Type Intraductal Papillary Mucinous Neoplasms Research Articles

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.

Cytology adds value to monoclonal antibody Das-1 testing for detection of high-risk pancreatic cysts

Determining the risk of malignancy in a pancreatic cyst (PC) is a clinical and diagnostic challenge. Monoclonal antibody (mAb) Das-1 test was shown to have high sensitivity, specificity, and accuracy in detecting high-risk (HR) cysts. Das-1 mAb test detects HR mucinous cysts with high-grade dysplasia (HGD), invasive carcinoma, and/or intestinal-type epithelium. Correlation of mAb Das-1 testing of PC fluids with cytomorphologic findings has not been evaluated. We correlated cytology with mAb Das-1 test results and resection histology in 26 PCs. There were 18 intraductal papillary mucinous neoplasms (IPMN), 1 intraductal oncocytic papillary neoplasm (IOPN), 4 mucinous cystic neoplasms (MCN), 2 serous cystadenomas, and 1 cystic pancreatic neuroendocrine tumor (PanNET). HR cysts included cysts with high-grade atypia on cytology or HGD on histology, invasive carcinoma, IOPNs, and cystic PanNETs. Intestinal type IPMNs were also HR cysts on histology. In 17 cases (65.38%), cytology and mAb Das-1 test correlated with histology. There were 2 (7.69%) mAb Das-1 test negative HR PCs diagnosed by cytology. Five (19.23%) mAb Das-1 test positive HR PCs had mucin only or cells with low-grade dysplasia on cytology. Two mAb Das-1 test positive HR PCs had nondiagnostic cytology. HR IOPN and cystic PanNET were not detected by mAb Das-1 test. The mAb Das-1 is a sensitive and specific biomarker for detecting HR mucinous PCs. Adding cytology to mAb Das-1 testing improves the sensitivity for the detection of nonmucinous HR PC. Together, cytology with mAb Das-1 testing is more accurate than either one alone.

Intraductal papillary mucinous neoplasms (IPMN): long term management and results at single HPB center

Introduction: IPMN origins within the cells of the pancreatic duct. Accepted as lesions that can progress to pancreatic cancer, TC, MRI and EUS should be used to identify risk factors to decide whether the patient should benefit from a surgical approach. Methods: Retrospective analysis of patients diagnosed of IPMN between 2015 and 2019. Variables analyzed include demographics, symptoms, images, surgical indication, type of lesion, presence of malignant disease and survival. The statistical studies performed will be described in each of the results reports and were performed using SPSS version 17. Results: 58 patients were diagnosed with IPMN: 48 were found pre-operatively (Group 1) while 10 post-resection (Group 2, 9.7%). G1: 73% were fem., 71% asymptomatic, 23 (48%) multifocal, 13 (27%) located the head of the pancreas, 8 (17%) in the body and 4 (8%) in the tail. Table 1 summarizes the analyzed. The average time to surgery was 22.4 +/- 29.4 months. In G2: 6 were associated to invasive AdenoCa, 2 to an Ampuloma, 1 to a NET and 1 in a pancreas divisum. Long term survival: 100% for G1 at 10 years, while in G2 is 100% and 86% at 1 and 10 years respectively. Recurrence rate: 22%. Conclusions: Those results highlight the value of following stablished guidelines in order to be successful with a conservative approach when an IPMN is diagnosed. In patients with IPMN I or III, surgery is recommended. Newly diagnosed IPMN II should be strictly followed due to an increased risk of malignancy.Tabled 1[Patients that underwent surgery with preo-operative diagnosis of IPMN.]Preo-operative DiagnosisGenderAgeSurgery or Follow upSurgical indicationPathology reportSurvival (month)AliveRecurrencyPatients with indication of surgeryIPMN IIPMN IIPMN IIPMN IIPMN IMFMFF8869723660Distal PancreatectomyCephalic duodenopancreatectomyDistal PancreatectomyDistal PancreatectomyPending SurgeryType of IPMNType of IPMNType of IPMNType of IPMNHigh CA19.9 in EUS. Size >4cmIPMN I with LGDIPMN I with MGDMixed type IPMN with LGDMicrocystic Serous Cystadenoma-2229271424YesYesYesYesYesNoNoYesNo-Patients with indication of surgeryIPMN IIIPMN IIIPMN IIIPMN IIFFMF74737166Cephalic duodenopancreatectomyCephalic duodenopancreatectomyDistal PancreatectomyPending SurgeryMural tumor with contrast enhacementMural tumor with contrast enhacementMural nodule >5mmSize >4cm. Atrofic pancreasIPMN I with MGDIPMN IIIPMN II with MGD-38108871YesYesYesYesNoYesNo-Patients with indication of surgeryIPMN IIIIPMN IIIIPMN IIIFFM706871Total DuodenopancreatectomyTotal DuodenopancreatectomyPending SurgeryHigh CEA in EUSGrowth >5mm/2 yearsDilatated WirsungMixed type IPMN with LGDMixed type IPMN with HGD-58453YesYesYesNoNo-Follow upIPMN IN=1F63Follow up--72Yes-Follow upIPMN IIN=30M=7F= 2363+/-13Follow up--12+/-13All-Follow upIPMN IIIN=5F=4M=160+/-14Follow up--20+/-8All- Open table in a new tab

Surgery for Ipmn of the Pancreas: Preoperative Factors Tipping the Scale of the Decision Making. A Bicentric Analysis

Purpose: In patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas the decision making depends on scaling the risk of malignancy with that of the surgical burden of a pancreatectomy. The aim of this study was to build a preoperative, disease-specific tool to predict surgical morbidity in surgery for IPMNs. Method: All resected IPMN at two Italian high-volume Institutions from 2012 to 2018 were eligible. Based on preoperative variables, logistic regression and classification tree analysis were applied to derive a predictive model identifying the risk of major morbidity (Clavien-Dindo >=3). Results: Among 524 included patients, 289 (55.2%) underwent pancreaticoduodenectomy (PD), 144 (27.5%) distal pancreatectomy (DP) and 91 (17.4%) total pancreatectomies (TP) with a diagnosis of main-duct (19%), branch-duct (12%) or mixed type (69%) IPMN. Postoperative pancreatic fistula rate and mortality were 11.8% and 3.5%, respectively. Ninety-eight (18.7%) patients developed major morbidity. Multivariate analysis revealed age, BMI and type of surgery to be independent predictors of major morbidity (all P< 0.05). The classification tree (AUC 0.70; CI 95% 0.63-0.77) segregated patients according to the type of surgery. Among DP, presence of preoperative diabetes identified two risk classes (5% and 25% of risk) for developing major morbidity, while among PD/TP, three different classes (15%, 20% and 36% of risk) were identified according to age and BMI. Conclusion: In presumed IPMNs, the disease-specific risk of major morbidity can be determined in the preoperative setting and used to personalize the possible surgical indication. The presence of diabetes and overweight tip the scale towards a less aggressive clinical management.

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.

Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm.

Intraductal papillary mucinous neoplasm (IPMN) is a precancerous lesion of pancreatic cancer. Although there are 4 types of IPMN, among which intestinal‐type IPMN is likely to progress into invasive cancer known as colloid carcinoma, no information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study was conducted to explore how the intestinal differentiation system is maintained during the tumor progression of intestinal‐type IPMN using surgical resection specimens. Results showed that Atoh1, a critical transcriptional factor for intestinal differentiation toward the secretory lineages of intestinal epithelial cells, was expressed in an invasive‐grade IPMN. To determine the function of Atoh1 in pancreatic cancer, we generated a pancreatic ductal adenocarcinoma (PDAC) cell line overexpressing Atoh1. In a xenograft model, we successfully induced an IPMN phenotype in PDAC cells via Atoh1 induction. Finally, for the first time, we discovered that GPA33 is expressed in intestinal‐type IPMN, thereby suggesting a novel target for cancer therapy. In conclusion, the intestinal differentiation system might be maintained during tumor progression of intestinal‐type IPMN. Further analysis of the function of Atoh1 in IPMN might be useful for understanding the molecular mechanism underlying the malignant potential during the tumor progression of IPMN.

Expression of CD117, CK17, CK20, MUC4, villin and mismatch repair deficiency in pancreatic intraductal papillary mucinous neoplasm

Among pancreatic intraductal papillary neoplasms, gastric, intestinal, and pancreatobiliary intraductal papillary mucinous neoplasm (IPMN), intraductal oncocytic papillary neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN) have been defined, differing regarding association with invasive carcinoma and prognosis. Immunohistochemistry (IHC) can help in the distinction of these neoplasms, but a proportion is unclassifiable using recommended markers. Hence, additional markers useful for the typing of pancreatic intraductal papillary neoplasms are needed. The reported frequencies of the different types of IPMNs in surgical series vary to some extent, and such data based on Danish patients are currently lacking. Besides, the role of mismatch repair (MMR) deficiency in these neoplasms has not been fully elucidated. We aimed to evaluate the frequency of different types of pancreatic intraductal papillary neoplasms in a Danish cohort. Furthermore, we aimed to examine the utility of CD117, CK17, CK20, MUC4, and villin as markers for their distinction, in addition to the recommended markers MUC1, MUC2, MUC5AC, MUC6 and CDX2, and to evaluate the frequency of MMR deficiency. We typed 40 consecutively resected pancreatic intraductal papillary neoplasms according to the WHO criteria from 2019. IHC for CD117, CDX2, CK17, CK20, MLH1, MSH2, MSH6, MUC1 (H23), MUC1 (Ma695), MUC2, MUC4, MUC5AC, MUC6, PMS2, and villin was performed and evaluated using a five-tiered semiquantitative scale. A subset of the tumours was examined with PCR for microsatellite instability (MSI). Most tumours were intestinal (40 %) and gastric (40 %) IPMNs, followed by pancreatobiliary (17 %) IPMNs and IOPN (3 %). All cases were MMR proficient. We found a higher expression of MUC4, CK20 and villin in intestinal compared to gastric IPMNs (p < 0.01, p < 0.001 and p < 0.001). MUC4 was more strongly expressed in intestinal compared to pancreatobiliary IPMNs, while the opposite was found for CK17 (p < 0.05 and p < 0.05). IOPN showed strong CD117 expression (score 4), while all gastric IPMNs were negative and 50 % and 29 % of intestinal and pancreatobiliary IPMNs only showed weak expression (score 1). Our data suggest that CK20, MUC4 and villin may aid in the identification of intestinal IPMNs, while CK17 and CD117 may aid in the identification of pancreatobiliary IPMNs and IOPN, in some cases. However, additional studies evaluating these markers in pancreatic intraductal papillary neoplasms are needed.

Intraductal papillary mucinous neoplasm complicated with intraductal bleeding in a young woman mimicked a cystic solid pseudo-papillary tumor: a case report

BackgroundThere are only 6 cases of intraductal papillary mucinous neoplasm (IPMN) complicated with intraductal hemorrhage have been reported in English literatures. All these 6 cases of IPMN occurred in the old people. The present rare case of IPMN complicated with intraductal hemorrhage occurred in a young woman, and mimicked a cystic solid pseudo-papillary neoplasm (SPN) on preoperative imaging findings.Case presentationA 29-year-old young woman complained of a sustained mild right upper quadrant abdominal pain. CT and MRI showed a lobulated, partly ill-defined cystic lesion located in the pancreatic head. Spotted calcification within cystic wall was seen on CT. The lesion was demonstrated as predominantly homogeneous hyperattenuation on CT and homogeneous high signal without decreased signal on fat suppression sequence on T1WI. After contrast administration, the cystic wall and septa of lesion was showed gradually mild to moderate degree of enhancement over time both on CT and MRI. No communication between lesion and the main duct was found on MRCP and the main pancreatic duct and common bile duct were not dilated. Considering patient’s age, gender and manifestations of lesion on CT and MRI (calcification, bleeding and gradually enhanced pattern), the present case mimicked as a cystic SPN. The lesion was pathologically confirmed a branch type IPMN after surgical resection.ConclusionWe propose that IPMN may need to be taken into account in the differential diagnosis when pancreatic cystic lesions occur in young women with bleeding, calcification, progressive enhancement of cystic wall and no communication with the main pancreatic duct.

Predictive Features of Malignancy in Branch Duct Type Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Meta-Analysis.

Simple SummaryCurrently, there are several guidelines that are widely used to establish the treatment strategy for branch duct type intraductal papillary mucinous neoplasms. Although there are some common grounds, there are discrepancies on which features they adopt, how much each feature is weighted, and how the features are combined. Furthermore, some of the features are based on lower level evidences or expert opinions. The aim of this meta-analysis was to investigate important clinical, radiological, and biochemical risk factors for malignancy and their impact as predictors. This study found symptom, size, cyst wall thickening, presence of mural nodule, change in main pancreatic duct caliber, lymphadenopathy, CA 19-9, and CEA as risk factors. Lymphadenopathy (odd ratio [OR]: 8.55), abrupt caliber change (OR: 7.41), and mural nodule (OR: 4.10) had the highest odd ratios. We expect the higher level evidences of this study to help shape better guidelines and reduce discrepancies among future guidelines.The current guidelines on branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) recommend various predictive features of malignancy as well as different treatment strategies. This study aimed to identify the risk factors for malignancy with higher level of evidence. A meta-analysis was performed on 40 literatures published between 2000 and 2019. These literatures included 6301 patients with pathologically proven IPMN. Malignancy was defined as high-grade dysplasia and invasive carcinoma. It was significantly associated with symptoms (odds ratio [OR] 1.35, confidence interval [CI] 1.01–1.79), size ≥ 3 cm (OR 1.90, CI 1.51–2.40), cystic wall thickening (OR 2.53, CI 1.50–4.27), mural nodule (OR 4.10, CI 3.38–4.97), main pancreatic duct dilatation (OR 2.98, CI 2.11–4.21), abrupt caliber change of the pancreatic duct (OR 7.41, CI 2.49–22.06), lymphadenopathy (OR 8.55, CI 3.25–22.51), elevated carbohydrate antigen 19-9 (OR 4.01, CI 2.55–6.28), and elevated carcinoembryonic antigen (OR 2.04, CI 1.60–2.61). Multilocular cysts and multiple cysts did not show a significant association with malignancy. This study examined the clinical, radiological, and biochemical features of BD-IPMN, often used as malignancy predictors according to the widely used guidelines. The results confirmed that all the features currently being used are valid.

分枝型膵管内乳頭粘液性腫瘍（BD-IPMN）を合併した，輪状膵に発生した膵頭部癌の1例

分枝型膵管内乳頭粘液性腫瘍（BD-IPMN）を合併した，輪状膵に発生した膵頭部癌の1例

Value of repeated cytology for intraductal papillary mucinous neoplasms of the pancreas with high risk potential of malignancy: Is it a promising method for monitoring a malignant transformation?

ObjectivesThe efficacy of and indications for cytological reexamination to detect malignant changes in branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) have not been studied in detail. We conducted a retrospective study to evaluate the efficacy and indications of cytological reexamination by using pancreatic juice (repeated cytology) for BD-IPMNs. MethodsForty-five patients who underwent repeated cytology after a diagnosis of benignancy by using initial cytology were recruited for this study. ResultsThirty-eight patients, excluding 7 patients with lack of surveillance period after the final cytology, were classified into Malignancy (n = 13) and Benignancy groups (n = 25) on the bases of the findings from resected specimens or changes in BD-IPMNs after repeated cytology. The sensitivity and specificity to detect malignant changes in BD-IPMNs by using repeated cytology were 62% and 100%, respectively. For the 12 patients with mural nodules (MNs) ≥ 5 mm (67% of them were malignant), the sensitivity was 50%, whereas, for the 26 patients without MNs ≥ 5 mm (19% of them were malignant), it was 80%. In addition, malignant changes in BD-IPMNs after initial cytology occurred in 62% of the patients with changes in the MNs and 27% of the patients with an increase in the cyst size. ConclusionRepeated cytology can play a role in the determination for surgery even after a diagnosis of benignancy by using initial cytology, especially for BD-IPMNs without MNs ≥5 mm. In addition, changes in the MNs or cyst size may be appropriate indications for repeated cytology.

Quality of indications in cystic lesions of the pancreas

Cystic tumors of the pancreas (PCN) have increasingly gained importance in the clinical routine as they are frequently diagnosed as an incidental finding due to the continuous improvement in cross-sectional imaging. A differentiation is made between non-neoplastic and neoplastic cysts, whereby the latter has a tendency to malignant transformation to avarying extent. Therefore, they can be considered as precursor lesions of pancreatic cancer (PDAC). In addition to a detailed patient history and examination, imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) with fine needle aspiration (FNA) are used for the differential diagnosis. The indications for surgical resection of these lesions are based on the current European guidelines from 2018; however, the content is not evidence-based but relies on knowledge and recommendations from experts. According to these consensus recommendations asymptomatic serous cystic neoplasms (SCN) are serous lesions with a low tendency for malignant transformation and can be monitored. In contrast resection is warranted for all mucinous cystic neoplasms (MCN) >4 cm and all solid pseudopapillary neoplasms (SPN). Intraductal papillary mucinous neoplasms (IPMN), which are differentiated into main duct (MD-IPMN) and branch duct type (BD-IPMN) IPMN based on the position in the pancreatic duct system, should be resected as MD-IPMN and mixed type (MT)-IPMN. The risk of malignant transformation in BD-IPMN is variable and depends on risk factors, which are defined clinically and by imaging morphology. The treatment management is therefore carried out on an individual basis following risk estimation. In order to quantify the quality of indications in PCN and thereby also contributing to optimized medical care, prospective long-term studies are urgently needed.

Epidemiology, clinical features and diagnostic work-up of cystic neoplasms of the pancreas: Interim analysis of the prospective PANCY survey

IntroductionA prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines. MethodsAn online data sheet was built. ResultsFifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up. ConclusionsThis prospective study offers a reliable real-life picture of the diagnostic work-up CPN.

Pure pancreatic hepatoid carcinoma: a surgical case report and literature review

BackgroundHepatoid carcinoma (HC) is an extra-hepatic neoplasm that shares the morphological and immunohistochemical features of hepatocellular carcinoma. Pancreatic HC exists as either pure or combined type. Pure pancreatic HC is extremely rare, with only a few cases reported in the literature to date. Because of the rarity of pure pancreatic HC, its clinical features including incidence, behavior, and prognosis remain unclear. We herein report the case of a 56-year-old man who developed pure pancreatic HC treated with surgical resection. We also include a review of the existing literature.Case presentationA 56-year-old male patient was admitted to our hospital after a pancreatic cyst was identified by abdominal ultrasonography on a comprehensive medical examination. Endoscopic ultrasound revealed a cystic mass measuring 13 mm in size in the pancreatic head and a low-density mass measuring 16 mm in size in the pancreatic tail, which was partially enhanced on contrast-enhanced ultrasound. Contrast-enhanced computed tomography (CT) revealed a branch duct type intraductal papillary mucinous neoplasm in the pancreatic head and an early enhanced nodule measuring approximately 10 mm in size in the pancreatic tail. Endoscopic ultrasound-guided fine-needle aspiration of the hypervascular tumor was performed. The hypervascular tumor was suspected to be a solid pseudopapillary neoplasm. Laparoscopic spleen-preserving distal pancreatectomy was performed. Histology was identical to hepatocellular carcinoma of the liver. Immunohistochemically, the tumor cells were positive for hepatocyte paraffin 1, and a canalicular pattern was confirmed on the polyclonal carcinoembryonic antigen staining. The patient was diagnosed with a moderately differentiated pancreatic HC. The patient was followed up without adjuvant chemotherapy, and there was no evidence of recurrence at 6 months post-operatively.ConclusionsWe present a case of moderately differentiated pure pancreatic HC. For the accurate preoperative diagnosis of pure pancreatic HC, biopsy is preferred to cytology or preoperative imaging studies such as CT. The prognosis of pure pancreatic HC depends on its differentiation.

3013 Fish Mouth Ampulla: Classic Main Duct Intraductal Papillary Mucinous Neoplasm

INTRODUCTION: Intraductal Papillary Mucinous Neoplasms (IPMNs) were first identified in 1982 and there have been increasing rates of diagnosis of IPMNs in recent years with the improvement of imaging modalities. Due to the indolent course of IPMNs, many patients may initially remain asymptomatic for many years. IPMNs should be acted on quickly after diagnosis as they can progress to malignancy. We present a case of a patient who presented with symptoms similar to pancreatitis but was found to have a main duct IPMN with the classic fish mouth appearance of the ampulla. CASE DESCRIPTION/METHODS: A 62-year-old male presented to an outside hospital with epigastric abdominal pain and nausea. RUQ Ultrasound revealed normal liver and gallbladder with heterogenous echotexture within an enlarged pancreas. Abdominal CT Scan revealed a low density heterogenous, contrast enhancing, possibly multicystic lesion at the uncinate process and near the pancreatic head measuring 3.6 × 3.6 cm with dilation of the pancreatic duct. MRCP revealed a dilated pancreatic duct at 6 mm and a cystic appearing pancreatic mass involving uncinate process and portion of the right pancreatic head concerning for intraductal papillary mucinous neoplasm. He was transferred to our facility for formal Gastroenterology evaluation. EGD was performed and revealed a markedly dilated ampulla with mucinous discharge, with classic “fish mouth” appearance. The pancreatic duct was diffusely dilated from the tail to ampulla, up to 17 mm in the head/neck. A cystic lesion measuring 41 × 35 mm adjacent to the main pancreatic duct extending to the uncinate was noted. FNA was performed and pathology confirmed the diagnosis of main duct IPMN. He successfully underwent a Whipple procedure. DISCUSSION: This case illustrates the importance of recognizing a classic endoscopic feature of main duct IPMN: the fish mouth ampulla of Vater. There are three types of IPMNs: main duct, side branch and mixed. MD-IPMNs have the most malignant potential of the three and should be acted on promptly with surgical referral for resection. Approximately 65% of MD-IPMNs are malignant, compared to 20% for side branch IPMNs. Due to the indolent course of IPMNs, many patients will remain asymptomatic for many years. Eventually, patients will present with symptoms similar to pancreatitis. Despite the lack of clear consensus for management of pancreatic cystic lesions between multiple guidelines, all agree that MD-IPMNs should be surgically resected due to the high malignant potential.

Main duct and mixed type intraductal papillary mucinous neoplasms without enhancing mural nodules: Duct diameter of less than 10 mm and segmental dilatation of main pancreatic duct are findings support surveillance rather than immediate surgery

ObjectiveThe guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMNs) recommend surgical resection of all main-duct (MD) and mixed-type IPMNs in surgically fit patients. We conducted this study to identify the rates of high-grade dysplasia (HGD) and invasive carcinoma according to the morphological features of the main pancreatic duct (MPD) in patients with MD and mixed IPMN. MethodsWe performed a retrospective study of 259 patients with histologically proven MD and mixed-type IPMNs who underwent surgery at six academic institutions. ResultsThe rate of HGD and invasive carcinoma was 11.1% (24/216) in patients without enhancing mural nodules (MNs) and 69.8% (30/43) in patients with MNs. Multivariate analysis showed that MPD diameter of ≥10 mm [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.155–5.505; P = 0.02], diffuse MPD dilatation (OR, 3.2; 95% CI, 1.152–8.998; P = 0.02), and presence of enhancing MNs in MPD (OR, 9.6; 95% CI, 3.928–23.833, P < 0.0001) were significant predictors of HGD and invasive carcinoma. Of the 216 patients without enhancing MNs, 79 patients (36.6%) having both segmental MPD dilatation and MPD diameter of <10 mm showed significantly lower rates of HGD and invasive carcinoma (3/79, 3.8%) than patients having both diffuse MPD dilatation and MPD diameter ≥10 mm (9/36, 25%, P = 0.001). ConclusionsMD and mixed-type IPMNs having segmental MPD dilatation with MPD dilation <10 mm and no enhancing MNs on imaging showed a significantly lower rate of HGD and invasive carcinoma, and watchful follow-up instead of immediate surgical resection might be possible in these patients.

Safety of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions: A single-center experience of 214 patients

Endoscopic ultrasound-guided ethanol ablation (EUS-EA) for pancreatic cystic lesions (PCLs) has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery. The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event (AE). A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital. The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA. The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain. A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows: serous cystic neoplasm (32.2%), mucinous cystic neoplasm (26.6%), branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) (29.4%), and pseudocyst (11.7%). Three patients (1.4%) experienced severe AEs. Overall, AEs occurred in 71 (33.2%) patients. BD-IPMN (OR: 2.87; 95% CI: 1.05-7.84; P = 0.040), multilocular cysts (OR: 3.59; 95% CI: 1.09-11.85; P = 0.036), suspected ethanol leakage during procedure (OR: 10.68; 95% CI: 1.98-57.53; P = 0.006), and sticky cystic fluid (OR: 3.83; 95% CI: 1.20-12.24; P = 0.024) were predictive factors for post-procedural acute pancreatitis. PCLs of uncinate process (OR: 2.99; 95% CI: 1.22-7.35; P = 0.017) and PCLs with exophytic portion (OR: 3.70; 95% CI: 1.96-7.01; P<0.001) were predictive factors for post-procedural abdominal pain. EUS-EA is a safe procedure with a very low rate of severe AEs. It seems possible to predict the AEs according to the features of the procedure and PCLs.

Expression of Matrix Metalloproteinases in Intraductal Papillary Mucinous Neoplasm of the Pancreas.

Intraductal papillary mucinous neoplasm (IPMN) has a variety of histological and morphological appearances. Matrix metalloproteinases (MMPs) have been considered to be associated with tumor progression or poor prognosis. The aim of this study was to elucidate the molecular basis of IPMN variation in different types of lesions. The expression of MMP-1,2,7,9 in 51 cases of IPMN were investigated. The MMP score was calculated as the sum of the score of staining distribution and the score of the intensity staining. MMP scores were correlated with histological grade, histological subtype, and type of invasion. MMP high expression groups (MMP score ≥5) had worse prognosis than low-expression groups. MMP expression varied between different types of IPMN, a result supporting differences in molecular basis of malignancies. These considerations may be helpful for optimal management or treatment according to various types of IPMN.

Endoscopic Ultrasound-guided Needle-based Confocal Laser Endomicroscopy: Appraisal Concerning In-vivo Imaging of Intraductal Papillary Mucinous Neoplasm

Differential diagnosis between benign and potentially malignant cystic pancreatic lesions may be difficult. Previously we have compared cyst fluid serine protease inhibitor Kazal type I (SPINK1) with some traditionally used tumour markers (amylase, CEA, Ca19-9) and found that it may be a new promising maker in the differential diagnosis of cystic pancreatic lesions. In the present study, we focused on cyst fluid SPINK1 levels in benign and potentially malignant cystic pancreatic lesions.Sixty-one patients operated on for cystic pancreatic lesion in Tampere University Hospital, Finland and in Verona University Hospital, Italy, were included. Cyst fluid was aspirated during surgery, stored at −70 °C, and analysed with immunofluorometric assay for SPINK1. The final diagnosis was acute pancreatitis with fluid collection (Acute FC) in 4 patients, chronic pseudocyst (PS) in 17 patients, serous cystadenoma (SCA) in 7 patients, mucinous cystadenoma (MCA) in 21 patients and intraductal papillary-mucinous neoplasm (IPMN) in 12 patients (9 main/mixed duct type and 3 branch duct type).The acute FC patients had high SPINK1 levels. Among chronic cysts, SPINK1 levels were significantly higher in patients with potentially malignant cysts (main/mixed duct IPMN and MCA) than with benign cysts (side branch IPMN and SCA), (median and range, [480 (13–3602) vs. 18 (0.1–278) μg/L]; p < 0.0001). In the subcohort of 24 patients with <3 cm chronic cyst, cyst fluid SPINK 1 levels were significantly lower in SCA or side branch IPMN (3 [2–116] μg/L) than in main duct IPMN or MCA (638 [66–3602] μg/L; p = 0.018). The best sensitivity and specificity to differentiate any size MCA or main/mixed type IPMN from SCA or side branch IPMN were 85% and 84% (AUC 0.94; cut-off value 118 μg/L). The best sensitivity and specificity to differentiate <3 cm MCA or main duct IPMN from SCA or side branch IPMN were 93% and 89% (AUC 0.98; cut-off value 146 μg/L).Cyst fluid SPINK1 may be a possible marker in the differential diagnosis of benign and potentially malignant cystic pancreatic lesions.

Age and cystic size are associated with clinical impact of endoscopic ultrasonography-guided fine-needle aspiration on the management of pancreatic cystic neoplasms

Objectives: The clinical impact of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in managing pancreatic cystic neoplasms (PCNs) remains controversial. The aim of this study was to identify which patients with PCNs would benefit from EUS-FNA.Methods: A retrospective study was performed on patients with PCNs who underwent EUS-FNA between January 2009 and June 2018. A discordant or a consistent diagnosis after EUS-FNA was analyzed and was correlated with the clinical demographic data and cystic features. Predictors of the change in the diagnosis after EUS-FNA were analyzed.Results: One hundred eighty-eight cases of PCNs were analyzed. EUS-FNA changed the diagnosis in 45.7% of all patients with PCNs and 54.5% patients with presumed branch ductal type intraductal papillary mucinous neoplasm (BD-IPMN) and impacted the recommendation in 35.6% of patients with PCNs and 50.5% patients with BD-IPMN. Patients with a discordant diagnosis after EUS-FNA were younger in age (54.8 ± 12.6 vs. 61.2 ± 14.2; p=.037) and had a cyst size larger than 3 cm than patients with a consistent diagnosis after EUS-FNA. The only worrisome feature (WF) that differed between patients with a discordant and a consistent diagnosis after EUS-FNA was the main pancreatic duct (MPD) between 5 and 9 mm (p=.013). In multivariate analysis, a cyst size >3 cm and age were independent predictors of diagnostic changes after EUS-FNA (OR: 5.33, 95% CI: 1.79–15.88, p = .003; OR: 0.96, 95% CI: 0.93–0.99, p = .031).Conclusions: EUS-FNA made a significant change in the management of nearly half of the patients with PCNs, especially in younger patients and in patients with a cyst size larger than 3 cm.