was discussed after consensus re-evaluation. The sensitivity, specificity, and accuracy of nCLE were calculated. Adverse events were recorded. RESULTS: Fifty-nine patients were included in this study. Final diagnoses were derived from surgery in 10 patients, cytology in 13, and imaging and multidisciplinary team review in 36. Three patients were excluded from final diagnosis due to problems with nCLE acquisition. Fifty-six patients were included in the final analysis. The sensitivity, specificity, and accuracy of nCLE were 80% [95% confidence interval (CI): 65-90], 100% (95%CI: 72-100), and 84% (95%CI: 72-93), respectively. Post-procedure acute pancreatitis occurred in 5%. CONCLUSION: EUS-nCLE performs better than standard EUS-FNA for the diagnosis of indeterminate PCL.

The Role of Video Capsule Endoscopy in Liver Disease.

In the setting of chronic liver disease, capsule endoscopy is safe and well tolerated, making it an appealing diagnostic procedure. It is used mainly for the surveillance of esophageal varices, investigation of anemia, and exploration of the small bowel for complications of portal hypertension. Capsule endoscopy is recognized as a viable alternative in patients unable or unwilling to undergo upper gastrointestinal endoscopy for investigations of esophageal varices. In evaluating the small bowel of patients with liver disease and unexplained anemia, capsule endoscopy increases recognition of mucosal abnormalities, although their clinical significance is often unclear.

Differential diagnosis of pancreatic cysts: A prospective study on the role of intra-cystic glucose concentration.

BACKGROUND: The accuracy and costs of current diagnostic methods in the differential diagnosis of pancreatic cystic lesions still has ample room for improvement. AIMS: The aim of the study was to confirm the diagnostic yield of intracystic glucose in the diagnosis of pancreatic cyst subtypes. METHODS: We prospectively recruited all patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration of pancreatic cyst at our Institution. RESULTS: Fifty-six patients were included in the study. We found that intracystic glucose concentration < 50 mg/dL was significantly more sensitive than a concentration of Carcinoembryonic Antigen > 192 ng/mL (93.6% vs 54.8%; p = 0.003) for the diagnosis of mucinous cysts. In terms of specificity, the two markers were not different (96% vs 100%; p = 1). Regarding the diagnosis of non-mucinous cysts, intracystic glucose concentration ≥ 50 mg/mL showed higher sensitivity than Carcinoembryonic Antigen level < 5 ng/mL (96% vs 72%) although a statistical significance could not be reached (p = 0.07). The two markers were not statistically different in terms of specificity (93.6% vs 87.1%; p = 0.62). CONCLUSION: Given its diagnostic performance and ease of measurement, intracystic glucose may replace Carcinoembryonic Antigen in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts.

Lumen-apposing metal stents in management of pancreatic fluid collections: The nobody's land of removal timing.

Pancreatic fluid collections (PFCs) develop as a result of damage to the major or peripheral pancreatic ducts, complication due to acute or chronic pancreatitis, trauma or iatrogenic causes. PFCs include pancreatic pseudocysts (PPs) and walled-off necrosis (WON). PFCs usually resolve spontaneously and are asymptomatic, but if they persist, increase in dimension or became symptomatics, therapeutic intervention is required. Available therapeutic interventions include surgical, percutaneous, and endoscopic drainage. The endoscopic approach is nowadays considered the first line-treatment of PFCs due to various advantages when compared with surgical or percutaneous drainage: decreased morbidity, length of hospital stay, and reduced costs. In the last few years, the endoscopic ultrasound (EUS)-guided transmural drainage, initially with plastic stents, gained popularity. More recently, fully covered self-expanding lumen-apposing metal stents (LAMS) have been demonstrated to be both, safe and effective with high clinical and technical success, reducing the risk of perforation, peritoneal leakage, migration and facilitating the drainage of necrotic contents. In the last few years, several studies evaluating the safety and efficacy of LAMS and their differences with plastic stents have been performed, but literature on the removal timing of this device and associated complications is still limited. The aim of this review is to analyze studies reporting information about the retrieval timing of LAMS and the related adverse events.

Wait-and-See Policy for a Small Pancreatic Schwannoma Diagnosed With Endoscopic Ultrasound With Fine-Needle Aspiration.

Pancreatic schwannomas are very rare tumors, usually diagnosed incidentally after surgery. In literature, only 17 patients underwent endoscopic ultrasound (EUS) with fine-needle aspiration and diagnosis was reached only in 9 subjects. We report the case of a woman in whom a computed tomography revealed a mass in the uncinate process of the pancreas. EUS-fine-needle aspiration demonstrated a 1.3 × 1.1 cm hypoechoic lesion, cytology revealed sheets of spindle cells, and immunocytochemistry led to the diagnosis of schwannoma. Relying on EUS features and on the low proliferation index, a follow-up program was set. Four years later, the patient is asymptomatic and the mass is unchanged.

Clustering in light nuclei and their effects on fusion and pre-equilibrium processes / Agrupamiento de núcleos ligeros y sus efectos en la fusión y procesos de pre-equilibrio

Summary The study of heavy ion nuclear reactionis an important tool to observe and disentangle different and competing mechanisms, which may arise in the different energy regimes. In particular, at relatively low bombarding energy, it is quite interesting the comparison between pre-equilibrium and thermal emission of light charged particles from hot nuclear systems [1-6]. Indeed, the nuclear structure of the interacting partners can be strongly correlated to the dynamics, especially at energies close to the Coulomb barrier, and this effect emerges when some nucleons or clusters of nucleons are either emitted or captured. In particular, a major attention has been devoted, in the last years, to the possible observation of cluster structure effects in the competing nuclear reaction mechanisms, especially when fast processes are involved. At this purpose, the four reactions 16O+30Si at 111 MeV, 16O+30Si at 128 MeV, 18O+28Si at 126 MeV, 19F+27Al at 133 MeV have been measured to study the onset of pre-equilibrium in an energy range where, for central collisions, complete fusion is expected to be the predominant mode. Experimental data were collected using the GARFIELD + RCo array [7], fully equipped with digital electronics at the LegnaroNational Laboratories. The comparison between experimental data and different model predictions have been performed: in particular, both dynamical models based either on Stochastic Mean Field (TWINGO) or Anti-symmetrized Molecular Dynamics and fully statistical models (GEMINI++) have been considered. Simulated events are filtered through a software replica of the apparatus, to take into account all possible distortions of the experimental distributions due to the finite size of the apparatus.

Resumen El estudio de la reacción nuclear iónica pesada es una herramienta importante para observar y esclarecer los diferentes mecanismos que compiten entre sí, que pueden surgir en los diferentes regímenes energéticos. En particular, a una energía de bombardeo relativamente baja, es bastante interesante la comparación entre el preequilibrio y la emisión térmica de partículas ligeras cargadas por sistemas nucleares calientes [1-6]. De hecho, la estructura nuclear del grupo que interactúa puede estar fuertemente correlacionada con la dinámica, especialmente en energías cercanas a la barrera de Coulomb, y este efecto surge cuando se emiten o capturan algunos nucleones o grupos de nucleones. En particular, se ha dedicado una gran atención, en los últimos años, a la posible observación de los efectos de la estructura del agrupamiento en los mecanismos de reacción nuclear competitivos, especialmente cuando se trata de procesos rápidos. Para este propósito, las cuatro reacciones 16O + 30Si a 111 MeV, 16O + 30Si a 128 MeV, 18O + 28Si a 126 MeV, 19F + 27Al a 133 MeV se han medido para estudiar el inicio del preequilibrio en un rango de energía en el cual, para colisiones centrales, se espera que la fusión completa sea el modo predominante. Los datos experimentales se recogieron utilizando la matriz GARFIELD + RCo [7], totalmente equipada con electrónica digital en los Laboratorios Nacionales Legnaro. La comparación entre los datos experimentales y las diferentes predicciones de modelos se han llevado a cabo: en particular, se han considerado los modelos dinámicos basados en el Campo Medio Estocástico (TWINGO) o Dinámica Molecular Antisimétrica y modelos completamente estadísticos (GEMINI ++). Los eventos simulados se filtran a través de una réplica de software del aparato, para tener en cuenta todas las posibles distorsiones de las distribuciones experimentales debido al tamaño finito del aparato.

A rare case of gastric fistulization of a main-duct intraductal papillary mucinous neoplasm.

We report a rare case of gastric fistulization in a patient with main-duct (MD) intraductal papillary mucinous neoplasm (IPMN). Fistulization to adjacent organs is a rare complication of this disease, mainly affecting the duodenum; the fact that the stomach was the only organ involved makes this case even more peculiar. The diagnosis of the fistula was made after examination with endoscopic ultrasound, since a previous computed tomography scan could not detect it.

Diagnosis and management of Zollinger-Ellison syndrome in 2018.

Zollinger-Ellison syndrome (ZES) is a clinical syndrome characterized by gastric acid hypersecretion due to the ectopic secretion of gastrin by a gastrinoma, a neuroendocrine tumor (NET) which mostly develops in the duodenum and in the pancreas. This syndrome was first described by Zollinger and Ellison in 1964; if left untreated, ZES can lead to multiple complications mainly due to gastric hypersecretion and some patients can suffer from the complications of an advanced metastatic disease. Although its clinical features are considered typical, the diagnosis of ZES is often challenging for the clinician. A previous review was published in 2005 by our group, but in 12 years many things have changed: the diagnostic tools have been improved and many different therapeutical options are now available.

Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy.

BACKGROUND: Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. MATERIALS AND METHODS: This was a retrospective, multicentre study (2010-2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. RESULTS: Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn's disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3-11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92-0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. CONCLUSION: In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.

Endoscopic imaging in the management of gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors deriving from the gastrointestinal (GI) neuroendocrine system. Since these neoplasms are usually very small, located deeply within the retroperitoneum or into an extramucosal site of the GI tract and, lastly, because they may be multi-sited, radiological imaging modalities, in combination with endoscopy, are the diagnostic workhorses in patients with GEP-NETs. Endoscopic approach is useful for detection, bioptic diagnosis and curative resection of small GEP-NETs of stomach, duodenum, jejuno-ileum, and colon-rectum. Moreover, endoscopic ultrasonography (EUS), associated with high frequency miniprobes, is a valuable procedure in regional staging of lesions of the GI wall and can provide information which has a remarkable impact on therapeutic choices. EUS is still the sole technique, in a substantial number of cases, providing a definitive diagnosis of pancreatic insulinoma and it detects and follows small lesions of the pancreas in patients with Multiple Endocrine Neoplasia type 1 syndrome. EUS should be performed in those cases in which morphological or molecular imaging modalities need to be supported because of negative or dubious results. In this review we describe the applications of endoscopic procedures in the management of GEP-NETs.

Endoscopic ultrasound in common bile duct dilatation with normal liver enzymes.

In recent years, the description of isolated bile duct dilatation has been increasingly observed in subjects with normal liver function tests and nonspecific abdominal symptoms, probably due to the widespread use of high-resolution imaging techniques. However, there is scant literature about the evolution of this condition and the impact of endoscopic ultrasound (EUS) in the diagnostic work up. When noninvasive imaging tests (transabdominal ultrasound, computed tomography or magnetic resonance cholangiopancreatography) fail to identify the cause of dilatation and clinical or biochemical alarm signs are absent, the probability of having biliary disease is considered low. In this setting, using EUS, the presence of pathologic findings (choledocholithiasis, strictures, chronic pancreatitis, ampullary or pancreatic tumors, cholangiocarcinoma), not always with a benign course, has been observed. The aim of this review has been to evaluate the prevalence of disease among non-jaundiced patients without signs of cytolysis and/or cholestasis and the assessment of EUS yield. Data point out to a promising role of EUS in the identification of a potential biliary pathology. EUS is a low invasive technique, with high accuracy, that could play a double cost-effective role: identifying pathologic conditions with dismal prognosis, in asymptomatic patients with negative prior imaging tests, and excluding pathologic conditions and further follow-up in healthy subjects.

Antiplatelet and anticoagulant drugs management before gastrointestinal endoscopy: do clinicians adhere to current guidelines?

BACKGROUND: Managing antiplatelet and anticoagulant drugs before endoscopy may be challenging. AIMS: To assess whether the pre-endoscopic management of antiplatelet/anticoagulant drugs is adherent to current guidelines and the influence of patients' characteristics, referring physician's specialty, type of endoscopic procedure and therapeutic regimen on adherence. METHODS: Two hundred and twenty patients taking aspirin, thienopyridines or warfarin and scheduled for upper endoscopy (± biopsies), variceal band ligation, colonoscopy (± biopsies or polypectomy), were prospectively analyzed. RESULTS: In 109 patients (49.5%) the management of antiplatelet/anticoagulant drugs was thoroughly compliant with guidelines. Neither demographic characteristics, nor in/outpatient status, nor type of endoscopic procedure, nor physician's specialty influenced the adherence but the therapeutic regimen had a significant impact (p < 0.0001) as compliance was less likely in patients on warfarin. Unwarranted drugs withholding was more frequent before colonoscopy than upper endoscopy (p = 0.0001). Warfarin was stopped longer than recommended more frequently than aspirin (p = 0.009). The International Normalized Ratio was properly checked before endoscopy in 47.7% of patients. Among the 55 patients who withheld warfarin, the decision about bridging to low molecular weight heparin was appropriate in 21 (38.2%). CONCLUSIONS: Compliance with guidelines is low especially in the management of warfarin, both among gastroenterologists and other physicians.