A Hidden Cause of Hypertransaminasemia: Liver Toxicity Caused by Chelidonium Majus L. : Report of Two Cases of Herb-Induced Liver Injury and Literature Review.

BACKGROUND: In instances where individuals manifest elevated transaminase levels without a clearly discernible cause, a comprehensive patient history proves invaluable in unveiling latent triggers. In this report, we present 2 cases of herb-induced liver injury (HILI) characterized by severe hypertransaminasemia attributed to the consumption of Chelidonium majus L . (also known as greater celandine [GC]), an agent considered an alternative therapeutic remedy. AREAS OF UNCERTAINTY: Exploring the occurrence and range of clinical manifestations in HILI linked to Chelidonium majus L ., while also investigating the potential triggers and predisposing factors for hepatotoxic reactions post Chelidonium majus L. usage, remains challenging due to the absence of definitive laboratory tests to identify the causative agent. DATA SOURCES: Two case reports were detailed, and a systematic literature review using PubMed was conducted including published literature till March 2023. Moreover, a manual search of reference lists of pertinent articles was performed to identify any additional relevant missed publications. RESULTS: In the first case, a 64-year-old woman presented with jaundice, revealing a 1-month history of using GC capsules to manage gallstones. Diagnostic assessment identified HILI, gallstones, and choledocolithiasis, with transaminase levels exceeding 1000 IU/L. After discontinuing GC and receiving intravenous therapy with amino acids and phospholipids, the patient's condition significantly improved. Subsequently, she underwent endoscopic common bile duct stone removal and cholecystectomy. In the second case, a 66-year-old woman presented with elevated liver function test results discovered incidentally during musculoskeletal pain evaluation. Upon further questioning, the patient disclosed regular consumption of GC tea for "health promotion." Following intravenous therapy using amino acids and phospholipids, her transaminase levels returned to normal. The literature review identified 38 cases of HILI associated with GC preparations, primarily in adult women aged 27-77 years, with a predominant reporting location in Germany. Various forms of GC were used, with treatment durations ranging from 1 week to a year. Discontinuation of GC generally led to recovery in these cases. CONCLUSION: Chelidonium majus L ., a potent herb often used in alternative medicine, has significant hepatotoxic potential, requiring physicians to be vigilant in cases of unexplained liver injury.

Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions.

Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1ß) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1ß, glucose, and CEA, and serum for Ngal and IL-1ß. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1ß and serum Ngal made no diagnostic contribution.

Informed consent for endoscopic procedures: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

All endoscopic procedures are invasive and carry risk. Accordingly, all endoscopists should involve the patient in the decision-making process about the most appropriate endoscopic procedure for that individual, in keeping with a patient's right to self-determination and autonomy. Recognition of this has led to detailed guidelines on informed consent for endoscopy in some countries, but in many no such guidance exists; this may lead to variations in care and exposure to risk of litigation. In this document, the European Society of Gastrointestinal Endoscopy (ESGE) sets out a series of statements that cover best practice in informed consent for endoscopy. These statements should be seen as a minimum standard of practice, but practitioners must be aware of and adhere to the law in their own country. 1: Patients should give informed consent for all gastrointestinal endoscopic procedures for which they have capacity to do so. 2: The healthcare professional seeking consent for an endoscopic procedure should ensure that the patient has the capacity to consent to that procedure. 3: For patients who lack capacity, healthcare personnel should at all times try to engage with people close to the patient, such as family, friends, or caregivers, to achieve consensus on the appropriateness of performing the procedure. 4: Where a patient lacks capacity to provide informed consent, the best interest decision should be clearly documented in the medical record. This should include information about the capacity assessment, reason(s) that the decision cannot be delayed for capacity recovery (or if recovery is not expected), who has been consulted, and where relevant the form of authority for the decision. 5: There should be a systematic and transparent disclosure of the expected benefits and harms that may reasonably affect patient choice on whether or not to undergo any diagnostic or interventional endoscopic procedure. Information about possible alternatives, as well as the consequences of doing nothing, should also be provided when relevant. 6: The information provided on the benefit and harms of an endoscopic procedure should be adapted to the procedure and patient-specific risk factors, and the preferences of the patient should be central to the consent process. 7: The consent discussion should be undertaken by an individual who is familiar with the procedure and its risks, and is able to discuss these in the context of the individual patient. 8: Patients should confirm consent to an endoscopic procedure in a private, unrushed, and non-coercive environment. 9: If a patient requests that an endoscopic procedure be discontinued, the procedure should be paused and the patient's capacity for decision making assessed. If a competent patient continues to object to the procedure, or if a conclusive determination of capacity is not feasible, the examination should be terminated as soon as it is safe to do so. 10: Informed consent should be sufficiently detailed to cover all findings that can be reasonably anticipated during an endoscopic examination. The scope of this consent should not be expanded, nor a patient's implicit consent for additional interventions assumed, unless failure to proceed with such interventions would result in immediate and predictable harm to the patient.

Unveiling Distinct Proteomic Signatures in Complicated Crohn's Disease That Could Predict the Disease Course.

Crohn's disease (CD) is characterized by a chronic, progressive inflammation of the gastrointestinal tract often leading to complications, such as strictures and fistulae. Currently, there are no validated tools anticipating short- and long-term outcomes at an early stage. This investigation aims to elucidate variations in protein abundance across distinct CD phenotypes with the objective of uncovering potential biomarkers implicated in disease advancement. Serum samples collected from 30 CD patients and 15 healthy age-matched controls (HC) were subjected to depletion of highly abundant proteins and to a label-free mass spectrometry analysis. Twenty-four proteins were shown to be significantly different when comparing CD with HC. Of these, WD repeat-containing protein 31 (WDR31), and proteins involved in the acute inflammatory response, leucine-rich alpha-2-glycoprotein (LRG1) and serum amyloid A1 (SAA1), were more abundant in the aggressive subgroup. Against standard biomarkers, a positive correlation between SAA1 and WDR31 and C-reactive protein (CRP) was found. In this study, a unique serum biomarker panel for aggressive CD was identified, which could aid in predicting the disease course.

Endoscopic management of subepithelial lesions including neuroendocrine neoplasms: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape), but EUS alone is not able to distinguish among all types of SEL.Strong recommendation, moderate quality evidence. 2: ESGE suggests providing tissue diagnosis for all SELs with features suggestive of gastrointestinal stromal tumor (GIST) if they are of size > 20 mm, or have high risk stigmata, or require surgical resection or oncological treatment.Weak recommendation, very low quality evidence. 3: ESGE recommends EUS-guided fine-needle biopsy (EUS-FNB) or mucosal incision-assisted biopsy (MIAB) equally for tissue diagnosis of SELs ≥ 20 mm in size.Strong recommendation, moderate quality evidence. 4: ESGE recommends against surveillance of asymptomatic gastrointestinal (GI) tract leiomyomas, lipomas, heterotopic pancreas, granular cell tumors, schwannomas, and glomus tumors, if the diagnosis is clear.Strong recommendation, moderate quality evidence. 5: ESGE suggests surveillance of asymptomatic esophageal and gastric SELs without definite diagnosis, with esophagogastroduodenoscopy (EGD) at 3-6 months, and then at 2-3-year intervals for lesions < 10 mm in size, and at 1-2-year intervals for lesions 10-20 mm in size. For asymptomatic SELs > 20 mm in size that are not resected, ESGE suggests surveillance with EGD plus EUS at 6 months and then at 6-12-month intervals.Weak recommendation, very low quality evidence. 6: ESGE recommends endoscopic resection for type 1 gastric neuroendocrine neoplasms (g-NENs) if they grow larger than 10 mm. The choice of resection technique should depend on size, depth of invasion, and location in the stomach.Strong recommendation, low quality evidence. 7: ESGE suggests considering removal of histologically proven gastric GISTs smaller than 20 mm as an alternative to surveillance. The decision to resect should be discussed in a multidisciplinary meeting. The choice of technique should depend on size, location, and local expertise.Weak recommendation, very low quality evidence. 8: ESGE suggests that, to avoid unnecessary follow-up, endoscopic resection is an option for gastric SELs smaller than 20 mm and of unknown histology after failure of attempts to obtain diagnosis.Weak recommendation, very low quality evidence. 9: ESGE recommends basing the surveillance strategy on the type and completeness of resection. After curative resection of benign SELs no follow-up is advised, except for type 1 gastric NEN for which surveillance at 1-2 years is advised.Strong recommendation, low quality evidence. 10: For lower or upper GI NEN with a positive or indeterminate margin at resection, ESGE recommends repeating endoscopy at 3-6 months and another attempt at endoscopic resection in the case of residual disease.Strong recommendation, low quality evidence.

Curriculum for ERCP and endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS. This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2: Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3: Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones > 10 mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 300 cases, a native papilla cannulation rate of ≥ 80 % (90 % after a period of mentored independent practice), complete stones clearance of ≥ 85 %, and successful stenting of distal biliary strictures of ≥ 90 % (90 % and 95 % respectively after a mentored period of independent practice). 4: The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥ 90 % of cases, and an FNA/FNB accuracy rate of ≥ 85 %. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS.

Serum JAK/STAT profile is related to the IL expression but not with the outcome in pancreatic adenocarcinoma patients.

Current genetic characterization of pancreatic ductal adenocarcinoma (PDAC) does not integrate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. The JAK/STAT pathway is an important factor of cytokine-mediated cancer inflammation, but its relationship with pancreatic carcinogenesis and the role of potential biomarkers is not established yet. Our study aimed to assess the significance of serum levels of JAK/STAT3 expression and inflammatory cytokines in PDAC in relation to the clinicopathological features and prognosis. This prospective cohort study included patients with proven adenocarcinoma and a matched group of controls without any malignancies. There were evaluated the serum expression of IL2, 6, 8, 17, JAK2, and STAT3 by ELISA assays in these two groups. The PDAC patients were followed up for 24 months. A Cox regression multivariate analysis model was used to determine factors influencing survival. The study comprised 56 patients with PDAC and 56 controls. The upregulated serum JAK2/STAT3 or cytokines were present in about half of the patients with PDAC, similar to controls. The expression of JAK2 in serum of PDAC patients was significantly associated with the expression of IL2 (p=0.03) and IL6 (p=0.02) but not with survival or metastasis development. Only age and the presence of lymph node metastases were associated with reduced survival in multivariate analyses. The STAT 3/JAK2 expression, although correlated with inflammatory status (IL2, IL6) was not overexpressed in PDAC compared to controls and proved no prognostic value.

Synchronous Pancreatic Tumours: Intraductal Papillary Mucinous Neoplasm with Pancreatic Ductal Adenocarcinoma and Neuroendocrine Tumour: A Case Presentation and Review of Literature.

Synchronous tumours of the pancreas are rare encounters, with few reported cases. Thus, new information can be brought about the diagnosis, proper management, and prognosis of cases. We believe that the presentation of this case can help to establish relevant conclusions. We report the case of a 54-year-old man, with the preoperative diagnosis of a cephalic intraductal papillary mucinous neoplasm (IPMN), who underwent a planned cephalic pancreatoduodenectomy with completion to total pancreatectomy based on the intraoperative extemporaneous histopathological examination of the resection margin. The final histopathological diagnosis was cephalic IPMN associated with invasive ductal adenocarcinoma (PDAC) and a small well-differentiated neuroendocrine tumour (NET) in the tail of the pancreas. No recurrence was detected in the 3 years of follow-up. We conducted a review of the literature to illustrate the particularities of the presented case; it identified 4 articles about the association of PDAC and NET and 8 articles regarding the association of IPMN with NET. Only 2 patients had a histopathological diagnosis of three synchronous tumours (IPMN, PDAC, and NET). We present a rare case of three synchronous pancreatic tumours, with a favourable evolution after a total pancreatectomy, only two other similar cases being reported in medical literature.

Contrast-enhanced harmonic versus standard endoscopic ultrasound-guided fine-needle aspiration in solid pancreatic lesions: a single-center prospective randomized trial.

BACKGROUND: Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can visualize necrotic areas and vessels inside lesions. CH-EUS findings combined with EUS-guided fine-needle aspiration (EUS-FNA) improves diagnosis in pancreatic solid masses. CH-EUS can also guide EUS-FNA (CH-EUS-FNA), potentially improving the diagnostic rate of EUS-FNA, but such superiority has not been proved in prospective studies. We aimed to assess whether CH-EUS-FNA is superior to standard EUS-FNA for specific diagnosis of solid pancreatic masses and what factors affect the diagnostic rate. METHODS: This randomized controlled study in one tertiary medical academic center included patients with suspected pancreatic solid masses on transabdominal ultrasound or computed tomography (CT) scan. Two passes with a 22-G standard FNA needle were done using EUS-FNA and CH-EUS-FNA in random order, and the visible core obtained was sent for histological analysis. Final diagnosis was based on EUS-FNA or surgical specimen results and on 12-month follow-up by imaging. RESULTS: 148 patients were evaluated. EUS-FNA and CH-EUS-FNA showed diagnostic sensitivities of 85.5 % and 87.6 %, respectively (not significantly different) and the combined sensitivity of the two passes was 93.8 %. The false-negative rate was not significantly different when hypoenhanced or hyperenhanced lesions were compared with the EUS-FNA results. No differences were seen for the results related to location, size, tumor stage, chronic pancreatitis features, or presence of biliary plastic stent. CONCLUSIONS: The diagnostic rates for samples obtained using 22-G needles with standard EUS-FNA and CH-EUS-FNA were not statistically significantly different.

SRED-ARCE Recommendations for Minimally Invasive Interventions During the COVID-19 Pandemic in Romania.

The Romanian Society of Digestive Endoscopy (SRED) and the Romanian Association of Endoscopic Surgery (ARCE) have decided to establish a joint working group to elaborate specific recommendations for organizing the diagnostic and the minimally invasive interventional procedures, in the context of the COVID-19 pandemic. The recommendations are based on the guidelines of the international societies of endoscopy and gastroenterology (ESGE / BSG / ASGE / ACG / AGA), respectively endoscopic surgery (EAES SAGES) (4-8), on the experience of countries severely affected by the pandemic (Italy, France, Spain, USA, Germany, etc.) and they will be applied within the limits of measures imposed at local and governmental level by the competent authorities. On the other hand, these recommendations should have a dynamic evolution, depending on the upward or downward trend of the COVID-19 pandemic at regional and local level, but also according to the findings of professional and academic societies, requiring regular reviews based on the publica tion of further recommendations or international clinical trials. The objectives of the SRED and ARCE recommendations target the endoscopic and laparoscopic surgery activities, to support their non discriminatory used for diagnostic or therapeutic purposes, pursuing the demonstrated benefits of these procedures, in safe conditions for patients and medical staff.

Technical aspects of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Guideline - March 2017.

For 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).

Harmonic Contrast-Enhanced Endoscopic Ultrasonography for the Guidance of Fine-Needle Aspiration in Solid Pancreatic Masses.

Purpose The global accuracy of fine-needle aspiration guided by endoscopic ultrasound (EUS-FNA) for pancreatic adenocarcinoma is about 85 %. The use of contrast agents during EUS to highlight vessels and the necrotic parts of pancreatic masses may improve biopsy guidance. Our aim was to assess whether the guidance of FNA by harmonic contrast-enhanced endoscopic ultrasound (CH-EUS) would increase diagnostic accuracy relative to conventional EUS-FNA in the same pancreatic masses. Patients and Methods In a prospective study, EUS-FNA was performed in patients with pancreatic masses on CT scan, followed by harmonic CH-EUS using SonoVue. A second cluster of CH-EUS-FNA was performed on contrast-enhanced images. The final diagnosis was based on the results of EUS-FNA and surgery, or the findings after 12 months' follow-up. Results The final diagnosis was adenocarcinoma (n = 35), chronic pancreatitis (n = 10), or other (n = 6). The diagnostic accuracy based on core histology was 78.4 % for EUS-FNA and 86.5 % for CH-EUS-FNA (p = 0.35). The accuracy increased to 94 % when the two methods' results were combined. The two false-negative EUS-FNA cases were correctly appreciated by CH-EUS. Neither core histology size nor the presence of necrosis was significant for the true-positive diagnosis of malignancy. Conclusion CH-EUS-FNA had an insignificant incremental effect on diagnostic accuracy compared with conventional EUS-FNA in our small group. The presence of necrosis did not influence the results of CEUS-FNA. Qualitative assessment of the contrast uptake within the lesion was useful in false-negative EUS-FNA cases.

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. METHODS: Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. RESULTS: In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. CONCLUSION: The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Quantitative contrast-enhanced harmonic EUS in differential diagnosis of focal pancreatic masses (with videos).

BACKGROUND: The role of EUS with contrast agents can be expanded through the use of time-intensity curve (TIC) analysis and computer-aided interpretation. OBJECTIVE: To validate the use of parameters derived from TIC analysis in an artificial neural network (ANN) classification model designed to diagnose pancreatic carcinoma (PC) and chronic pancreatitis (CP). SETTING: Prospective, multicenter, observational trial-endoscopy units from Romania, Denmark, Germany, and Spain. PATIENTS: A total of 167 consecutive patients with PC or CP. INTERVENTIONS: Contrast-enhanced harmonic EUS (CEH-EUS) and EUS-guided FNA (EUS-FNA), TIC analysis, and ANN processing. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for EUS-FNA, CEH-EUS, and the ANN. RESULTS: After excluding all of the recordings that did not meet the technical and procedural criteria, 112 cases of PC and 55 cases of CP were included. EUS-FNA was performed in 129 patients, and the diagnosis was confirmed by surgery (n = 15) or follow-up (n = 23) in the remaining cases. Its sensitivity and specificity were 84.82% and 100%, respectively, whereas the PPV and NPV were 100% and 76.63%, respectively. The sensitivity of real-time quantitative assessment of CEH-EUS was 87.5%, specificity 92.72%, PPV 96.07%, and NPV 78.46%. Peak enhancement, wash-in area under the curve, wash-in rate, and the wash-in perfusion index were significantly different between the groups. No significant differences were found between rise time, mean transit time, and time to peak. For the ANN, sensitivity was 94.64%, specificity 94.44%, PPV 97.24%, and NPV 89.47%. LIMITATIONS: Only PC and CP lesions were included. CONCLUSION: Parameters obtained through TIC analysis can differentiate between PC and CP cases and can be used in an automated computer-aided diagnostic system with good diagnostic results. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01315548.).

Proteomic identification of potential prognostic biomarkers in resectable pancreatic ductal adenocarcinoma.

Pancreatic cancer is a devastating disease with a mortality rate almost identical with its incidence. In this context, the investigation of the pancreatic cancer proteome has gained considerable attention because profiles of proteins may be able to identify disease states and progression more accurately. Therefore, our objective was to investigate the changes in the proteome of patients suffering from pancreatic ductal adenocarcinoma (PDAC) by a comprehensive quantitative approach. Comparative proteomic profiling by label-free LC-MS/MS analysis of nine matched pairs of tumor and nontumor pancreas samples was used to identify differences in protein levels characteristic for PDAC. In this analysis, 488 proteins were quantified by at least two peptides of which 99 proteins displayed altered levels in PDAC (p < 0.01, fold change >1.3). Screening of data revealed a number of molecules that had already been related to PDAC such as galectin-1 (LEG1), major vault protein, adenylyl cyclase-associated protein 1 (CAP1), but also a potential new prognostic biomarker prolargin (PRELP). The Kaplan-Meier survival analysis revealed a significant correlation of protein abundance of PRELP with postoperative survival of patients with PDAC. For selected proteins the findings were verified by targeted proteomics (SRM), validated by immunohistochemistry and Western blotting and their value as candidate biomarkers is discussed.

Endoscopic ultrasound guided radiofrequency ablation in pancreas.

Radiofrequency ablation of the pancreas represents a more effective tumor-destruction method compared to other ablation techniques. The endoscopic ultrasound guided radiofrequency ablation is indicated for locally advanced, non-metastatic pancreatic adenocarcinoma, without the need of general anesthesia and fast recovery. The main limitations are the encasement of the mesenteric vessels or of the common bile duct in the head pancreatic tumours. The technique is feasible, effective and relatively safe in porcine models, with minimal evidence of fat necrosis in intra-pancreatic and/or extra-pancreatic adipose tissue. It has been successfully applied on insulinomas and pancreatic adenocarcinoma in humans, with few complications, such as duodenal bleeding or mild abdominal pain. Other side effects as biliary fistula, pancreatic fistula or acute pancreatitis seen in intraoperative settings of radiofrequency ablation, have not been reported in endoscopic ultrasound guided radiofrequency ablation.

Multiple metastasis of malignant melanoma. The diagnostic role of ultrasonography starting from a parotid tumor.

We presented the case of a patient with a slowly developing right parotid tumor over the course of several years. Multimodal ultrasonography proved relevant for malignancy. Subsequent imaging identified tumors in numerous organs, considered metastases. Ultrasonography consolidated all identified aspects. Biopsy from an adrenal mass and histological examination evidenced the presence of a malignant, metastatic melanoma with cutaneous origin. Considerations are made regarding the role of ultrasonography in such cases.

Contrast-enhanced guided endoscopic ultrasound procedures.

Contrast-enhanced endoscopic ultrasound (CH-EUS) can overcome the limitations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours. Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions, further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS. This review details the knowledge based on the available data on contrast-guided procedures. The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions, which occur in select cases. Additionally, the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage, and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented. Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours, in which case CH-EUS can be used to reveal the incomplete tumour destruction.

Metabolic Dysfunction Associated Liver Disease in Patients Undergoing Coronary Computed Tomography Angiography.

In this single-center cross-sectional study on patients undergoing coronary computed tomography angiography (CCTA), we assessed the prognostic significance of metabolic dysfunction associated steatotic liver disease (MASLD), metabolic syndrome (MetS), and CCTA-derived parameters for predicting major adverse cardiovascular events (MACE). Over a mean follow-up of 26.9 months, 2038 patients were analyzed, with 361 (17.7%) experiencing MACE. MASLD was associated with a higher MACE incidence (25.90% vs. 14.71% without MASLD, p < 0.001). Cox regression revealed significant associations between MASLD, coronary calcium score (CCS), number of plaques (NoP), epicardial fat volume (EFV), and MACE, with hazard ratios of 1.843, 1.001, 1.097, and 1.035, respectively (p < 0.001 for all). A composite risk score integrating CCS, NoP, EFV, and MASLD demonstrated superior predictive value for MACE (AUC = 0.948) compared to individual variables (p < 0.0001 for all). In conclusion, MASLD is linked to an elevated risk of MACE, and a comprehensive risk-scoring system incorporating imaging and clinical factors enhances MACE prediction accuracy.

New-onset Diabetes Mellitus after EUS-guided Drainage with LAMS: A Pilot Study.

BACKGROUND AND AIMS: Walled-off necrosis (WON) is a serious complication of severe pancreatitis, patients with necrotizing pancreatitis having an increased risk of developing diabetes mellitus (DM). The aim of this study was to assess the frequency of new-onset diabetes (NOD) in patients with symptomatic WON after endoscopic ultrasound (EUS)-guided drainage with lumen-apposing metal stents (LAMS). METHODS: We retrospectively analyzed a prospectively collected database of patients with symptomatic WON treated by EUS-guided drainage with LAMS in a tertiary referral center. The patients were followed-up for at least 12 months after stent removal. These patients were compared with age- and sex-matched asymptomatic WON controls without interventional treatment and healthy controls to assess the one-year occurrence of DM. Diabetes was defined according to the American Diabetes Association criteria. RESULTS: Of the 50 patients with symptomatic WON included in the study (male/female ratio, 33:17; median age, 60 years), 13 patients (26%) had pre-existing DM and were excluded. Ten of the remaining 37 patients (27%) without prior DM developed NOD within one year after stent removal, this frequency being higher than in asymptomatic WON controls (18.9%, p=0.581) and healthy controls (2%, p = 0.002). In the symptomatic WON group, NOD patients compared to non-DM patients were older (63.5 vs. 56 years old, p=0.042), had more frequent necrosis > 50% of the pancreatic parenchyma (p=0.002) and had a body-tail location of WON (p<0.001). On multivariate analysis, the number of direct endoscopic necrosectomy (DEN) sessions was the only significant factor for NOD occurrence (OR=7.05, p=0.010). NOD patients had poor glycemic control and required more DEN sessions to achieve WON resolution than patients with prior DM (p=0.017). CONCLUSIONS: In patients with symptomatic WON treated by EUS-guided drainage, DM occurred in 27% of previously non-diabetic patients within one year of follow-up. Patients with extensive pancreatic necrosis were more likely to develop NOD, a high number of DEN sessions being a significant risk factor for NOD occurrence.