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Ohno E, Kuzuya T, Kawabe N, Nakaoka K, Tanaka H, Nakano T, Funasaka K, Miyahara R, Hashimoto S, Hirooka Y. Current status of endoscopic ultrasound in the diagnosis of intraductal papillary mucinous neoplasms. DEN OPEN 2025; 5:e413. [PMID: 39040523 PMCID: PMC11260769 DOI: 10.1002/deo2.413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 07/02/2024] [Accepted: 07/06/2024] [Indexed: 07/24/2024]
Abstract
The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.
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Affiliation(s)
- Eizaburo Ohno
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Teiji Kuzuya
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Naoto Kawabe
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Kazunori Nakaoka
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Hiroyuki Tanaka
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Takuji Nakano
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Kohei Funasaka
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Ryoji Miyahara
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
| | - Senju Hashimoto
- Department of Gastroenterology and HepatologyFujita Health University Bantane HospitalAichiJapan
| | - Yoshiki Hirooka
- Department of Gastroenterology and HepatologyFujita Health University School of MedicineAichiJapan
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Magahis PT, Chhoda A, Berzin TM, Farrell JJ, Wright DN, Rizvi A, Hanscom M, Carr-Locke DL, Sampath K, Sharaiha RZ, Mahadev S. Risk of Pancreatitis After Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2024; 119:2174-2186. [PMID: 38976379 DOI: 10.14309/ajg.0000000000002942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 06/21/2024] [Indexed: 07/10/2024]
Abstract
INTRODUCTION Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is frequently used to risk-stratify pancreatic cystic lesions (PCLs). Rising PCL incidence and developments in tissue acquisition and specimen analysis necessitate updated appraisal of EUS-FNA safety, particularly the risk of postprocedure pancreatitis, the most common EUS-FNA-related adverse event. Our systematic review aims to accurately quantify the risk of EUS-FNA-related pancreatitis to best inform decisions regarding EUS-FNA's optimal role in PCL workup. METHODS We performed systematic searches in 4 databases from inception to April 2024 for original English-language studies investigating EUS-FNA-related pancreatitis. We extracted data on demographics and EUS-FNA-related pancreatitis risk, severity, and risk factors. These were meta-analyzed through the DerSimonian Laird Method using a random-effects model. Meta-regression of pancreatitis risk was performed to delineate associations with clinical and procedural characteristics. RESULTS Sixty-four studies comprised 8,086 patients and reported 110 EUS-FNA-related pancreatitis events. Pooled risk of EUS-FNA-related pancreatitis was 1.4% (95% confidence intervals, -0.8% to 3.5%; I2 = 0.00), which was predominantly of mild severity (67%) and uniformly nonfatal. Pancreatitis risk lacked significant association with sample size, age, sex, cyst size, needle caliber, or passes, although we noted trends toward higher risk in studies published after 2015, those using higher gauge needles (19 G vs 22 G/25 G), and those performing EUS-guided through-the-needle biopsy. DISCUSSION We note with high certainty that pancreatitis after EUS-FNA of PCLs is infrequent and mild in severity with no mortality in the included cohort. EUS-guided through-the-needle biopsy may serve as a significant risk factor for EUS-FNA-related pancreatitis risk; however, further studies are needed to delineate other predisposing characteristics.
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Affiliation(s)
- Patrick T Magahis
- Weill Cornell Medical College, MD Program, New York, New York, USA
- Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA
| | - Ankit Chhoda
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Tyler M Berzin
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - James J Farrell
- Department of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
| | - Drew N Wright
- Samuel J. Wood Library, Weill Cornell Medical College, New York, New York, USA
| | - Anam Rizvi
- Weill Cornell Medical College, MD Program, New York, New York, USA
- Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA
| | - Mark Hanscom
- Weill Cornell Medical College, MD Program, New York, New York, USA
- Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA
| | - David L Carr-Locke
- Weill Cornell Medical College, MD Program, New York, New York, USA
- Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA
| | - Kartik Sampath
- Weill Cornell Medical College, MD Program, New York, New York, USA
- Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA
| | - Reem Z Sharaiha
- Weill Cornell Medical College, MD Program, New York, New York, USA
- Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA
| | - SriHari Mahadev
- Weill Cornell Medical College, MD Program, New York, New York, USA
- Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA
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Gopakumar H, Puli SR. Value of Endoscopic Ultrasound-Guided Through-the-Needle Biopsy in Pancreatic Cystic Lesions. A Systematic Review and Meta-Analysis. J Gastrointest Cancer 2024; 55:15-25. [PMID: 37341913 DOI: 10.1007/s12029-023-00949-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2023] [Indexed: 06/22/2023]
Abstract
BACKGROUND AND AIM Endoscopic ultrasound-guided through-the-needle biopsy (EUS-TTNB) has been used over the past few years to increase diagnostic accuracy for pancreatic cystic lesions (PCLs). However, many concerns remain regarding its widespread use. This systematic review and meta-analysis aimed to pool the data from high-quality studies to evaluate the utility of EUS-TTNB in diagnosing PCLs. METHODS Electronic databases (PubMed, Embase, and Cochrane Library) from January 2010 through October 2022 were searched for publications addressing the diagnostic performance of EUS-TTNB in the diagnosis of pancreatic cystic lesions. Pooled proportions were calculated using fixed (inverse variance) and random-effects (DerSimonian-Laird) models. RESULTS The initial search identified 635 studies, of which 35 relevant articles were reviewed. We extracted data from 11 studies that met the inclusion criterion, comprising a total of 575 patients. Mean patient age was 62.25 years ± 6.12 with females constituting 61.39% of the study population. Pooled sensitivity of EUS-TTNB in differentiating a PCL as neoplastic or non-neoplastic was 76.60% (95% CI = 72.60-80. 30). For the same indication, EUS TTNB had a pooled specificity of 98.90% (95% CI = 93.80-100.00). The positive likelihood ratio was 10.28 (95% CI = 4.77-22.15), and the negative likelihood ratio was 0.26 (95% CI = 0.22-0.31). The pooled diagnostic odds ratio for EUS-TTNB in diagnosing PCLs as malignant/pre-malignant vs. non-malignant was 41.34 (95% CI = 17.42-98.08). Pooled adverse event rates were 3.04% (95% CI = 1.83-4.54) for pancreatitis, 4.02% (95% CI = 2.61-5.72) for intra-cystic bleeding, 0.94% (95% CI = 0.33-1.86) for fever, and 1.73% (95% CI = 0.85-2.91) for other minor events. CONCLUSIONS EUS-TTNB has good sensitivity with excellent specificity in accurately classifying PCLs as neoplastic or non-neoplastic. Adding EUS-TTNB to EUS-FNA increases the accuracy of EUS-guided approach in diagnosing PCLs. However, it could significantly increase the risk of post-procedural pancreatitis.
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Affiliation(s)
- Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Ave, Peoria, IL, USA.
| | - Srinivas R Puli
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Ave, Peoria, IL, USA
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Du C, He Z, Gao F, Li L, Han K, Feng X, Wang X, Tang P, Chai N, Linghu E. Factors affecting the diagnostic value of liquid-based cytology by EUS-FNA in the diagnosis of pancreatic cystic neoplasms. Endosc Ultrasound 2024; 13:94-99. [PMID: 38947751 PMCID: PMC11213617 DOI: 10.1097/eus.0000000000000041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/02/2024] Open
Abstract
Background and Objectives This study retrospectively evaluated the value of liquid-based cytology (LBC) alone for diagnosing pancreatic cystic neoplasms (PCNs) in a large sample and initially estimated factors that might affect LBC diagnostic ability. Methods From April 2015 to October 2022, we prospectively enrolled 331 patients with suspected PCNs in our prospective database. Among them, 112 patients chosen to receive surgical resection were included. Only 96 patients who underwent EUS-guided cystic fluid LBC were finally studied. The diagnostic values of LBC for differentiating benign and malignant PCNs and subtypes of PCNs were evaluated. Results There were 71 female and 25 male patients with a mean age of 47.6 ± 14.4 years. The median cyst size was 43.4 mm. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LBC for the differentiation of benign and malignant PCNs were 96.9%, 57.1%, 100%, 100%, and 96.7%, respectively. The overall diagnostic accuracy of LBC for specific cyst types was 33.3% (32/96). Cysts located in the pancreatic body/tail or with irregular shapes were more likely to obtain a definite LBC diagnosis. At the same time, age, sex, tumor size, cystic fluid viscosity, operation time, needle type, and presence of septation were not significantly different. Conclusion Liquid-based cytology alone is useful for differentiating benign PCNs from malignant PCNs and can successfully characterize the PCN subtypes in one-third of patients. Pancreatic cystic neoplasms located in the body/tail or exhibiting irregular shapes are more likely to obtain a definite LBC diagnosis.
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Affiliation(s)
- Chen Du
- First Medical Center of PLA General Hospital, Beijing, China
| | - Zhengting He
- First Medical Center of PLA General Hospital, Beijing, China
| | - Fei Gao
- First Medical Center of PLA General Hospital, Beijing, China
| | - Longsong Li
- First Medical Center of PLA General Hospital, Beijing, China
| | - Ke Han
- First Medical Center of PLA General Hospital, Beijing, China
| | - Xiuxue Feng
- First Medical Center of PLA General Hospital, Beijing, China
| | - Xiangdong Wang
- First Medical Center of PLA General Hospital, Beijing, China
| | - Ping Tang
- First Medical Center of PLA General Hospital, Beijing, China
| | - Ningli Chai
- First Medical Center of PLA General Hospital, Beijing, China
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Cho SH, Seo DW. Endoscopic Interventions in Pancreatic Cystic Neoplasms. Gastrointest Endosc Clin N Am 2023; 33:867-877. [PMID: 37709417 DOI: 10.1016/j.giec.2023.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/16/2023]
Abstract
During the past two decades, there has been a significant evolution in endoscopic interventions in pancreatic cystic neoplasms (PCNs), ranging from diagnostic intervention (endoscopic ultrasound-guided through-the-needle biopsy [EUS-TTNB]) to therapeutic intervention (endoscopic ultrasound-guided pancreatic cystic ablation [EUS-PCA]). They have received attention as alternatives to conventional diagnostic and therapeutic modalities. EUS-TTNB can categorize PCN types accurately by providing histologic diagnoses that conventional diagnostic modalities cannot provide. As pancreatectomy entails high morbidities, EUS-PCA can be performed safely to treat PCNs in patients who refuse surgery or have high surgical risks.
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Affiliation(s)
- Sung Hyun Cho
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea.
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Sheik DA, Byers K, Thomas M, Rajesh UC, Ifuku K, Kirkwood K, Al-Haddad M, Craik CS, Davisson VJ. Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer. FRONTIERS IN GASTROENTEROLOGY (LAUSANNE, SWITZERLAND) 2023; 2:1258998. [PMID: 38846269 PMCID: PMC11156210 DOI: 10.3389/fgstr.2023.1258998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/09/2024]
Abstract
The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precursors currently relies on imaging and cyst fluid evaluations, including cytology and protein and genomic analyses. However, there are persistent limitations that obstruct the accuracy and quality of information for clinicians, including the limited volume of the complex, often acellular, and proteinaceous milieu that comprises pancreatic cyst fluid. The constraints of currently available clinical assays lead clinicians to the subjective and inconsistent application of diagnostic tools, which can contribute to unnecessary surgery and missed pancreatic cancers. Herein, we describe the pathway toward pancreatic cyst classification and diagnosis, the volume requirements for several clinically available diagnostic tools, and some analytical and diagnostic limitations for each assay. We then discuss current and future work on novel markers and methods, and how to expand the utility of clinical pancreatic cyst fluid samples. Results of ongoing studies applying SERS as a detection mode suggest that 50 μL of pancreatic cyst fluid is more than sufficient to accurately rule out non-mucinous pancreatic cysts with no malignant potential from further evaluation. This process is expected to leave sufficient fluid to analyze a follow-up, rule-in panel of markers currently in development that can stratify grades of dysplasia in mucinous pancreatic cysts and improve clinical decision-making.
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Affiliation(s)
- Daniel A. Sheik
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
| | - Kaleb Byers
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
| | - Mini Thomas
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
| | | | - Kelli Ifuku
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Kimberly Kirkwood
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Mohammed Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University (IU) School of Medicine, Indianapolis, IN, United States
| | - Charles S. Craik
- Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, United States
| | - V. Jo Davisson
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, IN, United States
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Marques F, van der Wijngaart W, Roxhed N. Absorbable cyst brushes. Biomed Microdevices 2023; 25:33. [PMID: 37610663 PMCID: PMC10447279 DOI: 10.1007/s10544-023-00674-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2023] [Indexed: 08/24/2023]
Abstract
Cytobrushes are used for low-invasive sample collection and screening in multiple diseases, with a significant impact on early detection, prevention, and diagnosis. This study focuses on improving the safety of cell brushing in hard-to-reach locations by exploring brush construction from absorbable materials. We investigated the efficacy of loop brushes made of absorbable suture wires of Chirlac, Chirasorb, Monocryl, PDS II, Vicryl Rapid, Glycolon, and Catgut during their operation in conjunction with fine-needle aspiration in an artificial cyst model. PDS II brushes demonstrated the highest efficiency, while Monocryl and Catgut also provided a significant brushing effect. Efficient brushes portrayed higher flexural rigidity than their counterparts, and their efficiency was inversely proportional to their plastic deformation by the needle. Our results open avenues for safer cell biopsies in hard-to-reach locations by utilizing brushes composed of absorbable materials.
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Affiliation(s)
- Filipe Marques
- KTH Royal Institute of Technology, Micro and Nanosystems, Malvinas väg 10, 100 44, Stockholm, Sweden
| | - Wouter van der Wijngaart
- KTH Royal Institute of Technology, Micro and Nanosystems, Malvinas väg 10, 100 44, Stockholm, Sweden.
| | - Niclas Roxhed
- KTH Royal Institute of Technology, Micro and Nanosystems, Malvinas väg 10, 100 44, Stockholm, Sweden.
- MedTechLabs, Bioclinicum, Karolinska University Hospital, Solna, Sweden.
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Ahmed W, Mirzaali M, Young C, Sanni L, Everett S, Paranandi B, Huggett MT, On W. EUS-guided through the needle microbiopsy: a useful adjunct in the investigation of pancreatic cystic lesions. BMJ Open Gastroenterol 2023; 10:e001184. [PMID: 37399433 DOI: 10.1136/bmjgast-2023-001184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 06/21/2023] [Indexed: 07/05/2023] Open
Abstract
OBJECTIVE Endoscopic ultrasound-guided through-the-needle microbiopsy (EUS-TTNB) forceps is a recent development that facilitates sampling of the walls of pancreatic cystic lesions (PCL) for histological analysis. We aimed to assess the impact of EUS-TTNB and its influence on patient management in a tertiary pancreas centre. DESIGN A prospective database of consecutive patients who underwent EUS-TTNB from March 2020 to August 2022 at a tertiary referral centre was retrospectively analysed. RESULTS Thirty-four patients (22 women) were identified. Technical success was achieved in all cases. Adequate specimens for histological diagnosis were obtained in 25 (74%) cases. Overall, EUS-TTNB led to a change in management in 24 (71%) cases. Sixteen (47%) patients were downstaged, with 5 (15%) discharged from surveillance. Eight (24%) were upstaged, with 5 (15%) referred for surgical resection. In the 10 (29%) cases without change in management, 7 (21%) had confirmation of diagnosis with no change in surveillance, and 3 (9%) had insufficient biopsies on EUS-TTNB. Two (6%) patients developed post-procedural pancreatitis, and 1 (3%) developed peri-procedural intracystic bleeding with no subsequent clinical sequelae. CONCLUSION EUS-TTNB permits histological confirmation of the nature of PCL, which can alter management outcomes. Care should be taken in patient selection and appropriately consented due to the adverse event rate.
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Affiliation(s)
- Wafaa Ahmed
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Mikaeil Mirzaali
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Caroline Young
- Department of Histopathology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Latifu Sanni
- Department of Histopathology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Simon Everett
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Bharat Paranandi
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Matthew T Huggett
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Wei On
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Accurate Identification of Mucinous Pancreatic Cystic Lesions Using Small-Volume Analytes. J Surg Res 2023; 284:322-331. [PMID: 36369049 DOI: 10.1016/j.jss.2022.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 07/26/2022] [Accepted: 08/19/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION The accurate identification of mucinous pancreatic cystic lesions (PCLs) is paramount for cancer risk stratification. Cyst fluid carcinoembryonic antigen (CEA), the only routinely used test, requires high volumes and has low sensitivity. We aimed to compare the performance of two investigational small-volume biomarkers, glucose and the protease gastricsin, to CEA for PCL classification. METHODS We obtained cyst fluid samples from 81 patients with pathologically confirmed PCLs from four institutions between 2003 and 2016. Gastricsin activity was measured using an internally quenched fluorescent substrate. Glucose levels were measured with a standard glucometer. CEA levels were obtained from the medical record. Models using Classification and Regression Trees were created to predict mucinous status. Model performance was evaluated using nested cross-validation. RESULTS Gastricsin activity, CEA, and glucose levels from patients with mucinous (n = 50) and nonmucinous (n = 31) PCLs were analyzed. Area under the curve (AUC) was similar for individual classifiers (gastricsin volume normalized [GVN] 0.88; gastricsin protein concentration normalized [GPN] 0.95; glucose 0.83; CEA 0.84). The combination of two classifiers did not significantly improve AUC, with CEA + GVN (0.88) performing similarly to CEA + GPN (0.95), GVN + glucose (0.87), GPN + glucose (0.95), and CEA + glucose (0.84). The three-analyte combination performed similarly to single and dual classifiers (GPN + glucose + CEA AUC 0.95; GVN + glucose + CEA AUC 0.87). After multiple comparison corrections, there were no significant differences between the individual, dual, and triple classifiers. CONCLUSIONS Gastricsin and glucose performed similarly to CEA and required <5% of the volume required for CEA; these classifiers may be useful in patients with limited cyst fluid. Future multicenter prospective studies are needed to validate and compare these novel small-volume biomarkers.
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10
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Paik WH. Endoscopic ultrasound-guided tissue acquisition: Needle types, technical issues, and sample handling. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2022. [DOI: 10.18528/ijgii220019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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11
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Quantitative MRI of Pancreatic Cystic Lesions: A New Diagnostic Approach. Healthcare (Basel) 2022; 10:healthcare10061039. [PMID: 35742090 PMCID: PMC9222599 DOI: 10.3390/healthcare10061039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/30/2022] [Accepted: 05/31/2022] [Indexed: 02/01/2023] Open
Abstract
The commonly used magnetic resonance (MRI) criteria can be insufficient for discriminating mucinous from non-mucinous pancreatic cystic lesions (PCLs). The histological differences between PCLs’ fluid composition may be reflected in MRI images, but cannot be assessed by visual evaluation alone. We investigate whether additional MRI quantitative parameters such as signal intensity measurements (SIMs) and radiomics texture analysis (TA) can aid the differentiation between mucinous and non-mucinous PCLs. Fifty-nine PCLs (mucinous, n = 24; non-mucinous, n = 35) are retrospectively included. The SIMs were performed by two radiologists on T2 and diffusion-weighted images (T2WI and DWI) and apparent diffusion coefficient (ADC) maps. A total of 550 radiomic features were extracted from the T2WI and ADC maps of every lesion. The SIMs and TA features were compared between entities using univariate, receiver-operating, and multivariate analysis. The SIM analysis showed no statistically significant differences between the two groups (p = 0.69, 0.21–0.43, and 0.98 for T2, DWI, and ADC, respectively). Mucinous and non-mucinous PLCs were successfully discriminated by both T2-based (83.2–100% sensitivity and 69.3–96.2% specificity) and ADC-based (40–85% sensitivity and 60–96.67% specificity) radiomic features. SIMs cannot reliably discriminate between PCLs. Radiomics have the potential to augment the common MRI diagnosis of PLCs by providing quantitative and reproducible imaging features, but validation is required by further studies.
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Abstract
Andrew Canakis.
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Affiliation(s)
- Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Linda S Lee
- Division of Gastroenterology Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA.
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13
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Crinò SF, Manfrin E. Through-The-Needle Biopsy: Shifting From Cytology to Histology for Preoperative Assessment of Pancreatic Cystic Lesions. Arch Pathol Lab Med 2021; 145:1193b-1193. [PMID: 34570891 DOI: 10.5858/arpa.2021-0207-le] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2021] [Indexed: 11/06/2022]
Affiliation(s)
- Stefano Francesco Crinò
- Departments of Medicine, Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute
| | - Erminia Manfrin
- Diagnostics and Public Health, University Hospital of Verona, Verona, Italy
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14
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Keane MG, Pereira SP. The Role of Confocal Endomicroscopy in the Diagnosis and Management of Pancreatic Cysts. EUROPEAN MEDICAL JOURNAL 2021. [DOI: 10.33590/emj/20-00182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Pancreatic cystic lesions are an increasingly common clinical finding. Current diagnostic techniques cannot reliably differentiate patients with high-risk lesions requiring surgical resection from those that can be safely surveyed or discharged. As a result, some patients may undergo unnecessary surgery with associated morbidity while others enter long-term surveillance with associated healthcare costs. Needle-based confocal laser endomicroscopy enables real time microscopic examination of the epithelial lining of a cyst wall at the time of a standard endoscopic ultrasound examination. The procedure is associated with low rates of adverse events, especially when the probe is loaded into the fine-needle aspiration needle before the procedure and examination times are limited. Needle-based confocal laser endomicroscopy has consistently been shown to have better diagnostic accuracy than cytology, which is often paucicellular and non-diagnostic in pancreatic cystic lesions. Studies have shown that diagnostic accuracy in needle-based confocal laser endomicroscopy is 84–95% in mucinous lesions and 39–99% in serous lesions. However, this technology is expensive and its place in diagnostic algorithms remains uncertain. Despite this, health economic analyses in certain health systems have been favourable, largely because of its potential to be able to discharge patients with benign lesions, such as serous cystic neoplasms, from long-term surveillance. Widespread adoption of this technology is unlikely but it has the potential to have an important role in indeterminate pancreatic cystic lesions.
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Affiliation(s)
- Margaret G Keane
- Johns Hopkins Hospital, Department of Gastroenterology and Hepatology, Baltimore, Maryland, USA
| | - Stephen P Pereira
- Institute for Liver and Digestive Health, University College London, Royal Free Hospital Campus, UK
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15
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Cystic pancreatic lesions: MR imaging findings and management. Insights Imaging 2021; 12:115. [PMID: 34374885 PMCID: PMC8355307 DOI: 10.1186/s13244-021-01060-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/17/2021] [Indexed: 12/14/2022] Open
Abstract
Cystic pancreatic lesions (CPLs) are frequently casual findings in radiological examinations performed for other reasons in patients with unrelated symptoms. As they require different management according to their histological nature, differential diagnosis is essential. Radiologist plays a key role in the diagnosis and management of these lesions as imaging is able to correctly characterize most of them and thus address to a correct management. The first step for a correct characterization is to look for a communication between the CPLs and the main pancreatic duct, and then, it is essential to evaluate the morphology of the lesions. Age, sex and a history of previous pancreatic pathologies are important information to be used in the differential diagnosis. As some CPLs with different pathologic backgrounds can show the same morphological findings, differential diagnosis can be difficult, and thus, the final diagnosis can require other techniques, such as endoscopic ultrasound, endoscopic ultrasound-fine needle aspiration and endoscopic ultrasound-through the needle biopsy, and multidisciplinary management is important for a correct management.
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16
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Sbeit W, Kadah A, Shahin A, Khoury T. The Yield of String Sign in Differentiating Mucinous from Non-Mucinous Pancreatic Cysts: A Retrospective Cross-Sectional Study. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:716. [PMID: 34356997 PMCID: PMC8305072 DOI: 10.3390/medicina57070716] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/08/2021] [Accepted: 07/14/2021] [Indexed: 12/22/2022]
Abstract
Background and Objectives: The diagnosis of pancreatic cysts is mostly based on a combination of morphological appearance and fluid analysis of amylase and carcinoembryonic antigen (CEA). We aimed to assess the capability of the string sign in differentiating mucinous from non-mucinous pancreatic cysts. Materials and Methods: All patients who were referred for endoscopic ultrasound (EUS) for pancreatic cysts assessment from 2015 to 2020 were retrospectively analyzed. Results: Our cohort consisted of 112 patients. Of them, 92 patients (82.1%) had mucinous cystic neoplasms (group A) and 20 patients (17.9%) had non-mucinous cystic neoplasms (group B). The average age in groups A and B was 71.3 and 60.4 years, respectively. String sign was positive in 47 patients (51.1%) and negative in 21 patients (22.8%) in group A, while in group B, string sign was negative in 19 patients (95%). String sign showed significant correlation with the diagnosis of mucinous cystic neoplasms (OR 64.2, 95% CI 8.1-508.6, p = 0.0001). Cytology confirmed mucinous cystic neoplasms that included 32 patients; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of string sign for mucinous cystic neoplasms were high, reaching 93.8%, 85.7%, 96.8%, and 75%, respectively, with an excellent accuracy rate of 92.3%. Conclusions: The string sign is highly accurate for predicting pancreatic mucinous cystic neoplasms, and should be used as an important aid for improving diagnostic accuracy.
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Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (A.K.); (A.S.)
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel
| | - Anas Kadah
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (A.K.); (A.S.)
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel
| | - Amir Shahin
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (A.K.); (A.S.)
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel
| | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (A.K.); (A.S.)
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel
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17
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Keane MG, Afghani E. A Review of the Diagnosis and Management of Premalignant Pancreatic Cystic Lesions. J Clin Med 2021; 10:1284. [PMID: 33808853 PMCID: PMC8003622 DOI: 10.3390/jcm10061284] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/04/2021] [Accepted: 03/09/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cystic lesions are an increasingly common clinical finding. They represent a heterogeneous group of lesions that include two of the three known precursors of pancreatic cancer, intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). Given that approximately 8% of pancreatic cancers arise from these lesions, careful surveillance and timely surgery offers an opportunity for early curative resection in a disease with a dismal prognosis. This review summarizes the current evidence and guidelines for the diagnosis and management of IPMN/MCN. Current pre-operative diagnostic tests in pancreatic cysts are imperfect and a proportion of patients continue to undergo unnecessary surgical resection annually. Balancing cancer prevention while preventing surgical overtreatment, continues to be challenging when managing pancreatic cysts. Cyst fluid molecular markers, such as KRAS, GNAS, VHL, PIK3CA, SMAD4 and TP53, as well as emerging endoscopic technologies such as needle-based confocal laser endomicroscopy and through the needle microbiopsy forceps demonstrate improved diagnostic accuracy. Differences in management and areas of uncertainty between the guidelines are also discussed, including indications for surgery, surveillance protocols and if and when surveillance can be discontinued.
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Affiliation(s)
| | - Elham Afghani
- Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA;
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18
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Geisler D, Khader SN. Educational Case: Pancreatic Cystic Disease: A Multimodal Diagnostic Approach to Determine Clinical Management. Acad Pathol 2021; 8:2374289521998031. [PMID: 35155743 PMCID: PMC8819742 DOI: 10.1177/2374289521998031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 11/30/2020] [Accepted: 01/14/2021] [Indexed: 11/17/2022] Open
Abstract
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 . 1
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Affiliation(s)
- Daniel Geisler
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Samer N. Khader
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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19
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Cho SY, Cho E, Park CH, Kim HJ, Koo JY. Septic shock due to Granulicatella adiacens after endoscopic ultrasound-guided biopsy of a splenic mass: A case report. World J Gastroenterol 2021; 27:751-759. [PMID: 33716452 PMCID: PMC7934004 DOI: 10.3748/wjg.v27.i8.751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 01/18/2021] [Accepted: 02/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Endoscopic ultrasound-guided fine needle aspiration or biopsy (EUS-FNA or FNB) has become a popular method for diagnosing various lesions of the gastrointestinal tract and surrounding tissue due to the accuracy and safety. To the best of our knowledge, no case report of severe infection after EUS-FNB of a solid lesion in the spleen has been described. Herein, we report a rare case of septic shock after EUS-FNB of a splenic mass.
CASE SUMMARY A 45-year-old male patient presented to the outpatient clinic due to an incidentally detected splenic mass. A definitive diagnosis could not be established based on the abdominal magnetic resonance imaging. EUS of the spleen showed a 6 cm-sized, relatively well-demarcated, heterogeneous mass, and EUS-FNB with a 22G needle was performed. Ten days after the procedure patient developed septic shock and a splenic abscess was identified. Blood culture revealed growth of Granulicatella adiacens. After the treatment with antibiotics the patient underwent surgical resection, and the pathological examination showed diffuse large B-cell lymphoma. The patient received chemotherapy and he is in complete remission.
CONCLUSION Infection of a splenic mass after EUS-FNB is a rare complication and prophylactic antibiotics might be considered.
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Affiliation(s)
- Seo-Yeon Cho
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, South Korea
| | - Eunae Cho
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, South Korea
| | - Chang-Hwan Park
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, South Korea
| | - Hee-Joon Kim
- Department of Surgery, Chonnam National University Hospital, Gwangju 61469, South Korea
| | - Joo-Yeon Koo
- Department of Pathology, Chonnam National University Hospital, Gwangju 61469, South Korea
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20
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Facciorusso A, Buccino VR, Sacco R. Needle-based confocal laser endomicroscopy in pancreatic cysts: a meta-analysis. Eur J Gastroenterol Hepatol 2020; 32:1084-1090. [PMID: 32282543 DOI: 10.1097/meg.0000000000001728] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
There is currently limited evidence supporting the use of needle-based confocal laser endomicroscopy in pancreatic cystic lesions. Aim of this study was to provide a pooled estimate of the diagnostic performance and safety profile of this technique in patients with pancreatic cysts. Computerized bibliographic search on the main databases was performed through November 2019. Pooled effects were calculated using a random-effects model by means of DerSimonian and Laird test. Primary endpoint was diagnostic accuracy. Secondary outcomes were pooled sensitivity, specificity, and mean procedural time. Ten studies enrolling 536 patients were included. Eight articles, of which five prospective series, compared confocal laser endomicroscopy to cytology/cystic fluid analysis. Most patients were female and body/tail was the most frequent location of pancreatic cysts. Mucinous cysts were prevalent in most of the included studies. Diagnostic accuracy with confocal laser endomicroscopy was 88.6% (83.7-93.4%) and sensitivity analysis according to study quality, design, and treatment arms confirmed the above reported result. Pooled sensitivity and specificity were 82.4% (74.7-90.1%) and 96.6% (94.3-99%), respectively. Both accuracy and sensitivity resulted higher in patients with mucinous cysts (91.4 and 94.9%, respectively). Confocal laser endomicroscopy clearly outperformed fine-needle aspiration in terms of diagnostic accuracy (odds ratio 3.94, 1.58-9.82; P = 0.003). A mean of 6.094 minutes (4.91-7.26) was needed to complete the procedure and no significant adverse event was registered. Our meta-analysis speaks in favor of the use of needle-based confocal laser endomicroscopy as a safe and effective tool in the diagnostic algorithm of pancreatic cysts.
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Affiliation(s)
- Antonio Facciorusso
- Department of medical sciences, Gastroenterology Unit, University of Foggia, Foggia, Italy
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21
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Ribaldone DG, Bruno M, Gaia S, Cantamessa A, Bragoni A, Caropreso P, Sacco M, Fagoonee S, Saracco GM, De Angelis C. Differential diagnosis of pancreatic cysts: A prospective study on the role of intra-cystic glucose concentration. Dig Liver Dis 2020; 52:1026-1032. [PMID: 32675041 DOI: 10.1016/j.dld.2020.06.038] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 06/20/2020] [Accepted: 06/26/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The accuracy and costs of current diagnostic methods in the differential diagnosis of pancreatic cystic lesions still has ample room for improvement. AIMS The aim of the study was to confirm the diagnostic yield of intracystic glucose in the diagnosis of pancreatic cyst subtypes. METHODS We prospectively recruited all patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration of pancreatic cyst at our Institution. RESULTS Fifty-six patients were included in the study. We found that intracystic glucose concentration < 50 mg/dL was significantly more sensitive than a concentration of Carcinoembryonic Antigen > 192 ng/mL (93.6% vs 54.8%; p = 0.003) for the diagnosis of mucinous cysts. In terms of specificity, the two markers were not different (96% vs 100%; p = 1). Regarding the diagnosis of non-mucinous cysts, intracystic glucose concentration ≥ 50 mg/mL showed higher sensitivity than Carcinoembryonic Antigen level < 5 ng/mL (96% vs 72%) although a statistical significance could not be reached (p = 0.07). The two markers were not statistically different in terms of specificity (93.6% vs 87.1%; p = 0.62). CONCLUSION Given its diagnostic performance and ease of measurement, intracystic glucose may replace Carcinoembryonic Antigen in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts.
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Affiliation(s)
| | - Mauro Bruno
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Silvia Gaia
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Alessandro Cantamessa
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Alberto Bragoni
- Department of Laboratory Medicine, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Paola Caropreso
- Department of Laboratory Medicine, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Marco Sacco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy; Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging, CNR c/o Molecular Biotechnology Centre, 10126 Turin, Italy
| | - Giorgio Maria Saracco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | - Claudio De Angelis
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
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22
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Springer S, Masica DL, Dal Molin M, Douville C, Thoburn CJ, Afsari B, Li L, Cohen JD, Thompson E, Allen PJ, Klimstra DS, Schattner MA, Schmidt CM, Yip-Schneider M, Simpson RE, Fernandez-Del Castillo C, Mino-Kenudson M, Brugge W, Brand RE, Singhi AD, Scarpa A, Lawlor R, Salvia R, Zamboni G, Hong SM, Hwang DW, Jang JY, Kwon W, Swan N, Geoghegan J, Falconi M, Crippa S, Doglioni C, Paulino J, Schulick RD, Edil BH, Park W, Yachida S, Hijioka S, van Hooft J, He J, Weiss MJ, Burkhart R, Makary M, Canto MI, Goggins MG, Ptak J, Dobbyn L, Schaefer J, Sillman N, Popoli M, Klein AP, Tomasetti C, Karchin R, Papadopoulos N, Kinzler KW, Vogelstein B, Wolfgang CL, Hruban RH, Lennon AM. A multimodality test to guide the management of patients with a pancreatic cyst. Sci Transl Med 2020; 11:11/501/eaav4772. [PMID: 31316009 DOI: 10.1126/scitranslmed.aav4772] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 01/07/2019] [Accepted: 06/24/2019] [Indexed: 12/12/2022]
Abstract
Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.
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Affiliation(s)
- Simeon Springer
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - David L Masica
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD 21287, USA.,Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Marco Dal Molin
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Christopher Douville
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD 21287, USA.,Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Christopher J Thoburn
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Bahman Afsari
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Lu Li
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Joshua D Cohen
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Elizabeth Thompson
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Peter J Allen
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
| | - David S Klimstra
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
| | - Mark A Schattner
- Department of Gastroenterology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
| | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Michele Yip-Schneider
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Rachel E Simpson
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | | | - Mari Mino-Kenudson
- Department of Histopathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - William Brugge
- Department of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Randall E Brand
- Department of Medicine, University of Pittsburgh, Pittsburgh PA 15213, USA
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Aldo Scarpa
- ARC-Net Research Centre, University and Hospital Trust of Verona, Verona 37134, Italy.,Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Rita Lawlor
- ARC-Net Research Centre, University and Hospital Trust of Verona, Verona 37134, Italy.,Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Giuseppe Zamboni
- Department of Pathology, Ospedale Sacro Cuore-Don Calabria, Negrar 37024, Italy
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
| | - Dae Wook Hwang
- Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Niall Swan
- Department of Histopathology, St. Vincent's University Hospital, Dublin D04 T6F4, Ireland
| | - Justin Geoghegan
- Department of Surgery, St. Vincent's University Hospital, Dublin D04 T6F4, Ireland
| | - Massimo Falconi
- Division of Pancreatic Surgery, Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
| | - Stefano Crippa
- Division of Pancreatic Surgery, Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
| | - Claudio Doglioni
- Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
| | - Jorge Paulino
- Department of Surgery, Centro Hepatobiliopancreático e Transplantação, Hospital Curry Cabral, Lisbon 1050-099, Portugal
| | | | - Barish H Edil
- Department of Surgery, University of Colorado, Aurora, CO 80045, USA
| | - Walter Park
- Department of Medicine, Stanford University Medical Center, Palo Alto, CA 94304, USA
| | - Shinichi Yachida
- Department of Hepatobiliary and Pancreatic Surgery, Pathology and Cancer Genomics, National Cancer Center Hospital and National Cancer Center Research Institute, Tokyo 104-0045, Japan
| | - Susumu Hijioka
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan
| | - Jeanin van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam Medical Center, Amsterdam 1017 ZX, Netherlands
| | - Jin He
- Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Matthew J Weiss
- Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Richard Burkhart
- Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Martin Makary
- Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Marcia I Canto
- Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Michael G Goggins
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Janine Ptak
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Lisa Dobbyn
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Joy Schaefer
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Natalie Sillman
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Maria Popoli
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Alison P Klein
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Cristian Tomasetti
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA. .,Department of Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Rachel Karchin
- Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD 21287, USA.,Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.
| | - Nickolas Papadopoulos
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Kenneth W Kinzler
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Bert Vogelstein
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA. .,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Christopher L Wolfgang
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA. .,Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Ralph H Hruban
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA.,Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
| | - Anne Marie Lennon
- Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA. .,Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.,Department of Radiology, Johns Hopkins University, Baltimore, MD 21287, USA
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Facciorusso A, Del Prete V, Antonino M, Buccino VR, Wani S. Diagnostic yield of EUS-guided through-the-needle biopsy in pancreatic cysts: a meta-analysis. Gastrointest Endosc 2020; 92:1-8.e3. [PMID: 32014422 DOI: 10.1016/j.gie.2020.01.038] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 01/22/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS There is currently limited evidence supporting the use of EUS-guided through-the-needle biopsy for sampling pancreatic cystic lesions. The aim of this meta-analysis was to provide a pooled estimate of the diagnostic performance of through-the-needle biopsy for sampling of pancreatic cysts. METHODS A bibliographic search on the main databases was performed in September 2019. Pooled effects were calculated using a random-effects model by means of the DerSimonian and Laird test. The primary outcome was sample adequacy. Additional endpoints were diagnostic accuracy, optimal histologic core procurement, mean number of needle passes, pooled specificity, and sensitivity. Adverse event rates were also analyzed. RESULTS Eleven studies enrolling 490 patients were included. Eight articles compared through-the-needle biopsy with cytology/cystic fluid analysis. Most patients were female, and the body/tail was the most frequent location of cystic lesions. Sample adequacy with through-the-needle biopsy was 85.3% (78.2%-92.5%), and subanalysis performed according to cyst morphology, size, and location confirmed the result. Through-the-needle biopsy clearly outperformed FNA both in terms of sample adequacy (odds ratio, 4.83; 95% confidence interval, 1.63-14.31; P =.004) and diagnostic accuracy (odds ratio, 3.44; 95% confidence interval, 1.32-8.96; P =.01). The pooled diagnostic accuracy rate, sensitivity, and specificity of through-the-needle biopsy were 78.8%, 82.2%, and 96.8%, respectively. A mean of 3.121 (2.98-3.25) passes through the cyst was needed to obtain adequate histologic samples. The incidence rates of mild bleeding and pancreatitis were 4% and 2%, respectively. CONCLUSION Our meta-analysis speaks in favor of the use of through-the-needle biopsy as a safe and effective tool in EUS-guided tissue acquisition of pancreatic cysts.
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Affiliation(s)
| | | | | | | | - Sachin Wani
- University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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Sahai AV. Through-the-needle biopsy of pancreas cysts: Who, what, where, when, and mostly… why? Gastrointest Endosc 2020; 92:9-10. [PMID: 32586569 DOI: 10.1016/j.gie.2020.03.3752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 03/13/2020] [Indexed: 02/08/2023]
Affiliation(s)
- Anand V Sahai
- Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada
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25
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SAGES TAVAC safety and efficacy analysis confocal laser endomicroscopy. Surg Endosc 2020; 35:2091-2103. [PMID: 32405892 DOI: 10.1007/s00464-020-07607-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/28/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Confocal laser endomicroscopy (CLE) is a novel endoscopic adjunct that allows real-time in vivo histological examination of mucosal surfaces. By using intravenous or topical fluorescent agents, CLE highlights certain mucosal elements that facilitate an optical biopsy in real time. CLE technology has been used in different organ systems including the gastrointestinal tract. There has been numerous studies evaluating this technology in gastrointestinal endoscopy, our aim was to evaluate the safety, value, and efficacy of this technology in the gastrointestinal tract. METHODS The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Technology and Value Assessment Committee (TAVAC) performed a PubMed/Medline database search of clinical studies involving CLE in May of 2018. The literature search used combinations of the keywords: confocal laser endomicroscopy, pCLE, Cellvizio, in vivo microscopy, optical histology, advanced endoscopic imaging, and optical diagnosis. Bibliographies of key references were searched for relevant studies not covered by the PubMed search. Case reports and small case series were excluded. The manufacturer's website was also used to identify key references. The United States Food and Drug Administration (U.S. FDA) Manufacturer And User facility and Device Experience (MAUDE) database was searched for reports regarding the device malfunction or injuries. RESULTS The technology offers an excellent safety profile with rare adverse events related to the use of fluorescent agents. It has been shown to increase the detection of dysplastic Barrett's esophagus, gastric intraepithelial neoplasia/early gastric cancer, and dysplasia associated with inflammatory bowel disease when compared to standard screening protocols. It also aids in the differentiation and classification of colorectal polyps, indeterminate biliary strictures, and pancreatic cystic lesions. CONCLUSIONS CLE has an excellent safety profile. CLE can increase the diagnostic accuracy in a number of gastrointestinal pathologies.
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Westerveld DR, Ponniah SA, Draganov PV, Yang D. Diagnostic yield of EUS-guided through-the-needle microforceps biopsy versus EUS-FNA of pancreatic cystic lesions: a systematic review and meta-analysis. Endosc Int Open 2020; 8:E656-E667. [PMID: 32355885 PMCID: PMC7164999 DOI: 10.1055/a-1119-6543] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 01/15/2020] [Indexed: 12/15/2022] Open
Abstract
Background and study aims Accurate diagnosis and risk stratification of pancreatic cysts (PCs) is challenging. The aim of this study was to perform a systematic review and meta-analysis to assess the feasibility, safety, and diagnostic yield of endoscopic ultrasound-guided through-the-needle biopsy (TTNB) versus fine-needle aspiration (FNA) in PCs. Methods Comprehensive search of databases (PubMed, EMBASE, Cochrane, Web of Science) for relevant studies on TTNB of PCs (from inception to June 2019). The primary outcome was to compare the pooled diagnostic yield and concordance rate with surgical pathology of TTNB histology and FNA cytology of PCs. The secondary outcome was to estimate the safety profile of TTNB. Results: Eight studies (426 patients) were included. The diagnostic yield was significantly higher with TTNB over FNA for a specific cyst type (OR: 9.4; 95 % CI: [5.7-15.4]; I 2 = 48) or a mucinous cyst (MC) (OR: 3.9; 95 % CI: [2.0-7.4], I 2 = 72 %). The concordance rate with surgical pathology was significantly higher with TTNB over FNA for a specific cyst type (OR: 13.5; 95 % CI: [3.5-52.3]; I 2 = 48), for a MC (OR: 8.9; 95 % [CI: 1.9-40.8]; I 2 = 29), and for MC histologic severity (OR: 10.4; 95 % CI: [2.9-36.9]; I 2 = 0). The pooled sensitivity and specificity of TTNB for MCs were 90.1 % (95 % CI: [78.4-97.6]; I 2 = 36.5 %) and 94 % (95 % CI: [81.5-99.7]; I 2 = 0), respectively. The pooled adverse event rate was 7.0 % (95 % CI: [2.3-14.1]; I 2 = 82.9). Conclusions TTNB is safe, has a high sensitivity and specificity for MCs and may be superior to FNA cytology in risk-stratifying MCs and providing a specific cyst diagnosis.
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Affiliation(s)
- Donevan R. Westerveld
- Department of Internal Medicine, University of Florida, Gainesville, Florida, United States
| | - Sandeep A. Ponniah
- Department of Internal Medicine, University of Florida, Gainesville, Florida, United States
| | - Peter V. Draganov
- Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida, United States
| | - Dennis Yang
- Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida, United States
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Cheesman AR, Zhu H, Liao X, Szporn AH, Kumta NA, Nagula S, DiMaio CJ. Impact of EUS-guided microforceps biopsy sampling and needle-based confocal laser endomicroscopy on the diagnostic yield and clinical management of pancreatic cystic lesions. Gastrointest Endosc 2020; 91:1095-1104. [PMID: 31881204 DOI: 10.1016/j.gie.2019.12.022] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 12/06/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS EUS-guided microforceps biopsy sampling (MFB) and needle-based confocal laser endomicroscopy (nCLE) are emerging diagnostic tools for pancreatic cystic lesions (PCLs). There is a paucity of data regarding their performance and impact. The aim of this study was to compare diagnostic outcomes and changes in clinical management resulting from MFB and nCLE use in PCLs. METHODS This was a single-center retrospective study of patients with PCLs who underwent combined EUS-guided FNA, MFB, and nCLE. Primary outcomes included diagnostic yield (specific PCL type) and change in clinical management for each modality compared with the current "composite standard" (CS) obtained by combining clinical, morphologic, cyst fluid cytology, and chemical analysis. RESULTS Forty-four cysts were studied in 44 patients. Technical success was 100% for EUS-FNA, 88.6% for MFB, and 97.7% for nCLE. Of 44 procedures, there was 1 adverse event (2.3%, an infected pseudocyst). Diagnostic yield for each individual modality was 34.1% for CS, 75.0% for MFB (P < .05 vs CS), and 84.1% for nCLE (P < .05 vs CS). Diagnostic yield for combined tests was 79.5% for CS/MFB, 88.6% for CS/nCLE, and 93.2% for CS/MFB/nCLE (P = not significant). Compared with the CS, the use of MFB, nCLE, and their combination led to overall change in clinical management in 38.6%, 43.2%, and 52.3% of cases, respectively. MFB and nCLE led to an overall increase in discontinuation of surveillance (MFB, 34.1% [P < .05]; nCLE, 31.8% [P < .05]), led by a reduction in the indication for follow-up radiologic or endoscopic studies (MFB, 34.1% [P < .05]; nCLE, 38.6% [P < .05]). Based on MFB and nCLE, 2 of 28 (7.1%) and 3 of 28 (10.7%) patients who would have undergone further surveillance were referred for surgery. CONCLUSIONS In the evaluation of PCLs, the use of combined EUS-guided FNA, MFB, and nCLE is safe. MFB and nCLE led to significant improvements in specific PCL diagnosis, which in turn has major impacts in clinical management.
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Affiliation(s)
- Antonio R Cheesman
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Hongfa Zhu
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Xiaoyan Liao
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Arnold H Szporn
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Nikhil A Kumta
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Satish Nagula
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Christopher J DiMaio
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Endoscopic Ultrasound-Guided Fine-Needle Aspiration Microhistology in Asymptomatic and Symptomatic Pancreatic Cystic Lesions. Pancreas 2020; 49:584-590. [PMID: 32282774 DOI: 10.1097/mpa.0000000000001525] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE This study aimed to analyze the usefulness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) microhistology to detect malignancy in pancreatic cystic lesions (PCLs). METHODS Patients with PCLs were identified and submitted to EUS-FNA from January 2010 to January 2017. The percentage of samples suitable for diagnostic classification by microhistology and the positive and negative likelihood ratios to detect malignancy in asymptomatic (APC) and symptomatic (SPC) PCLs were determined. RESULTS Endoscopic ultrasound-guided fine-needle aspiration was performed in 510 patients. The resulting material was processed by microhistology and useful for diagnosis in 432 (84.2%). Clinical characteristics of APC (341) and SPC (169) revealed that APC patients were younger (P = 0.004) and had smaller PCLs (23 vs 35 mm; P < 0.001). In APC, we found more preneoplastic (38.7% vs 30.2%; P = 0.0016) and a lower number of malignant PCLs (8.2% vs 24.3%; P < 0.001). In APC and SPC, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of microhistology to detect malignancy were 71.4%, 99.7%, 95.2%, 97.5%, and 97.4% (k = 0.80) and 58.5%, 96.9%, 85.7%, 87.9%, and 87.6%, respectively. CONCLUSIONS Endoscopic ultrasound-guided fine-needle aspiration was technically feasible. Microhistology was especially useful to detect neoplastic or malignant PCLs in APC patients.
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Tian G, Ye Z, Zhao Q, Jiang T. Complication incidence of EUS-guided pancreas biopsy: A systematic review and meta-analysis of 11 thousand population from 78 cohort studies. Asian J Surg 2020; 43:1049-1055. [PMID: 31974051 DOI: 10.1016/j.asjsur.2019.12.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 11/26/2019] [Accepted: 12/18/2019] [Indexed: 01/10/2023] Open
Abstract
A systematic review and meta-analysis were performed to estimate the incidence of possible complications following EUS-guided pancreas biopsy. Pancreatic cancer has a very poor prognosis with a high fatality rate. Early diagnosis is important to improve the prognosis of pancreatic cancer. We searched Pubmed, Embase, Web of Science, and Scopus databases for studies published from inception to Augest, 2018. Meta-analysis were conducted with random-effect models and heterogeneity was calculated with the Q, I2 and τ2 statistics. We enrolled 78 studies from 71 articles in the meta-analysis, comprising 11,652 patients. Pooled data showed that the whole complication incidences were low 0.210 × 10-4(95%CI -0.648 × 10-4, 1.068 × 10-4). And they were in bleeding 0.002 × 10-4 (95%CI -0.092 × 10-4, 0.097 × 10-4), pancreatitis 0.002 (95%CI -0.082 × 10-4, 0.086 × 10-4), abdominal pain 0 (95%CI -0.037 × 10-4, 0.038 × 10-4), fever 0 (95%CI -0.032 × 10-4, 0. 032 × 10-4), infection 0 (95%CI -0.030 × 10-4, 0.031 × 10-4), duodenal perforation 0 (95%CI -0.033 × 10-4, 0.034 × 10-4), pancreatic fistula 0 (95%CI -0.029 × 10-4, 0.029 × 10-4), abscess 0 (95%CI -0.029 × 10-4, 0.029 × 10-4) and sepsis 0 (95%CI -0.029 × 10-4, 0.030 × 10-4). Subgroup analysis based on the tumor size, site, needle type and tumor style also showed robust results. The pooled data showed EUS-guided pancreas biopsy could be a safe approach for the diagnosis of pancreatic lesions. More large-scale studies will be necessary to confirm the findings across different population.
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Affiliation(s)
- Guo Tian
- Department of Ultrasound Medicine, The First Afliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Zhengdu Ye
- Department of Ultrasound Medicine, The First Afliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qiyu Zhao
- Department of Ultrasound Medicine, The First Afliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian'an Jiang
- Department of Ultrasound Medicine, The First Afliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.
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30
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Keane MG, Dadds HR, El Sayed G, Luong TV, Davidson BR, Fusai GK, Thorburn D, Pereira SP. Clinical and radiological features that predict malignant transformation in cystic lesions of the pancreas: a retrospective case note review. ACTA ACUST UNITED AC 2020; 1:4. [PMID: 32322783 PMCID: PMC7176489 DOI: 10.12688/amrcopenres.12860.2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background: Pancreatic cystic lesions (PCL) are being detected with increasing frequency. Current methods of stratifying risk of malignant transformation are imperfect. This study aimed to determine the frequency of pancreatic malignancy in patients with PCL and define clinical and radiological features that predict malignant transformation in patients managed by surgery and/or surveillance. Methods: A retrospective cohort of adults who were evaluated in a tertiary hepatopancreaticobiliary centre between January 2000 - December 2013 with a confirmed PCL and followed up for at least 5 years. All cystic lesions were discussed at a weekly multidisciplinary meeting. Results: Of the 1,090 patients diagnosed with a PCL, 768 patients were included in the study: 141 patients were referred for immediate pancreatic resection, 570 entered surveillance while 57 had a malignant PCL which was unresectable at diagnosis (n=47) or were unfit for surgery (n=10). In those who were resected following presentation, malignancy was present in 38%. During follow-up 2% of those entering a surveillance programme underwent malignant transformation. Clinical and radiological features associated with a high-risk PCL included older age, symptoms, associated solid component or dilated main pancreatic duct. In intraductal papillary mucinous neoplasms, larger size was not a feature of malignant transformation (benign vs. malignant 30mm vs. 23mm; P= 0.012). Conclusion: The sensitivity of standard diagnostic tests leading to immediate surgery for high-risk PCL (malignant or mucinous) was 92% but with a specificity of just 5%. Surveillance of PCL without high-risk features within a multidisciplinary meeting was associated with a low incidence of cancer development, supporting the use of worrisome clinical and radiological features in the initial stratification of PCL.
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Affiliation(s)
- Margaret G Keane
- Institute for Liver and Digestive Health, University College London, London, NW3 2QG, UK.,Department of Gastroenterology, University College London Hospitals NHS Trust, London, UK
| | - Hannah R Dadds
- Institute for Liver and Digestive Health, University College London, London, NW3 2QG, UK
| | - Ghassan El Sayed
- Department of Gastroenterology, University College London Hospitals NHS Trust, London, UK
| | - Tu Vinh Luong
- Institute for Liver and Digestive Health, University College London, London, NW3 2QG, UK.,Department of Cellular Pathology, University College London, London, UK
| | - Brian R Davidson
- Institute for Liver and Digestive Health, University College London, London, NW3 2QG, UK.,Department of HPB Surgery, Royal Free Hospital, London, NW3 2QG, UK
| | - Guiseppe K Fusai
- Institute for Liver and Digestive Health, University College London, London, NW3 2QG, UK.,Department of HPB Surgery, Royal Free Hospital, London, NW3 2QG, UK
| | - Douglas Thorburn
- Institute for Liver and Digestive Health, University College London, London, NW3 2QG, UK
| | - Stephen P Pereira
- Institute for Liver and Digestive Health, University College London, London, NW3 2QG, UK.,Department of Gastroenterology, University College London Hospitals NHS Trust, London, UK
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Crinò SF, Bernardoni L, Brozzi L, Barresi L, Malleo G, Salvia R, Frulloni L, Sina S, Parisi A, Remo A, Larghi A, Gabbrielli A, Manfrin E. Association between macroscopically visible tissue samples and diagnostic accuracy of EUS-guided through-the-needle microforceps biopsy sampling of pancreatic cystic lesions. Gastrointest Endosc 2019; 90:933-943. [PMID: 31100310 DOI: 10.1016/j.gie.2019.05.009] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 05/06/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS EUS-guided through-the-needle biopsy (TTNB) sampling has been reported to improve diagnostic yield compared with cytology for the evaluation of pancreatic cystic lesions (PCLs). The number of macroscopically visible tissue samples needed to reach an adequate diagnosis is still unknown. METHODS This is a retrospective, single-center study on consecutive patients with PCLs with risk features (cyst >3 cm, thickened wall, cyst growth during follow-up, and mural nodules) who underwent TTNB sampling. The capability of differentiating mucinous versus nonmucinous cysts, ability to obtain a cyst-lining epithelium, definition of the grade of dysplasia, and specific diagnosis of cyst histotype were evaluated for 1, 2, or 3 TTNB macroscopically visible specimens. RESULTS Sixty-one patients were evaluated. A 100% histologic adequacy was reached by 2 samples (P = .05 versus 1). Compared with cytology, 1 TTNB specimen improved the possibility of defining cyst histotype (P < .0001), whereas 2 specimens increased all 4 diagnostic categories (P < .003). Two specimens also increased diagnostic yield compared with 1 sample (P < .085). The collection of a third sample did not improve the value of any diagnostic categories. A specific diagnosis was reached in 74% of patients with 2 histologic samples. The diagnostic reliability of TTNB sampling compared with surgical histology was 90%, with a 22.9% rate of adverse events. CONCLUSIONS Two TTNB macroscopically visible specimens reached 100% histologic adequacy and a specific diagnosis in 74% of patients. The collection of a third specimen did not add any additional information and should be avoided to possibly decrease the risk of adverse events.
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Affiliation(s)
- Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Lorenzo Brozzi
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Giuseppe Malleo
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Luca Frulloni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Sokol Sina
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | - Alice Parisi
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | - Andrea Remo
- Department of Pathology, Mater Salutis Hospital, Legnago, Verona, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, IRCCS, Fondazione Policlinico Universitario A. Gemelli, Roma, Italy
| | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
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Larghi A, Manfrin E, Fabbri C, Crinò SF, Correale L, Chiarello G, Barresi L, Van Velthuysen ML, Poley JW, Rahal D, Carrara S, Inzani F, Fornelli A. Interobserver agreement among expert pathologists on through-the-needle microforceps biopsy samples for evaluation of pancreatic cystic lesions. Gastrointest Endosc 2019; 90:784-792.e4. [PMID: 31323232 DOI: 10.1016/j.gie.2019.07.011] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 07/03/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS The recent development of microforceps for EUS through-the-needle biopsy (TTNB) sampling of the wall of pancreatic cystic lesions (PCLs) allows the collection of histologic specimens never handled and evaluated before by pathologists. We aimed to estimate the interobserver agreement among pathologists in evaluating such samples. METHODS TTNB specimen slides from 40 PCLs with worrisome features were retrieved and independently evaluated for specimen adequacy, presence of lining epithelium, grade of epithelial dysplasia, presence of ovarian type stroma, and specific diagnosis by 6 expert pathologists from 6 different tertiary care centers. The Gwet's AC1 was used to assess interobserver agreement. RESULTS An almost perfect agreement was observed for specimen adequacy (AC1, .82; 95% confidence interval [CI], .79-.98), presence of lesional epithelium (AC1, .90; 95% CI, .86-.92), epithelial dysplasia (AC1, .97; 95% CI, .95-.99), and ovarian-like stroma (AC1, .90; 95% CI, .86-.93). When considering all diagnoses separately, a moderate to substantial agreement was observed (AC1, .62; 95% CI, .57-.67), similarly to mucinous cysts versus serous adenoma versus other diagnoses (AC1, .65; 95% CI, .59-.70) and for mucinous cysts versus all other diagnoses (AC1,.74; 95% CI, .68-.84). The agreement for diagnosis of mucinous cystic neoplasm versus intraductal mucinous papillary neoplasm was almost perfect (AC1, .88; 95% CI, .81-.95). CONCLUSIONS Interobserver agreement between expert pathologists in the evaluation of TTNB samples from PCLs with worrisome features was close to perfection for all evaluated parameters, except definitive diagnosis. When mucinous cystic lesions were compared versus all other diagnoses, the agreement became substantial, thus indicating that TTNB specimens can provide important information for PCL management decisions.
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Affiliation(s)
- Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | - Carlo Fabbri
- Digestive Endoscopy and Gastroenterology, Azienda Unità Sanitaria Locale AUSL della Romagna, Ospedali di Forlì e Cesena, Cesena and Forli, Italy
| | - Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Loredana Correale
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Gaia Chiarello
- Pathology Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT, Palermo, Italy
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT, Palermo, Italy
| | | | - Jan Werner Poley
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Daoud Rahal
- Pathology Department, Humanitas Research Hospital, Milan, Italy
| | - Silvia Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Milan, Italy
| | - Frediano Inzani
- Department of Pathology, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Adele Fornelli
- Pathology Unit, Azienda USL Città di Bologna, Ospedale Maggiore, Bologna, Italy
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Endoscopic ultrasonography for the evaluation of pancreatic cystic neoplasms. J Med Ultrason (2001) 2019; 47:401-411. [PMID: 31605262 DOI: 10.1007/s10396-019-00980-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/11/2019] [Indexed: 12/12/2022]
Abstract
Endoscopic ultrasonography (EUS) is a modality with high spatial resolution that enables comprehensive observation of the entire pancreas and plays an important role in the diagnosis of pancreatic lesions. Recent advances in diagnostic imaging methods such as ultrasound, computed tomography, and magnetic resonance imaging have increased the incidental detection of pancreatic cystic lesions (PCLs). EUS has been recognized as an essential diagnostic method for the detection and evaluation of PCLs. EUS has two important roles: as a detailed (high-resolution) imaging diagnostic method and as an approach for collecting cyst fluid content by EUS-guided fine needle aspiration for pathological diagnosis or biomarker evaluation. Furthermore, in recent years, the usefulness of contrast-enhanced EUS for the differential diagnosis of PCLs or evaluation of grade of malignancy, and a novel imaging technique called needle-based confocal laser endomicroscopy to observe intraductal structures through a needle, has been reported. An understanding of the morphological characteristics of PCLs depicted by ultrasound imaging and of the benefits and limitations of EUS diagnosis in daily practice is needed.
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Keane MG, Wehnert N, Perez-Machado M, Fusai GK, Thorburn D, Oppong KW, Carroll N, Metz AJ, Pereira SP. A prospective trial of CONfocal endomicroscopy in CYSTic lesions of the pancreas: CONCYST-01. Endosc Int Open 2019; 7:E1117-E1122. [PMID: 31475228 PMCID: PMC6715431 DOI: 10.1055/a-0957-2976] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 05/02/2019] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Pancreatic cystic lesions (PCL) are common. While some harbor malignant potential, accurate preoperative diagnosis remains challenging. Needle-based confocal laser endomicroscopy (nCLE) via a 19G FNA needle enables real-time imaging of the cyst wall. This study evaluated the safety and utility of nCLE in patients with an indeterminate PCL undergoing EUS-FNA. Patients and methods The CONCYST study prospectively recruited patients with indeterminate PCL attending three hepatopancreaticobiliary (HPB) referral centers in the UK, with indeterminate PCL, who required EUS-FNA between July 2014 and October 2016. Following the procedure, all patients were followed up in telephone clinic for at least 12 months. Ethical approval for the study was granted by the National Research Ethics Service (14/LO/0040). Results Sixty-seven patient were recruited, 11 excluded and 56 included in the final analysis: 35 male, 21 female; median age 68 (range 28 - 80). Recognizable confocal images were obtained in 48 of 56 cases. Median nCLE scanning time was 5 minutes and did not exceed 10 minutes in any case. EUS-nCLE findings correlated with final diagnosis (based on imaging, cytology and multidisciplinary team review) in 43/56 (77 %) of cases, compared with 37/56 (66 %) for cytology alone ( P = 0.12). One patient experienced mild pruritus following the procedure and another developed an infected pseudocyst, which resolved with antibiotics. Conclusions EUS-nCLE under conscious sedation in the day case setting is safe and provides additional information to standard EUS-FNA for diagnosing indeterminate PCL.
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Affiliation(s)
- Margaret G. Keane
- Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London, UK
| | - Natascha Wehnert
- Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London, UK
| | - Miguel Perez-Machado
- Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London, UK
| | - Giuseppe K. Fusai
- Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London, UK
| | - Douglas Thorburn
- Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London, UK
| | - Kofi W. Oppong
- Department of Gastroenterology and HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK & Institute of Cellular Medicine Newcastle University, Newcastle upon Tyne, UK
| | - Nicholas Carroll
- Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
| | - Andrew J. Metz
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville VIC, Australia
| | - Stephen P. Pereira
- Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London, UK,Corresponding author Professor Stephen Pereira UCL Institute for Liver and Digestive HealthRoyal Free CampusPond St, London, NW3 2PFUK+442079356826
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Estrada P, Benson M, Gopal D, Buehler D, Pfau P. Cytology with rapid on‐site examination (ROSE) does not improve diagnostic yield of EUS‐FNA of pancreatic cystic lesions. Diagn Cytopathol 2019; 47:1184-1189. [DOI: 10.1002/dc.24291] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 04/28/2019] [Accepted: 07/17/2019] [Indexed: 01/31/2023]
Affiliation(s)
- Paul Estrada
- Section of Gastroenterology and Hepatology, Department of MedicineUniversity of Wisconsin School of Medicine and Public Health Madison Wisconsin
| | - Mark Benson
- Section of Gastroenterology and Hepatology, Department of MedicineUniversity of Wisconsin School of Medicine and Public Health Madison Wisconsin
| | - Deepak Gopal
- Section of Gastroenterology and Hepatology, Department of MedicineUniversity of Wisconsin School of Medicine and Public Health Madison Wisconsin
| | - Darya Buehler
- Department of Pathology and Laboratory MedicineUniversity of Wisconsin School of Medicine and Public Health Madison Wisconsin
| | - Patrick Pfau
- Section of Gastroenterology and Hepatology, Department of MedicineUniversity of Wisconsin School of Medicine and Public Health Madison Wisconsin
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Şahin D, Çiçek B, Akpolat İ, Şişman G, Tekkeşin N. Should pancreas cyst fluids be divided into two for cytological diagnosis and biochemical tests? TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:903-909. [PMID: 31231069 DOI: 10.5152/tjg.2019.19006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests. MATERIALS AND METHODS The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified. RESULTS 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high. CONCLUSION Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.
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Affiliation(s)
- Davut Şahin
- Department of Pathology-Cytopathology, Acıbadem Health Group, İstanbul, Turkey
| | - Bahattin Çiçek
- Department of Gastroenterology, Acıbadem Mehmet Ali Aydınlar University, İstanbul, Turkey
| | - İlkser Akpolat
- Department of Pathology, Acıbadem Mehmet Ali Aydınlar University, İstanbul, Turkey
| | - Gürhan Şişman
- Department of Gastroenterology, Acıbadem Mehmet Ali Aydınlar University Atakent Hospital, İstanbul, Turkey
| | - Nilgün Tekkeşin
- Department of Biochemistry, Memorial Şişli Hospital, İstanbul, Turkey
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Pritzker KPH, Nieminen HJ. Needle Biopsy Adequacy in the Era of Precision Medicine and Value-Based Health Care. Arch Pathol Lab Med 2019; 143:1399-1415. [PMID: 31100015 DOI: 10.5858/arpa.2018-0463-ra] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
CONTEXT.— Needle biopsy of diseased tissue is an essential diagnostic tool that is becoming even more important as precision medicine develops. However, the capability of this modality to efficiently provide samples adequate for diagnostic and prognostic analysis remains quite limited relative to current diagnostic needs. For physicians and patients, inadequate biopsy frequently leads to diagnostic delay, procedure duplication, or insufficient information about tumor biology leading to delay in treatment; for health systems, this results in substantial incremental costs and inefficient use of scarce specialized diagnostic resources. OBJECTIVE.— To review current needle biopsy technology, devices, and practice with a perspective to identify current limitations and opportunities for improvement in the context of advancing precision medicine. DATA SOURCES.— PubMed searches of fine-needle aspiration and core needle biopsy devices and similar technologies were made generally, by tissue site, and by adequacy as well as by health economics of these technologies. CONCLUSIONS.— Needle biopsy adequacy can be improved by recognizing the importance of this diagnostic tool by promoting common criteria for needle biopsy adequacy; by optimizing needle biopsy procedural technique, technologies, clinical practice, professional education, and quality assurance; and by bundling biopsy procedure costs with downstream diagnostic modalities to provide better accountability and incentives to improve the diagnostic process.
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Affiliation(s)
- Kenneth P H Pritzker
- From the Departments of Laboratory Medicine and Pathobiology, and Surgery, University of Toronto, Toronto, Ontario, Canada (Dr Pritzker); and the Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland (Dr Nieminen)
| | - Heikki J Nieminen
- From the Departments of Laboratory Medicine and Pathobiology, and Surgery, University of Toronto, Toronto, Ontario, Canada (Dr Pritzker); and the Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland (Dr Nieminen)
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Diagnostic ability of artificial intelligence using deep learning analysis of cyst fluid in differentiating malignant from benign pancreatic cystic lesions. Sci Rep 2019; 9:6893. [PMID: 31053726 PMCID: PMC6499768 DOI: 10.1038/s41598-019-43314-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 04/03/2019] [Indexed: 12/15/2022] Open
Abstract
The diagnosis of pancreatic cystic lesions remains challenging. This study aimed to investigate the diagnostic ability of carcinoembryonic antigen (CEA), cytology, and artificial intelligence (AI) by deep learning using cyst fluid in differentiating malignant from benign cystic lesions. We retrospectively reviewed 85 patients who underwent pancreatic cyst fluid analysis of surgical specimens or endoscopic ultrasound-guided fine-needle aspiration specimens. AI using deep learning was used to construct a diagnostic algorithm. CEA, carbohydrate antigen 19-9, carbohydrate antigen 125, amylase in the cyst fluid, sex, cyst location, connection of the pancreatic duct and cyst, type of cyst, and cytology were keyed into the AI algorithm, and the malignant predictive value of the output was calculated. Area under receiver-operating characteristics curves for the diagnostic ability of malignant cystic lesions were 0.719 (CEA), 0.739 (cytology), and 0.966 (AI). In the diagnostic ability of malignant cystic lesions, sensitivity, specificity, and accuracy of AI were 95.7%, 91.9%, and 92.9%, respectively. AI sensitivity was higher than that of CEA (60.9%, p = 0.021) and cytology (47.8%, p = 0.001). AI accuracy was also higher than CEA (71.8%, p < 0.001) and cytology (85.9%, p = 0.210). AI may improve the diagnostic ability in differentiating malignant from benign pancreatic cystic lesions.
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Barresi L, Tacelli M, Ligresti D, Traina M, Tarantino I. Tissue acquisition in pancreatic cystic lesions. Dig Liver Dis 2019; 51:286-292. [PMID: 30166219 DOI: 10.1016/j.dld.2018.08.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 07/31/2018] [Accepted: 08/02/2018] [Indexed: 02/06/2023]
Abstract
Despite the progress achieved by scientific research in recent years, pancreatic cystic lesions (PCLs) remain a challenging clinical problem. A significant percentage of benign PCLs are still wrongly sent to surgery, with all the related risks of a high number of surgery-related complications and mortality. Diagnosis of the type of PCL, and risk stratification for malignancy are essential for a correct management of these lesions. Several guidelines have identified some clinical and morphological aspects suggesting the need for more accurate exams. Endoscopic ultrasound fine needle aspiration (EUS-FNA) of cystic fluid for cytology is the advised method of tissue acquisition in several guidelines, and the most used technique around the world. However sensitivity and adequacy of this technique are limited by the low amount of cells dispersed in cystic fluid. Alternative techniques have been tested to target the cystic walls in an attempt to obtain microhistologic specimens in order to augment the probability of obtaining an adequate diagnostic sample. The aim of this review is to offer a critical overview of the existing literature on tissue acquisition in PCLs, and emphasize advantages and disadvantages of each technique, and unclear areas that need to be investigated with future research.
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Affiliation(s)
- Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy.
| | - Matteo Tacelli
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Dario Ligresti
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Mario Traina
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Ilaria Tarantino
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
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40
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Barresi L, Crinò SF, Fabbri C, Attili F, Poley JW, Carrara S, Tarantino I, Bernardoni L, Giovanelli S, Di Leo M, Manfrin E, Tacelli M, Bruno MJ, Traina M, Larghi A. Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: A multicenter study. Dig Endosc 2018; 30:760-770. [PMID: 29808529 DOI: 10.1111/den.13197] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 05/25/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Tissue acquisition in pancreatic cystic lesions (PCL) is the ideal method for diagnosis and risk stratification for malignancy of these lesions. Direct sampling from the walls of PCL with different devices has shown better results than cytology from cystic fluid. We carried out a retrospective, multicenter study to evaluate the feasibility, safety, and diagnostic yield of a micro-forceps, specifically designed to be used through a 19-gauge needle after endoscopic ultrasonography (EUS)-guided puncture of PCL. METHODS We retrospectively collected data from patients who underwent EUS-through-the-needle biopsy (EUS-TTNB) in PCL at six referral centers. RESULTS The sampling procedure was carried out in 56 patients (mean age 57.5 ± 13.1 years, M:F 17:39), and was technically successful in all of them (100%; 95% confidence interval [CI], 94-100%). Adverse events occurred in 9/56 (16.1%; 95% CI, 8-28%) patients, with self-limited intracystic hemorrhage the most common (7/56, 12.5%; 95% CI, 5-24%). All adverse events were mild, and resolved without any specific intervention. Specimens were considered adequate for histological diagnosis in 47/56 (83.9%; 95% CI, 72-92%). In two of these patients, despite the histological adequacy, a diagnosis could not be reached. In two other cases, a specimen sufficient for a cytological diagnosis was obtained. Overall diagnostic yield by combining cytological and histological samples was 47/56 (83.9%; 95% CI, 72-92%). CONCLUSION EUS-TTNB with micro-forceps in PCL is feasible, safe, and has a high diagnostic yield. Future prospective studies are needed to better assess the clinical impact of EUS-TTNB on the management of PCL.
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Affiliation(s)
- Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Stefano F Crinò
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Carlo Fabbri
- Department of Gastroenterology and Surgical Sciences, Bellaria-Maggiore Hospital, AUSL Bologna, University of Bologna, Bologna, Italy
| | - Fabia Attili
- Digestive Endoscopy Unit, Catholic University, Rome, Italy
| | - Jan W Poley
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Silvia Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Milan, Italy
| | - Ilaria Tarantino
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Laura Bernardoni
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Silvia Giovanelli
- Department of Gastroenterology and Surgical Sciences, Bellaria-Maggiore Hospital, AUSL Bologna, University of Bologna, Bologna, Italy
| | - Milena Di Leo
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Milan, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - Matteo Tacelli
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Mario Traina
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Catholic University, Rome, Italy
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Chen HY, Zhao J, Lu YF, Lv SY, Chen JY, Pan Y, Shi D, Xu XF, Yu RS. The "extracapsular cystic" sign in pancreatic serous cystic neoplasms: A clinicopathologic study of 177 patients with cystic pancreatic lesions. Eur J Radiol 2018; 106:167-172. [PMID: 30150040 DOI: 10.1016/j.ejrad.2018.08.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 07/30/2018] [Accepted: 08/02/2018] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To assess a new imaging feature that we have named the extracapsular cystic sign which can make a constructive contribution towards differentiating serous cystic neoplasms (SCNs) from other pancreatic cystic lesions. MATERIAL AND METHODS We retrospectively reviewed 177 CTs/MRIs of patients who underwent pancreatic resection of cystic lesions at two institutions from January 2011/2013, to September 2017. For each patient, demographic information, clinical presentation, especially imaging features were carefully investigated by two experienced abdominal radiologists, retrospectively. All statistical analyses were performed using SPSS V.23.0. RESULTS Twenty-one lesions had extracapsular cystic signs which were newly discovered, 17 (28.3%) of 60 SCNs and 4 (3.4%) (mucinous cystic neoplasm = 1, walled-off necrosis = 2, retention cyst = 1) of 117 Non-SCNs were included, from which indicating that the extracapsular cystic sign was more often detected on SCNs. As for 21 lesions, 86% (n = 18) were females, and mean age at diagnosis was 51.2 years. 71% (n = 15) located in the pancreatic body and tail. Average size was 27.2 mm (23.7-53.4), mean (SD) ratio of biggest daughter cyst to mother cyst was 0.51[0.14] (p = 0.99), average (SD) angle between two of them was 105.5° [14.9] (p = 0.84). The average time interval between last imaging examination and surgery was 8.4 days. CONCLUSIONS The new sign named the extracapsular cystic sign in SCNs may help differentiate SCNs from other pancreatic cystic lesions. Furthermore, this study supports an original diagnosis for SCNs when the sign of extracapsular cyst appears.
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Affiliation(s)
- Hai-Yan Chen
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jin Zhao
- Department of Radiology, Zhejiang Hospital, Hangzhou, China
| | - Yuan-Fei Lu
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Sang-Ying Lv
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jie-Yu Chen
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yao Pan
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dan Shi
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiu-Fang Xu
- Department of Radiology, Hangzhou Medical College, Hangzhou, China.
| | - Ri-Sheng Yu
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Alvarez-Sánchez MV, Napoléon B. New horizons in the endoscopic ultrasonography-based diagnosis of pancreatic cystic lesions. World J Gastroenterol 2018; 24:2853-2866. [PMID: 30018480 PMCID: PMC6048425 DOI: 10.3748/wjg.v24.i26.2853] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/28/2018] [Accepted: 06/16/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cystic lesions (PCLs) are increasingly being identified because of the widespread use of high-resolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and therefore, accurate diagnosis is crucial to determine the best management strategy, either surgical resection or surveillance. However, the current standard of diagnosis is not accurate enough due to limitations of imaging and tissue sampling techniques, which entail the risk of unnecessary burdensome surgery for benign lesions or missed opportunities of prophylactic surgery for potentially malignant PCLs. In the last decade, endoscopic innovations based on endoscopic ultrasonography (EUS) imaging have emerged, aiming to overcome the present limitations. These new EUS-based technologies are contrast harmonic EUS, needle-based confocal endomicroscopy, through-the-needle cystoscopy and through-the needle intracystic biopsy. Here, we present a comprehensive and critical review of these emerging endoscopic tools for the diagnosis of PCLs, with a special emphasis on feasibility, safety and diagnostic performance.
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Affiliation(s)
- María-Victoria Alvarez-Sánchez
- Instituto de Investigación Sanitaria Galicia Sur, Complejo Hospitalario Universitario de Pontevedra, Pontevedra 36003, Spain
| | - Bertrand Napoléon
- Department of Gastroenterology, Ramsay Générale de Santé Private Hospital Jean Mermoz, Lyon 69008, France
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Raman A, Lennon AM. Cyst Fluid Biomarkers - Diagnosis and Prediction of Malignancy for Cystic Lesions of the Pancreas. Visc Med 2018; 34:178-181. [PMID: 30140682 DOI: 10.1159/000490137] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Pancreatic cysts are common, and are identified in 2-13% of individuals undergoing cross-sectional imaging. Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are pancreatic cysts which are precursors to pancreatic adenocarcinoma. Currently available tools are imperfect at differentiating IPMNs and MCNs from other, benign types of pancreatic cysts. The role of molecular markers in the evaluation of pancreatic cysts and the identification of cysts with high-grade dysplasia or invasive adenocarcinoma is reviewed.
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Affiliation(s)
- Aadhithya Raman
- Department of Medicine, Surgery, Radiology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anne Marie Lennon
- Department of Medicine, Surgery, Radiology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Lariño-Noia J, de la Iglesia D, Iglesias-García J, Macías M, López Martín A, Legaz ML, Vila J, Reyes A, Abdulkader I, Domínguez-Muñoz JE. Endoscopic ultrasound cytologic brushing vs endoscopic ultrasound - fine needle aspiration for cytological diagnosis of cystic pancreatic lesions. A multicenter, randomized open-label trial. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 110:478-484. [PMID: 29685048 DOI: 10.17235/reed.2018.5449/2017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION the incidence of cystic pancreatic lesions (CPL) in the asymptomatic population is increasing. Achieving a preoperative diagnosis of CPL still remains a challenge. OBJECTIVES to evaluate the diagnostic accuracy of the cytological diagnosis of CPL from samples obtained by cytology brush versus standard endoscopic ultrasound fine needle aspiration (EUS-FNA). METHODS a multicenter, randomized, open-label trial was performed of EUS-cytology brush (EUS-EB) versus EUS-FNA for the cytological diagnosis of CPL. Patients that underwent EUS-FNA with a CPL > 15 mm were included and randomized into two groups: group I, EUS-EB; group II, EUS-FNA. The final diagnosis was based on the histological evaluation of surgical specimens and clinical parameters, imaging and a five year follow-up in non-operated patients. The main outcome was the diagnostic accuracy of both methods. Secondary outcomes were the diagnostic adequacy of specimens and the rate of adverse events. Data were compared using the Chi-squared test. An intention to treat (ITT) and per-protocol (PP) analysis were performed. RESULTS sixty-five patients were included in the study, 31 in group I and 34 in group II. Three patients initially randomized to group I were changed to group II as it was impossible to obtain a sample using the brush. The mean size of the CPL was 28.2 mm (range 16-60 mm). The diagnostic accuracy of EUS-EB was not superior to EUS-FNA, neither in the ITT nor the PP analysis (44.8% vs 41.1%, p = 0.77 and 38.4% vs 45.9%, p = 0.55). CONCLUSIONS EUS-EB does not improve the diagnostic accuracy of CPL in comparison with EUS-FNA.
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Affiliation(s)
- José Lariño-Noia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Spain
| | | | - Julio Iglesias-García
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Spain
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Elta GH, Enestvedt BK, Sauer BG, Lennon AM. ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts. Am J Gastroenterol 2018; 113:464-479. [PMID: 29485131 DOI: 10.1038/ajg.2018.14] [Citation(s) in RCA: 396] [Impact Index Per Article: 56.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 01/05/2018] [Indexed: 02/07/2023]
Abstract
Pancreatic cysts are very common with the majority incidentally identified. There are several types of pancreatic cysts; some types can contain cancer or have malignant potential, whereas others are benign. However, even the types of cysts with malignant potential rarely progress to cancer. At the present time, the only viable treatment for pancreatic cysts is surgical excision, which is associated with a high morbidity and occasional mortality. The small risk of malignant transformation, the high risks of surgical treatment, and the lack of high-quality prospective studies have led to contradictory recommendations for their immediate management and for their surveillance. This guideline will provide a practical approach to pancreatic cyst management and recommendations for cyst surveillance for the general gastroenterologist.
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Affiliation(s)
- Grace H Elta
- Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Brintha K Enestvedt
- Division of Gastroenterology, Oregon Health and Sciences University, Portland, Oregon, USA
| | - Bryan G Sauer
- Division of Gastroenterology, University of Virginia, Charlottesville, Virginia, USA
| | - Anne Marie Lennon
- Division of Gastroenterology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
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Abstract
Pancreatic cysts are extremely common, and are identified in between 2% to 13% on abdominal imaging studies. Most pancreatic cysts are pseudocysts, serous cystic neoplasms, mucinous cystic neoplasms, or intraductal papillary mucinous neoplasms. The management of pancreatic cysts depends on whether a cyst is benign, has malignant potential, or harbors high-grade dysplasia or invasive carcinoma. The diagnosis of pancreatic cysts, and assessment of risk of malignant transformation, incorporates clinical history, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound, and fine-needle aspiration of cyst fluid. This article reviews the cyst fluid markers that are currently used, as well as promising markers under development.
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Affiliation(s)
- Saowanee Ngamruengphong
- Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, 1800 Orleans Street, Sheikh Zayed Tower, Baltimore, MD 21287, USA
| | - Anne Marie Lennon
- Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, 1800 Orleans Street, Sheikh Zayed Tower, Room 7125JB3, Baltimore, MD 21287, USA.
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Barresi L, Tacelli M, Tarantino I, Cipolletta F, Granata A, Traina M. Improving the yield of EUS-guided histology. Endosc Ultrasound 2018; 7:301-305. [PMID: 30323157 PMCID: PMC6199905 DOI: 10.4103/eus.eus_45_18] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Matteo Tacelli
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Ilaria Tarantino
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Fabio Cipolletta
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Antonino Granata
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Mario Traina
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
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Jabbar KS, Arike L, Verbeke CS, Sadik R, Hansson GC. Highly Accurate Identification of Cystic Precursor Lesions of Pancreatic Cancer Through Targeted Mass Spectrometry: A Phase IIc Diagnostic Study. J Clin Oncol 2017; 36:367-375. [PMID: 29166170 DOI: 10.1200/jco.2017.73.7288] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose Pancreatic cystic lesions are common incidental findings on imaging, but up to half may be forerunners of pancreatic cancer. Therefore, accurate differential diagnosis is crucial for correct patient management. Unfortunately, currently available diagnostic methods cannot robustly identify premalignant and malignant pancreatic cystic lesions. Methods Cyst fluid samples obtained by routine endoscopic ultrasound-guided aspiration were used for the analyses. In a cohort of 24 patients, eight biomarker candidates for malignant potential and high-grade dysplasia/cancer were identified by an explorative proteomic approach. Subsequently, a quantitative analysis, using 30 heavy-labeled peptides from the biomarkers and parallel reaction monitoring mass spectrometry, was devised, tested in a training cohort of 80, and prospectively evaluated in a validation cohort of 68 patients. End points were surgical pathology diagnosis/clinical follow-up. Diagnostic assessments were blinded to mass spectrometry results. Results The optimal set of markers for detecting malignant potential was a panel of peptides from mucin-5AC and mucin-2, which could discriminate premalignant/malignant lesions from benign with an accuracy of 97% (95% CI, 89% to 99%) in the validation cohort. This result compared favorably with the accuracy of standard analyses: cyst fluid carcinoembryonic antigen (61%; 95% CI, 46% to 74%; P < .001) and cytology (84%; 95% CI, 71% to 92%; P = .02). A combination of proteins mucin-5AC and prostate stem-cell antigen could identify high-grade dysplasia/cancer with an accuracy of 96% (95% CI, 90% to 99%), and detected 95% of malignant/severely dysplastic lesions, compared with 35% and 50% for carcinoembryonic antigen and cytology ( P < .001 and P = .003, respectively). Conclusion Targeted mass spectrometry analysis of just three cyst fluid biomarkers provides highly accurate identification and assessment of cystic precursors to pancreatic adenocarcinoma. Additional studies should determine whether the method can facilitate timely cancer diagnosis, successful intervention, and prevention.
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Affiliation(s)
- Karolina S Jabbar
- Karolina S. Jabbar, Liisa Arike, and Gunnar C. Hansson, University of Gothenburg; Karolina S. Jabbar and Riadh Sadik, Sahlgrenska University Hospital, Gothenburg, Sweden; and Caroline S. Verbeke, University of Oslo, Oslo, Norway
| | - Liisa Arike
- Karolina S. Jabbar, Liisa Arike, and Gunnar C. Hansson, University of Gothenburg; Karolina S. Jabbar and Riadh Sadik, Sahlgrenska University Hospital, Gothenburg, Sweden; and Caroline S. Verbeke, University of Oslo, Oslo, Norway
| | - Caroline S Verbeke
- Karolina S. Jabbar, Liisa Arike, and Gunnar C. Hansson, University of Gothenburg; Karolina S. Jabbar and Riadh Sadik, Sahlgrenska University Hospital, Gothenburg, Sweden; and Caroline S. Verbeke, University of Oslo, Oslo, Norway
| | - Riadh Sadik
- Karolina S. Jabbar, Liisa Arike, and Gunnar C. Hansson, University of Gothenburg; Karolina S. Jabbar and Riadh Sadik, Sahlgrenska University Hospital, Gothenburg, Sweden; and Caroline S. Verbeke, University of Oslo, Oslo, Norway
| | - Gunnar C Hansson
- Karolina S. Jabbar, Liisa Arike, and Gunnar C. Hansson, University of Gothenburg; Karolina S. Jabbar and Riadh Sadik, Sahlgrenska University Hospital, Gothenburg, Sweden; and Caroline S. Verbeke, University of Oslo, Oslo, Norway
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Aronsson L, Andersson R, Swahn F, Ansari D. Does next-generation sequencing of cyst fluid improve management of pancreatic cystic neoplasms? Scand J Gastroenterol 2017; 52:1049-1051. [PMID: 28678564 DOI: 10.1080/00365521.2017.1349175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Pancreatic cystic lesions represent a heterogeneous group of diseases ranging from benign to malignant lesions. They are increasingly being detected due to the widespread use of cross-sectional imaging. Their management is a challenge because it is often not possible to reliably discriminate between malignant and nonmalignant lesions using current imaging technology. Next-generation sequencing (NGS) has the ability of both whole genome and targeted sequencing at a low cost and from a limited amount of DNA. NGS of cyst fluid aspired by endoscopic ultrasonography-guided fine-needle aspiration provides a valuable tool in biomarker research and may in the future help improve diagnosis and management of pancreatic cystic lesions.
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Affiliation(s)
- Linus Aronsson
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
| | - Roland Andersson
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
| | - Fredrik Swahn
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
| | - Daniel Ansari
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
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Zhu H, Jiang F, Zhu J, Du Y, Jin Z, Li Z. Assessment of morbidity and mortality associated with endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions: A systematic review and meta-analysis. Dig Endosc 2017; 29:667-675. [PMID: 28218999 DOI: 10.1111/den.12851] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 02/16/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM With increased availability of imaging technology, detection of pancreatic cystic lesions (PCL) is on the rise. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) improves the diagnosis accuracy of PCL. Systematic evaluation of morbidity and mortality associated with EUS-FNA for PCL has not been carried out. We conducted a systematic review and meta-analysis of morbidity and mortality associated with EUS-FNA. METHODS A literature search for relevant English-language articles was conducted on PubMed and EMBASE databases. Main outcome measures for this analysis were adverse effects of diagnostic EUS-FNA, and the associated morbidity and mortality, in patients with PCL. RESULTS Forty studies, with a combined subject population of 5124 patients with PCL, satisfied the inclusion criteria. Overall morbidity as a result of adverse events of EUS-FNA was 2.66% (95% confidence interval [CI]: 1.84-3.62%), and the associated mortality was 0.19% (95% CI: 0.09-0.32%). Common post-procedure adverse events included pancreatitis 0.92% (95% CI: 0.63-1.28%), hemorrhage 0.69% (95% CI: 0.42-1.02%), pain 0.49% (95% CI: 0.27-0.79%), infection 0.44% (95% CI: 0.27-0.66%), desaturation 0.23% (95% CI: 0.12-0.38%) and perforation 0.21% (95% CI: 0.11-0.36%). There was no peritoneal seeding in our study. Incidence of adverse events associated with prophylactic periprocedural antibiotic use was 2.77% (95% CI: 1.87-3.85%). CONCLUSIONS EUS-FNA is a safe procedure for diagnosis of PCL and is associated with a relatively low incidence of adverse events. Most adverse events were mild, self-limiting, and did not require medical intervention.
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Affiliation(s)
- Huiyun Zhu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Fei Jiang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Jianwei Zhu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Yiqi Du
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Zhendong Jin
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Zhaoshen Li
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
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