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Yamashige D, Hijioka S, Shimizu Y, Yanagisawa A, Nakamura M, Hara K, Kitano M, Koshita S, Takikawa T, Kin T, Takenaka M, Hanada K, Ueki T, Itoi T, Yamada R, Ohtsuka T, Hirono S, Kanno A, Takeyama Y, Masamune A. Clinical impact of epithelial types on postoperative outcomes for intraductal papillary mucinous neoplasms: a multicenter retrospective study. J Gastroenterol 2025:10.1007/s00535-025-02225-z. [PMID: 39966119 DOI: 10.1007/s00535-025-02225-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 02/02/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasms (IPMNs) are classified into three epithelial types with distinct biological behaviors. However, their effects on the postoperative outcomes remain unclear. METHODS This multicenter retrospective study included 556 patients with IPMNs who underwent surgical resection. The epithelial types were categorized into the gastric (n = 323), intestinal (n = 160), and pancreatobiliary (n = 73) types. Their associations with the development of extrapancreatic lesions; remnant high-risk lesions (HRLs), including metachronous pancreatic ductal adenocarcinoma (PDAC); and disease-specific survival (DSS) were analyzed. RESULTS Fifty-one patients (9.2%) developed extrapancreatic lesions. The 10-year cumulative incidence rates for the gastric, intestinal, and pancreatobiliary types were 9.3%, 9.1%, and 32.0%, respectively (P < 0.001). Multivariate analysis identified invasive carcinoma, the gastric, and pancreatobiliary types as independent predictors. Among 516 patients who did not undergo total pancreatectomy, 40 (7.8%) and 13 (2.5%) developed HRLs and metachronous PDAC, respectively. The 10-year cumulative incidence rates of HRLs and metachronous PDAC for the gastric, intestinal, and pancreatobiliary types were 7.0%, 16.2%, and 37.2% and 1.8%, 3.7%, and 22.7%, respectively (P = 0.001 and P = 0.012). In multivariate analysis, the pancreatobiliary type was an independent predictor of metachronous PDAC. Five-year DSS rates for the gastric, intestinal, and pancreatobiliary types were 92.5%, 96.0%, and 76.1% (P < 0.001), respectively. Multivariate analysis identified invasive carcinoma, the gastric, and pancreatobiliary types as independent prognostic factors for DSS. CONCLUSIONS IPMN epithelial type can independently affect postoperative outcomes. In particular, the pancreatobiliary type has significant impact on the development of metachronous PDAC. Therefore, postoperative surveillance should be tailored according to the epithelial type.
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Affiliation(s)
- Daiki Yamashige
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan.
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Akio Yanagisawa
- Department of Pathology and Laboratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Shinsuke Koshita
- Department of Gastroenterology, Sendai City Medical Center, Sendai, Japan
| | - Tetsuya Takikawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Toshifumi Kin
- Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Keiji Hanada
- Department of Gastroenterology, JA Onomichi General Hospital, Hiroshima, Japan
| | - Toshiharu Ueki
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Reiko Yamada
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Kagoshima University, Kagoshima, Japan
| | - Seiko Hirono
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Japan
| | - Atsushi Kanno
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi, Japan
| | - Yoshifumi Takeyama
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Qian K, Gao S, Jiang Z, Ding Q, Cheng Z. Recent advances in mitochondria-targeting theranostic agents. EXPLORATION (BEIJING, CHINA) 2024; 4:20230063. [PMID: 39175881 PMCID: PMC11335472 DOI: 10.1002/exp.20230063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 01/07/2024] [Indexed: 08/24/2024]
Abstract
For its vital role in maintaining cellular activity and survival, mitochondrion is highly involved in various diseases, and several strategies to target mitochondria have been developed for specific imaging and treatment. Among these approaches, theranostic may realize both diagnosis and therapy with one integrated material, benefiting the simplification of treatment process and candidate drug evaluation. A variety of mitochondria-targeting theranostic agents have been designed based on the differential structure and composition of mitochondria, which enable more precise localization within cellular mitochondria at disease sites, facilitating the unveiling of pathological information while concurrently performing therapeutic interventions. Here, progress of mitochondria-targeting theranostic materials reported in recent years along with background information on mitochondria-targeting and therapy have been briefly summarized, determining to deliver updated status and design ideas in this field to readers.
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Affiliation(s)
- Kun Qian
- State Key Laboratory of Drug ResearchMolecular Imaging CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
| | - Shu Gao
- State Key Laboratory of Drug ResearchMolecular Imaging CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
- School of PharmacyUniversity of Chinese Academy of SciencesBeijingChina
| | - Zhaoning Jiang
- State Key Laboratory of Drug ResearchMolecular Imaging CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
- School of PharmacyUniversity of Chinese Academy of SciencesBeijingChina
- Shandong Laboratory of Yantai Drug DiscoveryBohai Rim Advanced Research Institute for Drug DiscoveryYantaiShandongChina
| | - Qihang Ding
- Department of ChemistryKorea UniversitySeoulRepublic of Korea
| | - Zhen Cheng
- State Key Laboratory of Drug ResearchMolecular Imaging CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
- School of PharmacyUniversity of Chinese Academy of SciencesBeijingChina
- Shandong Laboratory of Yantai Drug DiscoveryBohai Rim Advanced Research Institute for Drug DiscoveryYantaiShandongChina
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Lucocq J, Hawkyard J, Robertson FP, Haugk B, Lye J, Parkinson D, White S, Mownah O, Zen Y, Menon K, Furukawa T, Inoue Y, Hirose Y, Sasahira N, Feretis M, Balakrishnan A, Zelga P, Ceresa C, Davidson B, Pande R, Dasari B, Tanno L, Karavias D, Helliwell J, Young A, Nunes Q, Urbonas T, Silva M, Gordon-Weeks A, Barrie J, Gomez D, van Laarhoven S, Doyle J, Bhogal R, Harrison E, Roalso M, Ciprani D, Aroori S, Ratnayake B, Koea J, Capurso G, Bellotti R, Stättner S, Alsaoudi T, Bhardwaj N, Jeffery F, Connor S, Cameron A, Jamieson N, Sheen A, Mittal A, Samra J, Gill A, Roberts K, Soreide K, Pandanaboyana S. Risk of Recurrence After Surgical Resection for Adenocarcinoma Arising From Intraductal Papillary Mucinous Neoplasia (IPMN) With Patterns of Distribution and Treatment: An International, Multicenter, Observational Study (ADENO-IPMN Study). Ann Surg 2024; 280:126-135. [PMID: 37873663 DOI: 10.1097/sla.0000000000006144] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
OBJECTIVE This international multicenter cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasm (IPMN). BACKGROUND Recurrence patterns and treatment of recurrence postresection of adenocarcinoma arising from IPMN are poorly explored. METHODS Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 and December 2020 at 18 pancreatic centers were identified. Survival analysis was performed using the Kaplan-Meier log-rank test and multivariable logistic regression by Cox-Proportional Hazards modeling. End points were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS Four hundred fifty-nine patients were included (median, 70 years; interquartile range, 64-76; male, 54%) with a median follow-up of 78.1 months. Recurrence occurred in 209 patients [45.5%; median time to recurrence, 12.8 months; early recurrence (within 1 years), 23.2%]. Eighty-three (18.1%) patients experienced a local regional recurrence, and 164 (35.7%) patients experienced a distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (hazard ratio 1.09; P =0.669) One hundred twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months ( P <0.001), with no significant difference between treatment modalities. There was no significant difference in survival between locations of recurrence ( P =0.401). CONCLUSIONS Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.
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Affiliation(s)
| | - Jake Hawkyard
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Francis P Robertson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Beate Haugk
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Jonathan Lye
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Daniel Parkinson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Steve White
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Omar Mownah
- Institute of Liver Studies, King's Healthcare Partners, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Yoh Zen
- Institute of Liver Studies, King's Healthcare Partners, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Krishna Menon
- Institute of Liver Studies, King's Healthcare Partners, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Takaaki Furukawa
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuki Hirose
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Sasahira
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Michael Feretis
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Anita Balakrishnan
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Piotr Zelga
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Carlo Ceresa
- Hepatobiliary and Pancreatic Surgery Unit, The Royal Free Hospital, London, UK
| | - Brian Davidson
- Hepatobiliary and Pancreatic Surgery Unit, The Royal Free Hospital, London, UK
| | - Rupaly Pande
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Bobby Dasari
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Lulu Tanno
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Dimitrios Karavias
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Jack Helliwell
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Alistair Young
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Quentin Nunes
- Department of Hepatopancreatobiliary Surgery, East Lancashire Teaching Hospitals NHS Trust, UK
| | - Tomas Urbonas
- Oxford Hepato-Pancreato-Biliary (HPB) Surgical Unit, Oxford University Hospitals NHS Foundation Trust, UK
| | - Michael Silva
- Oxford Hepato-Pancreato-Biliary (HPB) Surgical Unit, Oxford University Hospitals NHS Foundation Trust, UK
| | - Alex Gordon-Weeks
- Oxford Hepato-Pancreato-Biliary (HPB) Surgical Unit, Oxford University Hospitals NHS Foundation Trust, UK
| | - Jenifer Barrie
- Nottingham Hepato-Pancreatico-Biliary (HPB) Service, Nottingham University Hospitals NHS Foundation Trust, UK
| | - Dhanny Gomez
- Nottingham Hepato-Pancreatico-Biliary (HPB) Service, Nottingham University Hospitals NHS Foundation Trust, UK
| | - Stijn van Laarhoven
- Department of General Surgery, University Hospitals Bristol & Weston NHS Foundation trust, UK
| | - Joseph Doyle
- Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Ricky Bhogal
- Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Ewen Harrison
- Department of Clinical Surgery, University of Edinburgh, UK
| | - Marcus Roalso
- Department of Gastrointestinal Surgery, HPB unit, Stavanger University Hospital, Norway
- Department of Quality and Health Technology, University of Stavanger, Stavanger, Norway
| | - Debora Ciprani
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Somaiah Aroori
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Bathiya Ratnayake
- Hepato-Pancreatico-Biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, NZ
| | - Jonathan Koea
- Hepato-Pancreatico-Biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, NZ
| | - Gabriele Capurso
- San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
- Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy
| | - Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria
| | - Tareq Alsaoudi
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, UK
| | - Neil Bhardwaj
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, UK
| | - Fraser Jeffery
- Department of General and Vascular Surgery, Christchurch Hospital, New Zealand
| | - Saxon Connor
- Department of General and Vascular Surgery, Christchurch Hospital, New Zealand
| | - Andrew Cameron
- Wolfson Wohl Cancer Research Centre, University of Glasgow, UK
| | - Nigel Jamieson
- Wolfson Wohl Cancer Research Centre, University of Glasgow, UK
| | - Amy Sheen
- Department of Anatomical Pathology, New South Wales Health Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
| | | | - Jas Samra
- Royal North Shore Hospital, Sydney, NSW, Australia
| | - Anthony Gill
- Department of Anatomical Pathology, New South Wales Health Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
- Royal North Shore Hospital, Sydney, NSW, Australia
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Keith Roberts
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Kjetil Soreide
- Department of Gastrointestinal Surgery, HPB unit, Stavanger University Hospital, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Sanjay Pandanaboyana
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, UK
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Lucocq J, Hawkyard J, Haugk B, Mownah O, Menon K, Furukawa T, Inoue Y, Hirose Y, Sasahira N, Feretis M, Balakrishnan A, Ceresa C, Davidson B, Pande R, Dasari B, Tanno L, Karavias D, Helliwell J, Young A, Nunes Q, Urbonas T, Silva M, Gordon-Weeks A, Barrie J, Gomez D, Van Laarhoven S, Robertson F, Nawara H, Doyle J, Bhogal R, Harrison E, Roalso M, Ciprani D, Aroori S, Ratnayake B, Koea J, Capurso G, Bellotti R, Stättner S, Alsaoudi T, Bhardwaj N, Rajesh S, Jeffery F, Connor S, Cameron A, Jamieson N, Sheen A, Mittal A, Samra J, Gill A, Roberts K, Søreide K, Pandanaboyana S. Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study. Br J Surg 2024; 111:znae100. [PMID: 38659247 DOI: 10.1093/bjs/znae100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 03/23/2024] [Accepted: 03/26/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.
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MESH Headings
- Aged
- Female
- Humans
- Male
- Middle Aged
- Adenocarcinoma/pathology
- Adenocarcinoma/drug therapy
- Adenocarcinoma/mortality
- Adenocarcinoma/therapy
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/drug therapy
- Adenocarcinoma, Mucinous/therapy
- Adenocarcinoma, Mucinous/mortality
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Capecitabine/administration & dosage
- Capecitabine/therapeutic use
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/mortality
- Carcinoma, Pancreatic Ductal/drug therapy
- Carcinoma, Pancreatic Ductal/therapy
- Carcinoma, Pancreatic Ductal/surgery
- Chemotherapy, Adjuvant
- Gemcitabine
- Neoplasm Recurrence, Local/epidemiology
- Pancreatectomy
- Pancreatic Intraductal Neoplasms/pathology
- Pancreatic Intraductal Neoplasms/therapy
- Pancreatic Intraductal Neoplasms/mortality
- Pancreatic Intraductal Neoplasms/surgery
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/drug therapy
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/therapy
- Pancreatic Neoplasms/surgery
- Propensity Score
- Retrospective Studies
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Affiliation(s)
- James Lucocq
- Department of General Surgery, NHS Lothian, Edinburgh, UK
| | - Jake Hawkyard
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Beate Haugk
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Omar Mownah
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, London, UK
| | - Krishna Menon
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, London, UK
| | - Takaki Furukawa
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuki Hirose
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Sasahira
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Michael Feretis
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Anita Balakrishnan
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Carlo Ceresa
- Hepatobiliary and Pancreatic Surgery Unit, Royal Free Hospital, London, UK
| | - Brian Davidson
- Hepatobiliary and Pancreatic Surgery Unit, Royal Free Hospital, London, UK
| | - Rupaly Pande
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - Bobby Dasari
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - Lulu Tanno
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Dimitrios Karavias
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Jack Helliwell
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Alistair Young
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Quentin Nunes
- Department of Hepatopancreatobiliary Surgery, East Lancashire Teaching Hospitals NHS Trust, Blackburn, UK
| | - Tomas Urbonas
- Oxford Hepato-Pancreato-Biliary Surgical Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Michael Silva
- Oxford Hepato-Pancreato-Biliary Surgical Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Alex Gordon-Weeks
- Oxford Hepato-Pancreato-Biliary Surgical Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Jenifer Barrie
- Nottingham Hepato-Pancreatico-Biliary Service, Nottingham University Hospitals NHS Foundation Trust, Nottingham, UK
| | - Dhanny Gomez
- Nottingham Hepato-Pancreatico-Biliary Service, Nottingham University Hospitals NHS Foundation Trust, Nottingham, UK
| | - Stijn Van Laarhoven
- Department of General Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Francis Robertson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Hossain Nawara
- Department of General Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Joseph Doyle
- Gastrointestinal Unit, Royal Marsden NHS Foundation Trust, London, UK
| | - Ricky Bhogal
- Gastrointestinal Unit, Royal Marsden NHS Foundation Trust, London, UK
| | - Ewen Harrison
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK
| | - Marcus Roalso
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Debora Ciprani
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Somaiah Aroori
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Bathiya Ratnayake
- Hepato-pancreatico-biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, New Zealand
| | - Jonathan Koea
- Hepato-pancreatico-biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, New Zealand
| | - Gabriele Capurso
- Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria
| | - Tareq Alsaoudi
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Neil Bhardwaj
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Srujan Rajesh
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Fraser Jeffery
- Department of General and Vascular Surgery, Christchurch Hospital, Canterbury District Health Board, Christchurch, New Zealand
| | - Saxon Connor
- Department of General and Vascular Surgery, Christchurch Hospital, Canterbury District Health Board, Christchurch, New Zealand
| | - Andrew Cameron
- Wolfson Wohl Cancer Research Centre, Research Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Nigel Jamieson
- Wolfson Wohl Cancer Research Centre, Research Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Amy Sheen
- New South Wales Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Anubhav Mittal
- Department of Hepatopancreatobiliary Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Jas Samra
- Department of Hepatopancreatobiliary Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Anthony Gill
- New South Wales Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Department of Hepatopancreatobiliary Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Keith Roberts
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Sanjay Pandanaboyana
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
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Jung HS, Lee M, Han Y, Thomas AS, Yun WG, Cho YJ, Kluger MD, Jang JY, Kwon W. Inadequacy of the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system for invasive carcinoma associated with premalignant lesions in the pancreas: an analysis using the National Cancer Database. HPB (Oxford) 2024; 26:400-409. [PMID: 38114399 DOI: 10.1016/j.hpb.2023.11.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 09/09/2023] [Accepted: 11/28/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND Invasive carcinomas arising from premalignant lesions are currently staged by the same criteria as conventional pancreatic ductal adenocarcinoma. METHODS Clinicopathologic information and survival data were extracted through a thorough search of histology codes from National Cancer Database (2006-2016). A total of 723 patients with invasive intraductal papillary mucinous neoplasm and mucinous cystic neoplasm were analyzed. RESULTS The median age was 67 years, and 351 patients (48.5%) were male. There were 212 (29.3%), 232 (32.1%), 272 (37.6%), and 7 (1.0%) patients with T1, T2, T3, and T4 classification. Extrapancreatic extension (EPE) was present in 284 (39.3%). Age (HR = 1.504, 95% CI 1.196-1.891), R1 or R2 resection (HR = 1.585, 95% CI 1.175-2.140), and EPE (HR = 1.598, 95% CI 1.209-2.113) were independent prognostic factors for overall survival. Size criteria did not significantly affect survival. The median survival was 115.9 months for patients without EPE, compared to 34.2 months for those with EPE. EPE discriminated survival better than tumor size. DISCUSSION The T classification of the eighth edition AJCC staging system is not adequate for invasive carcinomas associated with premalignant lesions of the pancreas. They merit a separate, dedicated staging system that uses appropriate prognostic factors.
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Affiliation(s)
- Hye-Sol Jung
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Mirang Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Alexander S Thomas
- Division of GI/Endocrine Surgery, Department of Surgery, Columbia University Vagelos College of Physicians and Surgeons, New York, USA
| | - Won-Gun Yun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Young J Cho
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Michael D Kluger
- Division of GI/Endocrine Surgery, Department of Surgery, Columbia University Vagelos College of Physicians and Surgeons, New York, USA
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
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6
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Choi SJ, Kim SJ, Kim DW, Lee SS, Hong SM, Kim KW, Kim JH, Kim HJ, Byun JH. Large Duct Pancreatic Ductal Adenocarcinoma: A Morphological Variant of Pancreatic Ductal Adenocarcinoma With Distinct CT and MRI Characteristics. Korean J Radiol 2023; 24:1232-1240. [PMID: 38016682 PMCID: PMC10701001 DOI: 10.3348/kjr.2023.0521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 08/31/2023] [Accepted: 09/19/2023] [Indexed: 11/30/2023] Open
Abstract
OBJECTIVE To investigate the imaging characteristics of large duct pancreatic ductal adenocarcinoma (LD-PDAC) on computed tomography (CT) and magnetic resonance imaging (MRI). MATERIALS AND METHODS Thirty-five patients with LD-PDAC (63.2 ± 9.7 years) were retrospectively evaluated. Tumor morphology on CT and MRI (predominantly solid mass vs. solid mass with prominent cysts vs. predominantly cystic mass) was evaluated. Additionally, the visibility, quantity, shape (oval vs. branching vs. irregular), and MRI signal intensity of neoplastic cysts within the LD-PDAC were investigated. The radiological diagnoses rendered for LD-PDAC in radiology reports were reviewed. RESULTS LD-PDAC was more commonly observed as a solid mass with prominent cysts (45.7% [16/35] on CT and 37.1% [13/35] on MRI) or a predominantly cystic mass (20.0% [7/35] on CT and 40.0% [14/35] on MRI) and less commonly as a predominantly solid mass on CT (34.3% [12/35]) and MRI (22.9% [8/35]). The tumor morphology on imaging was significantly associated with the size of the cancer gland on histopathological examination (P = 0.020 [CT] and 0.013 [MRI]). Neoplastic cysts were visible in 88.6% (31/35) and 91.4% (32/35) of the LD-PDAC cases on CT and MRI, respectively. The cysts appeared as branching (51.6% [16/35] on CT and 59.4% [19/35] on MRI) or oval shapes (45.2% [14/35] on CT and 31.2% [10/35] on MRI) with fluid-like MRI signal intensity. In the radiology reports, 10 LD-PDAC cases (28.6%) were misinterpreted as diseases other than typical PDAC, particularly intraductal papillary mucinous neoplasms. CONCLUSION LD-PDAC frequently appears as a solid mass with prominent cysts or as a predominantly cystic mass on CT and MRI. Radiologists should be familiar with the imaging features of LD-PDAC to avoid misdiagnosis.
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Affiliation(s)
- Se Jin Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung Joo Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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7
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He X, Fan R, Sun J, Ren Y, Zhao X, Rui W, Yuan Y, Zou D. A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm. Front Oncol 2023; 13:1087852. [PMID: 36761937 PMCID: PMC9902908 DOI: 10.3389/fonc.2023.1087852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 01/05/2023] [Indexed: 01/26/2023] Open
Abstract
Background/Objectives There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion. Methods A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a. Results Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model. Conclusions This predictive model will help assess an individual's risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.
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Affiliation(s)
- Xiangyi He
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rong Fan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Sun
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanhao Ren
- School of Mathematical Sciences, Fudan University, Shanghai, China
| | - Xuesong Zhao
- Departments of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Rui
- Departments of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yaozong Yuan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Yaozong Yuan, ; Duowu Zou,
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Yaozong Yuan, ; Duowu Zou,
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8
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Habib JR, Kinny-Köster B, Amini N, Shoucair S, Cameron JL, Thompson ED, Fishman EK, Hruban RH, Javed AA, He J, Wolfgang CL. Predictors, Patterns, and Timing of Recurrence Provide Insight into the Disease Biology of Invasive Carcinomas Arising in Association with Intraductal Papillary Mucinous Neoplasms. J Gastrointest Surg 2022; 26:2311-2320. [PMID: 35915375 DOI: 10.1007/s11605-022-05428-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/10/2022] [Indexed: 01/31/2023]
Abstract
OBJECTIVES To identify predictors, patterns, and timing of recurrence after resection of invasive carcinomas arising in association with an IPMN. BACKGROUND Postoperative management of an invasive carcinoma arising in association with an intraductal papillary mucinous neoplasm (IPMN), a biologically distinct entity from PanIN-derived pancreatic ductal adenocarcinoma (PDAC), remains largely based on guidelines for PanIN-derived PDAC. To minimize treatment failure and inform disease-specific management, cancer recurrence must be better characterized. METHODS Patients were identified from a prospectively maintained registry between 1996 and 2018. Predictors of recurrence were evaluated by employing Cox regression models to determine risk-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). The patterns and timing of recurrence were recognized and compared utilizing a log-rank test, respectively. RESULTS Of the 213 patients included, 92 (43.2%) recurred with a median RFS of 23.7 months (16.7-30.7). The predominant pattern of recurrence included any systemic (65.2%). The median time to local recurrence was longer than systemic (21.6 versus 11.4 months, p = 0.05). Poor differentiation [HR: 3.01, 95%CI (1.06-8.61)] and nodal disease [N1, HR: 2.23, 95%CI (1.12-4.60); and N2, HR: 5.67 95%CI (2.93-10.99)] emerged as independent predictors of systemic recurrence. For local-specific recurrences, poor differentiation [HR: 3.73, 95%CI (1.04-13.45)] and an R1 margin [high-grade dysplasia or invasive carcinoma; HR: 2.66, 95%CI (1.14-6.21)] emerged as independent predictors. CONCLUSIONS The predominant pattern of recurrence after resection of invasive carcinomas arising in association with IPMNs is systemic, and occurs earlier than local recurrence. Poor differentiation and nodal disease are associated with systemic recurrence while poor differentiation and an R1 margin are associated with local recurrence. Future studies should investigate the role of systemic (chemotherapy) versus local (radiation) therapies and surveillance strategies in a personalized manner.
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Affiliation(s)
- Joseph R Habib
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Benedict Kinny-Köster
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Neda Amini
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sami Shoucair
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - John L Cameron
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elizabeth D Thompson
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elliot K Fishman
- Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ralph H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ammar A Javed
- Division of Hepatobiliary and Pancreatic Surgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA
| | - Jin He
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christopher L Wolfgang
- Division of Hepatobiliary and Pancreatic Surgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.
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9
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Pancreatic Incidentaloma. J Clin Med 2022; 11:jcm11164648. [PMID: 36012893 PMCID: PMC9409921 DOI: 10.3390/jcm11164648] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/03/2022] [Accepted: 08/08/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic incidentalomas (PIs) represent a clinical entity increasingly recognized due to advances in and easier access to imaging techniques. By definition, PIs should be detected during abdominal imaging performed for indications other than a pancreatic disease. They range from small cysts to invasive cancer. The incidental diagnosis of pancreatic cancer can contribute to early diagnosis and treatment. On the other hand, inadequate management of PIs may result in overtreatment and unneeded morbidity. Therefore, there is a strong need to evaluate the nature and clinical features of individual PIs. In this review, we summarize the major characteristics related to PIs and present suggestions for their management.
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10
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Takeda Y, Imamura H, Yoshimoto J, Fukumura Y, Yoshioka R, Mise Y, Kawasaki S, Saiura A. Survival comparison of invasive intraductal papillary mucinous neoplasm versus pancreatic ductal adenocarcinoma. Surgery 2022; 172:336-342. [PMID: 35197219 DOI: 10.1016/j.surg.2022.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 12/29/2021] [Accepted: 01/18/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND The aim of this study was to assess the relevance of highlighting T1a invasive intraductal papillary mucinous carcinoma as a separate subcategory and to compare the tumor biology between invasive intraductal papillary mucinous carcinoma and pancreatic ductal adenocarcinoma. METHODS A total of 144 and 328 consecutive patients with intraductal papillary mucinous neoplasms and pancreatic ductal adenocarcinoma, respectively, were analyzed. RESULTS Patients with T1a invasive intraductal papillary mucinous carcinoma comprised 25% (11/44) of the overall subject population with invasive intraductal papillary mucinous carcinoma with 5-year disease-specific survival rate being 100%. None of the patients with pancreatic ductal adenocarcinoma were classified as having T1a disease. When patients with invasive intraductal papillary mucinous carcinoma and pancreatic ductal adenocarcinoma were compared after excluding patients with T1a invasive intraductal papillary mucinous carcinoma, the 5-year disease-specific survival rates were 63% vs 40% in node-negative status (P = .018); and they were 20% vs 13% in node-positive status (P = .385). Subsequent analyses revealed that this survival superiority was limited to patients without evidence of lymphatic invasion. CONCLUSION T1a invasive intraductal papillary mucinous carcinoma is a clinical entity specifically observed in patients with intraductal papillary mucinous carcinoma, but not in patients with pancreatic ductal adenocarcinoma, and is associated with excellent postoperative survival outcomes. In the survival comparison after exclusion of patients with T1a tumors, when the analysis was limited to patients without lymphatic invasion or lymph node metastasis, the disease-specific survival rate remained higher in patients with invasive intraductal papillary mucinous carcinoma compared with those with pancreatic ductal adenocarcinoma, and this difference was considered as being attributable to the intrinsic indolent biological behavior of invasive intraductal papillary mucinous carcinoma. However, this survival advantage was lost once lymphatic invasion occurred.
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Affiliation(s)
- Yoshinori Takeda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
| | - Jiro Yoshimoto
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Seiji Kawasaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
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11
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Gavazzi F, Capretti G, Giordano L, Ridolfi C, Spaggiari P, Sollai M, Carrara S, Nappo G, Bozzarelli S, Zerbi A. Pancreatic ductal adenocarcinoma and invasive intraductal papillary mucinous tumor: Different prognostic factors for different overall survival. Dig Liver Dis 2022; 54:826-833. [PMID: 34219044 DOI: 10.1016/j.dld.2021.06.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 06/08/2021] [Accepted: 06/10/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND It is unclear whether invasive intraductal papillary mucinous neoplasm (IPMN) has different clinical and prognostic characteristics, beyond histological factors, when compared to pancreatic ductal adenocarcinoma (PDAC). AIMS compare prognostic features of resected PDAC and invasive IPMN METHODS: A retrospective study of patients resected for PDAC or invasive IPMN realized at Humanitas Cancer Center's Pancreatic Surgery Unit, Milan, Italy, between 2010 and 2016. Data recorded included patient demographics, onset symptoms, preoperative health status, tumor features, histology and surgical characteristics. Overall survival was estimated using Kaplan-Meier and prognostic factors for survival were assessed by multivariate Cox regression. RESULTS A total of 332 patients were included (PDAC, n = 289; invasive IPMN, n = 43). Patients with invasive IPMN had better overall survival than PDAC patients (median: 76.6 versus 25.6 months; 5-year OS rate: 65.4% vs. 14.2%; p < 0.001). PDAC histology was associated with a significantly higher risk of death than IPMN (hazard ratio 1.815, 95% CI: 1.02, 3.24; p = 0.044). Survival was also worse with PDAC in early-stage disease (IA-IB-IIA, N0). In multivariate analysis, independent predictors of worse survival included perineural invasion, preoperative ASA physical status ≥3 and pain at diagnosis. CONCLUSIONS Patients with IPMN had a better prognosis than PDAC patients, regardless of disease stage.
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Affiliation(s)
- Francesca Gavazzi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy.
| | - Giovanni Capretti
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy; Humanitas University Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
| | - Laura Giordano
- Division of Biostatistics, Department of Oncology, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Cristina Ridolfi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Paola Spaggiari
- Department of Pathology, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Mauro Sollai
- Department of Pathology, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Silvia Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Silvia Bozzarelli
- Department of Oncology, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy; Humanitas University Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
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12
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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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Szymoński K, Milian-Ciesielska K, Lipiec E, Adamek D. Current Pathology Model of Pancreatic Cancer. Cancers (Basel) 2022; 14:2321. [PMID: 35565450 PMCID: PMC9105915 DOI: 10.3390/cancers14092321] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/29/2022] [Accepted: 05/05/2022] [Indexed: 02/01/2023] Open
Abstract
Pancreatic cancer (PC) is one of the most aggressive and lethal malignant neoplasms, ranking in seventh place in the world in terms of the incidence of death, with overall 5-year survival rates still below 10%. The knowledge about PC pathomechanisms is rapidly expanding. Daily reports reveal new aspects of tumor biology, including its molecular and morphological heterogeneity, explain complicated "cross-talk" that happens between the cancer cells and tumor stroma, or the nature of the PC-associated neural remodeling (PANR). Staying up-to-date is hard and crucial at the same time. In this review, we are focusing on a comprehensive summary of PC aspects that are important in pathologic reporting, impact patients' outcomes, and bring meaningful information for clinicians. Finally, we show promising new trends in diagnostic technologies that might bring a difference in PC early diagnosis.
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Affiliation(s)
- Krzysztof Szymoński
- Department of Pathomorphology, Jagiellonian University Medical College, 31-531 Cracow, Poland;
- Department of Pathomorphology, University Hospital, 30-688 Cracow, Poland;
| | | | - Ewelina Lipiec
- M. Smoluchowski Institute of Physics, Jagiellonian University, 30-348 Cracow, Poland;
| | - Dariusz Adamek
- Department of Pathomorphology, Jagiellonian University Medical College, 31-531 Cracow, Poland;
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14
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Wiggins B, Banno F, Miller J. Acute Pancreatitis Secondary to Newly Diagnosed Intraductal Papillary Mucinous Neoplasm. Cureus 2022; 14:e24526. [PMID: 35651426 PMCID: PMC9138680 DOI: 10.7759/cureus.24526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2022] [Indexed: 11/18/2022] Open
Abstract
Acute pancreatitis (AP) is a common gastrointestinal cause of hospital admissions and is prevalent in the United States. AP etiologies include alcohol use, cholelithiasis, hypertriglyceridemia, hypercalcemia, autoimmune phenomena, medications, or idiopathic. Rarely, intraductal papillary mucinous neoplasms can cause AP, as we present in this case report.
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Hu F, Hu Y, Wang D, Ma X, Yue Y, Tang W, Liu W, Wu P, Peng W, Tong T. Cystic Neoplasms of the Pancreas: Differential Diagnosis and Radiology Correlation. Front Oncol 2022; 12:860740. [PMID: 35299739 PMCID: PMC8921498 DOI: 10.3389/fonc.2022.860740] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 02/04/2022] [Indexed: 12/18/2022] Open
Abstract
Although the probability of pancreatic cystic neoplasms (PCNs) being detected is raising year by year, their differential diagnosis and individualized treatment are still a challenge in clinical work. PCNs are tumors containing cystic components with different biological behaviors, and their clinical manifestations, epidemiology, imaging features, and malignant risks are different. Some are benign [e.g., serous cystic neoplasms (SCNs)], with a barely possible that turning into malignant, while others display a low or higher malignant risk [e.g., solid pseudopapillary neoplasms (SPNs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs)]. PCN management should concentrate on preventing the progression of malignant tumors while preventing complications caused by unnecessary surgical intervention. Clinically, various advanced imaging equipment are usually combined to obtain a more reliable preoperative diagnosis. The challenge for clinicians and radiologists is how to accurately diagnose PCNs before surgery so that corresponding surgical methods and follow-up strategies can be developed or not, as appropriate. The objective of this review is to sum up the clinical features, imaging findings and management of the most common PCNs according to the classic literature and latest guidelines.
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Affiliation(s)
- Feixiang Hu
- Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yue Hu
- Hefei Cancer Hospital, Chinese Academy of Sciences (CAS), Hefei, China
| | - Dan Wang
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China
| | - Xiaowen Ma
- Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yali Yue
- Children's Hospital, Fudan University, Shanghai, China
| | - Wei Tang
- Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wei Liu
- Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Puye Wu
- General Electric (GE) Healthcare, Shanghai, China
| | - Weijun Peng
- Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Tong Tong
- Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Clinical Utility and Limitation of Diagnostic Ability for Different Degrees of Dysplasia of Intraductal Papillary Mucinous Neoplasms of the Pancreas Using 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography. Cancers (Basel) 2021; 13:cancers13184633. [PMID: 34572860 PMCID: PMC8465733 DOI: 10.3390/cancers13184633] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 08/31/2021] [Accepted: 09/14/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Elucidating risk factors for different degrees of dysplasia of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is important in determining strategies for management. In this study, we searched for risk factors for different degrees of dysplasia of IPMNs. Our study indicated that there were no useful factors that significantly differentiated low-grade dysplasia and high-grade dysplasia; however, 18F-fluorodeoxyglucose–positron emission tomography/computed tomography is useful for differentiating between non-invasive and invasive IPMNs. Our results offer critical information that may determine surgical treatment strategies. Abstract The diagnostic value of 18F-fluorodeoxyglucose (FDG) uptake in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas remains unclear. This study aimed to assess the role of FDG uptake in the diagnosis of different degrees of dysplasia of IPMNs. We retrospectively analyzed the following three points in 84 patients with IPMNs: (1) risk factors to predict high-grade dysplasia (HGD) and invasive carcinoma (INV); (2) the relationship between FDG uptake and glucose transporter 1 (GLUT-1) expression; and (3) the relationship between FDG uptake and the presence of mural nodules. The histopathological diagnosis was low-grade dysplasia (LGD) in 43 patients, HGD in 16, and INV in 25. The maximum standardized uptake value (SUV-max) was significantly higher in INV than in LGD/HGD (p < 0.0001, p = 0.0136). The sensitivity and specificity to discriminate INV from LGD/HGD were 80.0% and 86.2%, respectively, using the receiver operator characteristic curve, when the optimal cutoff score of SUV-max was set at 4.03. Those values were not different between HGD and LGD. More than half of HGD patients had low GLUT-1 expression. Taken together, FDG-PET/CT is useful in distinguishing between non-invasive and invasive IPMN. Our results offer critical information that may determine surgical treatment strategies.
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Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights. Int J Mol Sci 2021; 22:ijms22136756. [PMID: 34201897 PMCID: PMC8268881 DOI: 10.3390/ijms22136756] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 06/18/2021] [Accepted: 06/20/2021] [Indexed: 12/18/2022] Open
Abstract
Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associated to clinical particularities and favorable pathological features, as well as debated outcomes. However, IPMNs and IPMCs include distinct subtypes of precursor (gastric, pancreato-biliary, intestinal) and invasive (tubular, colloid) lesions, also associated to specific characteristics. Notably, consistent data have shown intestinal IPMNs and associated colloid carcinomas, defining the “intestinal pathway”, to be associated with less aggressive features. Genomic specificities have also been uncovered, such as mutations of the GNAS gene, and recent data provide more insights into the mechanisms involved in IPMCs carcinogenesis. This review synthetizes available data on clinical-pathological features and outcomes associated with IPMCs and their subtypes. We also describe known genomic hallmarks of these lesions and summarize the latest data about molecular processes involved in IPMNs initiation and progression to IPMCs. Finally, potential implications for clinical practice and future research strategies are discussed.
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3D quantitative analysis of diffusion-weighted imaging for predicting the malignant potential of intraductal papillary mucinous neoplasms of the pancreas. Pol J Radiol 2021; 86:e298-e308. [PMID: 34136048 PMCID: PMC8186307 DOI: 10.5114/pjr.2021.106427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 10/25/2020] [Indexed: 11/17/2022] Open
Abstract
Purpose To investigate the predictors of intraductal papillary mucinous neoplasms of the pancreas (IPMNs) with high-grade dysplasia, using 2-dimensional (2D) analysis and 3-dimensional (3D) volume-of-interest-based apparent diffusion coefficient (ADC) histogram analysis. Material and methods The data of 45 patients with histopathologically confirmed IPMNs with high-grade or low-grade dysplasia were retrospectively assessed. The 2D analysis included lesion-to-spinal cord signal intensity ratio (LSR), minimum ADC value (ADCmin), and mean ADC value (ADCmean). The 3D analysis included the overall mean (ADCoverall mean), mean of the bottom 10th percentile (ADCmean0-10), mean of the bottom 10-25th percentile (ADCmean10-25), mean of the bottom 25-50th percentile (ADCmean25-50), skewness (ADCskewness), kurtosis (ADCkurtosis), and entropy (ADCentropy). Diagnostic performance was compared by analysing the area under the receiver operating characteristic curve (AUC). Inter-rater reliability was assessed by blinded evaluation using the intraclass correlation coefficient. Results There were 16 and 29 IPMNs with high- and low-grade dysplasia, respectively. The LSR, ADCoverall mean, ADCmean0-10, ADCmean10-25, ADCmean25-50, and ADCentropy showed significant between-group differences (AUC = 72-93%; p < 0.05). Inter-rater reliability assessment showed almost perfect agreement for LSR and substantial agreement for ADCoverall mean and ADCentropy. Multivariate logistic regression showed that ADCoverall mean and ADCentropy were significant independent predictors of malignancy (p < 0.05), with diagnostic accuracies of 80% and 73%, respectively. Conclusion ADCoverall mean and ADCentropy from 3D analysis may assist in predicting IPMNs with high-grade dysplasia.
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Choi M, Chong JU, Hwang HK, Seo HI, Yang K, Ryu JH, Roh Y, Kim DH, Lee JH, Lee WJ, Choi SH, Kang CM. Role of postoperative adjuvant therapy in resected invasive intraductal papillary mucinous neoplasm of the pancreas: A multicenter external validation. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:671-679. [PMID: 34028187 DOI: 10.1002/jhbp.996] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 04/04/2021] [Accepted: 04/12/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Adjuvant therapy is beneficial in prolonging survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, no clear guidelines are available on the oncologic effect of adjuvant therapy in resected invasive intraductal papillary mucinous neoplasms (inv-IPMN). METHODS In total, 551 patients with PDAC and 67 patients with inv-IPMN of the pancreas were reviewed. For external validation, 46 patients with inv-IPMN from six other Korean institutions were enrolled. Propensity score-matched analysis and stage-matched survival analysis were conducted. RESULTS The mean follow-up durations in the inv-IPMN and PDAC groups were 43.36 months (SD, 42.34 months) and 43.35 months (SD, 35.62 months), respectively. The 5-year overall survival (OS) was significantly better in the resected inv-IPMN group than in the PDAC group in the overall stage-matched analysis (P < .001). In the inv-IPMN cohort, OS was better in the surgery alone group (P = .042). In subgroup analysis, no significant survival difference was found between the adjuvant therapy and surgery alone groups according to the stage (stage I; P = .285, stage II or III; P = .077). Multicenter external validation did not show a better OS in the adjuvant therapy group (P = .531). On multivariable analysis, only perineural invasion (PNI) was identified as an adverse prognostic factor in resected inv-IPMN (HR 4.844; 95% CI 1.696-13.838, P = .003). CONCLUSIONS inv-IPMN has a more indolent course than PDAC. Current strategy of adjuvant therapy may not improve the OS in patients with resected inv-IPMN. Further investigations on the potential role of adjuvant therapy in inv-IPMN are mandatory.
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Affiliation(s)
- Munseok Choi
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Korea
| | - Jae Uk Chong
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Ho Kyoung Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyung-Il Seo
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Kwangho Yang
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Younghoon Roh
- Department of Surgery, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, Korea
| | - Dong Hyun Kim
- Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jin Ho Lee
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoon Choi
- Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongam-si, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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20
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Huang X, You S, Ding G, Liu X, Wang J, Gao Y, Zheng J. Sites of Distant Metastases and Cancer-Specific Survival in Intraductal Papillary Mucinous Neoplasm With Associated Invasive Carcinoma: A Study of 1,178 Patients. Front Oncol 2021; 11:681961. [PMID: 34178672 PMCID: PMC8221068 DOI: 10.3389/fonc.2021.681961] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 04/26/2021] [Indexed: 12/23/2022] Open
Abstract
Background To explore the impact of distant metastases on cancer-specific survival in patients with intraductal papillary mucinous neoplasm (IPMN) with associated invasive carcinoma and identify the risk factor of distant metastases in IPMN with associated invasive carcinoma. Methods Patients with IPMN with associated invasive carcinoma between 2010 and 2015 were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. The survival analyses were assessed by Kaplan-Meier analyses and log-rank test. The impact of distant metastases was evaluated by Cox regression model and the risk factors of distant metastases were identified by logistic regression analyses, respectively. Results The median cancer-specific survival time of patients with no metastases, isolated liver, isolated lung, and multiple site metastases were 19 months, 4 months, 7 months, and 3 months, respectively. In patients with isolated liver metastases, multivariate analysis after adjustment indicated that chemotherapy (Hazard Ratio [HR]=0.351, 95% confidence interval [CI]=0.256-0.481, P<0.001) was a protective prognostic factor for cancer-specific survival (CSS) in patients with isolated liver metastases. In isolated lung metastases subgroup, old age (HR=1.715, 95% CI=1.037-2.838, P=0.036) and chemotherapy (HR=0.242, 95% CI=0.134-0.435, P<0.001) were related to CSS in multivariable Cox regression analysis(P<0.05). Tumor located in the pancreatic body/tail (HR=2.239, 95% CI=1.140-4.400, P=0.019) and chemotherapy (HR=0.191, 95% CI=0.108-0.340, P<0.001) were independent prognostic factors for CSS in patients with multiple metastases. Finally, a nomogram was constructed for cancer-specific survival and the predicted C-index was 0.780 (95% CI=0.762-0.798). Conclusion The liver is the most common site of distant metastases in IPMN with associated invasive carcinoma. Tumor located in the pancreatic body/tail and chemotherapy are independent prognostic factors for CSS in patients with multiple metastases. Further, tumor located in body/tail is identified as a risk factor of distant metastases.
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Affiliation(s)
- Xiaoyi Huang
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Siting You
- Central Laboratory, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Guiling Ding
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Xingchen Liu
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Jin Wang
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Yisha Gao
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Jianming Zheng
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China
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21
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Should Contrast-Enhanced Harmonic Endoscopic Ultrasound Be Incorporated into the International Consensus Guidelines to Determine the Appropriate Treatment of Intraductal Papillary Mucinous Neoplasm? J Clin Med 2021; 10:jcm10091818. [PMID: 33921949 PMCID: PMC8122438 DOI: 10.3390/jcm10091818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/04/2021] [Accepted: 04/13/2021] [Indexed: 11/16/2022] Open
Abstract
This study aimed to investigate whether the incorporation of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) into the international consensus guidelines (ICG) for the management of intraductal papillary mucinous neoplasm (IPMN) could improve its malignancy diagnostic value. In this single-center retrospective study, 109 patients diagnosed with IPMN who underwent preoperative CH-EUS between March 2010 and December 2018 were enrolled. We analyzed each malignancy diagnostic value (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) by replacing fundamental B-mode EUS with CH-EUS as the recommended test for patients with worrisome features (WF) (the CH-EUS incorporation ICG) and comparing the results to those obtained using the 2017 ICG. The malignancy diagnostic values as per the 2017 ICG were 78.9%, 42.3%, 60.0%, and 64.7% for Se, Sp, PPV, and NPV, respectively. The CH-EUS incorporation ICG plan improved the malignancy diagnostic values (Se 78.9%/Sp, 53.8%/PPV, 65.2%/NPV 70.0%). CH-EUS may be useful in determining the appropriate treatment strategies for IPMN.
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22
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Sakai Y, Ohtsuka M, Sugiyama H, Mikata R, Yasui S, Ohno I, Iino Y, Kato J, Tsuyuguchi T, Kato N. Current status of diagnosis and therapy for intraductal papillary neoplasm of the bile duct. World J Gastroenterol 2021; 27:1569-1577. [PMID: 33958844 PMCID: PMC8058653 DOI: 10.3748/wjg.v27.i15.1569] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/13/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023] Open
Abstract
Bile duct epithelial tumours showing papillary neoplasm in the bile duct lumen are present in the intrahepatic and extrahepatic bile ducts. Clinicopathological images of these tumours are distinctive and diverse, including histological images with a low to high grade dysplasia, infiltrating and noninfiltrating characteristics, excessive mucus production, and similarity to intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The World Health Organization Classification of Tumours of the Digestive System in 2010 named these features, intraductal papillary neoplasm of the bile duct (IPNB), as precancerous lesion of biliary carcinoma. IPNB is currently classified into type 1 that is similar to IPMN, and type 2 that is not similar to IPMN. Many of IPNB spreads superficially, and diagnosis with cholangioscopy is considered mandatory to identify accurate localization and progression. Prognosis of IPNB is said to be better than normal bile duct cancer.
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Affiliation(s)
- Yuji Sakai
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Harutoshi Sugiyama
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Rintaro Mikata
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Izumi Ohno
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Yotaro Iino
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Jun Kato
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Toshio Tsuyuguchi
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Naoya Kato
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Kataoka J, Nitta T, Ota M, Fujii K, Takeshita A, Ishibashi T. Total pancreatectomy for pancreatic remnant carcinoma five years after pancreaticoduodenectomy: Report a case. Int J Surg Case Rep 2021; 81:105795. [PMID: 33773370 PMCID: PMC8024913 DOI: 10.1016/j.ijscr.2021.105795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/16/2021] [Accepted: 03/16/2021] [Indexed: 11/24/2022] Open
Abstract
A 76-year-old Japanese man had invasive intraductal papillary carcinoma (IPMC). IPMC recurred in the remnant pancreas five years after initial pancreaticoduodenectomy. Most likely, recurrence was due to multifocal disease that developed a new cyst. Remnant pancreatectomy is the preferred approach for remnant pancreatic carcinoma due to better median long-term survival outcome. Introduction and importance The prognosis of non-invasive intraductal papillary mucinous neoplasma (IPMN) is better than that of pancreatic cancer. However, if the first surgical finding revealed an invasive IPMC, the risk of recurrence was found to be 7–21%. Case presentation A 76-year-old Japanese man had undergone subtotal stomach-preserving pancreaticoduodenectomy for intraductal papillary mucinous carcinoma non-invasive type at our hospital. No signs of adenocarcinoma at the resection margin were found by pathological examination of frozen sections. Five years later, a blood analysis showed increased serum CA19-9 level. A contrast-enhanced computed tomography scan of the abdomen revealed a mass adjacent to the pancreaticogastrostomy anastomosis. The patient underwent a total pancreatectomy. The tumor was identified as a recurrent IPMC with subserosal invasion, but without nodal involvement. The resection margins were negative. The patient’s postoperative course was uneventful, and he was discharged after 12 days. He is being followed up without adjuvant chemotherapy. Discussion The prognosis of IPMN is better than that of pancreatic cancer. However the risk of recurrence in invasive IPMC was found to be 7–21%. Therefore, IPMC must be surveilled every three months using tumor markers and imaging. Local recurrence in remnant pancreas is usually treated with systemic therapy. The median long-term survival after total pancreatectomy (range 7–24 months) was shown to be better than when chemotherapy alone was used (range 10–13 months). Conclusion We chose secondary surgery in term of survival time although there are quality of life drawbacks that currently make total pancreatectomy more inappropriate in patients than chemotherapy.
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Affiliation(s)
- Jun Kataoka
- Department of Gastroenterological Center Surgery, Shunjukai Shiroyama Hospital, Osaka, Japan.
| | - Toshikatsu Nitta
- Department of Gastroenterological Center Surgery, Shunjukai Shiroyama Hospital, Osaka, Japan
| | - Masato Ota
- Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan
| | - Kensuke Fujii
- Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan
| | - Atsushi Takeshita
- Department of Pathology, Osaka Medical College Hospital, Osaka, Japan
| | - Takashi Ishibashi
- Department of Gastroenterological Center Surgery, Shunjukai Shiroyama Hospital, Osaka, Japan
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Kim K, Kim SJ. Diagnostic Role of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Characterization of Intraductal Papillary Mucinous Neoplasms: An Updated Systematic Review and Meta-analysis. Pancreas 2021; 50:353-361. [PMID: 33835966 DOI: 10.1097/mpa.0000000000001760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVES The purpose of the current study was to investigate the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (CT) for characterization of intraductal papillary mucinous neoplasms (IPMN) through a systematic review and meta-analysis. METHODS The PubMed and Embase database were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT for characterization of IPMN. RESULTS Across 14 studies (752 patients), the pooled sensitivity for F-18 FDG PET or PET/CT was 0.84 (95% confidence interval [CI], 0.77-0.89) with heterogeneity (I2 = 55.5, P = 0.01) and a pooled specificity of 0.95 (95% CI, 0.88-0.98) with heterogeneity (I2 = 83.9, P < 0.001). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 17.4 (95% CI, 6.5-46.8) and negative likelihood ratio (LR-) of 0.17 (95% CI, 0.12-0.25). The pooled diagnostic odds ratio was 101 (95% CI, 31-327). Hierarchical summary receiver operating characteristic curve and indicates that the areas under the curve were 0.93 (95% CI, 0.90-0.95). CONCLUSIONS The current meta-analysis showed a high sensitivity, specificity, diagnostic odds ratio, and the LR scatter gram of F-18 FDG PET or PET/CT for determination of characteristics of IPMN.
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Affiliation(s)
- Keunyoung Kim
- From the Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital
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25
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Izumo W, Higuchi R, Furukawa T, Yazawa T, Uemura S, Shiihara M, Yamamoto M. Importance of each high-risk stigmata and worrisome features as a predictor of high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas. Pancreatology 2020; 20:895-901. [PMID: 32624417 DOI: 10.1016/j.pan.2020.06.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/15/2020] [Accepted: 06/17/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND High-risk stigmata (HRS) and 'worrisome features' (WFs) are defined as predictive factors for malignancies of intraductal papillary mucinous neoplasms (IPMNs). We performed this study to determine the importance and odds ratio (OR) of each HRS and WFs as predictors for high-grade dysplasia (HGD). METHODS We analyzed 295 patients who underwent pancreatectomy for branch duct and mixed-type IPMN, and evaluated the association between HRS and WFs (as defined by the '2017 Fukuoka Consensus Guidelines') and HGD. RESULTS The proportions of patients with low-grade dysplasia (LGD), HGD, and invasive carcinoma were 47%, 28%, and 25%, respectively. Multivariate analysis comparing patients with LGD and HGD using all HRS and WFs revealed that an enhancing mural nodule ≥5 mm (OR: 4.1), pancreatitis (OR: 2.2), and thickened/enhancing cyst walls (OR: 2.2) were independent predictive factors for HGD. Based on the OR (the former factor is two points and the latter two factors are each one point), the incidence of HGD in patients with none (n = 43), one (n = 82), two (n = 25), three (n = 52), and four (n = 19) of these predictive factors were 9%, 26%, 52%, 62%, and 63%, respectively. Assuming a score of one or higher as a surgical indication, the sensitivity, specificity, positive predict value, and negative predict value of HGD were 95, 38, 44, and 91%. CONCLUSIONS Our derived scoring system using more important factors in HRS and WFs may be useful for predicting HGD and determining surgical indications of IPMN.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai, 980-8575, Japan
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Masahiro Shiihara
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
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26
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Rodrigues C, Hank T, Qadan M, Ciprani D, Mino-Kenudson M, Weekes CD, Ryan DP, Clark JW, Allen JN, Hong TS, Wo JY, Ferrone CR, Warshaw AL, Lillemoe KD, Fernandez-Del Castillo C. Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas. Pancreatology 2020; 20:722-728. [PMID: 32222340 DOI: 10.1016/j.pan.2020.03.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 03/13/2020] [Accepted: 03/15/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND There is limited data on the efficacy of adjuvant therapy (AT) in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMN). This single center retrospective cohort study aims to assess the impact of AT on survival in these patients. METHODS Patients undergoing surgery for invasive IPMN between 1993 and 2018 were included in the study. We compared the clinicopathologic features and evaluated overall survival (OS) using multivariate Cox regression adjusting for adjuvant therapy, age, T and N stage, perineural and lymphovascular invasion. We also assessed survival differences between surgery alone and AT in node negative (N0) and node positive (N+) subgroups. RESULTS 103 patients were included in the study; 69 underwent surgery alone while 34 also received AT. Patients in the AT group were significantly younger, presented at higher T and N stages and had more perineural and lymphovascular invasion. Median OS in the surgery alone group was 134 months and 65 months in the AT group, p = 0.052. On multivariate analysis, AT was not associated with improved OS; hazard ratio (HR) = 1.03 (0.52-2.05). In N0 patients, compared to surgery alone, AT was associated with a worse median OS (65 vs 167 months, p = 0.03), whereas in N+ patients there was a non-significant improvement (50.5 vs 20.4 months, p = 0.315). CONCLUSION AT did not improve survival in the overall cohort even after multivariate analysis. N0 patients have excellent survival, and AT should probably be avoided in them, whereas it may be considered in patients with N+ disease.
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Affiliation(s)
- Clifton Rodrigues
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Thomas Hank
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Debora Ciprani
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Colin D Weekes
- Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - David P Ryan
- Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Jeffrey W Clark
- Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Jill N Allen
- Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Theodore S Hong
- Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Jennifer Y Wo
- Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew L Warshaw
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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27
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Izumo W, Higuchi R, Furukawa T, Yazawa T, Uemura S, Shiihara M, Yamamoto M. Evaluation of preoperative prognostic factors in patients with resectable invasive intraductal papillary mucinous carcinoma. Surgery 2020; 168:994-1002. [PMID: 32139141 DOI: 10.1016/j.surg.2020.01.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/01/2020] [Accepted: 01/16/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Upfront surgery is the standard treatment for resectable invasive intraductal papillary mucinous carcinoma; however, recurrence is common. Therefore, we investigated the recurrence, surgical outcome, and preoperative prognostic factors for recurrence in patients with resectable invasive intraductal papillary mucinous carcinoma. METHODS We analyzed 111 patients who underwent upfront surgery for resectable invasive intraductal papillary mucinous carcinoma between 2000 and 2017 and evaluated the relationship among clinicopathologic factors, recurrence, and outcomes. RESULTS The 5-year recurrence-free survival and disease-specific survival rates were 61% and 74%, respectively. The median time to recurrence was 1.1 years. In multivariate analysis, carbohydrate antigen 19-9 ≥83 U/mL (hazard ratio: 2.8 and 3.1), tumor size ≥2.2 cm (hazard ratio: 3.5 and 4.7), and pathologic tubular adenocarcinoma grade 2 (hazard ratio: 3.1 and 5.2) were risk factors for a shorter recurrence-free survival and disease-specific survival, respectively. Lymph node metastasis (hazard ratio: 3.9) was also a risk factor for a shorter disease-specific survival. When examining outcomes according to preoperatively measurable factors (carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm), the 5-year recurrence rates in patients with none (n = 47), 1 (n = 46), and both (n = 18) risk factors were 17%, 48%, and 78%, respectively. Five-year disease-specific survival rates in patients with none, 1, and both preoperative risk factors were 95%, 69%, and 31%, respectively. CONCLUSION Carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm were independent preoperative risk factors for poor outcomes in patients with resectable invasive intraductal papillary mucinous carcinoma.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan.
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Masahiro Shiihara
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
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28
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Pyo JS, Kim NY, Son BK, Chung KH. Prognostic Implication of pN Stage Subdivision Using Metastatic Lymph Node Ratio in Resected Pancreatic Ductal Adenocarcinoma. Int J Surg Pathol 2019; 28:245-251. [DOI: 10.1177/1066896919886057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In this meta-analysis, we aimed to evaluate the prognostic implication of the metastatic lymph node ratio (mLNR) and its optimal criterion in pancreatic ductal adenocarcinoma (PDAC) with lymph node metastasis (LNM). The present study included 3735 patients with PDAC who had LNM, from 11 eligible studies. We carried out a meta-analysis to determine the correlation between a high mLNR and PDAC prognosis. The estimated mean numbers of examined and metastatic lymph nodes were 22.396 (95% confidence interval [CI] = 19.681-25.111) and 6.496 (95% CI = 4.646-8.345), respectively. A high mLNR was significantly correlated with worse overall survival (hazard ratio = 1.344, 95% CI = 1.276-1.416). In 3 subgroups based on high mLNR criteria (>0 and <0.2, ≥0.2 and <0.4, and ≥0.4), there were significant correlations between a high mLNR and worse survival. A cutoff of 0.200 showed the highest hazard ratio (1.391, 95% CI = 1.268-1.525), which was statistically significant. Our results showed that mLNR is a useful prognostic factor for PDAC with LNM. Although the optimal criterion of high mLNR may be 0.200, further cumulative studies are required before this can be applied in daily practice.
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Affiliation(s)
- Jung-Soo Pyo
- Department of Pathology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea
| | - Nae Yu Kim
- Department of Internal Medicine, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea
| | - Byoung Kwan Son
- Department of Internal Medicine, Eulji Hospital, Eulji University School of Medicine, Seoul, Republic of Korea
| | - Kwang Hyun Chung
- Department of Internal Medicine, Eulji Hospital, Eulji University School of Medicine, Seoul, Republic of Korea
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29
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Aronsson L, Bengtsson A, Torén W, Andersson R, Ansari D. Intraductal papillary mucinous carcinoma versus pancreatic ductal adenocarcinoma: A systematic review and meta-analysis. Int J Surg 2019; 71:91-99. [PMID: 31546033 DOI: 10.1016/j.ijsu.2019.09.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 09/16/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection. METHODS Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model. RESULTS A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09-0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05-0.25 and OR 0.38, 95% CI 0.26-0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12-23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71-7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32-0.57). CONCLUSION Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC.
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MESH Headings
- Adenocarcinoma, Mucinous/mortality
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Papillary/mortality
- Adenocarcinoma, Papillary/pathology
- Aged
- Breast Neoplasms/mortality
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/mortality
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Pancreatic Ductal/mortality
- Carcinoma, Pancreatic Ductal/pathology
- Female
- Humans
- Middle Aged
- Neoplasm Staging
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/pathology
- Survival Rate
- Pancreatic Neoplasms
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Affiliation(s)
- Linus Aronsson
- Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Surgery, Lund, Sweden
| | - Axel Bengtsson
- Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Surgery, Lund, Sweden
| | - William Torén
- Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Surgery, Lund, Sweden
| | - Roland Andersson
- Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Surgery, Lund, Sweden
| | - Daniel Ansari
- Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Surgery, Lund, Sweden.
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30
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Izumo W, Higuchi R, Furukawa T, Yazawa T, Uemura S, Matsunaga Y, Shiihara M, Yamamoto M. Comparison of patients with invasive intraductal papillary mucinous carcinoma and invasive ductal carcinoma of the pancreas: a pathological type- and stage-matched analysis. Scand J Gastroenterol 2019; 54:1412-1418. [PMID: 31680568 DOI: 10.1080/00365521.2019.1684554] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: We compared the pathological features and stage-matched outcomes of patients with invasive intraductal papillary mucinous carcinoma (IPMC) and invasive ductal carcinoma (IDC) of the pancreas to identify the reasons for these diseases' differing prognoses.Methods: We analyzed 114 and 560 patients who underwent curative pancreatectomy for invasive IPMC and IDC, respectively, and analyzed their clinicopathological factors.Results: The disease-specific survival (DSS) of patients with invasive IPMC was significantly superior to that of patients with IDC exhibiting all pathological types at all stages. The DSS of patients with invasive IPMC exhibiting tubular adenocarcinoma was significantly superior to that of their counterparts with IDC only among those with stage IIB (p = .045). When comparing patients with stage IIB tubular adenocarcinoma-type invasive IPMC to their counterparts with IDC, the tumor size (2.6 cm vs. 3.3 cm, p = .010), serum level of carbohydrate antigen 19-9 (253 vs. 474 U/mL, p = .035), number of metastatic lymph nodes (3.1 vs. 4.5, p = .033), vascular invasion rate (14% vs. 41%, p = .0019) and local invasion rate (79% vs. 95%, p = .0045) were lower in the former group. Moreover, the frequency of pathological tubular adenocarcinoma grade 1 was higher in patients with invasive IPMC than in those with IDC (38% vs. 12%, p = .0004) as was the R0 resection rate (90% vs. 65%, p = .0027).Conclusions: In pathological type- and stage-matched analyses, invasive IPMC was associated with a better prognosis than IDC only in patients with stage IIB, as factors governing tumor aggressiveness were milder in the former group than in the latter.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Yutaro Matsunaga
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Masahiro Shiihara
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
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31
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Hu Y, Johnston LE, Shami VM, Bauer TW, Adams RB, Stukenborg GJ, Zaydfudim VM. Comparative Effectiveness of Resection vs Surveillance for Pancreatic Branch Duct Intraductal Papillary Mucinous Neoplasms With Worrisome Features. JAMA Surg 2019; 153:225-232. [PMID: 29167899 DOI: 10.1001/jamasurg.2017.4587] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Yinin Hu
- Department of Surgery, University of Virginia School of Medicine, Charlottesville
| | - Lily E. Johnston
- Department of Surgery, University of Virginia School of Medicine, Charlottesville
| | - Vanessa M. Shami
- Department of Gastroenterology, University of Virginia School of Medicine, Charlottesville
| | - Todd W. Bauer
- Department of Surgery, University of Virginia School of Medicine, Charlottesville
| | - Reid B. Adams
- Department of Surgery, University of Virginia School of Medicine, Charlottesville
| | - George J. Stukenborg
- Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville,Surgical Outcomes Research Center, University of Virginia School of Medicine, Charlottesville
| | - Victor M. Zaydfudim
- Department of Surgery, University of Virginia School of Medicine, Charlottesville,Surgical Outcomes Research Center, University of Virginia School of Medicine, Charlottesville
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32
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Mateos RN, Nakagawa H, Hirono S, Takano S, Fukasawa M, Yanagisawa A, Yasukawa S, Maejima K, Oku-Sasaki A, Nakano K, Dutta M, Tanaka H, Miyano S, Enomoto N, Yamaue H, Nakai K, Fujita M. Genomic analysis of pancreatic juice DNA assesses malignant risk of intraductal papillary mucinous neoplasm of pancreas. Cancer Med 2019; 8:4565-4573. [PMID: 31225717 PMCID: PMC6712468 DOI: 10.1002/cam4.2340] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 04/24/2019] [Accepted: 04/25/2019] [Indexed: 12/14/2022] Open
Abstract
Intraductal papillary mucinous neoplasm (IPMN) of pancreas has a high risk to develop into invasive cancer or co‐occur with malignant lesion. Therefore, it is important to assess its malignant risk by less‐invasive approach. Pancreatic juice cell‐free DNA (PJD) would be an ideal material in this purpose, but genetic biomarkers for predicting malignant risk from PJD are not yet established. We here performed deep exome sequencing analysis of PJD from 39 IPMN patients with or without malignant lesion. Somatic alterations and copy number alterations (CNAs) detected in PJD were compared with the histologic grade of IPMN to evaluate their potential as a malignancy marker. Somatic mutations of KRAS, GNAS, TP53, and RNF43 were commonly detected in PJD of IPMNs, but no association with the histologic grades of IPMN was found. Instead, mutation burden was positively correlated with the histologic grade (r = 0.427, P = 0.015). We also observed frequent copy number deletions in 17p13 (TP53) and amplifications in 7q21 and 8q24 (MYC) in PJDs. The amplifications in 7q21 and 8q24 were positively correlated with the histologic grade and most prevalent in the cases of invasive carcinoma (P = 0.002 and 7/11; P = 0.011 and 6/11, respectively). We concluded that mutation burden and CNAs detected in PJD may have potential to assess the malignant progression risk of IPMNs.
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Affiliation(s)
- Raúl N Mateos
- Department of Computational Biology and Medical Science, The University of Tokyo, Chiba, Japan.,Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hidewaki Nakagawa
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Seiko Hirono
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Shinichi Takano
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Mitsuharu Fukasawa
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Akio Yanagisawa
- Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoru Yasukawa
- Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuhiro Maejima
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Aya Oku-Sasaki
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Kaoru Nakano
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Munmee Dutta
- Department of Computational Biology and Medical Science, The University of Tokyo, Chiba, Japan.,Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hiroko Tanaka
- Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Satoru Miyano
- Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Kenta Nakai
- Department of Computational Biology and Medical Science, The University of Tokyo, Chiba, Japan.,Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Masashi Fujita
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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33
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Marchegiani G, Andrianello S, Dal Borgo C, Secchettin E, Melisi D, Malleo G, Bassi C, Salvia R. Adjuvant chemotherapy is associated with improved postoperative survival in specific subtypes of invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas: it is time for randomized controlled data. HPB (Oxford) 2019; 21:596-603. [PMID: 30366881 DOI: 10.1016/j.hpb.2018.09.013] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 08/04/2018] [Accepted: 09/27/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Very little is known about adjuvant chemotherapy for invasive Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas. The aim was to assess whether adjuvant chemotherapy affects survival. METHODS Retrospective evaluation of invasive IPMNs. Patients treated with surgery alone or followed by adjuvant chemotherapy were compared in terms of survival. RESULTS A total of 102 invasive IPMNs were analyzed. Median follow-up was 72 (5-318) months and 18.6% received adjuvant chemotherapy. Overall, recurrence rate was 40.2%, while 5-year overall survival and disease specific survival (DSS) were 65.3% and 69.4%, respectively. N1 disease (HR5.58, CI95% 2.49-12.51, p < 0.01), tubular type (HR2.35, CI95% 1.71-4.82, p = 0.05) and G3 tumors (HR4.54, CI95% 2.12-15.49, <0.01) were predictors of reduced DSS. Overall, there was no difference in the 5-year DSS comparing patients treated with adjuvant chemotherapy to surgery alone (61.8 vs. 69.4%, p = 0.8). Adjuvant chemotherapy significantly improved DSS only in N1 (5-years-DSS 76 vs. 35.8%, p = 0.01) and tubular carcinomas (5-years-DSS 88.9 vs. 53%, p = 0.03). CONCLUSIONS Adjuvant therapy improves survival only in invasive IPMNs with nodal disease or tubular differentiation. Future trials are needed to improve the level of evidence about adjuvant chemotherapy.
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Affiliation(s)
- Giovanni Marchegiani
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Stefano Andrianello
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Chiara Dal Borgo
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Erica Secchettin
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Davide Melisi
- Department of Oncology, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Giuseppe Malleo
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Claudio Bassi
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy.
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34
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de Mestier L, Muller M, Cros J, Vullierme MP, Vernerey D, Maire F, Dokmak S, Rebours V, Sauvanet A, Lévy P, Hammel P. Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score. United European Gastroenterol J 2019; 7:358-368. [PMID: 31019704 DOI: 10.1177/2050640618824910] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 12/19/2018] [Indexed: 02/06/2023] Open
Abstract
Background About 5% of pancreatic ductal adenocarcinomas are inherited due to a deleterious germline mutation detected in 20% or fewer families. Pancreatic screening in high-risk individuals is proposed to allow early surgical treatment of (pre)malignant lesions. The outcomes of pancreatic surgery in high-risk individuals have never been correctly explored. Objectives To evaluate surgical appropriateness and search for associated factors in high-risk individuals. Methods A patient-level meta-analysis was performed including studies published since 1999. Individual classification distinguished the highest risk imaging abnormality into low-risk or high-risk abnormality, and the highest pathological degree of malignancy of lesions into no/low malignant potential or potentially/frankly malignant. Surgical appropriateness was considered when potentially/frankly malignant lesions were resected. Results Thirteen out of 24 studies were selected, which reported 90 high-risk individuals operated on. Low-risk/high-risk abnormalities were preoperatively detected in 46.7%/53.3% of operated high-risk individuals, respectively. Surgical appropriateness was consistent in 38 (42.2%) high-risk individuals, including 20 pancreatic ductal adenocarcinomas (22.2%). Identification of high-risk abnormalities was strongly associated with surgical appropriateness at multivariate analysis (P = 0.001). We proposed a score and nomogram predictive of surgical appropriateness, including high-risk abnormalities, age and existence of deleterious germline mutation. Conclusion Overall, 42.2% of high-risk individuals underwent appropriate surgery. The proposed score might help selecting the best candidates among high-risk individuals for pancreatic resection.
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Affiliation(s)
- Louis de Mestier
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Marie Muller
- Department of Digestive Oncology and Genetic Counselling, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Jérôme Cros
- Department of Pathology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Marie-Pierre Vullierme
- Department of Radiology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Dewi Vernerey
- Department of Methodology and Quality of Life in Oncology Unit, EA 3181, Minjoz University Hospital, Besançon, France
| | - Frédérique Maire
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Safi Dokmak
- Department of Hepatobiliary and Pancreatic Surgery, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Vinciane Rebours
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Alain Sauvanet
- Department of Hepatobiliary and Pancreatic Surgery, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Philippe Lévy
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Pascal Hammel
- Department of Digestive Oncology and Genetic Counselling, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
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35
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Abstract
OBJECTIVES The aims of the study were to compare survival outcomes between patients with pancreatic ductal adenocarcinoma (PDAC) and invasive intraductal papillary mucinous neoplasms (IPMN) and to determine candidates for adjuvant chemotherapy. METHODS A total of 579 consecutive patients, including 375 PDAC and 204 IPMN patients, were reviewed. Stage-matched comparisons of survival data were conducted using the Cox proportional hazards model and propensity analysis. To evaluate prognostic factors, univariate and multivariate Cox regression analyses were performed. RESULTS The overall survival for invasive IPMN was significantly longer than that for PDAC (hazard ratio, 2.34; P = 0.0001). When the analysis was limited to stage I patients, the 5-year overall survival rate of invasive IPMN patients was significantly better than that of PDAC patients (100% vs 74.1%, P = 0.0092); however, no difference was observed between stage II patients with invasive IPMN and PDAC (hazard ratio, 1.49; P = 0.09). The Cox proportional hazards model and propensity analysis demonstrated no difference in stage-matched survival. Multivariate analysis revealed that only T (≥3) was an independent prognostic factor for invasive IPMN. CONCLUSIONS Stage-matched analysis did not show a significant survival difference between invasive IPMN and PDAC patients, and T3 or higher was an independent prognostic factor for invasive IPMN.
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Abstract
Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
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Hughes I, GMT Powell A, Sarireh BA. Intraductal papillary mucinous neoplasm\'s 100 most significant manuscripts: A bibliometric analysis. INTERNATIONAL JOURNAL OF HEPATOBILIARY AND PANCREATIC DISEASES 2018. [DOI: 10.5348/100076z04dh2018ba] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Duconseil P, Périnel J, Autret A, Adham M, Sauvanet A, Chiche L, Mabrut JY, Tuech JJ, Mariette C, Régenet N, Fabre JM, Bachellier P, Delpéro JR, Paye F, Turrini O. Resectable invasive IPMN versus sporadic pancreatic adenocarcinoma of the head of the pancreas: Should these two different diseases receive the same treatment? A matched comparison study of the French Surgical Association (AFC). Eur J Surg Oncol 2017; 43:1704-1710. [PMID: 28687431 DOI: 10.1016/j.ejso.2017.06.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 05/25/2017] [Accepted: 06/08/2017] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To compare survival and impact of adjuvant chemotherapy in patients who underwent pancreaticoduodenectomy (PD) for invasive intraductal papillary mucinous neoplasm (IIPMN) and sporadic pancreatic ductal adenocarcinoma (PDAC). METHODS From 2005 to 2012, 240 patients underwent pancreatectomy for IIPMN and 1327 for PDAC. Exclusion criteria included neoadjuvant treatment, pancreatic resection other than PD, vascular resection, carcinoma in situ, or <11 examined lymph nodes. Thus, 82 IIPMN and 506 PDAC were eligible for the present study. Finally, The IIPMN group was matched 1:2 to compose the PDAC group according to TNM disease stage, perineural invasion, lymph node ratio, and margin status. RESULTS There was no difference in patient's characteristics, intraoperative parameters, postoperative outcomes, and histologic parameters. Overall survival and disease-free survival times were comparable between the 2 groups. In each group, overall survival time was significantly poorer in patients who did not achieve adjuvant chemotherapy (p = 0.03 for the IIPMN group; p = 0.03 for the PDAC group). In lymph-node negative patients of the IIPMN group, adjuvant chemotherapy did not have any significant impact on overall survival time (OR = 0.57; 95% CI [0.24-1.33]). Considering the whole population (i.e. patients with IIPMN and PDAC; n = 246), patients who did not achieve adjuvant chemotherapy had poorer survival (p < 0.01). CONCLUSIONS The courses of IIPMN and PDAC were similar after an optimized stage-to-stage comparison. Adjuvant chemotherapy was efficient in both groups. However, in lymph node negative patients, adjuvant chemotherapy seemed not to have a significant impact.
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Affiliation(s)
- P Duconseil
- Department of Surgery, Hôpital Nord, Marseille, France.
| | - J Périnel
- Department of Surgery, Hôpital Edouard-Herriot, HCL, UCBL1, Lyon, France
| | - A Autret
- Department of Biostatistics, Institut Paoli-Calmettes, Marseille, France
| | - M Adham
- Department of Surgery, Hôpital Edouard-Herriot, HCL, UCBL1, Lyon, France
| | - A Sauvanet
- Department of Surgery, Hôpital Beaujon, Paris, France
| | - L Chiche
- Department of Surgery, Maison du Haut-Lévêque, Bordeaux, France
| | - J-Y Mabrut
- Department of Surgery, Hôpital de la Croix Rousse, Lyon, France
| | - J-J Tuech
- Department of Surgery, Hôpital Charles Nicolle, Rouen, France
| | - C Mariette
- Department of Surgery, Hôpital Claude-Huriez, Lille, France
| | - N Régenet
- Department of Surgery, Hôpital Hôtel Dieu, Nantes, France
| | - J-M Fabre
- Department of Surgery, Hôpital Saint Eloi, Montpellier, France
| | - P Bachellier
- Department of Surgery, Hôpital de Hautepierre, Strasbourg, France
| | - J-R Delpéro
- Department of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - F Paye
- Department of Surgery, Hôpital Saint Antoine, Paris, France
| | - O Turrini
- Department of Surgery, Institut Paoli-Calmettes, Marseille, France
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Saito M, Hirokawa N, Usami Y, Someya M, Sakata KI. Differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma and pancreatic ductal adenocarcinoma on ultrasonography: the utility of echo intensity and contrast enhancement. Ultrasonography 2017; 36:260-269. [PMID: 28269978 PMCID: PMC5494864 DOI: 10.14366/usg.16039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 02/03/2017] [Accepted: 02/04/2017] [Indexed: 12/30/2022] Open
Abstract
Purpose The aim of this study was to investigate the utility of echo intensity and contrast enhancement in the differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma (IPMN-IC) and pancreatic ductal adenocarcinoma (PDAC) on ultrasonography. Methods This study included eight and 37 patients who had pathologically confirmed IPMN-IC and PDAC, respectively, and were enrolled for a comparative analysis of the sonographic features of the tumors. In the quantitative echo intensity evaluation, the two groups were compared with respect to the difference between the tumor intensity and the pancreatic intensity (TI-PI) and between the tumor intensity and the vascular intensity (TI-VI). In the quantitative contrast enhancement evaluation, the increase in echo intensity (ΔTI) and increase in echo intensity per unit of time (slope) were compared between the groups. The echo intensity and contrast enhancement were also compared between the two groups in patients with T3-T4 disease. In addition, the correlations of the histological type, tumor size, stromal type, and T factor with echogenicity and contrast enhancement were analyzed. Results IPMN-IC had significantly greater echo intensity and contrast enhancement than PDAC (TI-PI, P=0.004; TI-VI, P=0.001; ΔTI, P=0.012; slope, P=0.002). In T3-T4 disease, IPMN-IC also showed greater echo intensity and faster enhancement than PDAC. Echo intensity and contrast enhancement were correlated with histological type (TI-PI, P=0.003; TI-VI, P<0.001; ΔTI, P=0.007; slope, P<0.001). Conclusion IPMN-IC and PDAC can be differentiated by the quantitative evaluation of echo intensity and contrast enhancement.
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Affiliation(s)
- Masato Saito
- Department of Radiology, Sapporo Teishinkai Hospital, Sapporo, Japan
| | - Naoki Hirokawa
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yoko Usami
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masanori Someya
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Koh-Ichi Sakata
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current State of the Art and Ongoing Controversies. Ann Surg 2016; 263:908-17. [PMID: 26727096 DOI: 10.1097/sla.0000000000001567] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
With the widespread use and advances in radiographic imaging, Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are identified with increasing frequency. Although many studies have addressed its biology and treatment, true understanding of its natural history continues to elude us. Its malignant potential places careproviders in a clinical dilemma of balancing the morbidity of pancreatectomy against the risk of malignant transformation while under continuous surveillance. Recently, there have been conflicting data published in the literature, generating more uncertainty in the field. In this article, we critically analyze the contrasting consensus guidelines from the International Association of Pancreatology and the American Gastroenterology Association, and address lingering questions and controversies. We also synthesize newly published data in the context of current standard of care, and provide a comprehensive review and recommendations for the clinical diagnosis, treatment, and follow-up strategy in the management of patients with Intraductal Papillary Mucinous Neoplasms.
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Long-term surveillance is necessary after operative resection for intraductal papillary mucinous neoplasm of the pancreas. Surgery 2016; 160:306-17. [DOI: 10.1016/j.surg.2016.04.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 04/08/2016] [Accepted: 04/12/2016] [Indexed: 01/28/2023]
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Courtin-Tanguy L, Merdrignac A, Meunier B, Sulpice L. A weird polyp, 8 years after the Whipple procedure. Surgery 2016; 162:188-190. [PMID: 27457259 DOI: 10.1016/j.surg.2016.05.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 05/30/2016] [Accepted: 05/31/2016] [Indexed: 11/17/2022]
Affiliation(s)
- Laetitia Courtin-Tanguy
- CHU Rennes, Service de Chirurgie Hépatobiliaire et Digestive, Rennes, France; Université Rennes1, Faculté de médecine, Rennes, France; INSERM, U991, Foie métabolismes et cancer, Rennes, France
| | - Aude Merdrignac
- CHU Rennes, Service de Chirurgie Hépatobiliaire et Digestive, Rennes, France; Université Rennes1, Faculté de médecine, Rennes, France; INSERM, U991, Foie métabolismes et cancer, Rennes, France
| | - Bernard Meunier
- CHU Rennes, Service de Chirurgie Hépatobiliaire et Digestive, Rennes, France; Université Rennes1, Faculté de médecine, Rennes, France
| | - Laurent Sulpice
- CHU Rennes, Service de Chirurgie Hépatobiliaire et Digestive, Rennes, France; Université Rennes1, Faculté de médecine, Rennes, France; INSERM, U991, Foie métabolismes et cancer, Rennes, France; INSERM, U1414, Centre d'investigation Clinique, Rennes, France.
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Yoshida K, Nagasaka T, Umeda Y, Tanaka T, Kimura K, Taniguchi F, Fuji T, Shigeyasu K, Mori Y, Yanai H, Yagi T, Goel A, Fujiwara T. Expansion of epigenetic alterations in EFEMP1 promoter predicts malignant formation in pancreatobiliary intraductal papillary mucinous neoplasms. J Cancer Res Clin Oncol 2016; 142:1557-69. [PMID: 27095449 PMCID: PMC4899496 DOI: 10.1007/s00432-016-2164-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 04/11/2016] [Indexed: 12/19/2022]
Abstract
Purpose Although limited understanding exists for the presence of specific genetic mutations and aberrantly methylated genes in pancreatobiliary intraductal papillary mucinous neoplasms (IPMNs), the fundamental understanding of the dynamics of methylation expansion across CpG dinucleotides in specific gene promoters during carcinogenesis remains unexplored. Expansion of DNA methylation in some gene promoter regions, such as EFEMP1, one of the fibulin family, with tumor progression has been reported in several malignancies. We hypothesized that DNA hypermethylation in EFEMP1 promoter would expand with the tumor grade of IPMN. Methods A sample of 65 IPMNs and 30 normal pancreatic tissues was analyzed. IPMNs were divided into the following three subsets according to pathological findings: 31 with low-grade dysplasia (low grade), 11 with high-grade dysplasia (high grade), and 23 with associated invasive carcinoma (invasive Ca). Mutations in the KRAS or GNAS genes were analyzed by Sanger sequencing, and methylation status of two discrete regions within the EFEMP1 promoter, namely region 1 and region 2, was analyzed by bisulfite sequencing and fluorescent high-sensitive assay for bisulfite DNA (Hi-SA). Expression status of EFEMP1 was investigated by immunohistochemistry (IHC). Results KRAS mutations were detected in 39, 55, and 70 % of low-grade, high-grade, and invasive Ca, respectively. GNAS mutations were observed in 32, 55, and 22 % of low-grade, high-grade, and invasive Ca, respectively. The methylation of individual regions (region 1 or 2) in the EFEMP1 promoter was observed in 84, 91, and 87 % of low-grade, high-grade, and invasive Ca, respectively. However, simultaneous methylation of both regions (extensive methylation) was exclusively detected in 35 % of invasive Ca (p = 0.001) and five of eight IPMNs (63 %) with extensive methylation, whereas 20 of 57 (35.1 %) tumors of unmethylation or partial methylation of the EFEMP1 promoter region showed weak staining EFEMP1 in extracellular matrix (p = 0.422). In addition, extensive EFEMP1 methylation was particularly present in malignant tumors without GNAS mutations and associated with disease-free survival of patients with IPMNs (p < 0.0001). Conclusions Extensive methylation of the EFEMP1 gene promoter can discriminate invasive from benign IPMNs with superior accuracy owing to their stepwise accumulation of tumor progression. Electronic supplementary material The online version of this article (doi:10.1007/s00432-016-2164-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kazuhiro Yoshida
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Takeshi Nagasaka
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan.
| | - Yuzo Umeda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Takehiro Tanaka
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, 700-8558, Japan
| | - Keisuke Kimura
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Fumitaka Taniguchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Tomokazu Fuji
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Kunitoshi Shigeyasu
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Yoshiko Mori
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Hiroyuki Yanai
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, 700-8558, Japan
| | - Takahito Yagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Ajay Goel
- Center for Gastrointestinal Cancer Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, 75246, USA
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
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Fujita M, Itoi T, Ikeuchi N, Sofuni A, Tsuchiya T, Ishii K, Kamada K, Umeda J, Tanaka R, Tonozuka R, Honjo M, Mukai S, Moriyasu F. Effectiveness of contrast-enhanced endoscopic ultrasound for detecting mural nodules in intraductal papillary mucinous neoplasm of the pancreas and for making therapeutic decisions. Endosc Ultrasound 2016; 5:377-383. [PMID: 28000629 PMCID: PMC5206826 DOI: 10.4103/2303-9027.190927] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background and Objectives: There have been few studies to date evaluating the effectiveness of contrast-enhanced endoscopic ultrasound (CE-EUS) for detecting mural nodules in patients with branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas. We aim to evaluate the effectiveness of CE-EUS for detecting mural nodules in BD-IPMN. Patients and Methods: Of the 427 BD-IPMN patients, 21 patients (4.9%) in whom the presence of mural nodules was suggested by CE computed tomography (CT) or magnetic resonance imaging (MRI), or in whom the presence of nodule-like lesions as shown by fundamental EUS, were examined by CE-EUS. Results: The mean diameter of cystic lesions was 29.8 ± 12.8 mm. The mean diameter of mural nodules was 9.5 ± 5.7 mm. BD-IPMN was detected in the pancreatic head in 16 cases, pancreatic body in 2 cases, and pancreatic tail in 3 cases. The mean follow-up period was 17.2 ± 11.9 months. The detection rates of mural nodule-like lesions in BD-IPMN patients on CT, MRI, and fundamental EUS were 36.8%, 63.2%, and 100%, respectively. The detection rates of true mural nodules in BD-IPMN patients on CT, MRI, and fundamental EUS were 85.7%, 71.4%, and 100%, respectively. The echo levels of mural nodule-like lesions on fundamental EUS were hyperechoic in 6 patients, isoechoic in 9 patients, and hypoechoic in 6 patients. The final diagnosis was mucus lumps in 14 patients and mural nodules in 7 patients. The contrast patterns observed were avascular, isovascular, and hypervascular in 14, 3, and 4 patients, respectively. No patients showed a hypovascular pattern. Fourteen patients showing an avascular pattern were diagnosed as having mucus lumps, and they were able to avoid surgical resection. Of the 7 patients who were diagnosed as having mural nodules, 5 underwent surgical resection. The pathological findings were adenocarcinoma in 2 patients and adenoma in 3 patients. Of the 3 adenoma patients, fundamental EUS demonstrated a hypoechoic area in 1 patient and an isoechoic area in 2 patients. Of the 2 adenocarcinoma patients, 1 each showed a hypoechoic area and a hyperechoic area. It was difficult to distinguish between patients with adenoma and patients with adenocarcinoma using the echo levels obtained from fundamental EUS. Conclusions: CE-EUS may be useful for avoiding the overdiagnosis of BD-IPMN with mural nodule-like lesions. However, it has difficulty in distinguishing between clearly benign and malignant lesions in BD-IPMN.
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Affiliation(s)
- Mitsuru Fujita
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Nobuhito Ikeuchi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Atsushi Sofuni
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Takayoshi Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Kentaro Ishii
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Kentaro Kamada
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Junko Umeda
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Reina Tanaka
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Ryosuke Tonozuka
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Mitsuyoshi Honjo
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Shuntaro Mukai
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Fuminori Moriyasu
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
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Elkak AE. Cystic Tumours of the Pancreas: A Challenging Pathology, Diagnosis and Management. JOURNAL OF CANCER THERAPY 2016; 07:712-728. [DOI: 10.4236/jct.2016.710073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Nagata N, Kawazoe A, Mishima S, Wada T, Shimbo T, Sekine K, Watanabe K, Imbe K, Kojima Y, Kumazawa K, Mihara F, Tokuhara M, Edamoto Y, Igari T, Yanase M, Mizokami M, Akiyama J, Uemura N. Development of Pancreatic Cancer, Disease-specific Mortality, and All-Cause Mortality in Patients with Nonresected IPMNs: A Long-term Cohort Study. Radiology 2016; 278:125-34. [DOI: 10.1148/radiol.2015150131] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Qi X, Zhao X, Su J, Xu M, Zhang W, Sheng H, Li Z, Wang J. Malignant transformation and overall survival of morphological subtypes of intraductal papillary mucinous neoplasms of the pancreas: A network meta-analysis. Eur J Intern Med 2015; 26:652-7. [PMID: 26275457 DOI: 10.1016/j.ejim.2015.07.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 07/15/2015] [Accepted: 07/19/2015] [Indexed: 01/08/2023]
Abstract
BACKGROUND Emerging evidence suggests the predictive role of morphological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) of intraductal papillary mucinous neoplasms (IPMNs) in malignant transformation and overall survival. But results of these studies are currently discordant. METHODS A comprehensive literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted for eligible studies. Network meta-analysis using the random-effect model was carried out to detect differences in incidences of invasive IPMNs and hazard ratios from survival curves among four morphological subtypes. RESULTS 19 studies were included in the network comparison. The outcomes showed that pancreatobiliary-type (OR for odds ratio=25.87, 95% CI: 12.11-52.10, compared with gastric-type) and oncocytic-type (OR=18.59, 95% CI: 7.18-42.74) IPMNs had the highest risks of progressing to invasive IPMNs, followed by intestinal-type (OR=5.71, 95% CI: 2.85-10.61) and gastric-type IPMNs. With the gastric type as the baseline, pancreatobiliary-type IPMNs were found to have the worst prognosis (HR for hazard ratio=5.05, 95% CrI: 1.33-13.47) while no significant differences were found for the intestinal type (HR=1.90, 95% CrI: 0.59-4.58) and the oncocytic type (HR=3.29, 95% CrI: 0.75-9.71). CONCLUSION It is suggested that pancreatobiliary-type IPMNs are the most likely to become invasive and are associated with poor prognosis. In contrast, the other three subtypes have similar overall survivals even though the oncocytic- and intestinal-type IPMNs are predisposed to be more invasive than gastric-type IPMNs.
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Affiliation(s)
- Xiaolong Qi
- Department of General Surgery, 302 Hospital of PLA, Beijing 100039, China; Division of Surgical Oncology, Brigham and Women's Hospital, Boston, MA, USA
| | - Xin Zhao
- Department of General Surgery, 302 Hospital of PLA, Beijing 100039, China
| | - Junlei Su
- Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Mingxin Xu
- Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Weifeng Zhang
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029 China
| | - Hui Sheng
- Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Zhiwei Li
- Department of General Surgery, 302 Hospital of PLA, Beijing 100039, China.
| | - Jiping Wang
- Division of Surgical Oncology, Brigham and Women's Hospital, Boston, MA, USA.
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Fong ZV, Castillo CFD. Intraductal Papillary Mucinous Adenocarcinoma of the Pancreas: Clinical Outcomes, Prognostic Factors, and the Role of Adjuvant Therapy. VISZERALMEDIZIN 2015; 31:43-6. [PMID: 26288615 PMCID: PMC4433131 DOI: 10.1159/000373912] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Intraductal papillary mucinous adenocarcinoma (IPMCs) occur more frequently in main-duct intraductal papillary mucinous neoplasms. METHODS Review of the literature. RESULTS The prognosis of IPMCs depends on its histopathological subtype: colloid IPMCs have superior survival rates mainly secondary to more favorable pathological features, whereas tubular IPMCs have survival outcomes similar to that of conventional pancreatic adenocarcinomas. The epithelial background plays an equally important role in defining the biology of IPMCs: gastric IPMC subtypes demonstrate an overall worse survival outcome when compared to intestinal, pancreatobiliary, and oncocytic subtypes. Lymph node involvement is one of the strongest predictors of survival in IPMC, with a decreasing overall survival as the lymph node ratio increases. There is little evidence to support adjuvant chemoradiation in patients with IPMC. CONCLUSION Our current understanding of IPMC biology based on histopathological and epithelial background subtypes as well as clinicopathological predictors should influence patient counseling and selection for adjuvant therapy.
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Affiliation(s)
- Zhi Ven Fong
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Abstract
BACKGROUND Pancreatic cystic lesions (PCL) are common. They are increasingly detected as an incidental finding of transabdominal ultrasound or cross-sectional imaging. In contrast to other parenchymal organs, dysontogenetic pancreatic cysts are extremely rare. In symptomatic patients the most frequent PCL are acute and chronic pseudocysts. The majority of incidental cystic lesions, however, are neoplasias which have different risks of malignancy. METHODS PubMed was searched for studies, reviews, meta-analyses, and guidelines using the following key words: ('pancreatic cystic lesions' OR 'cystic pancreatic lesions' OR 'intraductal papillary mucinous neoplasia' OR 'mucinous cystic neoplasia' OR 'pancreatic cyst' OR 'pancreatic pseudocyst') AND (management OR treatment OR outcome OR prognosis OR diagnosis OR imaging OR 'endoscopic ultrasound' EUS-FNA OR EUS OR 'endoscopic ultrasonography' OR CT OR MRI). Retrieved papers were reviewed with regard to the diagnostic and therapeutic management of incidental PCL. RESULTS In addition to clinical criteria, transabdominal ultrasonography including contrast-enhanced ultrasonography, cross-sectional radiological imaging, and endoscopic ultrasound (EUS) are used for diagnostic characterization and risk assessment. EUS plays an outstanding role in differential diagnosis and prognostic characterization of incidental PCL. In a single examination it is possible to perform high-resolution morphological description, perfusion imaging, as well as fine-needle aspiration of cyst content, cyst wall, and solid components. An international consensus guideline has defined worrisome and high-risk criteria for the risk assessment of mucinous pancreatic cysts, which are mainly based on the results of EUS and cross-sectional imaging. Nevertheless, despite diagnostic progress and guideline recommendations, differential diagnosis and management decisions remain difficult. This review will discuss problems in and approaches to the diagnosis of incidental PCL. CONCLUSION An evidence-based algorithm for the diagnosis of incidental PCL is proposed.
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Affiliation(s)
- Christian Jenssen
- Department of Internal Medicine, Märkisch Oderland Hospital GmbH, Strausberg/Wriezen, Germany
| | - Stefan Kahl
- Department of Internal Medicine, DRK Kliniken Berlin - Köpenick, Berlin, Germany
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Yogi T, Hijioka S, Imaoka H, Mizuno N, Hara K, Tajika M, Tanaka T, Ishihara M, Shimizu Y, Hosoda W, Yatabe Y, Niwa Y, Yoshimura K, Bhatia V, Fujita J, Yamao K. Risk factors for postoperative recurrence of intraductal papillary mucinous neoplasms of the pancreas based on a long-term follow-up study: proposals for follow-up strategies. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:757-65. [PMID: 26148131 DOI: 10.1002/jhbp.280] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 07/02/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to examine the associations between postoperative clinicopathological features of intraductal papillary mucinous neoplasm (IPMN) and recurrence over a long follow-up period. METHODS We retrospectively assessed 153 IPMN patients who underwent resection. RESULTS The resected tumors showed low/intermediate-grade dysplasia (LGD/IGD), high-grade dysplasia (HGD), T1a (stromal invasion ≤5 mm), and invasive intraductal papillary mucinous carcinoma (IPMC), in 54.9%, 22.2%, 4.6%, and 18.3% of patients, respectively. The median follow-up period after surgery was 46.4 (6.0-216.3) months, with an overall recurrence rate of 17.0%; the recurrence rates by histological type were 6.0%, 5.9%, 42.9%, and 57.1% for LGD/IGD, HGD, T1a, and invasive IPMC, respectively. Multivariate analysis revealed that recurrences related with tumor location, mural nodule size, presence of invasive cancer, lymph node metastasis, IPMN in the remnant pancreas, and main pancreatic duct dilatation after surgery. Recurrence occurred within the remnant pancreas in all LGD-T1a patients and as extrapancreatic metastasis in all patients with invasive IPMC. Of the total recurrences, 15.4% occurred over 5 years postoperatively. CONCLUSIONS The postoperative follow-up protocol for patients with LGD-T1a should be similar to non-resected IPMN, and that for invasive IPMC should be the same as for pancreatic ductal adenocarcinoma patients.
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Affiliation(s)
- Tatsuji Yogi
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.,Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Susumu Hijioka
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hiroshi Imaoka
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Masahiro Tajika
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tsutomu Tanaka
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Makoto Ishihara
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasuhiro Shimizu
- Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Waki Hosoda
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasushi Yatabe
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasumasa Niwa
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kenichi Yoshimura
- Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan
| | - Vikram Bhatia
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Jiro Fujita
- Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Kenji Yamao
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
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