Branch-duct Intraductal Papillary Mucinous Neoplasms Research Articles

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.

Natural history of low-risk branch-duct intraductal papillary mucinous neoplasms and indeterminate pancreatic cysts: implications on surveillance intervals by cyst size.

The optimal surveillance strategy for low-risk branch-duct intraductal papillary mucinous neoplasms (BD-IPMN) remains unclear. We aim to evaluate the natural history of low-risk BD-IPMN/indeterminate pancreatic cysts to determine optimal surveillance intervals. We conducted a retrospective cohort study of patients with radiologically-diagnosed low-risk BD-IPMN/indeterminate pancreatic cysts from 1998 to 2021at a tertiary referral center. Low-risk BD-IPMN, worrisome features (WF) and high-risk stigmata (HRS) were defined as per existing guidelines. Patients were grouped into three categories based on cyst size at diagnosis: <10mm, 10-19mm and 20-29mm. The size distribution and cumulative incidence of WF and HRS development were charted annually for the first five years. We studied 1668 patients, with 794 (47.6%), 652 (39.1%) and 222 (13.3%) with cysts <10mm, 10-19mm and 20-29mm at baseline respectively. Overall WF and HRS development was seen in 11.7% and 1.4% of patients respectively, with higher proportion of WF (6.8 vs 9.8 vs 34.7%, p<0.001) and HRS (0.9 vs 1.4 vs 3.6%, p=0.011) development with increasing baseline size category. Cysts <10mm had 94.3%<30mm at five years, 2.0% WF at one year and a single case of HRS at two years. Cysts 10-19mm had 94.7%<30mm at five years, 2.2% WF at one year and the first incident case of HRS at one year. Cysts 20-29mm had 63.8%<30mm at five years, 9.5% WF and 1.1% (4 cases) HRS by one year. Baseline cyst size can be used to guide surveillance intervals for low-risk BD-IPMN/indeterminate pancreatic cysts.

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.

Diagnostic Performance of Surgical Indication for Branch-duct or Mixed-type Intraductal Papillary Mucinous Neoplasms of the Revised International Association of Pancreatology (IAP) 2023 Guidelines.

To evaluate the diagnostic performance of surgical indications of the revised International Association of Pancreatology (IAP) 2023 guidelines compared to the IAP 2017 and European 2018 guidelines. The revised IAP guidelines for surgical indications for branch duct (BD) intraductal papillary mucinous neoplasms (IPMN) include the presence of at least two worrisome features without mandatory endoscopic ultrasound. Among 663 patients who underwent resection for pathologically confirmed IPMN in a tertiary hospital between 2013 and 2023, 556 patients with BD or mixed-type IPMN were retrospectively reviewed. Diagnostic performances of the three guidelines for predicting high-grade dysplasia or IPMN with invasive carcinoma were compared. The primary outcome was the malignancy rate. Clinicopathological and radiological imaging data were analyzed. A total of 540, 451, and 490 patients met the surgical indications of the IAP, 2017, 2023, and European guidelines, respectively. Malignant IPMN was observed in 229 (41.2%) patients (high-grade dysplasia, n=99; invasive carcinoma, n=130). Surgical indication by the IAP 2023 guidelines showed higher specificity (29.1 vs. 4.9%, P<0.001), positive predictive value (48.6 vs. 42.4%, P=0.031), and accuracy (55.5 vs. 44.1%, P<0.001) than the IAP 2017 guidelines. It also had higher specificity than the European guidelines (18.7%, P=0.024). The IAP 2023 guidelines showed a superior AUC of surgical indication (0.623 vs. 0.582 for the European guidelines, P<0.001; and 0.524 for the IAP guidelines, P=0.008). The IAP 2023 guidelines showed better malignancy prediction than the IAP 2017 and European guidelines, potentially reducing unnecessary surgeries.

Unraveling the Long-term Natural History of Branch Duct Intraductal Papillary Mucinous Neoplasm: Beyond 10 years.

To describe the long-term natural history of Branch duct intraductal papillary mucinous neoplasm (BD-IPMN). The BD-IPMN is a known precursor of pancreatic cancer, yet its long-term natural history is largely unknown. We retrospectively reviewed patients with BD-IPMN who were followed at the Massachusetts General Hospital for at least ten years without surgical intervention. Patient and cyst characteristics, development of worrisome features (WF), need for surgery, and malignancy were recorded. The risk of pancreatic cancer in this cohort was compared with the general population by determining the Standardized Incidence Ratio (SIR). 316 patients with BD-IPMN who were followed for at least ten years without intervention were identified. The median age was 63 years, and the median follow-up was 13.5 years (range 10 - 28.8 years). Median cyst size at diagnosis was 1.2cm (IQR 0.8 - 1.7), was 1.8cm (IQR 1.2-2.6) at ten years, and increased to 2.0cm (IQR 1.3 - 3.0) by the end of surveillance. At the 10-year mark, 24% of patients had WF, and by the end of surveillance, an additional 20% had developed WF or high-risk stigmata. 8.2% of patients developed pancreatic malignancy (high-grade dysplasia or invasive cancer). The SIR for pancreatic cancer was 9.28 (95%CI of 5.82 - 14.06), with almost two-thirds of invasive cancers occurring within the pancreatic cyst. After ten years of surveillance for BD-IPMN without intervention, the disease continues to progress and one of every 12 patients will develop malignancy. The risk of pancreatic cancer appears to be nine times higher than in the comparable age-matched population.

KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms-an observational pilot study.

Intraductal papillary mucinous neoplasms (IPMNs) are potential precursor lesions of pancreatic cancer. We assessed the efficacy of screening for KRAS proto-oncogene, GTPase (KRAS), and GNAS complex locus (GNAS) mutations in cell-free DNA (cfDNA)-using digital droplet polymerase chain reaction (ddPCR) and circulating epithelial cell (CEC) detection-as biomarkers for risk stratification in IPMN patients. We prospectively collected plasma samples from 25 resected patients at risk of malignant progression, and 23 under clinical surveillance. Our findings revealed KRAS mutations in 10.4% and GNAS mutations in 18.8% of the overall cohort. Among resected IPMN patients, KRAS and GNAS mutation detection rates were 16.0% and 32.0%, respectively, whereas both rates were 4.0% in conservatively managed IPMN. GNAS mutations in cfDNA were significantly more prevalent in resected IPMN (P = 0.024) compared with IPMN under surveillance. No CECs were detected. The absence of KRAS and GNAS mutations could be a reliable marker for branch duct IPMN without worrisome features. The emergence of GNAS mutations could prompt enhanced imaging surveillance. Neither the presence of established worrisome features nor GNAS or KRAS mutations appear effective in identifying high-grade dysplasia among IPMN patients.

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.

Prospective multicenter surveillance study of branch-duct intraductal papillary mucinous neoplasm of the pancreas; risk of dual carcinogenesis

BackgroundThe natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC). MethodsThe Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints. ResultsAmong the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant. ConclusionCareful attention should be given to “dual carcinogenesis” during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349).

Clinical Perspectives on the Histomolecular Features of the Pancreatic Precursor Lesions: A Narrative Review.

Pancreatic cancer (PC) is a lethal cancer with poor prognoses. Identifying and characterizing pancreatic cystic lesions (PCLs) in the early detection and follow-up plans is thought to help detect pancreatic malignancy. Besides, the molecular features of PCLs are thought to unravel potentials for targeted therapies. We present a narrative review of the existing literature on the role of PCLs in the early detection, risk stratification, and medical management of PC. High-grade intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasia (PanIN) stage III are high-risk lesions for developing PC. These lesions often require thorough histomolecular characterization using endoscopic ultrasound (EUS), before a surgical decision is made. EUS is also useful in the risk assessment of PCLs with tentative plans-for instance, in branch-duct IPMNs (BD-IPMN)- where the final decision might change. Besides the operative decisions, recent improvements in the application of targeted therapies are expected to improve survival measures. Knowledge of molecular features has helped develop targeted therapies. In summary, the histomolecular characterization of PCLs is helpful in optimizing management plans in PC. Further improvements are still needed for the broad application of this knowledge in the clinical setting.

Impact of age, comorbidities and relevant changes on surveillance strategy of intraductal papillary mucinous neoplasms: a competing risk analysis

ObjectiveCost-effectiveness of surveillance for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. We combined different categories of risks of IPMN progression and of IPMN-unrelated mortality to improve surveillance strategies.DesignRetrospective analysis...

Reappraising imaging features of pancreatic acinar cystic transformation: be aware of differential diagnoses.

Imaging features of pancreatic acinar cystic transformation (ACT) have been published. We aimed to describe the clinical and radiological characteristics of patients with a presumed pancreatic ACT diagnosis, reappraising the value of these published imaging criteria. Single-center retrospective study (2003-2021) of consecutive patients with a presumed diagnosis of ACT as suggested by the local expert multidisciplinary case review board. Patients without available imaging (CT or MRI) for review were excluded. Patients were classified into "certain" ACT (if ≥ 2 imaging criteria and no differential diagnosis) or "uncertain" ACT (if ≥ 1 imaging criteria and suggested differential diagnoses). Sixty-four patients (35 males, [55%]) were included. ACT was considered "certain" for 34 patients (53%) and "uncertain" for 30 patients (47%). The number of ACT criteria did not differ between groups, with 91.2% of patients with ≥ 3 ACT imaging criteria in the "certain" group vs 93.3% in the "uncertain" group (p = 0.88). In the "uncertain" group, the main suggested differentials were branch-duct intraductal papillary mucinous neoplasm (18/30 patients, 60%), calcifying chronic pancreatitis (8/30 patients, 27%), both (three patients, 10%) and serous cystadenoma (one patient, 3%). Calcifications were significantly more frequent in the "uncertain" group (89% vs 63% in the "certain" group, p = 0.02). Published ACT imaging criteria are frequently associated with features suggesting differential diagnoses. They appear insufficient to reach a final diagnosis in a subset of patients. ACT displays a heterogeneous morphological imaging presentation challenging the non-invasive diagnostic work-up. Physicians' and radiologists' awareness of this entity is important to better understand its natural history and improve non-invasive diagnostic criteria. The criteria to help diagnose ACT are frequently associated with features suggestive of differentials. The main alternatives suggested when ACT diagnosis was "uncertain" were branch-duct intraductal papillary mucinous neoplasm and calcifying chronic pancreatitis. Published ACT diagnostic imaging criteria can be insufficient for a definite non-invasive diagnosis.

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.

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...

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.

Optimal Surveillance Interval of Branch Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas

Despite the increasing prevalence of intraductal papillary mucinous neoplasm (IPMN), data on the growth and malignant conversion rates based on long-term surveillance cohorts are limited. Many international guidelines recommend surveillance for benign lesions, but the optimal interval and duration are unclear. To determine the optimal surveillance protocol for IPMN and propose which patients may be exempted from surveillance. This large-scale, international cohort study examined data of 3825 patients with IPMN treated at 5 tertiary pancreatic centers. Included were patients with branch duct (BD) IPMN who underwent surveillance or surgery between January 1, 1988, and December 31, 2020. After a thorough review, 3656 patients were included in the analytic sample. Changes in cyst size, worrisome features or high-risk stigmata, and malignant conversion rates were assessed. Patients who underwent surveillance over 5 years were compared to suggest discontinuation of surveillance protocol. Clinical data collection began in January 1, 2021, and the mean (SD) follow-up duration was 84 (47.7) months. The data analysis was performed from May 2, 2022, through September 14, 2022. The patients with BD-IPMN were followed up based on International Association of Pancreatology guidelines. Patients with suspicious malignant neoplasms during surveillance underwent surgical resection. The main outcome of this study was the optimal follow-up interval and duration of BD-IPMN surveillance. The association among cyst size, growth rate, and progression was examined using descriptive statistics. Of the 3656 patients with BD-IPMN in the analytic sample (1973 [54.0%] female; mean [SD] age, 63.7 [10.2] years), 172 (4.7%) were confirmed to have malignant lesions through surgery. Considering cyst growth, the time to develop worrisome features, and malignant conversion, a 1.5-, 1-, and 0.5-year surveillance interval could be optimal for cysts smaller than 20 mm, 20 to 30 mm, and 30 mm, respectively, after initial short-term (6-month) follow-up. Patients with cysts smaller than 20 mm, no worrisome features, and no growth during 5-year surveillance did not show malignant conversion after 5 years of follow-up and had time to progression of greater than 10 years. These findings suggest that BD-IPMN surveillance may depend on the size of the cyst and morphologic changes at the initial 6-month follow-up. For patients with small cysts (ie, <20 mm) with no morphologic changes during the initial 5-year surveillance period, surveillance may be discontinued for those unfit for surgery or who have a limited life expectancy of 10 years or less.

Abstract A011: Proteomic expression using exosomes in intraductal papillary mucinous neoplasms (IPMN) patients to inform risk stratification

Abstract Introduction Intraductal papillary mucinous neoplasm (IPMN), the most common type of pancreatic mucinous cysts, harbor risks of malignant progression of approximately 50% and 5% when found in the main duct (MD) and branch duct (BD), respectively. Surgical resection is standard of care in patients with high-risk stigmata and in some “indeterminate” cases, while surveillance modalities, which may include invasive imaging, are recommended for cases of cysts with “worrisome features”. Given the poor prognosis of late-stage pancreatic cancer, it is critical to accurately risk-stratify patients with IPMNs. We conducted a pilot study to evaluate the association of IPMN features with protein markers using extracellular vesicles (EVs), including exosomes, isolated from the blood of patients with resected IPMNs. Experimental procedure We evaluated 19 patients with IPMNs who underwent surgical resection (Whipple or distal pancreatectomy). Blood was collected before surgery and the EVs were isolated from plasma using an alternating current electrokinetics (ACE) platform. The concentration of 52 EV proteins was measured using a multiplex immunoassay. Surgical explant pathology reports were available and reviewed on all 19 patients. Data are presented as average concentration and 95% CI, and p-values represent the two-tailed t-test. Results Average age was 69 years (range: 47-83) and, of the 19 patients, 12 (63%) were male. Seventeen patients never smoked or were former smokers (quit &amp;gt; 20 years) before sample collection. A total of 14 patients had acute or chronic pancreatitis (7 historical; 7 found in surgical explant) while 4 patients had previously undiagnosed pancreatic intraepithelial neoplasia (PanIN) at the time of surgery. In our EV analysis, we found multiple EV protein biomarkers to be elevated in patients with various IPMN characteristics. Marker A was significantly elevated in patients with high-grade dysplasia (n=10) compared to low-grade dysplasia (n=9) (10.8 [8.4-13.2] vs. 7.5 [5.8 - 9.2] pg/mL, respectively, p = 0.0241), as defined by surgical explant pathology. When examining 13 patients with main-duct or mixed-type IPMNs, markers B, C, and D were elevated compared to the 6 patients with branch-duct or unspecified IPMNs (marker B: 1.9 [1.4-2.3] vs. 1.1 [0.9-1.4] ng/mL, p=0.0099; marker C: 524.3 [400.2-648.4] vs. 318.8 [209.9-427.7] pg/mL, p=0.0102; marker D: 65.8 [43.8-87.7] vs. 39.9 [31.7-48.1] pg/mL, p=0.0281). Conclusions In this pilot study that evaluated 19 patients with IPMNs, we identified multiple EV proteins that are differentially expressed in subgroups of patients. Our findings suggest that these differentially expressed proteomic markers can lead to the development of an algorithm for IPMN risk-stratification and possibly help discern histopathologic grade. Future studies will expand on these preliminary results with the aim of identifying a panel of biomarkers that can risk-stratify IPMNs to guide medical decision-making. Citation Format: Harmeet Dhani, Roberta V. Alexander, Juan Pablo Hinestrosa, Jesus Izaguirre-Carbonell, Dove Keith, Paul R. Billings, Gregory Cote', Rosalie Sears. Proteomic expression using exosomes in intraductal papillary mucinous neoplasms (IPMN) patients to inform risk stratification [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A011.

In the presence of a stable branch duct IPMN for five years, do we have the right to stop monitoring?

In the presence of a stable branch duct IPMN for five years, do we have the right to stop monitoring?

Branch-duct intraductal papillary mucinous neoplasm (BD-IPMN): a retrospective study on neoplastic risk after 5 years surveillance

Objectives: Long term surveillance of branch-duct intraductal papillary mucinous neoplasms (BD-IPMN) remains controversial, particularly regarding cysts follow up &gt; 5 years. The primary endpoint of this study was to assess the risk of malignant transformation of presumed BD-IPMN during follow-up and identify clinical and morphological predictors of malignancy. Methods: We performed a retrospective analysis of data from all patients with a presumed BD-IPMN diagnosis at the CIUSSS de l’Estrie CHUS, from 2004-2018. Results: The final database included 380 patients with presumed BD-IPMN with a median follow up of 43,9 months (IQR 28,6-73,3 months). Mean age at diagnosis was 65,5 years [27-90], 159 patients (42,8%) were male and 17 patients (4,5%) underwent resection of their lesion during their surveillance period. In our cohort, 132 patients (34,7%) had a follow-up &gt; 5 years. Overall risk of malignancy was 2.1% [0.9%-4.1%]. During follow-up, neoplastic transformation was observed in 2/132 patients (1,5%) surveilled &gt; 5 years. Malignancy was significantly associated with cyst growth &gt; 2,5 mm/year (57,1% vs 5,8% p &lt; 0,001) dilated MPD (71,4% vs 4,9% p&lt;0,001), solid component (71,4% vs 1,3% p&lt;0,001), positive cytology (37,5% vs 0,5% p&lt;0,001), development of high-risk stigmatas (87,5% vs 1,9% p &lt;0,001) or worrisome features (87,5% vs 23,9% p&lt;0,001) during follow up and symptoms of jaundice (25% vs 0,5% p=0,002) and abdominal pain (50% vs 9,4% p=0,005). Conclusion: While overall malignancy risk remains low in presumed BD-IPMN, continuous surveillance should be pursued after 5 years in surgically fit individuals, particularly in patients who develop our identified risk factors.

Endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions: a comprehensive review.

Advancements in diagnostic radiology have amplified the incorporation of these techniques into routine clinical practice. Concurrently, the frequency of incidentally identifying pancreatic cystic lesions (PCLs) has surged. PCLs encompass diverse categories contingent upon their origin. Among them, branch duct-intraductal papillary mucinous neoplasms (BD-IPMN) and mucinous cystic neoplasms (MCN) are categorized as mucinous cystic lesions that have malignant potential. Even solid neoplasms occasionally show cystic degeneration. Therefore, precise differential PCL diagnosis is crucial to optimize clinical management strategies and detect malignant transformations. Endoscopic ultrasound (EUS) affords comprehensive visualization of the pancreas with high-resolution ultrasound, complemented by fine-needle aspiration (FNA) under real-time EUS guidance, which is a minimally invasive procedure for obtaining pathological samples. This synergy has established EUS and EUS-FNA as vital procedures in the management of PCLs, enabling differentiation of PCLs. Cyst fluid analysis has played a pivotal role in deciding the optimal management strategy. The efficacy of cytological analysis is limited by scant cytologic material. The "string sign" test evaluates fluid viscosity, and its simplicity warrants initial consideration. Amylase and tumor markers, such as CEA, have been studied, but they yield varied sensitivity and specificity. Glucose and genetic mutations (KRAS, GNAS) exhibit promise, while comprehensive genomic profiling underscores genetic insights. Through-the-needle biopsy and needle-based confocal laser endomicroscopy also show high diagnostic yield. EUS-FNA, however, entails risks like infection and needle tract seeding, emphasizing the need for proper utilization. Pancreatic cyst fluid analysis augments diagnostic accuracy and informs clinical decisions, making it a valuable adjunct to imaging.

Abdominal ultrasound in the characterization of branch-duct intraductal papillary mucinous neoplasms: A new tool for surveillance of low-risk patients?

BackgroundMagnetic resonance imaging (MRI) is regarded as gold-standard for intraductal papillary mucinous neoplasms (IPMNs) follow-up. Given the low risk of transformation and the increasing population under surveillance, there is growing interest in identifying optimal follow-up strategies. AimTo evaluate reliability of abdominal ultrasound (US) for characterization of low-risk IPMN, compared to MRI. MethodsProspective monocentric study among 79 consecutive patients with a suspected BD-IPMN on US. Each patient underwent confirmatory MRI. We evaluated Cohen's kappa statistic and concordance rate (CR) between MRI and US. ResultsOf 79 suspected IPMNs on US, MRI confirmed 71 BD-IPMNs. There was high agreement for cyst location and number (CR and kappa of 77.5 % and 81.7 % and 0.66±0.08 and 0.62±0.11 respectively). We found high agreement for cyst size (CR=96.5 %, kappa=0.93±0.05) and main pancreatic duct (MPD) dilatation (CR=100 %, kappa=1). There was a good agreement for thickened septa (CR=80.3 %, kappa=0.38±0.12). US seems inferior to MRI for the identification of mural nodules < 5 mm (CR=97.2 %, kappa=0). ConclusionsIn a cohort of low-risk BD-IPMN, US presented high agreement rate with MRI regarding location, number, and size. There was a good agreement for MPD dilatation and thickened septa, while US underperform for detection of mural nodules < 5 mm.