Diagnosis of Malignant Intraductal Papillary Mucinous Neoplasm by Cholangioscopy and Probe-Based Confocal Laser Endomicroscopy.

Diagnostic yield of EUS-FNA-based cytology distinguishing malignant and benign IPMNs: A systematic review and meta-analysis

Intraductal papillary mucinous tumor (IPMT) of the pancreas is a rare disease. Preoperative determination of the nature (benign or malignant IPMT) and extent of the disease may be challenging. Experience in this regard is still limited. Hara et al. performed a retrospective review of their extended experience in evaluating patients with IPMT by means of peroral pancreatoscopy (POPS) and intraductal ultrasound (IDUS) over a 13-yr period. Sixty consecutive IPMT patients were included in this study (POPS performed in all and IDUS performed in 40 patients). The authors assessed tumor type (elevated vs excavated), tumor morphology as per POPS (type I: granular; type II: fish-egg like without vascular images; type III: fish-egg like with vascular images; type IV: villous type; and type V: vegetative type), maximum tumor height as determined by IDUS, and tumor extent (head vs body vs tail; main pancreatic duct vs side branches). Results obtained with POPS and IDUS were correlated and compared with surgical pathology serving as the gold standard. The ability of CT, endoscopic ultrasound, and K-ras point mutations in pancreatic juice to distinguish benign (hyperplasia or adenoma) from malignant (carcinoma in situ or invasive carcinoma) IPMT were also studied. Relapse-free and overall survival of this retrospective cohort of patients in whom treatment was guided by POPS and IDUS findings were assessed. Forty of the 60 patients evaluated had protruding lesions (67%). Among them, most malignant tumors had a POPS morphology type III, IV, or V (P < 0.0001), with a reported sensitivity, specificity, and accuracy of 68%, 87%, and 75% for differentiating benign (hyperplasia or adenoma) from malignant (carcinoma in situ or invasive carcinoma) IPMT. Maximum tumor height as measured by IDUS (2.27 ± 1.5 mm in the benign group, and 5.96 ± 4.03 in the malignant group) was able to discriminate benign from malignant tumors (p < 0.001). Lesions protruding 4 mm or more on IDUS were malignant in 88% of cases, and the sensitivity, specificity, and accuracy of IDUS at that cutoff was 68%, 89%, and 78%, respectively. CT and endoscopic ultrasound had a sensitivity and accuracy ranging from 32% to 65%. When positive K-ras point mutation was considered as a malignant finding, sensitivity, specificity, and accuracy reached 87%, 15%, and 61%, respectively. Only one of the 60 patients resected (1.6%) had positive margins on surgical resection after POPS and IDUS had been performed. The 3-yr relapse-free and overall survival was 93% and 95%, respectively. Based on these results, Hara et al. concluded POPS and IDUS can reliably distinguish benign from malignant IPMT, determine tumor extent, and guide therapy. These new techniques may contribute to improvement in postoperative results.

Peroral pancreatoscopy and intraductal ultrasound for diagnosis of intraductal papillary mucinous tumors of the pancreas 1,2

Role of Endoscopic Ultrasound in the Diagnosis of Intraductal Papillary Mucinous Neoplasms: Correlation With Surgical Histopathology

This study aimed at determining the additional value of FDG PET/CT to contrast-enhanced CT in the differentiation between benign and malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas with mural nodules. This retrospective review of medical records was approved by our institutional review board. The preoperative PET/CT images of 16 non-diabetic patients with surgically proven IPMN, where mural nodules of 3mm or larger were shown by preoperative contrast-enhanced CT, were retrospectively evaluated. The 16 patients were divided into two groups: 7 patients with benign IPMN [adenoma (n=1) and borderline tumor (n=6)] and 9 patients with malignant IPMN [carcinoma in situ (CIS) (n=8) and invasive carcinoma (n=1)]. Nuclear medicine physician blinded to the pathologic assessment of malignancy of IPMN set a spherical volume of interest (VOI) over the mural nodules on PET/CT images and recorded the peak standardized uptake value (SUV(max)) in the VOI, referring the contrast-enhanced CT images. Statistical differences in the size of mural nodule, the diameter of main pancreatic duct (MPD), and SUV(max) of the tumors between benign IPMNs and malignant IPMNs were compared using the Mann-Whitney U test. Statistical significance was set at p<0.05. Additionally, the diagnostic accuracy of FDG PET for the detection of malignancy was calculated. The SUV(max) of the malignant IPMNs with mural nodules of 3mm or larger was higher than that of benign IPMNs (2.7±0.6 vs. 1.9±0.3, p<0.01). Meanwhile, there was no significant difference in mural nodule diameter and MPD diameter between the two groups. FDG PET/CT showed an excellent diagnostic accuracy for the differentiation between malignant and benign IPMNs with mural nodules: the sensitivity, specificity, PPV, NPV, and accuracy in malignant IPMN with mural nodule of FDG PET/CT were 77.8, 100, 100, 77.8, and 87.5 for the cutoff value of 2.3; and 100, 57.1, 75.0, 100, and 81.3 for the cutoff value of 2.0, respectively. The result of this study indicates that FDG PET/CT can provide additional information for the differentiation between benign and malignant IPMNs of the pancreas with mural nodules.

Evaluation of the Guidelines for Management of Pancreatic Branch-Duct Intraductal Papillary Mucinous Neoplasm

Epithelial-to-mesenchymal transition (EMT) is generally associated with increased tumor aggressiveness and poor prognosis. We evaluated EMT characteristics in intraductal papillary mucinous neoplasm (IPMN) tumor specimens and their potential role as biomarkers for malignancy, metastasis, and adverse patient outcomes. IPMN surgical specimens were identified and reviewed by two gastrointestinal pathologists. Immunohistochemical analysis of E-cadherin, vimentin, and ZEB-1 was performed. Samples were linked to clinicopathologic and outcome data for these patients. Western blot test was used to evaluate ZEB-1 expression in IPMN samples; 846 human miRNAs were profiled, and EMT-related differentially expressed miRNAs were validated using quantitative real-time polymerase chain reaction. Fifty-eight IPMN specimens and five normal pancreatic tissue samples were immunohistochemically stained and scored. E-cadherin expression was significantly lower in malignant versus low-grade IPMN (p < 0.05). Vimentin expression was increased in malignant IPMN tumor samples (p < 0.05). EMT was associated with increased lymph node metastasis and decreased survival of malignant IPMN patients (p < 0.05). ZEB-1, an imperative EMT regulator, was exclusively expressed by malignant IPMN tumors. miRNA hierarchical clustering demonstrated grouping of two main IPMN subgroups: low-grade IPMN versus high-grade IPMN and carcinoma. Twenty-four miRNAs were differentially expressed (14 up-regulated, 10 down-regulated). The EMT-regulatory miRNAs, miR-200c and miR-141, were down-regulated (twofold and 1.8-fold decrease, respectively) in malignant versus low-grade IPMN (p < 0.05). EMT may play a role in IPMN tumorigenesis and metastasis. EMT molecular deregulations could be utilized as potential novel biomarkers for the identification of high-risk IPMN patients.

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

Published studies have revealed the diagnostic yield of cytology obtained from endoscopic retrograde cholangiopancreatography (ERCP) in distinguishing malignant and benign intraductal papillary mucinous neoplasm (IPMN). However as a result of small sample sizes, the overall magnitude of benefit is unknown. Additionally, the optimal endoscopic procedure for cytology acquisition is also unclear. The aim of the present study was to evaluate the diagnostic yield of ERCP-based cytology in patients with IPMN and clarify the optimal sampling technique. Relevant studies with a reference standard of definitive surgical histology were identified via MEDLINE and SCOPUS. Malignant IPMN included invasive adenocarcinoma, carcinoma in situ, and high-grade dysplasia. For ERCP, studies using aspiration, brush, and lavage cytology were included. The main objective was the diagnostic yield (pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) of cytology obtained from ERCP to distinguish malignant and benign IPMN. Meta-analysis of 13 international studies with 483 IPMN patients was conducted. Pooled sensitivity was 35.1%, specificity 97.2%, and accuracy 92.9%. Among the three ERCP techniques, lavage cytology showed the best diagnostic ability (sensitivity 45.8%, specificity 97.9%). Malignant IPMN were observed in 45.1% (218/483) of patients in ERCP studies. Cytology from ERCP has good specificity but poor sensitivity in distinguishing benign from malignant IPMN. Newer techniques or markers are needed to improve diagnostic yield.

Objective To investigate the clinical features, diagnosis and treatment of pancreatic cystic neoplasms. Methods The clinical data of 62 patients with pancreatic cystic neoplasms who were admitted to the First Affiliated Hospital of Anhui Medical University from January 2010 to December 2014 were retrospectively analyzed. Benign neoplasms included benign mucinous cystic neoplasm (MCN) , serous cystic neoplasm (SCN) , solid pesudopapillary neoplasm (SPN) and intraductal papillary mucinous neoplasm (IPMN) and malignant neoplasms included borderline or malignant MCN and borderline or malignant IPMN. The sex, age, clinical symptoms, imaging features, laboratory results, surgical method, operation time, volume of intraoperative blood loss, perioperative complications, result of pathological examination and follow-up were analyzed. Patients were followed up by telephone interview and outpatient examination up to 31, December 2014 or death．Measurement data with normal distribution were presented by±s, while measurement data with non-normal distribution were presented by M (range). Univariate analysis of count data was done by chi-square test or Fisher exact probability. Multivariate analysis was done by Logistic regression model. Results Of the 62 patients with pancreatic cystic neoplasms, 31 were retreated due to upper digestive discomfort, 10 without specific features were found during the health examinations, 10 due to weight loss in near 2-3 months, 9 due to abdominal masses and 2 due to obstructive jaundice.Results of radiographic examinations showed that the diameter of the tumor is (60 ±35) mm, 11 of tumors located in the head and neck of pancreas and 51 located in the body and tail of pancreas.The cystic nodule or solid ingredients were detected in 33 patients and main pancreatic duct dilation in 6 patients.The positive diagnostic rates of B ultrasound, computed tomography (CT) , magnetic resonance imaging (MRI) , and endoscopic ultrasonography (EUS) and positron emission tomography-computed tomography (PET/ CT) were 85.5% (53/ 62) , 93.2% (55/ 59) , 94.1% (16/ 17) , 100.0% (3/ 3) and 100.0% (2/ 2) .Preoperative serum CEA and serum CA19-9 were 1.22 μg/ L(0.20-12.98 μg/ L) and 10.85 U/ mL (0.60-1 000.00 U/ mL) , while the percentage of patients with increasing CEA and CA19-9 were 4.8% (3/ 62) and 14.5% (9/ 62) , respectively.All the 62 patients received surgery, distal pancreatectomy (DP) combined with splenectomy were performed on 36 patients, pancreatoduodenectomy on 10 patients, partial pancreatic resection on 7 patients, spleen-preserving DP on 6 patients, cyst-resection on 2 patients and palliative Roux-en-Y anastomosis on 1 patient.The rate of surgical resection, operation time and volume of blood loss were 98.4% (61/ 62) , (219 ± 79) minutes and (299 ± 296) mL.After operation, 13 patients had different degrees of complication, and were improved by symptomatic treatment such as jejunitas, hemostasis and anti-infection.The results of pathological examination showed that 27 patients were with MCN (11 with malignant or borderline MCN) , 18 with SCN, 11 with SPN and 6 with IPMN (3 with malignant or borderline IPMN) .All the patients were followed up for 3-63 months with good prognoses, except for the death of 2 patients.The results of univariate analysis showed that age of onset, tumor diameter, preoperative serum CEA and preoperative serum CA19-9 were related factors affecting diagnosis of malignant tumor (χ2=18.798, 12.335, 7.281, 10.073, P <0.05 ) .The results of multivariate analysis showed that age≥65 years and preoperative serum CA19-9≥34.00 U/ mL were independent risk factors affecting diagnosis of malignant tumor ( RR =0.923, 0.994; 95% confidence interval : 0.863-0.987, 0.988-0.999; P <0.05). Conclusions B ultrasound, CT and MRI are the main diagnostic methods for pancreatic cystic neoplasms without specific clinical features.Patients with pancreatic cystic neoplasms have overall good prognosis.The results of multivariate analysis showed that age≥ 65 years and preoperative serum CA19-9≥34.00 U/ mL are independent risk factors affecting tumor malignancy. Key words: Pancreatic cystic neoplasms; Diagnosis; Therapy

Recently, intraductal papillary-mucinous tumor (IPMT) of the pancreas has increasingly been recognized. However, differential diagnosis between benign and malignant IPMT is often difficult using conventional imaging modalities. The purpose of this study was to retrospectively investigate the value of endoscopic ultrasonography (EUS) for differentiating malignant from benign IPMT. A total of 51 patients with IPMT were preoperatively examined by EUS. The endosonograhic findings were compared with histopathological findings of the resected specimens. In main duct type IPMT, the diameter of the main pancreatic duct (MPD) was > or =10 mm in seven of the eight malignant tumors, compared with two of the seven benign tumors (p < 0.05). In branch duct type IPMT, three of the four large tumors (>40 mm) with irregular thick septa were malignant lesions. In both main duct type IPMT and branch duct IPMT, eight patients had large mural nodules (>10 mm); seven of the eight tumors were malignant and one of the eight tumors was benign. When the tumor was diagnosed as malignant according to above three findings, EUS was able to differentiate between malignant and benign IPMT with an accuracy of 86%. Main duct type tumors with > or =10 mm dilated MPD, branch duct type tumors (>40 mm) with irregular septa, and large mural nodules (>10 mm) strongly suggest malignancy on EUS. EUS would be a useful modality for differentiating between benign and malignant IPMT.

Intraductal papillary-mucinous tumors of the pancreas: Differential diagnosis between benign and malignant tumors by endoscopic ultrasonography

To assess the reliability of 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and its contribution to surgical decision making. Pancreatic IPMNs are increasingly recognized, often as incidental findings, especially in people over age 70 and 80. Computed tomography (CT) and magnetic resonance (MR) are unreliable in discriminating a benign from a malignant neoplasm. 18-FDG PET as imaging procedure based on the increased glucose uptake by tumor cells has been suggested for diagnosis and staging of pancreatic cancer. From January 1998 to December 2005, 64 patients with suspected IPMNs were prospectively investigated with 18-FDG PET in addition to conventional imaging techniques [helical-CT in all and MR and magnetic resonance cholangiopancreatography (MRCP) in 60]. 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value (SUV). The validation of the diagnosis was made by a surgical procedure (n = 44), a percutaneous biopsy (n = 2), main duct cytology (n = 1), or follow-up (n = 17). Mean and median follow-up times were 25 and 27.5 months, respectively (range, 12-90 months). Twenty-seven patients (42%) were asymptomatic. Forty-two patients underwent pancreatic resection, 2 palliative surgery, and 20 did not undergo surgery. An adenoma was diagnosed in 13 patients, a borderline tumor in 8, a carcinoma in situ in 5, and an invasive cancer in 21; in 17 patients a tumor sampling was not performed and therefore the histology remained undetermined. Positive criteria of increased uptake on 18-FDG PET was absent in 13 of 13 adenomas and 7 of 8 borderline IPMNs, but was present in 4 of 5 carcinoma in situ (80%) and in 20 of 21 invasive cancers (95%). Conventional imaging technique was strongly suggestive of malignancy in 2 of 5 carcinomas in situ and in 13 of 21 invasive carcinomas (62%). Furthermore, conventional imaging had findings that would be considered falsely positive in 1 of 13 adenomas (8%) and in 3 of 8 borderline neoplasms (37.5%). Therefore, positive 18-FDG PET influenced surgical decision making in 10 patients with malignant IPMN. Furthermore, negative findings on 18-FDG PET prompted us to use a more limited resection in 15 patients, and offered a follow-up strategy in 18 patients (3 positive at CT scan) for the future development of a malignancy. 18-FDG PET is more accurate than conventional imaging techniques (CT and MR) in distinguishing benign from malignant (invasive and noninvasive) IPMNs. 18-FDG PET seems to be much better than conventional imaging techniques in selecting IPMNs patients, especially when old and asymptomatic, for surgical treatment or follow-up.

Objective:Intra-abdominal fat is a risk factor for pancreatic cancer (PC), but little is known about its contribution to PC precursors known as intraductal papillary mucinous neoplasms (IPMNs). Our goal was to evaluate quantitative radiologic measures of abdominal/visceral obesity as possible diagnostic markers of IPMN severity/pathology.Methods:In a cohort of 34 surgically-resected, pathologically-confirmed IPMNs (17 benign; 17 malignant) with preoperative abdominal computed tomography (CT) images, we calculated body mass index (BMI) and four radiologic measures of obesity: total abdominal fat (TAF) area, visceral fat area (VFA), subcutaneous fat area (SFA), and visceral to subcutaneous fat ratio (V/S). Measures were compared between groups using Wilcoxon two-sample exact tests and other metrics.Results:Mean BMI for individuals with malignant IPMNs (28.9 kg/m2) was higher than mean BMI for those with benign IPMNs (25.8 kg/m2) (P=0.045). Mean VFA was higher for patients with malignant IPMNs (199.3 cm2) compared to benign IPMNs (120.4 cm2),P=0.092. V/S was significantly higher (P=0.013) for patients with malignant versus benign IPMNs (1.25vs. 0.69 cm2), especially among females. The accuracy, sensitivity, specificity, and positive and negative predictive value of V/S in predicting malignant IPMN pathology were 74%, 71%, 76%, 75%, and 72%, respectively.Conclusions:Preliminary findings suggest measures of visceral fat from routine medical images may help predict IPMN pathology, acting as potential noninvasive diagnostic adjuncts for management and targets for intervention that may be more biologically-relevant than BMI. Further investigation of gender-specific associations in larger, prospective IPMN cohorts is warranted to validate and expand upon these observations.

Background The 2017 international consensus guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas are widely used. Purpose To evaluate the interobserver agreement and diagnostic performance of MRI assessment in predicting the malignant potential of IPMN according to radiologists' experience. Materials and Methods This multicenter retrospective study included 100 patients with pathologically proven pancreatic IPMN (77 patients with surgery, 23 patients with biopsy) who underwent contrast-enhanced MRI between 2016 and 2021. Eight post-fellowship radiologists (four more-experienced [8-20 years] and four less-experienced [1-4 years] reviewers) evaluated MRI for high-risk stigmata and worrisome features identified by the most recent 2017 guidelines. Interobserver agreement was determined using Fleiss κ statistics according to radiologist experience. The diagnostic performance for malignant IPMN was assessed using receiver operating characteristic curve analysis. Results Among 100 patients (mean age, 66 years ± 10 [SD]; 57 men), 52 (52%) had malignant IPMN. For high-risk stigmata, interobserver agreement was substantial for main pancreatic duct size of at least 10 mm (κ = 0.78; 95% CI: 0.75, 0.82), enhancing mural nodule of at least 5 mm (κ = 0.70: 95% CI: 0.66, 0.74), and at least one high-risk stigmata (κ = 0.73: 95% CI: 0.69, 0.76). The worrisome features showed fair to substantial interobserver agreement (κ range, 0.22-0.80). More-experienced reviewers demonstrated better agreement in the assessment of at least one high-risk stigmata than less-experienced reviewers (κ = 0.77 vs κ = 0.69, P < .001). The overall diagnostic performance of each reviewer was good for the prediction of malignant pancreatic IPMN (area under the receiver operating characteristic curve [AUC] range, 0.77-0.84; median AUC, 0.82), with substantial agreement (κ = 0.76). Conclusion The 2017 international consensus guidelines enabled good diagnostic performance and substantial interobserver agreement for high-risk stigmata but not worrisome features on the evaluation of the malignant pancreatic IPMN using MRI. Agreement tended to be better among more-experienced reviewers than among less-experienced reviewers. © RSNA, 2023 Supplemental material is available for this article.