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Background & Aims: Understanding the burden of pancreatic cystic lesions (PCLs) in the general population is important for clinicians and policymakers. In this systematic review, we sought to estimate the global prevalence of PCLs using magnetic resonance imaging (MRI) and to investigate factors that contribute to its variation., Methods: We searched MEDLINE, EMBASE, and Cochrane Central, from database inception through February 2023. We included full-text articles that reported the prevalence of PCLs using MRI in the general population. A proportional meta-analysis was performed, and the prevalence of PCLs was pooled using a random-effects model., Results: Fifteen studies with 65,607 subjects were identified. The pooled prevalence of PCLs was 16% (95% confidence interval [CI], 13%-18%; I 2  = 99%), most of which were under 10 mm. Age-specific prevalence of PCLs increased from 9% (95% CI, 7%-12%) at 50 to 59 years, to 18% (95% CI, 14%-22%) at 60 to 69 years, 26% (95% CI, 20%-33%) at 70 to 79 years, and 38% at 80 years and above (95% CI, 25%-52%). There was no difference in prevalence between sexes. Subgroup analysis showed higher PCL prevalence when imaging findings were confirmed by independent radiologist(s) (25%; 95% CI, 16%-33%) than when chart review alone was used (5%; 95% CI, 4%-7%; P < .01). There was no independent association of PCL prevalence with geographic location (Europe, North America, or Asia), MRI indication (screening vs evaluation of non-pancreatic pathology), enrollment period, sample size, magnet strength (1.5 vs 3 tesla), and MRI sequence (magnetic resonance cholangiopancreatography vs no magnetic resonance cholangiopancreatography)., Conclusion: In this systematic review, the global prevalence of PCLs using a highly sensitive noninvasive imaging modality ranged between 13% and 18%., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5-57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance.

This article reviews the types of pancreatic cysts encountered in Radiologic practice. It summarizes the malignancy risk of each of the following: serous cystadenoma, mucinous cystic tumor, intraductal papillary mucinous neoplasm main duct and side branch, and some miscellaneous cysts such as neuroendocrine tumor and solid pseudopapillary epithelial neoplasm. Specific reporting recommendations are given. The choice between radiology follow-up versus endoscopic analysis is discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pancreatic cystic lesions (PCLs) are a common incidental finding on cross-sectional imaging. Given the high signal to noise and contrast resolution, multi-parametric capability and lack of ionizing radiation, magnetic resonance imaging (MRI) has become the non-invasive method of choice to predict cyst type, risk stratify the presence of neoplasia, and monitor changes during surveillance. In many patients with PCLs, the combination of MRI and the patient's history and demographics will suffice to stratify lesions and guide treatment decisions. In other patients, especially those with worrisome or high-risk features, a multimodal diagnostic approach that includes endoscopic ultrasound (EUS) with fluid analysis, digital pathomics, and/or molecular analysis is often necessary to decide on management options. The application of radiomics and artificial intelligence in MRI may improve the ability to non-invasively stratify PCLs and better guide treatment decisions. This review will summarize the evidence on the evolution of MRI for PCLs, the prevalence of PCLs using MRI, and the MRI features to diagnose specific PCL types and early malignancy. We will also describe topics such as the utility of gadolinium and secretin in MRIs of PCLs, the limitations of MRI for PCLs, and future directions.

Background and Aims: Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period., Methods: We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality., Results: Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths)., Conclusions: Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objectives: To evaluate the value of MRI in differentiating benign (b-MCN) and malignant (m-MCN) MCN. European guidelines suggest that certain mucinous cystic neoplasms (MCN) of the pancreas can be conservatively managed., Methods: A retrospective single-center study of consecutive patients with resected MCN. MRIs were independently reviewed by two readers blinded to the pathological results. The authors compared b-MCN (i.e., mucinous-cystadenoma comprising high-grade dysplasia (HGD)) and m-MCN (i.e., cystadenocarcinoma)., Results: Sixty-three patients (62 women [98%]) with 63 MCN (6 m-MCN, 2 HGD) were included. m-MCN tumors had a tendency to be larger than b-MCN (median 86 [25-103] vs. 45 [17-130] mm, p = .055). The combination of signal heterogeneity on T2-weighted imaging, wall thickness ≥ 5 mm, the presence of mural nodules ≥ 9 mm, and enhancing septa had an area under the ROC curve of 0.97 (95% CI 0.91-1.00) for the diagnosis of m-MCN. A total of 24 (37%), 20 (32%), 10 (16%), 5 (8%), and 4 (6%) out of 63 MCNs showed 0, 1, 2, 3, and 4 of these features, respectively. The corresponding rate of m-MCN was 0%, 0%, 10%, 20%, and 100%, respectively, with a good-to-excellent inter-reader agreement. Patterns with a high NPV for m-MCN included an absence of enhancing septa or walls (NPV 97% and 100%, respectively), wall thickness < 3 mm (NPV 100%), and no mural nodules (NPV 100%)., Conclusions: A combination of 4 imaging features suggests malignant MCN on MRI. On the other hand, visualization of a thin non-enhancing wall with no mural nodules suggests benign MCN., Key Points: • A heterogenous signal on T2-weighted MRI, a ≥ 5-mm-thick wall, mural nodules ≥ 9 mm, and/or enhancing septa suggest malignant MCNs. • A thin non-enhancing wall with no mural nodules suggests benign MCNs. • MRI should be performed in the pre-therapeutic evaluation of MCN to help determine the therapeutic strategy in these patients., (© 2021. European Society of Radiology.)

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification. Endoscopic ultrasound-guided fine needle biopsy showed a proliferation of epithelial cells with fibrovascular cores. An immunohistochemical stain for p40 was positive in the lesional cells. A distal pancreatectomy revealed a unilocular, cystic, well-circumscribed, soft and friable mass measuring 1.0 × 1.0 × 0.8 cm. Histologically, the cyst was lined by nonkeratinizing stratified squamous epithelium with a complex papillary architecture, filling the cyst lumen. Molecular sequencing revealed a KRAS G12V missense mutation. While the lesion shared some histologic features with the previously described "squamoid cyst of the pancreatic ducts", the complex papillary architecture and presence of a KRAS mutation are unique to the entity we describe herein and we propose the name "intraductal papillary squamous neoplasm of the pancreas." Reporting the cytomorphologic features of this novel entity may help in identification of similar lesions and understanding of the clinicopathologic significance., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Guanine nucleotide-binding protein, alpha stimulating ( GNAS ) mutations are characteristic of intraductal papillary mucinous neoplasms (IPMNs). Pancreatic ductal adenocarcinomas (PDACs) harboring GNAS mutations originate in IPMNs. GNAS is a complex imprinted locus that produces five transcripts regulated by differential methylated regions, NESP55 , GNASAS , GNASXL , GNAS1A , and GNAS ., Aim: To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic cysts., Methods: GNAS locus methylation was analyzed in archival pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound with fine-needle aspiration by methylation specific-multiplex ligation dependent probe amplification. Results were normalized and analyzed using Coffalyser.Net software., Results: Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for KRAS and GNAS mutations were studied. The final diagnoses were surgical (11) and clinicopathological (41), including 30 benign cysts, 14 pre-malignant cyst, and eight malignant cysts. Methylation changes at NESP55, GNASAS, GNAS1A , and especially GNASXL were more frequent in malignant cysts, and NESP55 and GNASAS were useful for diagnosis. A combined variable defined as " GNAS locus methylation changes" was significantly associated with malignancy (6/8 malignant cysts and only 2/20 benign cysts) and improved classification. Hypermethylation in both maternally ( NESP55 ) and paternally ( GNASXL ) derived promoters was found in 3/3 PDACs., Conclusion: This is the first study to identify methylation changes in the GNAS locus, improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC., Competing Interests: Conflict-of-interest statement: The authors declare no potential financial interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Lymphoepithelial cysts (LECs) are extremely rare nonmalignant cysts of the pancreas. Asymptomatic LECs are managed conservatively, but symptomatic LECS have traditionally been managed with surgical resection. We report the first case of symptomatic infected LEC of the pancreas successfully managed with EUS guided endoscopic drainage with lumen-apposing metal stent. We also review the relevant literature and discuss the diagnosis and management of this rare cyst of the pancreas.

Background: The differential diagnosis of pancreatic cystic lesions (PCLs) is an increasingly common clinical challenge. Confocal laser endomicroscopy (CLE) may differentiate PCLs by imaging of the cyst wall. However, clinical experience is still limited, and better image definition and characterization of the cyst wall in a spectrum of cysts are needed. This experimental study aimed to expose detailed imaging characteristics of PCLs by CLE., Methods: Patients who underwent surgery of a PCL were enrolled. During surgery, intravenous fluorescein (2.5 ml of 10%) was injected just prior to the ligation of blood vessels supplying the pancreas. The freshly excised specimens were transected along the long axis to fully expose the luminal surface. A Gastroflex-UHD CLE probe (pCLE) was used manually to acquire images directly from the surface of cyst wall. The specimen subsequently underwent cross-sectional histology. All recorded data were analyzed by two investigators for predefined and original image findings of PCLs., Results: Ten cases were recruited into the study. All patients underwent surgery because of a mucinous cyst with worrisome features or a symptomatic PCL. Imaging was successful in all patients and differently shaped papillary projections (PP) were visualized in eight patients. Pathological examination of those patients confirmed 6 cases with Intraductal Papillary Mucinous Neoplasm (IPMN) and 2 cases with Mucinous Cystic Neoplasm (MCN). In two patients with serous cystadenoma, typical vascular network was visualized in one patient, and microcystic structures in the other. Three of the IPMNs were malignant. The loss of papillary margin integrity and significant fragmentation together with irregularity was detected in malignant IPMNs by CLE., Conclusions: Pancreatic cyst epithelial wall can be visualized successfully by pCLE in ex vivo surgical specimens. Different papillary projections have been seen in all cases of IPMNs and MCNs. CLE has potential for identifying IPMN subtypes and for grading dysplasia.

Background: The accurate diagnosis of cystic neoplasms of the pancreas (CNP) with current diagnostic methods is limited. Endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) is a new technique which can obtain images from the cyst wall during EUS-fine needle aspiration (EUS-FNA). The aim of this study was to assess the safety, feasibility, and diagnostic value of nCLE for CNP., Methods: Patients who underwent EUS-FNA to evaluate a CNP larger than 2 cm were enrolled. The cyst was punctured with 19-G FNA needle preloaded with an nCLE probe. The images from different areas of the cyst wall were recorded. Using the final diagnosis defined by surgery or EUS-FNA cyst fluid analysis, the accuracy of the confocal images was defined., Results: The procedure and image acquisition was successful in 18 of the 20 patients. Predefined typical structures for mucinous cysts were visualized in 8 of 12 (66%) cysts but none of the non-mucinous cysts. The superficial vascular network which is a typical finding of serous cysts was observed in 2 of 3 patients. The sensitivity, specificity, and diagnostic accuracy of the findings of epithelial structures by nCLE were 66, 100, and 80%, respectively, for a mucinous cyst diagnosis. All patients tolerated the procedure well, and no adverse effects were determined., Conclusion: nCLE was found to be safe and feasible with high technical success, in this pilot study. With an overall accuracy of 80%, it has the potential to contribute to the diagnosis of CNP with specific imaging.

Background and Aim: Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN)., Methods: Prospectively collected endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed retrospectively for GNAS and KRAS mutations and CEA results. IPMN were histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA, cytology). Performance characteristics of GNAS added to KRAS and CEA for the diagnosis of IPMN were calculated., Results: The study population consisted of 197 patients with cyst fluid test results. Cysts were histologically classified in 33 patients and by clinical criteria in 164 patients. The IPMN group included 108 patients and the non-IPMN group included 89 patients. GNAS was positive in 51 patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to 79.1% (P > 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4% to 80.7 % (P < 0.05), but did not achieve a diagnostic superiority to KRAS testing alone (80.7% vs 76.6%, P > 0.05). The diagnostic accuracy of the triple combination was significantly better than all single tests (P < 0.05)., Conclusion: GNAS mutation is a highly specific test for IPMN. When GNAS testing is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is achieved., (© 2016 Japan Gastroenterological Endoscopy Society.)

Aim: To identify the current indications and outcomes of total pancreatectomy at a high-volume center., Methods: A single institutional retrospective study of patients undergoing total pancreatectomy from 1995 to 2014 was performed., Results: One hundred and three patients underwent total pancreatectomy for indications including: Pancreatic ductal adenocarcinoma ( n = 42, 40.8%), intraductal papillary mucinous neoplasms ( n = 40, 38.8%), chronic pancreatitis ( n = 8, 7.8%), pancreatic neuroendocrine tumors ( n = 7, 6.8%), and miscellaneous ( n = 6, 5.8%). The mean age was 66.2 years, and 59 (57.3%) were female. Twenty-four patients (23.3%) underwent a laparoscopic total pancreatectomy. Splenic preservation and portal vein resection and reconstruction were performed in 24 (23.3%) and 18 patients (17.5%), respectively. The 90 d major complications, readmission, and mortality rates were 32%, 17.5%, and 6.8% respectively. The 1-, 3-, 5-, and 7-year survival for patients with benign indications were 84%, 82%, 79.5%, and 75.9%, and for malignant indications were 64%, 40.4%, 34.7% and 30.9%, respectively., Conclusion: Total pancreatectomy, including laparoscopic total pancreatectomy, appears to be an appropriate option for selected patients when treated at a high-volume pancreatic center and through a multispecialty approach., Competing Interests: Conflict-of-interest statement: Dr. Zakaria, Dr. Stauffer, Dr. Raimondo, Dr. Woodward, Dr. Wallace and Dr. Asbun report no biomedical financial interests or potential conflict of interest.