P. Carucci

Endosonography in decision making and management of gastrointestinal endocrine tumors.

OBJECTIVE gastroenteropancreatic (GEP) neuroendocrine tumors, suspected on clinical basis, are often difficult to localize. We report our experience with endoscopic ultrasonography (EUS) in the preoperative localization of pancreatic endocrine tumors (PETs), compared to other imaging modalities, and in staging and following up carcinoid tumors (CTs) of the gastrointestinal (GI) wall. METHODS 50 patients (20 males; mean age 54 years), 39 with suspected PETs and 11 with GI CTs underwent EUS (Olympus GF-UM2 or GF-UM3). EUS data could be compared with resected specimens in 25 out of the 39 PETs and five out of the 11 CTs. RESULTS in the PETs group 42 tumors (35<20 mm) were removed: 23 in the pancreas, eight in the duodenum, and 11 in the lymph nodes. EUS correctly localized 20 out of the 23 (87%) pancreatic tumors, included 11 out of the 12 (91.6%) insulinomas, three out of the eight (37.5%) duodenal gastrinomas, and ten out of the 11 (90.9%) metastatic lymph nodes. Furthermore EUS accurately evaluated the depth of parietal invasion of CTs in three out of four patients (75%) (two after and one prior to endoscopic resection). In three patients EUS was confirmed as normal on resected specimens (two pancreas and one stomach). In the PETs group, a correct localization was obtained by ultrasonography (US) only in 17.4% of cases, by computed tomography (CT) in 30.4%, by magnetic resonance imaging (MRI) in 25%, by angiography in 26.6%, and by somatostatin receptor scintigraphy in 15.4%. CONCLUSION EUS must be considered the first-intention method in localizing PETs and is helpful in decision making and management of GEP endocrine tumors.

Preliminary experience with a new cytology brush in EUS-guided FNA

BACKGROUND Despite the high diagnostic yield of EUS-guided FNA, room for technical improvements remains. Recently, the EchoBrush (Cook Endoscopy, Winston-Salem, NC), a disposable cytologic brush, was introduced to the market. To date, only 1 study, limited to 10 pancreatic cyst cases, using this device has been published. OBJECTIVE To assess the diagnostic yield of the EchoBrush in a cohort of consecutive patients, irrespective of the target lesion. DESIGN Case series. SETTING Tertiary care university hospital (Molinette Hospital, Turin, Italy). PATIENTS Thirty-nine consecutive patients (12 with solid pancreatic masses, 12 with pancreatic cysts, 7 with enlarged lymph nodes, and 8 with submucosal masses) were enrolled. INTERVENTIONS The material collected with the EchoBrush and with a standard FNA needle was double-blind evaluated by 2 cytopathologists. MAIN OUTCOME MEASUREMENTS Adequacy of the sample and sensitivity and specificity of the EchoBrush method. RESULTS Adequate material for cytologic analysis was collected in 17 of 39 patients (43.6%) with a single pass of the EchoBrush. Results were better for pancreatic lesions (for solid and cystic lesions, the adequacy was 58.3% and 50%, respectively); adequacy was low (28.6% and 25%, respectively) for lymph nodes and submucosal masses. The overall sensitivity and specificity were 57.9% and 31.2%, respectively. There were no adverse events with the procedure. LIMITATION Preliminary study. CONCLUSIONS This report suggests that the EchoBrush may provide adequate cellularity to diagnose solid and cystic pancreatic lesions. More extensive studies are needed to compare the EchoBrush and standard needles.

Diagnosis of deep-seated lymphomas by endoscopic ultrasound-guided fine needle aspiration combined with flow cytometry.

A. Stacchini, P. Carucci, D. Pacchioni, G. Accinelli, A. Demurtas, S. Aliberti, M. Bosco, M. Bruno, A. Balbo Mussetto, M. Rizzetto, G. Bussolati and C. De Angelis 
Diagnosis of deep‐seated lymphomas by endoscopic ultrasound‐guided fine needle aspiration combined with flow cytometry

Adrenaline plus cyanoacrylate injection for treatment of bleeding peptic ulcers after failure of conventional endoscopic haemostasis

BACKGROUND Endoscopic therapy is a safe and effective method for treating non-variceal upper gastrointestinal bleeding. However failure of therapy, in terms of continuing bleeding or rebleeding, is seen in up to 20%. Cyanoacrylate is a tissue glue used for variceal bleeding that has occasionally been reported as an alternative haemostatic technique in non-variceal haemorrhage. AIM To retrospectively describe personal experience using cyanoacrylate injection in the management of bleeding ulcers after failure of first-line endoscopic modalities. PATIENTS AND METHODS Between January 1995 and March 1998, 18 [12 M/6 F, mean age 68.1 years) out of 176 patients, referred to our Unit for non-variceal upper gastrointestinal bleeding, were treated with intralesional injection of adrenaline plus undiluted cyanoacrylate. Persistent bleeding after endoscopic haemostasis or early rebleeding were the indications for cyanoacrylate treatment. RESULTS Definitive haemostasis was achieved in 17 out of 18 patients treated with cyanoacrylate. One patient needed surgery. No early or late rebleeding occurred during the follow-up. No complications or instrument lesions related to cyanoacrylate were recorded. CONCLUSIONS In our retrospective series, cyanoacrylate plus adrenaline injection was found to be a potentially safe and effective alternative to endoscopic haemostasis when conventional treatment modalities fail in controlling bleeding from gastroduodenal ulcers.

Unexplained common bile duct dilatation with normal serum liver enzymes: diagnostic yield of endoscopic ultrasound and follow-up of this condition.

Background: There is scant literature about common bile duct (CBD) dilatation with normal liver function tests (LFTs). Aims: The aims of this study were to assess the diagnostic yield of endoscopic ultrasound (EUS) in patients with CBD dilatation, normal LFTs, and prior inconclusive imaging tests, and to assess the natural history of these subjects. Methods: We retrospectively reviewed our EUS database for patients referred for evaluation of CBD dilatation, normal LFTs, and prior inconclusive imaging. We excluded patients with a prior endoscopic retrograde cholangiopancreatography or a history of biliary obstruction, pancreatitis, or jaundice. Follow-up data were retrieved from medical records or by calling the general practitioners, referring specialists, patients, or their closest relatives. Results: A total of 57 patients were enrolled. The mean CBD diameter was 12.5±3.6 mm. The majority of patients (50.8%) were asymptomatic. Abnormal EUS findings were recorded in 12 (21%) subjects: 6 patients had a periampullary diverticulum, 2 had ampullary adenoma, 2 had signs of chronic pancreatitis, 1 had a cancer of the pancreatic head, and 1 had a 7 mm CBD stone. Neither age, sex, prior cholecystectomy, clinical presentation, CBD diameter, nor a dilated main pancreatic duct were predictors of abnormal EUS findings. None of the patients complained of biliary symptoms or showed abnormal LFTs on long-term follow-up. Conclusions: CBD dilatation with normal liver chemistry is not always a benign condition. Even when prior imaging tests are negative, EUS may allow to diagnose conditions overlooked by standard diagnostic imaging.

ENDOSCOPIC ULTRASOUND FINE‐NEEDLE ASPIRATION IN THE DIAGNOSIS OF INTRAPANCREATIC ACCESSORY SPLEEN

Intrapancreatic accessory spleens represent a potential pitfall in the diagnosis of pancreatic lesions by mimicking pancreatic neoplasms, in particular, neuroendocrine tumors. We report two cases of intrapancreatic accessory spleen discovered in patients with a previous history of neuroendocrine tumors. Case 1. A 39-year-old woman with a history of welldifferentiated pancreatic neuroendocrine tumor with liver metastases underwent follow-up endoscopic ultrasound (EUS) (Olympus GF-UCT140AL5; Olympus America, Melville, NY, USA) revealing a well-defined, homogeneous, hypoechoic lesion in the tail (Ø13 mm), suggesting a neuroendocrine localization; echo-Doppler showed arterial and venous supply. EUS-fine-needle aspiration (FNA) was carried out with a 22-G needle (Wilson-Cook, WinstonSalem, NC, USA), (Fig. 1). A dedicated cytopathologist carried out a rapid on-site evaluation (ROSE): two slides were smeared and remaining material preserved for cellblock preparation. Smears showed tangles of small blood vessels and a population of heterogeneous lymphocytes, intermixed with neutrophils, histiocytes and plasma cells (Fig. 2). Flow cytometry showed a polyclonal B and T cell population. Immunocytochemistry for cytokeratin AE1/AE3 on cell-block sections was negative.These findings were diagnostic for accessory spleen. Case 2. A 71-year-old man with a diagnosis of a welldifferentiated, somatostatin-producing neuroendocrine tumor underwent a pancreasectomy plus splenectomy in 2007. Follow-up EUS revealed a mass of 2 cm in the pancreatic head, hypo-isoechoic with smooth margins. EUS-FNA was carried out and ROSE smears showed mostly lymphocytes interspersed with other inflammatory cells. Cell-block sections showed characteristic features of both white and red pulp (lymphoid tissue with traversing vascular structures, lined by elongated, flat endothelial cells with typical beanshaped nuclei having a longitudinal cleft) and immunocytochemistry confirmed the previous findings: AE1/AE3, chromogranin and synaptophysin were CD68 KP-1 and CD8 stained the sinus endothelial lining cells, resulting in a diagnosis for accessory spleen. We confirm that EUS-FNA is a safe and sensitive test that allows an accurate diagnosis of intrapancreatic accessory spleen, ruling out neuroendocrine tumor and avoiding unnecessary surgery.

Place de l'échoendoscopie en Italie

RésuméL’échoendoscopie a fait ses débuts en Italie en 1981 grâce au travail d’un groupe de pionniers de l’Université de Bologne. A compter de cette date, l’échoendoscopie italienne a fait de considérables progrès en termes de technique et d’organisation tant sur le plan quantitatif que qualitatif, mais beaucoup de travail reste à faire surtout en ce qui concerne la ponction guidée sous écho-endoscopie (EUS-FNA) à visée diagnostique et thérapeutique. Dans ce domaine, une collaboration active entre le Groupe de Travail Italien pour l’échoendoscopie et les Clubs Français et Belge est largement souhaitable.SummaryEndoscopic Ultrasound in Italy started in 1981 thanks to the work of a pioneeristic group at the University of Bologna. In the following years endoscopic ultrasound in Italy has made good progress in terms of number of examinations, quality of the technique and organization, but a huge quantity of work still remains to be done particularly in the field of diagnostic and therapeutic EUS-FNA. For this purpose an active collaboration between the Italian Group of Work for Endosonography and the French and Belgian Clubs would really be highly desirable.

Endoscopic ultrasound-guided fine needle aspiration in the diagnosis of pelvic metastasis of hepatocellular carcinoma: case report and review of literature.

Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver. It shows a propensity to directly invade the portal and hepatic veins, but it also spreads by lymphatic and hematogenous routes. The most common extrahepatic metastatic sites of HCC are the lung, regional and distant lymph nodes, adrenal gland, and bone. More rarely, HCC can metastasize to the peritoneum, brain, rectum, heart, and ovary. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are very useful in identifying HCC metastases, but the procurement of a tissue sample for histological confirmation may be very challenging, especially when a suspected lesion is found in an unusual site. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has become widely accepted as a useful technique to obtain tissue samples from lesions of gastrointestinal tract and adjacent structures, including the liver, pancreas, mediastinum, abdomen, and pelvis. We present the first case in the literature of EUS-FNA diagnosis of HCC metastasizing close to the rectal wall.

P0364 : Clinic evaluation of circulating micrornas as potential biomarkers of hepatocellular carcinoma in patients with HBV chronic infection

CLINIC EVALUATION OF CIRCULATING MICRORNAS AS POTENTIAL BIOMARKERS OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HBV CHRONIC INFECTION / Caviglia, G.P.; Abate, M.L.; Petrini, E.; Gaia, S.; Manzini, P.; Carucci, P.; Rizzetto, M.; Smedile, A. .. In: JOURNAL OF HEPATOLOGY. ISSN 0168-8278. (2015), pp. 447-448. ((Intervento presentato al convegno 50th Annual Meeting of the European Association for the Study of the Liver tenutosi a Vienna, Austria nel 22-26 April, 2015. Original Citation: CLINIC EVALUATION OF CIRCULATING MICRORNAS AS POTENTIAL BIOMARKERS OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HBV CHRONIC INFECTION

P1028 NON-INVASIVE SCORE SYSTEM FOR FIBROSIS (NISF) IN CHRONIC LIVER DISEASE: A NEW MODEL COMBINING BIOCHEMICAL, ELASTOGRAPHIC AND ULTRASOUND DATA

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disorders characterised by hepatic steatosis, which may be benign (NAFL) or which may progress via inflammation and fibrosis to nonalcoholic steatohepatitis (NASH) and then to cirrhosis and liver failure. Liver biopsy is the standard diagnostic approach for NAFL/NASH. However it has limitations due to sampling site variability, cost and procedure-related morbidity. Appropriate NAFLD-specific circulating biomarkers may enable diagnosis, staging and monitoring of NAFL/NASH with fewer biopsies. Circulating fragments of cytokeratin-18 (K18), a marker of hepatocyte death, have been shown in several studies to indicate the transition from benign fatty liver to NASH, with a risk of fibrosis, in patients with NAFLD. Our goal was to develop a highly specific serum K-18 assay to monitor hepatic disease severity in patients with different stages of NAFLD. Methods: An assay to measure K18 fragments in serum using electrochemiluminescence (ECL) technology was developed using proprietary K18 fragment-specific antibodies: one labelled with an ECL-active ruthenium chelate reporter and a second antibody bound to paramagnetic beads. Results: Thirty known NAFL and NASH patient serums with assigned NAS scores were evaluated. K18 fragment concentrations in biopsy-proven NASH were elevated compared to NAFL (1232U/L and 345U/L respectively). The results also demonstrated good correlation with the M30 antibody assay. Conclusions: An ECL-based assay has been developed for the quantitation of serum K18 fragments. This new diagnostic test may enable routine monitoring in both central laboratories and physician’s offices of disease severity and progression in patients with NAFLD.