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Zhang ML, Pitman MB. Cytology of cystic lesions of the pancreas: Practical insights, pearls, and pitfalls. Cancer Cytopathol 2025; 133:e70011. [PMID: 40249200 DOI: 10.1002/cncy.70011] [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] [Received: 12/13/2024] [Revised: 01/26/2025] [Accepted: 01/29/2025] [Indexed: 04/19/2025]
Abstract
Pancreatic cyst fluid (PCF) specimens present significant interpretive challenges. Accurate preoperative diagnosis is essential for guiding patient management, as pancreatic cysts vary from benign to pre-malignant and malignant. Appropriate triage differentiates low-risk cysts requiring surveillance from high-risk cysts necessitating surgical resection, the latter of which have increased likelihood of progressing to or harboring invasive carcinoma. Optimal PCF assessment integrates radiological, cytological, biochemical, and molecular findings if available. Key biochemical markers such as carcinoembryonic antigen and glucose can improve the detection of neoplastic mucinous cysts. However, cytology remains the most specific modality for identifying high-risk cysts. Cytomorphologic interpretation is particularly challenging due to the scant cellularity and degenerative changes often present in these specimens. This review provides practical insights to improve the evaluation of pancreatic cysts, emphasizing the importance of a multidisciplinary approach and highlighting diagnostic pearls and common pitfalls to aid in accurate interpretation and optimal patient care.
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Affiliation(s)
- M Lisa Zhang
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Martha B Pitman
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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2
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Zare-Mehrjardi MJ, Hatami-Araghi M, Jafari-Khorchani M, Oushyani Roudsari Z, Taheri-Anganeh M, Abdolrahmat M, Ghasemi H, Aiiashi S. RNA biosensors for detection of pancreatic cancer. Clin Chim Acta 2025; 571:120237. [PMID: 40081786 DOI: 10.1016/j.cca.2025.120237] [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] [Received: 12/12/2024] [Revised: 03/06/2025] [Accepted: 03/06/2025] [Indexed: 03/16/2025]
Abstract
Pancreatic cancer is recognized as one of the most lethal types of cancer globally, characterized by a high mortality rate and a bleak prognosis, which greatly contributes to cancer-related deaths. Forecasts suggest that by 2030, pancreatic cancer will exceed other cancer types in prevalence. The disease presents considerable difficulties owing to the lack of prominent symptoms in its early stages, restricted options for early detection, rapid progression, and unfavorable outcomes. Presently, traditional methods for diagnosing pancreatic cancer primarily rely on imaging techniques. However, these methods often entail significant costs, require considerable time, and necessitate specialized skills for both operating the equipment and interpreting the resulting images. To overcome these obstacles, the use of biosensors has been proposed as a potentially valuable tool for the early detection of pancreatic cancer. MicroRNAs (miRs), a type of small non-coding RNA molecules, have emerged as highly sensitive molecular diagnostic tools that have the potential to function as precise indicators for a range of diseases, including cancer. Biosensors have been suggested as a potential solution for tackling these challenges, offering a promising approach for the early detection of pancreatic cancer. Small non-coding RNA molecules known as MicroRNAs (miRs) have become recognized as extremely sensitive molecular diagnostic tools and can act as precise biomarkers for different diseases, such as cancer. Moreover, this manuscript presents a thorough summary of the latest innovations in nano-biosensors that have been specifically developed for the identification of non-coding RNAs related to pancreatic cancer.
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Affiliation(s)
| | - Mahtab Hatami-Araghi
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Majid Jafari-Khorchani
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Zahra Oushyani Roudsari
- Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Mona Abdolrahmat
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hassan Ghasemi
- Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran.
| | - Saleh Aiiashi
- Abadan University of Medical Sciences, Abadan, Iran.
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Assawasirisin C, Qadan M, Aimprasittichai S, Kambadakone A, Servin-Rojas M, Warshaw AL, Lillemoe KD, Fernández-Del Castillo C. Pancreatic Serous Cystadenoma: A Continuing Diagnostic Challenge. Ann Surg 2025; 281:501-507. [PMID: 38230538 DOI: 10.1097/sla.0000000000006203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
OBJECTIVE To understand the natural history of serous cystadenoma (SCA), and the diagnostic accuracy of SCA and identify possible factors that lead to the correct diagnosis. BACKGROUND SCA is a benign cystic pancreatic neoplasm of the pancreas, accounting for ~15% of resected pancreatic cysts. Current recommendations are to proceed with surgical resection in symptomatic patients or when there is uncertainty regarding diagnosis. The latter continues to be a challenge since intentional resection of an SCA accounts for only a minority of resected cases. METHODS Retrospective single-institution review of patients who on final pathology had a diagnosis of pancreatic SCA and of patients who had this diagnosis and were managed nonoperatively. Demographic data, cyst characteristics, and growth rate were collected for analysis. RESULTS A total of 250 patients were analyzed. Median age was 62 (range: 22-89), 65% were females, and 34% had symptoms. Tumor size ranged from 0.6 to 20, with a median of 3.4 cm. The morphologic appearance was microcystic in 58%, macrocystic in 16%, mixed-type in 23%, and solid in 3%. Pancreatic duct dilation and pancreatic atrophy were found in 22% and 14%, respectively. The average growth rate was 1.8 mm/year regardless of tumor size. Of the 172 patients who underwent surgery, SCA was the preoperative diagnosis in only 33%. A correct diagnosis was independently associated with large tumors and cyst fluid carcinoembryonic antigen analysis. Pancreatic duct dilation was independently associated with an in-growing cyst and the presence of calcification. CONCLUSIONS SCA is a slow-growing pancreatic cystic neoplasm that is mostly asymptomatic but can lead to pancreatic duct dilation and atrophy in some patients. A surprisingly small number of correct preoperative diagnoses confirms that this entity continues to be a diagnostic challenge. A more thorough preoperative workup that includes endoscopic ultrasonography should improve the rate of misdiagnosis.
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Affiliation(s)
- Charnwit Assawasirisin
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
- Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Satita Aimprasittichai
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Avinash Kambadakone
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Andrew L Warshaw
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Bloomfield GC, Yusin G, Radkani P, Namgoong J, Haddad NG, Chalhoub W, Fishbein TM, Winslow ER. The Role of Markedly Elevated Cyst Carcinoembryonic Antigen in Risk-Stratifying Pancreatic Cysts. J Surg Res 2025; 307:189-196. [PMID: 40056782 DOI: 10.1016/j.jss.2025.01.027] [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] [Received: 03/05/2024] [Revised: 12/10/2024] [Accepted: 01/26/2025] [Indexed: 03/10/2025]
Abstract
INTRODUCTION Carcinoembryonic antigen (CEA) level is currently being used in algorithms of commercially available pancreatic cyst fluid analysis platforms. However, the evidence to date on its role in risk stratification for mucinous lesions is heterogenous. We therefore sought to examine the relationship between the magnitude of CEA elevation and the structural and molecular properties of pancreatic cysts. METHODS All patients who underwent pancreatic cyst fluid analysis at a single institution from 2012 to 2019 were retrospectively examined. Structural features on endoscopic ultrasound were analyzed as a function of cyst fluid CEA. A subset of patients who underwent surgical resection was separately analyzed. RESULTS A total of 634 pancreatic cyst fluid samples were obtained from 566 patients. Among all samples, 57% had normal cyst fluid CEA. Of those with elevated CEA, 22% had elevations <1000, 13% between 1000 and 10,000, and 8% > 10,000 ng/mL. The CEA >10,000 group had the highest rates of solid components (P = 0.039), mural nodules (P = 0.044), and mean number of DNA abnormalities (P < 0.001). The overall malignancy rate among all patients with cyst CEA >10,000 ng/mL was 14% (n = 7). Importantly, there was a strong association between the magnitude of the CEA elevation and the number of DNA abnormalities (P < 0.001) and the presence of oncogene mutations (P < 0.001). CONCLUSIONS In this large dataset of pancreatic cyst fluid aspirates, the magnitude of the CEA elevation was associated with worrisome features. Especially at its most extreme, elevated CEA should be further examined in the assessment of neoplastic risk for patients with an established diagnosis of a mucinous pancreatic cyst.
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Affiliation(s)
- Grace C Bloomfield
- Georgetown University School of Medicine, Washington, District of Columbia
| | - George Yusin
- Department of Surgery, MedStar Health, Baltimore, Maryland
| | - Pejman Radkani
- MedStar Georgetown Transplant Institute, Medstar Georgetown University Hospital, Washington, District of Columbia
| | - Jean Namgoong
- Georgetown University School of Medicine, Washington, District of Columbia
| | - Nadim G Haddad
- Department of Gastroenterology, Medstar Georgetown University Hospital, Washington, District of Columbia
| | - Walid Chalhoub
- Department of Gastroenterology, Medstar Georgetown University Hospital, Washington, District of Columbia
| | - Thomas M Fishbein
- MedStar Georgetown Transplant Institute, Medstar Georgetown University Hospital, Washington, District of Columbia
| | - Emily R Winslow
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
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Tomita D, Matsumura M, Fujisawa K, Okubo S, Shindoh J, Tamura T, Imamura T, Miura Y, Takazawa Y, Hashimoto M. Pancreatic groove cancer with large cystic lesion. Clin J Gastroenterol 2025; 18:242-247. [PMID: 39612050 DOI: 10.1007/s12328-024-02071-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 11/17/2024] [Indexed: 11/30/2024]
Abstract
Groove pancreatic cancer is a malignant tumor that originates from the groove between the pancreas, duodenum, and bile duct. Groove pancreatic cancer shares similarities with groove pancreatitis in terms of clinical symptoms and imaging findings, which often makes it difficult to distinguish between the two diseases. We describe the case of a patient with a cystic lesion associated with groove pancreatic cancer. A 54-year-old male patient presented with sudden vomiting, hematemesis, and persistent epigastric pain. Enhanced computed tomography revealed a hypoenhanced, ill-defined lesion extending from the pancreatic head to the duodenum, with a large duodenal cystic formation. Despite various diagnostic efforts, a definitive diagnosis of malignancy before surgery remained elusive. Intraoperative findings revealed that the tumor was resectable. Subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection and right hemicolectomy were performed. The resected specimen revealed groove pancreatic adenocarcinoma invading the duodenum and ascending colon. A large cyst was observed within the duodenal wall, the interior of which was lined with cancer cells. Despite postoperative chemotherapy, the patient succumbed to the disease 17 months after resection. This case emphasizes that when a groove area lesion with a huge paraduodenal cyst is observed, the possibility of groove pancreatic cancer should be considered.
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Affiliation(s)
- Daisuke Tomita
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Masaru Matsumura
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan.
| | - Kentoku Fujisawa
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Satoshi Okubo
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Junichi Shindoh
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Tetsuo Tamura
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Tsunao Imamura
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Yasuro Miura
- Department of Pathology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Yutaka Takazawa
- Department of Pathology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Masaji Hashimoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
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Wesali S, Molinaro A, Lindkvist B, Hedenström P, Sadik R. Endoscopic ultrasound is useful for the risk stratification of mucinous pancreatic cystic lesions: A long-term prospective study. Pancreatology 2024:S1424-3903(24)00834-2. [PMID: 39741057 DOI: 10.1016/j.pan.2024.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 11/18/2024] [Accepted: 12/13/2024] [Indexed: 01/02/2025]
Abstract
OBJECTIVES The aims of this prospective observational study were to test worrisome features on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a stratification tool in patients with mucinous pancreatic cystic lesions (PCLs), and to assess these patients' long-term risk of adenocarcinoma and mortality. METHODS Patients with suspected PCLs on cross-sectional imaging who underwent EUS-FNA at Sahlgrenska University Hospital between February 2007 and February 2018 were consecutively enrolled. The main inclusion criterion was the final diagnosis of a mucinous PCL. The results from EUS-FNA were analyzed in the context of outcome gathered from medical records of follow-up until February 2021. RESULTS Of 334 patients undergoing EUS-FNA, 171 (51 %) had a final diagnosis of a mucinous PCL. 29/171 (17 %) patients were diagnosed with HGD or adenocarcinoma <6 months after EUS-FNA, with 28/29 (97 %) patients having at least one worrisome feature on EUS-FNA. A solid component in mucinous PCLs on EUS was independently associated with the presence of HGD or adenocarcinoma (OR 23.6, 95 % CI 6.1-91.6, p < .001). A total of 4/142 (3 %) patients developed adenocarcinoma during the follow-up period (median = 61.4 months). Overall, in 80/82 (98 %) of the patients without worrisome features on EUS-FNA, HGD or adenocarcinoma was not detected. Six of the 21 (29 %) patients with HGD or adenocarcinoma who underwent surgery as initial management died from pancreatic cancer during follow-up. CONCLUSIONS EUS-FNA is useful for the risk stratification of mucinous PCLs. The low incidence of adenocarcinoma over time after a negative EUS-FNA may allow for a less resource intensive surveillance strategy.
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Affiliation(s)
- Sahar Wesali
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
| | - Antonio Molinaro
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Björn Lindkvist
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Per Hedenström
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Riadh Sadik
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Coban S, Zahid KS, Brugge WR. The future of EUS. ENDOSCOPIC ULTRASONOGRAPHY 2024:287-293. [DOI: 10.1002/9781119697893.ch31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Kwan MC, Pitman MB, Fernandez-Del Castillo C, Zhang ML. Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review. Gut 2024; 73:629-638. [PMID: 38195219 DOI: 10.1136/gutjnl-2023-331138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 12/27/2023] [Indexed: 01/11/2024]
Abstract
OBJECTIVE Elevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20 years of additional data and reassesses the diagnostic performance of CEA for differentiating mucinous from non-mucinous cysts. DESIGN 1169 pancreatic cysts (1999-2021) with CEA results were identified. 394 cases had histological confirmation as the diagnostic standard. Additionally, 237 cysts without histological confirmation demonstrated KRAS, GNAS, or RNF43 mutations by molecular testing and were combined with the histologically confirmed cysts for separate analysis on a total cohort of 631 cysts. RESULTS Median CEA was significantly higher in mucinous cysts (323.9 ng/mL, n=314) versus non-mucinous cysts (204.6 ng/mL, n=80) (p<0.001). Receiver operating characteristic curve analysis demonstrated an optimal CEA cut-off of 20 ng/mL (area under the curve: 80%), though the specificity was lower than desired (sensitivity 89%, specificity 64%). At the previously established threshold of 192 ng/mL, sensitivity and specificity were 56% and 78%, respectively. To achieve a specificity of 85% as originally reported, a CEA threshold of 250 ng/mL was needed; the 13 false positive cases at this threshold included 4 benign simple cysts, 2 squamoid cysts, 1 serous cystadenoma, 1 lymphoepithelial cyst and 5 more uncommon entities. All results remained similar within the total cohort after including additional cases with KRAS/GNAS/RNF43 mutations only. CONCLUSION Cyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered.
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Affiliation(s)
- Melanie C Kwan
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Martha Bishop Pitman
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Carlos Fernandez-Del Castillo
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - M Lisa Zhang
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Umar H, Mahnur H, Brooke G, Amitabh C. Management of Cystic Neoplasms of the Pancreas. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:438-454. [DOI: 10.1002/9781119756422.ch22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Pflüger MJ, Jamouss KT, Afghani E, Lim SJ, Rodriguez Franco S, Mayo H, Spann M, Wang H, Singhi A, Lennon AM, Wood LD. Predictive ability of pancreatic cyst fluid biomarkers: A systematic review and meta-analysis. Pancreatology 2023; 23:868-877. [PMID: 37230894 DOI: 10.1016/j.pan.2023.05.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 04/10/2023] [Accepted: 05/13/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts. METHODS We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC. RESULTS Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts. CONCLUSIONS Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.
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Affiliation(s)
- Michael Johannes Pflüger
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery CCM|CVK, Charité, Universitätsmedizin Berlin, Germany; Graduate School of Life Sciences, Utrecht University, The Netherlands
| | - Kevin Tony Jamouss
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elham Afghani
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Su Jin Lim
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Harrison Mayo
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Marcus Spann
- Johns Hopkins University School of Medicine, Welch Medical Library, Baltimore, MD, USA
| | - Hao Wang
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Aatur Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| | - Anne Marie Lennon
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA.
| | - Laura D Wood
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Rogowska JO, Durko Ł, Malecka-Wojciesko E. The Latest Advancements in Diagnostic Role of Endosonography of Pancreatic Lesions. J Clin Med 2023; 12:4630. [PMID: 37510744 PMCID: PMC10380545 DOI: 10.3390/jcm12144630] [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: 05/18/2023] [Revised: 06/29/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
Endosonography, a minimally invasive imaging technique, has revolutionized the diagnosis and management of pancreatic diseases. This comprehensive review highlights the latest advancements in endosonography of the pancreas, focusing on key technological developments, procedural techniques, clinical applications and additional techniques, which include real-time elastography endoscopic ultrasound, contrast-enhanced-EUS, EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. EUS is well established for T-staging and N-staging of pancreaticobiliary malignancies, for pancreatic cyst discovery, for identifying subepithelial lesions (SEL), for differentiation of benign pancreaticobiliary disorders or for acquisition of tissue by EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. This review briefly describes principles and application of EUS and its related techniques.
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Affiliation(s)
| | - Łukasz Durko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-647 Lodz, Poland
| | - Ewa Malecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-647 Lodz, Poland
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12
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Siddappa PK, Park WG. Pancreatic Cyst Fluid Analysis. Gastrointest Endosc Clin N Am 2023; 33:599-612. [PMID: 37245938 DOI: 10.1016/j.giec.2023.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Pancreatic cyst fluid analysis can help diagnose pancreatic cyst type and the risk of high-grade dysplasia and cancer. Recent evidence from molecular analysis of cyst fluid has revolutionized the field with multiple markers showing promise in accurate diagnosis and prognostication of pancreatic cysts. The availability of multi-analyte panels has great potential for more accurate prediction of cancer.
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Affiliation(s)
- Pradeep K Siddappa
- Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA
| | - Walter G Park
- Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA.
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13
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Approach to FNA of Pancreatic Cysts. Adv Anat Pathol 2022; 29:349-357. [DOI: 10.1097/pap.0000000000000378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Aziz H, Acher AW, Krishna SG, Cloyd JM, Pawlik TM. Comparison of Society Guidelines for the Management and Surveillance of Pancreatic Cysts: A Review. JAMA Surg 2022; 157:723-730. [PMID: 35731507 DOI: 10.1001/jamasurg.2022.2232] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
IMPORTANCE The identification of incidental pancreas cystic lesions (PCLs) has increased in recent decades with the expanded use and improved sensitivity of cross-sectional imaging. Because the overall risk of malignancy associated with PCLs is low, yet the relative morbidity of pancreatic surgery is high, evidence-based guidelines are necessary for appropriate surveillance and management. Therefore, this article provides a review of existing guidelines regarding surveillance and management of PCLs and highlights recent advances in the diagnostic evaluation of cysts and the postresection management of mucinous lesions. OBSERVATIONS There are 5 main guidelines related to the management of PCLs: the American Gastrointestinal Association (AGA) guidelines, the American College of Gastroenterology (ACG) guidelines, the American College of Radiology (ACR) recommendations, the European evidence-based guidelines, and the International Association of Pancreatology (IAP)/Fukuoka guidelines. These guidelines are based on retrospective studies that do not account or control for most tumor- and patient-specific factors. These guidelines also vary in scope, recommendations for surgical resection vs surveillance, as well as duration and type of follow-up. CONCLUSIONS AND RELEVANCE PCL guidelines should be viewed within the context of the data limitations on which they are based. PCL subtype-specific guidelines on surveillance and treatment are needed. In the future, the integration of cyst-specific genomic analysis, as well as evolutions in advanced diagnostic tools, such as cyst fluid next-generation sequencing and EUS-guided confocal laser endomicroscopy, may also better inform treatment guidelines. Owing to the current low-quality evidence on which many guidelines are based and the inherent morbidity of pancreas surgery, it is imperative that patients with PCLs are referred to institutions with advanced diagnostics and a multidisciplinary approach to patient surveillance and management.
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Affiliation(s)
- Hassan Aziz
- Department of Surgery, Tufts Medical Center, Boston, Massachusetts
| | - Alexandra W Acher
- Department of Surgery, University of Utah Hospital and Clinics, Salt Lake City, Utah
| | - Somashekar G Krishna
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus
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15
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Guzmán-Calderón E, Md BMM, Casellas JA, Aparicio JR. Intracystic Glucose Levels Appear Useful for Diagnosis of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis. Dig Dis Sci 2022; 67:2562-2570. [PMID: 34009555 DOI: 10.1007/s10620-021-07035-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 05/04/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) in the pancreatic cystic fluid is the most important biomarker for differentiating mucinous from non-mucinous pancreatic cystic lesions (PCLs). However, recent studies have shown that glucose levels in pancreatic cystic fluid can discriminate mucinous from non-mucinous cysts. AIMS To perform a meta-analysis to determine the utility of intracystic fluid glucose of pancreatic mucinous cysts compared with intracystic CEA. METHODS We conducted a systematic review of the literature in the PubMed, OVID Medline, and Cochrane databases. This meta-analysis considers studies published up to October 2020. RESULTS Six studies comprising 506 patients were selected; 61.2% of the population was female. Of the 480 PCLs, 287 (59.7%) were mucinous. Pooled sensitivity and specificity of cystic fluid glucose levels for mucinous PCLs were 91% and 85%, respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 6.33 and 0.11, respectively. Pooled diagnostic odds ratio (DOR) was 60.94. The pooled area under the summary receiver operating characteristic (SROC) curve was 0.959. Pooled sensitivity and specificity of pancreatic cystic fluid CEA levels were 61% and 93%. The PLR and NLR were 8.51 and 0.40, respectively. Pooled DOR was 23.52, and the pooled area under the SROC curve was 0.861. CONCLUSION Glucose has become a useful method and appears to be better than CEA for differentiating between mucinous PCLs and non-mucinous PCLs. We suggest that the analysis of glucose in PCLs be routinely performed for the differential diagnosis of these lesions.
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Affiliation(s)
- Edson Guzmán-Calderón
- Gastroenterology Unit of Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati s/n, Jesús María, Lima, Peru. .,Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru. .,Gastroenterology Unit of Angloamericana Clinic, Lima, Peru.
| | | | - Juan A Casellas
- Gastroenterology Unit Oh Hospital General Universitario de Alicante, Alicante, Spain
| | - José Ramón Aparicio
- Gastroenterology Unit Oh Hospital General Universitario de Alicante, Alicante, Spain
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16
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Intracystic Glucose and Carcinoembryonic Antigen in Differentiating Histologically Confirmed Pancreatic Mucinous Neoplastic Cysts. Am J Gastroenterol 2022; 117:478-485. [PMID: 35034045 DOI: 10.14309/ajg.0000000000001623] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 12/29/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Differentiating mucinous neoplastic pancreatic cysts (MNPC) from cysts without malignant potential can be challenging. Guidelines recommend using fluid carcinoembryonic antigen (CEA) to differentiate MNPC; however, its sensitivity and specificity vary widely. Intracystic glucose concentration has shown promise in differentiating MNPC, but data are limited to frozen specimens and cohorts of patients without histologic diagnoses. This study aimed to compare glucose and CEA concentrations in differentiating MNPC using fresh fluid obtained from cysts with confirmatory histologic diagnoses. METHODS This multicenter cohort study consisted of patients undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cysts during January 2013-May 2020. Patients were included if the cyst exhibited a histologic diagnosis and if both CEA and glucose were analyzed from fresh fluid. Receiver operating curve (ROC) characteristics were analyzed, and various diagnostic parameters were compared. RESULTS Ninety-three patients, of whom 59 presented with MNPC, met the eligibility criteria. The area under the receiver operating curve (AUROC) was 0.96 for glucose and 0.81 for CEA (difference 0.145, P = 0.003). A CEA concentration of ≥192 ng/mL had sensitivity of 62.7% and specificity of 88.2% in differentiating MNPC, whereas glucose concentration of ≤25 mg/dL had sensitivity and specificity of 88.1% and 91.2%, respectively. DISCUSSION Intracystic glucose is superior to CEA concentration for differentiating MNPC when analyzed from freshly obtained fluid of cysts with histologic diagnoses. The advantage of glucose is augmented by its low cost and ease of implementation, and therefore, its widespread adoption should come without barriers. Glucose has supplanted CEA as the best fluid biomarker in differentiating MNPC.
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17
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Ardeshna DR, Cao T, Rodgers B, Onongaya C, Jones D, Chen W, Koay EJ, Krishna SG. Recent advances in the diagnostic evaluation of pancreatic cystic lesions. World J Gastroenterol 2022; 28:624-634. [PMID: 35317424 PMCID: PMC8900547 DOI: 10.3748/wjg.v28.i6.624] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/30/2021] [Accepted: 01/19/2022] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cystic lesions (PCLs) are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population. It has become crucial to identify these PCLs and subsequently risk stratify them to guide management. Given the high morbidity associated with pancreatic surgery, only those PCLs at high risk for malignancy should undergo such treatment. However, current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs. Therefore, research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy. Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing. While cyst fluid glucose has reemerged as a potential biomarker, cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs. Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs. While most of these recent diagnostics are only practiced at selective tertiary care centers, they hold a promise that management of PCLs will only get better in the future.
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Affiliation(s)
- Devarshi R Ardeshna
- Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Troy Cao
- College of Medicine, Ohio State University, Columbus, OH 43210, United States
| | - Brandon Rodgers
- College of Medicine, Ohio State University, Columbus, OH 43210, United States
| | - Chidiebere Onongaya
- Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Dan Jones
- James Molecular Laboratory, Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Wei Chen
- Department of Pathology, Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eugene J Koay
- Department of GI Radiation Oncology, The University of Texas MD Anderson, Houston, TX77030, United States
| | - Somashekar G Krishna
- Division of Gastroenterology, Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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18
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Ragab KM, El-Kassas M, Madkour A, Okasha HH, Agwa RH, Ghoneem EA. Safety and efficacy of endoscopic ultrasound as a diagnostic and therapeutic tool in pediatric patients: a multicenter study. Ther Adv Gastrointest Endosc 2022; 15:26317745221136767. [PMID: 36407679 PMCID: PMC9669673 DOI: 10.1177/26317745221136767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 10/17/2022] [Indexed: 08/29/2023] Open
Abstract
BACKGROUND Despite the well-established diagnostic and therapeutic applications of endoscopic ultrasound (EUS) in adults, data about its use in children are limited. In this study, we tried to assess the feasibility, safety, and clinical impact of EUS in pediatric patients. METHODS Data of pediatric patients (<18 years) referred for EUS over a 3-year period to the endoscopy units of four Egyptian tertiary centers were retrospectively analyzed. Significant impact was defined as a new diagnosis or treatment attributed to the EUS procedure. RESULTS Twenty-four diagnostic and five therapeutic EUS procedures were conducted in 29 children with a median age of 9 years. Indications for EUS included assessment of solid pancreatic mass (n = 3), pancreatic cyst (n = 2), suspected chronic pancreatitis (n = 9), pancreatic pseudocyst (PPC) (n = 5), recurrent hypoglycemia (n = 1), bile duct mass (n = 1), subepithelial lesion (esophageal, duodenal or anorectal) (n = 4), mediastinal mass (n = 1), pelvic mass (n = 3), and mass at splenic hilum (n = 1). Therapeutically, five patients underwent cystogastrostomy for symptomatic PPC with 100% technical and clinical success. EUS was able to diagnose 21 out of the other 24 patients. EUS-guided tissue acquisition was performed in 11 patients with definitive histopathological diagnosis in 10 patients (91%). There was no procedure-related major complication, while minor complications occurred in two cases (transient pain in one case, temporary fever, and vomiting in two cases). CONCLUSION Standard linear EUS equipment and accessories can be used safely and effectively in selected pediatric patients for diagnostic and therapeutic purposes.
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Affiliation(s)
- Khalid Mohamed Ragab
- Hepatology and Gastroenterology Department,
Theodor Bilharz Research Institute, Cairo, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of
Medicine, Helwan University, Ain Helwan, Cairo 11795, Egypt
| | - Ahmad Madkour
- Endemic Medicine Department, Faculty of
Medicine, Helwan University, Cairo, Egypt
| | | | - Ramy Hassan Agwa
- Hepatology and Gastroenterology Department,
Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Elsayed Awad Ghoneem
- Hepatology and Gastroenterology Department,
Faculty of Medicine, Mansoura University, Mansoura, Egypt
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19
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Barutcuoglu B, Oruc N, Ak G, Kucukokudan S, Aydın A, Nart D, Harman M. Co-analysis of pancreatic cyst fluid carcinoembryonic antigen and glucose with novel cut-off levels better distinguishes between mucinous and non-mucinous neoplastic pancreatic cystic lesions. Ann Clin Biochem 2021; 59:125-133. [PMID: 34719238 DOI: 10.1177/00045632211053998] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic cyst fluid analysis plays an important role in distinguishing between mucinous and non-mucinous cyst lesions. We aimed to compare the diagnostic performances of cyst fluid carcinoembryonic antigen (CEA), CA 19-9, and glucose in differentiating mucinous from non-mucinous neoplastic pancreatic cystic lesions (PCLs) and determine the best cut-off levels. METHODS Patients' data were evaluated retrospectively. 102 patients' PCLs were grouped as non-neoplastic (n = 25), non-mucinous neoplastic (n = 20), mucinous neoplastic (n = 47) and pancreatic adenocarcinomas with cystic degeneration (n = 10); and CEA, CA 19-9, and glucose levels were compared. Receiver-operating characteristic analysis was performed, and the ideal cut-off values were determined. RESULTS Cyst fluid CEA and CA 19-9, levels were significantly higher (P < 0.001, P < 0.001, respectively) and glucose levels were significantly lower (P = 0.001) in mucinous than in non-mucinous neoplastic PCLs. Area under curve with 95% confidence interval of CEA, glucose and CEA and glucose test combination was 0.939 (95% CI = 0.885-0.993, P = 0.001), 0.809 (95% CI = 0.695-0.924, P < 0.001) and 0.937 (95% CI = 0.879-0.995), respectively. CEA cut-offs to rule-in and rule-out mucinous neoplastic were 135.1 ng/mL (sensitivity = 62%, specificity = 94.7%) and 6.12 ng/mL (sensitivity = 94.1%, specificity = 80.4%), respectively. Glucose cut-off of 2.8 mmol/L was chosen both to rule-in and rule-out mucinous neoplastic PCLs (sensitivity = 78%, specificity = 80%). Co-analysis of CEA and glucose to distinguish mucinous from non-mucinous neoplastic PCLs had sensitivity = 87.8%, specificity = 93.3%, and diagnostic accuracy = 89.3%. CONCLUSIONS We concluded that co-analysis of cyst fluid CEA (cut-off = 135.1 ng/mL) and glucose (cut-off = 2.8 mmol/L) at novel cut-offs had the best testing performance to rule-in mucinous neoplastic PCLs. To rule-out mucinous PCLs co-analysis of CEA (cut-off = 6.12 ng/mL) and glucose (cut-off = 2.8 mmol/L) added value to prediction.
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Affiliation(s)
- Burcu Barutcuoglu
- Department of Clinical Biochemistry, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Nevin Oruc
- Department of Gastroenterology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Güneş Ak
- Department of Clinical Biochemistry, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Serdar Kucukokudan
- Department of Medical Biochemistry, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Ahmet Aydın
- Department of Gastroenterology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Deniz Nart
- Department of Pathology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Mustafa Harman
- Department of Radiology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
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20
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Buerlein RCD, Shami VM. Management of pancreatic cysts and guidelines: what the gastroenterologist needs to know. Ther Adv Gastrointest Endosc 2021; 14:26317745211045769. [PMID: 34589706 PMCID: PMC8474323 DOI: 10.1177/26317745211045769] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 08/25/2021] [Indexed: 12/15/2022] Open
Abstract
The prevalence of pancreatic cysts has increased significantly over the last
decade, partly secondary to increased quality and frequency of cross-sectional
imaging. While the majority never progress to cancer, a small number will and
need to be followed. The management of pancreatic cysts can be both confusing
and intimidating due to the multiple guidelines with varying recommendations.
Despite the differences in the specifics of the guidelines, they all agree on
several high-risk features that should get the attention of any clinician when
assessing a pancreatic cyst: presence of a mural nodule or solid component,
dilation of the main pancreatic duct (or presence of main duct intraductal
papillary mucinous neoplasm), pancreatic cyst size ⩾3–4 cm, or positive cytology
on pancreatic cyst fluid aspiration. Other important criteria to consider
include rapid cyst growth (⩾5 mm/year), elevated serum carbohydrate antigen 19-9
levels, new-onset diabetes mellitus, or acute pancreatitis thought to be related
to the cystic lesion.
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Affiliation(s)
| | - Vanessa M Shami
- University of Virginia Digestive Health, 1215 Lee Street, Charlottesville, VA 22903, USA
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21
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Stigliano S, Covotta F, Di Matteo FM. A new micro‐forceps for endoscopic ultrasound‐guided through‐the‐needle biopsy in the diagnosis of pancreatic cystic lesions: Single center experience. JGH Open 2021; 5:1004-1008. [PMID: 34584967 PMCID: PMC8454469 DOI: 10.1002/jgh3.12601] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/15/2021] [Accepted: 06/15/2021] [Indexed: 12/15/2022]
Affiliation(s)
- Serena Stigliano
- Operative Endoscopy Department Campus Bio‐Medico University Hospital Rome Italy
- Department of Translational and Precision Medicine Sapienza University Rome Italy
| | - Francesco Covotta
- Operative Endoscopy Department Campus Bio‐Medico University Hospital Rome Italy
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22
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O'Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol 2021; 27:4045-4087. [PMID: 34326612 PMCID: PMC8311531 DOI: 10.3748/wjg.v27.i26.4045] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/24/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).
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Affiliation(s)
- Robert S O'Neill
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
| | - Alina Stoita
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
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23
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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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24
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Feng Y, Chang X, Zhao Y, Wu D, Meng Z, Wu X, Guo T, Jiang Q, Zhang S, Wang Q, Yang A. A new needle-based confocal laser endomicroscopy pattern of malignant pancreatic mucinous cystic lesions (with video). Endosc Ultrasound 2021; 10:200-206. [PMID: 32655084 PMCID: PMC8248307 DOI: 10.4103/eus.eus_35_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background and Objectives: The diagnosis of malignant pancreatic cystic lesions (PCLs) remains challenging. Needle-based confocal laser endomicroscopy (nCLE) is an emerging promising imaging technique capable of real-time in vivo microscopic imaging of the cyst wall. We aimed to develop and validate a new nCLE diagnostic criteria for malignant mucinous cystic lesions (MLs). Methods: Patients referred for EUS-FNA of indeterminate PCLs with at least one worrisome features according to Fukouka consensus were consecutively prospectively enrolled from July 2016 to July 2018. The final diagnosis was based on surgical histology, cytopathology, or committee consensus. Five investigators nonblindly reviewed nCLE features and identified potential diagnostic feature for malignant MLs, which was also reviewed in histology imaging accordingly. Furthermore, the nCLE diagnostic feature was evaluated with an independent nCLE dataset by two investigators in a double-blind manner. Results: A nCLE pattern of dark aggregates of neoplastic cells was identified as diagnostic for MLs, which was consistent with histological findings of irregular branching and budding in malignant MLs. An independent validation revealed that the accuracy, sensitivity, and specificity of this feature for the diagnosis of malignant MLs were 94%, 75%, and 100%, respectively. Conclusion: The new nCLE criterion is promising for diagnosis of malignant MLs which warrants further confirmation in large cohort.
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Affiliation(s)
- Yunlu Feng
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Xiaoyan Chang
- Department of Pathology, Peking Union Medical College Hospital, Beijing, China
| | - Yu Zhao
- Department of Pathology, Peking Union Medical College Hospital, Beijing, China
| | - Dong Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Zhilan Meng
- Department of Pathology, Peking Union Medical College Hospital, Beijing, China
| | - Xi Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Tao Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Qingwei Jiang
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Shengyu Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Qiang Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Aiming Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
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25
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Goyal H, Mann R, Gandhi Z, Perisetti A, Zhang Z, Sharma N, Saligram S, Inamdar S, Tharian B. Application of artificial intelligence in pancreaticobiliary diseases. Ther Adv Gastrointest Endosc 2021; 14:2631774521993059. [PMID: 33644756 PMCID: PMC7890713 DOI: 10.1177/2631774521993059] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Accepted: 01/11/2021] [Indexed: 02/05/2023] Open
Abstract
The role of artificial intelligence and its applications has been increasing at a rapid pace in the field of gastroenterology. The application of artificial intelligence in gastroenterology ranges from colon cancer screening and characterization of dysplastic and neoplastic polyps to the endoscopic ultrasonographic evaluation of pancreatic diseases. Artificial intelligence has been found to be useful in the evaluation and enhancement of the quality measure for endoscopic retrograde cholangiopancreatography. Similarly, artificial intelligence techniques like artificial neural networks and faster region-based convolution network are showing promising results in early and accurate diagnosis of pancreatic cancer and its differentiation from chronic pancreatitis. Other artificial intelligence techniques like radiomics-based computer-aided diagnosis systems could help to differentiate between various types of cystic pancreatic lesions. Artificial intelligence and computer-aided systems also showing promising results in the diagnosis of cholangiocarcinoma and the prediction of choledocholithiasis. In this review, we discuss the role of artificial intelligence in establishing diagnosis, prognosis, predicting response to treatment, and guiding therapeutics in the pancreaticobiliary system.
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Affiliation(s)
- Hemant Goyal
- The Wright Center for Graduate Medical Education, 501 S. Washington Avenue, Scranton, PA 18505, USA
| | - Rupinder Mann
- Academic Hospitalist, Saint Agnes Medical Center, Fresno, CA, USA
| | - Zainab Gandhi
- Department of Medicine, Geisinger Community Medical Center, Scranton, PA, USA
| | - Abhilash Perisetti
- Department of Gastroenterology and Hepatology, The University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Zhongheng Zhang
- Department of emergency medicine, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Neil Sharma
- Division of Interventional Oncology & Surgical Endoscopy (IOSE), Parkview Cancer Institute, Fort Wayne, IN, USA
- Indiana University School of Medicine, Fort Wayne, IN, USA
| | - Shreyas Saligram
- Division of Advanced Endoscopy, Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Texas Health, San Antonio, TX, USA
| | - Sumant Inamdar
- University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Benjamin Tharian
- University of Arkansas for Medical Sciences, Little Rock, AR, USA
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26
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Köker IH, Ünver N, Malya FÜ, Uysal Ö, Keskin EB, Şentürk H. Cyst Fluid Carcinoembryonic Antigen Level Difference between Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms. Clin Endosc 2020; 54:113-121. [PMID: 33302330 PMCID: PMC7939764 DOI: 10.5946/ce.2020.083] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 06/22/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND/AIMS The role of cyst fluid carcinoembryonic antigen (CEA) level in differentiating mucinous pancreatic cystic lesions (PCLs) is controversial. We investigated the role of cyst fluid CEA in differentiating low-risk (LR)-intraductal papillary mucinous neoplasms (IPMNs) from high-risk (HR)-IPMNs and LR-mucinous cystic neoplasms (MCNs). METHODS This was a retrospective study of 466 patients with PCLs who underwent endoscopic ultrasound-guided fine-needleaspiration over a 7-year period. On histology, low-grade dysplasia and intermediate-grade dysplasia were considered LR, whereas high-grade dysplasia and invasive carcinoma were considered HR. RESULTS Data on cyst fluid CEA levels were available for 50/102 mucinous PCLs with definitive diagnoses. The median CEA (range) levels were significantly higher in HR cysts than in LR cysts (2,624 [0.5-266,510] ng/mL vs. 100 [16.8-53,445]ng/mL, p=0.0012). The area under the receiver operating characteristic curve (AUROC) was 0.930 (95% confidence interval [CI], 0.5-0.8; p<0.001) for differentiating LR-IPMNs from LR-MCNs. The AUROC was 0.921 (95% CI, 0.823-1.000; p<0.001) for differentiating LR-IPMNs from HR-IPMNs. Both had a CEA cutoff level of >100ng/mL, with a negative predictive value (NPV) of 100%. CONCLUSION Cyst fluid CEA levels significantly vary between LR-IPMNs, LR-MCNs, and HR-IPMNs. A CEA cutoff level of >100ng/mL had a 100% NPV in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.
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Affiliation(s)
- Ibrahim Hakkı Köker
- Department of Gastroenterology, Bezmialem Vakif University Medicine Faculty, Istanbul, Turkey
| | - Nurcan Ünver
- Department of Pathology, Bezmialem Vakif University Medicine Faculty, Istanbul, Turkey
| | - Fatma Ümit Malya
- Department of General Surgery, Bezmialem Vakif University Medicine Faculty, Istanbul, Turkey
| | - Ömer Uysal
- Department of Biostatistics, Bezmialem Vakif University Medicine Faculty, Istanbul, Turkey
| | - Elmas Biberci Keskin
- Department of Gastroenterology, Bezmialem Vakif University Medicine Faculty, Istanbul, Turkey
| | - Hakan Şentürk
- Department of Gastroenterology, Bezmialem Vakif University Medicine Faculty, Istanbul, Turkey
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Wesali S, Demir MA, Verbeke CS, Andersson M, Bratlie SO, Sadik R. EUS is accurate in characterizing pancreatic cystic lesions; a prospective comparison with cross-sectional imaging in resected cases. Surg Endosc 2020; 35:6650-6659. [PMID: 33259018 PMCID: PMC8599246 DOI: 10.1007/s00464-020-08166-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 11/15/2020] [Indexed: 01/04/2023]
Abstract
Background Imaging modalities for characterizing pancreatic cystic lesions (PCLs) is a known uncertainty. The aim of this prospective study was to compare the diagnostic performance of endoscopic ultrasound morphology, cytology and cyst fluid carcinoembryonic antigen (EUS-FNA-CEA) with cross-sectional imaging in resected PCLs. Methods The cross-sectional imaging and EUS-FNA-CEA results were collected in an academic tertiary referral centre using histology of the surgical specimen as the diagnostic standard. Results Of 289 patients undergoing evaluation for PCL with cross-sectional imaging and EUS-FNA between February 2007 and March 2017, 58 underwent surgical resection providing a final diagnosis of the PCLs: 45 mucinous, 5 serous, 1 pseudocyst, 2 endocrine, 2 solid pseudopapillary neoplasms and 3 other. EUS-FNA-CEA was more accurate than cross-sectional imaging in diagnosing mucinous PCLs (95% vs. 83%, p = 0.04). Ninety-two percent of the PCLs with high-grade dysplasia or adenocarcinoma were smaller than 3 cm in diameter. The sensitivity of EUS-FNA-CEA and cross-sectional imaging for detecting PCLs with high-grade dysplasia or adenocarcinoma were 33% and 5% (p = 0.03), respectively. However, there was no difference in accuracy between the modalities (62% vs. 66%, p = 0.79). The sensitivity for detecting pancreatic adenocarcinomas only was 64% for EUS-FNA-CEA and 9% for cross-sectional imaging (p = 0.03). Overall, EUS-FNA-CEA provided a correct diagnosis in more patients with PCLs than cross-sectional imaging (72% vs. 50%, p = 0.01). Conclusions EUS-FNA-CEA is accurate and should be considered a complementary test in the diagnosis of PCLs. However, the detection of PCLs with high-grade dysplasia or adenocarcinoma needs to be improved. Cyst size does not seem to be a reliable predictor of high-grade dysplasia or adenocarcinoma. Electronic supplementary material The online version of this article (10.1007/s00464-020-08166-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sahar Wesali
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
| | - Mehmet A Demir
- Department of Clinical Pathology, Rigshospitalet, Copenhagen, Denmark
| | - Caroline S Verbeke
- Department of Pathology, University of Oslo, and Oslo University Hospital, Oslo, Norway
| | - Mats Andersson
- Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden.,Division of Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Svein Olav Bratlie
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Riadh Sadik
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
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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] [MESH Headings] [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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Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling. Cancers (Basel) 2020; 12:cancers12092383. [PMID: 32842508 PMCID: PMC7565268 DOI: 10.3390/cancers12092383] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 08/20/2020] [Indexed: 12/28/2022] Open
Abstract
The incidence of patients with pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasm (IPMN), is increasing. Current guidelines, which primarily consider radiological features and laboratory data, have had limited success in predicting malignant IPMN. The lack of a definitive diagnostic method has led to low-risk IPMN patients undergoing unnecessary surgeries. To address this issue, we discovered IPMN marker candidates by analyzing pancreatic cystic fluid by mass spectrometry. A total of 30 cyst fluid samples, comprising IPMN dysplasia and other cystic lesions, were evaluated. Mucus was removed by brief sonication, and the resulting supernatant was subjected to filter-aided sample preparation and high-pH peptide fractionation. Subsequently, the samples were analyzed by LC-MS/MS. Using several bioinformatics tools, such as gene ontology and ingenuity pathway analysis, we detailed IPMNs at the molecular level. Among the 5834 proteins identified in our dataset, 364 proteins were differentially expressed between IPMN dysplasia. The 19 final candidates consistently increased or decreased with greater IPMN malignancy. CD55 was validated in an independent cohort by ELISA, Western blot, and IHC, and the results were consistent with the MS data. In summary, we have determined the characteristics of pancreatic cyst fluid proteins and discovered potential biomarkers for IPMN dysplasia.
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Advances in the management of pancreatic cystic neoplasms. Curr Probl Surg 2020; 58:100879. [PMID: 34144739 DOI: 10.1016/j.cpsurg.2020.100879] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 08/09/2020] [Indexed: 12/11/2022]
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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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Lanke G, Lee JH. Similarities and differences in guidelines for the management of pancreatic cysts. World J Gastroenterol 2020; 26:1128-1141. [PMID: 32231418 PMCID: PMC7093312 DOI: 10.3748/wjg.v26.i11.1128] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 02/21/2020] [Accepted: 02/29/2020] [Indexed: 02/06/2023] Open
Abstract
Accurate diagnosis of Pancreatic cysts (PC) is key in the management. The knowledge of indications for surgery, the role of endoscopic ultrasound-guided fine needle aspiration, cyst fluid analysis, imaging, and surveillance of PC are all important in the diagnosis and management of PC. Currently, there are many guidelines for the management of PC. The optimal use of these guidelines with a patient-centered approach helps diagnose early cancer and prevent the spread of cancer.
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Affiliation(s)
- Gandhi Lanke
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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Hao S, Takahashi C, Snyder RA, Parikh AA. Stratifying Intraductal Papillary Mucinous Neoplasms by Cyst Fluid Analysis: Present and Future. Int J Mol Sci 2020; 21:ijms21031147. [PMID: 32050465 PMCID: PMC7037360 DOI: 10.3390/ijms21031147] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/04/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022] Open
Abstract
A significant proportion of patients with intraductal papillary mucinous neoplasms (IPMNs) undergo surgical resection in order to prevent or treat pancreatic cancer at the risk of significant perioperative morbidity. Efforts have been made to stratify the potential risk of malignancy based on the clinical and radiographic features of IPMN to delineate which cysts warrant resection versus observation. An analysis of the cyst fluid obtained by preoperative endoscopic examination appears to be correlative of cyst type and risk, whereas serum markers and radiographic findings have not yet reached a level of sensitivity or specificity that proves they are clinically meaningful. In this review, we investigate the current cyst fluid analysis studies and present those that have shown promise in effectively stratifying high-risk versus low-risk lesions. While new cyst fluid markers continue to be identified, additional efforts in testing panels and marker composites in conjunction with clinical algorithms have also shown promise in distinguishing dysplasia and the risk of malignancy. These should be tested prospectively in order to determine their role in guiding the surveillance of low-risk lesions and to evaluate the new markers detected by proteomics and genetic sequencing.
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Affiliation(s)
- Scarlett Hao
- Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA; (S.H.); (C.T.)
| | - Caitlin Takahashi
- Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA; (S.H.); (C.T.)
| | - Rebecca A. Snyder
- Division of Surgical Oncology, Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA;
| | - Alexander A. Parikh
- Division of Surgical Oncology, Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA;
- Correspondence: ; Tel.: +1-252-744-4110
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34
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Pancreatic cystic neoplasms: current and future approaches to identify patients at risk. JOURNAL OF PANCREATOLOGY 2019. [DOI: 10.1097/jp9.0000000000000033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Nicolas CT, Al Diffalha S, Reddy S. Diffuse histology-proven mucinous cystic neoplasm of the pancreas: A case report and review of literature. Int J Surg Case Rep 2019; 64:123-127. [PMID: 31634784 PMCID: PMC6806458 DOI: 10.1016/j.ijscr.2019.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 10/01/2019] [Accepted: 10/05/2019] [Indexed: 10/25/2022] Open
Abstract
INTRODUCTION Mucinous cystic neoplasms (MCN) are rare premalignant neoplasms of the pancreas that are typically found as single lesions in the pancreatic body and tail of women in the fifth and sixth decade of life, do not communicate with the pancreatic ductal system and are characterized by mucin-producing epithelium supported by ovarian-type stroma. PRESENTATION OF CASE We present here a case of diffuse pancreatic involvement by MCN in a 64-year-old woman with chronic pancreatitis. Pre-operative suspicion for MCN was low due to the multi-centric nature of the lesions and imaging/biochemical fluid analysis demonstrating connection with the pancreatic ductal architecture. The patient underwent total pancreatectomy with pathology showing multiple cysts lined by flat epithelium with focal ovarian-type stroma, consistent with low-grade MCN. DISCUSSION The presence of ovarian stroma on histological analysis is one of the defining characteristics of MCNs per WHO guidelines, and is mandatory for its diagnosis. Only one case of diffuse MCN has been previously described in the literature; however, in this case the authors were not able to reach a definitive histological diagnosis based on WHO criteria. CONCLUSION To our knowledge, this is the first report of diffuse histology-proven MCN of the pancreas.
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Affiliation(s)
- Clara T Nicolas
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Sameer Al Diffalha
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Sushanth Reddy
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States.
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Jhala N, Srimunta P, Jhala D. Role of Ancillary Testing on Endoscopic US-Guided Fine Needle Aspiration Samples from Cystic Pancreatic Neoplasms. Acta Cytol 2019; 64:124-135. [PMID: 31509835 DOI: 10.1159/000502372] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 07/22/2019] [Indexed: 12/11/2022]
Abstract
Pancreatic cysts are increasingly detected on imaging studies. Accurate determination of the cyst type is important to provide appropriate care for the patients. It is also very clear that not one single modality can provide adequate diagnostic information. A multidisciplinary approach is the key to the diagnosis of pancreatic cysts. In this setting, the role of ancillary testing, which includes biochemical testing (carcinoembryonic antigen and amylase levels in the cyst), molecular testing (e.g., KRAS, GNAS, VHL, and CTNB1), and/or immunohistochemical tests are very important to obtain an accurate diagnosis. This review will discuss helpful ancillary tests in common pancreatic cyst neoplasms and how to approach the diagnosis of pancreatic cysts.
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Affiliation(s)
- Nirag Jhala
- Department of Pathology and Laboratory Medicine, Temple University Hospital, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA,
| | - Piyachat Srimunta
- Visiting Fellow, Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA
| | - Darshana Jhala
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Pathology and Laboratory Services, CMC Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA
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Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions. Surg Endosc 2019; 34:2532-2540. [PMID: 31410626 PMCID: PMC7214514 DOI: 10.1007/s00464-019-07062-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Accepted: 08/05/2019] [Indexed: 12/14/2022]
Abstract
Background and aim The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs. Methods Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case. Results The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p < 0.001). nCLE significantly increased the interobserver agreement of 0.28 (p < 0.0001), from 0.36 (CI 95% 0.33–0.49) to 0.64 (CI 95% 0.61–0.67). nCLE improved the rates of full agreement among the five experts of 24% (p < 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76). Conclusion The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133. Electronic supplementary material The online version of this article (10.1007/s00464-019-07062-9) contains supplementary material, which is available to authorized users.
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Yang D, Trindade AJ, Yachimski P, Benias P, Nieto J, Manvar A, Ho S, Esnakula A, Gamboa A, Sethi A, Gupte A, Khara HS, Diehl DL, El Chafic A, Shah J, Forsmark CE, Draganov PV. Histologic Analysis of Endoscopic Ultrasound-Guided Through the Needle Microforceps Biopsies Accurately Identifies Mucinous Pancreas Cysts. Clin Gastroenterol Hepatol 2019; 17:1587-1596. [PMID: 30471456 DOI: 10.1016/j.cgh.2018.11.027] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/01/2018] [Accepted: 11/02/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS It is a challenge to accurately assess pancreatic cystic lesions (PCLs) and determine their risk. We compared the yield of tissue acquired with endoscopic ultrasound (EUS)-guided microforceps (through the needle tissue biopsy [TTNB]) with that of samples collected by EUS-guided fine-needle-aspiration (EUS-FNA), and the accuracy of analyses of each sample type in the diagnosis of mucinous PCLs. METHODS We performed a prospective open-label study of 114 consecutive adults (56.1% women; mean age, 64.2 y) undergoing EUS-FNA evaluation of PCLs (mean size, 35 mm) at 7 centers, from June 20, 2016, through August 31, 2018. Samples were collected from each cyst by FNA and microforceps; samples collected by FNA were analyzed by cytology and samples collected by TTNB were analyzed by histology. Acquisition yield was defined as the percentage of specimens collected that were adequate for cytologic or histologic analysis. Diagnoses of mucinous cysts were made based on identification of pancreatic mucinous epithelium by cytology analysis of FNA samples or histologic analysis of TTNB samples. Surgical specimens were used as the reference standard when available. RESULTS The EUS-guided microforceps were successfully inserted into 97.4% (111 of 114) of PCLs. Tissue acquisition yield was significantly higher with TTNB (95 of 114; 83.3%) than FNA (43 of 114; 37.7%) (P < .001). Sixty-one PCLs were determined to be mucinous based on TTNB analysis (53.5%) vs 11 with FNA analysis (9.6%) (P < .001). Among PCLs categorized as equivocal, based on the level of carcinoembryonic antigen, TTNB analysis found 50% (41 of 82) to be mucinous and FNA analysis found 8.5% (7 of 82) to be mucinous (P < .001). Findings from analyses of samples collected by TTNB were 100% concordant with findings from histologic analysis of surgical specimens (14 of 14), whereas only 3 of 14 findings from analysis of samples collected by FNA were in agreement with findings from surgical specimens (21.4%) (P < .001). Four of 5 mucinous PCLs with advanced neoplasia (80%) were detected with TTNB compared with none with FNA (P = .04). Self-limited intracystic bleeding occurred in 7 patients (6.1%), and acute pancreatitis in 6 patients (5.3%). CONCLUSIONS In a multicenter prospective study of patients undergoing EUS-FNA for evaluation of PCLs, we found TTNB collection of tissues for histologic analysis to be safe and feasible, with an acquisition yield of 83.3%. Histologic analysis of samples collected by TTNB identified a larger proportion of mucinous PCLs compared with cytologic analysis of samples collected by FNA-even among samples categorized as equivocal, based on the level of carcinoembryonic antigen. More samples collected by TTNB than FNA were found to have advanced neoplasia. Clinicaltrials.gov no: NCT02979509.
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Affiliation(s)
- Dennis Yang
- Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida.
| | - Arvind J Trindade
- Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, Northwell Health System, New Hyde Park, New York
| | - Patrick Yachimski
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Petros Benias
- Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, Northwell Health System, New Hyde Park, New York
| | - Jose Nieto
- Borland-Groover Clinic, Jacksonville, Florida
| | - Amar Manvar
- Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Sammy Ho
- Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Ashwini Esnakula
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida
| | - Anthony Gamboa
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Amrita Sethi
- Division of Digestive and Liver Disease, Columbia University, Medical Center-New York Presbyterian Hospital, New York, New York
| | - Anand Gupte
- Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida
| | - Harshit S Khara
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, Pennsylvania
| | - David L Diehl
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, Pennsylvania
| | - Abdul El Chafic
- Division of Gastroenterology and Hepatology, Ochsner Medical Center, New Orleans, Louisiana
| | - Janak Shah
- Division of Gastroenterology and Hepatology, Ochsner Medical Center, New Orleans, Louisiana
| | - Christopher E Forsmark
- Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida
| | - Peter V Draganov
- Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida
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Ivry SL, Knudsen GM, Caiazza F, Sharib JM, Jaradeh K, Ravalin M, O’Donoghue AJ, Kirkwood KS, Craik CS. The lysosomal aminopeptidase tripeptidyl peptidase 1 displays increased activity in malignant pancreatic cysts. Biol Chem 2019; 400:1629-1638. [DOI: 10.1515/hsz-2019-0103] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 05/27/2019] [Indexed: 12/15/2022]
Abstract
Abstract
Incidental detection of pancreatic cysts has increased dramatically over the last decade, but risk stratification and clinical management remain a challenge. Mucinous cysts are precursor lesions to pancreatic cancer, however, the majority are indolent. Current diagnostics cannot identify mucinous cysts that harbor cancer or reliably differentiate these lesions from nonmucinous cysts, which present minimal risk of malignant progression. We previously determined that activity of two aspartyl proteases was increased in mucinous cysts. Using a global protease activity profiling technology, termed multiplex substrate profiling by mass spectrometry (MSP-MS), we now show that aminopeptidase activity is also elevated in mucinous cysts. The serine aminopeptidase, tripeptidyl peptidase 1 (TPP1), was detected by proteomic analysis of cyst fluid samples and quantitation using targeted MS demonstrated that this protease was significantly more abundant in mucinous cysts. In a cohort of 110 cyst fluid samples, TPP1 activity was increased more than 3-fold in mucinous cysts relative to nonmucinous cysts. Moreover, TPP1 activity is primarily associated with mucinous cysts that harbor high-grade dysplasia or invasive carcinoma. Although only 59% accurate for differentiating these lesions, measurement of TPP1 activity may improve early detection and treatment of high-risk pancreatic cysts when used in conjunction with other promising biomarkers.
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Affiliation(s)
- Sam L. Ivry
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
- Pharmaceutical Sciences and Pharmacogenomics Graduate Program , University of California , San Francisco, San Francisco, CA , USA
| | - Giselle M. Knudsen
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Francesco Caiazza
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Jeremy M. Sharib
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Katrin Jaradeh
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Matthew Ravalin
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Anthony J. O’Donoghue
- Skaggs School of Pharmacy and Pharmaceutical Chemistry , University of California , San Diego, La Jolla, CA , USA
| | - Kimberly S. Kirkwood
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Charles S. Craik
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
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Okasha H, E Behiry M, Ramadan N, Ezzat R, Yamany A, El-Kholi S, Ahmed G. Endoscopic ultrasound-guided fine needle aspiration in diagnosis of cystic pancreatic lesions. Arab J Gastroenterol 2019; 20:86-90. [PMID: 31182342 DOI: 10.1016/j.ajg.2019.05.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 04/14/2019] [Accepted: 05/28/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND STUDY AIMS pancreatic cysts are commonly found lesions and proper diagnosis is very important for planning further management. The study aims to evaluate the role of cyst fluid amylase and tumour markers as cancer antigen (CA 19-9) and carcinoembryonic antigen (CEA) in addition to mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. PATIENTS AND METHODS This prospective study was conducted on 184 patients diagnosed to have pancreatic cystic lesions from January 2013 to January 2018. Fluid analysis for CA 19-9, CEA, amylase, mucin stain and cytopathology were done. We compared these data with the final diagnosis based on histopathology after surgical resection, positive cytopathology and long period of follow up of the patients for at least 18 months. RESULTS The highest AUC was that of cystic CEA with cut-off value of 160 ng/ml; it had a sensitivity of 60.4% and a specificity of 85%. The best cut-off value for cystic CA 19-9 was 1318 U/ml with a sensitivity of 64.1% and a specificity of 68.1%. The cut-off value of cyst amylase level was 5500 U/L, with 84.2% sensitivity and 37.1% specificity. The sensitivity of mucin stain in detecting mucinous cystic neoplasm was 85.45%, specificity was 86.05% with accuracy 85.87%. CONCLUSION Cyst fluid analysis by investigating amylase, mucin, CA 19-9, CEA and EUS examination improves the diagnosis of different pancreatic cysts.
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Affiliation(s)
- Hussein Okasha
- Internal Medicine, Faculty of Medicine, Cairo University, Egypt
| | - Mervat E Behiry
- Internal Medicine, Faculty of Medicine, Cairo University, Egypt.
| | - Nagwa Ramadan
- Internal Medicine, Faculty of Medicine, Cairo University, Egypt
| | - Reem Ezzat
- Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ahmed Yamany
- Internal Medicine, Faculty of Medicine, Cairo University, Egypt
| | | | - Ghada Ahmed
- Internal Medicine, Faculty of Medicine, Cairo University, Egypt
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Lopes CV. Cyst fluid glucose: An alternative to carcinoembryonic antigen for pancreatic mucinous cysts. World J Gastroenterol 2019; 25:2271-2278. [PMID: 31148899 PMCID: PMC6529890 DOI: 10.3748/wjg.v25.i19.2271] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 03/30/2019] [Accepted: 04/20/2019] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cystic lesions (PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts (pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions, it is imperative to identify mucinous cysts (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen (CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated.
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Affiliation(s)
- César Vivian Lopes
- Department of Gastroenterology and Digestive Endoscopy, Santa Casa Hospital, Porto Alegre 91410-000, Brazil
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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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Simpson RE, Cockerill NJ, Yip-Schneider MT, Ceppa EP, House MG, Zyromski NJ, Nakeeb A, Al-Haddad MA, Schmidt CM. Clinical criteria for integrated molecular pathology in intraductal papillary mucinous neoplasm: less is more. HPB (Oxford) 2019; 21:574-581. [PMID: 30293868 DOI: 10.1016/j.hpb.2018.09.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 08/13/2018] [Accepted: 09/03/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND For pancreatic cysts with negative cytology, Integrated Molecular Pathology (IMP) is a malignancy risk score integrating clinical criteria with pancreatic cyst fluid DNA profiling. Aside from main pancreatic duct (MPD) diameter, integrated clinical criteria are not International Consensus Guidelines High-Risk Stigmata. We predicted exclusion of clinical criteria except MPD diameter could simplify the IMP and better distinguish invasive/malignant disease. METHODS Records of >1100 patients with IPMN were reviewed retrospectively. Sensitivity, specificity, and accuracy of conventional IMP for invasive/malignant disease was compared to DNA profile including only MPD ≥10mm (IMP-10.) Invasive outcomes were invasive-IPMN/adenocarcinoma on surgical pathology, pathologic or radiographic evidence of invasive/metastatic disease during surveillance. Malignant outcomes included high grade dysplastic IPMN (HGD-IPMN). RESULTS 225 patients who met study criteria underwent 283 IMP evaluations: 98 followed by surgery, 185 followed by ≥ 23 months surveillance. IMP-10 had greater specificity (90.1% vs. 73.7%) and accuracy (89.8% vs. 74.2%) for invasive disease compared to IMP in surgery + surveillance patients, but lower sensitivity (77.8% vs. 88.9%). Trends were similar in surgery patients alone and malignant outcome analyses. CONCLUSION IMP-10 excludes less-reliable clinical factors resulting in greater accuracy in predicting invasive/malignant disease and fewer patients with benign disease being recommended for surgery.
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Affiliation(s)
- Rachel E Simpson
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Nathan J Cockerill
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Michele T Yip-Schneider
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA
| | - Eugene P Ceppa
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA
| | - Michael G House
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Nicholas J Zyromski
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Attila Nakeeb
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Mohammad A Al-Haddad
- Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA; Indiana University School of Medicine, Department of Medicine, Division of Gastroenterology, 702 Rotary Cir., Suite 225, Indianapolis, IN 46202, USA
| | - C M Schmidt
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA; Indiana University School of Medicine, Department of Biochemistry/Molecular Biology, 635 Barnhill Dr., Medical Sciences Building Rm 4053, Indianapolis, IN 46202, USA; Walther Oncology Center, 950 W. Walnut St., Indianapolis, IN 46202, USA; Indiana University Simon Cancer Center, 535 Barnhill Dr., Indianapolis, IN 46202, USA.
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Kamata K, Kitano M. Endoscopic diagnosis of cystic lesions of the pancreas. Dig Endosc 2019; 31:5-15. [PMID: 30085364 DOI: 10.1111/den.13257] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 08/02/2018] [Indexed: 12/13/2022]
Abstract
Endoscopic methods are increasingly used in the diagnosis of cystic lesions of the pancreas. The two major endoscopic approaches are endoscopic ultrasonography (EUS) and transpapillary diagnosis. EUS-guided fine-needle aspiration cytology and EUS-guided fine needle-based confocal laser endomicroscopy have been used in the differential diagnosis of mucinous and non-mucinous pancreatic cysts. EUS is the most sensitive modality for detecting mural nodules (MN) in intraductal papillary mucinous neoplasms (IPMN). Contrast-enhanced harmonic EUS (CH-EUS), as an add-on to EUS, is useful for identifying and characterizing MN. Recent studies show that CH-EUS has a sensitivity of 60-100% and a specificity of 75-92.9% for diagnosing malignant cysts. Intraductal ultrasonography and peroral pancreatoscopy are especially useful for detecting MN and IPMN. A recent meta-analysis showed that cytological assessment of pancreatic juice using a transpapillary approach had a pooled sensitivity, specificity, and accuracy of 35.1%, 97.2%, and 92.9%, respectively, for diagnosing malignant IPMN. Further studies are warranted to determine the indications for each of these novel techniques in assessing cystic lesions of the pancreas.
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Affiliation(s)
- Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
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Nakashima S, Yamada T, Sato G, Sakai T, Chinen Y, Itakura H, Kato R, Ueda M, Tsuda Y, Ohta K, Matsuyama J, Ikenaga M. A case of completely isolated advanced enteric duplication cyst cancer performed partial pancreatectomy. Int J Surg Case Rep 2018; 54:83-86. [PMID: 30553095 PMCID: PMC6297057 DOI: 10.1016/j.ijscr.2018.11.060] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 11/22/2018] [Accepted: 11/25/2018] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Enteric duplication cysts are rare and, in addition, isolated enteric duplication cysts are lower morbidity prevalence rate. These cysts lack a connection to the gastrointestinal tract or the adjacent mesenteric vasculature and have only been reported in 10 case reports. In these reports, only two reports were cases with malignant transformation. Our case was a report for the advanced cancer of the isolated enteric duplication cyst. CASE PRESENTATION The patient was a 43 year-old woman with slightly abdominal pain and mass formation. The abdominal contrast-enhanced computed tomography showed 130 × 100 × 90 mm huge cystic mass existed in right upper peritoneal cavity. The cystic mass had thickened wall and many enhanced nodules. As these imaging findings suggested a tumor originated from pancreas and the preoperative diagnose was suspect of mucinous cystic neoplasm. In operative findings, the tumor originated from pancreatic head and did not attach to gastrointestinal tract. Final pathology indicated the cyst was an isolated advanced enteric duplication cyst cancer and not originated from pancreas. CONCLUSION We experienced an extremely rare case of completely isolated advanced enteric duplication cyst cancer. Unique to this case, the preoperative diagnosis was suspect of mucinous cystic neoplasm arising from pancreas head and partial pancreatectomy was performed. However, in the pathological findings, this cyst diagnosed advanced enteric duplication cyst cancer.
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Affiliation(s)
- Shinsuke Nakashima
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Terumasa Yamada
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan.
| | - Go Sato
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Takaaki Sakai
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Yoshinao Chinen
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Hiroaki Itakura
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Ryo Kato
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Masami Ueda
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Yujiro Tsuda
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Katsuya Ohta
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Jin Matsuyama
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
| | - Masakazu Ikenaga
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Nishiiwata 3-4-5, Higashiosaka, Osaka, 567-8588, Japan
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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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Quantitative proteomic analysis of pancreatic cyst fluid proteins associated with malignancy in intraductal papillary mucinous neoplasms. Clin Proteomics 2018; 15:17. [PMID: 29713252 PMCID: PMC5907296 DOI: 10.1186/s12014-018-9193-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 04/04/2018] [Indexed: 12/13/2022] Open
Abstract
Background
The application of advanced imaging technologies for identifying pancreatic cysts has become widespread. However, accurately differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy.
Methods Cyst fluid samples were collected from nine IPMN patients (3 LGD, 3 HGD, and 3 invasive IPMN) during their pancreatectomies. An integrated proteomics approach that combines filter-aided sample preparation, stage tip-based high-pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data of pancreatic cyst fluid and discover marker candidates for IPMN malignancy. Biological processes of differentially expressed proteins that are related to pancreatic cysts and aggressive malignancy were analyzed using bioinformatics tools such as gene ontology analysis and Ingenuity pathway analysis. In order to confirm the validity of the marker candidates, 19 cyst fluid samples were analyzed by western blot.
Results A dataset of 2992 proteins was constructed from pancreatic cyst fluid samples. A subsequent analysis found 2963 identified proteins in individual samples, 2837 of which were quantifiable. Differentially expressed proteins between histological grades of IPMN were associated with pancreatic diseases and malignancy according to ingenuity pathway analysis. Eighteen biomarker candidates that were differentially expressed across IPMN histological grades were discovered—7 DEPs that were upregulated and 11 that were downregulated in more malignant grades. HOOK1 and PTPN6 were validated by western blot in an independent cohort, the results of which were consistent with our proteomic data. Conclusions This study demonstrates that novel biomarker candidates for IPMN malignancy can be discovered through proteomic analysis of pancreatic cyst fluid. Electronic supplementary material The online version of this article (10.1186/s12014-018-9193-1) contains supplementary material, which is available to authorized users.
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Hoshi H, Zaheer A, El Abiad RG, Maxwell JE, Chu LC, Gerke H, Chan CH. Management of pancreatic intraductal papillary mucinous neoplasm. Curr Probl Surg 2018; 55:126-152. [DOI: 10.1067/j.cpsurg.2018.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 03/11/2018] [Indexed: 12/16/2022]
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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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