Malignant Intraductal Papillary Mucinous Neoplasms Research Articles

Main Duct Thresholds for Malignancy Are Different in Intraductal Papillary Mucinous Neoplasms of the Pancreatic Head and Body-Tail

The risk of malignancy is uncertain for intraductal papillary mucinous neoplasms (IPMNs) with main pancreatic duct (MPD) of 5-9 mm. No study has correlated MPD size and malignancy considering the anatomic site of the gland (head versus body-tail). Our aim was to analyze the significance of MPD in pancreatic head/body-tail as a predictor of malignancy in main-duct/mixed IPMNs. Retrospective analysis of resected patients between 2009-2018 was performed. Malignancy was defined as high-grade dysplasia and invasive carcinoma. MPD diameter was measured with magnetic resonance imaging. Receiver operating characteristic curve (ROC) analysis was utilized to identify optimal MPD cut-off for malignancy. Independent predictors of malignancy were searched. Malignancy was detected in 74% of 312 identified patients. 213 patients (68.3%) had IPMNs of the pancreatic head and 99 (31.7%) of the body-tail. ROC analysis identified 9 and 7 mm as the optimal MPD cut-offs for malignancy in IPMNs of head and body-tail of the pancreas, respectively. Multivariate analysis confirmed that MPD ≥9 mm (pancreatic head) and ≥7 mm (body-tail) were independent predictors of malignancy along with macroscopic solid components, positive cytology and elevated CA 19-9. The risk of malignancy was low for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) unless high-risk stigmata or multiple worrisome features were present. Different thresholds of MPD dilation are associated with malignancy in IPMNs of the head and body-tail of the pancreas. The risk of malignancy for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) lacking high-risk stigmata or multiple worrisome features is low.

Robotic pancreatectomy for intraductal papillary mucinous neoplasm of the pancreas: A large-scale study.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a mucin-producing tumor that develops from the epithelial lining of the main pancreatic duct or branch pancreatic ducts. Here, we assessed the feasibility and safety of various robotic pancreatectomy approaches to treating IPMN, and short- and long-term outcomes of robotic IPMN resection. Data from patients who underwent robotic pancreatectomy for IPMN between 2012 and 2019 at our hospital were retrospectively analyzed. The survival outcomes for patients were compared using the Kaplan-Meier method and Cox regression analysis. Of the 174 patients who underwent robotic pancreatectomy, 120 and 54 patients had benign or malignant tumors, respectively. Patients with malignant IPMN had lost more weight in the 6months prior to surgery (P=.008), and a higher serum level of CA19-9 (P<.001) and CEA (P<.001). Postoperative pancreatic or biliary fistula occurred in 17 or 6 patients overall, respectively. The pathology of the IPMN (P=.030), tumor diameter (P=.016), mural nodule (P=.023), tumor capsule (P=.003) and CA19-9 (P=.024) values were all independent risk factors for survival. The median OS time after surgical resection for the malignant IPMN group was 29.0months (range, 21.6-36.4). The OS was significantly different in patients with IPMN according to their different pathology, tumor capsule, mural nodule group, CA19-9 level, or tumor diameter. This large-scale survey of 174 patients indicated that various robotic pancreatectomy approaches were feasible and safe for IPMN. Patients had an acceptable prognosis, indicating that robotic pancreatectomy represents a feasible potential therapeutic strategy for IPMN.

The diagnostic role of CT, MRI/MRCP, PET/CT, EUS and DWI in the differentiation of benign and malignant IPMN: A meta-analysis

PurposeThe objective of this study was to assess the diagnostic properties of computed tomography (CT), magnetic resonance imaging (MRI/MRCP) /Magnetic Resonance Cholangiopancreatography (MRCP), positron emission tomography/computed tomography (PET/CT), endoscopic ultrasound (EUS) and diffusion-weighted magnetic resonance imaging (DWI) in distinguishing benign and malignant intraductal papillary mucinous neoplasm (IPMN). Materials and methodsEligible databases were searched for eligible studies, published through July 2020 on the diagnostic accuracy of these modalities. Diagnostic accuracy parameters, including sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curves (SROC) were calculated. Meta-regression was performed to identify the source of heterogeneity. ResultsIn total, 28 studies were included. Pooled sensitivities for CT, MRI/MRCP, PET/CT, EUS and DWI were 0.7, 0.76, 0.8, 0.6 and 0.72, respectively. Pooled specificities were 0.78, 0.83, 0.9, 0.8 and 0.97. The DORs were 8, 16, 35, 6 and 88. The areas under the curve (AUC) of SROC for CT, MRI/MRCP/MRCP, PET/CT, EUS and DW were 0.8, 0.87, 0.92, 0.79 and 0.82, respectively. ConclusionPET/CT showed the highest AUC and the overall diagnostic accuracy results support the use of MRI/MRCP, PET/CT interchangeably as a first-line examination in the diagnosis of malignant IPMN. With regard to DWI, EUS and CT, each techniques have their advantages and supportive to MRI/MRCP.

Risk prediction for malignant intraductal papillary mucinous neoplasm of the pancreas: logistic regression versus machine learning

Most models for predicting malignant pancreatic intraductal papillary mucinous neoplasms were developed based on logistic regression (LR) analysis. Our study aimed to develop risk prediction models using machine learning (ML) and LR techniques and compare their performances. This was a multinational, multi-institutional, retrospective study. Clinical variables including age, sex, main duct diameter, cyst size, mural nodule, and tumour location were factors considered for model development (MD). After the division into a MD set and a test set (2:1), the best ML and LR models were developed by training with the MD set using a tenfold cross validation. The test area under the receiver operating curves (AUCs) of the two models were calculated using an independent test set. A total of 3,708 patients were included. The stacked ensemble algorithm in the ML model and variable combinations containing all variables in the LR model were the most chosen during 200 repetitions. After 200 repetitions, the mean AUCs of the ML and LR models were comparable (0.725 vs. 0.725). The performances of the ML and LR models were comparable. The LR model was more practical than ML counterpart, because of its convenience in clinical use and simple interpretability.

Assessment of malignant potential in intraductal papillary mucinous neoplasms of the pancreas using MR findings and texture analysis.

To investigate the utility of MR findings and texture analysis for predicting the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs). Two hundred forty-eight patients with surgically confirmed IPMNs (106 malignant [invasive carcinoma/high-grade dysplasia] and 142 benign [low/intermediate-grade dysplasia]) and who underwent magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) were included. Two reviewers independently analyzed MR findings as proposed by the 2017 international consensus guidelines. Texture analysis of MRCP was also performed. A multivariate logistic regression analysis was used to identify predictors for malignant IPMNs. Diagnostic performance was also analyzed using receiver operating curve analysis. Among MR findings, enhancing mural nodule size ≥ 5mm, main pancreatic duct (MPD) ≥ 10mm or MPD of 5 to 9mm, and abrupt change of MPD were significant predictors for malignant IPMNs (p< 0.05). Among texture variables, significant predictors were effective diameter, surface area, sphericity, compactness, entropy, and gray-level co-occurrence matrix entropy (p< 0.05). At multivariate analysis, enhancing mural nodule ≥ 5mm (odds ratios (ORs), 6.697 and 6.968, for reviewers 1 and 2, respectively), MPD ≥ 10mm or MPD of 5 to 9mm (ORs, 4.098 and 4.215, and 2.517 and 3.055, respectively), larger entropy (ORs, 1.485 and 1.515), and smaller compactness (ORs, 0.981 and 0.977) were significant predictors for malignant IPMNs (p< 0.05). When adding texture variable to MR findings, diagnostic performance for predicting malignant IPMNs improved from 0.80 and 0.78 to 0.85 and 0.85 in both reviewers (p< 0.05), respectively. MRCP-derived texture features are useful for predicting malignant IPMNs, and the addition of texture analysis to MR features may improve diagnostic performance for predicting malignant IPMNs. • Among the MR imaging findings, an enhancing mural nodule size ≥ 5mm and dilated main pancreatic ducts are independent predictors for malignant IPMNs. • Greater entropy and smaller compactness on MR texture analysis are independent predictors for malignant IPMNs. • The addition of MR texture analysis improved the diagnostic performance for predicting malignant IPMNs from 0.80 and 0.78 to 0.85 and 0.85, respectively.

External validation of nomogram for predicting malignant intraductal papillary mucinous neoplasm (IPMN): from the theory to the clinical practice using the Decision Curve Analysis model

External validation of nomogram for predicting malignant intraductal papillary mucinous neoplasm (IPMN): from the theory to the clinical practice using the Decision Curve Analysis model

CT-Based Radiomics Analysis to Predict Malignancy in Patients with Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas.

Simple SummaryThe management of intraductal papillary mucinous neoplasms of the pancreas (IPMN) remains controversial due to the relatively high rate of unnecessary surgery for low grade dysplasia (LGD) despite the last international recommendations. The aim of our retrospective study was to assess the performance of radiomic analysis on CT in differentiating benign from malignant IPMN. We confirmed in a training cohort (296 patients) and a validation cohort (112 patients) that a total of 85 radiomics features provided valuable additional and independent information for discriminating benign from malignant tumors in the training cohort with an area under the ROC curve (AUC) of 0.84 and an external validation with an AUC of 0.71 with higher performance when implementing clinical variables leading to the indication to surgery. We have demonstrated the capabilities of radiomics models comprising LGD versus high-grade dysplasia (HGD) versus invasive, LGD and HGD, HGD and invasive.To assess the performance of CT-based radiomics analysis in differentiating benign from malignant intraductal papillary mucinous neoplasms of the pancreas (IPMN), preoperative scans of 408 resected patients with IPMN were retrospectively analyzed. IPMNs were classified as benign (low-grade dysplasia, n = 181), or malignant (high grade, n = 128, and invasive, n = 99). Clinicobiological data were reported. Patients were divided into a training cohort (TC) of 296 patients and an external validation cohort (EVC) of 112 patients. After semi-automatic tumor segmentation, PyRadiomics was used to extract radiomics features. A multivariate model was developed using a logistic regression approach. In the training cohort, 85/107 radiomics features were significantly different between patients with benign and malignant IPMNs. Unsupervised clustering analysis revealed four distinct clusters of patients with similar radiomics features patterns with malignancy as the most significant association. The multivariate model differentiated benign from malignant tumors in TC with an area under the ROC curve (AUC) of 0.84, sensitivity (Se) of 0.82, specificity (Spe) of 0.74, and in EVC with an AUC of 0.71, Se of 0.69, Spe of 0.57. This large study confirms the high diagnostic performance of preoperative CT-based radiomics analysis to differentiate between benign from malignant IPMNs.

The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm

BackgroundPancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN.MethodsWe retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017.ResultsOf the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043).ConclusionsLBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.

Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling

The incidence of patients with pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasm (IPMN), is increasing. Current guidelines, which primarily consider radiological features and laboratory data, have had limited success in predicting malignant IPMN. The lack of a definitive diagnostic method has led to low-risk IPMN patients undergoing unnecessary surgeries. To address this issue, we discovered IPMN marker candidates by analyzing pancreatic cystic fluid by mass spectrometry. A total of 30 cyst fluid samples, comprising IPMN dysplasia and other cystic lesions, were evaluated. Mucus was removed by brief sonication, and the resulting supernatant was subjected to filter-aided sample preparation and high-pH peptide fractionation. Subsequently, the samples were analyzed by LC-MS/MS. Using several bioinformatics tools, such as gene ontology and ingenuity pathway analysis, we detailed IPMNs at the molecular level. Among the 5834 proteins identified in our dataset, 364 proteins were differentially expressed between IPMN dysplasia. The 19 final candidates consistently increased or decreased with greater IPMN malignancy. CD55 was validated in an independent cohort by ELISA, Western blot, and IHC, and the results were consistent with the MS data. In summary, we have determined the characteristics of pancreatic cyst fluid proteins and discovered potential biomarkers for IPMN dysplasia.

The Efficacy of 17 Cases of Pancreaticoduodenectomy Combined with Vascular Resection and Reconstruction by Using Robotic Operation System (with Video)

To explore the clinical efficacy of pancreaticoduodenectomy (PD) combined with vascular resection and reconstruction under robotic surgery system in the treatment of borderline resectable pancreatic cancer. The clinical data of 17 patients with borderline resectable pancreatic cancer who underwent PD combined with vascular resection and reconstruction (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760202) under robotic surgery system between August 2011 and September 2018 was analyzed retrospectively. There were 4 cases required conversion because of serious tumor invasion and soft pancreas texture, the other 13 cases were successfully completed. 16 cases (94%) achieved margin-negative resection (R0 resection), 14 cases combined with vein resection, and 3 cases combined with arterial resection. The mean operation time was (401±170) min, the mean blood loss was (647±345) mL, the mean postoperative length of hospital stay was (20±8) d. There was no perioperative death. Postoperative pathology findings and follow-up outcomes were as follows: 1 patient was diagnosed as intraductal papillary mucinous neoplasm (IPMN) and 1 patient was diagnosed as pancreatic neuroendocrine tumors (PNET) (Grade 1), 8 patients with pancreatic ductal adenocarcinoma (PDAC). 1 patient with pancreatic neuroendocrine carcinoma (PNEC) died because of tumor recurrence and metastasis during the follow-up period, the median (Min-Max) survival time was 12 (8-26) months. 5 patients with PDAC and 1 patient with malignant IPMN were currently in the follow-up period. It is safe and feasible to perform RPD with vascular resection and reconstruction. The patient's condition should be fully evaluated before surgery to select the most appropriate treatment.

S6 ribosomal protein phosphorylation is associated with malignancy of intraductal papillary mucinous neoplasm of the pancreas.

BackgroundGlucose metabolism of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is unclear. S6 ribosomal protein (S6) phosphorylation is involved not only in controlling cell growth but also in glucose metabolism in cancer. The aim of this study was to investigate the role of S6 phosphorylation and the significance of glucose metabolic changes in IPMN.MethodsRecords of 39 patients who underwent preoperative FDG‐PET and curative resection were enrolled in this study. S6 phosphorylation and GLUT1 expression were evaluated immunohistochemically in these patients. The effect of S6 phosphorylation on glucose uptake was examined in cancer cell lines. To examine the change of glucose metabolism in IPMN clinically, the relation between clinical factors including FDG‐PET and malignancy of IPMN was investigated.ResultsS6 phosphorylation and GLUT1 expression were significantly higher in carcinoma than in normal cells or adenoma. Cell lines with high level of S6 phosphorylation showed high glucose uptake, and inhibition of S6 phosphorylation reduced glucose uptake. In clinical examination, FDG‐PET was the independent factor related to the diagnosis of adenoma or carcinoma (odds ratio = 20.0, 95% confidence interval = 1.837‐539.9, P = .012). FDG‐PET detected carcinoma with a sensitivity of 81.8%, specificity of 96.4%, and accuracy of 92.3%.ConclusionS6 phosphorylation was associated with glucose uptake and malignancy of IPMN. Moreover, glucose uptake increased in malignant cells of IPMN, and FDG‐PET is useful for detecting malignancy of IPMN.

Prognosis of resected intraductal papillary mucinous neoplasm of the pancreas: using revised 2017 international consensus guidelines.

Although there has been considerable effort to define pre-operative features to predict the malignant potential of intraductal papillary mucinous neoplasms (IPMNs), the prognostic value of pre-operative clinical and MRI features has not been assessed. The aim of this study was to determine pre-operative clinical and MRI features that are predictive of disease-specific death or recurrence in patients undergoing pancreatic resection for IPMNs. We performed a retrospective analysis of 167 patients (mean age, 65years; 114 men and 53 women) who underwent pre-operative MRI and surgical resection of IPMN of pancreas between 2009 and 2019. We evaluated disease-specific survival (DSS) and recurrence-free survival (RFS). Prognostic factor analysis was performed using clinical and MRI features according to the 2017 international consensus guidelines. Of 167 patients, 86 (51.5%) had benign IPMNs and 81 (48.5%) had malignant IPMNs (48 [28.7%] invasive carcinoma and 33 [19.8%] high grade). On multivariable analysis, mural nodule size (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.04-1.18 and HR 1.07; 95% CI 1.03-1.12) and obstructive jaundice (HR 5.01; 95% CI 1.44-17.46 and HR 5.60; 95% CI 2.42-12.99) were the significant variables that were associated with DSS and RFS. The presence of lymphadenopathy (HR 50.7; 95% CI 4.0-643.0; P = 0.002) was the significant factor for DSS. IPMNs with mural nodule showed a significantly lower 5-year DSS (83.7% vs. 100%, P value < 0.01) and RFS (73.1% vs. 95.0%, P value < 0.01) compared with IPMNs with no mural nodule. Mural nodule size on MRI and obstructive jaundice were prognostic markers in the pre-operative evaluation of patients with IPMN of pancreas.

Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

BackgroundMalignant intraductal papillary mucinous neoplasm (IPMN) has poor prognosis. The carcinogenesis of IPMN is not clear. The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis. MethodsBy using immunohistochemistry, we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013. We also examined the expression of Ki-67, c-Myc and p-JNK. ResultsThe median immunostaining index of pSmad3C was 79.2% in low-grade dysplasia, 74.9% in high-grade dysplasia, and 42.0% in invasive carcinoma (P < 0.01), whereas that of pSmad3L was 3.4%, 4.3%, and 42.4%, respectively (P < 0.01). There was a negative relationship between the expression of pSmad3C and c-Myc (P < 0.001, r = -0.615) and a positive relationship between the expression of pSmad3L and c-Myc (P < 0.001, r = 0.696). Negative relationship between the expression of pSmad3C and Ki-67 (P < 0.01, r = -0.610) and positive relationship between the expression of pSmad3L and Ki-67 (P < 0.01, r = 0.731) were confirmed. p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells. The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58 (range, 0.05–0.93), 3.83 (range, 0.85–5.96), respectively (P = 0.02). The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91 (range, 0–36.9) and 82.1 (range, 46.2–97.1), respectively (P = 0.02). The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9 (range 5.7–30.8) and 90.9 (range 52.9–98.5), respectively (P = 0.02). ConclusionspSmad3L was upregulated in malignant IPMN. pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

Clinical Feasibility of Abbreviated Magnetic Resonance With Breath-Hold 3-Dimensional Magnetic Resonance Cholangiopancreatography for Surveillance of Pancreatic Intraductal Papillary Mucinous Neoplasm

To determine the clinical feasibility of abbreviated magnetic resonance image (MRI) using breath-hold 3-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) (aMRI-BH) for pancreatic intraductal papillary mucinous neoplasm (IPMN) surveillance. In this retrospective study, 123 patients with 158 pancreatic IPMNs (pathologically proven [n = 73] and typical image feature with ≥2-year stability [n = 85]) who underwent conventional MRI (cMRI) consisting of contrast-enhanced pancreatobiliary MRI with conventional and BH-3D-MRCP were included. Two readers independently evaluated aMRI-BH protocols consisting of heavily T2-weighted, precontrast T1-weighted, and BH-3D-MRCP sequences. The diagnostic performance of aMRI-BH for detecting malignant IPMNs was assessed using the following criteria: category 3, presence of mural nodule 5 mm or bigger and/or main pancreatic duct (MPD) 10 mm or bigger; category 2, more than one of the following: cyst size 30 mm or greater, mural nodule smaller than 5 mm, thickened cyst walls, MPD of 5 to 9 mm, lymphadenopathy, and an abrupt MPD caliber change with distal atrophy; and category 1, none of the above. Categories 2 or 3 were considered positive results of surveillance. Interreader agreement of image features by intraclass correlation and κ statistics were analyzed. The total acquisition times of cMRI and aMRI-BH were 32.7 ± 8 and 5.5 ± 2.1 minutes, respectively (P < 0.01). Among 158 IPMNs, 33 lesions were malignant. The aMRI-BH presented a sensitivity of 100% and a negative predictive value of 100% for evaluating malignant IPMNs in both readers, with substantial interreader agreements (intraclass correlation or к values, range: 0.73-0.93 for cMRI and 0.57-0.94 for aMRI-BH) in significant imaging features based on revised Fukuoka guidelines, except for thickened cyst walls and lymphadenopathy (к values: 0.10 and 1.00 for cMRI and 0.13 and 0.49 for aMRI-BH, respectively). The aMRI-BH provided high sensitivity and negative predictive value to evaluate malignant IPMNs by using predetermined criteria, and aMRI-BH might be a potential tool for pancreatic IPMN surveillance with significantly lower acquisition time.

The Role of Positron Emission Tomography in Clinical Management of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas represent a heterogeneous group of tumors, increasingly diagnosed in clinical practice. An early differential diagnosis between malignant and benign lesions is crucial to patient management and the choice of surgery or observation. The therapeutic approach is currently based on a patient’s clinical, biochemical, and morphological characteristics. The latest published International Consensus Guidelines (ICG) make no mention of the role of metabolic assessments of IPMNs. The aim of this study was to review the current literature, examining the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in IPMN management. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 10 articles were analyzed in detail, focusing on the value of PET as opposed to other standard imaging criteria. Data were retrieved on 419 patients. The 18-FDG-PET proved more sensitive, specific, and accurate than the ICG criteria in detecting malignant IPMNs (reaching 80%, 95%, and 87% vs. 67%, 58%, and 63%, respectively). Metabolic assessments may be used as an additional tool for the appropriate management of patients with doubtful imaging findings.

Pre-operative nomogram predicting malignant potential in the patients with intraductal papillary mucinous neoplasm of the pancreas: focused on imaging features based on revised international guideline.

To clarify the pre-operative imaging and clinical features differentiating malignant from benign intraductal papillary mucinous neoplasm (IPMN) of the pancreas and develop a nomogram for estimating the individualized risk of malignant IPMN. One hundred twenty-six patients with IPMN (72 benign and 54 malignant) who underwent pre-operative contrast-enhanced CT or MRI from 2010 to 2018 were retrospectively evaluated in two tertiary institutions. All lesions were pathologically proven by surgery or biopsy. Significant imaging and clinical findings for malignancy were assessed by univariate and multivariable logistic regression analyses. Based on the significant variables in the multivariable analysis, we developed a nomogram to predict malignant potential in patients with IPMNs, and the area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic value. Multivariable analysis revealed that enhancing mural nodule ≥ 5mm (odds ratio (OR), 48.30; 95% confidence interval (CI), 11.69-199.49), increased serum carbohydrate antigen 19-9 (CA19-9) (OR, 8.69; 95% CI, 2.04-36.92), main pancreatic duct (MPD) diameter ≥ 10mm (OR, 6.34; 95% CI, 1.21-33.30), and acute pancreatitis (OR, 4.77; 95% CI, 1.12-20.36) were independent significant parameters to predict malignant IPMN. Among them, enhancing mural nodule ≥ 5mm showed the highest OR and predictor point on the nomogram. The AUC for the nomogram was 0.955 (95% CI, 0.903-0.984). Pre-operative imaging findings could aid in predicting malignant potential of IPMN using the significant findings of enhancing mural nodule ≥ 5mm, increased serum CA19-9, MPD diameter ≥ 10mm, and acute pancreatitis. • Among pre-operative imaging and clinical features, enhancing mural nodule ≥ 5mm, increased serum CA19-9, main pancreatic duct diameter ≥ 10mm, and acute pancreatitis were independent significant parameters to predict malignant IPMN. • Enhancing mural nodule ≥ 5mm was a single predictor for malignant IPMN, with the highest diagnostic values compared to other significant parameters. • A constructed nomogram using these parameters could aid in predicting malignant potential in patients with IPMN of the pancreas.

Radiological and Pathological Assessment of the 2017 Revised International Association of Pancreatology Consensus Guidelines for Intraductal Papillary Mucinous Neoplasm, With an Emphasis on the Gastric Pyloric Gland Type.

This study aimed to assess the pitfalls of the current International Association of Pancreatology guidelines (IAPCG2017) for pancreatic intraductal papillary mucinous neoplasm (IPMN) and identify the criteria for future guidelines. Eighty surgically resected, consecutive IPMN cases were analyzed. Data including tumor site, IPMN duct type, and surgery type were collected. Based on radiological data, cases were retrospectively classified as high-risk stigmata (HRS) and non-HRS. Pathological grades and histological subtypes of IPMN cases were determined. Severe stromal sclerosis of the IPMN septa/marked parenchymal atrophy in the upstream pancreas was investigated pathologically. Positive/negative predictive values of the IAPCG2017 were calculated. Clinicopathological features of HRS-benign cases (pathologically benign IPMN cases meeting the HRS criteria) were extracted. The positive/negative predictive values were 72.7%/64.0%, 70.0%/34.6%, and 54.0%/63.3% for IAPCG2017, HRS-main pancreatic duct, and HRS-nodule criteria, respectively. The 15 HRS-benign cases (18.8%) included 13 pancreatoduodenectomies and 10 cases of gastric pyloric (GP) gland subtype. Severe upstream atrophy was significantly related to IPMN malignancy, unlike the severe sclerosis of IPMN septa. Benign IPMNs of GP subtype are sometimes categorized as HRS with the IAPCG2017. Collecting data on the natural course of GP-IPMN is necessary. To evaluate upstream atrophy may be of value to predict IPMN malignancy.

The value of 18F-FDG positron emission tomography to differentiate benign from malignant intraductal papillary mucinous neoplasms: A prospective multicenter study

To assess the value of 18F-FDG PET/CT in differentiating between benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Malignant or high-risk IPMN require surgical resection but surgery should be avoided in patients with IPMN carrying a low risk of malignancy. 18F-FDG PET has been studied mostly in small, single center, retrospective series. Prospective, non-comparative, multicenter French study. The primary endpoint was the specificity of PET/CT for identifying malignant IPMN (in situ or invasive carcinoma). Final diagnosis was obtained from pathological examination of the resected specimen. Among 120 patients analyzed, 99 had confirmed IPMN, including 24 with malignant lesions, namely 9 with carcinoma in situ and 15 with invasive carcinoma. The 18F-FDG PET/CT was positive in 44 and 31 patients in the overall and IPMN populations respectively. In the 99 IPMN patients, PET/CT showed 13 true positive, 18 false positive, 57 true negative and 11 false negative results. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of malignancy were 54.2%, 76.0%, 83.8% and 41.9% respectively, versus 64.9%, 75.9%, 82.9% and 54.5% in the overall population. We could not identify a cut-off value for SUVmax to distinguish benign from malignant lesions. Conventional imaging included computed tomography, magnetic resonance cholangiopancreatography and endoscopic ultrasound. In IPMN patients who underwent the 3 techniques, sensitivity, specificity, NPV and PPV were 66.7%, 84.4%, 84.4% and 66.7% respectively. In this study, 18F-FDG PET/CT did not perform better than conventional imaging to differentiate malignant from benign IPMN.

Mixed-type intraductal papillary mucinous neoplasm in a patient with pancreas divisum: pancreatoscopy through the Santorini duct with direct intraductal biopsy

View Large Image Figure ViewerDownload Hi-res image Download (PPT)A 72-year-old man with abdominal pain, hyperamylasemia/lipasemia, and dilatated main pancreatic duct shown by CT underwent MRCP (A, top left) that suggested a mixed-type intraductal papillary mucinous neoplasm (IPMN) with ectasia of multiple branch pancreatic ducts (A, top right) and of the entire dorsal duct (Santorini, 8 mm), draining the dorsal part of the pancreas through minor papilla (A, bottom left), with an incomplete ventral duct (Wirsung, A, bottom right), consistent with pancreas divisum (PD). EUS showed echoic material inside branch duct dilatations (B). Endoscopy showed a typical “fish-mouth” appearance of the minor papilla, draining mucus (C, top left). Pancreatography through the minor papilla confirmed dilatation of the Santorini duct (C, top right). Peroral pancreatoscopy through the minor papilla, with use of the SpyGlass system (Boston Scientific, Boston, Mass, USA), confirmed diffuse dorsal duct dilatation with mucinous material and papillary projections from the intraductal epithelium (C, bottom left). Histologic analysis of targeted intraductal biopsy specimens obtained with SpyBite forceps (Boston Scientific) (C, bottom right) demonstrated a mucin-producing papillary neoplasm with severely atypical cells, suggestive of malignancy (D, left: H&E, orig. mag. ×25). The patient underwent total pancreatectomy (D, middle); final pathologic examination demonstrated malignant IPMN (D, right: H&E, orig. mag. ×50). Patients with PD are at risk for the development of pancreaticobiliary tumors, including IPMN. In patients with PD and dorsal duct dilatation, the coexistence of main-duct IPMN should be considered. Our advice is to perform dorsal duct pancreatoscopy and direct biopsies to reach a final diagnosis. All authors disclosed no financial relationships. Commentary In 2020, most readers of Gastrointestinal Endoscopy should be familiar with the clinical manifestations of intraductal papillary mucinous tumors. Peroral pancreatoscopy with the use of ERCP has been performed in this setting for many years, both to confirm the diagnosis by imaging and perform biopsies and to quantify the extent of disease. Peroral pancreatoscopy can thus help to determine whether a patient would benefit most from a distal pancreatectomy, a pancreaticoduodenectomy, or a total pancreatectomy (as this patient underwent). This patient had pancreas divisum, which allowed peroral pancreatoscopy to be performed through the minor papilla, making the case even more interesting. It should be recognized that peroral pancreatoscopy carries the risk of causing post-ERCP pancreatitis, even in experienced hands, and appropriate steps should be taken to minimize the risk to the patient. Douglas G. Adler, MD, FASGE, GIE Senior Associate Editor, University of Utah School of Medicine, Salt Lake City, Utah Mohamed O. Othman, MD, Associate Editor for Focal Points

Analyzing Intraductal Papillary Mucinous Neoplasms Using Artificial Neural Network Methodologic Triangulation

Intraductal papillary mucinous neoplasms (IPMN) are a type of mucinous pancreatic cyst. IPMN have been shown to be pre-malignant precursors to pancreatic cancer, which has an extremely high mortality rate with average survival less than 1 year. The purpose of this analysis is to utilize methodological triangulation using artificial neural networks and regression to examine the impact and effectiveness of a collection of variables believed to be predictive of malignant IPMN pathology. Results indicate that the triangulation is effective in both finding a new predictive variable and possibly reducing the number of variables needed for predicting if an IPMN is malignant or benign.