Fabia Attili

The human gut microbiota and virome: Potential therapeutic implications

Abstract Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut “virome” composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut “virome” in the larger microbial ecosystem.

Fine-needle tissue acquisition from subepithelial lesions using a forward-viewing linear echoendoscope

BACKGROUND AND STUDY AIMS The overall diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for subepithelial lesions (SELs) is suboptimal. The aim of this study was to evaluate the diagnostic accuracy, defined as the proportion of correct diagnoses, obtained using the EUS-guided fine-needle tissue acquisition (FNTA) sampling technique performed with the newly developed forward-viewing EUS scope (FV-EUS). PATIENTS AND METHODS This was a retrospective analysis of a prospectively collected database including all consecutive patients with SELs who underwent EUS-FNTA using the FV-EUS scope from 2007 to 2011 in a tertiary referral center. All procedures were performed by a single expert endoscopist. RESULTS A total of 121 consecutive patients with SELs (13 in the esophagus, 96 in the stomach, 10 in the duodenum, 2 in the rectum) underwent sampling of the lesion using the FV-EUS scope. The procedure was technically feasible in all but one patient, and no complication related to EUS-FNTA occurred. Full histological assessment including immunostaining could be completed in 93.4% (113/121) of the patients. Considering neoplastic vs. non-neoplastic diseases, the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 92.8% (95%CI 86.3-96.8), 100% (95%CI 69.0-100%), infinity, and 0.07 (95%CI 0.04-0.14), respectively. CONCLUSIONS EUS-FNTA performed in conjunction with the FV-EUS scope for sampling SELs of the gastrointestinal tract was safe and provided a very high diagnostic accuracy. Studies comparing FV-EUS with standard curved linear echoendoscopes are needed to clarify whether these results are due to the sampling technique or the type of scope utilized.

Endoscopic ultrasound fine needle aspiration: Technique and applications in clinical practice

Since its initial report in 1992, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has now been incorporated into the diagnostic and staging algorithm for the evaluation of benign and malignant diseases of the gastrointestinal tract and of adjacent organs. Its introduction constitutes a major breakthrough in the endoscopic field and has gradually transformed EUS from a pure imaging modality into a more interventional procedure. In addition, the possibility of collecting samples, providing a definitive cytological and/or histological evidence of the presence of malignancy, has strongly contributed to changing EUS from a subjective, highly operator dependant procedure into a more objective one. This article will review the instrumentation, technique and the most important clinical applications of EUS-FNA.

Diagnostic and therapeutic role of endoscopy in gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms have substantially increased over the last decades. Because of the indolent clinical course of the disease even in advance stages and the rise in the incidental diagnosis of small asymptomatic lesions, the prevalence of gastroenteropancreatic neuroendocrine neoplasms is higher than that of pancreatic, gastric and oesophageal adenocarcinomas, making them the second most prevalent cancer type of the gastrointestinal tract. This increase in the overall prevalence of gastroenteropancreatic neuroendocrine neoplasms has been paralleled by a growth in the importance of the endoscopist in the care of these patients, who usually require a multidisciplinary approach. In this manuscript the diagnostic and therapeutic role of endoscopic for gastroenteropancreatic neuroendocrine neoplasms will be reviewed.

Interventional Endoscopic Ultrasonography

Opinion statementEndoscopic ultrasound (EUS) is not only a diagnostic tool but also an interventional and therapeutic procedure. Indeed, in addition to tissue acquisition, it can also drain fluid collections adjacent to the gastrointestinal tract, provide access to biliary and pancreatic ducts, biliary, pancreatic, and gallbladder drainage, pancreatic cyst ablation, and, finally, provide anti-tumoral treatments and interventional vascular procedures. Although several improvements have been made in the last decade, the full potential of interventional EUS is yet to be completely explored. Future areas of research are the development of dedicated tools and accessories, the standardization of the interventional procedures, and the widening of the use of EUS, while increasing the expertise worldwide. In addition, more data, based on well-performed, possibly randomized clinical trials, are needed to accurately determine the risks and long-term outcomes of these interventions. We firmly believe that interventional EUS can play a pivotal role in anti-tumor treatments, by the fine-needle injection of anti-tumoral agents, tumor ablation, and assisting radiation treatment with gold fiducial placement and the implantation of intralesional seeds. The goal of the near future will be to offer targeted therapy and monitoring of tumor treatment response in a more biologically driven manner than has been available in the past. Interventional EUS will be an essential part of the multidisciplinary approach to cancer treatment.

Intra-channel stent release technique for fluoroless endoscopic ultrasound-guided lumen-apposing metal stent placement: changing the paradigm

Background Recently, a novel lumen-apposing fully covered self-expanding metal stent (LA-FCSEMS) mounted on an electrocautery-enhanced delivery system has been developed to perform endoscopic ultrasound (EUS)-guided transluminal drainage. From early experience, however, release of the proximal flange of the stent has mostly been done using endoscopic view guidance to ensure proper positioning. Aim We describe a new technique that we have named the Intra-Channel Stent Release Technique (ICSRT) to perform stent placement under complete EUS control, without the use of either fluoroscopic or endoscopic views. Material and methods Data on all consecutive patients who underwent EUS-guided drainage using the new ICSRT between June 2014 and April 2016 were retrospectively retrieved from two institution databases. All EUS procedures were performed by experienced endoscopists with the patient under conscious or deep sedation. The total procedure and stent deployment time, and adverse events related to stent positioning with the ICSRT were evaluated. Results One hundred consecutive patients (51 women; mean age ± SD, 66 ± 15.2 years, range 34 – 95) underwent EUS-guided transluminal drainage with the Hot AXIOS™ device using the new ICSRT. The procedure was technically successful in all but one patient (1 %). The mean total procedural time was 21.9 minutes (range 7 – 50), while the mean time for stent placement was 3.2 minutes (range 1 – 15). No major adverse events occurred. Discussion The ICSRT has been used to deploy the newly developed lumen-apposing FCSEMS under complete EUS guidance without fluoroscopic and/or endoscopic assistance. The technique appears to be safe and highly effective and should be learned by all interventional endosonographers in order to be able to perform drainage in all clinical scenarios.

Forward-viewing linear echoendoscope: a new option in the endoscopic ultrasound armamentarium (with video).

The forward‐viewing linear echoendoscope (FV‐EUS) has been developed with the aim of overcoming limitations of standard curved linear‐array echoendoscopes (CLA‐EUS) and to further expand interventional applications of EUS. The main characteristic of the FV‐EUS is a shifting in the orientation of both endoscopic and ultrasound views from oblique to forward, with the exit of the working channel at the tip of the instrument. This allows exit of the devices parallel to the longitudinal axis of the endoscope, thus resulting in a more direct and stable access to the lesion while increasing the precision and force applied to the target. Accumulating evidence has shown that the FV‐EUS can be used instead of the standard CLA‐EUS scope for routine fine needle aspiration, with extremely good performance for subepithelial lesions and for difficult to reach locations. Several areas of use of this echoendoscope are yet to be better defined, such as its potential for therapeutic and interventional procedures, as well as for natural orifice transluminal endoscopic surgery. The current report provides an updated overview of the available evidence for both diagnostic and interventional uses of the FV‐EUS.

Accuracy and inter-observer agreement of the Procore™ 25 gauge needle for endoscopic ultrasound-guided tissue core biopsy.

BACKGROUND Scanty data on the performance of the new 25-gauge Procore™ biopsy needle are available. METHODS Consecutive patients who underwent endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using the 25G Procore™ were retrospectively retrieved. All samples were independently reviewed by 3 pathologists for the following: histological, cytological or no specimen, neoplasia, diagnostic or non-diagnostic. Diagnostic accuracy and inter-rater concordance among pathologists were calculated. RESULTS 94 patients underwent EUS-FNB of 101 sites (69 solid masses, 25 lymph nodes, 5 wall thickening). Forty-one biopsies (40.5%) were classified as histological samples by at least two pathologists, 29 as cytological (28.7%), 31 had no sample (30.7%). Good and almost perfect agreements among pathologists in defining cytological vs. histological samples (k 0.82; 95% CI: 0.74-0.90), diagnostic vs. non-diagnostic (k 0.95; 95% CI: 0.85-1.00) and neoplastic vs. non-neoplastic (k 0.94; 95% CI: 0.83-1.00). According to consensus rating, 61 cases were diagnostic samples (60.4%). Histological samples were more likely to lead to a correct diagnosis (OR, 4.1; 95% P=0.027), while neoplastic lesions were less likely to be correctly classified than benign (OR, 0.11; P=0.04). CONCLUSIONS EUS-FNB with the Procore™ 25G needle provided samples for histological examination in only 40% of the cases, with 31% of inadequate specimens, despite excellent results in term of inter-observer variability.

Single-session EUS-guided FNA and biliary drainage with use of a biflanged lumen apposing stent on an electrocautery enhanced delivery system: one-stop shop for unresectable pancreatic mass with duodenal obstruction

Endoscopic palliation of unresectable pancreatic cancer with obstruction of both the duodenum and the common bile duct (CBD) is cumbersome, with successful biliary drainage achieved in only 30% of the cases. In most of them, percutaneous biliary drainage is necessary. We present a patient with an unresectable mass of the pancreatic head causing both CBD and duodenal obstruction who, after an EUS-FNA with rapid onsite cytopathologic evaluation, which revealed pancreatic adenocarcinoma, underwent same-session EUS-guided biliary drainage with use of a newly developed biflanged lumenapposing fully covered metal stent (LAFCMS) mounted on an electrocautery-enhanced delivery system (Hot-AX

Transoesophageal endoscopic ultrasound-guided fine-needle aspiration of pleural effusion for the staging of non-small cell lung cancer

OBJECTIVES The efficacy of endoscopic ultrasound (EUS) for evaluating mediastinal adenopathy in lung cancer is nowadays proven. However, its accuracy for detection of malignant pleural effusion per se has not been yet investigated. Herein we report our experience with EUS for detecting pleural effusion during the staging procedure of non-small cell lung cancer (NSCLC) patients. METHODS Between January 2009 and December 2011, we performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) on 92 selected NSCLC patients to evaluate the T and N factors and to acquire bioptic material and when this was detected, to sample the pleural effusion. RESULTS In 10 patients (8 males and 2 females, mean age 66.9±9.2 years) a pleural effusion was detected and sampled. In 7 out of the 10 cases, the cytological examination of the fluid obtained by EUS-FNA tested positive for malignant cells, thereby upgrading the case to Stage IV, irrespective of T and N statuses. In 3 cases the cytology on the EUS-FNA material was proven to be negative for malignancy thereby allowing patients to be treated with curative intent without further delay. CONCLUSIONS EUS-FNA of the pleural fluid is a safe and simple procedure. Our data, albeit stemming from a limited study population, show that it can be efficient in selected NSCLC cases for obtaining useful material and information with significant impact on the staging and, therefore, on the planning of the optimum therapeutic strategy.