The Usefulness of the Serum Fibrinogen-to-Albumin Ratio as a Preoperative Predictor of High-Grade Dysplasia or Invasive Carcinoma in Intraductal Papillary Mucinous Neoplasm of the Pancreas

Pancreatic cyst guidelines: Which one to live by?

The 2024 Kyoto guidelines for the management of intraductal mucinous neoplasms (IPMNs) build on previous guidelines that consider worrisome features (WF) and high-risk stigmata (HRS) to recommend surveillance or resection. These new guidelines have not yet been validated. Patients undergoing pancreatectomy for an IPMN at an academic medical center between 2012 and 2023 were included. IPMNs were categorized as low-grade dysplasia (LGD), high-grade dysplasia (HGD), or invasive carcinoma (IC). Preoperative imaging was used to determine HRS and WF in accordance with the 2024 Kyoto guidelines. We compared IPMNs with LGD to those with HGD or IC using univariate analyses and evaluated logistic regression models with c-statistics. Of 211 patients, 84 (40%) had LGD, 49 (23%) had HGD, and 78 (37%) had IC. Among HRS, obstructive jaundice (p = 0.004), pancreatic duct ≥ 10mm (p < 0.001), and suspicious or positive cytology (p < 0.001) were significantly associated with HGD/IC. An increasing number of HRS were associated with higher rates of HGD/IC. Among WFs, an abrupt change in the caliber of pancreatic duct with distal pancreatic atrophy (p = 0.001) and cystic growth ≥ 2.5mm/year (p = 0.033) were significantly associated with higher rates of HGD/IC. Increasing numbers of WFs were also associated with higher rates of HGD/IC. The 2024 Kyoto model showed improved discrimination (area under the curve [AUC] = 0.849) compared with the 2017 Fukuoka model (AUC=0.780, p = 0.06). The risk of HGD/IC in IPMNs increased in a stepwise fashion as the number of WFs increased. The 2024 guidelines represent an advancement over the 2017 guidelines, notably with the inclusion of suspicious cytology as an HRS.

Tumor location predicts presence of high grade dysplasia and invasive carcinoma in intraductal papillary mucinous neoplasms of the pancreas

There are many reports about limited surgery for intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. However, there is no consensus on limited surgery for IPMNs. The primary objective of this study was to define the clinical indications for limited surgery for IPMNs. The data of 98 patients who underwent curative resections for IPMN were retrospectively analyzed. IPMNs were classified into four different pathological grades: low-grade dysplasia (LGD), intermediate-grade dysplasia (IGD), high-grade dysplasia (HGD), and invasive carcinoma (Inv-IPMN). Inv-IPMNs were divided into T1a, T1b, and T1c or over T1c (≥T1c). Based on preoperative radiological findings, IPMNs were stratified into the three groups using the 2012 International Consensus Guidelines: worrisome features, high-risk stigmata (HRS), and others. There were no positive lymph node cases and no recurrent cases of LGDs, IGDs, and HGDs. On the other hand, positive lymph node cases in T1a, T1b, and ≥T1c were seen in 37.5, 20, and 22.2% of cases, respectively. The recurrence rates of T1a, T1b, and ≥T1c were 50, 40, and 55.6%, respectively. Of the HRS cases, 30 (73.2%) were malignant and 25 (61%) were Inv-IPMN. HRS showed sensitivity of 92.6%, specificity of 77.5%, and accuracy of 81.6% to identify Inv-IPMN by preoperative imaging. Limited surgery such as parenchyma-sparing pancreatectomy should be avoided for all cases of Inv-IPMNs, because every Inv-IPMN including T1a has the potential for lymph node metastasis and recurrence. HRS had high preoperative diagnostic ability for predicting Inv-IPMN. For cases that meet HRS criteria, pancreatectomy with lymphadenectomy is needed, and limited surgery should be withheld.

Intraductal papillary mucinous neoplasms (IPMNs) progress from low-grade dysplasia to high-grade dysplasia (HGD) or invasive carcinoma (IC). High diagnostic accuracy is critical for surgical decision-making. We searched Medline, Embase, and Cochrane Library from January 1, 2015, to January 27, 2025. Eligible studies reported on resected IPMNs, assessing diagnostic features for HGD/IC. Two reviewers screened articles, extracted data, and assessed bias using the Newcastle-Ottawa scale. Descriptive statistics summarized outcomes. The performance of worrisome features (WFs) and high-risk stigmata (HRS) based on International Association of Pancreatology guidelines were evaluated. In the 53 studies, 12 953 patients were included. HRS including obstructive jaundice and enhancing mural nodules ≥5mm showed robust specificity forHGD/IC, while main pancreatic duct size ≥10mm showed variable diagnostic accuracy. WFs such as cyst size ≥3 cm performed poorly, while cyst growth rate >3.5 mm/year demonstrated higher sensitivity (88%) and specificity (91%). Although rare, abrupt caliber change with distal atrophy was a robust predictor of malignancy (median odds ratio: 3.01). Acute pancreatitis and lymphadenopathy displayed variable value. Incremental improvement in diagnostic accuracy was observed with additional HRS or WFs. Current diagnostic markers are valuable but provide limited guidance for surgical decision-making in IPMNs, highlighting the need for further refinement of diagnostic tools.

Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic neoplasm of the pancreas, encompassing a spectrum from benign to malignant lesions. Recently, the international guidelines for IPMN management were revised as the Kyoto guidelines, emphasizing the critical role of imaging in diagnosis, risk assessment, and surveillance. This article provides a comprehensive review of IPMN based on the updated guidelines, focusing on imaging-related aspects while elucidating the underlying pathological background. We present the three interrelated classification systems for IPMN: anatomical location (branch-duct, main-duct, or mixed type), histological subtype (gastric, intestinal, or pancreatobiliary), and degree of dysplasia (low-grade, high-grade, or associated invasive carcinoma). Understanding these classifications and their correlations is fundamental for imaging-based risk assessment and clinical decision-making. We discuss the two distinct carcinogenesis patterns in IPMN-sequential pattern resulting in high-grade dysplasia or invasive carcinoma associated with IPMN, and concomitant pattern leading to pancreatic ductal adenocarcinoma in IPMN-harboring pancreas. The article reviews high-risk stigmata and worrisome features that guide risk stratification, providing illustrative examples and highlighting potential diagnostic pitfalls. We also examine differential diagnoses including serous cystic neoplasm, mucinous cystic neoplasm, pancreatic intraepithelial neoplasia, pseudocysts, and large duct type pancreatic ductal adenocarcinoma. Finally, we review the current management algorithm and surveillance methods recommended by the Kyoto guidelines. This review aims to enhance radiologists' and clinicians' understanding of IPMN by integrating pathological knowledge with imaging findings, emphasizing that while high-risk stigmata are strong predictors of high-grade dysplasia or invasive carcinoma, surgical decisions should be individualized considering multiple factors including patient preferences, comorbidities, and life expectancy.

BackgroundWith the continuous advancement of cross-sectional imaging technology, the number of incidentally discovered intraductal papillary mucinous neoplasms (IPMN) of the pancreas has been increasing annually. More IPMN patients are suitable for regular follow-up than for surgical resection. This study aimed to explore the appropriate follow-up intervals for IPMN patients with multiple worrisome features (WFs) and high-risk stigmata (HRS).Material/MethodsIn this single-center retrospective study, IPMN patients with a follow-up period of more than 6 months up to June 2023 were included, and the intervals between the initial diagnosis and the onset of a newly developed WF/HRS were recorded.ResultsThe median time intervals between the appearance of newly developed WFs/HRS in patients without WFs/HRS and those with ≤2 WFs at initial diagnosis were significantly longer than that in patients with >2 WFs and those with HRS (30.0 months vs 21.0 months vs 7.0 months vs 10.0 months; p<0.001). Among postoperative patients, those with low-grade dysplasia were younger at initial diagnosis than those with high-grade dysplasia and invasive carcinoma (59.8 years old vs 69.4 years old; p=0.027).ConclusionsPatients with cysts ≥30 mm can undergo medical examinations biannually. For IPMN patients with cysts <30 mm and containing >2 WFs or HRS, a follow-up interval of 0.5–1.0 years may be appropriate, and regular follow-up of 1.5–2 years is reliable for patients with cysts <30 mm and ≤2 WFs. Moreover, advanced age may be an important risk factor for malignant progression of IPMN.

The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information. To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations. The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months). Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination. A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04 [95% CI, 2.94-87.40]; P = .001). These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.

Purpose: The 2012 International Consensus Guidelines for the Management of IPMN provide guidance on management of branch duct IPMN (BD-IPMN). The aim of this study was to test the accuracy of the guidelines in patients who underwent surgery for BD-IPMNs. Methods: A retrospective study of patients from a single, high-volume referral center evaluated patients with BD-IPMN who underwent surgical resection. Patients were classified into one of three categories based on the 2012 guidelines: high risk stigmata (HRS), worrisome features (WF), and low risk with no worrisome features (LR). Correlation with surgical pathology was undertaken. Surgical pathology was classified into low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive carcinoma (IC). Results: Over 15 years, 180 patients were found to have BD-IPMNs on surgical pathology. The mean age was 66.9±12.1 years (31-91 years) with 90 (50%) females. On pre-operative evaluation, 34 (18.9%) had HRS, 54 (30%) had WF, and 92 (51.1%) had LR based on the 2012 consensus guidelines. One hundred and fifty three (85%) had LGD, 16 (8.9%) had HGD, and 11 (6.1%) had IC on surgical pathology. Patients with HRS (24 LGD, 4 HGD, 6 IC) had significantly more IC (p=0.008) on surgical pathology than patients with WF or LR. Patients with WF (45 LGD, 7 HGD, 2 IC) were not significantly different from those with LR (p>0.1) with respect to degree of dysplasia or presence of cancer on surgical pathology. Among patients with LR; 84 had LGD, 5 had HDG, and 3 had IC. None of the eight patients (9.5%) with HGD/IC within the LR group had cyst size more than 3 cm; one patient had a HGD cyst with size of 2.7 cm and the rest were ≤2 cm. Conclusion: Patients with HRS according to the new guidelines were more likely to harbor malignancy, and thus surgery is recommended whenever feasible. WF did not appear to be associated with malignancy. Up to 9.5% of patients with LR were found to have HGD or IC, emphasizing the importance of continued surveillance in this low-risk group of patients.

This study was performed to evaluate the surgical indication for intraductal papillary mucinous neoplasm (IPMN) advocated by the 2017 revised International Association of Pancreatology consensus guidelines (IAPCG2017). The medical records of 63 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. Thirteen patients had main-duct IPMN, 25 had mixed IPMN, and 25 had branch-duct IPMN with frequencies of high-grade dysplasia or invasive carcinoma of 62, 24, and 28%, respectively. The sensitivity and specificity of high-risk stigmata for high-grade dysplasia or invasive carcinoma advocated by the IAPCG2017 were 90 and 67%, respectively. Of 17 patients with invasive carcinoma, all patients had high-risk stigmata, and 16 had an enhanced mural nodule (MN) of ≥ 5mm. The sensitivity and specificity of a ≥ 5-mm enhanced MN for predicting invasive carcinoma were 94% and 87%, respectively. Introducing a size threshold for enhanced MNs into the assessment of high-risk stigmata increases the specificity without jeopardizing the sensitivity. The surgical indication for any type of IPMN may be determined using only a ≥ 5-mm enhanced MN. When the type of IPMN is classified strictly, about half of IPMNs are mixed type, and most are benign. The surgical indication for mixed IPMN should be reconsidered.

Assessment of Malignancy Potential in Intraductal Papillary Mucinous Neoplasms of the Pancreas on MDCT

Does Pancreatic Cyst Stability Justify Stopping Intraductal Papillary Mucinous Neoplasm Surveillance?

Guidelines on Pancreatic Cystic Neoplasms: Major Inconsistencies With Available Evidence and Clinical Practice— Results From an International Survey

To determine whether uncinate duct dilatation (UDD) increases the risk of high-grade dysplasia or invasive carcinoma (HGD/IC) in Fukuoka-positive intraductal papillary mucinous neoplasms (IPMNs). Though classified as a branch duct, the uncinate duct is the primary duct of the pancreatic ventral anlage. We hypothesized that UDD, like main duct dilatation, confers additional risk for HGD/IC. A total of 467 patients met inclusion criteria in a retrospective cohort study of surgically resected IPMNs at the Massachusetts General Hospital. We used multivariable logistic regression to analyze the association between UDD (defined as ≥4mm) and HGD/IC, controlling for Fukuoka risk criteria. In a secondary analysis, the modeling was repeated in the 194 patients with dorsal branch duct IPMNs (BD-IPMNs) in the pancreatic neck, body, or tail. Mean age at surgery was 70, and 229 (49%) patients were female. In total, 267 (57%) patients had only worrisome features and 200 (43%) had at least 1 high-risk feature. UDD was present in 164 (35%) patients, of whom 118 (73%) had HGD/IC. On multivariable analysis, UDD increased the odds of HGD/IC by 2.8-fold, even while controlling for Fukuoka risk factors (95% CI: 1.8-4.4, P <0.001). Prevalence of HGD/IC in all patients with UDD was 73%, compared with 74% in patients with high-risk stigmata and 73% in patients with main duct IPMNs. In the secondary analysis, UDD increased the odds of HGD/IC by 3.2-fold in patients with dorsal BD-IPMNs (95% CI: 1.3-7.7, P =0.010). UDD confers additional risk for HGD/IC unaccounted for by current Fukuoka criteria. Further research can extend this study to Fukuoka-negative patients, including unresected patients.

Serum carbohydrate antigen 19-9 greater than 100 and risk of invasive carcinoma in pancreatic intraductal papillary mucinous neoplasms: Worrisome feature or high-risk stigmata?