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Kim DW, Koo B, Byun JH, Song IH, Lee H, Kim JH, Lee SS, Kim HJ, Song KB, Lee JH, Hwang DW. Prediction of main pancreatic duct involvement in intraductal papillary mucinous neoplasms on magnetic resonance imaging. Abdom Radiol (NY) 2025:10.1007/s00261-025-04801-6. [PMID: 39862288 DOI: 10.1007/s00261-025-04801-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 12/30/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025]
Abstract
PURPOSE To evaluate the measurement of main pancreatic duct (MPD) diameter on MRI for predicting MPD involvement in intraductal papillary mucinous neoplasms (IPMN). METHODS This retrospective study included 595 patients with surgically confirmed IPMN who underwent preoperative MRI from 2015 to 2022. Three independent readers measured the maximum MPD diameter on two-dimensional axial and coronal T2-weighted imaging. Inter-plane and inter-reader agreements were assessed using the intraclass correlation coefficient (ICC). Multivariable logistic regression identified clinical and radiological factors associated with MPD involvement. Accuracy, sensitivity, and specificity of MPD diameter cutoffs, including the 5-mm threshold from the 2024 International Consensus Guidelines, were calculated. RESULTS Of the 595 patients (mean age: 64.6 years ± 8.6, 394 men), 423 (71.1%) had IPMN with MPD involvement, whereas 172 (28.9%) did not have MPD involvement. The mean maximum MPD diameter was 7.9 ± 5.1 mm. Inter-plane agreement was excellent (ICC = 0.977-0.988), as was inter-reader agreement (ICC = 0.963). Only a large MPD diameter on MRI was independently associated with MPD involvement (odds ratio = 1.29 [95% confidence interval; 1.14-1.47], p <.01). Use of a maximum MPD diameter cutoff of ≥ 5 mm for MPD involvement yielded accuracy, sensitivity, and specificity of 76.0%, 79.2%, and 68.0%, respectively. CONCLUSION Despite excellent inter-plane and inter-reader agreement, the MRI-based prediction of MPD involvement in IPMN has limitations.
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Affiliation(s)
- Dong Wook Kim
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Korea
| | - Boyeon Koo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Korea
- Kangbuk Samsung Hospital, Seoul, Korea
| | - Jae Ho Byun
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Korea.
| | - In Hye Song
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Department of Pathology, Asan Medical Center, Seoul, Korea
| | - Hwajin Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Korea
| | - Jin Hee Kim
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Korea
| | - Seung Soo Lee
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Korea
| | - Hyoung Jung Kim
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Korea
| | - Ki Byung Song
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul, Korea
| | - Jae Hoon Lee
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul, Korea
| | - Dae Wook Hwang
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul, Korea
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Li P, Zhang H, Gao X, Chen L, Chen H, Yuan S, Chen W, Dai M. Difference in fecal and oral microbiota between pancreatic cancer and benign/low-grade malignant tumor patients. BMC Microbiol 2024; 24:527. [PMID: 39695939 DOI: 10.1186/s12866-024-03687-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Significant gaps exist in understanding the gastrointestinal microbiota in patients with pancreatic cancer (PCA) versus benign or low-grade malignant pancreatic tumors (NPCA). This study aimed to analyze these microbiota characteristics and explore their potential use in distinguishing malignant pancreatic lesions. METHODS Between September 2020 and May 2024, fecal and oral samples were collected from 121 patients undergoing surgical resection or diagnostic biopsy of pancreatic lesions, including 75 patients with PCA and 46 patients with NPCA, and 16s rRNA sequencing was performed. Random forest models based using fecal and oral microbiota data were developed to diagnose PCA and NPCA, with performance assessed using the leave-one-out cross validation method. RESULTS The Shannon index and PCoA analysis revealed significant differences in oral microbiota composition between PCA and NPCA (p < 0.001 and p = 0.001, respectively). Fecal microbiome richness differed significantly (p = 0.02), though composition similarity was noted (p = 0.238). LEfSe identified 16 and 23 genera with significant differences in fecal and oral microbiomes, respectively. Random forest classifiers based on fecal and oral microbiota achieved areas under the curves (AUCs) of 89.4% and 96.3%, respectively, for distinguishing PCA and NPCA. In the mucinous tumor cohort, oral and fecal microbiome classifiers outperformed CA19-9, yielding AUCs of 83.0% and 85.2%, respectively. CONCLUSION Fecal and oral microbiota compositions were significantly different between PCA and NPCA patients. Random forest classifiers utilizing fecal and oral microbiota data effectively distinguish between benign or low-grade malignant and malignant pancreatic lesions.
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Affiliation(s)
- Pengyu Li
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hanyu Zhang
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xingyu Gao
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Lixin Chen
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Haomin Chen
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Shuai Yuan
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Weijie Chen
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Menghua Dai
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Marchegiani G, Pollini T, Burelli A, Han Y, Jung HS, Kwon W, Rocha Castellanos DM, Crippa S, Belfiori G, Arcidiacono PG, Capurso G, Apadula L, Zaccari P, Noia JL, Gorris M, Busch O, Ponweera A, Mann K, Demir IE, Phillip V, Ahmad N, Hackert T, Heckler M, Lennon AM, Afghani E, Vallicella D, Dall'Olio T, Nepi A, Vollmer CM, Friess H, Ghaneh P, Besselink M, Falconi M, Bassi C, Goh BKP, Jang JY, Fernández-Del Castillo C, Salvia R. Surveillance for Presumed BD-IPMN of the Pancreas: Stability, Size, and Age Identify Targets for Discontinuation. Gastroenterology 2023; 165:1016-1024.e5. [PMID: 37406887 PMCID: PMC10548445 DOI: 10.1053/j.gastro.2023.06.022] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 06/11/2023] [Accepted: 06/14/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND & AIMS Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance. METHODS International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer. RESULTS Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5). CONCLUSIONS The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm.
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Affiliation(s)
- Giovanni Marchegiani
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy; Hepatopancreatobiliary and Liver Transplant Surgery, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Tommaso Pollini
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Anna Burelli
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hye-Sol Jung
- Department of Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | | | - Stefano Crippa
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Giulio Belfiori
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Laura Apadula
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Piera Zaccari
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - José Lariño Noia
- Endoscopy and Pancreatic Unit, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Myrte Gorris
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Olivier Busch
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | | | - Kulbir Mann
- Royal Liverpool University Hospital, Liverpool, United Kingdom
| | - Ihsan Ekin Demir
- Department of Surgery, Klinikum rechts der Isar School of Medicine, Technical University Munich, Munich, Germany
| | - Veit Phillip
- Department of Gastroenterology, Klinikum rechts der Isar, School of Medicine, Technical University Munich, Munich, Germany
| | - Nuzhat Ahmad
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Max Heckler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Anne Marie Lennon
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Elham Afghani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Davide Vallicella
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Tommaso Dall'Olio
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Angelica Nepi
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Charles M Vollmer
- Department of Surgery, Division of General Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar School of Medicine, Technical University Munich, Munich, Germany
| | - Paula Ghaneh
- University of Liverpool, Liverpool, United Kingdom
| | - Marc Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Bassi
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Brian Kim-Poh Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | | | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy.
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Marin AM, Batista M, Korte de Azevedo AL, Bombardelli Gomig TH, Soares Caldeira Brant R, Chammas R, Uno M, Dias Araújo D, Zanette DL, Nóbrega Aoki M. Screening of Exosome-Derived Proteins and Their Potential as Biomarkers in Diagnostic and Prognostic for Pancreatic Cancer. Int J Mol Sci 2023; 24:12604. [PMID: 37628784 PMCID: PMC10454563 DOI: 10.3390/ijms241612604] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 07/11/2023] [Accepted: 07/18/2023] [Indexed: 08/27/2023] Open
Abstract
In the oncological area, pancreatic cancer is one of the most lethal diseases, with 5-year survival rising just 10% in high-development countries. This disease is genetically characterized by KRAS as a driven mutation followed by SMAD4, CDKN2, and TP53-associated mutations. In clinical aspects, pancreatic cancer presents unspecific clinical symptoms with the absence of screening and early plasmatic biomarker, being that CA19-9 is the unique plasmatic biomarker having specificity and sensitivity limitations. We analyzed the plasmatic exosome proteomic profile of 23 patients with pancreatic cancer and 10 healthy controls by using Nanoscale liquid chromatography coupled to tandem mass spectrometry (NanoLC-MS/MS). The pancreatic cancer patients were subdivided into IPMN and PDAC. Our findings show 33, 34, and 7 differentially expressed proteins when comparing the IPMN vs. control, PDAC-No treatment vs. control, and PDAC-No treatment vs. IPMN groups, highlighting proteins of the complement system and coagulation, such as C3, APOB, and SERPINA. Additionally, PDAC with no treatment showed 11 differentially expressed proteins when compared to Folfirinox neoadjuvant therapy or Gemcitabine adjuvant therapy. So here, we found plasmatic exosome-derived differentially expressed proteins among cancer patients (IPMN, PDAC) when comparing with healthy controls, which could represent alternative biomarkers for diagnostic and prognostic evaluation, supporting further scientific and clinical studies on pancreatic cancer.
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Affiliation(s)
- Anelis Maria Marin
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil; (A.M.M.); (M.B.); (D.L.Z.)
| | - Michel Batista
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil; (A.M.M.); (M.B.); (D.L.Z.)
- Mass Spectrometry Facility RPT02H, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil
| | - Alexandre Luiz Korte de Azevedo
- Laboratory of Human Cytogenetics and Oncogenetics, Genetic Department, University of Parana State (UFPR), Curitiba 80060-000, Brazil; (A.L.K.d.A.); (T.H.B.G.)
| | - Talita Helen Bombardelli Gomig
- Laboratory of Human Cytogenetics and Oncogenetics, Genetic Department, University of Parana State (UFPR), Curitiba 80060-000, Brazil; (A.L.K.d.A.); (T.H.B.G.)
| | - Rodrigo Soares Caldeira Brant
- Mass Spectrometry Facility RPT02H, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil
| | - Roger Chammas
- Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Comprehensive Center for Precision Oncology (C2PO), Universidade de São Paulo, São Paulo 05508-220, Brazil; (R.C.); (M.U.); (D.D.A.)
| | - Miyuki Uno
- Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Comprehensive Center for Precision Oncology (C2PO), Universidade de São Paulo, São Paulo 05508-220, Brazil; (R.C.); (M.U.); (D.D.A.)
| | - Diogo Dias Araújo
- Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Comprehensive Center for Precision Oncology (C2PO), Universidade de São Paulo, São Paulo 05508-220, Brazil; (R.C.); (M.U.); (D.D.A.)
| | - Dalila Luciola Zanette
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil; (A.M.M.); (M.B.); (D.L.Z.)
| | - Mateus Nóbrega Aoki
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil; (A.M.M.); (M.B.); (D.L.Z.)
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Cattelani A, Perri G, Marchegiani G, Salvia R, Crinò SF. Risk Models for Pancreatic Cyst Diagnosis. Gastrointest Endosc Clin N Am 2023; 33:641-654. [PMID: 37245940 DOI: 10.1016/j.giec.2023.03.011] [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
The overall prevalence of pancreatic cysts (PCs) is high in the general population. In clinical practice PCs are often incidentally discovered and are classified into benign, premalignant, and malignant lesions according to the World Health Organization. For this reason, in the absence of reliable biomarkers, to date clinical decision-making relies mostly on risk models based on morphological features. The aim of this narrative review is to present the current knowledge regarding PC's morphologic features with related estimated risk of malignancy and discuss available diagnostic tools to minimize clinically relevant diagnostic errors.
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Affiliation(s)
- Alice Cattelani
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giampaolo Perri
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giovanni Marchegiani
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy.
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Vieira RMF, Souza Junior ASD, Kerche LE. CYSTIC PANCREATIC LESIONS: IMAGING VERSUS ANATOMOPATHOLOGICAL FINDINGS-HOW TO IMPROVE DIAGNOSTIC ACCURACY? ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1735. [PMID: 37255104 DOI: 10.1590/0102-672020230017e1735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 01/15/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND Pancreatic cystic lesions are a group of pancreatic neoplasms with different behavior and risk of malignancy. Imaging diagnosis and differentiation of these lesions remain a challenge. AIMS The aim of this study was to evaluate the agreement between computed tomography and/or magnetic resonance imaging and post-operative pathologic diagnoses of Pancreatic cystic lesions in a University Hospital of São Paulo State. METHODS A total of 39 patients with surgically diagnosed Pancreatic cystic lesions were enrolled, as a study cohort from 2009 to 2019. Preoperative radiological and final pathological diagnosis was correlated to measure computed tomography and/or magnetic resonance imaging diagnostic. Pancreatic adenocarcinoma, choledochal pancreatic cyst, mucinous cystadenoma, serous cystadenoma, intraductal papillary mucinous neoplasms, and pancreatic pseudocyst were classified as neoplastic cysts. RESULTS It was noted that 27 patients (69.23%) had preoperative computed tomography and magnetic resonance imaging, 11 patients (28.20%) had preoperative computed tomography only, and 1 patient had preoperative magnetic resonance imaging only. The values for diagnoses made only with computed tomography (p=0.47) and from the combination of computed tomography+magnetic resonance imaging (p=0.50) did also point to moderate agreement with the anatomopathological findings. The values pointed to a fair agreement for the diagnosis of mucinous cystadenoma (p=0.3), moderate agreement for intraductal papillary mucinous neoplasms (p= 0.41), good agreement for serous cystadenoma (p=0.79), and excellent agreement for choledochal pancreatic cyst (p=1), pancreatic pseudocyst (p=0.84), and Frantz tumor (p=1) (p<0.05). CONCLUSIONS The findings of computed tomography and/or magnetic resonance imaging have an equivalent diagnostic agreement with an anatomopathological diagnosis for differentiating benign from malignant Pancreatic cystic lesions and in suggesting a specific diagnosis. There is no statistical difference between the use of computed tomography alone and computed tomography+magnetic resonance imaging in the improvement of diagnostic accuracy.
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Affiliation(s)
- Rafael Mello Fontolan Vieira
- Cancer Regional Hospital, Hepatobiliopancreatic Oncological Digestive Surgery - Presidente Prudente (SP), Brazil
| | | | - Leandra Ernst Kerche
- Faculty of Medicine of Oeste Paulista, Functional Sciences Department - Presidente Prudente (SP), Brazil
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7
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Kaiser J, Hackert T, Hinz U, Mayer P, Tjaden C, Roth S, Pausch TM, Heger U, Heckler M, Al-Saeedi M, Büchler MW, Loos M. Surgery for intraductal papillary mucinous neoplasms in young patients: High-risk population. Surgery 2023:S0039-6060(23)00251-9. [PMID: 37225560 DOI: 10.1016/j.surg.2023.04.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 04/14/2023] [Accepted: 04/27/2023] [Indexed: 05/26/2023]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasms of the pancreas are uncommon in young individuals. Management of these patients is challenging because the risk of malignancy and recurrence after surgery remains unclear. The aim of the present study was to assess the long-term risk for intraductal papillary mucinous neoplasm recurrence after surgery for intraductal papillary mucinous neoplasms in patients ≤50 years of age. METHODS Perioperative and long-term follow-up data of patients who had undergone surgery for intraductal papillary mucinous neoplasms between 2004 and 2020 were extracted from a prospective unicentric database and retrospectively analyzed. RESULTS Seventy-eight patients underwent surgical treatment for benign intraductal papillary mucinous neoplasms (low-grade n = 22 and intermediate-grade n = 21) and malignant intraductal papillary mucinous neoplasms (high-grade n = 16 and intraductal papillary mucinous neoplasm-associated carcinoma n = 19). Severe postoperative morbidity (Clavien-Dindo ≥III) was found in 14 patients (18%). The median length of hospital stay was 10 days. No perioperative mortality was observed. The median length of follow-up was 72 months. Recurrence of intraductal papillary mucinous neoplasm-associated carcinoma was found in 6 patients (19%) with malignant intraductal papillary mucinous neoplasm and 1 patient (3%) with benign intraductal papillary mucinous neoplasm. CONCLUSION Surgery for intraductal papillary mucinous neoplasm is safe and can be performed with low morbidity and potentially no mortality in young patients. Given the high rate of malignancy (45%), these patients with intraductal papillary mucinous neoplasms represent a high-risk population, and prophylactic surgical treatment should be considered in these patients with long life expectancies. Regular clinical and radiologic follow-up examinations are important to rule out disease recurrence, which is high, especially in patients with intraductal papillary mucinous neoplasm-associated carcinoma.
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Affiliation(s)
- Joerg Kaiser
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany. https://twitter.com/joerg_kaiser
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Ulf Hinz
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Philipp Mayer
- Department of Radiology, Heidelberg University Hospital, Germany
| | - Christine Tjaden
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Susanne Roth
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Thomas M Pausch
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Ulrike Heger
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Max Heckler
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Mohammed Al-Saeedi
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Markus W Büchler
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Martin Loos
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany.
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8
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"Evolving Trends in Pancreatic Cystic Tumors: A 3-Decade Single-Center Experience With 1290 Resections". Ann Surg 2023; 277:491-497. [PMID: 34353996 DOI: 10.1097/sla.0000000000005142] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. SUMMARY BACKGROUND DATA Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. METHODS Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. RESULTS A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. CONCLUSIONS Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.
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9
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Jabłońska B, Gudz A, Hinborch T, Bujała B, Biskup K, Mrowiec S. Pancreatic Cystic Tumors: A Single-Center Observational Study. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:241. [PMID: 36837443 PMCID: PMC9964881 DOI: 10.3390/medicina59020241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 01/22/2023] [Accepted: 01/24/2023] [Indexed: 01/31/2023]
Abstract
Background and Objectives: The aim of the study was to analyze the prevalence and characteristics of pancreatic cystic tumors (PCTs). Material and Methods: A retrospective analysis of the medical records of 124 patients, 102 (69%) women and 46 (31%) men, who had undergone surgery for pancreatic cystic tumors in 2014-2018. Among 148 pancreatic cysts, 24 (16%) were non-neoplasmatic and 124 (84%) were neoplasmatic. The neoplasmatic cysts (n = 124) were included in our analysis. There were five main types of PCTs: IPMN (intraductal papillary mucinous neoplasm) (n = 45), MCN (mucinous cystic neoplasm) (n = 30), SCN (serous cystic neoplasm) (n = 28), SPN (solid pseudopapillary neoplasm) (n = 8), and CPEN (cystic pancreatic endocrine neoplasm) (n = 8), as well as mixed-type tumors (n = 5). Results: A statistically significant dependency between PCT type and age was proven (p= 0.0001): IPMNs were observed in the older group of patients with an average age of 66.12 (40-79) years while SPNs were noted in the youngest group of patients with an average age of 36.22 (22-55) years. A statistically significant association between PCT type and gender (p = 0.0001) was found: IPMNs occurred among 24 (53.33%) men and 21 (46.6%) women. In the MCN and SPN groups, all patients were female (100%). Among the SCN group, the majority were women (27 (96.43%)), and there was only 1 (3.57%) man. A statistically significant dependency between PCT type and size was proven (p = 0.0007). The mean size of IPMNs was the smallest 2.95 (0.6-10 cm) and the mean size of MCNs was the largest 6.78 (1.5-19 cm). A statistically significant dependency between PCT type and tumor location was proven (p = 0.000238). The most frequent location of IPMN was the pancreatic head: 27 (60%). MCN was most frequently located in the pancreatic tail (18 (60%)). Most (10/28) SCNs were found in the pancreatic tail (10 (35.71%)). CPENs were most frequently located in the pancreatic tail (three (37.5%)) and pancreatic body and tail (three (37.5%)). SPNs were located commonly in the pancreatic head (five (62.5%)). The type of surgery depended on the tumor location. The most frequent surgery for IPMNs was pancreatoduodenectomy (44.4%), while for MCNs and SCNs, it was distal pancreatectomy (81%). The postoperative morbidity and mortality were 34.68% and 1.61%, respectively. Postoperative pancreatic fistula (POPF) was the most frequent (29%) complication. Conclusions: IPMN was the most frequent resected PCT in our material. A statistically significant association between the type of cyst and location within the pancreas, size, local lymph node involvement, and patient's age and sex was proved. POPF was the most frequent postoperative complication. In patients with PCTs, due to substantial postoperative morbidity, adequate patient selection, considering both the surgical risk as well as the long-term risk of malignant transformation, is very important during qualification for surgery.
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Affiliation(s)
- Beata Jabłońska
- Department of Digestive Tract Surgery, Medical University of Silesia, Medyków 14 St., 40-752 Katowice, Poland
| | - Arkadiusz Gudz
- Student Scientific Society, Department of Digestive Tract Surgery, Medical University of Silesia, Medyków 14 St., 40-752 Katowice, Poland
| | - Tomasz Hinborch
- Student Scientific Society, Department of Digestive Tract Surgery, Medical University of Silesia, Medyków 14 St., 40-752 Katowice, Poland
| | - Bartosz Bujała
- Student Scientific Society, Department of Digestive Tract Surgery, Medical University of Silesia, Medyków 14 St., 40-752 Katowice, Poland
| | - Katarzyna Biskup
- Student Scientific Society, Department of Digestive Tract Surgery, Medical University of Silesia, Medyków 14 St., 40-752 Katowice, Poland
| | - Sławomir Mrowiec
- Department of Digestive Tract Surgery, Medical University of Silesia, Medyków 14 St., 40-752 Katowice, Poland
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10
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Giannone F, Crippa S, Aleotti F, Palumbo D, Belfiori G, Partelli S, Schiavo Lena M, Capurso G, Petrone MC, De Cobelli F, Arcidiacono PG, Falconi M. Improving diagnostic accuracy and appropriate indications for surgery in pancreatic cystic neoplasms: the role of EUS. Gastrointest Endosc 2022; 96:648-656.e2. [PMID: 35618030 DOI: 10.1016/j.gie.2022.05.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 05/14/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Pancreatic cystic neoplasms (PCNs) represent a difficult preoperative diagnosis despite improvements in imaging. In this study, we compared preoperative and final pathologic diagnosis in a large cohort of resected PCNs, evaluating diagnostic accuracy with a specific focus on the value of EUS. METHODS A retrospective analysis of patients undergoing resection between 2009 and 2019 for presumed PCNs was performed. Preoperative workup was reviewed by analyzing the role of imaging and EUS. Patients with a benign histology who did not show absolute indication were categorized as "delayable surgery." RESULTS Of 585 patients who were retrospectively analyzed, in 108 (18.5%) final histology did not confirm preoperative diagnosis. EUS was associated with a lower rate of incorrect diagnosis (16%; P = .03), but the risk of overtreatment was similar regardless of instrumental diagnostic path (33/131 vs 68/328, P = .298). Dilatation of the main pancreatic duct and cytologic sampling were the only variables independently associated with a correct diagnosis (P < .001 and P = .041, respectively). Based on clinical presentation and final histology, pancreatic resection could have been spared or delayed in 101 of 459 patients (22%), and this was influenced by age (odds ratio [OR], .97; P = .002), cyst larger than 30 mm (OR, 1.89; P = .005), and type of operation (OR, 3.46 [P < .001] and 3.18 [P = .023] for distal pancreatectomies and other resections, respectively). CONCLUSIONS The overall risk of unnecessary immediate surgery for PCNs is about 22% in a high-volume referral center. EUS with cytologic sampling is a useful procedure in the diagnostic management of PCNs, improving their diagnostic accuracy.
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Affiliation(s)
- Fabio Giannone
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of General, Digestive and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - Stefano Crippa
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita Salute San Raffaele University, Milan, Italy
| | - Francesca Aleotti
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Diego Palumbo
- Pancreas Translational and Clinical Research Center, Radiology Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giulio Belfiori
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita Salute San Raffaele University, Milan, Italy
| | - Marco Schiavo Lena
- Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Maria Chiara Petrone
- Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco De Cobelli
- Vita Salute San Raffaele University, Milan, Italy; Pancreas Translational and Clinical Research Center, Radiology Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Vita Salute San Raffaele University, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita Salute San Raffaele University, Milan, Italy
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11
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Del Chiaro M, Kirsch MJ, Schulick R. Commentary on: Multi-institutional Validation Study of Cyst Fluid Protein Biomarkers in Patients With Cystic Lesions of the Pancreas. Ann Surg 2022; 276:e133. [PMID: 35797412 DOI: 10.1097/sla.0000000000005505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Marco Del Chiaro
- Department of Surgery, Division of Surgical Oncology, University of Colorado School of Medicine, Aurora, CO
- Cancer Center, University of Colorado School of Medimaccine, Aurora, CO
| | - Michael J Kirsch
- Department of Surgery, Division of Surgical Oncology, University of Colorado School of Medicine, Aurora, CO
| | - Richard Schulick
- Department of Surgery, Division of Surgical Oncology, University of Colorado School of Medicine, Aurora, CO
- Cancer Center, University of Colorado School of Medimaccine, Aurora, CO
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12
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Kim GH, Choi K, Paik N, Lee KT, Lee JK, Lee KH, Han IW, Kang SH, Heo JS, Park JK. Diagnostic Concordance and Preoperative Risk Factors for Malignancy in Pancreatic Mucinous Cystic Neoplasms. Gut Liver 2022; 16:637-644. [PMID: 34933278 PMCID: PMC9289824 DOI: 10.5009/gnl210231] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 08/24/2021] [Accepted: 09/03/2021] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND/AIMS As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. METHODS Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. RESULTS Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. CONCLUSIONS In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4 cm in size, are asymptomatic and lack worrisome features on preoperative images.
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Affiliation(s)
- Ga Hee Kim
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyu Choi
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Namyoung Paik
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyu Taek Lee
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Kyun Lee
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Hyuck Lee
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - In Woong Han
- Departments of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Hoon Kang
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Seok Heo
- Departments of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joo Kyung Park
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
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13
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Kaiser J, Alhalabi KT, Hinz U, Mayer P, Tjaden C, Büchler MW, Hackert T, Loos M. Enucleation for low-grade branch duct intraductal papillary mucinous neoplasms: Long-term follow-up. Surgery 2022; 172:968-974. [PMID: 35680446 DOI: 10.1016/j.surg.2022.04.035] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 03/31/2022] [Accepted: 04/20/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Pancreatic enucleation allows resection of branch-duct intraductal papillary mucinous neoplasms with full parenchyma preservation. The aim of this study was to assess intraductal papillary mucinous neoplasms recurrence and functional outcomes during long-term follow-up after enucleation. METHODS Patient characteristics, as well as radiologic and clinicopathologic follow-up data of patients who underwent enucleation for branch-duct intraductal papillary mucinous neoplasms between 2004 and 2014, were analyzed. Quality of life was assessed using the EORTC QLQ-C30 and QLQ-PAN26 questionnaires. RESULTS Seventy-four patients underwent enucleation for low-grade branch-duct intraductal papillary mucinous neoplasms in 71 and high-grade branch-duct intraductal papillary mucinous neoplasms in 3 patients. Long-term follow-up data were available for 66 patients (89%; median follow-up: 87 months). Radiologic imaging (n = 56) showed intraductal papillary mucinous neoplasm recurrence in 10 patients (18%) including local recurrence at the site of enucleation in 3 patients (5%) and new onset intraductal papillary mucinous neoplasms manifestation in 7 patients (13%) at a distant site in the pancreatic remnant. Four patients (6%) underwent reoperation. Two of these patients had intraductal papillary mucinous neoplasm-associated carcinoma, one of them at the enucleation site. During the follow-up period, no intraductal papillary mucinous neoplasm-related deaths occurred and no new onsets of insulin-dependent diabetes mellitus were observed. QLQ-C30 revealed a global health status of 66.0% and overall functioning and symptom scores of 81.0% and 22.8%, respectively. Additionally, QLQ-PAN26 showed an overall symptom score of 26.5%. CONCLUSION Enucleation is an organ-preserving surgical treatment option for low-grade branch-duct intraductal papillary mucinous neoplasms with low local recurrence risk and excellent functional long-term outcome. However, postoperative life-long follow-up must be performed as for any type of partial pancreatectomy for intraductal papillary mucinous neoplasms due to the risk of recurrence and potential malignancy.
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Affiliation(s)
- Joerg Kaiser
- Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Germany
| | - Karam T Alhalabi
- Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Germany
| | - Philipp Mayer
- Department of Radiology, University Hospital of Heidelberg, Germany
| | - Christine Tjaden
- Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Germany
| | - Martin Loos
- Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Germany.
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14
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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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15
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Kaiser J, Scheifele C, Hinz U, Leonhardt CS, Hank T, Koenig AK, Tjaden C, Hackert T, Bergmann F, Büchler MW, Strobel O. IPMN-associated pancreatic cancer: Survival, prognostic staging and impact of adjuvant chemotherapy. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1309-1320. [PMID: 34920899 DOI: 10.1016/j.ejso.2021.12.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 11/23/2021] [Accepted: 12/06/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasm (IPMN)-associated carcinoma is a subtype of pancreatic cancer for which prognostic factors, the validity of the AJCC/UICC staging system and the role of adjuvant chemotherapy remain unknown. MATERIALS AND METHODS Clinicopathological, treatment and follow-up data of patients with IPMN-associated carcinoma undergoing resection between 2002 and 2018 were analyzed. Uni- and multivariable survival analyses were performed to identify prognostic factors. RESULTS Of 424 patients undergoing resection for IPMN-associated carcinoma, 77% patients had pancreatic ductal adenocarcinoma (IPMN-PDAC) and 23% had colloid carcinoma (IPMN-CC). Compared to IPMN-CC, IPMN-PDAC was diagnosed at more advanced tumor stages, more frequently involved lymph nodes, more frequently showed poor differentiation and were associated with higher rates of R1 resections. Resected IPMN-PDAC showed markedly shorter median overall survival than IPMN-CC (26.7 months vs. 91.3 months). The current AJCC/UICC staging system was validated for IPMN-associated carcinoma and for both of its subtypes. In multivariable analysis age ≥70 years, diabetes mellitus, high levels of Ca 19-9, IPMN-PDAC subtype, G3 tumors and higher AJCC/UICC stage were independently associated with shorter survival. Adjuvant therapy was not associated with improved survival in IPMN-associated carcinoma. Overall survival was comparable in patients receiving vs. not receiving adjuvant therapy. CONCLUSIONS Survival after resection of IPMN-associated carcinoma depends on tumor stage, on histologic tumor subtype, grading, and Ca 19-9 levels. The current 8th edition of the AJCC/UICC staging system is applicable for IPMN-associated carcinoma and for both of its subtypes IPMN-PDAC and IPMN-CC. The role of adjuvant therapy for IPMN-associated carcinoma remains unclear.
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Affiliation(s)
- Joerg Kaiser
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Cornelius Scheifele
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Carl-Stephan Leonhardt
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thomas Hank
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany; Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Anna-Katharina Koenig
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Christine Tjaden
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Frank Bergmann
- Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany; Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria.
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16
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Suresh V, Byers K, Rajesh UC, Caiazza F, Zhu G, Craik CS, Kirkwood K, Davisson VJ, Sheik DA. Translation of a Protease Turnover Assay for Clinical Discrimination of Mucinous Pancreatic Cysts. Diagnostics (Basel) 2022; 12:1343. [PMID: 35741154 PMCID: PMC9222202 DOI: 10.3390/diagnostics12061343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 11/29/2022] Open
Abstract
The classification of pancreatic cyst fluids can provide a basis for the early detection of pancreatic cancer while eliminating unnecessary procedures. A candidate biomarker, gastricsin (pepsin C), was found to be present in potentially malignant mucinous pancreatic cyst fluids. A gastricsin activity assay using a magnetic bead-based platform has been developed using immobilized peptide substrates selective for gastricsin bearing a dimeric rhodamine dye. The unique dye structure allows quantitation of enzyme-cleaved product by both fluorescence and surface enhanced Raman spectroscopy (SERS). The performance of this assay was compared with ELISA assays of pepsinogen C and the standard of care, carcinoembryonic antigen (CEA), in the same clinical sample cohort. A retrospective cohort of mucinous (n = 40) and non-mucinous (n = 29) classes of pancreatic cyst fluid samples were analyzed using the new protease activity assay. For both assay detection modes, successful differentiation of mucinous and non-mucinous cyst fluid was achieved using 1 µL clinical samples. The activity-based assays in combination with CEA exhibit optimal sensitivity and specificity of 87% and 93%, respectively. The use of this gastricsin activity assay requires a minimal volume of clinical specimen, offers a rapid assay time, and shows improvements in the differentiation of mucinous and non-mucinous cysts using an accurate standardized readout of product formation, all without interfering with the clinical standard of care.
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Affiliation(s)
- Vallabh Suresh
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, IN 47907, USA; (V.S.); (V.J.D.)
| | - Kaleb Byers
- Amplified Sciences, Inc., West Lafayette, IN 47906, USA; (K.B.); (U.C.R.)
| | | | - Francesco Caiazza
- Alaunus Biosciences, Inc., San Francisco, CA 94107, USA;
- Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA;
| | - Gina Zhu
- Department of Surgery, University of California, San Francisco, CA 94143, USA; (G.Z.); (K.K.)
| | - Charles S. Craik
- Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA;
| | - Kimberly Kirkwood
- Department of Surgery, University of California, San Francisco, CA 94143, USA; (G.Z.); (K.K.)
| | - Vincent Jo Davisson
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, IN 47907, USA; (V.S.); (V.J.D.)
- Amplified Sciences, Inc., West Lafayette, IN 47906, USA; (K.B.); (U.C.R.)
| | - Daniel A. Sheik
- Amplified Sciences, Inc., West Lafayette, IN 47906, USA; (K.B.); (U.C.R.)
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17
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Yokode M, Matsumori T, Uza N. Pancreatic duct biopsies using a novel device delivery system for preoperative evaluation of main duct intraductal papillary mucinous neoplasm. Dig Endosc 2022; 34:e83-e84. [PMID: 35322472 DOI: 10.1111/den.14280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/15/2022] [Accepted: 02/21/2022] [Indexed: 02/08/2023]
Affiliation(s)
- Masataka Yokode
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tomoaki Matsumori
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Norimitsu Uza
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Brunner M, Häberle L, Esposito I, Grützmann R. [Pancreatic cystic space-occupying lesions-Diagnostics, treatment and follow-up care : Current recommendations taking the current German S3 guidelines on pancreatic cancer into account]. Chirurg 2022; 93:461-475. [PMID: 35316346 DOI: 10.1007/s00104-022-01616-9] [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] [Accepted: 02/14/2022] [Indexed: 11/03/2022]
Abstract
Due to their increased detection pancreatic cystic space-occupying lesions are becoming increasingly relevant in the clinical routine and represent a morphologically and biologically heterogeneous and thus clinically demanding as well as potentially (pre)malignant entity. As a result, recommendations for the diagnostics and treatment of pancreatic cystic tumors have now been incorporated into the current German S3 guidelines on pancreatic cancer. The diagnostics of pancreatic cystic space-occupying lesions are based on the following three elements: collection of relevant clinical information, performance of high-resolution imaging procedures and if diagnostic uncertainty persists, puncture diagnostics. Differentiated diagnostics are of essential importance as these represent the basis for an adequate treatment decision. Pancreatic cystic lesions with a relevant risk of malignant transformation, e.g., main duct intraductal papillary mucinous neoplasms (IPMN), followed by mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and generally pancreatic cystic lesions with risk factors independent of the entity, should be resected, whereas a differentiated and individualized approach is necessary, especially for branch-duct IPMNs. The serous cystic neoplasms (SCN) have no malignant potential and do not require any treatment if they are asymptomatic. Important principles in surgery of pancreatic cancer, such as adequate surgical resection taking oncological standards into account and standardized appropriate histopathological processing of the specimens as well as intraoperative frozen section analysis also play an important role in pancreatic cystic space-occupying lesions. An annual follow-up seems to be meaningful, especially for IPMNs.
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Affiliation(s)
- Maximilian Brunner
- Klink für Allgemein- und Viszeralchirurgie, Universitätsklinikum der Friedrich-Alexander-Universität Erlangen, Erlangen, Deutschland
| | - Lena Häberle
- Institut für Pathologie, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland
| | - Irene Esposito
- Institut für Pathologie, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.
| | - Robert Grützmann
- Klink für Allgemein- und Viszeralchirurgie, Universitätsklinikum der Friedrich-Alexander-Universität Erlangen, Erlangen, Deutschland.
- , Krankenhausstr. 12, 91054, Erlangen, Deutschland.
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19
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Shipley LC, Ahmed AM. New and emerging technology in the diagnosis and treatment of pancreatic cysts. Transl Gastroenterol Hepatol 2022; 7:15. [PMID: 35548473 PMCID: PMC9081918 DOI: 10.21037/tgh-2020-09] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 06/05/2020] [Indexed: 08/27/2023] Open
Abstract
Pancreatic cysts have always presented as a diagnostic dilemma due to the difficulties in identifying patients with current imaging modalities that could most benefit from surgical intervention. Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystadenomas (MCNs) carry the highest malignant potential of all pancreatic cysts and pancreatic adenocarcinoma carries a high mortality as the fourth leading cause of cancer-related deaths. However, surgery to remove benign cysts also carries a high morbidity and occasional mortality. Opportunities to identify and reduce pre-cancer lesions must be aggressively pursued. Multidetector helical CT (MDHCT) or an up-to-date MRI is the first diagnostic tool to evaluate a suspected pancreatic lesion. Currently, review by a multidisciplinary group who specialize in pancreatic cysts and pancreatic cancer is advised to review factors such as a patient's comorbidities, the type of surgery needed to remove the cyst and the estimated morbidity and mortality associated with the procedure. Some recent data are emerging to assist with identifying those at highest risk such as cyst fluid analysis, laser endomicroscopy, and artificial intelligence (AI). This article reviews the current status, benefits, challenges and future prospects on diagnosis and treatment of pancreatic cysts. Further prospective randomized control trials are needed to determine the optimal management and treatment for patients with pancreatic cysts.
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Affiliation(s)
- Lindsey C. Shipley
- Department of Internal Medicine, University of Alabama, Birmingham, AL, USA
| | - Ali M. Ahmed
- Division of Gastroenterology and Hepatology, University of Alabama, Birmingham, AL, USA
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20
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Faccioli N, Santi E, Foti G, D’Onofrio M. Cost-effectiveness analysis of including contrast-enhanced ultrasound in management of pancreatic cystic neoplasms. LA RADIOLOGIA MEDICA 2022; 127:349-359. [PMID: 35230618 PMCID: PMC8989810 DOI: 10.1007/s11547-022-01459-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 01/21/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE Pancreatic cystic neoplasms (PCN) management consists of non-invasive imaging studies (CT, MRI), with a high resource burden. We aimed to determine the cost-effectiveness of including contrast-enhanced ultrasound (CEUS) in the management of PCN without risk features. MATERIALS AND METHODS By using a decision-tree model in a hypothetical cohort of patients, we compared management strategy including CEUS with the latest Fukuoka consensus, European and Italian guidelines. Our strategy for BD-IPMN/MCN < 1 cm includes 1 CEUS annually. For those between 1 and 2 cm, it includes CEUS 4 times/year during the first year, then 3 times/year for 4 years and then annually. For those between 2 and 3 cm, it comprises MRI twice/year during the first one, then alternating 2 CEUS and 1 MRI yearly. RESULTS CEUS surveillance is the dominant strategy in all scenarios. CEUS surveillance average cost is 1,984.72 €, mean QALY 11.79 and mean ICER 181.99 €. If willingness to pay is 30,000 €, 45% of patients undergone CEUS surveillance of BDIPMN/MCN < 1 cm would be within budget. CONCLUSION Guidelines strategies are very effective, but costs are relatively high from a policy perspective. CEUS surveillance may be a cost-effective strategy yielding a nearly high QALYs, an acceptable ICER, and a lower cost.
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Affiliation(s)
- Niccolo’ Faccioli
- Present Address: Department of Radiology, G.B. Rossi Hospital, Università di Verona, Piazzale L.A.Scuro 10, 37134 Verona, Italy
| | - Elena Santi
- Present Address: Department of Radiology, G.B. Rossi Hospital, Università di Verona, Piazzale L.A.Scuro 10, 37134 Verona, Italy
| | - Giovanni Foti
- IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy
| | - Mirko D’Onofrio
- Present Address: Department of Radiology, G.B. Rossi Hospital, Università di Verona, Piazzale L.A.Scuro 10, 37134 Verona, Italy
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21
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Gao J, Han F, Wang X, Duan S, Zhang J. Multi-Phase CT-Based Radiomics Nomogram for Discrimination Between Pancreatic Serous Cystic Neoplasm From Mucinous Cystic Neoplasm. Front Oncol 2021; 11:699812. [PMID: 34926238 PMCID: PMC8672034 DOI: 10.3389/fonc.2021.699812] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 11/15/2021] [Indexed: 12/25/2022] Open
Abstract
Purpose This study aimed to develop and verify a multi-phase (MP) computed tomography (CT)-based radiomics nomogram to differentiate pancreatic serous cystic neoplasms (SCNs) from mucinous cystic neoplasms (MCNs), and to compare the diagnostic efficacy of radiomics models for different phases of CT scans. Materials and Methods A total of 170 patients who underwent surgical resection between January 2011 and December 2018, with pathologically confirmed pancreatic cystic neoplasms (SCN=115, MCN=55) were included in this single-center retrospective study. Radiomics features were extracted from plain scan (PS), arterial phase (AP), and venous phase (VP) CT scans. Algorithms were performed to identify the optimal features to build a radiomics signature (Radscore) for each phase. All features from these three phases were analyzed to develop the MP-Radscore. A combined model comprised the MP-Radscore and imaging features from which a nomogram was developed. The accuracy of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration tests, and decision curve analysis. Results For each scan phase, 1218 features were extracted, and the optimal ones were selected to construct the PS-Radscore (11 features), AP-Radscore (11 features), and VP-Radscore (12 features). The MP-Radscore (14 features) achieved better performance based on ROC curve analysis than any single phase did [area under the curve (AUC), training cohort: MP-Radscore 0.89, PS-Radscore 0.78, AP-Radscore 0.83, VP-Radscore 0.85; validation cohort: MP-Radscore 0.88, PS-Radscore 0.77, AP-Radscore 0.83, VP-Radscore 0.84]. The combination nomogram performance was excellent, surpassing those of all other nomograms in both the training cohort (AUC, 0.91) and validation cohort (AUC, 0.90). The nomogram also performed well in the calibration and decision curve analyses. Conclusions Radiomics for arterial and venous single-phase models outperformed the plain scan model. The combination nomogram that incorporated the MP-Radscore, tumor location, and cystic number had the best discriminatory performance and showed excellent accuracy for differentiating SCN from MCN.
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Affiliation(s)
- Jiahao Gao
- Department of Radiology, Huashan Hospital North, Fudan University, Shanghai, China.,Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Fang Han
- Department of Radiology, Huashan Hospital North, Fudan University, Shanghai, China.,Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiaoshuang Wang
- Department of Radiology, Huashan Hospital North, Fudan University, Shanghai, China
| | - Shaofeng Duan
- Department of Life Sciences, GE Healthcare, Shanghai, China
| | - Jiawen Zhang
- Department of Radiology, Huashan Hospital North, Fudan University, Shanghai, China.,Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
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22
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Abstract
The incidence of pancreatic incidentalomas (PIs) detected in otherwise asymptomatic patients is growing with the increasing quality and use of advanced imaging techniques. PI can present as isolated main pancreatic duct dilation or as a solid or cystic lesion. Although historically thought to be relatively rare, PIs are rather common, particularly cystic lesions of the pancreas, which can be detected in up to 49% of the general population. With the poor prognosis of pancreatic cancer, PIs are an opportunity for prevention and early diagnosis, but when managed poorly, they can also lead to overtreatment and unnecessary morbidity. The management of PI should begin with a dedicated pancreas protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) to accurately characterize duct size, lesion characteristics and establish an accurate baseline for subsequent follow up. Diagnosis and subsequent management depends on the extent of main duct dilation and solid versus cystic appearance. Solid lesions are highly concerning for malignancy. Cystic lesions can be further categorized as intraductal papillary mucinous neoplasms of the pancreas (IPMNs) or mucinous cystic neoplasms (MCNs), both of which harbour malignant potential, or as serous cystic neoplasms (SCNs) that are benign. In this paper, we summarize the major challenges related to PI and present pragmatic suggestions for management.
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Affiliation(s)
- Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Robert J Torphy
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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23
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Marchegiani G, Andrianello S, Crippa S, Pollini T, Belfiori G, Gozzini L, Cassalia F, Caravati A, Luchini C, Doglioni C, Bassi C, Falconi M, Salvia R. Actual malignancy risk of either operated or non-operated presumed mucinous cystic neoplasms of the pancreas under surveillance. Br J Surg 2021; 108:1097-1104. [PMID: 34059873 DOI: 10.1093/bjs/znab131] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 03/25/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Despite the low malignant potential of pancreatic mucinous cystic neoplasms (MCNs), surgery is still performed. The aim of this pragmatic study was to assess the outcome of surgery and surveillance for patients presenting with a presumed MCN at the first evaluation. METHODS Data for patients with a presumed MCN observed from 2000 to 2016 at the Verona Pancreas Institute and San Raffaele Hospital were extracted from prospective databases. The endpoints were risk of malignancy at pathology and rate of misdiagnosis for the surgical series, expressed as an odds ratio (OR) with 95 per cent confidence interval, and disease-specific survival (DSS) for the surveillance cohort investigated by the Kaplan-Meier method. RESULTS A total of 424 patients were identified. In the surgical series (229 patients), the rate of misdiagnosis was 19.2 per cent. The rate of malignant MCNs was 10.9 per cent (25 patients). The overall rate of malignancy, including misdiagnoses, was 11.3 per cent (26 patients). Predictors of malignancy were mural nodules (OR 27.75, 95 per cent c.i. 4.44-173.61; P < 0.001), size at least 50 mm (OR 13.39, 2.01 to 89.47; P = 0.007), and carbohydrate antigen 19.9 level (OR 3.98, 1.19 to 13.30; P = 0.025). In the absence of mural nodules and enhancing walls, none of the resected presumed MCNs smaller than 50 mm were malignant. Only patients with high-risk stigmata undergoing surgery experienced a significantly reduced 5-year DSS compared with all other patients (88 versus 100 per cent; P = 0.031). CONCLUSION Presumed MCNs with mural nodules, enhancing walls or cysts of 50 mm or larger should be considered for upfront surgical resection owing to the high risk of malignancy. In the absence of these features, the incidence of malignancy is negligible, favouring surveillance in selected patients given the low risk of malignancy and the high rate of misdiagnosis. LAY SUMMARY Malignant degeneration of presumed pancreatic mucinous cystic neoplasms takes several years, if it occurs at all. Mural nodules, enhancing walls or cysts of 50 mm or larger call for surgical resection owing to an increased risk of malignancy; otherwise, surveillance seems a good option.
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Affiliation(s)
- G Marchegiani
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - S Andrianello
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - S Crippa
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - T Pollini
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - G Belfiori
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - L Gozzini
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - F Cassalia
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - A Caravati
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - C Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona Hospital Trust, Verona, Italy
| | - C Doglioni
- Department of Pathology, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - C Bassi
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - M Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - R Salvia
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
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24
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Yip-Schneider MT, Wu H, Allison HR, Easler JJ, Sherman S, Al-Haddad MA, Dewitt JM, Schmidt CM. Biomarker Risk Score Algorithm and Preoperative Stratification of Patients with Pancreatic Cystic Lesions. J Am Coll Surg 2021; 233:426-434.e4. [PMID: 34166836 PMCID: PMC8403144 DOI: 10.1016/j.jamcollsurg.2021.05.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/28/2021] [Accepted: 05/28/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Pancreatic cysts are incidentally detected in up to 13% of patients undergoing radiographic imaging. Of the most frequently encountered types, mucin-producing (mucinous) pancreatic cystic lesions may develop into pancreatic cancer, while nonmucinous ones have little or no malignant potential. Accurate preoperative diagnosis is critical for optimal management, but has been difficult to achieve, resulting in unnecessary major surgery. Here, we aim to develop an algorithm based on biomarker risk scores to improve risk stratification. STUDY DESIGN Patients undergoing surgery and/or surveillance for a pancreatic cystic lesion, with diagnostic imaging and banked pancreatic cyst fluid, were enrolled in the study after informed consent (n = 163 surgical, 67 surveillance). Cyst fluid biomarkers with high specificity for distinguishing nonmucinous from mucinous pancreatic cysts (vascular endothelial growth factor [VEGF], glucose, carcinoembryonic antigen [CEA], amylase, cytology, and DNA mutation) were selected. Biomarker risk scores were used to design an algorithm to predict preoperative diagnosis. Performance was tested using surgical (retrospective) and surveillance (prospective) cohorts. RESULTS In the surgical cohort, the biomarker algorithm outperformed the preoperative clinical diagnosis in correctly predicting the final pathologic diagnosis (91% vs 73%; p < 0.000001). Specifically, nonmucinous serous cystic neoplasms (SCN) and mucinous cystic neoplasms (MCN) were correctly classified more frequently by the algorithm than clinical diagnosis (96% vs 30%; p < 0.000008 and 92% vs 69%; p = 0.04, respectively). In the surveillance cohort, the algorithm predicted a preoperative diagnosis with high confidence based on a high biomarker score and/or consistency with imaging from ≥1 follow-up visits. CONCLUSIONS A biomarker risk score-based algorithm was able to correctly classify pancreatic cysts preoperatively. Importantly, this tool may improve initial and dynamic risk stratification, reducing overdiagnosis and underdiagnosis.
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Affiliation(s)
- Michele T Yip-Schneider
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Simon Cancer Center, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | - Huangbing Wu
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | | | - Jeffrey J Easler
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN
| | - Stuart Sherman
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN
| | - Mohammad A Al-Haddad
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | - John M Dewitt
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN
| | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Biochemistry/Molecular Biology, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Simon Cancer Center, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN.
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25
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Comparative analysis of glucose and carcinoembryonic antigen in the diagnosis of pancreatic mucinous cysts: a systematic review and meta-analysis. Gastrointest Endosc 2021; 94:235-247. [PMID: 33852901 DOI: 10.1016/j.gie.2021.03.935] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 03/31/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Pancreatic cystic fluid (PCF) analysis is useful to distinguish between different cyst types and to guide management. The aim of our study was to compare the diagnostic accuracy of glucose level with carcinoembryonic antigen (CEA) in PCF for mucinous cyst diagnosis. METHODS We identified studies with PCF obtained by EUS before surgery, with cysts classified as mucinous and nonmucinous according to surgical specimens. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic (ROC) curve analysis were conducted. RESULTS For CEA, we included 31 studies with 5268 patients, of which 2083 were referred for surgery. For glucose, we included 4 studies with 345 patients, of which 275 were referred for surgery. Glucose performed better than CEA for mucinous cysts diagnosis (premalignant and malignant) with sensitivities of .90 (95% confidence interval [CI], .85-.94) and .67 (95% CI, .65-.70), specificities of .82 (95% CI, .72-.89) and .80 (95% CI, 0.76-0.83), and areas under the ROC curve of .96 and .79, respectively. Glucose had a higher sensitivity (90%), with uncommon false-negative results, making it an excellent biomarker to exclude a mucinous cyst. Sensitivity analysis demonstrated that the findings of the current meta-analysis are robust. CONCLUSION Glucose level in PCF is more accurate than CEA for preoperative diagnosis of mucinous cysts. It may become a useful first-line test, particularly in small cysts with a limited volume of PCF. Larger studies are awaited to confirm glucose as the single test for mucinous cyst diagnosis.
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26
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Marchegiani G, Pollini T, Andrianello S, Tomasoni G, Biancotto M, Javed AA, Kinny-Köster B, Amini N, Han Y, Kim H, Kwon W, Kim M, Perri G, He J, Bassi C, Goh BK, Katz MH, Jang JY, Wolfgang C, Salvia R. Progression vs Cyst Stability of Branch-Duct Intraductal Papillary Mucinous Neoplasms After Observation and Surgery. JAMA Surg 2021; 156:654-661. [PMID: 34009303 DOI: 10.1001/jamasurg.2021.1802] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information. Objective To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations. Design, Setting, and Participants The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months). Main Outcomes and Measures Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination. Results A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04 [95% CI, 2.94-87.40]; P = .001). Conclusions and Relevance These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.
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Affiliation(s)
| | - Tommaso Pollini
- Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | | | - Giorgia Tomasoni
- Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Marco Biancotto
- Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Ammar A Javed
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland
| | | | - Neda Amini
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Youngmin Han
- Department of Surgery, Seoul National University Hospital, Seoul, South Korea
| | - Hongbeom Kim
- Department of Surgery, Seoul National University Hospital, Seoul, South Korea
| | - Wooil Kwon
- Department of Surgery, Seoul National University Hospital, Seoul, South Korea
| | - Michael Kim
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston
| | - Giampaolo Perri
- Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.,Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston
| | - Jin He
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Claudio Bassi
- Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Brian K Goh
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Matthew H Katz
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston
| | - Jin-Young Jang
- Department of Surgery, Seoul National University Hospital, Seoul, South Korea
| | | | - Roberto Salvia
- Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
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27
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Surci N, Marchegiani G, Andrianello S, Pollini T, Mühlbacher J, Jomrich G, Richwien P, Tamandl D, Schindl M, Bassi C, Salvia R, Sahora K. The faith of non-surveilled pancreatic cysts: a bicentric retrospective study. Eur J Surg Oncol 2021; 48:89-94. [PMID: 34148825 DOI: 10.1016/j.ejso.2021.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 05/06/2021] [Accepted: 06/02/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Incidental discovery of pancreatic cystic neoplasms (PCLs) is a common and steadily increasing occurrence. The aim of this study was to investigate a cohort of patients presenting with incidentally detected PCLs which were not included in a surveillance protocol, and to compare their risk of malignant evolution with that of systematically surveilled lesions. MATERIALS AND METHODS A population of PCLs which did not receive surveillance over a period >10 years (population A) was selected at the Medical University of Vienna. A group of "low risk" branch duct intraductal papillary mucinous neoplasm ≤15 mm in size upon diagnosis undergoing a regular follow-up of at least 5 years at the University of Verona was selected as control (population B). The incidence of pancreatic cancer (PC), cumulative risk of PC and disease-specific survival were compared. RESULTS Overall, 376 patients with non-surveilled PCLs were included in study group A and compared to 299 patients in group B. This comparison resulted in similar incidence rates of PC (1.6% vs 1.7%, p = 0.938), a strong similarity in terms of disease-specific mortality rates (1.3% vs 0.3%, p = 0.171) and the 5- and 10-year cumulative risk of PC (≅ 1% and 2%, p = 0.589) and DSS (≅ 100% and 98%, p = 0.050). CONCLUSION The "price to pay" for a negligence-based policy in the population of non-surveilled PCLs was reasonable, and the incidence of PC was comparable to that reported for a population of low-risk cysts enrolled to a standardized surveillance protocol.
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Affiliation(s)
- N Surci
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria; Department of General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, "GB Rossi" Hospital, Verona, Italy
| | - G Marchegiani
- Department of General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, "GB Rossi" Hospital, Verona, Italy.
| | - S Andrianello
- Department of General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, "GB Rossi" Hospital, Verona, Italy
| | - T Pollini
- Department of General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, "GB Rossi" Hospital, Verona, Italy
| | - J Mühlbacher
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - G Jomrich
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - P Richwien
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - D Tamandl
- Department of Radiology, Medical University of Vienna, General Hospital, Vienna, Austria
| | - M Schindl
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - C Bassi
- Department of General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, "GB Rossi" Hospital, Verona, Italy
| | - R Salvia
- Department of General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, "GB Rossi" Hospital, Verona, Italy
| | - K Sahora
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
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A Rare Case of Pancreatic Endometriosis Masquerading as Pancreatic Mucinous Neoplasm. Case Rep Surg 2021; 2021:5570290. [PMID: 34007507 PMCID: PMC8110415 DOI: 10.1155/2021/5570290] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/09/2021] [Accepted: 04/12/2021] [Indexed: 11/28/2022] Open
Abstract
Endometriosis is a relatively common condition among women, and pancreatic endometriosis has been reported on rare occasions. Such pancreatic lesions are difficult to diagnose and distinguish from other cystic lesions of the pancreas preoperatively. This report describes a case of pancreatic endometriosis in a 51-year-old female patient. Imaging demonstrated an enlarging cyst with findings concerning for a mucinous neoplasm. The patient underwent robotic distal pancreatectomy and splenectomy. Histopathology revealed an endometriotic cyst. Pancreatic endometriosis can be difficult to distinguish from other lesions of the pancreas. Surgical resection should be undertaken in cases where malignancy is suspected.
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Wu YA, Oba A, Beaty L, Colborn KL, Rodriguez Franco S, Harnke B, Meguid C, Negrini D, Valente R, Ahrendt S, Schulick RD, Del Chiaro M. Ductal Dilatation of ≥5 mm in Intraductal Papillary Mucinous Neoplasm Should Trigger the Consideration for Pancreatectomy: A Meta-Analysis and Systematic Review of Resected Cases. Cancers (Basel) 2021; 13:cancers13092031. [PMID: 33922344 PMCID: PMC8122854 DOI: 10.3390/cancers13092031] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/14/2021] [Accepted: 04/19/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study evaluates the diagnostic value of main pancreatic duct (MPD) diameter for detecting IPMN malignancy, using a meta-analysis of published data. The result suggests that malignancy is highly prevalent in IPMN with ductal dilatation of >5 mm. Abstract Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study tests the diagnostic value of the main pancreatic duct (MPD) diameter for detecting IPMN malignancy using a meta-analysis of published data of resected IPMNs. Collected from a comprehensive literature search, the articles included in this analysis must report malignancy cases (high-grade dysplasia (HGD) and invasive carcinoma (IC)) and MPD diameter so that two MPD cut-offs could be created. The sensitivity, specificity, and odds ratios of the two cutoffs for predicting malignancy were calculated. A review of 1493 articles yielded 20 retrospective studies with 3982 resected cases. A cutoff of ≥5 mm is more sensitive than the ≥10 mm cutoff and has pooled sensitivity of 72.20% and 75.60% for classification of HGD and IC, respectively. Both MPD cutoffs of ≥5 mm and ≥10 mm were associated with malignancy (OR = 4.36 (95% CI: 2.82, 6.75) vs. OR = 3.18 (95% CI: 2.25, 4.49), respectively). The odds of HGD and IC for patients with MPD ≥5 mm were 5.66 (95% CI: 3.02, 10.62) and 7.40 (95% CI: 4.95, 11.06), respectively. OR of HGD and IC for MPD ≥10 mm cutoff were 4.36 (95% CI: 3.20, 5.93) and 4.75 (95% CI: 2.39, 9.45), respectively. IPMN with MPD of >5 mm could very likely be malignant. In selected IPMN patients, pancreatectomy should be considered when MPD is >5 mm.
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Affiliation(s)
- Y.H. Andrew Wu
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
| | - Atsushi Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Laurel Beaty
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Kathryn L. Colborn
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Surgical Outcomes and Applied Research Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- The Heart Institute, Children’s Hospital Colorado, Aurora, CO 80045, USA
| | - Ben Harnke
- Strauss Health Sciences Library, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
| | - Cheryl Meguid
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
| | - Daniel Negrini
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- Department of Anesthesiology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil
| | - Roberto Valente
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- Department of Surgery and Perioperative Sciences, Umeå University Hospital, 907 37 Umeå, Sweden
| | - Steven Ahrendt
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- University of Colorado Cancer Center, Aurora, CO 80045, USA
| | - Richard D. Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- University of Colorado Cancer Center, Aurora, CO 80045, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (Y.H.A.W.); (A.O.); (L.B.); (K.L.C.); (S.R.F.); (C.M.); (D.N.); (R.V.); (S.A.); (R.D.S.)
- University of Colorado Cancer Center, Aurora, CO 80045, USA
- Correspondence:
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30
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Flick KF, Yip-Schneider MT, Sublette CM, Simpson RE, Colgate CL, Wu H, Soufi M, Dewitt JM, Mosley AL, Ceppa EP, Zhang J, Schmidt CM. A Quantitative Global Proteomics Approach Identifies Candidate Urinary Biomarkers That Correlate With Intraductal Papillary Mucinous Neoplasm Dysplasia. Pancreas 2020; 49:1044-1051. [PMID: 32769857 DOI: 10.1097/mpa.0000000000001628] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES A proteomic discovery study was performed to determine if urine possesses a unique biosignature that could form the basis for a noninvasive test able to predict intraductal papillary mucinous neoplasm (IPMN) dysplasia. METHODS Urine was collected from patients undergoing surgery for IPMN (72 low/moderate, 27 high-grade/invasive). Quantitative mass spectrometry-based proteomics was performed. Proteins of interest were identified by differential expression analysis followed by principal component analysis. RESULTS Proteomics identified greater than 4800 urinary proteins. Low/moderate and high-grade/invasive IPMN were distinguished by 188 proteins (P < 0.05). Following principal component analysis and heatmap visualization, vitamin D binding protein (DBP), apolipoprotein A1 (APOA1), and alpha-1 antitrypsin (A1AT) were selected. The proteomic abundance of DBP (median [interquartile range]) was significantly higher for high-grade/invasive than for low/moderate IPMN (219,735 [128,882-269,943] vs. 112,295 [77,905-180,773] normalized reporter ion intensity units; P = 0.001). Similarly, APOA1 was more abundant in the high-grade/invasive than low/moderate groups (235,420 [144,933-371,247] vs 150,095 [103,419-236,591]; P = 0.0007) as was A1AT (567,514 [358,544-774,801] vs 358,393 [260,850-477,882]; P = 0.0006). CONCLUSIONS Urinary DBP, APOA1, and A1AT represent potential biomarker candidates that may provide a noninvasive means of predicting IPMN dysplastic grade.
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Affiliation(s)
| | | | | | | | | | | | | | - John M Dewitt
- Division of Gastroenterology, Department of Medicine
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31
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Ozaki K, Ikeno H, Kaizaki Y, Maeda K, Higuchi S, Kosaka N, Kimura H, Gabata T. Pearls and pitfalls of imaging features of pancreatic cystic lesions: a case-based approach with imaging-pathologic correlation. Jpn J Radiol 2020; 39:118-142. [PMID: 32840742 DOI: 10.1007/s11604-020-01032-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 08/11/2020] [Indexed: 12/14/2022]
Abstract
A variety of neoplastic and non-neoplastic lesions of the pancreas can present with a predominantly cystic architecture. These lesions are increasingly being detected as incidental findings on routine cross-sectional imaging following technological advances in these techniques and their widespread use. The different histopathological behaviors show various common and uncommon imaging findings, and some cases show similar appearance in spite of different histopathology. Each lesion requires specific management because of the differing risk of progression to malignancy, and an accurate imaging diagnosis is crucial. The typical imaging characteristics that differentiate pancreatic cystic lesions have been well described and fully summarized. However, in addition to a small percentage of cases that shows uncommon imaging findings, a substantial percentage of cystic lesions shows overlapping imaging findings that can lead to radiological misdiagnosis. For appropriate diagnosis and optimal treatment strategy, it is important to know the uncommon and overlapping imaging findings of these lesions, in addition to familiarity with the typical aspects. In this article, we reconfirm the well-known characteristic imaging features of pancreatic cystic lesions and present several diagnostically challenging cases, focusing on the uncommon and overlapping imaging findings.
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Affiliation(s)
- Kumi Ozaki
- Department of Radiology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, 910-1193, Japan.
| | - Hiroshi Ikeno
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Yasuharu Kaizaki
- Department of Diagnostic Pathology, Fukui Prefectural Hospital, Fukui, Japan
| | - Kazuya Maeda
- Department of Surgery, Fukui Prefectural Hospital, Fukui, Japan
| | - Shohei Higuchi
- Department of Pathology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Nobuyuki Kosaka
- Department of Radiology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, 910-1193, Japan
| | - Hirohiko Kimura
- Department of Radiology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, 910-1193, Japan
| | - Toshifumi Gabata
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
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Paziewska A, Polkowski M, Goryca K, Karczmarski J, Wiechowska-Kozlowska A, Dabrowska M, Mikula M, Ostrowski J. Mutational Mosaics of Cell-Free DNA from Pancreatic Cyst Fluids. Dig Dis Sci 2020; 65:2294-2301. [PMID: 31925676 DOI: 10.1007/s10620-019-06043-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Accepted: 12/31/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND Pancreatic cyst fluids (PCFs) enriched in tumor-derived DNA are a potential source of new biomarkers. The study aimed to analyze germinal variants and mutational profiles of cell-free (cf)DNA shed into the cavity of pancreatic cysts. METHODS The study cohort consisted of 71 patients who underwent endoscopic ultrasound fine-needle aspiration of PCF. Five malignant cysts, 19 intraductal papillary mucinous neoplasms (IPMNs), 11 mucinous cystic neoplasms (MCNs), eight serous cystic neoplasms (SCNs), and 28 pseudocysts were identified. The sequencing of 409 genes included in Comprehensive Cancer Panel was performed using Ion Proton System. The mutation rate of the KRAS and GNAS canonical loci was additionally determined using digital PCR. RESULTS The number of mutations detected with NGS varied from 0 to 22 per gene, and genes with the most mutations were: TP53, KRAS, PIK3CA, GNAS, ADGRA2, and APC. The frequencies of the majority of mutations did not differ between non-malignant cystic neoplasms and pseudocysts. NGS detected KRAS mutations in malignant cysts (60%), IPMNs (32%), MCNs (64%), SCNs (13%), and pseudocysts (14%), with GNAS mutations in 20%, 26%, 27%, 13%, and 21% of samples, respectively. Digital PCR-based testing increased KRAS (68%) and GNAS (52%) mutations detection level in IPMNs, but not other cyst types. CONCLUSIONS We demonstrate relatively high rates of somatic mutations of cancer-related genes, including KRAS and GNAS, in cfDNA isolated from PCFs irrespectively of the pancreatic cyst type. Further studies on molecular mechanisms of pancreatic cysts malignant transformation in relation to their mutational profiles are required.
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Affiliation(s)
- Agnieszka Paziewska
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Roentgena 5, 02-781, Warsaw, Poland.,Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 5, 02-781, Warsaw, Poland
| | - Marcin Polkowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Roentgena 5, 02-781, Warsaw, Poland
| | - Krzysztof Goryca
- Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 5, 02-781, Warsaw, Poland.,Next Generation Sequencing Core Facility, Centre of New Technologies, University of Warsaw, 02-097, Warsaw, Poland
| | - Jakub Karczmarski
- Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 5, 02-781, Warsaw, Poland
| | | | - Michalina Dabrowska
- Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 5, 02-781, Warsaw, Poland
| | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 5, 02-781, Warsaw, Poland
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Roentgena 5, 02-781, Warsaw, Poland. .,Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 5, 02-781, Warsaw, Poland.
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33
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[Quality of indications in cystic lesions of the pancreas]. Chirurg 2020; 91:736-742. [PMID: 32642818 DOI: 10.1007/s00104-020-01217-4] [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: 10/23/2022]
Abstract
Cystic tumors of the pancreas (PCN) have increasingly gained importance in the clinical routine as they are frequently diagnosed as an incidental finding due to the continuous improvement in cross-sectional imaging. A differentiation is made between non-neoplastic and neoplastic cysts, whereby the latter has a tendency to malignant transformation to a varying extent. Therefore, they can be considered as precursor lesions of pancreatic cancer (PDAC). In addition to a detailed patient history and examination, imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) with fine needle aspiration (FNA) are used for the differential diagnosis. The indications for surgical resection of these lesions are based on the current European guidelines from 2018; however, the content is not evidence-based but relies on knowledge and recommendations from experts. According to these consensus recommendations asymptomatic serous cystic neoplasms (SCN) are serous lesions with a low tendency for malignant transformation and can be monitored. In contrast resection is warranted for all mucinous cystic neoplasms (MCN) >4 cm and all solid pseudopapillary neoplasms (SPN). Intraductal papillary mucinous neoplasms (IPMN), which are differentiated into main duct (MD-IPMN) and branch duct type (BD-IPMN) IPMN based on the position in the pancreatic duct system, should be resected as MD-IPMN and mixed type (MT)-IPMN. The risk of malignant transformation in BD-IPMN is variable and depends on risk factors, which are defined clinically and by imaging morphology. The treatment management is therefore carried out on an individual basis following risk estimation. In order to quantify the quality of indications in PCN and thereby also contributing to optimized medical care, prospective long-term studies are urgently needed.
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Ohno E, Kawashima H, Ishikawa T, Iida T, Suzuki H, Uetsuki K, Yashika J, Yamada K, Yoshikawa M, Gibo N, Aoki T, Kataoka K, Mori H, Hirooka Y, Fujishiro M. Can contrast-enhanced harmonic endoscopic ultrasonography accurately diagnose main pancreatic duct involvement in intraductal papillary mucinous neoplasms? Pancreatology 2020; 20:887-894. [PMID: 32651080 DOI: 10.1016/j.pan.2020.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/02/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Main pancreatic duct (MPD) involvement in branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is a high risk finding for malignant IPMNs. However, discrepancies exist in the identification of MPD involvement between imaging findings and pathological diagnosis. The purpose of this study was to evaluate the diagnostic accuracy of preoperative assessment of MPD involvement in IPMNs using contrast-enhanced harmonic endoscopic ultrasound (CH-EUS). METHODS This study involved 166 consecutive patients with BD-IPMNs who underwent surgical resection. CH-EUS was used to evaluate the MPD involvement according to the presence of mural nodules (MN) that advanced into the MPD or involved the MPD. The CH-EUS findings were compared with the pathological findings. Additionally, we analyzed the risk factors for malignant BD-IPMNs using multivariate analysis. RESULTS A total of 77, 51, and 38 patients were pathologically diagnosed with low-grade or intermediate-grade dysplasia, high-grade dysplasia and invasive IPMNs, respectively. MPD involvement was diagnosed using CH-EUS (MPD-inv.-EUS) in 90 (54.2%) patients with a sensitivity, specificity and accuracy of 83.5%, 87.0% and 84.9%, respectively. The malignancy rate in patients with MPD-inv.-EUS was 71.6% (63/90). Multivariate logistic regression analysis showed that MPD-inv.-EUS (OR, 3.61; 95% CI:1.45-8.98), age (OR, 5.70; 95% CI: 1.47-22.2), cyst size (OR, 2.45; 95% CI:1.04-5.78) and MN size (OR, 7.05; 95% CI:2.48-20.0) were significant for malignant BD-IPMNs. CONCLUSIONS MPD-inv.-EUS accurately represents the pathological involvement of IPMN and may be a useful predictor of malignant BD-IPMNs.
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Affiliation(s)
- Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hirotaka Suzuki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kota Uetsuki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Jun Yashika
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Yamada
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masakatsu Yoshikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Noriaki Gibo
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshinori Aoki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kunio Kataoka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroshi Mori
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Gastroenterological Oncology, Fujita Health University, Fujita Health University of Medicine, Toyoake, Aichi, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Brunner M, Belyaev O, Bösch F, Müller-Debus CF, Radulova-Mauersberger O, Wellner UF, Keck T, Uhl W, Werner J, Witzigmann H, Grützmann R. [Indications for the Surgical Management of Pancreatic Cystic Lesions]. Zentralbl Chir 2020; 145:344-353. [PMID: 32498095 DOI: 10.1055/a-1158-9536] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
A steady improvement in modern imaging as well as increasing age in society have led to an increasing number of cystic pancreatic tumours being detected. Pancreatic cysts are a clinically challenging entity because they span a broad biological spectrum and their differentiation is often difficult, especially in small tumours. Therefore, they require a differentiated indication for indication of surgery. To determine recommendations for the surgical indication in cystic tumours of the pancreas, a quality committee for pancreatic diseases of the German Society for General and Visceral Surgery performed a systematic literature search and created this review. Based on the current evidence, signs of malignancy and high-risk criteria (icterus due to cystic pancreatic duct obstruction in the bile duct, enhancing mural nodules ≥ 5 mm or solid components in the cyst or pancreatic duct ≥ 10 mm), as well as symptoms, are a surgical indication, independently of the cyst entity (except pseudocysts). If the entity of the pancreatic cyst is detectable by diagnostic imaging, all main duct IPMN and IPMN of the mixed type, all MCN > 4 cm and all SPN should be resected. SCN and branch-duct IPMN without worrisome features do not constitute an indication for surgery. The indication of operation in branch-duct IPMN with relative risk criteria and MCN < 4 cm is the subject of current discussions and should be individualised. By defining indication recommendations, the present work aims to improve the indication quality in cystic pancreatic tumours. However, the surgical indication should always be individualised, taking into account age, comorbidities and the patient's wishes.
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Affiliation(s)
- Maximilian Brunner
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Deutschland
| | - Orlin Belyaev
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum St. Josef-Hospital Bochum, Deutschland
| | - Florian Bösch
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, LMU, Klinikum der Universität München, Deutschland
| | | | | | | | - Tobias Keck
- Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Deutschland
| | - Waldemar Uhl
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum St. Josef-Hospital Bochum, Deutschland
| | - Jens Werner
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, LMU, Klinikum der Universität München, Deutschland
| | - Helmut Witzigmann
- Klinik für Allgemein- und Viszeralchirurgie, Städtisches Klinikum Dresden-Friedrichstadt, Deutschland
| | - Robert Grützmann
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Deutschland
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de la Fuente J, Majumder S. Molecular Diagnostics and Testing for Pancreatic Cysts. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2020; 18:158-171. [PMID: 31989386 DOI: 10.1007/s11938-020-00270-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW In current clinical practice, the diagnosis and management of pancreatic cystic lesions (PCLs) are based on guidelines that combine clinical and imaging findings. These guidelines usefully identify a large category of low-risk PCLs that do not require treatment. However, they have limited accuracy for diagnosis of advanced neoplasia in worrisome and high-risk PCLs. Novel molecular markers that can accurately detect advanced neoplasia in PCLs can transform the care of patients with PCLs. We reviewed the recent medical literature on molecular diagnostics of PCLs and summarized molecular biomarkers assayed in cyst fluid, pancreatic juice, and blood. RECENT FINDINGS Several studies have been recently published describing promising early results in genetic, epigenetic, and protein biomarkers from cyst fluid to help in both histologic diagnosis and detection of advanced neoplasia. The majority of studies have been completed using opportunistically collected archival cyst fluid and few report validation in independent sample sets. Results of ongoing multicenter prospective validation studies are awaited and will help define the best combination of cyst fluid molecular markers. In multifocal PCLs communicating with the pancreatic ductal system, a pancreatic juice biomarker is likely to be less invasive and more informative. Novel biomarkers in pancreatic juice and blood are in early phases of study. SUMMARY The field of molecular diagnostic biomarkers for PCLs is rapidly evolving with several promising candidate markers being prospectively evaluated. In the near future, these novel molecular markers, combined with advances in imaging technology, will transform clinical decision-making in the management of PCLs and improve patient outcomes.
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Affiliation(s)
- Jaime de la Fuente
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Sciences, 200 First St SW, Rochester, MN, 55905, USA
| | - Shounak Majumder
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Sciences, 200 First St SW, Rochester, MN, 55905, USA.
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Caravati A, Andrianello S, Pollini T, Biancotto M, Balduzzi A, Malleo G, Salvia R, Marchegiani G. Branch Duct Intraductal Papillary Mucinous Neoplasms: Recommendations for Follow-Up and Surgery. Scand J Surg 2020; 109:34-41. [PMID: 32009571 DOI: 10.1177/1457496919900414] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary mucinous neoplasms are the most common pre-malignant entities. Intraductal papillary mucinous neoplasms involving side branches overall harbor a low risk of malignancy, and in the recent past, a progressively more conservative approach has been consolidated. Purpose of this report is to summarize the evidence supporting the current practice for the management of branch duct intraductal papillary mucinous neoplasm and to offer a useful practical guide from first observation to post-operative follow-up. MATERIALS AND METHODS Review of the most important scientific literature on intraductal papillary mucinous neoplasms was made. In this review article, we also report the experience of a high volume center in managing Pancreatic cystic neoplasms. RESULTS The correct management during surveillance still is a matter of debate, since many guidelines have been published suggesting different clinical approaches. Recently, follow-up discontinuation has also been proposed in selected cases. CONCLUSION Despite significant improvements made by the increase of evidence, selecting surgical candidates because of an increased risk of malignant progression remains an unsolved issue and a hot topic for pancreatologists.
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Affiliation(s)
- A Caravati
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - S Andrianello
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - T Pollini
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - M Biancotto
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - A Balduzzi
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - G Malleo
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - R Salvia
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - G Marchegiani
- General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
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38
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Affiliation(s)
- Chieh Sian Koo
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore
| | - Khek Yu Ho
- Division of Gastroenterology and Hepatology, National University Hospital; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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39
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Yang J, Guo X, Zhang H, Zhang W, Song J, Xu H, Ma X. Differential diagnosis of pancreatic serous cystadenoma and mucinous cystadenoma: utility of textural features in combination with morphological characteristics. BMC Cancer 2019; 19:1223. [PMID: 31842793 PMCID: PMC6915993 DOI: 10.1186/s12885-019-6421-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 12/02/2019] [Indexed: 02/05/2023] Open
Abstract
Background Texture analysis of medical images has been reported to be a reliable method for differential diagnosis of neoplasms. This study was to investigate the performance of textural features and the combined performance of textural features and morphological characteristics in the differential diagnosis of pancreatic serous and mucinous cystadenomas. Methods We retrospectively reviewed 59 patients with pancreatic serous cystadenoma and 32 patients with pancreatic mucinous cystadenoma at our hospital. A three-dimensional region of interest (ROI) around the margin of the lesion was drawn manually in the CT images of each patient, and textural parameters were retrieved from the ROI. Textural features were extracted using the LifeX software. The least absolute shrinkage and selection operator (LASSO) method was applied to select the textural features. The differential diagnostic capabilities of morphological features, textural features, and their combination were evaluated using receiver operating characteristic (ROC) analysis, and the area under the receiver operating characteristic curve (AUC) was used as the main indicator. The diagnostic accuracy based on the AUC value is defined as follows: 0.9–1.0, excellent; 0.8–0.9, good; 0.7–0.8, moderate; 0.6–0.7, fair; 0.5–0.6, poor. Results In the differential diagnosis of pancreatic serous and mucinous cystadenomas, the combination of morphological characteristics and textural features (AUC 0.893, 95% CI 0.816–0.970) is better than morphological characteristics (AUC 0.783, 95% CI 0.665–0.900) or textural features (AUC 0.777, 95% CI 0.673–0.880) alone. Conclusions In conclusion, our preliminary results highlighted the potential of CT texture analysis in discriminating pancreatic serous cystadenoma from mucinous cystadenoma. Furthermore, the combination of morphological characteristics and textural features can significantly improve the diagnostic performance, which may provide a reliable method for selecting patients with surgical intervention indications in consideration of the different treatment principles of the two diseases.
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Affiliation(s)
- Jing Yang
- Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China
| | - Xinli Guo
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Hao Zhang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Weiwei Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jinen Song
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Hui Xu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China.
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40
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Aunan JR, Jamieson NB, Søreide K. Observation or resection of pancreatic intraductal papillary mucinous neoplasm: An ongoing tug of war. World J Gastrointest Oncol 2019; 11:1092-1100. [PMID: 31908715 PMCID: PMC6937444 DOI: 10.4251/wjgo.v11.i12.1092] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 09/03/2019] [Accepted: 09/26/2019] [Indexed: 02/05/2023] Open
Abstract
An increasing number of patients are being referred to pancreatic centres around the world due to often incidentally discovered cystic neoplasms of the pancreas. The evaluation and management of pancreatic cystic neoplasms is a controversial topic and with existing guidelines based on a lack of strong evidence there is discordance between centres and guidelines with regard to when to offer surgery and when to favour surveillance. The frequency, duration and modality of surveillance is also controversial as this is resource-consuming and must be balanced against the perceived benefits and risks involved. While there is consensus that the risk of malignancy should be balanced against the life-expectancy and comorbidities, the indications for surgery and surveillance strategies vary among the guidelines. Thus, the tug of war between surveillance or resection continues. Here we discuss the recommendations from guidelines with further accumulating data and emerging reports on intraductal papillary mucinous neoplasm in the literature.
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Affiliation(s)
- Jan Rune Aunan
- Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, Stavanger 4068, Norway
| | - Nigel B. Jamieson
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, United Kingdom
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G4 0SF, United Kingdom
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, Stavanger 4068, Norway
- Gastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, Stavanger 4068, Norway
- Department of Clinical Medicine, University of Bergen, Bergen 5003, Norway
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Antoñanzas J, Cienfuegos JA, Hurtado-Pardo L, Panadero P, Benito A, Pardo F, Rotellar F, Martí-Cruchaga P, Zozaya G, Valentí V, Hernández Lizoain JL. Intraductal papillary mucinous neoplasm (IPMN) of the pancreas: clinicopathological features and long-term outcomes following a pancreatectomy. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2019; 110:768-774. [PMID: 30168337 DOI: 10.17235/reed.2018.5646/2018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE the objective of this study was to analyze the anatomical and clinical features and long-term oncologic outcomes of 25 patients that underwent surgery due to intraductal papillary mucinous neoplasm of the pancreas. MATERIAL AND METHODS patients undergoing surgery for intraductal papillary mucinous neoplasm of the pancreas were identified from a prospective database of pancreatic resections. Demographic data, symptoms, type of surgery and type of lesion (branch type, main duct or mixed) were recorded. The lesions were classified into invasive (high grade dysplasia and carcinoma) and noninvasive (low- or intermediate-grade dysplasia). Postoperative complications were analyzed as well as the pattern of recurrence and disease-free survival at five and ten years. RESULTS the most common symptoms in the 25 patients (14 males and eleven females) were abdominal pain and weight loss. Eight (32%) cases were diagnosed incidentally. Twelve (48%) of the lesions were of the branch type, three affected the main duct and ten (40%) were mixed. Twelve cephalic duodenopancreatectomies and seven total pancreatectomies were performed; three were central; two, distal; and one, enucleation. Seven cases (32%) had an invasive phenotype. Three patients had locoregional and distant recurrence at six, 16 and 46 months after surgery with a median follow-up of 7.7 years. Disease-free survival at five and ten years for the noninvasive type was 94% and 57% for invasive phenotypes (p < 0.05). CONCLUSIONS intraductal papillary mucinous neoplasm is a heterogeneous entity with well differentiated phenotypes, which requires a tailored strategy and treatment, as established in the current consensus guidelines due to its malignant potential.
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Affiliation(s)
| | | | | | - Pablo Panadero
- Anatomía Patológica, Clínica Universidad de Navarra, España
| | | | - Fernando Pardo
- Cirugía General y del Aparato Digestivo, Clínica Universidad de Navarra, España
| | - Fernando Rotellar
- Cirugía General y del Aparato Digestivo, Clínica Universidad de Navarra, España
| | | | - Gabriel Zozaya
- Cirugía General y del Aparato Digestivo, Clínica Universidad de Navarra, España
| | - Víctor Valentí
- Cirugía General y Aparato Digestivo, Clínica Universidad de Navarra, España
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Pollini T, Andrianello S, Caravati A, Perri G, Malleo G, Paiella S, Marchegiani G, Salvia R. The management of intraductal papillary mucinous neoplasms of the pancreas. MINERVA CHIR 2019; 74:414-421. [PMID: 31795628 DOI: 10.23736/s0026-4733.19.08145-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are one of the most common preneoplastic entities among pancreatic cystic neoplasms (PCN). Their incidence is increasing due to an extensive use of cross-sectional imaging, but management still remains controversial. Among IPMNs, the main duct (MD-IPMN) and mixed (MT-IPMN) types harbor a high risk of malignant degeneration requiring resection in most of cases. The branch duct type (BD-IPMN), on the other side, can be safely surveilled as surgical resection is limited to selected cases deemed at high risk of malignant progression according to specific clinical and radiological features. An accurate diagnosis and a correct assessment of malignant potential are often hard to achieve, and clinical management still relies on the experience of the gastroenterologist/surgeon that is called to choose between a major pancreatic resection burdened by high morbidity and mortality rates and a life-long surveillance. The purpose of this report is to summarize the available evidence supporting the current practice for the management of IPMN and to offer a useful practical guide from first observation to postoperative follow-up.
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Affiliation(s)
- Tommaso Pollini
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy -
| | - Stefano Andrianello
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Andrea Caravati
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giampaolo Perri
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giuseppe Malleo
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giovanni Marchegiani
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
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Hasan A, Visrodia K, Farrell JJ, Gonda TA. Overview and comparison of guidelines for management of pancreatic cystic neoplasms. World J Gastroenterol 2019; 25:4405-4413. [PMID: 31496620 PMCID: PMC6710181 DOI: 10.3748/wjg.v25.i31.4405] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 07/15/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cysts are identified at an increasing frequency. Although mucinous cystic neoplasms represent a pre-malignant condition, the majority of these lesions do not progress to cancer. Over the last 10 years several societies have established guidelines for the diagnosis, initial evaluation and surveillance of these lesions. Here we provide an overview of five commonly used guidelines: 2015 American Gastroenterological Association, 2017 International Association of Pancreatology, American College of Gastroenterology 2018, European Study Group and American College of Radiology. We describe the similarities and differences between the methods used to formulate these guidelines, the population they target and their approaches towards initial evaluation and surveillance of cystic lesions.
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Affiliation(s)
- Aws Hasan
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY 10032, United States
| | - Kavel Visrodia
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY 10032, United States
| | - James J Farrell
- Division of Digestive Diseases, Department of Medicine, Yale University, New Haven, CT 06520, United States
| | - Tamas A Gonda
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY 10032, United States
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Faias S, Pereira L, Luís Â, Chaves P, Cravo M. Genetic testing vs microforceps biopsy in pancreatic cysts: Systematic review and meta-analysis. World J Gastroenterol 2019; 25:3450-3467. [PMID: 31341368 PMCID: PMC6639554 DOI: 10.3748/wjg.v25.i26.3450] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 04/17/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms. Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.
AIM To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.
METHODS We performed a literature search in Medline, Scopus, and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts, with endoscopic ultrasound with fine-needle aspiration (EUS-FNA) prior to surgery and surgical pathology as reference standard for diagnosis. We evaluated the diagnostic accuracy for: 1- benign cysts; 2- mucinous low-risk cysts; 3- high-risk cysts, and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis. We also assessed publication bias, heterogeneity, and study quality.
RESULTS Eight studies, including 1206 patients, of which 203 (17%) referred for surgery who met the inclusion criteria were analyzed in the systematic review, and seven studies were included in the meta-analysis. Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts. Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts, with sensitivities of 0.89 (95%CI: 0.79-0.95) and 0.57 (95%CI: 0.42-0.71), specificities of 0.88 (95%CI: 0.75-0.95) and 0.88 (95%CI: 0.80-0.93) and AUC of 0.9555 and 0.92, respectively. The diagnostic yield was higher in microforceps biopsies than in genetic analysis (0.73 vs 0.54, respectively) but the rates of correctly identified cysts were identical (0.73 with 95%CI: 0.62-0.82 vs 0.71 with 95%CI: 0.49-0.86, respectively).
CONCLUSION Genetic testing and microforceps biopsies are useful second tests, with identical results in benign pancreatic cysts. Genetic analysis performs better for low- and high-risk cysts but has lower diagnostic yield.
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Affiliation(s)
- Sandra Faias
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Luisa Pereira
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Centro de Matemática e Aplicações (CMA-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Ângelo Luís
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Centro de Investigação em Ciências da Saúde (CICS-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Paula Chaves
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Department of Pathology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
| | - Marília Cravo
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures 2674-514, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisboa 1099-023, Portugal
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KRAS in Cyst Fluid Obtained by Endoscopic Ultrasound-Fine-Needle Aspiration in Pancreatic Cystic Lesions: A Systematic Review and Meta-analysis. Pancreas 2019; 48:749-758. [PMID: 31206466 DOI: 10.1097/mpa.0000000000001325] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
To evaluate the diagnostic accuracy of KRAS mutation in pancreatic cystic fluid and compare it with carcinoembryonic antigen and cytology, we identified studies with cyst fluid obtained by endoscopic ultrasound prior to surgery. We classified cysts as malignant, premalignant, and benign. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic curve analysis were conducted. We analyzed 16 studies, with 3429 patients, including 731 referred for surgery. Carcinoembryonic antigen was better for clinically significant cysts (premalignant and malignant) with sensitivity = 0.58 (95% confidence interval [CI], 0.53-0.65), specificity = 0.9 (95% CI, 0.76-0.97), and area under the curve (AUC) = 0.69. Cytology performed better in malignant cysts, with sensitivity = 0.37 (95% CI, 0.27-0.48), specificity = 0.96 (95% CI, 0.93-0.98), and AUC = 0.78. Isolated, KRAS mutation failed the diagnosis of malignant and significant cysts, with sensitivities = 0.43 (95% CI, 0.34-0.43) and 0.46 (95% CI, 0.42-0.51), specificities = 0.62 (95% CI, 0.56-0.68) and 0.97 (95% CI, 0.92-0.99), and AUCs = 0.56 and 0.53, respectively. Carcinoembryonic antigen and cytology are more accurate than KRAS. Additional studies are lacking to recommend KRAS as a single diagnostic test.
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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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47
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Lee ES, Kim JH, Yu MH, Choi SY, Kang HJ, Park HJ, Park YS, Byun JH, Shin SS, Lee CH. Diagnosis and Surveillance of Incidental Pancreatic Cystic Lesions: 2017 Consensus Recommendations of the Korean Society of Abdominal Radiology. Korean J Radiol 2019; 20:542-557. [PMID: 30887737 PMCID: PMC6424832 DOI: 10.3348/kjr.2018.0640] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 11/30/2018] [Indexed: 02/06/2023] Open
Abstract
The occurrence of incidentally detected pancreatic cystic lesions (PCLs) is continuously increasing. Radiologic examinations including computed tomography and magnetic resonance imaging with magnetic resonance cholangiopancreatography have been widely used as the main diagnostic and surveillance methods for patients with incidental PCLs. Although most incidentally detected PCLs are considered benign, they have the potential to become malignant. Currently, we have several guidelines for the management of incidental PCLs. However, there is still debate over proper management, in terms of accurate diagnosis, optimal follow-up interval, and imaging tools. Because imaging studies play a crucial role in the management of incidental PCLs, the 2017 consensus recommendations of the Korean Society of Abdominal Radiology for the diagnosis and surveillance of incidental PCLs approved 11 out of 16 recommendations. Although several challenges remain in terms of optimization and standardization, these consensus recommendations might serve as useful tools to provide a more standardized approach and to optimize care of patients with incidental PCLs.
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Affiliation(s)
- Eun Sun Lee
- Department of Radiology, Chung-Ang University Hospital, Seoul, Korea
| | - Jung Hoon Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.
| | - Mi Hye Yu
- Department of Radiology, Konkuk University Medical Center, Seoul, Korea
| | - Seo Youn Choi
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Hyo Jin Kang
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.
| | - Hyun Jeong Park
- Department of Radiology, Chung-Ang University Hospital, Seoul, Korea
| | - Yang Shin Park
- Department of Radiology, Korea University Guro Hospital, Seoul, Korea
| | - Jae Ho Byun
- Department of Radiology, Asan Medical Center, Seoul, Korea
| | - Sang Soo Shin
- Department of Radiology, Chonnam National University Hospital, Gwangju, Korea
| | - Chang Hee Lee
- Department of Radiology, Korea University Guro Hospital, Seoul, Korea
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48
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Added value of apparent diffusion coefficient in distinguishing between serous and mucin-producing pancreatic cystic neoplasms. Eur Radiol 2019; 29:4660-4669. [DOI: 10.1007/s00330-019-6010-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 12/14/2018] [Accepted: 01/15/2019] [Indexed: 12/18/2022]
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49
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Ateeb Z, Valente R, Pozzi-Mucelli RM, Malgerud L, Schlieper Y, Rangelova E, Fernandez-Moro C, Löhr JM, Arnelo U, Del Chiaro M. Main pancreatic duct dilation greater than 6 mm is associated with an increased risk of high-grade dysplasia and cancer in IPMN patients. Langenbecks Arch Surg 2019; 404:31-37. [PMID: 30612152 DOI: 10.1007/s00423-018-1740-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 12/10/2018] [Indexed: 12/18/2022]
Abstract
INTRODUCTION IPMNs, considered precursor lesions of pancreatic adenocarcinoma (PDAC), might display histological alteration varying from low-grade dysplasia (LGD) to cancer. Nevertheless, the prevalence of PDAC is far below the prevalence of IPMN; therefore, not all of these precursor lesions finally progress to cancer. Preoperative features consistent with and finding at final histology of high-grade dysplasia (HGD) or cancer are currently lacking. The aim of this study is to correlate the presence of preoperative clinical features with the finding of advance lesions at final histology. METHODS This is retrospective cohort analysis of patients who underwent surgery for histologically confirmed IPMNs at Karolinska University Hospital, from 2008 to 2015. RESULTS MPD 6-9.9 mm and ≥ 10 mm were associated with an increased risk of HGD/cancer (respectively, OR 2.92, CI 1.38-6.20, p = 0.005 and OR 2.65, CI 1.12-6.25, p = 0.02). Preoperative high CA19.9 and jaundice were both associated with a higher risk of HGD/cancer at final histology (respectively, OR 4.15, CI 1.90-9.05, p = 0.0003 and OR 15.36, CI 1.94-121.22, p = 0.009). At sex- and age-adjusted multivariable logistic regression analysis, MPD between 6 and 9.9 mm (OR 2.64, CI 1.15-6.06, p = 0.02), jaundice (OR 12.43, CI 1.44-106.93, p = 0.02), and elevated CA19.9 (OR 3.71, CI 1.63-8.46, p = 0.001) remained associated with the occurrence of HGD/cancer. DISCUSSION The presence of MPD dilation ≥ 6 mm, jaundice, and elevated CA19.9 in IPMN patients are consistent with the finding for HGD/cancer at final histology, thus representing possible markers of advanced lesions suitable for earlier or preventive curative surgical treatment.
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Affiliation(s)
- Zeeshan Ateeb
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Roberto Valente
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
- Digestive and Liver Diseases Unit, Sapienza University of Rome, Rome, Italy
| | - Raffaella M Pozzi-Mucelli
- Division of Radiology, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Linnéa Malgerud
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Yasmine Schlieper
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Elena Rangelova
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Carlos Fernandez-Moro
- Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Johannes Matthias Löhr
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Urban Arnelo
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Marco Del Chiaro
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, C-313, Aurora, CO, 80045, USA.
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van der Naald N, Engelsman AF, Engelbrecht MRW, Verheij J, Besselink MG, Busch OR, van Gulik T. Tuberculosis presenting as a pancreatic cystic neoplasm. BMJ Case Rep 2018; 11:11/1/e225983. [PMID: 30567214 DOI: 10.1136/bcr-2018-225983] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 33-year-old Thai born woman was referred to our tertiary referral hospital with back and epigastric pain. Investigations included abdominal ultrasound and CT scan of the abdomen which demonstrated a 3 cm cystic lesion in the head of the pancreas, most likely a mucinous cystadenoma. Because of its malignant potential resection was advised. During surgical exploration, the tumour appeared unresectable, due to involvement of the common hepatic artery. PCR on biopsy revealed Mycobacterium tuberculosis The patient was referred to an infectious disease specialist, and a full recovery was achieved after 6 months of antimicrobials.
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Affiliation(s)
- Niels van der Naald
- Department of Surgery, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Anton F Engelsman
- Department of Surgery, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Marc R W Engelbrecht
- Department of Radiology, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Thomas van Gulik
- Department of Surgery, Amsterdam UMC, University of Amsterdam, The Netherlands
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