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Frulloni, Luca/0000-0001-7417-2655; Hart, Phil/0000-0003-4346-6196; Capurso, Gabriele/0000-0002-0019-8753; de-Madaria, Enrique/0000-0002-2412-9541; Lohr, Matthias/0000-0002-7647-198X; Frokjaer, Jens Brondum/0000-0001-8722-0070 WOS:000542363500001 PubMed: 32552502 The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added. National Societies Committee of the United European Gastroenterology (UEG) We gratefully acknowledge the support from the National Societies Committee of the United European Gastroenterology (UEG) for the conduct of these guidelines independent from other sources. No other funding was received.

Background and aimThe International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals).MethodsA modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed.ResultsConsensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline ATM mutation carriers with one affected first-degree relative are now considered eligible for surveillance. Experts agreed that preferred surveillance tests are endoscopic ultrasound and MRI/magnetic retrograde cholangiopancreatography, but no consensus was reached on how to alternate these modalities. Annual surveillance is recommended in the absence of concerning lesions. Main areas of disagreement included if and how surveillance should be performed for hereditary pancreatitis, and the management of indeterminate lesions.ConclusionsPancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

Pancreatic cancer (PC) is considered as one of the malignant tumors with poorest survival rate (less than 5% 5-year survival). Despite new developments in imaging techniques, surgery and oncologic treatments, survival rate remains unchanged. In order to improve the outcome of this disease, it would be of interest the development of a screening program trying to detect small asymptomatic tumors or precursor lesions at the time when the disease is still at a curable stage. Although screening in general population is not feasible nowadays, screening programs in high risk individuals may be of help in this setting. A specific population has been defined to be screened, those with a10-fold increased risk for developing the disease (inherited PC syndromes due to inherited gene mutations and individuals with a strong family history of PC with at least 2 first-degree relatives affected, but without a known genetic defect). Regarding the methods for screening, endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) appears to be the most accurate, mainly based in their ability to detect those small pancreatic tumors and precursor lesions (like IPMN and PanIN lesions). In these patients screening should start at the age of 45, or 15 years earlier than the earliest occurrence of PC in the family, whichever is the earlier age. Explorations should be schedule every 1 to 3 years, depending on initial findings.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P

BackgroundAlthough evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported.AimsWe aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19.MethodsAll consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ2 or Fisher’s exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors.ResultsBetween February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58–74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69–86.87)) and presence of GI symptoms (OR=6.17 (1.13–33.67)) were independently associated with major abnormalities at multivariate analysis.ConclusionIn this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy.Trial registration numberClinicalTrial.gov (ID: NCT04318366).

Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle.Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders.A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836).The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

Background and Aims Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage. Little is known about the incidental finding of early-stage PDAC. The aim of the current study was to determine the etiology of small solid pancreatic lesions (≤15 mm) to optimize clinical management. Methods Inclusion criterion for the retrospective study analysis was the incidental finding of primarily undetermined small solid pancreatic lesions ≤15 mm in 394 asymptomatic patients. Final diagnoses were based on histology or cytology obtained by imaging-guided biopsy (and at least 12-month follow-up) and/or surgery. Contrast-enhanced US or contrast-enhanced EUS was performed in 219 patients. Results The final diagnoses of 394 patients were as follows: 146 PDACs, 156 neuroendocrine tumors, 28 metastases into the pancreas from other primary sites, and 64 various other etiologies. Contrast-enhanced US allowed differential diagnosis of PDAC and non-PDAC in 189 of 219 patients (86%). Conclusions Approximately 40% of patients with small solid pancreatic lesions had very early stage PDAC. Approximately 60% of small solid pancreatic lesions ≤15 mm are not PDAC and, therefore, do not require radical surgery. Without preoperative diagnosis, an unacceptably large proportion of patients would be exposed to radical surgery with significant morbidity and mortality.

Background The prevalence of malignancy in patients with small solid pancreatic lesions is low; however, early diagnosis is crucial for successful treatment of these cases. Therefore, a method to reliably distinguish between benign and malignant small solid pancreatic lesions would be highly desirable. We investigated the role of endoscopic ultrasound (EUS) elastography in this setting. Methods Patients with solid pancreatic lesions ≤ 15 mm in size and a definite diagnosis were included. Lesion stiffness relative to the surrounding pancreatic parenchyma, as qualitatively assessed and documented at the time of EUS elastography, was retrospectively compared with the final diagnosis obtained by fine-needle aspiration/biopsy or surgical resection. Results 218 patients were analyzed. The average size of the lesions was 11 ± 3 mm; 23 % were ductal adenocarcinoma, 52 % neuroendocrine tumors, 8 % metastases, and 17 % other entities; 66 % of the lesions were benign. On elastography, 50 % of lesions were stiffer than the surrounding pancreatic parenchyma (stiff lesions) and 50 % were less stiff or of similar stiffness (soft lesions). High stiffness of the lesion had a sensitivity of 84 % (95 % confidence interval 73 % – 91 %), specificity of 67 % (58 % – 74 %), positive predictive value (PPV) of 56 % (50 % – 62 %), and negative predictive value (NPV) of 89 % (83 % – 93 %) for the diagnosis of malignancy. For the diagnosis of pancreatic ductal adenocarcinoma, the sensitivity, specificity, PPV, and NPV were 96 % (87 % – 100 %), 64 % (56 % – 71 %), 45 % (40 % – 50 %), and 98 % (93 % – 100 %), respectively. Conclusions In patients with small solid pancreatic lesions, EUS elastography can rule out malignancy with a high level of certainty if the lesion appears soft. A stiff lesion can be either benign or malignant.

MAIN RECOMMENDATIONSFor pancreatic solid lesions, ESGE recommends performing endoscopic ultrasound (EUS)-guided sampling as first-line procedure when a pathological diagnosis is required. Alternatively, percutaneous sampling may be considered in metastatic disease.Strong recommendation, moderate quality evidence.In the case of negative or inconclusive results and a high degree of suspicion of malignant disease, ESGE suggests re-evaluating the pathology slides, repeating EUS-guided sampling, or surgery.Weak recommendation, low quality evidence.In patients with chronic pancreatitis associated with a pancreatic mass, EUS-guided sampling results that do not confirm cancer should be interpreted with caution.Strong recommendation, low quality evidence.For pancreatic cystic lesions (PCLs), ESGE recommends EUS-guided sampling for biochemical analyses plus cytopathological examination if a precise diagnosis may change patient management, except for lesions ≤ 10 mm in diameter with no high risk stigmata. If the volume of PCL aspirate is small, it is recommended that carcinoembryonic antigen (CEA) level determination be done as the first analysis.Strong recommendation, low quality evidence.For esophageal cancer, ESGE suggests performing EUS-guided sampling for the assessment of regional lymph nodes (LNs) in T1 (and, depending on local treatment policy, T2) adenocarcinoma and of lesions suspicious for metastasis such as distant LNs, left liver lobe lesions, and suspected peritoneal carcinomatosis.Weak recommendation, low quality evidence.For lymphadenopathy of unknown origin, ESGE recommends performing EUS-guided (or alternatively endobronchial ultrasound [EBUS]-guided) sampling if the pathological result is likely to affect patient management and no superficial lymphadenopathy is easily accessible.Strong recommendation, moderate quality evidence.In the case of solid liver masses suspicious for metastasis, ESGE suggests performing EUS-guided sampling if the pathological result is likely to affect patient management, and (i) the lesion is poorly accessible/not detected at percutaneous imaging, or (ii) a sample obtained via the percutaneous route repeatedly yielded an inconclusive result.Weak recommendation, low quality evidence.

RECOMMENDATIONSFor routine EUS-guided sampling of solid masses and lymph nodes (LNs) ESGE recommends 25G or 22G needles (high quality evidence, strong recommendation); fine needle aspiration (FNA) and fine needle biopsy (FNB) needles are equally recommended (high quality evidence, strong recommendation).When the primary aim of sampling is to obtain a core tissue specimen, ESGE suggests using 19G FNA or FNB needles or 22G FNB needles (low quality evidence, weak recommendation).ESGE recommends using 10-mL syringe suction for EUS-guided sampling of solid masses and LNs with 25G or 22G FNA needles (high quality evidence, strong recommendation) and other types of needles (low quality evidence, weak recommendation). ESGE suggests neutralizing residual negative pressure in the needle before withdrawing the needle from the target lesion (moderate quality evidence, weak recommendation).ESGE does not recommend for or against using the needle stylet for EUS-guided sampling of solid masses and LNs with FNA needles (high quality evidence, strong recommendation) and suggests using the needle stylet for EUS-guided sampling with FNB needles (low quality evidence, weak recommendation).ESGE suggests fanning the needle throughout the lesion when sampling solid masses and LNs (moderate quality evidence, weak recommendation).ESGE equally recommends EUS-guided sampling with or without on-site cytologic evaluation (moderate quality evidence, strong recommendation). When on-site cytologic evaluation is unavailable, ESGE suggests performance of three to four needle passes with an FNA needle or two to three passes with an FNB needle (low quality evidence, weak recommendation).For diagnostic sampling of pancreatic cystic lesions without a solid component, ESGE suggests emptying the cyst with a single pass of a 22G or 19G needle (low quality evidence, weak recommendation). For pancreatic cystic lesions with a solid component, ESGE suggests sampling of the solid component using the same technique as in the case of other solid lesions (low quality evidence, weak recommendation).ESGE does not recommend antibiotic prophylaxis for EUS-guided sampling of solid masses or LNs (low quality evidence, strong recommendation), and suggests antibiotic prophylaxis with fluoroquinolones or beta-lactam antibiotics for EUS-guided sampling of cystic lesions (low quality evidence, weak recommendation). ESGE suggests that evaluation of tissue obtained by EUS-guided sampling should include histologic preparations (e. g., cell blocks and/or formalin-fixed and paraffin-embedded tissue fragments) and should not be limited to smear cytology (low quality evidence, weak recommendation).

""AIM: To evaluate the interobserver agreement among pathologists in grading the. quality of specimens obtained with a new 19-gauge endoscopic ultrasound histology. needle.. METHODS AND RESULTS: This multicentre prospective study involved 50 slides. prepared using material obtained with the new needle. Five experienced. pathologists independently reviewed all of the samples, and made assessments of. the following features: the presence of a core, the adequacy of the specimen, the. interpretability of the specimen, and the possibility of performing additional. analyses using the material. Interobserver agreement, determined by Fleiss' kappa. statistic and 95% confidence intervals (CIs), was used as the primary outcome. measure. Overall, the presence of a core was reported in 88% of cases with good. agreement among the pathologists (κ=0.61; 95% CI 0.52-0.70). The specimens were. adequate in 91.2% of cases, and Fleiss' κ was 0.73 (95% CI 0.61-0.81). The. interpretation of the specimens was reported to be 'easy' in approximately 87% of. cases, with moderate agreement among the pathologists (κ=0.44; 95% CI. 0.35-0.53). The possibility of performing additional analyses from the same. sample was rated as positive in approximately 91%, with good agreement (κ=0.66;. 95% CI 0.58-0.75).. CONCLUSIONS: There was excellent interobserver agreement among pathologists in. the assessment of the histological material, especially with regard to sample. adequacy.""

BACKGROUND: The option of obtaining tissue samples for histological examinationduring endoscopic ultrasound (EUS) has theoretical and practical advantages over cytology alone. The aim of this study was to evaluate the feasibility, yield, anddiagnostic accuracy of a new EUS 22-G fine-needle biopsy (FNB) device in patientswith solid pancreatic masses in a multicenter, prospective study.METHODS: All consecutive patients who underwent EUS-guided fine-needle biopsy(EUS-FNB) using a newly developed 22-G FNB needle between September 2010 andOctober 2010 were enrolled in the study. The EUS-FNB technique was standardizedamong the participating endoscopists. Only a single needle pass was performed.RESULTS: A total of 61 patients (35 males, mean age64.2±12.4years) with solidpancreatic masses with a mean size of 32.4±8.5mm (range13-90mm)participated. EUS-FNB was performed through the duodenum in 35 cases (57.4%) andwas technically feasible in all but one of the 61 (98.4%) patients withoutcomplications. Tissue samples for histological examination were obtained from 55 patients (90.2%) and were deemed adequate in 54 of the cases (88.5%). Thediagnoses established by EUS-FNB were adenocarcinoma (39 patients),neuroendocrine tumors (5), chronic focal pancreatitis (5), sarcoma (2), lymphoma (1), acinar cellular tumor (1), and pancreatic metastasis from renal cellcarcinoma (1). In an intention-to-treat (ITT) analysis, sensitivity, specificity,positive predictive value, negative predictive value, and accuracy for thehistologic diagnosis of a pancreatic mass were 87.5, 100, 100, 41.7, and 88.5%, respectively.CONCLUSIONS: EUS-FNB was technically feasible in 98% of patients with a solidpancreatic mass. A suitable sample for histological evaluation was obtained in88.5% of the cases after only one single needle pass. The apparently lownegative predictive value is likely to be improved by increasing the number ofneedle passes.

Background & Aims By using strain assessment, real-time endoscopic ultrasound (EUS) elastography provides additional information about a lesion's characteristics in the pancreas. We assessed the accuracy of real-time EUS elastography in focal pancreatic lesions using computer-aided diagnosis by artificial neural network analysis. Methods We performed a prospective, blinded, multicentric study at of 258 patients (774 recordings from EUS elastography) who were diagnosed with chronic pancreatitis (n = 47) or pancreatic adenocarcinoma (n = 211) from 13 tertiary academic medical centers in Europe (the European EUS Elastography Multicentric Study Group). We used postprocessing software analysis to compute individual frames of elastography movies recorded by retrieving hue histogram data from a dynamic sequence of EUS elastography into a numeric matrix. The data then were analyzed in an extended neural network analysis, to automatically differentiate benign from malignant patterns. Results The neural computing approach had 91.14% training accuracy (95% confidence interval [CI], 89.87%–92.42%) and 84.27% testing accuracy (95% CI, 83.09%–85.44%). These results were obtained using the 10-fold cross-validation technique. The statistical analysis of the classification process showed a sensitivity of 87.59%, a specificity of 82.94%, a positive predictive value of 96.25%, and a negative predictive value of 57.22%. Moreover, the corresponding area under the receiver operating characteristic curve was 0.94 (95% CI, 0.91%–0.97%), which was significantly higher than the values obtained by simple mean hue histogram analysis, for which the area under the receiver operating characteristic was 0.85. Conclusions Use of the artificial intelligence methodology via artificial neural networks supports the medical decision process, providing fast and accurate diagnoses.

Background EUS-guided FNA is an efficacious technique for sampling intraintestinal and extraintestinal mass lesions. However, cytology has limitations to its final yield and accuracy, which may be overcome if histological specimens are provided to the pathologist. Objective To evaluate feasibility, yield, and diagnostic accuracy of a newly developed 19-gauge, fine-needle biopsy (FNB) device. Design Multicenter, pooled, cohort study. Setting Five medical centers. Patients This study involved 109 consecutive patients with 114 intraintestinal or extraintestinal mass lesions and/or peri-intestinal lymph nodes. Intervention EUS-guided FNB (EUS-FNB) with a newly developed, 19-gauge, FNB device. Main Outcome Measurements Percentage of cases in which pathologists classified the sample quality as optimal for histological evaluation and the overall diagnostic accuracy compared with a composite criterion-standard diagnosis. Results We evaluated 114 lesions (mean [± standard deviation] size 35.1 ± 18.7 mm; 84 malignant [73.7%] and 30 [26.3%] benign). EUS-FNB was technically feasible in 112 lesions (98.24%). Sample quality was adequate for full histological assessment in 102 lesions (89.47%). In 98 cases (85.96%), diagnosis proved to be correct according to criterion-standard diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for diagnosis of malignancy were 90.2%, 100%, 100%, 78.9%, and 92.9%, respectively. Limitations Use of a surrogate criterion-standard diagnosis, including clinical follow-up when no surgical specimens were available, mainly in benign diagnoses. Conclusion Performing an EUS-FNB with a new 19-gauge histology needle is feasible for histopathology diagnosis of intraintestinal and extraintestinal mass lesions, offering the possibility of obtaining a core sample for histological evaluation in the majority of cases, with an overall diagnostic accuracy of over 85%.