EUS-guided tissue acquisition in the study of the adrenal glands: Results of a nationwide multicenter study.

BACKGROUND: There are limited data about the role of endoscopic ultrasound-guided tissue acquisition (EUS-TA), by fine needle aspiration (EUS-FNA) or biopsy (EUS-FNB), in the evaluation of the adrenal glands (AG). The primary aim was to assess the diagnostic yield and safety. The secondary aims were the malignancy predictors, and to create a predictive model of malignancy. METHODS: This was a retrospective nationwide study involving all Spanish hospitals experienced in EUS-TA of AGs. Inclusion period was from April-2003 to April-2016. Inclusion criteria: all consecutive cases that underwent EUS-TA of AGs. EUS and cytopathology findings were evaluated. Statistical analyses: diagnostic accuracy of echoendoscopist's suspicion using cytology by EUS-TA, as gold standard; multivariate logistic regression model to predict tumor malignancy. RESULTS: A total of 204 EUS-TA of AGs were evaluated. Primary tumor locations were lung70%, others19%, and unknown11%. AG samples were adequate for cytological diagnosis in 91%, and confirmed malignancy in 60%. Diagnostic accuracy of the endosonographer's suspicion was 68%. The most common technique was: a 22-G (65%) and cytological needle (75%) with suction-syringe (66%). No serious adverse events were described. The variables most associated with malignancy were size>30mm (OR2.27; 95%CI, 1.16-4.05), heterogeneous echo-pattern (OR2.11; 95%CI, 1.1-3.9), variegated AG shape (OR2.46; 95%CI, 1-6.24), and endosonographer suspicion (OR17.46; 95%CI, 6.2-58.5). The best variables for a predictive multivariate logistic model of malignancy were age, sex, echo-pattern, and AG-shape. CONCLUSIONS: EUS-TA of the AGs is a safe, minimally invasive procedure, allowing an excellent diagnostic yield. These results suggest the possibility of developing a pre-EUS procedure predictive malignancy model.

Refinement of screening for familial pancreatic cancer.

OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. METHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. RESULTS: 253 IAR with a median age of 48 (25-81) years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50 years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50 years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12 months (n=180) or IAR that decided to be screened at ≥24 months intervals (n=30). CONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.

PanGen-Fam: Spanish registry of hereditary pancreatic cancer.

PURPOSE: To describe the organisation of the registry and the preliminary results in terms of characteristics of high-risk pancreatic ductal adenocarcinoma (PDAC) families recruited to date and findings of the screening programme. To compare early onset sporadic cases (⩽50 years), sporadic cases (>50 years) and cases with family history of cancer, for PDAC possible risk factors. METHODS/PATIENTS: Families with hereditary cancer syndromes predisposing to PDAC were recruited from two main sources: Spanish hospitals participating in PanGenEU, a pan-European multicentre case-control study, and their genetic counseling unit. Individuals at high-risk of PDAC were enrolled into a screening programme, consisting of Endoscopic ultrasound, computerised tomography, magnetic resonance imaging. Genetic testing of candidate genes was offered according to each patient's risk. RESULTS: Among 577 consecutive PDAC cases, recruited via PanGenEU, 36 (6%) had ⩾2 first-degree relative with PDAC: Familial pancreatic cancer (FPC). So far PanGen-Fam has recruited 42 high-risk PDAC families; 25 (60%) had FPC. Five index cases with cancer were positive for BRCA2 and one for BRCA1 germline mutations. In the second year of prospective PDAC screening, one neuroendocrine tumour and a high-grade dysplasia lesion suspicious of carcinoma were diagnosed among 41 high-risk individuals. Furthermore EUS detected chronic-pancreatitis-like parenchymal changes in 15 patients. CONCLUDING STATEMENT: The identification and recruitment of PDAC high-risk families into the PanGen-Fam registry provides an opportunity to detect early onset cancer and precursor pancreatic cancer lesions at a potentially curative stage and to increase the knowledge of the natural history of the disease.

Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about endoscopic ultrasound (EUS)-guided sampling in gastroenterology, including EUS-guided fine needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB), of submucosal tumors, diffuse esophageal/gastric wall thickening, pancreatic solid masses and cystic-appearing lesions, mediastinal lesions unrelated to lung or esophageal cancer, cancer of the esophagus, stomach, and rectum, lymph nodes of unknown origin, adrenal gland masses, and focal liver lesions. False-positive cytopathological results and needle tract seeding are also discussed. The present Clinical Guideline describes the results of EUS-guided sampling in the different clinical settings, considers the role of this technique in patient management, and makes recommendations on circumstances that warrant its use. A two-page executive summary of evidence statements and recommendations is provided. A separate Technical Guideline describes the general technique of EUS-guided sampling, particular techniques to maximize the diagnostic yield depending on the nature of the target lesion, and sample processing. The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling.

Impact of endoscopic ultrasonography on the management of a prospective cohort of 700 consecutive patients referred for diagnostic endoscopic ultrasonography.

BACKGROUND: endoscopic ultrasonography (EUS) is a high accuracy technique for the study of many digestive diseases. The degree of knowledge about the impact of EUS on the management of these patients is inadequate. AIM: to determine the therapeutic impact of endoscopic ultrasonography (EUS) on a prospective cohort of patients. METHODS: all patients referred for EUS over a period of 2 years were prospectively evaluated in order to asses: 1. EUS provides new information not previously known; 2. theoretic impact of EUS on patient management; 3. real impact of EUS on final therapy; 4. changes in the aggressiveness of the therapeutic decision after EUS. RESULTS: 700 patients were included. Preoperative assessment of digestive tumors was the commonest indication. EUS provided "new information" in the 89% of the patients. With regard to endoscopist opinion, these findings should alter the management in 79% of patients ("theoretic impact"). However, EUS prompted a change in the management in 67% of patients ("real impact"). Final therapy post-EUS was less aggressive in 34% of patients. Changes in therapeutic decision were associated with EUS findings, alcohol intake and age ≥ 57 years old. CONCLUSIONS: 1) EUS findings, advanced age, and alcohol intake are associated with a change in the management in 2 out of every 3 patients referred for EUS. 2) Therapeutic decision (post-EUS) is less aggressive in a third of these patients, what should represent a significant economic saving.

Training model for teaching endoscopic submucosal dissection of gastric tumors.

INTRODUCTION: The elevated risk of complications and technical complexity of endoscopic submucosal dissection (ESD) has limited its implementation in our medical system. OBJECTIVE: To design and evaluate a training program for learning the ESD technique. METHODS: Four endoscopists with no experience with ESD underwent a 4-step training program: 1) review of the existing literature, didactic material, and theoretical aspects of ESD; 2) ESD training in an ex-vivo animal model; 3) ESD training in an in-vivo animal model (supervised by ESD expert); and 4) ESD performance in a patient. A standard gastroscope and an ESD knife (IT, Flex or Hook-knife Olympus) were employed. The classical ESD technique was performed: rising of the lesion, circumferential incision, and submucosal dissection. RESULTS: Ex-vivo animal model: 6 x swine stomach/esophagus -cost < 100 euro; 6 x ESD: antrum (n = 2), body (n = 3) and fundus/cardia (n = 1)-; size of resected specimen: 4-10 cm; ESD duration: 105-240 minutes; therapeutic success: 100%; complications: perforation (1/6: 16%) sealed with clips. In-vivo animal model: 6 ESD (antrum/body of stomach: 4; esophagus: 2); size: 2-5 cm; duration: 40-165 minutes; success: 100%; complications: 0%. PATIENT: ESD of a gastric lesion located in the antrum/body; size: 3 cm; duration 210 minutes; a complete resection was achieved; no complications. CONCLUSIONS: The results of the present study support the usefulness of this model for learning ESD in our system.

Linear EUS: the clinical impact of N staging in esophageal carcinoma.

This review article focuses on nodal staging of esophageal cancer. Transesophageal endoscopic ultrasound (EUS) is the most accurate technique for preoperative local-regional staging of esophageal carcinoma (TN staging), once the CT and/or the PET scan have excluded the presence of distant metastasis. EUS guided fine needle aspiration (EUS-FNA) helps improve diagnostic accuracy in esophageal cancer lymph node staging. In certain subgroup of patients who present with a number of EUS lymph node criteria, EUS FNA may be avoided without affecting diagnostic accuracy. In tumors of the distal esophagus detection and biopsy of celiac lymph nodes may be successfully performed by EUS and EUS FNA, and important therapeutic decissions may be derived from such a practice.

Endoscopic ultrasound and fine needle aspiration in inflammatory and cystic pancreatic pathology.

To achieve an accurate diagnosis on the nature of pancreatic cystic lesions may be difficult. This review article attempts to provide an overview of the potential role of endoscopic ultrasound (EUS) and EUS guided fine needle aspiration in the evaluation of cystic lesions of the pancreas.

Effect of Helicobacter pylori eradication therapy in rosacea patients.

OBJECTIVE: The causal relation between rosacea and Helicobacter pylori infection is discussed. We evaluated the clinical evolution of rosacea after infection eradication. PATIENTS AND METHODS: We have prospectively studied 44 patients diagnosed with rosacea. Helicobacter pylori infection was determined, and infected patients were treated with eradication therapy. The evolution of dermatological symptoms in a subgroup of 29 infected patients in whom eradication had been achieved was followed during 16.8 (+/- 17.8) months. Median age was 50.6 (+/- 14.1) years for 22 women (75.9%) and 7 men (24.1%). Clinical response according to gender and clinical subtype of rosacea was evaluated. RESULTS: Complete improvement was observed in 10 patients (34.5%; 95% CI: 18.6-54.3%), relevant improvement in 9 (31.1%; 95% CI: 16-51%), poor improvement in 5 (17.2%; 95% CI: 6.5-36.4%), and absence of improvement in 5 cases (17.2%; 95% CI: 6.5-36.4%). No significant differences in dermatological evolution according to sex were observed. Regarding subtype of rosacea there was a relevant improvement in 83.3% (95% CI: 64.1-93.8%) of cases with papulopustular type as opposed to 36.5% (95% CI: 20-56.1%) of cases with erythematous predominance, p = 0.02. CONCLUSIONS: Based on these results, the relation between Helicobacter pylori and rosacea is supported, and infection should be investigated in these patients because an appreciable percentage of patients diagnosed with rosacea and Helicobacter pylori infection can benefit from eradication therapy, mainly in the papulopustular subtype.

Long-term persistence of molecular disease after histological remission in low-grade gastric MALT lymphoma treated with H. pylori eradication. Lack of association with translocation t(11;18): a 10-year updated follow-up of a prospective study.

BACKGROUND: Localized low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma can regress after Helicobacter pylori eradication, but IgV(H) gene monoclonality may persist. We studied the long-term histological and molecular follow-up of 24 patients and the possible association of t(11;18) with the persistent monoclonality. PATIENTS AND METHODS: From January 1994, 24 untreated patients with stage I low-grade gastric MALT lymphoma associated with H. pylori were prospectively studied. They all received eradication treatment and were sequentially followed-up with endoscopies for histological and molecular studies. Rearrangement of the IgV(H) gene was studied by PCR analysis. MALT1 locus alterations were studied by FISH. RESULTS: Twenty-two of the 24 patients (91%) achieved disappearance of the lymphoma. Eighteen (82%) of the 22 histologically cured patients and 16 of the 19 (84%) with long follow-up had monoclonality. Three patterns of development of IgV(H) gene rearrangements were observed: four patients (21%) had polyclonal rearrangements; eight (58%) had maintained/intermittent monoclonality and four (21%) had occasional monoclonality, mostly after H. pylori reinfection. Only one patient (6%) with persistent monoclonality relapsed. The remaining 18 patients maintained the remission, despite the persistent monoclonality in 15, for a median of 66 months (range 20-113). t(11;18) was not found in any of the patients with persistent monoclonality. Time and the number of endoscopies performed were not related with the occurrence of monoclonality. CONCLUSIONS: In stage I low-grade gastric MALT lymphoma eradication of H. pylori achieves prolonged histological remission in 90% of patients, but molecular remission is not accomplished in most cases. Molecular disease persists for years, but is not associated with t(11;18).

Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma.

BACKGROUND: Preoperative identification of lymph node metastases associated with esophageal carcinoma may influence treatment. EUS is the most accurate method for locoregional staging of these tumors. The impact of EUS-guided fine-needle aspiration (EUS-FNA) on lymph node staging in esophageal carcinoma is unclear. METHODS: From May 1996 to May 1999, 74 patients with esophageal carcinoma underwent preoperative EUS. After October 1998 EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. The results of EUS with and without FNA were retrospectively reviewed and compared. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Ten of the 74 patients had to be excluded for lack of lymph node stage confirmation. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group). RESULTS: The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Complications comprised 1 patient who developed self-limited bleeding after dilation that did not preclude completion of the EUS (1%, 95% CI [0%, 7%]). CONCLUSIONS: EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.

EUS-guided fine-needle aspiration combined with flow cytometry and immunocytochemistry in the diagnosis of lymphoma.

BACKGROUND: Limited information is available regarding the use of EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of lymphoproliferative disorders. The aim of this study was to evaluate the yield of this technique in the primary diagnosis of lymphoma. METHODS: The records were reviewed of 38 consecutive patients with GI lesions and/or enlarged lymph nodes identified on imaging studies that raised a suspicion of lymphoma who underwent EUS-FNA of lymph nodes or the gut wall. Final diagnosis was based on clinical follow-up, imaging studies, or surgical findings. RESULTS: Twenty-three patients with lymphoma and 15 patients with benign disease or reactive lymphadenopathy were identified. The overall sensitivity, specificity, and accuracy of EUS-FNA cytology with flow cytometry/immunocytochemistry (FC/IC) for the diagnosis of lymphoma were, respectively, 74%, 93%, and 81%. When comparing patients who had EUS-FNA with FC/IC versus those who had EUS-FNA without FC/IC, sensitivity was 86% versus 44% (p = 0.04), specificity was 100% versus 90% (not significant), and accuracy was 89% versus 68% (not significant). CONCLUSION: EUS-FNA can provide cytology specimens diagnostic for lymphoma. Selective use of FC/IC in patients with suspected lymphoma improves the yield of EUS-FNA and may guide diagnostic evaluation and treatment decisions.

Initial experience with a steerable, phased vector array ultrasound catheter in the GI tract.

BACKGROUND: EUS requires a significant capital outlay. The ability to perform high-resolution phased array scanning and Doppler interrogation by using a catheter that interfaces with a standard US console could increase the accessibility of EUS. Recently, an electronic phased-array US catheter was developed for intracardiac use. To date, this technology has not been applied to the GI tract. The aim of this study is to determine the feasibility and imaging characteristics of a new phased array scanning US catheter in the GI tract. METHODS: Swine were placed under general anesthesia. This study used a 100 cm, 10F, torquable catheter with 4-way tip deflection to greater than 90 degrees. The catheter tip houses a phased vector array transducer with variable frequency (5.5-10 MHz) and variable focal distance. It has pulsed/color and power Doppler capability. The probe was passed through a therapeutic flexible sigmoidoscope into the upper GI tract. Acoustic coupling was achieved via a condom filled with water or by gastric water infusion. Needle visualization experiments were performed with a second endoscope (also passed per oral) with a standard EUS-guided fine needle aspiration needle. RESULTS: Acoustic coupling was easily achieved. Resolution of the GI wall into characteristic layers (esophagus 5, stomach 7) was demonstrated. At 5.5 MHz, tissue resolution and Doppler imaging were excellent to greater than 10 cm from the transducer. A 22-gauge EUS-guided fine needle aspiration needle was easily visualized at depth greater than 4 cm. Flow in gastric, hepatic, and pancreatic parenchymal vessels approximately 1 mm diameter was visualized by using power and color Doppler. CONCLUSIONS: This 10F array US catheter is capable of high-resolution two-dimensional imaging of the gut wall as well as high-quality Doppler imaging. The Doppler capabilities of this equipment may have new GI applications.