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The DYNC2H1 gene has been associated with short‐rib polydactyly syndrome (SRPS), among other skeletal ciliopathies. Two cases are presented of distinctive phenotypes resulting from splicing variants in DYNC2H1. The first is a 14‐week‐old fetus with enlarged nuchal translucency, oral hamartoma, malformed uvula, bifid epiglottis, short ribs, micromelia, long bone agenesis, polysyndactyly, heart defect, pancreatic cysts, multicystic dysplastic kidney, megabladder and trident acetabulum. A ciliopathies NGS panel revealed two compound heterozygous variants in DYNC2H1: c.7840‐18T>G r.7841_7964del p.Gly2614Aspfs*5 and c.11070G>A r.11044_11116del p.Ile3682Aspfs*2. Both variants were initially classified as variants of uncertain significance but were reclassified as likely pathogenic after PCR‐based RNA testing. The second is an 11‐year‐old overweight male with multiple accessory oral frenula, median cleft lip and alveolar ridge, polysyndactyly, brachydactyly, normal rib length, and hypogonadism. Exome sequencing revealed two compound heterozygous variants in DYNC2H1: c.6315del p.(Thr2106Glnfs*7), classified as likely pathogenic, and c.3303‐16A>G p.(?), classified as a variant of uncertain significance. PCR‐based RNA testing suggested that c.3303‐16A>G induces an in‐frame deletion: r.3303_3458del p.Asp1102_Arg1153del, although the normal transcript is still produced. These results are consistent with both SRPS type I/III in the first case and orofaciodigital syndrome in the second, an unprecedented description. This work thus improves the clinical and molecular knowledge of the phenotypes associated with splicing variants in the DYNC2H1 gene. [ABSTRACT FROM AUTHOR]

Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the proteome and transcriptome of patient pancreatic cyst fluid (PCF) (n = 32) and serum (n = 68), before integrating matched omic and biofluid data, to identify biomarkers of pancreatic cancer risk. Differential expression analysis, feature reduction, multi-omic data integration, unsupervised hierarchical clustering, principal component analysis, spearman correlations and leave-one-out cross-validation were performed using RStudio and CombiROC software. An 11-feature multi-omic panel in PCF [PIGR, S100A8, REG1A, LGALS3, TCN1, LCN2, PRSS8, MUC6, SNORA66, miR-216a-5p, miR-216b-5p] generated an AUC = 0.806. A 13-feature multi-omic panel in serum [SHROOM3, IGHV3-72, IGJ, IGHA1, PPBP, APOD, SFN, IGHG1, miR-197-5p, miR-6741-5p, miR-3180, miR-3180-3p, miR-6782-5p] produced an AUC = 0.824. Integration of the strongest performing biomarkers generated a 10-feature cross-biofluid multi-omic panel [S100A8, LGALS3, SNORA66, miR-216b-5p, IGHV3-72, IGJ, IGHA1, PPBP, miR-3180, miR-3180-3p] with an AUC = 0.970. Multi-omic profiling provides an abundance of potential biomarkers. Integration of data from different omic compartments, and across biofluids, produced a biomarker panel that performs with high accuracy, showing promise for the risk stratification of patients with pancreatic cystic lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cystic lesions (PCLs) can range from harmless growths to precursors of pancreatic cancer, making accurate diagnosis crucial for patient care. Traditional methods for managing PCLs, such as imaging and biopsies, often depend on the skill of the doctor interpreting the images, leading to variability in diagnosis and treatment. This review highlights the challenges in diagnosing and managing PCLs and discusses the potential for artificial intelligence (AI) to improve accuracy. AI techniques, such as automated image analysis and deep learning algorithms, can provide more consistent and reliable assessments of pancreatic cysts. These tools could help doctors better identify high-risk lesions that need treatment, while avoiding unnecessary procedures for benign cysts. AI-driven methods show promise in improving patient outcomes, offering earlier detection and more precise management, and ultimately helping to prevent pancreatic cancer. Pancreatic cystic lesions (PCLs) represent a spectrum of non-neoplasms and neoplasms with varying malignant potential, posing significant challenges in diagnosis and management. While some PCLs are precursors to pancreatic cancer, others remain benign, necessitating accurate differentiation for optimal patient care. Conventional approaches to PCL management rely heavily on radiographic imaging, and endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA), coupled with clinical and biochemical data. However, the observer-dependent nature of image interpretation and the complex morphology of PCLs can lead to diagnostic uncertainty and variability in patient management strategies. This review critically evaluates current PCL diagnosis and surveillance practices, showing features of the different lesions and highlighting the potential limitations of conventional methods. We then explore the potential of artificial intelligence (AI) to transform PCL management. AI-driven strategies, including deep learning algorithms for automated pancreas and lesion segmentation, and radiomics for analyzing heterogeneity, can improve diagnostic accuracy and risk stratification. These advanced techniques can provide more objective and reproducible assessments, aiding clinicians in decision-making regarding follow-up intervals and surgical interventions. Early results suggest that AI-driven methods can significantly improve patient outcomes by enabling earlier detection of high-risk lesions and reducing unnecessary procedures for benign cysts. Finally, this review emphasizes that AI-driven approaches could potentially reshape the landscape of PCL management, ultimately leading to improved pancreatic cancer prevention. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates a simple and cost-effective method to differentiate between mucinous and non-mucinous pancreatic cystic lesions (PCLs) during EUS–FNA. The proper identification of these lesions is crucial to ensure appropriate treatment. Current methods can be invasive or expensive; therefore, this research aims to validate the accuracy of using a conventional glucometer to measure glucose levels directly from the cyst fluid. The study found that glucose levels below 50 mg/dL were highly accurate in identifying mucinous PCLs. These findings could improve diagnostic protocols, providing a faster and more accessible way to effectively manage PCLs. Background: Pancreatic cystic lesions (PCLs) are frequently detected incidentally and vary from benign to malignant. Accurate differentiation between mucinous (M-PCLs) and non-mucinous PCLs (NM-PCLs) is essential for appropriate management. This study aims to validate the accuracy of on-site glucose measurement using a glucometer with a cut-off of 50 mg/dL for distinguishing M-PCLs from NM-PCLs. Methods: In this prospective multicenter study, conducted at three European academic hospitals, patients who underwent endoscopic ultrasound-guided fine-needle aspiration for PCLs between 2019 and 2020 were included. On-site glucose measurement was performed using a conventional glucometer. Data on demographics, clinical features, EUS findings, and histopathology were collected. Results: Fifty patients were enrolled, with 37 having glucose levels < 50 mg/dL and 13 ≥ 50 mg/dL. M-PCLs were more common in the <50 mg/dL group (81%) compared to the ≥50 mg/dL group (23%, p < 0.001). The median CEA was higher in the <50 mg/dL group (146 ng/mL) than in the ≥50 mg/dL group (3 ng/mL, p = 0.047). On-site glucose testing < 50 mg/dl demonstrated a sensitivity of 93.2%, a specificity of 76.5%, and an accuracy of 89% for detecting M-PCLs with an AUC of 0.74 and an OR of 14.29 (p < 0.001). In comparison, CEA > 192 ng/mL had a sensitivity of 55.6%, a specificity of 87.5%, and an accuracy of 75.8% for M-PCLs, with an AUC of 0.65 and an OR of 4.44. Conclusions: On-site glucose measurement using a glucometer with a cut-off of <50 mg/dL is a highly accurate, rapid, and cost-effective method for differentiating M-PCLs from NM-PCLs. Our results validate the glucose cut-off in a multicentric prospective cohort supporting its integration into standard diagnostic protocols for PCLs. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify the risk factors for pancreatic cancer through machine learning. Methods: We investigated the relationships between different risk factors and pancreatic cancer using a real-world retrospective cohort study conducted at West China Hospital of Sichuan University. Multivariable logistic regression, with pancreatic cancer as the outcome, was used to identify covariates associated with pancreatic cancer. The machine learning model extreme gradient boosting (XGBoost) was adopted as the final model for its high performance. Shapley additive explanations (SHAPs) were utilized to visualize the relationships between these potential risk factors and pancreatic cancer. Results: The cohort included 1,982 patients. The median ages for pancreatic cancer and nonpancreatic cancer groups were 58.1 years (IQR: 51.3–64.4) and 57.5 years (IQR: 49.5–64.9), respectively. Multivariable logistic regression indicated that kirsten rats arcomaviral oncogene homolog (KRAS) gene mutation, hyperlipidaemia, pancreatitis, and pancreatic cysts are significantly correlated with an increased risk of pancreatic cancer. The five most highly ranked features in the XGBoost model were KRAS gene mutation status, age, alcohol consumption status, pancreatitis status, and hyperlipidaemia status. Conclusion: Machine learning algorithms confirmed that KRAS gene mutation, hyperlipidaemia, and pancreatitis are potential risk factors for pancreatic cancer. Additionally, the coexistence of KRAS gene mutation and pancreatitis, as well as KRAS gene mutation and pancreatic cysts, is associated with an increased risk of pancreatic cancer. Our findings offered valuable implications for public health strategies targeting the prevention and early detection of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Mucinous epithelial pancreatic cystic lesions (PCLs) are premalignant lesions detectable through imaging techniques; however, distinguishing them from other PCLs with lower malignancy potential is challenging. Current methods like biochemical markers and genomic studies are not always reliable. Thermal liquid biopsy (TLB) is an innovative tool that analyzes the thermal profile of biological samples to detect disease-related alterations. In a retrospective study of 35 intracystic fluid samples obtained via fine needle aspiration, predictive models were developed using machine learning algorithms. Two classification models were created: TLB1, which differentiates mucinous from non-mucinous PCLs, demonstrating 92% sensitivity and 86% negative predictive value, and TLB2, which identifies benign and malignant mucinous lesions, achieving an area under the curve of 1.00. TLB shows promise in improving the differential diagnosis of PCLs and in detecting malignant transformations. Background/Objectives: Mucinous epithelial pancreatic cystic lesions (PCLs) are premalignant lesions readily detectable through imaging techniques such as multidetector computed tomography, magnetic resonance imaging, and endoscopic ultrasound (EUS). However, distinguishing these from other PCLs with lower or no malignant potential, and the early identification of those undergoing malignant transformation, remains a diagnostic challenge. Current methods, including biochemical markers in intracystic fluid (ICF) and genomic studies, offer some assistance but are not always reliable or accessible. Thermal liquid biopsy (TLB) is a novel diagnostic tool that examines the thermal profile (thermogram) of biological samples, reflecting their response to heat and thereby revealing characteristics of their overall composition or disease-induced alterations. Methods: In this retrospective study, a total of 35 ICF samples (49% mucinous) obtained via EUS-FNA (fine needle aspiration) were analyzed using TLB. Thermogram data were utilized to develop predictive models for differential diagnosis between mucinous and non-mucinous PCLs or malignancy detection through machine learning algorithms. Results: Two classification models were developed: TLB1 ("mucinous" vs. "non-mucinous" PCLs) and TLB2 ("benign mucinous" vs. "malignant mucinous" PCLs). The TLB1 model demonstrated a sensitivity of 92% and a negative predictive value of 86%, with an area under the curve (AUC) of 0.79 (0.59–0.99), indicating good discriminative ability between the two groups. The TLB2 model exhibited excellent predictive capability, with an AUC of 1.00. Conclusions: TLB analysis of PCLs is a promising tool that could significantly enhance the differential diagnosis of PCLs, enabling the efficient identification of mucinous lesions and even those undergoing malignant transformation. [ABSTRACT FROM AUTHOR]

Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are diverse premalignant tumors of the pancreas. They progress stepwise from adenoma to carcinoma and offer an opportunity for intervention prior to malignant transformation into pancreatic ductal adenocarcinoma (PDAC). The current study aimed to identify differentially expressed genes (DEGs) in invasive PDAC‐associated IPMN vs. noninvasive IPMN to understand the potential molecular changes involved in malignant transformation of IPMN into PDAC. Materials and Methods: Archived tissue and data from 12 patients with histologically proven invasive PDAC arising from IPMN specimens were assessed. Gene expression analysis was performed on RNA extracted from macro‐dissected tissue specimens using the NanoString nCounter PanCancer Progression assay. Statistical and pathway analysis was performed using SPSS v28 and Ingenuity Pathway Analysis, respectively. Results: A total of 159 genes had significantly (p < 0.05, q < 0.05) different expression in PDAC arising from IPMN compared with that from IPMN alone (91 overexpressed and 68 underexpressed). Interestingly, 14 of top 10 over‐ and underexpressed genes were predicted to translate secretory proteins, with SignalP scores approaching 1. A number of differential canonical pathways (e.g., LXR/RXR activation pathway, glycolysis I gluconeogenesis I, and hepatic fibrosis) and potential upstream regulators (e.g., TGFB1, THBS2, etc.) were also identified. Conclusion: A differential gene expression profile between PDAC arising from IPMN and IPMN alone was identified. Pathway analysis identified potential mechanisms involved in malignant transformation of IPMN to PDAC. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS)-guided tissue sampling includes the techniques of fine needle aspiration (FNA) and fine needle biopsy (FNB), and both procedures have revolutionized specimen collection from the gastrointestinal tract, especially from remote/inaccessible organs. EUS-FNB has replaced FNA as the procedure of choice for tissue acquisition in solid pancreatic lesions (SPLs) across various society guidelines. FNB specimens provide a larger histological tissue core (preserving tissue architecture) with fewer needle passes, and this is extremely relevant in today's era of precision and personalized molecular medicine. Innovations in needle tip design are constantly under development to maximize diagnostic accuracy by enhancing histological sampling capabilities. But, apart from the basic framework of the needle, various other factors play a role that influence diagnostic outcomes, namely, sampling techniques (fanning, aspiration or suction, and number of passes), collection methods, on-site evaluation (rapid, macroscopic, or visual), and specimen processing. The choice taken depends strongly on the endoscopist's preference, available resources at the disposal, and procedure objectives. Hence, in this review, we explicate in detail the concepts and available literature at our disposal on the topic of EUS-guided pancreatic tissue sampling to best guide any practicing gastroenterologist/endoscopist in a not-to-ideal set-up, which EUS-guided tissue acquisition technique is the "best" for their case to augment their diagnostic outcomes. [ABSTRACT FROM AUTHOR]

Purpose of Review: Given some pancreatic cysts require surveillance due to established malignant potential, efforts are being made to develop precise methods of early detection of advanced pancreatic neoplasia. This review focuses on genetic analysis of pancreatic cyst fluid for early detection of pancreatic cysts at high risk for neoplastic progression. Recent Findings: Expanded, targeted next generation sequencing pathways, such as PancreaSeq, are highly sensitive and specific not just for cyst type, but also prognosticating progression to advanced neoplasia. Currently published guidelines aiding in management of pancreatic cyst surveillance have been shown to have inferior diagnostic performance when compared to algorithms involving next-generation sequencing. Summary: Recent developments in novel next-generation sequencing pathways involving DNA/RNA based assays have increasingly allowed practitioners highly sensitive and specific modalities for early detection of advanced pancreatic neoplasia. [ABSTRACT FROM AUTHOR]

Introduction In recent years, the widespread utilisation of advanced imaging modalities has led to a surge in the detection rate of pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasms (IPMN). Consequently, this review aims to provide a comprehensive examination of IPMN, focusing on elucidating its intricate facets including definition, epidemiology, pathogenesis, classification, imaging modalities for diagnosis, analysis of pancreatic cyst fluid, evaluation of malignant potential, and identification of pertinent features. Brief Overview of Current Knowledge: IPMN represents a diagnostic conundrum owing to its variable biological behaviour encompassing both benign and malignant spectra, necessitating meticulous evaluation and risk stratification. Various imaging techniques such as MRI, CT, EUS and abdominal ultrasonography serve pivotal roles in the diagnostic algorithm and risk assessment of IPMN. Additionally, the analysis of pancreatic cyst fluid, incorporating biomarkers and the string sign test, assumes a critical role in discerning mucinous from non-mucinous cysts and gauging malignant potential. Discriminating high-risk stigmata and worrisome features serve as a compass for clinical decision-making regarding the imperative of surgical intervention versus vigilant surveillance. Summary Despite persistent challenges, the ongoing evolution of diagnostic modalities and risk assessment methodologies augur well for refining therapeutic strategies and enhancing clinical outcomes in managing IPMN. This review underscores the imperative of sustained research endeavours in the realm of pancreatic oncology to enrich our comprehension of IPMN pathophysiology and to optimise clinical care paradigms. [ABSTRACT FROM AUTHOR]

New tools are needed to determine the pancreatic cysts that require surgical resection. This study aimed to evaluate whether next-generation sequencing (NGS) is useful for identifying mucinous, malignant, or pre-malignant cysts leading to surgery. Laboratory, cytological, and histological data from 97 patients with worrisome features on imaging or an unclear pancreatic cystic lesion (PCL) who were indicated for further investigation and who underwent endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) between 2018 and 2022 were analyzed. A multidisciplinary team evaluated MRI, CT, EUS-FNA, and NGS findings. Among the 40 mucinous cysts, 53 % had KRAS and/or GNAS mutations, yielding a sensitivity of 53 % and specificity of 92 % compared to 33 and 100 % for cytology and 53 and 89 % for cystic fluid CEA. Combining NGS findings with CEA levels increased sensitivity and specificity in detecting mucinous lesions to 78 and 87 %, respectively. Surgically treated high-grade dysplasia PCLs did not show worrisome mutations in cyst fluid, while 80 % of the malignant lesions had mutations typical for advanced lesions. The advanced neoplasias showed 95 % specificity for worrisome gene mutations, with the highest diagnostic accuracy observed for NGS mutations, achieving an AUC of 0.777 in the ROC curve analysis compared to 0.631 for CEA. Patients with worrisome gene mutations were offered surgical treatment. NGS results contributed to the decision to operate in 11 out of 23 cases. In 71 % of all cases, NGS supported the diagnosis, with 3 % false positives and 12 % false negatives. NGS analysis of pancreatic cyst fluid demonstrates high specificity and may serve as an additional diagnostic tool to CEA. Combining cystic fluid CEA and NGS increases the accuracy in determining whether a lesion is mucinous and NGS showed a higher diagnostic accuracy in advanced lesions compared to CEA. While the absence of alarming NGS findings should not preclude surgical treatment, patients with alarming mutations should be considered for surgery. [ABSTRACT FROM AUTHOR]

A 67-year-old man was admitted to our hospital with jaundice. A closer examination revealed that he had obstructive jaundice due to bile duct obstruction caused by a multifocal cystic tumor of the pancreas. Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis of the distal bile duct and leakage of contrast medium into the pancreatic cyst. Pancreaticoduodenectomy was performed, and a pinhole fistula was found connecting the cyst and the bile duct. Histological examination led to the diagnosis of serous cystadenoma (SCA). Herein, we report a rare case of SCA with obstructive jaundice and penetration of the bile duct, which was treated by radical resection. [ABSTRACT FROM AUTHOR]

Background: This study aimed to report the long-term outcomes after surgical resection for invasive (I) intraductal papillary mucinous neoplasm (IPMN) and to define prognostic factors for survival. Methods: We retrospectively evaluated all consecutive pancreatic resections performed IPMN between January 1, 2007, and December 31, 2022. Multivariate Cox analysis identified risk factors for survival. Results: Surgery for IPMN was performed in 125 patients including 78 I-IPMN (62%). Ninety-day mortality rates was 1.6% (n = 2) with an overall morbidity rate of 44.4%. I-IPMN showed higher serum CA 19 − 9 serum values (p < 0.0001), more frequently jaundice (p = 0.008), more high-risk stigmata (p = 0.002) and diffuse IPMN form (p = 0.005) compared with non-invasive IPMN. The median overall survival for I-IPMN was 178.36 months (95% confidence interval [CI]: 87.01–NR) with overall survival rates at one, three, five, and 10 years of 91%, 75%, 72%, and 62%, respectively. Jaundice (hazard ratio [HR]: 4.23; 95% CI: 1.48–12.07; p = 0.006), T3 lesions (HR: 3.24; 95% CI: 1.65–6.39; p = 0.006), absence of lymph node involvement (HR: 0.15; 95% CI: 0.04–0.60; p = 0.0007), R1 margin status (HR: 2.96;95%CI:1.08-8:15;p = 0.03) and need for venous resection (HR: 4.30; 95% CI: 1.26–14.6; p = 0.006) were identified as independent risk factors for survival. Conclusions: Long-term survival and cure can be observed after surgical resection of pancreatic adenocarcinomas originating from I-IPMN when resected at early stage (Tis, T1, T2). I-IPMN spreading beyond pancreatic ducts (jaundice, T3 lesions, lymph nodes, Veins) have limited long-term survival. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the deadliest malignant tumors worldwide, known as the 'king of cancers due to its insidious onset, high malignancy, and high mortality rate. PC is highly malignant and progresses rapidly, but its onset is insidious with atypical early symptoms, making it difficult to detect early lesions through conventional imaging studies. It is usually only discovered when symptoms like jaundice, abdominal and back pain occur. Surgical resection is currently the only curative option for PC. However, due to the difficulty in early diagnosis, the majority of patients are already in the middle to late stages at the time of diagnosis, missing the opportunity for surgery. Studies have confirmed that the progression of pancreatic cancer is relatively slow, with the initial tumor cells requiring at least 15 years to gain metastatic ability. Therefore, timely detection of pancreatic cancer through tumor markers could significantly improve the survival rate of patients. The most widely used and diagnostically valuable tumor marker in clinical practice is Carbohydrate antigen 199 (CA199). However, due to about 3% ~ 7% of pancreatic cancer patients being Lewis antigen-negative blood types and not expressing CA19-9, its sensitivity is only 79% ~ 81%, which does not provide good efficacy for the diagnosis of pancreatic cancer. Pancreatic juice, as a fluid near the tumor, has attracted much attention as a good source of tumor-related biomarkers. Many studies have confirmed the accuracy of using proteins, DNA, and exosomes in pancreatic juice for the diagnosis of pancreatic cancer, showing great prospects for pancreatic juice as a source of tumor markers for the diagnosis of pancreatic cancer. Therefore, this thesis reviews the efficacy of pancreatic juice as a specimen for the diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background and Aim: Intraductal papillary mucinous neoplasm (IPMN)‐derived pancreatic ductal adenocarcinoma (PDAC) management is generally extrapolated from pancreatic intraepithelial neoplasia (PanIN)‐derived PDAC guidelines. However, these are biologically divergent, and heterogeneity further exists between tubular and colloid subtypes. Methods: Consecutive upfront surgery patients with PanIN‐derived and IPMN‐derived PDAC were retrospectively identified from international centers (2000–2019). One‐to‐one propensity score matching for clinicopathologic factors generated three cohorts: IPMN‐derived versus PanIN‐derived PDAC, tubular IPMN‐derived versus PanIN‐derived PDAC, and tubular versus colloid IPMN‐derived PDAC. Overall survival (OS) was compared using Kaplan–Meier and log‐rank tests. Multivariable Cox regression determined corresponding hazard ratios (HR) and 95% confidence intervals (95% CI). Results: The median OS (mOS) in 2350 PanIN‐derived and 700 IPMN‐derived PDAC patients was 23.0 and 43.1 months (P < 0.001), respectively. PanIN‐derived PDAC had worse T‐stage, CA19‐9, grade, and nodal status. Tubular subtype had worse T‐stage, CA19‐9, grade, nodal status, and R1 margins, with a mOS of 33.7 versus 94.1 months (P < 0.001) in colloid. Matched (n = 495), PanIN‐derived and IPMN‐derived PDAC had mOSs of 30.6 and 42.8 months (P < 0.001), respectively. In matched (n = 341) PanIN‐derived and tubular IPMN‐derived PDAC, mOS remained poorer (27.7 vs 37.4, P < 0.001). Matched tubular and colloid cancers (n = 112) had similar OS (P = 0.55). On multivariable Cox regression, PanIN‐derived PDAC was associated with worse OS than IPMN‐derived (HR: 1.66, 95% CI: 1.44–1.90) and tubular IPMN‐derived (HR: 1.53, 95% CI: 1.32–1.77) PDAC. Colloid and tubular subtype was not associated with OS (P = 0.16). Conclusions: PanIN‐derived PDAC has worse survival than IPMN‐derived PDAC supporting distinct outcomes. Although more indolent, colloid IPMN‐derived PDAC has similar survival to tubular after risk adjustment. [ABSTRACT FROM AUTHOR]

Pancreatic cystic lesions represent a challenging heterogeneous entity with a potential risk of malignant transformation. The diagnostics include in particular medical history taking with collection of relevant clinical information and high-resolution imaging, preferably using magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) and/or endoscopic ultrasonography. A differentiation between different cystic entities and identification of risk factors are crucial for making appropriate treatment decisions. Only a small proportion of pancreatic cystic neoplasms require surgery. Pancreatic cystic lesions with a relevant risk of malignancy, such as main duct intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and general cystic pancreatic lesions with risk factors regardless of the entity, should be resected, whereas an individualized approach is required for branch duct IPMN and serous cystic neoplasms (SCN) and dysontogenetic cysts require no treatment. Parenchyma-sparing and minimally invasive resection techniques should be preferred whenever possible for resecting pancreatic cystic tumors. Approximately 10% of patients develop recurrences over time. [ABSTRACT FROM AUTHOR]

Background: Endoscopic cysto-gastrostomy (ECG) has become the treatment of choice for pancreatic pseudocysts (PPCs). Endoscopic drainage of PPCs requires the creation of an anastomosis between the lumen of the PPCs and the lumen of the gastrointestinal tract. Various types of stents are used for this purpose. The aim of the study is to compare the indications, quantity, and results of using double pigtail plastic stents (DPPSs) and lumen-apposing fully covered metal stents (LAMSs) in ECG. Methods: A retrospective analysis was conducted of 39 patients (24 men, 15 women) treated for PPCs in the Department of Digestive Tract Surgery and the Department of Gastroenterology and Hepatology between October 2018 and February 2023. The mean age of patients was 51.13 (28–77). Data about etiology, cyst diameter, type, and complications of the stents were collected. Results: DPPSs were placed in smaller cysts (108 vs. 140 millimeters, p = 0.04) and were maintained for a longer duration compared to LAMSs (106 vs. 34 days, p = 0.001). Cyst recurrence was reported less frequently in patients with a LAMS (0 (0%) vs. 4 (19.05%), p = 0.05) and the therapeutic success was non-significantly higher in the LAMS group compared to the DPPS group (100% vs. 85.71%), p = 0.095. Conclusions: Both DPPSs and LAMSs are characterized by high therapeutic success and low complication rates in patients undergoing ECG for PPCs. [ABSTRACT FROM AUTHOR]

Superior mesenteric artery aneurysms are a rare pathology, and rupture due to a pancreatic cyst in the context of alcohol-induced pancreatitis is an even rarer condition. The first line of treatment is usually an endovascular approach. We present the case of a 51-year-old male with alcohol-induced pancreatitis, diagnosed with a superior mesenteric artery aneurysm with active bleeding in close contact with a large pancreatic cyst. A covered stent was used to treat this condition. The patient developed hemorrhagic shock 12 h after the procedure and an urgent laparotomy was performed. A second rupture of the arterial wall at the distal end of the stent was observed and in order to obtain distal perfusion, first, an infrarenal aorta to superior mesenteric artery bypass distal to the rupture was performed in order to exclude the aneurysm. Secondly, a bypass originating from the distal end of the first bypass to the distal end of the superior mesenteric artery was performed. The patient had an uneventful recovery and was discharged after 10 days. We reviewed the literature regarding the incidence and the therapeutic management of superior mesenteric artery aneurysm complicated by pancreatic cyst. An advanced search on PubMed from 2004 to 2024 returned 194 results and after applying the inclusion–exclusion criteria, 11 publications were selected. Although the endovascular approach is usually the first line of treatment with obvious advantages for the patient, a patient-tailored approach should be made in such cases and surgery could be the first option, when considering that the mechanism of aneurysm rupture is due to erosion of the arterial wall by the pancreatic enzymes. Surgery has the advantage of cyst drainage and aneurysm exclusion and in our case proved lifesaving. [ABSTRACT FROM AUTHOR]

Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. Consecutive patients undergoing pancreatic resection (2010–2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). 415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). Invasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN. [ABSTRACT FROM AUTHOR]

Background Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is increasingly being diagnosed incidentally on imaging. It has malignant potential, making it vital to establish the correct diagnosis, assess its malignant risk and follow a management strategy to prevent development of invasive carcinoma of the pancreas. Objective This review focuses on the epidemiology, natural history, risk factors, diagnosis and management of IPMN of the pancreas, and will provide practical points for general practitioners. Discussion IPMN of the pancreas can transform into invasive pancreatic carcinoma at a low rate of approximately 2%/year. Upon diagnosis of IPMN, it is risk stratified based on the presence of worrisome or high-risk stigmata, which guides further management. Management needs to be individualised based on IPMN and patient factors due to limitations with the current diagnostic tools. [ABSTRACT FROM AUTHOR]

In many applications, it is of interest to identify a parsimonious set of features, or panel, from multiple candidates that achieves a desired level of performance in predicting a response. This task is often complicated in practice by missing data arising from the sampling design or other random mechanisms. Most recent work on variable selection in missing data contexts relies in some part on a finite-dimensional statistical model, e.g., a generalized or penalized linear model. In cases where this model is misspecified, the selected variables may not all be truly scientifically relevant and can result in panels with suboptimal classification performance. To address this limitation, we propose a nonparametric variable selection algorithm combined with multiple imputation to develop flexible panels in the presence of missing-at-random data. We outline strategies based on the proposed algorithm that achieve control of commonly used error rates. Through simulations, we show that our proposal has good operating characteristics and results in panels with higher classification and variable selection performance compared to several existing penalized regression approaches in cases where a generalized linear model is misspecified. Finally, we use the proposed method to develop biomarker panels for separating pancreatic cysts with differing malignancy potential in a setting where complicated missingness in the biomarkers arose due to limited specimen volumes. [ABSTRACT FROM AUTHOR]

The American Journal of Gastroenterology published abstracts on innovative medical research related to pancreatic cancer, acute pancreatitis, and biliary drainage in liver transplant recipients. Studies included the use of artificial intelligence in detecting pancreatic lesions, GLP-1 receptor agonists in reducing pancreatic cancer risk, and the safety of endoscopic ultrasound-guided radiofrequency ablation. Research also focused on comparing biliary drainage techniques, self-expandable metallic stents in patients with malignant biliary obstruction, and readmission risks for ERCP patients. Further studies are needed to validate findings and improve patient outcomes in these areas. [Extracted from the article]

Background/Aim: This study evaluated the cumulative incidence of pancreatic cancer and worrisome features (WFs) in patients with pancreatic cysts (PCs) clinically considered as branch-duct intrapapillary mucinous neoplasm (BD-IPMN). Methods: Data from 177 patients followed for BD-IPMN were retrospectively analyzed. Suspected BD-IPMN was defined as PCs with confirmed communication with the main pancreatic duct (MPD) via imaging studies, while presumed BD-IPMN referred to PCs lacking clear MPD communication. Results: Among the patients, 30.5% were categorized as suspected BD-IPMN. The median age at diagnosis was 64 years, with a median cyst size of 13 mm. At diagnosis, 19 patients (10.7%) exhibited WFs, and none of the patients had high-risk stigmata. Over a follow-up period of 70.5 months, pancreatic cancer developed in three patients, resulting in a cumulative incidence of 4.0% (95% confidence interval [CI], 0.98 to 10.76%) at 96 months. For the 158 patients without initial WFs, the cumulative incidence of WFs was 5.1% (95% CI, 2.37 to 9.28%) at 24 months and 11.2% (95% CI, 6.34 to 17.53%) at 96 months. The development of WFs was lower in the presumed BD-IPMN group (p=0.102) and among patients aged under 75 (p=0.463), though these differences were not statistically significant. Notably, the incidence of WFs plateaued after two years in the elderly cohort. Conclusions: The cumulative incidence of pancreatic cancer and WFs in patients with low-risk PCs was notably low. Furthermore, discontinuing surveillance may be considered for elderly patients, especially those with no changes within the first two years of observation. [ABSTRACT FROM AUTHOR]

Pancreatic cystic neoplasms are lesions comprised of cystic components that show different biological behaviors, epidemiology, clinical manifestations, imaging features, and malignant potential and management. Benign cystic neoplasms include serous cystic neoplasms (SCAs). Other pancreatic cystic lesions have malignant potential, such as intraductal papillary mucinous neoplasms and mucinous cystic neoplasms. SCAs can be divided into microcystic (classic appearance), honeycomb, oligocystic/macrocystic, and solid patterns based on imaging appearance. They are usually solitary but may be multiple in von Hippel–Lindau disease, which may depict disseminated involvement. The variable appearances of SCAs can mimic other types of pancreatic cystic lesions, and cross-sectional imaging plays an important role in their differential diagnosis. Endoscopic ultrasonography has helped in improving diagnostic accuracy of pancreatic cystic lesions by guiding tissue sampling (biopsy) or cyst fluid analysis. Immunohistochemistry and newer techniques such as radiomics have shown improved performance for preoperatively discriminating SCAs and their mimickers. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively compare inter- and intra-reader agreement of abbreviated MRCP (aMRCP) with comprehensive MRI (cMRCP) protocol for detection of worrisome features, high-risk stigmata, and concomitant pancreatic cancer in pancreatic cyst surveillance. Methods: 151 patients (104 women, mean age: 69[10] years) with baseline and follow-up contrast-enhanced MRIs were included. This comprised 138 patients under cyst surveillance with 5-year follow-up showing no pancreatic ductal adenocarcinoma (PDAC), 6 with pancreatic cystic lesion-derived malignancy, and 7 with concomitant PDAC. The aMRCP protocol used four sequences (axial and coronal Half-Fourier Single-shot Turbo-spin-Echo, axial T1 fat-saturated pre-contrast, and 3D-MRCP), while cMRCP included all standard sequences, including post-contrast. Three blinded abdominal radiologists assessed baseline cyst characteristics, worrisome features, high-risk stigmata, and PDAC signs using both aMRCP and cMRCP, with a 2-week washout period. Intra- and inter-reader agreement were calculated using Fleiss' multi-rater kappa and Intra-class Correlation Coefficient (ICC). 95% confidence intervals (CI) were calculated. Results: Cyst size, growth, and abrupt main pancreatic duct transition had strong intra- and inter-reader agreement. Intra-reader agreement was ICC = 0.93–0.99 for cyst size, ICC = 0.71–1.00 for cyst growth, and kappa = 0.83–1.00 for abrupt duct transition. Inter-reader agreement for cyst size was ICC = 0.86 (aMRCP) and ICC = 0.83 (cMRCP), and for abrupt duct transition was kappa = 0.84 (aMRCP) and kappa = 0.69 (cMRCP). Thickened cyst wall, mural nodule and cyst-duct communication demonstrated varying intra-reader agreements and poor inter-reader agreements. Conclusion: aMRCP showed high intra- and inter-reader agreement for most pancreatic cyst parameters that highly rely on T2-weighted sequences. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) under endoscopic ultrasound (EUS) guidance has been developed and utilized over the last decade to provide the loco-regional treatment of solid and cystic pancreatic neoplastic lesions. The advantage of this approach relies on the close proximity of the EUS transducer to the target pancreatic lesion, which, coupled with the development of specifically designed RFA ablation devices, has made the procedure minimally invasive, with a clear reduction in adverse events as compared to the high morbidity of the surgical approach. EUS-RFA has been applied so far to pancreatic functional and non-functional neuroendocrine neoplasms, pancreatic ductal adenocarcinoma or metastases to the pancreas, and pancreatic neoplastic cysts. Excluding neuroendocrine tumors, for other indications, most of these procedures have been performed in patients who refused surgery or were at high surgical risk. More studies evaluating EUS-RFA in selected patients, not at surgical risk, are gradually becoming available and will pave the road to extend the indications for this therapeutic approach, also in association with other oncological therapies. The present manuscript will critically review the available evidence in the field of the EUS-guided RFA of solid and cystic pancreatic neoplasms. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aimed to clarify whether several single‐nucleotide polymorphisms (SNPs)‐related chronic pancreatitis such as carboxypeptidase A1 (CPA1), carboxypeptidase B1 (CPB1), Gamma‐glutamyltransferase 1 (GGT1), G‐protein‐coupled receptor Class C Group 6 Member A (GPRC6A), and serine protease inhibitor, Kazal type 1 (SPINK‐1) genotypes were associated with clinical characteristics of patients with intraductal papillary mucinous neoplasm (IPMN) and worrisome features of IPMN. Methods: We enrolled 100 patients with IPMN and 116 patients as a control. Serum p‐amylase, lipase, trypsin, phospholipase A2 (PLA2), and elastase‐1 levels were measured. An Olympus EUS (GF‐UCT 260) was used to perform endosonography in 100 patients with IPMN. Total EUS score was evaluated using endosonography. DNA was isolated from the duodenal tissue using a commercial system and polymerase chain reaction (PCR) was performed on 7500 Fast PCR System. Results: There were no associations between glucose tolerances, lipid levels and genotypes of CPA1, GGT1, GPRC6A, and SPINK‐1 in patients with IPMN. CPA1 genotype was significantly associated with the pathophysiology of IPMN. Then, GGT1 genotype was also significantly associated with EUS total score and the size of cyst more than 20 mm and more than 30 mm as one of worrisome features of IPMN. Conclusion: Genotypes of carboxypeptidase A1 and gamma‐glutamyltransferase 1 may be useful tools for the diagnosis and the predictor of worrisome features of IPMN. [ABSTRACT FROM AUTHOR]

The development of ultrasensitive electronic sensors for in vitro diagnostics is essential for the reliable monitoring of asymptomatic individuals before illness proliferation or progression. These platforms are increasingly valued for their potential to enable timely diagnosis and swift prognosis of infectious or progressive diseases. Typically, the responses from these analytical tools are recorded as digital signals, with electronic data offering simpler processing compared to spectral and optical data. However, preprocessing electronic data from potentiometric biosensor arrays is still in its infancy compared to more established optical technologies. This study utilized the Single‐Molecule with a Large Transistor (SiMoT) array, which has achieved a Technology Readiness Level of 5, to explore the impact of data preprocessing on electronic biosensor outcomes. A dataset consisting of plasma and cyst fluid samples from 37 patients with pancreatic precursor cyst lesions was analyzed. The findings revealed that standard signal preprocessing can produce misleading conclusions due to artifacts introduced by mathematical transformations. The study offers strategies to mitigate these effects, ensuring that data interpretation remains accurate and reflective of the underlying biochemical information in the samples. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: A choledochal cyst (CC), or biliary cyst, is a congenital or acquired anomaly of the biliary tree. Pancreas divisum (PD) is a rare congenital anomaly due to incomplete fusion of pancreatic ducts, which can complicate the clinical course of choledochal cysts. This rare combination is a surgical management challenge. This report presents the diagnosis and management of a 23-year-old woman with a combined choledochal cyst and pancreas divisum treated with pancreaticoduodenectomy. Case Report: This article presents the case of a 23-year-old woman who presented with severe, stabbing abdominal pain radiating to the back and epigastric tenderness and was diagnosed with pancreatitis. Initial imaging revealed a choledochal cyst, prompting further investigation with ERCP that showed concomitant PD. She was treated via pancreaticoduodenectomy. During the following 9 years, she was hospitalized over 2 dozen times for recurrent pancreatitis. Conclusions: This report presents a complex case of a combined choledochal cyst and pancreas divisum, which was surgically managed by pancreaticoduodenectomy. The association of CC with PD should be suspected in patients with recurrent acute pancreatitis and/or cholangitis with no identifiable cause. Surgical treatment of CC with PD depends on the classification of the CC, and complications can include recurrent pancreatitis, although the prognosis is often favorable. The purpose of this report is to emphasize that pancreaticoduodenectomy is unlikely to provide favorable outcomes for CC with PD, especially considering there is evidence that less extensive surgical interventions produce better outcomes. [ABSTRACT FROM AUTHOR]

The article provides an overview of pancreatic cysts, focusing on their increasing detection, varied risk of malignancy, and management strategies. Topics discussed include the types of pancreatic cysts and their malignancy risks, diagnostic approaches such as imaging and endoscopic ultrasonography, and guidelines for evaluating and managing cysts based on their potential for cancer.

Primary pancreatic hydatid cyst is a rare form of echinococcosis, even in endemic areas. The present study reports the case of a 67-year-old male patient with a primary pancreatic hydatid cyst who presented with severe epigastric pain, vomiting and fever for a period >2 weeks. An endoscopic ultrasound revealed a cystic lesion in the pancreatic head with a solid component. A computed tomography scan and magnetic resonance imaging confirmed the ultrasound finding. Under general anesthesia, the patient underwent total pancreatectomy and splenectomy. A histopathological examination confirmed a primary pancreatic hydatid cyst. Hydatid cysts rarely occur primarily in the pancreas. They may spread to the pancreas through the hematogenous route. Various procedures can be performed for cyst removal, depending on the size and location of the cysts. Open surgery, laparoscopy and hybrid options are available; however, to date, the gold standard is open surgery to prevent spillage and reduce the chance of recurrence. Although rare, primary pancreatic hydatid cysts can occur, with surgery being the main treatment modality due to the vague preoperative diagnosis based on imaging. [ABSTRACT FROM AUTHOR]

Aims and Background: Matrix metalloproteinase‐7 (MMP‐7) and Syndecan‐1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts. Methods: In this case–control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups. Serum MMP‐7 and SDC1 were measured by ELISA. The diagnostic accuracy of their levels for diagnosing PDAC and pancreatic cysts was computed, and their association with survival outcomes was evaluated. Results: MMP‐7 median serum levels were significantly elevated in the PDAC (7.3 ng/mL) and cyst groups (3.7 ng/mL) compared with controls (2.9 ng/mL) (p < 0.001 and 0.02, respectively), and also between the PDAC and cyst groups (p < 0.001), while SDC1 median serum levels were significantly elevated in PDAC (43.3 ng/mL) compared with either cysts (30.1 ng/mL, p < 0.001) or controls (31.2 ng/mL, p < 0.001). The receiver operating characteristic curve analysis area under the curve in PDAC versus controls was 0.90 and 0.78 for MMP‐7 and SDC1, respectively, while it was 1.0 for the combination of the two and CA 19‐9 (p < 0.001). The combination of the three biomarkers had a perfect sensitivity (100%). Conclusions: Due to its high sensitivity, this biomarker panel has the potential to rule out PDAC in suspected cases. [ABSTRACT FROM AUTHOR]

Introduction: Patients with intraductal papillary mucinous neoplasms (IPMNs) exhibit a high incidence of pancreatic cancer. An IPMN presents as a pancreatic cystic lesion (PCL). Artificial intelligence (AI) can be used to enhance ultrasonographic images. We retrospectively evaluated the utility of AI‐assisted ultrasonography in terms of PCL detection. Methods: In total, 969 patients who underwent artificial narrow intelligence‐assisted transabdominal ultrasound examinations (AI group) were compared with 943 patients who underwent non‐AI‐assisted examinations (control group). The morphological changes and the frequencies of newly detected PCLs were compared between the groups. Results: The PCL detection rate was significantly higher in the AI group than in the control group (1.25 ± 0.36 and 0.21 ± 0.15%, respectively; p =.008). AI‐assisted ultrasound evaluation was independently associated with enhanced PCL detection (odds ratio: 5.83, 95% confidence interval: 1.29–26.29, p =.02). PCLs smaller than 8 mm and all PCLs in the pancreatic tail were detected in the AI group. PCL morphological changes were more common in the AI group than in the control group (63.6 ± 14.5 and 16.7 ± 15.2%, respectively; p =.04). Conclusion: AI‐assisted transabdominal ultrasonography enhances the PCL detection rate. The use of AI is likely to increase the IPMN detection rate. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cystic lesions (PCLs) are frequent on MRI and are thought to be associated with pancreatic adenocarcinoma (PDAC) necessitating long‐term surveillance based on older studies suffering from selection bias. Purpose: To establish the percentage of patients with PCLs on MRI with a present or future PDAC. Study Type: Systematic review, meta‐analysis. Population: Adults with PCLs on MRI and a present or future diagnosis of PDAC were eligible. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus were searched to April 2022 (PROSPERO:CRD42022320502). Studies limited to PCLs not requiring surveillance, <100 patients, or those with a history/genetic risk of PDAC were excluded. Field Strength/Sequence: ≥1.5 T with ≥1 T2‐weighted sequence. Assessment: Two investigators extracted data, with discrepancies resolved by a third. QUADAS‐2 assessed bias. PDAC was diagnosed using a composite reference standard. Statistical Tests: A meta‐analysis of proportions was performed at the patient‐level with 95% confidence intervals (95% CI). Results: Eight studies with 1289 patients contributed to the percentage of patients with a present diagnosis of PDAC, and 10 studies with 3422 patients to the percentage with a future diagnosis. Of patients with PCLs on MRI, 14.8% (95% CI 2.4–34.9) had a PDAC at initial MRI, which decreased to 6.0% (2.2–11.3) for studies at low risk of bias. For patients without PDAC on initial MRI, 2.0% (1.1–3.2) developed PDAC during surveillance, similar for low risk of bias studies at 1.9% (0.7–3.6), with no clear trend of increased PDAC for longer surveillance durations. For patients without worrisome features or high‐risk stigmata, 0.9% (0.1–2.2) developed PDAC during surveillance. Of 10, eight studies had a median surveillance ≥3 years (range 3–157 months). Sources of bias included retrospectively limiting PCLs to those with histopathology and inconsistent surveillance protocols. Data Conclusion: A low percentage of patients with PCLs on MRI develop PDAC while on surveillance. The first MRI revealing a PCL should be scrutinized for PDAC. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

The article discusses the practice of prophylactic total gastrectomy in individuals with germline CDH1 gene mutations to prevent diffuse-type gastric cancer. It highlights the evolution of viewpoints on this surgery, cautioning against a one-size-fits-all approach due to the chronic morbidity it can cause. The authors recommend a more selective application of prophylactic total gastrectomy based on accumulating evidence of lower lifetime advanced gastric cancer risk, the indolent nature of intramucosal signet ring cell lesions, and the safety and effectiveness of endoscopic surveillance. The article emphasizes the importance of informed decision-making and consultation with experts in managing individuals with CDH1 P/LP variants. [Extracted from the article]

Pancreatic cancer is projected to become the second leading cause of cancer-related mortality in the United States by 2030. This is in part due to the paucity of reliable screening and diagnostic options for early detection. Amongst known pre-malignant pancreatic lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent. The current standard of care for the diagnosis and classification of pancreatic cystic lesions (PCLs) involves cross-sectional imaging studies and endoscopic ultrasound (EUS) and, when indicated, EUS-guided fine needle aspiration and cyst fluid analysis. However, this is suboptimal for the identification and risk stratification of PCLs, with accuracy of only 65-75% for detecting mucinous PCLs. Artificial intelligence (AI) is a promising tool that has been applied to improve accuracy in screening for solid tumors, including breast, lung, cervical, and colon cancer. More recently, it has shown promise in diagnosing pancreatic cancer by identifying high-risk populations, risk-stratifying premalignant lesions, and predicting the progression of IPMNs to adenocarcinoma. This review summarizes the available literature on artificial intelligence in the screening and prognostication of precancerous lesions in the pancreas, and streamlining the diagnosis of pancreatic cancer.

Pancreatic cystic lesions (PCLs) are increasingly diagnosed owing to the wide use of cross-sectional imaging techniques. Accurate identification of PCL categories is critical for determining the indications for surgical intervention or surveillance. The classification and management of PCLs rely on a comprehensive and interdisciplinary evaluation, integrating clinical data, imaging findings, and cyst fluid markers. EUS (endoscopic ultrasound) has become the widely used diagnostic tool for the differentiation of pancreatic cystic lesions, offering detailed evaluation of even small pancreatic lesions with high sensitivity and specificity. Additionally, endoscopic ultrasound–fine-needle aspiration enhances diagnostic capabilities through cytological analysis and the assessment of fluid viscosity, tumor glycoprotein concentration, amylase levels, and molecular scrutiny. These detailed insights play a pivotal role in improving the clinical prognosis and management of pancreatic neoplasms. This review will focus mainly on the latest recommendations for the differentiation, management, and treatment of pancreatic cystic lesions, highlighting their clinical significance. [ABSTRACT FROM AUTHOR]

Objective: Unusual or unexpected effect of treatment Background: Minimally invasive pancreatectomy has become the standard practice for the management of benign and malignant pancreatic tumors. Techniques such as robotic and laparoscopic approaches are known to reduce morbidity by offering benefits such as less blood loss, reduced pain, shorter hospital stays, and quicker recovery times. The indication for repeated minimally invasive pancreatectomy for recurrent or de novo pancreatic neoplasm after primary pancreatic surgery remains debated. Case Report: A 50-year-old woman was admitted to our hospital with a diagnosis of an intraductal papillary mucinous neoplasm in the pancreatic head. In 2010, she underwent laparoscopic single-branch resection for a branch-type tumor in the pancreatic uncinate process. During a 5-year follow-up, a de novo intraductal papillary mucinous neoplasm was detected, showing gradual growth and the presence of a mural nodule over the next 7 years. The patient’s CEA level was elevated to 7.0 ng/mL. Considering the tumor’s progression and the appearance of a mural nodule, we recommended a robot-assisted Whipple procedure. The operation began with laparoscopic adhesiolysis. After detachment of the adhesions and remobilization of the duodenum using the Kocher maneuver, the operation continued with the Da Vinci surgical system. The postoperative period was uneventful, and the patient was discharged on postoperative day 20. Pathological examination revealed intraductal papillary mucinous carcinoma in situ with negative resection margins. Conclusions: This case verifies the safety and feasibility of performing a robotic Whipple procedure for a newly diagnosed pancreatic neoplasm in patients who have previously undergone minimally invasive pancreatic surgery. [ABSTRACT FROM AUTHOR]

Extrahepatic malignancies are the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Of these cancers, pancreatic cancer is one of the most lethal; however, the link between NAFLD and pancreatic cancer remains unclear. Recently, various research results have been reported on the association between NAFLD and pancreatic cancer, and the results of compiling this information revealed the following. First, the prevalence of pancreatic cancer in patients with NAFLD is at 0.26%. Second, the currently evident pathogenesis includes intrapancreatic risk factors, such as: (1) non‐alcoholic fatty pancreas disease, and (2) intraductal papillary mucinous neoplasm; and extrapancreatic risk factors, such as: (1) insulin resistance and adipocytokines, (2) proinflammatory cytokines, and (3) dysbiosis. Finally, metformin and sodium–glucose cotransporter 2 inhibitors may reduce the risk of pancreatic cancer in diabetes patients with NAFLD. In this review, we summarize the recent evidence on the epidemiology and mechanisms for NAFLD‐related pancreatic cancer. We further discuss the impact of anti‐diabetic medication on pancreatic cancer. [ABSTRACT FROM AUTHOR]

Pancreatic cystic lesions (PCLs) pose a diagnostic challenge due to their increasing incidence and the limitations of cross-sectional imaging and endoscopic-ultrasound-guided fine-needle aspiration (EUS-FNA). EUS-guided through the needle biopsy (EUS-TTNB) has emerged as a promising tool for improving the accuracy of cyst type determination and neoplastic risk stratification. EUS-TTNB demonstrates superior diagnostic performance over EUS-FNA, providing critical preoperative information that can significantly influence patient management and reduce unnecessary surgeries. However, the procedure has risks, with an overall adverse event rate of approximately 9%. Preventive measures and further prospective studies are essential to optimize its safety and efficacy. This review highlights the potential of EUS-TTNB to enhance the diagnostic and management approaches for patients with PCLs. It examines the current state of EUS-TTNB, including available devices, indications, procedural techniques, specimen handling, diagnostic yield, clinical impact, and associated adverse events. [ABSTRACT FROM AUTHOR]

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29–83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy. [ABSTRACT FROM AUTHOR]

Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different management strategies, and implementation in patient care is inconsistent in the absence of dedicated infrastructure. To address the challenges of pancreatic cyst diagnosis and management, we established a multidisciplinary pancreas cyst clinic (PCC) within our health system. This clinic encompasses both tertiary care academic centers and community hospitals, with leadership from surgical oncology, gastroenterology, and radiology. Our PCC's primary goal is to provide accurate diagnosis and tailored management recommendations for all patients with pancreatic cysts. Additionally, we maintain a prospective database to study the disease's natural history and the outcomes of various treatment strategies. The clinic meets once per week for 45 min virtually via Zoom in the mornings. Patients are referred via electronic medical record (EMR) order, telephone call, or email from patient or referring provider. A dedicated advanced practice provider reviews referrals several times per day, calls patients to gather clinical data, ensures imaging is uploaded, and coordinates logistical aspects of the meeting during the dedicated time. Conferences are attended by representatives from surgery, radiology, medical pancreatology, and interventional gastroenterology. Each patient case is reviewed in detail and recommendations are submitted to referring providers and patients via an EMR message and letter. For patients requiring imaging surveillance, patients are followed longitudinally by the referring provider, gastroenterology team, or surgical team. For patients requiring endoscopic ultrasound (EUS) or surgical consultation, expedited referral to these services is made with prompt subsequent evaluation. A total of 1052 patients from our health system were evaluated between 2020 and 2021. Of these, 196 (18.6 %) underwent EUS, 41 (3.9 %) underwent upfront surgical resection, and the remainder were referred to gastroenterology (141–13.4 %), surgery (314–29.8 %), or back to their referring provider (597–56.7 %) for ongoing surveillance in collaboration with their primary care provider (PCP). Of cysts under surveillance, 61.3 % remained stable, 13.2 % increased in size, and 2 % decreased in size. A total of 2.3 % of patients were recommended to discontinue surveillance. The PCC provides infrastructure that has served to provide multidisciplinary review and consensus recommendations to patients with pancreatic cysts. This has served to improve the application of guidelines while providing individualized recommendations to each patient, while aiding non-expert referring providers throughout the region. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, ranking as the third factor in cancer‐related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT‐Single‐molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP‐X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP‐X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre‐invasive high‐grade or potentially malignant low‐grade pancreatic cysts from benign non‐mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1 mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field‐deployable liquid biopsy. [ABSTRACT FROM AUTHOR]