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Background: For premalignant main duct intraductal papillary mucinous neoplasms (MD-IPMN), laparoscopic duodenum and spleen-preserving subtotal or total pancreatectomy (LDSP-STP/TP) seems to be a viable option for parenchyma-sparing pancreatectomy. Patients and Methods: On the basis of the imaging features, family history, genomic alterations, intraoperative ultrasound examination, and frozen section evaluation, we have proposed patient selection strategies for the LDSP-STP/TP technique for the first time. Additionally, a comprehensive step-by-step overview of this technique has been provided. To date, we have performed five LDSP-STP procedures and one LDSP-TP procedure. Results: We successfully performed selective resection of the affected pancreatic parenchyma while preserving the duodenum, common bile duct (CBD), spleen, and splenic artery and vein. The operation time ranged from 295 to 495 min, with blood loss ranging from 100 to 300 mL. Postoperative pathological results revealed low-grade dysplasia in the resected pancreatic samples and margins. The patients resumed eating within 3–5 days after surgery, and all postoperative complications were classified as grade I according to the Clavien–Dindo classification. At the 3-month follow-up, there were no cases of CBD ischemic stenosis, splenic ischemia, or pseudocyst formation observed. For patients who received LDSP-STP, the longitudinal diameter of the remaining pancreatic tail ranged from 2.2 to 4.6 cm, and they demonstrated satisfactory long-term blood glycemic control. Conclusions: LDSP-STP/TP demonstrates technical feasibility and safety. It allows for the selective resection of the affected pancreatic parenchyma, thereby minimizing the impact of pancreatic functional impairment. However, it is crucial to validate this technique through long-term prospective observations. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the deadliest forms of cancer, characterized by high rates of metastasis, late detection, and poor prognoses. Artificial intelligence and machine learning (AI/ML) have proven to be highly effective in improving the current standard of care for many cancers, including PDAC. This review article provides a holistic overview of high-impact, transformative AI/ML applications in various areas of PDAC care. Reflecting a patient's medical journey, these areas include screening, diagnosis, treatment, and post-treatment surveillance. Obstacles and limitations in AI/ML applications within the context of PDAC are also discussed, along with potential solutions and future directions. Collectively, this review article offers novel approaches and meaningful insights, potentially leading to solutions for the multifaceted challenges inherent in PDAC. Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most formidable challenges in oncology, characterized by its late detection and poor prognosis. Artificial intelligence (AI) and machine learning (ML) are emerging as pivotal tools in revolutionizing PDAC care across various dimensions. Consequently, many studies have focused on using AI to improve the standard of PDAC care. This review article attempts to consolidate the literature from the past five years to identify high-impact, novel, and meaningful studies focusing on their transformative potential in PDAC management. Our analysis spans a broad spectrum of applications, including but not limited to patient risk stratification, early detection, and prediction of treatment outcomes, thereby highlighting AI's potential role in enhancing the quality and precision of PDAC care. By categorizing the literature into discrete sections reflective of a patient's journey from screening and diagnosis through treatment and survivorship, this review offers a comprehensive examination of AI-driven methodologies in addressing the multifaceted challenges of PDAC. Each study is summarized by explaining the dataset, ML model, evaluation metrics, and impact the study has on improving PDAC-related outcomes. We also discuss prevailing obstacles and limitations inherent in the application of AI within the PDAC context, offering insightful perspectives on potential future directions and innovations. [ABSTRACT FROM AUTHOR]

Background: We compared the results of preoperative pancreatic juice cytology (PJC) and final pathological diagnosis after resection in patients who underwent resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas to determine whether preoperative PJC can help determine therapeutic strategies. Methods: Of 1130 patients who underwent surgical resection IPMN at 11 Japanese tertiary institutions, the study included 852 patients who underwent preoperative PJC guided by endoscopic retrograde cholangiopancreatography (ERCP). Results: The accuracy of preoperative PJC for differentiation between cancerous and noncancerous lesions were 55% for IPMN overall; 59% for the branch duct type; 49% for the main pancreatic duct type; 53% for the mixed type, respectively. On classifying IPMN according to the diameters of the mural nodule (MN) and main pancreatic duct (MPD), the corresponding values for diagnostic performance were 40% for type 1 (MN ≥5 mm and MPD ≥ 10 mm); 46% for type 2 (MN ≥5 mm and MPD < 10 mm); 61% for type 3 (MN < 5 mm and MPD ≥ 10 mm); 72% for type 4 (MN < 5 mm and MPD < 10 mm), respectively. Conclusions: PJC in IPMN is not a recommended examination because of its low overall sensitivity and no significant difference in diagnostic performance by type, location, or subclassification. Although the sensitivity is low, the positive predictive value is high, so we suggest that pancreatic juice cytology be performed only in cases where the patient is not sure about surgery. [ABSTRACT FROM AUTHOR]

Objective: To identify risk factors associated with the progression of pancreatic cysts in patients undergoing surveillance. Background: Previous studies of intraductal papillary mucinous neoplasms (IPMNs) rely on surgical series to determine malignancy risk and have inconsistently identified characteristics associated with IPMN progression. Methods: We conducted a retrospective review of 2197 patients presenting with imaging concerning for IPMN from 2010 to 2019 at a single institution. Cyst progression was defined as resection or pancreatic cancer development. Results: The median follow-up time was 84 months from the presentation. The median age was 66 years, and 62% were female. Ten percent had a first-degree relative with pancreatic cancer, and 3.2% had a germline mutation or genetic syndrome associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). Cumulative incidence of progression was 17.8% and 20.0% at 12 and 60 months postpresentation, respectively. Surgical pathology for 417 resected cases showed noninvasive IPMN in 39% of cases and PDAC with or without associated IPMN in 20%. Only 18 patients developed PDAC after 6 months of surveillance (0.8%). On multivariable analysis, symptomatic disease [hazard ratio (HR)=1.58; 95% CI: 1.25-2.01], current smoker status (HR= 1.58; 95% CI: 1.16-2.15), cyst size (HR=1.26; 95% CI: 1.20-1.33), main duct dilation (HR=3.17; 95% CI: 2.44-4.11), and solid components (HR= 1.89; 95% CI: 1.34-2.66) were associated with progression. Conclusions: Worrisome features on imaging at presentation, current smoker status, and symptomatic presentation are associated with IPMN progression. Most patients progressed within the first year of presentation to Memorial Sloan Kettering Cancer Center (MSKCC). Further investigation is necessary to develop personalized cyst surveillance strategies. [ABSTRACT FROM AUTHOR]

Backgrounds: Intraductal papillary mucinous neoplasms (IPMN) are cystic neoplasms of the pancreatic ductal system. These incidental cystic lesions are increasingly found on radiological imaging and screened for malignant transformation. The Fukuoka consensus guidelines recommend screening with computed tomography, magnetic resonance imaging or endoscopic ultrasound. Branch duct IPMN (BD‐IPMN) have significantly lower malignancy and mortality rates compared to main duct IPMN. Our aim was to assess the cost‐effectiveness of guideline's recommendations for BD‐IPMN screening of cysts between 2 and 3 cm in an Australian context. Methods: Markov model decision analysis was used to calculate the incremental cost‐effectiveness ratio (ICER) of screening. The ICER was compared to a willingness to pay (WTP) threshold of $50 000. We performed scenario analysis to examine the effect of cyst size and non‐linearity of malignancy rate on ICER. Probabilistic sensitivity analyses (PSA) were performed on our input parameters. Results: Screening resulted in 586 quality adjusted life years gained and a net present value of $20 379 939, resulting in a base‐case ICER of $34 758. After scenario analysis for non‐linearity of malignancy rate the ICER increases to $64 555, which is above the WTP threshold. PSA indicates that ICER is most susceptible to the pre‐test malignancy rate. Conclusion: This cost analysis demonstrates that screening of 2–3 cm BD‐IPMN according to current guidelines is unlikely to be cost‐effective in an Australian context. To determine the true ICER, a cost analysis on real‐world data is required. [ABSTRACT FROM AUTHOR]

Differences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified. Forty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups. 1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%). Because characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds. [ABSTRACT FROM AUTHOR]

The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours includes a description of several new entities. In addition, numerous tumor variants were described and new concepts proposed, most of which have been based on recent molecular discoveries. However, there are still some controversial issues that remain to be resolved, and some of them are discussed in this review. [ABSTRACT FROM AUTHOR]

Abstract Background With increasing use and enhanced accuracy of cross-sectional imaging, the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has increased over the last few decades. The extent to which malignant transformation occurs remains unclear, making the management of IPMNs controversial. The aim of this study was to evaluate the progression rate and outcome of follow-up in patients with IPMNs. Methods A database of all patients diagnosed with IPMN at the Cantonal Hospital HFR Fribourg, Switzerland, between January 2006 and December 2019 with a follow-up of at least 6 months was analyzed retrospectively. Descriptive statistics were performed on patient demographics, IPMN characteristics, and follow-up data. Results A total of 56 patients were included in this study. Ten patients underwent primary surgery, 46 were enrolled in a surveillance program.21.7% (n = 5) of patients under surveillance presented with worrisome features of IPMN; progression rates were significantly higher in these patients (p = 0.043). Most progression occurred in the early follow-up period. Five patients underwent surgery due to progression, of which 2 presented high-grade dysplasia and 2 malignancy on postoperative histology. Conclusions The limited predictive value of current guidelines may lead to surgical overtreatment, and the decision to proceed with surgical resection should be made with caution. Further prospective analyses and the development of novel biomarkers are needed to better understand the natural history of IPMN and improve diagnostic precision.

Pancreatic cancer is among the leading causes of cancer death in the United States of America. Early detection and intervention are critical as a large majority of patients have either local or distant metastatic disease at the time of diagnosis. However, groove pancreatitis, a rare form of chronic pancreatitis, presents as a challenge for adequate and efficient differential diagnosis of pancreatic cancer as a result of similar clinical symptoms and imaging features. Furthermore, intraductal papillary mucinous neoplasms and pancreatic intraepithelial neoplasia are 2 of the precursor lesions that have been identified with pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasms are cystic tumors of the pancreas characterized by excessive mucin production in either the main pancreatic duct or its branches. Conversely, pancreatic intraepithelial neoplasia are microscopic lesions in the smaller pancreatic ducts. In this article, we report the case of a 46-year-old male with a diagnosis of groove pancreatitis, main duct intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia whose tumor was excised by means of a Whipple procedure. We focus on optimizing diagnosis and treatment through the application of radiological modalities.

Abstract Background Main pancreatic duct (MPD) dilation is a high-risk stigmata/worrisome feature of malignancy in intraductal papillary mucinous neoplasms (IPMNs). The threshold of MPD diameter in predicting malignancy may be related to the lesion location. This study aimed to separately identify the thresholds of MPD for malignancy of IPMNs separately for the head-neck and body-tail. Materials and methods A total of 185 patients with pathologically confirmed IPMNs were included. Patient demographic information, clinical data, and pathological features were obtained from the medical records. Those IPMNs with high-grade dysplasia or with associated invasive carcinoma were considered as malignant tumor. Radiological data including lesion location, tumor size, diameter of the MPD, mural nodule, and IPMN types (main duct, MD; branch duct, BD; and mixed type, MT), were collected on computed tomography or magnetic resonance imaging. Serum carbohydrate antigen 19-9 levels, serum carcinoembryonic antigen levels, and the medical history of diabetes mellitus, chronic cholecystitis, and pancreatitis were also collected. Results Malignant IPMNs were detected in 31.6% of 117 patients with lesions in the pancreatic head-neck and 20.9% of 67 patients with lesions in the pancreatic body-tail. In MPD-involved IPMNs, malignancy was observed in 54.1% of patients with lesions in the pancreatic head-neck and 30.8% of patients with lesions in the pancreatic body-tail (p

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. Methods We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. Results The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. Conclusions Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy.

We assessed whether there are differences in the diagnostic yield and safety of serial pancreatic juice aspiration cytologic examination (SPACE) among different indications. We retrospectively analyzed 226 patients who underwent SPACE. They were classified into group A (patients with pancreatic masses, including advanced adenocarcinoma, sclerosing pancreatitis, or autoimmune pancreatitis), group B (suspicious pancreatic carcinoma patients without obvious pancreatic masses, including small pancreatic carcinoma, carcinoma in situ, or benign pancreatic duct stenosis), and group C (intraductal papillary mucinous neoplasm, IPMN). There were 41, 66, and 119 patients, with malignancy diagnosed in 29, 14, and 22 patients, in groups A, B, and C, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69%, 100%, 100%, 57%, and 78% in group A; 79%, 98%, 92%, 94%, and 94% in group B; and 27%, 87%, 32%, 84%, and 76% in group C, respectively. PEP was observed in three (7.3%), three (4.5%), and fifteen (13%) patients in group A, B, and C, respectively (p = 0.20). SPACE is useful and safe in patients with suspicious small pancreatic carcinoma. However, it has limited efficacy and might not be recommended in patients with IPMN because of the high frequency of PEP. [ABSTRACT FROM AUTHOR]

Background: Predicting the risk of malignant transformation in pancreatic cyst patients is challenging. Aim: We retrospectively investigated the risk factors for malignant transformation in pancreatic cyst patients. Methods: Patients with pancreatic cysts diagnosed using imaging tests were followed from November 2008 to December 2021. A significant change was defined as the additional development of high-risk stigmata (HRS), worrisome features (WFs), or pancreatic cancer during monitoring. Results: In total, 479 patients were analyzed, with a median observation period of 50 months. Forty-four patients (9.2%) showed significant changes, and eight (1.7%) developed pancreatic cancer. The univariate analysis showed that the cyst diameter at diagnosis (≥ 14 mm), main pancreatic duct (MPD) diameter at diagnosis (≥ 3 mm), presence of multilocular cysts, and an inconsistent MPD caliber were significant predictive factors for a significant change. One point was assigned for each significant factor. We grouped the patients into three groups: the low-risk group (total score 0), medium-risk group (score 1–2), and high-risk group (score 3–4). The high-risk group had a higher risk of a significant change than the medium- and low-risk groups (age-adjusted HRs for the medium-risk and high-risk groups were 3.0 and 5.2 compared with the low-risk group). Conclusion: Stratification based on risk factors may help predict the development of significant changes in pancreatic cyst patients. [ABSTRACT FROM AUTHOR]

Objectives: To retrospectively analyze the characteristics of pancreatic cysts with respect to histopathological diagnosis and various diagnostic imaging tools. Methods: The clinical features of 136 patients and characteristics of histopathologically diagnosed cysts were retrospectively assessed. The diagnostic accuracy of endoscopic ultrasound (EUS), computed tomography (CT), and magnetic resonance imaging (MRI) for pancreatic cysts was compared. Risk factors for high‐grade dysplasia/invasive cancer in patients with intraductal papillary mucinous neoplasms (IPMNs) were also determined. Results: The final analysis included 30 serous cystic neoplasms (SCNs) (21.6%), 13 mucinous cystic neoplasms (MCNs) (9.4%), 65 IPMNs (46.8%), and 13 solid pseudopapillary neoplasms (SPNs) (9.4%). The percentage of women with MCNs, SPNs, SCNs, and IPMNs was 100.0, 76.9, 73.3, and 47.7%, respectively (P <.001). The percentages of patients over 60 years of age with IPMNs, SCNs, MCNs, and SPNs were 73.9, 23.3, 0, and 0%, respectively (P <.001). The percentage of cysts located in the body and tail of the pancreas in MCNs, SCNs, SPNs, and IPMNs was 100, 70, 53.9, and 46.2%, respectively (P <.001). A unique honeycomb appearance was observed in 26.7% of SCNs. The overall diagnostic accuracy of EUS, CT, and MRI for pancreatic cysts was 82.6, 72.5, and 73.9%, respectively. Lesion size and presence of solid components were independent predictors of high‐risk IPMNs. Conclusions: Patient characteristics and cyst features can help to differentiate pancreatic cyst types and identify high‐risk IPMNs. The diagnostic accuracy of EUS for pancreatic cysts is superior to that of CT and MRI. [ABSTRACT FROM AUTHOR]

Pancreatic cystic lesions (PCLs) are known precursors to pancreatic cancer, one of the deadliest types of cancer worldwide. Surgical removal or pancreatectomies remain the central approach to managing precancerous high-risk PCLs. Endoscopic ultrasound (EUS)-guided therapeutic management of PCLs is a novel management strategy for patients with prohibitive surgical risks. Various ablation techniques have been explored in previous studies utilizing EUS-guided fine needle injection (FNI) of alcohol and chemotherapeutic agents. This review article focuses on EUS-FNI and chemoablation, encompassing the evolution of chemoablation, pancreatic cyst selection, chemotherapy drug selection, including novel agents, and a discussion of its safety and efficacy. [ABSTRACT FROM AUTHOR]

Background: With increasing use and enhanced accuracy of cross-sectional imaging, the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has increased over the last few decades. The extent to which malignant transformation occurs remains unclear, making the management of IPMNs controversial. The aim of this study was to evaluate the progression rate and outcome of follow-up in patients with IPMNs. Methods: A database of all patients diagnosed with IPMN at the Cantonal Hospital HFR Fribourg, Switzerland, between January 2006 and December 2019 with a follow-up of at least 6 months was analyzed retrospectively. Descriptive statistics were performed on patient demographics, IPMN characteristics, and follow-up data. Results: A total of 56 patients were included in this study. Ten patients underwent primary surgery, 46 were enrolled in a surveillance program.21.7% (n = 5) of patients under surveillance presented with worrisome features of IPMN; progression rates were significantly higher in these patients (p = 0.043). Most progression occurred in the early follow-up period. Five patients underwent surgery due to progression, of which 2 presented high-grade dysplasia and 2 malignancy on postoperative histology. Conclusions: The limited predictive value of current guidelines may lead to surgical overtreatment, and the decision to proceed with surgical resection should be made with caution. Further prospective analyses and the development of novel biomarkers are needed to better understand the natural history of IPMN and improve diagnostic precision. [ABSTRACT FROM AUTHOR]

Resumen: El diagnóstico diferencial de las lesiones quísticas de páncreas incluye lesiones no neoplásicas y lesiones epiteliales neoplásicas. El diagnóstico preciso es imperativo, pues su manejo está determinado por el riesgo de progresión maligna, los síntomas asociados y otras características. La presente revisión intenta proporcionar una ruta crítica que facilite la caracterización y manejo de las lesiones quísticas de páncreas. Abstract: The differential diagnosis of pancreatic cystic lesions includes non-neoplastic lesions and neoplastic epithelial lesions. Given that management is determined by the risk for malignant progression, associated symptoms, and other characteristics, an accurate diagnosis is imperative. The present review attempts to provide a critical path that facilitates the characterization and management of pancreatic cystic lesions.

Abstract Background Largely due to incidental detection, asymptomatic pancreatic cystic lesions (PCLs) have become prevalent in recent years. Among them, intraductal papillary mucinous neoplasm (IPMN) infrequently advances to pancreatic ductal adenocarcinoma (PDAC). Conservative surveillance versus surgical intervention is a difficult clinical decision for both caregivers and PCL patients. Because RNF43 loss‐of‐function mutations and KRAS gain‐of‐function mutations concur in a subset of IPMN and PDAC, their biological significance and therapeutic potential should be elucidated. Methods Pancreatic Rnf43 knockout and Kras activated mice (Rnf43−/−; KrasG12D) were generated to evaluate their clinical significance in pancreatic pre‐neoplastic initiation and malignant transformation. Results Loss of Rnf43 potentiated the occurrence and severity of IPMN and PDAC in oncogenic Kras mice. The Wnt/β‐catenin signaling pathway was activated in pancreatic KrasG12D and Rnf43 knockout mice and the PORCN inhibitor LGK974 blocked pancreatic IPMN initiation and progression to PDAC accordingly. Conclusions Rnf43 is a tumor suppressor in the prevention of pancreatic malignant transformation. This genetically reconstituted autochthonous pancreatic Rnf43−/−; KrasG12D preclinical cancer model recapitulates the pathological process from pancreatic cyst to cancer in humans and can be treated with inhibitors of Wnt/β‐catenin signaling. Since the presence of RNF43 and KRAS mutations in IPMNs predicts future development of advanced neoplasia from PCLs, patients with these genetic anomalies warrant surveillance, surgery, and/or targeted therapeutics such as Wnt/β‐catenin inhibitors.

Background: Main pancreatic duct (MPD) dilation is a high-risk stigmata/worrisome feature of malignancy in intraductal papillary mucinous neoplasms (IPMNs). The threshold of MPD diameter in predicting malignancy may be related to the lesion location. This study aimed to separately identify the thresholds of MPD for malignancy of IPMNs separately for the head-neck and body-tail.Materials and Methods: A total of 185 patients with pathologically confirmed IPMNs were included. Patient demographic information, clinical data, and pathological features were obtained from the medical records. Those IPMNs with high-grade dysplasia or with associated invasive carcinoma were considered as malignant tumor. Radiological data including lesion location, tumor size, diameter of the MPD, mural nodule, and IPMN types (main duct, MD; branch duct, BD; and mixed type, MT), were collected on computed tomography or magnetic resonance imaging. Serum carbohydrate antigen 19-9 levels, serum carcinoembryonic antigen levels, and the medical history of diabetes mellitus, chronic cholecystitis, and pancreatitis were also collected.Results: Malignant IPMNs were detected in 31.6% of 117 patients with lesions in the pancreatic head-neck and 20.9% of 67 patients with lesions in the pancreatic body-tail. In MPD-involved IPMNs, malignancy was observed in 54.1% of patients with lesions in the pancreatic head-neck and 30.8% of patients with lesions in the pancreatic body-tail (p < 0.05). The cutoff value of MPD diameter for malignancy was 6.5 mm for lesions in the head-neck and 7.7 mm for lesions in the body-tail in all type of IPMNs. In MPD-involved IPMNs, the threshold was 8.2 mm for lesion in pancreatic head-neck and 7.7 mm for lesions in the body-tail. Multivariate analysis confirmed that MPD diameter ≥ 6.5 mm (pancreatic head-neck) and MPD diameter ≥ 7.7 mm (pancreatic body-tail) were independent predictors of malignancy (p < 0.05). Similar results were observed in MPD-involved IPMNs using 8.2 mm as a threshold.Conclusion: The thresholds of the dilated MPD may be associated with IPMNs locations. Thresholds of 6.5 mm for lesions in the head-neck and 7.7 mm for lesions in the body-tail were observed. For MPD-involved IPMNs alone, threshold for lesions in the head-neck was close to that in the body-tail. [ABSTRACT FROM AUTHOR]

Background: Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. Methods: We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. Results: The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. Conclusions: Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy. [ABSTRACT FROM AUTHOR]

The development of neural structures within tumors is now considered vital for carcinogenesis. However, the time course of this development in human pre‐invasive neoplasia has been incompletely described. Therefore, we performed a detailed analysis of nerves across the neoplastic spectrum in resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Histology and multiplexed immunochemistry demonstrated that nerve density increased from low‐grade (LG) to high‐grade dysplasia (HG) but did not further increase once invasive IPMN (INV IPMN) was present. Higher nerve density correlated with increasing expression of nerve growth factor (NGF) by the tumor cells. Intra‐tumoral nerves were immature and lacked markers of sympathetic, parasympathetic, and sensory lineages. Here, we show for the first time the presence of neural precursor cells (NPCs) within the stroma of pancreatic tumors. The density of these doublecortin (DCX)‐positive NPCs increased from LG to HG, but not from HG to INV IPMN. We conclude that peak neural density of tumors is reached in high‐grade dysplasia (often termed carcinoma in situ) rather than after invasion. These findings suggest that nerve–tumor interactions are important in IPMN progression and may serve as the basis for future mechanistic studies and novel therapeutic modalities. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Pancreatic Cystic Neoplasms (PCN) represent a diverse group of tumors, some of which may progress to pancreatic cancer. Considering their high prevalence in the general population, the development of reliable biomarkers is crucial. The ideal biomarker will accurately diagnose the subtype of PCN and assess the risk of high-grade dysplasia or invasive cancer. Cyst fluid analysis has emerged as a promising approach to accomplish this goal, yet no single marker has yet gained unanimous support for routine inclusion in PCN evaluation., Competing Interests: Disclosure A.V. Maker is an inventor of record on the following pending or issued patent: WO2018183603A1 (PCT/US2018/025,027). T. Pollini and L. Todeschini have no conflict of interest. Funding Authors acknowledge the support of the Inner Child Foundation and the Shorenstein Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Background Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs). Methods A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19–9 (CA19–9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs. Results Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78–17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19–9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19–9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79). Conclusions Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs.

Simple Summary: Intraductal papillary mucinous neoplasms (IPMN) are common premalignant precursors to pancreatic ductal adenocarcinoma (PDAC). However, current guidelines for clinical management of IPMN are suboptimal and limited to information obtained through anatomical imaging and cytology of biopsy samples. Our results have suggested that diffusion-weighted MRI, an imaging method sensitive to tumor cell density, architecture, and microenvironment is able to differentiate mouse models of IPMN versus PDAC. KPC (KrasG12D:Trp53R172H:Pdx1-Cre) and CKS (KrasG12D:Smad4L/L:Ptf1a-Cre) mice are genetically engineered mouse (GEM) models that capture features of human pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN), respectively. We compared these autochthonous tumors using quantitative imaging metrics from diffusion-weighted MRI (DW-MRI) and dynamic contrast enhanced (DCE)-MRI in reference to quantitative histological metrics including cell density, fibrosis, and microvasculature density. Our results revealed distinct DW-MRI metrics between the KPC vs. CKS model (mimicking human PDAC vs. IPMN lesion): the apparent diffusion coefficient (ADC) of CKS tumors is significantly higher than that of KPC, with little overlap (mean ± SD 2.24 ± 0.2 vs. 1.66 ± 0.2 , p < 10 − 10 ) despite intratumor and intertumor variability. Kurtosis index (KI) is also distinctively separated in the two models. DW imaging metrics are consistent with growth pattern, cell density, and the cystic nature of the CKS tumors. Coregistration of ex vivo ADC maps with H&E-stained sections allowed for regional comparison and showed a correlation between local cell density and ADC value. In conclusion, studies in GEM models demonstrate the potential utility of diffusion-weighted MRI metrics for distinguishing pancreatic cancer from benign pancreatic cysts such as IPMN. [ABSTRACT FROM AUTHOR]

Aim of our update is to present the "state of art" about pancreatic intraductal papillary mucinous neoplasms (IPMN) and underline some significant notions that can be helpful in clinical practice. IPMN of the pancreas can be defined as neoplasms derived from pancreatic ductal system that produce mucin. The real incidence and prevalence of IPMN are not well defined. The radiological classification subdivides IPMN in three categories, in according to ductal involvement. One of the most confounding factors about pancreatic IPMN regards the high heterogeneity of these lesions, from which derives a different biological behavior and a different management. Although there are no clinical signs related to pancreatic IPMN, patient's medical history and clinical examination are relevant. The differential diagnosis is relevant in order to detect potentially malignant lesions. Preoperative imaging should confirm the diagnosis of IPMN, indicate the risk of malignant cystic neoplasia, and define resectability. Data from literature showed that surgical treatment is indicated in case of main duct-IPMN, in concordance with the international consensus guidelines for management of IPMNs. Surgery is not mandatory in all patients with branch duct-IPMN, but only in 20% of cases or less; furthermore, in the absence of malignancy-related signs, careful non-operative management seems to be safe and effective in asymptomatic patients. [ABSTRACT FROM AUTHOR]

Hereditary pancreatic cancer, which includes patients with familial pancreatic cancer (FPC) and hereditary pancreatic cancer syndromes, accounts for about 10% of all pancreatic cancer diagnoses. The early detection of pre-cancerous pancreatic cysts has increasingly become a focus of interest in recent years as a potential avenue to lower pancreatic cancer incidence and mortality. Intraductal papillary mucinous cystic neoplasms (IPMNs) are recognized precursor lesions of pancreatic cancer. IPMNs have high prevalence in patients with hereditary pancreatic cancer and their relatives. While various somatic mutations have been identified in IPMNs, certain germline mutations associated with hereditary cancer syndromes have also been identified in IPMNs, suggesting a role in their formation. While the significance for the higher prevalence of IPMNs or similar germline mutations in these high-risk patients remain unclear, IPMNs do represent pre-malignant lesions that need close surveillance. This review summarizes the available literature on the incidence and prevalence of IPMNs in inherited genetic predisposition syndromes and FPC and speculates if IPMN and pancreatic cancer surveillance in these high-risk individuals needs to change. [ABSTRACT FROM AUTHOR]

Background: The association between intraductal papillary mucinous neoplasms (IPMNs) and colorectal cancer (CRC) and polyps is controversial. Objectives: To compare the prevalence of CRC and colorectal polyps among patients with IPMN and matched average risk individuals. Methods: A match cross-sectional historical study comparing colonoscopy findings of 310 patients with IPMN cysts who underwent at least one colonoscopy examination from 2004 through 2019, with 310 age- and gender-matched average risk participants who underwent a screening colonoscopy. CRC and polyps were assessed in both groups. The prevalence and odds ratio were calculated. Results: CRC was diagnosed in 16 of 310 patients with IPMN (5.2%), and at least one polyp was detected in 96 patients (31%). The prevalence of CRC was greater among patients with IPMN than in matched individuals [5.2% versus 1.3%, p = 0.012, prevalence odds ratio (POR) 4, confidence interval (CI) 1.29–16.44]. The overall prevalence of polyps was not higher among patients with IPMN than in matched individuals (31% versus 26.8%, p = 0.291, POR 1.22, CI 0.85–1.76). However, the prevalence of colorectal adenomas with high-grade dysplasia was higher in patients with IPMN than in matched individuals (4.2% versus 1%, p = 0.02, POR 4.33, CI, 1.19–23.7). The prevalence of large polyps (i.e. more than 20 mm in size) was also greater in patients with IPMN than in matched individuals (6.1% versus 1.9%, p = 0.011, POR 3.6, CI, 1.29–12.40). Conclusion: Patients with IPMN have a significantly higher prevalence of CRC and advanced polyps than the average risk population. In view of our findings, we suggest that once the diagnosis of IPMN is made, special consideration of CRC should be undertaken. [ABSTRACT FROM AUTHOR]

Background: Abrupt change in the caliber of the main pancreatic duct (MPD) with distal pancreatic atrophy (PA) was considered as one of worrisome features in the International Association of Pancreatology guideline and American College of Gastroenterology guideline for the management of intraductal papillary mucinous neoplasms (IPMNs). However, this feature was not included in other guidelines. Moreover, the association between PA alone and malignancy in IPMNs has not been fully evaluated. In the present study, we investigated the role of image-based PA in identifying malignant IPMNs or invasive carcinoma. Methods: A total of 186 patients with IPMNs were included for analysis. The tumor size, location, MPD diameter, presence of a mural nodule (MN), and PA were evaluated using magnetic resonance imaging. Demographic information and serum carbohydrate antigen 19-9 and carcinoembryonic antigen (CEA) levels were also collected. IPMNs with high-grade dysplasia and associated invasive carcinoma were regarded as malignant IPMNs. Results: PA was observed in 34 cases (18.3%). The occurrence of malignant IPMNs or invasive carcinoma in patients with PA were significantly higher than in those without PA (52.9% vs. 22.3%; 44.1% vs. 8.9%, all P < 0.01). Multivariate logistic regression analysis showed that PA was an independently associated factor for malignant IPMNs [odds ratio (OR) = 2.69, 95% confidence interval (CI): 1.07-6.78] or invasive carcinoma (OR = 7.78, 95%CI: 2.62-23.10) after modified with confounders. Subgroup analysis in MPD-involved IPMNs also indicated that PA was an independently associated factor for invasive carcinoma (OR = 9.72, 95%CI: 2.43-38.88). PA had a similar performance with MPD plus MN [the area under the curve (AUC) was both 0.71] in identifying malignancy. PA had a higher performance in identifying invasive carcinoma in MPD-involved IPMNs than MN (AUC = 0.71 vs. 0.65, P = 0.02). Conclusion: Our data showed that imaging-based PA was associated with malignancy or invasive carcinoma regardless of abrupt change in the caliber of MPD in IPMNs. PA had an acceptable performance in identifying malignant IPMNs. [ABSTRACT FROM AUTHOR]

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated. Materials and methods 226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients’ demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance. Results The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P

BackgroundAbrupt change in the caliber of the main pancreatic duct (MPD) with distal pancreatic atrophy (PA) was considered as one of worrisome features in the International Association of Pancreatology guideline and American College of Gastroenterology guideline for the management of intraductal papillary mucinous neoplasms (IPMNs). However, this feature was not included in other guidelines. Moreover, the association between PA alone and malignancy in IPMNs has not been fully evaluated. In the present study, we investigated the role of image-based PA in identifying malignant IPMNs or invasive carcinoma.MethodsA total of 186 patients with IPMNs were included for analysis. The tumor size, location, MPD diameter, presence of a mural nodule (MN), and PA were evaluated using magnetic resonance imaging. Demographic information and serum carbohydrate antigen 19-9 and carcinoembryonic antigen (CEA) levels were also collected. IPMNs with high-grade dysplasia and associated invasive carcinoma were regarded as malignant IPMNs.ResultsPA was observed in 34 cases (18.3%). The occurrence of malignant IPMNs or invasive carcinoma in patients with PA were significantly higher than in those without PA (52.9% vs. 22.3%; 44.1% vs. 8.9%, all P < 0.01). Multivariate logistic regression analysis showed that PA was an independently associated factor for malignant IPMNs [odds ratio (OR) = 2.69, 95% confidence interval (CI): 1.07-6.78] or invasive carcinoma (OR = 7.78, 95%CI: 2.62-23.10) after modified with confounders. Subgroup analysis in MPD-involved IPMNs also indicated that PA was an independently associated factor for invasive carcinoma (OR = 9.72, 95%CI: 2.43-38.88). PA had a similar performance with MPD plus MN [the area under the curve (AUC) was both 0.71] in identifying malignancy. PA had a higher performance in identifying invasive carcinoma in MPD-involved IPMNs than MN (AUC = 0.71 vs. 0.65, P = 0.02).ConclusionOur data showed that imaging-based PA was associated with malignancy or invasive carcinoma regardless of abrupt change in the caliber of MPD in IPMNs. PA had an acceptable performance in identifying malignant IPMNs.

We assessed whether there are differences in the diagnostic yield and safety of serial pancreatic juice aspiration cytologic examination (SPACE) among different indications. We retrospectively analyzed 226 patients who underwent SPACE. They were classified into group A (patients with pancreatic masses, including advanced adenocarcinoma, sclerosing pancreatitis, or autoimmune pancreatitis), group B (suspicious pancreatic carcinoma patients without obvious pancreatic masses, including small pancreatic carcinoma, carcinoma in situ, or benign pancreatic duct stenosis), and group C (intraductal papillary mucinous neoplasm, IPMN). There were 41, 66, and 119 patients, with malignancy diagnosed in 29, 14, and 22 patients, in groups A, B, and C, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69%, 100%, 100%, 57%, and 78% in group A; 79%, 98%, 92%, 94%, and 94% in group B; and 27%, 87%, 32%, 84%, and 76% in group C, respectively. PEP was observed in three (7.3%), three (4.5%), and fifteen (13%) patients in group A, B, and C, respectively (p = 0.20). SPACE is useful and safe in patients with suspicious small pancreatic carcinoma. However, it has limited efficacy and might not be recommended in patients with IPMN because of the high frequency of PEP.

Due to their increased detection pancreatic cystic space-occupying lesions are becoming increasingly relevant in the clinical routine and represent a morphologically and biologically heterogeneous and thus clinically demanding as well as potentially (pre)malignant entity. As a result, recommendations for the diagnostics and treatment of pancreatic cystic tumors have now been incorporated into the current German S3 guidelines on pancreatic cancer. The diagnostics of pancreatic cystic space-occupying lesions are based on the following three elements: collection of relevant clinical information, performance of high-resolution imaging procedures and if diagnostic uncertainty persists, puncture diagnostics. Differentiated diagnostics are of essential importance as these represent the basis for an adequate treatment decision. Pancreatic cystic lesions with a relevant risk of malignant transformation, e.g., main duct intraductal papillary mucinous neoplasms (IPMN), followed by mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and generally pancreatic cystic lesions with risk factors independent of the entity, should be resected, whereas a differentiated and individualized approach is necessary, especially for branch-duct IPMNs. The serous cystic neoplasms (SCN) have no malignant potential and do not require any treatment if they are asymptomatic. Important principles in surgery of pancreatic cancer, such as adequate surgical resection taking oncological standards into account and standardized appropriate histopathological processing of the specimens as well as intraoperative frozen section analysis also play an important role in pancreatic cystic space-occupying lesions. An annual follow-up seems to be meaningful, especially for IPMNs. [ABSTRACT FROM AUTHOR]

Purpose of review: The objective of this study is to answer few key questions in order to establish the best possible available diagnostic strategy for incidentally discovered pancreatic cystic lesions (PCLs). Recent findings: Advances in EUS-guided sampling techniques, cross-sectional and intracystic confocal imaging, molecular biomarkers analysis, determination of cyst fluid glucose, and artificial intelligence, appear to be associated with an improved diagnostic accuracy in distinguishing mucinous from non-mucinous PCLs. Summary: The diagnostic process has the aim of recognizing cysts with malignant potential and identifying those with high-risk stigmata and/or worrisome features. Clinicians should avoid performance of unnecessary tests from one side and misdiagnosis from the other, which can easily result in inadvertent surgery of an otherwise benign lesion or malignant progression of a precancerous cyst. Clinical studies to validate recent reported results utilizing novel diagnostic tests are needed, in order to gradually incorporate and combine them into updated guidelines. [ABSTRACT FROM AUTHOR]

Background: A "pandemic" of incidentally discovered pancreatic cyst neoplasms (PCNs) is ongoing. Among PCNs, intraductal papillary mucinous cystic neoplasms (IPMNs) are the most common and with their complex biology could represent a precursor lesion of pancreatic cancer. Although multiple guidelines exist to guide their treatment, there are still many "gray areas" on indications for surgery for IPMNs. Methods: The current indications for surgery of IPMNs were reappraised, considering potential discrepancies between available evidence and guidelines policies. The practice at a high-volume center for the diagnosis and treatment of PCN was presented and discussed. Results: Most IPMNs do not and will never require surgery, as they won't progress to malignancy. The current literature is solid in identifying high-grade dysplasia (HGD) as the right and timely target for IPMN resection, but how to precisely assess its presence remains controversial and guidelines lack of accuracy in this regard. Multiple tumorigenic pathways of progression of IPMNs exist, and their knowledge will likely lead to more accurate tests for malignancy prediction in the future. Conclusions: The surgical management of IPMNs still is a matter of debate. Indication for resection should be considered only in highly selected cases with the ideal target of HGD. Clinicians should critically interpret the guidelines' indications, refer to a multidisciplinary team discussion, and always consider the outcome of an adequate counselling with the patient. [ABSTRACT FROM AUTHOR]

Abstract Background Glucose metabolism of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is unclear. S6 ribosomal protein (S6) phosphorylation is involved not only in controlling cell growth but also in glucose metabolism in cancer. The aim of this study was to investigate the role of S6 phosphorylation and the significance of glucose metabolic changes in IPMN. Methods Records of 39 patients who underwent preoperative FDG‐PET and curative resection were enrolled in this study. S6 phosphorylation and GLUT1 expression were evaluated immunohistochemically in these patients. The effect of S6 phosphorylation on glucose uptake was examined in cancer cell lines. To examine the change of glucose metabolism in IPMN clinically, the relation between clinical factors including FDG‐PET and malignancy of IPMN was investigated. Results S6 phosphorylation and GLUT1 expression were significantly higher in carcinoma than in normal cells or adenoma. Cell lines with high level of S6 phosphorylation showed high glucose uptake, and inhibition of S6 phosphorylation reduced glucose uptake. In clinical examination, FDG‐PET was the independent factor related to the diagnosis of adenoma or carcinoma (odds ratio = 20.0, 95% confidence interval = 1.837‐539.9, P = .012). FDG‐PET detected carcinoma with a sensitivity of 81.8%, specificity of 96.4%, and accuracy of 92.3%. Conclusion S6 phosphorylation was associated with glucose uptake and malignancy of IPMN. Moreover, glucose uptake increased in malignant cells of IPMN, and FDG‐PET is useful for detecting malignancy of IPMN.

Pancreatic cystic lesions (PCLs) are known precursors to pancreatic cancer, one of the deadliest types of cancer worldwide. Surgical removal or pancreatectomies remain the central approach to managing precancerous high-risk PCLs. Endoscopic ultrasound (EUS)-guided therapeutic management of PCLs is a novel management strategy for patients with prohibitive surgical risks. Various ablation techniques have been explored in previous studies utilizing EUS-guided fine needle injection (FNI) of alcohol and chemotherapeutic agents. This review article focuses on EUS-FNI and chemoablation, encompassing the evolution of chemoablation, pancreatic cyst selection, chemotherapy drug selection, including novel agents, and a discussion of its safety and efficacy.

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs).Methods: A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs.Results: Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p <  0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01-1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78-17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19-9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19-9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79).Conclusions: Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs. [ABSTRACT FROM AUTHOR]

The incidence of pancreatic incidentalomas (PIs) detected in otherwise asymptomatic patients is growing with the increasing quality and use of advanced imaging techniques. PI can present as isolated main pancreatic duct dilation or as a solid or cystic lesion. Although historically thought to be relatively rare, PIs are rather common, particularly cystic lesions of the pancreas, which can be detected in up to 49% of the general population. With the poor prognosis of pancreatic cancer, PIs are an opportunity for prevention and early diagnosis, but when managed poorly, they can also lead to overtreatment and unnecessary morbidity. The management of PI should begin with a dedicated pancreas protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) to accurately characterize duct size, lesion characteristics and establish an accurate baseline for subsequent follow up. Diagnosis and subsequent management depends on the extent of main duct dilation and solid versus cystic appearance. Solid lesions are highly concerning for malignancy. Cystic lesions can be further categorized as intraductal papillary mucinous neoplasms of the pancreas (IPMNs) or mucinous cystic neoplasms (MCNs), both of which harbour malignant potential, or as serous cystic neoplasms (SCNs) that are benign. In this paper, we summarize the major challenges related to PI and present pragmatic suggestions for management. [ABSTRACT FROM AUTHOR]

ObjectivesTo assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.MethodsA systematic search of articles investigating the diagnostic performance of DWI for prediction of malignant potential in IPMNs was conducted from PubMed, Embase, and Web of Science from January 1997 to 10 February 2020. QUADAS-2 tool was used to evaluate the study quality. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and their 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic (SROC) curve was then plotted, and meta-regression was also performed to explore the heterogeneity.ResultsFive articles with 307 patients were included. The pooled sensitivity and specificity of DWI were 0.74 (95% CI: 0.65, 0.82) and 0.94 (95% CI: 0.78, 0.99), in evaluating the malignant potential of IPMNs. The PLR was 13.5 (95% CI: 3.1, 58.7), the NLR was 0.27 (95% CI: 0.20, 0.37), and DOR was 50.0 (95% CI: 11.0, 224.0). The area under the curve (AUC) of SROC curve was 0.84 (95% CI: 0.80, 0.87). The meta-regression showed that the slice thickness of DWI (p = 0.02) and DWI parameter (p= 0.01) were significant factors affecting the heterogeneity.ConclusionsDWI is an effective modality for the differential diagnosis between benign and malignant IPMNs. The slice thickness of DWI and DWI parameter were the main factors influencing diagnostic specificity.

Background: Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated. Materials and methods: 226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients' demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance. Results: The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P < 0.01) in both the training group and validation group. The prevalence of malignant IPMNs decreased with an increase in HDL-c levels both in patients with all types of IPMNs, as well as in those with branch-duct IPMNs (BD-IPMNs).Logistic analysis showed that low HDL-c levels were associated with malignant IPMNs (odds ratio (OR) = 20.56, 95 % confidence interval (CI): 2.58–163.64, P < 0.01) in all types of IPMNs and BD-IPMNs (OR = 17.6, 95 %CI: 1.16–268.46, P = 0.02).The predictive performance of mural nodules plus low HDL-c levels was higher than that of mural nodules alone or mural nodules plus cyst size for the identification of malignant BD-IPMNs. Conclusions: HDL-c levels may serve a potential biomarker for identifying malignant IPMNs and improve the predictive ability of malignancy in BD-IPMNs. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the preoperative clinicophysiological and postoperative clinicopathological predictors of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN). Methods: This was a retrospective observational study. We included 121 patients (73 men and 48 women; mean age: 68.7 years) who had undergone pancreatic resection for IPMN between 2007 and 2018. These patients were grouped into invasive carcinoma (IPMN-INV, N = 21) and low/high-grade IPMN (IPMN-LG/HG, N = 100) groups. Univariate and multivariate analyses of clinicophysiological parameters were carried out. These parameters were also compared between the IPMN-INV/HG (N = 53) and IPMN-LG (N = 68) groups. Survival analyses according to macroscopic type and IPMN subtypes were performed. Results: On univariate analysis, age (p = 0.038), carbohydrate antigen (CA) 19-9 (p < 0.001), IPMN macroscopic type (p = 0.001), IPMN subtype (p < 0.001), pancreatic duct diameter (p < 0.001), and mural nodule (p = 0.042), between IPMN-INV and IPMN-LG/HG were found to be significant prognostic factors of malignancy. CA 19-9 was found to be an independent prognostic factor of IPMN malignancy on multivariate analysis (p = 0.035). The 1-, 3-, and 5-year overall survival (OS) rates of the IPMN-INV and IPMN-LG/HG groups were 94.4/100%, 94.4/100%, and 67.2/100%, respectively. The OS rate in the IPMN-LG/HG group was significantly higher than that in the IPMN-INV group (p < 0.001). On univariate analysis, platelet (p = 0.043), CA 19-9 (p = 0.039), prognostic nutritional index (p = 0.034), platelet/lymphocyte ratio (p = 0.01), IPMN macroscopic type (p < 0.001), IPMN subtype (p < 0.001), pancreatic duct diameter (p = 0.036), and mural nodule (p = 0.032) between IPMN-INV/HG and IPMN-LG were found to be significant prognostic factors of malignancy. On multivariate analysis, CA 19-9 was found to be an independent prognostic factor (p = 0.042) between IPMN-INV/HG and IPMN-LG of malignancy. The 1-, 3-, and 5-year OS rates of the IPMN-INV/HG and IPMN-LG groups were 97.9/100%, 97.9/100%, and 82.6/100%, respectively. The OS rate was significantly higher in the IPMN-LG group than in the IPMN-INV/HG group (p = 0.03). No significant differences in survival were observed in patients with macroscopic tumors (p= 0.544). Conclusion: CA 19-9 is an independent invasive malignancy predictor of IPMN. [ABSTRACT FROM AUTHOR]

2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management. to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN. data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated. the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN. European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features. [ABSTRACT FROM AUTHOR]

Objectives: To assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Methods: A systematic search of articles investigating the diagnostic performance of DWI for prediction of malignant potential in IPMNs was conducted from PubMed, Embase, and Web of Science from January 1997 to 10 February 2020. QUADAS-2 tool was used to evaluate the study quality. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and their 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic (SROC) curve was then plotted, and meta-regression was also performed to explore the heterogeneity. Results: Five articles with 307 patients were included. The pooled sensitivity and specificity of DWI were 0.74 (95% CI: 0.65, 0.82) and 0.94 (95% CI: 0.78, 0.99), in evaluating the malignant potential of IPMNs. The PLR was 13.5 (95% CI: 3.1, 58.7), the NLR was 0.27 (95% CI: 0.20, 0.37), and DOR was 50.0 (95% CI: 11.0, 224.0). The area under the curve (AUC) of SROC curve was 0.84 (95% CI: 0.80, 0.87). The meta-regression showed that the slice thickness of DWI (p = 0.02) and DWI parameter (p= 0.01) were significant factors affecting the heterogeneity. Conclusions: DWI is an effective modality for the differential diagnosis between benign and malignant IPMNs. The slice thickness of DWI and DWI parameter were the main factors influencing diagnostic specificity. [ABSTRACT FROM AUTHOR]

Hereditary pancreatic cancer, which includes patients with familial pancreatic cancer (FPC) and hereditary pancreatic cancer syndromes, accounts for about 10% of all pancreatic cancer diagnoses. The early detection of pre-cancerous pancreatic cysts has increasingly become a focus of interest in recent years as a potential avenue to lower pancreatic cancer incidence and mortality. Intraductal papillary mucinous cystic neoplasms (IPMNs) are recognized precursor lesions of pancreatic cancer. IPMNs have high prevalence in patients with hereditary pancreatic cancer and their relatives. While various somatic mutations have been identified in IPMNs, certain germline mutations associated with hereditary cancer syndromes have also been identified in IPMNs, suggesting a role in their formation. While the significance for the higher prevalence of IPMNs or similar germline mutations in these high-risk patients remain unclear, IPMNs do represent pre-malignant lesions that need close surveillance. This review summarizes the available literature on the incidence and prevalence of IPMNs in inherited genetic predisposition syndromes and FPC and speculates if IPMN and pancreatic cancer surveillance in these high-risk individuals needs to change.

WNT signaling promotes the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) through wide-ranging effects on cellular proliferation, survival, differentiation, stemness, and tumor microenvironment. Of therapeutic interest is a genetically defined subset of PDAC known to have increased WNT/β-catenin transcriptional activity, growth dependency on WNT ligand signaling, and response to pharmacologic inhibitors of the WNT pathway. Here we review mechanisms underlying WNT ligand addiction in pancreatic tumorigenesis, as well as the potential utility of therapeutic approaches that functionally antagonize WNT ligand secretion or frizzled receptor binding.