Intraductal Papillary Mucinous Neoplasm Research Articles

Effect of Intravenous Contrast on CT Body Composition Measurements in Patients with Intraductal Papillary Mucinous Neoplasm

Background: The effect of differing post-contrast phases on CT body composition measurements is not yet known. Methods: A fully automated AI-based body composition analysis using DAFS was performed on a retrospective cohort of 278 subjects undergoing pre-treatment triple-phase CT for pancreatic intraductal papillary mucinous neoplasm. The CT contrast phases included noncontrast (NON), arterial (ART), and venous (VEN) phases. The software selected a single axial CT image at mid-L3 on each phase for body compartment segmentation. The areas (cm2) were calculated for skeletal muscle (SM), intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). The mean Hounsfield units of skeletal muscle (SMHU) within the segmented regions were calculated. Bland–Altman and Chi Square analyses were performed. Results: SM-NON had a lower percentage of bias [LOA] than SM-ART, −0.7 [−7.6, 6.2], and SM-VEN, −0.3 [−7.6, 7.0]; VAT-NON had a higher percentage of bias than ART, 3.4 [−18.2, 25.0], and VEN, 5.8 [−15.0, 26.6]; and this value was lower for SAT-NON than ART, −0.4 [−14.9, 14.2], and VEN, −0.5 [−14.3, 13.4];] and higher for IMAT-NON than ART, 5.9 [−17.9, 29.7], and VEN, 9.5 [−17.0, 36.1]. The bias in SMHU NON [LOA] was lower than that in ART, −3.8 HU [−9.8, 2.1], and VEN, −7.8 HU [−14.8, −0.8]. Conclusions: IV contrast affects the voxel HU of fat and muscle, impacting CT analysis of body composition. We noted a relatively smaller bias in the SM, VAT, and SAT areas across the contrast phases. However, SMHU and IMAT experienced larger bias. During threshold risk stratification for CT-based measurements of SMHU and IMAT, the IV contrast phase should be taken into consideration.

An Overview for Clinicians on Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas

An Overview for Clinicians on Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas

Abstract B037: Disks large-associated protein 5 (DLGAP5) is a putative prognostic biomarker for intraductal papillary mucinous neoplasm (IPMN) of pancreas

Abstract Pancreatic cancer is one of the deadliest malignant diseases, accounting for nearly 500,000 deaths worldwide each year. One of the pancreatic cancer precursors are mucinous pancreatic cystic lesions (PCL). Although only a minority of these PCLs undergo malignant transformation, the clinical significance is considerable, particularly given the prevalence of up to 45% in individuals over the age of 65. The most prevalent type of neoplastic PCL is intraductal papillary mucinous neoplasm (IPMN) and the management of different IPMN grades varies, with high- grade dysplasia and invasive carcinoma being indicated for surgery. However, the current guidelines for patient stratification are limited and often lead to either overtreatment or undertreatment, both of which are associated with high mortality and morbidity. Therefore, there is a pressing need to identify biomarkers associated with progression of IPMN from low to high grade that can be used for more accurate lesion assessment. Here we identified a novel biomarker highly correlated with IPMN progression – DLGAP5. Both mRNA as well as protein expression of DLGAP5 is positively associated with increased grade of IPMNs as determined by analysis of patient derived tumor samples. Additionally, in vitro experiments confirmed that knock down of DLGAP5 in pancreatic cancer cells leads to reduction of cell proliferation, and conversely, overexpression of DLGAP5 in IPMN precursor cells resulted in increased proliferation. Since one of the functions of DLGAP5 is microtubule stabilization, we hypothesized that the secretome of IPMN precursor cells will be altered by the expression of DLGAP5. Indeed, our mass spectrometry-based analysis of secreted proteins identified several hits (e.g. DKK1) that were correlated with DLGAP5 expression and were previously confirmed to be present in IPMN cyst fluid in patients. Subsequently, we aim to validate the correlation of the putative biomarkers in IPMN cyst fluid and serum with IPMN grade and patients’ clinical outcome in a prospective manner. To sum up, we validated DLGAP5 as an IPMN-progression biomarker and identified several secreted proteins that could serve as DLGAP5-surrogate biomarkers for stratification of the patients with IPMN and subsequent treatment optimalization. Citation Format: Radoslav Janostiak, Peter Mačinga, Lucia Csergeová, Ondřej Fabián, Eva Sticová, Jiří Zahradník, Martin Květoň, Tomáš Hucl. Disks large-associated protein 5 (DLGAP5) is a putative prognostic biomarker for intraductal papillary mucinous neoplasm (IPMN) of pancreas [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B037.

MS O08 - HPB Biomarkers for risk stratification of Intraductal Papillary Mucinous Neoplasm of the pancreas: A systematic review

Abstract Background Intraductal Papillary Mucinous Neoplasm (IPMN) of the pancreas is the precursor lesion from which pancreatic ductal adenocarcinoma (PDAC) arises in 10% of individuals. IPMNs may be associated with low-grade or high-grade dysplasia or an associated adenocarcinoma. Accurately determining low-risk from high-risk IPMN is crucial for early detection initiatives for PDAC, so treatment can be offered before invasive cancer in high-risk individuals but without causing harm to low-risk individuals. Currently, imaging forms the basis for stratification but this is costly, resource intense and is limited in accuracy. There is a need to develop biomarkers to improve the risk stratification of IPMN. Method A systematic review was conducted according to PRISMA-DTA guidelines by screening EMBASE, MEDLINE, CENTRAL and bibliographic reference lists for comparative studies. Studies were excluded if they were based on non-human subjects, not specific to IPMN, or determined IPMN from PDAC rather than low-grade from high-grade dysplasia in IPMN. Data extracted included study design, cohort demographics, specimen type, biomarker type, methodology for biomarker discovery, positive predictive value, negative predictive value, sensitivity, specificity or AUC value and were evaluated against the STARD checklist. Study quality was evaluated using the QUADAS-2 tool. Results We identified 1761 studies of which 88 were selected for analysis. Twenty-six studies identified biomarkers derived from serum/plasma, 25 from biopsy specimens, 18 from cystic fluid, 13 from radiological findings, 4 from pancreatic juice, 3 from clinical risk stratification and 1 urinary biomarker. Markers were based on proteins (43%), mRNA (1%), miRNA (14%), lncRNA (2%), DNA (16%), metabolites (1%), radiomics (19%), glycans (5%), inflammatory markers (5%) and clinical history (5%). We observed discriminatory values ranging from AUC 0.58-1, specificity 64-100% and sensitivity 56-90.9%. Conclusion This systematic review outlines the current evidence-base for potential biomarkers to determine low-risk from high-risk IPMNs of the pancreas. Current studies are limited by retrospective sample collection, limited cohort sizes and lack of external validation of candidate biomarkers. There is a need to develop and validate biomarkers in a longitudinal prospective cohort study of individuals undergoing IPMN screening with the ability to characterise low-risk to high-risk transformation which after external validation would be suitable for adoption into clinical practice.

Abstract A059: Serum EphA2 proteolytic fragment is a potent biomarker for diagnosing a very early stage of ductal pancreatic carcinoma

Abstract Erythropoietin-producing hepatocellular receptor A2 (EphA2) is a receptor tyrosine kinase, and its expression increases with malignant progression of cancer. Therefore, EphA2 is believed to be a candidate for molecular cancer therapy and many candidate drugs targeting EphA2 have been developed, but their effects are limited. The reason is its complex signaling functions. In fact, EphA2 has a tumor suppressor function regulated by the stimulation of the Ephrin-A ligand, while in the absence of ligand stimulation, it has a prooncogenic function in collaboration with EGFR and its downstream signaling molecules. The opposite functions of EphA2 make it difficult to develop it as a cancer drug target. We have previously demonstrated that a type-1 matrix membrane metalloprotease (MT1-MMP) at cancer cell surface interacted with EphA2 and selectively cleaved its N-terminal ligand binding site, converting it into a prooncogenic signaling transmitter (Koshikawa N et al., Cancer Research, 2015). We also found that the N- terminal fragment of EphA2 (termed EphA2-NF) released by MT1-MMP cleavage increased in sera from patients with gastric cancer and ductal pancreatic carcinoma (PDC) (Koshikawa N et al., Cell Death & Disease, 2017). In this study, we compare the expression of EphA2-NF in serum from a healthy donor (HD: 150 cases), patients with chronic pancreatic disease (87 cases), and PDC (578 cases) by automated chemiluminescence immunoassay with a specific EphA2-NF monoclonal antibody. As a result, PDC cases, including stage I/II PDC, show significantly higher levels of EphA2-NF than HD (Sato et al. Cancer Research Communications, 2023). Furthermore, PDC occurred in the intraductal papillary mucinous neoplasm (IPMN) cases with high levels of EphA2-NF during follow-up observation. Therefore, to verify that the EphA2 proteolytic cleavage occurred in the PDC onset, we analyzed 50 surgical resected tissues from patients with PDC and IPMN to detect the N and C-terminal regions of EphA2 by immunohistochemical staining. Interestingly, PDC, including early stage PDC cases, lacked the N-terminus of EphA2. Furthermore, the deletion of N-terminus of EphA2 was observed in all tested cases pathologically diagnosed as intraductal papillary mucinous adenocarcinoma (IPMC) (Sato S et al., Cancer Research Communications, 2023). These results suggest that serum EphA2-NF has the potential to revolutionize the early detection and management of PDC, providing a valuable tool to diagnose the disease in very early stages when treatment results may be more favorable. Collaborators: Masatoshi Nakagawa, Eisaku Yoshida and Toru Yoshimura (Research and Development, Abbott Japan LLC) Citation Format: Naohiko Koshikawa, Shinya Sato, Kouki Nio, Takeshi Terashima, Makoto Ueno, Taro Yamashita. Serum EphA2 proteolytic fragment is a potent biomarker for diagnosing a very early stage of ductal pancreatic carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A059.

Laparoscopic total pancreatectomy with total mesopancreas dissection using counterclockwise technique and tail-first approach.

Laparoscopic total pancreatectomy (LTP) is technically challenging and infrequently documented in the literature. In this paper, we present a new approach for performing fully LTP, a pancreatic tail-first approach with a counterclockwise technique, to accomplish total mesopancreas dissection and standard lymphadenectomy en bloc. Firstly, the tail and body of the pancreas without the spleen were dissected retrogradely, starting from the lower border of the body of pancreas and then from left to right. After that, a counterclockwise dissection of the tail and body of the pancreas was performed. The splenic artery and vein were divided at the terminal end of the pancreatic tail. The spleen was preserved. The entire body and tail of the pancreas were then pulled to the right side. This maneuver facilitated the isolation and dissection of arteries in the retropancreatic region more easily via laparoscopy, including the splenic artery, gastroduodenal artery, and supporting superior mesenteric artery first-approach. It also enabled total mesopancreas dissection. The inferior pancreaticoduodenal artery was resected last during this phase. The remainder of the dissection was like that of a laparoscopic pancreaticoduodenectomy with total mesopancreas dissection, involving two laparoscopic manual anastomoses. The operative time was 490 minutes and the total blood loss was 100 mL. Pathology revealed a low-grade intraductal papillary mucinous neoplasm extending from the head to the tail of the pancreas.

Intraductal Papillary Mucinous Neoplasm: New Insights Into Its Origin and Nomenclatures.

Mucinous cells can be detected sporadically or may constitute the primary tumor component in salivary gland tumors, as observed in the intraductal papillary mucinous neoplasm (IPMN). This low-grade tumor is composed of mucinous columnar cells organized into papillary cystic structures. The present study aimed to compare the mucous cells in IPMN with mucous cells present in mucoepidermoid carcinoma (MEC) and papillary cystadenoma (PC). Immunohistochemistry analysis was carried out to compare the mucous cells in IPMN with the sporadic mucous cells in MEC (n = 4) and PC (n = 3). The results indicated that IPMN cells were positive for CK7, CK18, DOG1, and NKX3.1 and negative for CK14, SMA, and p63. The mucous cells in both MEC and PC were positive for CK7 and negative for CK18, SMA, DOG1, and NKX3.1. The positive expression of CK14 and p63 revealed the presence of basal cells both in PC, cystic areas of MEC, and normal mucous salivary glands. The immunohistochemical profile of IPMN closely resembles that of the mucous cells of the minor salivary glands yet differs from the mucous cells observed in MEC and PCX. This suggests that IPMN is probably derived from the transformation of secretory cells of the minor mucous salivary gland and has no rimming/basal cells. For this reason, we propose that this tumor is designated as mucous acinic cell carcinoma.

Histological Subtypes Might Help Risk Stratification in Different Morphological Types of IPMNs: Back to the Future?

Background: Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated. Hence, our aim was to investigate the prevalence of histological subtypes and their possible association with HGD/C concerning morphologically different IPMNs. Methods: This was a retrospective review of demographics, risk factors, and histological features in a surgical cohort of patients having undergone resection for suspect malignant IPMNs at a high-volume tertiary center from 2007 to 2017. Results: A total of 273 patients were resected for IPMNs from during the study period, of which 188 were included in the final analysis. With sex- and age-adjusted multivariable logistic regression analysis across the entire cohort, gastric foveolar subtypes were associated with a reduced prevalence of HGD/C (OR = 0.30; 0.11–0.81, 95% CI, 95%CI; p = 0.01). With univariable logistic regression analysis, in the BD-IPMN subgroup, the pancreaticobiliary subtype was associated with an increased prevalence of HGD/C (OR = 18.50, 1.03–329.65, 95% CI; p = 0.04). In MD- and MT-IPMNs, the gastric foveolar subtype was associated with a decreased prevalence of HGD/cancer (OR = 0.30, 0.13–0.69, 95% CI; p = 0.004). Conclusions: In MD and MT-IPMNs, the gastric-foveolar subtype is associated with a lower prevalence of HGD/C, possibly identifying in such a high-risk group, a subgroup with more indolent behavior. In BD-IPMNs, the pancreaticobiliary subtype is associated with a higher prevalence of HGD/C, conversely identifying among those patients, a subgroup deserving special attention.

Intraductal papillary mucinous neoplasm: Overview of management.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is increasingly being diagnosed incidentally on imaging. Ithas malignant potential, making it vitalto establish the correct diagnosis, assessits malignant risk and follow a management strategy to prevent development of invasive carcinoma ofthe pancreas. 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. 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.

Pancreatic cystic neoplasms

Pancreatic cystic lesions represent achallenging 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.

Interobserver Agreement in Dysplasia Grading of Intraductal Papillary Mucinous Neoplasms: Performance of Kyoto Guidelines and Optimization of Endomicroscopy Biomarkers through Pathology Reclassification

Interobserver Agreement in Dysplasia Grading of Intraductal Papillary Mucinous Neoplasms: Performance of Kyoto Guidelines and Optimization of Endomicroscopy Biomarkers through Pathology Reclassification

Into the pancreas: an underwater world filled with an intraductal papillary mucinous neoplasm seen via peroral pancreatoscopy.

Into the pancreas: an underwater world filled with an intraductal papillary mucinous neoplasm seen via peroral pancreatoscopy.

Digital peroral pancreatoscopy to determine surgery for patients who have intraductal papillary mucinous neoplasms of the pancreas with mural nodules

Background and study aims: Since more than a few patients having intraductal papillary mucinous neoplasms of the pancreas (IPMNs) with mural nodules (MNs) are benign, clinical plans should be determined by using histocytological specimens especially for those patients with high-risk for surgery or with a small MN. Patients and methods: This study included 27 patients to evaluate the efficacy of peroral pancreatoscopy using a SpyGlass DS system (POPS-DS) for patients with MN-positive IPMN, mainly focusing on the ability of POPS-DS to detect malignancy. Results: Biopsy specimens obtained under POPS-DS guidance could be used for the histological evaluations of all patients with MNs in the main pancreatic duct and 67% of the patients with MNs in the branch ducts, whereas fluid specimens collected during POPS-DS could be used for histocytological evaluations for all patients. For the 13 patients who underwent surgery just after POPS-DS, the sensitivity, specificity, and accuracy of POPS-DS to detect malignancy were 89%, 100%, and 92%, respectively. For the 12 patients who underwent surveillance without surgery, the cumulative 3-year progression rates for 9 benign IPMNs and 3 malignant ones determined using POPS-DS were 0% and 100%, respectively. However, the sensitivity of POPS to detect IPMN epithelium in the resection margin was 20%. Only one patient developed procedure-related pancreatitis (mild). Conclusions: POPS-DS could be used to accurately detect malignancy for patients with MN-positive IPMN. Therefore, histocytological evaluations using POPS-DS can contribute to the selection of patients for whom surgery would be appropriate.

Development of an intraductal papillary mucinous neoplasm malignancy prediction scoring system.

Despite the presence of various guidelines, diagnosing malignant intraductal papillary mucinous neoplasm (IPMN) continues to pose challenges. Furthermore, although endoscopic ultrasonography (EUS) offers high-resolution images, it has not yet recognized as the primary tool for malignancy diagnosis. The study objective was to develop a simplified and user-friendly scoring system to improve the diagnostic accuracy of malignant IPMNs. Additionally, the utility of EUS and its effect on diagnostic accuracy were assessed. We retrospectively collected the clinical data on 160 cases of resected IPMN at Tokyo Medical and Dental University Hospital from January 2008 to December 2022. We examined clinical features, computed tomography (CT) and magnetic resonance imaging (MRI) findings, and EUS results if available. We then calculated the odds ratio of malignancy for these factors and developed an IPMN malignancy prediction (IMAP) scoring system. There were 89 (55.6%) cases of benign IPMNs and 71 (44.4%) of malignant IPMNs. Eight clinical and imaging findings, including age, diabetes mellitus status, jaundice, CA19-9 level, enhancing mural nodules ≥5mm, thickened wall, and main duct dilatation, were significantly associated with malignancy. The IMAP score was calculated by assigning 0 to 2 points to these factors based on the odds ratio. The area under the receiver operating characteristic curve for the IMAP score was 0.78 [95% confidence interval (CI): 0.71-0.85] based on CT/MRI alone and improved to 0.81 (95% CI: 0.74-0.87) when EUS was added. When the total exceeds 5 points, the positive predictive value becomes 100% (95% CI: 95.9-100). In conclusion, the IMAP scoring system has demonstrated promise as a clinically useful tool, offering both simplicity and sufficient accuracy. It holds potential as an important decision criterion for determining the treatment approach for IPMN. Additionally, EUS contributes to enhancing the diagnostic accuracy of the IMAP scoring system, thereby enabling more precise decision-making.

Small cyst size and lack of growth as negative predictors of malignant transformation in low-risk intraductal papillary mucinous neoplasms of the pancreas: A systematic review and meta-analysis.

For branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WFs) or high-risk stigmata (HRS), current guidelines recommend surveillance. However, these intraductal papillary mucinous neoplasm (IPMNs), especially the small and stable-sized ones, carry a low risk of malignant transformation. Our aim was to assess whether small cyst size and absence of rapid growth provide reassurance against the development of WFs/HRS and malignancy (high-grade dysplasia (HGD) or pancreatic cancer (PC)). PubMed/Medline, Embase, the Cochrane Library and the Web of Science Core Collection were systematically searched from inception to May 2023 to identify studies investigating surveillance outcomes of low-risk BD-IPMNs. Studies assessing baseline cyst size and/or growth in relation to WFs/HRS and/or HGD/PC were included. The Newcastle-Ottawa scale tool was used to assess study quality. Of the 1937 identified manuscripts, 21 studies were eligible for inclusion. The quality of these studies was considered reasonable. A negative association between cyst size and WFs/HRS development was found in 11 out of 13 relevant studies, but only one out of nine studies reported a negative association between size and malignancy. Regarding cyst growth, four out of six studies described a negative association with the development of WFs/HRS, and all six reported a negative association with malignancy. The pooled relative risk (RR) of developing WFs/HRS or malignancy for cysts ≤15mm was 0.37 (95% CI 0.25-0.57) and the RR of developing malignancy for cyst growth <2-2.5mm/year was 0.04 (95% CI 0.02-0.09)). This systematic review and meta-analysis shows that small and stable-sized low-risk BD-IPMNs are associated with a markedly low progression rate, with stable cyst size being the most reassuring feature. Because of substantial heterogeneity in definitions and reported outcome measures, prospective studies are needed to confirm that surveillance of small and stable sized cyst can be de-intensified or even discontinued.

8184 A Case With Primary Hyperparathyroidism Caries A New Variant Of Uncertain Significance (VUS) Of The Multiple Endocrine Neoplasia Type 1 (MEN1) Gene

Abstract Disclosure: E. Caliskan Guzelce: None. E. Fieg: None. C. Pallias: None. Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant disorder caused by mutations in the MEN1 tumor suppressor gene. MEN1 syndrome is classically characterized by a predisposition to tumors of the parathyroid glands, anterior pituitary, and pancreatic islet cells. However, the clinical spectrum of this disorder has been expanded: carcinoid tumors,adrenal adenomas and lipomas are more common than in the general population.We report a case whose personal and family history is highly suggestive of and consistent with a monogenic disorder such as MEN1, also found to be a carrier of a new variant of uncertain significance (VUS) of the MEN1 gene. A study performed with the French Universal Mutation Database (UMD) for the MEN1 gene showed that one-third of the missense MEN1 variants were VUSs, mainly due to the lack of clinical and segregation data. Therefore, it is very important to identify and report the subjects with VUS of the MEN1 gene. Case report: 68-year-old female with a past medical history significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, CKD stage 4, and nephrolithiasis, GERD who presented with chief complaints of nausea and upper abdominal/epigastric pain and dark stools and found to have moderate hypercalcemia c/w primary hyperparathyroidism, several pancreatic cystic lesions most likely branch duct intraductal papillary mucinous neoplasms, and multinodular goiter and adrenal adenoma. Family history significant for recurrent hyperparathyroidism and nephrolithiasis; her daughter and brother had nephrolithiasis; her daughter has undergone parathyroidectomy twice. The patient's mother died at a young age because of gastric ulcer-related complications. Hyperparathyroidism-related genes were analyzed; AP2S1, CASR, CDC73, CDKN1B, GNA11, RET, MEN1, and only a Variant of Uncertain Significance, c.247_249dup (p.Leu83dup), was identified in MEN1 gene. The patient’s daughter and granddaughter are found to have the same mutation. Conclusion: This variant, c.247_249dup, results in the insertion of 1 amino acid(s) of the MEN1 protein (p. Leu83dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). The literature has not reported this variant in individuals affected with MEN1-related conditions. Presentation: 6/3/2024

Clinical significance of intraductal papillary mucinous neoplasms incidentally detected in patients with extrapancreatic gastrointestinal malignancies with a focus on pancreatic cancer development

BackgroundIntraductal papillary mucinous neoplasm is occasionally detected in the preoperative images of patients with gastrointestinal malignancies. Despite numerous studies examining the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasm, limited data exist on the prevalence of intraductal papillary mucinous neoplasm in those with gastrointestinal malignancies. Given that intraductal papillary mucinous neoplasm is a known risk factor for pancreatic cancer, this study aimed to evaluate the prevalence of intraductal papillary mucinous neoplasm in patients who underwent radical surgery for extrapancreatic gastrointestinal malignancies and its impact on pancreatic cancer development. MethodsWe retrospectively reviewed the preoperative computed tomography images of patients who underwent radical surgery for gastrointestinal malignancies between January 2017 and December 2021 for the presence of intraductal papillary mucinous neoplasm. Patients were divided into intraductal papillary mucinous neoplasm and non–intraductal papillary mucinous neoplasm groups, and clinicopathologic features and long-term outcomes, including pancreatic cancer development, were compared between groups. ResultsA total of 814 patients who underwent radical surgery for extrapancreatic gastrointestinal malignancies were included. Among them, 81 patients (10.0%) had intraductal papillary mucinous neoplasm. The median observation period was 39 (0–79) months. Notably, pancreatic cancer developed in 5 patients with intraductal papillary mucinous neoplasm and 1 without. The 5-year cumulative incidences of pancreatic cancer were 8.8% and 0.2% in the intraductal papillary mucinous neoplasm and non–intraductal papillary mucinous neoplasm groups, respectively (P < .001). ConclusionIntraductal papillary mucinous neoplasm is frequently detected in the preoperative images of patients with gastrointestinal malignancies and is associated with a significantly higher risk of developing pancreatic cancer. Consequently, long-term surveillance for pancreatic cancer is crucial in patients with intraductal papillary mucinous neoplasm, particularly those with extrapancreatic gastrointestinal malignancies.

Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas After Liver Transplantation.

Intraductal papillary mucinous neoplasms (IPMNs) are the most commonly identified pancreatic cystic neoplasms. Incidentally detected IPMNs are common among liver transplant recipients. The risk of IPMN progression to pancreatic cancer in transplant recipients and the impact of immunosuppression on the risk of malignant transformation of IPMN are unclear. In this retrospective study of consecutive liver transplant recipients across Mayo Clinic over a 13-year period, patients were assessed for possible IPMN by automated chart review. Pancreatic cystic lesions were characterized as suspected IPMNs based on imaging criteria. Cox proportional hazards models were used to determine the association between IPMN progression (the development of cancer or worrisome features) and clinical and immunosuppression regimen characteristics. Of 146 patients with suspected IPMNs, progression occurred in 7 patients (2 cases of IPMN-associated cancer and 5 cases of worrisome features) over an average follow-up of 66.6 months. Immunosuppression type, medication number, and tacrolimus trough levels were not associated with IPMN progression (p >0.05). Combined kidney and liver transplantation (p=0.005) and pretransplant cholangiocarcinoma (p=0.012) were associated with IPMN progression. IPMN progression is rare after liver transplantation even over an extended follow-up period. The findings were notable for the absence of an association between IPMN progression and immunosuppression regimen. Larger studies are needed given the low incidence.

Genotypes of carboxypeptidase A1 and gamma-glutamyltransferase 1 may be useful tools for the diagnosis and the predictor of worrisome features of intraductal papillary mucinous neoplasm in Japan.

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. 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. 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. Genotypes of carboxypeptidase A1 and gamma-glutamyltransferase 1 may be useful tools for the diagnosis and the predictor of worrisome features of IPMN.

Pancreatic cancer arising in intraductal papillary mucinous neoplasms (IPMN): emerging data warrants further research.

Pancreatic cancer arising in intraductal papillary mucinous neoplasms (IPMN): emerging data warrants further research.