Quality of Tissue Samples Obtained by Endoscopic Ultrasound-Guided Liver Biopsy: A Randomized, Controlled Clinical Trial.

INTRODUCTION: Liver biopsy (LB) remains essential for the diagnosis and staging of parenchymal liver diseases. Endoscopic ultrasound-guided LB (EUS-LB) has emerged as an attractive alternative to percutaneous and transjugular routes. We aimed at comparing the adequacy of samples obtained by EUS-LB with percutaneous LB. METHODS: A single-center, randomized, controlled clinical trial was designed. Patients undergoing LB were randomly assigned to EUS-LB or percutaneous LB groups. EUS-LB was performed with a 19-gauge Franseen core needle through a transduodenal and transgastric route. Percutaneous LB was performed with a 16-gauge Tru-Cut needle. The main outcome was the percentage of adequate samples obtained. Secondary outcomes were the percentage of accurate histologic diagnosis, number of complete portal tracts (CPT), total and longest specimen length (TSL and LSL), sample fragmentation, adverse events, and patients' satisfaction. An adequate specimen was defined as TSL ≥20 mm and including ≥11 CPT. RESULTS: Ninety patients were randomized (44 to EUS-LB and 46 to percutaneous LB) and included in the analysis. The percentage of adequate tissue samples was 32.6% and 70.4% for percutaneous LB and EUS-LB, respectively ( P < 0.001). A final histologic diagnosis was provided in all cases but one. TSL was longer after EUS-LB (23.5 vs 17.5 mm, P = 0.01), whereas the number of CPT was similar in both groups. Sample fragmentation occurred more often after EUS-LB ( P < 0.001). No differences in adverse events were found. Satisfaction reported with both procedures was high. DISCUSSION: EUS-LB is safe and accurate and may be considered an alternative to percutaneous LB for the evaluation of parenchymal liver diseases.

Pancreatic Elastography Predicts Endoscopic Secretin-Pancreatic Function Test Result in Patients With Early Changes of Chronic Pancreatitis: A Prospective, Cross-Sectional, Observational Study.

INTRODUCTION: The endoscopic pancreatic function test (ePFT) has been proposed for the evaluation of patients with suspected early chronic pancreatitis (CP) in the appropriate clinical context, but the cost and duration of the test limit its clinical applicability. Pancreatic secretion decreases as pancreatic fibrosis develops in CP. Pancreatic fibrosis can be quantified by endoscopic ultrasound-elastography (EUS-E). We aim at evaluating whether EUS-E correlates with and could replace ePFT for the evaluation of patients with suspected CP. METHODS: A prospective, cross-sectional, and observational study of patients with clinical suspicion of CP and inconclusive EUS findings was conducted. EUS-E and ePFT were performed. Diagnosis of CP was supported if the ePFT result (bicarbonate peak) was abnormally low (<80 mEq/L). Correlation between EUS-E (strain ratio [SR]) and ePFT results was analyzed by linear regression. Diagnostic accuracy of EUS-E for CP was calculated using ePFT as a reference method. RESULTS: Sixty-one patients were included and analyzed. The mean peak bicarbonate concentration at the ePFT was 63.8 ± 23.6 mEq/L, and it was abnormally low in 50 patients (82.0%). The mean SR was 3.85 ± 1.24. Correlation between SR and bicarbonate secretion was highly significant ( r = 0.715, P < 0.0001). Diagnostic accuracy of EUS-E for CP was 93.4%. DISCUSSION: The degree of pancreatic fibrosis as evaluated by EUS-E correlates significantly with the secretin-stimulated pancreatic secretion of bicarbonate in patients with clinical suspicion of CP and inconclusive EUS findings of the disease. EUS-E could replace ePFT for the evaluation of these patients in clinical practice.

Rapid diagnosis of mucinous cystic pancreatic lesions by on-site cyst fluid glucometry.

INTRODUCTION: Available intracystic biomarkers show a limited accuracy for characterizing cystic pancreatic lesions (CPL). Glucose is an attractive alternative due to its availability, low cost and the possibility of on-site quantification by glucometry. AIM: To evaluate the diagnostic accuracy of on-site glucometry from samples obtained by EUS-FNA in the differential diagnosis between mucinous from non-mucinous CPL. METHODS: Retrospective, multicentre, cross-sectional study of patients who underwent EUS-FNA of a CPL. A derivation and a validation cohorts were evaluated. Intracystic glucose was quantified by on-site glucometry and colorimetry in the lab. Final diagnosis was based on surgical specimens or global evaluation of clinical and imaging data, cytology and intracystic CEA. Diagnostic accuracy was based on Receiver Operating Curve (ROC) curve analysis. Intraclass correlation coefficient (ICC) between on-site and lab glucose levels was calculated. RESULTS: Seventy two patients were finally analysed (40 in the derivation cohort and 32 in the validation cohort). Intracystic glucose levels by on-site glucometry was 12.3 ± 28.2 mg/dl for mucinous CPL and 103.3 ± 58.2 mg/dl for non-mucinous CPL, p < 0.001. For an optimal cut-off point of 73 mg/dl, on-site glucose had a sensitivity, specificity, and positive and negative predictive value for the diagnosis of mucinous CPL of 0.89, 0.90, 0.94, 0.82 respectively in the derivation cohort, and 1.0, 0.71, 0.91, 1.0 respectively in the validation cohort. Correlation of on-site and lab glucose quantification was very high (ICC = 0.98). CONCLUSION: On-site glucometry is a feasible, accurate and reproducible method for the characterization of CPL after EUS-FNA. It shows an excellent correlation with laboratory glucose values. REGISTRATION NUMBER: 2019/612.

Endoscopic drainage with local infusion of antibiotics to avoid necrosectomy of infected walled-off necrosis.

BACKGROUND: Current treatment of infected pancreatic necrosis (IPN) follows a step-up approach. Our group designed a step-up protocol that associates endoscopic drainage with local infusion of antibiotics through transmural nasocystic catheter. Aim of our study was to evaluate our step-up protocol for IPN in terms of proportion of patients avoiding necrosectomy. METHODS: Retrospective analysis of patients admitted with acute pancreatitis (AP) between January 2015 and December 2018. The number of patients who responded to each therapeutic step were analysed: step 1, systemic antibiotics; step 2, endoscopic transmural drainage and local infusion of antibiotics; step 3, endoscopic necrosectomy. RESULTS: 1158 patients with AP were included. 110 patients (8.4%) suffered from necrotising pancreatitis; 48 of them had IPN (42.6% of necrotising pancreatitis) and were treated with systemic antibiotics. Nineteen patients (39.6% of IPN) responded and did not required any invasive therapy. Six patients with IPN on systemic antibiotics died within the first 4 weeks of disease before step 2 could be applied. Urgent surgical necrosectomy in the first 4 weeks was performed in three additional patients. Endoscopic drainage and local antibiotic therapy was performed in the remaining 20 patients; 9 (45% of them) did well and 9 patients underwent necrosectomy (18.7% of IPN). Two patients died on drainage. Overall mortality of the total cohort of AP was 2.53% CONCLUSIONS: Addition of local infusion of antibiotics to endoscopic drainage avoids the need of necrosectomy in half of patients with IPN not responding to systemic antibiotics.

Bismuth-containing quadruple therapy versus concomitant quadruple therapy as first-line treatment for Helicobacter Pylori infection in an area of high resistance to clarithromycin: A prospective, cross-sectional, comparative, open trial.

BACKGROUND: Concomitant quadruple (CQT) or bismuth-containing quadruple therapy (BQT) is recommended as first-line treatment for Helicobacter pylori infection depending on antibiotic resistance. AIM: To compare the efficacy, safety, and compliance of CQT and BQT as first-line therapy for H. pylori eradication in real clinical practice in an area of high resistance to clarithromycin. METHODS: A prospective, open, comparative cross-sectional study including dyspeptic patients >18 years with H. pylori infection and with no previous eradication treatment was performed. CQT (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + metronidazole 500 mg, all given twice daily, for 14 days) or BQT (omeprazole 20 mg twice daily + 3 capsules of Pylera® 4 times a day, for 10 days) was prescribed at the discretion of the prescribing physician. Eradication was tested by 13 C-urea breath test. Efficacy was assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: One hundred and four consecutive patients were included (64.4% female, age 52.9 years). Fifty patients received CQT and 54 BQT. Eradication rate was similar with both therapies at the PP (CQT 97.9%, 95% CI: 93.9-100 vs BQT 96.2%, 95% CI: 90.9-100, P = 0.605) and ITT analyses (CQT 98.0%, 95% CI: 94-100 vs BQT 94.4%, 95% CI: 88.1-100, P = 0.346). The rate of adverse events was also similar with CQT (56%) and BQT (46.3%). One patient in each group discontinued the treatment due to significant adverse events. CONCLUSION: The use of CQT and BQT as first-line treatment against H. pylori is similarly effective and safe strategy in an area of high clarithromycin resistance.

Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis. METHODS: Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests. RESULTS: Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests. CONCLUSIONS: The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.

Increased Risk of Mortality Associated With Pancreatic Exocrine Insufficiency in Patients With Chronic Pancreatitis.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is a common serious complication in chronic pancreatitis (CP); however, little is known about its effect on mortality in these patients. In this study, we assessed the mortality risk of PEI in patients with CP. STUDY: A prospective, longitudinal cohort study conducted in patients with CP under long-term follow-up. CP and PEI were diagnosed using pancreatic imaging and the C-labeled mixed triglyceride breath test, respectively. Multivariate analysis was performed to evaluate the impact of PEI and other clinical features on mortality risk. RESULTS: Patients (N=430) were analyzed (79.1% male; mean age, 47.8 y) during a mean follow-up of 8.6±4.6 years. PEI prevalence was 29.3% and mortality was 10.9%. Most frequent causes of death were cancer (40.4%), infection (21.3%), and acute cardiovascular event (14.9%). Multivariate analyses showed associations between increased mortality and presence of PEI [hazard ratio (HR), 2.59; 95% confidence interval (CI), 1.42-4.71; P<0.003], liver cirrhosis (HR, 3.87; 95% CI, 1.95-7.69; P<0.001), age at diagnosis (HR, 1.05; 95% CI, 1.03-1.09; P<0.001), toxic etiology of CP (HR, 3.11; 95% CI, 1.11-8.70; P<0.05) and respiratory comorbidity (HR, 2.19; 95% CI, 1.12-4.31; P<0.03). Nutritional markers were significantly lower in patients with PEI versus those without PEI (P<0.001) and in those who died versus survivors (P<0.001). CONCLUSIONS: PEI was a significant independent risk factor for mortality in patients with CP. These results support further research into the optimal treatment of PEI to reduce mortality in this population.

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.

OBJECTIVE: The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. DESIGN: Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. RESULTS: A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. CONCLUSIONS: PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.

Feasibility of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) and biopsy (FNB) with a new slim linear echoendoscope.

BACKGROUND: Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) and biopsy (FNB) is considered a very accurate and safe tool for sampling extra-intestinal tumors. Standard echoendosocopes for FNA/FNB are large with a sharpened tip that can be associated with complications. A new slim linearechoendoscope have been developed trying to overcome this limitation. AIM: Of the present study was to evaluate the feasibility; safety and diagnostic yield of this newly developed slim echoendoscope for performing EUS-guided FNA/FNB. METHODS: A pilot observational study was performed. Consecutive patients submitted for a EUS-FNA/FNB were prospectively included in the study. Patients underwent EUS procedure using the new slim linear PENTAX-echoendoscope. Tissue acquisition was done with standard and histology needles. Feasibility and diagnostic yield were evaluated. A descriptive analysis was performed. RESULTS: 87 patients were included (mean age 66.7 years (range 24-90 years), 45 male. Mean size was of lesions sampled were 33.43 +/- 20.8 mm. Esophagus intubation and access to the second portion of the duodenum (D2) were considered easy in all 87 cases (100%). Nineteen procedures (21.8%) were performed from the esophagus, 42 (48.3%) from the stomach, 22 (25.3%) cases from duodenal bulb, and 4 (4.6%) cases from D2. EUS-FNB was feasible in 85 cases (97.7%), failed in 2 pancreatic lesions accessed from D2. Diagnostic yield was 86.21% (95%CI 77.4- 91.9) in the intention-to-treat analysis and 88.24% (95%CI 79.7- 93.5) in per-protocol analysis. There were no complications related to the technique. CONCLUSION: Performing a EUS-FNA/FNB with the newly designed slim scope is feasible and safe for cyto-histopathology diagnosis of intra-intestinal and extra-intestinal mass lesions.

Endoscopic Ultrasound-Guided Tissue Sampling for the Cytohistological Diagnosis of Focal Liver Lesions.

BACKGROUND: Focal liver lesions (FLL) often require cytohistological evaluation. Endoscopic Ultrasound (EUS)-guided tissue acquisition (EUS-TA) is highly accurate in diagnosing pancreatic and gastrointestinal malignancies. The aim of our study was to evaluate the role of EUS-TA in the characterization of FLL. METHODS: A retrospective analysis of a prospective database of patients who underwent EUS-TA for the evaluation of FLL. Diagnostic yield, adverse events and factors associated with diagnostic yield were evaluated as endpoints. The effect of variables such as needle size, lesion size, rapid on-site evaluation (ROSE) and the use of cytological or histological needles were analyzed. RESULTS: A total of 114 cases were included (mean age 68.05 ± 11.35 years, 64 male). A correct diagnosis was made using EUS-TA in 100 of the 114 cases (diagnostic yield of 88%). The EUS-TA of additional extrahepatic lesions during the same EUS procedure increased the diagnostic yield to 94%. No adverse events were reported. Multivariate analysis did not identify any factor influencing the diagnostic yield. CONCLUSIONS: EUS-TA is a highly accurate and safe technique for the differential diagnosis of FLL and could be considered as the primary approach in this setting.

Endoscopic Ultrasound (EUS) Guided Elastography.

Endoscopic ultrasound (EUS) is an essential technique for the management of several diseases. Over the years, new technologies have been developed to improve and overcome certain limitations related to EUS-guided tissue acquisition. Among these new methods, EUS-guided elastography, which is a real-time method for the evaluation of tissue stiffness, has arisen as one of the most widely recognized and available. At present, there are available two different systems to perform an elastographic evaluation: strain elastography and shear wave elastography. Strain elastography is based on the knowledge that certain diseases lead to a change in tissue hardness while shear wave elastography monitored shear-wave propagation and measures its velocity. EUS-guided elastography has shown in several studies high accuracy in differentiating benign from malignant lesions from many different locations, mostly in the pancreas and lymph nodes. Therefore, nowadays, there are well-established indications for this technology, mainly for supporting the management of pancreatic diseases (diagnosis of chronic pancreatitis and differential diagnosis of solid pancreatic tumors) and characterization of different diseases. However, there are more data on new potential indications for the near future. In this review, we will present the theoretical bases of this technology and we will discuss the scientific evidence to support its use.

Endoscopic ultrasonography: Enhancing diagnostic accuracy.

Endoscopic ultrasound (EUS) is an essential technique for the management of several diseases. Over the years, new technologies have been developed because to improve and overcome certain limitations related to EUS guided tissue acquisition. Among these new methods, EUS guided elastography and contrast enhanced EUS has arisen as the most widely recognized and available. We will review in this manuscript the different techniques of elastography and contrast enhancement. Nowadays, there are well establish indications for advance imaging, mainly for supporting the management of pancreatic diseases (diagnosis of chronic pancreatitis and differential diagnosis of solid and cystic pancreatic tumors) and characterization of lymph nodes. However, there are more data on new potential indications for the near future.

Emergent endoscopic ultrasound-guided cholecystoduodenostomy does not prevent R0 resection in a pancreaticoduodenectomy for pancreatic cancer.

Endoscopic ultrasound-guided biliary drainage, mainly choledochoduodenostomy, is commonly used as rescue therapy after Endoscopic Retrograde Cholangiopancreatography (ERCP) in malignant distal biliary obstruction due to un-resectable pancreatic cancer. An alternative when the cystic duct is patent and choledochoduodenostomy is not feasible is performing an Endoscopic Ultrasound-gallbladder drainage. The advent of the Lumen Apposing Metal Stents (LAMS) has shortened and simplified this procedure. However, many concerns exist about the performance of these procedures with metal stents preoperatively in resectable tumors. The evidence about Endoscopic Ultrasound-gallbladder drainage before surgery of pancreatic cancer is scarce. An emergent Endoscopic Ultrasound (EUS)-gallbladder drainage (cholecysto-duodenostomy) was performed due to acute cholangitis in the setting of a resectable pancreatic tumor. Surgery after neoadjuvant therapy was done three months later. A complete resection of tumor was feasible. EUS-guided gallbladder drainage using LAMS does not preclude performing a complete resection of a pancreatic head tumor.

Endoscopic Pancreatic Drainage Improves Exocrine Pancreatic Function in Patients With Unresectable Pancreatic Cancer: A Double-Blind, Prospective, Randomized, Single-Center, Interventional Study.

OBJECTIVES: Exocrine pancreatic insufficiency is a frequent and clinically relevant complication of pancreatic cancer probably secondary to pancreatic duct obstruction. We aimed at evaluating the impact of endoscopic pancreatic drainage on pancreatic function in patients with unresectable pancreatic cancer. METHODS: A double-blind, prospective, randomized, single-center, interventional study was designed. Patients undergoing endoscopic retrograde cholangiopancreatography for jaundice secondary to unresectable pancreatic cancer were randomized to biliary drainage (group A) or biliopancreatic drainage (group B). Pancreatic function was evaluated by 13C-mixed triglyceride breath test before and 2 weeks after endoscopic retrograde cholangiopancreatography. Breath test result is expressed as 13C-cumulative recovery rate. Abdominal symptoms and nutritional markers were evaluated as secondary outcomes. RESULTS: Twenty patients were included. Sixteen patients had exocrine pancreatic insufficiency, and 13 completed the study (7 in group A and 6 in group B). The median absolute improvement of 13C-cumulative recovery rate was of 23.75% (interquartile range, 9.62-31.74) after biliopancreatic drainage compared with -1.92% (interquartile range, -4.17 to 13.92) after biliary drainage (P = 0.015). Nutritional markers improved after biliopancreatic drainage, but not after biliary drainage. CONCLUSIONS: Biliopancreatic and not biliary endoscopic drainage is associated with a significant improvement of exocrine pancreatic function in patients with unresectable pancreatic cancer.

Gastrointestinal mucosal damage in patients with COVID-19 undergoing endoscopy: an international multicentre study.

BACKGROUND: Although evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported. AIMS: We aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19. METHODS: All 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. RESULTS: Between 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. CONCLUSION: In 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 NUMBER: ClinicalTrial.gov (ID: NCT04318366).

Differential diagnosis of solid pancreatic masses.

Solid pancreatic lesions include mainly adenocarcinoma, neuroendocrine tumors pancreatic cystic neoplasms with solid component, solid pseudopapillary tumor, pancreatoblastoma, pancreatic lymphoma, and pancreatic metastasis. The most frequent pancreatic lesion is the adenocarcinoma, representing between 70% and 95% of all solid pancreatic neoplasm. The diagnosis of these lesions can be a challenge and currently, there are different imaging techniques such as CT scan, EUS and MRI with high sensitivity and specificity. The most widely used technique for the initial evaluation is the CT scan with a sensitivity between 76% and 92% for the diagnosis of pancreatic cancer. The EUS has a sensitivity for the detection of pancreatic lesions of around 98% and is accepted to be the most sensitive technique for the detection of small pancreatic tumors (<2 cm). The MRI, with a very high soft-tissue contrast resolution, provides an accuracy in the detection and staging of adenocarcinoma of 90-100%. A multimodality approach is usually necessary in patients with clinical suspicion of pancreatic lesion. The EUS is required for the local evaluation of the relation of the lesion with vessels and for tissue acquisition and the CT scan and/or MRI is usually required for the local and distance staging in case of pancreatic cancer. The purpose of this review is to provide an overview of solid pancreatic lesions and the role of the different imaging techniques in their evaluation.

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer.

Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy. Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC. Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels. MAIN OUTCOME: adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as "percent of standard chemotherapy dose delivered." SECONDARY OUTCOMES: rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations. ANALYSIS: chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients. SAMPLE SIZE: based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval. Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.

Endoscopic ultrasound-based multimodal evaluation of the pancreas in patients with suspected early chronic pancreatitis.

BACKGROUND: Diagnosis of early chronic pancreatitis is a clinical challenge and hindered by the lack of a gold standard. Endoscopic ultrasound (EUS) and the endoscopic pancreatic function test (ePFT) are the most sensitive morphological and functional methods in this setting. EUS-elastography allows for the quantification (strain ratio) of pancreatic fibrosis, and the dynamic evaluation of the main pancreatic duct compliance provides additional information. We developed a multimodal EUS-based approach for the evaluation of the pancreas by integrating these four methods in a single procedure. OBJECTIVE: We aim to describe morphological and functional pancreatic abnormalities in patients with clinical suspicion of chronic pancreatitis and inconclusive EUS findings by using the multimodal EUS-based approach. METHODS: This was a prospective, cross-sectional, observational study of patients with clinically suspected chronic pancreatitis and indeterminate EUS criteria of the disease. EUS criteria of chronic pancreatitis, quantitative pancreatic elastography, ePFT and compliance of the main pancreatic duct were evaluated in a single procedure. RESULTS: In total, 53 patients with 3-4 EUS criteria of chronic pancreatitis were included (mean age 39.7 years, 29 male). Strain ratio was abnormally high in all patients. Peak bicarbonate concentration was decreased in 43 patients (81.1%) and the main pancreatic duct compliance was reduced in 41 patients (77.3%). Some 34 patients (64.1%) had abnormal results at EUS, elastography, ePFT and compliance of the main pancreatic duct. CONCLUSIONS: A multimodal EUS-based test for the morphological and functional evaluation of the pancreas is presented, which allows detecting mild pancreatic abnormalities in patients with suspected early chronic pancreatitis. The presence of abnormal morphological and functional evaluation of the pancreas could support the clinical suspicion of early chronic pancreatitis in the appropriate clinical setting.

EUS-FNA in cystic pancreatic lesions: Where are we now and where are we headed in the future?

EUS-FNA is often performed in the evaluation of Cystic Pancreatic Lesions (CPL) for a better preoperative characterization. The objective is to identify premalignant lesions as Mucinous Cystic Neoplasms, and/or a malignant transformation of them (adenocarcinoma). The role of cytological evaluation in this setting is discouraging and intracystic markers analysis, mainly CEA, lacks of a good specificity for the detection of mucinous neoplasms. New devices and approaches have emerged to overcome these problems as the cytology brush (Echobrush), the small mini-biopsy foceps, the cystoscopy and the needle Confocal LASER Endomicroscopy (nCLE), showing in some studies good rates of accuracy for distinguishing among mucinosus and non-mucinous neoplasms. However, intracystic molecular marker analysis, by identifying mutations in DNA of particular genes as KRAS,GNAS,VHL, CDKN2A and others constitute the most relevant advancement of last years and will contribute in the next future to a better management of CPL. The role of EUS-FNA according to international guidelines is still controversial. While 2012 Fukuoka guidelines are restrictive in their indications AGA 2015 guidelines support it when high risk features are present, enhancing the role of the cytological evaluation in taking decisions.