Mixed-type Intraductal Papillary Mucinous Neoplasms Research Articles

Robotic Ultrasound-Guided Central Pancreatectomy with Main Pancreatic Duct Endoscopy Evaluation for High-Risk, Mixed-Type Intraductal Papillary Mucinous Neoplasm.

Central pancreatectomy (CP) is a parenchymal-sparing technique indicated for the resection of selected lesions of the neck or proximal body of the pancreas.1,2 The risk of postoperative complications is theoretically doubled because the surgeon has to manage two cut surfaces of the pancreas. The video shows a fully robotic CP to treat a 62-year-old male patient with a mixed-type intraductal papillary mucinous neoplasm (IPMN) of the pancreatic neck, using ultrasound (US) and Wirsung endoscopic evaluation to guide the pancreatic resection and ensure optimal resection margins. A US-guided robotic CP was carried out, and an intraoperative endoscopic evaluation of the MPD was performed to determine the distal transection level. A transmesocolic, end-to-side, robot-sewn Wirsung-jejunostomy with internal MPD stenting was then created. The procedure was completed with a side-to-side jejunojejunostomy. The operative time was 290min, with negligible blood loss. During the postoperative course, the patient experienced bleeding from a branch of the gastroduodenal artery with subsequent fluid collection, which was successfully treated with angioembolization and percutaneous drainage. He was discharged home on postoperative day 22. Final pathology revealed a non-invasive IPMN with low-grade dysplasia and free surgical margins. At 12 months of follow-up, the patient was doing well, with no evidence of local recurrence and endocrine or exocrine pancreatic insufficiency. The combination of robotic surgery with intraoperative US and Wirsungoscopy may offer distinct technical advantages for challenging pancreatectomies that follow the principles of parenchymal-sparing surgery.

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...

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 > 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.

Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs)

BackgroundMain-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs. MethodsWe performed a retrospective study of 369 patients who underwent resections for MD- or MT-IPMN at two tertiary centers (2000–2019). Multivariable logistic regression analyses were performed for postoperative adverse events to compare the risks between intervention (ERCP, EUS-FNA with branch duct (BD) aspirated, EUS-FNA with MD aspirated from the duct directly or cyst/mass arising from MD) versus no-intervention group. Results33.1 % of patients had a preoperative ERCP and 69.4 % had EUS-FNA. Postoperative adverse events included: 30-day readmission (12.7 %), delayed gastric emptying (13.8 %), pancreatic fistula (10.3 %), abdominal abscess (5.7 %), cardiopulmonary adverse events (11.4 %), and mortality (1.4 %). The model was adjusted for potential confounders. There were no significant differences between the ERCP and no-ERCP groups for specific adverse events. Compared to no-EUS-FNA groups, groups of EUS-FNA with BD aspiration and EUS-FNA with MD aspiration from the main pancreatic duct directly or cyst/mass arising from MD did not show a significant increase in specific adverse events. ConclusionsPostoperative adverse events were not significantly increased among patients who had ERCP or EUS-FNA before surgical resection for MD- or MT-IPMNs. Endoscopic procedures directly sampling the MD can be safely pursued for diagnostic purposes in selected cases.

Enhancing Mural Nodules in the Main Pancreatic Duct of Main and Mixed Types of Intraductal Papillary Mucinous Neoplasms: Does Size Matter in Malignancy Risk?

Most guidelines recommend surgical resection of all main duct (MD) and mixed-type (MT) intraductal papillary mucinous neoplasms (IPMNs) in suitable patients. However, there is little evidence regarding the malignancy risk of enhancing mural nodules (EMNs) that are present only in the main pancreatic duct (MPD) in patients with MD- and MT-IPMNs. Therefore, this study aimed to identify the clinical and morphological features associated with malignancy in MD- and MT-IPMNs with EMNs only in the MPD. We retrospectively enrolled 50 patients with MD- and MT-IPMNs with EMNs only in the MPD on contrast-enhanced magnetic resonance imaging. We evaluated the clinical characteristics and preoperative radiologic imaging results of MPD morphology and EMN size and analyzed the risk factors associated with malignancy. Histological findings of EMNs were low-grade dysplasia (38%), malignant lesions (62%), high-grade dysplasia (34%), and invasive carcinoma (28%). On the receiver operating characteristic curve, the cutoff value of EMN size on magnetic resonance imaging for best predicting malignancy was 5 mm (sensitivity, 93.5%; specificity, 52.6%; area under the curve, 0.753). Multivariate analysis showed that only EMN >5 mm (odds ratio, 27.69; confidence interval, 2.75 to 278.73; p=0.050) was an independent risk factor for malignancy. EMNs of >5 mm are associated with malignancy in patients with MD- and MT-IPMNs with EMNs that are present only in the MPD, in accordance with the international consensus guidelines.

Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study

BackgroundThe degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. MethodsThis is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. ResultsOut of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0–252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. ConclusionOverall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.

MR Prediction of Malignant Switch With the Cyst Fluid's T2 Value in Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Preliminary Study.

We investigated whether the malignant switch of intraductal papillary mucinous neoplasm (IPMN) of the pancreas can be predicted by using the T1ϱ, T2, and apparent diffusion coefficient (ADC) values of cyst fluid. We retrospectively analyzed the magnetic resonance (MR) images of 60 patients (26 males, 34 females, mean age 61 years) with branch-duct type and mixed-type IPMNs. The IPMNs were diagnosed clinically in 39 patients and histologically in 21 patients. The malignant potential was classified by MR imaging based on the international consensus guidelines for the management of IPMN established in 2017. Morphologically, 42 patients had "worrisome features" and three had "high-risk stigmata." Histologically, 14 lesions were diagnosed as low-grade dysplasia and seven as intermediate-grade dysplasia. The T1ϱ, T2, and ADC values of cyst fluid in each patient's largest cyst were measured on the same slice, avoiding solid components. Spearman's rank correlation test was used to determine the correlation between the morphological malignancy and the T1ϱ, T2, and ADC values. These values were also compared between the low-grade and intermediate-grade groups by Mann-Whitney U-test. There was a significant rank-correlation between the morphological classification and T2 value (p=0.04). The T2 value of the intermediate-grade group was significantly higher than that of the low-grade group (p=0.03). No significant correlations were morphologically or histologically obtained regarding T1ϱ and ADC. The T2 value of cyst fluid together with other MR-signs may be useful for predicting the malignant switch in IPMN of the pancreas.

Prediction of malignancy in main duct or mixed-type intraductal papillary mucinous neoplasms of the pancreas.

Surgical indications of main duct-involved intraductal papillary mucinous neoplasm (IPMN), especially for main pancreatic duct (MPD) of 5-9 mm, remain controversial. We aimed to predict malignancy risk of main duct-involved IPMN. Total 258 patients with main duct-involved IPMN between 2000 and 2017 in our institute were retrospectively analyzed. Main duct IPMN was classified into segmental and diffuse-type by dilated MPD pattern. Clinicopathologic features and predictive factors for malignancy were analyzed. Among 258 patients, 47 and 211 had pure main duct (segmental: 27, diffuse type: 20) and mixed type, respectively. Malignant IPMN presented higher in main duct type (66.0%) compared to mixed type (46.9%). The diffuse type (72.2%) had more invasive carcinoma than the segmental type (40.7%). Invasive IPMN risk increased proportionally to the MPD diameter (5 ≤ MPD <10 mm vs 10 ≤ MPD < 15 mm vs MPD ≥ 15 mm; 23.4% vs 40.0% vs 48.6%). Symptoms, elevated serum carbohydrate antigen, MPD ≥10 mm, mural nodule, thickened wall, and distal atrophy were independent predictive factors for malignancy. Patients with MPD of 5-9 mm with at least one predictive factor had 35.0% of malignancy risk. The invasive IPMN risk was different according to the dilated main duct pattern. Patients with main duct type, diffuse type, MPD ≥10 mm, and MPD 5-9 mm with at least one predictive factor should be candidates for immediate surgery.

Branch-duct intraductal papillary mucinous neoplasm (IPMN): Are cyst volumetry and other novel imaging features able to improve malignancy prediction compared to well-established resection criteria?

ObjectivesCurrent guidelines base the management of intraductal papillary mucinous neoplasms (IPMN) on several well-established resection criteria (RC), including cyst size. However, malignancy may occur in small cysts. Since branch-duct (BD) IPMN are not perfect spheres, volumetric and morphologic analysis might better correlate with mucin production and grade of dysplasia. Nonetheless, their role in malignancy (high-grade dysplasia/invasive cancer) prediction has been poorly investigated. Previous studies evaluating RC also included patients with solid-mass-forming pancreatic cancer (PC), which may affect the RC yield. This study aimed to assess the role of volume, morphology, and other well-established RC in malignancy prediction in patients with BD- and mixed-type IPMN after excluding solid masses.MethodsRetrospective ethical review-board-approved study of 106 patients (2008–2019) with histopathological diagnosis of BD- and mixed-type IPMN (without solid masses) and preoperative MRI available. Standard imaging and clinical features were collected, and the novel imaging features cyst-volume and elongation value [EV = 1 − (width/length)] calculated on T2-weighted images. Logistic regression analysis was performed. Statistical significance set at two-tails, p < 0.05.ResultsNeither volume (odds ratio (OR) = 1.01, 95% CI: 0.99–1.02, p = 0.12) nor EV (OR = 0.38, 95% CI: 0.02–5.93, p = 0.49) was associated with malignancy. Contrast-enhancing mural nodules (MN), main pancreatic duct (MPD) ≥ 5 mm, and elevated carbohydrate antigen (CA) 19-9 serum levels (> 37 μmol/L) were associated with malignancy (MN OR: 4.32, 95% CI: 1.18–15.76, p = 0.02; MPD ≥ 5 mm OR: 4.2, 95% CI: 1.34–13.1, p = 0.01; CA19-9 OR: 6.72; 95% CI: 1.89 – 23.89, p = 0.003).ConclusionsVolume and elongation value cannot predict malignancy in BD- and/or mixed-type IPMN. Mural nodules, MPD ≥ 5 mm and elevated CA19-9 serum levels are associated with higher malignancy risk even after the exclusion of solid masses.Key Points• Novel and well-established resection criteria for IPMN have been evaluated after excluding solid masses.• BD-IPMN volume and elongation value cannot predict malignancy.• Main pancreatic duct ≥ 5 mm, mural nodules, and elevated carbohydrate antigen 19-9 levels are associated with malignancy.

Surgery for Intraductal Papillary Mucinous Neoplasms of the Pancreas: Preoperative Factors Tipping the Scale of Decision-Making

BackgroundDecision-making in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas depends on scaling the risk of malignancy with the surgical burden of a pancreatectomy. This study aimed to develop a preoperative, disease-specific tool to predict surgical morbidity for IPMNs.MethodsBased on preoperative variables of resected IPMNs at two high-volume institutions, classification tree analysis was applied to derive a predictive model identifying the risk factors for major morbidity (Clavien–Dindo ≥3) and postoperative pancreatic insufficiency.ResultsAmong 524 patients, 289 (55.2%) underwent pancreaticoduodenectomy (PD), 144 (27.5%) underwent distal pancreatectomy (DP), and 91 (17.4%) underwent total pancreatectomy (TP) for main-duct (18.7%), branch-duct (12.6%), or mixed-type (68.7%) IPMN. For 98 (18.7%) of the patients, major morbidity developed. The classification tree distinguished different probabilities of major complications based on the type of surgery (area under the surve [AUC] 0.70; 95% confidence interval [CI], 0.63–0.77). Among the DP patients, the presence of preoperative diabetes identified two risk classes with respective probabilities of 5% and 25% for the development of major morbidity, whereas among the PD/TP patients, three different classes with respective probabilities of 15%, 20%, and 36% were identified according to age and body mass index (BMI). Overall, history of diabetes, age, and cyst size segregated three different risk classes for new-onset/worsening diabetes.ConclusionsIn presumed IPMNs, the disease-specific risk of major morbidity and pancreatic insufficiency can be determined in the preoperative setting and used to personalize the possible surgical indication. Age and overweight status in case of PD/TP and diabetes in case of DP tip the scale toward less aggressive clinical management in the absence of features suggestive for malignancy.

Malignant potential and specific characteristics of pure main duct type intraductal papillary mucinous neoplasm

BackgroundAs the malignant potential of main duct (MD-) type intraductal papillary mucinous neoplasm (IPMN) has been discussed together with Mixed-type in most previous studies, the malignant potential of pure MD-type IPMN remains unclear. This study evaluated the specific characteristics and predictors of high-grade dysplasia (HGD) and invasive intraductal papillary mucinous carcinoma (IPMC) for pure MD-type IPMN. MethodsFrom 1,100 patients with IPMN, this study includes 387 patients that underwent surgery. We evaluated the specific characteristics of pure MD-type IPMN by comparing clinicopathological factors between MD-type (n = 79) and branch duct (BD-) type (n = 146) or Mixed-type IPMN (n = 162), and predictors of HGD/invasive IPMC in pure MD-type IPMN. ResultsThe rate of HGD/invasive IPMC was significantly higher in MD-type than in BD-type (70.9 vs. 48.6%, P = 0.001), although there was no difference between MD-type and Mixed-type IPMNs (P = 0.343). Recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with MD-type were better than those of patients with Mixed-type (P = 0.008 and P = 0.009, respectively). There were no significant differences in RFS, overall survival, and DSS between patients with MD-type and patients with BD-type IPMNs. Multivariate analysis showed two independent predictors of HGD/invasive IPMC in MD-type IPMN; mural nodule height ≥5 mm (P = 0.025, odds ratio [OR]; 16.949) and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained by preoperative endoscopic retrograde pancreatography ≥50 ng/ml (P = 0.039, OR; 9.091). ConclusionsMeasurement of mural nodule height and CEA in the pancreatic juice might be useful in determining surgical indication for pure MD-type IPMN, although further studies for confirmation are essential.

Indocyanine green fluorescence to ensure perfusion in middle segment-preserving pancreatectomy: a case report

BackgroundMiddle segment-preserving pancreatectomy (MSPP) is an alternative to total pancreatectomy that allows for the preservation of the endocrine and exocrine functions of the pancreas. However, maintaining perfusion to the pancreatic remnant is of critical importance. We describe the first case to our knowledge in which indocyanine green (ICG) fluorescence was used to confirm perfusion to the pancreatic remnant during MSPP.Case presentationA 79-year-old man with diabetes mellitus was referred to our hospital for treatment of a pancreatic tumor. Computed tomography revealed a hypovascular mass in the uncus of the pancreas and dilatation of the main pancreatic duct, measuring 13 mm in the tail of the pancreas. He was diagnosed with cancer of the pancreatic uncus via endoscopic ultrasound and fine-needle aspiration revealed a mixed-type intraductal papillary mucinous neoplasm (IPMN), along with high-risk stigmata in the tail of the pancreas. We performed MSPP and the length of the pancreatic remnant was 4.6 cm. The dorsal pancreatic artery was preserved and perfusion to the pancreatic remnant was confirmed by ICG fluorescence. Histopathological examination showed a pancreatic ductal adenocarcinoma in the uncus (pT1cN1M0, pStage 2B) and IPMN in the tail of the pancreas. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. The patient was transferred to a hospital 33 days after surgery. Insulin administration was necessary, but C-peptide was detectable and blood glucose was relatively well-controlled. He did not exhibit any exocrine dysfunction when pancreatic enzyme supplementation was administered.ConclusionICG fluorescence can be used to evaluate perfusion to the pancreatic remnant during MSPP.

Clinical Management of Pancreatic Premalignant Lesions

Clinical Management of Pancreatic Premalignant Lesions

Multifocal lesions in intraductal papillary mucinous neoplasms: Intraoperative pancreatic juice cytology

On radiological study, 25% to 41% of the patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have multifocal lesions. On the other hand, in pathological assessment, most of these patients had lots of micro premalignant lesions such as small IPMNs and pancreatic intraepitehrial neoplasms (PanINs) in the background pancreas, indicating that all the pancreas having IPMNs have a potential to develop multifocal lesions. There are 3 possible types of multifocal lesions in patients with IPMNs, namely multiple branch duct IPMNs (BD-IPMNs) by multicentric development, multiple main duct or mixed type IPMNs (MD- or Mix-IPMNs) by the mechanism of intraductal dissemination of the neoplastic cells [1,2], and the development of pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMNs [3,4]. Pancreatic juice cytology under endoscopic retrograde pancreatography is reported to leads early detection of concomitant PDAC during assessment of IPMNs [5], while it is often difficult to determine the location of malignant lesions when pancreatography and other imaging modalities cannot provide any significant abnormalities. Therefore, the role of intraoperative pancreatic juice cytology is to determine whether such lesions which are not detected by preoperative assessment might left in the remnant pancreas during partial pancreatectomy for IPMN. Previous report [6] demonstrated that in consecutive 48 patients who underwent intraoperative irrigation cytology in the remnant pancreas during partial pancreatectomy for IPMN, 5 patients had positive results and subsequently underwent additional resection of the pancreas. High-risk lesions including 4 PanIN-3 lesions and one invasive carcinoma were detected in all 5 additionally resected specimens. On the other hand, there might be possible patients who might have false negative result of intraoperative irrigation cytology [7] or peritoneal dissemination because of leakage of irrigation solution containing cells from high-risk lesions. In this presentation, roles and limitations of intraoperative pancreatic juice cytology will be discussed.

Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study.

Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct>10mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P=.014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P=.255). A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Intraductal papillary mucinous neoplasm of the pancreas: A 10-year experience at a single center

Background: The incidence of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the past years along with the development of diagnostic imaging tests. Objective: The aim of this study is to describe our experience on long-term management of patients with IPMNs in a reference center. Material and methods: We conducted a retrospective and descriptive analysis of patients with pancreatic neoplasms followed-up at the Department of General Surgery and Hepato-Biliary Surgery, Hospital Universitario Fundación Favaloro, between January 2010 and December 2019. The patients were classified into 2 groups: group A (diagnosis of IPMN made in the outpatient clinic), and group B (diagnosis of IPMN in the pathological examination). Results: Eighty-six patients were analyzed: 79 (90%) in group A and 7 in group B. In group A, a watchful waiting with monitoring (AM) was decided in 57 cases (66%). Of the remaining 22 patients, 18 (29%) patients underwent surgery (AS) and 4 are waiting for surgery. Survival at 5 years was 89% in group AM, 86% in group AS and 43% in group B (Breslow 0.001, log-rank test 0,001 vs. group A). Conclusion: The diagnosis and management of IPMNs is currently standardized. Surgery is indicated in MD-IPMN and mixed type IPMN. Patients with BD-IPMN type should be monitored due to the risk of malignant transformation. When surgery is indicated, long-term survival should be similar to that of the surveillance group.

Natural History and Optimal Treatment Strategy of Intraductal Papillary Mucinous Neoplasm of Pancreas

Background: With increasing detection of intraductal papillary mucinous neoplasms(IPMN), a tailored approach is needed. We explored the natural history of IPMN and suggest optimal treatment based on malignancy risk using nomogram and Markov decision model. Methods: Patients with IPMN, who underwent surveillance or surgery, were included. Change in worrisome features/high-risk stigmata and malignancy conversion rate was calculated through radiologic and pathologic reviews. Life expectancy and quality-adjusted life year (QALY) were compared using a nomogram predicting malignancy. Results: Overall, 2,006 patients with histologically confirmed or radiologically typical IPMN were enrolled. Of these, 1,773(88.4%) had branch duct(BD), 81(4.0%) had main duct and 152(7.6%) had mixed type at initial diagnosis. The cumulative risk of developing worrisome feature/ high-risk stigmata was 19.0% at 5-year and 35.0% at 10-year- follow-up. The progression of malignancy rate at 10-year follow-up was 79.9% for main and mixed type IPMN and 5.9% for BD-IPMN. Nomogram based malignancy risk prediction is well correlated with natural history based on pathologic biopsy and shows good stratification of the survival. Decision model recommends surgery to maximize overall survival and quality-adjusted life year for patients under 75-years old, especially those with over 35% malignancy risk Conclusion: Compared to the high risk of malignancy (79.9%) in main and mixed type IPMN, that (5.9%) of BD-IPMN are very indolent. The nomogram-based decision model suggests surgery rather than surveillance for patients with high malignancy rate. Optimal treatment strategy between surgery and surveillance should consider patient's health status, malignancy risk, and centre's experience.

Natural history and optimal treatment strategy of intraductal papillary mucinous neoplasm of the pancreas: Analysis using a nomogram and Markov decision model.

With the increase in detection of intraductal papillary mucinous neoplasms (IPMN), a tailored approach is needed. This study was aimed at exploring the natural history of IPMN and suggest optimal treatment based on malignancy risk using a nomogram and Markov decision model. Patients with IPMN who underwent surveillance or surgery were included. Changes in worrisome features/high-risk stigmata and malignancy conversion rate were assessed. Life expectancy and quality-adjusted life year (QALY) were compared using a nomogram predicting malignancy. Overall, 2006 patients with histologically confirmed or radiologically typical IPMN were enrolled. Of these, 1773 (88.4%), 81 (4.0%), and 152 (7.6%), respectively, had branch duct (BD)-, main duct-, and mixed-type IPMN at initial diagnosis. The cumulative risk of developing worrisome feature or high-risk stigmata was 19.0% and 35.0% at 5- and 10-year follow-up, respectively. The progression of malignancy rate at 10-year follow-up was 79.9% for main and mixed IPMNs and 5.9% for BD-IPMN. Nomogram-based malignancy risk prediction is well correlated with natural history based on pathologic biopsy and shows good stratification of survival. The decision model recommends surgery to maximize survival and QALY especially in those with >35% malignancy risk. Compared with main duct- and mixed-type IPMN, which have a high risk of malignancy (79.9%), BD-IPMN is very indolent (5.9%). The nomogram-based decision model suggests surgery rather than surveillance for patients with a high malignancy risk. The optimal treatment strategy between surgery and surveillance should consider patients' health status, malignancy risk, and centers' experience.

Prophylactic total pancreatectomy in individuals at high risk of pancreatic ductal adenocarcinoma (PROPAN): systematic review and shared decision-making programme using decision tables.

BackgroundIndividuals with a very high lifetime risk of developing pancreatic ductal adenocarcinoma; for example, hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm, may wish to discuss prophylactic total pancreatectomy but strategies to do so are lacking.ObjectiveTo develop a shared decision-making programme for prophylactic total pancreatectomy using decision tables.MethodsFocus group meetings with patients were used to identify relevant questions. Systematic reviews were performed to answer these questions.ResultsThe first tables included hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm. No studies focused on prophylactic total pancreatectomy in these groups. In 52 studies (3570 patients), major morbidity after total pancreatectomy was 25% and 30-day mortality was 6%. After minimally invasive total pancreatectomy (seven studies, 35 patients) this was, respectively, 13% and 0%. Exocrine insufficiency-related symptoms occurred in 33%. Quality of life after total pancreatectomy was slightly lower compared with the general population.ConclusionThe decision tables can be helpful for discussing prophylactic total pancreatectomy with individuals at high risk of pancreatic ductal adenocarcinoma.

A mixed-type intraductal papillary mucinous neoplasm of the pancreas with a histologic combination of gastric and pancreatobiliary subtypes in a 70-year-old woman: a case report

BackgroundIntraductal papillary mucinous neoplasms are rare papillary pancreatic neoplasms arising from major pancreatic ducts, characterized by duct dilation and mucin secretion. They comprise approximately 1% of all exocrine neoplasms and are classified according to their anatomical sites into main duct-type, branch duct-type, and mixed-type intraductal papillary mucinous neoplasms. Histological examination plays a crucial role in distinguishing and classifying intraductal papillary mucinous neoplasms into gastric, intestinal, pancreatobiliary, and oncocytic subtypes.Case presentationWe present the case of a 70-year-old Syrian woman who was admitted to our hospital due to an intermittent epigastric pain accompanied by diarrhea and weight loss with a recent diagnosis of diabetes mellitus. Following clinical, laboratory, and radiological examination, distal pancreatectomy involving the body and the tail of the pancreas was performed. Interestingly, histological examination of the resected specimens revealed the diagnosis of a mixed-type intraductal papillary mucinous neoplasm with a unique combination of gastric and pancreatobiliary subtypes.ConclusionTo the best of our knowledge, the combination of multiple histological subtypes of intraductal papillary mucinous neoplasms has been recorded in a few studies with reference to the challenging histological detection. Herein, we report a rare case with a significant histological combination, highlighting the difficulties in differential diagnosis due to the absence of ancillary techniques, with a brief review on diagnostic methods, histological characteristics and surgical recommendations.