Endoscopic Ultrasound-Guided Ablation of Pancreatic Mucinous Cysts.

Endoscopic ultrasound (EUS) has rapidly evolved from a diagnostic to a therapeutic tool with applications for various pancreaticobiliary diseases. As part of this evolution, EUS-guided chemoablation for neoplastic pancreatic cysts is developing as a minimally invasive treatment option for appropriately selected mucinous cysts, which can spare patients major resective surgery and may reduce progression to pancreatic cancer. Chemotherapeutic cyst ablation has demonstrated encouraging complete resolution rates, while an alcohol-free chemoablation protocol has demonstrated a significant decrease in adverse events without a compromise to complete ablation rates when compared with previous alcohol-based protocols. Most pancreatic cysts are small, low risk, and best managed by surveillance per accepted guidelines. Cysts with features suggestive of overt malignancy are best discussed by a multidisciplinary committee, and surgery is considered if appropriate. However, for patients in the middle ground with cysts that are structurally suitable for chemoablation, alcohol-free chemoablation has been shown to allow effective, safe, and durable results especially for those who are not ideal operative candidates. EUS-guided alcohol-free chemoablation is promising and continues to evolve; however, as a relatively novel treatment option it has areas of uncertainty that will require further investigation and development.

The Incidental Pancreatic Cyst: When to Worry About Cancer.

Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic lesions, determining when to recommend aggressive actions such as surgical resection or endoscopic ultrasound with sampling is difficult. In this article, we review the common types of cystic pancreatic lesions including serous cystadenoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm with imaging examples of each. We also discuss high-risk or worrisome imaging features that warrant a referral to a surgeon or endoscopist and provid several examples of these features. These imaging features adhere to the latest guidelines from the International Consensus Guidelines, American Gastroenterological Association (2015), American College of Gastroenterology (2018), American College of Radiology (2010, 2017), and European Guidelines (2013, 2018). Our focused article addresses the imaging dilemma of managing incidental cystic pancreatic lesions, weighing the options between imaging follow-up and aggressive interventions.

[Premalignant cystic neoplasms and neuroendocrine tumors of the pancreatic head-Is the Kausch-Whipple resection an adequate treatment?] / Prämaligne, zystische Neoplasien und neuroendokrine Tumoren des Pankreaskopfes ­ Ist die Kausch-Whipple-Resektion eine adäquate Therapie?

Currently, the most frequently used surgical treatment for symptomatic, benign, premalignant cystic and neuroendocrine neoplasms of the pancreatic head is the Whipple procedure or pylorus-preserving pancreatoduodenectomy (PD). However, when performed for treatment of benign tumors, PD is a multiorgan resection involving loss of pancreatic and extrapancreatic tissue and functions. PD for benign neoplasm is associated with the risk of considerable early postoperative complications and an in-hospital mortality of up to 5%. Following the Whipple procedure a new onset of diabetes mellitus is observed in 14-20% and new exocrine insufficiency in 25-45%, leading to metabolic dysfunction and impairment of quality of life persisting after resection of benign tumors. Symptomatic neoplasms are indication for surgery. Patients with asymptomatic pancreatic tumors are treated according to the criteria of surveillance protocols. The goal of surgical treatment for asymptomatic patients is, according to the guideline criteria, interruption of the surveillance program before the development of an advanced stage cancer associated with the neoplasm. Tumor enucleation and duodenum-preserving pancreatic head resection, either total or partial, are parenchyma-sparing resections for benign neoplasms of the pancreatic head. The first choice for small tumors is enucleation; however, enucleation is associated with an increased risk of pancreatic fistula B + C following pancreatic main duct injury. Duodenum-preserving total or partial pancreatic head resection has the advantage of low postoperative surgery-related complications, a mortality of < 0.5% and maintenance of the endocrine and exocrine pancreatic functions. Parenchyma-sparing pancreatic head resections should replace classical Whipple procedures for neoplasms of the pancreatic head.

[Applications of Artificial Intelligence in Pancreatic Cystic Lesion Imaging].

As the detection rate of pancreatic cystic lesions(PCL)increases,artificial intelligence(AI)has made breakthroughs in the imaging workflow of PCL,including image post-processing,lesion detection,segmentation,diagnosis and differential diagnosis.AI-based image post-processing can optimize the quality of medical images and AI-assisted models for lesion detection,segmentation,diagnosis and differential diagnosis significantly enhance the work efficiency of radiologists.This article reviews the application progress of AI in PCL imaging and provides prospects for future research directions.

Natural history and growth prediction model of pancreatic serous cystic neoplasms.

OBJECTIVE: Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical decision making of determining need for surgical resection. METHODS: Utilizing a prospectively maintained pancreatic cyst database from a single institution, patients with SCNs were identified. Diagnosis confirmation included imaging, cyst aspiration, pathology, or expert opinion. Cyst size diameter was measured by radiology or surgery. Patients with interval imaging ≥3 months from diagnosis were included. Flexible restricted cubic splines were utilized for modeling of non-linearities in time and previous measurements. Model fitting and analysis were performed using R (V3.50, Vienna, Austria) with the rms package. RESULTS: Among 203 eligible patients from 1998 to 2021, the mean initial cyst size was 31 mm (range 5-160 mm), with a mean follow-up of 72 months (range 3-266 months). The model effectively captured the non-linear relationship between cyst size and time, with both time and previous cyst size (not initial cyst size) significantly predicting current cyst growth (p < 0.01). The root mean square error for overall prediction was 10.74. Validation through bootstrapping demonstrated consistent performance, particularly for shorter follow-up intervals. CONCLUSION: SCNs typically have a similar growth rate regardless of initial size. An accurate predictive model can be used to identify rapidly growing outliers that may warrant surgical intervention, and this free model (https://riskcalc.org/SerousCystadenomaSize/) can be incorporated in the electronic medical record.

Performance of Intracystic Glucose Measurement for the Characterization of Pancreatic Cystic Lesions.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is essential for the classification of pancreatic cystic lesions (PCLs). Recently, intracystic glucose has been suggested as an alternative to carcinoembryonic antigen (CEA) level as a predictor of mucinous cystic lesions (M-PCLs). This study aims to evaluate the diagnostic performance of intra-cystic glucose in distinguishing between M-PCLs and non M-PCLs (NM-PCLs) and to analyze the possibility of on-site glucose measurement with a standard glucometer. METHODS: Patients with PCLs submitted to EUS-FNA with simultaneous intracystic glucose measurement between 2017 and 2022 were included. The diagnostic performance of glucose versus CEA for the differentiation between M-PCLs and NM-PCLs was compared to a final diagnosis based on the analysis of surgical specimen, intracystic biopsy or, if this data was unavailable, multidisciplinary evaluation. A cut-off of <50 mg/dL was used for the diagnosis of MCLs. Additionally, the agreement between on-site glucose determination with a standard glucometer and laboratory glucose measurement was assessed. RESULTS: Mucinous lesions accounted for 56% of all PCLs. The median values of glucose and CEA for M-PCLs were 18 mg/dL and 286 ng/mL, respectively. Intracystic glucose had a sensitivity and specificity of 93.2% and 76.5%, respectively, for the diagnosis of MCLs (versus 55.6% and 87.5%, respectively, for CEA). The area under the curve was 0.870 for on-site glucose (versus 0.806 for CEA). An excellent correlation was observed between on-site and laboratory glucose measurement (ρ=0.919). CONCLUSIONS: The measurement of intracystic glucose showed superior performance compared with CEA in distinguishing between M-PCLs and NM-PCLs, with excellent correlation between on-site and conventional lab glucose measurement. Thus, on-site intracystic glucose appears to be an excellent biomarker for the characterization of PCLs due to its low cost, high availability, and the need for a minimal cyst fluid volume for its determination.

Pancreatic Cysts Greater Than 1 cm Are Associated With an Increased Risk for Developing Pancreatic Cancer in Individuals From Pancreatic-Cancer Prone Kindreds Undergoing Surveillance.

BACKGROUND: The International Cancer of the Pancreas Screening Consortium recommended annual imaging for individuals at increased risk for developing a pancreatic ductal adenocarcinoma (PDAC) who did not have concerning pancreatic findings or a cyst <3 cm without worrisome features. We aimed to determine if 3-cm cyst size accurately predicted advanced precursor lesions in high-risk individuals undergoing surveillance. METHODS: Imaging for high-risk individuals (HRIs) undergoing PDAC surveillance from 2007 to 2021 was reviewed and pancreatic abnormalities were recorded including dominant cyst size and number of cysts. Subjects were excluded if they had the following: (1) no follow-up imaging after baseline, (2) solid lesion at baseline, or (3) development of solid lesion without having cyst on prior imaging. RESULTS: Five of the 77 HRIs found to have a cystic lesion on surveillance developed a PDAC: 3 with cystic lesion >1 cm as compared with only 2 of 67 HRIs with cystic lesions <1 cm (P < 0.05). None of these cysts developed worrisome findings and 4/5 PDACs did not arise from visualized cystic precursor lesion. CONCLUSIONS: Patients with a cyst ≥1 cm were at increased risk for developing PDAC compared with patients with cyst <1 cm. Pancreatic ductal adenocarcinoma usually did not arise from a recognized cystic lesion.

Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions.

Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1ß) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1ß, glucose, and CEA, and serum for Ngal and IL-1ß. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1ß and serum Ngal made no diagnostic contribution.

Pancreatic cyst prevalence and detection with photon counting CT compared with conventional energy integrating detector CT.

PURPOSE: To calculate the prevalence of pancreatic cysts on photon counting CT (PCCT) and compare with that of 128-slice conventional energy-integrating detector CT (EIDCT). METHOD: A retrospective single institution database search identified all contrast-enhanced abdominal CT examinations performed at an outpatient facility that has both a PCCT and EIDCT between 4/11/2022 and 7/26/2022. The presence and size of pancreatic cysts were recorded. In patients with PCCT reported pancreatic cysts, prior CT imaging (EIDCT) was reviewed for reported pancreatic cysts. Fisher's exact test was used to compare the pancreatic cyst detection rate for PCCT and EIDCT. Wilcoxon rank sum test was used to compare cyst size and patient age. A p <.05 indicated statistical significance. RESULTS: 2494 patients were included. Our pancreatic cyst detection rate was 4.9 % (49/1009) with PCCT and 3.0 % (44/1485) for EIDCT (p =.017). For CT angiograms, pancreatic cysts were detected in 6.6 % (21/319) with PCCT and 0.0 % (0/141) with EIDCT (p <.001). Pancreatic cyst detection rate was not statistically different for portal venous, enterography, renal mass, pancreas, 3-phase liver, or venogram protocols (all p >.05). Mean[SD] pancreatic cyst size was 13.7[9.7]mm for PCCT and 15.3[14.7] for EIDCT (p =.95). 55.1 % (27/49) of PCCT and 61.4 % (27/44) of EIDCT that described pancreatic cysts had prior contrast-enhanced EIDCTs. Of these, 40.7 % (11/27) of PCCT and 14.8 % (4/27) of EIDCT described pancreatic cysts were not previously reported (p =.027). CONCLUSIONS: Photon-counting CT afforded greater pancreatic cyst detection than conventional energy-integrating detector CT, particularly with CT angiograms.

[A Case of Lymphoepithelial Cyst of the Pancreas for Which Malignancy Could Not Be Ruled Out Difficult Preoperative Diagnosis].

Lymphoepithelial cyst(LEC)of the pancreas is a relatively rare benign cystic disease of the pancreas. In this report, we describe a case of LEC in which a malignant tumor could not be ruled out by preoperative diagnosis and surgery was performed. The patient was a 72-year-old man. A simple CT scan of the chest and abdomen performed as a follow-up for another disease incidentally revealed a mass in the pancreatic tail. Enhanced CT of the abdomen showed a tumor approximately 3 cm in size at the pancreatic tail with no contrast effect. MRCP showed moderate signal on T2WI, high signal on T1WI, and high signal on T2WI on some cysts inside the pancreas. PET-CT showed slight uptake of FDG. Both tumor markers CEA and CA19-9 were normal. Therefore, malignant disease such as pancreatic IPMC could not be ruled out, and laparoscopic distal pancreatectomy plus splenectomy was performed. The pathology results showed a diagnosis of pancreatic lymphoepithelial cyst with slight differentiation into sebaceous gland.

Diagnosis and management of pancreatic cystic lesions for the non-gastroenterologist.

Although most pancreatic cystic lesions do not progress to cancer, they create concern for patients and their primary care physicians. The lack of consensus guidelines on diagnosis and surveillance of these lesions can lead to a management conundrum. We review current guidelines on diagnosis and management.

[Histopathologic diagnosis of solid and cystic pancreatic lesions with a focus on ductal adenocarcinoma : A vademecum for daily practice]. / Histopathologische Diagnostik von soliden und zystischen Pankreasläsionen mit Hauptaugenmerk auf dem duktalen Adenokarzinom : Ein Vademecum für den Alltag.

Pancreas pathology is constantly evolving and can present various challenges for pathologists. This paper is focused on providing helpful hints for daily routine diagnostics. During histopathological analysis of pancreas biopsies, pancreatic ductal adenocarcinoma must be distinguished not only from other solid neoplasms, but especially from its mimicker, autoimmune pancreatitis. This can be achieved by a systematic workup following clear diagnostic criteria. When analyzing samples from cystic pancreatic lesions, mucin-producing neoplasms must be detected due to their role as pancreatic cancer precursors; molecular analyses can help considerably with their detection and distinction. During frozen section examination, evaluation of the pancreatic neck margin and analysis of unclear lesions of the liver are two important tasks, which are explained further in this article. A special challenge is the evaluation of neoadjuvant treated pancreatic cancer, which requires a detailed macroscopic and microscopic workup. Finally, current advances in precision oncology and emerging approaches for pancreatic cancer within this field are discussed. With the advancement of technical possibilities and their increasingly broad implementation, the classification systems in pancreatic pathology will continue to gain in complexity, but also in accuracy.

Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review.

OBJECTIVE: Elevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20 years of additional data and reassesses the diagnostic performance of CEA for differentiating mucinous from non-mucinous cysts. DESIGN: 1169 pancreatic cysts (1999-2021) with CEA results were identified. 394 cases had histological confirmation as the diagnostic standard. Additionally, 237 cysts without histological confirmation demonstrated KRAS, GNAS, or RNF43 mutations by molecular testing and were combined with the histologically confirmed cysts for separate analysis on a total cohort of 631 cysts. RESULTS: Median CEA was significantly higher in mucinous cysts (323.9 ng/mL, n=314) versus non-mucinous cysts (204.6 ng/mL, n=80) (p<0.001). Receiver operating characteristic curve analysis demonstrated an optimal CEA cut-off of 20 ng/mL (area under the curve: 80%), though the specificity was lower than desired (sensitivity 89%, specificity 64%). At the previously established threshold of 192 ng/mL, sensitivity and specificity were 56% and 78%, respectively. To achieve a specificity of 85% as originally reported, a CEA threshold of 250 ng/mL was needed; the 13 false positive cases at this threshold included 4 benign simple cysts, 2 squamoid cysts, 1 serous cystadenoma, 1 lymphoepithelial cyst and 5 more uncommon entities. All results remained similar within the total cohort after including additional cases with KRAS/GNAS/RNF43 mutations only. CONCLUSION: Cyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered.

Pancreatic cysts: can surveillance interval for small low-risk lesions be lengthened?

BACKGROUND: Surveillance of pancreatic cysts are necessary due to risk of malignant transformation. However, reported progression rates to advanced neoplasia are variable and the high frequency of surveillance scans may pose a considerable burden on healthcare resources. PURPOSE: To validate the effectiveness of the Fukuoka Guidelines surveillance regime and determine if a longer surveillance interval can be established. MATERIAL AND METHODS: All magnetic resonance imaging (MRI) studies of the pancreas performed at our institution between January 2014 and December 2016 with at least one pancreatic cystic lesion and follow-up MRI or computed tomography (CT) over at least two years were reviewed for size, worrisome feature (WF), and high-risk stigmata (HRS) at diagnosis and follow-up imaging (up to year 6). Reference standards for advanced neoplasia were based on endoscopic ultrasound, fine needle aspiration cytology, or the presence of ≥2 WF or ≥1 HRS on imaging. Comparison of MRI features of progression and outcomes of diagnostic endpoints between lesions <20 mm and ≥20 mm was performed. RESULTS: A total of 270 patients were included (201 cysts <20 mm, 69 cysts ≥20 mm). Compared with cysts <20 mm, cysts ≥20 mm were more likely to be associated with WF or HRS (40.6% vs. 12.4%; P ≤0.00001), demonstrate increase in size of ≥5 mm in two years (20.3% vs. 10.9%; P = 0.049), and develop advanced neoplasia (24.6% vs. 0.5%; P <0.00001). CONCLUSION: Pancreatic cysts <20 mm have a low risk of developing WF and HRS and surveillance interval may be lengthened.

The Deception of Pancreas Cyst Surveillance: A Case Study.

Pancreatic cysts are a growing pandemic around the world. Intrapapillary mucinous neoplasms are the most common type of pancreatic cysts and given their premalignant nature, guidelines recommend surveillance. This case study and discussion addresses the five existing guidelines published to help clinicians manage patients with intraductal papillary mucinous neoplasms and illustrates how, despite guidelines and close surveillance, intraductal papillary mucinous neoplasms can transform into pancreatic adenocarcinoma.