Intraductal Papillary Mucinous Neoplasm Research Articles

Outcomes of pancreatectomy for histologically proven intraductal papillary mucinous neoplasm with reference to Fukuoka guidelines.

Intraductal papillary mucinous tumour (IPMN) of pancreas is increasingly recognized to have malignant potential. Fukuoka guidelines are commonly used to select patients with IPMN for resection due to high chance of malignancy, which includes high-grade dysplasia (HGD) or invasive carcinoma (IC). A retrospective study on consecutive patients who have undergone pancreatectomy with IPMN as the final pathology was performed. Operative and survival outcomes were analysed. The positive predictive values (PPV) of high-risk stigmata (HRS) and worrisome features (WF) of Fukuoka guidelines for HGD/IC were determined. Between August 2011 and September 2020, various types of pancreatectomy were performed for 36 patients with histologically proven IPMN. They included 26 pancreaticoduodenectomy, 7 distal pancreatectomy, 2 central pancreatectomy, and 1 total pancreatectomy. There were 30 branch duct type IPMN, 5 main duct type, and 1 mixed type. There was no 30-day mortality. Overall complications and pancreatic fistula occurred in 44.4% and 5.6% of patients, respectively. Patients without HGD/IC had 100% survival at 5 years with no recurrent disease. There were 13 patients with HGD/IC, their 1-, 3-, 5-year overall and disease-free survival were 84.6%, 76.9%, 67.3% and 84.6%, 68.4%, 58.6%, respectively, both significantly shorter than non-HGD/IC group (P = 0.002 and 0.001, respectively). The PPV of HRS and WF for HGD/IC were 33.3% and 23.5%, respectively. The combined PPV of HRS and WF for HGD/IC was 38.0%. Survival after pancreatectomy for IPMN was favourable, but was significantly worse in the presence of HGD/IC. Fukuoka guidelines were useful in predicting malignant IPMN.

A genome-wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy.

Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer, but not all IPMNs progress to cancer. The objective of this study was to identify the germline genetic variants associated with IPMN clinical progression by conducting the first genome-wide association study (GWAS) and computing a polygenic hazard score (PHS) in 338 patients with IPMN. The study population was divided into two subsets, and a Cox analysis adjusted for sex, age, cyst size at diagnosis, and the top 10 principal components was performed. A PHS was calculated using the genotypes of common variants associated with IPMN progression identified. Eight loci with significant associations (p<5×10-8) were identified, and the most significant was 7q21.11-rs117620617 (hazard ratio, 16.35; 95% confidence interval, 6.93-38.60; p=1.80×10-10). All variants were associated with inflammatory processes, suggesting that alleles that predispose to an inflammatory prone phenotype may promote progression. The PHS indicated a statistically significant association (hazard ratio, 18.05; 95% confidence interval, 7.96-45.80; p=6.18×10-11) with IPMN progression among individuals who had the highest number of effect alleles (fourth quartile) compared with those who had the lowest number (first quartile). The current results study advance the understanding of individual predisposition to IPMN progression and underscore the potential use of genetics in the stratification of patients who have IPMN.

The impact of lymph node involvement on adjuvant chemotherapy and survival in patients with resected invasive intraductal papillary mucinous neoplasm: a propensity score matching study based on SEER database and external validation

Background: Limited knowledge and guidelines exist for invasive intraductal papillary mucinous neoplasm (IPMN). This study aims to explore the significance of lymph node involvement on adjuvant chemotherapy (ACT) for invasive IPMN. Materials and Methods: Patients diagnosed with invasive IPMN were selected from both the SEER database and our hospital. Kaplan-Meier analysis, Cox proportional hazards model, and propensity score matching (PSM) were employed in this study. Results: In the SEER group, multivariate analysis involving 775 patients revealed that several factors including age, tumor differentiation, AJCC-T staging, N staging, and TNM stage significantly influenced overall survival (OS) and cancer-specific survival (CSS). Turning to the Zhongshan Hospital group (ZS group), which had 94 recruited patients, multivariate analysis for OS, CSS, and recurrence-free survival (RFS) showed that AJCC N staging emerged as the most significant risk factor, with HR values of 4.664, 4.955, and 3.175, respectively. In subgroup analysis, ACT provided survival advantages for patients with positive lymph node metastasis (LNM). In a PSM analysis focused on patients with positive LNM, the comparison revealed that ACT emerged as a critical factor influencing both OS and CSS (both p&lt;0.005). Especially, these patients younger than 60 year old, or those with AJCC-T2-N+ staging were found to get apparently benefit from ACT as revealed by our subgroup interaction analysis. Conclusion: LNM plays a pivotal role in the management of invasive IPMN patients underwent surgery, and ACT might be a beneficial therapeutic option for individuals concurrent with LNM, particularly among those younger than 60 year old, or with AJCC-T2-N+ staging.

Decisional Control Preferences in Managing Intraductal Papillary Mucinous Neoplasms of the Pancreas.

To evaluate patient preferences for decision-making role in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and to identify individual characteristics associated with those preferences. Management of IPMNs is rooted in uncertainty with current guidelines failing to incorporate patients' preferences and values. A representative sample of participants aged 40-70 were recruited to evaluate a clinical vignette where they were given the option to undergo surveillance or surgical resection of their IPMN. Their preferred role in the decision-making process for the vignette was evaluated using the Control Preference Scale. The relationship between control preference and variables including cancer anxiety, health literacy, and education level was analyzed. Of the 520 participants in the study, most preferred an active role (65%), followed by shared (29%), and passive roles (6%) in the decision-making process. Lower health literacy was significantly associated with a more passive control preference (p = 0.003). Non-active preference was significantly associated with Latino race compared to White race (odds ratio = 0.52, p = 0.009) in multivariate analysis. We found no significant association between control preference and education level or cancer anxiety. Most patients preferred an active role in IPMN treatment decisions. Lower health literacy and Latino race were associated with a preference for non-active decision roles. Clinicians should strive to align patient involvement in IPMN treatment decisions with their patient's preferred role.

High Diagnostic Yield of Fine Needle Biopsy for Pancreatic Serous Cystadenomas - a Multi-Center Study.

Distinguishing serous cystadenoma, a benign pancreatic cyst, from potentially malignant mucinous pancreatic cystic lesions carries significant clinical and prognostic implications; and while endoscopic ultrasound-guided fine needle aspiration is the standard diagnostic tool, its low diagnostic yield often results in additional workup. This study evaluates diagnostic yield of fine needle biopsy (FNB) on lesions suggestive of serous cystadenoma on endoscopic ultrasound. Patients with microcystic EUS appearance were identified through retrospective chart review in two institutions. Prior cross sectional imaging diagnosis was also obtained. All microcystic lesions with classic "honeycomb" appearance for serous cystadenoma on EUS were targeted for FNB and their pathology evaluated. Patients were identified through database search from 2015 to 2022 and procedure information was obtained through a retrospective chart review from two large academic centers. Thirty-one patients with suspected serous cystadenoma who underwent EUS-FNB were included. EUS FNB was successful in obtaining diagnosis in 96.8% of patients. Serous cystadenoma was diagnosed via EUS FNB in 27 of 31 patients (87.1%). Of the remaining four patients, there was one invasive pancreatic ductal adenocarcinoma, one pancreatic neuroendocrine tumor, one intraductal papillary mucinous neoplasm, and one nondiagnostic sample. EUS-FNB sampling for histopathology is a safe and accurate diagnostic tool for pancreatic serous cystadenoma. When microcytic lesions are found on endoscopic ultrasound, our study results suggest that fine needle biopsy for histopathology should be considered as the initial diagnostic evaluation tool given the demonstrated improved diagnostic yield for serous cystadenoma.

Trends and Impact of Endoscopic Ultrasound Utilization for Suspected Intraductal Papillary Mucinous Neoplasms

Trends and Impact of Endoscopic Ultrasound Utilization for Suspected Intraductal Papillary Mucinous Neoplasms

Exploring thenew Kyoto guidelines for managing pancreatic cysts: an overview and comparison with previous guidelines.

The rising use of diagnostic imaging has led to an increase in the incidental detection of pancreatic cysts, with reported incidences of 1.2-2.6% on Computed Tomography and 2.4-49.1% on Magnetic Resonance Imaging. While many of these cysts are asymptomatic and benign, the enhanced imaging techniques have also revealed malignant and premalignant lesions. Mucinous neoplasms, including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms, are particularly concerning due to their potential for malignant transformation. Recent studies highlight significant variations in dysplasia across IPMN types, with main duct IPMNs showing a higher likelihood of high-grade dysplasia or invasive carcinoma compared to branch duct IPMNs. Management and follow-up of these lesions remain controversial due to inconsistent guidelines. This article reviews and compares six major guidelines: the 2015 American Gastroenterological Association guidelines, the 2017 International Association of Pancreatology (IAP/Fukuoka) guidelines, the 2017 American College of Radiology guidelines, the 2018 American College of Gastroenterology guidelines, the 2018 European Study Group guidelines, and the newly released, 2024 Kyoto guidelines. We summarize key differences in risk factors, surveillance protocols, and surgical referral criteria, with a focus on the updated 2024 Kyoto guidelines and the implications of recent research advancements.

Mural nodules and prevalence of high-grade dysplasia in branch duct intraductal papillary mucinous neoplasm of the pancreas undergoing resection.

A mural module (MN) within a branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) could be a potential target for local treatment. The main aim was to describe the location of the highest grade of dysplasia relative to the mural module to assess the relevance of local treatment. Observational study of patients who underwent a pancreatic resection for suspected high-risk IPMN because of a mural module within a BD-IPMN (2012-2022). All patients had preoperative imaging confirming the enhancing mural module. The mural module was considered as a theoretical appropriate target for local destruction if no cancer or high-grade dysplasia (HGD) was described elsewhere than in the mural module. Eighty-two patients (male: 44 (54%); mean age: 65 ± 9.2 years) were included. The mean size of BD-IPMN containing the mural module was 32 ± 14.8 mm. The mural module mean diameter was 10.5 ± 5.6 mm, and the main pancreatic duct (MPD) mean diameter was 5.2 ± 3.6 mm. Six patients presented invasive carcinoma (7%), 37 had HGD (45%), and 39 (48%) had exclusively low-grade dysplasia. The mural module was dysplastic in 70 cases (85%). The mural module was considered a relevant target for local ablation in 45 patients (55%), whereas 37 patients (45%) had HGD/invasive carcinoma distant from the mural module. HGD was exclusively present in the mural module in 6/82 patients (7%). Factors independently associated with 'relevant indication for local treatment' were female gender (P = 0.004; OR = 5.2, 95% c.i. 1.7 to 15.9) and MPD < 5 mm (P < 0.0001; OR = 8.6, 95% c.i. 2.7 to 26.8). In resected pancreata, BD-IPMN mural modules are associated with HGD distant from the mural module almost half of cases. The findings question the safety of local treatment, supporting pancreatectomy as the best approach.

Long-term survival after resection of invasive pancreatic intraductal papillary mucinous neoplasm.

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

New Surgical Criteria for Intraductal Papillary Mucinous Neoplasm Based on the Age-Adjusted Charlson Comorbidity Index Values and Presence of Solid Component.

Objectives: The present study aimed to validate the new international guidelines for IPMN and determine the surgical criteria for patients with IPMN exhibiting high-risk stigmata (HRS). Methods: We enrolled 115 IPMN patients exhibiting HRS who were diagnosed between 2004 and 2021. Of the 115 patients, 79 underwent surgery (surgical group) and 36 did not undergo surgery (non-surgical group). The overall survival (OS) of each group was compared, and multivariate analysis was performed to identify factors associated with OS. Results: There was no significant difference in the estimated 5-year OS in the surgical and non-surgical groups (67% vs. 74%; p = 0.75). The presence of a solid component (SC) (hazard ratio [HR], 6.92; 95% confidence interval [CI], 3.30-14.5) and a high score of age-adjusted Charlson comorbidity index (ACCI) (≥5) (HR, 2.27; 95% CI, 1.11-4.64) were independent predictors of poor OS. In the presence of an SC, the surgical group had a significantly better OS than the non-surgical group (estimated 5-year OS, 38% vs. 18%; p = 0.031). In the absence of an SC, the prognosis of patients with a high ACCI was significantly poorer than those with a low ACCI in the surgical group (estimated 5-year OS, 59% vs. 93%; p = 0.005). Conclusions: An SC and a high ACCI are important prognostic factors in IPMN patients exhibiting HRS. Thus, patients with an SC should undergo surgical resection. However, conservative management may be the optimal treatment in patients without an SC and with a high ACCI.

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

Currently, there is no reliable method of discerning between low-risk and high-risk intraductal papillary mucinous neoplasms (IPMNs). Operative resection is utilized in an effort to resect those lesions with high-grade dysplasia (HGD) prior to the development of invasive disease. The current guidelines recommend resection for IPMN that involve the main pancreatic duct. Resecting lesions with HGD before their progression to invasive disease and the avoidance of resection in those patients with low-grade dysplasia is the optimal clinical scenario. Therefore, the importance of developing preoperative models able to discern HGD in IPMN patients cannot be overstated. Low-risk patients should be managed with nonsurgical treatment options (typically MRI surveillance), while high-risk patients would undergo resection, hopefully prior to the formation of invasive disease. Current research is evolving in multiple directions. First, there is an ongoing effort to identify reliable markers for predicting malignant transformation of IPMN, mainly focusing on genomic and transcriptomic data from blood, tissue, and cystic fluid. Also, multimodal models of combining biomarkers with clinical and radiographic data seem promising for providing robust and accurate answers of risk levels for IPMN patients.

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 &amp; 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.

Bronchial salivary gland-type mucinous adenocarcinoma harboring a GNAS mutation: a novel lung cancer entity? A case report.

We report a case of a 65-year-old man with a 1.0-cm mass in the left main bronchus, exhibiting overlapping morphological, immunohistochemical, and genetic features with both pancreatic intraductal papillary mucinous neoplasm (IPMN) with associated invasive carcinoma and salivary gland IPMN. Based on its close proximity to the bronchial submucosal glands and the expression of NKX3.1 (an established immunohistochemical marker for mucinous acinar cells of the minor salivary glands), we propose that the tumor originates from the mucinous acinar cells of the bronchial salivary gland. Therefore, we suggest naming it bronchial salivary gland-type mucinous adenocarcinoma. Interestingly, a GNAS mutation, known as a highly specific marker for pancreatic IPMN, was detected by next-generation sequencing in our case. We believe that this tumor may represent a novel lung cancer entity.

Spatial Transcriptomics of IPMN Reveals Divergent Indolent and Malignant Lineages.

Intraductal papillary mucinous neoplasms (IPMN) occur in 5-10% of the population, but only a small minority progress to pancreatic ductal adenocarcinoma (PDAC). The lack of accurate predictors of high-risk disease leads both to unnecessary operations for indolent neoplasms as well as missed diagnoses of PDAC. Digital spatial RNA profiling (DSP-RNA) provides an opportunity to define and associate transcriptomic states with cancer risk. Whole-transcriptome DSP-RNA profiling was performed on 10 IPMN specimens encompassing the spectrum of dysplastic changes from normal duct to cancer. Ductal epithelial regions within each tissue were annotated as normal duct (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or invasive carcinoma (INV). Gene expression count data was generated by Illumina sequencing and analyzed with R/Bioconductor. Dimension reduction analysis exposed three clusters reflecting IPMN transcriptomic states denoted "normal-like" ( cNL ), "low-risk" ( cLR ) and "high-risk" ( cHR ). In addition to specific marker genes, the three states exhibited significant enrichment for the exocrine, classical, and basal-like programs in PDAC. Specifically, exocrine function diminished in cHR , classical activation distinguished neoplasia from cNL , and basal-like genes were specifically upregulated in cHR . Intriguingly, markers of cHR were detected in NL and LGD regions from specimens with PDAC but not low-grade IPMN. DSP-RNA of IPMN revealed low-risk (indolent) and high-risk (malignant) expression programs that correlated with the activity of exocrine and basal-like PDAC signatures, respectively, and distinguished pathologically low-grade from malignant specimens. These findings contextualize IPMN pathogenesis and have the potential to transform existing risk stratification models. Current consensus guidelines for management of intraductal papillary mucinous neoplasms (IPMN) of the pancreas utilize clinical and radiographic criteria for risk stratification. Unfortunately, the estimated positive predictive value of these criteria for IPMN-associated pancreatic ductal adenocarcinoma (PDAC) is under 50%, indicating that over half of pancreatectomies are performed for benign disease. Moreover, nearly 15% of patients who were deemed "low risk" by the same criteria harbored PDAC. Surgical resection of IPMN has maximal benefit when performed prior to the development of PDAC, as evidence of carcinoma has been associated with a high rate of recurrence and poor overall survival. Thus, the development of molecular diagnostics that improve the accuracy of IPMN risk classification would have immediate relevance for patient care, both in terms of better selecting patients for potentially curative operations, as well as sparing patients with low-risk lesions from invasive procedures.

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.