Intraductal Papillary Mucinous Neoplasm Research Articles

Quantifying Patient Risk Threshold in Managing Pancreatic Intraductal Papillary Mucinous Neoplasms.

We aimed to better understand patients' treatment preferences and quantify the level of cancer risk at which treatment preferences change (risk threshold) to inform better counseling of patients with intraductal papillary mucinous neoplasms (IPMNs). The complexity of IPMN management provides an opportunity to align treatment with individual preference. We surveyed a sample of healthy volunteers simulating a common scenario: undergoing an imaging study that incidentally identifies an IPMN. In the scenario, the estimated risk of cancer in the IPMN was 5%. Patients were asked their treatment preference (surgery or surveillance), to quantify the level of cancer risk in the IPMN at which their treatment preference would change (i.e. risk threshold), and their level of cancer anxiety as measured on a 5-point Likert scale. We examined associations between participant characteristics, treatment preferences, and risk threshold using multivariable linear regression. The median risk threshold among the 520 participants was 25% (IQR 2.3-50%). The risk threshold had a bimodal distribution: 40% of participants had a risk threshold between 0-10% and 47% had a risk threshold above 30%. When informed that the risk of cancer was 5%, 62% of participants (n=323) preferred surveillance, and the remaining 38% (n=197) preferred surgery. After adjusting for potential confounders, participants who expressed "worry" or "extreme worry" about the malignancy risk of IPMN had significantly lower risk thresholds than participants who were "not at all worried" (Coefficient -12, 95%CI -21 to -2, P=0.015 and Coefficient -18, 95%CI -29 to -8, P<0.001, respectively). Participants varied in treatment preference and risk threshold of incidentally identified IPMNs. Given the uncertainty in estimating the true malignant potential of IPMNs, a better understanding of a patient's risk threshold, as influenced by patient concern about malignancy, will help inform the shared decision-making process.

Oncological Outcomes and Patterns of Recurrence after the Surgical Resection of an Invasive Intraductal Papillary Mucinous Neoplasm versus Primary Pancreatic Ductal Adenocarcinoma: An Analysis from the German Cancer Registry Group of the Society of German Tumor Centers.

Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The available literature has shown controversial results regarding prognosis and clinical outcomes after the resection of invasive IPMN. This study aims to characterize the oncologic outcomes and metastatic progression pattern after the resection of non-metastatic invasive IPMN. Data were obtained from 24 clinical cancer registries participating in the German Cancer Registry Group of the Society of German Tumor Centers (ADT). Patients with invasive IPMN (n = 217) as well as PDAC (n = 5794) between 2000 and 2021 were included and compared regarding oncological outcomes. Invasive IPMN was significantly smaller in size (p < 0.001) and of a lower tumor grade (p < 0.001), with fewer lymph node metastases (p < 0.001), lymphangiosis (p < 0.001), and consequently a higher R0 resection rate (88 vs. 74%) compared to PDAC. Moreover, invasive IPMN was associated with fewer local (11 vs. 15%) and distant recurrences (29 vs. 46%) and metastasized more frequently in the lungs only (26% vs. 14%). Invasive IPMN was associated with a longer median OS (29 vs. 19 months) and DFS (31 vs. 15 months) compared to PDAC and stayed independently prognostic in multivariable analyses. These survival differences were most pronounced in early tumor stages. Interestingly, postoperative chemotherapy was not associated with improved overall survival in surgically resected invasive IPMN. Invasive IPMN is a rare pancreatic entity with increasing incidence in Germany. It is associated with favorable histopathological features at the time of resection and longer OS and DFS compared to PDAC, particularly before the locoregional spread has occurred. Invasive IPMNs are associated with lung-only metastasis. The benefit of postoperative chemotherapy after the resection of invasive IPMN remains uncertain.

International Evidence-based Kyoto Guidelines for the Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas

International Evidence-based Kyoto Guidelines for the Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas

#2955 Incidental findings in a renal magnetic resonance imaging study for evaluation of chronic kidney disease in type 2 diabetes population

Abstract Background and Aims Novel Magnetic Resonance Imaging (MRI) techniques are potential methods to non-invasively assess and quantify functional, structural and pathophysiological changes in chronic kidney disease (CKD) that may improve diagnosis, prognosis and treatment of these patients. Advances in imaging techniques are also likely to result in the detection of unexpected and asymptomatic incidental findings. We retrospectively analyzed the overall prevalence of incidental findings in the participants of our previously reported study utilizing a non-contrast multiparametric MRI protocol in patients with type 2 DM (T2DM) as compared to healthy controls. Method The subjects of this sub-study were participants of our original prospective, single-center, observational study, in which several MRI biomarkers were evaluated to differentiate diabetic versus healthy kidneys, and various stages of CKD. A complete medical history and physical examination were performed. The inclusion criteria for the T2DM cohort were: Age 18-70 years, type II DM with CKD staged 3-4 (estimated glomerular filtration rate [eGFR] 15-60 ml/min/1.73 m2, body mass index (BMI) 18-35 and provision of written informed consent. The control group comprised of healthy volunteers who were age- and sex-matched and had the following inclusion criteria: Age 18-70 years, eGFR &amp;gt;80 ml/min/1.73 m2, UACR &amp;lt;30 mmol/g, BMI 18-35 and provision of written informed consent. Exclusion criteria for the diabetic group were any apparent cause/s of CKD other than diabetes, previous kidney transplantation, pregnancy, contraindication for MRI examination, heart failure (NYHA class III or IV), allergies to iodine-based contrast agents. Factors that excluded healthy participants were pregnancy, contraindication for MRI examination, allergy to iodine-based contrast agents and any active or chronic disease/diagnosis. Measured GFR (mGFR) was assessed in all participants using iohexol clearance. An MRI scan using a wide range of non-contrast techniques was performed at baseline. Total scan time for patients did not exceed 45 min per session and no gadolinium-based contrast agents were used in any of the MRI examinations. All patients with incidental findings on MRI were further evaluated and referred to appropriate specialists for management. Results A total of 38 T2DM patients with CKD and 20 age- and gender-matched healthy volunteers who completed the study were included in the analysis. Of the T2DM patients, 2 were found to have CKD stage 2 by mGFR and 36 CKD stages 3–4. Clinically significant incidental findings (excluding 4 cases of renal cysts requiring only follow-up without further intervention) were found in 13 of the 38 (34%) T2DM patients. The most frequent findings were intraductal papillary mucinous neoplasm (IPMN) in 7 patients, followed by 3 cancers (1 case of kidney cancer, 1 bladder cancer and 1 lymphoma) and 3 cases of adrenal gland mass later diagnosed to be benign adenoma on further investigation. In contrast, of the 20 healthy volunteers, 2 (10%) were found to have significant incidental findings, which were IPMN in both. The follow-up duration varied between 2-6 years. The patient with bladder cancer had metastatic disease and died shortly after the diagnosis, the one with kidney cancer is under observation and the one with lymphoma underwent adequate treatment and is under remission. The cases of IPMN are being followed up regularly at our surgical department. Conclusion Clinically important incidental findings on renal MRI appear to be more common in T2DM patients than in healthy volunteers, which would have been missed without MRI examination. Mechanisms for reporting and strategies for dealing with incidental findings need to be taken into account in such investigational imaging studies. The detection of incidental findings also poses various practical and ethical issues. Further larger studies with long-term follow-up are needed to delineate the clinical relevance, natural course and management of such incidental findings.

PanIN or IPMN? Redefining Lesion Size in 3 Dimensions.

Pancreatic ductal adenocarcinoma (PDAC) develops from 2 known precursor lesions: a majority (∼85%) develops from pancreatic intraepithelial neoplasia (PanIN), and a minority develops from intraductal papillary mucinous neoplasms (IPMNs). Clinical classification of PanIN and IPMN relies on a combination of low-resolution, 3-dimensional (D) imaging (computed tomography, CT), and high-resolution, 2D imaging (histology). The definitions of PanIN and IPMN currently rely heavily on size. IPMNs are defined as macroscopic: generally >1.0cm and visible in CT, and PanINs are defined as microscopic: generally <0.5cm and not identifiable in CT. As 2D evaluation fails to take into account 3D structures, we hypothesized that this classification would fail in evaluation of high-resolution, 3D images. To characterize the size and prevalence of PanINs in 3D, 47 thick slabs of pancreas were harvested from grossly normal areas of pancreatic resections, excluding samples from individuals with a diagnosis of an IPMN. All patients but one underwent preoperative CT scans. Through construction of cellular resolution 3D maps, we identified >1400 ductal precursor lesions that met the 2D histologic size criteria of PanINs. We show that, when 3D space is considered, 25 of these lesions can be digitally sectioned to meet the 2D histologic size criterion of IPMN. Re-evaluation of the preoperative CT images of individuals found to possess these large precursor lesions showed that nearly half are visible on imaging. These findings demonstrate that the clinical classification of PanIN and IPMN fails in evaluation of high-resolution, 3D images, emphasizing the need for re-evaluation of classification guidelines that place significant weight on 2D assessment of 3D structures.

Genetic assessment of IPMN for predicting concomitant pancreatic ductal adenocarcinoma.

Krüppel-like transcription factor 4(KLF4) mutations are more frequently observed in low-grade lesions than in high-grade lesions of intraductal papillary mucinous neoplasms (IPMN) of the pancreas. However, the role of KLF4 mutations in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study clarified the rate and effect of KLF4 mutations in IPMN with concomitant PDAC. DNA was extracted from 65 formalin-fixed and paraffin-embedded samples from 52 patients including 13 IPMN with concomitant PDAC and 39 IPMN alone. A comprehensive screening was performed using next-generation sequencing (NGS) for the 5 IPMNs with concomitant PDAC and 5 IPMNs alone, followed by targeted sequencing for KLF4, GNAS, and KRAS mutations. In NGS screening, KRAS mutations were observed in all samples except for one, GNAS mutation in two IPMNs with concomitant PDAC, and a KLF4 mutation in one IPMN with concomitant PDAC. Targeted sequence detected KLF4 mutations in 11 of the 52 IPMNs. Concomitant PDAC developed only in the non-intestinal, non-invasive, and branch duct IPMN cases, and KLF4 mutations were more frequent in this IPMN type than in the other type (36% vs. 10%, p = 0.04). For this IPMN type with KLF4 mutation, PDAC-prediction sensitivity, specificity, and accuracy were 63%, 82%, and 79%, respectively. For selected IPMNs with non-intestinal, non-invasive, and branch duct, genetic assessment might be a helpful tool for predicting the possible development of concomitant PDAC, although a prospective validation study using a larger study population is needed.

A rare case report ofIntracholecystic papillary-tubular neoplasm of the gall bladder

The understanding of Intracholecystic Papillary Neoplasm (ICPN) in the gallbladder is a recent development, hypothesized to have similarities in clinical and pathological traits with Intraductal Papillary Mucinous Neoplasm (IPMN) of the pancreas and Intraductal Papillary Neoplasm of the Bile Duct (IPNB). In this report, we present an uncommon instance of Intracholecystic Papillary-Tubular Neoplasms in a 38-year-old male. Although Intracholecystic Papillary Neoplasm (ICPN) is uncommon in the gallbladder lining, it typically presents a more favorable prognosis in contrast to gallbladder adenocarcinoma. Nonetheless, it still possesses the potential for metastatic spread to other organs. Our discussion delves into this patient’s case within the context of current literature on ICPN, while also delineating future avenues for enhancing clinical comprehension. Moreover, we emphasize the importance of implementing screening protocols, taking into account identified risk factors, to elucidate the natural course of the disease and deter its progression into invasive gallbladder carcinoma.

Comparison with surgically resected mucinous cystic neoplasm of pancreas and branch-duct type intraductal papillary mucinous neoplasm considering clinico-radiological high-risk features: a reassessment of current guidelines.

To perform a comparative analysis of surgically resected mucinous cystic neoplasm (MCN) of pancreas and branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) considering clinico-radiological high-risk predictors for malignant tumors using the current management guidelines. 224 patients who underwent surgical resection and had histopathologically confirmed MCNs (benign 73; malignant 17) or BD-IPMNs (benign 110; malignant 24) and had pre-operative CT or MRI were retrospectively reviewed. Tumors classified as either high-grade dysplasia or invasive carcinoma were considered malignant, whereas those with low-grade dysplasia were considered benign. Imaging features were analyzed by two radiologists based on selected high-risk stigmata or worrisome features proposed by prevalent guidelines except tumors with main pancreatic duct dilatation (> 5mm) were excluded. MCNs and BD-IPMNs showed significant differences in aspects like tumor size, location, the presence and size of enhancing mural nodules, the presence of wall or septal thickening, and multiplicity. Multivariate analyses revealed tumor size (OR, 1.336; 95% CI, 1.124-1.660, p = 0.002) and the presence of enhancing mural nodules (OR, 67.383; 95% CI, 4.490-1011.299, p = 0.002) as significant predictors of malignant MCNs. The optimal tumor size differentiating benign from malignant tumor was 8.95cm, with a 70.6% sensitivity, 89% specificity, PPV of 27.6%, and NPV of 96.9%, demonstrating superior specificity than the guideline-suggested threshold of 4.0cm. For malignant BD-IPMNs, the presence of enhancing mural nodules (OR, 15.804; 95% CI, 4.439-56.274, p < 0.001) and CA 19 - 9 elevation (OR, 19.089; 95%CI, 2.868-127.068, p = 0.002) as malignant predictors, with a size of enhancing mural nodule threshold of 5.5mm providing the best malignancy differentiation. While current guidelines may be appropriate for managing BD-IPMNs, our results showed a notably larger optimal threshold size for malignant MCNs than that suggested by current guidelines. This warrants reconsidering existing guideline thresholds for initial risk stratification and management of MCNs.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Optimal age to discontinue long-term surveillance of intraductal papillary mucinous neoplasms: comparative cost-effectiveness of surveillance by age

ObjectiveCurrent guidelines recommend long-term image-based surveillance for patients with low-risk intraductal papillary mucinous neoplasms (IPMNs). This simulation study aimed to examine the comparative cost-effectiveness of continued versus discontinued surveillance at...

Dysbiosis Signature of Fecal Microbiota in Patients with Pancreatic Adenocarcinoma and Pancreatic Intraductal Papillary Mucinous Neoplasms.

Pancreatic cancer (PC) ranks as the seventh leading cause of cancer-related deaths, with approximately 500,000 new cases reported in 2020. Existing strategies for early PC detection primarily target individuals at high risk of developing the disease. Nevertheless, there is a pressing need to identify innovative clinical approaches and personalized treatments for effective PC management. This study aimed to explore the dysbiosis signature of the fecal microbiota in PC and potential distinctions between its Intraductal papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC) phenotypes, which could carry diagnostic significance. The study enrolled 33 participants, including 22 diagnosed with PDAC, 11 with IPMN, and 24 healthy controls. Fecal samples were collected and subjected to microbial diversity analysis across various taxonomic levels. The findings revealed elevated abundances of Firmicutes and Proteobacteria in PC patients, whereas healthy controls exhibited higher proportions of Bacteroidota. Both LEfSe and Random Forest analyses indicated the microbiome's potential to effectively distinguish between PC and healthy control samples but fell short of differentiating between IPMN and PDAC samples. These results contribute to the current understanding of this challenging cancer type and highlight the applications of microbiome research. In essence, the study provides clear evidence of the gut microbiome's capability to serve as a biomarker for PC detection, emphasizing the steps required for further differentiation among its diverse phenotypes.

Oncogenic GNAS drives a pyloric-type transcriptomic program in pancreatic intraepithelial papillary mucinous neoplasms

BACKGROUND &amp; AIMS: Intraductal Papillary Mucinous Neoplasms (IPMNs) are cystic lesions of the pancreas which can serve as precursors for pancreatic ductal adenocarcinoma (PDAC). Recently, we showed that acinar to ductal metaplasia (ADM), an injury repair program associated with pancreatic tumorigenesis, is characterized by a pyloric-type transcriptomic program similar to gastric spasmolytic polypeptide expressing metaplasia (SPEM), suggesting common mechanisms of reprogramming between the stomach and pancreas. The aims of this study were to assay IPMN for SPEM markers and to identify molecular drivers of this program. METHODS: Published RNA-seq studies of IPMN were assessed for SPEM markers, which were validated by immunostaining in patient samples. Murine cell lines expressing KrasG12D +/- GNASR201C were manipulated to identify distinct and overlapping transcriptomic programs driven by each oncogene. A PyScenic-based regulon analysis was performed to identify drivers of SPEM in the pancreas. Expression of candidate drivers was evaluated in patient samples by RNA-seq and immunostaining and a role for SPDEF was investigated. RESULTS: SPEM markers were identified in human IPMN. GNASR201C drove expression of these markers in murine cell lines and siRNA targeting of GNASR201C or KrasG12D demonstrates that GNASR201C amplifies a mucinous phenotype. Regulon analysis identified a role for transcription factors SPDEF, CREB3L1, and CREB3L4, which are expressed in patient samples. CONCLUSIONS: De novo expression of a pyloric-type/SPEM phenotype has been identified in pancreatitis, oncogenic KrasG12D-driven pancreatic neoplasia, and in KrasG12D;GNASR201C-driven IPMN, suggesting common mechanisms of reprogramming between these lesions and the stomach. IPMN-specific GNASR201C drives a SPEM phenotype characterized by the formation of mucus producing cells at the expense of other lineages. AMR was supported by NIH T32GM139400. AM is supported by the MD Anderson Pancreatic Cancer Moon Shot Program, the Sheikh Khalifa Bin Zayed Al-Nahyan Foundation and NIH (U01CA200468, U54CA274371, U24CA274274, R01CA220236). M.C.B.T is supported by a Vanderbilt Digestive Disease Research Center Pilot and Feasibility Grant (P30 DK058404) and a Nikki Mitchell Foundation Pancreas Club Seed Grant. M.C.B.T and N.J. are supported by The Department of Defense (DOD W81XWH2211121-1). The DelGiorno laboratory is supported by the Vanderbilt Ingram Cancer Center Support Grant (NIH/NCI P30 CA068485), the Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal Cancer (NIH/NCI 5P50 CA236733), the Vanderbilt Digestive Disease Research Center (NIH/NIDDK P30 DK058404), an American Gastroenterological Association Research Scholar Award (AGA2021-13-02), NIH/NIGMS R35 GM142709, The Department of Defense (DOD W81XWH2211121), The Sky Foundation, Inc (AWD00000079), and Linda’s Hope (Nashville, TN). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CT findings and clinical effects of high grade pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms.

To investigate the common CT findings of high-grade (HG) PanIN and clinical effects in the remnant pancreas in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Two hundred fifty-one patients with surgically confirmed IPMNs (118 malignant [invasive carcinoma/high-grade dysplasia] and 133 benign [low-grade dysplasia]) were retrospectively enrolled. The grade of PanIN (233 absent/low-grade and 18 high-grade) was recorded, and all patients underwent serial CT follow-up before and after surgery. Two radiologists analyzed CT findings of high-risk stigmata or worrisome features according to 2017 international consensus guidelines. They also analyzed tumor recurrence on serial follow-up CT after surgery. Statistical analyses were performed to identify significant predictors and clinical impact on postoperative outcomes of HG PanIN. PanIN grade showed a significant association with IPMN grade (p = 0.012). Enhancing mural nodules ≥5 mm, abrupt main pancreatic duct (MPD) changes with distal pancreatic atrophy, increased mural nodule size and MPD diameter were common findings in HG PanIN (P<0.05). In multivariate analysis, abrupt MPD change with distal pancreatic atrophy (odds ratio (OR) 6.59, 95% CI: 2.32-18.72, <0.001) and mural nodule size (OR, 1.05; 95% CI, 1.02-1.08, 0.004) were important predictors for HG PanIN. During postoperative follow-up, HG PanIN (OR, 4.98; 95% CI, 1.22-20.33, 0.025) was significantly associated with cancer recurrence in the remnant pancreas. CT can be useful for predicting HG PanIN using common features, such as abrupt MPD changes and mural nodules. In HG PanIN, extra caution is needed to monitor postoperative recurrence during follow-up.

ASO Visual Abstract: Outcomes of Neoadjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Neoplasm Compared with De Novo Pancreatic Adenocarcinoma

ASO Visual Abstract: Outcomes of Neoadjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Neoplasm Compared with De Novo Pancreatic Adenocarcinoma

Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas.

Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication. In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes. The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis. For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis.

Comprehensive Assessment of the Intrinsic Pancreatic Microbiome.

We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome. Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation. Pancreatic samples were collected at the time of resection from 109 patients. Samples included tumor tissue (control, n=20; IPMN, n=20; PDAC, n=19) and pancreatic cyst fluid (IPMN, n=30; SCA, n=10; MCN, n=10). Assessment of bacterial DNA by quantitative PCR and 16S ribosomal RNA gene sequencing was performed. Downstream analyses determined the relative abundances of individual taxa between groups and compared intergroup diversity. Whole-genome sequencing data from 140 patients with PDAC in the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were analyzed to validate findings. Sequencing of pancreatic tissue yielded few microbial reads regardless of diagnosis, and analysis of pancreatic tissue showed no difference in the abundance and composition of bacterial taxa between normal pancreas, IPMN, or PDAC groups. Low-grade dysplasia (LGD) and high-grade dysplasia (HGD) IPMN were characterized by low bacterial abundances with no difference in tissue composition and a slight increase in Pseudomonas and Sediminibacterium in HGD cyst fluid. Decontamination analysis using the CPTAC database confirmed a low-biomass, low-diversity intrinsic pancreatic microbiome that did not differ by pathology. Our analysis of the pancreatic microbiome demonstrated very low intrinsic biomass that is relatively conserved across diverse neoplastic conditions and thus unlikely to drive malignant transformation.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic tumors.

Surgery is a cornerstone in the management of pancreatic cancer and precancerous pancreatic lesions. However, many patients are not suitable candidates for surgery at the time of diagnosis for various reasons. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) appears to be a promising treatment option for patients who are ineligible for surgery for management of pancreatic adenocarcinoma (PDAC), and pancreatic neuroendocrine tumors (PNETs), and pancreatic cystic lesions (PCLs). EUS-RFA may serve as an adjunct to chemotherapy or palliative measures for inoperable cases of PDAC. Given its feasibility and efficacy, EUS-RFA has an evolving niche as a minimally invasive and potentially definitive treatment for PNETs and high-risk PCLs such as intraductal papillary mucinous neoplasms (IPMNs). EUS-RFA is a generally well tolerated procedure, with abdominal pain and acute pancreatitis being the most common adverse effects, though the risk can be mitigated through prophylactic measures. There is an increasing body of evidence to support the use of EUS-RFA in managing pancreatic lesions, either as definitive, adjunctive, or palliative treatment, depending on lesion type.

Defining the Minimal and Optimal Thresholds for Lymph Node Resection and Examination for Intraductal Papillary Mucinous Neoplasm Derived Pancreatic Cancer: A Multicenter Retrospective Analysis.

To establish minimal and optimal lymphadenectomy thresholds for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and evaluate their prognostic value. Current guidelines recommend a minimum of 12-15 lymph nodes (LNs) in PDAC. This is largely based on pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, a biologically distinct entity from IPMN-derived PDAC. Multicenter retrospective study including consecutive patients undergoing upfront surgery for IPMN-derived PDAC was conducted. The minimum cut-off for lymphadenectomy was defined as the maximum number of LNs where a significant node positivity difference was observed. Maximally selected log-rank statistic was used to derive the optimal lymphadenectomy cut-off (maximize survival). Kaplan-Meier curves and log-rank tests were used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox-regression was used to determine hazard ratios (HR) with 95% confidence intervals (95%CI). In 341 patients with resected IPMN-derived PDAC, the minimum number of LNs needed to ensure accurate nodal staging was 10 (P=0.040), whereas ≥20 LNs was the optimal number associated with improved OS (80.3 vs. 37.2mo, P<0.001). Optimal lymphadenectomy was associated with improved OS [HR:0.57 (95%CI 0.39-0.83)] and RFS [HR:0.70 (95%CI 0.51-0.97)] on multivariable Cox-regression. On sub-analysis the optimal lymphadenectomy cut-offs for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were 20 (P<0.001), 23 (P=0.160), and 25 (P=0.008). In IPMN-derived PDAC, lymphadenectomy with at least 10 lymph nodes mitigates under-staging, and at least 20 lymph nodes is associated with the improved survival. Specifically, for pancreatoduodenectomy and total pancreatectomy, 20 and 25 lymph nodes were the optimal cut-offs.

Effective abdominal ultrasonographic detection of pancreatic cystic lesions using artificial intelligence‐assisted noise reduction

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

The diagnostic value of abbreviated MRI protocol in the surveillance of Branch-Duct intraductal papillary mucinous neoplasm

PurposeTo assess the diagnostic value of abbreviated protocol (AP) MRI to detect the degeneration signs in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) in patients undergoing a routine MRI follow-up. MethodsThis dual-center retrospective study include patients with BD-IPMN diagnosed on initial comprehensive protocol (CP) MRI who underwent routine MRI follow-up. CP included axial and coronal T2-weighted images (T2WI), axial T1-weighted images (T1WI) before and after contrast administration, 3D MR cholangiopancreatography (MRCP) and diffusion-weighted images (DWI). Two APs, eliminating dynamic sequences ± DWI, were extracted from CP. Two radiologists evaluated the APs separately for IPMN degeneration signs according to Fukuoka criteria and compared the results to the follow-up CP. In patients who underwent EUS, imaging findings were correlated with pathological results. Per-patient and per-lesion sensitivity, specificity, PPV, NPV, and accuracy of APs were calculated. Additionally, the acquisition time for different protocols was calculated. ResultsOne hundred-fourteen patients (56.1 % women, median age: 71 years) with 256 lesions were included. Degeneration signs were observed in 24.6 % and 12.1 % per-patient and per-lesion, respectively. Regarding APs, the per patient sensitivity, specificity, PPV, NPV, and accuracy in the detection of the degeneration signs were 100 %, 93.5 %, 83.3 %, 100 %, and 95.1 %, respectively. No additional role for DWI was detected. AP without DWI economized nearly half of CP acquisition time (388 versus 663 s, respectively). ConclusionAP can confidently replace CP for BD-IPMN follow-up with high sensitivity and PPV while offering benefits such as patient comfort, improved MRI accessibility, and reduced dedicated time for image analysis. DWI necessitates special consideration. Clinical Relevance StatementOur data suggest that APs safely detect all degeneration signs of IPMN. While there is an overestimation of mural nodules due to the lack of contrast injection, this occurs in a negligible number of patients.